Diabetes Mellitus and Fluid Imbalance: The Need for Adequate Hydration.

The effect of hydration in modulating metabolic disease risk is a comparatively recent concept. Diabetic patients are at increased risk of dehydration due to osmotic diuresis. Undiagnosed or undertreated hyperglycemia may lead to electrolyte imbalance and elevated renal burden of glucose excretion, which may alter fluid reabsorption in the kidney. Also, the presence of one or more contributory factors, such as inadequate fluid intake, strenuous exercise, high temperatures, alcohol consumption, diarrhea, acute illnesses, fever, nausea, and vomiting, may put diabetic patients at increased risk of dehydration and electrolyte imbalance. Certain antidiabetic agents used by diabetic patients may cause fluid retention/deficits and/or electrolyte abnormalities in a few patients. Thus, drinking ample amounts of water and fluids with appropriate electrolyte composition is important to prevent dehydration. Successful management of dehydration in patients with diabetes is an unmet need and can best be accomplished by maintaining adequate hydration status.

Does Adopting Western Low-density Lipoprotein Cholesterol Targets Expose Indians to a Higher Risk of Cardiovascular Events? Expert Opinion From the Lipid Association of India.

Adverse cardiovascular (CV) events have declined in Western countries due at least in part to aggressive risk factor control, including dyslipidemia management. The American and European (Western) dyslipidemia treatment guidelines have contributed significantly to the reduction in atherosclerotic cardiovascular disease (ASCVD) incidence in the respective populations. However, their direct extrapolation to Indian patients does not seem appropriate for the reasons described below. In the US, mean low-density lipoprotein cholesterol (LDL-C) levels have markedly declined over the last 2 decades, correlating with a proportional reduction in CV events. Conversely, poor risk factor control and dyslipidemia management have led to increased CV and coronary artery disease (CAD) mortality rates in India. The population-attributable risk of dyslipidemia is about 50% for myocardial infarction, signifying its major role in CV events. In addition, the pattern of dyslipidemia in Indians differs considerably from that in Western populations, requiring unique strategies for lipid management in Indians and modified treatment targets. The Lipid Association of India (LAI) recognized the need for tailored LDL-C targets for Indians and recommended lower targets compared to Western guidelines. For individuals with established ASCVD or diabetes with additional risk factors, an LDL-C target of <50 mg/dL was recommended, with an optional target of ≤30 mg/dL for individuals at extremely high risk. There are several reasons that necessitate these lower targets. In Indian subjects, CAD develops 10 years earlier than in Western populations and is more malignant. Additionally, Indians experience higher CAD mortality despite having lower basal LDL-C levels, requiring greater LDL-C reduction to achieve a comparable CV event reduction. The Indian Council for Medical Research-India Diabetes study described a high prevalence of dyslipidemia among Indians, characterized by relatively lower LDL-C levels, higher triglyceride levels, and lower high-density lipoprotein cholesterol (HDL-C) levels compared to Western populations. About 30% of Indians have hypertriglyceridemia, aggravating ASCVD risk and complicating dyslipidemia management. The levels of atherogenic triglyceride-rich lipoproteins, including remnant lipoproteins, are increased in hypertriglyceridemia and are predictive of CV events. Hypertriglyceridemia is also associated with higher levels of small, dense LDL particles, which are more atherogenic, and higher levels of apolipoprotein B (Apo B), reflecting a higher burden of circulating atherogenic lipoprotein particles. A high prevalence of low HDL-C, which is often dysfunctional, and elevated lipoprotein(a) [Lp(a)] levels further contribute to the heightened atherogenicity and premature CAD in Indians. Considering the unique characteristics of atherogenic dyslipidemia in Indians, lower LDL-C, non-HDL-C, and Apo B goals compared to Western guidelines are required for effective control of ASCVD risk in Indians. South Asian ancestry is identified as a risk enhancer in the American lipid management guidelines, highlighting the elevated ASCVD risk of Indian and other South Asian individuals, suggesting a need for more aggressive LDL-C lowering in such individuals. Hence, the LDL-C goals recommended by the Western guidelines may be excessively high for Indians and could result in significant residual ASCVD risk attributable to inadequate LDL-C lowering. Further, the results of Mendelian randomization studies have shown that lowering LDL-C by 5-10 mg/dL reduces CV risk by 8-18%. The lower LDL-C targets proposed by LAI can yield these incremental benefits. In conclusion, Western LDL-C targets may not be suitable for Indian subjects, given the earlier presentation of ASCVD at lower LDL-C levels. They may result in greater CV events that could otherwise be prevented with lower LDL-C targets. The atherogenic dyslipidemia in Indian individuals necessitates more aggressive LDL-C and non-HDL-C lowering, as recommended by the LAI, in order to stem the epidemic of ASCVD in India.

Prevalence of coronary calcium deposits in Sheehan's syndrome patients on long term replacement treatment.

PURPOSE: Sheehan's Syndrome (SS) is one of the most important causes of hypopituitarism in developing countries with patients having varying degrees and severity of anterior pituitary hormone deficiency including growth hormone deficiency (GHD). SS is characterized by increased clustering of metabolic and proinflammatory risk factors predisposing them to increased cardiovascular morbidity and mortality. Coronary calcium deposits (CCD), a marker for significant coronary atherosclerosis, is used for evaluation in asymptomatic individuals of global cardiac risk to develop events related to coronary heart disease (CHD). This study therefore aimed to evaluate the prevalence of coronary artery disease in patients with SS appropriately replaced for pituitary hormone deficiencies but untreated for GHD. METHODS: Thirty patients previously diagnosed with SS and stable on a conventional replacement treatment for at least 6 months before the study and thirty age and Body Mass Index (BMI) matched controls were enrolled in this observational study. The subjects underwent detailed clinical, biochemical, and hormone analysis. Coronary multidetector computed tomography was performed in 19 SS patients and 19 healthy participants by a 16-row multislice scanner. Non contrast acquisitions were performed to detect coronary calcifications. Calcium was quantified by the Agatston score (AS) in all subjects. AS > 10 indicates increased CHD risk. RESULTS: The mean (± SD) age was 38.30 ± 10.73 years and the diagnostic delay was 11.35 ± 4.74 years. Patients with SS had significantly higher mean triglyceride, total cholesterol, and low density lipoprotein (LDL) cholesterol and lower HDL cholesterol concentrations on conventional replacement therapy. The prevalence of CCD was significantly higher in patients of SS compared to controls (42.1% vs. 5.3%; P = 0.023). The presence of CCD and AS > 10 were detected in 42.1% and 31.6% of patients respectively. The presence of significant calcification (Agatston score > 10) was documented in 75% of patients (6/8) of the SS patients with CCD compared to none in the control group (P = 0.019). (Left anteriordescending, 1; left circumflex, 2; right coronary artery, 2 and posterior descending, 1) CONCLUSION: Since coronary artery calcium is an independent predictor of CHD events, the presence of significant prevalence of CCD in patients with SS compared to healthy matched controls, undermines the importance of early risk stratification of SS individuals with plethora of conventional cardiovascular risk factors that are at relatively high risk to avoid the adverse vascular consequences.

Indian Reality of Clinical Practice and Patient Profile in Diabetes Care: Lessons from the IMPACT survey.

India shoulders a heavy burden of diabetes mellitus (DM), the management of which is suboptimal globally.& Objectives: Insulin Management: Practical Aspects in Choice of Therapy (IMPACT) survey was designed to gain insight into the ground (in-clinic) reality of DM management by physicians in India. METHODS: A survey consisting of 12 multiple-choice questions was conducted by SurveyMonkey® , focusing on practice profile, patient profile, and other aspects of DM management. RESULTS: The survey included 2424 physicians. Majority of them were general physicians (58.5%) followed by diabetologists (31.1%). Most (49.2%) of the respondents specified that the ideal time for a DM consultation is 15 min. However, 73.4% of them provided consultation of <10& min because of heavy patient load. Nearly half of the respondents reported that their patients consumed a diet with carbohydrate content of 60% to 80%, and 79.4% of them admitted that <50% of their patients adhered to dietary advice. About 73.5% of the respondents believed controlling fasting plasma glucose (FPG) level alone would not adequately control postprandial plasma glucose (PPG) level, and 93.0% of them preferred an insulin therapy at the initiation that controls both FPG and PPG levels. CONCLUSION: Limited consultation time, high-carbohydrate diet, and a need for choosing insulin regimens that provide control for both PPG and FPG levels are some ground realities of DM management in India. These realities need to be factored in while choosing treatment options to achieve the desired glycemic control and improve the status of diabetes care.

Current Role of Dapagliflozin in Clinical Practice.

Dapagliflozin is the first in a novel class of glucose-lowering agents known as sodium-glucose co-transporter-2 (SGLT2) inhibitors which was approved by USFDA in management of type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise to improve glycemic control in adults initially, followed by to reduce the risk of hospitalization for heart failure (HHF) in adults with T2DM and established cardiovascular disease or multiple cardiovascular risk factors. Most recently, it is approved to reduce the risk of cardiovascular death and in adults with heart failure (HF) with reduced ejection fraction (NYHA class II-IV). Dapagliflozin has been studied in a wide range of patients with diabetes and plethora of evidence has confirmed its efficacy as a monotherapy as well as an add-on to the oral therapies and insulin, when compared to placebo. Additional advantages include weight reduction which has been consistently demonstrated in Phase III studies and good tolerability. Also there is a demonstrable reduction in systolic blood pressure in patients treated with SGLT2 inhibitors. DECLARE TIMI 58 study clearly demonstrated that Dapagliflozin was non inferior in reducing major adverse cardiovascular events (MACE) in patients with T2DM and high CV risk compared with placebo. 27% risk reduction in heart failure hospitalisation was noted along without increased risk of amputation. DAPA HF evaluated the efficacy and safety of the dapagliflozin in patients with HF and reduced ejection fraction, irrespective of the presence or absence of diabetes. Patients with symptomatic HF due to reduced ejection fraction treated with dapagliflozin had positive outcomes with reduction in cardiovascular deaths and HF events. The DAPA-CKD trial which was conducted to assess the efficacy and safety of dapagliflozin in patients with chronic kidney disease (CKD), with or without type 2 diabetes found that it significantly lowered the risk of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes in patients with CKD, regardless of the presence or absence of diabetes. Ongoing trials like DELIVER, DAPA ACT HF-TIMI 68, DICTATE-AHF, HF readmission study, DAPA MI Study, Effectiveness of Dapagliflozin for Weight Loss, will throw more light on the precise effects of dapagliflozin in several clinical scenarios. To conclude - Dapagliflozin was well studied not only in T2DM but also in HF and CKD patients with positive results and good safety profile.

IMPACT India: Insights for Insulin Therapy in Routine Clinical Practice.

OBJECTIVE: Widely used in the management of diabetes, insulin therapy is influenced by several patient preferences and physician choices. This article reports the findings of the IMPACT survey, designed to assess insights on various factors which influence the choice of insulin therapy in India. METHODS: We administered a questionnaire which focused on the practice and patient profiles and the preferred regimens in specific clinical situations using a case scenario. Respondents were asked about preferred insulin regimens for various phases of life, comorbid conditions, dietary choices and psychological factors. RESULTS: Overall, 314 doctors participated in the survey. Majority were general physicians (51%) and diabetologists (37%). In clinical practice, the most preferred regimens included premix insulin BD in adults (59%) and elderly (53%), and basal bolus therapy in pregnant women (>47%) and in acute illness (62%). Both regimens were equally preferred for symptomatic patients (41% basal bolus and 38% premix insulin) and those with renal or hepatic failure (36% each). Premix insulin was preferred for patients with high carbohydrate intake (73%) while basal bolus was preferred for patients with variable meal timings (39%) and in pronounced postprandial glucose excursions (45%). Insulin co-formulation and high-mix insulins were not a part of the survey questionnaire. SUMMARY: Indian physicians exercise logic in the choice of insulin regimens. Preference is based on patient characteristics including glucophenotype, dietary patterns, psychosocial needs, clinical situations, and comorbid conditions.

Consensus on Initiation and Intensification of Premix Insulin in Type 2 Diabetes Management.

INTRODUCTION: Premix insulin is the most commonly used insulin preparation in India. The first Indian premix guidelines were developed in 2009 and thereafter were updated in 2013. There is a need to revisit the Indian premix insulin guidelines, in view of emerging evidence and introduction of newer co-formulations. OBJECTIVE: The present consensus has been developed to evaluate available premix formulations, examine existing evidence related to premix formulations, and evolve consensus statement of recommendations on the topic. METHODS: A meeting of experts from across India was conducted at Chennai in July 2016. The expert committee evaluated each premix insulin regimen with reference to 1) Current recommendations by various guidelines, 2) Approved pack inserts and 3) Published scientific literature. The information was debated and discussed within the expert group committee, to arrive at seven consensus-based recommendations for initiation and intensification with premix insulin. RESULTS: Recommendations based on consensus on initiation and intensification of premix insulin in type 2 diabetes mellitus (T2DM) management were developed for the following situations. 1) Initiation of premix insulin co-formulation at diagnosis, 2) Initiation of once daily (OD) premix insulin/co-formulation, 3) Initiation of twice daily (BID) premix insulin/co-formulation 4) Intensification with BID and thrice daily (TID) premix insulin/co-formulation. Three recommendations pertained to the use of premix insulin in other forms of diabetes, or in specific situations: 5) Use of premix insulin in gestational diabetes mellitus 6) Use of premix insulin in type 1 Diabetes Mellitus (T1DM) 7) Premix insulin use during Ramadan. CONCLUSIONS: In the setting of high carbohydrate consumption in India, or in patients with predominant post prandial hyperglycemia, premix insulin/co-formulation can offer effective and convenient glycemic control. This paper will help healthcare practitioners initiate and intensify premix insulin effectively.

Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of Type 2 Diabetes in India.

INSTRUCTION: Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM) and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate insulin dosing and titration is also critical to the successful achievement of tight glycaemic control. OBJECTIVE: To provide simple and easily implementable guidelines to primary care physicians on appropriate insulin dosing and titration of various insulin regimens for both initiation and intensification. METHODOLOGY: Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from approved pack inserts, and published scientific literature. These evaluations were then factored into the national context based on the expert committee representatives patient-physician experience in their clinical practice and common therapeutic practices followed in India. RESULTS: Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose (FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL). CONCLUSIONS: The consensus based recommendations mentioned in this paper will be a useful reference tool for health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal glucose control.

South Asian consensus guideline: Use of GLP-1 receptor agonists during Ramadan: Update 2016 Revised Guidelines on the use of GLP-1A in Ramadan.

This guidance is an update to the South Asian Consensus Guideline: Use of GLP1RA in Diabetes during Ramadan, published in the Indian Journal of Endocrinology and Metabolism in 2012. A five country working group has collated evidence and experience to suggest guidelines for the safe and rational use of glucagon-like peptide1 receptor agonists during Ramadan. The suggestions contained herewith are based upon recently published evidence as well as available basic pharmacological data.

Update to South Asian consensus guideline: Use of newer insulins in diabetes during Ramadan Revised Guidelines on the use of insulin in Ramadan.

This guidance is an update to the South Asian Consensus Guideline: Use of Insulin in Diabetes during Ramadan, published in the Indian Journal of Endocrinology and Metabolism in 2012. A five country working group has collated evidence and experience to suggest guidelines for the safe and rational use of insulin degludec (IDeg) and insulin degludec aspart (IDegAsp) during Ramadan. The suggestions contained herewith are based on the pharmacokinetic and pharmacodynamics properties of these novel insulins.

Goitre and urinary iodine excretion survey in schoolchildren of Kashmir Valley.

BACKGROUND: An extensive survey on schoolchildren in Kashmir Valley in 1995 showed a high prevalence of goitre, making it imperative to have a relook at our iodine status, 15 years postiodization. OBJECTIVE: To study the total prevalence of goitre and urinary iodine excretion (UIE) in Kashmiri schoolchildren, 15 years postiodization. DESIGN: A cross-sectional survey, covering 9576 schoolchildren, aged 5-15 years (5988 in 6-12 year age group) was conducted. Goitres were graded as per WHO/UNICEF/ICCIDD. UIE was measured by the arsenic acid reduction in ceric ions method and was estimated in 208 subsampled children. Results were compared with that of 1995 survey. RESULTS: The overall prevalence of goitre in the present study was 3·8% (95% CI: 3·4-4·2) and 3·7% (95% CI: 3·2-4·2) in those aged 6-12 years. No significant difference in prevalence of goitre was observed between boys and girls overall (3·6% vs 4·1%. P > 0·2), nor in the 6-12 year age group (3·3% vs 4·0%, P > 0·1). There was a significant trend of increasing prevalence of goitre with age (P < 0·005). UIE ranged from 12 to 397 µg/g.creatinine (median, 104); 11% subjects had UIE of <50 µg/g.creatinine. Overall, prevalence of goitre was significantly lower (3·8% vs 45·2%, P < 0·001), and mean UIE was significantly higher (123·6 ± 5·3 vs 49·60 ± 3·55 µg/g.creatinine, P < 0·001), compared to that in the 1995 survey. CONCLUSION: The marked improvement in overall iodine nutrition in Kashmir Valley- one and a half decades after implementation of salt iodization should encourage healthcare providers to make tangible efforts for implementation of iodization programmes in areas with iodine deficiency.

Expert eValuation of Efficacy and Rationality of Vildagliptin "EVER-Vilda": An Indian Perspective.

Vildagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor is effective in reducing HbA1c levels in patients with type 2 diabetes (T2DM) when administered as monotherapy, dual or triple combination therapy. In India, Vildagliptin is commonly prescribed in T2DM patients because it reduces mean amplitude of glycemic excursion (MAGE), has lower risk of hypoglycemia and is weight neutral. Early combination therapy with vildagliptin and metformin is effective and well-tolerated in patients with T2DM, regardless of age or ethnicity. In view of already existing data on vildagliptin and the latest emerging clinical evidence, a group of endocrinologists, diabetologists and cardiologists convened for an expert group meeting to discuss the role and various combinations of vildagliptin in T2DM management. This practical document aims to guide Physicians and Specialists regarding the different available strengths and formulations of vildagliptin for the initiation and intensification of T2DM therapy.