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Dynamic positron emission tomography (PET) imaging was performed using sequential tracer injections ([[sup.15]O][H.sub.2]O, [[sup.11]C]3-O-methylglucose [3-OMG], and [[sup.18]F]fluorodeoxyglucose [FDG]) to quantify, respectively, skeletal muscle tissue perfusion (glucose delivery), kinetics of bidirectional glucose transport, and glucose phosphorylation to interrogate the individual contribution and interaction among these steps in muscle insulin resistance (IR) in type 2 diabetes (T2D). PET imaging was performed in normal weight nondiabetic subjects (NW) (n = 5), obese nondiabetic subjects (OB) (n = 6), and obese subjects with T2D (n = 7) during fasting conditions and separately during a 6-h euglycemic insulin infusion at 40 mU x [m.sup.-2] x [m.sup.-1]. Tissue tracer activities were derived specifically within the soleus muscle with PET images and magnetic resonance imaging. During fasting, NW, OB, and T2D subjects had similar [[sup.11]C]3-OMG and [[sup.18]F]FDG uptake despite group differences for tissue perfusion. During insulin-stimulated conditions, IR was clearly evident in T2D (P < 0.01), and [[sup.18]F]FDG uptake by muscle was inversely correlated with systemic IR (P < 0.001). The increase in insulin-stimulated glucose transport was less (P < 0.01) in T2D (twofold) than in NW (sevenfold) or OB (sixfold) subjects. The fractional phosphorylation of [[sup.18]F]FDG during insulin infusion was also significantly lower in T2D (P < 0.01). Dynamic triple-tracer PET imaging indicates that skeletal muscle IR in T2D involves a severe impairment of glucose transport and additional impairment in the efficiency of glucose phosphorylation. Diabetes 2014;63:1058-1068 | DOI: 10.2337/DB13-1249, The rate of glucose uptake into skeletal muscle during insulin-stimulated conditions is a strong determinant of systemic insulin sensitivity (and insulin resistance [IR]). Much of the control of glucose uptake [...]

OBJECTIVE--To determine which measures--impaired fasting glucose (IFG), elevated Hb[A.sub.1c], or both--best predict incident diabetes in older adults. RESEARCH DESIGN AND METHODS--From the Health, Aging, and Body Composition study, we selected [...]

Intramyocellular triacylgiycerol (IMTG) accumulation is highly associated with insulin resistance and metabolic complications of obesity (lipotoxicity), whereas comparable IMTG accumulation in endurance-trained athletes is associated with insulin sensitivity (the athlete's paradox). Despite these findings, it remains unclear whether changes in IMTG accumulation and metabolism per se influence muscle-specific and systemic metabolic homeostasis and insulin responsiveness. By mediating the rate-limiting step in triacylglycerol hydrolysis, adipose triglyceride lipase (ATGL) has been proposed to influence the storage/production of deleterious as well as essential lipid metabolites. However, the physiological relevance of ATGL-mediated triacylglycerol hydrolysis in skeletal muscle remains unknown. To determine the contribution of IMTG hydrolysis to tissue-specific and systemic metabolic phenotypes in the context of obesity, we generated mice with targeted deletion or transgenic overexpression of ATGL exclusively in skeletal muscle. Despite dramatic changes in IMTG content on both chow and high-fat diets, modulation of ATGL-mediated IMTG hydrolysis did not significantly influence systemic energy, lipid, or glucose homeostasis, nor did it influence insulin responsiveness or mitochondrial function. These data argue against a role for altered IMTG accumulation and lipolysis in muscle insulin resistance and metabolic complications of obesity., Obesity is a global public health problem and a major risk factor for insulin resistance and type 2 diabetes. These disorders are characterized by excess lipid accumulation in multiple tissues, [...]

The specific cellular underpinnings or mechanisms of insulin resistance (IR) are not clear. Here I present evidence to support a causal association between mitochondrial energetics and IR. A large body of literature indicates that mitochondrial capacity for oxidative metabolism is lower in human obesity and type 2 diabetes. Whether or not mitochondria play a causal role in IR is hotly debated. First, IR can be caused by many factors, many of which may or may not involve mitochondria. These include lipid overload, oxidative stress, and inflammation. Thus the first tenet of an argument supporting a role for mitochondria in IR is that mitochondria derangements can cause IR, but IR does not have to involve mitochondria. The second tenet of this argument is that animal models in which oxidative metabolism are completely abolished are not always physiologically or pathologically relevant to human IR, in which small metabolic perturbations can have profound effects over a prolonged period. Lastly, mitochondria are complex organelles, with diverse functions, including links with cell signaling, oxidative stress, and inflammation, which in turn can be connected with IR. In summary, mitochondrial 'deficiency' is not merely a reduced energy generation or low fatty acid oxidation; this concept should be expanded to numerous additional important functions, many of which can cause IR if perturbed., The most common forms of human skeletal muscle insulin resistance (IR) are associated with 1) obesity, particularly abdominal obesity and excess accumulation of lipids in nonadipose tissues such as liver [...]

OBJECTIVE--Chronic exercise and obesity both increase intramyocellular triglycerides (IMTGs) despite having opposing effects on insulin sensitivity. We hypothesized that chronically exercise-trained muscle would be characterized by lower skeletal muscle diacylglycerols (DAGs) and ceramides despite higher IMTGs and would account for its higher insulin sensitivity. We also hypothesized that the expression of key skeletal muscle proteins involved in lipid droplet hydrolysis, DAG formation, and fatty-acid partitioning and oxidation would be associated with the lipotoxic phenotype. RESEARCH DESIGN AND METHODS--A total of 14 normal-weight, endurance-trained athletes (NWA group) and 7 normal-weight sedentary (NWS group) and 21 obese sedentary (OBS group) volunteers were studied. Insulin sensitivity was assessed by glucose clamps. IMTGs, DAGs, ceramides, and protein expression were measured in muscle biopsies. RESULTS--DAG content in the NWA group was approximately twofold higher than in the OBS group and ~50% higher than in the NWS group, corresponding to higher insulin sensitivity. While certain DAG moieties clearly were associated with better insulin sensitivity, other species were not. Ceramide content was higher in insulin-resistant obese muscle. The expression of OXPAT/ perilipin-5, adipose triglyceride lipase, and stearoyl-CoA desaturase protein was higher in the NWA group, corresponding to a higher mitochondrial content, proportion of type 1 myocytes, IMTGs, DAGs, and insulin sensitivity. CONCLUSIONS--Total myocellular DAGs were markedly higher in highly trained athletes, corresponding with higher insulin sensitivity, and suggest a more complex role for DAGs in insulin action. Our data also provide additional evidence in humans linking ceramides to insulin resistance. Finally, this study provides novel evidence supporting a role for specific skeletal muscle proteins involved in intramyocellular lipids, mitochondrial oxidative capacity, and insulin resistance. Diabetes 60:2588-2597, 2011, Skeletal muscle insulin resistance (IR) is associated with obesity and physical inactivity and is crucial for the development of type 2 diabetes (1). Unfortunately, the causes of IR within muscle [...]

OBJECTIVE--We tested the primary hypotheses that sphingolipid and diacylglycerol (DAG) content is higher within insulin-resistant muscle and that the association between intramyocellular triglycerides (IMTG) and insulin resistance is muscle fiber type specific. RESEARCH DESIGN AND METHODS--A nested case-control analysis was conducted in 22 obese (BMI >30 kg/[m.sup.2]) women who were classified as insulin-resistant (IR; n = 12) or insulin-sensitive (IS; n = 10), determined by hyperinsulinemic-euglycemic clamp (>30% greater in IS compared with IR, P < 0.01). Sphingolipid and DAG content was determined by high-performance liquid chromatography-tandem mass spectrometry. Fiber type-specific IMTG content was histologically determined. Gene expression was determined by quantitative PCR. RESULTS--Total (555 ± 53 vs. 293 ± 54 pmol/mg protein, P = 0.004), saturated (361 ± 29 vs. 179 ± 34 pmol/mg protein, P = 0.001), and unsaturated (198 ± 29 vs. 114 ± 21 pmol/mg protein, P = 0.034) ceramides were higher in IR compared with IS. DAG concentrations, however, were similar. IMTG content within type I myocytes, but not type II myocytes, was higher in IR compared with IS subjects (P = 0.005). Insulin sensitivity was negatively correlated with IMTG within type I myocytes (R = -0.51, P = 0.026), but not with IMTG within type II myocytes. The proportion of type I myocytes was lower (41 vs. 59%, P < 0.01) in IR subjects. Several genes involved in lipid droplet and fatty acid metabolism were differentially expressed in IR compared with IS subjects. CONCLUSIONS--Human skeletal muscle insulin resistance is related to greater IMTG content in type I but not type II myocytes, to greater ceramide content, and to alterations in gene expression associated with lipid metabolism., Skeletal muscle insulin resistance is a key factor in the development of type 2 diabetes, although the exact mechanisms that underlie insulin resistance in humans remain elusive. Considerable efforts have [...]

Background: Sarcopenia is thought to be accompanied by increased muscle fat infiltration. However, no longitudinal studies have examined concomitant changes in muscle mass, strength, or fat infiltration in older adults. Objective: We present longitudinal data on age-related changes in leg composition, strength, and muscle quality (MQ) in ambulatory, well-functioning men and women. We hypothesized that muscle cross-sectional area (CSA) and strength would decrease and muscular fat infiltration would increase over 5 y. Design: Midthigh muscle, subcutaneous fat (SF), and intermuscular fat (IMF) CSAs and isokinetic leg muscle torque (MT) and MQ (MT/quadriceps CSA) were examined over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678). Results: Men experienced a 16.1% loss of MT, whereas women experienced a 13.4% loss. Adjusted annualized decreases in MT were 2--5 times greater than the loss of muscle CSA in those who lost weight and in those who remained weight-stable. Weight gain did not prevent the loss of MT, despite a small increase in muscle CSA. Only those who gained weight had an increase in SF (P < 0.001), whereas those who lost weight also lost SF (P < 0.001). There was an age-related increase in IMF in men and women (P < 0.001), and IMF increased in those who lost weight, gained weight, or remained weight-stable (all P < 0.001). Conclusions: Loss of leg MT in older adults is greater than muscle CSA loss, which suggests a decrease in MQ. Additionally, aging is associated with an increase in IMF regardless of changes in weight or SF. Am J Clin Nutr 2009;90:1579-85. doi: 10.3945/ajcn.2009.28047.

OBJECTIVE--A loss of skeletal muscle mass is frequently observed in older adults. The aim of the study was to investigate the impact of type 2 diabetes on the changes in [...]

OBJECTIVE--Poor peripheral nerve function is prevalent in diabetes and older populations, and it has great potential to contribute to poor physical performance. RESEARCH DESIGN AND METHODS--Cross-sectional analyses were done for [...]

Background: Although obesity is strongly associated with diabetes, the greater prevalence of diabetes in persons of African ancestry than in those of other ancestries cannot be explained simply by differences in total or central adiposity. Objective: We examined whether skeletal muscle composition is associated with diabetes in 1249 men of African ancestry aged [greater than or equal to] 40 y. Design: Anthropometry and fasting serum glucose were measured, and lower-leg skeletal muscle composition was assessed with peripheral quantitative computerized tomography (pQCT). Results: The prevalence of diabetes in this population was high (21%). We observed an age-associated adipose tissue remodeling in skeletal muscle and greater intermuscular (IMAT) and lesser subcutaneous (SAT) adipose tissue area with advancing age (P < 0.0001). Multivariate stepwise logistic regression identified more IMAT and less SAT to be significantly associated with a greater prevalence of diabetes. Even among normal-weight men [body mass index (BMI; in kg/[m.sup.2]) < 25], diabetic men had significantly (P = 0.01) more IMAT than did those without diabetes. Greater IMAT was also associated with a greater prevalence of hyperglycemia in men with a family history of diabetes than in those without such history (P for interaction = 0.02). Conclusions: These findings underscore the independent associations of subcutaneous and intermuscular fat among men of African ancestry, an effect that may be modified by a family history of diabetes. Further studies are needed to identify the genetic and physiologic mechanisms that influence the distribution and remodeling of adipose tissue in skeletal muscle with aging.'

Background and Purpose Muscle atrophy is common in patients with rheumatoid arthritis (RA). Although neuromuscular electrical stimulation (NMES) is a viable treatment for muscle atrophy, there is no evidence about the use of NMES in patients with RA. The purposes of this multiple-patient case report are: (1) to describe the use of NMES applied to the quadriceps femoris muscles in conjunction with an exercise program in patients with RA; (2) to report on patient tolerance and changes in lean muscle mass, quadriceps femoris muscle strength (force-producing capacity), and physical function; and (3) to explore how changes in muscle mass relate to changes in quadriceps femoris muscle strength, measures of physical function, and patient adherence. Case Description Seven patients with RA (median age=61 years, range=39-80 years) underwent 16 weeks of NMES and volitional exercises. Lean muscle mass and strength of the quadriceps femoris muscle and physical function were measured before and after treatment. Outcomes One patient did not tolerate the NMES treatment, and 2 patients did not complete at least half of the proposed treatment. Patients who completed the NMES and volitional exercise program increased their lean muscle mass, muscle strength, and physical function. Discussion Because of the small sample, whether NMES combined with exercises is better than exercise alone or NMES alone could not be determined. However, the outcomes from this multiple-patient case report indicate that NMES is a viable treatment option to address muscle atrophy and weakness in patients with RA. Strategies to increase tolerance and adherence to NMES are warranted., More than 50% of patients with rheumatoid arthritis (RA) are affected by rheumatoid cachexia. (1) Rheumatoid cachexia is characterized by altered energy and metabolic abnormalities that result in the loss [...]

OBJECTIVE--It has been shown that adults with either long-standing type 1 or type 2 diabetes had lower skeletal muscle strength than nondiabetic adults in cross-sectional studies. The aim of the [...]

Background: Because serum concentrations of leptin, a hormone produced by adipocytes, can be relatively reliably and inexpensively measured, it may be considered complementary to, or even a substitute for, body mass index (BMI) as a measure of adiposity. Objective: We examined the ability of BMI and leptin concentrations, separately and together, to estimate total percentage fat in older adults. Design: Total percentage fat measured by dual-energy X-ray absorptiometo and fasting serum leptin concentrations were measured in 2911 well-functioning 70-79-y-old participants (42% black, 51% women) in the Health, Aging, and Body Composition Study. Results: Mean ([+ or -] SD) total percentage fat was 29.2 [+ or -] 5.0% in men and 40.5 4- 5.7% in women, and the geometric mean ([+ or -] SD) serum leptin concentration was 5.6 [+ or -] 2.5 ng/mL in the men and 16.4 [+ or -] 2.3 ng/mL in the women. Among men, total percentage fat was strongly associated with both BMI ([R.sup.2] = 0.56) and leptin ([R.sup.2] = 0.57) in separate linear regression analyses and in a combined linear regression analysis ([R.sup.2] = 0.68). Similarly, among women, total percentage fat was associated with both BMI ([R.sup.2] = 0.65) and leptin ([R.sup.2] = 0.54) separately and in combination (model [R.sup.2] = 0.71). Independent relations of BMI and leptin with total percentage fat were also found among both black and white participants. With the population divided into quintiles according to percentage fat, BMI and serum leptin correctly classified 49% of men and 50% of women in the correct quintile. Conclusions: Among older adults, total percentage fat was better estimated by using both serum leptin concentrations and BMI than by using either alone. However, their performance does not suggest that they can substitute for more accurate measures. KEY WORDS Leptin, body composition, anthropometry, dual-energy X-ray absorptiometry, race, epidemiology, Health, Aging, and Body Composition Study, Health ABC

Background: Recent findings suggest that higher levels of intermuscular adipose tissue (IMAT) are associated with glucose dysregulation, lower levels of muscle strength, and a heightened risk of disability. Although several studies have described adaptations in muscle after reduced physical activity, the change in IMAT in healthy young adults is unknown. Objective: The objective was to determine whether reduced lower limb activity alters IMAT in healthy young adults and to assess whether this change affects muscle strength loss. Design: The subjects (6 men and 12 women aged 19-28 y) underwent a 4-wk control period, which was followed by 4 wk of unilateral lower limb suspension. Volumes of whole muscle, subcutaneous adipose tissue, and IMAT were assessed by using magnetic resonance imaging in the thigh and call Muscle strength was assessed during maximal voluntary isometric contractions. Results: No changes were observed in the control period. Reduced physical activity decreased thigh and calf muscle volumes by 7.4% and 7.9% (P < 0.001), respectively; no significant change in subcutaneous adipose tissue was observed. Additionally, IMAT increased in both regions; the increase was larger in the calf (20%) than in the thigh (14.5%) (P [less than or equal to] 0.005) and was partially explained by the loss in muscle ([R.sup.2] = 26%). The loss in strength was greater in the thigh (20.4%) than in the calf (15%). Strength loss was associated with increases in 1MAT (P = 0.039) after adjustment for the loss in muscle, initial strength, initial IMAT, and initial muscle volume. Conclusions: IMAT accumulates markedly after reduced activity in healthy young adults. Increases in IMAT may contribute to losses in muscle strength associated with reduced physical activity, but the mechanism responsible is yet to be determined. KEY WORDS Unilateral limb suspension, bed rest, physical inactivity, intermuscular adipose tissue

OBJECTIVE--Age, diabetes, and elevated inflammatory markers independently increase the risk of functional decline. We examined the effect of C-reactive protein (CRP) and interleukin-6 (IL-6) on the incident mobility limitation in [...]

Adequate skeletal muscle strength is essential for physical functioning and low muscle strength is a predictor of physical limitations. Older adults with diabetes have a two-to threefold increased risk of physical disability. However, muscle strength has never been investigated with regard to diabetes in a population-based study. We evaluated grip and knee extensor strength and muscle mass in 485 older adults with diabetes and 2,133 without diabetes in the Health, Aging, and Body Composition study. Older adults with diabetes had greater arm and leg muscle mass than those without diabetes because they were bigger in body size. Despite this, muscle strength was lower in men with diabetes and not higher in women with diabetes than corresponding counterparts. Muscle quality, defined as muscle strength per unit regional muscle mass, was significantly lower in men and women with diabetes than those without diabetes in both upper and lower extremities. Furthermore, longer duration of diabetes (≥ 6 years) and poor glycemic control (Hb[A.sub.1c] > 8.0%) were associated with even poorer muscle quality. In conclusion, diabetes is associated with lower skeletal muscle strength and quality. These characteristics may contribute to the development of physical disability in older adults with diabetes., In the U.S., people aged 65 years and older will make up most of the diabetic population in the next 25 years. Furthermore, the proportion of the diabetic population aged [...]

Background: Weight loss may contribute to the loss of lean mass with age. Objective: The objective was to evaluate the relation between weight loss or weight gain and changes in lean mass and fat mass in older adults. Design: We observed changes in weight and body composition during a 4-y period in 2163 men (47%) and women (53%) aged 70-79 y in the Health, Aging and Body Composition Study cohort. Whole-body and appendicular bone-free lean mass and fat mass were measured by using dual-energy X-ray absorptiometry. Results: Weight loss and weight gain were common. In both weight losers and weight gainers, changes in lean mass as a percentage of initial lean mass were substantially smaller than changes in fat mass as a percentage of initial fat mass. However, the difference between the change in lean mass and that in fat mass was more pronounced with weight gain than with weight loss, especially in men. Small amounts of lean loss and fat gain were noted with weight stability. In multivariate models, weight loss was strongly associated with lean mass loss in both men and women, especially in men whose weight loss was concurrent with a hospitalization. Conclusions: With weight change, a greater proportion of lean mass than of fat mass was conserved, but, especially in older men, significantly more lean mass was lost with weight loss than was gained with weight gain. These findings suggest that weight loss, even with regain, could accelerate sarcopenia in older adults. KEY WORDS Body composition, sarcopenia, weight loss, older adults

Background: Low albumin concentrations in older persons increase the risk of poor health outcomes, including functional decline. Objective: The aim of the study was to investigate the association between serum albumin concentration and skeletal muscle loss (sarcopenia) in old age. Design: Serum albumin concentration was measured in 1882 black and white men and women aged 70-79 y participating in the Health, Aging and Body Composition Study. Five-year changes in appendicular skeletal muscle mass (ASMM), total-body fat-free mass (FFM), and trunk lean mass (TLM) were measured by using dual-energy X-ray absorptiometry. Confounders included health and lifestyle factors, which are markers of inflammation and protein intake. Results: A low albumin concentration ( KEY WORDS Sarcopenia, dual-energy X-ray absorptiometry, body composition, aging, protein, inflammation

Background: The manner in which fat depot volumes and distributions, particularly the adipose tissue (AT) between the muscles, vary by race is unknown. Objective: The objective was to quantify a previously unstudied and novel intermuscular AT (IMAT) depot and subcutaneous AT, visceral AT (VAT), and total-body skeletal muscle mass in healthy sedentary African American (AA), Asian, and white adults by whole-body magnetic resonance imaging. IMAT is the AT between muscles and within the boundary of the muscle fascia. Design: Analyses were conducted on 227 women [AA (n = 79): body mass index (BMI; in kg/[m.sup.2]), 29.0 [+ or -] 5.5; age, 45.7 [+ or -] 16.9 y; Asian (n = 38): BMI, 21.7 [+ or -] 2.9; age, 47.2 [+ or -] 19.9 y; whites (n = 110): BMI, 24.9 [+ or -] 5.4; age, 43.7 [+ or -] 16.2 y]) and 111 men [AA (n = 39): BMI, 25.6 [+ or -] 3.2; age, 45.5 [+ or -] 18.8 y; Asian (n = 13): BMI, 24.9 [+ or -] 2.5; age, 45.6 [+ or -] 25.0 y; white (n = 59): BM1, 25.8 [+ or -] 3.8; age 44.5 [+ or -] 16.3 y]. Results: IMAT depots were not significantly different in size between race groups at low levels of adiposity; however, with increasing adiposity, AAs had a significantly greater increment in the proportion of total AT (TAT) than did the whites and Asians (58, 46, and 44 g IMAT/kg TAT, respectively: P = 0.001). VAT depots were not significantly different in size at low levels of adiposity but, with increasing adiposity, VAT accumulation was greater than IMAT accumulation in the Asians and whites; no significant differences were observed in AAs. Conclusion: Race differences in AT distribution extend to IMAT, a depot that may influence race-ethnicity differences in dysglycemia. KEY WORDS Muscle, adipose tissue, race, aging, body composition, fatness

OBJECTIVE--To create a simple prediction rule that could perform as well as the 2-h postchallenge plasma glucose (PCPG) test to predict those at risk for diabetes. We created a prediction [...]

The current study addresses a novel hypothesis of subcellular distribution of mitochondrial dysfunction in skeletal muscle in type 2 diabetes. Vastus lateralis muscle was obtained by percutaneous biopsy from 11 volunteers with type 2 diabetes; 12 age-, sex-, and weight-matched obese sedentary nondiabetic volunteers; and 8 lean volunteers. Subsarcolemmal and intermyofibrillar mitochondrial fractions were isolated by differential centrifugation and digestion techniques. Overall electron transport chain activity was similar in type 2 diabetic and obese subjects, but subsarcolemmal mitochondria electron transport chain activity was reduced in type 2 diabetic subjects (0.017 [+ or -] 0.003 vs. 0.034 [+ or -] 0.007 units/mU creatine kinase [CK], P = 0.01) and sevenfold reduced compared with lean subjects (P < 0.01). Electron transport chain activity in intermyofibrillar mitochondria was similar in type 2 diabetic and obese subjects, though reduced compared with lean subjects. A reduction in subsarcolemmal mitochondria was confirmed by transmission electron microscopy. Although mtDNA was lower in type 2 diabetic and obese subjects, the decrement in electron transport chain activity was proportionately greater, indicating functional impairment. Because of the potential importance of subsarcolemmal mitochondria for signal transduction and substrate transport, this deficit may contribute to the pathogenesis of muscle insulin resistance in type 2 diabetes., Skeletal muscle has a high reliance on oxidative phosphorylation. Distribution of energy within myocytes is served not only by the ATP-phosphocreatine shuttle but also by subcellular compartmentalization of mitochondria in [...]

Background: Among US adults, serum leptin concentrations are higher in women than in men and are higher in blacks than in whites independent of anthropometric measures of body fatness. Objective: Using radiographic measures of body fat, we determined the best correlates of leptin and whether adiposity can explain sex and race differences in leptin concentrations in older adults. Design: This was a cross-sectional analysis of fasting serum leptin concentrations and body fat measured by dual-energy X-ray absorptiometry (DXA), abdominal computed tomography, and standard anthropometry in 3026 well-functioning 70-79-y-old participants (42% black, 51% women) of the Health, Aging, and Body Composition Study. Results: Geometric mean ([+ or -] SE) leptin concentrations (ng/mL) were higher in the women than in the men (16.5 [+ or -] 0.3 and 5.7 [+ or -] 0. 1, respectively) and in the black women than in the white women (20.2 [+ or -] 0.6 and 13.9 [+ or -] 0.4, respectively), but did not differ significantly between the white and black men (5.8 [+ or -] 0.2 and 5.5 [+ or -] 0.2, respectively). Percentage fat estimated from DXA showed the highest correlation with leptin (82 = 0.56 for both sexes). Addition of abdominal visceral fat minimally increased the correlation. In the multivariate analysis, the association with sex was eliminated after adjustment for percentage fat and visceral fat in both whites (P = 0.051) and blacks (P = 0.34). Among women, higher leptin concentrations in blacks remained after adjustment for percentage fat and visceral fat (mean race difference = 4.95 ng/mL; P < 0.001). Among men, an association with black race emerged after adjustment for these factors (mean race difference = 1.42 ng/mL; P < 0.001). Conclusions: Among older adults, higher serum leptin concentrations in women are explained by a greater percentage of body fat. Higher leptin concentrations in blacks are not explained by percentage of body fat. Am J Clin Nutr 2004;80:576-83. KEY WORDS Leptin, body composition, anthropometry, dual-energy X-ray absorptiometry, computed tomography, race, epidemiology, Health, Aging, and Body Composition Study, Health ABC Study

OBJECTIVE--To examine whether adiponectin is independently associated with diabetes and whether adiponectin and other adipocytokines account for the relationship between fat and diabetes. RESEARCH DESIGN AND METHODS--A nested case-control study [...]

Background: Skeletal muscle lipid is associated with obesity and type 2 diabetes and may be altered by diet, physical activity, and weight loss. Objective: We explored the utility of magnetic resonance imaging (MRI) for quantifying the lipid concentration of muscle tissue in vivo. Design: Fat-selective MR images of the lower leg were taken in 8 normal-weight [body mass index (in kg/[m.sup.2]) [less than or equal to] 24.9] and 8 obese (body mass index > 29.9) subjects to obtain spatial maps of lipid signal intensity within muscle tissue. Fast-spiral-sequence (echo time = 5.6-13.8 ms, repetition time = 1 s, 8 interleaves) MRI scans were conducted at 3.0 T by using an extremity transmit-receive coil. Lipid concentrations within muscle were determined from manually drawn regions of interest in the tibialis anterior (TA), soleus, and medial head of the gastrocnemius (MHG) muscle groups. Results: There was extremely good agreement (mean [R.sup.2] = 0.985) between the fat signal intensity and the actual lipid concentration of standards containing 2.5, 5.0, and 10.0 g lipid/dL, which were placed on the subject's leg during each scan. The lipid content of both the soleus (2.99 [+ or -] 0.37 g/dL) and the MHG (3.80 [+ or -] 0.68 g/dL) was higher (P < 0.05) than that of the TA (1.83 [+ or -] 0.28 g/dL). Lipid content was more than two-fold higher (P < 0.05) in the MHG of obese subjects (5.48 [+ or -] 1.18 g/dL) than in the MHG of normal-weight subjects (2.54 [+ or -] 0.47 g/dL), but did not differ significantly in the TA or soleus. Conclusions: MRI can be used to quantify lipid within human muscle tissue. MRI can also be used to detect differences in muscle lipid content among various muscle groups and between normal-weight and obese subjects. KEY WORDS Skeletal muscle, triacylglycerol, obesity, body fat, magnetic resonance imaging

The object of this study was to establish the association between the metabolic syndrome and oxidized LDL (oxLDL) and to determine the risk for coronary heart disease (CHD) in relation to the metabolic syndrome and levels of oxLDL. OxLDL was measured in plasma from 3,033 elderly participants in the Health, Aging, and Body Composition study. The metabolic syndrome was defined according to criteria established in the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. We observed that the metabolic syndrome was associated with higher levels of oxLDL due to a higher fraction of oxLDL, not to higher levels of LDL cholesterol. Individuals with the metabolic syndrome had twice the odds of having high oxLDL (> 1.90 mg/dl) compared with those not having the metabolic syndrome, after adjusting for age, sex, ethnicity, smoking status, and LDL cholesterol. Among those participants who had the metabolic syndrome at study entry, incidence rates of future CHD events were 1.6-fold higher, after adjusting for age, sex, ethnicity, and smoking status. OxLDL was not an independent predictor of total CHD risk. However, those with high oxLDL showed a greater disposition to myocardial infarction (relative risk 2.25, 95% confidence interval 1.22-4.15). We concluded that the metabolic syndrome, a risk factor for CHD, is associated with higher levels of circulating oxLDL that are associated with a greater disposition to atherothrombotic coronary disease., Oxidized LDL (oxLDL) has been shown to play an important role in the pathogenesis of atherosclerosis (1-3). We and others have demonstrated an association between cardiovascular disease (CVD) and oxidation [...]

Skeletal muscle insulin resistance entails dysregulation of both glucose and fatty acid metabolism. This study examined whether a combined intervention of physical activity and weight loss influences fasting rates of fat oxidation and insulin-stimulated glucose disposal. Obese (BMI >30 kg/[m.sup.2]) volunteers (9 men and 16 women) without diabetes, aged 39 ± 4 years, completed 16 weeks of moderate-intensity physical activity combined with caloric reduction. Body composition was determined by dual-energy X-ray absorptiometry and computed tomography. Glucose disposal rates ([R.sub.d]) were measured during euglycemic hyperinsulinemia (40 mU * [m.sup.-2] * [min.sup.-1]), and substrate oxidation was determined via indirect calorimetry. Fat mass and regional fat depots were reduced and V[O.sub.2max] improved by 19%, from 38.8 ± 1.2 to 46.0 ± 1.0 ml * kg fat-free mass [(FFM).sup.-1] * [min.sup.-1] (P < 0.05). Insulin sensitivity improved 49 ± 10% (6.70 ± 0.40 to 9.51 ± 0.51 mg * [min.sup.-1] * kg FF[M.sup.-1]; p < 0.05). Rates of fat oxidation following an overnight fast increased (1.16 ± 0.06 to 1.36 ± 0.05 mg * [min.sup.-1] * kg FF[M.sup.-1]; P < 0.05), and the proportion of energy derived from fat increased from 38 to 52%. The strongest predictor of the improved insulin sensitivity was enhanced fasting rates of fat oxidation, accounting for 52% of the variance. In conclusion, exercise combined with weight loss enhances postabsorptive fat oxidation, which appears to be a key aspect of the improvement in insulin sensitivity in obesity., Obesity and physical inactivity are risk factors for the development of type 2 diabetes and other aspects of the metabolic syndrome and are attributed to insulin resistance (1-5). Currently, it [...]

OBJECTIVE -- We examined whether regional adipose tissue distribution, specifically that of skeletal muscle fat and Visceral abdominal fat aggregation, is characteristic of elderly individuals with hyperinsulinemia, type 2 diabetes, [...]

This article discusses the relationship between low leg muscle mass and poor leg performance in the aged. An analysis of body fat, muscle mass, body composition, and race is presented.

Results suggest that perceived exertion monitoring is beneficial for regulating the periodicity of resistance exercise training. Data indicate that blood lactate and muscle activity contribute toward establishing the relationship between perceived exertion ratings and resistance exercise intensity.