Adiposity, inflammation and hyperglycaemia in rural and urban Indian men: Coronary Risk of Insulin Sensitivity in Indian Subjects (CRISIS) Study.

AIMS/HYPOTHESIS: The aim of this study was to investigate whether the higher prevalence of insulin resistance and glucose intolerance in urban compared with rural Indian men is related to their higher adiposity (percentage body fat) and the associated inflammatory state. METHODS: We studied 149 rural, 142 urban slum and 150 urban middle-class male residents (age 30-50 years), who were selected by stratified random sampling. We measured body fat (bioimpedance), waist circumference, glucose tolerance (75 g OGTT), insulin resistance [homeostasis model assessment (HOMA-IR)], beta cell function (insulinogenic index) and inflammatory markers (total leucocyte count, IL-6, TNF-alpha and C-reactive protein). RESULTS: Adiposity, waist circumference, HOMA-IR, insulinogenic index and both fasting and 120 min plasma glucose concentrations increased progressively from rural through to urban slum and urban middle-class men. Inflammatory markers were higher in urban than in rural men. Adiposity was strongly related to HOMA-IR (r = 0.57, p < 0.001) and to insulinogenic index and glycaemic parameters (r = 0.25, p < 0.001 for both). Adiposity explained approximately two thirds of the difference in HOMA-IR between the urban middle-class men and the rural and slum residents, but its contribution to the difference in insulinogenic index and 120 min plasma glucose concentration was not significant. Inclusion of C-reactive protein, IL-6 and total leucocyte count in the models did not further explain these results, nor did the inclusion of waist circumference. There was a significant residual difference after these adjustments. CONCLUSIONS/INTERPRETATION: Adiposity is a major contributor to the difference in insulin resistance between rural and urban Indian men; there was no additional contribution from inflammation or central obesity. Other unmeasured factors also seem to contribute to the metabolic differences between rural and urban men.

Body fat measurement in Indian men: comparison of three methods based on a two-compartment model.

UNLABELLED: Obesity is a major risk factor for diabetes and related disorders. The current classification of obesity is based on body mass index (BMI, kg/m(2)), which is a surrogate for the total body fat. Since the relationship between BMI and body fat varies in different populations, an independent validation of the BMI-body fat relationship in the population of interest is desirable. OBJECTIVES: (1) To study the validity of field methods of measuring body fat (multiple skinfolds and bioimpedance) against a criterion method (deuterium dilution) and (2) To compare the prevalence of obesity (WHO 2000 criteria for BMI) with adiposity (body fat >25%) in middle-aged Indian men in rural and urban Pune. DESIGN: Community-based multistage stratified random sampling of middle-aged men from rural and urban Pune for study of body composition and cardiovascular risk. A third of these men, selected to represent wide BMI distribution, were studied for body fat measurements by specific methods. SUBJECTS: A total of 141 healthy men, approximately similar number from rural, urban slums and middle class from Pune. They were 39.3 (+/-6.2) y old and had a BMI of 21.9 (+/-3.7) kg/m(2). MEASUREMENTS: Anthropometry (height, weight and multiple skinfold thicknesses) by trained observers using standardised technique to calculate body fat by Durnin and Womersley's equation. Total body water and body fat by bioelectrical impedance analysis (BIA) and deuterium oxide dilution (D(2)O). RESULTS: Mean total body fat was 14.3 kg (23.0%) by anthropometry, 16.5 kg (26.0%) by BIA and 15.3 kg (24.6%) by D(2)O method. Although there was a good correlation between fat estimation by three methods (r= approximately 0.9, P<0.001 all), compared to D(2)O method anthropometry underestimated body fat by 1.0 kg and BIA overestimated fat by 1.2 kg (P<0.001 both). Using the standard cut-point of 25% body fat for 'adiposity' 29.5% rural, 46.0% slum and 75.0% middle class men were adipose. These proportions were considerably higher than the number of men who were 'preobese' (BMI> or =25-29.9 kg/m(2), 9.0% rural, 22.0% urban slums and 27.0% urban middle class) and 'obese' (BMI >30 kg/m(2), 4.0% urban slums, none in rural and urban middle class). CONCLUSION: We recommend that future studies assessing risk for chronic diseases in Indians should measure adiposity by anthropometry (multiple skinfolds) or BIA (calibrated for Indians) rather than relying only on BMI cut-points.

Circulating lipids and cardiovascular risk in newly diagnosed non-insulin-dependent diabetic subjects in India.

Circulating concentrations of total cholesterol, triglycerides, non-esterified fatty acids (NEFA), glycerol, and 3-hydroxybutyrate (3-HB) were measured in 133 subjects with normal glucose tolerance (NGT), 78 with impaired-glucose-tolerance (IGT) and 189 non-insulin dependent (Type 2) diabetic (NIDDM) patients. Plasma cholesterol concentration was similar in the three groups; NGT (4.2 (2.3-7.5) mmol l-1, median (range)), IGT (4.7 (2.7-6.3)) and NIDDM (4.3 (2.3-6.9)). Plasma triglycerides (NGT 0.88 (0.37-2.80), IGT 1.26 (0.43-3.82) and NIDDM 1.38 (0.62-3.91) mmol l-1) and NEFA (NGT 0.81 (0.29-1.58), IGT 1.02 (0.33-1.87) and NIDDM 1.02 (0.48-2.77) mmol l-1) were higher in the two hyperglycaemic groups, but blood 3-HB concentration was similar in the three groups. Plasma cholesterol concentration in these subjects is lower than that reported in white Caucasians in the UK and USA and migrant Indian NIDDM patients in the UK. In NIDDM patients plasma cholesterol concentration was related to age, body mass index (BMI), and plasma glucose concentration while plasma triglyceride concentration was related to plasma NEFA and insulin (IRI) concentration. Evidence of ischaemia on electrocardiography in patients with diabetes was associated with higher age, blood pressure, plasma triglyceride, glucose, and IRI concentrations.

Ketosis resistance in fibrocalculous pancreatic diabetes: II. Hepatic ketogenesis after oral medium-chain triglycerides.

A majority of patients with fibrocalculous pancreatic diabetes (FCPD) do not become ketotic even in adverse conditions. It is not clear whether this ketosis resistance is due to reduced fatty acid release from adipose tissue or to impaired hepatic ketogenesis. We tested hepatic ketogenesis in FCPD patients using a ketogenic challenge of oral medium-chain triglycerides (MCTs) and compared it with that in matched insulin-dependent diabetes mellitus (IDDM) patients and healthy controls. After oral MCTs, FCPD patients showed only a mild increase in blood 3-hydroxybutyrate (3-HB) concentrations (median: fasting, 0.13 mmol/L; peak, 0.52) compared with IDDM patients (fasting, 0.44; peak, 3.39) and controls (fasting, 0.04; peak, 0.75). Plasma nonesterified fatty acid (NEFA) concentrations were comparable in the two diabetic groups (FCPD: fasting, 0.50 mmol/L; peak, 0.79; IDDM: fasting, 0.91; peak, 1.04). Plasma C-peptide concentrations were low and comparable in the two diabetic groups. Plasma glucagon concentrations were higher in IDDM patients in the fasting state, but declined to levels comparable to those in FCPD patients after oral MCTs. Plasma carnitine concentrations were comparable in the two groups of patients. It is concluded that the failure to stimulate ketogenesis under these conditions could be partly due to inhibition of a step beyond fatty acid entry into the mitochondria.

Urinary albumin excretion rate (AER) in newly-diagnosed type 2 Indian diabetic patients is associated with central obesity and hyperglycaemia.

Urinary albumin excretion rate (AER) was measured in non-diabetic controls (n = 143) and newly diagnosed impaired glucose tolerant (IGT, n = 64) and non-insulin-dependent (type 2) diabetic patients (n = 146). AER progressively increased from non-diabetic [3.7 (1.1-51.3) micrograms/min, median (5-95th centile)] to IGT [4.8 (1.3-53.7)] and diabetic [7.3 (1.4-91.6)] groups. Eight percent of non-diabetic, 19% of IGT and 23% of type 2 diabetic patients showed 'microalbuminuria' (AER, 20-200 micrograms/min) (non-diabetic vs diabetic P less than 0.01, non-diabetic vs IGT NS, IGT vs diabetic NS). AER was directly related to waist-hip ratio (P less than 0.001) and HbA1 (P less than 0.01) in diabetic patients; 80% of diabetic patients with microalbuminuria were men (P less than 0.06 compared to 'normoalbuminuric' diabetic patients). Association of AER with waist-hip ratio was present in men as well as women. Thus, in the newly diagnosed type 2 Indian diabetic patients AER is associated with central obesity in addition to its well known association with hyperglycaemia. Our findings offer a possible explanation for the increased risk of proteinuria in diabetic men than in women because men are centrally more obese. It could also explain previous reports of higher AER in migrant Asian diabetic patients in the U.K. compared to native white Caucasian diabetic patients because Asians are known to be more centrally obese.