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Objective: Impaired glucose tolerance (IGT) has been associated with alterations in numerous coronary heart disease risk factors, including postprandial hyperlipidemia. An excess visceral adipose tissue accumulation is also predictive of IGT and of an exaggerated postprandial lipemia. The objective of the present study was therefore to compare the respective contributions of visceral adipose tissue accumulation versus IGT with the variation in postprandial lipemia.Research Design and Methods: Potential differences in postprandial triglyceride (TG)-rich lipoprotein (TRL) levels following a standardized breakfast with a high fat content were examined among men characterized by normal glucose tolerance (NGT) or IGT. Sixty-seven men were classified according to their glucose tolerance status (<7.8 mmol/l [NGT] or between 7.8 and 11.1 mmol/l [IGT] 2 h after a 75-g oral glucose test).Results: Men with IGT showed the highest TRL-TG concentrations (P < 0.05) at the 4-, 6-, and 8-h time points compared with men with NGT. These higher postprandial TRL-TG levels among men with IGT were also accompanied by a greater postprandial TG total area under the incremental curve in all TRL fractions (large, medium, and small) (P < 0.05). Furthermore, subjects characterized by IGT had also the highest visceral adipose tissue accumulation (P < 0.009). When subgroups of IGT and NGT men were individually matched (n = 11) for similar visceral adipose tissue accumulation, no significant difference was found in postprandial responses of all TRL-TG fractions between the two groups.Conclusions: These results provide evidence that visceral adipose tissue accumulation is an important factor involved in the deterioration of postprandial lipemia noted among men with IGT. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of age on glucose metabolism by examining 1) glucose metabolism in young and middle-aged subjects when total or regional adiposity is taken into account and 2) in vitro glucose transport in adipose tissue explants from young and middle-aged women paired for total and abdominal adiposity.Research Design and Methods: Study 1: body composition, subcutaneous abdominal and visceral adipose tissue areas, and fasting and oral glucose-stimulated glucose and insulin were measured in 84 young and 81 middle-aged men and in 110 young and 91 middle-aged women. Study 2: glucose uptake in subcutaneous abdominal and visceral adipose tissue explants were measured in eight young and eight middle-aged women.Results: Study 1: young and middle-aged men showed similar subcutaneous abdominal tissue area, whereas fat mass and visceral adipose tissue were greater in middle-aged than in young men (P < 0.01). Fat mass and subcutaneous and visceral adipose tissue areas were greater in middle-aged as compared with young women (P < 0.01). Fasting plasma glucose and the glucose response to an oral glucose tolerance test were significantly higher in middle-aged than in young men and women (P < 0.001). Statistical control for visceral adipose tissue area eliminated the difference seen in glucose response in men and women. Study 2: glucose transport in subcutaneous and omental adipose tissue did not differ between young and middle-aged women.Conclusions: 1) Visceral obesity, more than age per se, correlates with glucose intolerance in middle-aged subjects; 2) aging does not influence in vitro adipose tissue glucose uptake. [ABSTRACT FROM AUTHOR]

Diabetes and obesity have long been known to be related. The recently characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been implicated as a molecular link between impaired glucose tolerance (IGT) and obesity in mice. A search for sequence variants at the human resistin locus identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An investigation into the association of these SNPs with diabetes and obesity revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage disequilibrium, that are associated with BMI. In nondiabetic individuals from the Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537 mutation (allelic frequency = 0.04) was significantly associated with an increase in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two populations were combined and adjusted for age and sex, both the g.-537 (odds ratio [OR] 2.72, 95% CI 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were associated with an increased risk for a BMI > or =30 kg/m(2). In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Elevated plasma free fatty acids (FFAs) are one important link between excess visceral adiposity, insulin resistance, and the development of type 2 diabetes. Effects of lifestyle interventions on FFA metabolism are poorly known. This open-label study was conducted to test the effects of a 1-year healthy eating/physical activity intervention program on plasma FFA homeostasis in 117 viscerally obese men with dyslipidemia associated with insulin resistance (waist circumference ≥90 cm, triglycerides ≥ 1.69 mmol/L, and/or HDL-cholesterol <1.03 mmol/L). RESEARCH DESIGN AND METHODS--Body weight, body composition, and fat distribution were assessed by dual-energy X-ray absorptiometry/computed tomography. Oral loads of lipid (60 g fat/m² body surface area) and glucose (75 g) were measured before and after the intervention. RESULTS--After 1 year of lifestyle intervention, visceral adiposity was reduced by -26% (95% CI -29 to -23), whereas cardiorespiratory fitness improved by +20% (95% CI +16 to +24). After 1 year, the suppression of FFAs after the glucose load improved, whereas insulin concentrations were drastically reduced. After the oral lipid load, the late increase in FFA was reduced together with reduced circulating insulin. We calculated an insulin sensitivity index to reflect the concentration of insulin needed tomanage plasma FFAs after the oral lipid load, which increased after the intervention and was associated with improved glucose tolerance, independent of changes in visceral or total adiposity. CONCLUSIONS--A 1-year healthy eating/physical activity intervention improved the suppression of FFAs after oral glucose and lipid load tests in viscerally obese men, possibly due to improved responsiveness to insulin. This insulin-mediated regulation of postprandial plasma FFA levels could be a link between visceral obesity and impaired glucose homeostasis. [ABSTRACT FROM AUTHOR]

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n = 662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 ± 0.2 and +0.22 ± 0.2 µU ⋅ min-1 ⋅ ml-1) than in the TT genotype (+0.27 ± 0.3 and -0.97 ± 0.3 µU ⋅ min-1 ⋅ ml-1 (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites. [ABSTRACT FROM AUTHOR]

We investigated the associations between the hepatic lipase gene (LIPC) -514C>T polymorphism and lipases, lipoproteins, and insulin sensitivity (Si) responses to exercise training. Hepatic lipase and lipoprotein lipase activities, plasma lipoprotein levels, and Si were measured in the sedentary state and post-exercise training in the Health, Risk Factors, Exercise Training, and Genetics (HERITAGE) Family Study (n=662). The LIPC -514C allele frequency was 0.516 (blacks) and 0.796 (whites). Baseline and post-exercise training hepatic lipase activities were 40% higher in CC homozygotes (P < 0.0001) in both races. Black CC homozygotes had lower baseline lipoprotein lipase activity, HDL cholesterol, HDL3, and apolipoprotein (apo)A-1 concentrations. White CC homozygotes had lower baseline HDL cholesterol, apoA-1, LDL cholesterol, and apoB levels that remained low post-exercise training. Baseline Si was not associated with the LIPC genotypes. However, training-induced improvements in Si both in blacks and whites were greater in CC homozygotes (+1.25 +/- 0.2 and +0.22 +/- 0.2 microU.min(-1).ml(-1)) than in the TT genotype (+0.27 +/- 0.3 and -0.97 +/- 0.3 microU.min(-1).ml(-1)) (P = 0.008 and P = 0.002, respectively). The LIPC -514C allele was associated with higher hepatic lipase activity in sedentary and physically active states and better Si responses to regular exercise both in black and white individuals. The benefits from an exercise program on Si are likely to be substantial in the general population given the high frequency of the LIPC -514C allele, particularly in whites.