Limited predictive ability of surrogate indices of insulin sensitivity/resistance in Asian-Indian men

Insulin resistance is highly prevalent in Asian Indians and contributes to worldwide public health problems, including diabetes and related disorders. Surrogate measurements of insulin sensitivity/resistance are used frequently to study Asian Indians, but these are not formally validated in this population. In this study, we compared the ability of simple surrogate indices to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In this cross-sectional study of Asian-Indian men (n = 70), we used a calibration model to assess the ability of simple surrogate indices for insulin sensitivity [quantitative insulin sensitivity check index (QUICKI), homeostasis model assessment (HOMA2-IR), fasting insulin-to-glucose ratio (FIGR), and fasting insulin (FI)] to predict an insulin sensitivity index derived from the reference glucose clamp method (SI(Clamp)). Predictive accuracy was assessed by both root mean squared error (RMSE) of prediction as well as leave-one-out cross-validation-type RMSE of prediction (CVPE). QUICKI, FIGR, and FI, but not HOMA2-IR, had modest linear correlations with SI(Clamp) (QUICKI: r = 0.36; FIGR: r = -0.36; FI: r = -0.27; P < 0.05). No significant differences were noted among CVPE or RMSE from any of the surrogate indices when compared with QUICKI. Surrogate measurements of insulin sensitivity/resistance such as QUICKI, FIGR, and FI are easily obtainable in large clinical studies, but these may only be useful as secondary outcome measurements in assessing insulin sensitivity/resistance in clinical studies of Asian Indians.     

Comparison between surrogate indexes of insulin sensitivity and resistance and hyperinsulinemic euglycemic clamp estimates in mice

Insulin resistance contributes to the pathophysiology of diabetes, obesity, and their cardiovascular complications. Mouse models of these human diseases are useful for gaining insight into pathophysiological mechanisms. The reference standard for measuring insulin sensitivity in both humans and animals is the euglycemic glucose clamp. Many studies have compared surrogate indexes of insulin sensitivity and resistance with glucose clamp estimates in humans. However, regulation of metabolic physiology in humans and rodents differs and comparisons between surrogate indexes and the glucose clamp have not been directly evaluated in rodents previously. Therefore, in the present study, we compared glucose clamp-derived measures of insulin sensitivity (GIR and SI(Clamp)) with surrogate indexes, including quantitative insulin-sensitivity check index (QUICKI), homeostasis model assessment (HOMA), 1/HOMA, log(HOMA), and 1/fasting insulin, using data from 87 mice with a wide range of insulin sensitivities. We evaluated simple linear correlations and performed calibration model analyses to evaluate the predictive accuracy of each surrogate. All surrogate indexes tested were modestly correlated with both GIR and SI(Clamp). However, a stronger correlation between body weight per se and both GIR and SI(Clamp) was noted. Calibration analyses of surrogate indexes adjusted for body weight demonstrated improved predictive accuracy for GIR [e.g., R = 0.68, for QUICKI and log(HOMA)]. We conclude that linear correlations of surrogate indexes with clamp data and predictive accuracy of surrogate indexes in mice are not as substantial as in humans. This may reflect intrinsic differences between human and rodent physiology as well as increased technical difficulties in performing glucose clamps in mice.     

Current approaches for assessing insulin sensitivity and resistance in vivo: advantages, limitations, and appropriate usage

Insulin resistance contributes to the pathophysiology of diabetes and is a hallmark of obesity, metabolic syndrome, and many cardiovascular diseases. Therefore, quantifying insulin sensitivity/resistance in humans and animal models is of great importance for epidemiological studies, clinical and basic science investigations, and eventual use in clinical practice. Direct and indirect methods of varying complexity are currently employed for these purposes. Some methods rely on steady-state analysis of glucose and insulin, whereas others rely on dynamic testing. Each of these methods has distinct advantages and limitations. Thus, optimal choice and employment of a specific method depends on the nature of the studies being performed. Established direct methods for measuring insulin sensitivity in vivo are relatively complex. The hyperinsulinemic euglycemic glucose clamp and the insulin suppression test directly assess insulin-mediated glucose utilization under steady-state conditions that are both labor and time intensive. A slightly less complex indirect method relies on minimal model analysis of a frequently sampled intravenous glucose tolerance test. Finally, simple surrogate indexes for insulin sensitivity/resistance are available (e.g., QUICKI, HOMA, 1/insulin, Matusda index) that are derived from blood insulin and glucose concentrations under fasting conditions (steady state) or after an oral glucose load (dynamic). In particular, the quantitative insulin sensitivity check index (QUICKI) has been validated extensively against the reference standard glucose clamp method. QUICKI is a simple, robust, accurate, reproducible method that appropriately predicts changes in insulin sensitivity after therapeutic interventions as well as the onset of diabetes. In this Frontiers article, we highlight merits, limitations, and appropriate use of current in vivo measures of insulin sensitivity/resistance.     

Validation of simple indexes to assess insulin sensitivity during pregnancy in Wistar and Sprague-Dawley rats

Insulin resistance plays a role in the pathogenesis of diabetes, including gestational diabetes. The glucose clamp is considered the gold standard for determining in vivo insulin sensitivity, both in human and in animal models. However, the clamp is laborious, time consuming and, in animals, requires anesthesia and collection of multiple blood samples. In human studies, a number of simple indexes, derived from fasting glucose and insulin levels, have been obtained and validated against the glucose clamp. However, these indexes have not been validated in rats and their accuracy in predicting altered insulin sensitivity remains to be established. In the present study, we have evaluated whether indirect estimates based on fasting glucose and insulin levels are valid predictors of insulin sensitivity in nonpregnant and 20-day-pregnant Wistar and Sprague-Dawley rats. We have analyzed the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI), and the fasting glucose-to-insulin ratio (FGIR) by comparing them with the insulin sensitivity (SI(Clamp)) values obtained during the hyperinsulinemic-isoglycemic clamp. We have performed a calibration analysis to evaluate the ability of these indexes to accurately predict insulin sensitivity as determined by the reference glucose clamp. Finally, to assess the reliability of these indexes for the identification of animals with impaired insulin sensitivity, performance of the indexes was analyzed by receiver operating characteristic (ROC) curves in Wistar and Sprague-Dawley rats. We found that HOMA-IR, QUICKI, and FGIR correlated significantly with SI(Clamp), exhibited good sensitivity and specificity, accurately predicted SI(Clamp), and yielded lower insulin sensitivity in pregnant than in nonpregnant rats. Together, our data demonstrate that these indexes provide an easy and accurate measure of insulin sensitivity during pregnancy in the rat.     

Fatness, fitness, and insulin sensitivity among 7- to 9-year-old children

Objective: The purpose of this study was to examine the relationships among fatness and aerobic fitness on indices of insulin resistance and sensitivity in children. Research Design and Methods: A total of 375 children (193 girls and 182 boys) 7 to 9 years of age were categorized by weight as normal‐weight, overweight, or obese and by aerobic fitness based on a submaximal physical working capacity test (PWC). Fasting blood glucose (GLU) and insulin (INS) were used to calculate various indices of insulin sensitivity (GLU/INS), the homeostasis model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI). Surrogate measures of pancreatic β cell function included the insulinogenic index (INS/GLU) and the HOMA estimate of pancreatic β‐cell function (HOMA %B). Results: Insulin sensitivity and secretion variables were significantly different between the normal‐weight children and the overweight and obese subjects. Fasting insulin (FI), HOMA, QUICKI, and INS/GLU were significantly different between the overweight and obese subjects. Likewise, the high fitness group possessed a better insulin sensitivity profile. In general, the normal‐weight–high fit group possessed the best insulin sensitivity profile and the obese‐unfit group possessed the worst insulin sensitivity profile. Several significant differences existed among the six fat‐fit groups. Of particular note are the differences within BMI groups by fitness level and the comparison of values between the normal‐weight–unfit subjects and the overweight and obese subjects with high fitness. Conclusions: The results indicate that aerobic fitness attenuates the difference in insulin sensitivity within BMI categories, thus emphasizing the role of fitness even among overweight and obese children.     

Improved indices of insulin resistance and insulin secretion for use in genetic and population studies of type 2 diabetes mellitus.

Homeostasis model assessment (HOMA) provides indices of insulin secretion (beta) and insulin resistance (R) derived from fasting plasma glucose (FPG) and fasting plasma insulin (FPI) levels. However, these indices could not account for a significant heritability of fasting plasma glucose (FPG) (h2 = 0.75, P<0.01) in a group of 214 female twins. This result is consistent with a misclassification between effects due to insulin secretion and resistance in the HOMA indices. We report here evidence of such misclassification in the HOMA indices and describe a minor modification to the model which corrects it. Direct measures of insulin resistance (euglycaemic clamp) and secretion (i.v. glucose bolus) were obtained in 43 non-diabetic subjects. Heritability was estimated by statistical modelling of genetic and environmental influences in data from 214 non-diabetic female subjects. Modified HOMA (HOMA') indices were obtained from beta' = (Ln(FPI) - c)/FPG and R' = (Ln(FPI) - c)*FPG where c is a constant derived from regression analysis of Ln(FPI) vs FPG. Indices from both models correlated with the direct measures similarly (r = 0.63 (R), 0.49 (R'), 0.45 (beta), 0.39 (beta'), all P< 0.01). Directly measured insulin resistance and secretion were not significantly correlated (r = 0.13, P = 0.21). However, unmodified HOMA-beta and R were strongly related (r = 0.78, P<0.0001 vs. 0.13) demonstrating substantial misclassification. The relationship between beta' and R' (r = 0.13) was not different from that between the two direct measures and significant heritability of beta' (h2 = 0.68, P<0.01) and R' (h2 = 0.59, P<0.05) was evident in the twin data. The proposed modification to HOMA significantly reduces misclassification and reveals separate components of insulin resistance and insulin secretion in the heritability of FPG.     

Effects of short-term chromium supplementation on insulin sensitivity and body composition in overweight children: randomized, double-blind, placebo-controlled study

Excessive body weight is inversely associated with insulin sensitivity in children and adults. Chromium supplementation produces modest improvement in insulin sensitivity in adults. The aim of this study was to examine the beneficial effects of chromium supplementation on insulin sensitivity and body composition in overweight children simultaneously modifying lifestyle. Twenty-five overweight children aged 9–12 years were randomized to receive either 400 μg of chromium chloride or placebo in double-blind fashion, during a 6-week lifestyle modification regimen that included nutritional education and 3×90 min of aerobic physical activity weekly. Insulin sensitivity was demonstrated using homeostasis model assessment-insulin resistance and quantitative insulin sensitivity check index (QUICKI). Changes in body mass index (BMI; kg/m²), BMI Z-score, waist circumference, body composition and fasting plasma glucose were measured. Although no significant benefit of chromium supplementation over placebo was evident for BMI, BMI Z-score and fasting insulin level, children who received chromium chloride demonstrated more positive changes versus the placebo group in HOMA (−1.84±1.07 vs. 0.05±0.42, P=.05), QUICKI (0.02±0.01 vs. −0.002±0.01, P=.05), lean body mass (2.43±0.68kg vs. 1.36±1.61kg, P=.02) and percentage body fat (−3.32±1.29% vs. 0.65±1.05%, P=.04). The desirable effects of chromium supplementation on insulin sensitivity and body composition were more apparent in pre-pubertal children. These results suggest that short-term chromium supplementation can improve insulin sensitivity and body composition in overweight children.     

Altered insulin sensitivity, insulin secretion and lipid profile in non-diabetic prostate carcinoma

Insulin can influence cancer risk through its effect on cell proliferation, differentiation and apoptosis. Although hyperinsulinemia is considered as a risk factor in the pathogenesis of various cancers, the data related to insulin sensitivity, insulin secretion and lipid profile is lacking in non-diabetic prostate carcinoma cases. The present study was undertaken to evaluate lipid profile parameters and insulin sensitivity and secretion using surrogate markers derived from the measurements of fasting glucose and fasting insulin. The study group comprises 27 prostate carcinoma cases and 27 controls having similar age. Fasting serum insulin, glucose and lipid profile parameters were estimated in both the groups. Insulin sensitivity was assessed by Homeostasis model assessment of insulin sensitivity and Quantitative insulin sensitivity check index. Insulin secretion was assessed by insulinogenic index. Fasting serum insulin, insulinogenic index and LDL-cholesterol were significantly increased (p < 0.05) and HOMA-IS, QUICKI and HDL-cholesterol was significantly decreased (p < 0.05) in carcinoma cases compared to controls. PSA level was significantly associated with fasting insulin (R2 = 0.150, beta = 0.387, p = 0.046) and QUICKI (R2 = 0.173, beta = -0.416, p = 0.031). Fasting insulin was significantly correlated with triglyceride (r = 0.404, p = 0.037) and HDL-cholesterol (r = -0.474, p = 0.013). The present study concludes that hyperinsulinemia associated with reduced insulin sensitivity may play a role in the pathogenesis of prostate carcinoma.     

Insulin sensitivity and beta-cell function in healthy cats: assessment with the use of the hyperglycemic glucose clamp.

A hyperglycemic clamp (HGC) was developed for use in conscious cats. In 21 healthy, normal glucose tolerant cats glucose disposal rate (M), insulin sensitivity (ISI (HGC)), and beta-cell response (I) at arterial plasma glucose of 9 mmol.l (-1) were measured. The HGC was tolerated well and steady state glucose infusion was achieved. Compared to values reported for humans, M values for the cats were low, which appeared to relate to both a low ISI (HGC) and a low I. HGC measures correlated with fasting plasma glucose and insulin concentrations as well as with their HOMA (homeostasis model assessment) and QUICKI (quantitative insulin sensitivity check index) counterparts. Also, I and ISI (HGC) correlated with their counterparts derived from intravenous glucose tolerance tests. In conclusion, this is the first report of hyperglycemic glucose clamping in cats. The procedure (HGC) allows for measurements of glucose disposal, beta-cell response and insulin sensitivity. Compared to human data, both insulin sensitivity and insulin secretion appeared to be low in cats. This is compatible with the carnivorous nature of this species, for which insulin resistance would be advantageous during periods of restricted food availability.     

Estimates of in vivo insulin action in humans: comparison of the insulin clamp and the minimal model techniques

The insulin clamp technique, which is often assumed to measure the ability of insulin to stimulate glucose uptake, actually measures both insulin-independent and insulin-dependent glucose uptake. In contrast, the minimal model technique, recently introduced by Bergman, Philips and Cobelli (1981), attempts to directly estimate insulin sensitivity (insulin-dependent glucose uptake = S1) by measurement of plasma glucose and insulin values during a 3 hour intravenous glucose tolerance test (IVGTT). In the present study estimates of insulin action derived from the insulin clamp and the minimal model technique were compared in 20 humans with varying degrees of glucose tolerance. The insulin response during the IVGTT was too low to permit calculation of S1 in 5 subjects - 4 with Type II diabetes and 1 with normal glucose tolerance. Although the correlation coefficient between the two tests in the other 15 patients was statistically significant (r = 0.53, P less than 0.05), this statement is somewhat misleading. Thus, S1 in the 4/7 patients with Type II diabetes in whom it could be measured was zero, and the correlation between estimates of insulin action with the two techniques in the 11 non-diabetic patients was not statistically significant (r = 0.41, P = NS) when these 4 patients were removed from the analysis. In conclusion, these data indicate that there was only a weak correlation between estimates of insulin action assessed with the insulin clamp and the minimal model techniques. One explanation for this observation is that the insulin-independent component of total glucose disposal both varies widely among patients and contributes significantly to glucose uptake as assessed by the insulin clamp technique.(ABSTRACT TRUNCATED AT 250 WORDS)     

Insulin resistance (HOMA) in relation to plasma cortisol,IGF-I and IGFBP-3. A study in normal short-statured and GH-deficient children

OBJECTIVE: To investigate the possible contribution of plasma cortisol and growth hormone (GH) as reflected by insulin-like growth factor-I (IGF-I)/insulin-like growth factor-binding protein-3 (IGFBP-3) on insulin action in short-statured children. METHODS: In this study, insulin resistance (HOMA) was determined in 34 normal short-statured (age 9.4 +/- 3.5 years) and in 19 GH-deficient children (age 10.4 +/- 2.2 years). HOMA was examined in relation to fasting plasma cortisol, IGF-I, IGFBP-3 and in addition to birthweight and body mass index (BMI). RESULTS: Birthweight was not correlated to insulin resistance. In GH-deficient children, BMI was significantly augmented and was associated with HOMA (p < 0.02). In both groups of patients, fasting plasma cortisol was related to HOMA (normal: r = 0.295, p < 0.05, GH-deficient: r = 0.495, p < 0.02). Only in normal short-statured children IGF-I (r = 0.338, p < 0.03) and IGFBP-3 (r = 0.493, p < 0.002) were associated with insulin resistance. CONCLUSION: The results indicated that at a young age cortisol contributed to insulin resistance in short-statured children. In normal short-statured children HOMA was associated with IGF-I and IGFBP-3. Possibly GH, a known cause of insulin resistance, contributed to HOMA as IGF-I and IGFBP-3 do not mediate insulin resistance but reflect growth hormone secretion. The results in GH-deficient children supported this conclusion as in the absence of GH insulin resistance was not associated with IGF-I/IGFBP-3.     

Chemerin as biomarker for insulin sensitivity in males without typical characteristics of metabolic syndrome

To allow early detection and prevention of metabolic disorders, circulating levels of adipokines involved in insulin sensitivity were compared with the hyperinsulinemic-euglycemic clamp. Twenty non-obese normo-glycaemic men (age 32.1 ± 6 years) underwent a clamp procedure. Levels of leptin, adiponectin, resistin, visfatin, omentin and chemerin levels were determined in fasting blood samples. Pearson correlation coefficients between the M-value for insulin sensitivity and fasting levels of chemerin (r = -0.63, P = 0.003) and leptin (r = -0.54, P = 0.013) performed better than conventional surrogate measures of insulin sensitivity (HOMA-IR: r = -0.45, P = 0.048; Quicki: r = 0.36, P = 0.12). However, only the relation between M-value(LBM) and chemerin remained significant when adjusting for BMI and fasting insulin levels (r = -0.559, P = 0.016). In conclusion, fasting levels of chemerin might be used as biomarker to identify insulin resistance in healthy men without typical characteristics of metabolic disorders.     

Comparison of several insulin sensitivity indices derived from basal plasma insulin and glucose levels with minimal model indices.

Some techniques for the evaluation of insulin resistance (IR), such as the clamp technique, are not viable for the study of large populations; and for this reason, alternative approaches based on fasting plasma glucose (FPG) and plasma insulin (FPI) have been proposed. The aim of this study was to compare the IR calculations obtained from FPI and FPG values with the insulin sensitivity (IS) index derived from the minimal model. Eighty-seven healthy subjects with a wide range of body mass index (18 - 44 kg x m -2) and 16 DM2 non-obese patients were included in the study. All of the patients underwent a frequently sampled intravenous glucose tolerance test (FSIGTT), and the minimal model of glucose was used for the estimation of insulin sensitivity (IS MINIMAL ). The HOMA-IR index, the Avignon index, and the quotient FPG/FPI were used to calculate basal steady-state IR. The basal IR value that best correlated with IS was Log (1/HOMA-IR) (r = 0.70, p < 0.001). All of the basal indices showed a high correlation with each other. In conclusions, insulin sensitivity indices as determined from the basal glycaemia and insulinemia values are not good estimators for metabolic reality from the perspective of the minimal model. Nevertheless, they might well have an IR screening value for epidemiological studies, as long as there is no pancreatic beta-cell dysfunction.     

Exercise and diet induced weight loss improves measures of oxidative stress and insulin sensitivity in adults with characteristics of the metabolic syndrome

Obesity and insulin resistance (IR) increase the risk for coronary heart disease; however, much of this risk is not attributable to traditional risk factors. We sought to determine whether weight loss associated with supervised aerobic exercise beneficially alters biomarkers of oxidative stress and whether these alterations are associated with improvements in measures of insulin resistance. Twenty-five sedentary and overweight to obese [body mass index (BMI) = 33.0 +/- 0.8 kg/m(2)] individuals, with characteristics of the metabolic syndrome, participated in a 4- to 7-mo weight loss program that consisted of energy restriction (reduced by approximately 500 kcal/day) and supervised aerobic exercise (5 days/wk, 45 min/day at 60% Vo(2 max); approximately 375 kcal/day). IR and insulin sensitivity were assessed by the calculation of the homeostasis model assessment (HOMA) and quantitative insulin sensitivity check index (QUICKI), respectively. Oxidative stress was assessed by oxidized LDL (oxLDL), myeloperoxidase (MPO), and low- and high- density lipoprotein (LDL and HDL) lipid hydroperoxide concentrations in serum. Indexes for antioxidative status included apolipoprotein A1 (apoA1) concentrations and paraoxonase-1 (PON1) activity and protein concentrations. Exercise- and diet-induced weight loss ( approximately 10%) significantly (P < 0.05) increased insulin sensitivity and reduced IR, oxLDL, and LDL lipid hydroperoxides but did not alter HDL lipid hydroperoxides or MPO concentrations. Lifestyle modification impacted systemic antioxidative status by increasing apoA1 concentrations and reducing serum PON1 protein and activity. Changes in oxidative stress were not associated with alterations in HOMA or QUICKI. Diet- and exercise-induced weight loss ( approximately 10%) improves measures of insulin sensitivity and beneficially alters biomarkers of oxidative status.     

Elevated plasma proinsulin/insulin ratio is a marker of reduced insulin secretory capacity in healthy young men.

AIM: To examine whether reduced insulin secretory capacity or increased insulin secretory demand is associated with elevated ratio of plasma proinsulin to immunoreactive insulin (PI/IRI ratio) in non-diabetic subjects. SUBJECTS AND METHODS: We measured various indices of insulin secretory function and insulin sensitivity by frequently sampled intravenous glucose tolerance test (FSIGT) and hyerglycemic glucose clamp in 21 healthy young men. We then examined the relationships between these indices and PI, IRI, or PI/IRI ratio in the fasting state. RESULTS: Insulin sensitivity index (SI) measured by FSIGT correlated inversely with basal IRI (r=-0.53, P < 0.01) and PI levels (r=-0.57, P < 0.01), but there was no significant correlation between SI and PI/IRI ratio (r=0.26, NS). On the other hand, PI/IRI ratio correlated inversely with insulin secretory indices, such as acute insulin responses during FSIGT (r =-0.46, P < 0.01) and hyperglycemic glucose clamp (r=-0.54, P < 0.01) and submaximum insulin response during hyperglycemic glucose clamp (r=-0.59, P < 0.01). CONCLUSIONS: These results indicate that elevated PI/IRI ratio may serve as a marker of reduced insulin secretory function in non-diabetic subjects.     

Is a small muscle mass index really detrimental for insulin sensitivity in postmenopausal women of various body composition status?

Objectives: We sought to determine if a small muscle mass index (MMI) is actually detrimental for insulin sensitivity when studying a large group of postmenopausal women displaying various body composition statuses and when age and visceral fat mass (VFM) are taken into account. Methods: A cross-sectional study was conducted in 99 healthy postmenopausal women with a BMI of 28?4 kg/m(2). Fat mass and total fat-free mass (FFM) were obtained from DXA and VFM and MMI were estimated respectively by the equation of Bertin and by: Total FFM (kg)/height (m)(2). Fasting plasma insulin and glucose were obtained to calculate QUICKI and HOMA as an insulin sensitivity index. Results: Total MMI and VFM were both significantly inversely correlated with QUICKI and positively with HOMA even when adjusted for VFM. A stepwise linear regression confirmed Total MMI and VFM as independent predictors of HOMA and plasma insulin level. Conclusions: A small muscle mass might not be detrimental for the maintenance of insulin sensitivity and could even be beneficial in sedentary postmenopausal women. The impact of muscle mass loss on insulin sensitivity in older adults needs to be further investigated.     

Effects of growth hormone therapy on glucose metabolism and insulin sensitivity indices in prepubertal children with Prader-Willi syndrome

In Prader-Willi syndrome (PWS) growth hormone therapy (GHT) improves height, body composition, agility and muscular strength. In such patients it is necessary to consider the potential diabetogenic effect of GHT, since they tend to develop type 2 diabetes, particularly after the pubertal age. The aim of our study was to investigate the effects of GHT on glucose and insulin homeostasis in PWS children. An oral glucose tolerance test (OGTT) was performed in 24 prepubertal PWS children (15 male, 9 female, age: 5.8 +/- 2.8 years), 16 were obese (group A) and 8 had normal weight (group B), before and after 2.7 +/- 1.3 years GHT (0.22 +/- 0.03 mg/kg/week) and, only at baseline, in 35 prepubertal children with simple obesity (19 male, 16 female) (group C). Fasting glucose and insulin, glucose tolerance, insulin sensitivity index (ISI), homeostasis model assessment of insulin resistance (HOMA-IR), quick insulin check index (QUICKI), area under the curves (AUC) of glucose and insulin were estimated. At the start of GHT, all PWS children were normoglycaemic and normotolerant but two developed impaired glucose tolerance after 2.2 and 1.9 years of therapy, respectively. At baseline, group A showed lower fasting insulin levels, HOMA-IR and AUC of insulin, higher ISI, QUICKI and AUC of glucose than group C. Comparing groups A and B, AUC of insulin was higher and ISI lower in group A. During GHT, a significant increase of fasting insulin and glucose, a worsening of insulin resistance (HOMA-IR) and insulin sensitivity (QUICKI) was found only in group A while ISI did not change. The AUC of glucose decreased in both groups instead AUC of insulin did not change. BMI-SDS decreased in group A and increased in group B. The increased insulin resistance and decreased insulin sensitivity in obese PWS patients, as well as the occurrence of impaired glucose tolerance during GHT, suggest that a close monitoring of glucose and insulin homeostasis is mandatory, especially in treated obese PWS children.     

Circulating serum adiponectin concentrations do not differ between obese and non-obese caucasians and are unrelated to insulin sensitivity.

Reduced serum levels of adiponectin in obesity and insulin resistance seem paradoxical, since adipose tissue is the only source of adiponectin, and reports on that subject are contradictory. The aim of this study was to investigate the concentrations of adiponectin in non-obese and obese normoglycemic humans, and to determine the correlation between adiponectin and HOMA index of insulin sensitivity. Based on the WHO definition of obesity, 145 obese subjects and 49 non-obese controls (aged 20-55 years) were studied. The serum adiponectin concentrations did not differ between subjects and controls (p=0.6398) and were not correlated with HOMA index (r=-0.0211; p=0.8048, and r=-0.0523; p=0.4757, for subjects and controls, respectively). Adiponectin was not correlated with HOMA index in females (r=-0.0521; p=0.6546, and r=-0.0825; p=0.3981, for female subjects and controls, respectively) as well as in males (r=0.0033; p=0.9791, and r=0.0123; p=0.9131, for male subjects and controls, respectively). These results lead to the conclusion that neither the concentrations of adiponectin differ between obese and non-obese humans, nor does any relationship between adiponectin concentration and insulin sensitivity exist.     

Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0-33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat (r = 0.82, P < 0.001) and liver fat (r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal (r = 0.60, P = 0.008), intra-abdominal (r = 0.75, P = 0.0001) and liver (r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal (r = -0.72, P = 0.001) and intra-abdominal (r = -0.55, P = 0.015) but not liver (r = -0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.     

Association between gestational diabetes and biomarkers: a role in diagnosis

Background: We investigated the association between markers of insulin resistance, chronic inflammation, and adipokines and GDM.

Methods: In our case-cohort study in Johannesburg we included women with GDM and controls. We tested the ability of biomarkers to identify women at high risk of GDM.

Results: Of the 262 pregnant women, 83 (31.7%) had GDM. Women with GDM were heavier (p?=?0.04) and had more clinical risk factors (p?=?0.008). We found a significant difference in fasting insulin (p?p?=?0.046), HOMA (p?p?Conclusions: Insulin sensitivity markers are promising tools to identify women at high risk of GDM.