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Diabetes Guidelines Kevin H McKinney MD University of Texas Medical Branch at Galveston Division of Endocrinology/Stark Diabetes Center DIABETES MELLITUS •Inability of the body to metabolize blood sugar •A disease of inadequate insulin secretion and action •Hyperglycemia is the main manifestation COMPLICATIONS Chronic hyperglycemia may cause: –retinal damage –chronic kidney disease –nerve damage –vascular disease COMPLICATIONS (cont.) •Blindness •Dialysis •Lower Limb Amputation •Stroke •Myocardial infarction •Claudication PRIMARY CLASSES OF DIABETES MELLITUS •Type 1 –Autoimmune destruction of islets –No insulin secretion •Type 2 Diabetes –Insulin resistance with progressive insulin secretory defect –90% are obese PREVALENCE OF TYPE 1 DIABETES IN THE US • 1 million people • Caucasians constitute the majority of type 1 diabetics • Most prominent during childhood PREVALENCE OF TYPE 2 DIABETES IN THE US • Most common type of diabetes among all ethnic groups • 17 million patients with known diabetes • 45% of children and teens with new diagnoses PREVALENCE OF TYPE 2 DIABETES IN THE US • Caucasian women experience higher prevalence rates than men (57% vs. 26%) • By age 70, African American prevalence rates increase to 42% of the population METABOLIC SYNDROME • • • • • • Insulin resistance (type 2 diabetes) Hypertension Dyslipidemia Polycystic ovary syndrome Hyperuricemia Hypercoagulability PREVALENCE OF METABOLIC SYNDROME IN THE US •Third NHANES Study (Prevalence Rates) –21.6% African American Adults –31.9% Mexican American Adults –23.8% Caucasian Adults OBESITY—A PUBLIC HEALTH PROBLEM Rise in metabolic syndrome is related to increasing prevalence of obesity Multifactorial causes for obesity including – A sedentary lifestyle – Decline in exercise – Increased access to unhealthy foods – Greater food portions GESTATIONAL DIABETES • Occurs after the onset of pregnancy • Is secondary to the production of human placental lactogen and other hormones needed to sustain pregnancy • Most common in people of color GESTATIONAL DIABETES •If untreated, may result in fetal macrosomia •Fetal macrosomia may lead to –Cesarean section –Shoulder dystocia –Fetal hypoglycemia •High risk women should be screened at first prenatal visit •Low-risk women should be screened from 24 to 28 weeks of gestation Hospitalization Costs for Chronic Complications of Diabetes in the US Ophthalmic Others disease Renal disease Neurologic disease Total costs Peripheral 12 billion vascular US $ disease Cardiovascular disease CVD accounts for 64% of total costs American Diabetes Association. Economic Consequences of Diabetes Mellitus in the US in 1997. Alexandria, VA: American Diabetes Association, 1998:1-14. DISPARITIES IN DIABETES COMPLICATIONS IN AFRICAN AMERICANS • Contributing factors –Average delay in diagnosis of 4-7 years –Longer duration of poorly controlled type 2 diabetes –Development of equally devastating complications MICROVASCULAR COMPLICATIONS OF DIABETES •Diabetic retinopathy –46% higher in African Americans and 86% higher in Mexican Americans than in Caucasians •Diabetic Nephropathy –African Americans, Latinos, and Native Americans have 3-4 times higher rates of renal failure than Caucasians DIABETIC NEUROPATHY •Primary contributor to the loss of limb protection through the diminution or absence of pain and sensory perception. •Diminution or absence of pain and sensory perception leads to limb trauma, open ulcers and polymicrobial foot infections often culminating in gangrene that is treated by limb amputation. •Lower extremity limb amputation is 2-3 times higher in African Americans and Mexican Americans than in Caucasians. MACROVASCULAR RISKS OF DIABETES • Risk of stroke, coronary artery disease, and peripheral vascular disease is increased 2-4 times in all patients with diabetes. • The presence of diabetes is viewed as an independent risk factor for first acute myocardial infarction compared to those with recurrent myocardial infarction without diabetes. MACROVASCULAR RISKS OF DIABETES • The rates for myocardial infarction and stroke among African Americans, Asian Americans and Hispanic Americans are the same or lower than in Caucasians; however, the mortality from CAD is disproportionately high in minorities. • Cardiovascular disease (CVD) remains the leading cause of death in individuals with diabetes, up to 70% of type 2 diabetes patients. RISK REDUCTION OF MACROVASCULAR COMPLICATIONS –Glycemic Control –Smoking Cessation –Blood Pressure Control –Lipoprotein Management –Prothrombotic State Improvement SCREENING GUIDELINES • Adults 45 years of age and older esp with BMI > 25 – Fasting Plasma Glucose at 3 year intervals • Overweight or obese individuals with risk factors for diabetes, African Americans, Latinos – Fasting Plasma Glucose screened at an earlier age and more frequently • Children with BMI > 85th percentile – Screened at age 10 and every 2 years thereafter DIAGNOSTIC CRITERIA • Fasting Plasma Glucose > 126 mg/dL • Casual Blood Sugar > 200 mg/dL or greater as with diabetic symptoms • 2-hour postprandial serum glucose of 200 mg/dL as stimulated by a glucose tolerance test • Test reconfirmation required PRE-DIABETIC STATES • Impaired glucose tolerance (IGT) – 2-hour glucose between 140 and 199 • Impaired fasting glucose (IFG) – Fasting glucose beteween 100 and 125 • Above are risk factors for future diabetes and cardiovascular disease Diabetes Prevention Program Screened 158,177 OGTT, then randomize 3819 randomized Lifestyle 1079 Metformin 1073 3% Wt loss 31% Risk Reduction Placebo 1082 Thiazolidinedione 585 ~10 month followup 5% Wt loss 58 % Risk Reduction Diabetes Rate 11 % per year 23 % Risk Reduction Diabetes Prevention Program Research Gp, NEJM 346(6): 393 -403, 2002. TREATMENT GOALS FOR DIABETES MELLITUS Maintaining: • Pre-meal blood glucose in the range of 90 mg/dL to 130 mg/dL • Bedtime blood glucose in the range of 100 mg/dL to 140 mg/dL • A hemoglobin A1c value from 6.5% to 7% over 3 months Increased A1c Raises Vascular Event Risk 80 Adjusted Incidence per 1000 Patient-Years (%) 60 Microvascular Complications Myocardial Infarction 40 20 0 0 5 6 7 8 9 10 11 Updated Mean A1c (%)* * Updated mean A1c is adjusted for age, sex, and ethnic group, expressed for white men aged 50-54 years at diagnosis and with mean duration of diabetes of 10 years. Stratton IM et al. BMJ. 2000;321:405-412. Established Modifiable Cardiovascular Risk Factors In Type 2 Diabetes UKPDS 23 •Position in Model •First •Second Variable Low-density lipoprotein cholesterol High-density lipoprotein cholesterol P Value* <.0001 .0001 •Third •Fourth •Fifth Hemoglobin A1c Systolic blood pressure Smoking .0022 .0065 .056 * Significant for CAD (n = 280). P values are significance of risk factors after controlling for all other risk factors in model. Adjusted for age and sex in 2693 white patients with type 2 diabetes with dependent variable as time to first event. Turner RC et al. BMJ. 1998;316:823-828. TREATMENT GOALS FOR DIABETES MELLITUS (Cont.) Maintaining: • Blood pressure < 130/80 mm Hg • LDL Cholesterol < 100 mg/dL, triglycerides < 150 mg/dL, and HDL cholesterol > 40 mg/dL in men (> 50 mg/dL in women) • High risk cardiovascular patients should aim for LDL cholesterol < 70 mg/dL MANAGEMENT PLAN • Must be individualized for each individual patient • Diabetes education: initial and subsequent • Lifestyle modifications – Diet (improve your nutrition) – Exercise (increase your activity) • Home blood glucose monitoring – At least once/day for oral medications – Three times daily for insulin users • Medications FOLLOW-UP CARE • Annual eye exam • Physician visits every 3 months, more frequently for poor control – Fundoscopic exam – Foot exam • HbA1c quarterly for poor control, every biannually for good control • Lipogram yearly • Microalbumin yearly Natural History of Type 2 Diabetes Obesity IGT * Diabetes Uncontrolled Hyperglycemia Plasma Glucose 120 (mg/dL) Post-Meal Glucose Fasting Glucose Relative -Cell Function 100 (%) Insulin Resistance Insulin Secretion -20 -10 0 10 20 30 *IGT = impaired glucose tolerance. Years of Diabetes Adapted from International Diabetes Center (IDC), Minneapolis, M innes ota. MEDICAL NUTRITIONAL THERAPY • Must be individualized for each patient – Children must be allowed enough calories for growth, development, and activity – Pregnant women, elderly also deserve special consideration • Permanent low-carbohydrate diets not recommended – “carbohydrate counting” can be done with insulin users MEDICAL NUTRITIONAL THERAPY (cont) • Weight management – One should aim for 500-1000 Calorie reduction in intake per day – 1000-1200 Calories/day for women, 1200-1600 Calories/day for men for weight reduction – Bariatrics? • Activity should consist of 3-5 sessions per week – 30-45 minutes for health – Weight loss: 1 hour of walking, 30 minutes of vigorous exercise ORAL MEDICAL THERAPY • First line: metformin useful except where contraindicated • Sulfonylureas or meglitinides also frequently used • Second line: thiazolidinediones • Used uncommonly: acarbose INSULIN • Traditional regimens – Type 1: Basal insulin (NPH, glargine) with bolus regular or short-acting insulin (lispro, aspart, glulisine) by sliding scale; split-mix regimen; insulin pump – Type 2: split-mix regimen; fixed combination (70/30, 50/50, 75/25); basalbolus • Transitional type 2 insulin regimens: oral agents with bedtime NPH or glargine ADJUNCTS • Cardiovascular – Aspirin • Renal – ACE inhibitor/Angiotensin receptor blocker • Hypertension – Diuretics • Cholesterol – Statins WHEN TO REFER • Poor control for 6 months despite patient adherence and physician manipulation (HbA1c >10%) • Multiple episodes of decompensation (DKA, HONK) • Frequent hypoglycæmic episodes Reference • American Diabetes Association. Diabetes Care 28:S4, 2005 Jan. • American Association of Clinical Endocrinologists. Endocrine Practice 8:S40, 2002 Jan/Feb.
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