Cardiovascular risk factors in non-insulin-dependent diabetics compared to non-diabetic controls: a population-based survey among Asians in Singapore

Abstract

Cardiovascular risk factors were compared between 126 people with non-insulin-dependent diabetes mellitus (NIDDM) and 530 non-diabetics (controls), in a random sample of people (Chinese, Malays, and Asian Indians) aged 40–69 years from the general population of Singapore. Data were adjusted for age and ethnicity. For both genders, people with NIDDM had higher mean body mass indices, waist-hip ratios and abdominal diameters. They also had a higher prevalence of hypertension, higher mean levels of fasting serum triglyceride, slightly lower mean levels of serum high-density-lipoprotein cholesterol, and higher mean levels of plasma plasminogen activator inhibitor-1 and tissue plasminogen activator (antigen). These factors are components of syndrome X (metabolic syndrome) and increase the risk of atherosclerosis and thrombosis. In contrast, there were no important differences for cigarette smoking, serum total and low-density-lipoprotein cholesterol, serum apolipoproteins A1 and B, plasma factor VIIc and plasma prothrombin fragment 1+2. Females with NIDDM, but not males, had a higher mean serum fibrinogen level than non-diabetics, which could explain why NIDDM has a greater cardiovascular effect in females than males. Serum lipoprotein(a) concentrations were lower in people with NIDDM. Mean levels of serum ferritin, a pro-oxidant, were higher in people with NIDDM than controls, but there were no important differences for plasma vitamins A, C and E, and serum selenium, which are anti-oxidants.

Introduction

People with non-insulin-dependent diabetes mellitus (NIDDM) are about three times as likely as non-diabetics to get coronary heart disease (CHD), and furthermore cardiovascular disease occurs early in the course of diabetes [1]. The classical risk factors for CHD are cigarette smoking, hypertension, and dyslipidaemias (high low-density-lipoprotein (LDL) cholesterol, low high-density-lipoprotein (HDL) cholesterol, and high fasting triglyceride). NIDDM seems to be linked with hypertension and dyslipidaemia through insulin resistance, which tends to be associated with centralised adiposity [2], and syndrome X (metabolic syndrome). This is characterised by increased insulin resistance, glucose intolerance, hypertension, and dyslipidaemia with high fasting triglyceride and low HDL-cholesterol [3].

With regard to haemostatic (thrombotic) factors, blood fibrinogen is an established risk factor and factor VIIc and plasminogen activator inhibitor type 1 (PAI-1) are probable risk factors for CHD [4]. Syndrome X could also link NIDDM with haemostatic factors as it is being expanded and called the `athero-thrombogenic syndrome'. It can include increased PAI-1 [5].

Lipoprotein (Lp)(a) has LDL-like properties which could increase atherosclerosis [6]and, being structurally similar to plasminogen, inhibits plasminogen binding to the endothelial cell with reduced plasmin generation and fibrinolysis [7]. However Lp(a) has not been shown to be a cardiovascular risk factor in prospective as opposed to case-control studies and its role is not fully clear [8].

There is evidence that oxidative free-radicals have a role in the development of degenerative diseases including CHD 9, 10. There is further evidence that anti-oxidants (including vitamins A, C and E, and selenium) are protective against CHD, though it is considered inconclusive 11, 12, 13. Iron is a pro-oxidant and high levels of blood ferritin, which measures stored iron, is a possible risk factor for CHD, though this is considered unproven 13, 14. Diabetics are usually put on a special diet and so possibly their dietary intake of anti-oxidants and pro-oxidants are different from non-diabetics.

Singapore has a population of 3.3 million people composed of Chinese 76%, Malays 14%, Indians (South Asians) 7%, and others 3% whose origins have been described [15]. The country has undergone rapid economic development and the commonest causes of death are now cardiovascular diseases and cancers. The Singapore Thyroid and Heart Study found that NIDDM was common and highest in Indians, then Malays, and then Chinese [16]. The National University of Singapore Heart Study is a further population-based survey of cardiovascular risk factors, including the newer ones not studied previously, and this paper compares a range of cardiovascular risk factors between people with NIDDM and non-diabetics (controls).