Background The aim of this meta‐analysis was to determine the association of common type 1 diabetes (T1D) and type 2 diabetes (T2D) gene variants (protein tyrosine phosphatase non‐receptor 22 [PTPN22] rs2476601C/T, insulin [INS] rs689A/T and transcription factor 7‐like 2 [TCF7L2] rs7903146C/T) with latent autoimmune diabetes in adults (LADA). Methods A systematic search of electronic databases was conducted up to 2017 and data from 16 independent case‐control studies for three gene variants were pooled. The pooled allele and genotype frequencies for each T1D and T2D gene variant were used to calculate odds ratios (ORs) with 95% confidence intervals (CIs) to assess the strength of the association. Heterogeneity tests and evaluation of publication bias were performed for all studies. Results In all, 8869 cases and 20 829 controls pooled from 16 case‐control studies were included in the analysis. For rs2476601, a significant association was found for homozygote TT (OR 2.67; 95% CI 1.92‐3.70; P < 0.0001), heterozygote CT (OR 1.61; 95% CI 1.44‐1.79; P < 0.0001), and the T allele (OR 1.62; 95% CI 1.48‐1.78; P < 0.0001). Overall, a significant inverse association was observed for rs689 in the TT genotype (OR 0.43; 95% CI 0.30‐0.64; P < 0.0001), AT genotype (OR 0.53; 95% CI 0.45‐0.62; P < 0.0001), and T allele (OR 0.61; 95% CI 0.52‐0.71; P < 0.0001). For the rs7903146 polymorphism, the T allele (OR 1.19; 95% CI 1.00‐1.40; P = 0.04) may be associated with the risk of LADA. Conclusion The rs2476601C/T, rs689A/T, and rs7903146C/T polymorphisms were found to be associated with the risk of LADA, thereby indicating that, genetically, LADA could be an admixture of both T1D and T2D.

The process of carcinogenesis and its progression involves an intricate interplay between a number of signaling networks, metabolic pathways and the microenvironment. These include an alteration in the cellular redox metabolism and deregulation of cell cycle checkpoints. Similar to the dichotomy of redox signaling in cancer cell fate and state determination, a diverging effect of an irreversible cell cycle arrest or senescence on carcinogenesis has been demonstrated. In this regard, while overwhelming oxidative stress has a damaging effect on tissue architecture and organ function and promotes death execution, a mild “pro‐oxidant” environment is conducive for cell proliferation, growth and survival. Similarly, cellular senescence has been shown to elicit both a tumor suppressor and an oncogenic effect in a context‐dependent manner. Notably, there appears to be a crosstalk between these two critical regulators of cell fate and state, particularly from the standpoint of the divergent effects on processes that promote or abate carcinogenesis. This review aims to provide an overview of these overarching themes and attempts to highlight critical intersection nodes, which are emerging as potential diagnostic and/or therapeutic targets for novel anticancer strategies.

Further genetic association studies on a larger number of IRSA couples, as well as evaluation of more MMP polymorphisms and their expression profiling are needed to establish the potential role of MMP polymorphisms in IRSA.

To assess the burden of type 2 diabetes (T2D) and its genetic profile in endogamous populations of India given the paucity of data, we aimed to determine the prevalence of T2D and estimate its heritability using family-based cohorts from three distinct Endogamous Ethnic Groups (EEGs) representing Northern (Rajasthan [Agarwals: AG]) and Southern (Tamil Nadu [Chettiars: CH] and Andhra Pradesh [Reddys: RE]) states of India. For comparison, family-based data collected previously from another North Indian Punjabi Sikh (SI) EEG was used. In addition, we examined various T2D-related cardiometabolic traits and determined their heritabilities. These studies were conducted as part of the Indian Diabetes Genetic Studies in collaboration with US (INDIGENIUS) Consortium. The pedigree, demographic, phenotypic, covariate data and samples were collected from the CH, AG, and RE EEGs. The status of T2D was defined by ADA guidelines (fasting glucose ≥ 126 mg/dl or HbA1c ≥ 6.5% and/or use of diabetes medication/history). The prevalence of T2D in CH (N = 517, families = 21, mean age = 47y, mean BMI = 27), AG (N = 530, Families = 25, mean age = 43y, mean BMI = 27), and RE (N = 500, Families = 22, mean age = 46y, mean BMI = 27) was found to be 33%, 37%, and 36%, respectively, Also, the study participants from these EEGs were found to be at increased cardiometabolic risk (e.g., obesity and prediabetes). Similar characteristics for the SI EEG (N = 1,260, Families = 324, Age = 51y, BMI = 27, T2D = 75%) were obtained previously. We used the variance components approach to carry out genetic analyses after adjusting for covariate effects. The heritability (h2) estimates of T2D in the CH, RE, SI, and AG were found to be 30%, 46%, 54%, and 82% respectively, and statistically significant (P ≤ 0.05). Other T2D related traits (e.g., BMI, lipids, blood pressure) in AG, CH, and RE EEGs exhibited strong additive genetic influences (h2 range: 17% [triglycerides/AG and hs-CRP/RE] - 86% [glucose/non-T2D/AG]). Our findings highlight the high burden of T2D in Indian EEGs with significant and differential additive genetic influences on T2D and related traits.

Introduction: To harmonise the diagnostic processes of polycystic ovary syndrome (PCOS) and enable clinicians to provide better patient care, it is critical to understand the knowledge gaps in PCOS diagnosis. We evaluated how clinicians in endocrinology, family medicine, general practice and gynaecology diagnose PCOS. Methods: This cross-sectional survey involved 208 clinicians from specific subspecialties across various healthcare settings in Singapore. Results: A total of 160 responses were included in the final analysis. Among all the diagnostic criteria, the Rotterdam 2003 criteria was most frequently used (66.3%). More than half of the gynaecologists reported having a standardised workplace protocol while the majority from other specialties reported otherwise. A large percentage of respondents (60.5%) were unable to identify the correct PCOS clinical features, which is concerning. Only 8.8% of respondents used clinical and biochemical hyperandrogenism, menstrual disturbances and pelvic ultrasound to diagnose PCOS without performing unnecessary and incorrect investigations. Most clinicians recognised insulin resistance/type 2 diabetes mellitus and fertility problems as complications while only a few recognised psychological complications. Many clinicians (37.3%) sought standardisation of PCOS diagnosis and management guidelines for improvement in PCOS care and 81.9% of respondents would appreciate standardised educational materials. Conclusion: This is the first study to the best of our knowledge that gives an insight into the diagnostic and management processes of PCOS among various healthcare institutions in Singapore. This study calls for greater harmonisation of diagnostic processes and holistic evidence-based management of patients with PCOS through standardised workplace protocols and patient education resources. Keywords: Diabetes, endocrinology, family medicine, obstetrics and gynaecology, polycystic ovary syndrome, public health