Early screening for foot problems in people with diabetes is the need of the hour: 'Save the Feet and Keep Walking Campaign' in India.

INTRODUCTION: Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India. RESEARCH DESIGN AND METHODS: A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023. RESULTS: Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet. CONCLUSIONS: One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare.

Responsible Use of Oral Corticosteroids in People with Comorbid Diabetes: An Expert Consensus.

Globally, diabetes mellitus (DM) is a substantial contributor to morbidity and mortality. Comorbidities and intercurrent illnesses in people with diabetes may necessitate the use of steroids. Acute as well as chronic use of steroids contributes substantially to the development of various complications. Despite this, there are no standard guidelines or consensus to provide a unified approach for the rational use of steroids in people with diabetes. Also, there is scant harmonization among clinicians with the use of different steroids in routine practice. To address the inconsistencies in this clinical arena, the consensus working group (CWG) formulated a unified consensus for steroid use in people with diabetes. In people with diabetes, the use of steroids causes hyperglycemia and may precipitate diabetic ketoacidosis (DKA). An increase in weight is directly related to the dose and duration of the steroid therapy. Steroid-related alterations in hyperglycemia, dyslipidemia, and hypertension (HTN) add to the increased risk of cardiovascular (CV) disease. The risk of complications such as infections, osteoporosis, myopathy, acne, cataracts, and glaucoma may increase with the use of steroids. Appropriate and timely monitoring of these complications is necessary for early detection and treatment of such complications. Given the systemic effects of various antihyperglycemic drugs, there is a possibility of aggravating or diminishing the specific complications. Preference to a safer steroid is required matching the steroid dose equivalence and individualizing patient management. In conclusion, short-, intermediate-, or long-term use of steroids in people with diabetes demands their rational use and holistic approach to identify, monitor, and treat the complications induced or aggravated by the steroids.

Public Health System's Preparedness to Address Polycystic Ovarian Syndrome: A Rapid Assessment Survey of Health-care Providers in India.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common endocrine disorders largely affecting women of reproductive age group. OBJECTIVES: This study aimed to understand the Indian public health-care systems' preparedness in addressing PCOS. MATERIALS AND METHODS: A multicentric rapid assessment cross-sectional study was undertaken among 173 health-care providers serving across various public health-care facilities in India. This study was a component of a larger task force study that aimed to estimate the community-based prevalence of PCOS in India. Information on PCOS cases reported that knowledge about PCOS diagnosis, management practices, availability of diagnostic facilities, and drugs was explored. RESULTS: Irregular menstrual cycle was the most commonly reported PCOS symptom. Most of the health-care providers (HCPs) lacked correct knowledge about diagnostic criteria and investigation needed for the diagnosis of PCOS. Diagnostic facilities and drugs were inadequate. However, some facilities had access to investigations through public-private partnerships. Awareness programs on PCOS in the community were negligible, and PCOS cases were not documented. Training HCPs on PCOS along with the availability of specialists and strengthening diagnostic facilities were some major demands from the HCPs. CONCLUSION: Results suggest the need for training HCPs, strengthening infrastructure with good referral linkages, and adequate supply of drugs to help improve PCOS management at public health-care facilities in India. There is a need to develop national technical and operational guidelines to address PCOS using a multidisciplinary approach across all levels of care. Creating demand for services and advocating healthy lifestyles through community awareness can help early diagnosis and prevention of complications.

Common Hematological Reference Indices Among Healthy Reproductive Age Indian Women-Data Subset from Nationwide Study.

Despite the negative implications on women's health, pregnancy, and fetal outcomes, population-based studies on hematological indices among reproductive age women in India have received inadequate attention. This study aimed to generate normative ranges for various hematological parameters among these women. After ethics approval, apparently healthy (n = 5884) women (aged 18-40 years) were recruited from six eco-geographic zones of India. After various exclusions (n = 5412), including women having anemia, data of clinically, and biochemically healthy women (n = 472) was analysed to generate centiles (2.5 and 97.5th) and correlations. The mean age and mean BMI of women was 29.3 ± 6.5 years and 23.25 ± 3.26 kg/m2 with BP of 112.26 ± 8.9/74.04 ± 6.7 mmHg. The reference intervals for hemoglobin (12-15.1 gm/dl), RBC (3.68-5.55 millions/µl), WBC (4.1-11.26*109/L), platelet count (1.32-4.42*105/µl), and erythrocyte sedimentation rate (4.35-41.65 mm/hr) were different from currently used reference values (p < 0.05). However, these haematological indices did not vary among various age categories, geographical zones, ethnicities and rural or urban origins. Pearson's correlation revealed a statistically significant association between ESR, WBC, monocytes, and platelets with homeostasis model assessment of insulin resistance (HOMA-IR). Women with HOMA-IR > 2 displayed a statistically significant differences in parameters like MCV, ESR, eosinophil and platelet counts as compared to the women with HOMA-IR < 2. This study provides a pioneering reference data of hematological indices among women of reproductive age in India. Despite the small sample size results can be extrapolated to the national population given the representative sampling of various geographical zones. This may pave way for future comprehensive large-scale studies on the subject. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01714-6.

Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Global Warming and Endocrinology: The Hyderabad Declaration of the South Asian Federation of Endocrine Societies.

Global warming and endocrine disorders are intertwined issues posing significant challenges. Greenhouse gases emanating from human activities drive global warming, leading to temperature rise and altered weather patterns. South Asia has experienced a noticeable temperature surge over the past century. The sizable population residing in the region heightens the susceptibility to the impact of global warming. In addition to affecting agriculture, water resources, and livelihood, environmental changes interfere with endocrine functioning. Resulting lifestyle changes increase the risk of metabolic and endocrine disorders. Individuals with diabetes face heightened vulnerability to extreme weather due to impaired thermoregulation. A high ambient temperature predisposes to heat-related illnesses, infertility, and nephropathy. Additionally, essential endocrine drugs and medical devices are susceptible to temperature fluctuations. The South Asian Federation of Endocrine Societies (SAFES) calls for collaboration among stakeholders to combat climate change and promote healthy living. Comprehensive approaches, including the establishment of sustainable food systems, promotion of physical activity, and raising awareness about environmental impacts, are imperative. SAFES recommends strategies such as prioritizing plant-based diets, reducing meat consumption, optimizing medical device usage, and enhancing accessibility to endocrine care. Raising awareness and educating caregivers and people living with diabetes on necessary precautions during extreme weather conditions are paramount. The heat sensitivity of insulin, blood glucose monitoring devices, and insulin pumps necessitates proper storage and consideration of environmental conditions for optimal efficacy. The inter-connectedness of global warming and endocrine disorders underscores the necessity of international collaboration guided by national endocrine societies. SAFES urges all stakeholders to actively implement sustainable practices to improve endocrine health in the face of climate change.

Plasma levels and dietary intake of minerals in patients with type 2 diabetes and chronic kidney disease: A case-control study.

BACKGROUND AND AIM: Diabetic kidney disease (DKD) is the primary cause of chronic kidney disease (CKD) worldwide. Altered mineral levels leading to adverse outcomes are widely reported in diabetes but limited in DKD, in the Indian scenario, hence this study was taken up to address this issue. METHODS: A hospital-based case-control study was taken up with 54 healthy controls (C) and 140 subjects with type 2 diabetes wherein 74 subjects with diabetes and CKD formed the DKD group, and 66 subjects with diabetes but no CKD formed the diabetic no-chronic kidney disease (DNCKD) group. High-resolution inductively coupled plasma mass spectrometry was used to evaluate the blood levels of minerals (calcium (Ca), vanadium (V), chromium (Cr), manganese (Mn), iron (Fe), cobalt (Co), copper (Cu), zinc (Zn), and selenium (Se)), and a raw food-based food frequency questionnaire for dietary intakes. Estimated glomerular filtration rate (eGFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m2) and albuminuria. Spearman's rank correlation was used to evaluate the relationship between the categorical variables. RESULTS: The median values of plasma Ca in the DKD group were significantly lower compared with the DNCKD and C groups (10.5 mg/dL vs. 11.0 mg/dL and 11.7 mg/dL, p<0.001). Furthermore, plasma Ca levels lowered with declining kidney function, as evidenced by the eGFR and albuminuria segregation. Dietary intake of minerals did not correlate with the corresponding plasma levels. However, in the DKD group, eGFR correlated positively with the plasma levels of Ca (r= 0.422, p=0.001), Cr (r= 0.351, p=0.008), Mn (r= 0.338, p=0.011), Fe (r= 0.403, p=0.002), Cu (r= 0.274, p=0.041) and negatively with Se (r= -0.486, p<0.001). CONCLUSION: Plasma Ca levels are lower in the DKD group with a strong positive association with eGFR, indicating its role in predicting the onset and progression of kidney function decline.

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.

Effectiveness of Dapagliflozin as Add-On to Metformin with or without Other Oral Antidiabetic Drugs in Type 2 Diabetes Mellitus: A Multicentre, Retrospective, Real-World Database Study.

BACKGROUND: Real-world Indian studies evaluating effectiveness of dapagliflozin as an add-on to other oral antidiabetic drugs (OAD) in patients with type 2 diabetes mellitus (DM) are scarce. METHODS: An electronic medical record (EMR)-based, retrospective, multicentre study was conducted to evaluate the effectiveness of dapagliflozin as add-on therapy in adult patients with inadequately controlled DM on metformin with or without other OAD. Baseline characteristics (visit 1: metformin or metformin plus OAD treatment for at least 30 days) and treatment-related outcomes (visit 2: follow-up) considered between 60 and 140 days after adding/switching dapagliflozin [glycated haemoglobin (HbA1c), body mass index (BMI), systolic blood pressure (SBP) and diastolic blood pressure (DBP)] were analysed. RESULTS: A total of 3616 patients were screened from 478 centres. Most patients had received dapagliflozin (D) + metformin (M) + at least one other OAD [D + M + OAD, n = 2907 (80.4%), 408 followed-up with HbA1c reported], while 709 patients (19.6%, 138 followed-up with HbA1c reported) received dapagliflozin + metformin (D + M). Treatment with dapagliflozin as an add-on therapy resulted in significant change in HbA1c (-1.1 ± 1.44%; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.6 ± 1.41%; p < 0.05 for HbA1c subgroup ≥ 8%) at visit 2 compared with visit 1. Significant change in body weight (-1.4 ± 3.31 kg; p < 0.05 for HbA1c subgroup ≥ 7.5%; - 1.5 ± 3.22 kg; p < 0.05 for HbA1c subgroup ≥ 8%) was observed at visit 2. Similarly, a significant change in BMI was noted for the HbA1c subgroup ≥ 7.5% (-1.0 ± 8.38 kg/m2). However, the change in BMI in the HbA1c subgroup ≥ 8% was noted to be -1.4 ± 10.4 kg/m2, which was not statistically significant (p = 0.08). In the overall study population, significant change in the SBP (-4.5 ± 14.9 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -4.5 ± 15.1 mmHg; p < 0.0001 for HbA1c subgroup ≥ 8%) was observed at visit 2 compared with visit 1. On identical lines, significant change in DBP (-1.5 ± 8.94 mmHg; p < 0.05 for HbA1c subgroup ≥ 7.5%; -1.4 ± 8.91 mmHg; p < 0.05 for HbA1c subgroup ≥ 8%) was noted. CONCLUSIONS: Dapagliflozin showed significant improvement in glycemic parameter, BMI and BP when added to metformin, with or without other OADs in a real-world scenario.

Defining and Diagnosing Obesity in India: A Call for Advocacy and Action.

The prevalence of overweight and obesity has more than doubled since 1980, and it is predicted that around two-thirds of the global burden of the disease will be attributed to chronic non-communicable diseases. Developing countries are experiencing a more dramatic rise in the prevalence of obesity in recent years. As per National Family Health Survey-5 (NFHS-5), one in every four Indians is now having obesity. It has been reported that being overweight and obese is a significant problem among different socioeconomic spectrums of men and women in India, especially among the elderly, people residing in urban regions, and diverse socioeconomic strata. There is an urgent need to identify obesity as a chronic disease requiring immediate attention, mandating timely screening, timely treatment, and economical ways of achieving and managing weight loss across the country. In this review, the authors have discussed various aspects of overweight and obesity and critically appraised the current status of obesity in India, its public health implications, the significance of screening, the role of BMI and other parameters in diagnosing obesity, and the need for treatment and cost-effective prescriptions.

Diabetes Care And Transgender Health: Clinical Pearls.

Diabetes and other cardiometabolic diseases occur across the world, and do not discriminate between populations. This communication reviews the epidemiology and etiology of diabetes in the transgender population, and highlights clinical issues that must be kept in mind while evaluating and managing the condition. It adds value to existing literature by equipping health care professionals with specific skills designed to enhance diabetes care delivery, and results, in transgender individuals.

Prevalence, Regional Variations, and Predictors of Overweight, Obesity, and Hypertension Among Healthy Reproductive-Age Indian Women: Nationwide Cross-Sectional Polycystic Ovary Syndrome Task Force Study.

BACKGROUND: A clear understanding of the anthropometric and sociodemographic risk factors related to BMI and hypertension categories is essential for more effective disease prevention, particularly in India. There is a paucity of nationally representative data on the dynamics of these risk factors, which have not been assessed among healthy reproductive-age Indian women. OBJECTIVE: This cross-sectional polycystic ovary syndrome (PCOS) task force study aimed to assess the anthropometric and sociodemographic characteristics of healthy reproductive-age Indian women and explore the association of these characteristics with various noncommunicable diseases. METHODS: We conducted a nationwide cross-sectional survey from 2018 to 2022 as part of the Indian Council of Medical Research-PCOS National Task Force study, with the primary aim of estimating the national prevalence of PCOS and regional phenotypic variations among women with PCOS. A multistage random sampling technique was adopted, and 7107 healthy women (aged 18-40 years) from 6 representative geographical zones of India were included in the study. The anthropometric indices and sociodemographic characteristics of these women were analyzed. Statistical analysis was performed to assess the association between exposure and outcome variables. RESULTS: Of the 7107 study participants, 3585 (50.44%) were from rural areas and 3522 (49.56%) were from urban areas. The prevalence of obesity increased from 8.1% using World Health Organization criteria to 40% using the revised consensus guidelines for Asian Indian populations. Women from urban areas showed higher proportions of overweight (524/1908, 27.46%), obesity (775/1908, 40.62%), and prehypertension (1008/1908, 52.83%) categories. A rising trend of obesity was observed with an increase in age. Women aged 18 to 23 years were healthy (314/724, 43.4%) and overweight (140/724, 19.3%) compared with women aged 36 to 40 years with obesity (448/911, 49.2%) and overweight (216/911, 23.7%). The proportion of obesity was high among South Indian women, with 49.53% (531/1072) and 66.14% (709/1072), using both World Health Organization criteria and the revised Indian guidelines for BMI, respectively. BMI with waist circumference and waist-to-height ratio had a statistically significant linear relationship (r=0.417; P<.001 and r=0.422; P<.001, respectively). However, the magnitude, or strength, of the association was relatively weak (0.3<|r|<0.5). Statistical analysis showed that the strongest predictors of being overweight or obese were older age, level of education, wealth quintile, and area of residence. CONCLUSIONS: Anthropometric and sociodemographic characteristics are useful predictors of overweight- and obesity-related syndromes, including prehypertension, among healthy Indian women. Increased attention to the health of Indian women from public health experts and policy makers is warranted. The findings of this study can be leveraged to offer valuable insights, informing health decision-making and targeted interventions that mitigate risk factors of overweight, obesity, and hypertension. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/23437.

Normative range of various serum hormonal parameters among Indian women of reproductive age: ICMR-PCOS task force study outcome.

Background: The hormonal profile varies considerably with age, gender, ethnicity, diet or physiological state of an individual. Limited population-specific studies have studied the variations in hormonal parameters among apparently healthy women. We aimed to analyse the biological reference interval for various hormonal parameters in the reproductive-aged healthy Indian women. Methods: Out of 3877 participants that were clinically evaluated, 1441 subjects were subjected to laboratory investigations. All participants underwent a detailed clinical, biochemical and hormonal profiling. The hormone analysis was carried out at a single centre using a uniform methodology. Among the participants evaluated for biochemical and hormonal parameters, subjects that presented any abnormal profile or had incomplete investigations (n = 593) were excluded for further analysis. Findings: The mean age (±SD) of the subjects retained in the final analysis (n = 848) was 29.9 (±6.3) years. In the present study, the biological reference interval (2.5th-97.5th centile) observed were: serum T4: µg/dL (5.23-12.31), TSH: µg/mL (0.52-4.16) and serum prolactin: ng/mL (5.13-37.35), LH: mIU/mL (2.75-20.68), FSH: mIU/mL 2.59-15.12), serum total testosterone: ng/mL (0.06-0.68), fasting insulin: mIU/mL (1.92-39.72), morning cortisol: µg/dL (4.71-19.64), DHEAS:µg/dL (50.61-342.6) and SHBG: nmol/L (21.37-117.54). Unlike T4, TSH, LH, and E2, the biological reference interval for prolactin, FSH, testosterone, C-peptide insulin and DHEAS varied when the subjects were stratified by age (p < 0.05). The comparative analysis showed marginal differences in the normative ranges for the hormones analysed among different populations. Interpretation: Our first large composite data on hormonal measures will benefit future endeavours to define biological reference intervals in reproductive-aged Indian women. Funding: The study was financially supported by the grant-in-aid from ICMR vide file No:5/7/13337/2015-RBMH.

Variation in normative values of major clinical biochemistry analytes in healthy reproductive-age women in India: A subset of data from a National Indian Council of Medical Research-Polycystic Ovary Syndrome task force study.

OBJECTIVES: Clinical biochemistry reference intervals (RIs) play a crucial role in interpreting patient test results and making informed clinical decisions. Using data from an ongoing Indian Council of Medical Research-National task force study on healthy women, normative ranges for commonly analyzed biochemical analytes were established. MATERIALS AND METHODS: A.total of 13,181 women of reproductive age (18-40 years) were recruited from different urban and rural regions of the country, of which 9898 women signed an informed consent were included. Among these, women having features of hyperandrogenism, menstrual cycle irregularities, and comorbidities were excluded. RIs of 22 analytes were computed in the remaining 938 women controls. To estimate the 95% range of the reference distribution, the limits of the 2.5th percentile and the 97.5th percentile were used in the study. RESULTS: Mean ± standard deviation of age and body mass index of participants was 30.12 ± 6.32 years and 22.8 ± 3.36 kg/m2 respectively. Centiles (2.5th-97.5th) of liver function parameters, lipid parameters, glycaemic parameters, and renal parameters are presented. No significant difference in analytes was observed in relation to the area of residence, and age groups except in albumin (P = 0.03). The distribution of most of the parameters was consistent with the various RI studies conducted in India as well as other countries. CONCLUSION: This is the first study generating biochemical RIs data among a large representative sample of healthy reproductive-age women recruited using a robust design across the country. The resource may serve as a reference range for common biochemical analytes for future in this age group.

Practical and Pragmatic Usage of T3 in Hypothyroidism.

Hypothyroidism is one of the common endocrine disorders encountered in clinical practice. Though thyroxine (T4) remains the treatment of choice in most clinical situations, with the recent introduction of oral triiodothyronine (T3) in South Asian countries, it is important to know about its utility in clinical practice. In this brief communication, we delineate potential clinical indications for T3 therapy, while highlighting possible concerns and caveats.

The 5A model for non- communicable disease advocacy.

We share a comprehensive 5A model which puts in perspective a clear-cut method to approach and address non communicable disease (NCD) advocacy. We suggest that the first step towards NCD control is awareness amongst health care professionals, and acceptance of their responsibility towards public health. Once this is done, active assertion follows, and leads to action on the ground. Regular audit, however, is necessary, to ensure effective and efficient advocacy for NCD. This model should be followed in all health care settings, including primary care diabetes.

Fixed-Dose Combination of Dapagliflozin + Sitagliptin + Metformin in Patients with Type 2 Diabetes Poorly Controlled with Metformin: Phase 3, Randomized Comparison with Dual Combinations.

INTRODUCTION: This study compared efficacy and safety of triple drug fixed-dose combination (FDC) of dapagliflozin (DAPA) + sitagliptin (SITA) + metformin (MET) extended release (ER) with SITA + MET sustained release (SR) and DAPA + MET ER in patients with type 2 diabetes poorly controlled with metformin. METHODS: This phase 3, randomized, open-label, active-controlled study included adult patients with glycated hemoglobin (HbA1c) ≥ 8% (64 mmol/mol) and ≤ 11% (97 mmol/mol), randomized in 1:1:1 ratio to receive either FDC of DAPA + SITA + MET ER (10 mg + 100 mg + 1000 mg) tablets once daily (n = 137) or co-administration of SITA + MET SR (100 mg + 1000 mg) tablets once daily (n = 139) or FDC of DAPA + MET ER (10 mg + 1000 mg) tablets once daily (n = 139). Primary endpoint was mean change in HbA1c from baseline to week 16. RESULTS: Mean baseline HbA1c was approximately 9% (75 mmol/mol) in each treatment group. At week 16, adjusted mean reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER (- 1.73% [- 19.0 mmol/mol]) compared to SITA + MET SR (- 1.28% [- 14.1 mmol/mol]; difference of - 0.46% [- 5.1 mmol/mol], p < 0.001) and DAPA + MET ER (- 1.33% [- 14.6 mmol/mol]; difference - 0.4% [4.4 mmol/mol], p < 0.001). Similarly, at week 12, reduction in HbA1c from baseline was significantly greater with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0006) and DAPA + MET ER (p = 0.0276). At week 16, DAPA + SITA + MET ER showed significant reduction in postprandial blood glucose compared to DAPA + MET ER (p = 0.0394) and significant reduction in fasting blood glucose with DAPA + SITA + MET ER compared to SITA + MET SR (p = 0.0226). The proportion of patients achieving HbA1c < 7.0% (53 mmol/mol) at week 16 was significantly higher with DAPA + SITA + MET ER (38.5%) versus SITA + MET SR (12.8%) (p < 0.001) and DAPA + MET ER (21.3%) (p = 0.0023). All study medications were well tolerated. CONCLUSION: Triple FDC of DAPA + SITA + MET ER tablets once daily was significantly better in achieving glycemic control versus dual combination once daily in patients with type 2 diabetes poorly controlled with metformin without any significant safety concerns. TRIAL REGISTRATION: CTRI/2021/11/038176, registered on 22 November 2021.

Type 2 diabetes is a progressive disease in which the risks of microvascular and macrovascular complications and mortality are strongly associated with hyperglycemia. Achieving glycemic control remains the main goal of treatment to prevent these complications. Estimates in 2019 showed that 77 million individuals had diabetes in India, which is expected to rise over 134 million by 2045. Considering the progressive nature of the disease, many guidelines recommend use of dual or triple drug therapy based on glycated hemoglobin (HbA1c) level. Use of fixed-dose combination (FDC) helps to improve therapy compliance and can provide optimum therapeutic benefits. Mechanisms of action of dipeptidyl peptidase 4 (DPP4) and sodium­glucose cotransporter 2 (SGLT2) inhibitors are complementary to that of metformin with low risk of hypoglycemia. Studies have shown beneficial effects of adding both DPP4 inhibitors and SGLT2 inhibitors after metformin monotherapy. This phase 3 study was designed to assess efficacy and safety of triple FDC of dapagliflozin + sitagliptin + metformin extended release in comparison with combipack of sitagliptin + metformin sustained release and FDC of dapagliflozin + metformin ER in patients with type 2 diabetes inadequately controlled with metformin monotherapy. The study demonstrated superiority of triple FDC of dapagliflozin + sitagliptin + metformin ER over dual combinations in terms of reduction in HbA1c and percentage of patients achieving target HbA1c at the end of week 16. The current study provides evidence for considering triple FDC of dapagliflozin + sitagliptin + metformin ER as an alternative option with minimal risk of hypoglycemia and weight gain, while considering oral triple-combination therapy for patients to achieve their glycemic target.

Expert Opinion on the Diagnosis and Management of Male Hypogonadism in India.

Male hypogonadism (MH) is a clinical and biochemical syndrome caused by inadequate synthesis of testosterone. Untreated MH can result in long-term effects, including metabolic, musculoskeletal, mood-related, and reproductive dysfunction. Among Indian men above 40 years of age, the prevalence of MH is 20%-29%. Among men with type 2 diabetes mellitus, 20.7% are found to have hypogonadism. However, due to suboptimal patient-physician communication, MH remains heavily underdiagnosed. For patients with confirmed hypogonadism (either primary or secondary testicular failure), testosterone replacement therapy (TRT) is recommended. Although various formulations exist, optimal TRT remains a considerable challenge as patients often need individually tailored therapeutic strategies. Other challenges include the absence of standardized guidelines on MH for the Indian population, inadequate physician education on MH diagnosis and referral to endocrinologists, and a lack of patient awareness of the long-term effects of MH in relation to comorbidities. Five nationwide advisory board meetings were convened to garner expert opinions on diagnosis, investigations, and available treatment options for MH, as well as the need for a person-centered approach. Experts' opinions have been formulated into a consensus document with the aim of improving the screening, diagnosis, and therapy of men living with hypogonadism.