Elsevier

Atherosclerosis

Volume 128, Issue 1, 3 January 1997, Pages 113-119
Atherosclerosis

Plasma lipoproteins and incidence of non-insulin-dependent diabetes mellitus in Pima Indians: protective effect of HDL cholesterol in women

https://doi.org/10.1016/S0021-9150(96)05978-3Get rights and content

Abstract

The role of plasma lipoproteins in the development of non-insulin-dependent diabetes mellitus (NIDDM) was studied in 787 non-diabetic (2-h glucose<11.1 mmol/l) Pima Indians (265 men and 522 women). Subjects were followed for a mean of 9.8 (range: 1.8–16.4) years, during which 261 (76 men and 185 women) developed NIDDM. In men and women, very-low-density lipoprotein (VLDL) cholesterol, VLDL triglyceride, low-density lipoprotein triglyceride and total triglyceride, controlled for age, predicted NIDDM (P<0.01 for each). These effects diminished when controlled for age, sex, body mass index, systolic blood pressure and 2-h glucose. However, high-density lipoprotein (HDL) cholesterol, controlled for age, body mass index, systolic blood pressure and 2-h glucose, was a significant protective factor for NIDDM in women (hazard rate ratio (HRR)=0.35, 95% CI (0.23–0.54), P<0.001, 90th compared with 10th percentile) but not in men (HRR=1.04, 95% CI (0.53–2.05), P=0.915). This association remained significant in women when controlled for fasting or 2-h plasma insulin concentrations, other estimates of insulin resistance or alcohol consumption. The protective effect of HDL cholesterol was similar among women with normal (2-h glucose<7.8 mmol/l) or impaired (7.8 mmol/l≤2-h glucose<11.1 mmol/l) glucose tolerance at baseline. These results indicate that lipoprotein disorders are an early accompaniment of the abnormalities that lead to NIDDM.

Introduction

A number of correlated factors, including insulin resistance, hyperinsulinemia, hypertension, high concentrations of very-low-density-lipoprotein (VLDL) triglycerides, and low concentrations of high-density-lipoprotein (HDL) cholesterol, are associated with impaired glucose tolerance and non-insulin-dependent diabetes mellitus (NIDDM) [1]. Whereas, it is well established that insulin resistance and NIDDM worsen lipid abnormalities, it is unclear whether lipid abnormalities lead to insulin resistance or NIDDM 2, 3, 4, 5, 6. In some studies, lipid abnormalities predicted the development of NIDDM, but they may not be causal because their effects diminished in analyses controlled for confounding by glucose concentrations [4]or insulin resistance 2, 6.

Pima Indians have a high incidence of NIDDM and are generally insulin resistant and obese 7, 8, but they have, on average, low plasma total cholesterol levels 9, 10, 11. The present study examined the relationship between plasma lipoprotein concentrations and risk of developing NIDDM in 787 Pima men and women aged≥15 years followed for a mean of 9.8 years.

Section snippets

Research design

Since 1965, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) has conducted a longitudinal study of NIDDM in the Gila River Indian Community in central Arizona [7]. The inhabitants of this Community are primarily Pima or Tohono O'odham Indians. All residents aged≥5 years are invited to participate in biennial research examinations. At each examination, height and weight are measured with the subject wearing light clothing and no shoes; body mass index (BMI) is

Results

Table 1 shows characteristics of the subjects at baseline. 46 (17.4%) men and 126 (24.1%) women had impaired glucose tolerance at baseline.

The subjects were followed for a mean of 9.8 (range: 1.8–16.4) years, during which 76 men and 185 women developed NIDDM. Table 2 presents HRRs and 95% confidence intervals for variables potentially related to NIDDM. Multivariate proportional hazards models for lipoproteins and NIDDM incidence were fit separately for men and women because of the different

Discussion

In a population with a high incidence of NIDDM and insulin resistance 7, 8, and, on average, low plasma HDL and total cholesterol 9, 10, 11, a high HDL cholesterol was a strong protector from diabetes in women. The HDL cholesterol's protective effect was independent of glucose tolerance, insulin resistance and alcohol consumption, but was found only in women. On the other hand, high levels of VLDL cholesterol and VLDL, LDL and total triglycerides were predictive of NIDDM in men and women, but

Acknowledgements

The authors would like to thank the members of the Gila River Indian Community who participated in the study, the DAES staff for their assistance, and Dr. Steven Haffner for reviewing this manuscript.

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