Environmental modulators of type 1 diabetes mellitus

In genetically susceptible subjects, type 1 diabetes (T1D) appears to be a chronic immune- mediated disease with a subclinical prodromal period characterized by selective loss of insulin-releasing pancreatic beta cells. However, only a relatively small proportion of genetically susceptible subjects progress to clinical disease, which indicates that environmental factors are needed to trigger and drive the disease process in genetically predisposed subjects. In this article we provide a selective review on environmental factors involved in the pathogenesis of T1D. Accumulating evidence suggests that the proportion of subjects with high-risk human leukocyte antigen (HLA) genotypes has decreased over the last decades among patients with newly diagnosed T1D, whereas the proportion of those with low-risk or even protective HLA genotypes has increased. These findings indicate that increased environmental pressure is responsible for progression to clinical diabetes in patients with less genetic predisposition. The birth cohort studies indicate that the first signs of beta cell autoimmunity may be induced during infancy before age 3, which implies that dietary factors for beta cell autoimmunity and T1D may be active in that time period, during which early nutrition provides essential exogenous exposure. Progression to clinical T1D typically needs the combination of genetic disease susceptibility, a diabetogenic trigger, and a high exposure to a driving antigen. The triggers appear to be enteroviruses and rotaviruses as well as components of the infant diet including cows milk and gluten, while the Mediterranean diet appears protective. The only definite enterovirus responsible for T1D is congenital rubella, which may be complicated by late development of T1D. There is a temporal association between enteroviral infection and future development of antibodies resulting in T1D. Clinical studies indicate that islet cell antibodies develop 3 months after birth and seroconversion of enterovirus RNA in serum to antibodies occurs more significantly in subjects with T1D compared to controls. Omega-3 fatty acids, cocoa flavonoids, sour milk and cottage cheese have been found to be protective against autoimmunity in T1D. These foods likely promote the gut microbiome, which is deteriorated by the Western diet resulting in an increased production of lipid mediators; protectin, and resolving lipoxins, which are anti-inflammatory

The efficacy of Tadalafil and Tadalafil + Dapoxetine in managing sexual dysfunction in individuals with type-2 diabetes mellitus: A clinical study

Objective: The present study was aimed to evaluate effect of metabolic parameters on erectile dysfunction (ED) in individuals with type-2 diabetes mellitus (T2DM) and to assess the efficacy of Tadalafil and Tadalafil + Dapoxetine combination. Materials and Methods: A prospective, observational, cross-sectional, bicentric study included 216 males with T2DM who are not treated with phosphodiesterase 5 inhibitors and without chronic kidney disease. The data were obtained from demographic questionnaire, clinical laboratory reports of glycometabolic parameters namely body mass index (BMI), hemoglobin A1c (HbA1c), testosterone, vitamin B12 (VitB12), and lipid profile and analyses of the International Index of Erectile Function (IIEF) questionnaire. The effect of physical and metabolic parameters on IIEF sub-domains namely erectile function; orgasmic function; sexual desire (SD); intercourse satisfaction; and overall satisfaction was evaluated. A statistical significance was evaluated using χ2 test or t-test. Result: SD is most significantly lower in subjects with imbalanced physiological and metabolic characteristics including BMI, HbA1c, testosterone, VitB12, triglyceride, high-density lipoprotein, and low-density lipoprotein. Both Tadalafil and Tadalafil + Dapoxetine significantly improved almost all IIEF parameters without any pronounced effect of either. Similarly, both the treatments improved all the IIEF parameters for subjects with high BMI except for SD. In subjects with cardiac comorbidities, the use of either treatment significantly enhanced all the IIEF scores. Conclusion: The findings of this study outline the need of careful examination of sexual dysfunction in healthcare clinics for diabetic individuals. An imbalanced physiological and metabolic profile leads to ED in individuals with T2DM. Additionally, the presence of co-morbidities further elevates the odds of ED prevalence. The treatment with Tadalafil and Tadalafil + Dapoxetine drug combination shows promising results in improving the ED but a study with larger pool of subjects is needed to determine the additional benefits of Dapoxetine

Type 1 diabetes registry in developing countries: Perspective from India

India has been a prey to rising tide of non-communicable diseases. It is becoming increasingly important to evolve strategies to ensure effective prevention, diagnosis and treatment of this rising burden. Available Indian data reveal different opinions regarding type 1 diabetes (T1D). Such variation in data leads to uncertainty in healthcare planning and management. This ununiformity in data and the absence of protocol make a task challenging. Many patients consult non-specialists and even doctors from different streams. On the part of the patients, the diagnostic and screening testing are a great burden. T1D registry is of great relevance to India. It helps in ensuring good clinical practice and errors. Endocrinologists and paediatricians can audit themselves using such a registry. The overall goal is to improve population health. The objective is to reduce morbidity and mortality while maximising the cost-effectiveness. Such a registry helps in fund allocation and healthcare planning and contributes to the formulation of pragmatic management guidelines. However, healthcare professionals are reluctant to share their data. This may be due to fear of being audited by peers or regulators and record maintenance. We must work towards creating a national registry of T1D. This should involve multiple centres across the country, as it will help enhance awareness about T1D and improve standard of care. The results of which can be used to advocate for greater allocation of resources to T1D care. An effective registry will help children claim their rightful place under the sun

Possibilities and challenges of a large international benchmarking in pediatric diabetology-The SWEET experience

Aim: Despite the existence of evidence-based guidelines for the care of children with diabetes, widespread gaps in knowledge, attitude, and practice remain. The purpose of this paper is to present a review of benchmarking practices and results of this process within SWEET, moreover focusing on current challenges and future directions. Methods: Biannually, members electronically transfer de-identified clinic data for 37 parameters to the SWEET database. Each center receives benchmarking and data validation reports. Results: In 2015, 48 centers have contributed data for 20 165 unique patients (51.6% male). After exclusion for missing data 19 131 patients remain for further analysis. The median age is 14.2 years, with a median diabetes duration 4.8 years; 96.0% of patients have type 1, 1.1% type 2, and 2.9% other diabetes types. Data completeness has increased over time. In 2015, median HbA1c of all patients’ (diabetes type 1) medians was 7.8% (61.7 mmol/mol) with 39.1%, 41.4%, and 19.4% of patients having HbA1c < 7.5% (58 mmol/mol), 7.5%-9% (58-75 mmol/mol) and >9% (75 mmol/mol), respectively. Although HbA1c has been stable over time [7.7%-7.8% (60.7-61.7 mmol/mol)], there remains wide variation between centers. Fourteen centers achieve a median HbA1c < 7.5% (58 mmol/mol). Conclusions: Our vision is that the participation in SWEET is encouraging members to deliver increasingly accurate and complete data. Dissemination of results and prospective projects serve as further motivation to improve data reporting. Comparing processes and outcomes will help members identify weaknesses and introduce innovative solutions, resulting in improved and more uniform care for patients with diabetes

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study

Objective To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET). Methods Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included. World Health Organization growth charts were used to calculate height and body mass index z-scores. Multiple hierarchic regression models adjusting for known confounders were applied. Results Data on 22 941 subjects (51.8% male) were analyzed with a median and interquartile range for age 14.8 years (11.2, 17.6), diabetes duration 5.6 years (3.1, 8.9), and height z-score 0.34 (-0.37, 1.03). Children were taller in the youngest age groups: adjusted height z-scores of 0.31 (+/- 0.06) and 0.39 (+/- 0.06), respectively; with shorter diabetes duration (<2 years: 0.36 [+/- 0.06]; 2-<5 years: 0.34 [+/- 0.06]; >= 5 years: 0.21 [+/- 0.06]) and if they were pump users: 0.35 +/- 0.05 vs 0.25 +/- 0.05 (>three injections/day and 0.19 +/- 0.06 [0-3 injections daily]), respectively. High hemoglobin A1c (HbA1c) and low to normal weight were associated with a lower height z-score. Trends were identical in all models except for gender. No gender differences were found except in the final height model where females exhibited higher z-score than males. Conclusion For youths treated at centers offering modern diabetes management, major growth disturbances are virtually eliminated. For children with a young age at onset, high HbA1c, injections, and/or non-intensive diabetes, treatment still requires attention in order to attain normal growth

Efficacy and safety of fixed dose combination of Sitagliptin, metformin, and pioglitazone in type 2 Diabetes (IMPACT study): a randomized controlled trial

Abstract Background Due to the progressive decline in β-cell function, it is often necessary to utilize multiple agents with complementary mechanisms of action to address various facets and achieve glycemic control. Thus, this study aimed to evaluate the efficacy and safety of a fixed-dose combination (FDC) of metformin/sitagliptin/pioglitazone (MSP) therapy vs. metformin/sitagliptin (MS) in type 2 diabetes mellitus (T2DM). Methods In this phase 3, multicenter, double-blind study, patients with T2DM who exhibited inadequate glycemic control with HbA1c of 8.0–11.0% while taking ≥1500 mg/day metformin for at least 6 weeks were randomized to receive either FDC of MSP (1000/100/15 mg) or MS (1000/100 mg) per day for 24 weeks. The primary outcome measure was the change in HbA1c, and secondary outcomes included changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), and body weight from baseline to 24 weeks along with safety and tolerability. Results Among the 236 patients randomized, 207 (87.71%) successfully completed the study. All baseline characteristics were comparable between the FDC of MSP and MS groups. There was a subsequent significant reduction of HbA1c in FDC of MSP (− 1.64) vs. MS (− 1.32); between groups was [− 0.32% (95% CI, − 0.59, − 0.05)], P = 0.0208. Similar reductions were found in FPG [− 13.2 mg/dL (95% CI, − 22.86, − 3.71)], P = 0.0068, and PPG [− 20.83 mg/dL (95% CI, − 34.11, − 7.55)], P = 0.0023. There were no significant changes in body weight. A total of 27 adverse effects (AEs) and one severe AE were reported, none of which were related to the study drug. Conclusion The FDC of MSP demonstrated significant efficacy in managing glycemic indices and could serve as a valuable tool for physicians in the management of Indian patients with T2DM. Trial registration Clinical Trials Registry of India, CTRI/2021/10/037461