clinical correlation type-ii diabetes

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

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

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1992Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1992BRFSS, 1992

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1993Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1993BRFSS, 1993

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1994Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1994BRFSS, 1994

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1995Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1995BRFSS, 1995

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1996Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1996BRFSS, 1996

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

Prevalence of Obesity* Among U.S. AdultsBRFSS, 1997Prevalence of Obesity* Among U.S. AdultsPrevalence of Obesity* Among U.S. AdultsBRFSS, 1997BRFSS, 1997

(*Approximately 30 pounds overweight)(*Approximately 30 pounds overweight)

<10% 10% to 15% >15% N/A

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)

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%

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

Su

m o

f T

run

k S

kin

fold

s, m

m

boys girls

Andersen et. al. (JAMA 1998)

Case #153 yo

diabetesMI

62 yo hypertension

stroke

72 yohypertension

69 yo healthy

39 yoobese

hypertensionCH 236TG 499HDL 28

38 yoobese

CH 204TG 204HDL 42

48 yostroke

9 yohealthyCH ?

12 yoobese

CH 210TG 201HDL 38

15 yoobese

HypertensionType IIdiabetesCH 226TG 320HDL 30

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

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

Acanthosis Nigricans

• Occurs in skin fold areas, especially neck and arm pits

• Associated with hyperinsulinemia

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)

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)

Risk Factors for Premature Atherosclerotic Heart Disease

• Dyslipidemia (high LDL, low HDL)

• Diabetes

• Hypertension

• Obesity

• Sedentary lifestyle

• Smoking

• Male sex

Coronary Heart Disease

010

2030

4050

60E

sti

ma

ted

10

Ye

ar

Ra

te (

%)

men

women

BP SystolicCholesterolHDL-CDiabetesCigarettesLHV by ECG

12022050---

16022050---

16026050---

16026035---

16026035+--

16026035++-

16026035+++

Wilson, AmJHypertens, 1994)

Effect of Multiple Risk Factors on Atherosclerosis in the Aorta and Coronary Arteries in Children and

Young Adults

0

2

4

6

8In

tim

al-

Su

rfa

ce

In

vo

lve

me

nt

(%)

Aorta Coronary Arteries

Number of Risk Factors

0 01 12

23

3

Berenson et. al (NEJM 1998)

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

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

8Data missing

From 1997 Youth Risk Behavior Survey

Syndrome X

• Metabolic syndrome associated with greatly increased risk for premature cardiovascular disease

• Syndrome– Obesity– Hypertension– Insulin resistance– Dyslipidemia

• Increased triglycerides• Low HDL cholesterol

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

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

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.

Complications of Diabetes

• Retinopathy

• Nephropathy

• Neuropathy

• Atherosclerosis

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

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.

Beneficial Effects of Exercise in Type II Diabetes

exercise

increased glucoseutilization

increased insulinsensitivity

decreased counter-regulatory hormones

decreased hepaticgluconeogenesis

improved bloodglucose control