Acanthosis nigricans independently predicts hepatic fibrosis in people with type 2 diabetes in North India.

BACKGROUND: Acanthosis nigricans (AN) is a skin condition characterized by hyperpigmentation and thickening, often found in individuals with insulin resistance. Despite this well-established association, the potential link between AN and hepatic fibrosis in people with type 2 diabetes (T2D) has yet to be thoroughly explored. METHODOLOGY: We recruited a total of 300 people with T2D, half of whom had AN (n, 150), and the other half without AN (n, 150). We evaluated body composition, biochemistry, and hepatic fat analysis (using the controlled attenuation parameter, CAP), as well as assessments of hepatic stiffness (using the kilopascal, kPa) using Fibroscan. We used multivariable regression analysis to find independent predictors of AN and their relationship to hepatic fibrosis. Furthermore, we developed a prediction equation and AUC for hepatic fibrosis. RESULTS: Upon comparison between AN vs. NAN group, following were significatly higher; weight, BMI, hepatic transaminases, liver span, CAP, and kPa. After adjusting for age, weight, body mass index, diabetes duration, and specific anti-hyperglycaemic drugs (gliclazide, DPP-4 inhibitors, pioglitazone, and Glucagon-like peptide-1 receptor agonists), adjusted OR for AN were, liver span, 1.78 (95% CI: 0.91-3.49, p = 0.09), CAP, 7.55 (95% CI: 0.93-61.1, p = 0.05), and kPa, 2.47 (95% CI: 1.50-4.06, p = 0.001). A ROC analysis of predictive score for hepatic fibrosis showed optimal sensitivity and specificity at a score cut-off of 25.2 (sensitivity 62%, specificity 63%), with an AUC of 0.6452 (95% CI: 0.61235-0.76420). CONCLUSION: Acanthosis nigricans has the potential to be used as an easy-to-identify clinical marker for risk of hepatic fat and fibrosis in Asian Indians with T2D, allowing for early detection and management strategies.

Shortening of leucocyte telomere length is independently correlated with high body mass index and subcutaneous obesity (predominantly truncal), in Asian Indian women with abnormal fasting glycemia.

INTRODUCTION: Leucocyte telomere length (LTL) is linked to accelerate aging and premature mortality. In this research, we aimed to explore the relations between biochemical and anthropometry markers and LTL in Asian Indian women with abnormal fasting glycemia (impaired fasting glucose). RESEARCH DESIGN AND METHODS: In this study, 797 pre-diabetic women (obese, 492; non-obese, 305) were recruited. Demographic and clinical profiles, anthropometry, and fasting blood glucose were evaluated. LTL was quantified by a quantitative PCR. LTL was expressed as the relative telomere length or telomere repeat:single copy gene (T:S) ratio. The subjects were separated into quartiles according to the LTL. RESULTS: The average LTL was significantly decreased with increasing age. The average LTL was significantly shorter in obese women with abnormal fasting glycemia (p<0.05). R-squared (R2) statistic for multivariable linear model after adjusted for age, family income, education and hypertension showed that LTL was inversely correlated with body mass index (BMI), waist and hip circumference, waist-hip and waist-to-height ratio, truncal skinfolds (subscapular, and subscapular/triceps ratio, central and total skinfolds), fat mass (kg) and % body fat. The relationship between obesity measures and LTL (using the LTL quartile 1 as reference) identified central skinfolds (R2=0.92, p<0.0001), Σ4SF (R2=0.90, p<0.0001), BMI (R2=0.93, p<0.0001) and % body fat (R2=0.91, p<0.0001) as independent predictors of LTL. CONCLUSIONS: Besides age, obesity and subcutaneous adiposity (predominantly truncal) are major contributors to telomere shortening in Asian Indian women with abnormal fasting glycemia (impaired fasting glucose).

Dapagliflozin Improves Body Fat Patterning, and Hepatic and Pancreatic Fat in Patients With Type 2 Diabetes in North India.

CONTEXT: Excess hepatic and pancreatic fat may contribute to hyperglycemia. OBJECTIVE: The objective of this study was to examine the effect of dapagliflozin (an SGLT2 inhibitor) on anthropometric profile, liver, and pancreatic fat in patients with type 2 diabetes mellitus (T2DM). METHODS: This is an observational interventional paired study design without a control group. Patients (n = 30) were given dapagliflozin 10 mg/day (on top of stable dose of metformin and/or sulfonylureas) for 120 days. Changes in anthropometry (circumferences and skinfold thickness), surrogate markers of insulin resistance, body composition, liver, and pancreatic fat (as measured by magnetic resonance imaging (MRI)-derived proton density fat fraction [FF]) were evaluated. RESULTS: After 120 days of treatment with dapagliflozin, a statistically significant reduction in weight, body mass index (BMI), body fat, circumferences, and all skinfold thickness was seen. A statistically significant reduction in blood glucose, glycated hemoglobin A1c, hepatic transaminases, fasting insulin, homeostatic model assessment of insulin resistance (HOMA-IR), and postprandial C-peptide was noted, while HOMA-ß, postprandial insulin sensitivity, and fasting adiponectin were statistically significantly increased. There was no change in lean body mass. Compared to baseline there was a statistically significant decrease in mean liver FF (from 15.2% to 10.1%, P < .0001) and mean pancreatic FF (from 7.5% to 5.99%, P < .0083). Reduction in liver fat was statistically significant after adjustment for change in body weight. CONCLUSION: Dapagliflozin, after 120 days of use, reduced pancreatic and liver fat and increased insulin sensitivity in Asian Indian patients with T2DM.

The Effect of the Severity of Obstructive Sleep Apnea on Leukocyte Telomere Length, 25 Hydroxy Vitamin D, and Parathyroid Hormonal Concentrations in Asian Indians.

Background: Obstructive sleep apnea (OSA) is a common disorder in which breathing repeatedly stops during sleep. Leukocyte telomere length (LTL) and OSA are linked with an increased risk of oxidative stress and inflammation. The possible link between LTL and OSA in Asian Indians has not been evaluated. Thus, the present study aims to compare the link between LTL and OSA in Asian Indians. Methods: In this study, 300 subjects (120 obese with OSA, 110 obese without OSA, and 70 non-obese without OSA) were included after overnight polysomnography and a fasting blood sample. Clinical, anthropometry, metabolic markers, insulin, 25-hydroxyvitamin D [25(OH) D], and parathyroid hormones (PTH) levels were investigated. LTL was investigated by a QPCR. Univariate and stepwise multivariate linear regression analyses adjusting for age, gender, BMI, and % body fat were conducted while treating LTL as a dependent variable in relation to AHI and other covariates. Results: Obese subjects with OSA had significantly decreased 25(OH)D and increased PTH levels. The mean telomere length (T/S) ratio was significantly shorter in patients with OSA. The adjusted correlation analysis showed that shortening of telomere length correlated with increasing age, apnea-hypopnea index (AHI), oxygen desaturation index, and RDI. Univariate analysis showed that LTL revealed a trend toward a negative correlation with a mean age (ß + SE, -0.015 + 0.0006; p = 0.01) and positive correlation with AHI [ß +slandered error (SE), 0.042 + 0.017; p = 0.008]. In the multiple regression analysis, LTL was positively associated with AHI (ß + SE, 0.281 + 0.04; p = 0.001) after adjusting for age, sex, BMI, and % body fat. Even when adjusted for confounding factors, 25(OH)D, and PTH levels, LTL still was related to AHI (ß + SE, 0.446 + 0.02; p = 0.05). Conclusion: Our study indicates the presence of an association between LTL and OSA and a significant impact of OSA severity and telomeres shortening in Asian Indians.

High prevalence of post COVID-19 fatigue in patients with type 2 diabetes: A case-control study.

BACKGROUND: Post COVID-19 syndrome (PCS) has emerged as a major roadblock in the recovery of patients infected with SARS-CoV-2. Amongst many symptoms like myalgia, headache, cough, breathlessness; fatigue is is most prevalent and makes the patient severely debilitated. Research on PCS, in particular fatigue, in patients with diabetes has not been done. METHODOLOGY: In this prospective study, we included patients with type 2 diabetes (T2D) who had COVID-19 (mild to moderate severity), and matched T2D patients who did not suffer from COVID-19. Demography, anthropometry, glycemic measures, treatment, and details of COVID-19 were recorded. Symptoms were scored using Chalder Fatigue Scale (reported as fatigue score, FS) and handgrip strength (in kg) was recorded by Jamar Hydraulic Hand Dynamometer. RESULTS: A total of 108 patients were included (cases, 52, controls, 56). Both groups were matched for age, duration of diabetes, BMI, TSH, serum albumin and vitamin D levels. T2D patients who had COVID-19 showed significantly more fatigue when compared with patients who did not have COVID-19 but both groups had comparable handgrip strength. Furthermore, patients with T2D with previous COVID-19 infection and who had FS > 4 have had significant higher inflammation markers during acute illness, and post COVID-19, had increased post prandial blood glucose levels, lost more weight, had reduced physical activity and showed significantly lower handgrip strength as compared to those with FS < 4. CONCLUSION: Patients with T2D who had COVID-19 infection as compared to those without had significantly more fatigue after the acute illness, and those with higher FS had reduced handgrip strength indicating sarcopenia, even after careful matching for common contributory factors to fatigue at baseline. Rehabilitation of those with FS>4 after acute infection would require careful attention to nutrition, glycemic control and graduated physical activity protocol.

Association of IRS1 (Gly972Arg) and IRS2 (Gly1057Asp) genes polymorphisms with OSA and NAFLD in Asian Indians.

AIM AND OBJECTIVE: The aim of the study was to investigate the relationships between insulin receptor substrate (IRS) 1 (Gly972Arg) and IRS2 (Gly1057Asp) genes with obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) in Asian Indians. METHOD: A total of 410 overweight/obese subjects (130 with OSA with NAFLD, 100 with OSA without NAFLD, 95 without OSA and with NAFLD and 85 without OSA and without NAFLD) were recruited. Degree of NAFLD was based on liver ultrasound and of OSA on overnight polysomnography. Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by gene sequencing. RESULT: Mean values of blood pressure, body fat markers, blood glucose, lipids, liver function, and markers of insulin resistance were significantly increased in OSA and NAFLD subjects (p<0.05). In addition, according to age (years) categories, blood pressure, blood glucose, lipids, obesity markers, and markers of insulin resistance were significantly higher in 45-60 years group as compared to 20-45 years group (p<0.05). In IRS1 gene, the genotype frequency (%) of Arg/Arg was significantly higher in NAFLD and OSA subjects. In addition, Gly/Arg genotype of IRS1 gene was associated with significantly higher body mass index, fat mass, %body fat, triglycerides, cholesterol, alkaline phosphate, aspartate transaminase, fasting insulin and HOMA-IR levels in OSA and NAFLD subjects. No significant difference in genotype frequencies of IRS2 was observed between four groups. Further we found that subjects carrying IRS1 Gly/Arg (OR 4.49, 95% C.I. 1.06-12.52, p = 0.002) genotype possess a much higher risk of OSA and NAFLD compared to IRS2 Gly/Asp (OR 1.01, 95% C.I. 0.8-2.56, p = 0.05). In sub group analysis of IRS1 Gly/Arg have significant differences between the mild, moderate and severe group (P<0.05). In addition, patients with the 'Gly' allele were inclined to develop more severe OSA. CONCLUSION: We concluded that Asian Indian subject carrying the allele Gly972Arg polymorphism of IRS1 is predisposed to develop OSA and NAFLD.

Metabolic alterations and systemic inflammation in overweight/obese children with obstructive sleep apnea.

AIM AND OBJECTIVE: Systemic inflammation has been documented in obstructive sleep apnea (OSA). However studies on childhood OSA and systemic inflammation are limited. This study aimed to determine the relation between OSA in overweight/obese children and various inflammatory markers. MATERIAL AND METHODS: In this cross sectional study, we enrolled 247 overweight/ obese children from pediatric outpatient services. We evaluated demographic and clinical details, anthropometric parameters, body composition and estimation of inflammatory cytokines such as interleukin (IL) 6, IL-8, IL-10, IL-17, IL-18, IL-23, macrophage migration inhibitory factor (MIF), high sensitive C-reactive protein (Hs-CRP), tumor necrosis factor-alpha (TNF-α), plasminogen activator inhibitor-1 (PAI-1) and leptin levels. Overnight polysomnography was performed. FINDINGS: A total of 247 children (190 with OSA and 57 without OSA) were enrolled. OSA was documented on polysomnography in 40% of patients. We observed significantly high values body mass index, waist circumference (WC), % body fat, fasting blood glucose (FBG), alanine transaminase (ALT), alkaline phosphate, fasting insulin and HOMA-IR in children with OSA. Inflammatory markers IL-6, IL-8, IL-17, IL-18, MIF, Hs CRP, TNF- α, PAI-1, and leptin levels were significantly higher in OSA patients (p<0.05). There was strong positive correlation of IL-6, IL-8, IL-17, IL-23, MIF, Hs CRP, TNF-A, PAI-1 and leptin with BMI, % body fat, AHI, fasting Insulin, triglyceride, FBG, WC, HOMA-IR, AST and ALT. CONCLUSION: Children with OSA have increased obesity, insulin resistance and systemic inflammation. Further studies are require to confirm our findings and evaluate their utility in diagnosis of OSAs, assessing severity and possible interventions.

Polymorphisms in vitamin D receptor and parathyroid hormone genes in the development and progression of obstructive sleep apnea in Asian Indians.

OBJECTIVES: Vitamin D plays a role in multiple aspects of human physiology, and vitamin D receptor (VDR) and parathyroid hormone (PTH) genes are associated with obesity. No data are available, to our knowledge, on the possible relationship between obstructive sleep apnea (OSA) and genetic variations of VDR and PTH genes. This study aimed to assess the significance of vitamin D and PTH, as well as VDR, and PTH gene polymorphisms with body composition and biochemical investigations in Asian Indians with and without OSA. METHODS: In this study, 120 obese subjects with OSA, 110 obese subjects without OSA, and 70 nonobese subjects without OSA were recruited. Clinical, body composition, anthropometry, and biochemical investigations, as well as a full overnight polysomnography were measured. Genotyping related to VDR (BsmI, ApaI FokI, and TaqI) and PTH (BstBI and DraII) genes were investigated with a quantitative real-time polymerase chain reaction. RESULTS: The mean values of the lower serum 25(OH) D (12.9 ± 3.8; P = 0.0001) and higher serum PTH levels (61.9 ± 12.5; P = 0.0001) were observed in obese subjects with OSA. There was an indirect correlation between serum 25(OH) D levels and OSA severity (P < 0.001). VDR (BsmI and FokI) and PTH (BstBI and DraII) genes were significantly associated with OSA (P < 0.05). Analyses of VDR haplotype combination variants (BBFFAATt [odds ratio: 3.45; 95% confidence interval, 0.986-4.567] and BbFFAaTt [odds ratio: 2.86; 95% confidence interval, 1.345-4.981) were more frequent in obese subjects with OSA (P = 0.001). The BBDD and bbDd haplotypes of the PTH gene seems to be a predisposing factor for OSA (P < 0.05). CONCLUSIONS: Lower serum 25(OH) D levels were significantly observed in patients with OSA and correlate with disease severity. Also, VDR and PTH mutations were found to be highly related with OSA in Asian Indians.

Author Correction: Vitamin D Supplementation in Overweight/obese Asian Indian Women with Prediabetes Reduces Glycemic Measures and Truncal Subcutaneous Fat: A 78 Weeks Randomized Placebo-Controlled Trial (PREVENT-WIN Trial).

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

rs7903146 (C/T) polymorphism of Transcription factor 7 like 2 (TCF7L-2) gene is independently associated with non-alcoholic fatty liver disease in Asian Indians.

BACKGROUND AND AIMS: Transcription factor 7 like 2 (TCF7L-2) polymorphism has been associated with adipocyte metabolism and insulin resistance. Genetic investigations of non-alcoholic fatty liver disease (NAFLD) with obesity, type 2 diabetes mellitus (T2DM) and atherosclerosis are unknown. This study was designed to investigate the association of rs7903146 (C/T) polymorphism of TCF7L-2 gene with non-alcoholic fatty liver disease (NAFLD) in Asian Indians. METHODS: In this case-control study 162 non-diabetic subjects with NAFLD and 173 body mass index (BMI)-matched controls without NAFLD were recruited. Abdominal ultrasound, clinical and biochemical investigations, fasting insulin levels and value of homeostasis model assessment of insulin resistance (HOMA-IR) was measured. Single nucleotide polymorphism rs7903146 (C/T) was genotyped by polymerase chain reaction-restriction fragment length polymorphisms. RESULTS: The distribution of rs7903146 (C/T) alleles, the dominant model (CT + TT) and higher frequency (31%) of C/T genotype were significantly associated with NAFLD. C/T genotype of TCF7L2 gene was associated with significantly higher levels of BMI (p = 0.02), abdominal obesity (p < 0.05), fasting blood glucose (p = 0.05), hepatic transaminases (p < 0.05) and markers of insulin resistance (p < 0.05) in subjects with NAFLD. Using a multivariate analysis after adjusting for age and sex, TCF7L2 polymorphism was independently associated with presence of NAFLD [(OR: 3.234 (95% CI: 1.219-4.160, p = 0.002)]. CONCLUSION: TCF7L2 (C/T) gene was Independently associated with NAFLD in Asian Indians.

Vitamin D Supplementation in Overweight/obese Asian Indian Women with Prediabetes Reduces Glycemic Measures and Truncal Subcutaneous Fat: A 78 Weeks Randomized Placebo-Controlled Trial (PREVENT-WIN Trial).

Vitamin D deficiency may contribute to etiology of type 2 diabetes in Asian Indians. The objectives of this study was to evaluate effect of vitamin D supplementation on glycemic profile and body composition in prediabetic and vitamin D deficient overweight/obese Asian Indian women. In this open-label randomized placebo-controlled trial (78 weeks duration), 121 females (aged 20-60 years) with prediabetes and vitamin D deficiency were randomly allocated in intervention (n, 61) and placebo (n, 60) groups. The primary outcome variables were fasting blood glucose (FBG), 2-h blood glucose post OGTT (2-h BG), hemoglobin A1c (HbA1C), and reversal to normoglycemia. In Intention-to-treat analysis, at the end of intervention, we observed significant decrease in FBG [-5.0 (-12.6-2.4), p = 0.04], 2-h blood glucose post OGTT [-11(-49.3-26.9), p = 0.02], hemoglobin A1c [-0.41 (5.89, 6.55), p = 0.05] and increase in 25(OH) D [7.5 (-6.0-20.9), p = 0.002] levels in intervention as compared to the placebo group. Changes in glycemic category based on FBG were as follows; intervention group: normal FBG, 58.6%; impaired fasting glucose (IFG), 39%; and type 2 diabetes mellitus (T2DM), 2.4%; placebo group: normal FBG, 48.8%; IFG, 46.3%; and T2DM, 4.9%. Changes in category of 2-hour glucose post OGTT after intervention were as follows; intervention group: normal glucose tolerance (NGT) 51.2% and prediabetes, 48.8%; placebo group: NGT, 43.9%; prediabetes, 53.7% and T2DM, 2.4%. After intervention, subscapular skinfold (visit Ist compared to visit IIIrd) and suprailiac skinfold (visit IInd compared to visit IIIrd) were significantly lower in intervention group vs. control group. In conclusion, we observed significant reduction in FBG, 2-hour glucose post OGTT, HbA1c, and truncal subcutaneous fat and reversal to normoglycemia in overweight/obese prediabetic vitamin D deficient Asian Indian women after 78 weeks of vitamin D supplementation.

Nutrition and physical activity in Asian Indians with non-alcoholic fatty liver: A case control study.

AIM: We tested the hypothesis that Asian Indians with non-alcoholic fatty liver disease (NAFLD) would have imbalanced diets and lower intensity of physical activity than those without NAFLD. METHODS: We studied dietary intake, intensity of physical activity and anthropometric and metabolic profiles in subjects with NAFLD and in healthy controls. Complete clinical, biochemical, dietary and physical activity profiles were studied for 169 cases and 173 controls in a prospective manner. Bivariate and multivariate analyses were carried out to identify the predictors of NAFLD [odds ratio (OR) and 95% confidence intervals (95%CI)]. RESULTS: The mean dietary intakes of total energy, carbohydrate, protein, total fat, saturated fat and total cholesterol were significantly higher, while intake of monounsaturated fatty acids and polyunsaturated fatty acids was significantly lower in cases as compared to controls (p < 0.01 for all). Further, mean physical activity in a day (expressed as MET.Minutes) and total energy expenditure were significantly lower in cases than in controls (33.3 ±â€¯3.6 vs.36.2 ±â€¯0.5, p = 0.001 and 2707.6 ±â€¯505.6 vs. 2904.3 ±â€¯690.3, p = 0.02, respectively). On multivariate analysis, percentage dietary total fat intake (OR: 13.4; 95% CI: 4.6-39.3, p = 0.001), homeostatis model assessment for insulin resistance (OR: 6.9; 95% CI: 3.2-14.8, p = 0.001) abdominal obesity (OR: 2.7; 95% CI: 1.5-5.0, p = 0.001) and high serum triglycerides (OR: 2.1; 95%CI: 1.2-3.8, p = 0.007) were associated with an increased risk for development of NAFLD. CONCLUSION: Decrease in intake of total dietary fats and improvement of insulin resistance, abdominal obesity and blood triglycerides should be important measures for management of NAFLD in Asian Indians in north India.

High fasting C-peptide levels and insulin resistance in non-lean & non-obese (BMI >19 to < 25 kg/m2) Asian Indians with type 2 diabetes are independently associated with high intra-abdominal fat and liver span.

BACKGROUND AND OBJECTIVES: We aimed to compare C-peptide levels & measures of insulin resistance in non-lean & non-obese Asian Indian patients with type 2 diabetes (T2DM) vs. non-lean, non-diabetic controls and to correlate with anthropometric measures, volumes of abdominal adipose tissue depots, pancreas, & liver span. METHODS: Non-lean, non-obese (BMI >19 and < 25 kg/m2) Asian Indian patients with T2DM, (cases n, 87), diagnosed within one year, on metformin mono therapy, were compared to BMI-matched non-diabetic subjects (controls, n, 37). Measures of glycaemia, insulin and C-peptide levels (fasting and post-prandial), lipid profile, and hepatic transaminases were analysed. Abdominal adipose tissue volumes [subcutaneous & intra-abdominal], pancreatic volume and liver span were assessed using 1.5 Tesla MRI scan. RESULTS: In cases, the mean values of HbA1c, fasting and post prandial insulin and C-peptide levels, and 3 measures of insulin resistance were significantly higher than controls, but not for HOMA-B. Higher fasting C-peptide levels correlated significantly with HOMA-IR (r = 0.42, p < 0.001), Fasting Insulin Resistance Index (r = 0.42, p < 0.001), Bennett's Index (r = 0.38, p < 0.05), and volumes of SCAT and IAAT only in cases. The independent predictors of higher fasting C-peptide level were IAAT volume (ß = 0.057; p = 0.002), liver span (ß = 0.057, p = 0.005) and fasting insulin levels (ß = 0.35, p = 0.02). CONCLUSION: Higher fasting and post-prandial C-peptide levels and surrogate measures of insulin resistance in non-obese Asian Indian patients with T2DM are independently associated with IAAT volume and liver span.

Non-alcoholic fatty liver disease is an independent risk factor for inflammation in obstructive sleep apnea syndrome in obese Asian Indians.

INTRODUCTION: Obstructive sleep apnea (OSA) has been estimated to affect 4-11% of the population and causes systemic inflammation which leads to metabolic syndrome (MS). Non-alcoholic fatty liver disease (NAFLD) is also associated with MS whether NAFLD is an additional risk factor for the systemic inflammation that occurs in OSA is unclear. OBJECTIVE: In this study, we aimed to analyze the association of OSA and NAFLD with MS and systemic inflammation in Asian Indians. METHODS: Total 240 (132 males and 108 females) overweight/obese subjects [body mass index (BMI > 23 kg/m2)] were recruited; of these, 124 subjects had OSA with NAFLD, 47 had OSA without NAFLD, 44 did not have OSA but had NAFLD and 25 had neither OSA nor without NAFLD. Severity of NAFLD was based on abdomen ultrasound and of OSA on overnight polysomnography. Clinical examinations, anthropometry, body composition, metabolic parameters, and inflammatory biomarkers were recorded. RESULTS: Serum levels of leptin, macrophage migration inhibitory factor (MIF), interleukin-6 (IL-6), high sensitive C-reactive protein (Hs-CRP), and tumor necrosis factor alpha (TNF-α) were significantly higher, and adiponectin levels were significantly lower in OSA with NAFLD subjects. Prevalence of MS was significantly increased in OSA and NAFLD subjects (p = 0.001). There was a strong association and correlation between leptin, IL-6, Hs-CRP, MIF, and TNF-α in OSA and NAFLD subjects. Multivariate logistic regression showed that OSA was positively associated with the NAFLD [odds ratio (OR), (95% confidence interval (CL) 3.12 (2.58-7.72), (P = 0.002)]. CONCLUSION: NAFLD is an additional risk factor in OSA subject which contributes to systemic inflammation in Asian Indians.

Correction: Association of inflammatory genes in obstructive sleep apnea and non alcoholic fatty liver disease in Asian Indians residing in north India.

[This corrects the article DOI: 10.1371/journal.pone.0199599.].

Association of inflammatory genes in obstructive sleep apnea and non alcoholic fatty liver disease in Asian Indians residing in north India.

BACKGROUND: Previous studies have indicated that variants of the high sensitive C-reactive protein (CRP), Interleukin (IL)-6 and leptin receptor (LEPR) genes are associated with the presence of obstructive sleep apnea (OSA) but not in non-alcoholic fatty liver disease (NAFLD) in Asian Indians. The study was conducted to investigate the association of CRP rs1130864 (1444C/T), IL-6 rs1800795 (-174G/C) and LEPR rs1137101 (Q223R) genes with OSA and NAFLD in Asian Indians residing in North India. METHODS: 240 overweight/ obese subjects [body mass index (BMI>23kg/m2)], 124 with OSA and with NAFLD (group 1), 47 with OSA without NAFLD (group 2), 44 without OSA and with NAFLD (group 3) and 25 without OSA and without NAFLD (group 4) were recruited in this study. The severity of NAFLD was based on abdomen liver ultrasound and of OSA on overnight polysomnography. Clinical details, anthropometry profile, body composition, biochemical parameters and inflammatory markers were measured. Polymerase chain reaction and restriction fragment length polymorphism of CRP, IL-6 and LEPR gene was performed. The associations of these polymorphisms with clinical, anthropometric and biochemical profiles were investigated. The genotypes were confirmed by DNA sequencing analysis. RESULTS: The C, T and R alleles of IL-6, CRP and LEPR genes was more frequent in OSA and NAFLD subjects and significantly correlated with higher protein levels. The prevalence of variant genotypes C/T of CRP, G/C of IL-6 and Q/R of LEPR genes was significantly higher in OSA subjects as compared to non OSA subjects. Further, C/C genotype of IL-6 (G/C), T/T of CRP (C/T) and RR genotype of LEPR (Q/R) was associated with significantly higher BMI, fat mass (kg), % body fat, waist circumference, serum triglycerides, total cholesterol, alkaline phosphate, aspartate transaminase and fasting insulin levels in OSA and NAFLD subjects. Using a multivariate analysis, the combined effect of three polymorphisms of CRP, IL-6 and LEPR gene variants on OSA and NAFLD risk was evaluated. Odds ratio for OSA and NAFLD with the combination of the three gene polymorphisms increased to 2.84 (95% CI: 1.08-6.54; p = 0.04) even when adjusted for sex, age and BMI. CONCLUSION: Polymorphisms of pro-inflammatory cytokine genes were associated with increased risk of OSA and NAFLD in Asian Indians.

Lower vitamin D levels are associated with higher blood glucose levels in Asian Indian women with pre-diabetes: a population-based cross-sectional study in North India.

BACKGROUND: Asian Indian women are predisposed to develop obesity, metabolic syndrome and vitamin D deficiency. Relationship of vitamin D deficiency with blood glucose levels has not been explored in Asian Indian women with pre-diabetes. OBJECTIVE: We evaluated the associations of serum 25-hydroxy vitamin D (25(OH)D) concentrations among adult women with the pre-diabetes residing in North India (Delhi). METHODS: This cross-sectional population-based study involved 797 women with pre-diabetes aged 20-60 years. Blood pressure, body mass index (BMI), fasting blood glucose (FBG), extent of sun exposure and serum 25(OH)D levels were assessed. For purpose of analysis, serum 25(OH)D levels (nmol/L) were categorized in quintiles as follows: 0-21.5 (first quintile), 21.51-35.60 (second quintile), 35.61-46.50 (third quintile), 46.51-62.30 (fourth quintile) and >62.31 (fifth quintile). RESULT: The prevalence (%) of vitamin D deficiency, insufficiency and sufficiency was 68.6, 25.9 and 5.5, respectively. Mean age (p=0.004), systolic (p=0.05) and diastolic (p=0.04) blood pressure, weight (p=0.03), BMI (p=0.04) and FBG (p=0.02) were significantly higher in subjects with vitamin D deficiency as compared with those with vitamin D insufficiency and sufficiency. Unadjusted mean values of FBG were significantly decreased in fourth (p=0.02) and fifth quintiles (p=0.030) of 25(OH)D levels as compared with second quintile. Furthermore, after adjusting for age and family income FBG levels were significantly increased in first quintile (compared with fourth (p=0.012) and fifth (p=0.018) quintiles) and second quintile (compared with fourth (p=0.003) and fifth (p=0.004) quintiles) of 25(OH)D levels, respectively. CONCLUSION: Lower vitamin D levels are associated with higher blood glucose values in Asian Indian women with pre-diabetes. These findings need confirmation in case-control and prospective studies.

High circulating plasma dipeptidyl peptidase- 4 levels in non-obese Asian Indians with type 2 diabetes correlate with fasting insulin and LDL-C levels, triceps skinfolds, total intra-abdominal adipose tissue volume and presence of diabetes: a case-control study.

AIM: To evaluate circulating plasma dipeptidyl peptidase-4 (DPP4) levels in non-obese Asian Indians with type 2 diabetes mellitus (T2DM), and to correlate these with metabolic profile and measures of anthropometry, skinfolds, abdominal adipose tissue depots, pancreatic volume, and liver span. METHODOLOGY: Non-obese (body mass index (BMI) <25 kg/m2) patients with T2DM (cases, n=93), diagnosed within 1 year from recruitment, on metformin therapy and BMI-matched, and non-diabetic subjects (controls, n=40) were compared. Measurements of blood glucose, glycosylated hemoglobin, plasma insulin levels, lipid profile, hepatic transaminases and plasma DPP4 levels, and quantification of abdominal fat depots, pancreatic volume and liver span (MRI scan), were done. RESULTS: Significantly higher (p<0.001) circulating plasma DPP4 levels were observed in cases as compared to controls. Specifically, in patients with T2DM with non-alcoholic fatty liver disease (NAFLD) (n=48), the mean plasma DPP4 level (52.6±27.8 ng/mL) was significantly higher (p<0.05) as compared with those without NAFLD (n=43; 47±28.3 ng/mL). Significant positive correlation was observed for circulating plasma DPP4 levels with waist-to-hip ratio, total intra-abdominal adipose volume, and liver span. Fasting serum insulin, low-density lipoprotein cholesterol (LDL-C), triceps skinfolds, total intra-abdominal adipose tissue volume and presence of T2DM were significant determinants of circulating plasma DPP4 levels. CONCLUSION: Non-obese Asian Indian patients with T2DM and on metformin therapy have significantly higher circulating plasma DPP4 levels as compared to non-obese non-diabetic controls, and these levels correlate with fasting insulin and LDL-C levels, upper limb subcutaneous adipose tissue, intra-abdominal adiposity and presence of diabetes.

High Plasma Glucagon Levels Correlate with Waist-to-Hip Ratio, Suprailiac Skinfold Thickness, and Deep Subcutaneous Abdominal and Intraperitoneal Adipose Tissue Depots in Nonobese Asian Indian Males with Type 2 Diabetes in North India.

We aimed to correlate plasma glucagon levels with anthropometric measures and abdominal adipose tissue depots. Nonobese males (n = 81; BMI < 25 kg/m2) with T2DM of less than one-year duration and nonobese males without diabetes (n = 30) were evaluated for the following: anthropometry (BMI, waist circumference, W-HR, and truncal skinfolds), whole-body DEXA (for body fat and fat-free mass), and MRI scan (for volumes of subcutaneous abdominal adipose tissue (SCAT) including superficial and deep, intra-abdominal visceral adipose tissue (including intraperitoneal adipose tissue (IPAT), retroperitoneal adipose tissue, liver span and fatty liver, and pancreatic volume)). Plasma glucose and glucagon, serum insulin, hepatic transaminases, and lipid profile were measured. Significantly higher levels of fasting and postprandial glucagon (p < 0.001) and fasting and postprandial insulin (p < 0.001) were seen in patients with T2DM. The mean values of fasting and postprandial plasma glucagon levels were higher in T2DM patients with NAFLD (n = 37) as compared to T2DM patients without NAFLD (n = 44). Four independent predictors were derived for fasting glucagon levels in patients with T2DM, namely, W-HR, suprailiac skinfold thickness, IPAT, and deep SCAT (p < 0.05; r2 = 0.84). These observations in Asian Indians may have significance for diabetes therapies which impact glucagon levels.

Glucose tolerance & insulin secretion & sensitivity characteristics in Indian children with cystic fibrosis: A pilot study.

Background & objectives: Cystic fibrosis (CF) is a life-limiting genetic condition resulting in chronic respiratory infections, pancreatic enzyme insufficiency and associated complications. This pilot study was undertaken to assess the glucose tolerance and insulin secretion and sensitivity among Indian children with CF. Methods: Children with CF under regular follow up at the Paediatric Pulmonology Clinic of a tertiary care hospital in New Delhi, India, were enrolled. Children who had a history of acute exacerbation or intake of systemic steroids within the last two weeks were excluded. Anthropometry, pulmonary function and disease severity (Shwachman) score were assessed. Fasting venous sample was drawn to assess glucose, insulin, haemoglobin and calcium. Oral glucose tolerance test was performed, and blood glucose and insulin were assessed at 30, 60, 90 and 120 min. Insulin secretion and sensitivity indices were calculated. Results: Twenty nine patients with a mean age of 11.2±4.1 yr were enrolled. Stunting, thinness, anaemia and hypocalcaemia were present in 31.0, 13.8, 37.0 and 48.3 per cent of the patients, respectively. Abnormal glucose tolerance (AGT) was present in 21.4 per cent. Insulin secretion was similar in individuals with AGT and normal glucose tolerance (NGT), but insulin sensitivity index was lower (0.12±0.02 vs 0.15±0.01, P<0.001) and homeostatic model assessment of insulin resistance higher [1.63 (0.53-1.76) vs 0.83 (0.28-4.43), P<0.05] in individuals with AGT compared to NGT. Interpretation & conclusions: AGT was observed in 21.4 per cent of children with CF. The CF patients with AGT had significantly lower insulin sensitivity compared to patients with NGT. Future multicentric studies with a large sample should be conducted to assess insulin secretion and sensitivity indices in CF patients compared to healthy controls.