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Background: Recent studies have shown a high prevalence of Type-2-diabetes (T2DM) (24%) and prediabetes (18.1%) in Kerala. There is no community based study from South Asia regarding the prevalence of type 2 diabetes and its precursors in the young adult population. This community based study was done to find the prevalence of type 2 diabetes and its precursors in South Indian adult youth (18-30 years age) of Thiruvananthapuram district. Research Design and Methods: Cross sectional design was used for this study. Multistage cluster sampling was used to enrol community dwelling youth of 18 to 30 years, residing in Thiruvananthapuram district. Six panchayath wards from rural and urban regions and 4 from coastal area were randomly selected as the primary sampling units. Trained staff nurses conducted the survey with the help of accredited-social-health-activists (ASHA). Socio-demographic data, anthropometry, clinical features of insulin resistance, and random capillary glucose (CG) and blood pressure were assessed and recorded. Oral Glucose tolerance test or HbA1c was done for participants with a CG =130 mg/dl for diagnosis of diabetes and prediabetes. Results: A total of 1031 participants were included from the rural (n = 394), coastal (n = 269) and urban (n = 368) areas. Prevalence of hyperglycaemia i.e., T2DM and pre-diabetes was 0.48% (n = 5) and 2.4% (n = 25) respectively. Family-history of T2DM was present in 35.1% subjects. Prevalence of overweight, obesity and abdominal-obesity was 28.2%, 16.1% and 28.4% respectively. Clinical-features of insulin resistance (CFIR) were present in 27.1% subjects (acanthosis [17.7%], skin tags [1.7%] and PCOS phenotype [10.7%]). Among various anthropometric measurements and their derivatives, CFIR correlated best (r = 0.24, P < 0.01) with the product of BMI and the sum of abdominal circumference and hip circumference (Trivandrum Medical College [TMC] -adiposity-index), which is a newly proposed parameter. Hyperglycaemia was more common in males, did not correlate with waist hip ratio, and correlated best again with TMC-adiposity-index ((r = 0.13, P < 0.01). Conclusions: The burden of insulin resistance in the young South Indian population, hitherto unknown in any community based study, has been studied for the first time. The prevalence of precursors of T2DM is high in this population. Early identification of 'at risk' individuals could provide a window of opportunity for preventing or delaying future diabetes and its long term complications. TMC adiposity index could become a valuable tool in the anthropometric assessment for predicting future T2DM. [ABSTRACT FROM AUTHOR]

To study the association and possible predictive role of visfatin, resistin, fetuin-A and chemerin with incident type 2 diabetes (T2DM) among Asian Indians with prediabetes. Their association with insulin resistance, β-cell function, glycaemia and anthropometry were also studied. This is a nested case–control study of a large 2-year prospective prevention trial in persons at high risk of developing T2DM. Baseline HbA1c values between 6.0% (42 mmol/mol) and 6.2% (44 mmol/mol) were chosen for this analysis (n = 144). At follow-up, persons with incident T2DM (HbA1c ≥ 6.5%, 48 mmol/mol) were grouped as cases (n = 72) and those reverted to normoglycaemia, (HbA1c < 5.7% (39 mmol/mol) as controls (n = 72). Insulin resistance showed the strongest association with incident T2DM ((Odds Ratio (OR): 23.22 [95%CI 6.36–84.77]; p < 0.0001). Baseline visfatin (OR: 6.56 [95%CI 2.21–19.5]; p < 0.001) and fetuin-A (OR: 1.01 [95%CI (1.01–1.04)]; p < 0.0001) independently contributed to the conversion of prediabetes to T2DM. The contribution was significantly higher when their elevated levels coexisted (OR: 12.63 [95%CI 3.57–44.63]; p < 0.0001). The area under the curve was 0.77 ± SE 0.4 (95%CI 0.69–0.85) and 0.80 ± SE 0.04 (95%CI 0.73–0.88) for visfatin (median 17.7 ng/ml, sensitivity and specificity: 75%, p < 0.0001) and fetuin-A (mean 236.2 µg/ml, sensitivity: 71%, specificity: 75%, p < 0.0001) respectively. Higher baseline visfatin and fetuin-A concentrations are strongly associated with incident T2DM and are predictive of future diabetes. [ABSTRACT FROM AUTHOR]

Background: Sleep restores physiology and neurochemical components of our body and is essential for physical and mental health. Sleep disorders (SDs) are associated with insulin resistance and metabolic disorders. The association between SDs and diabetes needs to be understood in the Indian population. Purpose: The purpose was to investigate the association between SD and diabetes in the Indian population. Methods: As a part of nationwide Niyantrita Madhumeha Bharata Abhiyaan-2017 (NMB-2017), a cross-sectional study was conducted and data was collected from seven zones of India, after screening through the Indian Diabetes Risk Score (IDRS). The sleep quality was assessed on a scale of 1 to 4 (very good = 1, very bad = 4). The time taken to fall asleep (sleep latency) was assessed on a scale of 0 to 5 ("0" = nil and "5" = >1.5 h). Stress was assessed by the perceived stress scale. Results: Bad sleep quality was positively (odds ratio 1.055, CI [1.001, 1.113], and P <.01) associated with self-reported known diabetes. Increased time taken to fall in sleep (sleep latency) was associated significantly with IDRS high risk (odds ratio 1.085, CI [1.008, 1.168], and P =.01), with an average sleep latency /time takes to fall in sleep (maximum range 5 [>1.5 h], mode 2 [10 to 30 min]) minutes. Moderate stress was significantly associated with bad sleep quality (odds ratio 1.659). Conclusion: A positive association of bad sleep quality and stress with diabetes, and an increased sleep latency in the IDRS high-risk population point to the role of modifiable risk factors. Behavioral modification and stress reduction by using yoga may be beneficial in the better management of diabetes. [ABSTRACT FROM AUTHOR]

Background: Sleep restores physiology and neurochemical components of our body and is essential for physical and mental health. Sleep disorders (SDs) are associated with insulin resistance and metabolic disorders. The association between SDs and diabetes needs to be understood in the Indian population. Purpose: The purpose was to investigate the association between SD and diabetes in the Indian population. Methods: As a part of nationwide Niyantrita Madhumeha Bharata Abhiyaan-2017 (NMB-2017), a cross-sectional study was conducted and data was collected from seven zones of India, after screening through the Indian Diabetes Risk Score (IDRS). The sleep quality was assessed on a scale of 1 to 4 (very good = 1, very bad = 4). The time taken to fall asleep (sleep latency) was assessed on a scale of 0 to 5 ("0" = nil and "5" = >1.5 h). Stress was assessed by the perceived stress scale. Results: Bad sleep quality was positively (odds ratio 1.055, CI [1.001, 1.113], and P < .01) associated with self-reported known diabetes. Increased sleep time (sleep latency) was associated significantly with IDRS high risk (odds ratio 1.085, CI [1.008, 1.168], and P = .01), with an average sleep latency (maximum range 5 [>1.5 h], mode 2 [10 to 30 min]) minutes. Moderate stress was significantly associated with bad sleep quality (odds ratio 1.659). Conclusion: A positive association of bad sleep quality and stress with diabetes, and an increased sleep latency in the IDRS high-risk population point to the role of modifiable risk factors. Behavioral modification and stress reduction by using yoga may be beneficial in the better management of diabetes. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes is a heterogeneous disease and its categorization into different clusters has revealed distinct subgroups from all over the world including India but no such study has been done till date in north India. Aims and Objectives: To identify clusters intype 2 diabetes mellitus by k means clustering and to describe different characteristics of patients in each of the identified clusters. Methods: Optimal number of clusters i.e., the K value was decided by two step clustering and the subtypes of the clusters were obtained by K means clustering using SPSS version 29 software. Variables which were used for clustering were age atdiagnosis, BMI, HbA1c, HOMA islet and HOMA insulin resistance (based on fasting C-peptide levels) along with waist circumference which has important role in type 2 diabetes mellitus physiology in south east Asians. Results: Total number of participants were 520, out of which 47.7% were males and females were 52.3%. The optimal number of clusters i.e., K = 4 was determined based on silhouette width. Using this K value K means clustering was done which resulted in formation of clusters differing in phenotypic characters. Cluster 1 severe insulin deficient diabetes (SIDD), Cluster 2 Mild age-related diabetes (MARD), Cluster 3 severe insulin resistant diabetes (SIRD), Cluster 4 mild obesity related diabetes (MOD). Phenotypically these clusters were same as defined by Ahlqvist et al in Scandinavian population. When compared with these Swedish clusters, MOD cluster was most common in our study population (37.1% vs 21.6%). SIDD cluster was more common than in Swedish study (21.3% vs 17.5%). In Swedish study MARD cluster was most common (39.1%) where as in our study it constituted 24.2% of patients. Conclusion: This study suggests that clusters in type 2 diabetes can be replicated in different ethnicities and highlights importance of including waist circumference in clustering in Asian Indians. Further studies are needed to look at differences in treatment response when treatment targeting the basic pathophysiological mechanism in different clusters is given to the respective clusters. [ABSTRACT FROM AUTHOR]

Background: The clustering of risk factors of cardiovascular disease (CVD) in individuals hasbeen defined as Metabolic Syndrome (MetS) and helps us to identify populations at risk for future CVD. The prevalence of MetS in Indian population has been shown to be one in three persons, which may be higher if we consider urban populations alone. The major forerunner of all the components of MetS is Insulin resistance, which is measured by a hyperinsulinemic euglycemic clamp. However, this method is cumbersome and an easier, albeit less accurate method of measurement is Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). HOMA-IR, however, requires the measurement of Plasma Insulin levels, which may be inaccurate due to poor standardization and is also not widely available. Thus, we attempted to study the performance of lipid based biochemical markers of insulin resistance for the diagnosis of MetS. In this study, we analyzed three lipid based indices, Triglyceride Glucose index (TyG index), Triglyceride: High Density Lipoprotein (TG:HDL) ratio and Lipid Accumulation Product (LAP). There exists a lack of Indian data on these surrogate Indian insulin resistance markers. Aim of the Study: To compare the efficacy of novel biomarkers of Insulin resistance with HOMA-IR in the diagnosis of MetS in South Indian population. To estimate a population specific cutoff for these biomarkers for our population. Methods: This was a cross sectional study and included apparently healthy population presenting to our hospital for routine Master Health Checkup medical assessment and apparently healthy population residing in Kallindhiri, a village near Madurai. The height, weight, waist circumference, hip circumference and blood pressure were measured for all the patients. A fasting serum sample was collected for the measurement of fasting lipid profile, fasting plasma glucose and fasting serum insulin levels. Based on the data collected, Body Mass Index (BMI), Waist hip ratio, Waist height ratio, HOMA-IR, TyG index, TG:HDL ratio and LAP were calculated. The diagnostic efficacy of these indices was compared against the presence of MetS based on the NCEP ATP III criteria. Receiver Operating Characteristic Curve was performed to discriminatedecision levels (cut-offs) of serum markers in early diagnosis of MetS. The results were considered significant with p value less than 0.05. Results: We included a total of 192 patients in our study, consisting of 36% (n = 70) males and 63% (n = 122) females. All the baseline characteristics except height, weight and HDL cholesterol were comparable between the male and female groups. The calculated value of HOMA-IR, TyG index, TG:HDL ratio and LAP showed an increasing trend with increasing levels of BMI. The mean value of HOMA IR in patients without MetS was 0.99 +/- 0.781, whereas in the patients with MetS was 2.32+/-1.27 (p value-<0.001). The mean value of TyG index in patients without MetS was 4.51+/-0.18, whereas the mean value in patients with MetS was 4.83 +/- 0.203 (p value-<0.001). The mean value of TG:HDL ratio in female patients without MetS was 2.01 +/- 0.522, whereas the mean value in patients with MetS was 4.69 +/- 2.62 (p value-<0.001). The mean value of TG:HDL ratio in male patients without MetS was 2.11+/- 0.59, whereas the mean value in patients with MetS was 5.06 +/- 2.31 (p value-<0.001). The mean value of Lipid Accumulation Product in male patients without MetS was 24.30+/- 21.24, whereas the mean value in patients with MetS was 59.34 +/- 22.72 (p value-<0.001). The mean value of Lipid accumulation Product ratio in female patients without MetS was 27.34+/- 15.69, whereas the mean value in patients with MetS was 63.78 +/- 20.27 (p value-<0.001). Based on the Receiver Operating characteristics (ROC) curve plotted for the data, a population specific cutoff for these indices was computed. The Area Under Curve (AUC) was highest for LAP (0.917). The AUC for TG: HDL ratio was 0.886, TyG index was 0.885 and HOMA-IR was 0.829. Based on the ROC curves our proposed cutoff for South Indian population for HOMA-IR was 1.23, with a sensitivity of 78.9% and specificity of 80%. The cutoff for TyG index in our population was 4.65, with sensitivity of 80.7% and specificity of 81%. The population specific cutoff for TG: HDL ratio computed by us was 3.44 in males and 2.6 in females. The male specific cutoff exhibited a sensitivity of 79.2% and specificity of 78% and the female specific cutoff showed a sensitivity of 81.8% and specificity of 82%. %. The population specific cutoff for LAP computed by us was 38.8 in males and 44.2 in females. The male specific cutoff exhibited a sensitivity of 83.3% and specificity of 85% and the female specific cutoff showed a sensitivity of 84.8% and specificity of 85%. Conclusion: The cutoffs for the novel indices of insulin resistance which have been previously studied in Caucasian populations cannot be applied to Indian populations due to distinct ethnic characteristics. The diagnostic accuracy of these novel biomarkers of Insulin Resistance are better than the biochemical gold standard of HOMA-IR based on the ROC curves. In our study, we found the ideal cutoff for HOMA-IR in our population to be 1.23. We propose a cutoff of 4.65 for TyG index, 3.44 for TG:HDL ratio in males and 2.6 in females, and a LAP cutoff of 38.8 in males and 44.2 in females for the early diagnosis of MetS, and we advocate to bring these indices for screening in routine clinical settings. [ABSTRACT FROM AUTHOR]

Background and aim Insulin resistance plays a crucial role in the pathogenesis of type 2 diabetes and cardiovascular diseases. Recently, paraoxonase-1(PON1) is reported to have an ability to reduce insulin resistance by promoting glucose transporter-4 (GLUT-4) expression in vitro. Single nucleotide polymorphism (SNP) in PON1 is associated with variability in enzyme activity and concentration. Based on this we aimed to investigate the association of PON1 (Q192R and L55M) polymorphisms with the risk of developing insulin resistance in adult South Indian population. Methods Two hundred and eighty seven (287) Type 2 diabetes patients and 293 healthy controls were enrolled in this study. All the study subjects were genotyped for PON1 (Q192R and L55M) missense polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) method. Fasting serum insulin level was measured by ELISA. Results The distribution of QR/RR and LM/MM genotypes were significantly higher in type 2 diabetes patients compared with healthy controls. Moreover, the R and M alleles were significantly associated with type 2 diabetes with an Odds Ratio of 1.68 (P < 0.005) and 2.24 (P < 0.005) respectively. SNP 192 Q > R genotypes were found to be significantly associated with higher BMI, cholesterol, triglycerides, LDL, fasting serum insulin and HOMA-IR. Further, the mutant allele or genotypes of PON1 L55M were associated with higher BMI, triglycerides, VLDL, fasting serum insulin and HOMA-IR among adult type 2 diabetes patients. Conclusion PON1 (Q192R and L55M) polymorphisms may play a crucial role in pathogenesis and susceptibility of insulin resistance thus leads to the development of type 2 diabetes in South Indian population. [ABSTRACT FROM AUTHOR]

Several algorithms and guidelines have been proposed by countries and international professional bodies; however, no recent updated management algorithm is available for Asian Indians. Specifically, algorithms developed and validated in developed nations may not be relevant or applicable to patients in India because of several factors: early age of onset of diabetes, occurrence of diabetes in nonobese and sometimes lean people, differences in the relative contributions of insulin resistance and β-cell dysfunction, marked postprandial glycemia, frequent infections including tuberculosis, low access to healthcare and medications in people of low socioeconomic stratum, ethnic dietary practices (e.g., ingestion of high-carbohydrate diets), and inadequate education regarding hypoglycemia. All these factors should be considered to choose appropriate therapeutic option in this population. The proposed algorithm is simple, suggests less expensive drugs, and tries to provide an effective and comprehensive framework for delivery of diabetes therapy in primary care in India. The proposed guidelines agree with international recommendations in favoring individualization of therapeutic targets as well as modalities of treatment in a flexible manner suitable to the Indian population. [ABSTRACT FROM AUTHOR]

Background: This study examined the association in a South Indian population with gestational diabetes mellitus (GDM) of type 2 diabetes risk variants that have previously conferred susceptibility to GDM in other populations. Subjects and Methods: The study groups comprised 518 women with GDM and 910 pregnant women with normal glucose tolerance (NGT). Women with GDM were recruited from a tertiary diabetes center in Chennai, in south India, and NGT women were selected from antenatal clinics also in Chennai. Genomic DNA was isolated from whole blood using the phenol chloroform method. Twelve previously reported GDM-associated single nucleotide polymorphisms (SNPs) in or near nine loci were genotyped using the MassARRAY™ system (Sequenom, San Diego, CA). Results: Among the 12 SNPs genotyped, 11 SNPs were in Hardy-Weinberg equilibrium and had a call rate of >95%. Of the 11 SNPs previously associated with GDM in other populations, significant association was observed only with the rs7754840 and rs7756992 SNPs of the CDK5 regulatory subunit associated protein 1-like 1 ( CDKAL1) gene in this population. The minor alleles of the SNPs rs7754840 and rs7756992 showed significant susceptibility to GDM with an odds ratio of 1.34 (95% confidence interval, 1.12-1.60; P=0.0013) and 1.45 (95% confidence interval, 1.21-1.72; P=0.00004), respectively. Conclusions: The rs7754840 and rs7756992 SNPs of the CDKAL1 gene were found to be associated with GDM in this south Indian population. This is the first study describing genetic susceptibility of GDM in Asian Indians. [ABSTRACT FROM AUTHOR]

Background and Aims Betatrophin is emerging as a marker for compensatory beta cell proliferation. While betatrophin has been mainly investigated in adults, there is a lack of data on betatrophin levels in youth-onset type 2 diabetes mellitus (T2DM-Y). The aim of this study was to determine levels of betatrophin and its association with T2DM-Y in Asian Indian participants. Methods We recruited 100 individuals with normal glucose tolerance (NGT; n = 50) and newly-diagnosed cases (within 18 months of first diagnosis) of T2DM-Y ( n = 50) with onset between 12 and 24 years of age from a large tertiary diabetes center in Chennai in southern India. Insulin resistance was measured by homeostatic model (HOMA-IR) and insulin secretion by oral disposition index (DIO). Betatrophin levels were measured by enzyme-linked immunosorbent assay. Results Betatrophin levels were significantly lower in the T2DM-Y group compared with the NGT group (803 vs 1104 pg/ml, p < 0.001). Betatrophin showed a significant inverse correlation with waist circumference ( p = 0.035), HOMA-IR ( p < 0.001), fasting and 2 h postprandial glucose ( p < 0.01), glycated hemoglobin ( p = 0.019) and a positive correlation with fasting C-peptide ( p < 0.001) and DIO ( p = 0.012). In regression analysis, betatrophin was independently associated with T2DM-Y even after adjustment for age, gender, and waist circumference (OR per standard deviation: 0.562, 95% CI: 0.342–0.899, p = 0.019). However, the association was lost when HOMA-IR was included in the model (OR: 1.141, 95% CI: 0.574–2.249; p = 0.646). Conclusion Betatrophin levels are lower in T2DM-Y and this association is likely mediated through insulin resistance. [ABSTRACT FROM AUTHOR]

Aims: We assessed the relative associations of β-cell dysfunction and insulin sensitivity with baseline glycemic status and incident glycemic progression among Asian Indians in the United States. Methods: A 5-sample oral glucose tolerance test was obtained at baseline. Normoglycemia, impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and type 2 diabetes (T2DM) were defined by ADA criteria. The Matsuda Index (ISIM) estimated insulin sensitivity, and the Disposition Index (DIo) estimated β-cell function. Visceral fat was measured by abdominal CT. After 2.5 years, participants underwent a 2-sample oral glucose tolerance test. Standardized polytomous logistic regression was used to examine associations with prevalent and incident glycemia. Results: Mean age was 57 ± 8 years and BMI 26.1 ± 4.6 kg/m2. Log ISIM and log DIo were associated with prediabetes and T2DM after adjusting for age, sex, BMI, family history of diabetes, hypertension, and smoking. After adjusting for visceral fat, only DIo remained associated with prediabetes (OR per SD 0.17, 95% CI: 0.70, 0.41) and T2DM (OR 0.003, 95% CI: 0.0001, 0.03). Incidence rates (per 1,000 person-years) were: normoglycemia to IGT: 82.0, 95% CI (40, 150); to IFG: 8.4, 95% CI (0, 41); to T2DM: 8.6, 95% CI (0, 42); IGT to T2DM: 55.0, 95% CI (17, 132); IFG to T2DM: 64.0, 95% CI (3, 316). The interaction between sex and the change in waist circumference (OR 1.8, per SD 95% CI: 1.22, 2.70) and the change in log HOMA-β (OR 0.37, per SD 95% CI: 0.17, 0.81) were associated with glycemic progression. Conclusions: The association of DIo with baseline glycemia after accounting for visceral fat as well as the association of the change in log HOMA-β with incident glycemic progression implies innate β-cell susceptibility in Asian Indians for glucose intolerance or dysglycemia. [ABSTRACT FROM AUTHOR]

Background: Obesity is an important risk factor for non-alcoholic fatty liver disease (NAFLD); however, NAFLD does occur in lean subjects. This study was aimed to evaluate the magnitude, clinical, pathological, and metabolic profiles of NAFLD in normal body mass index (BMI) subjects (defined as lean NAFLD) in comparison to overweight or obese NAFLD and lean healthy control. Materials and Methods: 336 subjects (205 consecutive NAFLD, and 131 healthy controls) were studied. Results: Among 205 NAFLD patients, 27 (13.2%) were lean, while 141 (68.8%) and 37 (18%) patients were obese and overweight, respectively. The lean NAFLD compared to obese NAFLD had significantly lesser degree of fasting hyperinsulinemia (P<0.001), homeostasis model assessment insulin resistance (HOMA-IR, P<0.001), and lower prevalence of diabetes mellitus (P=0.01) and metabolic syndrome (P<0.001). The profiles of serum lipids were similar between all 3 BMI categories, and 89% of lean NAFLD were dyslipidemic. Compared to obese subjects, patients with lean NAFLD had less hepatic necro-inflammation (P=0.05) and fibrosis (P<0.001). However, the proportion of steatohepatitis and advanced fibrosis were similar between all BMI categories. The profiles of overweight NAFLD were similar to those of lean NAFLD, except for higher HOMA-IR, uric acids and male gender in overweight group. Despite being lean, the mean BMI of lean NAFLD were still higher than unselected lean healthy controls (P=0.02). Conclusions: Lean NAFLD patients have less severe disease, minor, or no insulin resistance, but are frequently dyslipidemic and have BMI higher than lean healthy control. [ABSTRACT FROM AUTHOR]

There is little data on the type of vegetable oil used and the prevalence of metabolic syndrome (MS) in Asian Indians. Food frequency questionnaire was used to document the type of cooking oil in 1875 adults in Chennai city. MS was assessed by new harmonizing criteria. The prevalence of MS was higher among sunflower oil users (30.7%) than palmolein (23.2%) and traditional oil (17.1%, p < 0.001) users. The higher prevalence of MS in sunflower oil group persisted even when stratified according to body mass index, except in obese groups. The risk of MS was further compounded by quantity of refined cereals consumed. Higher LA% E and linoleic acid/alpha-linolenic acid ratio in sunflower oil probably contributes to increased risk of MS. [ABSTRACT FROM AUTHOR]

What is already known about this subject South Asian children at birth are thinner, but more adipose and more resistant to insulin than White Caucasian children., South Asian adults are more adipose and more insulin resistant, but their greater adiposity does not fully explain the difference in insulin resistance., South Asian children at 8 y are more insulin resistant than White Caucasian children., What this study adds The BMI of South Asian children at 6 y is distributed normally, while that of White Caucasian children is heavily skewed., South Asian children at 6 y are slimmer, and the boys, but not the girls, are more adipose., South Asian boys, but not girls are more insulin resistant. Both genders metabolically less healthy, but their adiposity explains only part of the difference., Background/Aims The concept of the 'thin-fat' Indian baby is well established, but there is little comparative data in older children, and none that examines the metabolic correlates. Accordingly, we investigated the impact of body composition on the metabolic profiles of Asian Indian and white UK children. Methods Body mass index ( BMI), waist circumference, sum of four skin-folds, % body fat (by dual-energy X-ray absorptiometry), glucose, insulin, insulin resistance (Homeostasis Model Assessment), trigylcerides, cholesterol [total, low-density lipoprotein, high-density lipoprotein { HDL}, total/ HDL ratio] and blood pressure (systolic, diastolic and mean arterial) were measured in 262 white Caucasian children from Plymouth, UK (aged 6.9 ± 0.2 years, 57% male), and 626 Indian children from rural villages around Pune, India (aged 6.2 ± 0.1 years, 53% male). Results Indian children had a significantly lower BMI (boys: −2.1 kg m−2, girls: −3.2 kg m−2, both P < 0.001), waist circumference ( P < 0.001) and skin-fold thickness ( P < 0.001) than white UK children, yet their % body fat was higher (boys +4.5%, P < 0.001, girls: +0.5%, P = 0.61). Independently of the differences in age and % body fat, the Indian children had higher fasting glucose (boys +0.52 mmol L−1, girls +0.39 mmol L−1, both P < 0.001), higher insulin (boys +1.69, girls +1.87 mU L−1, both P < 0.01) and were more insulin resistant (boys +0.25, girls +0.28 HOMA-IR units, both P < 0.001). Conclusions The 'thin-fat' phenotype observed in Indian babies is also apparent in pre-pubertal Indian children who have greater adiposity than white UK children despite significantly lower BMIs. Indian children are more insulin resistant than white UK children, even after adjustment for adiposity. [ABSTRACT FROM AUTHOR]

India leads the world with largest number of diabetic subjects earning the dubious distinction of being termed the "diabetes capital of the world". According to the Diabetes Atlas 2006 published by the International Diabetes Federation, the number of people with diabetes in India currently around 40.9 million is expected to rise to 69.9 million by 2025 unless urgent preventive steps are taken. The so called "Asian Indian Phenotype" refers to certain unique clinical and biochemical abnormalities in Indians which include increased insulin resistance, greater abdominal adiposity i.e., higher waist circumference despite lower body mass index, lower adiponectin and higher high sensitive C-reactive protein levels. This phenotype makes Asian Indians more prone to diabetes and premature coronary artery disease. At least a part of this is due to genetic factors. However, the primary driver of the epidemic of diabetes is the rapid epidemiological transition associated with changes in dietary patterns and decreased physical activity as evident from the higher prevalence of diabetes in the urban population. Even though the prevalence of microvascular complications of diabetes like retinopathy and nephropathy are comparatively lower in Indians, the prevalence of premature coronary artery disease is much higher in Indians compared to other ethnic groups. The most disturbing trend is the shift in age of onset of diabetes to a younger age in the recent years. This could have long lasting adverse effects on nation's health and economy. Early identification of at-risk individuals using simple screening tools like the Indian Diabetes Risk Score (IDRS) and appropriate lifestyle intervention would greatly help in preventing or postponing the onset of diabetes and thus reducing the burden on the community and the nation as a whole. [ABSTRACT FROM AUTHOR]

The article presents a study which examined the role of retinol-binding protein 4 in obese patients with metabolic syndrome. The researchers evaluated the role of adipocytokine in the development of obesity-related insulin resistance and proatherogenic lipid profile. The study indicated that retinol-binding protein 4 is a potential marker of metabolic syndrome with limited prediction of proatherogenic risk among Asian Indians

Objectives: Obesity is associated with high levels proinflammatory cytokines like tumour necrosis factor alpha (TNF-α), which may play an important role in the genesis of insulin resistance. We evaluated the relationship of -308G/A polymorphism of TNF-α gene with obesity and insulin resistance in Asian Indians in north India. Methods: This cross-sectional study included 151 apparently healthy individuals (79 males, 72 females) 18-50 yrs of age from New Delhi, India. Body composition by dual-energy x-ray absorptiometry (DEXA) and abdominal fat by magnetic resonance imaging (MRI) were measured. Biochemical measurements included OGTT, lipids, fasting insulin, hs-CRP and TNF-α levels. We analysed -308G/A polymorphism of TNF-α gene and studied its association with obesity and biochemical parameters. Results: At comparable BMI, abdominal obesity was more prevalent in females (50%) as compared to males (20%). The wild genotype (GG) was present in 78.8%, GA in 17.9%, and AA in 3.3% subjects. Measures of body composition, abdominal fat distribution, lipids, insulin, hs-CRP and TNF-α levels were not influenced by the presence of -308G/A polymorphism. Serum TNF-α levels correlated significantly with fasting insulin in both genders. Conclusion: TNF-α levels correlate with fasting insulin but not with indicators of body composition in Asian Indians. The -308G/A polymorphism of TNF-α gene is not associated with differences in the serum levels of TNF-α in Asian Indians. [ABSTRACT FROM AUTHOR]

Abstract: Background: Klotho, an anti-aging gene, is a functional candidate for metabolic syndrome. We conducted a cross-sectional study to evaluate the association of the genetic variants of Klotho with metabolic syndrome and surrogates of insulin resistance in Asian Indians. Methods: We recruited 428 clinically normal subjects for the study. Genotyping was done by polymerase chain reaction and restriction fragment length polymorphism. Results: Significant and borderline associations of the KL-VS (OR=15.88 [95%CI, 2.56–98.70], p =0.003) and C1818T (OR=0.28 [95%CI, 0.07–1.07], p =0.063) variants of the Klotho gene, respectively, were observed with metabolic syndrome. The association of the KL-VS variant with metabolic syndrome could be linked to its observed influence on high blood glucose (OR=6.92 [95% CI=1.75–27.44], p =0.006), high blood pressure (OR=5.21 [95%CI=1.00–38.43], p =0.046), insulin resistance (OR=3.59, [95%CI=1.01–12.79], p =0.048) and trend towards its association with hypertriglyceridemia (OR=3.69 [95%CI=0.92–14.77], p =0.065). Conclusions: The genetic variants of Klotho might predict risk for metabolic syndrome and insulin resistance in Asian Indians. However, larger studies in other ethnic populations are warranted to determine the role of these gene variants in the etiology of metabolic syndrome. [Copyright &y& Elsevier]

Abstract: Objectives: : The aim of the study was to assess the association between visceral and subcutaneous fat with glucose intolerance, adipocytokines, inflammatory markers and carotid IMT in Asian Indians. Design and methods: : Subjects with NGT (n =85), IGT (n =49) and T2DM (n =93) were randomly selected from CURES. Total abdominal, visceral and subcutaneous fat were measured using Helical CT scan. Adiponectin, hs-CRP, TNF-alpha, oxidized LDL, visfatin and leptin and IMT and insulin resistance were assessed. Results: : Total abdominal fat (p =0.041) and the visceral fat (p =0.039) but not subcutaneous fat progressively increased from NGT, IGT and T2DM subjects. With increasing quartiles of visceral fat, there was a significant increase in insulin resistance (p =0.040); significant decrease in adiponectin (p =0.043) and increase in TNF-alpha (p =0.028), hs-CRP (p =0.043), OX-LDL (p =0.034) and visfatin (p =0.040), and carotid IMT (p =0.047) was observed. Conclusion: : Visceral fat levels increased with increasing glucose intolerance and are associated with decreased levels of adiponectin and increased levels of hs-CRP, TNF-alpha, oxidized LDL, visfatin, HOMA-IR and IMT. [Copyright &y& Elsevier]

Background: Asian Indians as an ethnic group are at particularly high risk of insulin resistance and central obesity. It is now emerging convincingly that these disorders begin in childhood. No satisfactory reference curves and cut-off points for overall or central adiposity exist for Indian children. Aim: To present reference curves and age- and sex-specific cut-off points for the body mass index (BMI) and waist circumference (WC) of affluent Asian Indian children. Subjects and methods: Cole's LMS method was applied to longitudinal data on a cohort of 320 affluent, physically active children representing the five major geographical regions of India to derive smoothed BMI and WC centile curves. Age- and sex-specific cut-off points for overall and central adiposity were derived by identifying centiles analogous to adult Asian Indian cut-off values. Results: Adult BMI cut-offs for overweight/obesity corresponded to the 87th/96th and the 82nd/93rd centiles in boys and girls, respectively. Adult WC cut-offs for men and women corresponded to the 95th and 96th centiles in boys and girls, respectively. Age- and sex-specific BMI and WC cut-off points for Asian Indian children aged 3--18 years are described for the first time. Conclusions: These reference data could be used to identify affluent Asian Indian children with an elevated risk of developing obesity-related disorders and provide a baseline for future studies. [ABSTRACT FROM AUTHOR]

Background & objectives: The objective of the study was to determine whether visceral or subcutaneous component of abdominal fat was associated with insulin resistance and metabolic syndrome in non-diabetic Asian Indians. Method: This cross-sectional study had on 120 individuals with normal glucose tolerance (49 males and 71 females). A single slice CT scan at L4- L5 was done for measurement of visceral and subcutaneous abdominal fat. Metabolic syndrome was defined according to the South Asian Modified National Cholesterol Education Program Adult Treatment Panel III criteria (SAM-NCEP) criteria. Insulin Sensitivity Index (ISI-Matsuda) was used to assess insulin sensitivity/resistance. Results: Linear regression analysis revealed that visceral, but not subcutaneous fat was associated with serum triglycerides (R²=0.457, β= 0.34; P=0.006), HDL cholesterol (R²=0.430, β= -0.051; P=0.018) and ISI-Mutsuda (R²=0.437, β= -0.05; P=0.039) after adjusting for age, gender and BMI. Visceral fat showed significant association with metabolic syndrome (OR: 1.013, 95% CI: 1.001- 1.025; P=0.041) even after adjusting for age, gender, body mass index and glycated haemoglobin whereas subcutaneous fat did not show such an association. Interpretation & conclusions: These results indicate that in non-diabetic Asian Indians, visceral, but not subcutaneous component of abdominal fat is associated with insulin resistance, cardiovascular risk factors and metabolic syndrome. [ABSTRACT FROM AUTHOR]

Objective Biochemical measures for assessment of insulin resistance are not cost-effective in resource-constrained developing countries. Using classification and regression tree (CART) and multivariate logistic regression, we aimed to develop simple predictive decision models based on routine clinical and biochemical parameters to predict insulin resistance in apparently healthy Asian Indian adolescents. Design Community based cross-sectional study. Subjects and patients Data of apparently healthy 793 adolescents (aged 14–19 years) were used for analysis. WHO's multistage cluster sampling design was used for data collection. Methods and measurements Homeostasis Model of Assessment value > 75th centile was used as cut-off for defining the main outcome variable insulin resistance. CART was used to develop the decision tree models and multivariate logistic regression used to develop the clinical prediction score. Results Three classification trees and an equation for prediction score were developed and internally validated. The three decision trees were termed as CART I, CART II and CART III, respectively. CART I based on anthropometric parameters alone has sensitivity 88·2%, specificity 50·1% and area under receiver operating characteristic curve (aROC) 77·8%. CART II based on anthropometric and routine biochemical parameters has sensitivity 94·5%, specificity 38·3% and aROC 73·6%. CART III based on all anthropometric, biochemical and clinical parameters together has sensitivity 70·7%, specificity 79·2% and aROC 77·4%. Prediction score for insulin resistance = 1 × (waist circumference) + 1·1 × (percentage body fat) + 1·6 × (triceps skin-fold thickness) – 1·9 × (gender). A score cut-off of > 0 (using values marked for each) was a marker of insulin resistance in the study population (sensitivity 82·4%, specificity 56·7%, and aROC 73·4%). Conclusion These simple and cost-effective classification rules may be used to predict insulin resistance and implement population based preventive interventions in Asian Indian adolescents. [ABSTRACT FROM AUTHOR]

The relationship between insulin resistance and abdominal fat distribution was studied in Indian patients with PCOS. Subcutaneous fat, together with a family history of type 2 diabetes mellitus, was the best marker of insulin resistance. [Copyright &y& Elsevier]

Abstract: Objective: To study hepatic gluconeogenesis pathway in non-diabetic Asian Indian males having non-alcoholic fatty liver disease (NAFLD) using in vivo (31P) phosphorous magnetic resonance spectroscopy (MRS) and correlate these data with anthropometry and insulin resistance. Research design and methods: Forty non-diabetic patients with NAFLD and 20 healthy controls were divided into (i) obese with NAFLD (group I, n =20), (ii) non-obese with NAFLD (group II, n =20) and (iii) non-obese without NAFLD (group III, n =20). Anthropometric and biochemical profiles, short insulin tolerance test (SITT), liver ultrasound, and 31P MRS (to determine hepatic gluconeogenesis metabolite; phosphomonoesters (PMEs), inorganic phosphate (Pi) and their ratios with respect to ATP) were done. Results: Insulin resistance (Kitt value) was highest in group I (p <0.05; compared to other two groups), but was also higher in group II as compared to group III (p =ns). The values of PME/Pi, PME/γATP, PME/βATP, PME/tATP ratios were higher (p <0.05) in group I compared to other two groups. Interestingly, non-obese subjects with NAFLD also showed more derangements of hepatic gluconeogenesis metabolites than non-obese subjects without NAFLD. Positive correlation was observed between PME and other ratios in relation to body mass index, waist circumference, body fat percentage and fasting serum insulin levels in all the three groups. Conclusions: Derangements in hepatic gluconeogenesis as assessed non-invasively using 31P MRS, was observed in obese and non-obese, non-diabetic Asian Indians with NAFLD. Further research is warranted whether this investigation in NAFLD subjects could be developed as a non-invasive tool to assess those predisposed to develop hyperglycemia. [Copyright &y& Elsevier]

Abstract: We report the determination of intramyocellular lipids (IMCLs) of the soleus muscle of patients with type 2 diabetes mellitus (T2DM) using proton magnetic resonance spectroscopy. In addition, the various anthropometric and biochemical profiles of these patients were determined, including estimation of C-reactive protein (CRP), an inflammatory marker of coronary heart disease, and insulin resistance [Homeostasis Model Assessment (HOMA-IR)]. The estimated CRP level and the IMCL content in these patients were correlated with body mass index, percentage of body fat, other measures of abdominal obesity, serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. The IMCL content (P=.04), CRP (P=.008) and insulin resistance (P=.0007) were significantly higher in T2DM patients compared to healthy controls. However, IMCL content did not correlate with values of fasting insulin, HOMA-IR or CRP in either group. These findings have strong implications of increased cardiovascular risk in Asian Indians with T2DM. The absence of relationship between CRP and IMCL needs to be explored further in a study using a large sample size. [Copyright &y& Elsevier]

OBJECTIVE -- The objectives of this study were to determine age- and sex-specific concentrations of adiponectin in Asian Indian teenagers and adults and to assess whether its blood levels correlated with insulin resistance and other cardiometabolic parameters. RESEARCH DESIGN AND METHODS-- We studied 196 teenagers (94 boys, 102 girls) 12-18 years of age, selected from a cohort of 2,640 individuals from a cross-sectional school-based survey in Chennai, India. For comparison, adiponectin and plasma insulin were measured in 84 healthy adults. Correlation of adiponectin with plasma levels of insulin, proinsulin, insulin resistance, anthropometry, and family history of diabetes were studied. RESULTS-- Adiponectin showed a sex dimorphism, with girls having higher values (in micro;g/ml) (10.3 ± 5.0) than boys (8.4 ± 3.5) (P < 0.0001), and it showed a positive correlation with HDL cholesterol in boys only and not with other lipid parameters, insulin resistance, proinsulin, anthropometry, and family history of diabetes. In the adults, adiponectin correlated with fasting glucose and inversely with triglycerides. CONCLUSIONS-- In Asian Indian adults and teenagers, adiponectin did not correlate directly with measures of insulin sensitivity, overweight, and other cardiometabolic variables. This was at variance with several reports in other populations showing an inverse association of adiponectin with insulin resistance, proinsulin, and BMI, suggesting ethnic differences in the relationship of adiponectin with insulin sensitivity. The role of adiponectin in relation to action of insulin needs more detailed studies in Asian Indians. [ABSTRACT FROM AUTHOR]

OBJECTIVE--Type 2 diabetes has become a global epidemic, and Asian Indians have a higher susceptibility to diabetes than Europeans. We investigated whether Indians had any metabolic differences compared with Northern European Americans that may render them more susceptible to diabetes. RESEARCH DESIGN AND METHODS--We studied 13 diabetic Indians, 13 nondiabetic Indians, and 13 nondiabetic Northern European Americans who were matched for age, BMI, and sex. The primary comparisons were insulin sensitivity by hyper-insulinemic-euglycemic clamp and skeletal muscle mitochondrial capacity for Oxidative phosphorylation (OXPHOS) by measuring mitochondrial DNA copy number (mtDNA), OXPHOS gene transcripts, citrate synthase activity, and maximal mitochondrial ATP production rate (MAPR). Other factors that may cause insulin resistance were also measured. RESULTS--The glucose infusion rates required to maintain identical glucose levels during the similar insulin infusion rates were substantially lower in diabetic Indians than in the nondiabetic participants (P < 0.001), and they were lower in nondiabetic Indians than in nondiabetic Northern European Americans (P < 0.002). mtDNA (P < 0.02), OXPHOS gene transcripts (P < 0.01), citrate synthase, and MAPR (P < 0.03) were higher in Indians irrespective of their diabetic status. Intramuscular triglyceride, C-reactive protein, interleukin-6, and tumor necrosis factor-α concentrations were higher, whereas adiponectin concentrations were lower in diabetic Indians. CONCLUSIONS--Despite being more insulin resistant, diabetic Indians had similar muscle OXPHOS capacity as nondiabetic Indians, demonstrating that diabetes per se does not cause mitochondrial dysfunction. Indians irrespective of their diabetic status had higher OXPHOS capacity than Northern European Americans, although Indians were substantially more insulin resistant, indicating a dissociation between mitochondrial dysfunction and insulin resistance. Diabetes 57:1166-1175, 2008 [ABSTRACT FROM AUTHOR]

Background: Asian Indians have a high prevalence of insulin resistance that may underlie their higher tendency to develop type 2 diabetes mellitus and early-onset atherosclerosis. Objective: To investigate the relationship between dietary nutrients and insulin resistance in Asian Indian adolescents and young adults. Design: Dietary nutrient intake values (24-hour dietary recall and monthly consumption data) and fasting serum insulin levels were studied in 352 (311 males and 41 females) healthy adolescents and young adults (mean age 18.0 ± 2.3 years; range 14–25 years). Bivariate and multivariate logistic regression analyses were performed with hyperinsulinemia as the outcome variable and various dietary nutrients and anthropometric variables as covariates. Results: Mean fasting serum insulin levels were 107.4 ± 35.0 pmol/l (36.5–230.4 pmol/l). The intake of polyunsaturated fatty acids (PUFAs) was higher, saturated fat and the ω–6 to ω–3 PUFA ratio were in the upper limit, and ω–3 PUFAs (% caloric intake, En) were lower than the recommended dietary allowance for Asian Indians. The PUFAs (% En), BMI, percent body fat and waist circumference were significantly higher in the hyperinsulinemic group compared with the normoinsulinemic group (p = 0.021, 0.0021, 0.0006, and 0.0041, respectively). Multiple regression analysis showed that the lowest tertile of ω–6 (<3% En) PUFA intake [adjusted OR (95% CI) = 0.3 (0.1–0.7)] and BMI [adjusted OR (95% CI) = 2.9 (1.4–6.0)] were the significant independent predictors of fasting hyperinsulinemia. Conclusion: For prevention and amelioration of insulin resistance in Asian Indian adolescents and young adults, it is prudent to have normal BMI and low intake of ω–6 PUFAs. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Recent data indicate a rise in obesity both in children and adolescents in developing countries. The overall prevalence of overweight/obesity in urban children in New Delhi has shown an increase from 16% in 2002 to about 24% in 2006-2007. Our recent data show that the prevalence among adolescent children was 29% in private schools and 11.3% in government funded schools. While India already has highest number of patients with type 2 diabetes mellitus (T2DM) globally, rapid rise of obesity in children is the prime reason for increasing insulin resistance, the metabolic syndrome, dyslipidemia, polycystic ovarian syndrome and raised levels of C-reactive protein. Excess body fat, thick truncal subcutaneous fat, and abdominal adiposity are important predisposing factors for development of insulin resistance in Asian Indian children. As compared to other ethnic groups, children with ancestral origin in South Asia manifest adiposity, insulin resistance and metabolic perturbations earlier in life and these derangements are of higher magnitude than white Caucasian children. Since the metabolic syndrome and obesity track into adulthood, these clinical entities need to be recognized early for effective prevention of T2DM and coronary heart disease. Therapeutic lifestyle changes, maintenance of high levels of physical activity and normal weight are most important prevention strategies. Both high-risk surveillance and cost-effective population intervention programs are urgently needed. In this context, we have launched one of the largest program ("MARG", The Path) to curb childhood obesity in India. [ABSTRACT FROM AUTHOR]

Introduction. The relationship between insulin resistance and atherosclerosis (ATH) in non-diabetic hypertensive patients from the Asian Indian population remains poorly understood. To resolve this issue, the present study was designed to analyze whether insulin sensitivity in a non-diabetic individual is related to the development of ATH.(by using IMT as an index) and whether this relationship is dependent on the presence of other cardiovascular disease (CVD) risk factors such as dyslipidemia and hypertension. Methodology. This study included 68 healthy controls with no diabetes and hypertension and 41 hypertensive patients who underwent four-point oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT). A biochemical profile, β mode ultrasonography for intima media thickness of carotid artery, and ECG determination was carried out. Results. Hypertensive patients in our study exhibited significantly increased abdominal obesity. Blood pressure, fasting and 2 hr plasma glucose (4.62 ± 0.08 and 5.55 ± 0.17 mmol/l), and triglyceride (1.47 ± 0.067 mmol/l) levels were compared to those of control subjects (p < 0.05). The fasting insulin levels and HOMA-IR were also significantly increased and Composite Insulin Sensitivity Index (CISI) reduced compared to controls with p < 0.01. Intima media thickness of the left (0.08 ± 0.01) and right (0.069 ± 0.008) CA were both significantly increased in hypertensives (p < 0.01). Correlation analysis showed that IMT of the left carotid artery was significantly associated with triglyceride levels (r = 0.813, p < 0.05) but not with insulin measures such as HOMA-IR and CISI. Conclusion. Hyperinsulinemia was observed in our non-diabetic hypertensive patients, but no association was found between IMT and insulin resistance. That IMT of hypertensives was associated with triglyceride levels suggests that high levels of insulin may be related to the development of ATH indirectly through its effects on lipid metabolism in our population. [ABSTRACT FROM AUTHOR]

The relationship between C-reactive protein (CRP), a marker of subclinical inflammation, and intramyocellular lipid (IMCL) content, a novel correlate of insulin resistance, has not previously been investigated. We estimated IMCL content in soleus muscle in 30 healthy Asian Indian males using proton magnetic resonance spectroscopy (1H MRS), and correlated it with body mass index (BMI), measures of abdominal obesity, percentage of body fat (%BF), serum lipoproteins, fasting and post-oral glucose load serum insulin levels and other surrogate markers of insulin resistance. Soleus muscle IMCL content was significantly correlated with age (ρ = 0·64, P < 0·001), BMI (ρ = 0·41, P < 0·05), %BF (ρ = 0·53, P ≤ 0·01), waist circumference (ρ = 0·45, P < 0·05) and waist-to-hip circumference ratio (ρ = 0·58, P < 0·01) but did not correlate significantly with insulin resistance measured by the homeostasis model assessment (HOMA-IR) or CRP levels. CRP levels did not correlate with the HOMA-IR value. Soleus muscle IMCL content correlated significantly with measures of generalized and abdominal obesity but not with insulin sensitivity or CRP levels in healthy Asian Indian males. Studies are needed in other ethnic groups to corroborate these data. [ABSTRACT FROM AUTHOR]

Abstract: Cardiovascular disease (CVD) rates have been reported in several parts of the world and have been found to be unusually high in people originating from the Indian subcontinent. High coronary disease rates appear to be common to South Asian groups of different geographic origin, religion, and language. This presents a challenge for understanding the development of coronary heart disease. The high rates in Asian Indians are only partly explained with respect to elevated serum cholesterol, smoking, or hypertension. Low plasma high-density lipoprotein cholesterol, high plasma triacylglycerols, and high prevalence of type 2 diabetes mellitus have been consistently found in Asian Indians suggesting a state of insulin resistance. This review examines published data on the risk factors and prevalence of CVD in Indiana populations. Further studies are needed to determine if metabolic disturbances related to insulin can account for the high rates of CVD in Asian Indians and to identify possibilities for prevention. [Copyright &y& Elsevier]

OBJECTIVE: The objectives were to study the relationships of insulin resistance with generalized and abdominal obesity, and body fat patterning in urban postpubertal Asian Indian children. DESIGN: Cross-sectional, population-based epidemiological study. SUBJECTS: In all, 250 (155 males and 95 females) healthy urban postpubertal children. MEASUREMENTS: Anthropometric profile, percentage of body fat (%BF), fasting serum insulin, and lipoprotein profile. RESULTS: Fasting insulin correlated significantly with body mass index (BMI), %BF, waist circumference (WC), central and peripheral skinfold thicknesses and sum of four skinfold thicknesses (Σ4SF) in both sexes, and with systolic blood pressure and waist-to hip circumference ratio (W-HR) in males only. Consistent increase in fasting insulin was noted with increasing values of central skinfold thickness at each tertile of peripheral skinfold thickness, WC, and %BF. Central skinfold thickness correlated with fasting insulin even after adjusting for WC, W-HR, and %BF. The odds ratios (OR) (95% CI) of hyperinsulinemia (fasting insulin concentrations in the highest quartile) were 4.7 (2.4–9.4) in overweight subjects, 8(4.1–15.5) with high %BF, 6.4 (3.2–12.9) with high WC, 3.7 (1.9–7.3) with high W-HR, 6.8 (3.3–1 3.9) with high triceps skinfold thickness, 8 (4.1–1 5.7) with high subscapular skinfold thickness, and 10.1(5–20.5) with high Σ4SF. In step-wise multiple logistic regression analysis, %BF [OR (95% CI): 3.2 (1.4–7.8)] and ?4SF [OR (95% CI): 4.5 (1.8–11.3)] were independent predictors of hyperinsulinemia, similar to insulin resistance assessed by HOMA (homeostatic model of assessment) in the study. CONCLUSION: A high prevalence of insulin resistance in postpubertal urban Asian Indian children was associated with excess body fat, abdominal adiposity, and excess truncal subcutaneous fat. Primary prevention strategies for coronary heart disease and diabetes mellitus in Asian Indians should focus on the abnormal body composition profile in childhood. [ABSTRACT FROM AUTHOR]

Abstract Aims Intramyocellular lipids (IMCL) appears to be important in the pathogenesis of insulin resistance. Correlation of IMCL content of soleus muscle with insulin sensitivity has been reported in the Caucasian population. In the present study, IMCL content was estimated in the soleus muscle of both non-obese healthy males and Type 2 diabetic males, and correlated with the anthropometric parameters, blood glucose, plasma lipids, and insulin resistance in Asian Indians from North India. Methods Twenty males (Type 2 diabetes mellitus 10; healthy controls 10) with body mass index (BMI) ≤ 25 kg/m2 were recruited in the study. In both healthy and diabetic groups, five subjects had percentage body fat (%BF) ≤ 25, and other five subjects had percentage BF > 25. The following were assessed in all subjects: body composition, fasting blood glucose, lipid profile, insulin levels, insulin resistance by homeostasis model assessment, and proton magnetic resonance spectroscopy (1 H MRS) study of the soleus muscle. Results IMCL content was approximately two times higher in Type 2 diabetic males compared with healthy males (P < 0.05). Amongst healthy males, IMCL content was significantly higher (P < 0.05) in subjects with percentage BF > 25 compared with subjects with percentage BF ≤ 25. Similarly, IMCL content was high in subjects with waist–hip ratio (WHR) > 0.95 compared with subjects with WHR ≤ 0.95. In healthy males but not in diabetic males, positive significant correlation of IMCL content of soleus muscle was observed with waist circumference (r = 0.73, P < 0.05) and WHR (r = 0.71, P < 0.05). However, IMCL content did not correlate significantly to insulin resistance in both the groups. Conclusions 1 H MRS study of soleus muscle in a small sample of non-obese Asian Indians showed higher IMCL content in Type 2 diabetics compared with healthy subjects. Non-obese healthy male subjects having high percentage BF and WHR also had high IMCL content, and it significantly correlated to waist circumference and WHR. However, lack of relationship of IMCL content with insulin resistance in Asian Indians needs further study. Diabet. Med. 20, 361–367 (2003). [ABSTRACT FROM AUTHOR]

Background: The role of glucokinase (GCK) in the pathogenesis of maturity-onset diabetes of the young is well established. However, its role in the common form of type 2 diabetes is far from convincing. We investigated the role of the G-to-A polymorphism in the hepatic GCK promoter on insulin sensitivity and beta cell function in 63 normotensive Asian Indians with normal glucose tolerance. As proposed by Matsuda and DeFronzo, hepatic insulin sensitivity (ISIH) and total body insulin sensitivity (ISIM) were estimated from the oral glucose tolerance test. Beta cell function was estimated using %B from the Homeostasis Model Assessment and insulingenic index (dI/dG). Result: We identified 38 GG, 24 GA, and one AA subjects. The AA subject was pooled with the GA subjects during the analysis. No difference was noted in the demographic features between the two genotypic groups (GG vs. GA/AA). Compared to the GG group, the GA/AA group had a lower ISIH (p=0.002), a lower ISIM (p=0.009), a higher %B (p=0.014), and a higher dI/dG (p=0.030). Multivariate analysis revealed that this polymorphism is an independent determinant for ISIH (p=0.019) and along with age, waist-hip ratio, gender, and diastolic blood pressure accounted for 51.5% of t he variation of ISIH. However, this polymorphism was a weak, but independent determinant for ISIM (p=0.089) and %B (p=0.083). Furthermore, it had no independent effect on dI/dG (p=0.135). Conclusions: These data suggest that the G-to-A polymorphism in the hepatic GCK promoter is associated with hepatic insulin resistance in Asian Indians. [ABSTRACT FROM AUTHOR]

Introduction: Studies have shown that systemic levels of branched-chain amino acids (BCAAs) and aromatic amino acids (AAAs) are elevated in cardiometabolic diseases (CMDs) in populations resident in high income countries. However, little is known about the association of BCAAs and AAAs with metabolic syndrome and its components in Asian Indian (AI) and Black African (BA) populations. Objective: The aim of this study was to describe the association of BCAAs and AAAs with the metabolic syndrome, its individual components and insulin resistance in AI and BA populations. Methods: Serum samples collected from AI (n = 349) and BA (n = 369) subjects were used to measure levels of BCAAs and AAAs by ultra-pressure liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Anthropometric, demographic and cardiometabolic variables were measured in all subjects. Results: The sum of BCAAs and AAAs was higher in AIs compared to BAs. The BCAAs and AAAs were positively associated with insulin resistance, metabolic syndrome and its individual components. This was particularly the case for AI subjects, in unadjusted regression models. However, these associations were non-significant after adjusting for co-variates, particularly visceral adipose tissue (VAT). Triglyceride levels were significantly associated with valine and leucine levels in BAs even after adjustment for co-variates. Lastly, we found that fasting circulatory BCAA and AAA levels are strongly correlated with VAT in both populations. Conclusion: This study identified specific associations of serum valine and leucine levels with triglycerides in BAs. The association of amino acids with CMDs was observed in AIs, but was found to be the result of confounding by VAT. Further studies are required to determine whether BCAAs and AAAs are aetiological factors in CMDs and how VAT modulates their serum levels. [ABSTRACT FROM AUTHOR]

The author comments on the study "Visceral and Subcutaneous Abdominal Fat in Relation to Insulin Resistance & Metabolic Syndrome in Non-Diabetic South Indians," by S. Sandeep et al. published in the same issue. It has found that visceral fat and not subcutaneous fat increases risk of metabolic syndrome. She believes that mechanistic studies are needed to verify the correlation between visceral fat and metabolic syndrome. She adds that the study should have examined the role of hyperplasia versus hypertrophy in subcutaneous abdominal fat.

Asian Indians are highly susceptible to Type 2 Diabetes (T2D) and constitute the largest diabetic population in the world. The underlying etiology for this increased susceptibility for T2D among Asian Indians remains to be defined. To determine whether Asian Indians are more insulin resistant and whether their insulin resistance is associated with any differences in muscle gene transcript levels, we studied 13 non-diabetic (fasting glucose < 100 mg/dl) Asian Indians (Age=47.2±2.4 y, BMI=23.8±0.5 kg/m²) and 13 gender-matched Americans of North European origin (European Americans; Age=46.6±2.2 y, BMI=24.5±0.8 kg/m2). Insulin sensitivity was measured by hyperinsulinemic (1.5 mU/kg FFM/min) euglycemic clamp. To maintain identical plasma glucose levels, Asian Indians required a substantially lower glucose infusion rate than European American controls (42.3 ± 4.0 vs. 68.3 ± 4.2 µmol/Kg FFM/min,p<0.001). Percutaneous needle biopsy samples were collected for gene array analysis. Total RNA was extracted from snap frozen muscle biopsy samples, amplified, labeled with fluorescent probe, fragmented and hybridized to the U133 Pins 2.0 Affymetrix genechip and GCRMA software was used to analyze microarray data. Out of about 47,000 transcripts surveyed, 58 genes transcript levels were altered (52 increased and 6 decreased) in Asian Indians compared to European Americans. Examples are as follows: Lipid metabolism: Fatty acid binding protein 7 (↑3.7); Glucose metabolism: GAPDH (↑1.03), Lactate dehydrogenase A (↑1.3); Chaperone: heat shock proteins 70 (↓0.65); and Energy metabolism: NADH1 (↑1.07), ATP synthase (↑1.1), Cytochrome C oxidase Va (↑1.20), Cytochrome C oxidase VLLc (↑1.1). In conclusion, nondiabetic Asian Indians are significantly more insulin resistant and have altered skeletal muscle gene transcript levels involving multiple metabolic pathways including mitochondrial bioenergetics. The results indicate potential mechanisms for higher susceptibility of Asian Indians to become diabetic. [ABSTRACT FROM AUTHOR]

Provides information on several studies about insulin action to be presented at the 65th Scientific Sessions of the American Diabetes Association at the San Diego Convention Center in California from June 10 to 14, 2005. Correlation of low birth weight with adult insulin resistance in Asian Indian children; Effect of high-fat feed to induced insulin resistance on male and female rats; Background on the mechanism of pancreatic islet cell insulin resistance in high-fat-diet obese rats.

Abstract: The prevalence of Gestational Diabetes Mellitus (GDM) diagnosed by WHO criterion (2-hPG≥7.8mmol/L) was 13.4%. By International Association of Diabetes and Pregnancy Study Groups criteria of FPG≥5.1mmol/L, prevalence of GDM was 3.2%. FPG may not be suitable for diagnosis of GDM in Asian Indians due to high insulin resistance in addition to pregnancy hormonal effect. [Copyright &y& Elsevier]

Abstract: Background: Cost-effective method to assess insulin resistance is needed for Asian Indians. Methods: We compared HOMA with SITT methods in 40 subjects. Results: Values obtained from both methods did not show any correlation. Conclusions: Both methods should be evaluated against hyperinsulinemic clamp to determine suitability in Asian Indians. [Copyright &y& Elsevier]

Asian Indians (AI) are insulin resistant and have a higher risk of diabetes compared to Caucasians (C). However, potential abnormalities in insulin secretion and their relationship to the severity of insulin resistance in AI have not been carefully studied. To address this question we examined l) first (0-10 min) and second (l0-120 min) phase insulin secretion during a 2-hr hyperglycemic clamp at +90 mg/dl, 2) insulin secretion in response to a non-glucose secretagogue (arginine, 5 gm IV) at euglycemia and at the end of the hyperglycemic clamp, and 3) insulin sensitivity (M) during a 1 mU/kg⋅min hyperinsulinemic euglycemic clamp. Four healthy AI and 6 C of similar age (29±2 vs 38±6 yrs) and BMI (25.3±2.3 vs 24.7±1.3 kg/msup2;) were studied. AI and C had similar FPG (94±2 vs 90±2. mg/dl), but AI had higher fasting insulin levels (9.1±2.2 vs 3.4±0.6 µU/ml, p<0.05) and were very insulin resistant during the euglycemic clamp (M = 4.0±0.5 vs 9.7±0.6 mg/kg/min, p<0.001). During the hyperglycemic clamp, first phase (321±106 vs 102±22 µU/ml⋅0 min, p<0.05) and second phase (4920±959 vs 1340±174 pU/ml. 110 min, p<0.01) insulin secretion were significantly increased in AI vs C. The insulin responses to arginine at euglycemia (314±43 vs 145±9 µU/ml. l0 min, p<0.01) and hyperglycemia (2399±415 vs 1203±235 #U/ml. 10 min, p<0.05) also were significantly higher in AI. All measures of insulin secretion were inversely correlated with M (r = -0.69 to -0.82, p<0.05 to 0.005). The glucose disposition index (M x first phase insulin secretion) was increased moderately (by 29%), but not significantly, in AI vs C. Conclusion: Non-diabetic AI are characterized by l) marked insulin resistance, 2) enhanced first- and second-phase insulin responses to hyperglycemia, 3) increased insulin response to arginine at euglycemia and hyperglycemia, and 4) a moderate increase in the glucose disposition index. These data suggest that beta cell function remains intact in non-diabetic AI despite the presence of significant insulin resistance. [ABSTRACT FROM AUTHOR]