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
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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)