Visceral Adiposity, Not Abdominal Subcutaneous Fat Area, Is Associated With an Increase in Future Insulin Resistance in Japanese Americans

Diabetes, May 2008

OBJECTIVE—Visceral adiposity is generally considered to play a key role in the metabolic syndrome. We sought to determine whether greater visceral adiposity directly measured by computed tomography (CT) is associated with increased future insulin resistance independent of other adipose depots. RESEARCH DESIGN AND METHODS— We followed 306 nondiabetic Japanese Americans over 10–11 years. Baseline variables included BMI; waist circumference; and abdominal, thoracic, and thigh fat areas measured by CT. Total fat area was estimated by the sum of all of these fat areas. Visceral adiposity was measured as intra-abdominal fat area at the umbilicus level. Total subcutaneous fat area was defined as total fat area minus intra-abdominal fat area. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMA-IR), fasting plasma insulin level, Matsuda index, and area under the oral glucose tolerance test curve (AUC) of insulin. RESULTS— Both baseline intra-abdominal fat area (P = 0.002) and HOMA-IR (P < 0.001) were independently associated with increased HOMA-IR at 10–11 years in a multiple linear regression model after adjustment for abdominal subcutaneous fat area, age, sex, 2-h plasma glucose level, and incremental insulin response. Intra-abdominal fat area remained a significant predictor of increased HOMA-IR at 10–11 years even after adjustment for total subcutaneous fat area, total fat area, BMI, or waist circumference, but no other measure of CT-measured regional or total adiposity was significantly related with HOMA-IR at 10–11 years in models that contained intra-abdominal fat area. Similar results were obtained for predicting future fasting plasma insulin level, Matsuda index, and AUC of insulin. CONCLUSIONS— Greater visceral adiposity is associated with an increase in future insulin resistance.

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Visceral Adiposity, Not Abdominal Subcutaneous Fat Area, Is Associated With an Increase in Future Insulin Resistance in Japanese Americans

Tomoshige Hayashi 1 2 Edward J. Boyko 0 2 Marguerite J. McNeely 0 Donna L. Leonetti 3 Steven E. Kahn 0 2 Wilfred Y. Fujimoto 0 0 Department of Medicine, University of Washington , Seattle, Washington ; and the 1 Department of Preventive Medicine and Environmental Health, Graduate School of Medicine, Osaka City University , Osaka, Japan ; the 2 Epidemiologic Research and Information Center, Veterans Affairs Puget Sound Health Care System ; the 3 Department of Anthropology, University of Washington , Seattle, Washington OBJECTIVEVisceral adiposity is generally considered to play a key role in the metabolic syndrome. We sought to determine whether greater visceral adiposity directly measured by computed tomography (CT) is associated with increased future insulin resistance independent of other adipose depots. RESEARCH DESIGN AND METHODSWe followed 306 nondiabetic Japanese Americans over 10 -11 years. Baseline variables included BMI; waist circumference; and abdominal, thoracic, and thigh fat areas measured by CT. Total fat area was estimated by the sum of all of these fat areas. Visceral adiposity was measured as intra-abdominal fat area at the umbilicus level. Total subcutaneous fat area was defined as total fat area minus intra-abdominal fat area. Insulin resistance was evaluated by homeostasis model assessment for insulin resistance (HOMAIR), fasting plasma insulin level, Matsuda index, and area under the oral glucose tolerance test curve (AUC) of insulin. RESULTSBoth baseline intra-abdominal fat area (P 0.002) and HOMA-IR (P 0.001) were independently associated with increased HOMA-IR at 10 -11 years in a multiple linear regression model after adjustment for abdominal subcutaneous fat area, age, sex, 2-h plasma glucose level, and incremental insulin response. Intra-abdominal fat area remained a significant predictor of increased HOMA-IR at 10 -11 years even after adjustment for total subcutaneous fat area, total fat area, BMI, or waist circumference, but no other measure of CT-measured regional or total adiposity was significantly related with HOMA-IR at 10 -11 years in models that contained intra-abdominal fat area. Similar results were obtained for predicting future fasting plasma insulin level, Matsuda index, and AUC of insulin. CONCLUSIONSGreater visceral adiposity is associated with an increase in future insulin resistance. Diabetes 57:12691275, 2008 - A drome and each of its components is complex lthough the pathogenesis of the metabolic synand not fully understood, both insulin resistance and central adipose tissue appear to be important. Moreover, central obesity has been reported to correlate strongly with insulin resistance (17). However, excess central obesity can accumulate either intraperitoneally or subcutaneously, and this has led to a debate whether visceral or abdominal subcutaneous fat is more strongly associated with insulin resistance (17). Some studies have reported that excess visceral fat is more strongly associated with insulin resistance than any other adipose tissue compartment (15). Others have reported that excess abdominal subcutaneous fat is more strongly associated with insulin resistance than visceral fat (6,7). Because these studies were all cross-sectional, conclusions about temporal sequence and cause and effect relationships cannot be made. Although the glucose clamp is considered to be the gold standard test for examining insulin resistance, practical considerations limit its use in large-scale epidemiologic research. The homeostasis model assessment for insulin resistance (HOMA-IR) was developed to serve as a surrogate measure of insulin resistance that only requires assessment of basal glucose and insulin concentrations (8), and it, along with fasting plasma insulin, has frequently been used in epidemiological studies to assess insulin sensitivity (9). Because fasting plasma insulin and HOMA-IR reflect mainly hepatic insulin resistance in the basal state, other surrogate measures have been developed to assess whole-body insulin sensitivity, such as the Matsuda index derived from the oral glucose tolerance test. This measure has been reported to be highly correlated with the rate of whole-body insulin disposal during the euglycemic insulin clamp (10). The purpose of this study was to determine whether greater visceral adiposity directly measured by computed tomography (CT) was associated independent of other adipose depots, with a future increase in insulin resistance as assessed by multiple measures, including HOMA-IR, fasting plasma insulin, the Matsuda index, and the insulin area under the oral glucose tolerance test curve (AUC) (10). RESEARCH DESIGN AND METHODS The study population consisted of second- and third-generation (mean age 50.3 years) Japanese Americans enrolled in the Japanese American Community Diabetes Study who did not have type 2 diabetes at entry or during the 10to 11-year follow-up. Details about selection and recruitment have been described (...truncated)


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Tomoshige Hayashi, Edward J. Boyko, Marguerite J. McNeely, Donna L. Leonetti, Steven E. Kahn, Wilfred Y. Fujimoto. Visceral Adiposity, Not Abdominal Subcutaneous Fat Area, Is Associated With an Increase in Future Insulin Resistance in Japanese Americans, Diabetes, 2008, pp. 1269-1275, 57/5, DOI: 10.2337/db07-1378