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Coronary Risk of Insulin Sensitivity in Indian Subjects (CRISIS)


Funded By: International Atomic Energy Agency, Austria,
and Nestle Foundation, Switzerland
Month & Year of Commencement:  June 1999
Current Status:  Completed

Principal Investigator: Dr. C.S.Yajnik, Director, Diabetes Unit, KEM Hospital & Research Center, Pune, India
Co-Investigator: Prof. John Yudkin, Professor in Department of International Health, University College London, UK

» Background
» Objectives
» Methodology and Design
» Results

Background

The cause of the rising epidemic of type 2 diabetes and coronary heart disease (CHD) in India is not very clear. It is strongly related to rapid socioeconomic development and urbanization. The prevalence of both these conditions is at least 4 times higher in urban than in rural Indians. The susceptibility to these conditions is probably a combination of ‘genetic' factors and the ‘epigenetic' programming in early life. The precipitating factors are usually found in the postnatal lifestyle factors including, diet, physical inactivity and psychosocial stress. All these factors promote obesity- generalized as well as central.

The metabolic and cardiovascular risk of obesity is thought to operate through adiposity (body fat percent) and recently adipocytes have been shown to be an active endocrine organ which secretes a number of chemicals (adipokines) which promote inflammation, a procoagulant state and endothelial dysfunction. Together these contribute to increased risk of type 2 diabetes and CHD. There is little information on proper measurements of body fat content and its distribution in Indians, most of the reports are based on anthropometric measurements.

The CRISIS study investigates the relationship between body fat percent and its distribution to risk factors for type 2 diabetes and CHD in middle-aged rural and Indian men. We specifically included a group of urban slum residents to study the effect of crowding and unhygienic environment on these risk factors. We measured body fat and its distribution by anthropometry, bioelectrical impedance, deuterated water, DXA, MRI and CT-scan.


Objectives

  • To validate epidemiological markers of obesity against reference measurements of body fat and its distribution
  • To study the association between body fat measurements and risk factors for type 2 diabetes and CHD
  • To assess the possible intermediary role of adipocytokines (proinflammatory and procoagulant) in this relationship.


Methodology and Design

150 male subjects aged 30 to 50 years were selected by multistage random sampling from three areas (rural, urban slum and urban middle class) in and around the city of Pune, Maharashtra.
Following subjects were excluded: known diabetic, hypertensive and CHD patients, those suffering from chronic infective/inflammatory disorders and those not willing to be studied. Those with an acute infective illness were rescheduled 4 weeks later.
Results

  • The mean age of these men was 38 y and body mass index (BMI) 22.0 kg/m 2 .
  • There was a progressive increase in weight, BMI, waist circumference and waist-hip ratio, and body fat percent from rural to urban slum and middle class residents. Despite their relatively low BMI and small number of obese individuals (WHO criteria) over 75% of urban middle class men were adipose (body fat >25%).
  • There was a progressive increase in circulating glucose, cholesterol and triglyceride concentrations, and the calculated insulin resistance (HOMA-R). The number of subjects with diabetes and hypertension also increased progressively.
  • Levels of inflammatory markers (total leucocyte count, IL-6, CRP) were higher in the urban compared to rural men, as were the levels of PAI-1. However, the carotid IMT were similar in the three groups of men.
  • The rural-urban difference in insulin resistance and glycemia was partly explained by adiposity. There was no further contribution of central obesity or inflammatory state. After the effect of adiposity was accounted for, there was a residual difference in the rural-urban men suggesting factors not measured in the study also contribute to the difference.
  • The higher risk of CHD in the urban compared to rural men was not explained by atherosclerosis as measured by carotid IMT but contributed by procoagulant state.
  • We developed an equation to calculate body fat from bioimpedance measurements in Indian men.
Urbanization is associated with higher body fat percent and central adiposity. These contribute to the higher risk of type 2 diabetes and CHD. As yet unidentified factors in the urban environment also seem to contribute.


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