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      Insulin Resistance and Body Fat Distribution in South Asian Men Compared to Caucasian Men

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          Abstract

          Objective

          South Asians are susceptible to insulin resistance even without obesity. We examined the characteristics of body fat content, distribution and function in South Asian men and their relationships to insulin resistance compared to Caucasians.

          Research Design and Methods

          Twenty-nine South Asian and 18 Caucasian non-diabetic men (age 27±3 and 27±3 years, respectively) underwent euglycemic-hyperinsulinemic clamp for insulin sensitivity, underwater weighing for total body fat, MRI of entire abdomen for intraperitoneal (IP) and subcutaneous abdominal (SA) fat and biopsy of SA fat for adipocyte size.

          Results

          Compared to Caucasians, in spite of similar BMI, South Asians had higher total body fat (22±6 and 15±4% of body weight; p-value<0.0001), higher SA fat (3.5±1.9 and 2.2±1.3 kg, respectively; p-value = 0.004), but no differences in IP fat (1.0±0.5 and 1.0±0.7 kg, respectively; p-value = 0.4). SA adipocyte cell size was significantly higher in South Asians (3491±1393 and 1648±864 µm2; p-value = 0.0001) and was inversely correlated with both glucose disposal rate (r-value = −0.57; p-value = 0.0008) and plasma adiponectin concentrations (r-value = −0.71; p-value<0.0001). Adipocyte size differences persisted even when SA was matched between South Asians and Caucasians.

          Conclusions

          Insulin resistance in young South Asian men can be observed even without increase in IP fat mass and is related to large SA adipocytes size. Hence ethnic excess in insulin resistance in South Asians appears to be related more to excess truncal fat and dysfunctional adipose tissue than to excess visceral fat.

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          Most cited references14

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          Relation of central obesity and insulin resistance with high diabetes prevalence and cardiovascular risk in South Asians.

          The hypothesis that the high mortality from coronary heart disease (CHD) in South Asians settled overseas compared with other populations is due to metabolic disturbances related to insulin resistance was tested in a population survey of 3193 men and 561 women aged 40-69 years in London, UK. The sample was assembled from industrial workforces and general practitioners' lists. In comparison with the European group, the South Asian group had a higher prevalence of diabetes (19% vs 4%), higher blood pressures, higher fasting and post-glucose serum insulin concentrations, higher plasma triglyceride, and lower HDL cholesterol concentrations. Mean waist-hip girth ratios and trunk skinfolds were higher in the South Asian than in the European group. Within each ethnic group waist-hip ratio was correlated with glucose intolerance, insulin, blood pressure, and triglyceride. These results confirm the existence of an insulin resistance syndrome, prevalent in South Asian populations and associated with a pronounced tendency to central obesity in this group. Control of obesity and greater physical activity offer the best chances for prevention of diabetes and CHD in South Asian people.
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            Fat cell enlargement is an independent marker of insulin resistance and 'hyperleptinaemia'.

            The aim of this study was to explore whether fat cell size in human subcutaneous and omental adipose tissue is independently related to insulin action and adipokine levels. Fat cells were prepared from abdominal subcutaneous biopsies obtained from 49 type 2 diabetic and 83 non-diabetic subjects and from omental biopsies obtained from 37 non-diabetic subjects. Cell size and insulin action on glucose uptake capacity in vitro were assessed in isolated fat cells. Insulin sensitivity in vivo was assessed with euglycaemic-hyperinsulinaemic clamps. Fasting blood samples were collected and adipokines and NEFA were measured. Negative correlations were found between subcutaneous fat cell size and insulin sensitivity assessed as M-value during clamp and as insulin action on glucose uptake in fat cells in vitro. This was seen in non-diabetic subjects after including age, sex and BMI in the analyses. No such relationship was found in type 2 diabetic subjects. In both groups, subcutaneous fat cell size correlated positively and independently with plasma levels of leptin but not to any of the other assessed adipokines. In non-diabetic subjects, omental fat cell size was independently and negatively correlated with insulin action in subcutaneous, but not omental, fat cells in vitro. Fat cell enlargement is associated with insulin resistance in non-diabetic individuals independently of BMI. This was not seen in type 2 diabetic subjects, suggesting that after development of type 2 diabetes other factors, not related to fat cell size, become more important for the modulation of insulin resistance.
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              Relationship between generalized and upper body obesity to insulin resistance in Asian Indian men.

              It has been proposed that excessive insulin resistance in Asian Indians living in urban areas or migrated to western countries is responsible for the higher incidence of type 2 diabetes and coronary heart disease observed in this population. To evaluate whether Asian Indians are more insulin resistant than Caucasians and to define the role of generalized and truncal adiposity, we performed hydrodensitometry, skinfold measurements, and euglycemic-hyperinsulinemic clamps in 21 healthy Asian Indian men and 23 Caucasian men of similar age and body fat content. The glucose disposal rate (Rd) was significantly lower in the Asian Indians than in the Caucasians (3.7+/-1.3 vs. 5.3+/-2.0 mg/min x kg lean body mass, respectively; P = 0.003). Despite similar total body fat content, Asian Indians had higher truncal adiposity than Caucasians (sum of truncal skinfolds, 117+/-37 and 92.4+/-38 mm, respectively). In both Asian Indians and Caucasians, the insulin sensitivity index (Rd/plasma insulin concentrations) was inversely correlated with both total body fat (r = -0.49; P<0.03 and r = -0.67; P<0.001, respectively) and sum of truncal skinfold thickness (r = -0.55; P<0.001 and r = -0.61; P<0.002, respectively). After adjustment for total body fat and truncal skinfold thickness, Asian Indians still had a significantly lower glucose disposal rate (P = 0.04). These results show that Asian Indian men are more insulin resistant than Caucasian men independently of generalized or truncal adiposity. The excessive insulin resistance in Asian Indians is probably a primary metabolic defect and may account for the excessive morbidity and mortality from diabetes and coronary heart disease in this population.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                PLoS ONE
                plos
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2007
                29 August 2007
                : 2
                : 8
                : e812
                Affiliations
                [1 ]Department of Internal Medicine, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
                [2 ]Division of Endocrinology and Metabolism, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
                [3 ]Center for Human Nutrition, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
                [4 ]Division of Gastrointestinal and Endocrine Surgery, University of Texas Southwestern Medical Center at Dallas, Dallas, Texas, United States of America
                University of California, Los Angeles, United States of America
                Author notes
                * To whom correspondence should be addressed. E-mail: Manisha.chandalia@ 123456utsouthwestern.edu (MC); Nicola.abate@ 123456utsouthwestern.edu (NA)

                Conceived and designed the experiments: NA MC. Performed the experiments: MC PS PL TS EL. Analyzed the data: NA MC. Contributed reagents/materials/analysis tools: NA MC. Wrote the paper: SG MC.

                Article
                07-PONE-RA-01215R1
                10.1371/journal.pone.0000812
                1950568
                17726542
                e2372785-0068-4433-9eaa-2b8e45ad283f
                Chandalia et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                History
                : 3 May 2007
                : 6 August 2007
                Page count
                Pages: 7
                Categories
                Research Article
                Diabetes and Endocrinology/Obesity
                Diabetes and Endocrinology/Type 2 Diabetes

                Uncategorized
                Uncategorized

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