NUTR 521

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NUTR 521 Lipids and Diabetes 1. CHD Risk in
Type I and II diabetes 2. Lipid profile
alterations in Type I and II diabetes 3.
Details about diabetic dyslipidemia 4.
Angptl3 - a new mediator of dyslipidemia
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Risk of CHD in Type I and II diabetes
US prevalence of diabetes 3 (8,000,000 people),
90 with NIDDM 75 of people with diabetes die
from CHD or stroke Type 1 and type 2 diabetes
are associated with a two- to fourfold increased
risk of CHD There is a higher 1-year mortality
rate following a first MI
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Survival Post-MI in Diabetic and Nondiabetic Men
and Women Minnesota Heart Survey
WOMEN
MEN
100 80 60 40 0
100 80 60 40 0
No diabetes
No diabetes
n1628
n568
Diabetes
Survival ()
Survival ()
Diabetes
n228
n156
0
20
40
60
80
0
20
40
60
80
Months Post-MI
Months Post-MI
Adapted from Sprafka JM et al. Diabetes Care
199114537-543.
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Risk of CHD in Type I and II diabetes
Middle-aged people with diabetes have the
equivalent risk of MI as non-diabetic people who
have already had an MI
Haffner et al, NEJM 339(4)229-234, 1998
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Risk of CHD in Type I and II diabetes
In women with diabetes, death from CHD has
increased 23 over the past 30 years
(non-diabetic women, 27 decrease) In men with
diabetes, death from CHD decreased 13 over past
30 years (non-diabetic men, 36 decrease) 97 of
adults with type II diabetes have one or more
lipid abnormalities Treatment of lipid disorders
reduces CHD risk
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Study n LDL lowering () CHD risk () 1
prevention Helsinki Heart (92) 135 -6.1 -61
(NS) 2 prevention CARE (96) 586 -28 -25
(p0.05) 4S (97) 202 -37 -55 (p0.002)
Adapted Table 2, from Haffner, Diab Care 21160,
1998
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Scandinavian Simvastatin Survival Study Trials
Ginsberg Illingworth, Am J Cardiol 889H, 2001
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Cholesterol and Recurrent Events Trial
Ginsberg Illingworth, Am J Cardiol 889H, 2001
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Diabetes Control and Complications Trial
DCCT, Am J Cardiol 75894, 1995
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Dullaart, Netherlands J Med 4644, 1995
Ginsberg Illingworth, Am J Cardiol 889H, 2001
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Diabetic Dyslipidemia Type I Diabetes Increased
Decreased VLDL HDL TG Type II
Diabetes Increased Decreased Apo B Apo
AI VLDL HDL TG Small, Dense LDL
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Why? Postprandial lipemia Increased VLDL
production Altered lipoprotein
composition (small dense LDL) Altered HDL
metabolism
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Chylomicron transport metabolism in
non-diabetic state
Ginsberg Diab Care 14839, 1991
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Chylomicron transport metabolism in diabetic
state (type I or type II diabetes)
Ginsberg Diab Care 14839, 1991
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Goldberg, J Clin Endo Metab 86965, 2001
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Goldberg, J Clin Endo Metab 86965, 2001
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Endogenous lipid transport metabolism in
non-diabetic state
Ginsberg Diab Care 14839, 1991
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Type I Diabetes
HSL
Ginsberg Diab Care 14839, 1991
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Type I Diabetes
Dullaart, Netherlands J Med 4644, 1995
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Type II Diabetes
HSL
Ginsberg Diab Care 14839, 1991
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Adeli et al, Trends Cardiovasc Med 11170, 2001
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Goldberg, J Clin Endo Metab 86965, 2001
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Goldberg, J Clin Endo Metab 86965, 2001
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Reverse cholesterol transport in non-diabetic
state
Quintao et al, Diab Metab Res Rev 16237, 2000
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Reverse cholesterol transport in diabetic state
Quintao et al, Diab Metab Res Rev 16237, 2000
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Diabetic Dyslipidemia
Increased TG - increased VLDL production increas
ed FFA, apoB and MTP availability Small,
diminished LPL activity dense LDL - altered
removal via LDLR increased CETP
activity increased HL activity Low HDLc -
increased CETP activity decreased HDL due to
diminished LPL activity enhanced removal
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A mouse model of obesity, diabetes diabetic
dyslipidemia
Koishi et al, Nat Gen 30151, 2002
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Chylomicron
LDL
VLDL
HDL
Koishi et al, Nat Gen 30151, 2002
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Mode of inheritance autosomal recessive
Angiopoeitin-like protein 3 (Angptl3)
Koishi et al, Nat Gen 30151, 2002
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KK/san
C57BL/6
Koishi et al, Nat Gen 30151, 2002
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KK/san
C57BL/6
Koishi et al, Nat Gen 30151, 2002
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KK/san
C57BL/6
Koishi et al, Nat Gen 30151, 2002
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Koishi et al, Nat Gen 30151, 2002
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Rossetti Goldberg, Nat Med 8112, 2002