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Hypertriglyceridemia predicts small dense LDL and increased IDL-cholesterol levels in NIDDM
244
Wednesday 12 October 1994: Poster Abstracts Diabetes
separately in diabetics (DM, history, drugs or fasting blood glucase >6.7 mmol/l, n = 186) and &ormo$ycemic subjects (I?G, n = 871 ). The proportion of hvoerinsulinemics (FI > 20 mu/l1 rose with age from- 9.9% to 23% in the 65 and’8S-year-olds; respectively. Body mass index (BMI) and serum TG were higher and both HDL-C and LDL-C, as well as objective health score, were lower in DM than NG (P e 0.01). FI correlated positively with TG and HDL-C in both DM and NG, but there was no correlation LDL-C. However, division of FI into quartiles revealed a ‘reverse U’-type association, with a drop in LDL-C with increasing PI. Moreover, the prevalence of hyperinsulinemia in hypercholesterolemic (>6.5 mmol/l) subjects was reduced (relative risk 0.56, 95% CI 0.32-0.99). The lower LDL-C in the hyperinsulinemic subjects can reflect selective mortality, but the results may also imply insulin effects on cholesterol metabolism. Low-dose HMG-CoA reductase inhibitor therapy in gemtibrozil-treated dyslipidemic diabetic patients with CAD Crespin SR, Washington Univ. Sch. of Med., 777 S. New Ballas Rd., St. Louis, MO 631417, USA
(245(
We have previously reported that gemfibrozil therapy in 442 hypertriglyceridemic NIDDM patients resulted in a 26:&Z fall in TG and a 12.2% increase in HDL-C at 20 weeks (Vinik et al Diabetes Care 1993; 16: 374). However, this therapy produced no significant change in LDL-C levels. The objective of this study was to test the hypothesis that small doses (defined as less than 50% of the recommended starting dose) of HMG-CoA reductase inhibitors would lower LDLC to 5 100 mg/dl in CAD-NIDDM on gemtibrozil while simultaneously avoiding significant side effects. Patients with established CAD and NIDDM who had received gemfibrozil for at least 6 months but still had LDL levels 2 130 mg/dl were randomized to either pravastatin, 10 mg daily or simvastatin, 5 mg daily. On this regimen, TC fell 29% and LDL-C fell 36% in both groups. There was no significant difference between 10 mg of pravastatin and 5 mg of simvastatin daily in their effect. HDL-C levels were unchanged in both groups. No significant clinical side effects or any significant biochemical abnormalities, including CPK and transaminases, occurred. In conclusion, small doses of HMG-CoA reductase inhibitors (substantially less than the recommended starting doses) are very effective in NIDDM patients already receiving gemfibrozil. The addition of the HMG-CoA reductase inhibitors lowered LDL-C to less than 100 mg/dl, which meets current ADA and ATPII consensus guidelines. Hypertriglyceridemia predicts small dense LDL and increased IDL-cholesterol levels in NIDDM Duel1 PJ& Div. of Endocrinol., Diabetes, & Nutrition, L465, Ore-
12461
gon Health Sciences Univ., Portland, OR 97201-3098,
USA
Hypertriglyceridemia is a risk factor for atherosclerosis, particularly in patients with non-insulin-dependent diabetes (NIDDM), but the pathophysiologic link between hypertriglyceridemia and atherosclerosis remains obscure. Although triglycerides may not be inherently atherogenic, hypertriglyceridemia in NIDDM is believed to be a marker for other atherogenic dyslipidemic abnormalities. This hypothesis was tested in 46 men id women: 18 with NIDDM. 16 non-diabetic with tvoe IV hvoerlibidemia and 12 normals. L&proteins were analyzii by ro&e &asurements and also by analysis of 30-35 sequential aliquots isolated by vertical ultracentrifugation. Levels of lipoprotein cholesterol (C) and TG were comparably elevated and HDL-C was reduced in NIDDM and type IV. LDL size (indicated by Rf) was smallest in NIDDM.
TC
vc
LC
1 299*240 62i55 138*42 2 268&85 98*92 134*45 3 2011t23 21i9 123*12
HC
TG
LDL Rf
42ztlO 4OilO 62*13
684i821 618i601 135i52
0.237&040.245+0.05 0.33OiO.03
I, NIDDM; 2, Type IV; 3, normal; VC, VLDL-C; LC, LDL-C; HC, HDL-C. TG levels were inversely correlated with the LDL relative flotation (Rf) in subjects with NIDDM (r = -0.55, P < 0.05). but not in type IV subjects (r = -0.004) or normals (r = -0.09). TG levels were directly related to the plasma IDL-C concentration in subjects with NIDDM (r = 0.65, P < 0.02), but not type IV subjects (r = 0.13) or normals (r = 0.07). Body weight was not contributory. Thus, the TG level was predictive of decreased density and size of LDL and increased concentrations of IDLC in subjects with NIDDM. In conclusion, hypertriglyceridemia appears to be a marker for atherogenic lipoprotein abnormalities in subjects with NIDDM. 1247]
HDL subparticles and coronary artery disease in NIDDM Nguyen TT, Hallaway BJ, Hodge D, Bailey K, Kottke
mT. BA, Mayo Clinic, Rochester, MN, USA
Lower HDL-C levels are associated with coronary artery disease (CAD) in NIDDM. HDL particles, however, am heterogeneous and little is known of the relationship between HDL subparticles and CAD in NIDDM. The aim of this study was to compare HDL subparticles with apo A-I (LpA-I) and those with apo A-I and apo A-II (LpA-I/A-II) in subjects with and without NIDDM and to study the relationship between HDL subparticles and CAD in NIDDM. Lipids, apo A-I and HDL subparticles were measured in 240 subjects with NIDDM and 248 age and gender-matched controls. Subjects with NIDDM had increased TG (2.3 + 1.8 vs 1.4 f 0.8 mmol/l, P < O.OOl),and decreased HDL-C (0.9 f 0.3 vs 1.2 + 0.3 mmoyl, P < O.OOl), apo A-I (124.7 f 22.4 vs 139.8 + 24.1 mg/dl, P < 0.001) and LpA-I/A-II (82.4 f 18.2 vs 94.9 + 16.7 mg/dl, P < 0.001). LpA-I levels were similar in both groups. Diabetic subjects with CAD (n = 109) had higher TG (2.7 + 1.9 vs 2.3 & 1.8 mmol/l, P= 0.02) and lower HDL-C (0.8 + 0.2 vs 1.0 + 0.3 mmol/l, P < O.OOl), apo A-I (115.5 f 20.1 vs 132.3 *21.4mg/dl, P
1248]
Boeleln I 117, PO Box 7057, 1007 MB Amsterdam; Dept. of Biothem., Erasmus Univ., Rotterdam, The Netherlands
We wanted to assess the long-term effects of fish oil added to a linoleic acid-enriched diet on CETP and LCAT activity, both measured with excess exogenous substrate, in non-insulin-dependent diabetes (NIDDM) patients. All 16 NIDDM patients (60 f 6 years, 12 M/4 F) consumed a saturated fat-enriched diet (polyunsaturated/saturated (P/S) ratio 0.3) before being randomly allocated to two treatment groups. During the following 4 months one group (n = 9) received fish oil capsules (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid daily) with a linoleic acid-enriched diet (P/S 1.0) while the
Atherosclerosis X, Montreal, October 1994
Wednesday 12 October 1994: Poster Abstracts Diabetes
separately in diabetics (DM, history, drugs or fasting blood glucase >6.7 mmol/l, n = 186) and &ormo$ycemic subjects (I?G, n = 871 ). The proportion of hvoerinsulinemics (FI > 20 mu/l1 rose with age from- 9.9% to 23% in the 65 and’8S-year-olds; respectively. Body mass index (BMI) and serum TG were higher and both HDL-C and LDL-C, as well as objective health score, were lower in DM than NG (P e 0.01). FI correlated positively with TG and HDL-C in both DM and NG, but there was no correlation LDL-C. However, division of FI into quartiles revealed a ‘reverse U’-type association, with a drop in LDL-C with increasing PI. Moreover, the prevalence of hyperinsulinemia in hypercholesterolemic (>6.5 mmol/l) subjects was reduced (relative risk 0.56, 95% CI 0.32-0.99). The lower LDL-C in the hyperinsulinemic subjects can reflect selective mortality, but the results may also imply insulin effects on cholesterol metabolism. Low-dose HMG-CoA reductase inhibitor therapy in gemtibrozil-treated dyslipidemic diabetic patients with CAD Crespin SR, Washington Univ. Sch. of Med., 777 S. New Ballas Rd., St. Louis, MO 631417, USA
(245(
We have previously reported that gemfibrozil therapy in 442 hypertriglyceridemic NIDDM patients resulted in a 26:&Z fall in TG and a 12.2% increase in HDL-C at 20 weeks (Vinik et al Diabetes Care 1993; 16: 374). However, this therapy produced no significant change in LDL-C levels. The objective of this study was to test the hypothesis that small doses (defined as less than 50% of the recommended starting dose) of HMG-CoA reductase inhibitors would lower LDLC to 5 100 mg/dl in CAD-NIDDM on gemtibrozil while simultaneously avoiding significant side effects. Patients with established CAD and NIDDM who had received gemfibrozil for at least 6 months but still had LDL levels 2 130 mg/dl were randomized to either pravastatin, 10 mg daily or simvastatin, 5 mg daily. On this regimen, TC fell 29% and LDL-C fell 36% in both groups. There was no significant difference between 10 mg of pravastatin and 5 mg of simvastatin daily in their effect. HDL-C levels were unchanged in both groups. No significant clinical side effects or any significant biochemical abnormalities, including CPK and transaminases, occurred. In conclusion, small doses of HMG-CoA reductase inhibitors (substantially less than the recommended starting doses) are very effective in NIDDM patients already receiving gemfibrozil. The addition of the HMG-CoA reductase inhibitors lowered LDL-C to less than 100 mg/dl, which meets current ADA and ATPII consensus guidelines. Hypertriglyceridemia predicts small dense LDL and increased IDL-cholesterol levels in NIDDM Duel1 PJ& Div. of Endocrinol., Diabetes, & Nutrition, L465, Ore-
12461
gon Health Sciences Univ., Portland, OR 97201-3098,
USA
Hypertriglyceridemia is a risk factor for atherosclerosis, particularly in patients with non-insulin-dependent diabetes (NIDDM), but the pathophysiologic link between hypertriglyceridemia and atherosclerosis remains obscure. Although triglycerides may not be inherently atherogenic, hypertriglyceridemia in NIDDM is believed to be a marker for other atherogenic dyslipidemic abnormalities. This hypothesis was tested in 46 men id women: 18 with NIDDM. 16 non-diabetic with tvoe IV hvoerlibidemia and 12 normals. L&proteins were analyzii by ro&e &asurements and also by analysis of 30-35 sequential aliquots isolated by vertical ultracentrifugation. Levels of lipoprotein cholesterol (C) and TG were comparably elevated and HDL-C was reduced in NIDDM and type IV. LDL size (indicated by Rf) was smallest in NIDDM.
TC
vc
LC
1 299*240 62i55 138*42 2 268&85 98*92 134*45 3 2011t23 21i9 123*12
HC
TG
LDL Rf
42ztlO 4OilO 62*13
684i821 618i601 135i52
0.237&040.245+0.05 0.33OiO.03
I, NIDDM; 2, Type IV; 3, normal; VC, VLDL-C; LC, LDL-C; HC, HDL-C. TG levels were inversely correlated with the LDL relative flotation (Rf) in subjects with NIDDM (r = -0.55, P < 0.05). but not in type IV subjects (r = -0.004) or normals (r = -0.09). TG levels were directly related to the plasma IDL-C concentration in subjects with NIDDM (r = 0.65, P < 0.02), but not type IV subjects (r = 0.13) or normals (r = 0.07). Body weight was not contributory. Thus, the TG level was predictive of decreased density and size of LDL and increased concentrations of IDLC in subjects with NIDDM. In conclusion, hypertriglyceridemia appears to be a marker for atherogenic lipoprotein abnormalities in subjects with NIDDM. 1247]
HDL subparticles and coronary artery disease in NIDDM Nguyen TT, Hallaway BJ, Hodge D, Bailey K, Kottke
mT. BA, Mayo Clinic, Rochester, MN, USA
Lower HDL-C levels are associated with coronary artery disease (CAD) in NIDDM. HDL particles, however, am heterogeneous and little is known of the relationship between HDL subparticles and CAD in NIDDM. The aim of this study was to compare HDL subparticles with apo A-I (LpA-I) and those with apo A-I and apo A-II (LpA-I/A-II) in subjects with and without NIDDM and to study the relationship between HDL subparticles and CAD in NIDDM. Lipids, apo A-I and HDL subparticles were measured in 240 subjects with NIDDM and 248 age and gender-matched controls. Subjects with NIDDM had increased TG (2.3 + 1.8 vs 1.4 f 0.8 mmol/l, P < O.OOl),and decreased HDL-C (0.9 f 0.3 vs 1.2 + 0.3 mmoyl, P < O.OOl), apo A-I (124.7 f 22.4 vs 139.8 + 24.1 mg/dl, P < 0.001) and LpA-I/A-II (82.4 f 18.2 vs 94.9 + 16.7 mg/dl, P < 0.001). LpA-I levels were similar in both groups. Diabetic subjects with CAD (n = 109) had higher TG (2.7 + 1.9 vs 2.3 & 1.8 mmol/l, P= 0.02) and lower HDL-C (0.8 + 0.2 vs 1.0 + 0.3 mmol/l, P < O.OOl), apo A-I (115.5 f 20.1 vs 132.3 *21.4mg/dl, P
1248]
Boeleln I 117, PO Box 7057, 1007 MB Amsterdam; Dept. of Biothem., Erasmus Univ., Rotterdam, The Netherlands
We wanted to assess the long-term effects of fish oil added to a linoleic acid-enriched diet on CETP and LCAT activity, both measured with excess exogenous substrate, in non-insulin-dependent diabetes (NIDDM) patients. All 16 NIDDM patients (60 f 6 years, 12 M/4 F) consumed a saturated fat-enriched diet (polyunsaturated/saturated (P/S) ratio 0.3) before being randomly allocated to two treatment groups. During the following 4 months one group (n = 9) received fish oil capsules (1.8 g eicosapentaenoic acid and 1.2 g docosahexaenoic acid daily) with a linoleic acid-enriched diet (P/S 1.0) while the
Atherosclerosis X, Montreal, October 1994