LIVE INDIA: Effectiveness of Gla-100 in a Post hoc Pooled Analysis of FINE ASIA and GOAL Registries.

INTRODUCTION: Real-world evidence on insulin glargine 100 U/ml (Gla-100) initiation in Indian type 2 diabetes mellitus (T2DM) individuals is limited. The present study aimed to evaluate the effectiveness of Gla-100 in insulin-naïve T2DM participants from India. METHODS: This post hoc analysis includes real-world data of insulin-naïve Indian participants with T2DM who started Gla-100 treatment in two Asian registries: FINE ASIA and GOAL. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), body weight, insulin dose, and incidence of hypoglycemia from baseline to 6 months were assessed. RESULTS: A total of 955 participants with T2DM were identified and analyzed. The mean [standard deviation (SD)] age and duration of diabetes were 54.7 (9.8) years and 9.8 (6.3) years, respectively. Mean HbA1c and FPG were significantly reduced after 6 months of Gla-100 treatment [- 2.07 (1.4) %; - 94.4 (65.2) mg/dl, respectively]. HbA1c targets of < 7.0% and < 7.5% were achieved by 292 (30.6%) and 589 (61.7%) study participants, respectively. The overall incidence of hypoglycemia was low (n = 52; 5.4%); only two participants (0.2%) reported severe hypoglycemia. Insulin was titrated with a mean (SD) increment of 2.5 (5.6) U/day after 6 months, leading to a mean Gla-100 dose of 18.2 (8.9) U/day. Mean body weight remained unchanged from baseline to 6 months (- 0.1 kg). CONCLUSION: In routine clinical practice, Gla-100 significantly improved glycemic parameters after 6 months of treatment with a low risk of hypoglycemia and no weight change in participants with T2DM.

Clinical and Demographic Profile of Diabetic Patients from Central India - Results from Diabetes Registry.

Objective: This study was done to analyse the demographic profile and presentation of diabetes in Central India. Design: Data was collected for this cross-sectional study from an electronic diabetes registry from 2014 to 2019. Demographic details, patient history and presence or absence of co-morbid conditions, duration of diabetes, age of onset of diabetes, drug history, personal history, presence of micro and/or macrovascular complications and investigations done were obtained. Statistical Analysis: The association between each factor and the outcome was studied in terms of prevalence ratio (PR) using the R-3.0.0 programming (R Foundation for Statistical Computing, Vienna, Austria) language. Statistical significance was evaluated at a 5% level. Results: Among 12,434 patients, 54.95% were below 50 years and 45.05% were above 50 years. 50.21% were females and 49.79% were males. The mean age was 47.49 ± 14.78 years and the mean body mass index (BMI) was 26.85 ± 5.19 kg/m2 with 62.29% of obese patients (>25 kg/m2). The mean overall duration of diabetes was 7.64 ± 7.63 years. Mean Glycosylated Haemoglobin (HbA1c) in patients <=50 years was 8.60 ± 2.63 and 8.90 ± 1.91 for over 50. 65.59% had uncontrolled blood sugars. 25.19% of patients had hypertension and 18.1% had dyslipidaemia. Coronary artery disease (CAD), nephropathy, neuropathy and retinopathy were observed in 21.49%, 9.60%, 33.65% and 14.65%, respectively. The adjusted PR of cardiovascular disease (CVD) was 5.374 times higher for patients over 50 (P < 0.0001); 3.775 times higher for males (P < 0.0001), 1.64 times higher for patients with BMI >25 kg/m2 (P < 0.0001) and 3.643 times higher in hypertensive cases (P < 0.0001). Similar associations were observed with nephropathy, neuropathy and retinopathy. Conclusion: From a large population study on diabetes, it was found a majority of the type 2 diabetes mellitus (T2DM) cases (65%) are sub-optimally controlled with HbA1c levels. Also, microvascular complications were related to the sub-optimal glycaemic control, but not the macro-vascular complications.

Basal Insulin Titration: Moving Towards a More Patient-Centric Approach with Gla-100 in India.

Owing to the progressive nature of the disease, patients with type 2 diabetes mellitus (T2DM) eventually require adjustment or titration of insulin doses to achieve the desired glycemic control. Titration inertia, or the inability to dose-titrate, is one of the key barriers to optimized insulin therapy and is common in Asian countries such as India. Simple and effective titration algorithms involving the use of basal insulin, which has the lowest hypoglycemia risk, that can be individualized by physicians and easily followed by patients aid in tackling titration inertia. In this context, insulin glargine 100 U/mL (Gla-100) appears to be the ideal insulin to overcome titration inertia, owing to its low risk of hypoglycemia and effective glycemic control. Different guidelines recommend the use of basal insulin, such as Gla-100, and encourage a patient-centric approach for dose titration. Although the effective implementation of the patient-centric approach in India is challenging, it is nevertheless achievable.

Suboptimal glycemic control among subjects with diabetes mellitus in India: a subset analysis of cross-sectional wave-7 (2016) data from the International Diabetes Management Practices Study (IDMPS).

OBJECTIVE: To assess the real-world management practices of subjects with type 2 diabetes mellitus (T2DM) and type 1 diabetes mellitus (T1DM) in India. METHODS: This cross-sectional study was conducted between 7 March 2016 and 15 May 2016 in India as part of the seventh wave (2016) of the International Diabetes Management Practices Study (IDMPS). Adult subjects with T1DM or T2DM visiting physicians during a 2-week recruitment period were included. RESULTS: A total of 55 physicians included 539 subjects who met eligibility criteria. Of 495 subjects with T2DM, 303 were treated with oral glucose lowering drugs (OGLDs) only, 158 were treated with OGLD + insulin, and 27 received insulin only. Among 44 subjects with T1DM receiving insulin, 13 (29.5%) were also treated with OGLD therapy. The most commonly used insulin regimens were basal alone (69/184; 37.5%) and premixed alone (63/184; 34.2%) in subjects with T2DM, and basal + prandial insulin (24/44; 54.5%) in subjects with T1DM. Proportions of subjects achieving glycemic targets were low [glycated haemoglobin (HbA1c) <7%: T1DM = 7.3% (3/44), T2DM = 25.2% (106/495); as targeted by the treating physician: T1DM = 31.8% (14/44), T2DM = 32.1% (59/185); global target: T1DM = 4.8% (2/42) and T2DM = 1.7% (8/482)]. In subjects with T2DM, HbA1c <7% was noted in 11/22 subjects receiving insulin only and 76/260 receiving only OGLDs. Lack of experience in self-managing insulin dosing, poor diabetes education and failure to titrate insulin dosages were the main reasons for non-achievement of glycemic targets. CONCLUSION: Timely insulinization, education and empowerment of people with diabetes may help improve glycemic control in India.

Pathogenic gene expression of epicardial adipose tissue in patients with coronary artery disease.

Background & objectives: Coronary artery disease (CAD), a leading cause of mortality and morbidity worldwide has multifactorial origin. Epicardial adipose tissue (EAT) has complex mechanical and thermogenic functions and paracrine actions via various cytokines released by it, which can have both pro- and anti-inflammatory actions on myocardium and adjacent coronaries. The alteration of EAT gene expression in CAD is speculated, but poorly understood. This study was undertaken to find out the difference in gene expression of epicardial fat in CAD and non-CAD patients. Methods: Twenty seven patients undergoing coronary artery bypass graft (CABG) and 16 controls (non-CAD patients undergoing valvular heart surgeries) were included in the study and their EAT samples were obtained. Gene expressions of uncoupling protein-1, monocyte chemoattractant protein-1 (MCP-1), adiponectin, adenosine A1 receptor (ADORA-1), vascular cell adhesion molecule-1 (VCAM-1) and tumour necrosis factor-alpha (TNF-α) were studied by real-time reverse transcription-polymerase chain reaction. Glucose, insulin, lipid profile, high-sensitivity C-reactive protein, homocysteine, vitamin D, TNF-α and leptin levels were estimated in fasting blood samples and analyzed. Results: Leptin levels were significantly higher in CABG group as compared to controls (P <0.05), whereas other metabolic parameters were not significantly different between the two groups. MCP-1, VCAM-1 and TNF-α were upregulated in the CABG group as compared to controls. Further, multivariate analysis showed significantly reduced adjusted odds ratio for MCP-1 [0.27; 95% confidence interval: 0.08-0.91] in the CABG group as compared to controls (P <0.05). Interpretation & conclusions: Our findings showed an alteration in EAT gene expression in CAD patients with significant upregulation of MCP-1. Further studies with a large sample need to be done to confirm these findings.

Forum for Injection Technique (FIT), India: The Indian recommendations 2.0, for best practice in Insulin Injection Technique, 2015.

As injectable therapies such as human insulin, insulin analogs, and glucagon-like peptide-1 receptor agonists are used to manage diabetes, correct injection technique is vital for the achievement of glycemic control. The forum for injection technique India acknowledged this need for the first time in India and worked to develop evidence-based recommendations on insulin injection technique, to assist healthcare practitioners in their clinical practice.

A randomized placebo-controlled trial of the efficacy of denosumab in Indian postmenopausal women with osteoporosis.

INTRODUCTION: Osteoporosis is a serious condition affecting up to 50% of Indian postmenopausal women. Denosumab reduces bone resorption by targeting the receptor activator of nuclear factor-κB ligand. This study assessed the efficacy and safety of denosumab in Indian postmenopausal women with osteoporosis. MATERIALS AND METHODS: In this double-blind, multicenter, phase 3 study, 250 Indian postmenopausal women aged 55 to 75 years (T-score <-2.5 and >-4.0 at the lumbar spine or total hip; serum 25(OH) D levels ≥20 ng/mL) were randomized to receive one subcutaneous dose of denosumab 60 mg or placebo. All subjects received oral calcium ≥1000 mg and vitamin D3 ≥ 400 IU daily. The primary end point was mean percent change in bone mineral density (BMD) at the lumbar spine from baseline to Month 6. Secondary end points included mean percent change from baseline in BMD at total hip, femoral neck, and trochanter at Month 6 and median percent change from baseline in bone turnover markers at Months 1, 3, and 6. RESULTS: Total 225 subjects (denosumab = 111, placebo = 114) completed the six-month study. Baseline demographics were similar between groups. A 3.1% (95% confidence interval, 1.9%, 4.2%) increase favoring denosumab versus placebo was seen for the primary end point (P < 0.0001). Denosumab demonstrated a significant treatment benefit over placebo for the secondary end points. There were no fractures or withdrawals due to adverse events. CONCLUSIONS: Consistent with results from studies conducted in other parts of the world, denosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a six-month period in Indian postmenopausal women.

Cord blood levels of insulin and glucose in full-term pregnancies.

OBJECTIVES: This pilot study was undertaken to know the normal values of cord blood insulin and glucose levels in full-term normal pregnancies and pregnancies complicated with maternal conditions like pregnancy induced hypertension (PIH), thyroid dysfunction and Gestational Diabetes Mellitus (GDM). METHOD: Full-term pregnancies from Ketkar maternity hospital, Nagpur, since January 2011 were included in the study. A total of 121 cases have been studied. Demographic and clinical data of the included cases was obtained from the hospital records. Cord blood sample was analyzed for serum insulin and plasma glucose levels. These two metabolic parameters were used to derive (Homeostatic Model Assessment) HOMA index for insulin resistance and Glucose-to-Insulin Ratio (GIR). The data on physical and metabolic parameters was analyzed using parametric statistical significance tests for means and correlation using R-package RESULT: The difference in glucose concentration was found insignificant (p > 0.05) across complicated and uncomplicated pregnancies. However, for the comparison 'no complications' vs PIH, the insulin levels differed significantly at 10% (p = 0.09). Accordingly, for the same comparison, GIR also indicated significant difference at 10% (p = 0.07) between the two maternal groups. The mean cord blood glucose level was higher in PIH cases compared to un-complicated maternal cases; while the mean insulin level was lower in PIH cases as compared to non-complicated cases, as a result mean GIR was higher in PIH category. HOMA did not show significant difference in any comparison. The relationship of metabolic parameters and the derived variables with birth weight in the two maternal groups showed insignificant relationships between birth weight and dependent variables (p > 0.05). CONCLUSION: The levels of insulin and glucose in normal full-term pregnancies was found to be 6.75 +/- 2.96 mIU/ ml and 91.69 +/- 27.05 mg/dl respectively with GIR of 13.57 +/- 7.47 and HOMA 1.57 +/- 0.83. Low serum insulin levels with normal or high GIR was noted in pregnancies complicated by PIH. Insulin resistance as measured by HOMA IR is increased in patients with hypothyroidism. Hyperinsulinemia is seen in babies with birth weight less than 2.5 kg or more than 3.5 kg.

Forum for injection techniques, India: the first Indian recommendations for best practice in insulin injection technique.

Advances in the treatment of diabetes have led to an increase in the number of injectable therapies, such as human insulin, insulin analogues, and glucagon-like peptide-1 analogues. The efficacy of injection therapy in diabetes depends on correct injection technique, among many other factors. Good injection technique is vital in achieving glycemic control and thus preventing complications of diabetes. From the patients' and health-care providers' perspective, it is essential to have guidelines to understand injections and injection techniques. The abridged version of the First Indian Insulin Injection technique guidelines developed by the Forum for Injection Technique (FIT) India presented here acknowledge good insulin injection techniques and provide evidence-based recommendations to assist diabetes care providers in improving their clinical practice.

Fetal origin of vascular aging.

Aging is increasingly regarded as an independent risk factor for development of cardiovascular diseases such as atherosclerosis and hypertension and their complications (e.g. MI and Stroke). It is well known that vascular disease evolve over decades with progressive accumulation of cellular and extracellular materials and many inflammatory processes. Metabolic syndrome, obesity and diabetes are conventionally recognized as risk factors for development of coronary vascular disease (CVD). These conditions are known to accelerate ageing process in general and vascular ageing in particular. Adverse events during intrauterine life may programme organ growth and favour disease later in life, popularly known as, 'Barker's Hypothesis'. The notion of fetal programming implies that during critical periods of prenatal growth, changes in the hormonal and nutritional milieu of the conceptus may alter the full expression of the fetal genome, leading to permanent effects on a range of physiological.

Health-related quality of life in the VA Feasibility Study on glycemic control and complications in type 2 diabetes mellitus.

OBJECTIVE: The Veterans Affairs Cooperative Study in Diabetes Mellitus Type 2 Feasibility Trial (VA CSDM) studied standard and intensive glycemic treatment groups, achieving and maintaining for 27 months a difference in HbA1c of 2.1% (9.2% vs. 7.1%, respectively). A substudy planned in advance examined health status as assessed by a health status questionnaire obtained at baseline and 24 months. DESIGN AND METHODS: A randomized, prospective trial was carried out at five VA Medical Centers from 1990 to 1993. The sample involved 153 male veterans 40-69 years of age and with diabetes duration of 8+/-4 years, who were suboptimally controlled with standard glucose lowering treatment. The participants were randomized to intensive and standard treatment groups. In addition to a variety of indicators of glycemic control and complications, health-related qualify of life data were assessed using a 20-question version of the Medical Outcome Study instrument. Scores were evaluated at baseline and 24 months for changes between the treatment groups. RESULTS: The two groups were similar at baseline with respect to age, duration of diabetes, complications, comorbidities, and reported physical activity. The intensive treatment group had more frequent, mandatory self-glucose monitoring (vs. occasional measurement in the standard) and received two or more daily insulin injections (only one in the standard). This group had three times the number of clinic visits and 10-fold higher reported incidence of mild/moderate hypoglycemia. There were no significant changes in the health status over time in either the standard or intensive treatment groups, nor was there a difference between the two groups. CONCLUSIONS: Intensive glucose control in advanced Type 2 diabetes mellitus (DM) has no effect on health status over 2 years. The successful lowering of glycemia does not improve health-related quality of life nor do the increased demands of an intensive therapy regimen worsen it.

Testosterone treatment enhances regional brain perfusion in hypogonadal men.

The positive effect of testosterone replacement therapy on psychosocial well-being in hypogonadal men has been demonstrated by various psychometric tests. However, there is no report available that objectively demonstrates the effect of testosterone on the function of the central nervous system in men. In this report we studied cerebral perfusion in seven hypogonadal men on testosterone replacement therapy. The blood perfusion to the central nervous system was assessed using single-photon emission-computed tomography. (99 m)Tc-hexamethyl-propylene-amine oxime crosses the blood brain barrier and localizes in brain tissue, depending on the intensity of the local blood flow. Psychosocial well-being was assessed with an Androgen Deficiency in Aging Men questionnaire. The study demonstrated that testosterone replacement enhanced cerebral perfusion in midbrain and superior frontal gyrus (Brodman area 8) at 3-5 wk of treatment. At 12-14 wk the study continued to show increased perfusion in midbrain in addition to the appearance of a new activated region in the midcingulate gyrus (Brodman area 24). The results of this study provide objective evidence that testosterone and /or its metabolites increased cerebral perfusion in addition to the improvement in cognitive function.