Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease

Coronary heart disease in insulin-dependent (IDDM) and in non-insulin-dependent diabetes (NIDDM) is associated with lipid and lipoprotein changes favouring atherosclerosis. Whether lipid and lipoprotein abnormalities are associated also with peripheral vascular disease in both types of diabetes is largely unknown. Therefore, we studied lipid and lipoprotein levels and their association with claudication in a representative sample of diabetic and non-diabetic subjects in East Finland. Altogether 87 subjects had IDDM (43 men, 44 women), 264 subjects NIDDM (126 men, 138 women) and 120 subjects were non-diabetic controls (63 men, 57 women). Patients with IDDM had an increased level of HDL and HDL2-cholesterol and patients with NIDDM a decreased level of HDL and HDL2-cholesterol and an increased level of total, LDL and VLDL triglycerides than did non-diabetic subjects. Analyses in both types of diabetes by claudication status revealed that total and LDL-cholesterol and total and VLDL triglycerides tended to be higher and HDL and HDL2-cholesterol lower in those having claudication as compared to those without a claudication symptom. Similarly, total cholesterol/HDL-cholesterol ratio and LDL-cholesterol/HDL-cholesterol ratio were also more atherogenic in patients with claudication than in those without claudication. In conclusion, our results indicate that in both types of diabetes peripheral vascular disease is associated with lipid and lipoprotein abnormalities favouring atherosclerosis.     

5-year incidence of atherosclerotic vascular disease in relation to general risk factors, insulin level, and abnormalities in lipoprotein composition in non-insulin-dependent diabetic and nondiabetic subjects

The 5-year incidence of myocardial infarction and claudication was examined in a group of middle-aged patients (n = 133, 70 men and 63 women) with newly diagnosed non-insulin-dependent diabetes and nondiabetic control subjects (n = 144, 62 men and 82 women). The effects of general risk factors, plasma insulin level, and lipoprotein abnormalities on the incidence of myocardial infarction and claudication were also evaluated by univariate analyses in both diabetic patients and nondiabetic subjects and by multivariate analyses combining both groups. The age-adjusted incidence of myocardial infarction was higher both in diabetic men (19.4%) and diabetic women (11.0%) than in nondiabetic men (3.2%, p = 0.009) and nondiabetic women (3.0%, p = 0.047). Similarly, the age-adjusted incidence of claudication was higher among the diabetic patients (20.3% vs. 8.0% for men, p = 0.06; 21.8% vs. 4.2% for women, p = 0.003). None of the general risk factors (i.e., low density lipoprotein [LDL] cholesterol, blood pressure, smoking, and high density lipoprotein [HDL] cholesterol) showed an association with the risk of myocardial infarction either in the diabetic or nondiabetic groups of subjects, but an ischemic electrocardiographic abnormality at the baseline examination predicted myocardial infarction in diabetic men. In univariate analyses in diabetic subjects, high serum total cholesterol, low HDL cholesterol, high very low density lipoprotein (VLDL) cholesterol, and high total, LDL and VLDL triglycerides, and in nondiabetic subjects, high VLDL cholesterol and LDL triglycerides were associated with the appearance of claudication. In multivariate analyses including both diabetic and control subjects, only diabetes had an independent association with myocardial infarction, whereas smoking, high LDL triglycerides or VLDL cholesterol, and high fasting plasma insulin showed independent relations to claudication. The present results indicate that changes in lipoprotein composition characteristic of non-insulin-dependent diabetes are atherogenic and increase the risk of atherosclerotic vascular disease. Furthermore, high plasma insulin might also be involved in atherogenesis, independent of lipoprotein abnormalities.     

Familial aggregation of non-insulin dependent diabetes and coronary heart disease are accompanied by different effects on serum lipids, lipoproteins and apolipoproteins

This study was designed to investigate whether the presence of non-insulin-dependent diabetes mellitus (NIDDM) or coronary heart disease (CHD) in probands have different effects on serum lipid, lipoprotein and apolipoprotein concentrations in the first-degree relatives. Altogether 161 probands (114 men, 47 women) and 788 first-degree relatives of these probands (174 brothers, 246 sisters, 180 sons, 188 daughters) were included in the analyses. The presence of NIDDM in the proband was associated with lowered total, LDL and HDL cholesterol and apolipoprotein A1 and elevated total triglyceride levels in the brothers (P less than 0.05) and elevated total and LDL cholesterol levels in the sisters (P less than 0.05). Total LDL and VLDL cholesterol and apolipoprotein B were higher (P less than 0.05) and HDL/total cholesterol ratio and apolipoprotein A1/B ratio lower (P less than 0.05) in the daughters of the nondiabetic and diabetic probands were pooled, CHD in the proband was associated particularly with low apolipoprotein A1/B ratio. In conclusion, (1) the presence of NIDDM in the proband appears to be associated in siblings with more profound lipid and lipoprotein changes (especially low HDL cholesterol and high total triglycerides) than a history of CHD in the proband, (2) a history of CHD in the proband is associated in children with apolipoprotein changes favouring atherosclerosis (low apolipoprotein A1, high apolipoprotein B, low apolipoprotein A1/B ratio). Different effects of a history of NIDDM and CHD in the proband on lipid, lipoprotein and apolipoprotein levels in the first-degree relatives warrants more population-based studies.     

Plasma lipoproteins and apolipoproteins in insulin-dependent and young non-insulin-dependent Arab women

Summary Plasma lipids, lipoproteins and apolipoproteins (apo) were analysed in 30 young Arab IDDM and 50 young insulin-requiring NIDDM women. The mean age of IDDM and NIDDM groups was 20.2 and 34.5 years, and mean duration of diabetes was 5.7 and 4.6 years, respectively. Two groups of 40 and 60 healthy women (matched for age and BMI) provided corresponding control groups. In comparison with control subjects, diabetics showed marked increases in the following parameters: total cholesterol (TC), low density lipoprotein (LDL) cholesterol, total triglycerides (TG), very low density lipoprotein (VLDL) triglycerides, phospholipids, apoB, LDL apoB, glucose and glycosylated hemoglobin (HbA_1c) as well as the ratios of total cholesterol/high density lipoprotein (HDL) cholesterol, LDL-cholesterol/HDL-cholesterol, LDL cholesterol/high density lipoprotein 2 (HDL₂) cholesterol and apoB/apoAI. Plasma LCAT activity, concentrations of HDL₃ apoAI and apoAII in plasma and lipoprotein fractions were normal in both the diabetic groups. Levels of C-peptide, HDL, HDL₂ and HDL₃ cholesterol, plasma apoAI, HDL apoAI and HDL₂ apoAI were markedly decreased in the diabetic groups as compared to their corresponding controls. There was no significant correlation between fasting glucose or HbA_1c and any of the above parameters. Despite insulin therapy in both the diabetic groups studied, abnormalities in lipids, apoB and apoAI still persisted. Our data suggest a possible higher risk of atherosclerosis in these patients.     

Racial differences in lipid and lipoprotein levels in diabetes.

Racial differences in plasma lipid and lipoprotein levels were investigated in 145 patients with non-insulin-dependent diabetes mellitus (NIDDM). Black men had higher high-density lipoprotein (HDL) cholesterol levels, lower triglyceride levels, and an improved atherogenic index compared with white men. Premenopausal black women were also found to have higher HDL cholesterol levels, lower triglyceride levels, and a lower atherogenic index than their white counterparts. Adjustment for age, waist to hip ratio (WHR), hemoglobin A1c (HbA1c), and physical activity did not eliminate the significant differences found. There were no racial differences found regarding total and low-density lipoprotein (LDL) cholesterol. Metabolic control as measured by HbA1c was significantly correlated with the triglyceride level in black women. These data confirm that racial differences exist in plasma lipid levels among patients with NIDDM.     

Factors associated with plasma lipids and lipoproteins in type 1 diabetes mellitus: the EURODIAB IDDM Complications Study.

AIM: To assess the determinants and prevalence of hyperlipidaemia in Type 1 diabetic patients in the EURODIAB IDDM Complications Study. METHODS: Standardized questionnaire data were obtained and anthropometric and biochemical measurements performed on 3159 Type 1 diabetic patients, randomly selected from 31 diabetes clinics. Plasma lipid levels were determined centrally, using enzymatic methods RESULTS: Plasma total cholesterol, high-density lipoprotein cholesterol (HDL-C), and HDL subfractions were higher in women than in men, while plasma triglycerides were higher in men (P < 0.001). Total cholesterol, low-density lipoprotein cholesterol (LDL-C) and HDL-C and HDL-C subfractions were, as expected, significantly associated with age and HbA1c in both sexes. Age and HbA1c adjusted values of triglyceride, total cholesterol, LDL-C, HDL-C and HDL3-C in men and triglyceride and HDL2-C in women showed significant associations with central obesity, measured as the waist to hip ratio (WHR). Current smokers had lipid profiles characteristic of insulin resistance in comparison to nonsmokers. Significant positive associations were observed between hypertension and plasma triglycerides, total cholesterol and LDL-C in men and women. In men, degree of physical activity was negatively associated with triglyceride and positively related to HDL-C and HDL3-C. The prevalence of LDL-hypercholesterolaemia (LDL-C > 3.35 mmol/L) was 45% in men and in women, while plasma triglyceride levels > 1.7 mmol/L were observed in 12% of men and 8% of women. CONCLUSION: The results of this study indicate that lipid levels in Type 1 diabetic patients are strongly influenced by smoking habit and central obesity in a way that is characteristic of the insulin resistance syndrome.     

Lipids, diabetes, and coronary heart disease: insights from the Framingham Study

Both risk factors and the incidence of cardiovascular disease are higher in diabetic patients. Total serum cholesterol has the same impact on coronary heart disease (CHD) incidence in diabetic patients as in nondiabetic individuals. Abnormal blood lipids in diabetic patients include elevated very low-density lipoproteins (VLDL) and triglyceride and reduced levels of high-density lipoproteins (HDL). These are associated with obesity and precede the onset of diabetes. Diabetes increases the risk of all clinical manifestations of CHD, has a greater impact in women, and predisposes to cardiac failure and fatal outcome. In men, it predisposes to silent myocardial infarctions. CHD risk reduction in the diabetic patient requires multifactorial control. In evaluating the lipid-induced CHD risk, the level of low-density lipoprotein (LDL) cholesterol is not as valuable as the LDL/HDL cholesterol ratio, which is the most reliable criterion. Triglyceride levels make no independent contribution. Most CHD preventive measures, including weight control, exercise, avoidance of cigarettes, and improvement of glucose tolerance also increase HDL cholesterol, reduced levels of which are chiefly responsible for the poor LDL/HDL ratio in diabetics. Weight control merits a high priority because of its favorable influence on the lipid profile, glucose tolerance, and blood pressure.     

Lipids and lipoproteins as risk factors for coronary heart disease in men with abnormal glucose tolerance: the Honolulu Heart Program

Abstract. Objectives. To evaluate lipids and lipoproteins as risk factors for coronary heart disease (CHD) in older men with non-insulin-dependent diabetes (NIDDM) or abnormal glucose tolerance compared with normoglycaemic men. Design. A prospective, population-based cohort study based on the lipoprotein examination (1970–72) of the Honolulu Heart Program. Follow-up was through to December 1988. Setting. Honolulu, Hawaii. Subjects. Japanese-American men, ages 51–72 at baseline: 2042 with 1 h glucose < 12.5 mmol l^?1 (normal group); 376 on oral hypoglycaemic agents or with 1 h glucose ≥ 12.5 mmol l^?1 after 50 g oral glucose challenge (abnormal glucose tolerance group). None had prevalent coronary heart disease (CHD) or stroke at baseline. Main outcome measures. Incident CHD: definite nonfatal myocardial infarction (MI) or fatal CHD. Results. There were 221 incident cases in the normal group, and 65 in the abnormal glucose tolerance group. Total and high-density lipoprotein (HDL) cholesterol were significant predictors of incident CHD in men with NIDDM or abnormal glucose tolerance after controlling for age, body-mass index, systolic blood pressure, pack-years of cigarettes and alcohol consumption (P < 0.05). Total, low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterol were significant predictors in normal men, and HDL cholesterol was of borderline significance. Conclusions. Abnormal lipids and lipoproteins are significant, independent predictors of CHD in subjects with NIDDM or abnormal glucose tolerance. Attention to lipid and lipoproteins as CHD risk factors should be part of clinical management of these patients.     

Lipids in type 2 diabetes

Type 2 diabetes increases the risk of cardiovascular disease two- to fourfold compared to the risk in nondiabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors, the cause for an excess risk of cardiovascular disease remains unknown. Lipid and lipoprotein abnormalities in type 2 diabetes include particularly elevated levels of total and very low-density lipoprotein triglycerides and reduced levels of high-density lipoprotein (HDL) cholesterol. Total and low-density lipoprotein (LDL) cholesterol levels are usually normal if glycemic control is adequate but LDL particles are small and dense. According to prospective population-based studies, total cholesterol is a similar risk factor for coronary heart disease (CHD) in patients with type 2 diabetes as it is in nondiabetic subjects. High total triglycerides and low HDL cholesterol may be even stronger risk factors for CHD in patients with type 2 diabetes than in nondiabetic subjects. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol by statins, and the lowering of total triglycerides and the raising of HDL cholesterol by fibrates, are at least as beneficial in diabetic patients as in nondiabetic subjects in the prevention of cardiovascular disease.     

Regulation of low-density lipoprotein particle size distribution in NIDDM and coronary disease: importance of serum triglycerides

Summary An increase of low-density lipoprotein triglycerides (LDL-Tg) was found to be an independent coronary artery disease (CAD) risk factor for non-insulin-dependent diabetic (NIDDM) patients in a recent prospective study. We examined the composition and size of LDL particles in 50 NIDDM men with angiographically verified CAD (NIDDM+ CAD+) and in 50 NIDDM men without CAD (NIDDM+ CAD–) as compared to 50 non-diabetic men with CAD (NIDDM– CAD+) and 31 non-diabetic men without CAD (NIDDM– CAD–). The groups had similar ranges of age and BMI LDL particle size was determined by gradient gel electrophoresis, and LDL was isolated by sequential ultracentrifugation for compositional analyses. Serum Tg was increased in NIDDM patients as compared to non-diabetic subjects (p<0.05), and in patients with CAD as compared to subjects without the disease (p<0.05). LDL cholesterol was lower in NIDDM patients than in non-diabetic subjects (p<0.001). Mean diameter of LDL particles was less than 255 å, but closely comparable in all groups. The presence of NIDDM was associated with increases of Tg and protein but lowering of free cholesterol in LDL (p<0.005 for all). In multivariate regression analyses neither NIDDM nor CAD were associated with LDL particle size, but serum Tg was the major determinant of LDL size in both NIDDM and non-diabetic subjects (p<0.001). When the patients were divided into quartiles according to fasting serum Tg levels, the LDL particle size and free cholesterol content decreased, but Tg and protein contents of LDL particles increased from the lowest to the highest Tg quartile (analysis of variance p<0.001 for all). When the subjects were categorized into two groups according to the median of VLDL-Tg (1.10 mmol/l) LDL size was associated with VLDL-Tg in the high but not in the low VLDL-Tg group. We conclude that in NIDDM patients with or without CAD serum Tg is the major determinant of the properties of LDL particles. The clinical implication is that in NIDDM serum Tg should be as low as possible to prevent atherogenic changes in LDL.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - CAD coronary artery disease - HDL high-density lipoprotein - LDL low-density lipoprotein - VLDL very-low-density lipoprotein - apoB apolipoprotein B - HL hepatic lipase - LPL lipoprotein lipase - CETP cholesteryl ester transfer protein - PL phospholipids - ANOVA analysis of variance - Tg triglycerides - FC free cholesterol     

Analysis of plasma lipids and apolipoproteins in insulin-dependent and noninsulin-dependent diabetics

Plasma triglycerides, cholesterol, high-density lipoprotein (HDL) cholesterol, and apolipoproteins (apo) A-I, A-II, C-II, and C-III were determined and analyzed in 170 diabetic patients and 46 age-matched healthy normal subjects. The diabetics were separated into two groups: insulin-dependent diabetes mellitus (IDDM, n = 78) and noninsulin-dependent diabetes mellitus (NIDDM, n = 92). Significantly increased triglycerides, low HDL cholesterol, and normal cholesterol levels were found in the diabetics. The lipid profiles were similar in the IDDM and NIDDM groups. Plasma apo A-I, but not apo A-II, was low in both groups of diabetics. However, only in the IDDM subjects was there a statistically significant decrease in apo A-I when compared to normal subjects. The decreased apo A-I level negatively correlated with plasma triglycerides. Apo C-II and apo C-III were slightly increased in the diabetics compared to normal subjects. Apo C-II and apo C-III levels significantly correlated with plasma triglycerides (apo C-II, r = 0.70, P less than 0.0001; apo C-III, r = 0.71, P less than 0.0001). Only apo C-II correlated with total cholesterol. Thirty-eight to forty-two percent of the IDDM and NIDDM subjects had a clinical diagnosis of coronary artery disease (CAD) and/or peripheral arteriovascular disease (PAD). In the IDDM subjects, but not in the NIDDM subjects the incidence of CAD and/or PAD was associated with the decreased apo A-I levels as evaluated by a univariate analysis.(ABSTRACT TRUNCATED AT 250 WORDS)     

Apolipoprotein E polymorphism in men and women from a Spanish population: allele frequencies and influence on plasma lipids and apolipoproteins.

The apolipoprotein (apo) E phenotype and its influence on plasma lipid and apolipoprotein levels were determined in men and women from a working population of Madrid, Spain. The relative frequencies of alleles epsilon(2), epsilon(3) and epsilon(4) for the study population (n=614) were 0.080, 0.842 and 0.078, respectively. In men, apo E polymorphism was associated with variations in plasma triglyceride and very low-density lipoprotein (VLDL) lipid levels. It was associated with the proportion of apo C-II in VLDL, and explained 5.5% of the variability in the latter parameter. In women apo E polymorphism was associated with the concentrations of plasma cholesterol and low-density lipoprotein (LDL) and high-density lipoprotein (HDL) related variables. The allelic effects were examined taking allele epsilon(3) homozygosity as reference. In men, allele epsilon(2) significantly increased VLDL triglyceride and VLDL cholesterol concentrations, and this was accompanied by an increase of the apo C-II content in these particles. Allele epsilon(4) did not show any significant influence on men's lipoproteins. In women, allele epsilon(2) lowered LDL cholesterol and apo B levels, while allele epsilon(4) increased LDL cholesterol and decreased the concentrations of HDL cholesterol, HDL phospholipid and apo A-I. These effects were essentially maintained after excluding postmenopausal women and oral contraceptive users from the analysis. In conclusion: (1) the population of Madrid, similar to other Mediterranean populations, exhibits an underexpression of apo E4 compared to the average prevalence in Caucasians, (2) gender interacts with the effects of apo E polymorphism: in women, it influenced LDL and HDL levels, whereas in men it preferentially affected VLDL, and (3) allele epsilon(2) decreased LDL levels in women, while it increased both VLDL lipid levels and apo C-II content in men, but, in contrast to allele epsilon(4), it did not show an impact on HDL in either sex.     

Relation of plasma lipids to insulin resistance, nonesterified fatty acid levels, and body fat in men from three ethnic groups: relevance to variation in risk of diabetes and coronary disease

Afro-Caribbean men in the United Kingdom have a favorable lipoprotein profile and are at low risk of coronary heart disease (CHD) compared with Europeans and South Asians, but are at high risk of non-insulin-dependent diabetes mellitus (NIDDM) compared with Europeans. To investigate these differences, a cross-sectional comparison was undertaken for measures of lipoprotein metabolism, body composition, and insulin's glucoregulatory and antilipolytic actions in 92 healthy men (42 to 61 years) of Afro-Caribbean, South Asian, or European origin. Afro-Caribbean men were more insulin-resistant than Europeans (insulin sensitivity [Si], 1.96 v3.01 min(-1) x microU(-1) x mL, P < .01). They nevertheless had a more favorable lipoprotein profile, with lower levels of very-low-density lipoprotein (VLDL) cholesterol (0.21 v 0.40 mmol/L, P < .01) and triglycerides (0.34 v 0.74 mmol/L, P < .01), lower serum total triglycerides, higher high-density lipoprotein 2 (HDL2) cholesterol, and larger low-density lipoprotein (LDL) particle size. These differences were not accounted for by differences in nonesterified fatty acid (NEFA) levels, the sensitivity of suppression of NEFA levels to insulin, or body composition. South Asians were also more insulin-resistant than Europeans but had a less favorable lipoprotein profile. Afro-Caribbean men in the United Kingdom are as insulin-resistant as South Asian men but less susceptible to the lipid disturbances that characteristically accompany insulin resistance. This favorable lipid pattern may relate to more effective VLDL metabolism rather than a reduced supply of NEFA as substrate for triglyceride synthesis.     

The association between adiponectin and diabetes in the Korean population

As indicators of obesity, waist circumference (WC), body mass index (BMI), and adiponectin are well-known risk factors for diabetes mellitus. The objectives of this study were to measure the independent association between these obesity indicators and diabetes and to examine the combined effect of these indicators on diabetes in a Korean population. The WC, BMI, and serum adiponectin were measured in 4459 healthy Koreans and were classified into tertile groups for men and women. The independent and combined associations of the obesity indicators with diabetes were measured using logistic regression analyses. Diabetes was defined as fasting serum glucose greater than 126 mg/dL or taking medication. Levels of adiponectin were inversely associated with BMI and WC and directly associated with age and high-density lipoprotein (HDL) cholesterol (P < .001). After adjusting for age, BMI, WC, and other lifestyle factors, low levels of adiponectin were associated with an increased prevalence of diabetes. Further adjustment for HDL cholesterol and triglyceride attenuated this association in women but not men. The combined effects of WC and adiponectin on diabetes progressively increased; however, the interaction of these 2 variables was not statistically significant. The combined effect of BMI and adiponectin on diabetes showed similar results. These results suggest that adiponectin was associated with diabetes. The association was independent of BMI and WC and was partly modified by HDL and triglyceride. There were no effect modifications of adiponectin with WC and BMI on diabetes.     

Obesity and lipoprotein cholesterol in the Framingham offspring study

This study examines the relationship between obesity and low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and very-low-density lipoprotein (VLDL) cholesterol in 4260 young adult men and women. The strongest association between obesity and LDL cholesterol was found in 20–29 yr-old males, the weakest in 40–49-yr-old males. Conversely, in women the relationship between LDL cholesterol and obesity was modest except in the oldes (40–49 yr) age group. An inverse relationship between obesity and HDL cholesterol was of similar shape and strength in all sex and age-specific groups. When the ratio of total cholesterol (TCHOL) to HDL cholesterol was compared in lean and grossly obese 20–29-yr-old males, substantial differences were found. Since other data show this index of the lipoprotein profile to be the single best indicator of CHD risk, it would appear that the atherogenic potential of obesity is greater than would be suggested by the relatively weak association between obesity and TCHOL or any single lipoprotein cholesterol. These data also suggest that the impact of obesity as a risk factor for CHD may have been underestimated. The paucity of lean males 40–49-yr-old prevents firm conclusions about the CHD risk in such a group. Indirect evidence indicates that lean 40–49-yr-old men would have a markedly more favorable lipoprotein profile and consequently a much lower risk of CHD.     

The codon 64 polymorphism of the beta3-adrenergic receptor gene is not associated with coronary heart disease or insulin resistance in nondiabetic subjects and non-insulin-dependent diabetic patients.

Hyperinsulinemia has been shown to predict coronary heart disease (CHD) events in both nondiabetic subjects and patients with non-insulin-dependent diabetes mellitus (NIDDM). Therefore, defects in genes that regulate insulin action could be responsible for an increased risk of CHD. The Trp64Arg polymorphism of the beta3-adrenergic receptor gene has been linked with abdominal obesity, insulin resistance, and early-onset NIDDM. Therefore, we screened for this polymorphism among 185 unrelated nondiabetic subjects (101 men and 84 women; age, 56+/-1 years [mean +/- SEM]; body mass index [BMI], 27.8+/-0.3 kg/m2) with angiographically confirmed CHD (stenosis > 50% in > or = two coronary arteries), among 119 unrelated patients with NIDDM (90 men and 29 women; age, 62+/-1 years; BMI, 28.7+/-0.4 kg/m2; 95 had CHD by the same criteria and 24 had definite myocardial infarction [MI]), and among 82 healthy men (age, 54+/-1 years; BMI, 26.3+/-0.4 kg/m2) from our previous study. The frequency of the Trp64Arg allele of the beta3-adrenergic receptor gene was similar in nondiabetic patients with CHD (8%), NIDDM patients with CHD (7%), and nondiabetic subjects without CHD (7%). No association was found between cardiovascular risk factors and the codon 64 polymorphism of the beta3-adrenergic receptor gene in patients with CHD. Similarly, this polymorphism was not significantly related to insulin resistance in nondiabetic and NIDDM subjects with CHD evaluated by the euglycemic clamp technique. These results indicate that the Trp64Arg allele of the beta3-adrenergic receptor gene does not contribute to the risk of CHD in nondiabetic subjects and NIDDM patients.     

Relatively more atherogenic coronary heart disease risk factors in prediabetic women than in prediabetic men

Summary Men with non-insulin-dependent diabetes mellitus (NIDDM) have a twofold increased risk of coronary heart disease and women with NIDDM have a fourfold increased risk. The reasons for this higher relative risk in NIDDM women than in NIDDM men is not completely understood. Since some studies suggest that duration of clinical diabetes and degree of hyperglycaemia have only a modest effect on coronary heart disease risk, we hypothesized that women who eventually convert to NIDDM might have a more atherogenic pattern of lipids and blood pressure relative to subjects who do not convert than male converters, even in the prediabetic period. We examined this issue in Mexican-American subjects in the 8-year follow-up of the San Antonio Heart Study. Seventy-nine out of 801 men converted to NIDDM compared to 133 out of 1131 women. In both men and women, conversion to NIDDM was significantly associated with increased body mass index, fasting insulin and glucose, higher triglyceride and blood pressure and lower high density lipoprotein (HDL) cholesterol. The relative differences between converters and non-converters was significantly greater for women than for men; this interaction term for gender by conversion status was statistically significant for fasting insulin, triglyceride, HDL cholesterol and diastolic blood pressure. Thus, the higher relative risk for coronary heart disease in women with NIDDM relative to men with NIDDM may be partially due to their greater burden of cardiovascular risk factors even prior to the onset of diabetes. [Diabetologia (1997) 40: 711–717] Received: 7 November 1996 and in revised form: 11 March 1997     

Coronary heart disease risk factor profiles in black patients with non-insulin-dependent diabetes mellitus: paradoxic patterns.

PURPOSE: Non-insulin-dependent diabetes mellitus (NIDDM) in black Americans consists of two variants: one with insulin resistance and one with normal insulin sensitivity. This study examined whether cardiovascular disease risk factors are significantly different between the two variants. PATIENTS AND METHODS: Twenty-two black patients with NIDDM in near-normoglycemic remission who were receiving no pharmacologic therapy for NIDDM were evaluated for insulin sensitivity by the euglycemic insulin clamp, plasma insulin levels, degree of obesity, glucose metabolism, serum total, high-density lipoprotein (HDL), and low-density lipoprotein (LDL) cholesterol levels, and fasting plasma triglyceride levels. RESULTS: Fifty-nine percent of these patients had normal insulin sensitivity (glucose disposal rate in response to a 1 mU.kg-1.minute-1 insulin infusion greater than 6.0 mg.kg-1.minute-1). The insulin-sensitive patients were less obese (body mass index [BMI] 26.5 +/- 0.6 versus 30.8 +/- 0.9 kg/m2) and had lower fasting plasma insulin levels (56.9 +/- 7.8 versus 88.0 +/- 6.0 pmol/L), lower serum cholesterol (4.47 +/- 0.30 versus 6.39 +/- 0.26 mmol/L), lower serum LDL cholesterol (2.77 +/- 0.31 versus 4.51 +/- 0.27 mmol/L), and lower fasting plasma triglyceride levels (0.83 +/- 0.08 versus 1.45 +/- 0.16 mmol/L) than the insulin-resistant patients. Serum HDL cholesterol was not different between the two groups and was in the high-normal range (1.31 +/- 0.08 and 1.19 +/- 0.07 mmol/L). Univariate analysis demonstrated that serum total cholesterol, LDL cholesterol, and fasting plasma triglycerides were highly correlated with insulin-mediated glucose disposal and fasting plasma insulin. The differences in insulin sensitivity and lipid profiles were independent of obesity, as they were present in six insulin-resistant and six insulin-sensitive patients matched for BMI. CONCLUSIONS: Black patients with the insulin-sensitive variant of NIDDM have a low risk factor profile for cardiovascular disease as compared with those with the insulin-resistant variant, who have a high risk factor profile. A high prevalence of the insulin-sensitive variant of NIDDM in the black population might explain the lower prevalence of angina and myocardial infarction in black patients with NIDDM as compared with white patients with NIDDM.     

Lecithin:cholesterol acyltransferase activity, plasma and lipoprotein lipids and obesity in men and women

Lecithin:cholesterol acyltransferase (LCAT) activity, lipid concentration, lipoprotein lipid concentrations and cholesteryl ester linoleic acid proportion were determined in the plasma of 85 subjects randomly selected from a population during a health screen survey. Mean fractional LCAT rate was significantly higher in men than in women. Molar LCAT rate correlated with low density lipoprotein (LDL) cholesterol concentration in men and with nearly all lipoprotein lipid concentrations in women. Most of these relationships were dependent on plasma unesterified cholesterol (UC) concentration. Fractional LCAT rate was correlated only with HDL cholesterol concentration in women and this relation was dependent on the influence of obesity. An inverse relationship between plasma cholesteryl ester (PCE) linoleic acid proportion and molar LCAT rate in women was also explained by influences of obesity on the data. Both fractional and molar LCAT rates were positively correlated with obesity (Quetelet's Index and subscapular skinfold thickness) in women but not in men. This study showed the influence of sex on nearly all correlations involving LCAT activity in combined groups of men and women.     

Long-term association of cardiovascular risk factors with impaired insulin secretion and insulin resistance

The study aim was to investigate the association of cardiovascular risk factors with insulin resistance and impaired insulin secretion in an 8-year prospective population study in nondiabetic subjects. Cardiovascular risk factors of 271 subjects aged 16 to 61 years were measured at baseline, and insulin sensitivity and acute-phase insulin secretion were assessed by an intravenous glucose tolerance test (IVGTT) and Bergman's minimal model 8 years later. In logistic regression analysis, baseline high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) cholesterol (P < .001 and P = .006, respectively), total, low-density lipoprotein (LDL), and VLDL triglycerides (P = .004, P = .048, and P = .002, respectively), apolipoprotein A1 (P = .010), and uric acid (P < .001) were associated with insulin resistance after adjustment for age and the body mass index (BMI). Systolic blood pressure (P = .042) and VLDL cholesterol (P = .018) were associated with impaired insulin secretion after adjustment for age and the BMI. This 8-year longitudinal study demonstrates that dyslipidemia, high blood pressure, and uric acid are associated with insulin resistance, whereas high systolic blood pressure and VLDL cholesterol are associated with impaired first-phase insulin secretion.