David E Kelley

..This new emphasis reflects greater awareness of the importance of responding to individual and cultural dietary preferences and the need to address treatment of both hyperglycemia and dyslipidemia in diabetes mellitus...

..34; P < 0.01). In summary, fatty liver is relatively common in overweight and obese volunteers with type 2 DM and is an aspect of body composition related to severity of insulin resistance, dyslipidemia, and inflammatory markers...

..This review has evaluated the effectiveness of physical activity in the treatment and prevention of Type 2 diabetes mellitus (DM)...

..01). We conclude that there is an impaired bioenergetic capacity of skeletal muscle mitochondria in type 2 diabetes, with some impairment also present in obesity...

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..An effort to modify skeletal muscle in individuals with obesity and type 2 DM so that the capacity for fat oxidation and metabolic flexibility is improved should be among the goals of treatment for these disorders...

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..This inflexibility in fuel selection by skeletal muscle appears to be related to the accumulation of imTG and is an important aspect of IR of skeletal muscle in obesity and type 2 DM...

..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...

..Potential explanations for this difference between weight loss and physical activity are discussed in this article...

..The purpose of this paper is to examine the effect of physical activity on glucose tolerance in relation to obesity...

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..In particular, clinically significant weight loss fully corrected insulin resistance in type 2 diabetes at the step of glucose phosphorylation and largely, but incompletely, corrected insulin resistance at the glucose transport step...

..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...

..Both are known to improve insulin resistance, and we tested the hypothesis that physical activity, rather than improved insulin resistance, is required to increase mitochondrial capacity of muscle...

..The specific activity of NADH oxidase (per mg cardiolipin) and NADH oxidase/citrate synthase and NADH oxidase/beta-HAD ratios are reduced two- to threefold in both T2DM and obesity...

..These dynamic PET imaging studies indicate that both quantity and quality of specific AT depots have distinct roles in systemic insulin resistance and may help explain the metabolically obese but normal-weight phenotype...

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..01). In conclusion, exercise enhances mitochondria ETC activity in older human skeletal muscle, particularly in subsarcolemmal mitochondria, which is likely related to the concomitant increases in mitochondrial biogenesis...

..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...

..Specifically, the metabolic syndrome was found to be a predictor of 4-year cardiovascular risk only when associated with significant angiographic CAD...

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..In summary, in healthy volunteers there is robust dose-responsive insulin stimulation of glucose transport in skeletal muscle...

..6 AU. The percentage of type I fibers significantly increased (P < 0.05) from 35.4 +/- 2.1 to 40.1 +/- 2.3%. In conclusion, exercise training increases IMCL in older persons in parallel with an enhanced capacity for fat oxidation...

..There was also a significant improvement in aPWV at completion of weight loss intervention, from 740 to 690 cm/s (P < 0.05). CONCLUSIONS: Moderate weight loss improves arterial stiffness in type 2 diabetes...

..05). These findings indicate an important interaction between transport and phosphorylation in the insulin resistance of obesity and type 2 diabetes...

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..This change in the size of lipid droplets, likely coupled with a concomitant increase in oxidative enzyme capacity, is correlated to improved IS...

..We undertook a double-blinded, randomized-order, crossover study to examine the vildagliptin mechanisms of action on islet function and glucose utilization. Research..

..This ratio tended to be higher in Ob and T2DM. In summary, there is decreased muscle Glyc in T2DM yet a disproportional Glyc-to-OX-Enz relationship that is related to IR, although not as robustly as the IMCL-to-OX-Enz ratio...

..We conclude that improved skeletal muscle ETC activity following moderate WL and improved aerobic capacity contributes to associated alleviation of insulin resistance...

..The primary purpose of this study was to evaluate the acute effect of exercise of differing intensity on plasma glucose and insulin responses to an oral glucose challenge...

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..05). DISCUSSION: During moderate exercise, obese sedentary men have increased rates of fatty-acid oxidation from nonplasma sources and reduced rates of CHO oxidation, particularly muscle glycogen, compared with lean sedentary men...

..Plasma long-chain AcylCN species are increased in obesity and T2DM, suggesting that more fatty acids can enter mitochondria. In T2DM, many shorter species accumulate, suggesting that they have a generalized complex oxidation defect...

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..In obesity, skeletal muscle accumulates triglyceride. Recent work from Hulver and colleagues (2005) in the October issue of Cell Metabolism implicates stearoyl-CoA desaturase as part of the underlying molecular mechanism...

..In this review, we examine recent studies utilizing dynamic in-vivo PET imaging in assessing insulin resistance in humans...

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..In obesity, skeletal muscle insulin resistance may be associated with smaller mitochondria...

..NADH is quantitatively analyzed with a detection limit of 3-5 pmol by HPLC using a reverse-phase Hypersil ODS column connected to a fluorescence detector...

..Data on > 2500 orlistat-treated patients with DM-2 are reviewed and summarised. Orlistat therapy led to greater weight loss and improved metabolic control in overweight and obese patients with DM-2...

..The assay is linear over the range between 0.3 and 3.0mg of tissue (R(2)=0.998). The assay provides good reproducibility and accuracy (within 5-10%)...

..A clearer understanding of the physiology of obesity will allow physicians who treat the obese to develop better strategies to promote weight loss and improve the well-being of millions of individuals...

..Defining mechanisms by which dysregulation of fatty acid metabolism and persistent lipid oversupply alter insulin action may help to target more effective strategies to prevent or treat type 2 diabetes...

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..We conclude that dynamic PET imaging of [(11)C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle...

..These findings support the concept that the capacity of skeletal muscle to oxidize fat under appropriate physiological conditions is related to leanness, aerobic fitness, and insulin sensitivity...

..In summary, T2DM, compared with similarly obese nondiabetic men and women, is associated with less leg FM and greater trunk FM and hepatic fat...

..Skeletal muscle lipid is associated with obesity and type 2 diabetes and may be altered by diet, physical activity, and weight loss...

..Thus, our results suggest a potential mechanism contributing to leptin resistance, by which circulating CRP binds to leptin and attenuates its physiological functions...

..These data provide important clues to clinical observations that genetic variants of apoD are associated with abnormal lipid metabolism and increased risk of metabolic syndrome...

..Both are associated with cardiovascular disease (CVD). However, the contribution of obesity to cardiovascular risk, independent of the presence of the metabolic syndrome, remains controversial...

..A comparison of the mass spectral properties of the three derivatives of these saturated and unsaturated fatty acids is described...

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..In conclusion, the capacity for lipid oxidation may be an important mediator of the association between excess muscle lipid accumulation and insulin resistance...

..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...

..91, P < 0.001). These findings indicate an important interaction between transport and phosphorylation in the control of insulin-stimulated glucose metabolism in skeletal muscle...

..Moreover, the previous findings of reduced free testosterone concentrations with hypertension or hyperinsulinemia or as a risk factor for developing type 2 diabetes, conditions in which SHBG is reduced, may have been methodology-related...

..To determine whether an intermittent very-low-calorie diet (VLCD) improves weight loss and glycemic control more than moderate caloric restriction alone...

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..The objective of this study is to compare the effect of intraperitoneal versus subcutaneous insulin injection on hepatic glucose production (HGP) and systemic glucose utilization (Rd) in patients with NIDDM...

..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...

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..This strongly suggests that these two distinct fat distribution phenotypes should both be considered in IR as important determinants of cardiometabolic risk...

..This study describes baseline physical activity (PA) patterns of individuals with type 2 diabetes mellitus (T2DM) enrolled in the multicenter Look AHEAD Study using an objective measure of PA (accelerometry)...

..We speculate that this reduced GLUT gene expression and glucose uptake contribute towards mortality from ischemic heart disease seen in adults born with IUGR...

..The present method provided accurate and precise measures of concentration as well as enrichment when analyzed with gas chromatography combustion-isotope ratio-mass spectrometry...

..01). In summary, based on single-fiber analysis, skeletal muscle in obese and type 2 diabetic subjects mani-fests disturbances of oxidative enzyme activity and increased lipid content that are independent of the effect of fiber type...

..The purified 1-pyrenylmethyl esters of PGF(2alpha) were quantitatively analyzed by reverse-phase HPLC with fluorescent detection, with a detection limit of 5-10 pg...

..02). These findings support previous studies that suggest serotonergic underpinnings to the neurobiology of diabetes and have shown diabetes-induced neurological changes in hippocampus...

..Thus, within the particulate fraction, the relative contributions of hexokinase I and hexokinase II were 81 and 19%, whereas within the cytosolic fraction, the relative contributions for hexokinase I and hexokinase II were 37 and 63%...

..Outcomes analyses should consider the potential for the confounding of BMI with demographic and clinical characteristics...

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..The contribution of glyceroneogenesis to triglyceride-glycerol is not affected by short (4 hours) infusion of insulin in type 2 diabetes mellitus...

..Key questions that remain are how metabolic flexibility is lost in obese and diabetic individuals and by what means it may be regained...

..After Year 4, participants are offered monthly individual visits. The intervention is delivered by a multidisciplinary team that includes medical staff who monitor participants at risk of hypoglycemic episodes...

..However, muscle total creatine (TCr) following creatine supplementation did not differ statistically between LOV and Omni diet groups (148.6 4.5 vs. 141.7 4.5 mmol kg-1 d.m.)...

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..This redistribution of control is triggered by the robust stimulation of glucose transport, which in turn unmasks a greater dependence upon delivery and glucose phosphorylation...

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..This report describes 1-year changes in CVD risk factors in a trial designed to examine the long-term effects of an intensive lifestyle intervention on the incidence of major CVD events...

..Little is known, however, about the cross-correlation between these techniques and their test-retest reliability...

..32, p=0.03). We conclude that early steps of adipogenesis may be impaired in T2DM independently of obesity due, in part, to an upregulation of the MMP2 transcription...