Selected guidelines. (Featured CME Topic: Diabetes Mellitus).
American Diabetes Association: Clinical Practice Recommendations 2001 (Full text published in Diabetes Care 2001; 24: S1-S132.)
* Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.
DEFINITION AND DESCRIPTION OF DIABETES MELLITUS
Metabolic disease characterized by hyperglycemia caused by defective insulin secretion and/or action, resulting in long-term multi-organ complications. Symptoms include polyuria; polydipsia; weight loss, sometimes with polyphagia; blurred vision; growth impairment; and susceptibility to infections. Long-term complications include retinopathy; nephropathy; peripheral neuropathy; autonomic neuropathy; atherosclerotic cardiovascular, peripheral vascular, and cerebrovascular disease; hypertension; abnormalities of lipoprotein metabolism; periodontal disease; and psychosocial dysfunction. Two etiopathogenic categories: type 1 diabetes and type 2 diabetes.
CLASSIFICATION OF DIABETES MELLITUS AND OTHER CATEGORIES OF GLUCOSE REGULATION
Proposed changes to the 1979 National Diabetes Data Group (NDDG)/World Health Organization (WHO) classification by the current Expert Committee include the following:
* Elimination of the terms insulin-dependent diabetes mellitus and non-insulin-dependent diabetes mellitus and their acronyms (IDDM and NIDDM) and the class termed malnutrition-related diabetes;
* Retention of the terms type 1 and type 2 diabetes using Arabic numerals rather than roman numerals, the stage termed impaired glucose tolerance (IGT), and the class termed gestational diabetes mellitus (GDM);
* The degree of hyperglycemia is proportional to the acuteness of the metabolic abnormality and its treatment rather than the underlying nature of the process itself.
Type 1 diabetes develops due to [beta]-cell destruction usually resulting in absolute insulin deficiency.
* Immune-mediated diabetes results from cellular-mediated autoimmune destruction of the [beta]-cells or the pancreas, has strong HLA associations, and causes patients to become insulin dependent and at risk for ketoacidosis.
* Idiopathic diabetes are forms of type 1 diabetes with no known etiologies.
Type 2 diabetes, the most prevalent form of diabetes, results from a combination of insulin resistance and an insulin secretory defect. The insulin secretion is insufficient to compensate for the insulin resistance. Auto-immune destruction of [beta]-cells does not occur ketoacidosis seldom occurs spontaneously, and insulin treatment is often not needed for survival. Patients with this type are usually obese or have increased percentage of body fat and may go undiagnosed for years because the hyperglycemia develops gradually. Patients have an increased risk for developing macrovascular and microvascular complications.
* GDM is the onset or first recognition of any degree of glucose intolerance during pregnancy.
Other Specific Types of Diabetes
* Genetic defects impairing the secretion or action of insulin;
* Diseases of the pancreas destroying the [beta]-cells;
* Endocrinopathies including acromegaly, Cushing's syndrome, glucagonoma, pheochromocytoma, hyperthyroidism, somatostatinoma, and aldosteronoma;
* Drug- or chemical-induced through use of vacor, pentamidine, nicotinic acid, glucocorticoids, thyroid hormone, diazoxide, [beta] adrenergic agonists, thiazides, dilantin, [beta] interferon, and others;
* Infections such as congenital rubella and cytomegalovirus.
DIAGNOSTIC CRITERIA FOR DIABETES MELLITUS
* Random plasma glucose concentration [greater than or equal to]200 mg/dL (11.1 mmol/L) plus symptoms of diabetes, or
* Fasting plasma glucose (FPG, no caloric intake for at least 8 hours) [greater than or equal to]126 mg/dL (7.0 mmol/L)
* FPG < 110 mg/dL (6.1 mmol/L) = normal fasting glucose
* FPG (110 mg/dL (6.1 mmol/L) and <126 mg/dL (7.0 mmol/L) = impaired fasting glucose (IFG)
* FPG (126 mg/dL (7.0 mmol/L) = provisional diagnosis of diabetes (the diagnosis must be confirmed), or
* 2-h Postload glucose (PG) (200 mg/dL (11.1 mmol/L) during an oral glucose tolerance test (OGTT). The test should be performed as described by WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
* Criteria for testing diabetes in asymptomatic, undiagnosed individuals include the following:
* All individuals [greater than or equal to]45 years old and, if normal, retested every three years;
* Younger individuals and more frequently in individuals who are obese;
* have a first-degree relative with diabetes;
* are members of a high-risk ethnic population (African American, Hispanic American, Native American, Asian American, Pacific Islander);
* have delivered a baby weighing > 9 lb or have been diagnosed with GDM;
* are hypertensive, have an HDL cholesterol level [less than or equal to] mg/dL (0.90 mmol/L) and/or a triglyceride level [greater than or equal to] 250 mg/dL (2.82 mmol/L); or
* have had IGI or IFG.
Screening for Type 2 Diabetes
* Incidence of type 2 diabetes is increasing in both adults and children - expected to rise from 7.4% in 1995 to approximately 9% in adults by 2025.
* About one-third of all patients with diabetes may be undiagnosed.
* Screening tests identify asymptomatic individuals likely to develop diabetes; diagnostic tests are performed on those who have symptoms of the disease. Because type 2 diabetes is often asymptomatic in early stages, screening is appropriate for adults or children with substantial risk.
* FPG test is the best screening tool and also a part of diagnostic testing.
* FPG is easy, fast, convenient, acceptable to patients, and less expensive than others.
* Risk factors as listed above.
* High-risk adults should be tested at 3-year intervals beginning at age 45. Testing should be considered at a younger age or more frequently in patients with one or more risk factors.
* The American Diabetes Association recommends that overweight children and adolescents with two risk factors be screened and tested at age 10 or younger.
IMPLICATIONS OF THE DIABETES CONTROL AND COMPLICATIONS TRIAL (DCCT)
The Diabetes Control and Complications Trial studied the complications of diabetes mellitus as related to elevation of plasma glucose concentration. The trial included only type 1 patients divided into two groups: one treated conventionally and another treated intensively.
The American Diabetes Association (ADA) concluded from the DCCT that:
* Blood glucose control significantly influences development of complications in type 1 patients;
* There is a direct relationship between blood glucose level and risk of complications;
* Any improvement in blood glucose control slows development/progression of microvascular complications;
* Hypoglycemia is the main danger of tight control of blood glucose;
* Tight control is not recommended in children under age 2 and should be used with caution in children ages 2-7 or in older patients with atherosclerosis.
STANDARDS OF MEDICAL CARE FOR PATIENTS WITH DIABETES MELLITUS
Specific Goals of Treatment
* DCCT results demonstrated that intensive treatment reduces the risk of retinopathy, nephropathy, and neuropathy by 50%-75%
* Average [HbA.sub.lC] was 7.2% in intensively treated groups and 9.0% in conventionally treated groups.
* Whole blood glucose goals: 80-120 mg/dL preprandial average, additional action for <80 and >140; 100-140 mg/dL bedtime average, and additional action for <100 and >160.
* Plasma value goals: 90-130 mg/dL preprandial average, additional action for <90 and >150, 110-150 mg/dL bedtime average, and additional action for <110 and >180.
* Goals may be achieved by frequent self-monitoring of blood glucose (SMBG), medical nutrition therapy, self-management/problem-solving education, and hospitalization for initiation of therapy.
Treatment goals should be based on the same guidelines as for type 1: patient's ability to carry out treatment regimen, patient's risk for hypoglycemia, and other factors such as advanced age or advanced cardiovascular disease (CVD) that may increase risk or decrease benefit.
Medical history is important for diagnosing patients with previously unrecognized diabetes. Elements of diabetics' medical history to consider include symptoms and test results related to diabetes diagnosis; [HbA.sub.lc] records; eating habits, nutritional intake, exercise, and weight history; growth and development in children; previous treatment program details; current diabetes treatment; details of acute complications such as ketoacidosis and hypoglycemia; prior or current infections; symptoms/treatment of chronic eye, kidney, nerve, genitourinary, bladder, and gastrointestinal function; heart, peripheral vascular, foot, and cerebrovascular complications; medications affecting blood glucose levels; risk factors for atherosclerosis (smoking, hypertension, obesity, dyslipidemia, family history); endocrine disorders; family history of diabetes/ other endocrine disorders; gestational history; lifestyle/cultural/psychosocial/educational/economic factors likely to influence diabetes management; and tobacco/alco hol use.
Aspects of particular interest in the initial physical exam include height/weight and sexual maturation in children and adolescents; blood pressure; pulse evaluation; thyroid palpation; ophthalmoscopic, oral, cardiac, abdominal, hand/finger, foot, skin, and neurological exams.
Tests necessary for the diagnosis of diabetes include fasting plasma glucose level; [HbA.sub.lc], fasting lipid profile; serum creatinine in adults (in children if proteinuria is present); urinalysis, including tests for microalbuminuria; urine culture if abnormal sediment or other symptoms; thyroid-stimulating hormone (TSH) level in type 1 patients; electrocardiogram in adults.
A management plan involving the patient should include the following: short- and long-term goals, medications, nutrition instructions, lifestyle changes, self-management education, monitoring instructions, specialty consultations such as podiatry services as needed, dental hygiene, pneumococcal/ influenza vaccines, contraceptive and blood glucose control education for women of childbearing age, and agreement on continuing support/follow-up.
Frequency of visits is determined by type of diabetes, blood glucose level goals and degree of achievement, treatment changes, and complications.
Interim history at each visit should include hypoglycemia/hyperglycemia frequency, cause, and severity; SMBG results; patient adjustments of the therapeutic regimen; adherence problems; complication symptoms; other illnesses; medications; psychosocial issues; lifestyle changes; and tobacco/alcohol use.
Follow-up examination should include weight, blood pressure, height and sexual maturation in younger patients, funduscopy and foot examination in at-risk patients.
Continuing testing should include [HbA.sub.1c] at least twice a year; annual fasting lipid profile, unless low risk; annual microalbumin measurement if indicated; and optional fasting plasma glucose level.
Evaluation of Management Plan
Blood pressure, dyslipidemia, hypoglycemia, self-care, exercise, referral follow-up, pychosocial adjustment, nutrition, blood glucose levels, self-management skills, diabetes knowledge, goal achievement, complications and problems should be reviewed regularly.
Children and Adolescents
Persons younger than 18 account for about three-fourths of all newly diagnosed type 1 cases.
Diabetes management of children and adolescents must be integrated with their unique physical and emotional needs. Health care providers should provide goals, self-management education, and a nutritional assessment at the time of initial diagnosis; however, overaggressive dietary manipulation in the very young requires caution.
Adherence is the major issue with patients and their parents.
Health care providers should share pertinent information on diabetic children with schools and/or daycare personnel.
Control of hypertension reduces the progression rate of diabetic nephropathy and complications of hypertensive nephropathy, cerebrovascular disease, and cardiovascular disease.
Unless urgent, lifestyle changes are the first step in the treatment of hypertension.
Desired blood pressure is <130/80 (age-adjusted to 90th percentile in children).
Persistent albuminuria at 30-299 mg/24 h denotes early stage diabetic nephropathy and increased risk of cardiovascular disease.
In type 1 diabetes, achievement of near normoglycemia will delay microalbuminuria onset and its progression to clinical albuminuria.
ACE inhibitors delay progression from microalbuminuria to clinical albuminuria and slow the decline in glomerular filtration rate (GFR) in clinical albuminuria.
Creatinine clearance should be assessed.
Timed or overnight urine collections or albumin-to-creatinine ratios should be determined to evaluate treatment effect and to detect adverse drug effects.
If GFR falls to < 70 mL/[min.sup.-1]/1.73 [m.sup.-2], serum creatinine increases to >2.0 mg/dL, or if difficulties occur with hypertension/hyperkalemia, the patient should be referred to a renal specialist.
Testing for coronary heart disease (CHD) is warranted in the following situations: typical or atypical cardiac symptoms, resting electrocardiogram suggestive of ischemia or infarction, peripheral or carotid occlusive arterial disease, sedentary lifestyle in patients 35 years or older with plans to begin an exercise program, or two or more cardiac risk factors.
There is increased obesity and lipid abnormality risk independent of glycemic control in type 2 diabetes.
LDL cholesterol goal for adults is [less than or equal to]100 mg/dL. For patients with triglyceride levels [greater than or equal to]1,000 mg/dL, immediate attention is needed to lower the level to <400 mg/dL, and further reduction to goals of <200 mg/dL would be beneficial.
A secondary goal is to raise HDL cholesterol to >45 mg/dL in men and >55 in women.
For children with risk factors in addition to diabetes, LDL cholesterol goal is <110 mg/dL.
NUTRITION RECOMMENDATIONS AND PRINCIPLES FOR PEOPLE WITH DIABETES MELLITUS - MEDICAL NUTRITION THERAPY (MNT)
Maintenance of near-normal blood glucose levels, achievement of optimal serum lipid levels, provision of adequate caloric intake to attain/maintain normal weights, prevention and treatment of complications, and improvement of overall health through optimal nutrition. MNT should be planned individually based on the patient's lifestyle factors.
Insufficient evidence exists to recommend higher or lower intake levels than average intake levels for the general population, ~10%-20% of daily caloric intake from protein; however, reduced protein intake should be considered with the onset of nephropathy.
A registered dietician knowledgeable in MNT for diabetes should design protein-restricted meal plans.
Total Fat, Saturated Fat, and Cholesterol
The recommended percentage of calories from fat is dependent on lipid problems and treatment goals for glucose, lipids, and weight.
The National Cholesterol Education Program (NCEP) recommends that all individuals over 2 years limit total fat consumption to <30% of total calories, saturated fat to <10% of calories, and monounsaturated fat to between 10%-15% of calories.
A decrease in dietary fat intake should be considered if obesity and weight loss are primary concerns.
Reducing saturated fat and cholesterol intake helps decrease the risk of CVD.
Changes in dietary fat intake necessitate monitoring of glycemic and lipid status and body weight to measure the effectiveness of the nutrition recommendations.
Carbohydrate and Sweeteners
The total carbohydrate consumption is of more importance than the source of the carbohydrate.
The calories and carbohydrate content from all nutritive sweeteners must be accounted for in the meal plan and have the potential to affect blood glucose levels.
Sucrose does not impair blood glucose control when it is substituted gram for gram for other carbohydrates in the total carbohydrate. content of the diet. The glycemic response is similar to that of bread, rice, and potatoes.
Fructose raises plasma glucose less than sucrose and most starches but in large amounts has potential adverse effects on serum cholesterol and LDL cholesterol. There is no reason for individuals with diabetes to abstain from eating fruits and vegetables.
Consumption is the same as for the general population, 20-35 g dietary fiber from soluble and insoluble fiber sources.
Consumption of large amounts of soluble fiber has a positive impact on serum lipids.
Consumption is the same as for the general population, no more than 3,000 mg/day.
For patients with mild to moderate hypertension, [less than or equal to]2,400 mg/day of sodium is recommended; and [less than or equal to]2,000 mg/day is recommended for patients with hypertension and nephropathy.
Consumption is the same as for the general population, no more than two drinks per day for men and no more than one drink per day for women (1 alcoholic beverage = 12 oz. beer, 5 oz. wine, or 1 1/2 oz. distilled spirits).
Alcohol inhibits glucogenesis and must be consumed with food by patients taking insulin or oral glucose-lowering agents; otherwise hypoglycemia may result, even at blood alcohol levels less than mild intoxication.
If consumed with food, alcohol does not affect blood glucose levels; however, the calories from alcohol must be calculated as part of the total caloric intake and is best substituted for fat calories.
Micronutrients: Vitamins and Minerals
Additional vitamin and mineral supplementation is unnecessary if there is adequate dietary intake.
Chromium replacement has no known benefit.
DIABETES MELLITUS AND EXERCISE
Physical activity is paramount in health promotion and disease prevention. A direct correlation exists between the epidemic proportion of patients with type 2 diabetes, the decreasing levels of activity, and increasing prevalence of obesity.
Evaluation of the Patient Before Exercise
A detailed medical evaluation including medical history, physical examination, diagnostic studies, and screening for macrovascular and microvascular complications and signs of disease affecting the heart and blood vessels, eyes, kidneys, and nervous system should be completed.
* Cardiovascular system: A graded exercise test or radionuclide stress test is recommended for patients at high risk for underlying cardiovascular disease based on one of the following criteria: age >35 years, type 2 diabetes of >10 years' duration or type 1 diabetes of >15 years' duration, presence of any other risk factor for coronary artery disease, or presence of microvascular disease, peripheral vascular disease, or autonomic neuropathy.
* Peripheral arterial disease: In the evaluation of peripheral arterial disease (PAD), a dorsalis pedis and posterior tibial pulse does not rule out ischemic changes in the forefoot.
* Retinopathy: The degree of retinopathy determines the risk associated with exercise; hence an individualized exercise regimen is needed.
* Nephropathy: No recommendations exist for patients with incipient or overt nephropathy, although patients with overt nephropathy are often limited in activity level due to a reduced capacity for exercise.
* Peripheral neuropathy (PN): Weight bearing and repetitive exercises should be limited in patients with significant PN, as they may cause ulceration and fractures. Exercises that are contraindicated include treadmill use, prolonged walking, jogging, and step exercises. Recommended exercises include swimming, bicycling, rowing, chair exercises, arm exercises, and other non-weight-bearing exercises. Evaluation of PN includes checking the deep tendon reflexes, vibratory sense, position sense and touch sense.
* Autonomic neuropathy: Patients with autonomic neuropathy have a- reduced exercise capacity and are at increased risk for an adverse cardiovascular event while exercising. Manifestations of cardiac autonomic neuropathy (CAN) include a resting tachycardia of >100 beats per minute, orthostasis, or other disturbances in autonomic nervous system function involving the skin, pupils, gastrointestinal, or genitourinary systems.
Preparing for Exercise
All exercise regimens should begin with a warm-up period and end with a cool-down period.
Trauma to the feet should be minimized, especially for individuals with PN, by wearing proper footwear and using silica gel or air midsoles to prevent blisters and to keep the feet dry.
Plenty of fluids should be taken prior to and during exercise, taking special precautions when exercising in extremely hot or cold environments.
For young individuals with diabetes, high-resistance exercise with weights or moderate weight training programs are acceptable.
For older individuals with diabetes, only moderate weight training using light weights with high repetitions can be used.
Exercise and Type 2 Diabetes
Long-term exercise programs have a beneficial effect on carbohydrate metabolism and insulin sensitivity, have been effective in reducing triglyceride-rich VLDL and blood pressure levels, and may enhance weight loss.
An association exits between aerobic fitness and fibrinolysis.
Exercise may be helpful in preventing or delaying the onset of type 2 diabetes.
Exercise and Type 1 Diabetes
Hypoglycemia can occur at any time before, during, or after exercising but can be avoided by following some general guidelines:
* Avoiding exercise if fasting glucose levels are >250 mg/dL and ketosis is present, and use caution if glucose levels are >300 mg/dL and no ketosis is present prior to exercise.
* Consuming additional carbohydrates if glucose levels are <100 mg/dL prior to exercise.
* Monitoring blood glucose before and after exercise to identify when changes in insulin or food intake are necessary and to learn how the glycemic response differs among various exercises.
* Adjusting the regimen to allow safe participation in all forms of physical activity consistent with the individual's desires and goals.
* To avoid hypoglycemia, have carbohydrate foods available during and after exercise.
Exercise in the Elderly
A decrease in fitness is preventable through regular exercise.
A decrease in physical activity in part causes a decrease in insulin sensitivity with aging.
PREVENTIVE FOOT CARE IN PEOPLE WITH DIABETES
Foot ulcers and amputations are principal causes of morbidity, disability, emotional dysfunction, and physical costs for patients with diabetes.
Prevention or delay of adverse outcomes is achievable through early identification and management of risk factors, including patients who have had diabetes [greater than or equal to] 10 years; are male; have poor glucose control; have cardiovascular, retinal, or renal complications; have peripheral neuropathy with loss of protective sensation; have altered biomechanics in the presence of neuropathy evidenced by increased pressure or bony deformity; have peripheral vascular disease; have a history of ulcers; or have severe nail pathology.
All patients with diabetes should have an annual foot exam that includes assessment of protective sensation, foot structure and biomechanics, vascular status, and skin integrity. For patients with one or more risk factors, more frequent exams should be done. If neuropathy is present, a visual inspection of the feet should be completed at every visit.
Prevention and Management of High-Risk Conditions
Smoking cessation can reduce the risk of vascular disease complications.
Patients with neuropathy or plantar erythemas should wear well-fitted walking/athletic shoes that cushion and redistribute pressure and be made aware of the implications of sensory loss and the ways to detect early problems.
A foot care specialist should debride calluses, and patients with extreme bony deformities may need custom-molded shoes.
Further vascular assessment should be done for patients with symptoms of claudication.
Patients at risk for foot conditions need to know the consequences of impaired protective sensation, the importance of proper daily foot inspections, and proper foot care.
MANAGEMENT OF DYSLIPIDEMIA IN ADULTS WITH DIABETES
CHD is two to four times more prevelant in patients with type 2 diabetes. A broad approach to prevention will be necessary in type 2 patients.
Prevelance of Dyslipidemia in Type 2 Diabetes
The most common pattern is elevated triglyceride levels and decreased HDL cholesterol levels. The median triglyceride level in type 2 diabetic patients is <200 mg/dL (2.30 mmol/L) and 85%-95% of patients have triglyceride levels < 400 mg/dL (4.5 mmol/L).
Lipoprotein Risk Factors for CHD
Predictors for CUD include smoking, blood pressure, total cholesterol, and triglyceride levels; but HDL may be the most consistent predictor of CUD.
In patients with a history of CHD:
* Simvastatin lowers CHD incidence and total mortality in diabetic patients with elevated LDL cholesterol.
* Pravastatin reduces CHD in diabetic patients with average LDL levels.
* Gemfibrozil reduces cardiovascular events by 24%.
Modification of Lipoproteins by Medical Nutrition Therapy and Physical Activity
Exercise and weight loss will decrease triglyceride and LDL cholesterol levels and will increase HDL cholesterol levels.
MNT therapy reduces LDL levels 15-25 mg/dL (0.40-0.65 mmol/L). For high-risk patients, if the level exceeds the goal by >25 mg/dL (0.65 mmol/L), pharmacology therapy may be necessary along with behavioral therapy. For other patients, behavioral interventions should be assessed every 6 weeks with consideration of pharmacological therapy between 3 and 6 months.
Saturated fat intake should be decreased, and carbohydrate and monounsaturated fat intake should be increased.
Modification of Lipoproteins by Glucose-Lowering Agents
Glucose-lowering agents usually lower triglyceride levels but only modestly raise HDL levels. Thiazolidinediones may increase HDL and LDL levels.
Treatment Goals for Lipoprotein Therapy
For adults with diabetes, measurements of LDL, HDL, total cholesterol, and triglyceride levels should be done every year and every 2 years if values are in the low-risk range.
For children with diabetes, measurement of lipoproteins should be considered after age 2.
CHD risk by lipoprotein levels in type 2 patients is as follows:
* A high-risk patient has an LDL level [greater than or equal to]130 mg/dL, an HDL level <35 mg/dL, and a triglyceride level [greater than or equal to]400 mg/dL.
* A borderline patient has an LDL level 100-129 mg/dL, an HDL level 35-45 mg/dL, and a triglyceride level 200-399 mg/dL.
* A low-risk patient has an LDL level <100 mg/dL, an HDL level >45 mg/dL, and a triglyceride level <200 mg/dL.
Optimal lipoprotein levels for diabetic patients are as follows:
* LDL level <100 mg/dL (2.60 mmol/L).
* HDL level >45 mg/dL (1.15 mmol/L). Although HDL levels are pharmacologically difficult to raise, fibrates can significantly raise the levels without affecting glycemic control.
* Triglyceride level < 200 mg/dL (2.30 mmol/L).
Recommendations for treatment of elevated LDL cholesterol are as follows:
* For diabetic patients without preexisting CHD or CVD, pharmacological therapy should begin after behavioral interventions.
* For patients with CHD, CVD) or very high LDL level, the therapies should begin together.
Treatment priorities for dyslipidemia are as follows:
* LDL cholesterol lowering using HMG CoA reductase inhibitor (statin) as the first choice and bile-acid-binding resin or fenofibrate as the second choice.
* HDL cholesterol raising using behavioral interventions and, when difficult, nicotinic acid with caution, or fibrates.
* Triglyceride lowering using fibric acid derivative (gemfibrozil, fenofibrate) or statins while maintaining glycemic control.
* Combined hyperlipidemia using improved glycemic control plus high dose statin as the first choice, the latter plus fibric acid derivative as the second choice, and improved glycemic control plus resin plus fibric acid derivative or improved glycemic control plus statin plus nicotinic acid as the third choice. The latter is associated with an increased risk of myositis.
Considerations in the Treatment of Adults with Type 1 Diabetes
Type 1 patients tend to have normal levels of lipoprotein.
Improved glycemic control may be more important in type 1 diabetics than in type 2 in order to lower risk of CHD.
ASPIRIN THERAPY IN DIABETES
Patients with diabetes at high risk for cardiovascular events should use low-dose aspirin therapy.
A low dose of aspirin has no significant adverse effects on renal function or on blood pressure control, whereas nonsteroidal anti-inflammatory drugs may increase risk for chronic renal disease and may impair blood pressure control in hypertensive patients.
Suppression of thromboxane synthesis is equally achievable with 75 mg of enteric-coated aspirin as with higher doses of either plain or enteric-coated aspirin.
In patients with CVD), the benefits of ACE inhibitors have been reduced when used in conjunction with aspirin therapy.
Use as secondary prevention strategy in diabetics with large vessel disease who have a history of myocardial infarction, vascular bypass procedure, stroke or transient ischemic attack, peripheral vascular disease, claudication, and/or angina.
Use as a primary prevention strategy in type 1 or type 2 diabetics with the following criteria: a family history of CHD), cigarette smoking, hypertension, obesity, albuminuria, cholesterol >200 mg/dL, LDL cholesterol >100 mg/dL, HDL cholesterol <45 mg/dL in men and <55 mg/dL in women, triglycerides >200 mg/dL, and age >30 years.
Use enteric-coated aspirin in doses of 81-325 mg/day.
Aspirin therapy is not recommended for patients with aspirin allergy, bleeding tendency, anticoagulant therapy; recent gastrointestinal bleeding, clinically active hepatic disease, or for patients <21 years due to the increased risk of Reye's syndrome.
SMOKING AND DIABETES
Smoking cessation is recommended. Health care providers have not given enough attention to smoking cessation.
PRE-CONCEPTION CARE OF WOMEN WITH DIABETES
The primary cause of mortality and serious morbidity in infants of diabetic mothers is major congenital malformations. Women of child-bearing age should receive counseling about the risk of malformations related to unplanned pregnancies and poor metabolic control to reduce the number of malformations.
The use of contraceptive methods does not specifically cause any adverse conditions.
Specific Goals of Treatment
Rates of congenital malformations and spontaneous abortions associated with levels of [HbA.sub.1c] up to 1% above normal are the same for diabetic and nondiabetic pregnancies. However, the number of complications decreases as the [HbA.sub.1c] level continues to decrease. Therefore, the general goal is the achievement of [HbA.sub.1c] levels <1% above normal for optimal development during organogenesis without undue risk of hypoglycemia in the mother.
To achieve treatment goals, the mother must continue to adhere to self-management skills such as using an appropriate meal plan, SMBG, self-administering insulin and self-adjusting insulin doses, treating hypoglycemia, incorporating physical activity, and practicing stress-reducing and coping techniques.
Medical and Obstetrical History
Medical and obstetrical history should include duration and type of diabetes; acute complications, including history of infections, ketoacidosis, and hypoglycemia; chronic complications, including retinopathy, nephropathy, hypertension, atherosclerotic vascular disease, and autonomic and peripheral neuropathy; diabetes management, including insulin regimen, prior or current use of oral glucose-lowering agents, SMBG regimens and results, MNT, and physical activity; concomitant medical conditions and medications; thyroid disease, in particular for patients with type 1 diabetes; menstrual/pregnancy history; contraceptive use; and support system, including family and work environment.
Physical examination should include blood pressure measurement, including testing for orthostatic changes; dilated retinal exam by an ophthalmologist or other eye specialist knowledgeable about diabetic eye disease; cardiovascular exam for evidence of cardiac or peripheral vascular disease and, if they exist, patients should be screened for coronary artery disease (CAD) prior to attempting pregnancy to ensure that they can endure the increased cardiac demands; and neurological exam, including examination for evidence of autonomic neuropathy.
Laboratory evaluation should include maternal [HbA.sub.1c], the main tool for malformation risk assessments in the infant; serum creatine and urinary excretion of total protein and/or albumin; measurement of serum thyroid-stimulating hormone and/or free thyroxine level in women with type 1 diabetes because of the 5%-10% coincidence of hyper-or hypothyroidism; and any other needed tests dictated by exams or history. A patient is at increased risk for hypertensive conditions if protein excretion >190 mg/24 h and is at increased risk for intrauterine growth retardation if protein excretion >400 mg/24 h. No specific treatments are available.
Initial management plan should include:
* Fetal and neonatal complications, effects of pregnancy on maternal diabetic complications, risks of obstetrical complications that occur with increased frequency in diabetic pregnancies, the need for effective contraception until glycemia is well controlled, the cost-benefit relationship between preconception care and prevention of malformations, and counseling about the risk and prevention of congenital anomalies.
* Selection of anti-hyperglycemic therapy.
* A strategy to attain low-risk glycemia. One such strategy has two steps.
* The first step is to set goals for SMBG using pre- and postprandial goals as follows:
a. Before meals: capillary whole-blood glucose 70-100 mg/dL (3.9-5.6 mmol/L), or capillary plasma glucose 80-110 mg/dL (4.4-6.1 mmol/L);
b. Two hours after meals: capillary whole-blood glucose <140 mg/dL (<7.8 mmol/L) at 2 h, or capillary plasma glucose <155 mg/dL (<8.6 mmol/L) at 2 h.
* The second step involves implementing the treatment plan and monitoring [HbA.sub.1c] levels every 1-2 months until stable. Counsel the patient about the associated risk of her level. If the optimal level is not reached, modification of the treatment regimen may be necessary.
Patients should be seen every 1-2 months after the initial visit, as well as have phone contact with their physicians for modification to insulin dose and other areas of treatment.
The risk of severe hypoglycemia is increased in patients with type 1 diabetes when attempting to reach normal glycemic control.
Retinopathy may hasten during pregnancy.
Hypertension often accompanies or complicates diabetes. ACE inhibitors, ([beta]-blockers, and diuretics should be avoided.
In evaluating nephropathy, a baseline assessment should be completed prior to conception and monitored regularly because of the risk of proteinuria and the influence of renal insufficiency on fetal growth and development.
Other special considerations include neuropathy and cardiovascular disease and their complications. Complications should be identified, evaluated, and treated before conception.
Screening for Albuminuria
If urinalysis is positive for albuminuria, it needs to be quantified.
If urinalysis is negative for albuminuria, test for microalbuminuria.
Three methods for screening microalbuminuria are available: measurement of the albumin-to-creatinine ratio in a random spot collection; 24 h collection with creatinine, allowing the simultaneous measurement of creatinine clearance, and timed collection. Screening should be done annually.
Transient elevations in urinary albumin excretion may develop if conditions such as short-term hyperglycemia, exercise, urinary tract infections, marked hypertension, heart failure, or acute febrile illness occur.
More specific methods are necessary to confirm all positive reagent strip tests.
Continued monitoring is recommended although the role of annual urine protein dipstick testing and microalbuminuria assessment is less clear after diagnosis and introduction of ACE inhibitor therapy/blood pressure control.
Glycemic control significantly reduces the advancement of microalbuminuria and overt nephropathy.
Since systolic and diastolic hypertension dramatically accelerate the development of nephropathy, reducing the rate of fall of GFR is achievable with an aggressive antihypertensive regimen.
Goals of therapy include decreasing blood pressure to and maintaining it at <130 mm Hg systolic and <85 mm Hg diastolic. The initial goal for patients who have isolated systolic hypertension with a systolic pressure of 180 mm Hg is to lower the systolic blood pressure to <160 mm Hg and to decrease the systolic blood pressure by 20 mm Hg for those with systolic pressure of 160-179 mm Hg.
A major aspect in the control of hypertension is lifestyle modifications such as weight loss, reduction of salt and alcohol consumption, and exercise.
Use of Antihypertensive Agents
Initial therapy for patients with underlying nephropathy should include treatment with ACE inhibitors.
ACE inhibitors are recommended for all type 1 patients with microalbuminuria because of the large percentage of patients who advance from microalbuminuria to overt nephropathy and subsequently to end-stage renal disease (ESRD).
A prescribed protein-restricted diet of 0.6 g/[kg.sup.-1]/[day.sup.-1] moderately slows the rate of fall of GFR. The recommended prescribed protein intake is approximately that of the adult RDA of 0.8 g/[kg.sup.-1]/[day.sup.-1] (~10% of daily calories).
Other Aspects of Treatment
Other aspects of treatment include radio-contrast media which are particularly nephrotoxic in patients with diabetic nephropathy, and azotemic patients should be hydrated prior to receiving any procedures requiring unavoidable contrast.
For patients with diabetes longer than 20 years, nearly all with type 1 and >60% with type 2 have some degree of retinopathy. Retinopathy was diagnosed in up to 21% of type 2 patients when first diagnosed with diabetes.
Several mechanisms can cause vision loss including macular edema or capillary nonperfusion, new blood vessels and contraction of the accompanying fibrous tissue, and bleeding blood vessels.
The progression of retinopathy is directly proportional to baseline retinopathy. A 34%- 76% reduction in retinopathy progression and a 25% reduction in overall microvascular complications occurred with intensive therapy, early treatment being most effective.
Management of blood pressure and serum lipids may be important in managing diabetic retinopathy, while pregnancy may aggravate the condition.
Laser photocoagulation surgery reduces the risk of further visual loss but does not reverse already diminished acuity.
Type 1 and type 2 patients ages 10-29 should have an initial examination within 3-5 years after diagnosis of diabetes and routine follow-up yearly. The recommended first examination for type 2 patients 30 years and older is at the time of diagnosis of diabetes and subsequent visits yearly. Women with preexisting diabetes and planning pregnancy should be initially examined prior to conception and during first trimester and follow-ups pending the results of first-trimester exam.
Prompt care is required for patients with any level of macular edema, severe nonproliferative diabetic retinopathy (NPDR), or any proliferative diabetic retinopathy (PDR).
GESTATIONAL DIABETES MELLITUS
Definition, Detection, and Diagnosis
GDM is glucose intolerance at onset or first recognition during pregnancy. It complicates 7% of all pregnancies, or 200,000 cases annually.
High-risk characteristics include marked obesity, personal history of GDM, glycosuria, or strong family history of diabetes. Initial prenatal visit should include GDM risk assessment.
Low-risk status requires all of the following characteristics: under 25 years of age, normal weight before pregnancy, member of an ethnic group with a low prevalence of GDM, no diabetes in first-degree relatives, no history of abnormal glucose tolerance or poor obstetric outcome.
Evaluation of women with average or high-risk characteristics should be done by performing a diagnostic OGTT without prior plasma/serum glucose screening or by performing a glucose challenge test (GCT) and a diagnostic OGTT on the subset of women exceeding the glucose threshold value on the GCT.
Obstetric and Perinatal Considerations
Risk of intrauterine fetal death during the final 4-8 weeks of gestation may be increased by fasting hyperglycemia (>105 mg/dL or >5.8 mmol/L).
GDM increases risk of fetal macrosomia, neonatal hypoglycemia, jaundice, polycythemia, hypocalcemia, maternal hypertension, need for cesarean delivery, and maternal development of diabetes after pregnancy. Obesity increases the risk of type 2 after GDM, while islet cell-directed autoimmunity symptoms increase the risk of type 1.
Therapeutic Strategies During Pregnancy
Daily SMBG is preferred to intermittent office monitoring, with the purpose of detecting hyperglycemia severe enough to pose risk to the fetus.
Urine glucose monitoring is not useful.
Blood pressure and urine protein levels should be monitored to detect hypertension.
Patients at risk for fetal demise require extensive monitoring, especially if fasting glucose levels exceed 105 mg/dL (5.8 mmol/L) or pregnancy extends past term.
Ultrasonography can help identify fetuses that will benefit from maternal insulin therapy.
GDM patients should receive individualized MNT consistent with blood glucose, caloric, and nutrient goals. Noncaloric sweeteners are allowed in moderation.
Calories in obese women (BMI >30) should be restricted 30%-33%, and carbohydrates restricted to 35%-40% of calories.
Insulin, when used along with MNT, reduces fetal morbidities. Human insulin should be used, and SMGB determines dosage and timing.
In the absence of maternal insulin therapy, measuring the fetal abdominal circumference early in the third trimester identifies infants with no excess risk of macrosomia.
Oral glucose-lowering agents are not recommended during pregnancy.
Moderate exercise lowers maternal glucose concentrations.
GDM is not of itself an indication for cesarean or early delivery.
Breast-feeding is encouraged for GDM mothers.
Long-term Therapeutic Considerations
Maternal glycemic status should be reclassified 6 weeks after delivery, and reassessment done at 3-year intervals if glucose levels are normal.
Children of GDM women should be monitored for obesity and/or glucose tolerance abnormalities.
TESTS OF GLYCEMIA IN DIABETES
Blood Glucose Testing by Patients
Glycemic status indicates effectiveness and provides a basis for change in therapy.
Health care providers should encourage daily SMBG in order to maintain blood glucose levels as close to normal as possible, with frequency and timing determined by individual needs.
Testing costs, lack of understanding of benefits and use of results on the part of patients and health care providers, patients' discomfort with finger-prick blood sampling, and testing inconvenience are barriers to
increasing the use of SMBG.
Patients using SMBG must know whether their monitor and strips provide whole blood or plasma results, and health care providers should regularly evaluate patients' monitoring and data interpretation techniques.
Blood Glucose Testing by Health Care Providers for Routine Outpatient Management of Diabetes
Because of SMBG, routine laboratory blood glucose testing is no longer necessary except to supplement information, detect unrecognized symptoms, and check accuracy.
Urine ketone testing is important, especially in type 1 patients, pregnant patients with preexisting diabetes, and gestational diabetes.
Blood ketone, as opposed to urine ketone, tests are preferred for diagnosing and monitoring ketoacidosis.
SMBG is the preferred method of daily monitoring of glycemic status, but urine glucose testing is an alternative. Patients should be told that the latter provides no information about blood glucose levels below the renal threshold.
Although blood and urine glucose tests and urine ketone tests are helpful for daily diabetes management, they do not provide a quantitative and reliable measure of glycemia over an extended period.
GHb (glycated hemoglobin, glycohemoglobin, glycosylated hemoglobin, [HbA.sub.lc], or [HbA.sub.l] reflects the previous 2-3 months of glycemic control.
[HbA.sub.lC] value predicts risk for development of many diabetic complications and is the preferred standard for evaluating glycemic control.
[HbA.sub.lc] testing is recommended for all patients with diabetes, with frequency determined by individual needs. Accurate data interpretation depends on the understanding of the relationship between test results and average blood glucose, kinetics of [HbA.sub.lc] and specific test limitations.
Goal of therapy is an [HbA.sub.lc] of <7%; treatment should be reevaluated when [HbA.sub.lc] values are consistently above 8%.
Glycated serum protein (GSP) level provides an index of glycemia over a shorter period of time than does hemoglobin glycation - the preceding 1-2 weeks as opposed to 2-3 months.
HYPERGLYCEMIC CRISES IN PATIENTS WITH DIABETES MELLITUS
Ketoacidosis and hyperosmolar hyperglycemia are the most serious acute metabolic complications of diabetes, and the prognosis for both is reduced by old age, coma, or hypotension.
The origin of both diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) is a reduction in the action of circulating insulin along with elevation of counterregulatory hormones.
DKA and HHS are associated with glycosuria and consequent osmotic diuresis with loss of water, sodium, potassium, and other electrolytes.
Infection, cerebrovascular accident, alcohol abuse, pancreatitis, myocardial infarction, trauma, drugs, new onset diabetes, hyperglycemia, and insulin discontinuation or reduction are precipitating factors for DKA or HHS.
Psychological problems and eating disorders may be a contributing factor in 20% of recurrent ketoacidosis in younger type 1 diabetics.
HHS develops over several days to weeks, whereas the evolution of DKA is shorter.
Patient history includes polyuria, polydipsia, polyphagia, weight loss, vomiting, abdominal pain in DKA, dehydration, weakness, clouding of sensorium, and coma. Physical manifestations may include poor skin turgor, Kussmaul respirations in DKA, tachycardia, hypotension, change in mental status, shock, and ultimately coma.
Hypothermia is a poor prognostic indicator, and abdominal pain can be either a result or a cause of DKA.
Initial lab testing should include plasma glucose, blood urea nitrogen/creatinine, serum ketones, electrolytes, osmolality, urinalysis, urine ketones by dipstick, arterial blood gases, complete blood count with differential, and electrocardiogram. Urine/blood/throat cultures, [HbA.sub.1c], and chest x-ray should be included if indicated.
Patients with low-normal or low serum potassium concentration need careful cardiac monitoring and more vigorous potassium replacement. Stupor or coma without definitive elevation of effective osmolality should be investigated.
Ketoacidosis is not necessarily an indicator of DKA; it also occurs in starvation ketosis and alcoholic ketoacidosis (AKA).
Treatment requires frequent patient monitoring; dehydration, hyperglycemia, and electrolyte imbalance correction; and comorbid precipitating event identification.
Fluid therapy involves expansion of intravascular/extravascular volume and restoration of renal perfusion. Effectiveness is evaluated by blood pressure improvement, fluid input/output measurement, and clinical examination.
In pediatric patients, the need for vascular volume expansion must be weighed against the risk of cerebral edema.
Regular insulin by continuous IV infusion is the preferred treatment, with mild DKA patients first receiving a "priming" dose of 0.4-0.6 U/kg body weight, half as an intravenous bolus and half as a subcutaneous or intramuscular injection.
Insulin therapy decreases phosphate concentration.
A multidose regimen may be used after DKA resolution and when patients are able to take fluids orally.
Some patients may be discharged on oral medications and dietary therapy.
When serum levels fall below 5.5 mEq/L, assuming adequate urine output, potassium replacement is indicated.
Bicarbonate use is controversial.
DKA and HHS complications include hypoglycemia due to overzealous insulin treatment, hypokalemia due to insulin administration and treatment of acidosis with bicarbonate, hyperglycemia secondary to interruption/discontinuance of insulin therapy, hypoxemia, noncardiogenic pulmonary edema, and rare but frequently fatal cerebral edema.
DKA and HHS cases can be reduced by better access to medical care, proper education, and effective communication with a health care provider.
Sick-day management involving the patient and/or a family member who can accurately measure/record vital information should be reviewed periodically.
Annual DKA incidence rate is 4.6-8.0/1,000 patients with diabetes. HHS accounts for less than 1% of all primary diabetic hospitalizations.
One out of every two health care dollars is spent on adult patients with type 1 diabetes. Resources should be spent on the education of primary care providers and school personnel.
PANCREAS TRANSPLANTATION FOR PATIENTS WITH TYPE 1 DIABETES
Pancreas transplantation significantly improves diabetic patients' quality of life.
Transplantation is usually performed 20 or more years after onset of diabetes, and it has not been determined if earlier transplant prevents complications.
The transplant procedure requires lifelong immunosuppressants, and patients have significant morbidity as well as a small risk of mortality.
Tertiary care centers with kidney transplant programs are the best choices for pancreas transplantation and follow-up.
Pancreas transplantation is recommended for diabetic patients with end-stage renal disease who have had or plan to have a kidney transplant.
When kidney transplantation is not a factor a pancreas transplant should be done only in patients with frequent, acute, and severe metabolic complications; severe clinical and emotional problems with insulin therapy; and consistent failure of insulin-based management to prevent acute complications.
Although experimental at this time, pancreatic islet cell transplants offer more advantages than whole-gland transplants.
This section includes details on the following:
* Mixing insulin;
* Syringes (disposal and reuse);
* Syringe alternatives;
* Injection technique (dose preparation, procedures, and injection site); and
* Patient management (dosing, self-monitoring, and hypoglycemia).
CONTINUOUS SUBCUTANEOUS INSULIN INFUSION (CSII)
CSII candidates must know how to use the insulin pump, monitor blood glucose, and interpret data.
Patients must be motivated to improve glucose control and work with health care providers to assume responsibility for self-care.
IMMUNIZATION AND THE PREVENTION OF INFLUENZA AND PNEUMOCOCCAL DISEASE IN PEOPLE WITH DIABETES
The Advisory Committee on Immunization Practices (ACIP) recommends annual influenza vaccination for all diabetic patients 6 months of age and older.
Diabetics are susceptible to pneumococcal infection and should be vaccinated to reduce invasive disease.
Revaccination should be considered only under special circumstances, including once for patients older than 64 years of age if they were immunized before age 65 more than 5 years ago.
Education for health care personnel and publicity/education for patients are essential for effective immunization strategies.
The lack of vaccine delivery systems in private and public sectors is a major hindrance to immunization.
Successful treatment of diabetes includes patient self-management training in nutrition.
Patients can obtain reliable data from nutrition and ingredient labels on food, but labels do not compensate for inadequate nutritional knowledge.
Nutritional meaning of foods is a part of overall food consumption and health status understanding.
ROLE OF FAT REPLACERS IN DIABETES MEDICAL NUTRITION THERAPY
Fat replacers are defined as ingredients that imitate one or more functions of fat in food.
Fat replacers are classifed according to their nutrient source; categories include carbohydrate-based, protein-based, and fat-based.
The FDA concluded that there is no harm in currently available fat replacers.
Used appropriately, fat replacers may help diabetics reduce total and saturated fat intake, as well as risk of dyslipidemia in type 2 patients.
CARE OF CHILDREN WITH DIABETES IN THE SCHOOL AND DAY CARE SETTING
Diabetes affects 1.7 out of 1,000 people under the age of 20.
Development of complications depends on blood glucose control.
Because of blood glucose monitoring, meal plans, and medication schedules, children with diabetes require appropriate care in schools or daycare settings.
School and daycare personnel must be educated in the management and treatment of diabetes, including effects of physical activity, nutrition, and insulin.
Parents/guardians, health care providers, and school or daycare personnel should develop individual diabetes health care plans with specific information on blood glucose monitoring and insulin administration/storage, meals and snacks, hypoglycemia/hyperglycemia symptoms and treatment, ketone testing, and response to abnormal ketone levels.
Responsibilities of parents/guardians and school/daycare providers are listed in this section.
Specialized diabetes camps with skilled medical staff are available for children and youth with diabetes.
(*.) Prepared by Kathy F. Caughron and Esther L. Smith.
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|Title Annotation:||treatment of diabetes|
|Publication:||Southern Medical Journal|
|Date:||Jan 1, 2002|
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