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.

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-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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Fetuin-A in newly detected type 2 diabetes mellitus as a marker of non-alcoholic fatty liver disease.

INTRODUCTION: Fetuin-A has been implicated in the causation of metabolic disorders such as obesity, diabetes, and hepatic steatosis. Numerous studies have shown the association between levels of fetuin-A in type 2 diabetes mellitus (T2DM) and non-alcoholic fatty liver disease (NAFLD). The levels of fetuin-A in newly detected type 2 diabetic (NDD) patients and its relationship with the presence of NAFLD have not been studied. OBJECTIVE: To study the fetuin-A levels in patients with NDD and its relationship with NAFLD. METHODS: A total of 60 NDD patients were studied. The diagnosis of NAFLD was made on the basis of transient elastography. Serum fetuin-A and serum fasting insulin were measured along with other investigations. RESULTS: The percentage of patients with NAFLD in NDD was 53.33%. Fetuin-A levels were significantly higher in NDD with NAFLD compared to those without NAFLD. There was no association of fetuin-A with age, systolic and diastolic blood pressure, fasting blood sugar (FBS), hemoglobin (Hb)A1c, fasting insulin, homeostatic model assessment-insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and markers of advanced fibrosis. Fetuin-A levels beyond 1166.5 mcg/mL could predict the development of NAFLD with odds ratio (OR) of 4.33 (95% CI: 1.364-13.77), which remained significant after adjustment for various confounding factors. CONCLUSION: Fetuin-A is a reliable marker of NAFLD in NDD and is positively associated with insulin resistance (IR). The observation in this study suggests that high serum fetuin-A levels in patients with NAFLD do not merely reflect the effects of insulin resistance, but also a more extensive distortion of liver architecture.

Type 2 diabetes reversal with digital twin technology-enabled precision nutrition and staging of reversal: a retrospective cohort study.

BACKGROUND: Type 2 diabetes reversal has been viewed in the literature primarily as a dichotomous event (reversed or not reversed), even though this viewpoint may not be optimal for clinicians or patients. This cohort study's objectives were to define stages of type 2 diabetes reversal and measure changes in reversal stages before and after 90 days of digital twin-enabled precision nutrition therapy. METHODS: This study defines seven stages of diabetes reversal. The study is a retrospective pre/post comparison of changes in reversal stage, hemoglobin A1c (HbA1c), weight, body mass index (BMI), and other metrics measured before and after precision nutrition therapy. Reversal stages were defined as Stage 0: HbA1c < 5.7% without medication for > 1 year, Stage 1: HbA1c < 5.7% without medication for < 1 year, Stage 2: HbA1c < 6.5% without medication, Stage 3: estimated HbA1c (eA1c) between 5.7 and 6.4% without medication, Stage 4: estimated HbA1c (eA1c) between 5.7 and 6.4% with metformin monotherapy, Stage 5: dual oral therapy, Stage 6: > = 3 medications. RESULTS: Reversal stage information was available for 463 patients at baseline and 90 days. At baseline, the proportions of patients in each reversal stage were Stages 1 and 2: 0%, Stage 3: 1%, Stage 4: 8%, Stage 5: 6%, and Stage 6: 85%. After 90 days, the proportions in each reversal stage were Stage 1: 2%, Stage 2: 9%, Stage 3: 32%, Stage 4: 39%, Stage 5: 7%, and Stage 6: 11%, indicating significant progress. Reversal stage progression rates varied by patient subgroup. CONCLUSIONS: Type 2 diabetes patients reached differing reversal stages during 90 days of precision nutrition therapy. Use of reversal stages may benefit patients during therapy. TRIAL REGISTRATION: This was a retrospective study that was approved by the Medisys Clinisearch Ethical Review Board (without registration number) in 2019.

Management of diabetes mellitus through teleconsultation during COVID-19 and similar scenarios - Guidelines from Indian Council of Medical Research (ICMR) expert group.

INTRODUCTION: Emergence of COVID-19 pandemic has led to increased use of telemedicine in health care delivery. Telemedicine facilitates long-term clinical care for monitoring and prevention of complications of diabetes mellitus. GUIDELINES: Precise indications for teleconsultation, clinical care services which can be provided, and good clinical practices to be followed during teleconsultation are explained. Guidance on risk assessment and health education for diabetes risk factors, counselling for blood glucose monitoring, treatment compliance, and prevention of complications are described. CONCLUSION: The guidelines will help physicians in adopting teleconsultation for management of diabetes mellitus, facilitate access to diabetes care and improve health outcomes.

Retrospective study of glycemic variability, BMI, and blood pressure in diabetes patients in the Digital Twin Precision Treatment Program.

The objective of this retrospective observational cohort study was to measure glycemic variability and reductions in body mass index (BMI), blood pressure (BP), and use of antihypertensive medications in type 2 diabetes (T2D) patients participating in the digital twin-enabled Twin Precision Treatment (TPT) Program. Study participants included 19 females and 45 males with T2D who chose to participate in the TPT Program and adhered to program protocols. Nine additional enrollees were excluded due to major program non-adherence. Enrollees were required to have adequate hepatic and renal function, no myocardial infarction, stroke, or angina ≤ 90 days before enrollment, and no history of ketoacidosis or major psychiatric disorders. The TPT program uses Digital Twin technology, machine learning algorithms, and precision nutrition to aid treatment of patients with T2D. Each study participant had ≥ 3 months of follow-up. Outcome measures included glucose percentage coefficient of variation (%CV), low blood glucose index (LBGI), high blood glucose index (HBGI), systolic and diastolic BP, number of antihypertensive medications, and BMI. Sixty-four patients participated in the program. Mean (± standard deviation) %CV, LBGI, and HBGI values were low (17.34 ± 4.35, 1.37 ± 1.37, and 2.13 ± 2.79, respectively) throughout the 90-day program. BMI decreased from 29.23 ± 5.83 at baseline to 27.43 ± 5.25 kg/m2. Systolic BP fell from 134.72 ± 17.73 to 124.58 ± 11.62 mm Hg. Diastolic BP decreased from 83.95 ± 10.20 to 80.33 ± 7.04 mm Hg. The percent of patients taking antihypertensive medications decreased from 35.9% at baseline to 4.7% at 90 days. During 90 days of the TPT Program, patients achieved low glycemic variability and significant reductions in BMI and BP. Antihypertensive medication use was eliminated in nearly all patients. Future research will focus on randomized case-control comparisons.

Factors affecting achievement of glycemic targets among type 2 diabetes patients in South Asia: Analysis of the CARRS trial.

OBJECTIVE: To assess the predictors of achieving and maintaining guideline-recommended glycemic control in people with poorly controlled type 2 diabetes. METHODS: We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial (n = 1146), to identify groups that achieved guideline-recommended glycemic control (HbA1c < 7%) and those that remained persistently poorly controlled (HbA1c > 9%) over a median of 28 months of follow-up. We used generalized estimation equations (GEE) analysis for each outcome i.e. achieving guideline-recommended control and persistently poorly controlled and constructed four regression models (demographics, disease-related, self-care, and other risk factors) separately to identify predictors of HbA1c < 7% and HbA1c > 9% at the end of the trial, adjusting for trial group assignment and site. RESULTS: In the final multivariate model, adherence to prescribed medications (RR: 1.46, 95%CI: 1.09, 1.95), adherence to diet plans (RR: 1.79, 95% CI: 1.43, 2.23) and middle-aged: 50-64 years (RR: 1.32; 95% CI: 1.02-1.71) were associated with achieving guideline-recommended control (HbA1c < 7%). Presence of microvascular complications (RR: 0.70; 95%CI: 0.53-0.92) reduced the probability of achieving guideline-recommended glycemic control (HbA1c 7%). Further, longer duration of diabetes (>15 years), RR: 1.41; 95% CI: 1.15, 1.72, hyperlipidemia, RR: 1.19; 95% CI: 1.06, 1.34 and younger age group (35-49 years vs. >64 years: RR: 0.61; 95% CI: 0.47-0.79) were associated with persistently poor glycemic control (HbA1c > 9%). CONCLUSION: To achieve and maintain guideline-recommended glycemic control, care delivery models must put additional emphasis and effort on patients with longer disease duration, younger people and those having microvascular complications and hyperlipidemia.

Serum CCL 18 Levels in Women with Polycystic Ovarian Syndrome.

BACKGROUND: Polycystic ovarian syndrome (PCOS) is one of the most common metabolic disorders seen in women of the reproductive age group, with the majority of them having insulin resistance. There is a need to identify sensitive markers of insulin resistance. CC chemokine ligand 18 (CCL 18) secreted from white adipose tissue is upregulated in individuals with insulin resistance. OBJECTIVES: To study the correlation between serum CCL 18 levels and insulin resistance in PCOS. MATERIALS AND METHODS: This case-control study included 45 PCOS women and an equal number of age and body mass index (BMI) matched controls. Estimation of serum CCL 18, serum testosterone, fasting plasma glucose, fasting insulin, HbA1c, and ultrasonography of abdomen and pelvis was done and HOMA IR was calculated. RESULTS: Serum CCL 18 level was higher in women with PCOS when compared to controls. The mean level of serum CCL 18 (ng/mL) in the PCOS group and control group was 28.32 ± 4.17 and 11.90 ± 4.91, respectively (P < 0.001). Blood pressure, waist circumference, waist-hip ratio, modified Ferriman Gallway score (FG) score serum total testosterone, fasting serum insulin, and HOMA IR showed a relationship with serum CCL 18 levels. Serum CCL 18 was an independent predictor of PCOS (P < 0.05). A serum CCL 18 cutoff level of 18.84 ng/mL showed 93.3% sensitivity and 91.7% specificity in distinguishing PCOS subjects from healthy individuals. CONCLUSION: There is a significant correlation of serum CCL 18 level with insulin resistance in PCOS subjects and serum CCL levels can be considered as a marker of PCOS.

Efficacy and Safety of Remogliflozin Etabonate, a New Sodium Glucose Co-Transporter-2 Inhibitor, in Patients with Type 2 Diabetes Mellitus: A 24-Week, Randomized, Double-Blind, Active-Controlled Trial.

BACKGROUND: Metformin is the first-line treatment for type 2 diabetes mellitus (T2DM), but many patients either cannot tolerate it or cannot achieve glycemic control with metformin alone, so treatment with other glucose-lowering agents in combination with metformin is frequently required. Remogliflozin etabonate, a novel agent, is an orally bioavailable prodrug of remogliflozin, which is a potent and selective sodium-glucose co-transporter-2 inhibitor. OBJECTIVE: Our objective was to evaluate the efficacy and safety of remogliflozin etabonate compared with dapagliflozin in subjects with T2DM in whom a stable dose of metformin as monotherapy was providing inadequate glycemic control. METHODS: A 24-week randomized, double-blind, double-dummy, active-controlled, three-arm, parallel-group, multicenter, phase III study was conducted in India. Patients aged ≥ 18 and ≤ 65 years diagnosed with T2DM, receiving metformin ≥ 1500 mg/day, and with glycated hemoglobin (HbA1c) levels ≥ 7 to ≤ 10% at screening were randomized into three groups. Every patient received metformin ≥ 1500 mg and either remogliflozin etabonate 100 mg twice daily (BID) (group 1, n = 225) or remogliflozin etabonate 250 mg BID (group 2, n = 241) or dapagliflozin 10 mg once daily (QD) in the morning and placebo QD in the evening (group 3, n = 146). The patients were followed-up at weeks 1 and 4 and at 4-week intervals thereafter until week 24. The endpoints included mean change in HbA1c (primary endpoint, noninferiority margin = 0.35), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), bodyweight, blood pressure, and fasting lipids. Treatment-emergent adverse events (TEAEs), safety laboratory values, electrocardiogram, and vital signs were evaluated. RESULTS: Of 612 randomized patients, 167 (group 1), 175 (group 2), and 103 (group 3) patients with comparable baseline characteristics completed the study. Mean change ± standard error (SE) in HbA1c from baseline to week 24 was - 0.72 ± 0.09, - 0.77 ± 0.09, and - 0.58 ± 0.12% in groups 1, 2, and 3, respectively. The difference in mean HbA1c of group 1 versus group 3 (- 0.14%, 90% confidence interval [CI] - 0.38 to 0.10) and group 2 versus group 3 (- 0.19%; 90% CI - 0.42 to 0.05) was noninferior to that in group 3 (p < 0.001). No significant difference was found between group 1 or group 2 and group 3 in change in FPG, PPG, and bodyweight. The overall incidence of TEAEs was comparable across study groups (group 1 = 32.6%, group 2 = 34.4%, group 3 = 29.5%), including adverse events (AEs) of special interest (hypoglycemic events, urinary tract infection, genital fungal infection). Most TEAEs were mild to moderate in intensity, and no severe AEs were reported. CONCLUSION: This study demonstrated the noninferiority of remogliflozin etabonate 100 and 250 mg compared with dapagliflozin, from the first analysis of an initial 612 patients. Remogliflozin etabonate therefore may be considered an effective and well-tolerated alternative treatment option for glycemic control in T2DM. TRIAL REGISTRATION: CTRI/2017/07/009121.