What's New in Type 2 Diabetes Mellitus for the Primary Care Physician
What's New in Type 2 Diabetes Mellitus for the Primary Care Physician
Authors: Indu Rao, MD, Kettering Medical Center Clara Weifenbach Fellow in Women's Health; Stephen D. McDonald, MD, Endocrinologist, Program Director, Kettering Medical Center Internal Medicine Residency, Wright State University Eugene Kettering Professor of Medicine.
Peer Reviewers: Keith Doram, MD, Assistant Professor of Medicine, Loma Linda University School of Medicine, Riverside General Hospital-University Medical Center; A. Barry Warner, DO, Director, Division of Encrinology, University of South Alabama College of Medicine, Associate Professor of Medicine, Pediatrics, Family Practice, and Community Medicine.
Editor's Note-The majority of care for type 2 diabetes is provided by primary care physicians. Understanding the new classification, diagnostic criteria and recommendations is essential for efficient management of diabetes. Type 2 diabetes is under-diagnosed and under-treated. Often the diagnosis is made late when complications have already developed. Recently the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus released new diagnostic criteria in an attempt to identify the undiagnosed type 2 diabetic population. The effect on primary care physicians of the new diagnostic criteria will be tremendous, as currently 50% of type 2 diabetics are undiagnosed.
Over the last few years, several advances have been made in understanding the pathophysiology and developing medications that target the various pathophysiologic mechanisms. The American Diabetes Association has established standards of care for the management of diabetes and prevention and treatment of complications. Recommendations for screening for asymptomatic type 2 diabetes have also been published. With these new strategies primary care providers will be better equipped to manage type 2 diabetes effectively.
The goal of this article is to present the latest information regarding the classification, diagnostic criteria, pathogenesis and medications available for effective management of type 2 diabetes mellitus. The current screening recommendations and management of the complications of diabetes is also reviewed.
Epidemiology and Scope of the Problem
In the United States, 8 million adults have diagnosed diabetes mellitus, 90-95% of whom have type 2 diabetes.1 For every person who is diagnosed with diabetes, there is one who is undiagnosed but is at risk of developing complications.1-3 Thus, about 15 million people, representing one in every 17 people or approximately 6% of the entire United States population, have diabetes. In addition, 35-40 million adults have impaired glucose tolerance with a high risk of progression to diabetes.1,4 By middle adult life, one in 4-5 persons has either diabetes or impaired glucose tolerance. Almost half of the Medicare population is afflicted with diabetes.
Over the past 30 years, the prevalence rate of diabetes in the United States has tripled. Some of this increase is due to longer survival of people with diabetes. The prevalence of diabetes increases with age from less than 2% before the age of 45 to 18% by the age of 74. Certain ethnic populations, such as the Pima Indians of Arizona, Hispanics, blacks, and Asians, have diabetes rates that are 1.5-2 times the rates observed in non-Hispanic whites.1,5
Diabetes causes substantial morbidity and premature mortality. Diabetes is the leading cause of blindness, renal failure, and lower extremity amputations in the United States.1 Twenty percent of all deaths in the United States are from diabetic complications.6 Mortality rates are 2-4 times those for non-diabetic patients, and life expectancy is about 7-10 years shorter in diabetics.1 The most common cause of mortality in patients with diabetes is from ischemic heart disease.1
Type 2 diabetes is often present for 10-12 years before clinical diagnosis.7 During this asymptomatic phase, microvascular and macrovascular disease progress, and at the time of diagnosis, about 20% of patients have diabetic retinopathy and 5-10% have proteinuria.7 Most of our effort is spent taking care of complications because diagnosis is made late in the course of the disease. Intervention strategies can delay the onset and progression of complications. A recent audit showed that many diabetic patients receive substandard quality of care.8 Patients are not seen as frequently as required by the American Diabetes Association standards. Meticulous blood glucose control is not strictly implemented, and not all diabetics are monitored with serial HbA1C measurements. Annual screening for dyslipidemia, retinopathy, and nephropathy is not routinely performed. Regular foot examination is neglected in a large percentage of patients, and referrals to diabetic educators and nutrition experts are not conducted as often as they should be.
Chronic diabetic complications account for the enormous economic implications of this disease. Along with the toll it takes in terms of morbidity and mortality, diabetes and its complications are major depletors of heath care resources and worker productivity. Fifteen percent of all U.S. health care dollars ($105 billion in 1992) is consumed by diabetic care.1 Half of this huge cost is for direct medical care, and the other half is for societal costs (e.g., lost-productivity, long-term disability, rehabilitation, and premature death). A substantial proportion of the economic burden is in the treatment of advanced complications such as hemodialysis, for which the annual cost of treatment exceeds $2 billion.1,2
To reverse the current trend of increasing prevalence and immense use of resources to treat diabetic complications, physician and patient attitudes should change from treatment of acute symptomatic situations to prevention strategies. Screening of asymptomatic diabetes should be conducted in high-risk populations. Patients with impaired glucose tolerance should be counseled about lifestyle modifications that may prevent the progression to diabetes in this population. Once diabetes is detected, before the onset of complications, aggressive initial therapy should be initiated to keep blood glucose and HbA1C in the target range. Overwhelming data show that the debilitating complications of diabetes mellitus are preventable. The Diabetes Control and Complications Trial (DCCT) and the Wisconsin End Stage Diabetic Retinopathy (WESDR) trial have shown that intensive treatment to control hyperglycemia delays the onset and progression of diabetic complications. Early screening and interventions strategies for diabetic complications that delay the progression to end stage disease should be instituted. These strategies have been projected to reduce blindness, kidney failure, and amputations from diabetes by 60-80%.6
Definition of Diabetes Mellitus
Diabetes mellitus is a chronic disorder characterized by impaired metabolism of glucose, fats, and protein due to insufficient insulin secretion, tissue insensitivity to insulin's actions, or both. The resulting hyperglycemia is responsible for the symptoms and long-term complications of diabetes. (See Figure 1.)
A Classification of Diabetes Mellitus Based on Etiology
Diabetes mellitus is not a single disease entity but a condition with a heterogeneous etiology. In 1979, the National Diabetes Data Group (NDDG) and World Health Organization (WHO) proposed the classification based on the pharmacological management of diabetes.9,10 Over the last 18 years, several scientific advances regarding the etiology and pathophysiology of the different causes of diabetes have accumulated, prompting the need for a new classification based on etiology. In 1995, the American Diabetes Association commissioned an International Expert Committee to develop a new classification. In July 1997, the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus released the new guidelines for the classification and diagnosis of diabetes.11 (See Table 1.)
Type 1 diabetes mellitus refers to cases due to auto-immune or idiopathic pancreatic beta-cell destruction. These patients are prone to ketoacidosis due to an absolute lack of insulin. Less than 5% of diabetics have type 1 diabetes. The remaining 90-95% of diabetics have type 2 diabetes, which results from insulin resistance coupled with an insulin secretory defect.
Gestational diabetes mellitus (GDM) is retained as defined by WHO and NDDG. Malnutrition-related diabetes has been eliminated in the current classification because the evidence that diabetes can be directly caused by protein deficiency is not convincing. Other specific causes of diabetes mellitus such as enzyme deficiencies, genetic defects, drug-induced causes, endocrinopathies, and diseases of the exocrine pancreas are classified as secondary diabetes.
The names IDDM and NIDDM have been discarded. The current classification favors use of the terms type 1 and type 2 diabetes mellitus. Arabic numerals 1 and 2 are used instead of roman numerals to avoid confusing the lay public, who may mistake the roman numeral II for the number 11.11
The concept of an intermediate stage between normal glucose and diabetes remains unchanged. When an oral glucose tolerance test (OGTT) is used to diagnose diabetes, a two-hour post-glucose value between 140 and 200 mg/dL is called impaired glucose tolerance (IGT). (Normal is defined as a 2-hour post-glucose < 140 mg/dL; diabetes, a 2-hour post-glucose ³ 200 mg/dL). The American Diabetes Association now discourages the use of the OGTT in the diagnosis of diabetes and recommends the use of the fasting plasma glucose (FPG) instead.11 When using an FPG to diagnose diabetes, the intermediate stage between normal glucose and diabetes has been named impaired fasting glucose (IFG). The clinical implications of the intermediate metabolic stage are:
1. the progression to diabetes in a significant proportion of these patients.
2. the risk of developing micro- and macrovascular complications. Diagnosis of Diabetes Mellitus
A confirmed FPG of 126 mg/dL or greater is now the definitive criteria for the diagnosis of diabetes mellitus.11 (See Table 2.) A significant proportion of type 2 diabetes is not diagnosed when the old criteria of an FPG of 140 mg/dL is used. The two-hour OGTT is more sensitive and identifies all patients with diabetes, but it is an expensive and cumbersome test. If an FPG level of 126 mg/dL is used as a cut-off point for the diagnosis of diabetes, then all patients with an abnormal OGTT are included. This obviates the need for the laborious OGTT. At an FPG ³ 126 mg/dL, the incidence of micro- and macrovascular complications increases dramatically. The advantages of the FPG include ease of administration, convenience, acceptability to patients, and lower cost. For these reasons, the FPG is now used to diagnose diabetes mellitus. HbA1C measurement is currently not recommended for the diagnosis of diabetes.11
Criteria for the Diagnosis of Diabetes Mellitus 1. Fasting plasma glucose 126 mg/dL or greater (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 hours.
2. Classic symptoms of diabetes (polydipsia, polyuria, unexplained weight loss) plus casual plasma glucose concentration 200 mg/dL or greater (11.1 mmol/L). Casual refers to any time of the day without regard to time since last meal.
3. Two-hour post glucose ³ 200 mg/dL during an OGTT. Confirm each of the above criteria on a subsequent day with any of the same above-mentioned tests.
Table 1. Comparison Between the Old and New Classifications of Diabetes Mellitus
|
NDDG Classification (1979) |
New Classification (1997) |
|
Based on treatment |
Based on etiology |
|
Insulin Dependent |
Type 1 Diabetes Mellitus |
|
Non Insulin Dependent |
Type 2 Diabetes Mellitus |
|
Gestational Diabetes |
Gestational Diabetes Mellitus |
|
Secondary (other) causes |
Secondary (other) causes |
|
Malnutrition related Diabetes |
(eliminated) |
|
Impaired Glucose Tolerance |
Impaired Glucose Tolerance |
|
(did not exist) |
Impaired Fasting Glucose |
Screening for Asymptomatic Type 2 Diabetes Mellitus
A significant proportion of patients are asymptomatic but are at high risk of developing micro- and macrovascular complications of diabetes. Fifty percent of type 2 diabetics remain undiagnosed and may present with diabetic tissue damage at the time of diagnosis. The major portion of the morbidity, mortality, and economic burden of diabetes is associated with its complications. Early detection and, consequently, early treatment will reduce the burden of type 2 diabetes and its complications. This provides the rationale for screening for asymptomatic diabetes mellitus.
The preferred screening test is the FPG. Screen all individuals aged 45 years and older. If the FPG is normal, repeat in three years.
The following groups of people are considered high-risk. Frequency of screening in this group has currently not been defined, but it should be less than three years.11 Age < 45 years and presence of any of the following:
a. Obesity ( 120% desirable body weight or BMI 27 kg/m2)
b. First-degree relative with diabetes
c. Members of high-risk ethnic population (e.g., black, Hispanic, American Indian)
d. Delivery of a baby weighing more than 9 lbs. or diagnosis of GDM
e. Hypertension ( 140/90 mmHg)
f. HDL cholesterol level less than 35 mg/dL and/or trigly-ceride level greater than 250 mg/dL
g. Previous diagnosis of impaired glucose tolerance or impaired fasting glucose
Table 2. Interpretation of Fasting Plasma Glucose Values
|
FPG (mg/dL) |
Interpretation |
|
Less than 110 |
Normal Fasting Glucose |
|
110 to 125 |
Impaired Fasting Glucose |
|
126 and Above |
Provisional Diagnosis of Diabetes |
Pathogenesis of Type 2 Diabetes Mellitus
Over the last decade, much of the pathophysiologic mechanisms of type 2 diabetes has been characterized. Several new drugs targeting these different mechanisms have been approved for treatment of type 2 diabetes. Understanding the pathophysiology is crucial to a rational use of the new medications for effective management of type 2 diabetes.
The Four Defects in Type 2 Diabetes 1. Insulin resistance resulting in inefficient peripheral glucose use
2. Increased rate of endogenous hepatic glucose production
3. Declining beta-cell function causing reduced insulin secretion
4. Impaired priming of the pancreas by the gut after an oral glucose load
Abnormal metabolism of glucose inside the cell causes insulin resistance. In the fed state, the main action of insulin is to stimulate the uptake of glucose from the circulation by insulin-sensitive tissues (mainly muscle and adipose tissue). Once inside the cell, glucose is either metabolized to yield energy by means of glycolysis or is stored as glycogen for later use. Insulin-mediated glucose metabolism is impaired in type 2 diabetes and is the cause of insulin resistance.12 Glucose use by tissues is impaired, and excess glucose accumulates in the bloodstream. The hyperglycemia stimulates the pancreas to produce more insulin in an effort to overcome the insulin resistance. The simultaneous elevation of both glucose and insulin is strong suggestive evidence that insulin resistance is present.
Increased hepatic glucose output determines fasting hyperglycemia. The basal rate of glucose release by the liver is the single most important determinant of the severity of fasting hyperglycemia in the diabetic patient.12 Insulin suppresses production of glucose by the liver in normal individuals. In type 2 diabetes, hepatic glucose metabolism is impaired and insulin fails to suppress hepatic glucose output by the liver. Glucose is underused for energy, and fat is used as the alternate fuel. Products of fat metabolism act as substrates for the production of glucose by the liver through the process of gluconeogenesis. The liver overproduces and underuses glucose, causing worsening hyperglycemia.13
Hyperglycemia is both the cause and the result of impaired insulin secretion by the beta cells of the pancreas. The third major abnormality in patients with type 2 diabetes is a relative deficiency of insulin secretion. Normally, when a subject is infused with an intravenous glucose load, insulin secretion occurs in two phases. First phase insulin secretion occurs within the first 10 minutes. This facilitates immediate glucose disposal and prevents post-prandial hyperglycemia. The second phase of insulin secretion lasts for the duration of hyperglycemia and determines the fasting blood glucose. In diabetics, the first phase insulin secretion is lost early, and, eventually, the second phase is also lost. Since tight control of blood sugar may improve first phase secretion, early and aggressive management of type 2 diabetes is indicated.14
Although beta cell dysfunction is genetically predetermined, chronic hyperglycemia has been shown to impair insulin secretion by the pancreas. This effect, called glucotoxicity, perpetuates the hyperglycemia once diabetes is established. Glucotoxicity is reversible. This means that control of hyperglycemia in itself will result in enhanced secretion of insulin by the pancreas.15
The gut primes the pancreas for an impending glucose load. Pancreatic secretion of insulin is significantly greater when oral administration of glucose is used instead of the intravenous route. Two peptides released by the gut, gastric inhibitory peptide (GIP) and glucagon-like-peptide (GLP-1), augment glucose-stimulated insulin secretion by the pancreas. The effect of these two peptides is enhanced disposal of postprandial hyperglycemia.16
Table 3. Oral Antidiabetic Agents Target the Pathophysiologic Mechanisms of Type 2 Diabetes
|
Oral Hypoglycemic agent |
Mechanism of Action |
Total Dose |
Doses per Day |
Adverse Effects |
Contraindication |
Comments |
|
Sulfonylureas |
Increase insulin secretion from both beta cells of pancreas |
2nd generation Sulfonylureas |
1 |
Hypoglycemia |
Type 1 Diabetes, |
Least expensive oldest drug available with well known side effects |
|
Biguanides |
Decreases Hepatic Output of Glucose |
1-2.5g |
2-3 |
Lactic acidosis |
Renal failure severe congestive heart failure, before procedures requiring IV contrast |
Cuases weight improves lipids profile, does not cause hypoglycemia. GI side effects decreased by starting with low dose and increasing slowly to maximum |
|
Alpha-Glucosidase Inhibitors |
Delays digestion and absorption of glucose from the gut |
75-300mg |
3 with meals |
Abdominal bloating, flatulence, diarrhea |
Cirrhosis, inflammatory bowel disease, other chronic intestinal diseases |
Reduces postprandial hyperglycemia |
|
Thiazolidinediones |
Decreases Insulin resistance |
200-600mg |
1 with food |
Dizziness, GI disturbances, reversible increase in transaminases |
Liver diseases, congestive heart failure |
Does not cause hypoglycemia, improves blood pressure and lipid profile, has antioxidant properties, decreases insulin requirements, most expensive, needs liver enzyme monitoring |
Toward a More Rational Management of Type 2 Diabetes Mellitus
Until 1995, the only available oral agents in the United States were the sulfonylureas. Medical therapy of type 2 diabetes was limited to the use of sulfonylureas and insulin. Over the last two years, several new medications with differing mechanisms of action have acquired FDA approval, allowing less frequent use of insulin. Oral anti-diabetic agents target the pathophysiologic mechanisms of hyperglycemia, allowing a more rational management of type 2 diabetes.13,17 (See Table 3.)
Table 4. Target Glycemic Control
|
Biochemical Index |
Values in Non-Diabetics |
Goal for Non-Diabetics |
Action When Required |
|
Preprandial glucose |
<115 |
80-120 |
<80;> 140 |
|
Bedtime glucose |
<120 |
100-140 |
<100;> 160 |
|
Hemoglobin A1c (%) |
<6 |
<7 |
>8 |
Management
The two basic goals in the management of diabetes are control of hyperglycemia and screening and prevention of complications. (See Table 4.)
Persistent hyperglycemia is the hallmark of diabetes and is responsible for the debilitating complications. Normalization or near-normalization of fasting and post-prandial glucose levels is the most important goal in the management of diabetes mellitus, because it prevents acute and long-term complications. The Diabetes Control and Complications Trial (DCCT) showed that intensive treatment to lower blood glucose delayed the onset and progression of microvascular complications in type 1 diabetes.18 There is now growing evidence to show that this holds true for type 2 diabetes as well.19-22
Patient-centered care involves teamwork and training. People with diabetes should receive their treatment and care from a physician-coordinated team. This includes physicians (primary care practitioners and sub-specialists), diabetic educators, nurses, dietitians, mental health professionals, and other resources as felt necessary. Patient education is of utmost importance, as this places a major responsibility of care on the patient, and the value of continuing education by means of refresher courses should be encouraged.
Meal-planning and exercise are cornerstones in diabetic management. A standardized ADA diet is no longer recommended. Diabetics should be taught meal planning, and this should be tailored to fit as closely as possible to the patient's tastes, cultural preferences, convenience, and financial capabilities. A diabetic nutrition specialist may be consulted to aid with this aspect of treatment. The goal should be improved glucose, lipid, and blood pressure control. Even mild to moderate weight loss (5-10 kg) results in improved diabetic control.23
Use these general guidelines to achieve nutritional goals in type 2 diabetes:
• Space meals by spreading nutrient intake throughout the day.
• Use moderate caloric restriction of 250-500 calories less than average intake.
• Reduce total fat intake, especially saturated fats .
• Decrease cholesterol intake to less than 300 mg/d; if elevated LDL is present, decrease to 200 mg/d.
• Include 20-35 g of dietary fiber from a wide variety of food sources.
About 10-20% of the daily caloric intake should be derived from protein and the rest from fat and carbohydrates. The percentage of fat is dependent upon the lipid profile. With a normal lipid profile, total fat should supply less than 30% of calories, with less than 10% from saturated fat. The percentage from saturated fat should be further decreased to 7%, if elevated LDL is present. In the presence of elevated triglycerides, calories from total fat should be less than 20%, with less than 10% from saturated fat. More than 20% of calories should come from monosaturated fats.
Table 5. Guidelines for Choosing Oral Hypoglycemic Therapy
|
FPG (mg/dL) |
Drugs of choice |
|
125-140 |
Troglitazone, metformin if patient obese glimepiride if patient not obese |
|
140-200 |
Metformin, troglitazone if patient obese |
|
>200 |
Metformin, troglitazone, sulfonylurea |
|
Postprandial hyperglycemia |
Acarbose may be used as initial monotherapy or added to above |
Exercise Recommendations:1
• Obtain an exercise stress electrocardiogram in patients over 35 years before embarking on an exercise program.
• Start with mild exercises, such as walking or riding a stationary bike, and gradually increase exercise sessions.
• Include aerobic exercise at 50-70% of individual's maximum oxygen uptake lasting 20-45 minutes, 3-4 days/week.
• Encourage low intensity warm-up and cool-down exercises to improve flexibility and prevent injuries.
• Do not exercise when short of breath. Perceived exertion may be a better indicator of exercise intensity than the pulse rate. Although lifestyle modifications are a frustrating aspect of diabetic management, they are an essential part of glycemic control and improve blood glucose by decreasing insulin resistance and improving peripheral glucose use. Reinforce the value of meal planning and exercise at every visit.
Failure of nonpharmacological therapy is an indication to start oral hypoglycemic medications. In about two-thirds of type 2 diabetics, blood glucose control will be achieved with diet and exercise.22 In the remaining one-third of patients, oral hypoglycemic agents will be necessary. If after 3-6 months of nonpharmacological therapy, the HbA1C remains above 7%, add an oral antidiabetic agent. When the FPG is above 200 mg/dL, an oral hypoglycemic agent may be started at the outset, in conjunction with lifestyle modifications.
With the array of medications now available, choice of initial therapy can be geared to suit the patient's profile.1,17 (See Table 5.) Oral hypoglycemic agents are used in conjunction with lifestyle modifications.
Initial monotherapy with sufonylureas and metformin will undergo secondary failure at a rate of 5-10% per year.1 This will manifest as poor blood glucose control after 3-5 years of initially adequate control. When secondary failure occurs, combination therapy will be required. Principles guiding combination therapy: • Do not substitute one drug for another but add a drug with a different mechanism of action.
• Add metformin or troglitazone, if fasting hyperglycemia is the main problem.
• Use acarbose or sufonylurea for post-prandial hyperglycemia. Up to three oral medications with different mechanisms of action may be tried before instituting insulin therapy.13
As beta-cell failure occurs, insulin will be required for effective blood glucose control. Initially, the addition of a single injection of bedtime intermediate acting insulin or dinnertime combination insulin will control hyperglycemia. The body mass index (BMI) may be used to choose the type of insulin therapy.24 In nonobese subjects (BMI < 30), use bedtime intermediate insulin (NPH/lente) along with daytime oral hypoglycemic agent.25 When the BMI is greater than 30, dinnertime 70/30 or other intermediate/regular combination insulin may control hyperglycemia. Start with 10-15 units of intermediate-acting insulin insulin and increase by five units weekly until target glycemia achieved. If more than 35 units of insulin are required, troglitazone may be added to decrease insulin requirements. Metformin and acarbose may also be used in conjunction with insulin therapy.
In time, failure of single injection insulin will occur, and this is heralded by pre-dinner glucose values of more than 170 mg/dL. Multiple insulin injections will become necessary. At this point, individualized insulin regimens will need to be worked out, preferably in conjunction with an endocrinologist.
Daily measurement of blood glucose by the patient, coupled with periodic HbA1C assessment is necessary to monitor the adequacy of glycemic control. Self blood glucose monitoring (SMBG) at least 2-3 times per day provides the patient useful feedback regarding the success or failure of blood sugar control. Confirm the accuracy of patient results with simultaneous laboratory testing.
Hemoglobin A1C reflects glycemic control over a period of 2-3 months. It should be performed routinely in all diabetics. Obtain the first HbA1C level at the initial assessment. Then check the level every three months until the target level of 7% is achieved. Thereafter, it may be done semi-annually to ensure ongoing control of hyperglycemia.21
Table 6. NCEP Guidelines for Treatment of Hyperlipidemia
|
Patient Category |
Therapy if LDL |
Required (mg/dL) |
LDL Goal (mg/dL) |
|
Diet |
Medication |
||
|
Without CHD (<2 risk factors) |
>160 |
>190 |
<160 |
|
Without CHD (>2 risk factors) |
>130 |
>160 |
<130 |
|
With CHD |
>100 |
>130 |
<100 |
|
CHD - Coronary Heart Disease; LDL - Low Density Lipoprotein |
|||
|
Reinforce advantages of smoking cessation |
Macrovascular complications
Patients with type 2 diabetes have had insulin resistance and impaired fasting glucose for many years prior to their diagnosis of diabetes. The insulin resistance syndrome (metabolic syndrome or syndrome X) includes hypertension, hypertrigly-ceridemia, low HDL levels, and abnormal fibrinolytic system, thus conferring enhanced atherogenecity.26 A two- to five-fold increase in the prevalence of cardiovascular, cerebrovascular, and peripheral vascular disease is seen in diabetics as compared to non-diabetics.
Diabetes is an independent major risk factor for atherosclerotic coronary artery disease.1 Other cardiovascular risk factors include hypertension, hyperlipidemia, smoking, and obesity through insulin resistance. Ischemic heart disease occurs at a younger age in diabetics, affecting males and females alike. The atypical clinical manifestations of coronary artery disease in diabetics delay diagnostic and potentially lifesaving interventions. Myocardial infarction portends a poorer prognosis, and angioplasty results are less successful in diabetics. Aggressive cardiovascular risk factor reduction in diabetics is a must. Recommendations for risk factor modification are as follows:21
Table 7. Definitions of Urinary Protein Excretion
|
Category |
Spot collection |
24-hour collection |
|
Normal |
<30 |
<30 |
|
Microalbuminuria |
30-300 |
30-300 |
|
Clinical albuminuria |
>300 |
>300 |
Check the blood pressure at every visit. Hypertension is present in one-third of patients at the time of diagnosis of type 2 diabetes. The goal of therapy is to maintain blood pressure below 130/85 mmHg. This is achieved by weight loss, low sodium intake (< 2 g/d), exercise, and decreased alcohol intake. Antihypertensive medications of choice are angiotensin converting enzyme inhibitors (ACEI), calcium channel blockers, and alpha-1 blockers, as these medications do not have adverse effects on hyperglycemia or lipid profile. Use diuretics and beta-blockers with caution, as both worsen insulin resistance and the lipid profile. Beta-blockers confer a protective effect in patients who have had a myocardial infarction and therefore should not be withheld in this population.
Obtain a fasting lipid profile annually. Diabetes has an adverse effect on the lipid profile. The common abnormal lipid pattern in diabetics is elevated very low density lipoprotein (VLDL), a reduction in HDL, and an LDL portion that contains a greater proportion of small, dense, atherogenic LDL particles. Follow the NCEP (National Cholesterol Education Program Adult Treatment Panel II report) guidelines for treatment of dyslipidemia. (See Table 6.) This is based on the number of cardiovascular risk factors present and presence of coronary artery disease.27
Table 8. Screening for Abnormalities that Predispose to Foot Ulcers
|
Evaluation |
What to Examine |
What to Look For |
Recommended Interventions |
|
Neurological Examination |
Sensory examination using |
Absent Sensation |
Footwear modification, splints as needed |
|
Vascular Examination |
Palpation of peripheral pulses |
Absent peripheral pulses |
Smoking cessation; |
|
Abnormal gait and footwear patterns |
Plantar surface of foot |
Calluses at pressure points; |
Refer to podiatrist for complete assessment and special footwear |
|
Musculoskeletal evaluation |
Foot and ankle joint range of motion |
Abnormal range of motion; |
Orthopedic consultation for appropriate treatment |
Microvascular Complications
Diabetic Retinopathy. Up to 21% of patients with type 2 diabetes have retinopathy at the time of diagnosis. Five to 10% of type 2 diabetics go on to become blind.1 The reasons for vision loss in patients with diabetic retinopathy include macular edema, retinal detachment, and vitreous hemorrhage. Two other complications of diabetes, cataracts and glaucoma, can lead to visual loss. Patients with vision-threatening retinopathy may not have symptoms. Annual evaluation by means of dilated funduscopic examination is a valuable strategy because patients with asymptomatic macular edema and proliferative retinopathy can be identified.21 Timely intervention with laser photocoagulation in these patients can prevent visual loss.29
Diabetic Nephropathy
Twenty to thirty percent of type 2 diabetics develop nephropathy, and one-fifth of these patients progress to end-stage renal disease. Evidence of diabetic nephropathy first presents as microalbuminuria. At this stage, dipstick urinalysis examination will be negative for protein. For the detection of microalbuminuria, the spot collection method is easily performed in the office setting, although many physicians prefer to use a 24-hour collection of urine. As urinary albumin excretion rates increase, overt nephropathy develops. (See Table 7.) Then the glomerular filtration rate falls, and patients eventually develop end-stage renal failure, requiring dialysis. Albuminuria is also a marker of greatly increased cardiovascular morbidity and mortality, and so aggressive intervention to reduce cardiovascular risk factors is indicated.
Annual screening for microalbuminuia is recommended. Interventions at the stage of microalbuminuria effectively delay the progression to overt nephropathy and renal failure.21 These include:
1. strict glycemic control.
2. control of hypertension.
3. use of angiotensin converting enzyme inhibitors (ACEI).
4. restriction of protein intake to 0.8 g/kg/d with the onset of overt nephropathy.
5. referral to nephrologist when GFR is less than 70 mL/min or serum creatinine is greater than 2 mg /dL.
Diabetic Foot Care
Unperceived, excessive, and repetitive pressure on plantar bony surfaces due to the presence of sensory neuropathy predisposes to neuropathic foot ulcers and joint destruction (Charcot's joint). (See Figure 2.) History of previous ulcers or infections further increase the risk of ulcer development and progression to lower extremity amputation. Once amputation of one limb has occurred, the prognosis for the contralateral limb is poor. Appropriate screening and intervention can prevent diabetic foot ulcers.21,30
A simple method to test the presence of sensory neuropathy is the use of a 10 g nylon monofilament. This is pressed against the skin to the point of buckling. Patients who cannot feel the monofilament are at risk for ulceration and require special care that entails education in lifelong foot care, therapeutic footwear, and periodic callus and nail care.30 Annual screening using the sensory monofilament for loss of protective sensation is recommended. (See Table 8.)
Diabetic Neuropathy
Table 9 shows the treatment of symptoms of diabetic neuropathy.
Table 9. Treatment of Symptoms of Diabetic Neuropathy29
|
Symptom |
Therapy |
|
Dysesthesias |
Topical capsaicin, or bedtime amitriptyline; start at 25mg; maximum up to 200mg; If orthostatic hypotension present, use nortriptyline, start at 10 mg at night. |
|
Diabetic Gastroparesis |
Erythromycin 750 mg/d is the least expensive; if ineffective us metoclopramide 30mg/d or cisapride 10mg qid |
|
Diabetic diarrhea |
Tetracycline 200-500mg at the beginning of attack; if ineffective, use diphenoxilate 2.5 mg with atropine 0.025 mg (Lomotil) 2 tabs or 10mL liquid |
|
Orthostatic Hypotension |
Increase salt intake, wear elastic tights, sleep with head of bed elevated; if ineffective, add fludrocortisone, 0.1-0.2 mg once daily |
Summary
Diabetes is a common, chronic disease that is serious, treatable, and undertreated. Primary care providers treat the large majority ( 90%) of type 2 diabetics. With the new diagnostic criteria, an effort should be made to identify all diabetics who would benefit from early treatment to prevent debilitating complications. Understanding the pathophysiology provides a rational basis for the efficient control of blood sugar using the various oral hypoglycemics that are currently available. (See Figure 3 for an algorithm of diabetes in perspective.) Tight control of blood glucose is paramount. Early detection of complications should prompt interventions that prevent their progression to blindness, renal failure, or amputations. Cardiac disease is the major cause of death in type 2 diabetes; aggressive cardiovascular risk factor modification is mandatory. Finally a team-oriented approach to management is beneficial, and the most critical member of the team is the patient.
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