Review on the role of nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome pathway in diabetes: mechanistic insights and therapeutic implications.

This review explores the pivotal role of the nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in the pathogenesis of diabetes and its complications, highlighting the therapeutic potential of various oral hypoglycemic drugs targeting this pathway. NLRP3 inflammasome activation, triggered by metabolic stressors like hyperglycemia, hyperlipidemia, and free fatty acids (FFAs), leads to the release of pro-inflammatory cytokines interleukin-1ß and interleukin-18, driving insulin resistance, pancreatic ß-cell dysfunction, and systemic inflammation. These processes contribute to diabetic complications such as nephropathy, neuropathy, retinopathy, and cardiovascular diseases (CVD). Here we discuss the various transcriptional, epigenetic, and gut microbiome mediated regulation of NLRP3 activation in diabetes. Different classes of oral hypoglycemic drugs modulate NLRP3 inflammasome activity through various mechanisms: sulfonylureas inhibit NLRP3 activation and reduce inflammatory cytokine levels; sodium-glucose co-transporter 2 inhibitors (SGLT2i) suppress inflammasome activity by reducing oxidative stress and modulating intracellular signaling pathways; dipeptidyl peptidase-4 inhibitors mitigate inflammasome activation, protecting against renal and vascular complications; glucagon-like peptide-1 receptor agonists attenuate NLRP3 activity, reducing inflammation and improving metabolic outcomes; alpha-glucosidase inhibitors and thiazolidinediones exhibit anti-inflammatory properties by directly inhibiting NLRP3 activation. Agents that specifically target NLRP3 and inhibit their activation have been identified recently such as MCC950, Anakinra, CY-09, and many more. Targeting the NLRP3 inflammasome, thus, presents a promising strategy for managing diabetes and its complications, with oral hypoglycemic drugs offering dual benefits of glycemic control and inflammation reduction. Further research into the specific mechanisms and long-term effects of these drugs on NLRP3 inflammasome activity is warranted.

An overview of therapeutic options of obesity management in India: the Integrated Diabetes and Endocrinology Academy (IDEA) 2023 Congress update.

INTRODUCTION: With newer anti-obesity medications (AOMs) being introduced at a rapid pace, it is prudent to make a concise and updated clinical practice document that may help busy clinicians in daily clinical practice. A group of metabolic physicians, diabetologists, endocrinologists, and bariatric surgeons assembled during the Integrated Diabetes and Endocrine Academy 2023 Congress (IDEACON, July 2023, Kolkata, India) to compile an update of pharmacotherapeutic options for managing people with obesity in India. AREAS COVERED: After an extensive review of the literature by experts in different domains, this update provides all available information on the management of obesity, with a special emphasis on both currently available and soon-to-be-available AOMs, in people with obesity. EXPERT OPINION: Several newer AOMs have been shown to reduce body weight significantly, thus poised to make a paradigm shift in the management of obesity. While the tolerability and key adverse events associated with these AOMs appear to be acceptable in randomized controlled trials, pharmacovigilance is vital in real-world settings, given the absence of sufficiently long-term studies. The easy availability and affordability of these drugs is another area of concern, especially in developing countries like India.

Analysing uric acid levels to assess the effectiveness of dapagliflozin.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors are an innovative diabetes treatment that lowers blood sugar levels without insulin. A growing body of evidence suggests that blood sugar levels are tightly correlated with uric acid levels in their blood and urine. To alleviate type 2 diabetes (T2DM) suffering, we tested dapagliflozin on serum and urinary uric acid levels of patients with T2DM and measured its efficacy in reducing uric acid levels. METHODS: A study was conducted on 60 people with T2DM. Patients were treated with Dapagliflozin doses of 10 mg daily for 3 months. Three months later, we measured body weight, fasting, and postprandial blood glucose levels, Hemoglobin A1C (HbA1c), serum lipids, renal function tests, routine urine, and serum uric acid. RESULTS: A number of clinical parameters of T2DM patients were compared to those of healthy subjects of the same age group. A comprehensive analysis of all parameters was conducted to evaluate dapagliflozin's impact. After 90 days of dapagliflozin treatment, serum uric acid levels dropped significantly from 9.0 to 8 mg/dL in the dapagliflozin group, as well as uric acid percentage in urine changed from 16.1 to 23.6 %. After three months of treatment, HbA1C levels decreased from 9.8 % to 8.5 %. CONCLUSION: Following treatment with dapagliflozin, the patients' Homeostatic Model Assessment for Insulin Resistance decreased to 4.0. Further, multivariate correlation analysis showed a correlation of serum uric acid with glycemic profile positively. In conclusion, dapagliflozin lowers uric acid levels and increases insulin sensitivity in diabetic patients to improve their glycemic control.

Study of Neurocognitive Function in Type 2 Diabetes Mellitus Patients Using P300 Event-Related Potential.

BACKGROUND: Diabetes mellitus is the most prevailing metabolic disease. It causes structural and functional alterations in several organs, including the central nervous system. Altered glucose metabolism, atherosclerosis, and inflammation of blood vessels are seen in diabetes. This may lead to neuronal degeneration and decline in cognition. Event-related potential P300 can detect cognitive decline before the emergence of obvious neurological manifestations. OBJECTIVE: The aim of this study is to assess and compare the P300 latencies in subjects with type 2 diabetes mellitus and in nondiabetic subjects and to determine the influence of type 2 diabetes mellitus on cognitive functions. MATERIALS AND METHODS: In this study our sample size was 248 subjects, with type 2 diabetes mellitus patients (n = 124) and healthy controls (n = 124) between the age group of 31 and 60 years. This cross-sectional comparative study was conducted at SRM Medical College Hospital and Research Centre. The subjects were evaluated by a structured interview and they were assessed with a general health questionnaire to rule out any subpsychiatric illness. Fasting and postprandial blood glucose, HbA1c level, lipid profile, and creatinine were estimated. P300 amplitude and peak latencies were recorded using the standard auditory oddball paradigm. RESULTS: The latencies of P300 were significantly increased and the amplitude of P300 was significantly reduced in the diabetic group when compared to the control group (P < .001). P300 latency has a positive correlation with the HbA1c levels (r = 0.136) and the duration of diabetes (r = 0.231). CONCLUSION: Prolongation of P300 latencies and the decreased amplitude in diabetic subjects may suggest the existence of a cognitive decline in individuals with type 2 diabetes compared to healthy individuals.