clinical correlation type-ii diabetes
TRANSCRIPT
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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
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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
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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
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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
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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
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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
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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
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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
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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)
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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%
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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)
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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
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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
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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
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Acanthosis Nigricans
• Occurs in skin fold areas, especially neck and arm pits
• Associated with hyperinsulinemia
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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)
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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)
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Risk Factors for Premature Atherosclerotic Heart Disease
• Dyslipidemia (high LDL, low HDL)
• Diabetes
• Hypertension
• Obesity
• Sedentary lifestyle
• Smoking
• Male sex
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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)
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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)
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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
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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
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Syndrome X
• Metabolic syndrome associated with greatly increased risk for premature cardiovascular disease
• Syndrome– Obesity– Hypertension– Insulin resistance– Dyslipidemia
• Increased triglycerides• Low HDL cholesterol
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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
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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
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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.
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Complications of Diabetes
• Retinopathy
• Nephropathy
• Neuropathy
• Atherosclerosis
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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
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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.
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Beneficial Effects of Exercise in Type II Diabetes
exercise
increased glucoseutilization
increased insulinsensitivity
decreased counter-regulatory hormones
decreased hepaticgluconeogenesis
improved bloodglucose control