Clinical correlation type-ii diabetes
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This document describes a case involving a 15-year-old male referred for evaluation of obesity and high cholesterol detected on screening. On examination, he was found to have a BMI over the 95th percentile, high blood pressure, skin changes, and laboratory tests showed prediabetes, high triglycerides, and low HDL cholesterol. Based on his medical history, physical exam, and lab results, he meets criteria for metabolic syndrome and is at high risk for cardiovascular disease. Lifestyle modifications including a healthier diet, increased physical activity, and weight loss are recommended to improve his condition and reduce risks.
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Clinical correlation type-ii diabetes
- 1. Case #1 • 15 yo white male • Referred for evaluation and treatment of obesity and hyperlipidemia detected on routine screening • Otherwise healthy • Past medical history is unremarkable • No current medications
- 2. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1991 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1991BRFSS, 1991 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 3. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1992 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1992BRFSS, 1992 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 4. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1993 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1993BRFSS, 1993 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 5. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1994 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1994BRFSS, 1994 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 6. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1995 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1995BRFSS, 1995 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 7. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1996 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1996BRFSS, 1996 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 8. Prevalence of Obesity* Am ong U.S. Adult s BRFSS, 1997 Prevalence of Obesity* Am ong U.S. Adult sPrevalence of Obesity* Am ong U.S. Adult s BRFSS, 1997BRFSS, 1997 (*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight) <10% 10% to 15% >15% N/A
- 9. Trend in Overweight Prevalence for Youths 6- 17 yrs 0 5 10 15 NHES II/III, 1963- 70 NHANES I, 1971-74 NHANES II, 1976-1980 NHANES III, 1988-94 Troiano et. al (Pediatrics 1998)
- 10. Case #1 • Activity – Watching TV, playing video games • Diet – Frequent high-fat fast foods, high-sugar snacks – Skips breakfast • Analysis of 3-day food diary – Average 3360 kcal/day – Diet composition (% of total calories) • Protein 18% • Fat 36% • Carbohydrate 46%
- 11. Effect of Television Watching on US Children: 8-16 years old 20 25 30 < 2 2 to 3 4 and up Hours of TV per Day SumofTrunk Skinfolds,mm boys girls Andersen et. al. (JAMA 1998)
- 12. Case #1 53 yo diabetes MI 62 yo hypertension stroke 72 yo hypertension 69 yo healthy 39 yo obese hypertension CH 236 TG 499 HDL 28 38 yo obese CH 204 TG 204 HDL 42 48 yo stroke 9 yo healthy CH ? 12 yo obese CH 210 TG 201 HDL 38 15 yo obese Hypertension Type II diabetes CH 226 TG 320 HDL 30
- 13. Case #1 • Social – Freshman in high school. Described as “average” student. – Smokes 2-3 cigarettes/day – Denies alcohol/substance abuse – Mother accompanies patient to clinic. Parents are separated. Lives with mother, who works two jobs. – Has few friends
- 14. Case #1 • Physical exam – BP 142/90 right arm sitting (normal 135/85) – Ht 178 cm (90th percentile) – Wt 96 kg (> 95th percentile) – BMI (wt/ht2 ) 30.3 (> 95th percentile) – Hyperpigmented, rough plaques on neck, groin, inner thigh (acanthosis nigricans) – Mild hepatomegaly
- 15. Acanthosis Nigricans • Occurs in skin fold areas, especially neck and arm pits • Associated with hyperinsulinemia
- 16. Case #1 • Fasting serum lipid profile – Total cholesterol 220 mg/dl, repeat 226 mg/dl (normal < 200 mg/dL) – Triglycerides 320 mg/dL (normal < 200 mg/dL) – HDL cholesterol 30 mg/dL (normal > 35 mg/dL) – LDL cholesterol 131 mg/dl (normal < 130 mg/dL)
- 17. Case #1 • Other lab – Normal thyroid profile – 8 AM serum cortisol 19 µg/dL (normal 5-23 µg/dL) – Fasting glucose 190 mg/dL (diabetic >115 mg/dL) – Glucose tolerance test • 60 min 223 mg/dL (diabetic > 200 mg/dL) • 90 min 233 mg/dL (diabetic > 200 mg/dL) • 120 min 188 mg/dL (diabetic > 140 mg/dL) – Fasting insulin 48 mU/L (normal 7-24 mU/L) – Serum/urine ketones negative – Serum transaminases • ALT 119 U/L (normal 5-45 U/L) • AST 98 U/L (normal 5-45 U/L)
- 18. Risk Factors for Premature Atherosclerotic Heart Disease • Dyslipidemia (high LDL, low HDL) • Diabetes • Hypertension • Obesity • Sedentary lifestyle • Smoking • Male sex
- 19. Coronary Heart Disease 0 10 20 30 40 50 60 Estimated10Year Rate(%) men women BP Systolic Cholesterol HDL-C Diabetes Cigarettes LHV by ECG 120 220 50 - - - 160 220 50 - - - 160 260 50 - - - 160 260 35 - - - 160 260 35 + - - 160 260 35 + + - 160 260 35 + + + Wilson, AmJHypertens, 1994)
- 20. Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and Young Adults 0 2 4 6 8 Intimal-SurfaceInvolvement (%) Aorta Coronary Arteries Number of Risk Factors 0 01 12 2 3 3 Berenson et. al (NEJM 1998)
- 21. Obesity and Inflammation • N-HANES III • 3512 kids (age 8-16) • Kids with elevated CRP (>.22mg/dL) or WBC > 10,000 • Overweight (>85%) vs < 85% • Odds Ratio (OR) of 3.7 (M) and 3.1 for correlation of CRP with overweight • Also elevated risk for WBC M Visser et al Pediatrics e13, January 2001
- 22. 68.7 - 62.5 % (8) 62.3 - 52.7 % (8) 51.2 - 41.9 % (8) 38.9 - 0.8 % (8) % of High School Students Not Enrolled in Physical Education Class, 1997 8 Data missing From 1997 Youth Risk Behavior Survey
- 23. Syndrome X • Metabolic syndrome associated with greatly increased risk for premature cardiovascular disease • Syndrome – Obesity – Hypertension – Insulin resistance – Dyslipidemia • Increased triglycerides • Low HDL cholesterol
- 24. Insulin Resistance • Associated with Type II diabetes • Closely linked with obesity (direction?) • Decreased insulin-stimulated glucose transport and metabolism in adipocytes and skeletal muscle • Impaired suppression of hepatic glucose output • Tissue specific signaling abnormalities • “Dose” of body fat affects resistance, especially central fat
- 26. Complications of Obesity • Cardiovascular-hypertension, heart disease • Insulin resistance/Type II diabetes mellitus • Hyperlipidemia • Growth-advanced bone age, increased height, early menarche • Psychosocial • Hepatobiliary-non-alcoholic steatohepatitis, cholelithiasis • Pulmonary-sleep apnea, Pickwickian syndrome • Orthopedic-slipped capital femoral epiphysis, Blount disease • Cancer-endometrial, breast, prostate, colon • CNS-pseudotumor cerebri
- 27. Obesity and Diabetes Risk 0 20 40 60 80 100 <20 20-25 25-30 30-35 35-40 >40 Body Mass Index Knowler WC, et al. Am J Epidemiol. 1981;113:144-156.
- 28. Complications of Diabetes • Retinopathy • Nephropathy • Neuropathy • Atherosclerosis
- 29. Non-Alcoholic Steatohepatitis (NASH) • Associated with obesity and insulin resistance • Presents with hepatomegaly and mild serum transaminase elevation • Lipid accumulation within hepatocytes with inflammation and fibrosis/cirrhosis • Pathogenesis: “two hit” hypothesis – 1st hit: triglyceride accumulation – 2nd hit: generation of reactive oxygen species and lipid peroxidation
- 30. Goals for Therapy for Type II Diabetes • Focus on glucose and lipid goals – Modify fat intake – Improve food choices – Space meals throughout the day • If obese, reduce calories for moderate weight loss • Increase physical activity • Monitor blood glucose, glycohemoglobin, lipids, blood pressure • Add diabetes medication, if needed American Diabetes Assoc.
- 31. Beneficial Effects of Exercise in Type II Diabetes exercise increased glucose utilization increased insulin sensitivity decreased counter- regulatory hormones decreased hepatic gluconeogenesis improved blood glucose control
Editor's Notes
- Obesity has become an epidemic in both adults and children in the U.S. and represents a major public health problem. Primary care physicians will be seeing more children and adolescents with obesity. Obesity is frequently associated with dyslipidemia.
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- A sedentary lifestyle contributes to the development of obesity, as well as representing an independent risk factor for premature cardiovascular disease. Fast foods and snacks usually represent a source of excess calories contributing to weight gain. The average daily caloric intake is excessive for this patient. A more reasonable intake would be 2000 kcal/day with increased regular physical activity. The composition of the diet should be changed to decrease total calories from fat to 30% with no more than 10% of total calories from saturated fat.
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- Note the positive family history for dyslipidemia, obesity, hypertension, diabetes, and premature (&lt; 55 yoa) stroke and myocardial infarction. Type II diabetes has a particularly strong familial incidence. It is imperative that the patient’s 12 yo sister receive attention as soon as possible. The 9 yo sister should have her lipids checked and be monitored closely for the development of obesity, hypertension and diabetes.
- Note that this adolescent is a smoker, which represents a significant cardiovascular risk. He denies alcohol and substance abuse. However, ethanol ingestion can cause/contribute to the patient’s abnormal lipid profile and elevated serum transaminases. His home situation is probably not conducive to a healthy lifestyle. Obese adolescents are frequently social outcasts because of their appearance. This frequently contributes to depression, which makes treatment of obesity extremely difficult.
- Note that the patient is hypertensive and obese with a body mass index (BMI) greater than the 95th percentile for age. The acanthosis nigricans is associated with obesity and insulin resistance. The hepatomegaly is probably indicative of non-alcoholic steatohepatitis.
- Acanthosis nigricans is a frequent finding in children and adolescents with obesity and insulin resistance.
- The total and LDL cholesterol are mildly elevated. However, there is a significant elevation of the triglycerides and depression of the HDL cholesterol. This profile is common in obese individuals, particularly in the setting of insulin resistance and diabetes. The elevated triglycerides may have only a modest effect on the development of premature atherosclerosis, but the low HDL cholesterol level is a significant risk factor. Note that the LDL cholesterol may be calculated by the Friedewald equation: LDL cholesterol = total cholesterol - HDL cholesterol - triglycerides/5. The equation is not valid if the triglyceride level is greater than 400 mg/dL.
- The normal thyroid profile and cortisol level rule out hypothyroidism and Cushing’s disease, respectively, as causes of obesity in this patient. The high fasting glucose level, as well as the abnormal glucose tolerance test, make the diagnosis of diabetes. The high fasting insulin level and lack of ketones indicate type II diabetes. Type II diabetes is associated with defects in both insulin secretion and insulin action. Plasma insulin levels may be normal, decreased or increased. Levels are usually elevated early and become decreased late in the course of the disease. However, insulin levels are inadequate to overcome the patient’s coexisting insulin resistance and, as a result, hyperglycemia results. Although individuals with type II diabetes do not require insulin for survival and do not develop ketoacidosis as seen in type I diabetes, approximately 40-50% will require exogenous insulin for adequate blood glucose control and to prevent complications as the disease progresses. The elevated transaminases, as well as the previously noted hepatomegaly, suggest non-alcoholic steatohepatitis, which is associated with obesity and insulin-resistance.
- Note that this patient has all of these risk factors for premature atherosclerotic heart disease.
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- The patient has all of the criteria for Syndrome X, which is associated with a strikingly increased risk of premature cardiovascular disease.
- Adequate long-term control of blood glucose levels can prevent these complications of diabetes.
- This patient most likely has NASH, since he has hepatomegaly and elevated serum transaminase levels in the setting of obesity and insulin resistance.
- This patient should reduce his total daily caloric intake to achieve a gradual weight loss. Weight reduction may dramatically impact on insulin resistance and blood glucose control. Rapid weight loss is not desirable, and usually results in prompt regaining of weight. Intake of high caloric density fast and snack foods should be reduced or eliminated. He should eat breakfast, as well as regular meals, every day to improve control of his blood sugar and appetite. He should reduce his total fat intake to no more than 30% of total calories, reduce saturated fats to no more than 10% of total calories, and ingest no more than 300 mg of cholesterol per day. Increased dietary fiber intake will help with control of blood sugar and improve the lipid profile.
- Regular exercise has beneficial metabolic effects in the patient with type II diabetes. The patient should be advised to undertake 30 minutes of vigorous aerobic exercise 5 times per week. He should also be discouraged from spending so much time watching TV and playing computer games. Swimming, if available, is a good form of exercise for the obese patient. Walking or bike riding should also be encouraged.