Associations of multiple lipoprotein and apolipoprotein measures with worsening of glycemia and incident type 2 diabetes in 6607 non-diabetic Finnish men

doi:10.1016/j.atherosclerosis.2015.03.034

Atherosclerosis

Volume 240, Issue 1, May 2015, Pages 272-277

https://doi.org/10.1016/j.atherosclerosis.2015.03.034 Get rights and content

Abstract

Objective

We investigated the association of various lipoprotein traits, apolipoproteins and their ratios with the deterioration of glycemia, incident type 2 diabetes, insulin resistance and insulin secretion in a large population-based Metabolic Syndrome Men (METSIM) Study.

Research design and methods

The METSIM Study includes 10,197 Finnish men, aged 45–73 years, and examined in 2005–2010. From 6607 non-diabetic participants without statin treatment at baseline, 386 developed incident type 2 diabetes during a 5.9-year follow-up. A total of 3330 non-diabetic participants without statin treatment had both baseline and follow-up visit data, and were included in statistical analyses of the worsening of glycemia.

Results

Compared to single lipid and lipoprotein measurements, lipoprotein and apolipoprotein ratios were better predictors of the glucose area under the curve and incident type 2 diabetes after adjustment for confounding factors. The apolipoprotein B/LDL cholesterol ratio was the strongest predictor of the worsening of glycemia, whereas the apolipoprotein A1/HDL cholesterol ratio was the strongest predictor of incident type 2 diabetes. The associations of lipoprotein traits, apolipoproteins and their ratios with insulin sensitivity were stronger than those with insulin secretion.

Conclusions

The apolipoprotein B/LDL cholesterol and apolipoprotein A1/HDL cholesterol ratios were the strongest predictors of the worsening of glycemia and incident type 2 diabetes, respectively.

Introduction

Type 2 diabetes is associated with atherogenic dyslipidemia, including elevated levels of plasma triglycerides (TG), very-low density lipoprotein (VLDL) particles, post-prandial triglyceride-rich lipoprotein remnants and apoliporotein B (apoB), and low levels of high density lipoprotein cholesterol (HDL-C) [1], [2]. These atherogenic changes precede type 2 diabetes by several years and are associated with high risk of cardiovascular events in type 2 diabetes [3], [4], [5], [6].

The compositional changes of lipoprotein particles occur in type 2 diabetes, including the formation of atherogenic small dense LDL (sd-LDL) and small HDL (s-HDL) particles, and the predominance of large VLDL particles. In prospective studies, increased levels of triglycerides [7], sd-LDL [8], large VLDL particles (l-VLDL), and s-HDL [8], [9], [10], have been shown to be associated with increased risk of diabetes, whereas increased levels of large HDL particles [11], [12] and apoA1 [11] have been shown to be protective of diabetes. Also lipoprotein ratios, which reflect the proportion of atherogenic to antiatherogenic lipoproteins, have been proposed as potential markers for the future risk of type 2 diabetes [13], [14].

Results from previously published studies have been inconsistent with regard to what are the best lipoprotein and apolipoprotein markers predicting the progression to overt type 2 diabetes. One report previously showed that apoB level is a better predictor for the future risk of type 2 diabetes compared with LDL cholesterol (LDL-C) and HDL cholesterol (HDL-C) [15]. Another study reported that the apoA1/HDL-C ratio is superior to other lipid variables in predicting the development of type 2 diabetes [16]. However, none of the previous studies has evaluated lipoprotein and apolipoprotein traits and their ratios as predictors for the worsening of glycemia and changes in insulin sensitivity and insulin secretion in non-diabetic participants.

We investigated the various lipoprotein and apolipoprotein traits and their ratios as predictors for the worsening of glycemia and incident type 2 diabetes in a 5.9-year population-based follow-up study. We also investigated the associations of lipoprotein traits, apolipoproteins and ratios with insulin resistance and insulin secretion.

Section snippets

Subjects and clinical measurement at the baseline study

The Metabolic Syndrome in Men (METSIM) Study, comprising 10,197 Finnish men aged from 45 to 70 years and randomly selected from the population register of Kuopio, Eastern Finland (population 95,000), was performed in 2005–2010 at the University of Eastern Finland. The present report includes 6607 non-diabetic participants without statin treatment at baseline (age 56 ± 7 years, body mass index (BMI) 26.6 ± 3.8 kg/m², mean ± SD). Participants with previously diagnosed type 1 diabetes (N = 25),

Clinical and laboratory characteristics of the study population

We compared selected clinical and laboratory traits between participants who remained non-diabetic and participants who developed type 2 diabetes during the prospective METSIM study (Supplementary Table 1). Compared to participants who did not develop diabetes, participants with incident type 2 diabetes were more obese, older, less physically active, had lower levels of apoA1, HDL-C and large HDL particles, higher levels of apoB, small and large VLDL particles, and the ratios of apoA1/HDL-C,

Conclusions

In a 5.9-year follow-up of our large population-based METSIM study we evaluated the associations of different lipoprotein traits, apolipoproteins and their ratios with the worsening of glycemia, incident type 2 diabetes, and potential mechanisms explaining these associations. Our results suggest that compared to single lipoprotein measurements, lipoprotein and apolipoprotein ratios such as apoA1/HDL-C and apoB/LDL-C are better predictors for the worsening of glycemia and incident type 2

Conflicts of interest

The authors have declared no conflicts of interest.

Acknowledgments

This work has been supported by the grants from the Finnish Diabetes Research Foundation (M.L.), the Academy of Finland (to M.L. and A.S.), the Finnish Cardiovascular Research Foundation (to M.L.), the Strategic Research Funding from the University of Eastern Finland, Kuopio (to M.L.), Finland, EVO Grant 5263 from the Kuopio University Hospital (to M.L.), the Sigrid Juselius Foundation (M.A.-K.), the Novo Nordisk Foundation (M.A.-K.), and the Strategic Research Funding from the University of

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Associations of multiple lipoprotein and apolipoprotein measures with worsening of glycemia and incident type 2 diabetes in 6607 non-diabetic Finnish men

Abstract

Objective

Research design and methods

Results

Conclusions

Introduction

Section snippets

Subjects and clinical measurement at the baseline study

Clinical and laboratory characteristics of the study population

Conclusions

Conflicts of interest

Acknowledgments

Atherosclerosis

Clin. Biochem.

Int. J. Cardiol.

Med. Clin. North Am.

Diabetic dyslipidaemia

Curr. Opin. Lipidol.

Diabetic dyslipidaemia: from basic research to clinical practice

Diabetologia

Overproduction of very low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic syndrome

Arterioscler. Thromb. Vasc. Biol.

Asymptomatic hyperglycemia is associated with lipid and lipoprotein changes favoring atherosclerosis

Arteriosclerosis

Clinical review 124. Diabetic dyslipidemia: causes and consequences

J. Clin. Endocrinol. Metab.

Nuclear magnetic resonance lipoprotein abnormalities in prediabetic subjects in the Insulin Resistance Atherosclerosis Study

Circulation

Lipoprotein particles and incident type 2 diabetes in the multi- ethinic study of atherosclerosis Advanced online publication

Diabetes Care

Lipoprotein particle size and concentration by nuclear magnetic resonance and incident type 2 diabetes in women

Diabetes

Prospective study of small LDLs as a risk factor for non-insulin dependent diabetes mellitus in elderly men and women

Circulation

HDL cholesterol subfractions and risk of developing type 2 diabetes among Pima Indians

Diabetes Care

Role of HDL cholesterol and estimates of HDL particle composition in future development of type 2 diabetes in the general population: the PREVEND study

J. Clin. Endocrinol. Metab.