Pre-Basal Insulin Analog Era: Paving the Way for Modern Day Basal Insulins.

Prior to the discovery of insulins, diabetes was managed predominantly by dietary interventions. Discovery of insulin and its first human trial highlighted the need for higher purity insulin thereby steering the subsequent journey of insulin development. Considering the limitations of the early preparations like short duration of action and need for several injections per day, attempts at protracting the duration of insulin action were made. This led to the development of intermediate-acting Neutral Protamine Hagedorn (NPH) and the Lente family of insulins. This review provides insights into the discovery of insulins and the shortcomings of early protracted release preparations, which in turn, gave impetus to the search for a 'true' basal insulin, which could mimic the endogenous human basal insulin secretion.

Expert Opinion: Optimum Clinical Approach to Combination-Use of SGLT2i + DPP4i in the Indian Diabetes Setting.

The Asian-Indian phenotype of type 2 diabetes mellitus is uniquely characterized for cardio-metabolic risk. In the context of implementing patient-centric holistic cardio-metabolic risk management as a priority, the choice of various combinations of antidiabetic agents should be individualized. Combined therapy with two classes of antidiabetic agents, namely, dipeptidyl peptidase 4 inhibitors and sodium-glucose co-transporter-2 inhibitors, target several pathophysiological pathways. The wide-ranging clinical outcomes associated with this combination, including improvement of glycemia and adiposity, reduction of metabolic and vascular risk, safety, and simplicity for sustainable compliance, are extremely relevant to the Asian Indian patient population living with T2DM. In this review we describe the available evidence in detail and present a rational practical guidance for the optimum clinical use of this combination in this patient population.

Real-World Observational Study of Glimepiride and Metformin Fixed-Dose Combination Along With Insulin in the Management of Type 2 Diabetes Mellitus: Indian Experience.

Background Type 2 diabetes mellitus (T2DM) is associated with a significant burden on both patients and the healthcare system. This study aimed to evaluate the demographics of patients with T2DM receiving different strengths of glimepiride and metformin combination along with insulin. This study also examined the concomitant conditions and therapies, duration of therapies, dosage titration, glycated hemoglobin (HbA1c) levels, hypoglycemic events, and weight changes during the course of therapy. Methods This retrospective, multicenter (347), observational study included adult patients with T2DM who received glimepiride and metformin combination along with insulin. Data related to demographic characteristics, duration of disease, co-morbidities, concomitant medications, and dosage pattern was collected from medical records authenticated by physicians during routine care. Results A total of 7058 patients were included in the study. The median age of included patients was 55 years and around 29% were aged >60 years and 60% were men. The majority of patients (83.3%) had insulin treatment initiation after glimepiride and metformin combination while other patients (16.7%) received glimepiride and metformin combination after insulin initiation. The mean HbA1c levels significantly decreased with a mean change of 1.33%. In one-third of the patients, down-titration of the insulin dose was done, indicating the insulin-sparing effect with the addition of the glimepiride and metformin combination. The most common comorbid condition was hypertension (64.7%). Of 3705 patients, 33.2% patients had weight loss and 66.8% had weight gain. A total of 432 patients reported hypoglycemic events. Physician global evaluation of efficacy and tolerability showed a good to excellent on the scale (97.3% and 96.6%). Conclusion This study presented good HbA1c lowering with glimepiride and metformin combination with insulin, ensuring a positive clinical outcome. Good to excellent efficacy and tolerability were observed in patients with T2DM across the age groups, in early as well as long-standing disease.

Capacity and confidence building for general practitioners on optimum insulin use.

Type 2 diabetes is characterised by a progressive decline in insulin secretion, and sooner or later patients require insulin therapy. However, physicians are reluctant to initiate insulin therapy because of perceived inadequacy in managing insulin therapy, cost and lack of benefits. Experts from across the country met at a workshop during 12th National Insulin Summit which was held in September at Hyderabad and came up with key recommendations to build capacity and confidence in general practitioners for insulin usage. Barriers can be overcome through self-education and training; effective patient education; imparting coping skill training to patients; and bridging gaps to improve adherence. Moreover, optimum insulinization requires knowledge about the available options for initiation and intensification of insulin therapy; various insulin regimens; dosing and titration; and choosing effective and simple insulin therapy as per patient characteristics. Hence, the objective of this review article is to help build capacity and confidence among general practitioners on optimising insulin therapy.

Effects of short-term testosterone replacement on areal bone mineral density and bone turnover in young hypogonadal males.

CONTEXT: Effect of parenteral testosterone esters administration on bone-mineral density (BMD) and bone turnover in young age onset male hypogonadism is not studied in Indian subjects. AIMS: To prospectively study the effect of short-term (6 months) replacement therapy with parenteral testosterone enanthate-propionate combination on BMD and bone turnover markers in hypogonadal adult patients. SETTINGS AND DESIGN: Prospective, tertiary care academic center. MATERIALS AND METHODS: Thirteen young, otherwise healthy hypogonadal males (age 25.5 ± 4.9 yrs, serum testosterone 2.56 ± 4.29 nmol/l) were subjected to BMD measurements (DXA) and estimation of urinary Crosslaps™ and serum osteocalcin at baseline. Twelve healthy age and BMI-matched males served as controls for BMD measurements. The hypogonadal patients were administered parenteral testosterone esters (as mixed enanthate and propionate) 250 mg i.m. every 2-3 weeks, and prospectively followed for 6 months. BMD and bone markers were studied at the end of 6 months. STATISTICAL ANALYSIS USED: Mann-Whitney nonparametric test, paired t-test and Pearson's test of two-tail significance. RESULTS: At baseline, BMD was significantly lower in hypogonadal males as compared to that in controls. With testosterone replacement, there was significant improvement in BMD, both at trabecular and cortical sites, There was a decline in bone turnover with treatment (Ur Crosslaps™:creatinine ratio: pretreatment 72.8 ± 40.4, post-treatment 35.5 ± 23.8 µg/mmol, P = 0.098; serum osteocalcin: pre-treatment 41.0 ± 16.8, post-treatment 31.7 ± 2.1 ng/ml, P = 0.393). CONCLUSIONS: Short-term parenteral testosterone replacement significantly improves BMD at the hip, lumbar spine and forearm in hypogonadal young males.

Unique case reports associated with ovarian failure: necessity of two intact x chromosomes.

Premature ovarian failure is defined as the loss of functional follicles below the age of 40 years and the incidence of this abnormality is 0.1% among the 30-40 years age group. Unexplained POF is clinically recognized as amenorrhoea (>6 months) with low level of oestrogen and raised level of Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH > 20 IU/l) occurring before the age of 40. It has been studied earlier that chromosomal defects can impair ovarian development and its function. Since there is paucity of data on chromosomal defects in Indian women, an attempt is made to carry out cytogenetic evaluation in patients with ovarian failure. Cytogenetic analysis of women with ovarian defects revealed the chromosome abnormalities to be associated with 14% of the cases analyzed. Interestingly, majority of the abnormalities involved the X-chromosome and we report two unique abnormalities, (46,XXdel(Xq21-22) and q28) and (mos,45XO/46,X+ringX) involving X chromosome in association with ovarian failure. This study revealed novel X chromosome abnormalities associated with ovarian defects and these observations would be helpful in genetic counseling and apart from, infertility clinics using the information to decide suitable strategies to help such patients.