Direct comparison among oral hypoglycemic agents and their association with insulin resistance evaluated by euglycemic hyperinsulinemic clamp: the 60's study. Chitosan improves insulin sensitivity as determined by the euglycemic-hyperinsulinemic clamp technique in obese subjects. Longitudinal changes in insulin release and insulin resistance in nonobese pregnant women. How good a marker is insulin level for insulin resistance? Exercise training augments the peripheral insulin-sensitizing effects of pioglitazone in HIV-infected adults with insulin resistance and central adiposity. Vildagliptin added to metformin on β-cell function after a euglycemic hyperinsulinemic and hyperglycemic clamp in type 2 diabetes patients. Effect of Oral L-Carnitine Administration on Insulin Sensitivity and Lipid Profile in Type 2 Diabetes Mellitus Patients Effects of sustained insulin-induced hypoglycemia on cardiovascular autonomic regulation in type 1 diabetes. Metformin Plus Low-Dose Glimeperide Significantly Improves Homeostasis Model Assessment for Insulin Resistance (HOMAIR) and β-Cell Function (HOMAβ-cell) Without Hyperinsulinemia in Patients With Type 2 Diabetes Mellitus Insulin resistance and insulin secretory dysfunction as precursors of non-insulin-dependent diabetes mellitus. Prospective studies of Pima Indians. Antioxidants prevent health-promoting effects of physical exercise in humans Effects of Aerobic Versus Resistance Exercise Without Caloric Restriction on Abdominal Fat, Intrahepatic Lipid, and Insulin Sensitivity in Obese Adolescent Boys Vitamin D supplementation for the prevention of type 2 diabetes in overweight adults: study protocol for a randomized controlled trial A polymorphism (K121Q) of the human glycoprotein PC-1 gene coding region is strongly associated with insulin resistance. Both resistance training and aerobic training reduce hepatic fat content in type 2 diabetic subjects with nonalcoholic fatty liver disease (the RAED2 Randomized Trial). α-Hydroxybutyrate Is an Early Biomarker of Insulin Resistance and Glucose Intolerance in a Nondiabetic Population A comparison of troglitazone and metformin on insulin requirements in euglycemic intensively insulin-treated type 2 diabetic patients. Effect of whole grains on insulin sensitivity in overweight hyperinsulinemic adults. Lipid-Induced Insulin Resistance Is Associated With an Impaired Skeletal Muscle Protein Synthetic Response to Amino Acid Ingestion in Healthy Young Men Strength training increases insulin action in healthy 50- to 65-yr-old men. Reversal of muscle insulin resistance by weight reduction in young, lean, insulin-resistant offspring of parents with type 2 diabetes Changes in glucose turnover parameters and improvement of glucose oxidation after 4-week magnesium administration in elderly noninsulin-dependent (type II) diabetic patients. Efficacy of increased resistant starch consumption in human type 2 diabetes
The aim of the study was to compare the long-term effect of 4 antidiabetic treatment protocol s on insulin resistance evaluated by euglycemic hyperinsulinemic clamp in type 2 diabetes mellitus patients . Two hundred seventy-one type 2 diabetes mellitus patients with poor glycemic control and who were overweight were enrolled in this study . Patients were r and omized and titrated to take pioglitazone , metformin , pioglitazone + metformin , or glimepiride + metformin for 15 months . They underwent a euglycemic hyperinsulinemic clamp at baseline , after 3 months , and after 15 months . Anthropometric and metabolic measurements were assessed at baseline , after 3 months , and after 15 months . There was a decrease in glycated hemoglobin in all groups , but glycated hemoglobin value was lower in the group treated with pioglitazone + metformin compared with the groups treated with metformin alone and with pioglitazone alone . There was a decrease in fasting plasma glucose and postpr and ial plasma glucose values in all groups , but values obtained with pioglitazone + metformin were lower compared with values in the groups treated with metformin alone and with pioglitazone alone . Fasting plasma insulin and postpr and ial plasma insulin values were higher in the group treated with glimepiride + metformin compared with the other groups . After 15 months , glucose infusion rate and total glucose requirement values observed in the groups treated with pioglitazone alone and with pioglitazone + metformin were higher compared with the values in the group treated with metformin alone and with glimepiride + metformin ; furthermore , values obtained in the group treated with pioglitazone + metformin were higher than the value obtained with pioglitazone alone . Pioglitazone-metformin-based therapeutic control is associated with the most quantitatively relevant improvement in insulin resistance-related parameters , whereas the sulfonylurea-metformin-including protocol has less relevant effects In accordance with obesity is associated with insulin resistance and dyslipidemia and chitosan decrease weight and lipids , but its effect on insulin sensitivity is unknown . Our hypothesis for the research was that chitosan improves insulin sensitivity estimated with the euglycemic-hyperinsulinemic clamp technique in obesity . We undertook this study with the objective to determine the effect of chitosan on insulin sensitivity using the euglycemic-hyperinsulinemic clamp technique in obese patients during a 3-month period . A r and omized , double-blind clinical trial was carried out in 12 obese adults without diabetes mellitus . During a 3-month period , 6 patients received chitosan ( 750 mg , 3 times per day ) 30 minutes before meals , and the other 6 subjects received placebo .  Serum glucose , total cholesterol , high-density lipoprotein cholesterol , and triglycerides ( TG ) were measured . Insulin sensitivity was estimated with the euglycemic-hyperinsulinemic clamp technique before and after the intervention . Insulin sensitivity increased significantly with the administration of chitosan ( 2.4 + /- 1.4 vs 3.6 + /- 1.4 mg kg(-1 ) min(-1 ) ; P = .043 ) . In addition , there was a decrease in weight ( 90.7 + /- 14.2 vs 84.7 + /- 13.7 kg ; P = .027 ) , body mass index ( 34.3 + /- 2.7 vs 31.6 + /- 2.2 kg/m(2 ) ; P = .028 ) , waist circumference ( 106 + /- 12 vs 99 + /- 9 cm ; P = .028 ) and TG ( 2.4 + /- 0.9 vs 1.6 + /- 0.9 mmol/L ; P = .028 ) in the chitosan group . In conclusion , 3-month administration of chitosan increased insulin sensitivity  in obese patients and demonstrated a decrease in weight , body mass index , waist circumference , and TG To assess the longitudinal changes in insulin release and insulin sensitivity in nonobese normal women during gestation , six women were evaluated with oral glucose tolerance testing , body composition analysis , intravenous glucose tolerance tests , and the hyperinsulinemic-euglycemic clamp before conception , at 12 to 14 weeks , and at 34 to 36 weeks ' gestation . There was a significant increase in the insulin/glucose ratio ( p = 0.028 ) during the oral glucose tolerance test during gestation . There was also a significant 3.0- to 3.5-fold increase throughout gestation in first-phase ( p = 0.001 ) and second-phase ( p = 0.0001 ) insulin release during the intravenous glucose tolerance test . Peripheral insulin sensitivity was estimated as the glucose infusion rate ( in milligrams per kilogram fat-free mass per minute ) during the hyperinsulinemic-euglycemic clamp . There was a significant ( p = 0.0003 ) 56 % decrease in insulin sensitivity through 36 weeks ' gestation . These results are the first to prospect ively evaluate the longitudinal changes in maternal carbohydrate metabolism from the time before conception through late gestation with newer methods such as the hyperinsulinemic-euglycemic clamp Epidemiologic studies have correlated fasting and postload insulin levels with the risk of coronary heart disease , assuming that insulin levels are reliable markers of insulin resistance . However , this assumption has not been systematic ally studied . The author measured insulin response to an oral glucose load and quantitated insulin resistance using the euglycemic hyperinsulinemic clamp technique to evaluate the correlation between insulin level and the degree of insulin resistance in individuals with varying degrees of glucose tolerance . Subjects were r and omly selected from previous population studies done in 1987 - 1989 at the Department of Medicine of the University of Kuopio in east Finl and . Altogether , 50 subjects with normal glucose tolerance , 28 with impaired glucose tolerance , and 54 with non-insulin-dependent diabetes mellitus were studied . Correlations of insulin resistance ( whole-body glucose uptake in clamp studies ) with fasting or postload insulin levels were remarkably consistent , ranging from -0.58 to -0.74 ( p < 0.01 ) in subjects with normoglycemia . In contrast , corresponding correlations were substantially weaker in subjects with impaired glucose tolerance and non-insulin-dependent diabetes . Among these subjects , only the fasting insulin level correlated significantly with insulin resistance ( -0.47 , p < 0.05 and -0.48 , p < 0.01 , respectively ) . The authors conclude that in population studies , only the fasting insulin level should be used as a marker of insulin resistance , particularly in subjects with abnormal glucose tolerance The prevalence and incidence of insulin resistance and type 2 diabetes mellitus ( DM ) are higher in people treated for human immunodeficiency virus-1 ( HIV ) infection than in the general population . Identifying safe and effective interventions is a high priority . We evaluated whether the peroxisome proliferator-activated receptor-γ agonist pioglitazone with exercise training improves central and peripheral insulin sensitivity more than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity . Forty-four HIV-infected adults with baseline insulin resistance and central adiposity were r and omly assigned to 4 mo of pioglitazone ( 30 mg/day ) with or without supervised , progressive aerobic , and resistance exercise training ( 1.5 - 2 h/day , 3 days/wk ) . The hyperinsulinemic euglycemic clamp was used to evaluate alterations in central and peripheral insulin sensitivity . Thirty-nine participants completed the study . Hepatic insulin sensitivity improved similarly in both groups . Exercise training augmented the beneficial effects of pioglitazone on peripheral insulin sensitivity . Greater improvements in peripheral insulin sensitivity were associated with reductions in total body and limb adipose content rather than increases in limb adiposity or pioglitazone-induced increases in adiponectin concentration . We conclude that supplementing pioglitazone with increased physical activity improved insulin sensitivity more effectively than pioglitazone alone in HIV-infected adults with insulin resistance and central adiposity . Pioglitazone alone did not significantly increase limb adipose content . Potential cardiovascular benefits of these interventions in HIV need investigation BACKGROUND This study evaluated the effect of vildagliptin + metformin on glycemic control and β-cell function in type 2 diabetes patients . SUBJECTS AND METHODS One hundred seventy-one type 2 diabetes patients , naive to antidiabetes therapy and with poor glycemic control , were instructed to take metformin for 8±2 months up to a mean dosage of 2,500±500 mg/day ; then they were r and omly assigned to add vildaglipin 50 mg twice a day or placebo for 12 months . We evaluated at 3 , 6 , 9 , and 12 months : body mass index , glycemic control , fasting plasma insulin , homeostasis model assessment insulin resistance index ( HOMA-IR ) , homeostasis model assessment β-cell function index ( HOMA-β ) , fasting plasma proinsulin , proinsulin/fasting plasma insulin ratio , C-peptide , glucagon , adiponectin , and high-sensitivity C-reactive protein . Before and at 12 months after the addition of vildagliptin , patients underwent a combined euglycemic hyperinsulinemic and hyperglycemic clamp , with subsequent arginine stimulation , to assess insulin sensitivity and insulin secretion . RESULTS After 12 months of treatment , vildagliptin + metformin gave a better decrease of body weight , glycemic control , HOMA-IR , and glucagon and a better increase of HOMA-β compared with placebo + metformin . Regarding the measures of β-cell function , treatment-induced changes in M-value , first- and second-phase C-peptide response to glucose , and C-peptide response to arginine were significantly higher in the vildagliptin + metformin group compared with the placebo + metformin group . CONCLUSION The addition of vildagliptin to metformin gave a better improvement of glycemic control , insulin resistance , and β-cell function  compared with metformin alone Aim : It was the aim of this study to evaluate the effect of oral L-carnitine administration on insulin sensitivity and lipid profile in subjects with type 2 diabetes mellitus . Subjects and Methods : A r and omized , double-blind , placebo-controlled clinical trial was carried out in 12 subjects with type 2 diabetes . Six subjects received L-carnitine 1 g orally 3 times a day before meals for a period of 4 weeks . Six other individuals took a placebo for the same period of time , as the control group . Before and after the intervention , insulin sensitivity and the lipid profile were estimated . To assess insulin sensitivity , the euglycemic-hyperinsulinemic clamp technique was performed . Wilcoxon ’s signed rank and the Mann-Whitney U test were used for the statistical analyses . Results : There were no significant differences in basal clinical characteristics between the 2 groups . Insulin sensitivity and the basal lipid profile were similar . There were no significant changes in either group after the intervention in insulin sensitivity ( 3.2 ± 1.2 vs. 4.5 ± 1.7 mg/kg/min , p = 0.115 , and 3.5 ± 0.6 vs. 3.5 ± 0.4 mg/kg/min , p = 0.917 , for the placebo and L-carnitine groups , respectively ) and in lipid profile . Conclusion : L-Carnitine orally administered for a period of 4 weeks did not modify insulin sensitivity or the lipid profile Effects of hypoglycemia on cardiac autonomic regulation may contribute to the occurrence of adverse cardiac events . This study assessed the effects of sustained hyperinsulinemic hypoglycemia on cardiovascular autonomic regulation in type 1 diabetic patients and their nondiabetic counterparts . The study consisted of 16 type 1 diabetic patients and 8 age-matched healthy control subjects who underwent euglycemic and hypoglycemic clamp procedures in a r and om order .  Heart rate variability was measured from continuous electrocardiogram recordings by time and frequency domain methods , along with Poincare plot analysis during both a hyperinsulinemic-euglycemic and hypoglycemic clamp at three different glucose levels ( 4.5 - 5.5 , 3.0 - 3.5 , and 2.0 - 2.5 mmol/l ) . Controlled hypoglycemia result ed in an increase of supine heart rate in both the diabetic patients ( from 72 + /- 9 to 80 + /- 11 bpm , P < 0.01 ) and the control subjects ( from 59 + /- 5 to 65 + /- 5 bpm , P < 0.05 ) and progressive reductions of the high-frequency spectral component and beat-to-beat heart rate variability ( SD1 ; P < 0.05 in the diabetic patients and P < 0.01 in control subjects ) . No significant changes in heart rate variability occurred during the euglycemic clamp . We conclude that hypoglycemia results in a reduction of cardiac vagal outflow in both diabetic and nondiabetic subjects . Altered autonomic regulation may contribute to the occurrence of cardiac events during hypoglycemia Objective : Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic β-cells , which have been studied by using euglycemic/hyperinsulinemic clamps . However , it is difficult to study insulin resistance and β-cell failure by these techniques in humans . Therefore , the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and β-cell activity by using a mathematical model , Homeostasis Model Assessment for insulin resistance ( HOMAIR ) and β-cell function ( HOMAβ-cell ) . Research design and methods : Seventy type 2 diabetic patients were r and omly assigned to one of three therapeutic regimens : ( A ) metformin + American Diabetic Association (ADA)-recommended diet + physical activity ; ( B ) metformin + low-dose glimepiride + ADA diet + physical activity ; or ( C ) ADA diet + physical activity ( no drugs ) . Blood sample s were obtained before and after the treatment to determine serum levels of fasting and post-pr and ial blood glucose , fasting insulin , and glycosylated hemoglobin ( HbA1c ) , and HOMAIR and HOMAβ-cell were calculated . Results : Fasting and post-pr and ial levels of glucose , HbA1c , and fasting insulin and calculated HOMAIR and HOMAβ-cell values before treatment were significantly higher than the respective values after treatment for all groups of patients ( P < 0.01 ) . Significant differences were also found when comparing the treatment-induced reduction in fasting blood glucose ( 51.8 % ; P < 0.01 ) , post-pr and ial blood glucose ( 55.0 % ; P < 0.05 ) , and HOMAIR ( 65.3 % ; P < 0.01 ) in patients of Group B with that in patients receiving other therapeutic options ( Groups A and C ) . Conclusions : Metformin plus low-dose glimepiride ( plus ADA diet and physical activity ) is a more effective treatment for type 2 diabetes than either metformin plus ADA diet and physical activity or ADA diet and physical activity alone . Determination of HOMAIR and HOMAβ-cell values is an inexpensive , reliable , less invasive , and less labor-intensive method than other tests to estimate insulin resistance and β-cell function in patients with type 2 diabetes mellitus BACKGROUND The relative roles of obesity , insulin resistance , insulin secretory dysfunction , and excess hepatic glucose production in the development of non-insulin-dependent diabetes mellitus ( NIDDM ) are controversial . We conducted a prospect i ve study to determine which of these factors predicted the development of the disease in a group of Pima Indians . METHODS A body-composition assessment , oral and intravenous glucose-tolerance tests , and a hyperinsulinemic -- euglycemic clamp study were performed in 200 non-diabetic Pima Indians ( 87 women and 113 men ; mean [ + /- SD ] age , 26 + /- 6 years ) . The subjects were followed yearly thereafter for an average of 5.3 years . RESULTS Diabetes developed in 38 subjects during follow-up . Obesity , insulin resistance ( independent of obesity ) , and low acute plasma insulin response to intravenous glucose ( with the degree of obesity and insulin resistance taken into account ) were predictors of NIDDM : The six-year cumulative incidence of NIDDM was 39 percent in persons with values below the median for both insulin action and acute insulin response , 27 percent in those with values below the median for insulin action but above that for acute insulin response , 13 percent in those with values above the median for insulin action and below that for acute insulin response , and 0 in those with values originally above the median for both characteristics . CONCLUSIONS Insulin resistance is a major risk factor for the development of NIDDM : A low acute insulin response to glucose is an additional but weaker risk factor Exercise promotes longevity and ameliorates type 2 diabetes mellitus and insulin resistance . However , exercise also increases mitochondrial formation of presumably harmful reactive oxygen species ( ROS ) . Antioxidants are widely used as supplements but whether they affect the health-promoting effects of exercise is unknown . We evaluated the effects of a combination of vitamin C ( 1000 mg/day ) and vitamin E ( 400 IU/day ) on insulin sensitivity as measured by glucose infusion rates ( GIR ) during a hyperinsulinemic , euglycemic clamp in previously untrained ( n = 19 ) and pretrained ( n = 20 ) healthy young men . Before and after a 4 week intervention of physical exercise , GIR was determined , and muscle biopsies for gene expression analyses as well as plasma sample s were obtained to compare changes over baseline and potential influences of vitamins on exercise effects . Exercise increased parameters of insulin sensitivity ( GIR and plasma adiponectin ) only in the absence of antioxidants in both previously untrained ( P < 0.001 ) and pretrained ( P < 0.001 ) individuals . This was paralleled by increased expression of ROS-sensitive transcriptional regulators of insulin sensitivity and ROS defense capacity , peroxisome-proliferator-activated receptor gamma ( PPARγ ) , and PPARγ coactivators PGC1α and PGC1β only in the absence of antioxidants ( P < 0.001 for all ) . Molecular mediators of endogenous ROS defense ( superoxide dismutases 1 and 2 ; glutathione peroxidase ) were also induced by exercise , and this effect too was blocked by antioxidant supplementation . Consistent with the concept of mitohormesis , exercise-induced oxidative stress ameliorates insulin resistance and causes an adaptive response promoting endogenous antioxidant defense capacity . Supplementation with antioxidants may preclude these health-promoting effects of exercise in humans The optimal exercise modality for reductions of abdominal obesity and risk factors for  type 2 diabetes in youth is unknown . We examined the effects of aerobic exercise ( AE ) versus resistance exercise ( RE ) without caloric restriction on abdominal adiposity , ectopic fat , and insulin sensitivity and secretion in youth . Forty-five obese adolescent boys were r and omly assigned to one of three 3-month interventions : AE , RE , or a nonexercising control . Abdominal fat was assessed by magnetic resonance imaging , and intrahepatic lipid and intramyocellular lipid were assessed by proton magnetic resonance spectroscopy . Insulin sensitivity and secretion were evaluated by a 3-h hyperinsulinemic-euglycemic clamp and a 2-h hyperglycemic clamp . Both AE and RE prevented the significant weight gain that was observed in controls . Compared with controls , significant reductions in total and visceral fat and intrahepatic lipid were observed in both exercise groups . Compared with controls , a significant improvement in insulin sensitivity ( 27 % ) was observed in the RE group . Collapsed across groups , changes in visceral fat were associated with changes in intrahepatic lipid ( r = 0.72 ) and insulin sensitivity ( r = −0.47 ) . Both AE and RE alone are effective for reducing abdominal fat and intrahepatic lipid in obese adolescent boys . RE but not AE is also associated with significant improvements in insulin sensitivity Background Despite Australia ’s sunny climate , low vitamin D levels are increasingly prevalent . Sun exposure is limited by long working hours , an increase in time spent indoors , and sun protection practice s , and there is limited dietary vitamin D fortification . While the importance of vitamin D for bone mineralization is well known , its role as a protective agent against chronic diseases , such as type 2 diabetes and cardiovascular disease , is less understood . Observational and limited intervention studies suggest that vitamin D might improve insulin sensitivity and secretion , mainly via its anti-inflammatory properties , thereby decreasing the risk of development and progression of type 2 diabetes . The primary aim of this trial is to investigate whether improved plasma concentrations of 25-hydroxyvitamin D ( 25(OH)D ) , obtained through vitamin D supplementation , will increase insulin sensitivity and insulin secretion . A secondary aim is to determine whether these relationships are mediated by a reduction in underlying sub clinical inflammation associated with obesity . Methods / Design Fifty overweight but otherwise healthy nondiabetic adults between 18 and 60 years old , with low vitamin D levels ( 25(OH)D < 50 nmol/l ) , will be r and omly assigned to intervention or placebo . At baseline , participants will undergo a medical review and anthropometric measurements , including dual X-ray absorptiometry , an intravenous glucose tolerance test , muscle and fat biopsies , a hyperinsulinemic euglycemic clamp  , and question naires assessing diet , physical activity , sun exposure , back and knee pain , and depression . The intervention group will receive a first dose of 100,000 IU followed by 4,000 IU vitamin D ( cholecalciferol ) daily , while the placebo group will receive apparently identical capsules , both for a period of 16 weeks . All measurements will be repeated at follow-up , with the primary outcome measure expressed as a change from baseline in insulin sensitivity and secretion for the intervention group compared with the placebo group . Secondary outcome measures will compare changes in anthropometry , cardiovascular risk factors , and inflammatory markers . Discussion The trial will provide much needed clinical evidence on the impact of vitamin D supplementation on insulin resistance and secretion and its underlying mechanisms , which are relevant for the prevention and management of type 2 diabetes . Trial registration Clinical trials.gov ID : NCT02112721 The genes responsible for insulin resistance are poorly defined . Plasma cell differentiation antigen ( PC-1 ) glycoprotein inhibits insulin receptor signaling and is associated with insulin resistance . We describe here a novel polymorphism in exon 4 of the PC-1 gene ( K121Q ) and demonstrate that it is strongly associated with insulin resistance in 121 healthy nonobese ( BMI < 30 kg/m2 ) nondiabetic ( by oral glucose tolerance test [ OGTT ] ) Caucasians from Sicily . Compared with 80 KK subjects , Q allele carriers ( n = 41 , 39 KQ and 2 QQ ) showed higher glucose and insulin levels during OGTT ( P < 0.001 by two-way analysis of variance ) and insulin resistance by euglycemic clamp ( M value = 5.25 + /- 1.38 [ n = 24 ] vs. 6.30 + /- 1.39 mg x kg(-1 ) x min(-1 ) [ n = 49 ] , P = 0.005 ) . Q carriers had higher risk of being hyperinsulinemic and insulin resistant ( odds ratio [ CI ] : 2.99 [ 1.28 - 7.0 ] , P < 0.001 ) . Insulin receptor autophosphorylation was reduced ( P < 0.01 ) in cultured skin fibroblasts from KQ versus KK subjects . Skeletal muscle PC-1 content was not different in 11 KQ versus 32 KK subjects ( 33 + /- 16.1 vs. 17.5 + /- 15 ng/mg protein , P = 0.3 ) . These results suggest a cause-effect relationship between the Q carrying genotype and the insulin resistance phenotype , and raise the possibility that PC-1 genotyping could identify individuals who are at risk of developing insulin resistance , a condition that predisposes to type 2 diabetes and coronary artery disease UNLABELLED Although lifestyle interventions are considered the first-line therapy for nonalcoholic fatty liver disease ( NAFLD ) , which is extremely common in people with type 2 diabetes , no intervention studies have compared the effects of aerobic ( AER ) or resistance ( RES ) training on hepatic fat content in type 2 diabetic subjects with NAFLD . In this r and omized controlled trial , we compared the 4-month effects of either AER or RES training on insulin sensitivity ( by hyperinsulinemic euglycemic clamp ) , body composition ( by dual-energy X-ray absorptiometry ) , as well as hepatic fat content and visceral ( VAT ) , superficial ( SSAT ) , and deep ( DSAT ) subcutaneous abdominal adipose tissue ( all quantified by an in-opposed-phase magnetic resonance imaging technique ) in 31 sedentary adults with type 2 diabetes and NAFLD . After training , hepatic fat content was markedly reduced ( P < 0.001 ) , to a similar extent , in both the AER and the RES training groups ( mean relative reduction from baseline [ 95 % confidence interval ] -32.8 % [ -58.20 to -7.52 ] versus -25.9 % [ -50.92 to -0.94 ] , respectively ) . Additionally , hepatic steatosis ( defined as hepatic fat content > 5.56 % ) disappeared in about one-quarter of the patients in each intervention group ( 23.1 % in the AER group and 23.5 % in the RES group ) . Insulin sensitivity during euglycemic clamp was increased , whereas total body fat mass , VAT , SSAT , and hemoglobin A1c were reduced comparably in both intervention groups . CONCLUSION This is the first r and omized controlled study to demonstrate that resistance training and aerobic training are equally effective in reducing hepatic fat content among type 2 diabetic patients with NAFLD Background Insulin resistance is a risk factor for type 2 diabetes and cardiovascular disease progression . Current diagnostic tests , such as glycemic indicators , have limitations in the early detection of insulin resistant individuals . We search ed for novel biomarkers identifying these at-risk subjects . Methods Using mass spectrometry , non-targeted biochemical profiling was conducted in a cohort of 399 nondiabetic subjects representing a broad spectrum of insulin sensitivity and glucose tolerance ( based on the hyperinsulinemic euglycemic clamp and oral glucose tolerance testing , respectively ) . Results R and om forest statistical analysis selected α-hydroxybutyrate ( α – HB ) as the top-ranked biochemical for separating insulin resistant ( lower third of the clamp-derived MFFM = 33 [ 12 ] µmol·min−1·kgFFM −1 , median [ interquartile range ] , n = 140 ) from insulin sensitive subjects ( MFFM = 66 [ 23 ] µmol·min−1·kgFFM −1 ) with a 76 % accuracy . By targeted isotope dilution assay , plasma α – HB concentrations were reciprocally related to MFFM ; and by partition analysis , an α – HB value of 5 µg/ml was found to best separate insulin resistant from insulin sensitive subjects . α – HB also separated subjects with normal glucose tolerance from those with impaired fasting glycemia or impaired glucose tolerance independently of , and in an additive fashion to , insulin resistance . These associations were also independent of sex , age and BMI . Other metabolites from this global analysis that significantly correlated to insulin sensitivity included certain organic acid , amino acid , lysophospholipid , acylcarnitine and fatty acid species . Several metabolites are intermediates related to α-HB metabolism and bio synthesis . Conclusions α – hydroxybutyrate is an early marker for both insulin resistance and impaired glucose regulation . The underlying biochemical mechanisms may involve increased lipid oxidation and oxidative stress Troglitazone and metformin lower glucose levels in diabetic patients without increasing plasma insulin levels . We compared the insulin sparing actions of these two agents and their effects on insulin sensitivity and insulin secretion in 20 type 2 diabetic patients . To avoid the confounding effect of improved glycemic control on insulin action and secretion , patients were first rendered euglycemic with 4 weeks of continuous subcutaneous insulin infusion ( CSII ) before r and omization to CSII plus troglitazone ( n = 10 ) or CSII plus metformin ( n = 10 ) ; euglycemia was maintained for another 6 - 7 weeks . Insulin sensitivity was assessed by a hyperinsulinemic-euglycemic clamp 1 ) at baseline , 2 ) after 4 weeks of CSII , and 3 ) after CSII plus either troglitazone or metformin . The 24-h glucose , insulin , and C-peptide profiles were performed on the day before the second and third glucose clamps . Good glycemic control was achieved with CSII alone and was maintained with CSII plus an oral agent ( mean 24-h glucose : troglitazone , 6.2+/-0.6 mmol/l ; metformin , 6.2 + /-0.3 mmol/l ) . Insulin requirements decreased 53 % with troglitazone compared with CSII alone ( 48+/-4 vs. 102+/-13 U/day , P < 0.001 ) , but only 31 % with metformin ( 76+/-13 vs. 110+/-18 U/day , P < 0.005 ) . The 24-h C-peptide profiles were similar . Normal fasting hepatic glucose output was maintained with both agents despite lower insulin levels than on CSII alone . Insulin sensitivity did not change significantly with CSII alone or with CSII plus metformin , but improved 29 % with CSII plus troglitazone ( P < 0.005 vs. CSII alone ) and was then 45 % higher than in the CSII plus metformin patients ( P < 0.005 ) . In conclusion , metformin has no effect on insulin-stimulated glucose disposal independent of glycemic control in type 2 diabetes . Troglitazone ( 600 mg/day ) has greater insulin-sparing effects than metformin ( 1,700 mg/day ) in CSII-treated euglycemic patients . This is probably explained by the peripheral tissue insulin-sensitizing effects of troglitazone BACKGROUND Epidemiologic studies have found whole-grain intake to be inversely associated with the risk of  type 2 diabetes and heart disease . OBJECTIVE We tested the hypothesis that whole-grain consumption improves insulin sensitivity in overweight and obese adults . DESIGN This controlled experiment compared insulin sensitivity between diets ( 55 % carbohydrate , 30 % fat ) including 6 - 10 servings/d of breakfast cereal , bread , rice , pasta , muffins , cookies , and snacks of either whole or refined grains . Total energy needs were estimated to maintain body weight . Eleven overweight or obese [ body mass index ( in kg/m(2 ) ) : 27 - 36 ] hyperinsulinemic adults aged 25 - 56 y participated in a r and omized crossover design . At the end of each 6-wk diet period , the subjects consumed 355 mL ( 12 oz ) of a liquid mixed meal , and blood sample s were taken over 2 h. The next day a euglycemic hyperinsulinemic clamp test was administered . RESULTS Fasting insulin was 10 % lower during consumption of the whole-grain than during consumption of the refined-grain diet ( mean difference : -15 + /- 5.5 pmol/L ; P = 0.03 ) . After the whole-grain diet , the area under the 2-h insulin curve tended to be lower ( -8832 pmol.min/L ; 95 % CI : -18720 , 1062 ) than after the refined-grain diet . The rate of glucose infusion during the final 30 min of the clamp test was higher after the whole-grain diet ( 0.07 x 10(-4 ) mmol.kg(-1).min(-1 ) per pmol/L ; 95 % CI : 0.003 x 10(-4 ) , 0.144 x 10(-4 ) ) . CONCLUSION Insulin sensitivity may be an important mechanism whereby whole-grain foods reduce the risk of type 2 diabetes and heart disease The ability to maintain skeletal muscle mass appears to be impaired in insulin-resistant conditions , such as type 2 diabetes , that are characterized by muscle lipid accumulation . The current study investigated the effect of acutely increasing lipid availability on muscle protein synthesis .  Seven healthy young male volunteers underwent a 7-h intravenous infusion of l-[ring-2H5]phenylalanine on two r and omized occasions combined with 0.9 % saline or 10 % Intralipid at 100 mL/h . After a 4-h “ basal ” period , a 21-g bolus of amino acids was administered and a 3-h hyperinsulinemic-euglycemic clamp was commenced ( “ fed ” period ) . Muscle biopsy specimens were obtained from the vastus lateralis at 1.5 , 4 , and 7 h. Lipid infusion reduced fed whole-body glucose disposal by 20 % . Furthermore , whereas the mixed muscle fractional synthetic rate increased from the basal to the fed period during saline infusion by 2.2-fold , no change occurred during lipid infusion , despite similar circulating insulin and leucine concentrations . This “ anabolic resistance ” to insulin and amino acids with lipid infusion was associated with a complete suppression of muscle 4E-BP1 phosphorylation . We propose that increased muscle lipid availability may contribute to anabolic resistance in insulin-resistant conditions by impairing translation initiation The insulin resistance associated with aging may be due , in part , to reduced levels of physical activity in the elderly . We hypothesized that strength training increases insulin action in older individuals . To test this hypothesis , 11 healthy men 50 - 63 yr old [ mean 58 + /- 1 ( SE ) yr ] underwent a two-step hyperinsulinemic-euglycemic glucose clamp with concurrent indirect calorimetry and an oral glucose tolerance test ( OGTT ) before and after 16 wk of strength training . The training program increased overall strength by 47 % ( P < 0.001 ) . Fat-free mass ( FFM ; measured by hydrodensitometry ) increased ( 62.4 + /- 2.1 vs. 63.6 + /- 2.1 kg ; P < 0.05 ) and body fat decreased ( 27.2 + /- 1.8 vs. 25.6 + /- 1.9 % ; P < 0.001 ) with training . Fasting plasma glucose levels and glucose levels during the OGTT were not significantly lower after training . In contrast , fasting plasma insulin levels decreased ( 85 + /- 25 vs. 55 + /- 10 pmol/l ; P < 0.05 ) and insulin levels decreased ( P < 0.05 , analysis of variance ) during the OGTT . Glucose infusion rates during the hyperinsulinemic-euglycemic glucose clamp increased 24 % ( 13.5 + /- 1.7 vs. 16.7 + /- 2.2 mumol.kg FFM-1.min-1 ; P < 0.05 ) during the low ( 20 mU.m-2.min-1 ) insulin infusion and increased 22 % ( 55.7 + /- 3.3 vs. 67.7 + /- 3.9 mumol.kg FFM-1.min-1 ; P < 0.05 ) during the high ( 100 mU.m-2.min-1 ) insulin infusion . These increases were accompanied by a 40 % increase ( n = 7 ; P < 0.08 ) in nonoxidative glucose metabolism during the high insulin infusion . These results demonstrate that strength training increases insulin action and lowers plasma insulin levels in middle-aged and older men To examine the role of intramyocellular lipid ( IMCL ) accumulation as well as circulating cytokines , branched-chain amino acids and acylcarnitines in the pathogenesis of muscle insulin resistance in healthy , young , lean insulin-resistant offspring of parents with type 2 diabetes ( IR offspring ) , we measured these factors in plasma and used 1H magnetic resonance spectroscopy to assess IMCL content and hyperinsulinemic-euglycemic clamps using [ 6,6 - 2H2 ] glucose to assess rates of insulin-stimulated peripheral glucose metabolism before and after weight reduction . Seven lean ( body mass index < 25 kg/m2 ) , young , sedentary IR offspring were studied before and after weight stabilization following a hypocaloric ( 1,200 Kcal ) diet for ∼9 wks . This diet result ed in an average weight loss of 4.1 ± 0.6 kg ( P < 0.0005 ) , which was associated with an ∼30 % reduction of IMCL from 1.1 ± 0.2 % to 0.8 ± 0.1 % ( P = 0.045 ) and an ∼30 % improvement in insulin-stimulated muscle glucose uptake [ 3.7 ± 0.3 vs. 4.8 ± 0.1 mg/(kg – min ) , P = 0.01 ] . This marked improvement in insulin-stimulated peripheral insulin responsiveness occurred independently of changes in plasma concentrations of TNF-α , IL-6 , total adiponectin , C-reactive protein , acylcarnitines , and branched-chain amino acids . In conclusion , these data support the hypothesis that IMCL accumulation plays an important role in causing muscle insulin resistance in young , lean IR offspring , and that both are reversible with modest weight loss The aim of the present study was to investigate the effects of magnesium supplementation on glucose uptake and substrate oxidation in noninsulin-dependent ( type II ) diabetic patients . Nine elderly non-obese noninsulin-dependent ( type II ) diabetic patients , treated by diet only , participated in the study , which was design ed as r and omized , double blind , and cross-over . Each patient was followed up for a pre study period of 3 weeks before inviting him/her to receive placebo or magnesium supplementation ( 15.8 mmol/day ) for 4 weeks . At the end of each treatment period , a euglycemic hyperinsulinemic glucose clamp with simultaneous D-[3 - 3H]glucose infusion and indirect calorimetry was performed . Magnesium supplementation result ed in significantly increased plasma and erythrocyte magnesium levels , whereas body weight and fasting plasma glucose did not change . In the last 60 min of the glucose clamp , insulin-mediated glucose disappearance , total body glucose disposal ( 24.5 + /- 0.4 vs. 28.2 + /- 0.7 mumol/kg.min ; P < 0.005 ) , and glucose oxidation ( 13.0 + /- 0.4 vs. 16.3 + /- 0.8 mumol/kg.min ; P < 0.01 ) were increased after chronic magnesium supplementation . Endogenous glucose production , nonoxidative glucose disposal , lipid and protein oxidation , and insulin MCR were not affected . In conclusion , a 4-week magnesium supplementation improves insulin sensitivity and glucose oxidation in the course of a euglycemic-hyperinsulinemic glucose clamp in noninsulin-dependent diabetic patients . Long term studies are needed to determine whether magnesium supplementation is useful in the management of type II diabetes Resistant starch ( RS ) has been shown to beneficially affect insulin sensitivity in healthy individuals and those with metabolic syndrome , but its effects on human type 2 diabetes ( T2DM ) are unknown . This study aim ed to determine the effects of increased RS consumption on insulin sensitivity and glucose control and changes in postpr and ial metabolites and body fat in T2DM . Seventeen individuals with well-controlled T2DM ( HbA1c 46.6±2 mmol/mol ) consumed , in a r and om order , either 40 g of type 2 RS ( HAM-RS2 ) or a placebo  , daily for 12 weeks with a 12-week washout period in between . At the end of each intervention period , participants attended for three metabolic investigations : a two-step euglycemic – hyperinsulinemic clamp combined with an infusion of [ 6,6 - 2H2 ] glucose , a meal tolerance test ( MTT ) with arterio-venous sampling across the forearm , and whole-body imaging . HAM-RS2 result ed in significantly lower postpr and ial glucose concentrations ( P=0.045 ) and a trend for greater glucose uptake across the forearm muscle ( P=0.077 ) ; however , there was no effect of HAM-RS2 on hepatic or peripheral insulin sensitivity , or on HbA1c . Fasting non-esterified fatty acid ( NEFA ) concentrations were significantly lower ( P=0.004 ) and NEFA suppression was greater during the clamp with HAM-RS2 ( P=0.001 ) . Fasting triglyceride ( TG ) concentrations and soleus intramuscular TG concentrations were significantly higher following the consumption of HAM-RS2 ( P=0.039 and P=0.027 respectively ) . Although fasting GLP1 concentrations were significantly lower following HAM-RS2 consumption ( P=0.049 ) , postpr and ial GLP1 excursions during the MTT were significantly greater ( P=0.009 ) . HAM-RS2 did not improve tissue insulin sensitivity in well-controlled T2DM , but demonstrated beneficial effects on meal h and ling , possibly due to higher postpr and ial GLP1
Insulin mediated inhibition of lipolysis was decreased in patients , reflected by increased non-esterified fatty acid levels .
Insulin resistance is a prominent feature of patients with type 1 diabetes mellitus and involves hepatic , peripheral and adipose tissues
OBJECTIVE The aim of this study was to perform a systematic review and meta- analysis on insulin resistance in adult patients with type 1 diabetes mellitus compared to healthy controls , assessed by hyperinsulinemic euglycemic clamp studies .