Effective exercise modality to reduce insulin resistance in women with type 2 diabetes. Intensive therapy in adult insulin-dependent diabetes mellitus is associated with improved insulin sensitivity and reserve: a randomized, controlled, prospective study over 5 years in newly diagnosed patients. A lifestyle intervention in primary care prevents deterioration of insulin resistance in patients with impaired glucose tolerance: A randomised controlled trial The A1 chieve study - an observational non-interventional study of patients with type 2 diabetes mellitus initiating or switched to insulin analogue therapy: subgroup analysis of the Gulf population. The A1chieve study: a 60 000-person, global, prospective, observational study of basal, meal-time, and biphasic insulin analogs in daily clinical practice. Direct comparison among oral hypoglycemic agents and their association with insulin resistance evaluated by euglycemic hyperinsulinemic clamp: the 60's study. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Improvement in medication adherence and self-management of diabetes with a clinical pharmacy program: a randomized controlled trial in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital Free fatty acid-induced hepatic insulin resistance is attenuated following lifestyle intervention in obese individuals with impaired glucose tolerance. Quantitative insulin sensitivity check index: a simple, accurate method for assessing insulin sensitivity in humans. Prevention of diabetes mellitus in subjects with impaired glucose tolerance in the Finnish Diabetes Prevention Study: results from a randomized clinical trial. Study on Lifestyle Intervention and Impaired Glucose Tolerance Maastricht (SLIM): preliminary results after one year How good a marker is insulin level for insulin resistance? Lifestyle Intervention and Adipokine Levels in Subjects at High Risk for Type 2 Diabetes The IMPROVE study--a multinational, observational study in type 2 diabetes: baseline characteristics from eight national cohorts. A Model-Based Method for Assessing Insulin Sensitivity From the Oral Glucose Tolerance Test. Diabetes Care 2001;24:539–548 Improvement of insulin sensitivity in patients with type 2 diabetes mellitus after oral administration of alpha-lipoic acid.
OBJECTIVE The purpose of this study was to evaluate whether a combined resistance and aerobic training program would improve insulin sensitivity compared with aerobic training alone in postmenopausal women with type 2 diabetes . A second objective was to relate the improved insulin sensitivity to changes in abdominal adipose tissue ( AT ) and thigh muscle density . RESEARCH DESIGN AND METHODS A total of 28 obese postmenopausal women with type 2 diabetes were r and omly assigned to one of three 16-week treatments : control , aerobic only training ( Ae only ) , or aerobic plus resistance training ( Ae+RT ) . Pre- and posttreatment outcome measures included glucose disposal by hyperinsulinemic-euglycemic clamp and computed tomography scans of abdominal AT and mid-thigh skeletal muscle . RESULTS Glucose infusion rates increased significantly ( P < 0.05 ) in the Ae+RT group . Both exercise groups had reduced abdominal subcutaneous and visceral AT and increased muscle density . The Ae+RT training group exhibited a significantly greater increase in muscle density than the Ae only group . Improved glucose disposal was independently associated with changes in subcutaneous AT , visceral AT , and muscle density . Muscle density retained a relationship with glucose disposal after controlling for abdominal AT . CONCLUSIONS Adding resistance training to aerobic training enhanced glucose disposal in postmenopausal women with type 2 diabetes . The improved insulin sensitivity is related to loss of abdominal subcutaneous and visceral AT and to increased muscle density Optimal blood glucose levels and normal insulin sensitivity are aims in the treatment of insulin-dependent diabetes mellitus ( IDDM ) . Insulin sensitivity and insulin reserve are closely interrelated . It is essential to know more about both of these parameters at clinical diagnosis , because their preservation may delay the occurrence of diabetes-related complications . B-cell function is likely to be retained for a longer period in patients with adult onset of the disease compared with children . In this study , intensive insulin treatment was initiated in newly diagnosed adult patients to determine if it preserved endogenous insulin secretion longer than conventional therapy .  Forty-nine patients with newly diagnosed diabetes were carefully categorized as having IDDM according to clinical and serological criteria . They were r and omized to an  intensive ( I group ) or conventional ( C group ) insulin therapy  and evaluated for 5 years . Every 6 months , a check-up included glucagon-stimulated C-peptide ( GSCP ) , hyperglycemic glucose clamp with arginine bolus , euglycemic-hyperinsulinemic clamp , and screening for  microalbuminuria  , retinopathy , and neuropathy  . At the end of the study , hemoglobin A1c ( HbA1c ) was 6.3 % + /- 1.9 % in the I patients and 8.1 % + /- 2.1 % in the C patients ( P < .001 ) . Blood glucose concentrations less than 3.5 mmol/L were more frequent in the I group than in the C group ( P < .05 ) . Insulin sensitivity ( M/I ) and GSCP were higher in intensively treated patients after 5 years ( M/I , I group 40 + /- 10 nmol x kg(-1 ) x min(-1 ) x pmol/L1 v C group 21 + /- 11 , P < .005 ; GSCP , I group 0.6 + /- 0.2 nmol/L v C group 0.19 + /- 0.11 , P < .005 ) . The prevalence of peripheral neuropathy was significantly lower in the I group at the end of the study . In conclusion , intensive therapy is more effective in the preservation of insulin action and reserve . In our patients , no case of severe hypoglycemia was observed , indicating that intensive therapy was safe in these patients Aims : We hypothesised that the expected increase in insulin resistance over three years ’ time in individuals with impaired glucose tolerance ( IGT ) and /or impaired fasting glucose could be attenuated by an intervention with focus on physical activity in ordinary primary care . Methods : We conducted a r and omised controlled trial with 96 participants over three years . Examination of the participants included anthropometric measures , blood pressure , body weight and height , blood sample s , an oral glucose tolerance test , and question naires about diet and lifestyle . The study subjects were r and omised to either an intense intervention with information , group sessions , referral to physical activity and a step-counter ( n = 31 ) , a less intense intervention without the group sessions ( n = 35 ) , or care as usual group ( CAUG ) ( n = 30 ) . Differences between the groups were analysed with general linear models adjusted for age , gender , baseline values and time in the intervention . Results : Individual insulin resistance increased in the CAUG . Due to having a similar effect , we combined the two intervention groups into a combined intervention group ( CIG ; n = 66 ) in the analyses . In individuals with IGT , the increase in the homeostatic model assessment -insulin resistance differed significantly between those in the CAUG and the CIG ( Δ = 0.8 ; CI : 0.1–1.6 ; p = 0.034 ) . Likewise , diastolic blood pressure decreased more in the CIG than in the CAUG ( Δ = 5.1 ; CI : 0.1–10.0 ; p = 0.047 ) . A total of 17 individuals developed Type 2 diabetes , 23 % were in the CIG and 33 % in the CAUG ; so there was a 32 % reduced risk in the intervention group . Conclusions : A lifestyle intervention focused on physical activity is feasible in ordinary primary care and prevents deterioration in insulin sensitivity in individuals with IGT over a three-year period AIM To evaluate the safety and effectiveness of insulin analogues ( insulin aspart , insulin detemir and biphasic insulin aspart 30 , alone or in combination ) in type 2 diabetes mellitus ( T2DM ) patients in routine clinical practice in the Gulf as a subgroup of the A(1 ) chieve multi-national study . METHODS A total of 10,704 T2DM Gulf patients with uncontrolled T2DM on oral antidiabetics ± insulins other than insulin aspart , insulin detemir or biphasic insulin aspart 30 , who initiated or switched to study insulins  were included and followed up for 24 weeks in the context of the A(1 ) chieve study . RESULTS Baseline HbA(1c ) ( ± SD ) was poor : 9.7 ± 1.7 % . At Week 24 , an improvement in HbA(1c ) of -2.3 ± 1.6 % was observed in the entire cohort , and -2.4 ± 1.5 % and -2.1 ± 1.7 % for insulin-naïve patients and prior insulin users respectively . Overall , rates of hypoglycaemia increased in those new to insulin therapy , whereas a reduction was observed in those switching from other insulins . A marginal reduction in body weight ( -0.8 ± 4.4 kg ) was noted in the entire cohort , whereas the overall lipid profile and systolic blood pressure ( -6.2 ± 15.3 mmHg ) improved . CONCLUSIONS Initiating or switching to insulin analogues was well tolerated and result ed in significant improvements in glycaemic control in T2DM patients in the Gulf While evidence d-based guidelines promote glycated hemoglobin ( HbA(1c ) ) targets < 7.0 % in order to reduce the long-term risk of diabetic complications , many individuals with type 2 diabetes do not achieve these targets . Fear of hypoglycemia provides a major barrier to improving blood glucose control as a result of delayed insulin initiation and failure to appropriately titrate insulin following initiation . Modern insulin analogs were design ed to achieve improved blood glucose control with similar hypoglycemic risk compared with non-analog insulins ( or similar blood glucose control with reduced hypoglycemic risk ) . While this has been demonstrated in r and omized controlled trials , there is a need to confirm these findings in an everyday clinical setting . The A(1)chieve study will evaluate adverse events and effectiveness of premix ( biphasic insulin aspart 30 [ NovoMix 30 ] ) , basal ( insulin detemir [ Levemir ] ) , and meal-time ( insulin aspart [ NovoRapid ] ) insulin analogs in people with type 2 diabetes in near-routine clinical practice . A(1)chieve is an international , prospect i ve , multi-center , open-label , non-interventional , 24-week study of people with type 2 diabetes using an insulin analog .  The study will recruit 60 000 people from 30 countries across four continents ( Asia , Africa , South America , and Europe ) . The primary aim of the study is to assess the adverse event profile of the study insulins in routine clinical practice , including rates of hypoglycemia . In addition , effectiveness ( HbA(1c ) , fasting plasma glucose , and postpr and ial plasma glucose ) and patient quality of life outcomes will be measured . Comprehensive epidemiological data will be collected at baseline , including recent plasma glucose results and hypoglycemic episodes , prevalence of diabetes-related complications , and measures of current st and ards of care . Thus , A(1)chieve should provide important information about how insulin analogs perform in daily clinical practice 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 OBJECTIVE Several methods have been proposed to evaluate insulin sensitivity from the data obtained from the oral glucose tolerance test ( OGTT ) . However , the validity of these indices has not been rigorously evaluated by comparing them with the direct measurement of insulin sensitivity obtained with the euglycemic insulin clamp technique . In this study , we compare various insulin sensitivity indices derived from the OGTT with whole-body insulin sensitivity measured by the euglycemic insulin clamp technique . RESEARCH DESIGN AND METHODS In this study , 153 subjects ( 66 men and 87 women , aged 18 - 71 years , BMI 20 - 65 kg/m2 ) with varying degrees of glucose tolerance ( 62 subjects with normal glucose tolerance , 31 subjects with impaired glucose tolerance , and 60 subjects with type 2 diabetes ) were studied . After a 10-h overnight fast , all subjects underwent , in r and om order , a 75-g OGTT and a euglycemic insulin clamp , which was performed with the infusion of [3 - 3H]glucose . The indices of insulin sensitivity derived from OGTT data and the euglycemic insulin clamp were compared by correlation analysis . RESULTS The mean plasma glucose concentration divided by the mean plasma insulin concentration during the OGTT displayed no correlation with the rate of whole-body glucose disposal during the euglycemic insulin clamp ( r = -0.02 , NS ) . From the OGTT , we developed an index of whole-body insulin sensitivity ( 10,000/square root of [ fasting glucose x fasting insulin ] x [ mean glucose x mean insulin during OGTT ] ) , which is highly correlated ( r = 0.73 , P < 0.0001 ) with the rate of whole-body glucose disposal during the euglycemic insulin clamp . CONCLUSIONS Previous methods used to derive an index of insulin sensitivity from the OGTT have relied on the ratio of plasma glucose to insulin concentration during the OGTT . Our results demonstrate the limitations of such an approach . We have derived a novel estimate of insulin sensitivity that is simple to calculate and provides a reasonable approximation of whole-body insulin sensitivity from the OGTT OBJECTIVE : To evaluate the impact of a clinical pharmacy program on health outcomes in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital in Brazil . METHOD : A r and omized controlled trial with a 6-month follow-up period was performed in 70 adults , aged 45 years or older , with type 2 diabetes who were taking insulin and who had an HbA1c level ≥8 % . Patients in the control group ( CG ) ( n = 36 ) received st and ard care , patients in the intervention group ( IG ) ( n = 34 ) received an individualized pharmacotherapeutic care plan and diabetes education . The primary outcome measure was change in HbA1c . Secondary outcomes included diabetes and medication knowledge , adherence to medication , insulin injection and home blood glucose monitoring techniques and diabetes-related quality of life . Outcomes were evaluated at baseline and 6 months using question naires . RESULTS : Diabetes knowledge , medication knowledge , adherence to medication and correct insulin injection and home blood glucose monitoring techniques significantly improved in the intervention group but remained unchanged in the control group . At the end of the study , mean HbA1c values in the control group remained unchanged but were significantly reduced in the intervention group . Diabetes-related quality of life significantly improved in the intervention group but worsened significantly in the control group . CONCLUSION : The program improved health outcomes and result ed in better glycemic control in patients with type 2 diabetes undergoing insulin therapy OBJECTIVE The objective of the study was to examine the effects of an exercise/diet lifestyle intervention on free fatty acid (FFA)-induced hepatic insulin resistance in obese humans . RESEARCH DESIGN AND METHODS Obese men and women ( n = 23 ) with impaired glucose tolerance were r and omly assigned to either exercise training with a eucaloric ( EU ; approximately 1800 kcal ; n = 11 ) or hypocaloric ( HYPO ; approximately 1300 kcal ; n = 12 ) diet for 12 wk . Hepatic glucose production ( HGP ; milligrams per kilogram fat-free mass(-1 ) per minute(-1 ) ) and hepatic insulin resistance were determined using a two-stage sequential hyperinsulinemic ( 40 mU/m(2 ) . min(-1 ) ) euglycemic ( 5.0 mm ) clamp with [3-(3)H]glucose . Measures were obtained at basal , during insulin infusion ( INS ; 120 min ) , and insulin plus intralipid/heparin infusion ( INS/FFA ; 300 min ) . RESULTS At baseline , basal HGP was similar between groups ; hyperinsulinemia alone did not completely suppress HGP , whereas INS/FFA exhibited less suppression than INS ( EU , 4.6 + /- 0.8 , 2.0 + /- 0.5 , and 2.6 + /- 0.4 ; HYPO , 3.8 + /- 0.5 , 1.2 + /- 0.3 , and 2.3 + /- 0.4 , respectively ) . After the intervention the HYPO group lost more body weight ( P < 0.05 ) and fat mass ( P < 0.05 ) . However , both lifestyle interventions reduced hepatic insulin resistance during basal ( P = 0.005 ) and INS ( P = 0.001 ) conditions , and insulin-mediated suppression of HGP during INS was equally improved in both groups ( EU : -42 + /- 22 % ; HYPO : -50 + /- 20 % , before vs. after , P = 0.02 ) . In contrast , the ability of insulin to overcome FFA-induced hepatic insulin resistance and HGP was improved only in the HYPO group ( EU : -15 + /- 24 % vs. HYPO : -58 + /- 19 % , P = 0.02 ) . CONCLUSIONS Both lifestyle interventions are effective in reducing hepatic insulin resistance under basal and hyperinsulinemic conditions . However , the reversal of FFA-induced hepatic insulin resistance is best achieved with a combined exercise/caloric-restriction intervention Insulin resistance plays an important role in the pathophysiology of diabetes and is associated with obesity and other cardiovascular risk factors . The " gold st and ard " glucose clamp and minimal model analysis are two established methods for determining insulin sensitivity in vivo , but neither is easily implemented in large studies . Thus , it is of interest to develop a simple , accurate method for assessing insulin sensitivity that is useful for clinical investigations . We performed both hyperinsulinemic isoglycemic glucose clamp and insulin-modified frequently sample d iv glucose tolerance tests on 28 nonobese , 13 obese , and 15 type 2 diabetic subjects . We obtained correlations between indexes of insulin sensitivity from glucose clamp studies ( SI(Clamp ) ) and minimal model analysis ( SI(MM ) ) that were comparable to previous reports ( r = 0.57 ) . We performed a sensitivity analysis on our data and discovered that physiological steady state values [ i.e. fasting insulin ( I(0 ) ) and glucose ( G(0 ) ) ] contain critical information about insulin sensitivity . We defined a quantitative insulin sensitivity check index ( QUICKI = 1/[log(I(0 ) ) + log(G(0 ) ) ] ) that has substantially better correlation with SI(Clamp ) ( r = 0.78 ) than the correlation we observed between SI(MM ) and SI(Clamp ) . Moreover , we observed a comparable overall correlation between QUICKI and SI(Clamp ) in a totally independent group of 21 obese and 14 nonobese subjects from another institution . We conclude that QUICKI is an index of insulin sensitivity obtained from a fasting blood sample that may be useful for clinical research Type 2 diabetes mellitus is increasing worldwide largely as a result from increasing obesity and sedentary lifestyle . The Finnish Diabetes Prevention Study ( DPS ) is the first individually r and omized controlled clinical trial to test the feasibility and efficacy of lifestyle modification in high-risk subjects . We r and omly assigned 522 ( 172 men , 350 women ) middle-aged ( mean age 55 yr ) , overweight ( mean body mass index 31 kg/m(2 ) ) subjects with impaired glucose tolerance either to the lifestyle intervention or control group .  Each subject in the intervention group received individualized counseling aim ed at reducing weight and intake of total and saturated fat , and increasing intake of fiber and physical activity . An oral glucose tolerance test was performed annually to detect incident cases of diabetes and to measure changes in metabolic parameters . The mean ( + /- SD ) weight reduction from baseline to year 1 and to year 2 , respectively , was 4.2 + /- 5.1 kg and 3.5 + /- 5.5 in the intervention group and 0.8 + /- 3.7 kg and 0.8 + /- 4.4 in the control group ( P < 0.001 between the groups ) . At the time of first analysis of the outcome data the mean duration of follow-up was 3.2 yr . The risk of diabetes was reduced by 58 % ( P < 0.001 ) in the intervention group compared with the control group . The reduction in the incidence of diabetes was directly associated with number and magnitude of lifestyle changes made . In conclusion , the DPS is the first controlled trial demonstrating that type 2 diabetes can be prevented by changes in lifestyle in high-risk subjects AIMS : Important risk factors for the progression from impaired glucose tolerance to type II diabetes mellitus are obesity , diet and physical inactivity . The aim of this study is to evaluate the effect of a lifestyle-intervention programme on glucose tolerance in Dutch subjects with impaired glucose tolerance ( IGT ) . METHODS : A total of 102 subjects were studied , r and omised into two groups . Subjects in the intervention group received regular dietary advice , and were stimulated to lose weight and to increase their physical activity . The control group received only brief information about the beneficial effects of a healthy diet and increased physical activity . Before and after the first year , glucose tolerance was measured and several other measurements were done . RESULTS : Body weight loss after 1 y was higher in the intervention group . The 2-h blood glucose concentration decreased 0.8±0.3 mmol/l in the intervention group and increased 0.2±0.3 mmol/l in the control group ( P<0.05 ) . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity . CONCLUSION : A lifestyle-intervention programme according to general recommendations is effective and induces beneficial changes in lifestyle , which improve glucose tolerance in subjects with IGT . Body weight loss and increased physical fitness were the most important determinants of improved glucose tolerance and insulin sensitivity 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 OBJECTIVE —We investigated whether circulating adipokine concentrations can be altered by lifestyle intervention according to general recommendations in subjects at risk for diabetes as well as the potential of leptin , adiponectin , and resistin as biomarkers for lifestyle-induced improvements in glucose metabolism and insulin resistance . RESEARCH DESIGN AND METHODS —In the Study on Lifestyle intervention and Impaired glucose tolerance Maastricht , 147 men and women with impaired glucose tolerance ( IGT ) were r and omized to either a combined diet- and -exercise intervention or a control program . At baseline and after 1 year , an oral glucose tolerance test , an exercise test , and anthropometric measurements were performed . After 1 year , complete data of 103 subjects ( 50 intervention and 53 control subjects ) were obtained . RESULTS —Lifestyle intervention reduced plasma leptin concentrations ( −14.2 % ) in IGT subjects but did not alter plasma adiponectin ( −0.3 % ) or resistin ( −6.5 % ) concentrations despite marked improvements in glucose tolerance and insulin resistance . CONCLUSIONS —Changes in leptin concentration were related to improvements in insulin sensitivity independent of changes in body composition AIMS The IMPROVE study is a multinational , open-label , non-r and omised , 26-week observational study assessing the safety and effectiveness of biphasic insulin aspart 30 ( BIAsp 30 ) treatment in type 2 diabetes in routine clinical practice . The principal aims of this report were to characterise the baseline population and physicians ' treatment decisions . METHODS Patients with type 2 diabetes who required insulin and whose physician had decided to initiate BIAsp 30 were eligible . At baseline , demographic data and detailed medical histories were collected and physicians recorded their reasons for starting BIAsp 30 , the glycaemic targets set and the regimens chosen . RESULTS Data from 51,286 patients were included in analyses . Baseline glycaemic control was poor in all eight countries in the present analysis and in all pre study treatment groups [ no therapy , oral antidiabetic drugs ( OADs ) only , insulin with or without OADs ] , and the rates of vascular complications were high . Although the management of each of the three main measures of glycaemic control were key reasons for starting BIAsp 30 , target- setting for postpr and ial glucose levels was variable . A twice-daily regimen was used to start BIAsp 30 therapy for 80 % or more of patients . CONCLUSIONS The IMPROVE baseline data reaffirm the global nature of poor glycaemic control in type 2 diabetes and echo the concerns that initiation of therapy , particularly insulin , is commonly delayed in clinical practice . Although postpr and ial glucose control was a key driver for physicians ' choice of BIAsp 30 , this was not consistently reflected in the targets set OBJECTIVE Available insulin sensitivity ( IS ) methods based on the oral glucose tolerance test ( OGTT ) are empirical . We used a glucose-insulin model to derive an OGTT-based IS ( oral glucose insulin sensitivity [ OGIS ] ) index , which predicts glucose clearance in a glucose clamp . We vali date d OGIS against clamp data . RESEARCH DESIGN AND METHODS OGIS requires glucose and insulin concentrations from a 75-g OGTT at 0 , 2 , and 3 h ( 3-h OGTT ) or at 0 , 1.5 , and 2 h ( 2-h OGTT ) . The formula includes six constants optimized to match the clamp results . For this purpose , 15 lean nondiabetic subjects ( BMI < 25 kg/m2 ) , 38 obese nondiabetic subjects ( BMI > 25 kg/m2 ) , and 38 subjects with type 2 diabetes r and omly underwent an OGTT and a 120 mU x min(-1 ) x m(-2 ) insulin infusion euglycemic clamp . Glucose clearance ( Cl CLAMP )  , calculated as the ratio of  glucose infusion to concentration during the last hour of the clamp , was compared with OGIS . OGIS was also tested on an independent group of 13 subjects with impaired glucose tolerance ( IGT ) . RESULTS OGIS and Cl CLAMP  were correlated in the whole group ( R = 0.77 , P < 0.0001 ) , in the subgroups ( lean : R = 0.59 ; obese : R = 0.73 ; type 2 diabetes : R = 0.49 ; P < 0.02 ) , and in the independent IGT group ( R = 0.65 , P < 0.02 ) . Reproducibility of OGIS and Cl CLAMP  were similar ( coefficients of variation : OGIS 7.1 % , Cl CLAMP 6.4 % ) . OGIS was as effective as  Cl CLAMP  in discriminating between groups ( for OGIS , lean vs. obese : 440 + /- 16 vs. 362 + /- 11 ml x min(-1 ) x m(-2 ) , p < 0.001 ; lean vs. type 2 diabetes : 440 + /- 16 vs. 239 + /- 7 , P < 0.0001 ; obese vs. type 2 diabetes : 362 + /- 11 vs. 239 + /- 7 , P < 0.0001 ; results were similar for Cl CLAMP ) . The relationships between IS and BMI , fasting plasma insulin , and insulin secretion ( calculated from the OGTT insulin concentration ) were examined . OGIS yielded results similar to Cl CLAMP and fully consistent with established physiological principles . The performance of the index for the 3-h and 2-h OGTT was similar . CONCLUSIONS OGIS is an index of IS in good agreement with the clamp . Because of its simplicity ( only three blood sample s required ) , this method has potential use for clinical investigation including large-scale epidemiological studies BACKGROUND Amelioration of insulin resistance could improve both glycaemic control and cardiovascular risk factors in patients with type 2 diabetes mellitus .  Alpha-lipoic acid has been shown to improve insulin action after parenteral administration . OBJECTIVE the aim of the study was to assess the effect of oral administration of alpha-lipoic acid on insulin sensitivity in patients with type 2 diabetes . DESIGN twelve patients ( mean+/-sD ; age 52.9+/-9.9 yrs ; body mass index 33.9+/-7.4 kg/m(2 ) ) were treated with oral alpha-lipoic acid , 600 mg twice daily over a period of 4 weeks . twelve subjects with normal glucose tolerance served as a control group in terms of insulin sensitivity ( Is ) . Is was measured by a 2h manual hyperinsulinaemic ( insulin infusion rate-40 mU/m(2 ) body surface area/min ) euglycaemic ( blood glucose kept at 5 mmol/l ) clamp technique and expressed as a glucose disposal rate ( M ) and insulin sensitivity index ( IsI ) . RESULTS At the end of the treatment period , Is of diabetic patients was significantly increased : M from 3.202+/-1.898 to 5.951+/-2.705 mg/kg/min ( mean+/-sD ) , p<0.01 ; and IsI from 4.706+/-2.666 to 7.673+/-3.559 mg/kg/min per mIU/l x 100 ( mean+/-sD ) , p<0.05 . the difference was not statistically significant between the Is of diabetic patients after alpha-lipoic acid therapy and control subjects . CONCLUSION short-term oral alpha-lipoic acid treatment increases peripheral insulin sensitivity in patients with type 2 diabetes mellitus
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 .