Effects of Metabolic Surgery on Diabetic Kidney Disease and Diabetic Retinopathy Among Obese Asian Indians with Type 2 Diabetes.

INTRODUCTION: To evaluate the effect of metabolic surgery on microvascular changes associated with diabetic retinopathy (DR) and diabetic kidney disease (DKD) in obese Asian Indians with type 2 diabetes (T2DM), one year after metabolic surgery. METHODS: This is a follow up study in 21 obese Asian Indians with T2DM who underwent metabolic surgery (MS). Diabetic microvascular complications were assessed before and one-year post surgery using urinary albumin, protein creatinine ratio, eGFR, retinal colour photography and Optical coherence tomography (OCT). RESULTS: Microalbuminuria (54±26 vs 28±16 vs 21±6 µg/mg, p<0.001) and protein creatinine ratio (0.4±0.1 vs 0.2±0.03 vs 0.1±0.02, p<0.05) reduced significantly 6 months and one year after Metabolic surgery (MS) respectively compared to baseline values. Estimated Glomerular Filtration (eGFR) rate and creatinine was stable and there was no decline in renal function one year after MS. DR was present in eight individuals at baseline. After metabolic surgery, 12 % of individuals achieved regression of DR and 12% individuals showed a one step regression from severe to moderate non proliferative DR while 12 % individuals progressed from moderate to severe non proliferative DR. Of the 14 (53.8%) individuals who had micro or macroalbuminuria at baseline, 43% individuals reverted back to normoalbuminuria. There was also a reduction in the usage of anti- hypertensive medications after MS. CONCLUSION: In obese Asian Indians with T2DM, metabolic surgery reduced urinary microalbuminuria and protein creatinine ratios at one-year post MS. MS resulted in stable D. Retionpathy status one-year post surgery. MS may help to improve in stabilisation of the microvascular complications in obese patients with T2DM.

Insulin gene mutations linked to permanent neonatal diabetes mellitus in Indian population.

BACKGROUND AND AIM: Neonatal diabetes mellitus (NDM) is a rare monogenic disorder of pancreatic beta cell mass and/or function. In the present study we aimed to evaluate the INS gene mutations in a cohort of children with Permanent Neonatal Diabetes Mellitus (PNDM) and to explore the clinical and genetic characteristics of PNDM caused by INS mutations. METHODS: Direct sequencing of all exons of INS genes was carried out in 189 children with PNDM. Clinical and biochemical data were collected and correlated. The pathogenicity of mutations was determined based on the American College of Medical Genetics and Genomics and Association of Medical Pathology guidelines. RESULTS: Two novel mutations (His34Pro, Leu35Met) in a compound heterozygous state and seven known mutations (Gly32Ser, Phe48Cys, Arg89Cys, Cys96Tyr, Ser98Ile, Try108Asp and Cys109Phe) in the INS gene were identified in 8 patients out of the total of 189 PNDM children studied. Four mutations were involved in defects with disulphide bond formation and hence were in crucial regions of the gene. All the mutations were de novo in origin. CONCLUSIONS: This is the first comprehensive study from India to investigate the insulin gene mutations in PNDM and to show that INS gene mutations also contribute to the causation of PNDM.

Beneficial Primary Outcomes of Metabolic Surgery with Changes in Telomere Length and Mitochondrial DNA in Obese Asian Indians with Dysglycemia.

INTRODUCTION: Although metabolic surgery has been shown to offer beneficial primary outcome results in obese individuals / obese Type 2 diabetes mellitus (T2DM) patients, there is paucity of information on the underlying mechanisms. In the recent years, estimations of non-invasive molecular parameters viz., telomere length and mtDNA copy number (mtDNAcn) assume significance as robust biomarkers. However, there is lack of evidence about this especially, in the Indian context. To assess the changes in the telomere length and mtDNAcn levels after metabolic surgery in obese Asian Indians with dysglycemia along with routine measurements of anthropometry, glycemic/lipidimic parameters and inflammatory markers. METHODS: This study is a prospective one-year follow-up study of 16 obese individuals with dysglycemia who underwent metabolic surgery at a tertiary diabetes centre in South India. Telomere length, mtDNAcn, serum adiponectin, glycated haemoglobin and high- sensitivity C-reactive protein (hs-CRP) levels were analysed before surgery and at 6 and 12 months after surgery. RESULTS: There was a significant reduction in weight (p<0.001), BMI (p<0.001), waist circumference (p<0.001), fasting and postprandial glucose (p<0.05), HbA1c (p<0.001), triglycerides (p<0.05), hs CRP (p<0.05) and increase in serum adiponectin (p<0.05) at 6 and 12 months post-surgery compared to the preoperative status. There was a significant reduction in mtDNAcn (p<0.001) and a significant increase in telomere length (p<0.001) at 6 and 12 months post metabolic surgery. CONCLUSION: We report an increase in telomere length and decrease in circulatory mtDNA copy number levels at 6 and 12 months post metabolic surgery in obese individuals with T2DM in India.

Retrospective analysis (2009-2017) of factors associated with progression and regression of non-alcoholic fatty liver disease (Hepatic steatosis) in patients with type 2 diabetes seen at a tertiary diabetes centre in Southern India.

AIM: To identify the profiles and factors associated with progression/regression of ultrasound-derived hepatic steatosis with type 2 diabetes mellitus seen at a tertiary diabetes center in southern India. METHODS: Participants were individuals with type 2 diabetes mellitus with at least two consecutive ultrasound measurements available. Hepatic steatosis was assessed using high-resolution B-mode ultrasonography. Admittedly ultrasonography has lower sensitivity and specificity, however, it is the only modality available in a routine clinical setting to screen for hepatic steatosis. Progression or regression of hepatic steatosis was assessed after a mean follow-up of 3.0 ± 2.1 years and correlated with clinical and biochemical parameters. RESULTS: A total of 1835 participants with type 2 diabetes mellitus were studied, of whom 88.6% had some form of hepatic steatosis at baseline which included mild steatosis (grade 1) in 982 (53.5%), moderate steatosis (grade 2) in 628 (34.2%) and severe steatosis (grade 3) in 15 (0.8%). Hepatic steatosis progression, regression or no change in grade of hepatic steatosis were seen in 21.5%, 26.6% and 51.9% of participants. Increase in body weight, body mass index, glycated haemoglobin, serum triglycerides and gamma glutamyl transferase were the factors associated with progression of hepatic steatosis, whereas regression showed reduction in body weight, body mass index, fasting plasma glucose and glycated haemoglobin. CONCLUSION: Among South Indian type 2 diabetes patients with hepatic steatosis, severity of steatosis progressed in 1/3rd while it regressed in 1/4th. These retrospective data need proper ascertainment in controlled studies.

Outcomes of metabolic surgery in obese patients with type 2 diabetes with respect to impact on beta cell function, insulin sensitivity and diabetes remission - A study from south India.

BACKGROUND AND AIMS: Metabolic surgery is gaining popularity as a procedure for the treatment of morbid obesity among patients with type 2 diabetes (T2DM). The aim of the study was to evaluate the effects of metabolic surgery on beta cell function, insulin sensitivity and glycemic status in obese Asian Indian patients. METHODS: This is a prospective study of 26 patients with T2DM who underwent metabolic surgery. Complete diabetes remission was defined as FPG<100 mg/dl and HbA1c < 6%, without antidiabetic medications one-year post surgery. Anthropometry, HOMA-IR (insulin resistance), HOMA-insulin sensitivity, beta cell function and antidiabetic drug usage were measured at baseline, 6 months and 12 months post-surgery. RESULTS: The overall duration of diabetes was 10.3 ± 5.4 years. At one year, 7 (27%) of 26 T2DM patients, achieved diabetes remission while the other 19 had improvement in diabetes status. ROC curves showed that those who had diabetes duration <8.5 years achieved remission. There was a significant decrease in HOMA-IR [3.7 ± 1.8 vs 1.4 ± 0.9 vs1.2 ± 0.6, p < 0.001] and improvement in HOMA-Insulin sensitivity [34 ± 17 vs 93 ± 50 vs 112 ± 62, p < 0.001] from baseline to 6 and 12 months post-surgery respectively. There was a significant (p < 0.001) reduction in the usage of anti-diabetes medications post-surgery. The limitations of this study are small sample size and limited follow up period of 1 year. CONCLUSIONS: Among T2DM patients, metabolic surgery resulted in significant improvement in beta cell function and insulin sensitivity along with reduction in anti-diabetes medication. Diabetes remission was mainly seen in those who had duration of diabetes <8.5 years.