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Objective: MODY (maturity onset diabetes of the young) is a rare, monogenic, autosomal dominant form of diabetes occurring in young (< 25 years) individuals. It has a wide phenotypic variability and can be misdiagnosed as type 1 diabetes mellitus (T1DM). Appropriate detection of MODY has therapeutic and genetic implications. This study aimed to detect MODY among long standing, clinically diagnosed T1DM patients with preserved C-peptide levels. Methods: This was a hospital-based cross-sectional study from central South India which included 100 clinically diagnosed T1DM patients (according to ADA criteria), with a duration of > 3 years. MODY probability score, urinary C-peptide to creatinine ratio (UCPCR), and relevant biochemical investigations were performed. Targeted next-generation sequencing (NGS) for MODY-related genes (13 genes) was done for individuals with UCPCR > 0.2. Results: A UCPCR value of > 0.2 (suggestive of preserved endogenous insulin secretion) was observed in eight individuals. The mean HbA1c values were lower, and the MODY probability score was higher in individuals with preserved endogenous insulin (8.07% vs 9.53% and 2.8% vs 1.5%; p-value: 0.005 and 0.004 respectively). One of the eight individuals (12.5%) had a non-pathogenic gene variant in KLF11. Conclusion: In a South Indian cohort of T1DM with preserved C-peptide, we could not find any case of MODY through targeted NGS. UCPCR can be used as a screening tool to identify cases needing genetic testing for MODY. Larger studies utilizing whole exome sequencing should be conducted to know the actual prevalence of MODY among T1DM. [ABSTRACT FROM AUTHOR]

Compound heterozygous Sickle Haemoglobin (HbS) beta (ß) thalassaemia arises from the mutations associated with sickle cell and ß thalassaemia and significantly affects populations in low income countries like India. Elevated levels of Haemoglobin A2 (HbA2) represent the primary indicator for identifying carriers of ß thalassaemia. However, it's worth noting that sometimes, High Performance Liquid Chromatography (HPLC) encounters challenges in confirming a final diagnosis when levels of HbA2 and HbS fall outside the diagnostic range. A nine-year-old male and his sister 11-year-old female patient presented with high-grade fever and jaundice since two weeks. Following admission, Complete Blood Count (CBC) and HPLC of both children were done. Hb of male and female child revealed 1.8 g/dL and 1.5 g/dL, respectively. HPLC of male child revealed Haemoglobin F (HbF) 27.4%, HbS 56.3%, HbA2 3.8% and of female child revealed HbF 39.2%, HbS 43.5%, HbA2 3%. HPLC reports of both children were suggestive of differential of compound heterozygous HbS ß thalassaemia and HbS homozygous. Later, HPLC of their parents was also done. HPLC of father was suggestive of thalassaemia trait and of mother suggestive of sickle cell trait, following which final diagnosis of both children was given as compound heterozygous HbS ß thalassaemia. Diagnosing these compound heterozygous haemoglobinopathies can be challenging. As their is resemblance in clinicopathological features of sickle cell anaemia and ß thalassaemia disorders, it is important to carefully differentiate between them although prognosis is better than thalassaemia major or sickle cell anaemia. [ABSTRACT FROM AUTHOR]

Background and aims: Type 2 diabetes mellitus (T2DM) is characterized by progressive metabolic deterioration due to a decline in β-cell function. The relation between glucagon and insulin secretion in the setting of T2DM is still not clear. The present study evaluated relationship between glucagon level, glycemic status, and β-cell indices in newly diagnosed Indian T2DM patients. Methods: Patients with HbA1c > 8.5% and/or fasting plasma glucose > 200 mg/dl were treated with insulin for 6 months (May 2017 to December 2018). Metabolic parameters and hormonal tests (insulin, glucagon, C-peptide in the fasting state, and 2-h meal stimulated C-peptide) were assessed at baseline and after 6 months of insulin treatment. Results: Seventy-five newly diagnosed T2DM patients were enrolled in the study, of which 56 completed the study. At baseline a significant correlation was observed between fasting plasma glucagon and plasma glucose (r = 0.33, p = 0.04), insulin level (r = − 0.38, p = 0.004), and HOMA B (r = − 0.347, p = 0.009). After 6 months of insulin treatment, a significant (p = 0.001) change in glycemic status (− 35.28%), fasting glucagon level (− 45.84%), and an increase in fasting and meal stimulated C-peptide (144.44%) was observed. A significant inverse correlation between percentage change of plasma glucagon and plasma insulin was noted (r = − 0.282, p = 0.035). Conclusion: Among newly diagnosed T2DM patients with moderate to severe hyperglycemia fasting glucagon correlated positively with glycemic status and negatively with insulin levels at baseline. Early and intensive insulin treatment was associated with good glycemic control and improvement in glucagon and insulin levels. A modest reciprocal correlation was noted between α- and β-cell function in these patients. [ABSTRACT FROM AUTHOR]

Background: Osteocalcin (OC), also known as bone Gla (gamma-carboxyglutamic acid) protein, is a marker of bone formation. OC has effect on glucose and fat metabolism. Role of OC in type 2 diabetes mellitus (T2DM) is not well studied in Indian population. Our study aimed to see the relationship between OC and parameters of glucose metabolism in type 2 diabetes mellitus. Methods: This cross-sectional study included 120 subjects with T2DM. In each subject, fasting insulin, serum osteocalcin (measured by ELISA), fasting plasma glucose (FPG), post prandial plasma glucose (PPG), and glycated Hb (HbA1c) were measured. HOMA 2.0 model was used to measure insulin resistance (HOMA-IR) and β-cell function (HOMA-β). Then, serum osteocalcin levels were correlated with HOMA-IR, HOMA-β, FPG, PPG, and HbA1c. Results: Serum OC levels reduced with increase in insulin resistance (HOMA-IR) (r = −0.274, p = 0.004); however, there was no association with the beta cell function. OC had negative association with FPG (r = −0.14, p = 0.12) and PPG (r = −0.123, p = 0.18); however, it was statistically insignificant. Glycated hemoglobin (HbA1c) was significantly reduced in diabetic patients with higher OC levels (r = −0.208, p = 0.025). Conclusion: Serum OC has significant association with insulin resistance and HbA1c in subjects with T2DM, which might suggest possible role of serum OC in glucose metabolism in T2DM. [ABSTRACT FROM AUTHOR]

Mehani, a polyherbal formulation (PHF) containing five herbs has been used in the diabetes treatment for more than 20 years in India. Few data are available for its polypharmacological properties in treating interlinked diseases. Hence, the present study investigates the in vitro and in vivo antidiabetic and associated anti-inflammatory activity of Mehani. Glucose uptake activity of aqueous and hydroalcoholic extracts of PHF, individual herbs and sub fractionations (alkaloid, polyphenol) were evaluated in C2C12 mouse skeletal muscle cells. In vitro antidiabetic enzymatic assay, anti glycation activity was assessed for all the extracts. Active compounds were determined using HPLC analysis. Genes involved in glucose uptake and inflammatory pathways at mRNA level, GLUT4 protein expression and translocation were analyzed. Also, In vivo hypoglycemic, hypolipidemic and antioxidant activities were investigated in the best acting extracts in diabetic wistar rats. Aqueous (AQF) and polyphenolic (PPF) extracts showed insulin stimulated glucose uptake of 2.2±0.26 and 2.0±0.13 fold when compared to the untreated control. AQF exerted anti hyperglycemic action on GLUT4 via PI3K-AKT pathway, while PPF via AMPK pathway. Both inhibited the LPS induced activation of TNFα, IL6 and IL10 cytokines at mRNA level. Particularly, AQF showed increased GLUT4 protein expression and translocation. Gallic acid, cinnamic acid derivatives and D-pinitol (new finding) were the major bioactives identified through HPLC analysis. AQF (400 mg/kg b.w) treated diabetic rats showed significant reduction in blood glucose, HbA1c levels after 21 days of treatment. Increased serum cholesterol (67.5± 3.53 mg/dL), TGL (123.5±3.53) levels in diabetic rats were significantly reduced in AQF treated rats. Also, improvement in the antioxidant levels (SOD, CAT, GSH and GST) with reduction in liver enzymes was observed. AQF possessed hepatoprotective and renoprotective activities and efficiently restored the pancreatic beta cell integrity. To conclude, aqueous Mehani extract can be used as a safe, complimentary medicine to treat diabetes and associated diseases. [Display omitted] • The polypharmacological properties of Mehani formulation is investigated here • In vitro study shows that Aqueous (AQF) and polyphenolic (PPF) Mehani extract exerted anti-hyperglycemic action on GLUT4 via PI3K-AKT pathway and AMPK pathway respectively in C2C12 cells. Particularly AQF increased the GLUT4 expression and translocation. • Both inhibited the LPS induced activation of TNFα, IL6 and IL10 cytokines RAW 264.7 cells. • Gallic acid, cinnamic acid derivatives and D-pinitol (new finding) were the major bioactives identified through HPLC analysis • AQF (400 mg/kg b.w) possessed In vivo hypoglycemic, hypolipidemic and antioxidant activities in diabetic wistar rats. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disease that results from the destruction of pancreatic beta cells, leading to insulin deficiency. It is one of the most common chronic diseases in childhood, with an increasing incidence worldwide. Material and methods: Present Observational study was conducted at Department of Paediatrics, Dr.D.Y.Patil Medical College, Pimpri, Pune. Data was collected through medical record review and questionnaires completed by patients and their caregivers. The data collected included demographic information, clinical features, laboratory results, and treatment history. Results: In the present study, there were 6 (14.3%) diabetic children, 4 boys (16%) and 2 girls (11.8%) are products of third degree consanguineous marriage. The age of onset of Type 1 Diabetes mellitus in <6 year olds is 28.6%, in 6-10 year age group 54.8% and in children greater than 10 years, it is 7 percent. Polyuria, polydipsia and abdominal pain were the commonest symptoms observed in 38 (90.5%), 23 boys and 15 girls, 31 (73.8%), 18 boys and 13 girls and 30 (71.4%), 20 boys and 10 girls respectively. Altered sensorium was serious symptom observed in 4 boys and 3 girls, total 7 (16.7%). Fever in 17 (40.5%), vomiting in 16 (38.1%) and polyphagia in 15 (35.7%) were other important symptoms. Conclusion: Type 1 Diabetes Mellitus is one of the common chronic autoimmune disease in children, with rising prevalence in India, leading to major complications. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 diabetes mellitus (T1DM) is a long-standing metabolic disease caused by autoimmune beta cell destruction leading to absence or lowered insulin production. T1DM is associated with various other autoimmune disorders, including autoimmune thyroid disease, Celiac disease, and Addison disease. Detection of these antibodies is crucial to prevent morbidity related to unrecognized disease. Indian data regarding prevalence of these antibodies in T1DM is lacking, particularly antibodies against 21 hydroxylase. Patients and Methods: Total 100 patients with T1DM were taken into the study, in all patients anti-transglutaminase (anti-tTG) IgA, anti-thyroid peroxidase (anti-TPO) were done, and 21 hydroxylase anti bodies were done in 86 cases. Descriptive statistics were reported using mean, SD, numbers, and percentages. Student's t-test was used to assess the differences between the groups. Results: Fifteen cases were found to be TPOAb positive (eight had hypothyroidism, two had sub-clinical hypothyroidism, and five cases had normal thyroid function). tTGAb were positive in four cases, three were positive for 21-Hyroxylase antibody, and all had normal cortisol levels. Conclusion: Organ-specific autoimmune antibodies were elevated in T1DM when compared to general population. Screening of all these antibodies in T1DM patient should become standard of care. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) is a collective clinical entity that exacerbates metabolic syndrome (MetS). As the gold-standard test to quantify IR involves intravenous insulin loading and repeated blood glucose monitoring, many indices have been developed for IR assessment for convenience. This study tested the ideal cut-off values and clinical utility of IR indices in identifying MetS. Methods: We recruited 150 subjects, 75 MetS patients and 75 healthy controls, then obtained written informed consent to participate in this study. We collected fasting blood samples for glucose and lipid profiles and calculated nineteen indices of IR and insulin secretion using validated formulae. We determined the precision of these IR indices using the area under the curve (AUC) in a receiver operating characteristic analysis. Results: Subjects with MetS have significantly higher IR coupled with lower insulin sensitivity and beta-cell function than controls. Among the surrogate markers of IR tested, the homeostatic model assessment of insulin resistance (HOMA-IR), HOMA-adiponectin (HOMA-AD), triglyceride-glucose (TyG) index, HOMA-1%S (insulin sensitivity), quantitative insulin sensitivity check index (QUICKI), McAuley index, single-point insulin sensitivity estimator (SPISE), and HOMA-2%B (beta-cell function) showed the highest AUC values for detecting MetS. Conclusion: Our study results suggest that the ideal cut-off and AUC values identified for HOMA-IR, HOMA-AD, the TyG index, HOMA-1%S, QUICKI, the McAuley index, SPISE, and HOMA-2%B offer a clinical approach to the early detection and risk stratification for MetS among people in southern India. [ABSTRACT FROM AUTHOR]

Background: Data on prevalence and burden of end-organ damage in fibrocalculous pancreatic diabetes (FCPD) from eastern India is scant. This study investigated the burden of end-organ damage and exocrine pancreatic defect in FCPD patients in Eastern India. Materials and Methods: Consecutive FCPD patients underwent evaluation of glycemic control, C-peptide, fecal elastase, body fat percent, tests for cardiac autonomic neuropathy (CAN), neuropathy, nephropathy, and retinopathy which were compared with data from type-1 diabetes (T1DM) and type-2 diabetes (T2DM). Results: Data from 101 FCPD, 41 T1DM, 40 T2DM, and 40 controls were analyzed. Body fat percent was lowest in FCPD and T1DM. Similarly, fasting and stimulated C-peptide was significantly lowest in T1DM, followed by FCPD. Significant elevations in stimulated C-peptide were observed in FCPD. Fecal elastase was lowest in FCPD. Exocrine pancreas defect in FCPD, T1DM, and T2DM was 100%, 53.66%, 27.5%, respectively. HbA1c was worst in FCPD. About 40% of FCPD patients had CAN while 13.33% had borderline CAN. Isolated parasympathetic dysfunction was the commonest (66.67%) among them. FCPD patients with CAN had lower fecal elastase, higher HbA1c, microalbuminuria, steatorrhea, neuropathy, retinopathy, and nephropathy, compared to those without CAN. On binary logistic regression, diabetes duration was a significant predictor of end-organ damage in FCPD. Fecal elastase and body fat percent were independent predictors for insulin therapy in FCPD. Conclusion: CAN is common in FCPD while exocrine pancreas defect is most severe in FCPD followed by T1DM and T2DM. Fecal elastase has an important prognostic role for insulinization in FCPD. Role of pancreatic enzyme replacement on glycemic control in diabetes with exocrine pancreas defect needs investigation. [ABSTRACT FROM AUTHOR]

Context: Tamarindus indica L. (Leguminosae) is widely used as a traditional medicine for the management of diabetes mellitus (DM) in India, in addition to its anti-inflammatory activity. The present study has been designed to understand the correlation involved between antidiabetic and anti-inflammatory action of aqueous seed extract of T. indica (TSE) in diabetic rats. Objective: In view of the fact that fatty acid synthesis and insulin release from islets of pancreas are regulated by sterol regulatory element-binding proteins (SREBP-1c) and cytosolic calcium, respectively, the objectives of present study were to determine the influence of TSE on SREBP-1c mRNA and to investigate the intracellular islets calcium [Ca2+]I involvement and β -cell mass preservation in insulin secretagogue action of TSE. Materials and methods: The effect of 4 weeks oral treatment (120 and 240 mg/kg) of high-performance liquid chromatography (HPLC) standardized TSE was studied in streptozotocin (STZ)-induced diabetic male Wistar rats. Reverse transcription-PCR (RT-PCR) and a spectrofluorometer were used for mRNA concentration and islets [Ca2+]I determination, respectively. The TUNEL assay was followed to study the pancreatic apoptosis. Results: TSE (120 and 240 mg/kg) showed positive correlation with [Ca2+]I and insulin release. The anti-inflammatory action of TSE was significant on nitric oxide (NO) and tumor necrosis factor-α (TNF-α) in addition to a favorable effect on β -cell neogenesis and improved mRNA concentration of SREBP-1c. Discussion and conclusion: The results suggest that anti-inflammatory action of Tamarind seeds on β -cell cells of islets and cytokines contribute toward its antidiabetic activity by way of complex mechanisms of [Ca2+]I handling and through SREBP-1c gene in liver. [ABSTRACT FROM AUTHOR]

[Display omitted] • GPR119 agonist based analogues for treating Diabetes mellitus. • Modifying GPCR activity for modern drug development. • Future perspectives and directions were discussed. Diabetes mellitus type 2 (T2D) is a group of genetically heterogeneous metabolic disorders whose frequency has gradually risen worldwide. Diabetes mellitus Type 2 (T2D) has started to achieve a pandemic level, and it is estimated that within the next decade, cases of diabetes might get double due to increase in aging population. Diabetes is rightly called the 'silent killer' because it has emerged to be one of the major causes, leading to renal failure, loss of vision; besides cardiac arrest in India. Thus, a clinical requirement for the oral drug molecules monitoring glucose homeostasis appears to be unmet. GPR119 agonist, a family of G-protein coupled receptors, usually noticed in β-cells of pancreatic as well as intestinal L cells, drew considerable interest for type 2 diabetes mellitus (T2D). GPR119 monitors physiological mechanisms that enhance homeostasis of glucose, such as glucose-like peptide-1, gastrointestinal incretin hormone levels, pancreatic beta cell-dependent insulin secretion and glucose-dependent insulinotropic peptide (GIP). In this manuscript, we have reviewed the work done in the last five years (2015–2020) which gives an approach to design, synthesize, evaluate and study the structural activity relationship of novel GPR119 agonist-based lead compounds. Our article would help the researchers and guide their endeavours in the direction of strategy and development of innovative, effective GPR119 agonist-based compounds for the management of diabetes mellitus type 2. [ABSTRACT FROM AUTHOR]

The article presents a calendar of conferences of the American Diabetes Association (ADA), scheduled from September 2006 to June 2007. The Consensus Conference on IFG and IGT: Implications for Diabetes Care will be held in Chicago, Illinois. The Clinical Research Symposium on Beta-Cell Function will be held in Chicago. The Third Madras Diabetes Research Foundation-ADA Postgraduate Course on Diabetes will be held in Chennai, India.