Expert Opinion by Clinicians on the Use of Insulin Therapy in People with Hepatic Impairment.

People with type 2 diabetes mellitus (T2DM) have a higher risk of developing chronic liver disease (CLD) and its complications. T2DM, obesity, and insulin resistance are all strongly associated with nonalcoholic fatty liver disease (NAFLD). Conversely, people suffering from cirrhosis have reduced glucose tolerance in approximately 60% of cases, diabetes in 20% of cases, and insulin-mediated glucose clearance is lowered by 50% as compared with those who do not have cirrhosis. An exploratory review was conducted using existing published evidence from clinical studies on dosing and titrations of individual insulin formulations in people with CLD to optimize insulin dosage titration for minimizing hypoglycemia risk.pThis article discusses current hyperglycemia treatment techniques for patients with CLD as well as the consensus recommendations on insulin use in special populations with T2DM and hepatic impairment. Based on available evidence and expert diabetologists' recommendations, careful insulin dose titration, customized glycemic targets, and frequent glucose screening are recommended for optimal glycemic management without hypoglycemia in CLD. Long-acting insulin should be avoided or used when short-acting insulin fails to provide adequate glycemic control with raised fasting blood sugar levels. While the patient's glucose profile is being evaluated, the prandial insulin dose can be lowered by 25% initially. The dose can be titrated based on the patient's postprandial glycemic expression and whether their food intake meets the Child-Pugh scores A and B categories. Titrating premixed insulins is difficult for patients in class C since their appetite and overall health are constantly compromised and in flux.

Prescribing Patterns and Response to Antihyperglycemic Agents Among Novel Clusters of Type 2 Diabetes in Asian Indians.

Aim: To assess the prescribing patterns and response to different classes of antihyperglycemic agents in novel clusters of type 2 diabetes (T2D) described in India. Materials and Methods: We attempted to replicate the earlier described clusters of T2D, in 32,867 individuals with new-onset T2D (within 2 years of diagnosis) registered between October 2013 and December 2020 at 15 diabetes clinics located across India, by means of k-means clustering utilizing 6 clinically relevant variables. Individuals who had follow-up glycated hemoglobin (HbA1c) up to 2 years were included for the drug response analysis (n = 13,247). Results: Among the 32,867 participants included in the study, 20,779 (63.2%) were males. The average age at diagnosis was 45 years and mean HbA1c at baseline was 8.9%. The same four clusters described in India earlier were replicated. Forty percent of the study participants belonged to the mild age-related diabetes cluster, followed by insulin-resistant obese diabetes (27%), severe insulin-deficient diabetes (21%), and combined insulin-resistant and insulin-deficient diabetes (12%) clusters. The most frequently used antihyperglycemic agents were sulfonylureas, metformin, and dipeptidyl peptidase-4 inhibitors apart from insulin. While there were significant differences in HbA1c reduction between drugs across clusters, these were largely driven by differences in the baseline (pretreatment) HbA1c. Conclusions: In this new cohort, we were able to reliably replicate the four subtypes of T2D earlier described in Asian Indians. Prescribing patterns show limited usage of newer antihyperglycemic agents across all clusters. Randomized clinical trials are required to establish differential drug responses between clusters.

Type 2 Diabetes in Women: Differences and Difficulties.

BACKGROUND: Lifestyle modification, along with medication, has improved the quality of life of patients with type 2 diabetes (T2D), but the treatment of diabetes in women still lacks a gender-centric approach. METHODS: Expert opinions to improve diabetes management in women were collated from the open discussion forum organized by the sixth Jothydev's Professional Education Forum Diabetes Convention, which included global diabetes care experts and the general public. The review is also based on the studies published in electronic databases such as PubMed and Google Scholar that discussed the problems and challenges faced by the Indian diabetes care sector in treating women with diabetes. RESULTS: The complex interplay of biological, socioeconomic, psychosocial, and physiological factors in women with type 2 diabetes has not been well addressed to date. Biological factors such as neurohumoral pathways, sex hormones, genetic predisposition as well as gender-based environmental and behavioural differences must be considered for modern personalized diabetes treatment. Most importantly, pregnant women with diabetes deserve special attention. This vulnerable phase has a marked impact on the future health of both the mother and the offspring. CONCLUSION: The review provides an overview of the challenges and issues that exist in the clinical management of diabetes and its complications among women in India. Women-centric clinical approaches should be encouraged for the effective management of diabetes in Indian women.

Hypoglycemia at the time of Covid-19 pandemic.

BACKGROUND: Hypoglycemia is the limiting factor in the glycemic management of diabetes, which need to be addressed critically to avoid complications. Lockdown because of new coronavirus strain (COVID-19) pandemic has further complicated the issue of hypoglycemia due to limitations in access to food, outpatient clinics, pathological services and medicines. AIM: To assess the factors associated with the risk of hypoglycemia during April-May 2020 lockdown in people with type 2 diabetes mellitus. METHODOLOGY: We analyzed the data retrospectively from 146 patients of type 2 diabetes mellitus (T2DM) reporting to the emergency department (ED) during lockdown period with symptoms suggestive of hypoglycemia. RESULTS: The majority of patients were male (90/146) with a mean age of 59.88 ± 10.09 years and a mean random blood glucose level of 57.67 ± 9.00 mg/dL. Two-third of patients (70.83%) had level 1 hypoglycemia, while level 2 hypoglycemia was reported in 29.16% of patients. A combination of Metformin and Sulfonylureas (SU) was most commonly associated with the risk of hypoglycemia (65.75%) followed by insulin (33.56%). Subjects who received insulin reported a lower blood glucose value (50.75 ± 8.20 mg/dL) as compared to those receiving a combination of metformin and SU (60.95 ± 7.10 mg/dl). 330.56% of patients who had received prophylaxis hydroxychloroquine (HCQ) 400 mg twice a day along with the routine anti-hyperglycemic agents without their dose adjustment reported hypoglycemia. Patients with hypertension, micro-vascular, macro-vascular complications, and coexistent with each other had a higher propensity to the risk of hypoglycemia (46.58%, 33.56%, 23.29%, and 32.88%) respectively. CONCLUSION: The COVID-19 lockdown has shown to influence the risk of hypoglycemia in patients with T2DM, especially those receiving SU, insulin, HCQ especially in patients with associated co-morbidities. Patient education, support, and telemedicine plays a pivotal role to prevent hypoglycemia.

Management of periodontal disease in patients with diabetes- good clinical practice guidelines: A joint statement by Indian Society of Periodontology and Research Society for the Study of Diabetes in India.

There is a huge body of literature suggesting an association and a bidirectional relationship between periodontal disease and diabetes. Diabetes and periodontal diseases are both chronic diseases with a high prevalence. Dentists/periodontists, in their daily clinical practice, very often attend to diabetes patients with diverse oral health conditions and cater to their dental treatment needs. Safe and effective periodontal therapy in this population requires a broad understanding of diabetes, medical management of diabetes, and essential modifications to dental/periodontal therapy that may be required. This paper describes a joint statement put forth by the Indian Society of Periodontology and the Research Society for the Study of Diabetes in India aiming to provide expert consensus and evidence-based guidelines for optimal clinical management of periodontal conditions in diabetes patients or patients at risk for diabetes. Although this paper is not envisioned to be a comprehensive review of this topic, it intends to provide the guidelines for dental professionals and periodontists.

A phase II, single-arm, open-label, multicenter study to evaluate the efficacy and safety of P276-00, a cyclin-dependent kinase inhibitor, in patients with relapsed or refractory mantle cell lymphoma.

INTRODUCTION: Overexpression of cyclin D1 is a hallmark feature of mantle cell lymphoma (MCL). Many of the oncogenic effects of cyclin D1 are mediated through cyclin-dependent kinases (CDKs). P276-00 is a potent small molecule inhibitor of CDK4-D1, CDK1-B, and CDK9-T, with promising activity in preclinical models. In phase I studies of P276-00 in patients with refractory solid neoplasms, it was well-tolerated with a mild trend toward single-agent efficacy. PATIENTS AND METHODS: A phase II study of P276-00 was conducted in patients with relapsed or refractory MCL at the recommended dose of 185 mg/m(2)/day from days 1 to 5 of a 21-day cycle. Thirteen patients were enrolled in the present study. RESULTS: Of the 13 patients, 11 experienced disease progression, 1 patient was withdrawn because of an adverse event (AE), and 1 patient died. Also, 11 patients (84.6%) experienced a treatment-emergent AE deemed related to P276-00. Of the 13 patients, 9 (69.2%) received ≥ 2 cycles of treatment, which was the predefined threshold to be evaluable for efficacy. Treatment was discontinued early in 2 patients because of AEs (1 of which was attributed to P276-00 administration) and in 2 patients because of disease progression. Finally, 2 patients experienced stable disease for an estimated median duration of 60.5 days (range, 58-63 days). The estimated median time to progression for the predefined efficacy population was 43 days (range, 38-58 days). CONCLUSION: Given the results observed in the present study, if evaluation of CDK inhibition in MCL continues, it should be considered earlier in the disease course or as a part of combination strategies for relapsed or refractory disease.