Insulin Sensitivity In Individuals Research Articles

Effect of antioxidant supplementation on insulin sensitivity in response to endurance exercise training

While production of reactive oxygen and nitrogen species (RONS) is associated with some of the beneficial adaptations to regular physical exercise, it is not established whether RONS play a role in the improved insulin-stimulated glucose uptake in skeletal muscle obtained by endurance training. To assess the effect of antioxidant supplementation during endurance training on insulin-stimulated glucose uptake, 21 young healthy (age 29 ± 1 y, BMI 25 ± 3 kg/m(2)) men were randomly assigned to either an antioxidant [AO; 500 mg vitamin C and 400 IU vitamin E (α-tocopherol) daily] or a placebo (PL) group that both underwent a supervised intense endurance-training program 5 times/wk for 12 wk. A 3-h euglycemic-hyperinsulinemic clamp, a maximal oxygen consumption (Vo(2max)) and maximal power output (P(max)) test, and body composition measurements (fat mass, fat-free mass) were performed before and after the training. Muscle biopsies were obtained for determination of the concentration and activity of proteins regulating glucose metabolism. Although plasma levels of vitamin C (P < 0.05) and α-tocopherol (P < 0.05) increased markedly in the AO group, insulin-stimulated glucose uptake increased similarly in both the AO (17.2%, P < 0.05) and the PL (18.9%, P < 0.05) group in response to training. Vo(2max) and P(max) also increased similarly in both groups (time effect, P < 0.0001 for both) as well as protein content of GLUT4, hexokinase II, and total Akt (time effect, P ≤ 0.05 for all). Our results indicate that administration of antioxidants during strenuous endurance training has no effect on the training-induced increase in insulin sensitivity in healthy individuals.

Magnesium improves the beta-cell function to compensate variation of insulin sensitivity: double-blind, randomized clinical trial

Given that role of magnesium in insulin secretion is uncertain, our objective was to determine whether oral supplementation with magnesium chloride (MgCl(2)) improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia. Eligible individuals were non-diabetic, normo-tensive men and non-diabetic, normo-tensive, non-pregnant women with serum magnesium levels ≤0·70 mM/L; they were enrolled in a randomized double-blind clinical trial to receive either 50 mL of 5% MgCl(2) solution or 50 mL of inactive solution daily for 3 months. The primary trial end point was a change in the AUC of the hyperbolic model of beta-cell function (HMbCF) derived from the fasting state. Individuals, caregivers and personnel who assessed the outcomes were all blinded to the group assignments. A total of 54 and 52 individuals were assigned to the MgCl(2) and placebo groups, respectively; five individuals in the MgCl(2) group and four in the placebo group dropped out. There were no serious adverse events or side effects because of MgCl(2) or placebo. At the beginning of the study, the AUC of the HMbCF was similar in both groups (AUC = 7·591 and 7·895 cm(2)); at the end of follow-up, the curve of the MgCl(2) group showed a hyperbolic distribution (AUC = 18·855 cm(2)), whereas in the placebo group, there were no changes (AUC = 7·631 cm(2)). MgCl(2) 2·5 g daily improves the ability of beta-cells to compensate for variations in insulin sensitivity in non-diabetic individuals with significant hypomagnesaemia.

Acute hypoxia and exercise improve insulin sensitivity (SI2*) in individuals with type 2 diabetes

hypoxia has been shown to increase glucose uptake in skeletal muscle using the contraction-stimulated pathway, independent of the actions of insulin. Yet, the same stress has also been linked with causing insulin resistance and hyperglycaemia. The aim of this study was to examine the effects of acute hypoxia with and without exercise on insulin sensitivity (S(I)(2*) in individuals with type 2 diabetes. eight type 2 diabetic patients completed 60 min of the following: (1) normoxic rest; (2) hypoxic rest [O(2) = 14.6 (0.4)%]; (3) normoxic exercise and (4) hypoxic exercise [O(2) = 14.6 (0.4)%]. Exercise trials were set at 90% of lactate threshold. Each condition was followed by a labelled intravenous glucose tolerance test to provide estimations of insulin sensitivity (S(I)(2*) and β-cell function. Two-compartmental analysis showed that insulin sensitivity (S(I)(2*) was higher following hypoxic rest compared with normoxic rest (p = 0.047). Insulin sensitivity (S(I)(2*) was also higher following hypoxic exercise [4.37 (0.48) × 10(-4) /min (µU/mL)] compared with normoxic exercise [3.24 (0.51) × 10(-4) /min (µU/mL)] (p = 0.048). Acute insulin response to glucose was reduced following hypoxic rest versus normoxic rest (p = 0.014). this study demonstrated that (1) hypoxic-induced improvements in glucose tolerance in the 4 h following exposure can be attributed to improvements in peripheral insulin sensitivity (S( I)(2*) and (2) exercise and hypoxia have an additive effect on insulin sensitivity (S(I)(2*) in type 2 diabetic patients. Acute hypoxia may therefore improve short-term glycaemic control in individuals with type 2 diabetes. The application of these findings in the clinic will require further investigation.

Relationships between fat deposition in the liver and skeletal muscle and insulin sensitivity in Japanese individuals: a pilot study

Purpose:To evaluate the relationships between insulin sensitivity (IS), body fat accumulation, and aerobic capacity in middle- to older-aged Japanese participants with visceral adiposity.Participants and methods:Aerobic capacity was measured during an incremental ramp exercise test. Computed tomography was used to measure visceral (VFA) and subcutaneous (SFA) fat area, the fat in liver-to-spleen ratio (L/S), and low-density skeletal muscle area (LDMA). IS was assessed using euglycemic-hyperinsulinemic clamps.Results:A total of 11 males and 9 females, age 58 ± 9 years (mean ± standard deviation), body mass index 29 ±4.1 kg/m2, and VFA 190 ±53 cm2 participated in this study. In unadjusted models, VFA, LDMA, and L/S were significantly correlated with IS, which remained in adjusted models for LDMA and L/S, but not for VFA. In multiple stepwise regression analysis including sex, age, body fat, VFA, SFA, alcohol consumption, and aerobic capacity (oxygen uptake at the lactate threshold), L/S, and LDMA accounted for 70% of the total variance in IS. Percentage body fat and SFA, but not VFA, were significantly correlated with high molecular-weight adiponectin levels (r = 0.58, P < 0.01 and r = 0.54, P < 0.05, respectively). IS and L/S were significantly and negatively correlated with tumor necrosis factor-α (r = −0.67 and −0.63, respectively; both P < 0.01) and plasminogen activator inhibitor-1 (r = −0.58, P < 0.01 and −0.52, P < 0.05, respectively), whereas LDMA was not.Conclusion:These findings indicate that ectopic fat deposition in the liver and skeletal muscle may be associated with peripheral IS independently of body fat accumulation and aerobic capacity in middle- to older-aged Japanese individuals with visceral adiposity. Because of the small sample size, additional larger studies are needed to provide further insight into these preliminary findings.

Novel adiponectin-resistin (AR) and insulin resistance (IRAR) indexes are useful integrated diagnostic biomarkers for insulin resistance, type 2 diabetes and metabolic syndrome: a case control study

BackgroundAdiponectin and resistin are adipokines which modulate insulin action, energy, glucose and lipid homeostasis. Meta-analyses showed that hypoadiponectinemia and hyperresistinemia are strongly associated with increased risk of insulin resistance, type 2 diabetes (T2DM), metabolic syndrome (MS) and cardiovascular disease. The aim of this study was to propose a novel adiponectin-resistin (AR) index by taking into account both adiponectin and resistin levels to povide a better indicator of the metabolic homeostasis and metabolic disorders. In addition, a novel insulin resistance (IRAR) index was proposed by integration of the AR index into an existing insulin resistance index to provide an improved diagnostic biomarker of insulin sensitivity.MethodsIn this case control study, anthropometric clinical and metabolic parameters including fasting serum total adiponectin and resistin levels were determined in 809 Malaysian men (208 controls, 174 MS without T2DM, 171 T2DM without MS, 256 T2DM with MS) whose ages ranged between 40-70 years old. Significant differences in continuous variables among subject groups were confirmed by ANCOVA or MANCOVA test using 1,000 stratified bootstrap samples with bias corrected and accelerated (BCa) 95% CI. Spearman's rho rank correlation test was used to test the correlation between two variables.ResultsThe AR index was formulated as 1+log10(R0)-log10(A0). The AR index was more strongly associated with increased risk of T2DM and MS than hypoadiponectinemia and hyperresistinemia alone. The AR index was more strongly correlated with the insulin resistance indexes and key metabolic endpoints of T2DM and MS than adiponectin and resistin levels alone. The AR index was also correlated with a higher number of MS components than adiponectin and resistin levels alone. The IRAR index was formulated as log10(I0G0)+log10(I0G0)log10(R0/A0). The normal reference range of the IRAR index for insulin sensitive individuals was between 3.265 and 3.538. The minimum cut-off values of the IRAR index for insulin resistance assessment were between 3.538 and 3.955.ConclusionsThe novel AR and IRAR indexes are cost-effective, precise, reproducible and reliable integrated diagnostic biomarkers of insulin sensitivity for screening subjects with increased risk of future development of T2DM and MS.

Functional Dilator Capacity is Independently Associated with Insulin Sensitivity and Age in Central Obesity and is not Improved by High Dose Statin Treatment

To test the hypothesis that: (i) functional microvascular dilator capacity is independently associated with insulin sensitivity and age in individuals with central adiposity at risk of cardiovascular disease (CVD); and (ii) functional microvascular dilator capacity is improved by high dose statin treatment. Functional dilator capacity (measured as change in laser Doppler blood flux from baseline during post occlusive reactive hyperemia [peak flux%resting flux; PF%RF] and flowmotion (power spectral density [PSD] analysis)) were assessed in 40 people with central adiposity and one or more other CVD risk factors. Measurements were made at rest and during acute hyperinsulinaemia before and six months after high dose atorvastatin (40 mg daily) or placebo. Insulin-induced change in PF%RF was independently associated with insulin sensitivity (M/I) (r = 0.46 p = 0.02) and age (r = -0.46 p = 0.02), which together explained almost half of the variance in PF%RF (adjusted r² = 0.37, p = 0.008). Whilst atorvastatin decreased LDL cholesterol by 51% (p < 0.001), PF%RF and flowmotion remained unchanged. Insulin sensitivity and age are independently associated with an insulin-induced change in functional microvascular dilator capacity in individuals with central adiposity at risk of CVD. Dilator capacity is not improved by six months high dose statin treatment.

A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals

Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or ‘pre-diabetes’. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog®, and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or ‘pre-diabetes’, GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance.Copyright © 2010 John Wiley & Sons, Ltd.

Effect of Exercise Training with and without Metformin on Insulin Sensitivity in Individuals with Prediabetes

Habitual exercise or metformin both independently act to delay/prevent the progression from prediabetes to type 2 diabetes, in part by, improving insulin sensitivity. Insulin sensitivity could be potentially enhanced further by combining the two treatments but this approach has not been tested under controlled experimental conditions. PURPOSE: To evaluate the impact of exercise training and metformin on insulin sensitivity in men and women with prediabetes compared to either treatment alone. We hypothesized that the combination of exercise and metformin would improve insulin sensitivity more than either treatment alone. METHODS: In a double-blind, placebo-controlled design, 32 subjects with prediabetes were randomized to placebo (P; 6F, 2M), metformin (M; 5F, 3M), exercise training and placebo (EP; 5F, 3M), or exercise training and metformin (EM; 5F, 3M) and were well-matched for age, weight, fitness, etc. Individuals were provided 2000mg/d of M or P over 12 weeks and 16 subjects participated in a progressive aerobic and resistance training program. Outcomes included: insulin sensitivity (measured 28hr post-exercise by euglycemic hyperinsulinemic (80 mU/m2/min) clamp), non-oxidative glucose disposal (NOGD) and FFA suppression. Pre- to post changes across conditions were compared using a 2-way repeated measures analysis of variance. RESULTS: Compared to P, all interventions enhanced insulin sensitivity (M by 58%; EM by 75%; EP by 95%; P < 0.02). NOGD also increased across all non-P conditions (P < 0.04), and the change in insulin sensitivity was strongly correlated with the change in NOGD (r = 0.84; P < 0.05), indicating that higher insulin sensitivity was related to increased glucose storage. Only EP increased FFA suppression (P < 0.01) but there was still a weak correlation between the change in insulin sensitivity and the change in FFA suppression (r = -0.38; P < 0.05), suggesting higher insulin sensitivity may be a factor explaining increases in FFA suppression. CONCLUSIONS: Twelve weeks of either exercise training or metformin considerably enhances whole-body insulin sensitivity in individuals with prediabetes. There was no additive effect of combining treatments and subtle differences among condition means suggesting that adding metformin could blunt the full impact of exercise training alone. There was some indication that the responses to treatments varied according to the pathophysiology of the individuals (i.e. impaired glucose tolerance alone or with impaired fasting glucose). Funded by: NIH 5 R56 DK081038

Impact of glucocorticoids on insulin resistance in the critically ill

Glucocorticoids (GCs) have been shown to reduce insulin sensitivity in healthy individuals. Widely used in critical care to treat a variety of inflammatory and allergic disorders, they may inadvertently exacerbate stress-hyperglycaemia. This research uses model-based methods to quantify the reduction in insulin sensitivity from GCs in critically ill patients, and thus their impact on glycaemic control. A model-based measure of insulin sensitivity ( S I ) was used to quantify changes between two matched cohorts of 40 intensive care unit (ICU) patients. Patients in one cohort received GC treatment, while patients in the control cohort did not. All patients were admitted to the Christchurch hospital ICU between 2005 and 2007 and spent at least 24 h on the SPRINT glycaemic control protocol. A 31% reduction in whole-cohort median insulin sensitivity was seen between the control cohort and patients receiving glucocorticoids with a median dose equivalent to 200 mg/d of hydrocortisone per patient. Comparing percentile patients as a surrogate for matched patients, reductions in median insulin sensitivity of 20%, 25%, and 21% were observed for the 25th-, 50th- and 75th-percentile patients, respectively. These cohort and percentile patient reductions are less than or equivalent to the 30–62% reductions reported in healthy subjects especially when considering the fact that the GC doses in this study are 1.3–4.0 times larger than those in studies of healthy subjects. This reduced suppression of insulin sensitivity in critically ill patients could be a result of saturation due to already increased levels of catecholamines and cortisol common in critically illness. Virtual trial simulation showed that reductions in insulin sensitivity of 20–30% associated with glucocorticoid treatment in the ICU have limited impact on glycaemic control levels within the context of the SPRINT protocol.

The effect of acute exercise on undercarboxylated osteocalcin in obese men

The purpose of this study was to examine if the reduction in glucose post-exercise is mediated by undercarboxylated osteocalcin (unOC). Obese men were randomly assigned to do aerobic or power exercises. The change in unOC levels was correlated with the change in glucose levels post-exercise. The reduction in glucose post-acute exercise may be partly related to increased unOC. Osteocalcin (OC) in its undercarboxylated (unOC) form may contribute to the regulation of glucose homeostasis. As exercise reduces serum glucose and improves insulin sensitivity in obese individuals and individuals with type 2 diabetes (T2DM), we hypothesised that this benefit was partly mediated by unOC. Twenty-eight middle-aged (52.4 ± 1.2 years, mean ± SEM), obese (BMI = 32.1 ± 0.9 kg m(-2)) men were randomly assigned to do either 45 min of aerobic (cycling at 75% of VO(2peak)) or power (leg press at 75% of one repetition maximum plus jumping sequence) exercises. Blood samples were taken at baseline and up to 2 h post-exercise. At baseline, unOC was negatively correlated with glucose levels (r = -0.53, p = 0.003) and glycosylated haemoglobin (HbA1c) (r = -0.37, p = 0.035). Both aerobic and power exercises reduced serum glucose (from 7.4 ± 1.2 to 5.1 ± 0.5 mmol L(-1), p = 0.01 and 8.5 ± 1.2 to 6.0 ± 0.6 mmol L(-1), p = 0.01, respectively). Aerobic exercise significantly increased OC, unOC and high-molecular-weight adiponectin, while power exercise had a limited effect on OC and unOC. Overall, those with higher baseline glucose and HbA1c had greater reductions in glucose levels after exercise (r = -0.46, p = 0.013 and r = -0.43, p = 0.019, respectively). In a sub-group of obese people with T2DM, the percentage change in unOC levels was correlated with the percentage change in glucose levels post-exercise (r = -0.51, p = 0.038). This study reports that the reduction in serum glucose post-acute exercise (especially aerobic exercise) may be partly related to increased unOC.

Increased Reactive Oxygen Species Production and Lower Abundance of Complex I Subunits and Carnitine Palmitoyltransferase 1B Protein Despite Normal Mitochondrial Respiration in Insulin-Resistant Human Skeletal Muscle

OBJECTIVEThe contribution of mitochondrial dysfunction to skeletal muscle insulin resistance remains elusive. Comparative proteomics are being applied to generate new hypotheses in human biology and were applied here to isolated mitochondria to identify novel changes in mitochondrial protein abundance present in insulin-resistant muscle.RESEARCH DESIGN AND METHODSMitochondria were isolated from vastus lateralis muscle from lean and insulin-sensitive individuals and from obese and insulin-resistant individuals who were otherwise healthy. Respiration and reactive oxygen species (ROS) production rates were measured in vitro. Relative abundances of proteins detected by mass spectrometry were determined using a normalized spectral abundance factor method.RESULTSNADH- and FADH2-linked maximal respiration rates were similar between lean and obese individuals. Rates of pyruvate and palmitoyl-dl-carnitine (both including malate) ROS production were significantly higher in obesity. Mitochondria from obese individuals maintained higher (more negative) extramitochondrial ATP free energy at low metabolic flux, suggesting that stronger mitochondrial thermodynamic driving forces may underlie the higher ROS production. Tandem mass spectrometry identified protein abundance differences per mitochondrial mass in insulin resistance, including lower abundance of complex I subunits and enzymes involved in the oxidation of branched-chain amino acids (BCAA) and fatty acids (e.g., carnitine palmitoyltransferase 1B).CONCLUSIONSWe provide data suggesting normal oxidative capacity of mitochondria in insulin-resistant skeletal muscle in parallel with high rates of ROS production. Furthermore, we show specific abundance differences in proteins involved in fat and BCAA oxidation that might contribute to the accumulation of lipid and BCAA frequently associated with the pathogenesis of insulin resistance.

High-intensity exercise and carbohydrate-reduced energy-restricted diet in obese individuals

Continuous high glycemic load and inactivity challenge glucose homeostasis and fat oxidation. Hyperglycemia and high intramuscular glucose levels mediate insulin resistance, a precursor state of type 2 diabetes. The aim was to investigate whether a carbohydrate (CHO)-reduced diet combined with high-intensity interval training (HIIT) enhances the beneficial effects of the diet alone on insulin sensitivity and fat oxidation in obese individuals. Nineteen obese subjects underwent 14days of CHO-reduced and energy-restricted diet. Ten of them combined the diet with HIIT (4min bouts at 90% VO(2peak) up to 10 times, 3 times a week). Oral glucose insulin sensitivity (OGIS) increased significantly in both groups; [diet-exercise (DE) group: pre 377±70, post 396±68mLmin(-1)m(-2); diet (D) group: pre 365±91, post 404±87mLmin(-1)m(-2); P<0.001]. Fasting respiratory exchange ratio (RER) decreased significantly in both groups (DE group: pre 0.91±0.06, post 0.88±0.06; D group: pre 0.92±0.07, post 0.86±0.07; P=0.002). VO(2peak) increased significantly in the DE group (pre 27±5, post 32±6mLkg(-1)min(-1); P<0.001), but not in the D group (pre 26±9, post 26±8mLkg(-1)min(-1)). Lean mass and resistin were preserved only in the DE group (P<0.05). Fourteen days of CHO-reduced diet improved OGIS and fat oxidation (RER) in obese subjects. The energy-balanced HIIT did not further enhance these parameters, but increased aerobic capacity (VO(2peak)) and preserved lean mass and resistin.

Effects of a Single Exercise Bout on Insulin Sensitivity in Black and White Individuals

Previous research suggests non-Hispanic blacks (blacks) are more insulin resistant than non-Hispanic whites (whites). Physical activity can play an important role in reducing insulin resistance. However, it is unknown whether racial differences exist in response to exercise. Therefore, the purpose of this study was to compare metabolic responses to a single bout of exercise in blacks and age-, sex-, and body mass index-matched whites. Whole-body insulin sensitivity, glucose storage, glucose oxidation, and respiratory exchange ratio (RER) were assessed during a hyperinsulinemic-euglycemic clamp in normoglycemic blacks (n = 11) and whites (n = 10). Outcome measures were evaluated in a sedentary control condition and 12 h after treadmill walking at 75% of maximal heart rate for 75 min. In the control condition, there were no differences in insulin sensitivity between blacks and whites (P = 0.54). During the clamp, glucose oxidation and insulin-stimulated RER values were significantly higher in blacks compared with whites (P = 0.04 and P < 0.01, respectively). Despite similar RER values during exercise, RER values at 60, 90, and 120 min after exercise in blacks were also significantly higher compared with whites (P < 0.05). After exercise, there were no significant improvements in insulin sensitivity (P = 0.57) or glucose storage (P = 0.42) in blacks or whites; however, glucose oxidation was significantly lower in both racial groups (P < 0.05). These data suggest that insulin sensitivity is similar in blacks and age-, sex-, and body mass index-matched whites, but the glucose disposal pathways (storage vs. oxidation) are somewhat different. Compared with whites, blacks appear to have a greater capacity to increase glucose oxidation immediately after exercise and during insulin stimulation.

Fitness Abrogates the Ability of Free Fatty Acids (FFA) to Inhibit Insulin's Microvascular Action

Insulin acutely (within 20 min) increases microvascular blood volume (MBV) within human forearm muscle as measured by contrast enhanced ultrasound (CEU). This serves to increase insulin delivery to muscle and facilitates insulin's metabolic action. This vascular effect of insulin is impaired by the insulin resistance that accompanies either chronic obesity or acute (within 2-4hr) increases in the circulating levels of FFA. Interestingly, and as yet unexplained, raising plasma FFA via infusion of Intralipid has less effect on insulin sensitivity in individuals who are highly trained. It is not known whether training affects the ability of FFA to inhibit insulin-induced microvascular recruitment. PURPOSE: The current study was undertaken to address whether the level of fitness (VO2 max) or adiposity (% body fat) predicted MBV and/or glucose infusion rate (GIR) during a euglycemic insulin clamp. METHODS: A group (n =11) of young (18-35), lean (BMI≤25), healthy subjects received Intralipid 20% + heparin for 5 hrs (3hr prior to and throughout a 2hr, 1mU/kg/min insulin clamp). MBV as measured by CEU was obtained continuously during the first 30 min of the clamp. Fitness level was assessed by conducting an exercise test (Bruce protocol) to obtain VO2 max in a subset (n=8) on a separate day. RESULTS: We found that VO2 max was a strong predictor of MBV (r = 0.74 p <0.05) the GIR likewise strongly correlated with MBV(r = 0.75, p= 0.01) supporting the hypothesis that insulin's vascular action is a significant contributor to its metabolic effects. We also observed the expected inverse relationship between VO2 max and % body fat (r = -0.79, p= 0.02). CONCLUSION: Fitness limits the ability of elevated FFA to block both insulin's vasodilatory and metabolic effects. The increased microvascular surface area in response to insulin seen in those with higher VO2 max can facilitate exchange of insulin and glucose with muscle interstitium thereby contributing to the higher GIR. In addition the lower body fat %, therefore greater % lean body mass, may also contribute to the higher GIR. Taken together these findings suggest that a more fit person is less likely to develop either vascular or metabolic insulin resistance in response to elevated circulation FFA. The mechanism for the protective effect of fitness is unclear. Supported by NIH Grant RO1 DK073759

Skeletal muscle HNE is related to insulin resistance in sedentary individuals

The relationships among skeletal muscle lipid peroxidation (HNE), intramyocellular lipid content (IMCL), and insulin sensitivity were studied in sedentary adults. We assessed IMCL, glucose uptake (GDR), homeostasis model assessment index (HOMA), BMI, body fat (DXA), waist girth (WAIST), and skeletal muscle HNE adducts in 9 insulin‐sensitive (IS), 13 insulin‐resistant (IR), and 10 adults with type 2 diabetes (DB).GDR and HOMA differed among IS, IR, and DB (GDR: 16.6 ±2.6, 9.3 ± 1.6, 6.6 ± 2.1, p &lt; 0.01; HOMA: 2.0 ± 0.7, 5.2 ± 3.7, 7.0 ± 5.1, p &lt; 0.05. HNE was higher in DB than IS (971 ± 436 vs. 609 ± 170; p &lt; 0.05) and correlated with GDR (R = −0.43, p &lt; 0.05), HOMA (R = 0.43, p &lt; 0.05), and BMI (R = 0.42, p &lt; 0.05), but not with IMCL, WAIST, or DXA. IMCL was higher in DB than in IS and IR (8.1 ± 3.8 vs. 2.0 ± 1.0 and 3.8 ± 2.8, p &lt; 0.01) and correlated with GDR (R = −0.56, p &lt; 0.01). IMCL was the primary predictor of GDR (R2 = 0.31, p &lt; 0.01), while HNE was that of HOMA (R2 = 0.18, p &lt; 0.05).Our data show that (1) skeletal muscle HNE and IMCL are both determinants of the severity of insulin resistance assessed by hyperinsulinemic clamp or HOMA in sedentary adults; (2) HNE and IMCL are not related and thus impact GDR independently. These results reveal, for the first time, a negative relationship between skeletal muscle HNE and insulin sensitivity in sedentary individuals and underscore the importance of lipid peroxidation in insulin resistance.Funded by NIH (DK‐038764, HL‐055782), Department of Veterans Affairs (Merit Review), and Gatorade Sport Science Institute's Student Grant Program.

The relationship between heat shock protein 72 expression in skeletal muscle and insulin sensitivity is dependent on adiposity

Decreased gene expression of heat shock protein 72 (HSP72) in skeletal muscle is associated with insulin resistance in humans. We aimed to determine whether HSP72 protein expression in insulin-sensitive tissues is related to criterion standard measures of adiposity and insulin resistance in a young healthy human population free of hyperglycemia. Healthy participants (N = 17; age, 30 ± 3 years) underwent measurement of body composition (dual-energy x-ray absorptiometry), a maximum aerobic capacity test (V̇ o 2max), an oral glucose tolerance test, and a hyperinsulinemic-euglycemic clamp (M) to access insulin sensitivity. Skeletal muscle and subcutaneous adipose tissue biopsies were obtained by percutaneous needle biopsy. HSP72 protein expression in skeletal muscle was inversely related to percentage body fat ( r = −0.54, P < .05) and remained significant after adjustment for age and sex ( P < .05). Insulin sensitivity was also related to HSP72 protein expression in skeletal muscle ( r = 0.52, P < .05); however, this relationship disappeared after adjustment for percentage body fat ( P = .2). In adipose tissue, HSP72 protein expression was not related to adiposity or insulin sensitivity. Physical activity and aerobic fitness did not show any association with HSP72 protein expression in either tissue studied. A lower expression of HSP72 protein in human skeletal muscle was associated with increased adiposity and decreased insulin sensitivity in healthy individuals. These findings are consistent with rodent data suggesting that HSP72 stimulates fat oxidation with consequent reduction in fat storage and adiposity.

Fitness and Weight Cycling in Relation to Body Fat and Insulin Sensitivity in Normal-Weight Young Women

A direct link has been established between insulin resistance and obesity; however, the influence of body fat content on insulin sensitivity in normal-weight individuals has not been explored. The aim of this cross-sectional study was to examine differences in insulin sensitivity, glycemic control, and blood lipid levels in normal-weight, healthy participants differing in their body fat. Physical activity, cardiorespiratory fitness, weight cycling, nutrient intake, and eating behavior were also assessed. Two groups of normal-weight (body mass index <25) young, healthy women were recruited: a high-body-fat group with body fat >30% of body weight (n=15) and a low-body-fat group (fat ≤30%, n=17). Data were collected between November 2003 and March 2004. Participants were matched for age and body fat distribution (assessed by the waist-to-hip ratio). The high-body-fat group displayed lower values of insulin sensitivity compared to the low-body-fat group (1/homeostasis model assessment of insulin resistance 1.003±0.083 vs 1.385±0.158, respectively; P<0.05), whereas no differences were observed on blood lipid levels and glycemic control between groups. High-body-fat participants had lower cardiorespiratory fitness (25.2±1.2 vs 28.2±1.4 mL/kg/min in the low-body-fat group, P<0.05) and higher incidence of weight cycling of 1.0 to 2.5 kg loss per lifetime (18±3 kg vs 8±2 kg in the low-body-fat group, P<0.05). The latter variable was the only factor significantly associated with body fat. These data suggest that increased adiposity in normal weight, healthy women may adversely affect insulin sensitivity and that it may be related to differences in physical fitness and eating behavior.

Insulin sensitivity (Si) assessment in lean and overweight subjects using two different protocols and updated software

Background. The standard frequently-sampled intravenous glucose tolerance test (FSIVGTT) is an alternative procedure to the clamp technique for estimating the insulin sensitivity (Si) parameter. The goal of this study was to compare Si in lean and overweight individuals in addition to assessing intra-individual reproducibility using two different protocols and updated software. Methods. FSIVGTT was carried out in 14 lean (BMI ≤ 25 kg/m2) and 14 overweight (BMI>25 kg/m2) subjects using two different protocols; full (29 samples) and short (12 samples). For reproducibility assessment four normal subjects (triplicate on three and twice on one) were recruited to undergo the same procedure at 1-week intervals. Data analysis was performed using COMAL and Minmod Millennium software. Results. Mean Si (10−4min−1[pmol/l]−1) values were significantly different between lean and overweight subjects (p < 0.001) but not between the two protocols using both software packages. For the full and short protocols, Si values were more closely related in lean versus overweight subjects using either COMAL (r = 0.98, p < 0.001), (r = 0.89, p < 0.001) or Minmod Millennium (r = 0.99, p < 0.001), (r = 0.85, p < 0.001) software respectively. The intra-individual reproducibility (%CV) of Si (COMAL) in full versus short protocol was 18.3 ± 11.1% and 13.7 ± 1.9% respectively. Reproducibility values for Si (Minmod Millenium) in full versus short protocols were 14.3 ± 3.8 and 14.9 ± 1.9% respectively. Conclusions. Si can be assessed accurately by a short protocol FSIVGTT in normal individuals. The short protocol may give less acceptable results for insulin sensitivity in individuals who have normal glucose tolerance but high BMI.

Oral Carnitine Therapy and Insulin Resistance

To the Editor: Ruggenenti et al1 report that oral administration of acetyl-l-carnitine results in a substantial, sustained, and simultaneous improvement in insulin sensitivity and blood pressure in insulin-resistant individuals. Carnitine is essential for mitochondrial import and subsequent β-oxidation of long-chain fatty acids and in the sequestration and mitochondrial export of inhibitory acetyl-coenzyme A units as acetyl-carnitine, actions that favor glucose oxidation. Mitochondrial dysfunction associated with incomplete β-oxidation and accumulation of intramyocellular lipids may contribute …

What reduction in BMI SDS is required in obese adolescents to improve body composition and cardiometabolic health?

ObjectiveTo study the impact of body mass index (BMI) SD score (SDS) improvement through lifestyle modification on metabolic risk and body composition over 12 months.DesignProspective cohort study.SettingHospital outpatient weight management...