clinical correlation- type-ii diabetes

Case #115 yo white maleReferred for evaluation and treatment of obesity and hyperlipidemia detected on routine screeningOtherwise healthyPast medical history is unremarkableNo current medications

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1991

(*Approximately 30 pounds overweight)

Let's use this first slide to acquaint you with the scenario. This is data on people who are 30 pounds overweight. The colors of the states tell us what percentage of their adults fit this category. White shows no data available and some states come and go depending on participation. Light blue is less that 10%, medium blue is 10-15% and dark blue is over 15% of the population. Remember that the Healthy People 2010 objective is to have 15% or Less of the population obese.

Trend in Overweight Prevalence for Youths 6-17 yrsTroiano et. al (Pediatrics 1998)

Chart2

5

5.5

6

12

Sheet1

% of high school students eating 5 a day

1Arkansas

1Mississippi

1South Carolina

1Alabama

1Tennessee

1Missouri

1West Virginia

2nevada

2South Dakota

2Montana

2nebraska

2ohio

2utah

2idaho

2wyoming

3georgia

3ILLINOIS

3rhode island

3district of columbia

3colorado

3michigan

3california

4delaware

4new jersey

4alaska

4MAINE

4hawaii

4new hampshire

trend in overwight prevalence in youths 6-17

5NHES II/III, 1963-705

5.5NHANES I, 1971-745.5

6NHANES II, 1976-19806

12NHANES III, 1988-9412

Sheet1

0

0

0

0

Sheet2

Sheet3

MBD000A4331.unknown

Case #1ActivityWatching TV, playing video gamesDietFrequent high-fat fast foods, high-sugar snacksSkips breakfastAnalysis of 3-day food diaryAverage 3360 kcal/dayDiet composition (% of total calories)Protein 18%Fat 36%Carbohydrate 46%

Effect of Television Watching on US Children: 8-16 years oldAndersen et. al. (JAMA 1998)

Chart3

21.725.9

23.927.4

2529.3

boys

girls

Hours of TV per Day

Sum of Trunk Skinfolds, mm

Sheet1


1Arkansas

1Mississippi

1South Carolina

1Alabama

1Tennessee

1Missouri

1West Virginia

2nevada

2South Dakota

2Montana

2nebraska

2ohio

2utah

2idaho

2wyoming

3georgia

3ILLINOIS

3rhode island


3colorado

3michigan

3california

4delaware

4new jersey

4alaska

4MAINE

4hawaii

4new hampshire



5.5NHANES I, 1971-745.5

6NHANES II, 1976-19806

12NHANES III, 1988-9412

Fibrous Plaques

10.51

10.71

111

11.81

22

20.82

21.12

22.752

7.3

TV and BMI

boysgirls

< 221.725.9

2 to 323.927.4

4 and up2529.3

2

3

3

Sheet1

5

5.5

6

12

Sheet2

Sheet3

boys

girls

Hours of TV per Day


MBD000A4331.unknown

Case #1

Case #1SocialFreshman in high school. Described as average student.Smokes 2-3 cigarettes/dayDenies alcohol/substance abuseMother accompanies patient to clinic. Parents are separated. Lives with mother, who works two jobs.Has few friends

Case #1Physical examBP 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

Acanthosis NigricansOccurs in skin fold areas, especially neck and arm pitsAssociated with hyperinsulinemia

Case #1Fasting serum lipid profileTotal 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)

Case #1Other labNormal thyroid profile8 AM serum cortisol 19 g/dL (normal 5-23 g/dL) Fasting glucose 190 mg/dL (diabetic >115 mg/dL)Glucose tolerance test60 min223 mg/dL (diabetic > 200 mg/dL)90 min233 mg/dL (diabetic > 200 mg/dL)120 min188 mg/dL (diabetic > 140 mg/dL)Fasting insulin 48 mU/L (normal 7-24 mU/L)Serum/urine ketones negativeSerum transaminasesALT 119 U/L (normal 5-45 U/L)AST98 U/L (normal 5-45 U/L)

Risk Factors for Premature Atherosclerotic Heart DiseaseDyslipidemia (high LDL, low HDL)DiabetesHypertensionObesitySedentary lifestyleSmokingMale sex

Coronary Heart DiseaseWilson, AmJHypertens, 1994)

Chart3

8.75.5

13.79.2

16.511.3

23.417

28.827.7

3836.8

57.556.4

men

women

Estimated 10 Year Rate (%)

Sheet1


1Arkansas

1Mississippi

1South Carolina

1Alabama

1Tennessee

1Missouri

1West Virginia

2nevada

2South Dakota

2Montana

2nebraska

2ohio

2utah

2idaho

2wyoming

3georgia

3ILLINOIS

3rhode island


3colorado

3michigan

3california

4delaware

4new jersey

4alaska

4MAINE

4hawaii

4new hampshire



5.5NHANES I, 1971-745.5

6NHANES II, 1976-19806

12NHANES III, 1988-9412

Fibrous Plaques

10.51

10.71

111

11.81

22

20.82

21.12

22.752

7.3

TV and BMI

boysgirls140

< 221.725.91057

2 to 323.927.4240

4 and up2529.3

2

3

3

Coronary Heart Disease

menwomen

8.75.5

13.79.2

16.511.3

23.417

28.827.7

3836.8

57.556.4

Sheet1

5

5.5

6

12

Sheet2

0

0

0

0

0

0

0

0

0

Sheet3

boys

girls

Hours of TV per Day


men

women

Estimated 10 Year Rate (%)

MBD000A4331.unknown

Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and Young AdultsAortaCoronary Arteries Number of Risk Factors00112233Berenson et. al (NEJM 1998)

Chart1

0.5

0.7

1

1.8

0.8

1.1

2.75

7.3

Intimal-Surface Involvement (%)

Sheet1


1Arkansas

1Mississippi

1South Carolina

1Alabama

1Tennessee

1Missouri

1West Virginia

2nevada

2South Dakota

2Montana

2nebraska

2ohio

2utah

2idaho

2wyoming

3georgia

3ILLINOIS

3rhode island


3colorado

3michigan

3california

4delaware

4new jersey

4alaska

4MAINE

4hawaii

4new hampshire



5.5NHANES I, 1971-745.5

6NHANES II, 1976-19806

12NHANES III, 1988-9412

Fibrous Plaques

10.51

10.71

111

11.81

22

20.82

21.12

22.752

7.3

Sheet1

5

5.5

6

12

Sheet2

0

0

0

0

0

0

0

0

0

Sheet3

MBD000A4331.unknown

Obesity and InflammationN-HANES III3512 kids (age 8-16)Kids with elevated CRP (>.22mg/dL) or WBC > 10,000Overweight (>85%) vs < 85%Odds Ratio (OR) of 3.7 (M) and 3.1 for correlation of CRP with overweightAlso elevated risk for WBCM Visser et al Pediatrics e13, January 2001

% of High School Students Not Enrolled in Physical Education Class, 19978Data missingFrom 1997 Youth Risk Behavior Survey

Syndrome XMetabolic syndrome associated with greatly increased risk for premature cardiovascular diseaseSyndromeObesityHypertensionInsulin resistanceDyslipidemiaIncreased triglyceridesLow HDL cholesterol

Insulin ResistanceAssociated with Type II diabetesClosely linked with obesity (direction?)Decreased insulin-stimulated glucose transport and metabolism in adipocytes and skeletal muscleImpaired suppression of hepatic glucose outputTissue specific signaling abnormalitiesDose of body fat affects resistance, especially central fat

Complications of ObesityCardiovascular-hypertension, heart diseaseInsulin resistance/Type II diabetes mellitusHyperlipidemiaGrowth-advanced bone age, increased height, early menarche PsychosocialHepatobiliary-non-alcoholic steatohepatitis, cholelithiasisPulmonary-sleep apnea, Pickwickian syndromeOrthopedic-slipped capital femoral epiphysis, Blount diseaseCancer-endometrial, breast, prostate, colonCNS-pseudotumor cerebri

Obesity and Diabetes Risk

Knowler WC, et al. Am J Epidemiol. 1981;113:144-156.

Complications of DiabetesRetinopathyNephropathyNeuropathyAtherosclerosis

Non-Alcoholic Steatohepatitis(NASH)Associated with obesity and insulin resistancePresents with hepatomegaly and mild serum transaminase elevationLipid accumulation within hepatocytes with inflammation and fibrosis/cirrhosisPathogenesis: two hit hypothesis1st hit: triglyceride accumulation2nd hit: generation of reactive oxygen species and lipid peroxidation

Goals for Therapy for Type II DiabetesFocus on glucose and lipid goalsModify fat intakeImprove food choicesSpace meals throughout the dayIf obese, reduce calories for moderate weight lossIncrease physical activityMonitor blood glucose, glycohemoglobin, lipids, blood pressureAdd diabetes medication, if neededAmerican Diabetes Assoc.

Beneficial Effects of Exercise in Type II Diabetesexerciseincreased glucoseutilizationincreased insulinsensitivitydecreased counter-regulatory hormonesdecreased hepaticgluconeogenesisimproved bloodglucose control

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. 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.Note the positive family history for dyslipidemia, obesity, hypertension, diabetes, and premature (< 55 yoa) stroke and myocardial infarction. Type II diabetes has a particularly strong familial incidence. It is imperative that the patients 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 patients 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 Cushings 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 patients 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.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.

clinical correlation- type-ii diabetes

Documents