Compare Insulin Sensitivity Research Articles

Validation of Insulin Sensitivity and Secretion Indices Derived from the Liquid Meal Tolerance Test

A liquid meal tolerance test (LMTT) has been proposed as a useful alternative to more labor-intensive methods of assessing insulin sensitivity and secretion. This substudy, conducted at the conclusion of a randomized, double-blind crossover trial, compared insulin sensitivity indices from a LMTT (Matsuda insulin sensitivity index [MISI] and LMTT disposition index [LMTT-DI]) with indices derived from minimal model analysis of results from the insulin-modified intravenous glucose tolerance test (IVGTT) (insulin sensitivity index [S(I)] and disposition index [DI]). Participants included men (n = 16) and women (n = 8) without diabetes but with increased abdominal adiposity (waist circumference ≥102 cm and ≥89 cm, respectively) and mean age of 48.9 years. The correlation between S(I) and the MISI was 0.776 (P < 0.0001). The respective associations between S(I) and MISI with waist circumference (r = -0.445 and -0.554, both P < 0.05) and body mass index were similar (r = -0.500 and -0.539, P < 0.05). The correlation between DI and LMTT-DI was 0.604 (P = 0.002). These results indicate that indices of insulin sensitivity and secretion derived from the LMTT correlate well with those from the insulin-modified IVGTT with minimal model analysis, suggesting that they may be useful for application in clinical and population studies of glucose homeostasis.

Effects of Intensity and Volume on Insulin Sensitivity During Acute Bouts of Resistance Training

This study evaluated the effects of various resistance exercise protocols on 24-hour postexercise insulin sensitivity. Seventeen participants with impaired fasting glucose (100-125 mg/dL) completed 4 separate bouts of resistance exercise under moderate intensity (65% 1 repetition maximum [1RM]) or high intensity (85% 1RM) conditions within the confines of single set and multiple set protocols. Intravenous fasting blood was taken at baseline and 24 hours postexercise for each exercise condition to measure fasting plasma glucose (G0) and fasting serum insulin (I0) to calculate insulin sensitivity (homeostasis model assessment-insulin resistance = (G0*I0)/405). A minimum of 3 days washout was given between each exercise protocol. A 4 x 2 factorial analysis of variance was performed to compare insulin sensitivity and fasting glucose within subjects and between treatments. All of the exercise protocols improved subsequent insulin sensitivity (p = 0.002) and G0 (p = 0.001). In comparison with single set, there was a significantly greater decrease in G0 (p = 0.021) 24 hours after multiple set bouts. High intensity showed significant decreases in insulin sensitivity as compared with moderate intensity protocols (p = 0.046). Effect size data suggest a dose response relationship between program variables of volume and intensity and 24-hour postexercise insulin sensitivity. High-intensity protocols resulted in greater effect sizes for insulin sensitivity (0.83 multiple set; 0.53 single set) as compared with moderate-intensity protocols. The high-intensity, multiple set bout yielded the greatest treatment effect in both fasting glucose (0.61) and insulin sensitivity (0.83). Overall, single set protocols were less effective than multiple set protocols in lowering fasting blood glucose. Findings suggest a dose-response relationship between volume and intensity on insulin sensitivity and fasting blood glucose. Results indicate that resistance exercise is an effective treatment for acutely enhancing insulin sensitivity and regulating blood glucose in individuals with impaired fasting glucose.

Depression, depression treatment, and insulin sensitivity in adults at risk for type 2 diabetes

Aims To compare insulin sensitivity (Si) in adults at risk for type 2 diabetes (T2DM) who were categorized as non-depressed, treated for depression and untreated depression after controlling for physical activity (PA). Methods Baseline data was analyzed from individuals enrolled in a diabetes prevention program ( n = 56). Si was calculated using the whole-body insulin sensitivity method. The Centers for Epidemiologic Studies Depression Scale (CESD) was used to assess depressive symptoms and depressed cases were identified using a cutoff of ≥16. Depression treatment was identified using a self-report form validated by medical chart review. The PA subscale of the Health Promoting Lifestyle Profile was used to determine PA levels. Results One third of participants had elevated depressive symptoms; 19% were taking antidepressant medication. Mean Si was 3.1 (±1.9). In ANOVA, depressed individuals showed significantly lower Si ( M = 1.8 ± 0.9) than non-depressed individuals ( M = 3.4 ± 1.8). However, individuals taking antidepressant medications had Si similar to non-depressed individuals ( M = 3.7 ± 2.3: p = .63). In ANCOVA this association remained after controlling for PA. Conclusions These data suggest that in adults at high risk for T2DM, depression treatment may improve insulin resistance observed in depression. Healthcare practitioners are encouraged to screen, treat, or refer their patients with depression for treatment.

Discipline-specific insulin sensitivity in athletes

Objective Weight status and abnormal liver function are the two factors that influence whole-body insulin sensitivity. The main goal of the study was to compare insulin sensitivity in athletes ( n = 757) and physically active controls ( n = 670) in relation to the two factors. Methods Homeostatic metabolic assessment for insulin resistance (HOMA-IR), weight status, and abnormal liver function (alanine aminotransferase and aspartate aminotransferase) were determined from 33 sports disciplines under morning fasted condition. This study was initiated in autumn 2006 and repeated in autumn 2007 ( n = 1508) to ensure consistency of all observations. Results In general, HOMA-IR and blood pressure levels in athletes were significantly greater than those in physically active controls but varied widely with sport disciplines. Rowing and short-distance track athletes had significantly lower HOMA-IR values and archery and field-throwing athletes had significantly higher values than the control group. Intriguingly, athletes from 22 sports disciplines displayed significantly greater body mass index values above control values. Multiple regression analysis showed that, for non-athlete controls, body mass index was the only factor that contributed to the variations in HOMA-IR. For athletes, body mass index and alanine aminotransferase independently contributed to the variation of HOMA-IR. Conclusion This is the first report documenting HOMA-IR values in athletes from a broad range of sport disciplines. Weight status and abnormal liver function levels appear to be the major contributors predicting insulin sensitivity for the physically active population.

Obese But Not Normal-Weight Women With Polycystic Ovary Syndrome Are Characterized by Metabolic and Microvascular Insulin Resistance

A high proportion of women with the polycystic ovary syndrome (PCOS) are obese. It is unclear whether normal-weight women with PCOS are at a greater risk of diabetes and cardiovascular disease than obese women without PCOS. It is also unclear whether risks of diabetes and cardiovascular disease in obese women and those with PCOS are additive. To determine whether the risk of diabetes and cardiovascular disease in PCOS is independent of the risk associated with obesity, this prospective controlled study compared insulin sensitivity and microvascular function in normal-weight and obese women with and without PCOS. The 4 PCOS groups were comprised of 19 normal-weight and 16 obese women with PCOS, and 14 normal-weight and 13 obese women controls without PCOS matched for age and body mass index. Before and after insulin infusion to produce hyperinsulinemia, metabolic insulin sensitivity (M/I value) was measured by means of the isoglycemic hyperinsulinemic clamp, and microvascular insulin sensitivity was assessed by analysis of microvascular endothelium-dependent and independent vasodilatation using iontophoresis of acetylcholine (Ach) and sodium nitroprusside (SNP) in combination with laser Doppler flowometry in the skin. For the latter, area under the response curves to Ach and SNP were measured. Analysis of metabolic insulin sensitivity showed that both groups of obese women had a significantly lower M/I value than normal-weight women (P ≤ 0.001) and that obese PCOS women had a lower M/I value than obese controls (P ≤ 0.02). In contrast, there was no difference in the M/I value between normal-weight PCOS women and controls. Before insulin infusion, there was no significant difference in microvascular responses to Ach among the 4 groups. During insulin infusion, Ach responses were significantly reduced in obese compared with normal-weight women; a similar difference was found for normal-weight women with or without PCOS. Compared to baseline values, SNP-dependent vasodilatation was not increased during insulin infusion in the 4 groups (P = ns). This report is the first to show that normal-weight women with PCOS may be at relatively normal risk of metabolic and cardiovascular disease and that obese woman with PCOS may be at increased risk. The investigators conclude from these findings that the focus of management in women with PCOS should be on weight control.

Physical Inactivity and Obesity Underlie the Insulin Resistance of Aging

OBJECTIVEAge-associated insulin resistance may underlie the higher prevalence of type 2 diabetes in older adults. We examined a corollary hypothesis that obesity and level of chronic physical inactivity are the true causes for this ostensible effect of aging on insulin resistance.RESEARCH DESIGN AND METHODSWe compared insulin sensitivity in 7 younger endurance-trained athletes, 12 older athletes, 11 younger normal-weight subjects, 10 older normal-weight subjects, 15 younger obese subjects, and 15 older obese subjects using a glucose clamp. The nonathletes were sedentary.RESULTSInsulin sensitivity was not different in younger endurance-trained athletes versus older athletes, in younger normal-weight subjects versus older normal-weight subjects, or in younger obese subjects versus older obese subjects. Regardless of age, athletes were more insulin sensitive than normal-weight sedentary subjects, who in turn were more insulin sensitive than obese subjects.CONCLUSIONSInsulin resistance may not be characteristic of aging but rather associated with obesity and physical inactivity.

Insulin resistance in subjects with a history of thyrotoxic periodic paralysis (TPP)

Hyperinsulinaemia has been suggested as an important factor for developing hypokalaemic paralysis in patients with thyrotoxic periodic paralysis (TPP). Since hyperinsulinaemia is a common feature of insulin resistance, there may be a causal relationship between insulin resistance and TPP. To compare insulin sensitivity between subjects with a history of TPP and others with a history of thyrotoxicosis without periodic paralysis. Insulin sensitivity measured by euglycaemic hyperinsulinaemic clamp and 75-g oral glucose tolerance test (OGTT) were performed nonselectively in 10 subjects with a history of TPP (TPP group) and 10 age- and sex-matched subjects with a history of simple thyrotoxicosis (control group). All participants had euthyroidism and fasting plasma glucose of < 5.55 mmol/l at the time of the study. Body mass index and waist circumference of the TPP group were higher than that of the control group. One of 10 (10%) subjects in the TPP group and 6 of 10 (60%) in the control group had BMI of < 23 kg/m2. Areas under the curve (AUC) of plasma glucose after OGTT were comparable, while the AUC of serum insulin of the TPP group was higher than in the control group. The TPP group had lower insulin sensitivity than the control group. The subjects with a history of TPP were more obese and had lower insulin sensitivity than those with a history of simple thyrotoxicosis. Insulin resistance with compensatory hyperinsulinaemia may be a key feature of the pathogenesis of TPP.

An acute bout of endurance exercise but not sprint interval exercise enhances insulin sensitivity

An acute bout of endurance exercise (EE) enhances insulin sensitivity, but the effects of sprint interval exercise (SIE) have not yet been described. We sought to compare insulin sensitivity at baseline and after an acute bout of EE and SIE in healthy men (n = 8) and women (n = 5) (age, 20.7 +/- 0.3 years; peak oxygen consumption (VO2 peak), 42.6 +/- 1.7 mL.kg(-1).min(-1); <1.5 days.week(-1) structured exercise; body fat, 21.1 +/- 1.9%). Subjects underwent 3 oral glucose tolerance tests (OGTT(s)) the day after each of the following 3 conditions: no exercise, baseline (OGTT(B)); SIE at approximately 125% VO(2 peak) (OGTT(SIE)); and EE at approximately 75% VO(2 peak )(OGTT(EE)). SIE and EE sessions were randomized for each subject. Subjects consumed identical meals the day preceding each OGTT. Two insulin sensitivity indices - composite whole-body insulin sensitivity index (ISI-COMP) and ISI-hepatic insulin sensitivity (HOMA) - were calculated, using previously validated formulas (ISI-COMP = 10 000/ radical(glucose(fasting)) x insulin(fasting) x glucose(mean OGTT) x insulin(mean OGTT)); ISI-HOMA = 22.5/(insulin(fasting) x glucose(fasting)), and the plasma concentrations of cytokines interleukin-6 and tumor necrosis factor-alpha were measured. There were no differences by sex for any condition (men vs. women, p > 0.05). Pearson's correlation coefficients between ISI-COMP and ISI-HOMA for each condition were highly correlated (p < 0.01), and followed similar patterns of response. ISI-COMP(EE) was 71.4% higher than ISI-COMP(B) (8.4 +/- 1.4 vs. 4.9 +/- 1.0; p < 0.01) and 40.0% higher than ISI-COMPSIE (8.4 +/- 1.4 vs. 6.0 +/- 1.5; p < 0.05), but there was no difference between ISI-COMP(B) and ISI-COMP(SIE) (p = 0.182). VO(2 peak) was highly correlated with both ISI-COMP and ISI-HOMA during baseline and SIE test conditions (p < 0.02). These findings demonstrate that an acute bout of EE, but not SIE, increases insulin sensitivity relative to a no-exercise control condition in healthy males and females. While these findings underscore the use of regular EE as an effective intervention strategy against insulin resistance, additional research examining repeated sessions of SIE on insulin sensitivity is warranted.

A potential role for skeletal muscle caveolin-1 as an insulin sensitivity modulator in ageing-dependent non-obese type 2 diabetes: studies in a new mouse model

Type 2 diabetes mellitus is a common age-dependent disease. We discovered that male offspring of non-diabetic C57BL/6 and DBA/2 mice, called JYD mice, develop type 2 diabetes when they grow old. JYD mice show characteristics of insulin resistance, hyperglycaemia and hyperinsulinaemia in old age without obesity. We postulated that the mechanism of age-dependent type 2 diabetes in this model relates to caveolin-1 status in skeletal muscle, which appears to regulate insulin sensitivity in the mice. We compared insulin sensitivity in aged C57BL/6 and JYD mice using glucose and insulin tolerance tests and (18)F-fluorodeoxyglucose positron emission tomography. We also determined insulin signalling molecules and caveolin proteins using western blotting, and altered caveolin-1 levels in skeletal muscle of C57BL/6 and JYD mice using viral vector systems, to examine the effect of this on insulin sensitivity. In 30-week-old C57BL/6 and JYD mice, the basal levels of IRS-1, Akt and peroxisome proliferator-activated receptor-gamma decreased, as did insulin-stimulated phosphorylation of Akt and insulin receptor beta. However, caveolin-1 was only increased about twofold in 30-week-old JYD mice as compared with 3-week-old mice, whereas an eightfold increase was seen in C57BL/6 mice. Downregulation of caveolin-1 production in C57BL/6 mice caused severe impairment of glucose and insulin tolerance. Upregulation of caveolin-1 in aged diabetic JYD mice significantly improved insulin sensitivity with a concomitant increase of glucose uptake in the skeletal muscle. The level of skeletal muscle caveolin-1 is correlated with the progression of age-dependent type 2 diabetes in JYD mice.

Diagnosis of Hyperglycemia in a Cohort of Brazilian Subjects

Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) represent intermediate states between normal fasting glucose (NFG) or normal glucose tolerance (NGT), respectively, and diabetes (1). The regulation of fasting and glucose concentrations after an oral glucose load is dependent on different physiological mechanisms (2), and current evidence suggests that IFG and IGT have different pathophysiologies (3,4). Measurement of fasting plasma glucose (FPG) is the most frequently used screening test for diabetes. However, the oral glucose tolerance test (OGTT) might be a preferable test because FPG underestimates the severity of glucose intolerance (5,6) and because IFG and IGT define two distinct populations with only partial overlap (5,7,8). The present study was undertaken to compare insulin sensitivity and insulin secretion profiles associated with different stages of hyperglycemia as assessed by FPG only or by FPG and 2-h plasma glucose during an OGTT. We analyzed data from 900 subjects without previously known diabetes who underwent an OGTT for diagnostic purposes at Fleury Institute, Sao Paulo, Brazil. A double-glycemic status was determined for each subject. A first set was based on FPG only as follows: NFG (FPG …

Prevalence of Glutamic Acid Decarboxylase Antibody Positivity and its Association with Insulin Secretion and Sensitivity in Autoimmune Thyroid Disease: A Pilot Study

Type 1 diabetes and autoimmune thyroid disease are commonly associated. Few studies have addressed islet-cell autoimmunity and its relation with glucose homeostasis in Hashimoto's thyroiditis. The aims of this study were: (1) to determine the prevalence of islet-cell autoimmunity, and (2) to compare insulin sensitivity and secretion patterns between normal glucose tolerant glutamic acid decarboxylase antibodies (GA-D-Ab) positive and negative patients with Hashimoto's thyroiditis. Two hundred fifty-three consecutive patients with Hashimoto's thyroiditis were recruited. After excluding 38 patients with diabetes mellitus, 215 were screened for presence of GAD-Ab. Nine GAD-Ab positive and 8 age, sex and body mass index (BMI) matched GAD-Ab negative patients from the same cohort were included. Frequently sampled intravenous glucose tolerance tests (FSIGTT) were applied. Using glucose and insulin data from FSIGTT, fasting glucose to insulin ratio, HOMA-IR and HOMA-beta-cell function, using the minimal model analysis (MIN-MOD) program, the first phase insulin secretion in response to glucose, the insulin sensitivity index and glucose sensitivity index were calculated. Eleven patients were positive for GAD-Ab (5.1%). There was no difference in any insulin sensitivity or secretion parameters between the GAD-Ab positive and negative patients. Our results suggest that the prevalence GAD-Ab in Hashimoto's thyroiditis is around 5%. GAD-Ab antibody positivity per se does not appear to be associated with any disturbances in insulin sensitivity or insulin secretion in this specific population. The presence of islet-cell autoimmunity does not seem to influence insulin secretion or action in normal glucose tolerant subjects with Hashimoto's thyroiditis in this pilot study. Whether the presence of GAD-Ab per se or along with other antibodies impairs insulin dynamics or predicts the development of diabetes in autoimmune thyroiditis remains to be determined in future studies.

Comparison of insulin sensitivity assessment indices with euglycemic-hyperinsulinemic clamp data after a dietary and exercise intervention in older adults

Multiple indices to assess insulin sensitivity calculated from mathematical equations based on fasting blood parameters or oral glucose tolerance data have been developed. Although these indices have frequently been validated using euglycemic-hyperinsulinemic clamp data, the utility of each equation in measuring change in insulin sensitivity over time remains uncertain. We examined change in insulin sensitivity in response to a 12-week diet and exercise intervention in 31 older men and women with impaired glucose tolerance using a euglycemic-hyperinsulinemic clamp and 10 commonly used insulin sensitivity equations. Mean glucose disposal as calculated from clamp data was significantly higher after the intervention compared with baseline (5.92 ± 0.38 vs 5.18 ± 0.30 mg · kg fat free mass −1 · min −1, P = .013). In contrast, none of the examined indices indicated a significant change in insulin sensitivity over time (all P > .3). A limits of agreement approach to compare insulin sensitivity calculated from each equation with the measure of glucose disposal from the clamp indicated overall imperfect agreement between measures (agreement limits ranged from ±2.48 to ±4.23 mg · kg fat free mass −1 · min −1) despite significant bivariate correlations between indices and clamp data. The wide variability in the 95% prediction limits of agreement among equations suggests that these equations vary substantially from a euglycemic-hyperinsulinemic clamp in their ability to assess insulin sensitivity. Despite the observed limited agreement using this statistical approach, changes in several calculated indices were significantly correlated with changes in clamp data, suggesting that these indices may have some utility in tracking improvements in insulin sensitivity. Further research is necessary to examine agreement between indices and clamp data in larger, more heterogeneous populations and in response to other interventions where the magnitude of change in insulin sensitivity may be larger.

Comparison of euglycemic clamp data with surrogate index measures of insulin sensitivity

Equations to assess insulin sensitivity using fasting blood values or oral glucose tolerance data have been developed. We examined change in insulin sensitivity in response to a 12-wk diet and exercise intervention in 31 older adults with impaired glucose tolerance using a euglycemic-hyperinsulinemic clamp and 10 commonly used insulin sensitivity equations. Glucose disposal as calculated from clamp data was significantly higher following the intervention compared to baseline (5.9 ± 0.4 vs. 5.2 ± 0.3 mg · kg fat-free mass−1 · min−1, P = .01). In contrast, none of the examined indices indicated a significant change in insulin sensitivity over time (all P > .3). A 95% limits of agreement approach to compare insulin sensitivity calculated from each equation with the measure of glucose disposal from the clamp indicated imperfect agreement between measures (agreement limits ranged from ± 2.5 to 4.2 mg · kg FFM−1 · min−1), despite significant correlations between indices and clamp data. Correlations of changes in index values with changes in clamp data signify that these indices may have some practical utility. In terms of assessing improvements in insulin sensitivity, however, the wide variability in the prediction limits of agreement among indices suggests that these equations may be inadequate to assess change in insulin sensitivity, especially in comparison to the clamp technique. R01AG15385, F32AG21374, and M01RR14288.

Ethnicity Modifies the Effect of Obesity on Insulin Resistance in Pregnancy: A Comparison of Asian, South Asian, and Caucasian Women

Women of Asian and South Asian descent are at increased risk of developing gestational diabetes mellitus compared with Caucasians, despite lower body mass index (BMI). Nevertheless, there has been limited study of insulin action during pregnancy in these ethnic groups. The objective of the study was to compare insulin sensitivity in pregnancy in Asian, South Asian, and Caucasian subjects and to determine whether the impact of obesity on insulin action is modified by ethnicity. A cross-sectional study was performed in outpatients undergoing oral glucose tolerance testing in late pregnancy. Participants were stratified into three groups: 1) Caucasian (n = 116); 2) South Asian (n = 31); and 3) Asian (n = 28). Insulin sensitivity was measured using the oral glucose tolerance test (IS(OGTT)) index of M. Matsuda and R. DeFronzo, previously validated in pregnancy. There were no significant ethnic differences in insulin sensitivity despite variation in prepregnancy BMI (Caucasians, 25.2 kg/m(2); South Asians, 23.3 kg/m(2); Asians, 21.4 kg/m(2); overall P = 0.0001). On multiple linear regression analysis, the strongest independent determinants of IS(OGTT) were gestational diabetes mellitus (t = -5.71; P < 0.0001) and BMI (t = -5.43; P < 0.0001). Importantly, both Asian (t = -2.87; P = 0.0047) and South Asian (t = -2.46; P = 0.015) ethnicity also emerged as negative, independent determinants of IS(OGTT). Furthermore, Asian ethnicity significantly modified the association of prepregnancy BMI with IS(OGTT) (interaction term, t = -2.29; P = 0.0231). Asian and South Asian ethnicity are both independently associated with increased insulin resistance in late pregnancy. Prepregnancy BMI has a much greater effect on insulin resistance in pregnancy in Asian women than in Caucasians. Ethnicity thus emerges as a factor that modulates the effect of obesity on insulin resistance in pregnancy.

Iron Stores, Blood Donation, and Insulin Sensitivity and Secretion

Epidemiologists have observed that blood donation is associated with decreased risk of type 2 diabetes and cardiovascular disease. We investigated the relationship between iron stores and insulin sensitivity, after controlling for known confounding factors, and compared insulin sensitivity between blood donors and individuals who had never donated blood (nondonors). In 181 men, insulin sensitivity and insulin secretion were evaluated through frequently sampled intravenous glucose tolerance tests with minimal model analysis. Men who donated blood between 6 months and 5 years before inclusion (n = 21) were carefully matched with nondonors (n = 66) for age, body mass index, waist-to-hip ratio, and cardiovascular risk profile, including blood lipids, blood pressure, and smoking status. Frequent blood donors (2-10 donations) had increased insulin sensitivity [3.42 (1.03) vs 2.45 (1.2) x 10(-4) x min(-1) x mIU/L; P = 0.04], decreased insulin secretion [186 (82) vs 401.7 (254) mIU/L x min; P <0.0001], and significantly lower iron stores [serum ferritin, 101.5 (74) vs 162 (100) microg/L; P = 0.017] than nondonors, but the 2 groups had similar blood hematocrits and blood hemoglobin concentrations. Blood donation is simultaneously associated with increased insulin sensitivity and decreased iron stores. Stored iron seems to impact negatively on insulin action even in healthy people, and not just in classic pathologic conditions associated with iron overload (hemochromatosis and hemosiderosis). According to these observations, it is imperative that a definition of excessive iron stores in healthy people be formulated.

The Comparison of Insulin Sensitivity in Non-diabetic Hemodialysis Patients Treated with and without Recombinant Human Erythropoietin

Patients with end-stage renal disease (ESRD) are known to have insulin resistance. Treatment with EPO is associated with improvement in insulin sensitivity in uremic patients. The aim of this study was to compare insulin sensitivity and pancreatic B cell function in adult non-diabetic uremic hemodialysis patients treated with or without rHuEPO. Three groups of subjects were included to the study: hemodialysis patients treated with rHuEPO [EPO(+) group] or without rHuEPO [EPO(-) group], and healthy controls. Anthropometrical parameters, lipid levels, fasting glucose and insulin levels were measured in all subjects. Homeostasis Model Assessment (HOMA) was used to compare insulin sensitivity. ANOVA, independent t-test, and Pearson correlation were used for statistical analysis. Mean insulin level of control group (20.04 +/- 7.2 pmol/l) was significantly lower than EPO(+) group (p < 0.04) and EPO(-) group (p < 0.0001). HOMA-(%B) levels in the EPO(+) group were significantly lower than in the EPO(-) group (106 +/- 42, 140 +/- 63 respectively, p < 0.02). HOMA-(%B) levels in the control group (66 +/- 17) were significantly lower than in the EPO(+) and EPO(-) group (p < 0.005 and p < 0.0001 respectively). HOMA-(%S) levels in the EPO(+) groups was significantly higher than in the EPO(-) group (91 +/- 40, 56 +/- 26, respectively; p < 0.01). HOMA-(%S) levels of control group (125 +/- 24 ) was significantly higher than EPO(+) and EPO(-) groups (p < 0.02, p < 0.0001 respectively). We found a positive correlation between duration of erythropoietin treatment and insulin sensitivity (r = 0.484, p < 0.002). Firstly, patients treated with EPO are insulin sensitive compared to patients not treated with EPO. Secondly, duration of erythropoietin treatment is positively correlated with insulin sensitivity in hemodialysis patients.

Insulin sensitivity in women with polycystic ovary syndrome.

The aim of our study was to compare insulin sensitivity in lean and obese European polycystic ovary syndrome (PCOS) women with lean healthy women. We performed the euglycemic hyperinsulinemic clamp in 83 women with PCOS [53 lean with body mass index (BMI) of 21.5 +/- 1.8 kg/m2 and 30 obese with BMI of 29.6 +/- 3.7 kg/m2] and in 15 healthy women with BMI of 21.6 +/- 1.8 kg/m2 to determine glucose disposal (M) and the insulin sensitivity index (ISI). Statistical evaluation was done using Kruskal-Wallis ANOVA followed by Kruskal-Wallis multiple-comparison z-value test. The basal blood glucose was significantly higher in lean and obese PCOS women than in controls (P < 0.02). Fasting insulin was significantly higher in both lean and obese PCOS women than in controls (P < 0.000001). Obese PCOS women were more insulin resistant than controls (P < 0.02 for M and P < 0.0008 for ISI); lean PCOS women did not differ from controls in M or ISI. Posthepatic insulin delivery was significantly higher in both lean and obese PCOS women compared with controls (P < 0.000008). We conclude that lean PCOS women are not more insulin resistant than healthy controls. Insulin hypersecretion, on the other hand, is present even in lean PCOS women.

The hormonal phenotype of Nonclassic 3 beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females is associated with insulin-resistant polycystic ovary syndrome and is not a variant of inherited HSD3B2 deficiency.

To test our hypothesis that the hormonal phenotype of mild 3beta-hydroxysteroid dehydrogenase (HSD3B) deficiency in hyperandrogenic females (HF) is related to insulin-resistant polycystic ovary syndrome (PCOS), we compared insulin sensitivity and gonadotropin secretion in HF with compromised ( downward arrow ) adrenal HSD3B phenotype despite normal HSD3B2 genes (n = 6) to those in HF with classic PCOS (n = 9) of similar ages (14-36 yr). The same was examined in premature pubarche (PP) girls with (n = 4) and without the descending HSD3B phenotype (n = 5). The descending HSD3B phenotype was defined by ACTH-stimulated Delta(5)-precursor steroid levels and Delta(5)-precursors to Delta(4)-product steroid ratios higher than those in normal females (n = 30 for adult, n = 12 for pubertal). Classic PCOS HF had elevated testosterone levels and normal ACTH-stimulated hormonal profiles. The insulin sensitivity index determined by the frequently sampled iv glucose-tolbutamide test (FSIVGTT) in all HF with descending HSD3B phenotype and in all HF with classic PCOS, regardless of body mass index (BMI), was lower than in all eight normal BMI and five high BMI normal females. Integrated incremental insulin determined by FSIVGTT, the area under the curve for insulin, and fasting and 2 h glucose load insulin levels determined by an oral glucose tolerance test in both HF groups were higher (P < 0.01-0.0001) than those in normal females with normal or high BMI. LHRH-stimulated LH levels and LH/FSH ratios in both HF groups were higher (P < 0.01) than those in normal females. No statistical differences were found in the insulin sensitivity and gonadotropin parameter between the two PP girl groups. The insulin sensitivity index in each half of PP girls with the descending HSD3B phenotype was lower than or similar to that in control PP girls with a similar weight length index. The fasting glucose to insulin ratio in three of four PP girls with the descending HSD3B phenotype was lower than that in control PP girls, but one of four with the descending HSD3B phenotype had a higher fasting glucose to insulin ratio than the control PP girls. The findings of insulin sensitivity and gonadotropin data in both HF with the descending HSD3B phenotype and classic PCOS indicate significant insulin resistance and LH hypersecretion in both. These suggest that the descending HSD3B phenotype in HF is associated with a variant of insulin-resistant PCOS. The variable insulin sensitivity parameter in the small number of PP girls with the descending HSD3B phenotype warrants a further large scale study to examine this phenotype association with childhood insulin resistance.

Revised QUICKI provides a strong surrogate estimate of insulin sensitivity when compared with the minimal model.

To compare insulin sensitivity (Si) from a frequently sampled intravenous glucose tolerance test (FSIGT) and subsequent minimal model analyses with surrogate measures of insulin sensitivity and resistance and to compare features of the metabolic syndrome between Caucasians and Indian Asians living in the UK. In all, 27 healthy male volunteers (14 UK Caucasians and 13 UK Indian Asians), with a mean age of 51.2+/-1.5 y, BMI of 25.8+/-0.6 kg/m(2) and Si of 2.85+/-0.37. Si was determined from an FSIGT with subsequent minimal model analysis. The concentrations of insulin, glucose and nonesterified fatty acids (NEFA) were analysed in fasting plasma and used to calculate surrogate measure of insulin sensitivity (quantitative insulin sensitivity check index (QUICKI), revised QUICKI) and resistance (homeostasis for insulin resistance (HOMA IR), fasting insulin resistance index (FIRI), Bennetts index, fasting insulin, insulin-to-glucose ratio). Plasma concentrations of triacylglycerol (TAG), total cholesterol, high density cholesterol, (HDL-C) and low density cholesterol, (LDL-C) were also measured in the fasted state. Anthropometric measurements were conducted to determine body-fat distribution. Correlation analysis identified the strongest relationship between Si and the revised QUICKI (r=0.67; P=0.000). Significant associations were also observed between Si and QUICKI (r=0.51; P=0.007), HOMA IR (r=-0.50; P=0.009), FIRI and fasting insulin. The Indian Asian group had lower HDL-C (P=0.001), a higher waist-hip ratio (P=0.01) and were significantly less insulin sensitive (Si) than the Caucasian group (P=0.02). The revised QUICKI demonstrated a statistically strong relationship with the minimal model. However, it was unable to differentiate between insulin-sensitive and -resistant groups in this study. Future larger studies in population groups with varying degrees of insulin sensitivity are recommended to investigate the general applicability of the revised QUICKI surrogate technique.

Comparison of the insulin action parameters from hyperinsulinemic clamps with homeostasis model assessment and QUICKI indexes in subjects with different endocrine disorders.

The aim of this study was to compare insulin sensitivity expressed by the hyperinsulinemic clamp and by the homeostasis model assessment (HOMA) and QUICKI indexes in subjects with various disorders influencing insulin action. We examined 41 type 2 diabetic patients, 20 insulinoma patients, 32 women with polycystic ovary syndrome, 16 patients with primary hyperaldosteronism, 12 patients with essential high renin hypertension, and 47 healthy subjects. The metabolic clearance rate of glucose and the insulin sensitivity index calculated from the clamps were compared with both the HOMA and QUICKI indexes. The relationship of insulin action to body mass index, serum cholesterol, and triglycerides as well as to systolic and diastolic blood pressures was also evaluated. Body mass index was very strongly associated with the insulin sensitivity index (r = -0.70; P < 0.0001) in the entire cohort of 168 subjects. Cholesterol, triglycerides, and blood pressure influenced insulin action in the healthy subjects and type 2 diabetic patients. A significant relationship was observed between the insulin sensitivity index and the HOMA or QUICKI indexes in healthy subjects (r = -0.66; P < 0.0001), type 2 diabetic patients (r = -0.68; P < 0.0001), and women with polycystic ovary syndrome (r = -0.65; P < 0.0001). We did not find any relationship between the above variables in the patients with insulinoma or primary hyperaldosteronism. The HOMA and QUICKI indexes do not offer the same information as glucose clamps in the rare cases with differently impaired peripheral or hepatic insulin action.