SGLT2-inhibition and Vascular Euphoria a Reconciliation of Vascular Health and Disease Homeostasis.

The concept of SGLT2-inhibition, once regarded as a non-physiological approach to glycemia control, now finds a foundational relevance in risk-modification for cardiovascular, kidney, and metabolic outcomes, spanning beyond type-2 diabetes. Major studies have proven meaningful improvements in various clinical outcomes, with different SGLT2-i agents. Apart from glycosuria, SGLT2-inhibition is associated with several patho-physiological effects, which may contribute to the clinical benefits seen with these agents. This narrative review is an attempt to appraise the different patho-physiological effects mediated by SGLT2-inhibition, based on contemporary evidence. The review classifies these effects in the acronym of EUPHORIA, and grades the possible relevance of each effect, in improving clinical outcomes.

Fixed-dose combination in management of type 2 diabetes mellitus: Expert opinion from an international panel.

Type 2 diabetes mellitus (T2DM) is a progressive disease with multifactorial etiology. The first-line therapy includes monotherapy (with metformin), which often fails to provide effective glycemic control, necessitating the addition of add-on therapy. In this regard, multiple single-dose agents formulated as a single-dose form called fixed-dose combinations (FDCs) have been evaluated for their safety, efficacy, and tolerability. The primary objective of this review is to develop practice-based expert group opinion on the current status and the causes of concern regarding the irrational use of FDCs, in Indian settings. After due discussions, the expert group analyzed the results from several clinical evidence in which various fixed combinations were used in T2DM management. The panel opined that FDCs (double or triple) improve patient adherence, reduce cost, and provide effective glycemic control and, thereby, play an important role in the management of T2DM. The expert group strongly recommended that the irrational metformin FDC's, banned by Indian government, should be stopped and could be achieved through active participation from the government, regulatory bodies, and health ministry, and through continuous education of primary care physicians and pharmacists. In T2DM management, FDCs play a crucial role in achieving glycemic targets effectively. However, understanding the difference between rational and irrational FDC combinations is necessary from the safety, efficacy, and tolerability perspective. In this regard, primary care physicians will have to use a multistep approach so that they can take informed decisions.

Unravelling the utility of modern sulfonylureas from cardiovascular outcome trials and landmark trials: expert opinion from an international panel.

AIM: The primary objective of this review is to develop practice-based expert group opinions on the cardiovascular (CV) safety and utility of modern sulfonylureas (SUs) in cardiovascular outcome trials (CVOTs). BACKGROUND: The United States Food and Drug Administration issued new guidance to the pharmaceutical industry in 2008 regarding the development of new antihyperglycemic drugs. The guidance expanded the scope for the approval of novel antihyperglycemic drugs by mandating CVOTs for safety. A few long-term CVOTs on dipeptidyl peptidase 4 inhibitors, glucagon-like peptide 1 receptor agonists, and sodium-glucose cotransporter 2 inhibitors have been completed, while others are ongoing. SUs, which constitute one of the key antihyperglycemic agents used for the management of type 2 diabetes mellitus (T2DM), have been used as comparator agents in several CVOTs. However, the need for CVOTs on modern SUs remains debatable. In this context, a multinational group of endocrinologists convened for a meeting and discussed the need for CVOTs of modern SUs to evaluate their utility in the management of patients with T2DM. At the meeting, CVOTs of modern SUs conducted to date and the hypotheses derived from the results of these trials were discussed. REVIEW RESULTS: The expert group analyzed the key trials emphasizing the CV safety of modern SUs and also reviewed the results of various CVOTs in which modern SUs were used as comparators. Based on literature evidence and individual clinical insights, the expert group opined that modern SUs are cardiosafe and that since they have been used as comparators in other CVOTs, CVOTs of SUs are not required. CONCLUSION: Modern SUs can be considered a cardiosafe option for the management of patients with diabetes mellitus and CV disease; thus CVOTs among individuals with T2DM are not required.

Intensive glucose therapy and clinical implications of recent data: a consensus statement from the Global Task Force on Glycaemic Control.

BACKGROUND: There is compelling evidence showing that achieving good glycaemic control reduces the risk of microvascular complications in people with type 1 and type 2 diabetes. Likewise, there is clear evidence to show that achieving good glycaemic control reduces the risk of macrovascular complications in type 1 diabetes. The UKPDS 10-year follow up suggests that good glycaemic control also reduces the risk of macrovascular complications in type 2 diabetes. Despite this, recent results from ACCORD, ADVANCE and VADT present conflicting results and data from the ACCORD trial appear to suggest that very low HbA(1c) targets (<6.0%) may, in fact, be dangerous in certain patient populations. AIM: To review recent results from ACCORD, ADVANCE and VADT and provide clear guidance on the clinical significance of the new data and their implications for the practising physician treating patients with type 2 diabetes. METHODS: A Pubmed search was used to identify major randomised clinical trials examining the association between glycaemic control and diabetes-associated complications. The data was reviewed and discussed by the GTF through a consensus meeting. The recommendations for clinical practice in this statement are the conclusions of these analyses and discussions. RESULTS: Evidence from ACCORD, ADVANCE, VADT and UKPDS suggests that certain patient populations, such as those with moderate diabetes duration and/or no pre-existing CVD, may benefit from intensive blood glucose control. These trials highlight the benefit of a multifactorial treatment approach to diabetes. However, ACCORD results indicate that aggressive HbA(1c) targets (<6.0%) may not be beneficial in patients with existing CVD and a longer duration of diabetes. CONCLUSIONS: Glycaemic control remains a very important component of treatment for type 2 diabetes and contrasting results from the ACCORD, ADVANCE and VADT should not discourage physicians from controlling blood glucose levels.

Diagnosis and Management of Hypothyroidism: Addressing the Knowledge-Action Gaps.

Hypothyroidism presents a large epidemiological burden in India. As a result of subtle and nonspecific clinical symptoms and signs, the condition often goes undiagnosed and is not adequately treated when it is detected. There is heterogeneity in the diagnostic and treatment approaches to hypothyroidism. As a result of the physiological changes in thyroid hormones with age and illness, it is important to tailor the diagnosis and management of this condition in specific populations including pregnant women, infants, children, geriatric patients, and those with comorbid conditions. Enhanced understanding and education of physicians and patients can help to improve the outcomes of treatment in hypothyroidism which should be focused on patient-centered care. Policies and reforms should be crafted and implemented at the national level to curb public health challenges of hypothyroidism. This publication summarizes the recommendations of a national advisory board meeting to identify and bridge the gaps in understanding of the diagnosis and treatment of hypothyroidism in India. As a complement to clinical judgment, these recommendations will foster the diagnosis and management of hypothyroidism in the community and clinics for the benefit of the patients. FUNDING: Merck Ltd, India.

Gestational diabetes mellitus--guidelines.

The Diabetes In Pregnancy Study group India (DIPSI) is reporting practice guidelines for GDM in the Indian environment. Due to high prevalence, screening is essential for all Indian pregnant women. DIPSI recommends that as a pregnant woman walks into the antenatal clinic in the fasting state, she has to be given a 75g oral glucose load and at 2 hrs a venous blood sample is collected for estimating plasma glucose. This one step procedure of challenging women with 75 gm glucose and diagnosing GDM is simple, economical and feasible. Screening is recommended between 24 and 28 weeks of gestation and the diagnostic criteria of ADA are applicable. A team approach is ideal for managing women with GDM. The team would usually comprise an obstetrician, diabetes physician, a diabetes educator, dietitian, midwife and pediatrician. Intensive monitoring, diet and insulin is the corner stone of GDM management. Oral agents or analogues though used are still controversial. Until there is evidence to absolutely prove that ignoring maternal hyperglycemia when the fetal growth patterns appear normal on the ultrasonogram, it is prudent to achieve and maintain normoglycemia in every pregnancy complicated by gestational diabetes. The maternal health and fetal outcome depends upon the care by the committed team of diabetologists, obstetricians and neonatologists. A short term intensive care gives a long term pay off in the primary prevention of obesity, IGT and diabetes in the offspring, as the preventive medicine starts before birth.

Human rabies: modes of transmission.

In contrast to past experience, transmission of rabies by routes other than bite or licking by rabid animals has been identified in recent years. Man to man spread via corneal transplant is a well recognised phenomenon now. Airborne infection in caves as well as in laboratories among workers dealing with rabies virus has been well documented. There is also a potential risk of infection to attendants of rabies patients. Hence, adequate protective measures should be adopted.

Diabetes in rural Pondicherry, India: a population-based studyof the incidence and risk factors.

BACKGROUND: For India, the 'diabetes capital' of the world, it is essential to know the incidence of type 2 diabetes mellitus (T2DM) and its key determinants. As two thirds of Indians live in rural areas, a study was undertaken to assess the incidence and risk factors of T2DM in rural Pondicherry, India. METHODS: In a population-based cohort study initiated in 2007, a sample of 1223 adults > 25 years ofage from two villages of Pondicherry were selected using cluster random sampling. Data on risk factor exposure were collected using a structured questionnaire, anthropometric tests and fasting blood glucose assessment. During house visits, 1223 of 1403 invited subjects participated. Of these, 71 (5.8%) were found to have diabetes. In 2010-2011, 85% of the non-diabetics (979/1152) were followed up using the same protocol. We calculated the risk of T2DM per annum standardized by age and sex. Population estimates of the risk factors associated with T2DM were analysed using the Generalized Estimating Equation model and the Population Attributable Risk (PAR) for T2DM calculated. RESULTS: During 2937 person-years (PY) of follow-up, 63 new cases of T2DM occurred, giving an incidence rate of 21.5/1000 PY. Almost one third (31.7%) of cases occurred in people aged below 40 years. The incidence was double among males (28.7/1000 PY; 95% confidence interval (CI): 21.0-38.7) compared with females (14.6/1000 PY; 95% CI: 9.4-21.7). Applying these rates to rural populations, it is estimated that each year 8.7 million people develop T2DM in rural India. Nearly half of the T2DM incidence was attributed to overweight/obesity and alcohol usage. CONCLUSION: T2DM incidence was 2% per year in adults in rural Pondicherry, India, with the rate increasing twice as fast in men. Increasing age, obesity, alcohol use and a family history of T2DM independently predicted the development of diabetes. As half of T2DM incidence was attributed to overweight/obesity and alcohol use, health promotion interventions focusing on maintaining an optimal weight and decreasing alcohol consumption may be effective in reducing the rise in T2DM cases.

Baseline characteristics of the IMPROVE control study population: A study to evaluate the effectiveness of a standardized healthcare professionals training program.

INTRODUCTION: The IMPROVE Control Training program was designed by Indian Academy of Diabetes (IAD), and a non-intervention study was conducted to evaluate the effectiveness of this standardized healthcare professionals (HCPs) training program on achieving treatment goals in patients with diabetes mellitus and its impact on standard of care. MATERIALS AND METHODS: This multi-center, parallel group, open-label, non-randomized, non-intervention study included patients with type 2 diabetes who had an HbA1c >9 at time of diagnosis or an HbA1c >7% even after 6 months of initiation of therapy with anti-diabetic agents (Oral anti diabetic agents (OADs) and/or insulin). The data recorded at baseline included demographic characteristics, medical history, and the treatment regimens. RESULTS: The study included 20,493 patients with diabetes, of which 13,295 (64.9%) were men. The mean [standard deviation (SD)] duration of diabetes was 6.4 (4.2) years and 6608 (32.2%) reported complications of diabetes. Poor glycemic control [HbA1c = 9.4 (1.3), FPG (mg/dl) = 181.2 (45.7); mean (SD)] was observed. The postprandial glucose was also high [post-breakfast, lunch, and dinner values in mg/dl were 263.6 (68.5), 278.1 (69.6), and 250.2 (63.7), respectively] in these patients. Failure of OADs was the most common reason cited for initiation of insulin. Premixed insulin was rated the regimen of choice for initiating therapy by the physicians (62.2% vs. 34.5% who preferred basal insulin). CONCLUSION: The baseline results confirm the poor glycemic control and the delayed initiation and/or inadequacy of treatment in subjects with type 2 diabetes. These results also highlight the need for early and optimal insulin-based therapy.

Physicians' perceptions of a national consensus guideline on insulin therapy: Data from the IMPACT study.

INTRODUCTION: The effectiveness and impact of the Indian insulin guideline in clinical practice was evaluated by the Improving Management Practices and Clinical Outcomes in Type 2 Diabetes (IMPACT) Study. The study also evaluated the participating physicians' perceptions on the use of IIG versus RCP for management of diabetes. MATERIALS AND METHOD: This 26 week multicenter, open label, randomized, prospective study aimed to evaluate effectiveness of Indian insulin guideline (IIG) versus routine clinical practice (RCP) in patients with type 2 diabetes (T2D). RESULTS: Out of 426 physicians who completed the physicians' perception questionnaire, 189 (44.4%) felt that it was "easy" to initiate insulin in their patients using IIG. Cost of therapy (52.3%), followed by poor adherence (40.3%), and lack of motivation among physicians (40.4%) were the most important reasons cited for delay in initiation of insulin therapy. Two hundred and thirty three (54.7%) physicians felt that insulin titration was made "easy" in their patients using IIG, while 104 (24.4%) had a neutral approach. A total of 222 physicians (52.1%) felt it was "convenient" applying IIG in their practice, and 239 (67.8%) physicians felt "satisfied" with using IIG for achieving the targeted HbA1c <7%. One hundred and seventy seven (41.5%) physicians felt that there was scope for improving the IIG further by simplifying and revising the titration charts [117 (27.5%)]. CONCLUSION: Primary care physicians in India have perceived the IIG to be easy algorithm to initiate and titrate insulin therapy. These results will encourage the use and facilitate future revision of the guideline.