DIABETES MELLITUS

Diabetes mellitus is a failure to control blood sugar levels so that they become too high. It is classified into two categories. Type 1 diabetes (also called juvenile diabetes) is characterized by an acute destruction of insulin-secreting beta cells in the pancreas by autoantibodies. Insulin is a hormone essential to maintaining blood sugar at a normal level. Diabetes results in the abolition of insulin secretion by the pancreas, severe hyperglycemia (high blood sugar ) and production of ketones. Type 2 diabetes (also called adult onset diabetes) is characterized by a gradually increasing blood sugar level resulting from a combination of resistance to the action of insulin at the cellular level and a gradual decline of insulin secretion by the pancreas.

Diabetes mellitus is a common disease in the older population. The vast majority of elderly subjects have type 2 diabetes, which means that the degree of hyperglycemia is variable and rarely results in the production of ketones. Since the degree of hyperglycemia is variable and elderly subjects are often not aware of the symptoms of high blood sugar (see below), there may be a few years of asymptomatic disease before a diagnosis of diabetes is made.

Prevalence

The most recent health and nutrition survey in the United States demonstrated that the prevalence of diabetes approaches 20 percent in Caucasian persons over age seventy, and may be as high as 50 percent in certain ethnic groups (Harris et al.). Canadian data suggest a similar picture with about 12 percent of people age sixty-five and older affected (Roc et al.). As of 2000 in North America, the group of people over sixty-five represents about 13 percent of the total population. Assuming that the trend of aging persists, this group will likely represent around 21 percent of the population by 2020. If the prevalence of diabetes remains the same, there is likely to be a marked increase in the absolute number of elderly diabetic patients by the middle of twenty-first century.

Clinical presentation and diagnosis

At least half of elderly individuals with diabetes are unaware that they have the disease, and often the diagnosis is made after the complications of the disease are established (Harris et al.). Although the reasons for late diagnosis of diabetes are unclear, it may be related to a lack of awareness of the diagnostic criteria on the part of physicians, lack of interaction by elderly patients with a physician, and the fact that elderly patients frequently do not manifest the classic symptoms of hyperglycemia: excessive secretion of urine, excessive thirst, and excessive appetite. Symptoms do not generally occur until blood glucose levels are substantially elevated, possibly because the level at which sugar spills into the urine increases with age. When patients do have symptoms, they are often nonspecific (e.g., failure to thrive, low energy, confusion, frequent urination, with or without incontinence, various infections), and may not always trigger the measurement of a plasma glucose level or a consultation with a physician. This phenomenon, along with the fact that identification and management of diabetes can relieve many of these symptoms, improve the quality of life, and prevent or delay subsequent chronic illnesses, highlights the importance of screening for diabetes in elderly individuals.

The diagnosis of diabetes may be accomplished by measuring fasting plasma glucose. It is currently recommended that fasting glucose be measured every three years in elderly persons and yearly in persons with risk factors for the development of diabetes, such as obesity, hypertension, and a strong family history of diabetes. The diagnosis of diabetes is made by a fasting plasma glucose of at least 7.0 millimol/liter on two occasions. A diagnosis can also be made when a patient is found to have a glucose of at least 11.1 millimol/liter two hours after a 75 gram oral glucose load (American Diabetes Association, 1997), but for practical reasons a glucose tolerance test is not generally performed.

Complications

As a result of high blood sugar levels; abnormalities of lipid levels, blood pressure regulation, and blood coagulation; and oxidative stress, elderly patients with diabetes develop a number of complications. The long-term complications of diabetes are classified as microvascular (mainly kidney and eye problems) and macrovascular (vascular problems related to heart, brain, and lower limbs). Diabetes is a leading cause of blindness, kidney failure leading to hemodialysis, heart problems (angina and infarction), and limb amputation in the elderly diabetic population.

Treatment

All clinicians agree that blood glucose levels should be controlled sufficiently well to reduce the symptoms of hyperglycemia. There is less consensus regarding the optimal degree of blood sugar control in elderly diabetic patients. This is due in part to the fact that no randomized controlled trials involving elderly subjects have definitively assessed whether tight blood glucose control reduces the risk of disease and disability in this age group. The United Kingdom Prospective Diabetes Study (UKPDS) recruited middle-aged patients with type 2 diabetes and randomized them to either intensive blood glucose control with metformin, sulfonylurea, or insulin or a control group with conventional treatment. The UKPDS data did demonstrate that improved glycemic control reduces the risk of microvascular complications related to diabetes, and perhaps macrovascular complications in middle-aged patients. Furthermore, in observational studies of elderly subjects, improved glycemic control is associated with a reduced risk of microvascular and macrovascular complications related to diabetes (Kuusisto et al.; Morisaki et al.), as well as with improved cognitive function (Meneilly et al.). Based on these data, it is recommended that goals for control in elderly patients should be less than 7 millimol/liter before meals and less than 10 millimol/liter after meals.

Nonpharmacological intervention. Achieving optimal blood sugar control in elderly persons with diabetes is challenging. These patients take numerous medications, have multiple comorbidities, and often live in challenging social situations. Because of the complex nature of these patients and the need for lifestyle modifications, a team approach is essential. A structured diabetes teaching program will improve blood sugar control, compliance with therapy, and quality of life in older patients. Self-monitoring of blood sugar level at home is possible with a portable device called a glucometer. The self-monitoring of blood sugar constitutes a key aspect of diabetic management. Levels of HbA1c (glycosilated hemoglobin) and/or fructosamine are the standard laboratory measures of long-term glycemic control in older individuals, and should be assessed at regular intervals (Meltzer et al.).

Exercise programs have been shown to improve the sense of well-being, glucose levels, and lipid levels in elderly patients with diabetes (Agurs-Collins et al.). Unfortunately, concomitant health problems often prevent elderly patients from participating in exercise programs, and optimal activity levels may be difficult to achieve. Thus exercise programs of even low and moderate intensity are of value in selected elderly patients.

Elderly patients with diabetes have diets that are too low in complex carbohydrates and too high in saturated fats, and they frequently do not comply with a diabetic diet. As noted above, multidisciplinary interventions have been shown to improve compliance with dietary therapy in aged diabetics. For community-dwelling elderly subjects, weight loss programs have been shown to result in substantial improvements in blood sugar control (Reaven et al.). In contrast, for frail elderly nursing home residents, diabetic diets complicate and increase the cost of care, and do not improve blood sugar control.

Pharmacological intervention. The principal metabolic defect in lean elderly patients with diabetes is profound impairment in glucose-induced insulin secretion. Medications that stimulate insulin secretion, such as sulfonylureas, have been widely used for the treatment of diabetes in elderly patients that is not controlled with dietary therapy. This kind of medication is associated with an increased risk of hypoglycemia, especially in the elderly. Chlorpropamide and glyburide are the sulfonylureas associated with the greatest risk of hypoglycemia in the elderly. Observational studies and small, randomized controlled trials suggest that glipizide and gliclazide are associated with a lower risk of hypoglycemia in the older population with diabetes (Brodows; Tessier et al.). In general, initial doses of these drugs should be half those for younger people, and should be increased more slowly. The role of newer insulin-stimulating drugs, such as repaglinide, remains to be determined for elderly patients with diabetes.

The UKPDS suggests that metformin, a member of the biguanide family, is an effective agent in obese middle-aged patients, and may be more beneficial than sulfonylureas in reducing the risk of morbid events. The main effect of metformin is to reduce insulin resistance. This drug results in substantial improvements in blood sugar control in obese elderly patients (Lalau et al.). Metformin should not be given to patients with creatinine values (blood indicator of kidney function) above 180 microns/liter, chronic liver disease, or significant congestive heart failure. Based on clinical experience, sulfonylureas and metformin can often be given in combination to elderly patients with diabetes to improve blood sugar control.

Because of their ability to improve insulin resistance, thiazolidinediones (pioglitazone and rosiglitazone) may also be a useful class of drugs for obese elderly patients. This class of drug improves insulin resistance. Pending the results of further studies in the elderly, this class of drugs should be reserved for the treatment of obese elderly patients whose blood sugar is not optimally controlled with another kind of antidiabetic medication. When thiazolidinediones are prescribed for the elderly, liver function should be monitored at regular intervals.

Alpha glucosidase inhibitors are a class of drugs that interfere with the action of the enzymes responsible for the digestion of complex carbohydrates and disaccharides at the brush border of the intestine. This class of drugs slows the absorption of glucose through the small intestine. Acarbose is the first of these drugs released for clinical use. A study has been published on the efficacy of this drug for elderly diabetes patients (Meneilly et al.). At present, acarbose should be considered as first-line therapy for lean elderly patients with a modest increase in fasting glucose levels.

Insulin therapy substantially improves blood sugar control with no adverse effect on the quality of life in patients who are inadequately controlled by oral agents (Tovi and Engfeldt). Elderly patients can make substantial errors when trying to mix different kinds of insulin in the same syringe (e.g., the rapid-acting R or Toronto insulin with the intermediate-acting N or NPH insulin). For this reason, insulin preparations that do not require mixing are preferable for them. In type 2 diabetes, insulin therapy is usually started ". . .with one dose of intermediate acting insulin in addition to pills given at different times of the day such as metformin and glyburide." However, many patients who are started on one daily dose of insulin need a second injection in order to control blood sugar.

Management of hypertension and excess lipids

Traditional risk factors for cardiovascular disease, such as smoking, hypertension, and excess lipids, are associated with an increased risk of diabetes-related complications in the elderly. Modification of these risk factors may reduce the risk of these complications.

Studies suggest that treatment of hypertension with drugs such as the thiazide diuretics and calcium channel blockers reduces mortality and the risk of vascular complications related to diabetes in the elderly (Tuomilehto et al.; Curb et al.). In the Systolic Hypertension in the Elderly Patient study (SHEP), patients with systolic hypertension and type 2 diabetes who were treated with a thiazide diuretic, had a significantly lower incidence of cardiovascular events than subjects receiving a placebo. The absolute risk reduction with active treatment compared with the placebo was twice as great for diabetic as for nondiabetic patients who participated in this study. The Systolic Hypertension in Europe Trial (SystEur) undertook a similar subgroup analysis of older patients with both hypertension and type 2 diabetes. Among the nondiabetic participants who were started on a calcium-channel blocker, nitrendipine, a 55 percent reduction of mortality was observed compared to the placebo group. In the group receiving active treatment, reduction of overall mortality was significantly higher among the diabetic patients than among the nondiabetic ones.

There are no data from randomized trials in the elderly diabetic population to determine the benefits of treatment of excess lipids. Subgroup analysis of middle-aged patients with diabetes (Pyorala et al.; Goldberg et al.) and subjects sixty-five or older (LIPID Study Group) who enrolled in prevention trials suggesting that reduction of low-density lipoprotein (LDL) cholesterol can significantly decrease vascular events in this population.

Perspective

Considering the aging trend in American society, an increased prevalence of diabetes is expected among the elderly population. The economic and sociological impacts of this health problem will dramatically increase by the middle of the twenty-first century. More research will be necessary to understand the disease and the mechanisms involved in the progression of associated complications.

Daniel Tessier Tamas FÜrlÖp Graydon S. Meinelly

See also Cholesterol; Diet; Disease Presentation; Heart Disease; High Blood Pressure.

BIBLIOGRAPHY

Agurs-Collins, T. D.; Kumanyika, S. K.; Ten Have, T. R. et al. "A Randomized Controlled Trial of Weight Reduction and Exercise for Diabetes Management in Older African-American Subjects." Diabetes Care 20 (1997): 1503–1511.

American Diabetes Association. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. "Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus" 20 (1997): 1183–1197. Brodows, R. G. "Benefits and Risks with Glyburide and Glipizide in Elderly NIDDM Patients." Diabetes Care 15 (1992): 75–80.

Curb, J. D.; Pressel, S. L.; Cutler, J. et al. "Effect of Diuretic Based Antihypertensive Treatment on Cardiovascular Risk in Older Diabetic Patients with Isolated Systolic Hypertension." Journal of the American Medical Association 276 (1996): 1886–1892.

Goldberg, R. B.; Mellies, M. J.; Sacks, F. et al. "Cardiovascular Events and Their Reduction with Pravastatin in Diabetic and Glucose-Intolerant Myocardial Infarction Survivors with Average Cholesterol Levels: Subgroup Analyses on the Cholesterol and Recurrent Events (CARE) Trial." Circulation 98 (1998): 2513–2519.

Harris, M. I.; Flegal, K. M.; Cowie, C. C. et al. "Prevalence of Diabetes, Impaired Fasting Glucose, and Impaired Glucose Tolerance in U.S. Adults. The Third National Health and Nutrition Examination Survey, 1988–1994." Diabetes Care 21 (1998): 518–1924.

Kuusisto, J.; Mykkanen, L.; Pyorala, K. et al. "NIDDM and Its Metabolic Control Predict Coronary Heart Disease in Elderly Subjects." Diabetes 43 (1994): 960–967.

Lalau, J. D.; Vermersch, A.; Hary, L. et al. "Type 2 Diabetes in the Elderly: An Assessment of Metformin." International Journal of Clinical Pharmacology and Therapeutic Toxicology 28 (1990): 329–332.

LIPID Study Group. "Prevention of Cardiovascular Events and Death with Pravastatin in Patients with Coronary Heart Disease and a Broad Range of Initial Cholesterol Levels." New England Journal of Medicine 339 (1998): 1349–1357.

Meneilly, G. S.; Cheung, E.; Tessier, D. et al. "The Effect of Improved Glycemic Control on Cognitive Functions in the Elderly Patient with Diabetes." Journal of Gerontology 48 (1993): M117–M121.

Meneilly, G. S.; Ryan, E. A.; Radzuik, eJ. et al. "Effect of Acarbose on Insulin Sensitivity in Elderly Patients with Diabetes." Diabetes Care 23 (2000): 1162–1167.

Meltzer S.; Leiter, L.; Daneman, D.; Gerstein,HJ. C. et al. "1998 Clinical Practice Guidelines for the Management of Diabetes in Canada." Canadian Medical Association Journal 159 (8 suppl) (1998): S1–S29.

Morisaki, N.; Watanabe, S.; Kobayashi, J. et al. "Diabetic Control and Progression of Retinopathy in Elderly Patients: Five-Year Follow-up Study." Journal of the American Geriatric Society 42 (1994): 142–145.

Pyorala, K.; Pedersen, T. R.; Kjekshus, J. et al. "Cholesterol Lowering with Simvastatin Improves Prognosis of Patients with Coronary Heart Disease: A Subgroup Analysis of the Scandinavian Simvastatin Survival Study (4S)." Diabetes Care 20 (1997): 614–620.

Reaven, G. M., and Staff of the Palo Alto GRECC Aging Study Unit. "Beneficial Effects of Weight Loss in Older Patients with NIDDM." Journal of American Geriatric Society 33 (1985): 93–95.

Rockwood, K.; Tar, M. H.; Phillips, S.; and Mcdowell, I. "Prevalence of Diabetes Mellitis in Elderly People in Canada." Age Ageing 27 (1998): 573–577.

Tessier, D.; Dawson, K.; Tetrault, J. P. et al. "Glibenclamide vs. Gliclazide in Type 2 Diabetes of the Elderly." Diabetic Medicine 11 (1994): 974–980.

Tovi, J., and Engfeldt, P. "Well-being and Symptoms in Elderly Type 2 Diabetes Patients with Poor Metabolic Control: Effect of Insulin Treatment." Practical Diabetes International 15 (1998): 73–77.

Tuomilehto, J.; Rastenyte, D.; Birkenhager, W. H. et al. "Effects of Calcium-Channel Blockade in Older Patients with Diabetes and Systolic Hypertension. Systolic Hypertension in Europe Trial Investigators." New England Journal of Medicine 340 no. 9 (1999): 677–684.

United Kingdom Prospective Diabetes Study. "Intensive Blood Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes (UKPDS33)." Lancet 352, no. 9131 (12 September 1998): 837–853.

DIABETES MELLITUS

The term "diabetes mellitus" represents a group of conditions characterized by abnormally high blood glucose levels (hyperglycemia). In 1997, nearly 16 million people in the United States had diabetes; approximately 10.3 million were diagnosed with the conditions, while an estimated 5.4 million were undiagnosed. Diabetes may be complicated by uncontrolled hyperglycemia, and treated diabetes may be complicated by abnormally low blood glucose levels (hypoglycemia). Maternal diabetes is associated with an increased incidence of major birth defects. Over time, diabetes may cause complications involving the eyes (retinopathy), kidneys (nephropathy), and nerves (neuropathy). Diabetes is also associated with an increased incidence of cardiovascular disease, including stroke, heart attack, and peripheral vascular disease. In the United States today, diabetes is a leading cause of birth defects, blindness, kidney failure, and nontraumatic leg amputations. It is also a major contributor to cardiovascular disease. Diabetes is the seventh leading cause of death in the United States, and medical care for people with diabetes is estimated to cost over $100 billion per year.

When diabetes is associated with marked hyperglycemia, it produces characteristic symptoms and signs; particularly increased thirst (polydipsia), increased urination (polyuria), and unexplained weight loss. At other times, hyperglycemia sufficient to cause changes in the eyes, kidneys, and nerves, and to increase the risk of cardiovascular disease, may be present without clinical symptoms. During this asymptomatic period, an abnormality in glucose metabolism may be demonstrated by measuring fasting venous glucose or venous glucose after an oral glucose challenge.

DIAGNOSIS

When a patient is symptomatic and the plasma glucose is unequivocally elevated, a diagnosis of diabetes presents no difficulty. When a patient is without clinical symptoms, a diagnosis of diabetes is more difficult. According to a 1997 American Diabetes Association (ADA) report, there are three ways to diagnose diabetes (see Table 1). All require measurement of venous plasma glucose, and each must be confirmed on a subsequent day by any one of the three methods. In general, the oral glucose tolerance test is not recommended for routine clinical use and is performed only in patients with elevated but nondiagnostic fasting plasma-glucose levels with a high index of suspicion for diabetes.

CLASSIFICATION

Once a diagnosis of diabetes mellitus is established, it is necessary to differentiate the various forms of the syndrome. Prior to 1979, diabetes was

Table 1

classified on the basis of age at diagnosis as either juvenile-onset diabetes mellitus (JODM) or adult-onset diabetes mellitus (AODM). In the late 1970s and early 1980s, a new classification system recognized two major forms of diabetes: insulin-dependent diabetes mellitus (IDDM or type I diabetes) and non-insulin-dependent diabetes mellitus (NIDDM or type II diabetes). In 1997, the American Diabetes Association recommended modifications to this classification system that eliminated the terms "insulin-dependent diabetes mellitus" and "non-insulin-dependent diabetes mellitus" and their acronyms. The terms "type 1" and "type 2" were retained, with Arabic numerals replacing the Roman numerals. Other specific types of diabetes were also recognized.

Type 1 diabetes is caused by pancreatic beta cell (B-cell) destruction. Immune-mediated type 1 diabetes results from cell-mediated autoimmune destruction of the B-cells of the pancreatic islets. This type of diabetes also has strong genetic or human leukocyte antigen (HLA) associations that can be either predisposing or protective. Another form of type 1 diabetes, termed "idiopathic" type 1 diabetes, is strongly inherited but lacks immunologic evidence for B-cell autoimmunity and is not HLA-associated. Most patients with

Table 2

idiopathic type 1 diabetes are of African or Asian descent.

Type 1 diabetes accounts for approximately 5 percent of diagnosed diabetes in the United States—approximately 500,000 Americans have type 1 diabetes. Type 1 diabetes commonly occurs in childhood and adolescence, but it can occur at any age. Patients with type 1 diabetes are prone to ketoacidosis (decompensated diabetes with hyperglycemia and presence of abnormal acids [ketones] in the blood). Many affected patients have no family history of diabetes. Although most patients with type 1 diabetes are lean when they are diagnosed, the presence of obesity is not incompatible with the diagnosis.

Type 2 diabetes is characterized by both impairment of insulin secretion and defects in insulin action. It is often unclear which abnormality is the primary cause of hyperglycemia. Although patients with this type of diabetes may have insulin levels that appear normal or elevated, insulin levels are always low relative to the elevated plasma glucose levels. Thus, insulin secretion is defective in these patients and insufficient to compensate for the degree of insulin resistance. Although the specific origin of type 2 diabetes is not known, autoimmune destruction of B-cells does not occur. Although type 2 diabetes is associated with a strong genetic predisposition, the genetics of this form of diabetes are complex and not clearly defined.

Type 2 diabetes accounts for approximately 95 percent of diagnosed diabetes in the United States (9.8 million cases), and for the vast majority of the cases of undiagnosed diabetes. The risk of type 2 diabetes increases with age, obesity, and physical inactivity. As such, it is often regarded as a disease associated with a modern Western lifestyle. Type 2 diabetes occurs more frequently in women with prior gestational diabetes and in individuals with hypertension and dyslipidemia. Affected patients often have a family history of diabetes. Type 2 diabetes is more common in African Americans, Hispanic Americans, and Native Americans than in non-Hispanic white Americans. Ketoacidosis seldom occurs spontaneously in type 2 diabetes, but it may arise in association with the stress of another illness. Approximately 70 percent of patients with type 2 diabetes are obese.

TREATMENT

Large, prospective, randomized, controlled clinical trials in both type 1 and type 2 diabetes have demonstrated that normal or near-normal blood glucose control can delay or prevent the development of major birth defects and the development and progression of complications affecting the eyes, kidneys, and nerves. Accordingly, the goals for management for both type 1 and type 2 diabetes are to achieve glucose levels as close to the nondiabetic range as possible while minimizing the side-effects of treatment (hypoglycemia and weight gain).

In nondiabetic subjects, blood glucose levels are between 70 and 90 mg/dl (milligrams per deciliter) in the fasting state and rise to 120 to 140 mg/dl one to two hours after meals. These values reflect normal glucose tolerance. Average glucose levels may be assessed by measurement of glycosylated hemoglobin (hemoglobin A1c), is a measure of the average blood glucose level over the previous two to four months. In nondiabetic subjects, hemoglobin A1c is generally less than 6.1 percent, and in poorly controlled diabetic subjects, it may rise to 12 percent or higher.

In general, the goals of treatment are to achieve blood glucose and hemoglobin A1c levels as close to the nondiabetic range as possible with diet, physical activity, and medications.

Diet. In type 1 diabetes, diet is designed to provide adequate nutrients for growth and development and for the maintenance of ideal body weight. The recommended diet includes approximately 20 percent of daily calories from protein, 30 percent from fat, and 50 percent from complex carbohydrates. Simple sugars are limited to prevent excessive glucose excursions, and carbohydrate content is distributed into regular meals and

Table 3

snacks so that a similar quantity of carbohydrate is consumed at approximately the same time each day.

In type 2 diabetes, caloric content is adjusted to achieve and maintain an ideal body weight or, in those who are obese, to produce gradual weight loss or at least weight maintenance. Dietary composition may also be adjusted in light of intercurrent conditions. For example, sodium may be restricted for patients with hypertension, and both total fat and saturated fat may be restricted for those with high cholesterol.

Exercise. Exercise lowers blood glucose and improves glucose tolerance in diabetics. Other benefits of exercise are reductions in LDL cholesterol and triglycerides levels, and improvements in HDL cholesterol, improvements in blood pressure, improved cardiovascular fitness, and an increased sense of well-being and quality of life. Because exercise may potentiate the hypoglycemic effect of injected insulin and may, paradoxically, result in elevated blood glucose levels and the rapid development of ketosis in type 1 diabetic patients in poor metabolic control, the goal of management in type 1 diabetes is to permit people to enjoy and participate safely in physical and sport activities. In type 2 diabetes, exercise is frequently prescribed as an adjunct to reduced-calorie diets for weight reduction and to improve insulin resistance.

Medications. Because patients with type 1 diabetes are absolutely insulin deficient, treatment requires insulin injections. Although one or two injections per day are often adequate to prevent symptoms of hyperglycemia, intensive therapy employing three or four insulin injections per day, or continuous subcutaneous insulin infusion, may be necessary to achieve near-normal glucose control.

Both oral medications and injected insulin are used for the treatment of type 2 diabetes. Four groups of oral agents are currently available: insulin secretagogues, which enhance nutrient-stimulated insulin secretion; the biguanides, which suppress abnormal glucose production by the liver; the thiazolidinediones, which reduce insulin resistance at the level of muscle and fat; and the alpha-glucosidase inhibitors, which slow the breakdown and absorption of carbohydrates and reduce postprandial glucose excursions. To the extent that these four groups of oral medications have different mechanisms of action, they can be used clinically in combination. When oral agents are ineffective in controlling hyperglycemia or achieving glycemic goals, insulin is added or substituted.

MONITORING

Self-monitoring of blood glucose is integral to modern diabetes therapy. A lancet is used to obtain a small drop of blood, which is placed on a reagent strip and inserted in a small battery-powered meter. The meter reports the blood glucose level in less than a minute. Results of self-monitoring of blood glucose are used to guide adjustments in diet, exercise, and medications, for the monitoring and treatment of hypoglycemia, and in the home management of intercurrent illness.

INCIDENCE AND PREVALENCE

The number of people developing diabetes and the number of people with diabetes are increasing worldwide. In 2000, it was estimated that 154 million persons, or 4.2 percent of the world's population, twenty years of age and older had diabetes. By the year 2025, it is estimated that nearly 300 million persons, or 5.4 percent of the world's population, twenty years of age and older will have diabetes. The major part of this increase will occur in developing countries due to the aging of the population and increasing urbanization (associated with increased body weight and decreased physical activity).

In 1994, there were 939,000 Americans newly diagnosed with diabetes, with a disproportionate number among the elderly and minority populations. The incidence of diagnosed diabetes was3.61 cases per 1,000 persons per year in 1994 (see Table 2).

In 1994, about 8 million persons in the United States (3.1 percent of the population) reported that they had diabetes. The prevalence of diagnosed diabetes increases with age (see Table 3).

MORTALITY

Diabetes is the seventh leading cause of deaths in the United States. The highest death rates due to diabetes are observed in older Americans and in minority populations. Death certificates underestimate diabetes mortality because of underreporting of diabetes. Only about 10 percent of people with diabetes who die have diabetes listed as the underlying cause of death on their death certificates, and only about 40 percent have it listed anywhere on their death certificates. Diabetes was the underlying cause of death for approximately 57,000 Americans in 1994, and diabetes was recorded on the death certificate of approximately 182,000 Americans. In 1994, black women had the highest death rates due to diabetes, followed by white women and men. That same year, 44 percent of all diabetes-related deaths (80,000 deaths) had cardiovascular disease listed as the underlying cause. Of these deaths, approximately 60 percent were caused by ischemic heart disease and 15 percent by stroke.

COMPLICATIONS AND COMORBIDITIES ASSOCIATED WITH DIABETES

Diabetic Ketoacidosis (DKA). Ketoacidosis is an acute metabolic complication of diabetes associated with hyperglycemia, nausea, vomiting, abdominal pain, dehydration, ketonemia, and acidosis. In 1994, DKA was the primary diagnosis for 89,000 hospital discharges and a listed diagnosis for 113,000 hospital discharges. Clinical trials have demonstrated that improved education in self-management and improved access to care can prevent up to 70 percent of DKA hospitalizations.

Adverse Outcomes of Pregnancy. Each year in the United States, type 1 diabetes complicates approximately 7,000 pregnancies and type 2 diabetes complicates approximately 12,000 pregnancies. Up to 1,700 infants (9%) of mothers with pregnancies complicated by diabetes (in the U.S.) are born with birth defects affecting the brain, spinal cord, heart, kidneys, and skeleton. Clinical trials have demonstrated that with intensive glycemic control before conception and during the first trimester, the incidence of major birth defects may be reduced to 2 percent, the rate that occurs in infants of nondiabetic mothers.

Diabetic Eye Disease. Diabetes is the leading cause of new cases of legal blindness in Americans between twenty and seventy-four years of age. As many as 40,000 Americans become blind each year as a result of diabetes. In type 1 diabetes, most legal blindness is due at least in part to diabetic retinopathy. Timely diagnosis and appropriate laser treatment can prevent up to 90 percent of blindness due to diabetic retinopathy. In type 2 diabetes, cataract, glaucoma, and senile macular degeneration are more frequent causes of blindness.

Diabetic Kidney Disease. Diabetic nephropathy is characterized by hypertension, proteinuria, and progressive renal insufficiency. Diabetes is now the leading cause of end-stage renal disease (kidney failure requiring dialysis or kidney transplant for survival). In 1997, over 33,000 Americans developed end-stage renal disease due to diabetes. Early detection, aggressive blood pressure control, and treatment with angiotensin-converting enzyme inhibitors can reduce the progression of diabetic nephropathy by about 60 percent.

Amputations. Diabetic neuropathy, peripheral vascular disease, and infection predispose people with diabetes to gangrene and amputations. More than half of all nontraumatic lower extremity amputations (LEAs) occur in people with diabetes. In 1994, there were approximately 67,000 diabetes-related hospital discharges with LEA reported as a procedure in the United States. Clinical trials have demonstrated that early detection of insensitive and deformed feet and multidisciplinary foot-care programs can reduce the rate of amputation by more than 50 percent.

Cardiovascular Disease Cardiovascular disease (CVD) is the leading cause of morbidity and

Table 4

mortality in people with diabetes. Stroke, heart attack, and peripheral vascular disease are two to four times more common in people with diabetes than in people without diabetes. In 1994, there were 1,144,000 diabetes-related hospital discharges that had CVD listed as the primary discharge diagnosis (see Table 4). Part of the increased incidence of cardiovascular disease in people with diabetes is due to the greater prevalence of cardiovascular risk factors, including hypertension, dyslipidemia, and cigarette smoking. Clinical trials have demonstrated that pharmacologic treatments for hypertension and dyslipidemia are as effective, if not more effective, in people with diabetes compared to people without diabetes.

COSTS OF DIABETES

Health care costs incurred by people with diabetes include non-diabetes-related and diabetes-related costs. In the United States, in 1992, the direct cost of non-diabetes-related and diabetes-related medical care incurred by people with diabetes was estimated to be $105.2 billion. The direct cost of medical care attributable to diabetes was estimated to be $45.2 billion and the indirect cost of diabetes was estimated to be $46.6 million (see Table 5).

In 1992, per capita health care expenditures for people with diabetes averaged $9,493, compared to $2,604 for people without diabetes. When adjusted for age, per capita health care expenditures for people with diabetes were approximately

Table 5

$3,800 higher for people with diabetes than for people without diabetes ($6,425 versus $2,604).

The fact that 62 percent of direct health care costs among people with diabetes and 82 percent of costs directly attributable to diabetes are incurred in the hospital setting suggests that the majority of costs are associated with the treatment of the late, chronic complications of diabetes.

SCREENING FOR TYPE 2 DIABETES

One-third of diabetes in the United States is undiagnosed, and one-third to one-half of all diabetes worldwide is undiagnosed. This finding, combined with the fact that glycemic management can prevent or delay the development of complications, and the fact that diabetic patients may already have complications at clinical diagnosis, have lead some to call for public health screening for type 2 diabetes. In general, screening is appropriate in asymptomatic populations when six specific conditions are met (see Table 6).

Table 6

Diabetes imposes substantial morbidity and mortality on the population. The natural history of type 2 diabetes is well understood, and with systematic testing, diabetes can be diagnosed in asymptomatic, preclinical, subjects. Unfortunately, although it is clear that intensified management can improve outcomes, no studies have demonstrated the effectiveness or safety of early treatment. Likewise, there is no consensus as to the optimal approach to screening for type 2 diabetes. Ideally, a screening test should be both sensitive and specific. Generally, however, trade-offs must be made between sensitivity and specificity (increasing sensitivity reduces specificity, and increasing specificity reduces sensitivity). In some health systems, the costs of screening and treatment are reasonable, but in others they are simply unaffordable. Finally, although it is recognized that screening must be an ongoing process, no empirical data exist to indicate the optimal screening frequency.

Questionnaires that use self-reported demographic, behavioral, and past medical history to assign a person to a higher or lower risk group; fasting, random, and postprandial urine glucose tests; fasting, random, and postprandial capillary whole blood and capillary plasma glucose tests; fasting, random, and postprandial venous whole blood and plasma glucose tests; and hemoglobin A1c have all been evaluated as screening tests for diabetes. In general, questionnaires perform rather poorly as screening tests for diabetes. Measurement of glycosuria using a cut-off point greater than or equal to a trace value generally has a low sensitivity and a high specificity. Capillary or venous whole blood or plasma glucose determinations have generally performed better than urine glucose testing. With both urine and blood testing, random, postprandial, and glucose-loaded tests perform better than fasting tests. There is little consensus, however, as to optimal cut-points for defining positive tests. Screening with hemoglobin A1c has suffered from lack of standardization of the assay. Even as this problem has been addressed, the test has generally been found to be specific but less sensitive than glucose measurements.

Accordingly, the American Diabetes Association has recommended that clinicians should be vigilant and recognize clinical histories and signs suggestive of diabetes that warrant testing. Generally, screening of high-risk individuals for type 2 diabetes should be performed only as part of ongoing medical care, understanding that the evidence is incomplete and questions remain as to the benefits and risks of early treatment, the optimal screening methods and cut-points, and screening frequency. Community-based screening for diabetes is generally associated with a low yield and poor follow-up, and it probably does not represent a good use of resources.

William H. Herman

Liza L. Ilag

(see also: Cardiovascular Diseases; Glycosylated Hemoglobin; Noncommunicable Disease Control; Nutrition; Screening )

Bibliography

Centers for Disease Control and Prevention (1997). Diabetes Surveillance, 1997. Atlanta, GA: CDC.

DCCT Research Group (1993). "The Effect of Intensive Treatment of Diabetes on the Development and Progression of Long-Term Complications in Insulin-Dependent Diabetes Mellitus." New England Journal of Medicine 329: 977–986.

Engelgau, M. M.; Venkat Narayan, K. M.; and Herman, W. H. (2000). "Screening for Type 2 Diabetes." Diabetes Care 23:1563–1580.

Fox-Ray, N.; Mills, S.; and Thamer, M. (1993). Direct and Indirect Costs of Diabetes in the United States in 1992. Alexandria, VA: American Diabetes Association.

King, H.; Aubert, R. E.; and Herman, W. H. (1998). "Global Burden of Diabetes, 1995–2025: Prevalence, Numerical Estimates, and Projections." Diabetes Care 21:1414–1431.

Lebovitz, H. E., ed. (1998) Therapy for Diabetes Mellitus and Related Disorders, 3rd edition. Alexandria, VA: American Diabetes Association.

National Diabetes Data Group (1995). Diabetes in America, 2nd edition. Bethesda, MD: National Institute of Health.

Rubin, R. J.; Altman, W. M.; and Mendelson, D. N. (1994). "Health Care Expenditures for People with Diabetes Mellitus, 1992." Journal of Clinical Endocrinolical Metabolism 78:809a–809f.

UK Prospective Diabetes Study (UKPDS) Group (1998). "Intensive Blood-Glucose Control with Sulphonylureas or Insulin Compared with Conventional Treatment and Risk of Complications in Patients with Type 2 Diabetes." Lancet 352:857–853. (Published erratum appears in Lancet 354:602.

Diabetes mellitus

Definition

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or when cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, tiredness, excessive thirst, and hunger.

Description

Diabetes mellitus is a chronic disease that causes serious health complications including renal (kidney) failure, heart disease, stroke , and blindness. Approximately 14 million Americans (about 5% of the population) have diabetes. Unfortunately, as many as one-half of them are unaware that they have it.

Background

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for cells. Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin binds to receptor sites on the outside of cells and acts like a key to open a door-way

into the cell through which glucose can enter. Some of the glucose can be converted to concentrated energy sources like glycogen or fatty acids and saved for later use. When there is not enough insulin produced or when the doorway no longer recognizes the insulin key, glucose stays in the blood instead of entering the cells.

The body will attempt to dilute the high level of glucose in the blood, a condition called hyperglycemia, by drawing water out of the cells and into the bloodstream. The excess sugar is excreted in the urine. It is not unusual for people with undiagnosed diabetes to be constantly thirsty, to drink large quantities of water, and to urinate frequently as their bodies try to get rid of the extra glucose. This creates high levels of glucose in the urine.

At the same time that the body is trying to get rid of glucose from the blood, the cells are starving for glucose and sending signals to the body to eat more food, thus making patients extremely hungry. To provide energy for the starving cells, the body also tries to convert fats and proteins to glucose. The breakdown of fats and proteins for energy causes acid compounds called ketones to form in the blood. Ketones also will be excreted in the urine. As ketones build up in the blood, a condition called ketoacidosis can occur. If left untreated, ketoacidosis can lead to coma and death.

Types of diabetes mellitus

Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces little or no insulin. It is characterized by a sudden onset and occurs more frequently in populations descended from northern European countries (Finland, Scotland, Scandinavia)

than in those from southern European countries, the Middle East, or Asia. In the United States, approximately 3 people in 1,000 develop Type I diabetes. This form also is called insulin-dependent diabetes because people who develop this type need to have injections of insulin 1–2 times per day.

Brittle diabetics are a subgroup of Type I where patients have frequent and rapid swings of blood sugar levels between hyperglycemia (a condition where there is too much glucose or sugar in the blood) and hypoglycemia (a condition where there are abnormally low levels of glucose or sugar in the blood). These patients may require several injections of different types of insulin or an insulin pump during the day to keep their blood sugar within a fairly normal range.

The more common form of diabetes, Type II, occurs in approximately 3–5% of Americans under 50 years of age, and increases to 10–15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. In 2003, a report noted that nearly one-third of the U.S. population over age 20 has this form of diabetes but remains undiagnosed. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and do not exercise . It also is more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures are also more likely to develop Type II diabetes than those who remain in their original countries.

Type II is considered a milder form of diabetes because of its slow onset (sometimes developing over the course of several years) and because it can usually be controlled with diet and oral medication. The consequences of uncontrolled and untreated Type II diabetes, however, are just as serious as those for Type I. This form also is called noninsulin-dependent diabetes, a term that is somewhat misleading. Many people with Type II diabetes can control the condition with diet and oral medications, however, insulin injections sometimes are necessary.

Another form of diabetes, called gestational diabetes, can develop during pregnancy and generally resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of pregnancy in about 2% of pregnancies. The condition usually is treated by diet, however, insulin injections may be required. Women who have diabetes during pregnancy are at higher risk for developing Type II diabetes within 5–10 years.

Diabetes also can develop as a result of pancreatic disease, alcoholism , malnutrition, or other severe illnesses that stress the body.

Causes & symptoms

The causes of diabetes mellitus are unclear, however, there seem to be both hereditary (genetic factors passed on in families) and environmental factors involved. Research has shown that some people who develop diabetes have common genetic markers. In Type I diabetes, an autoimmune response is believed to be triggered by a virus or another microorganism that destroys the cells that produce insulin. In Type II diabetes, age, obesity , and family history of diabetes play a role.

In Type II diabetes, the pancreas may produce enough insulin, however, cells have become resistant to the insulin produced and it may not work as effectively. Symptoms of Type II diabetes can begin so gradually that a person may not know that he or she has it. Early signs are tiredness, extreme thirst, and frequent urination. Other symptoms may include sudden weight loss, slow wound healing, urinary tract infections, gum disease , or blurred vision. It is not unusual for Type II diabetes to be detected while a patient is seeing a doctor about a health concern that was caused by the yet undiagnosed diabetes.

Individuals who are at high risk of developing Type II diabetes mellitus include people who:

• are obese (more than 20% above their ideal body weight)
• have a relative with diabetes mellitus
• belong to a high-risk ethnic population (African-American, Native American, Hispanic, or Native Hawaiian)
• have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lb (4 kg)
• have high blood pressure (140/90 mmHg or above)
• have a high density lipoprotein cholesterol level less than or equal to 35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL
• have had impaired glucose tolerance or impaired fasting glucose on previous testing

Several common medications can impair the body's use of insulin, causing a condition known as secondary diabetes. These medications include treatments for high blood pressure (furosemide, clonidine, and thiazide diuretics), drugs with hormonal activity (oral contraceptives, thyroid hormone, progestins, and glucocorticorids), and the anti-inflammation drug indomethacin. Several drugs that are used to treat mood disorders (such as anxiety and depression ) also can impair glucose absorption. These drugs include haloperidol, lithium carbonate, phenothiazines, tricyclic antidepressants, and adrenergic agonists. Other medications that can cause diabetes symptoms include isoniazid, nicotinic acid, cimetidine, and heparin.

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually (over several years) in overweight adults over the age of 40. The classic symptoms include feeling tired and sick, frequent urination, excessive thirst, excessive hunger, and weight loss.

Ketoacidosis, a condition due to starvation or un-controlled diabetes, is common in Type I diabetes. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins. Symptoms include abdominal pain, vomiting , rapid breathing, extreme tiredness, and drowsiness. Patients with ketoacidosis will also have a sweet breath odor. Left untreated, this condition can lead to coma and death.

With Type II diabetes, the condition may not become evident until the patient presents for medical treatment for some other condition. A patient may have heart disease, chronic infections of the gums and urinary tract, blurred vision, numbness in the feet and legs, or slow-healing wounds . Women may experience genital itching .

Diagnosis

Diabetes is suspected based on symptoms. Urine tests and blood tests can be used to confirm a diagnosis of diabetes based on the amount of glucose in the urine and blood. Urine tests also can detect ketones and protein in the urine which may help diagnose diabetes and assess how well the kidneys are functioning. These tests also can be used to monitor the disease once the patient is under treatment.

Urine tests

Clinistix and Diastix are paper strips or dipsticks that change color when dipped in urine. The test strip is compared to a chart that shows the amount of glucose in the urine based on the change in color. The level of glucose in the urine lags behind the level of glucose in the blood. Testing the urine with a test stick, paper strip, or tablet is not as accurate as blood testing, however it can give a fast and simple reading.

Ketones in the urine can be detected using similar types of dipstick tests (Acetest or Ketostix). Ketoacidosis can be a life-threatening situation in Type I diabetics, so having a quick and simple test to detect ketones can assist in establishing a diagnosis sooner.

Another dipstick test can determine the presence of protein or albumin in the urine. Protein in the urine can indicate problems with kidney function and can be used to track the development of renal failure. A more sensitive test for urine protein uses radioactively tagged chemicals to detect microalbuminuria, small amounts of protein in the urine, which may not show up on dipstick tests.

Blood tests

Fasting glucose test. Blood is drawn from a vein in the patient's arm after the patient has not eaten for at least eight hours, usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A plasma level of 7.8 mmol/L (200 mg/L) or greater can indicate diabetes. The fasting glucose test is usually repeated on another day to confirm the results.

Postprandial glucose test. Blood is taken right after the patient has eaten a meal.

Oral glucose tolerance test. Blood samples are taken from a vein before and after a patient drinks a sweet syrup of glucose and other sugars. In a non-diabetic, the level of glucose in the blood goes up immediately after the drink and then decreases gradually as insulin is used by the body to metabolize, or absorb, the sugar. In a diabetic, the glucose in the blood goes up and stays high after drinking the sweetened liquid. A plasma glucose level of 11.1 mmol/L (200 mg/dL) or higher at two hours after drinking the syrup and at one other point during the two-hour test period confirms the diagnosis of diabetes.

A diagnosis of diabetes is confirmed if a plasma glucose level of at least 11.1 mmol/L, a fasting plasma glucose level of at least 7 mmol/L; or a two-hour plasma glucose level of at least 11.1 mmol/L during an oral glucose tolerance test.

In 2002, scientists announced that a new simple blood test to screen for diabetes had been developed. Prior to that time, community-wide screening procedures had not proven cost-effective. The new screening test proved cost-effective if conducted in physician offices on patients with three known risk factors of obesity, self-reported high blood pressure, and family history of diabetes.

Home blood glucose monitoring kits are available so diabetics can monitor their own levels. A small needle or lancet is used to prick the finger and a drop of blood is collected and analyzed by a monitoring device. Some patients may test their blood glucose levels several times during a day and use this information to adjust their diet or doses of insulin.

Treatment

There is currently no cure for diabetes. Diet, exercise, and careful monitoring of blood glucose levels are the keys to manage diabetes so that patients can live a relatively normal life. Diabetes can be life-threatening if not properly managed, so patients should not attempt to treat this condition without medical supervision. Treatment of diabetes focuses on two goals: keeping blood glucose within normal range and preventing the development of long-term complications. Alternative treatments cannot replace the need for insulin but they may enhance insulin's effectiveness and may lower blood glucose levels. In addition, alternative medicines may help to treat complications of the disease and improve quality of life.

Diet

Diet and moderate exercise are the first treatments implemented in diabetes. For many Type II diabetics, weight loss may be an important goal to help them to control their diabetes. A well-balanced, nutritious diet provides approximately 50–60% of calories from carbohydrates, approximately 10–20% of calories from protein, and less than 30% of calories from fat. The number of calories required depends on the patient's age, weight, and activity level. The calorie intake also needs to be distributed over the course of the entire day so surges of glucose entering the blood system are kept to a minimum. In 2002, a Korean study demonstrated that eating a combination of whole grains and legume powder was beneficial in lowering blood glucose levels in men with diabetes.

Keeping track of the number of calories provided by different foods can be complicated, so patients are usually advised to consult a nutritionist or dietitian. An individualized, easy-to-manage diet plan can be set up for each patient. Both the American Diabetes Association and the American Dietetic Association recommend diets based on the use of food exchange lists. Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing the foods they eat as long as they don't exceed the number of exchanges prescribed. The food exchange system, along with a plan of moderate exercise, can help diabetics lose excess weight and improve their overall health. Certain foods will be emphasized over others to promote a healthy heart as well.

Supplements

CHROMIUM PICOLINATE. Several studies have had conflicting results on the effectiveness of chromium picolinate supplementation for control of blood glucose levels. In one study, approximately 70% of the diabetics receiving 200 micrograms of chromium picolinate daily reduced their need for insulin and medications. While some studies have shown that supplementation caused significant weight loss, and decreases in blood glucose and serum triglycerides, others have shown no benefit. Chromium supplementation may cause hypoglycemia and other side effects.

MAGNESIUM. Magnesium deficiency may interfere with insulin secretion and uptake and worsen the patient's control of blood sugar. Also, magnesium deficiency puts diabetics at risk for certain complications, especially retinopathy and cardiovascular disease.

VANADIUM. Vanadium has been shown to bring blood glucose to normal levels in diabetic animals. Also, people who took vanadium were able to decrease their need for insulin.

Chinese medicine

Non-insulin dependent diabetics who practiced daily qigong for one year had decreases in fasting blood glucose and blood insulin levels. Acupuncture may relieve pain in patients with diabetic neuropathy. Acupuncture also may help to bring blood glucose to normal levels in diabetics who do not require insulin.

Best when used in consultation with a Chinese medicine physician, some Chinese patent medicines that alleviate symptoms of or complications from diabetes include:

• Xiao Ke Wan (Emaciation and Thirst Pill) for diabetics with increased levels of sugar in blood and urine.
• Yu Quan Wan (Jade Spring Pill) for diabetics with a deficiency of Yin.
• Liu Wei Di Huang Wan (Six Ingredient Pill with Rehmannia) for stabilized diabetics with a deficiency of Kidney Yin.
• Jin Gui Shen Wan (Kidney Qi Pill) for stabilized diabetics with a deficiency of Kidney Yang.

Herbals

Herbal medicine can have a positive effect on blood glucose and quality of life in diabetics. The results of clinical study of various herbals are:

• Wormwood (Artemisia herba-alba ) decreased blood glucose.
• Gurmar (Gymnema sylvestre ) decreased blood glucose levels and the need for insulin.
• Coccinia indica improved glucose tolerance.
• Fenugreek seed powder (Trigonella foenum graecum ) decreased blood glucose and improved glucose tolerance.
• Bitter melon (Momordica charantia ) decreased blood glucose and improved glucose tolerance.
• Cayenne pepper (Capsicum frutescens ) can help relieve pain in the peripheral nerves (a type of diabetic neuropathy).

Other herbals that may treat or prevent diabetes and its complications include:

• Bilberry (Vaccinium myrtillus ) may lower blood glucose levels and maintain healthy blood vessels.
• Garlic (Allium sativum ) may lower blood sugar and cholesterol levels.
• Onions (Allium cepa ) may help lower blood glucose levels.
• Ginkgo (Ginkgo biloba ) improves blood circulation.

Yoga

Studies of diabetics have shown that practicing yoga leads to decreases in blood glucose, increased glucose tolerance, decreased need for diabetes medications, and improved insulin processes. Yoga also enhances the sense of well-being.

Biofeedback

Many studies have been performed to test the benefit of adding biofeedback to the diabetic's treatment plan. Relaxation techniques, such as visualization, usually were included. Biofeedback can have significant effects on diabetes including improved glucose tolerance and decreased blood glucose levels. In addition, biofeedback can be used to treat diabetic complications and improve quality of life.

Allopathic treatment

Traditional treatment of diabetes begins with a well balanced diet and moderate exercise. Medications are prescribed only if the patient's blood glucose cannot be controlled by these methods.

Oral medications

Oral medications are available to lower blood glucose in Type II diabetics. Drugs first prescribed for Type II diabetes are in a class of compounds called sulfonylureas and include tolbutamide, tolazamide, acetohexamide, chlorpropamide, glyburide, glimeperide, and glipizide. The way that these drugs work is not well understood, however, they seem to stimulate cells of the pancreas to produce more insulin. New medications that are available to treat diabetes include metformin, acarbose, and troglitizone. These medications are not a substitute for a well planned diet and moderate exercise. Oral medications are not effective for Type I diabetes, in which the patient produces little or no insulin.

Insulin

Patients with Type I diabetes need daily injections of insulin to help their bodies use glucose. Some patients with Type II diabetes may need to use insulin injections if their diabetes cannot be controlled. Injections are given subcutaneously—just under the skin, using a small needle and syringe. Purified human insulin is most commonly used, however, insulin from beef and pork sources also is available. Insulin may be given as an injection of a single dose of one type of insulin once a day. Different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. In 2002, reports announced that early research shows a synthetic insulin called insulin glargine might show promise for patients at risk for hypoglycemia from insulin therapy. Clinical trials showed that when used in combination with certain other short-acting insulins, it safely regulated blood glucose for longer durations and was well tolerated by patients.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A patient with symptoms of hypoglycemia may be hungry, sweaty, shaky, cranky, confused, and tired. Left untreated, the patient can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like candy, sugar cubes, or juice.

Surgery

Transplantation of a healthy pancreas into a diabetic patient is a successful treatment, however, this transplant usually is done only if a kidney transplant is performed at the same time. It is not clear if the potential benefits of transplantation outweigh the risks of the surgery and subsequent drug therapy.

Expected results

Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. It also doubles the risk of heart disease and increases the risk of stroke. Eye problems including cataracts, glaucoma , and retinopathy also are more common in diabetics. Kidney disease is a common complication of diabetes and may require kidney dialysis or a kidney transplant. Babies born to diabetic mothers have an increased risk of birth defects and distress at birth.

Diabetic peripheral neuropathy is a condition where nerve endings, particularly in the legs and feet, become less sensitive. Diabetic foot ulcers are a problem since the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contributes to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters , or callouses becoming infected and difficult to treat. Severely infected tissue breaks down and rots, often necessitating amputation of toes, feet, or legs.

Prevention

Research continues on ways to prevent diabetes and to detect those at risk for developing diabetes. While the onset of Type I diabetes is unpredictable, the risk of developing Type II diabetes can be reduced by maintaining ideal weight and exercising regularly. The physical and emotional stress of surgery, illness, and alcoholism can increase the risks of diabetes, so maintaining a healthy lifestyle is critical to preventing the onset of Type II diabetes and preventing further complications of the disease.

In early 2002, researchers announced that patients at high risk for developing diabetes who took an ACE inhibitor called ramipril reduced their risk of developing diabetes substantially. Another report at Duke University showed that sustained intensive exercise could forestall development of diabetes or cardiovascular disease in high-risk patients. The benefits of long-term exercise even continue one month after exercising stops. In 2003, advances in genetics found a key gene that may explain why some people are more susceptible to the disease than others.

Resources

BOOKS

Foster, Daniel W. "Diabetes Mellitus." In Harrison's Principles of Internal Medicine. 14th ed. Edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998.

Garber, Alan J. "Diabetes Mellitus." In Internal Medicine. Edited by Jay H. Stein, et al. St. Louis: Mosby, 1998.

Karam, John H. "Diabetes Mellitus & Hypoglycemia." In Current Medical Diagnosis & Treatment 1998. 37th ed. Edited by L.M. Tierney, Jr., S.J. McPhee, and M.A. Papadakis. Stamford, CT: Appleton & Lange, 1998.

McGrady, Angele and James Horner. "Complementary/Alternative Therapies in General Medicine: Diabetes Mellitus." In Complementary/Alternative Medicine: An Evidence Based Approach. Edited by John W. Spencer and Joseph J. Jacobs. St. Louis: Mosby, 1999.

Sherwin, Robert S. "Diabetes Mellitus." In Cecil Textbook of Medicine. 20th ed. Edited by J. Claude Bennett and Fred Plum. Philadelphia, PA: W.B. Saunders Company, 1996.

Smit, Charles Kent, John P. Sheehan, and Margaret M. Ulchaker. "Diabetes Mellitus." In Family Medicine, Principles and Practice. 5th ed. Edited by Robert B. Taylor. New York: Springer-Verlag, 1998.

Ying, Zhou Zhong and Jin Hui De. "Endocrinology." In Clinical Manual of Chinese Herbal Medicine and Acupuncture. New York: Churchill Livingston, 1997.

PERIODICALS

"Exercise Can Forestall Diabetes in At-Risk Patients." Diabetes Week (March 25, 2002):2.

Fox, Gary N., and Zijad Sabovic. "Chromium Picolinate Supplementation for Diabetes Mellitus." The Journal of Family Practice 46 (1998): 83-86.

Hartnett, Terry."Early Results Show Promise for Synthetic Insulin." Diabetes Week (March 18, 2002):4.

Jenkins, David JA, et al."Type 2 Diabetes and the Vegetarian Diet." American Journal of Clinical Nutrition (September 2003):610S.

"Mouse, Stripped of a Key Gene, Resists Diabetes." Biotech Week (September 24, 2003):557.

"Nearly One-third of Diabetes Undiganosed, According to New Government Data." Medical Letter on the CDC & FDA (September 28, 2003):13.

"Ramipril Cuts Diabetes Risk." Family Practice News 32, no. 3 (February 1, 2002):10.

"Simple Blood Test Could Detect New Cases of Diabetes." Diabetes Week (January 21, 2002):4.

"Whole Grain and Legume Powder Diet Benefits Diabetics and the Healthy." Diabetes Week (January 7, 2002):8.

"Trends in the Prevalence and Incidence of Self-Reported Diabetes Mellitus-United States, 1980-1994." Morbidity & Mortality Weekly Report 46 (1997): 1014-1018.

"Updated Guidelines for the Diagnosis of Diabetes in the US." Drugs & Therapy Perspectives 10 (1997): 12-13.

ORGANIZATIONS

American Diabetes Association. 1660 Duke Street, Alexandria, VA 22314. (703) 549-1500. Diabetes Information and Action Line: (800) DIABETES. http://www.diabetes.org.

American Dietetic Association. 430 North Michigan Avenue, Chicago, IL 60611. (312) 822-0330. http://www.eatright.org.

Juvenile Diabetes Foundation International. 120 Wall Street, New York, NY 10005-4001. (212) 785-9595. (800) JDF-CURE.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (301) 654-3327.

National Institutes of Health. National Institute of Diabetes, Digestive and Kidney Diseases. 9000 Rockville Pike, Bethesda, MD 20892. (301) 496-3583. http://www.niddk.nih.gov.

OTHER

Centers for Disease Control and Prevention Diabetes. http://www.cdc.gov/nccdphp/ddt/ddthome.htm.

"Insulin-Dependent Diabetes." National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No. 94-2098.

"Noninsulin-Dependent Diabetes." National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No. 92-241.

Belinda Rowland

Teresa G. Odle

Diabetes Mellitus

Definition

Diabetes mellitus is a condition in which the pancreas no longer produces enough insulin or cells stop responding to the insulin that is produced, so that glucose in the blood cannot be absorbed into the cells of the body. Symptoms include frequent urination, lethargy, excessive thirst, and hunger. The treatment includes changes in diet, oral medications, and in some cases, daily injections of insulin.

Description

Diabetes mellitus is a chronic disease that causes serious health complications including renal (kidney) failure, heart disease, stroke, and blindness. Approximately 17 million Americans have diabetes. Unfortunately, as many as one-half are unaware they have it.

Background

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of cell and acts like a key to open a doorway into the cell through which glucose can enter. Some of the glucose can be converted to concentrated energy sources like glycogen or fatty acids and saved for later use. When there is not enough insulin produced or when the doorway no longer recognizes the insulin key, glucose stays in the blood rather entering the cells.

The body will attempt to dilute the high level of glucose in the blood, a condition called hyperglycemia, by drawing water out of the cells and into the bloodstream in an effort to dilute the sugar and excrete it in the urine. It is not unusual for people with undiagnosed diabetes to be constantly thirsty, drink large quantities of water, and urinate frequently as their bodies try to get rid of the extra glucose. This creates high levels of glucose in the urine.

At the same time that the body is trying to get rid of glucose from the blood, the cells are starving for glucose and sending signals to the body to eat more food, thus making patients extremely hungry. To provide energy for the starving cells, the body also tries to convert fats and proteins to glucose. The breakdown of fats and proteins for energy causes acid compounds called ketones to form in the blood. Ketones also will be excreted in the urine. As ketones build up in the blood, a condition called ketoacidosis can occur. This condition can be life threatening if left untreated, leading to coma and death.

Types of diabetes mellitus

Type I diabetes, sometimes called juvenile diabetes, begins most commonly in childhood or adolescence. In this form of diabetes, the body produces little or no insulin. It is characterized by a sudden onset and occurs more frequently in populations descended from Northern European countries (Finland, Scotland, Scandinavia) than in those from Southern European countries, the Middle East, or Asia. In the United States, approximately three people in 1,000 develop Type I diabetes. This form also is called insulin-dependent diabetes because people who develop this type need to have daily injections of insulin.

Brittle diabetics are a subgroup of Type I where patients have frequent and rapid swings of blood sugar levels between hyperglycemia (a condition where there is too much glucose or sugar in the blood) and hypoglycemia (a condition where there are abnormally low levels of glucose or sugar in the blood). These patients may require several injections of different types of insulin during the day to keep the blood sugar level within a fairly normal range.

The more common form of diabetes, Type II, occurs in approximately 3-5% of Americans under 50 years of age, and increases to 10-15% in those over 50. More than 90% of the diabetics in the United States are Type II diabetics. Sometimes called age-onset or adult-onset diabetes, this form of diabetes occurs most often in people who are overweight and who do not exercise. It is also more common in people of Native American, Hispanic, and African-American descent. People who have migrated to Western cultures from East India, Japan, and Australian Aboriginal cultures also are more likely to develop Type II diabetes than those who remain in their original countries.

Type II is considered a milder form of diabetes because of its slow onset (sometimes developing over the course of several years) and because it usually can be controlled with diet and oral medication. The consequences of uncontrolled and untreated Type II diabetes, however, are the just as serious as those for Type I. This form is also called noninsulin-dependent diabetes, a term that is somewhat misleading. Many people with Type II diabetes can control the condition with diet and oral medications, however, insulin injections are sometimes necessary if treatment with diet and oral medication is not working.

Another form of diabetes called gestational diabetes can develop during pregnancy and generally resolves after the baby is delivered. This diabetic condition develops during the second or third trimester of pregnancy in about 2% of pregnancies. In 2004, incidence of gestational diabetes were reported to have increased 35% in 10 years. Children of women with gestational diabetes are more likely to be born prematurely, have hypoglycemia, or have severe jaundice at birth. The condition usually is treated by diet, however, insulin injections may be required. These women who have diabetes during pregnancy are at higher risk for developing Type II diabetes within 5-10 years.

Diabetes also can develop as a result of pancreatic disease, alcoholism, malnutrition, or other severe illnesses that stress the body.

Causes and symptoms

Causes

The causes of diabetes mellitus are unclear, however, there seem to be both hereditary (genetic factors passed on in families) and environmental factors involved. Research has shown that some people who develop diabetes have common genetic markers. In Type I diabetes, the immune system, the body's defense system against infection, is believed to be triggered by a virus or another microorganism that destroys cells in the pancreas that produce insulin. In Type II diabetes, age, obesity, and family history of diabetes play a role.

In Type II diabetes, the pancreas may produce enough insulin, however, cells have become resistant to the insulin produced and it may not work as effectively. Symptoms of Type II diabetes can begin so gradually that a person may not know that he or she has it. Early signs are lethargy, extreme thirst, and frequent urination. Other symptoms may include sudden weight loss, slow wound healing, urinary tract infections, gum disease, or blurred vision. It is not unusual for Type II diabetes to be detected while a patient is seeing a doctor about another health concern that is actually being caused by the yet undiagnosed diabetes.

Individuals who are at high risk of developing Type II diabetes mellitus include people who:

• are obese (more than 20% above their ideal body weight)
• have a relative with diabetes mellitus
• belong to a high-risk ethnic population (African-American, Native American, Hispanic, or Native Hawaiian)
• have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lbs (4 kg)
• have high blood pressure (140/90 mmHg or above)
• have a high density lipoprotein cholesterol level less than or equal to 35 mg/dL and/or a triglyceride level greater than or equal to 250 mg/dL
• have had impaired glucose tolerance or impaired fasting glucose on previous testing

Several common medications can impair the body's use of insulin, causing a condition known as secondary diabetes. These medications include treatments for high blood pressure (furosemide, clonidine, and thiazide diuretics ), drugs with hormonal activity (oral contraceptives, thyroid hormone, progestins, and glucocorticorids), and the anti-inflammation drug indomethacin. Several drugs that are used to treat mood disorders (such as anxiety and depression) also can impair glucose absorption. These drugs include haloperidol, lithium carbonate, phenothiazines, tricyclic antidepressants, and adrenergic agonists. Other medications that can cause diabetes symptoms include isoniazid, nicotinic acid, cimetidine, and heparin. A 2004 study found that low levels of the essential mineral chromium in the body may be linked to increased risk for diseases associated with insulin resistance.

Symptoms

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually (over several years) in overweight adults over the age of 40. The classic symptoms include feeling tired and sick, frequent urination, excessive thirst, excessive hunger, and weight loss.

Ketoacidosis, a condition due to starvation or uncontrolled diabetes, is common in Type I diabetes. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins. Symptoms include abdominal pain, vomiting, rapid breathing, extreme lethargy, and drowsiness. Patients with ketoacidosis will also have a sweet breath odor. Left untreated, this condition can lead to coma and death.

With Type II diabetes, the condition may not become evident until the patient presents for medical treatment for some other condition. A patient may have heart disease, chronic infections of the gums and urinary tract, blurred vision, numbness in the feet and legs, or slow-healing wounds. Women may experience genital itching.

Diagnosis

Diabetes is suspected based on symptoms. Urine tests and blood tests can be used to confirm a diagnose of diabetes based on the amount of glucose found. Urine can also detect ketones and protein in the urine that may help diagnose diabetes and assess how well the kidneys are functioning. These tests also can be used to monitor the disease once the patient is on a standardized diet, oral medications, or insulin.

Urine tests

Clinistix and Diastix are paper strips or dipsticks that change color when dipped in urine. The test strip is compared to a chart that shows the amount of glucose in the urine based on the change in color. The level of glucose in the urine lags behind the level of glucose in the blood. Testing the urine with a test stick, paper strip, or tablet that changes color when sugar is present is not as accurate as blood testing, however it can give a fast and simple reading.

Ketones in the urine can be detected using similar types of dipstick tests (Acetest or Ketostix). Ketoacidosis can be a life-threatening situation in Type I diabetics, so having a quick and simple test to detect ketones can assist in establishing a diagnosis sooner.

Another dipstick test can determine the presence of protein or albumin in the urine. Protein in the urine can indicate problems with kidney function and can be used to track the development of renal failure. A more sensitive test for urine protein uses radioactively tagged chemicals to detect microalbuminuria, small amounts of protein in the urine, that may not show up on dipstick tests.

Blood tests

FASTING GLUCOSE TEST. Blood is drawn from a vein in the patient's arm after a period at least eight hours when the patient has not eaten, usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A plasma level of 7.8 mmol/L (200 mg/L) or greater can indicate diabetes. The fasting glucose test is usually repeated on another day to confirm the results.

POSTPRANDIAL GLUCOSE TEST. Blood is taken right after the patient has eaten a meal.

ORAL GLUCOSE TOLERANCE TEST. Blood samples are taken from a vein before and after a patient drinks a thick, sweet syrup of glucose and other sugars. In a non-diabetic, the level of glucose in the blood goes up immediately after the drink and then decreases gradually as insulin is used by the body to metabolize, or absorb, the sugar. In a diabetic, the glucose in the blood goes up and stays high after drinking the sweetened liquid. A plasma glucose level of 11.1 mmol/L (200 mg/dL) or higher at two hours after drinking the syrup and at one other point during the two-hour test period confirms the diagnosis of diabetes.

A diagnosis of diabetes is confirmed if there are symptoms of diabetes and a plasma glucose level of at least 11.1 mmol/L, a fasting plasma glucose level of at least 7 mmol/L; or a two-hour plasma glucose level of at least 11.1 mmol/L during an oral glucose tolerance test.

Home blood glucose monitoring kits are available so patients with diabetes can monitor their own levels. A small needle or lancet is used to prick the finger and a drop of blood is collected and analyzed by a monitoring device. Some patients may test their blood glucose levels several times during a day and use this information to adjust their doses of insulin.

Treatment

There is currently no cure for diabetes. The condition, however, can be managed so that patients can live a relatively normal life. Treatment of diabetes focuses on two goals: keeping blood glucose within normal range and preventing the development of long-term complications. Careful monitoring of diet, exercise, and blood glucose levels are as important as the use of insulin or oral medications in preventing complications of diabetes. In 2003, the American Diabetes Association updated its Standards of Care for the management of diabetes. These standards help manage health care providers in the most recent recommendations for diagnosis and treatment of the disease.

Dietary changes

Diet and moderate exercise are the first treatments implemented in diabetes. For many Type II diabetics, weight loss may be an important goal in helping them to control their diabetes. A well-balanced, nutritious diet provides approximately 50-60% of calories from carbohydrates, approximately 10-20% of calories from protein, and less than 30% of calories from fat. The number of calories required by an individual depends on age, weight, and activity level. The calorie intake also needs to be distributed over the course of the entire day so surges of glucose entering the blood system are kept to a minimum.

Keeping track of the number of calories provided by different foods can become complicated, so patients usually are advised to consult a nutritionist or dietitian. An individualized, easy to manage diet plan can be set up for each patient. Both the American Diabetes Association and the American Dietetic Association recommend diets based on the use of food exchange lists. Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing which foods they eat as long as they stick with the number of exchanges prescribed.

For many Type II diabetics, weight loss is an important factor in controlling their condition. The food exchange system, along with a plan of moderate exercise, can help them lose excess weight and improve their overall health.

Oral medications

Oral medications are available to lower blood glucose in Type II diabetics. In 1990, 23.4 outpatient prescriptions for oral antidiabetic agents were dispensed. By 2001, the number had increased to 91.8 million prescriptions. Oral antidiabetic agents accounted for more than $5 billion dollars in worldwide retail sales per year in the early twenty-first century and were the fastest-growing segment of diabetes drugs. The drugs first prescribed for Type II diabetes are in a class of compounds called sulfonylureas and include tolbutamide, tolazamide, acetohexamide, and chlorpropamide. Newer drugs in the same class are now available and include glyburide, glimeperide, and glipizide. How these drugs work is not well understood, however, they seem to stimulate cells of the pancreas to produce more insulin. New medications that are available to treat diabetes include metformin, acarbose, and troglitizone. The choice of medication depends in part on the individual patient profile. All drugs have side effects that may make them inappropriate for particular patients. Some for example, may stimulate weight gain or cause stomach irritation, so they may not be the best treatment for someone who is already overweight or who has stomach ulcers. Others, like metformin, have been shown to have positive effects such as reduced cardiovascular mortality, but but increased risk in other situations. While these medications are an important aspect of treatment for Type II diabetes, they are not a substitute for a well planned diet and moderate exercise. Oral medications have not been shown effective for Type I diabetes, in which the patient produces little or no insulin.

Constant advances are being made in development of new oral medications for persons with diabetes. In 2003, a drug called Metaglip combining glipizide and metformin was approved in a dingle tablet. Along with diet and exercise, the drug was used as initial therapy for Type 2 diabetes. Another drug approved by the U.S. Food and Drug Administration (FDA) combines metformin and rosiglitazone (Avandia), a medication that increases muscle cells' sensitivity to insulin. It is marketed under the name Avandamet. So many new drugs are under development that it is best to stay in touch with a physician for the latest information; physicians can find the best drug, diet and exercise program to fit an individual patient's need.

Insulin

Patients with Type I diabetes need daily injections of insulin to help their bodies use glucose. The amount and type of insulin required depends on the height, weight, age, food intake, and activity level of the individual diabetic patient. Some patients with Type II diabetes may need to use insulin injections if their diabetes cannot be controlled with diet, exercise, and oral medication. Injections are given subcutaneously, that is, just under the skin, using a small needle and syringe. Injection sites can be anywhere on the body where there is looser skin, including the upper arm, abdomen, or upper thigh.

Purified human insulin is most commonly used, however, insulin from beef and pork sources also are available. Insulin may be given as an injection of a single dose of one type of insulin once a day. Different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. The small battery-operated pump is worn outside the body and is connected to a needle that is inserted into the abdomen. Pumps can be programmed to inject small doses of insulin at various times during the day, or the patient may be able to adjust the insulin doses to coincide with meals and exercise.

Regular insulin is fast-acting and starts to work within 15-30 minutes, with its peak glucose-lowering effect about two hours after it is injected. Its effects last for about four to six hours. NPH (neutral protamine Hagedorn) and Lente insulin are intermediate-acting, starting to work within one to three hours and lasting up to 18-26 hours. Ultra-lente is a long-acting form of insulin that starts to work within four to eight hours and lasts 28-36 hours.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A patient with symptoms of hypoglycemia may be hungry, cranky, confused, and tired. The patient may become sweaty and shaky. Left untreated, the patient can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like a candy, sugar cubes, juice, or another high sugar snack.

Surgery

Transplantation of a healthy pancreas into a diabetic patient is a successful treatment, however, this transplant is usually done only if a kidney transplant is performed at the same time. Although a pancreas transplant is possible, it is not clear if the potential benefits outweigh the risks of the surgery and drug therapy needed.

Alternative treatment

Since diabetes can be life-threatening if not properly managed, patients should not attempt to treat this condition without medicial supervision. A variety of alternative therapies can be helpful in managing the symptoms of diabetes and supporting patients with the disease. Acupuncture can help relieve the pain associated with diabetic neuropathy by stimulation of cetain points. A qualified practitioner should be consulted. Herbal remedies also may be helpful in managing diabetes. Although there is no herbal substitute for insulin, some herbs may help adjust blood sugar levels or manage other diabetic symptoms. Some options include:

• fenugreek (Trigonella foenum-graecum ) has been shown in some studies to reduce blood insulin and glucose levels while also lowering cholesterol
• bilberry (Vaccinium myrtillus ) may lower blood glucose levels, as well as helping to maintain healthy blood vessels
• garlic (Allium sativum ) may lower blood sugar and cholesterol levels
• onions (Allium cepa ) may help lower blood glucose levels by freeing insulin to metabolize them
• cayenne pepper (Capsicum frutescens ) can help relieve pain in the peripheral nerves (a type of diabetic neuropathy)
• gingko (Gingko biloba ) may maintain blood flow to the retina, helping to prevent diabetic retinopathy

Any therapy that lowers stress levels also can be useful in treating diabetes by helping to reduce insulin requirements. Among the alternative treatments that aim to lower stress are hypnotherapy, biofeedback, and meditation.

Prognosis

Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. It also doubles the risks of heart disease and increases the risk of stroke. Eye problems including cataracts, glaucoma, and diabetic retinopathy also are more common in diabetics.

Diabetic peripheral neuropathy is a condition where nerve endings, particularly in the legs and feet, become less sensitive. Diabetic foot ulcers are a particular problem since the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contribute to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters, or callouses becoming infected and difficult to treat. In cases of severe infection, the infected tissue begins to break down and rot away. The most serious consequence of this condition is the need for amputation of toes, feet, or legs due to severe infection.

Heart disease and kidney disease are common complications of diabetes. Long-term complications may include the need for kidney dialysis or a kidney transplant due to kidney failure.

Babies born to diabetic mothers have an increased risk of birth defects and distress at birth.

Prevention

Research continues on diabetes prevention and improved detection of those at risk for developing diabetes. While the onset of Type I diabetes is unpredictable, the risk of developing Type II diabetes can be reduced by maintaining ideal weight and exercising regularly. The physical and emotional stress of surgery, illness, pregnancy, and alcoholism can increase the risks of diabetes, so maintaining a healthy lifestyle is critical to preventing the onset of Type II diabetes and preventing further complications of the disease.

KEY TERMS

Cataract— A condition where the lens of the eye becomes cloudy.

Diabetic peripheral neuropathy— A condition where the sensitivity of nerves to pain, temperature, and pressure is dulled, particularly in the legs and feet.

Diabetic retinopathy— A condition where the tiny blood vessels to the retina, the tissues that sense light at the back of the eye, are damaged, leading to blurred vision, sudden blindness, or black spots, lines, or flashing lights in the field of vision.

Glaucoma— A condition where pressure within the eye causes damage to the optic nerve, which sends visual images to the brain.

Hyperglycemia— A condition where there is too much glucose or sugar in the blood.

Hypoglycemia— A condition where there is too little glucose or sugar in the blood.

Insulin— A hormone or chemical produced by the pancreas, insulin is needed by cells of the body in order to use glucose (sugar), the body's main source of energy.

Ketoacidosis— A condition due to starvation or uncontrolled Type I diabetes. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins. Symptoms include abdominal pain, vomiting, rapid breathing, extreme tiredness, and drowsiness.

Kidney dialysis— A process where blood is filtered through a dialysis machine to remove waste products that would normally be removed by the kidneys. The filtered blood is then circulated back into the patient. This process also is called renal dialysis.

Pancreas— A gland located behind the stomach that produces insulin.

Resources

PERIODICALS

Crutchfield, Diane B. "Oral Antidiabetic Agents: Back to the Basics." Geriatric Times, May 1, 2003: 20.

"Gestational Diabetes Increases 35% in 10 Years." Health & Medicine Week, March 22, 2004: 220.

Kordella, Terri. "New Combo Pills." Diabetes Forecast, March 2003: 42.

"New Drugs." Drug Topics, November 18, 2002: 73.

"Research: Lower Chromium Levels Linked to Increased Risk of Disease." Diabetes Week, March 29, 2004: 21.

"Standards of Medical Care for Patients with Diabetes Mellitus: American Diabetes Association." Clinical Diabetes, Winter 2003: 27.

"Wider Metformin Use Recommended." Chemist & Druggist, January 11, 2003: 24.

ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard Street, Alexandria, VA 22311. (800) 342-2383. 〈http://www.diabetes.org〉.

American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606-6995. (312) 899-0040. 〈http://www.eatright.org〉.

Juvenile Diabetes Foundation. 120 Wall St., 19th Floor, New York, NY 10005. (800) 533-2873. 〈http://www.jdf.org〉.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892-3560. (800) 860-8747. Ndic@info.niddk.nih.gov. 〈http://www.niddk.nih.gov/health/diabetes/ndic.htm〉.

OTHER

Centers for Disease Control. 〈http://www.cdc.gov/nccdphp/ddt/ddthome.htm〉.

"Insulin-Dependent Diabetes." National Institute of Diabetes and Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No.94-2098.

"Noninsulin-Dependent Diabetes." National Institute of Diabetesand Digestive and Kidney Diseases. National Institutes of Health, NIH Publication No.92-241.

Diabetes mellitus

Definition

Diabetes mellitus is a chronic disease in which the body is not able to correctly process glucose for cell energy due to either an insufficient amount of the hormone insulin or a physical resistance to the insulin the body does produce. Without proper treatment through medication and/or lifestyle changes, the high blood glucose (or blood sugar) levels caused by diabetes can cause long-term damage to organ systems throughout the body.

Description

There are three types of diabetes mellitus: type 1 (also called juvenile diabetes or insulin-dependent diabetes), type 2 (also called adult-onset diabetes), and gestational diabetes. While type 2 is the most prevalent, consisting of 90 to 95 percent of diabetes patients in the United States, type 1 diabetes is more common in children. Gestational diabetes occurs in pregnancy and resolves at birth.

Every cell in the human body needs energy in order to function. The body's primary energy source is glucose, a simple sugar resulting from the digestion of foods containing carbohydrates (primarily sugars and starches). Glucose from the digested food circulates in the blood as a ready energy source for any cells that need it. However, glucose requires insulin in order to be processed for cellular energy.

Insulin is a hormone or chemical produced by cells in the pancreas, an organ located behind the stomach. Insulin bonds to a receptor site on the outside of a cell. It acts like a key to open a doorway into the cell through which glucose can enter. When there is not enough insulin produced (as is the case with type 1 diabetes) or when the doorway no longer recognizes the insulin key (which happens in type 2 and gestational diabetes), glucose stays in the bloodstream rather entering the cells. The high blood glucose, or blood sugar, levels that result are known as hyperglycemia .

Type 1 diabetes

Type 1 diabetes occurs when the beta cells of the pancreas are damaged and stop producing the hormone insulin. While the exact cause of this cell damage is not completely understood, it is thought to be a combination of environmental and autoimmune factors. Despite the name juvenile diabetes, type 1 diabetes can be diagnosed at any stage of life, although diagnosis in childhood through young adulthood is most common.

Children who develop type 1 diabetes must eventually take regular insulin injections to keep blood glucose levels under control and do the job of the pancreas. Regular home testing of blood sugar levels is also important to make sure that the treatment is working effectively and to avoid a diabetic emergency such as hypoglycemia (low blood sugar) or hyperglycemia (high blood sugar).

Type 2 diabetes

The hallmark characteristic of type 2 diabetes is insulin resistance. The pancreas typically produces enough insulin (often too much insulin); however, cells are resistant to the insulin and it may not work as effectively. Type 2 is the most common form of diabetes, and most individuals with the disease are adults. However, children and adolescents can develop type 2 diabetes too, particularly if they are overweight and have a history of type 2 diabetes in their family .

Type 2 diabetes is treated with diet, exercise , and in some cases, oral medication and/or insulin. Self-monitoring of blood glucose levels is also important to assess how well treatment is working.

Demographics

An estimated 18.2 million Americans live with diabetes, and over 5 million of those remain undiagnosed. Up to 95 percent of diabetes patients in the United States have type 2 diabetes; the vast majority of Americans with diabetes are over 20 years of age. Those under 20 represent only 206,000 of the total cases of diabetes in the United States.

While type 2 diabetes is a growing problem among American youth due to climbing obesity rates and more sedentary lifestyles, type 1 diabetes is more prevalent in children and adolescents. An estimated one in 400 to 500 children have type 1 diabetes.

The American Diabetes Association reports that in 2002, diabetes cost Americans an estimated $132 billion in direct medical costs and indirect expenses such as lost productivity and disability payments.

Causes and symptoms

The causes of diabetes are not completely understood; however, there seem to be both genetic and environmental factors involved in the development of both type 1 and type 2 diabetes, meaning that a person may have a genetic predisposition to developing diabetes, but it takes an environmental factor such as a viral infection or excessive weight gain to actually make the disease surface.

Research has shown that some people who develop diabetes have common genetic markers. In type 1 diabetes, the immune system, the body's defense system against infection, is believed to be triggered by a virus or another microorganism that causes an autoimmune reaction that eventually destroys the insulin-producing cells (i.e., beta cells) in the pancreas. Up to 90 percent of cases of type 1 diabetes are the autoimmune subtype, sometimes called type 1A or immune-mediated diabetes.

The other subtype of type 1 diabetes is called idiopathic, or type 1B diabetes. People who have idiopathic type 1 diabetes also experience beta cell destruction, but it is due to a chromosomal abnormality or an unknown cause rather than any autoimmune process. Only tests for islet cell antibodies and other autoimmune markers can differentiate between the two subtypes, and because testing can be costly and treatment for both is the same (i.e., insulin), a physician may not necessarily order tests for autoimmunity.

Finally, damage caused by diseases of the pancreas (such as pancreatitis), endocrine disorders (e.g., endocrine tumors), and drugs or toxins can also destroy beta cell function.

In type 2 diabetes, family history, age, weight, activity level, and ethnic background can all play a role in the genesis of the disease. Individuals who are at high risk of developing type 2 diabetes mellitus include the following groups:

• people who are overweight or obese (more than 20 percent above their ideal body weight)
• people who have a parent or sibling with type 2 diabetes
• those who belong to a high-risk ethnic population (African-American, Native American, Asian-American, Hispanic, or Pacific Islander)
• people who live a sedentary lifestyle (i.e., exercise less than three times a week)
• women who have been diagnosed with gestational diabetes or have delivered a baby weighing more than 9 lbs (4 kg)
• people with high blood pressure (140/90 mmHg or above)
• people with high density lipoprotein cholesterol (HDL, or "good" cholesterol) level less than or equal to 35 mg/dl and/or a triglyceride level greater than or equal to 250 mg/dl

Several common medications can cause chronic high blood sugar levels and/or promote insulin resistance. These include atypical antipsychotics, beta blockers, corticosteroids, diuretics, estrogens, lithium, protease inhibitors, niacin, and some thyroid preparations.

Both type 1 and type 2 diabetes share similar symptoms caused by chronically high blood glucose levels.

Symptoms of both type 1 and type 2 diabetes include:

• excessive thirst
• frequent urination
• weight loss
• increased appetite
• unexplained fatigue
• slow healing cuts, bruises , and wounds
• frequent or lingering infections (e.g., urinary tract infection)
• mood swings and irritability
• blurred vision
• headache
• high blood pressure
• dry and itchy skin
• tingling, numbness , or burning in hands or feet

Symptoms of diabetes can develop suddenly (over days or weeks) in previously healthy children or adolescents, or can develop gradually, particularly in the case of type 2 diabetes.

Children and adolescents sometimes develop a condition known as diabetic ketoacidosis (DKA) at the time of their diagnosis. Ketones are acid compounds that form in the blood when the body breaks down fats and proteins for energy. When blood sugars are high (i.e., over 249 mg/dl, or 13.8 mmol/L) for prolonged periods of time, ketones build up in the bloodstream to dangerous levels. Symptoms of DKA include abdominal pain , excessive thirst, nausea and vomiting , rapid breathing, extreme lethargy, and drowsiness. Patients with ketoacidosis will also have a fruity or sweet breath odor. Left untreated, this condition can lead to coma and has the potential to be fatal. DKA is more common in people with type 1 diabetes, although it can occur in type 2 diabetes as well.

Symptoms of type 2 diabetes can begin so gradually that a person may not know that he or she has it. It is not unusual for type 2 diabetes to be detected while a patient is seeing a doctor about another health concern that is actually being caused by the yet undiagnosed diabetes, such as heart disease, chronic infections (e.g., urinary tract infections, yeast infections), blurred vision, numbness in the feet and legs, or slow-healing wounds.

When to call the doctor

If left untreated, diabetes is a life-threatening condition. Any child displaying symptoms of diabetes should be taken to a doctor or emergency care facility for evaluation immediately.

Diagnosis

Diagnosis of diabetes is suspected based on symptoms and confirmed by blood tests that measure the level of glucose in blood plasma. Dipstick or reagent test strips that measure glucose in the urine can only detect glucose levels above 180 mg/dl and are non-specific, so they are not useful in the diagnosis of diabetes. However, they are a non-invasive way to obtain a fast and simple reading that a physician might use as a basis for ordering further diagnostic blood tests for diabetes, particularly in children.

Blood tests are the gold standard for the diagnosis of both type 1 and type 2 diabetes in children and adults. The American Diabetes Association recommends that a random plasma glucose, fasting plasma glucose, or oral glucose tolerance test (OGTT) be used for diagnosis of diabetes. The OGTT is commonly used as a screening measure for gestational diabetes. Fasting plasma glucose is the test of choice unless a child is exhibiting classic symptoms of diabetes, in which case a random (or casual) plasma glucose test is acceptable.

Unless hyperglycemia is obvious (e.g., blood glucose levels are extremely high or the child experiences DKA), the fasting or random plasma glucose test should be confirmed on a subsequent day with a repeat test.

Fasting plasma glucose test

Blood is drawn from a vein in the child's arm following an eight-hour fast (i.e., no food or drink), usually in the morning before breakfast. The red blood cells are separated from the sample and the amount of glucose is measured in the remaining plasma. A fasting plasma glucose level of 126 mg/dl (7.0 mmol/l) or higher indicates diabetes (with a confirming retest on a subsequent day).

Random plasma glucose test

Blood is drawn at any time of day, regardless of whether the patient has eaten. A random plasma glucose concentration of 200 mg/dl (11.1 mmol/l) or higher in the presence of symptoms indicates diabetes.

Oral glucose tolerance test

Blood samples are taken both before and several times after a patient drinks 75 grams of a glucose-based beverage. If plasma glucose levels taken two hours after the glucose drink is consumed are 200 mg/dl (11.1 mmol/L) or higher, the test is diagnostic of diabetes (and should be confirmed on a subsequent day if possible).

Although the same diagnostic blood tests are used for both types of diabetes, whether a child is diagnosed as type 1 or type 2 can typically be determined based on her personal and medical history. The majority of children diagnosed in childhood are type 1, but if blood test results indicate prediabetes and a child is significantly overweight and has a history of type 2 diabetes in her family, type 2 is a possibility.

Further blood tests can help to differentiate between type 1 and type 2 when the diagnosis is unclear. One of these is an assessment of c-peptide levels, a protein released along with insulin that can help a physician determine whether or not a patient is producing sufficient amounts of insulin. The other is a GAD (Glutamic Acid Decarboxylase) autoantibody test. The presence of GAD autoantibodies may indicate the beginning of the autoimmune process that destroys pancreatic beta cells.

Treatment

Children with type 1 diabetes must take insulin injections or infusions. Their dosage needs may change over time. Sometimes children will experience a decreased need for insulin once blood sugars are brought under control following diagnosis. Their insulin needs may go down, and in some cases, they can stop taking injections for a time. This phenomenon, known as the honeymoon period, can last anywhere from a few days to months.

Children with diabetes and their parents should learn to operate a home blood glucose monitor. Home testing can prevent dangerous highs and lows and help parents and children understand how food and exercise impact blood sugar levels. Blood glucose levels taken before meals are also used to calculate dose size of insulin. A small needle or lancet is used to prick the finger or alternate site and a drop of blood is collected on a test strip that is inserted into a monitor. The monitor then calculates and displays the blood glucose reading on a screen. Although individual blood glucose targets should be determined by a medical professional in light of a child's medical history, the general goal is to keep them as close to normal (i.e., 90 to 130 mg/dl or 5 to 7.2 mmol/L before meals) as possible.

Insulin

Children with type 1 diabetes need daily injections of insulin to help their bodies use glucose. The amount and type of insulin required depends on the height, weight, age, food intake, and activity level of the individual diabetic patient. Some patients with type 2 diabetes may also need to use insulin injections if their diabetes cannot be controlled with diet, exercise, and oral medication. Injections are given subcutaneously, that is, just under the skin, using a small needle and syringe, an insulin pen injector, an insulin infusion pump, or a jet injector device. Injection sites can be anywhere on the body where there is a layer of fat available, including the upper arm, abdomen, or upper thigh.

Insulin may be given as an injection of a single dose of one type of insulin once a day, or different types of insulin can be mixed and given in one dose or split into two or more doses during a day. Patients who require multiple injections over the course of a day may be able to use an insulin pump that administers small doses of insulin on demand. The small battery-operated pump is worn outside the body and is connected to a cannula (a thin, flexible plastic tube) that is inserted into the abdomen called an insertion set. Pumps are programmed to infuse a small, steady infusion of insulin (called a basal dose) throughout the day, and larger doses (called boluses) before meals. Because of the basal infusion, pumps can offer many children much tighter control over their blood glucose levels and more flexibility with their diet than insulin shots afford them.

Regular insulin is fast-acting and starts to work within 15 to 30 minutes, with its peak glucose-lowering effect about two hours after it is injected. Its effects last for about four to six hours. NPH (neutral protamine Hagedorn) and Lente insulin are intermediate-acting, starting to work within one to three hours and lasting up to 18 to 26 hours. Ultra-lente is a long-acting form of insulin that starts to work within four to eight hours and lasts 28 to 36 hours. Peakless, or basal-action insulin (insulin glargine, or Lantus) starts working in 15 minutes and has a duration of between 18 and 26 hours.

Nutritional concerns

Because dietary carbohydrates are the primary source of glucose for the body (the other source being the liver), it is very important that children with diabetes learn to read labels and be aware of the amount of carbohydrates in the foods they eat. Children and their parents are usually advised to consult a registered dietitian (RD) to create an individualized, easy to manage food plan that fits their family's health and lifestyle needs. A well-balanced, nutritious diet provides approximately 50 to 60 percent of calories from carbohydrates, approximately 10 to 20 percent of calories from protein, and less than 30 percent of calories from fat. The number of calories required depends on age, weight, and activity level. An RD can also teach the family how to use either the dietary exchange lists or carbohydrate counting system to monitor food intake.

Each food exchange contains a known amount of calories in the form of protein, fat, or carbohydrate. A patient's diet plan will consist of a certain number of exchanges from each food category (meat or protein, fruits, breads and starches, vegetables, and fats) to be eaten at meal times and as snacks. Patients have flexibility in choosing which foods they eat as long as they stick with the number of exchanges prescribed by their RD based on their caloric requirements.

Carbohydrate counting involves totaling the grams of carbohydrates in the foods your child eats to ensure the child does not exceed her goal for the day. In the simple-carb counting method, one carbohydrate choice or unit equals 15 grams of carbohydrates (which is equivalent to one starch or fruit exchange in the exchange method). The number of carb choices allowed daily is based on caloric requirements.

Children with type 1 diabetes who use fast-acting insulin before meals may find that carb counting gives them tighter control of their blood glucose levels, since they can compute the number of insulin units based on both their carbohydrate intake (called the carbohydrate to insulin ratio) and before-meal blood glucose readings.

Dietary changes and moderate exercise are usually the first treatments implemented in type 2 diabetes. Weight loss may be an important goal in helping overweight children and adolescents control their blood sugar levels. Exercise helps keep blood glucose levels down and has other health benefits, as well.

Oral medications

Children with type 2 diabetes may be prescribed oral medications if they are unable to keep their blood glucose levels under control with dietary and exercise measures. As of 2004, metformin was the only oral medication approved by the U.S. FDA for use in children over age ten. Metformin (trade name Glucophage) is in the biguanide class of drugs and works by reducing the amount of glucose the liver produces and the amount of circulating insulin in the body. Other adult type 2 diabetes medications, such as sulfonylureas and meglitinide drugs, which work by increasing insulin production, may be prescribed off-label for pediatric use.

Transplants

Transplantation of a healthy pancreas into a patient with type 1 diabetes can eliminate the need for insulin injections; however, this transplant is typically done only if a kidney transplant is performed at the same time. Although a pancreas transplant is possible, it is not clear if the potential benefits outweigh the risks of the surgery and life-long drug therapy needed to prevent organ rejection, particularly in the case of children.

A second type of transplant procedure, as of 2004 in experimental clinical trials and not available to children, is an islet cell transplant. In this type of treatment, insulin-producing islet cells are harvested from a donor pancreas and injected into the liver of a recipient, where they attach to new blood vessels and (ideally) begin producing insulin. A lifetime regimen of immunosuppressive drugs is required to prevent rejection of the transplanted cells.

Prognosis

As of 2004 diabetes is a chronic and incurable disease. While stem cell research holds great promise for future therapies and potential cures, as of the early 2000s the best hope for keeping children well with diabetes and avoiding long-term complications is maintaining good blood glucose control. The landmark Diabetes Control and Complications Trial (DCCT) found that patients with type 1 diabetes who kept their blood sugar levels as close to normal as possible reduced their risk for developing diabetic eye disease by 76 percent, for diabetic kidney disease by 50 percent, and for diabetic neuropathy by 60 percent.

Diabetes and its related complications was the sixth leading cause of death in 2000. According to the National Institutes of Health, cardiovascular, or heart and blood vessel disease, is the leading cause of diabetes-related death. Uncontrolled diabetes is a leading cause of blindness, end-stage renal disease, and limb amputations. Eye problems including cataracts, glaucoma, and diabetic retinopathy also are more common in people with diabetes.

Diabetic neuropathy is the result of nerve damage caused by uncontrolled diabetes. Autonomic neuropathy affects the autonomic nervous system and can cause gastroparesis (nerve damage of the stomach), neurogenic bladder (nerve damage of the urinary bladder), and a host of other problems with involuntary functions of the nervous system.

In peripheral neuropathy (PN), nerve damage in the extremities (e.g., the legs and feet) causes numbness, pain, and burning. Diabetic foot ulcers are a particular problem since frequently the patient does not feel the pain of a blister, callous, or other minor injury. Poor blood circulation in the legs and feet contribute to delayed wound healing. The inability to sense pain along with the complications of delayed wound healing can result in minor injuries, blisters, or calluses becoming infected and difficult to treat. The most serious consequence of this condition is the potential for amputation of toes, feet, or legs due to severe infection.

Diabetic kidney disease is another common complications of diabetes. Long-term complications may include the need for kidney dialysis or a kidney transplant due to kidney failure. Diabetes is the number one cause of chronic kidney failure in America.

Children and adults with the autoimmune form of type 1 diabetes are also at greater risk for other autoimmune disorders, including thyroid disease, celiac sprue (sometimes called gluten intolerance), autoimmune hepatitis, myasthenia gravis, and pernicious anemia.

Prevention

As of 2004 research continues on diabetes prevention and improved detection of those at risk for developing diabetes. While the onset of type 1 diabetes is unpredictable, the risk of developing type 2 diabetes may be reduced by maintaining ideal weight and exercising regularly. Both physical and emotional stress can cause increases in blood glucose levels, so getting regular immunizations and well-child check-ups, practicing good sleep and hygiene habits, encouraging emotional and social growth, and maintaining a stress-controlled lifestyle is important for children with type 1 or type 2 diabetes.

Parental concerns

Parents of children with diabetes must work with their child's teachers and school administrators to ensure that their child is able to test her blood sugars regularly, take insulin as needed, and have access to food or drink to treat a low. Someone at school should also be trained in how to administer a glucagon injection, an emergency treatment for a hypoglycemic episode when a child loses consciousness.

Section 504 of the Rehabilitation Act of 1973 enables parents to develop both a Section 504 plan (which describes a child's medical needs) and an individualized education plan (IEP) (which describes what special accommodations a child requires to address those needs). An IEP should cover such issues as blood glucose monitoring, dietary plans, and treating highs and lows. If school staff has little to no experience with diabetes, bringing in a certified diabetes educator (CDE) to offer basic training may be useful.

Children with diabetes can lead an active life and enjoy most of the activities and foods their peers do, with a few precautions to avoid blood sugar highs or lows. A certified diabetes educator that has experience working with children can help them understand the importance of regular testing as well as methods for minimizing discomfort. Diabetes summer camps, where children can learn about diabetes care in the company of peers and counselors who also live with the disease, may be useful from both a health and a social standpoint. In addition, peer support groups can sometimes help children come to terms with their diabetes.

Hypoglycemia, or low blood sugar, can be caused by too much insulin, too little food (or eating too late to coincide with the action of the insulin), alcohol consumption, or increased exercise. A child with symptoms of hypoglycemia may be hungry, cranky, confused, and tired. The patient may become sweaty and shaky. Left untreated, a child can lose consciousness or have a seizure. This condition is sometimes called an insulin reaction and should be treated by giving the patient something sweet to eat or drink like candy, juice, glucose gel, or another high sugar snack. A child who loses consciousness due to a low should never be given food or drink due to the risk of choking . In these cases, a glucagon injection should be administered and the child should be taken to the nearest emergency care facility.

While exercise can lower blood glucose levels, children with diabetes can and do excel in sports . Proper hydration, frequent testing, and a before-game or practice snack can prevent hypoglycemia. Coaches or another onsite adult should be aware of a child's medical condition and be prepared to treat a hypoglycemic attack if necessary.

The other potential danger to a child with diabetes—diabetic ketoacidosis—is uncommon and most likely to occur prior to a diagnosis. It may also happen if insulin is discontinued or if the body is under stress due to illness or injury. Ketones in the urine can be detected using dipstick tests (e.g., Ketostix), or detected using a home ketone blood monitor. Early detection facilitates early treatment and can prevent full-blown DKA.

Because the symptoms of DKA can mimic the flu, and the flu can increase blood sugar levels, a child who comes down with a flu-like illness should be monitored closely and tested regularly. An increase in insulin may also be necessary; parents of children with diabetes should talk with their pediatrician about a sick day plan for their child before they need it.

KEY TERMS

Diabetic retinopathy —A condition seen most frequently in individuals with poorly controlled diabetes mellitus where the tiny blood vessels to the retina, the tissues that sense light at the back of the eye, are damaged. This damage causes blurred vision, sudden blindness, or black spots, lines, or flashing light in the field of vision.

Glucagon —A hormone produced in the pancreas that changes glycogen, a carbohydrate stored in muscles and the liver, into glucose. It can be used to relax muscles for a procedure such as duodenography. An injectable form of glucagon is sometimes used to treat insulin shock.

Honeymoon phase —A period of time shortly following diagnosis of type 1 diabetes during which a child's need for insulin may decrease or disappear altogether. The honeymoon phase is transitional, and insulin requirements eventually increases again.

Hyperglycemia —A condition characterized by excessively high levels of glucose in the blood. It occurs when the body does not have enough insulin or cannot use the insulin it does have to turn glucose into energy.

Hypoglycemia —A condition characterized by abnormally low levels of glucose in the blood.

Insulin —A hormone or chemical produced by the pancreas that is needed by cells of the body in order to use glucose (sugar), a major source of energy for the human body.

Ketoacidosis —Usually caused by uncontrolled type I diabetes, when the body isn't able to use glucose for energy. As an alternate source of energy, fat cells are broken down, producing ketones, toxic compounds that make the blood acidic. Symptoms of ketoacidosis include excessive thirst and urination, abdominal pain, vomiting, rapid breathing, extreme tiredness, and drowsiness.

Off-label use —Prescribing a drug for a population (e.g., pediatric) or condition for which it was not originally approved by the U.S. FDA. For example, sulfonylurea drugs are not FDA approved for use in children with type 2 diabetes due to a lack of clinical studies in pediatric populations, but a physician may prescribe them in an off-label use of the drug.

Prediabetes —A precursor condition to type 2 diabetes, sometimes called impaired glucose tolerance or impaired fasting glucose. Prediabetes is clinically defined as individuals who have elevated blood glucose levels that are not diagnostic of type 2 diabetes but are above normal (for the fasting plasma glucose test, this measurement would be 100 to 125 mg/dL (5.6 to 6.9 mmol/L).

See also Hypoglycemia.

Resources

BOOKS

The American Diabetes Association Complete Guide to Diabetes, 3rd ed. Alexandria, VA: American Diabetes Association, 2002.

Brackenridge, Betty, and Richard Rubin. Sweet Kids: How to Balance Diabetes Control and Good Nutrition with Family Peace, 2nd ed. Alexandria, VA: American Diabetes Association, 2002.

Ford-Martin, Paula, with Ian Blumer. The Everything Diabetes Book. Avon, MA: Adams Media, 2004.

ORGANIZATIONS

American Diabetes Association. 1701 North Beauregard St., Alexandria, VA 22311. Web site: <www.diabetes.org>.

American Dietetic Association. 216 W. Jackson Blvd., Chicago, IL 60606–6995. Web site: <www.eatright.org>.

Children with Diabetes. 5689 Chancery Place, Hamilton, OH 45011. Web site: <www.childrenwithdiabetes.org>.

Juvenile Diabetes Research Foundation. 120 Wall St., 19th Floor, New York, NY 10005. Web site: <www.jdrf.org>.

National Diabetes Information Clearinghouse. 1 Information Way, Bethesda, MD 20892–3560. Web site: <www.niddk.nih.gov/health/diabetes/ndic.htm>.

WEB SITES

"2004 Clinical Practice Recommendations." Diabetes Care, January, 2004. Available online at <http://care.diabetesjournals.org/content/vol27/suppl_1/> (accessed December 26, 2004).

Ford-Martin, Paula. "About Diabetes" Available online at <http://diabetes.about.com> (accessed December 26, 2004).

Mendosa, David. David Mendosa's Diabetes Directory. Available online at <www.mendosa.com/diabetes.htm> (accessed December 26, 2004).

Paula Ford-Martin Altha Roberts Edgren Teresa G. Odle