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.

Cost-effectiveness of a multicomponent quality improvement care model for diabetes in South Asia: The CARRS randomized clinical trial.

OBJECTIVES: To assess the cost-effectiveness of a multicomponent strategy versus usual care in people with type 2 diabetes in South Asia. DESIGN: Economic evaluation from healthcare system and societal perspectives. SETTING: Ten diverse urban clinics in India and Pakistan. PARTICIPANTS: 1146 people with type 2 diabetes (575 in the intervention group and 571 in the usual care group) with mean age of 54.2 years, median diabetes duration: 7 years and mean HbA1c: 9.9% (85 mmol/mol) at baseline. INTERVENTION: Multicomponent strategy comprising decision-supported electronic health records and non-physician care coordinator. Control group received usual care. OUTCOME MEASURES: Incremental cost-effectiveness ratios (ICERs) per unit achievement in multiple risk factor control (HbA1c <7% (53 mmol/mol) and SBP <130/80 mmHg or LDLc <2.58 mmol/L (100 mg/dL)), ICERs per unit reduction in HbA1c, 5-mmHg unit reductions in systolic BP, 10-unit reductions in LDLc (mg/dl) (considered as clinically relevant) and ICER per quality-adjusted life years (QALYs) gained. ICERs were reported in 2020 purchasing power parity-adjusted international dollars (INT$). The probability of ICERs being cost-effective was considered depending on the willingness to pay (WTP) values as a share of GDP per capita for India (Int$ 7041.4) and Pakistan (Int$ 4847.6). RESULTS: Compared to usual care, the annual incremental costs per person for intervention group were Int$ 1061.9 from a health system perspective and Int$ 1093.6 from a societal perspective. The ICER was Int$ 10,874.6 per increase in multiple risk factor control, $2588.1 per one percentage point reduction in the HbA1c, and $1744.6 per 5 unit reduction in SBP (mmHg), and $1271 per 10 unit reduction in LDLc (mg/dl). The ICER per QALY gained was $33,399.6 from a societal perspective. CONCLUSIONS: In a trial setting in South Asia, a multicomponent strategy for diabetes care resulted in better multiple risk factor control at higher costs and may be cost-effective depending on the willingness to pay threshold with substantial uncertainty around cost-effectiveness for QALYs gained in the short term (2.5 years). Future research needs to confirm the long-term cost-effectiveness of intensive multifactorial intervention for diabetes care in diverse healthcare settings in LMICs.

Digital Twin-Enabled Personalized Nutrition Improves Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes: Results of a 1-Year Randomized Controlled Study.

OBJECTIVE: Postprandial hyperglycemia drives insulin resistance and inflammation, leading to metabolic dysfunction-associated fatty liver disease (MAFLD). Prediction of postprandial glycemic responses by digital twin (DT) technology can fashion a personalized nutrition, activity, and sleep to treat type 2 diabetes (T2D) and MAFLD. This study examines the effects of DT-enabled personalized nutrition, activity, and sleep on glycemic status, surrogate markers of MAFLD, and magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) in patients with T2D. METHODS: In an open-label randomized trial (2:1), 319 people with T2D were eligible to intervention (DT) or standard care (SC). DT patients followed personalized meal plans with foods suggested by artificial intelligence with least predicted postprandial glycemic response. The primary end point was to compare change in hemoglobin A1c (HbA1c) and medicine reduction between the DT and SC groups. Key secondary end points included remission to compare liver function test scores and visceral adiposity using MRI. RESULTS: HbA1C was significantly better for DT than for SC (-2.9 [1.8] vs -0.3 [1.2]; P < .001) at 1 year with 72.7% remission of T2D. In patients with abnormal baseline values, significant improvements were seen in DT vs SC patients from baseline to 1 year in nonalcoholic fatty liver disease liver fat score (mean [SD]; -2.5 [2.0] vs -0.1 [1.5]; P < .001) and nonalcoholic fatty liver disease fibrosis score (-1.20 [0.9] vs -0.1 [1.0]; P < .001), respectively. Improvements are seen with DT compared with SC in other liver fat, fibrosis score, and %liver fat by MRI-PDFF. CONCLUSION: At 1 year, DT-enabled personalized treatment significantly improved hyperglycemia and surrogate markers of MAFLD and MRI-PDFF.

Prevalence of Pancreatic Exocrine Insufficiency among Patients with Diabetes Mellitus in India.

AIMS: We aimed to assess the prevalence of pancreatic exocrine insufficiency (PEI) in Indian patients with type 1 diabetes (T1D) or type 2 diabetes (T2D) using a unique diagnostic criterion. METHODS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. RESULTS: This multicenter study included patients aged ≥18 years with diabetes for at least 5 years. The sociodemographic characteristics, lifestyle habits, and clinical characteristics of patients were assessed. Patients were administered the PEI questionnaire (PEI-Q), and fecal elastase-1 (FE) concentration was measured. Patients were diagnosed to have PEI if they satisfied any two of the following three criteria: (a) a PEI-Q total symptom score of ≥0.60; (b) presence of malnutrition using the European Society of Clinical Nutrition and Metabolism diagnostic criteria for malnutrition; or (c) FE concentration <100 µg/gm stool. CONCLUSIONS: Pancreatic exocrine insufficiency (PEI) was found to be prevalent in nearly one-fourth of Indian patients with diabetes, using composite diagnostic criteria.

Simplifying Type 2 DM Care with Linagliptin: A Position Paper.

INTRODUCTION: The burden of type 2 diabetes mellitus (T2DM) is raising dramatically both internationally and in India. It is often observed that multiple therapies or combinations of different drugs are usually required to successfully control hyperglycemia in patients with T2DM. To facilitate effective control of glucose levels, many new agents have been developed over the past few years. MATERIALS AND METHODS: Multiple Advisory Board Meetings were conducted with 87 leading key opinion leaders (KOLs) from diabetes specialty PAN India to understand the simplicity aspect of linagliptin therapy in T2DM patients. DISCUSSION: Linagliptin is a xanthine-based, non-peptidomimetic, selective dipeptidyl peptidase 4 (DPP-4) inhibitor with a different pharmacological profile when compared to other DPP-4 inhibitors already available in India. It is known to decrease the risk of hypoglycemia compared to sulphonylurea (SU), is weight neutral, and no dose modification is required over a broad range of patient populations. This consensus paper discusses the clinical efficacy of DPP-4 inhibitors and linagliptin in T2DM. It also highlights the evidence for the safety of linagliptin in T2DM patients with renal impairment (RI), cardiovascular (CV) risk, and heart failure (HF). CONCLUSION: Linagliptin therapy is simplifying the management of T2DM with good efficacy and its use across a wide range of patients without any dose modification.

Effectiveness of a Multicomponent Quality Improvement Strategy to Improve Achievement of Diabetes Care Goals: A Randomized, Controlled Trial.

BACKGROUND: Achievement of diabetes care goals is suboptimal globally. Diabetes-focused quality improvement (QI) is effective but remains untested in South Asia. OBJECTIVE: To compare the effect of a multicomponent QI strategy versus usual care on cardiometabolic profiles in patients with poorly controlled diabetes. DESIGN: Parallel, open-label, pragmatic randomized, controlled trial. (ClinicalTrials.gov: NCT01212328). SETTING: Diabetes clinics in India and Pakistan. PATIENTS: 1146 patients (575 in the intervention group and 571 in the usual care group) with type 2 diabetes and poor cardiometabolic profiles (glycated hemoglobin [HbA1c] level ≥8% plus systolic blood pressure [BP] ≥140 mm Hg and/or low-density lipoprotein cholesterol [LDLc] level ≥130 mg/dL). INTERVENTION: Multicomponent QI strategy comprising nonphysician care coordinators and decision-support electronic health records. MEASUREMENTS: Proportions achieving HbA1c level less than 7% plus BP less than 130/80 mm Hg and/or LDLc level less than 100 mg/dL (primary outcome); mean risk factor reductions, health-related quality of life (HRQL), and treatment satisfaction (secondary outcomes). RESULTS: Baseline characteristics were similar between groups. Median diabetes duration was 7.0 years; 6.8% and 39.4% of participants had preexisting cardiovascular and microvascular disease, respectively; mean HbA1c level was 9.9%; mean BP was 143.3/81.7 mm Hg; and mean LDLc level was 122.4 mg/dL. Over a median of 28 months, a greater percentage of intervention participants achieved the primary outcome (18.2% vs. 8.1%; relative risk, 2.24 [95% CI, 1.71 to 2.92]). Compared with usual care, intervention participants achieved larger reductions in HbA1c level (-0.50% [CI, -0.69% to -0.32%]), systolic BP (-4.04 mm Hg [CI, -5.85 to -2.22 mm Hg]), diastolic BP (-2.03 mm Hg [CI, -3.00 to -1.05 mm Hg]), and LDLc level (-7.86 mg/dL [CI, -10.90 to -4.81 mg/dL]) and reported higher HRQL and treatment satisfaction. LIMITATION: Findings were confined to urban specialist diabetes clinics. CONCLUSION: Multicomponent QI improves achievement of diabetes care goals, even in resource-challenged clinics. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and UnitedHealth Group.

Spectrum of phenotype and genotype of congenital isolated hypogonadotropic hypogonadism in Asian Indians.

BACKGROUND: Congenital isolated hypogonadotropic hypogonadism (IHH) is caused due to defect in GnRH neuronal development, migration and action. Although genetic aetiology of IHH is increasingly being studied, Asian Indian data on phenotypic spectrum and genetic basis are scarce. OBJECTIVE: To investigate the phenotypic and genotypic spectrum of IHH in Asian Indian subjects. DESIGN, SETTING AND SUBJECTS: A cohort of 135 IHH probands were characterized phenotypically for reproductive and nonreproductive features and screened for rare sequence variations (RSVs) in five genes KAL1, FGFR1, FGF8, GNRHR and KISS1R. RESULT: Of 135 probands [56 normosmic IHH (nIHH) and 79 Kallmann syndrome (KS)], 20 were familial cases. KS group had more male dominance (M:F ratio of 8:1) as compared to nIHH group (M:F ratio of 1·5:1). Complete absence of puberty was more prevalent in KS probands (81% in KS vs 46% in nIHH). The prevalence of MRI abnormalities was more in anosmic group (92·8%) as compared to hyposmic (37·5%) and normosmic groups (15·4%). No particular nonreproductive phenotypic predominance was seen in any group. Genotyping revealed rare sequence variation (RSV) detection rate of 15·5% in five genes studied: (KAL1 - 4·4%, FGFR1 - 4·4%, GNRHR - 6·7%, oligogenicity - 1·5%). Prevalence of RSV was more common in familial cases (35%) as compared to sporadic (12·2%). GNRHR RSV p.C279Y (not reported in patients of ethnicities other than south Asians) was recurring in four unrelated patients. CONCLUSION: In our cohort, 60% were KS with majority of males and a severe reproductive phenotype as against nIHH. Contribution of the genetic burden for the five genes studied was 15·5%. RSV p.C279Y in GNRHR may have a founder effect originating from south Asia. This study provides a model for molecular and phenotypic representation of Asian Indian subjects with IHH.

A Study of salt and fat Consumption pattern in Regional Indian diet among hypertensive and dyslipidemic PaTients - SCRIPT study.

BACKGROUND: Cardiovascular diseases are leading cause of mortality and morbidity. There is an increasing prevalence of hypertension and dyslipidemia due to globalization and adoption of westernized dietary habits in India. These transitions are manifest in dietary patterns and health outcomes. OBJECTIVE: To study the dietary salt and fat intake among patients diagnosed with hypertension and dyslipidemia in India. METHODS: SCRIPT study was a pilot exploratory, cross-sectional, observational, descriptive, multi-center study. It was conducted across hospitals and clinics in five metro cities of India, represented into four regional zones. In each region (North, n = 113; East, n = 98; West, n = 83; South, n = 152), patients diagnosed with hypertension and dyslipidemia were enrolled in the study. Socio-demographic and treatment details were recorded. Participants were interviewed by a dietician and their dietary intake was assessed by a three-day recall of food item questionnaire/ food diary. RESULTS: Overall the mean total daily salt consumption was 10.9 grams. Region-wise, the mean daily salt consumption in North, East, West and South were 14.13, 9.81, 10.12 and 9.38 grams respectively. The daily salt consumption in the North was significantly higher than other regions (P=0.012). The daily consumption of saturated fats (total saturated fat, ghee and butter) in the North was higher and statistically significantly in comparison to West, South and East (P <0.05). Overall, fats contributed to 24.1%, proteins contributed to 12.7% and carbohydrate contributed to 63.2% of total energy per day. The percentage of fat and protein contributing to total energy per day was within the acceptable range. CONCLUSIONS: Our study documented higher dietary salt intake than that recommended in India. There is an urgent need to address the issue of high salt and saturated fat consumption. Nutritional strategies for reducing salt intake, saturated fat and balancing energy nutrients should be urgently applied in Indian hypertensive and dyslipidemia patients.

Consensus Statement on Management of Post-Prandial Hyperglycemia in Clinical Practice in India.

Postprandial hyperglycemia (PPHG) is a detrimental factor in the evolution of diabetes related complications. Numerous studies have established the role of PPHG in development of atherosclerosis and associated cardiovascular conditions. It is seen that management of PPHG can be more troublesome than fasting plasma glucose (FPG). Currently, there are various strategies both monitoring as well as therapeutic to control PPHG but there is no uniformity in practicing these strategies. In the absence of any standard guidelines, widespread variations in the management of PPHG are observed among physicians and diabetologists. The objective of this document is to set forth uniform guidelines to manage PPHG. This will not only result in optimal management and prevention of long term complications of diabetes but also better co-ordination and collaboration among the care providers. Moreover, an Indian perspective that can take into consideration the issues relevant to Indian patient pool will be effective. An expert committee comprising of prominent physicians and researchers associated with diabetes care provided their inputs to provide a basic platform for the formulations of guidelines. Their inputs were supplemented by extensive literature search to collect the relevant evidences. An initial draft was prepared which was reviewed by the core committee. Inputs from other experts were also sought and an initial guideline version was formulated that was presented in a conference, discussed and debated among experts. The guidelines on PPHG were then finalized and published.

Clinical and Hormonal Profile of Classical 21-Hydroxylase Deficiency Congenital Adrenal Hyperplasia: Experience from a Tertiary Centre In India.

Introduction: Congenital adrenal hyperplasia (CAH) is a rare autosomal recessive disorder requiring treatment with steroids. Both over and under-treatment can have an impact on growth outcomes. Aims: The aim of this study was to study the clinical and hormonal profile of a cohort of individuals with classical 21-hydroxylase CAH and to assess the factors influencing growth outcomes in these individuals. Methods: In this cross-sectional study, individuals with classical CAH were included. Baseline data were obtained from electronic medical records. Anthropometric measurements and hormonal profiles were assessed. Quantitative variables were expressed as mean ± standard deviation or median (interquartile range) and qualitative variables as percentages. To measure the correlation between variables, Spearman's rank correlation was used. Results: Of the 27 patients with classical 21-hydroxylase CAH, 13 had salt wasting and 14 had simple virilizing phenotype. The median height standard deviation score (SDS) of the cohort was -1 SDS (-2.00 to 0.2) with 24% having short stature (height < -2 SDS). There was no significant difference in height SDS depending on the age, gender, type of CAH or onset of central precocious puberty. There was no significant correlation between glucocorticoid dose and height SDS (r = 0.104). Obesity was a common finding (40% adults, 41.1% children). However, there was no significant correlation between BMI and glucocorticoid dose (r = 0.419). Conclusions: Short stature was a significant finding as noted in earlier studies. However, the high prevalence of obesity was a new finding that could not be explained by the dose of steroids alone.

Bone Mineral Density and Bone Turnover Marker in a Subclinical Thyrotoxic State in Young Premenopausal Women.

BACKGROUND: Subclinical thyrotoxicosis (SCH) is characterized by normal serum thyroid hormone levels and low thyrotropin levels. The impact of this condition on the skeletal system may vary depending on its cause, yet the relationship is not fully comprehended in premenopausal women. Studies are scarce about its effects on bone health in our population. OBJECTIVES: This study aims to evaluate the bone mineral density (BMD) and bone turnover markers in premenopausal women with SCH and determine if any differences exist based on the condition's etiology. METHODS: A cross-sectional study was conducted at Ramaiah Medical College involving 36 participants for one year and six months after approval from the Ethics Committee. The carboxy-terminal telopeptide of type I collagen in blood and BMD were measured at the lumbar vertebrae (L1-L4) and femoral neck by dual-energy x-ray absorptiometry (Hologic v 2.0, Hologic, Massachusetts, U.S.). Statistical analysis was done using IBM SPSS Statistics for Windows, Version 20 (Released 2011; IBM Corp., Armonk, New York, United States).  Results: The mean age of the study population was 35.2 ± 7.2 years. The etiology was Graves' disease [n=11 (33.3%)], iatrogenic [n=14(38.8%)], toxic adenoma [n=6 (15.1%)], and multi-nodular goiter [n=5 (15.1%)]. The mean BMI was 23.5 ± 3.8 kg/m2, and the mean levels of corrected calcium, phosphorus, and 25 hydroxy-vitamin D were 9.12 ± 0.25 mg/dl, 2.95 ± 0.34 mg/dl, and 29.4 ± 6.4 ng/ml, respectively. The mean BMD at hip and spine was 0.81 ±0.16 g/cm2 and 0.92±0.08 g/cm2 respectively. The mean Z-score was (-0.02 ± 0.8) and (-0.92± 0.08) at the hip and spine. No significant difference was observed in the BMD at the hip (p = 0.14) or spine (p = 0.44) between the endogenous and exogenous subclinical thyrotoxic subgroups. At the same time, the carboxy-terminal telopeptide of type I collagen was significantly different between the two groups (p<0.05). CONCLUSION: In our cross-sectional study of premenopausal women with SCH, BMD at the hip or spine as measured by dual-energy X-ray absorptiometry did not reveal any significant reduction. The subclinical thyrotoxic state may not have an adverse effect on bone health in premenopausal females with sufficient levels of serum 25-hydroxy-vitamin D in the short term.

Digital Twin in Managing Hypertension Among People With Type 2 Diabetes: 1-Year Randomized Controlled Trial.

Background: Digital twin (DT)-guided lifestyle changes induce type 2 diabetes (T2D) remission but effects on hypertension (HTN) in this population are unknown. Objectives: The purpose of this study was to assess effects of DT vs standard of care (SC) on blood pressure (BP), anti-HTN medication, HTN remission, and microalbuminuria in participants with T2D. Methods: This is a secondary analysis of a randomized controlled trial in India of 319 participants with T2D. Participants were randomized to DT group (N = 233), which used artificial intelligence-enabled DT technology, or SC group (N = 86). A Home Blood Pressure Monitoring system guided anti-HTN medication adjustments. BP, anti-HTN medications, HTN remission rates, and microalbuminuria were compared between groups. Results: Among the 319 participants, 44 in DT and 15 in SC group were on anti-HTN medications, totaling 59 (18.4%) participants. DT group achieved significant reductions in systolic blood pressure (-7.6 vs -3.2 mm Hg; P < 0.007) and diastolic blood pressure (-4.3 vs -2.2 mm Hg; P = 0.046) after 1 year compared with SC group. 68.2% of DT group remained off anti-HTN medications compared to none in SC group. Among participants with HTN, DT subgroup achieved higher rates of normotension (40.9% vs 6.7%; P = 0.0009) and HTN remission (50% vs 0%; P < 0.0001) than SC subgroup. DT group had a higher rate of achieving normoalbuminuria (92.4% vs 83.1%; P = 0.018) at 1 year compared with SC group. Conclusions: Artificial intelligence -enabled DT technology is more effective than SC in reducing BP and anti-HTN medications and inducing HTN remission and normoalbuminuria in participants with HTN and T2D. (A Novel WholeBody Digital Twin Enabled Precision Treatment for Reversing Diabetes; CTRI/2020/08/027072).

Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergo metformin monotherapy. This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Study of Effects of Gender-Affirming Hormone Therapy on Bone Mineral Density in Individuals with Gender Dysphoria.

Introduction: Gender affirming hormone therapy (GAHT) is the mainstay treatment in transitioning individuals and has positive physical and psychological effects. Among the things to monitor in transgender patients on long-term hormones, bone health is an essential consideration. As the calcium intake in the Indian population is less, and many gender-incongruent individuals may not take adequate calcium in their diet, we needed data on the bone health of Indians with gender dysphoria as the information available globally may not apply to our population. Materials and Methods: The study was performed to assess bone mineral density in individuals with gender dysphoria who were on gender-affirming hormonal therapy for at least 6 months. It was a hospital-based cross-sectional study of bone mineral density measured at two sites - hip and spine in individuals with gender dysphoria on GAHT for at least six months. Results: A total of 30 individuals were included in this study. The mean age of individuals with Gender dysphoria was found to be 28.17 ± 6.15 years, and the age range was 19-42 years. Out of the 30 individuals, 14 were transgender males, and the remaining 16 were transgender females. Bone mineral density at the hip and spine in transgender males was 1.047 ± 0.124 g/cm2 and 1.065 ± 0.115 g/cm2, which was better compared to transgender females in whom the bone mineral density at hip and spine was 0.899 ± 0.873 g/cm2 and 0.854 ± 0.099 g/cm2 (P = 0.001 for hip; P = 0.000 for spine). The Z score at hip and spine were better in transgender males as compared to transgender females (P < 0.001 for hip; P < 0.001 for spine) when compared to genetic sex and at the spine (P = 0.001) when compared to affirmed sex. In this study, we observed that the transgender females who underwent orchidectomy had a lower mean Z score at spine compared to individuals who did not undergo the procedure. Conclusions: The current study results indicate that GAHT does have positive effects on bone health in transmen.

Study of FGF21 Levels in Transgender People and its Association with Metabolic Parameters.

Background: Fibroblast growth factor (FGF21) is a metabolic regulator whose role in humans is unidentified. FGF21 has generated a lot of potential of becoming a therapeutic agent for the management of type 2 diabetes mellitus and dyslipidaemia. The role of FGF21 in gender dysphoria individuals has not been studied. Objective: Primary objective was to assess FGF21 levels in transgender individuals and compare with controls and secondary objective was to compare FGF21 levels with lipid and glucose parameters in transgender people. Results: Twenty-three transfemales and 21 transmales were included in the study and compared with 44 controls. Height and fasting blood glucose of transfemales was statistically greater than transmales, with no other differences in baseline characteristics. Although FGF21 levels were numerically greater in transfemales (183.50 ± 97.39), it was not statistically significant. FGF21 levels did not vary statistically when compared to controls although it was numerically higher. Univariate analysis was done in transgender patients and FGF21 levels were positively correlated with serum total cholesterol and serum LDL cholesterol in transfemales but not in transmales. Multivariate analysis was also done taking 50th centile and 75th centile of FGF21 levels of controls and was found that only serum total cholesterol and serum LDL positively correlated with FGF21 levels in transfemales with 75th centile as cutoff. Conclusion: FGF21 levels correlated positively with serum triglycerides and serum LDL cholesterol in transfemales but not in transmales. Hence, FGF21 levels can be used as a marker for the development of metabolic syndrome in transfemales.

Evolution of Guideline Recommendations on Insulin Therapy in Type 2 Diabetes Mellitus Over the Last Two Decades: A Narrative Review.

The prevalence of type 2 diabetes mellitus has been increasing worldwide. As the therapeutic options for type 2 diabetes mellitus have evolved over the last 2 decades, national and global guidelines related to type 2 diabetes mellitus pharmacotherapy issued by various organizations have tended to vary in their recommendations. This narrative review aimed to analyze the key recommendations by major global and national guidelines on the initiation of insulin therapy in patients with type 2 diabetes mellitus over the last 20 years. Strategies for insulin therapy for titration and intensification were also assessed. All guidelines recommend initiation of insulin (basal/ premixed/other formulations) when glycemic targets are not achieved despite lifestyle measures and oral antidiabetic drugs. In the recent decade, early initiation of insulin has been recommended when the glycated hemoglobin levels are >10% or blood glucose levels are ≥300 mg/dL (16.7 mmol/L). Initiation is recommended at a dose of 10 units or 0.1-0.2 U/kg. Titration is advised to achieve the optimal dosage, while intensification is recommended when glycemic targets are not achieved despite titrating to an acceptable level. Glucose monitoring at periodic intervals is recommended for adequate glycemic control. The guidelines further suggest that the choice of insulin should be individualized, considering the clinical status of patients with type 2 diabetes mellitus. The physicians as well as patients should be a part of the decisions made regarding the therapeutic choice of regimen, preparation, and delivery device.

Solar ponds-a mini review.

A solar pond is a simple system that collects and stores heat for thermal and electrical applications. Heat storage and heat extraction are the key factors in the solar pond. Salt is added to the pond with fresh water to form a salinity gradient solar pond (SGSP). The solar pond comprises of three zones, namely, the upper convective zone (UCZ), the non-convective zone (NCZ) and the lower convective zone (LCZ). The LCZ is also called the storage zone. Generally, the LCZ stores the heat energy of the incoming solar radiation, and this heat may be used for various applications. In this paper, a review is done on the study of solar ponds with various designs and modifications, heating methods, use of floating devices, use of baffle plates, use of heat exchangers, use of flat plate collectors, use of different types of insulation, etc.

Indian Phenotype Characteristics Among Patients with Type 2 Diabetes Mellitus: Insights from a Non-interventional Nationwide Registry in India.

Background: Indian patients with type 2 diabetes mellitus (T2D) constitute one-sixth of affected adults globally. Here, we evaluate the association of body mass index (BMI) with body fat percentage (BF%) and glycated haemoglobin (HbA1c) levels among patients with T2D in India. Method: This was a cross-sectional Indian registry study across 845 geographically diverse zones between December 2017 and August 2019. Results: Of 37,927 patients, 55.6% were men, with a mean ± standard deviation age of 54.2 ± 11.5 years and HbA1c of 8.3 ± 1.71%. Mean ± standard deviation BMI and BF% were 27.0 ± 4.6 kg/m2 and 32.0 ± 8.0%, respectively. Overall, 15.4% of patients were overweight, and 25.0% were obese. Despite fewer males (20.7%) having BMI-based obesity than females (31.2%), around three-quarters of both sexes had BF%-defined obesity (males 77.2%; females 71.2%). One-third of males (34.6%) and 41.9% of females had BF%-defined obesity despite normal BMI. The association was substantiated by a moderately significant correlation (r=0.51) between BMI and BF% in the overall population (p<0.0001). Conclusion: This pan-India registry presents a real-world reflection of the Asian Indian phenotype: high BF% despite lower BMI in people with T2D. This highlights the importance of primordial and primary prevention, and may guide decisions on the choice of agents for glycaemic control, with a preference for drugs that promote weight loss or are weight neutral.

Impact of Partial Meal Replacement on Glycemic Levels and Body Weight in Indian Patients with Type 2 Diabetes (PRIDE): A Randomized Controlled Study.

INTRODUCTION: Partial meal replacement (PMR) offers potential glycemic and weight control benefits in type 2 diabetes mellitus (T2DM) patients. We evaluated the clinical impact of PMR (diabetes-specific nutritional supplement [DSNS]) in overweight/obese Indian patients with T2DM. METHODS: PRIDE, a 12-week, phase IV, open-label, multicenter study randomized (1:1) newly diagnosed T2DM patients (≤ 1 year) to either DSNS plus standard of care (SOC; diabetes treatment with dietary counseling) group (PMR) or SOC alone group (SOC). The primary endpoint was mean change in glycated hemoglobin (HbA1c) from baseline to week 12. Secondary endpoints were changes in glucose profiles, body weight, waist circumference, lipid profile, and factors impacting quality-of-life (QoL) at week 6 and 12 from baseline. Safety was assessed throughout the study. RESULTS: Of the 176 patients enrolled, 171 (n = 85 in PMR group; n = 86 in SOC group) were included in the modified intent-to-treat population. The mean reduction in HbA1c at week 12 from baseline in PMR group was significant compared to the SOC group (- 0.59 vs. - 0.21%, p = 0.002). At week 12, the PMR group showed significant reduction in mean body weight (- 2.19 vs. - 0.22 kg; p = 0.001) and waist circumference (- 2.34 vs. - 0.48 cm; p = 0.001) compared to SOC group. Mean fasting plasma glucose and post-prandial glucose significantly reduced from baseline at week 6 and 12 in each group (p < 0.05). No significant change was observed in lipid profile. QoL parameters (treatment adherence, general well-being, and energy fulfilment) in the PMR were significantly better than SOC group (p < 0.05). Patients were satisfied with the taste of DSNS. No serious adverse events were reported. CONCLUSIONS: DSNS is an encouraging option for PMR strategy, as it significantly improved HbA1c, body weight, waist circumference, and overall well-being among overweight/obese Indian T2DM patients. TRIAL IDENTIFICATION NO: CTRI/2019/10/021595.

Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. METHODS: A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. RESULTS: Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). CONCLUSIONS: Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.