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Biomedical subjects

B H Goodpaster

Publications and source records attributed to B H Goodpaster.

At least 19 recordsLinked to original sources

Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The Health ABC Study.

AIMS: We investigated whether low subcutaneous thigh fat is an independent risk factor for unfavourable glucose and lipid levels, and whether these associations differ between sexes, and between white and black adults. Our secondary aim was to investigate which body composition characteristics (lean tissue, fat tissue) are reflected by anthropometric measures (waist and thigh circumference). METHODS: Anthropometric measurements and computed tomography of the abdomen and of the thigh were performed for all participants of the Health, Aging and Body Composition Study, who were aged 70-79 years. Fasting glucose, triglycerides and HDL-cholesterol, and 2-h postload glucose were determined. RESULTS: After excluding those already diagnosed with diabetes or dyslipidaemia, we analysed data from 2,106 participants. After adjustment for abdominal subcutaneous and visceral fat, and intermuscular thigh fat, larger thigh subcutaneous fat area was statistically significantly associated with lower ln-transformed triglycerides [standardised beta (95% CI) -0.12 (-0.20 to -0.04) in men and -0.13 (-0.21 to -0.05) in women] and higher ln-HDL-cholesterol [0.10 (0.02 to 0.19) and 0.09 (0.01 to 0.18), respectively]. The associations with lower glucose levels were strong in men [-0.11 (-0.20 to -0.02) for fasting and -0.14 (-0.23 to -0.05) for postload glucose], but not statistically significant in women [-0.02 (-0.10 to 0.07) and -0.04 (-0.13 to 0.05), respectively]. There were no differences in the associations between white and black persons. Waist circumference was more strongly associated with abdominal subcutaneous fat, and this association became stronger with increasing BMI, whereas the association with visceral fat became weaker. Thigh circumference was equally dependent on thigh fat and thigh muscle in men, whereas in women the fat component was the main contributor. CONCLUSION: Larger subcutaneous thigh fat is independently associated with more favourable glucose (in men) and lipid levels (in both sexes) after accounting for abdominal fat depots, which are associated with unfavourable glucose and lipid levels. Anthropometric measures reflect different fat depots at different levels of BMI at the abdomen, and reflect both fat and lean tissue at the thigh. These results emphasise the importance of accurate measures of regional body composition when investigating potential health risks.

Abdomen↗

Fat content in individual muscle fibers of lean and obese subjects.

OBJECTIVE: To examine skeletal muscle intracellular triglyceride concentration in different fiber types in relation to obesity. DESIGN: Skeletal muscle fiber type distribution and intracellular lipid content were measured in vastus lateralis samples obtained by needle biopsy from lean and obese individuals. SUBJECTS: Seven lean controls (body mass index (BMI) 23.0+/-3.3 kg/m(2); mean+/-s.d.) and 14 obese (BMI 33.7+/-2.7 kg/m(2)) individuals; both groups included comparable proportions of men and women. MEASUREMENTS: Samples were histochemically stained for the identification of muscle fiber types (myosin ATPase) and intracellular lipid aggregates (oil red O dye). The number and size of fat aggregates as well as their concentration within type I, IIA and IIB muscle fiber types were measured. The cellular distribution of the lipid aggregates was also examined. RESULTS: The size of fat aggregates was not affected by obesity but the number of lipid droplets within muscle fibers was twice as abundant in obese compared to lean individuals. This was seen in type I (298+/-135 vs 129+/-75; obese vs lean, P<0.05), IIA (132+/-67 vs 79+/-29; P<0.05), and IIB (103+/-63 vs 51+/-13; P<0.05) muscle fibers. A more central distribution of lipid droplets was observed in muscle fibers of obese compared to lean subjects (27.2+/-5.7 vs 19.7+/-6.4%; P<0.05). CONCLUSION: The higher number of lipid aggregates and the disposition to a greater central distribution in all fiber types in obesity indicate important changes in lipid metabolism and/or storage that are fiber type-independent.

Adult↗

Effects of exercise on glucose homeostasis in Type 2 diabetes mellitus.

PURPOSE: This review has evaluated the effectiveness of physical activity in the treatment and prevention of Type 2 diabetes mellitus (DM). METHODS: The available literature was reviewed through a computerized search (MEDLINE, 1966--2000) to classify studies examining the influence of physical activity on the treatment and prevention of Type 2 DM. Additional studies were reviewed through ancestral searches from their bibliographies. RESULTS: It is not possible at the present time to discern from the available literature whether a dose-response relationship exists between exercise volume or intensity and improvements in glucose control in Type 2 DM. Large-scale, prospective studies indicate that higher levels of physical activity are clearly associated with a lower incidence of Type 2 DM. However, no randomized controlled trials have been conducted to address the dose-response effect of exercise or physical activity on diabetes treatment or prevention. CONCLUSION: It is uncertain whether there is a dose-response effect of exercise on improved glucose control in Type 2 DM. There does appear to be, however, a limited amount of evidence suggesting that increasing levels of physical activity contribute to better diabetes prevention. Clearly, additional studies are needed to determine the influence of physical activity on the treatment and prevention of Type 2 DM.

Adult↗

Attenuation of skeletal muscle and strength in the elderly: The Health ABC Study.

Although loss of muscle mass is considered a cause of diminished muscle strength with aging, little is known regarding whether composition of aging muscle affects strength. The skeletal muscle attenuation coefficient, as determined by computed tomography, is a noninvasive measure of muscle density, and lower values reflect increased muscle lipid content. This investigation examined the hypothesis that lower values for muscle attenuation are associated with lower voluntary isokinetic knee extensor strength at 60 degrees/s in 2,627 men and women aged 70-79 yr participating in baseline studies of the Health ABC Study, a longitudinal study of health, aging, and body composition. Strength was higher in men than in women (132.3 +/- 34.5 vs. 81.4 +/- 22.0 N x m, P < 0.01). Men had greater muscle attenuation values (37.3 +/- 6.5 vs. 34.7 +/- 7.0 Hounsfield units) and muscle cross-sectional area (CSA) at the midthigh than women (132.7 +/- 22.4 vs. 93.3 +/- 17.5 cm(2), P < 0.01 for both). The strength per muscle CSA (specific force) was also higher in men (1.00 +/- 0.21 vs. 0.88 +/- 0.21 N x m x cm(-2)). The attenuation coefficient was significantly lower for hamstrings than for quadriceps (28.7 +/- 8.7 vs. 41.1 +/- 6.9 Hounsfield units, P < 0.01). Midthigh muscle attenuation values were lowest (P < 0.01) in the eldest men and women and were negatively associated with total body fat (r = -0.53, P < 0.01). Higher muscle attenuation values were also associated with greater specific force production (r = 0.26, P < 0.01). Multivariate regression analysis revealed that the attenuation coefficient of muscle was independently associated with muscle strength after adjustment for muscle CSA and midthigh adipose tissue in men and women. These results demonstrate that the attenuation values of muscle on computed tomography in older persons can account for differences in muscle strength not attributed to muscle quantity.

Adipose Tissue↗

Plasma fatty acids, adiposity, and variance of skeletal muscle insulin resistance in type 2 diabetes mellitus.

Skeletal muscle insulin resistance (IR) is typically severe in type 2 diabetes mellitus (DM). However, the factors that account for interindividual differences in the severity of IR are not well understood. The current study was undertaken to examine the respective roles of plasma FFA, regional adiposity, and other metabolic factors as determinants of the severity of skeletal muscle IR in type 2 DM. Twenty-three subjects (12 women and 11 men) with type 2 DM underwent positron emission tomography imaging using [18F]2-fluoro-2-deoxyglucose during euglycemic insulin infusions (120 mU/min x m2) to measure skeletal muscle IR, using Patlak analysis of the tissue activity curves. Body composition analysis included body mass index, fat mass, and fat-free mass by dual energy x-ray tomography, and computed tomography determinations of visceral adiposity, thigh adipose tissue distribution, and muscle composition. Body mass index, fat mass, subfascial adiposity in the thigh, and visceral adipose tissue (VAT) were all significantly related to skeletal muscle IR (r = -0.48 to -0.63; P < 0.01). However, the strongest simple correlate of IR in skeletal muscle was insulin-suppressed plasma FFA (r = -0.81; P < 0.001). VAT was the sole component of adiposity that significantly correlated with insulin-suppressed plasma FFA concentration (r = 0.64; P < 0.001). These findings indicate that the severity of skeletal muscle IR in type 2 DM is closely related to the IR of suppressing lipolysis and that plasma fatty acids and VAT are key elements mediating the link between obesity and skeletal muscle IR in type 2 DM.

Adipose Tissue↗

Skeletal muscle lipid content and insulin resistance: evidence for a paradox in endurance-trained athletes.

We examined the hypothesis that an excess accumulation of intramuscular lipid (IMCL) is associated with insulin resistance and that this may be mediated by the oxidative capacity of muscle. Nine sedentary lean (L) and 11 obese (O) subjects, 8 obese subjects with type 2 diabetes mellitus (D), and 9 lean, exercise-trained (T) subjects volunteered for this study. Insulin sensitivity (M) determined during a hyperinsulinemic (40 mU x m(-2)min(-1)) euglycemic clamp was greater (P < 0.01) in L and T, compared with O and D (9.45 +/- 0.59 and 10.26 +/- 0.78 vs. 5.51 +/- 0.61 and 1.15 +/- 0.83 mg x min(-1)kg fat free mass(-1), respectively). IMCL in percutaneous vastus lateralis biopsy specimens by quantitative image analysis of Oil Red O staining was approximately 2-fold higher in D than in L (3.04 +/- 0.39 vs. 1.40 +/- 0.28% area as lipid; P < 0.01). IMCL was also higher in T (2.36 +/- 0.37), compared with L (P < 0.01). The oxidative capacity of muscle determined with succinate dehydrogenase staining of muscle fibers was higher in T, compared with L, O, and D (50.0 +/- 4.4, 36.1 +/- 4.4, 29.7 +/- 3.8, and 33.4 +/- 4.7 optical density units, respectively; P < 0.01). IMCL was negatively associated with M (r = -0.57, P < 0.05) when endurance-trained subjects were excluded from the analysis, and this association was independent of body mass index. However, the relationship between IMCL and M was not significant when trained individuals were included. There was a positive association between the oxidative capacity and M among nondiabetics (r = 0.37, P < 0.05). In summary, skeletal muscle of trained endurance athletes is markedly insulin sensitive and has a high oxidative capacity, despite having an elevated lipid content. In conclusion, the capacity for lipid oxidation may be an important mediator of the association between excess muscle lipid accumulation and insulin resistance.

Adult↗

Skeletal muscle triglyceride. An aspect of regional adiposity and insulin resistance.

Recent evidence derived from four independent methods indicates that an excess triglyceride storage within skeletal muscle is linked to insulin resistance. Potential mechanisms for this association include apparent defects in fatty acid metabolism that are centered at the mitochondria in obesity and in type 2 diabetes. Specifically, defects in the pathways for fatty acid oxidation during postabsorptive conditions are prominent, leading to diminished use of fatty acids and increased esterification and storage of lipid within skeletal muscle. These impairments in fatty acid metabolism during fasting conditions may be related to a metabolic inflexibility in insulin resistance that is not limited to defects in glucose metabolism during insulin-stimulated conditions. Thus, there is substantial evidence implicating perturbations in fatty acid metabolism during accumulation of skeletal muscle triglyceride and in the pathogenesis of insulin resistance. Weight loss by caloric restriction improves insulin sensitivity, but the effects on fatty acid metabolism are less conspicuous. Nevertheless, weight loss decreases the content of triglyceride within skeletal muscle, perhaps contributing to the improvement in Insulin action with weight loss. Alterations in skeletal muscle substrate metabolism provide insight into the link between skeletal muscle triglyceride accumulation and insulin resistance, and they may lead to more appropriate therapies to improve glucose and fatty acid metabolism in obesity and in type 2 diabetes.

Adipose Tissue↗

Intramuscular lipid content is increased in obesity and decreased by weight loss.

The triglyceride content of skeletal muscle samples determined by lipid extraction correlates with the severity of insulin-resistant glucose metabolism in muscle. To determine whether this reflects increased triglyceride within muscle fibers and to test the hypothesis that the lipid content in muscle fibers is increased in obesity, the present study was undertaken using quantitative histochemistry of Oil Red O staining of vastus lateralis muscle. A percutaneous muscle biopsy was performed in 9 lean subjects, 15 obese subjects without type 2 diabetes mellitus (DM), and 10 obese subjects with type 2 DM (body mass index [BMI], 23.4+/-1.0, 33.6+/-0.6, and 36.0+/-1.1 kg x m(-2) for lean, obese, and DM, respectively). Eight obese and 7 DM subjects had a weight loss and reassessment of muscle lipid content. Transverse muscle cryosections were examined by light microscopy with quantitative image analysis (grayscale images obtained by analog to digital conversion) to determine a lipid accumulation index (LAI) based on the percentage of cross-sectional fiber area occupied by lipid droplets. Muscle fiber lipid content was greater in obese individuals with DM than in lean individuals (3.62%+/-0.65% v 1.42%+/-0.28%, P < .05) but was not different in obese individuals without DM (2.53%+/-0.41%). Weight loss reduced the LAI from 3.43%+/-0.53% to 2.35%+/-0.31%. In summary, lipid accumulation within muscle fibers is significantly increased in obesity and is reduced by weight loss. This provides important information regarding the accumulation and distribution of skeletal muscle triglyceride in type 2 DM and obesity.

Adult↗

Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus.

BACKGROUND: Adipose tissue (AT) content of the thigh is generally not considered to be associated with insulin resistance (IR), but it is unclear whether the distribution of AT in the thigh is a determinant of IR. OBJECTIVE: We investigated whether subcompartments of AT within the thigh are determinants of IR. DESIGN: Midthigh AT, muscle composition, and insulin sensitivity were compared in 11 obese patients with type 2 diabetes mellitus (DM); 40 obese, glucose-tolerant (GT) and 15 lean, GT volunteers; and 38 obese subjects who completed a weight-loss program. Midthigh AT area measured with computed tomography was partitioned into 3 components: subcutaneous AT (SCAT), AT beneath the fascia (SFAT), and AT infiltrating muscle groups (IMAT). Muscle attenuation characteristics were determined. RESULTS: Obese DM and obese GT subjects had lower insulin sensitivity than lean GT subjects. SCAT was greater in obesity, yet did not correlate with insulin sensitivity. SFAT was approximately 8% of total thigh AT and correlated with insulin sensitivity. IMAT was highest in obese DM, and although it accounted for only approximately 3% of thigh AT, it was a strong correlate of insulin sensitivity. Mean attenuation was highest in lean subjects and was associated with higher insulin sensitivity. Weight loss reduced the amount of thigh AT, the proportion of thigh IMAT, and the amount of low-density thigh muscle. CONCLUSIONS: SFAT and IMAT are markers of IR in obesity and DM although they are much smaller than SCAT, which does not predict IR. Muscle composition reflecting increased fat content is also associated with IR.

Absorptiometry, Photon↗

Composition of skeletal muscle evaluated with computed tomography.

Computed tomography (CT) can yield quantitative imaging data from detailed maps of linear attenuation coefficients within tissue. The attenuation characteristics of skeletal muscle and adipose tissue can be quantified in vivo to provide information about the composition of skeletal muscle and the distribution of adipose tissue within muscle. Several studies have taken advantage of this utility to quantify skeletal muscle composition and fatty infiltration of muscle, in particular to quantify the attenuation characteristics of muscle as a marker of its lipid content. In this manner we found that the mean muscle attenuation of skeletal muscle reflects an increase in its fat content in obesity, and that this regional body composition parameter is strongly related to insulin-resistant glucose metabolism. In addition, muscle composition and adipose tissue distribution within muscle may be altered with clinical weight-loss interventions. CT may also provide important information about the changes in muscle mass and composition with aging and disease, which may, in turn, affect the muscle's function. In summary, CT can provide important quantitative data on the composition of muscle, and the distribution of adipose tissue within it, and this may be important in examining the relationships among skeletal muscle metabolism, lipid accumulation within muscle, and muscle function.

Adipose Tissue↗

Subdivisions of subcutaneous abdominal adipose tissue and insulin resistance.

Whereas truncal (central) adiposity is strongly associated with the insulin resistant metabolic syndrome, it is uncertain whether this is accounted for principally by visceral adiposity (VAT). Several recent studies find as strong or stronger association between subcutaneous abdominal adiposity (SAT) and insulin resistance. To reexamine the issue of truncal adipose tissue depots, we performed cross-sectional abdominal computed tomography, and we undertook the novel approach of partitioning SAT into the plane superficial to the fascia within subcutaneous adipose tissue (superficial SAT) and that below this fascia (deep SAT), as well as measurement of VAT. Among 47 lean and obese glucose-tolerant men and women, insulin-stimulated glucose utilization, measured by euglycemic clamp, was strongly correlated with both VAT and deep SAT (r = -0.61 and -0.64, respectively; both P < 0.001), but not with superficial SAT (r = -0.29, not significant). Also, VAT and deep SAT followed a highly congruent pattern of associations with glucose and insulin area under the curve (75-g oral glucose tolerance test), mean arterial blood pressure, apoprotein-B, high-density lipoprotein cholesterol, and triglyceride. Superficial SAT had markedly weaker association with all these parameters and instead followed the pattern observed for thigh subcutaneous adiposity. We conclude that there are two functionally distinct compartments of adipose tissue within abdominal subcutaneous fat and that the deep SAT has a strong relation to insulin resistance.

Abdomen↗

Skeletal muscle attenuation determined by computed tomography is associated with skeletal muscle lipid content.

The purpose of this investigation was to validate that in vivo measurement of skeletal muscle attenuation (MA) with computed tomography (CT) is associated with muscle lipid content. Single-slice CT scans performed on phantoms of varying lipid concentrations revealed good concordance between attenuation and lipid concentration (r(2) = 0.995); increasing the phantom's lipid concentration by 1 g/100 ml decreased its attenuation by approximately 1 Hounsfield unit (HU). The test-retest coefficient of variation for two CT scans performed in six volunteers was 0.51% for the midthigh and 0.85% for the midcalf, indicating that the methodological variability is low. Lean subjects had significantly higher (P < 0.01) MA values (49.2 +/- 2.8 HU) than did obese nondiabetic (39.3 +/- 7.5 HU) and obese Type 2 diabetic (33.9 +/- 4. 1 HU) subjects, whereas obese Type 2 diabetic subjects had lower MA values that were not different from obese nondiabetic subjects. There was also good concordance between MA in midthigh and midcalf (r = 0.60, P < 0.01), psoas (r = 0.65, P < 0.01), and erector spinae (r = 0.77, P < 0.01) in subsets of volunteers. In 45 men and women who ranged from lean to obese (body mass index = 18.5 to 35.9 kg/m(2)), including 10 patients with Type 2 diabetes mellitus, reduced MA was associated with increased muscle fiber lipid content determined with histological oil red O staining (P = -0.43, P < 0. 01). In a subset of these volunteers (n = 19), triglyceride content in percutaneous biopsy specimens from vastus lateralis was also associated with MA (r = -0.58, P = 0.019). We conclude that the attenuation of skeletal muscle in vivo determined by CT is related to its lipid content and that this noninvasive method may provide additional information regarding the association between muscle composition and muscle function.

Adult↗

Reexamining the sarcopenia hypothesis. Muscle mass versus muscle strength. Health, Aging, and Body Composition Study Research Group.

The association of muscle mass and muscle strength with lower-extremity performance, as measured by timed repeated chair stands, was investigated using preliminary data from 3,075 Black and White participants (70-79 years old) in the Health, Aging, and Body Composition Study. Leg muscle mass (LM) was measured by dual-energy X-ray absorptiometry (Hologic QDR 4500). The maximal isokinetic torque of the leg extensors (LS) was measured at 60 degrees/s using a Kin-Com isokinetic dynamometer. Men were stronger, had greater LM, and better performance than women. As expected, low LS was associated with poorer performance after adjusting for race, study site, and body fat. Low LM was associated with poorer performance in men and women, with a potential threshold effect in women only. When LS and LM were modeled simultaneously, only LS remained independently associated with performance. In conclusion, muscle strength, but not muscle mass, is independently associated with lower-extremity performance.

Absorptiometry, Photon↗

Visceral obesity and insulin resistance are associated with plasma aldosterone levels in women.

OBJECTIVE: Both obesity and insulin resistance increase the risk of hypertension and other cardiovascular diseases, but the mechanisms linking these abnormalities are unknown. The current study was undertaken to examine the effects of obesity, fat distribution, and insulin resistance on plasma levels of aldosterone and other adrenal steroids that might contribute to sequelae of obesity. RESEARCH METHODS AND PROCEDURES: Twenty-eight normotensive premenopausal women and 27 normotensive men with a wide range of body fat underwent measurements of visceral adipose tissue by CT scan, total fat mass by dual energy X-ray absorptiometry, blood pressure, insulin sensitivity, and plasma levels of three adrenal steroid hormones. RESULTS: Plasma aldosterone in women correlated directly with visceral adipose tissue (r=0.66, p<0.001) and inversely with insulin sensitivity (r=-0.67, p<0.001), and these associations were independent of plasma renin activity. There were no corresponding correlations in men. Plasma aldosterone was significantly correlated with plasma cortisol and dehydroepiandrosterone sulfate in women. Seventeen women and 15 men completed a weight-reduction regimen, losing an average of 15.1+1.2 kg. After weight loss, plasma aldosterone was significantly lower and insulin sensitivity higher; however, the correlations of aldosterone with visceral adipose tissue and insulin sensitivity in women persisted (p = 0.09 and 0.07, respectively). Although none of the women were hypertensive, blood pressure correlated with plasma aldosterone both before and after weight loss. DISCUSSION: We conclude that visceral adiposity and insulin resistance are associated with increased plasma aldosterone and other adrenal steroids that may contribute to cardiovascular diseases in obese women.

Absorptiometry, Photon↗

Effects of physical activity on insulin action and glucose tolerance in obesity.

PURPOSE: The purpose of this paper is to examine the effect of physical activity on glucose tolerance in relation to obesity. METHODS: We reviewed current literature, with particular emphasis on randomized clinical trials, to prepare an evidence-based evaluation of the effects of physical activity on glucose intolerance in obesity. RESULTS: This literature review indicates that physical activity has favorable effects on reducing insulin resistance in obesity and among patients with type 2 diabetes mellitus. Improvement in glucose tolerance is less consistently observed and is related to intensity of exercise, collateral changes in adiposity, the interval between exercise and testing of glucose tolerance, and the baseline severity of glucose intolerance. CONCLUSION: A review of currently published clinical trial data supports the conclusion that physical activity can reduce insulin resistance and improve glucose intolerance in obesity.

Diabetes Mellitus, Type 2↗

Effects of weight loss on regional fat distribution and insulin sensitivity in obesity.

Weight loss (WL) decreases regional depots of adipose tissue and improves insulin sensitivity, two parameters that correlate before WL. To examine the potential relation of WL-induced change in regional adiposity to improvement in insulin sensitivity, 32 obese sedentary women and men completed a 4-month WL program and had repeat determinations of body composition (dual-energy X-ray absorptiometry and computed tomography) and insulin sensitivity (euglycemic insulin infusion). There were 15 lean men and women who served as control subjects. VO2max was unaltered with WL (39.2 +/- 0.8 vs. 39.8 +/- 1.1 ml x fat-free mass [FFM](-1) x min(-1)). The WL intervention achieved significant decreases in weight (100.2 +/- 2.6 to 85.5 +/- 2.1 kg), BMI (34.3 +/- 0.6 to 29.3 +/- 0.6 kg/m2), total fat mass (FM) (36.9 +/- 1.5 to 26.1 +/- 1.3 kg), percent body fat (37.7 +/- 1.3 to 31.0 +/- 1.5%), and FFM (59.2 +/- 2.3 to 55.8 +/- 2.0 kg). Abdominal subcutaneous and visceral adipose tissue (SAT and VAT) were reduced (494 +/- 19 to 357 +/- 18 cm2 and 157 +/- 12 to 96 +/- 7 cm2, respectively). Cross-sectional area of low-density muscle (LDM) at the mid-thigh decreased from 67 +/- 5 to 55 +/- 4 cm2 after WL. Insulin sensitivity improved from 5.9 +/- 0.4 to 7.3 +/- 0.5 mg x FFM(-1) x min(-1) with WL. Rates of insulin-stimulated nonoxidative glucose disposal accounted for the majority of this improvement (3.00 +/- 0.3 to 4.3 +/- 0.4 mg x FFM(-1) x min(-1)). Serum leptin, triglycerides, cholesterol, and insulin all decreased after WL (P < 0.01). After WL, insulin sensitivity continued to correlate with generalized and regional adiposity but, with the exception of the percent decrease in VAT, the magnitude of improvement in insulin sensitivity was not predicted by the various changes in body composition. These interventional weight loss data underscore the potential importance of visceral adiposity in relation to insulin resistance and otherwise suggest that above a certain threshold of weight loss, improvement in insulin sensitivity does not bear a linear relationship to the magnitude of weight loss.

Abdomen↗

Role of muscle in triglyceride metabolism.

It has long been recognized that skeletal muscle can contain modest stores of triglyceride and that this depot of fuel can make a major contribution to energy production during exercise. More recently, an adverse effect of muscle triglyceride has begun to be defined within the context of insulin resistance. Animal and clinical investigations have revealed a significant relation between increased muscle triglyceride and insulin resistance, at least among mostly sedentary individuals. These observations have stimulated the development, or at least the refinement, of new methodologies to assess this aspect of 'regional' fat deposition. In parallel, there has also been important new work designed to enable better understanding of the factors that regulate muscle triglyceride and to determine whether fatty acids taken up by skeletal muscle are oxidized or stored, and how these pathways might be either altered by the presence of insulin resistance or, in turn, contribute to the pathogenesis of insulin resistance.

Animals↗

Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat.

Whether visceral adipose tissue has a uniquely powerful association with insulin resistance or whether subcutaneous abdominal fat shares this link has generated controversy in the area of body composition and insulin sensitivity. An additional issue is the potential role of fat deposition within skeletal muscle and the relationship with insulin resistance. To address these matters, the current study was undertaken to measure body composition, aerobic fitness, and insulin sensitivity within a cohort of sedentary healthy men (n = 26) and women (n = 28). The subjects, who ranged from lean to obese (BMI 19.6-41.0 kg/m2), underwent dual energy X-ray absorptiometry (DEXA) to measure fat-free mass (FFM) and fat mass (FM), computed tomography to measure cross-sectional abdominal subcutaneous and visceral adipose tissue, and computed tomography (CT) of mid-thigh to measure muscle cross-sectional area, muscle attenuation, and subcutaneous fat. Insulin sensitivity was measured using the glucose clamp technique (40 mU.m-2.min-1), in conjunction with [3-3H]glucose isotope dilution. Maximal aerobic power (VO2max) was determined using an incremental cycling test. Insulin-stimulated glucose disposal (Rd) ranged from 3.03 to 16.83 mg.min-1.kg-1 FFM. Rd was negatively correlated with FM (r = -0.58), visceral fat (r = -0.52), subcutaneous abdominal fat (r = -0.61), and thigh fat (r = -0.38) and positively correlated with muscle attenuation (r = 0.48) and VO2max (r = 0.26, P < 0.05). In addition to manifesting the strongest simple correlation with insulin sensitivity, in stepwise multiple regression, subcutaneous abdominal fat retained significance after adjusting for visceral fat, while the converse was not found. Muscle attenuation contributed independent significance to multiple regression models of body composition and insulin sensitivity, and in analysis of obese subjects, muscle attenuation was the strongest single correlate of insulin resistance. In summary, as a component of central adiposity, subcutaneous abdominal fat has as strong an association with insulin resistance as visceral fat, and altered muscle composition, suggestive of increased fat content, is an important independent marker of insulin resistance in obesity.

Abdomen↗