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.

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.

Wide-field imaging with smartphone based fundus camera: grading of severity of diabetic retinopathy and locating peripheral lesions in diabetic retinopathy.

AIM: To assess the performance of smartphone based wide-field retinal imaging (WFI) versus ultra-wide-field imaging (UWFI) for assessment of sight-threatening diabetic retinopathy (STDR) as well as locating predominantly peripheral lesions (PPL) of DR. METHODS: Individuals with type 2 diabetes with varying grades of DR underwent nonmydriatic UWFI with Daytona Plus camera followed by mydriatic WFI with smartphone-based Vistaro camera at a tertiary care diabetes centre in South India in 2021-22. Grading of DR as well as identification of PPL (DR lesions beyond the posterior pole) in the retinal images of both cameras was performed by senior retina specialists. STDR was defined by the presence of severe non-proliferative DR, proliferative DR or diabetic macular oedema (DME). The sensitivity and specificity of smartphone based WFI for detection of PPL and STDR was assessed. Agreement between the graders for both cameras was compared. RESULTS: Retinal imaging was carried out in 318 eyes of 160 individuals (mean age 54.7 ± 9 years; mean duration of diabetes 16.6 ± 7.9 years). The sensitivity and specificity for detection of STDR by Vistaro camera was 92.7% (95% CI 80.1-98.5) and 96.6% (95% CI 91.5-99.1) respectively and 95.1% (95% CI 83.5-99.4) and 95.7% (95% CI 90.3-98.6) by Daytona Plus respectively. PPL were detected in 89 (27.9%) eyes by WFI by Vistaro camera and in 160 (50.3%) eyes by UWFI. However, this did not translate to any significant difference in the grading of STDR between the two imaging systems. In both devices, PPL were most common in supero-temporal quadrant (34%). The prevalence of PPL increased with increasing severity of DR with both cameras (p < 0.001). The kappa comparison between the 2 graders for varying grades of severity of DR was 0.802 (p < 0.001) for Vistaro and 0.753 (p < 0.001) for Daytona Plus camera. CONCLUSION: Mydriatic smartphone-based widefield imaging has high sensitivity and specificity for detecting STDR and can be used to screen for peripheral retinal lesions beyond the posterior pole in individuals with diabetes.

Role of cystatin C in the detection of sight-threatening diabetic retinopathy in Asian Indians with type 2 diabetes.

AIM: To study the association between cystatin C and sight-threatening diabetic retinopathy (STDR) in Asian Indians with type 2 diabetes (T2DM). METHODS: In a cross-sectional study carried out at two tertiary centres in India in 2022, individuals with T2DM underwent clinical and ophthalmic assessments and estimation of serum cystatin C. Grading of DR was done by retina specialists. STDR was defined by the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) and/or diabetic macular edema. Receiver operating characteristic (ROC) curves were used to identify cystatin C cut-off value for detecting STDR. RESULTS: Among 420 individuals with T2DM (mean age 56 ± 9 years; mean duration of diabetes 14.5 ± 7.9 years), 121 (24.1 %) had No-DR, 119 (28.3 %) had No-STDR and 200 (49.6 %) had STDR. Mean cystatin C level was significantly higher in individuals with STDR compared to those with no-STDR and No-DR (1.34 vs 1.06 vs 0.93 mg/L, p < 0.001). Cystatin C cut-off value ≥1.11 mg/L had a C statistic of 0.944 (95 % CI: 0.909-0.968, p < 0.001), 96.8 % sensitivity and 78.2 % specificity for detection of STDR. CONCLUSION: Elevated serum cystatin C was strongly associated with STDR and could possibly be used as a biomarker for screening for sight-threatening diabetic retinopathy.

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.

Plausible diagnostic value of urinary isomeric dimethylarginine ratio for diabetic nephropathy.

Altered circulatory asymmetric and symmetric dimethylarginines have been independently reported in patients with end-stage renal failure suggesting their potential role as mediators and early biomarkers of nephropathy. These alterations can also be reflected in urine. Herein, we aimed to evaluate urinary asymmetric to symmetric dimethylarginine ratio (ASR) for early prediction of diabetic nephropathy (DN). In this cross-sectional study, individuals with impaired glucose tolerance (IGT), newly diagnosed diabetes (NDD), diabetic microalbuminuria (MIC), macroalbuminuria (MAC), and normal glucose tolerance (NGT) were recruited from Dr. Mohans' Diabetes Specialties centre, India. Urinary ASR was measured using a validated high-throughput MALDI-MS/MS method. Significantly lower ASR was observed in MIC (0.909) and MAC (0.741) in comparison to the NGT and NDD groups. On regression models, ASR was associated with MIC [OR: 0.256; 95% CI: 0.158-0.491] and MAC [OR 0.146; 95% CI: 0.071-0.292] controlled for all the available confounding factors. ROC analysis revealed ASR cut-point of 0.95 had C-statistic of 0.691 (95% CI: 0.627-0.755) to discriminate MIC from NDD with 72% sensitivity. Whereas, an ASR cut-point of 0.82 had C-statistic of 0.846 (95% CI: 0.800 - 0.893) had 91% sensitivity for identifying MAC. Our results suggest ASR as a potential early diagnostic biomarker for DN among the Asian Indians.

1,5 Anhydroglucitol in gestational diabetes mellitus.

OBJECTIVE: 1,5 Anhydroglucitol (1,5 AG) is reported to be a more sensitive marker of glucose variability and short-term glycemic control (1-2 weeks) in patients with type1 and type 2 diabetes. However, the role of 1,5 AG in gestational diabetes mellitus (GDM) is not clear. We estimated the serum levels of 1,5 AG in pregnant women with and without GDM. METHODS: We recruited 220 pregnant women, 145 without and 75 with GDM visiting antenatal clinics in Tamil Nadu in South India. Oral glucose tolerance tests (OGTTs) were carried out using 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) and GDM was diagnosed based on the International Association of Diabetes and Pregnancy Study Group criteria. Serum 1,5 AG levels were measured using an enzymatic, colorimetric assay kit (Glycomark®, New York, NY). Receiver operating characteristic (ROC) curves were used to identify 1,5 AG cut-off points to identify GDM. RESULTS: The mean levels of the 1,5 AG were significantly lower in women with GDM (11.8 ±â€¯5.7 µg/mL, p < 0.001) compared to women without GDM (16.2 ±â€¯6.2 µg/mL). In multiple logistic regression analysis, 1.5 AG showed a significant association with GDM (odds ratio [OR]: 0.876, 95% confidence interval [CI]: 0.812-0.944, p < 0.001) after adjusting for potential confounders. 1,5 AG had a C statistic of 0.693 compared to Fructosamine (0.671) and HbA1c (0.581) for identifying GDM. A 1,5 AG cut-off of 13.21 µg/mL had a C statistic of 0.6936 (95% CI: 0.6107-0.7583, p < 0.001), sensitivity of 67.6%, and specificity of 65.3% to identify GDM. CONCLUSION: 1,5AG levels are lower in pregnant women with GDM compared to individuals without GDM.

The 1h post glucose value best predicts future dysglycemia among normal glucose tolerance subjects.

AIM: To analyse the OGTT glycemic parameters - fasting, 1h and 2h plasma glucose values singly and in various combinations; with respect to their prediction of future dysglycemia in subjects with normal glucose tolerance (NGT). METHODS: Electronic medical records of individuals who underwent an OGTT between 1991 and 2016 at a tertiary diabetes centre were analysed. NGT subjects who had at least one more follow up OGTT (n=1356) were selected for the study. Regarding their prediction of future dysglycemia, the glycemic parameters-Fasting plasma glucose (FPG), 1h plasma glucose (1HrPG) and 2h plasma glucose (2HrPG) were analysed separately and also in different combinations. HbA1c and the combined use of HbA1c and FPG were also compared. Receiver operating characteristic (ROC) curve analysis was performed to assess the capability of various glycemic parameters to discriminate between NGT and dysglycemia. The WHO criteria were used to define dysglycemia as the presence of prediabetes (Impaired fasting glucose and/or Impaired glucose tolerance) or diabetes. RESULTS: 318(23.4%) developed prediabetes (median follow up 3.5years) and 134(10%) developed diabetes (median follow up 5.6years). The 1hrPG had a significantly higher AUC (0.684, 0.716) compared to FPG (0.560 and 0.593) and 2hrPG (0.644 and 0.618) for prediabetes and diabetes respectively. Adding the FPG or the 2hrPG to the 1HrPG did not significantly improve the AUC beyond 1HrPG alone. The 1HrPG also predicted diabetes better than HbA1c as well as the combined use of HbA1c and FPG. CONCLUSION: The 1HrPG value during OGTT is a good predictor of future dysglycemia among NGT subjects.

Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values.

AIM: The aim of this study was to compare the metabolic profiles of subjects with normal glucose tolerance (NGT) with and without elevated 1-h postglucose (1HrPG) values during an oral glucose tolerance test (OGTT). METHODOLOGY: The study group comprised 996 subjects without known diabetes seen at tertiary diabetes center between 2010 and 2014. NGT was defined as fasting plasma glucose <100 mg/dl (5.5 mmol/L) and 2-h plasma glucose <140 mg/dl (7.8 mmol/L) after an 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) OGTT. Anthropometric measurements and biochemical investigations were done using standardized methods. The prevalence rate of generalized and central obesity, hypertension, dyslipidemia, and metabolic syndrome (MS) was determined among the NGT subjects stratified based on their 1HrPG values as <143 mg/dl, ≥143-<155 mg/dl, and ≥155 mg/dl, after adjusting for age, sex, body mass index (BMI), waist circumference, alcohol consumption, smoking, and family history of diabetes. RESULTS: The mean age of the 996 NGT subjects was 48 ± 12 years and 53.5% were male. The mean glycated hemoglobin for subjects with 1HrPG <143 mg/dl was 5.5%, for those with 1HrPG ≥143-<155 mg/dl, 5.6% and for those with 1HrPG ≥155 mg/dl, 5.7%. NGT subjects with 1HrPG ≥143-<155 mg/dl and ≥155 mg/dl had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, triglyceride, total cholesterol/high-density lipoprotein (HDL) ratio, triglyceride/HDL ratio, leukocyte count, and gamma glutamyl aminotransferase (P < 0.05) compared to subjects with 1HrPG <143 mg/dl. The odds ratio for MS for subjects with 1HrPG ≥143 mg/dl was 1.84 times higher compared to subjects with 1HrPG <143 mg/dl taken as the reference. CONCLUSION: NGT subjects with elevated 1HrPG values have a worse metabolic profile than those with normal 1HrPG during an OGTT.

Relationship of glycemic control markers - 1,5 anhydroglucitol, fructosamine, and glycated hemoglobin among Asian Indians with different degrees of glucose intolerance.

OBJECTIVE: 1,5 anhydroglucitol (1,5 AG) is emerging as a marker of short-term glycemic control. We measured levels of 1,5 AG, fructosamine (FA), and glycated hemoglobin (HbA1c) in Asian Indians with different degrees of glucose intolerance. MATERIALS AND METHODS: We recruited 210 individuals with normal glucose tolerance (NGT; n = 60), impaired glucose tolerance (IGT; n = 50), and Type 2 diabetes mellitus (T2DM; n = 100) from a large tertiary diabetes center in Chennai in Southern India. Anthropometric measurements were obtained using standardized techniques. Serum 1,5 AG (enzymatic colorimetric assay), FA (NBT/kinetic), and HbA1c (high-performance liquid chromatography) estimations were performed. RESULTS: 1,5 AG levels were significantly lower in the T2DM followed by IGT compared with the NGT group (7.9 vs. 18.8 vs. 21.8 µg/ml, P < 0.05). FA and HbA1c were higher in T2DM and IGT compared with NGT individuals (313 vs. 237 vs. 200 µmol/L, P < 0.001) (8.3 vs. 5.8 vs. 5.3%, P < 0.001).1,5 AG showed a significant negative correlation with FA (r = -0.618, P < 0.001) and HbA1c (r = -0.700, P < 0.001). 1,5 AG decreased with increasing quartiles of postprandial glucose (P for trend <0.001). However, even among individuals with HbA1c ≤7%, 27% individuals had decreased 1,5 AG plasma level (<10 µg/ml). CONCLUSION: Circulatory levels of 1,5 AG correlate negatively with FA and HbA1c, and may provide an additional marker to assess glycemic control in patients with Type 2 diabetes.