Fortifying Micronutrient Supplementation in India: Indian Expert consensus.

Micronutrients play a key role in human health, being involved in energy metabolism, immunity, cellular functioning, growth, and development. Deficiencies in micronutrients occur in individuals of all ages due to several factors, including inadequate diets, disease states, and overweight/obesity. Guidelines from the Indian Council of Medical Research (ICMR) National Institute of Nutrition (NIN) Expert Group on Nutrient Requirements for Indians (2023) have specified the Recommended Dietary Allowances (RDA) for macronutrients and micronutrients. In addition, a healthy diet is crucial for overall health and should be the first step toward addressing micronutrient deficiencies. When diet is inadequate, micronutrient supplements can be provided to compensate. An expert panel of Indian doctors was convened to develop a pathway toward micronutrient supplementation among the Indian population. This Consensus Statement recognizes that different populations have varying needs for specific micronutrients, and ensuring adequate intake of such micronutrients can improve health outcomes. The panel provided recommendations for dietary practices and micronutrient supplementation when diet is inadequate. Addressing micronutrient deficiencies at the primary care level can prevent chronic deficiencies and their consequences. This Consensus Statement can serve as a primer for physicians to monitor and address deficiencies and thus help individuals maintain their health.

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.

Intermittent Use of Continuous Glucose Monitoring: A New Paradigm in Treatment of Type 2 Diabetes.

OBJECTIVES: To suggest how continuous glucose monitoring (CGM) may be used intermittently in individuals with type 2 diabetes (T2D). MATERIALS AND METHODS: The use of CGM is largely in those with type 1 diabetes (T1D), in whom it makes sense to use CGM continuously as CGM provides a valuable tool to not only adjust their insulin doses but also to match it with their diet, physical activity, and other lifestyle modifications. In the case of T2D, however, especially for those not on insulin, the use of CGM may not be needed on a continuous basis. The use of CGM on an intermittent basis is rarely discussed in the literature. This article tries to provide clinical situations where CGM can be used intermittently. RESULTS: Intermittent use of CGM defined as the "use of CGM once in 2 or 3 months or a fixed frequency," and may be useful in several situations in those with T2D. We suggest the following indications for the intermittent use of CGM in T2D-newly diagnosed patients where treatment is being started, uncontrolled diabetes where treatment is being altered, starting intensive lifestyle modification, during infections, during preoperative control, in children and adolescents with T2D, as a motivational tool to improve behavioral modification, after metabolic surgery, and in patients on steroids, apart from other indications. CONCLUSION: Intermittent use of CGM in T2D can be useful in special situations and can also be cost saving particularly in resource-constrained regions of the world.

SGLT2i as a First-line Antihyperglycemic in the Management of Type 2 Diabetes in the Context of Indians: A Systematic Review and Consensus.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) have been used for almost a decade and have proven to be effective not only in managing Type 2 diabetes (T2D), but their cardio and renal protective features make them very useful in managing patients with risk of multiple comorbidities. This systematic review was undertaken by the authors because there is no evidence currently available in India that has studied the suitability of SGLT2i as a first-line agent in patients newly diagnosed with T2D in India. MATERIALS AND METHODS: First, literature was searched to identify features that are considered important when deciding on a first-line agent for managing T2D. A total of 5 broad topics were identified-glycemic control, extra glycemic effects, antihyperglycemic combination therapy, safety, and cost-effectiveness. These domains had further subheadings, and a total of 16 domains were identified. Metformin is the drug of choice as a first-line agent in such situations and has been considered the gold standard for evaluating the effects of SGLT2i across these domains. A systematic literature review on each domain was conducted to compare SGLT2i with the gold standard in Indian patients newly diagnosed with T2D. Evidence was graded (levels of evidence (LoE)-A, B, and C), and recommendations (class of recommendation (CoR)-I, II, and III) were classified by the expert group as defined in the methodology. RESULTS: According to the systematic reviews conducted, 11 domains had Level A evidence, 2 domains (impact on lipids and gut microbiome) had Level B, and 3 domains had Level C (ß-cell function, renal protection, and glycemic variability) evidence. Based on evidence and expert opinion, the authors recommend SGLT2i as a first-line agent for managing newly diagnosed patients with T2D with a Class I recommendation for 13 domains and Class II for the remaining 3 (impact on lipids, gut microbiome, and ß-cell function). Although a poorer level of evidence (Level C) was available for the glycemic variability domain, the authors still reported this as Class I recommendations according to their expert opinion and consensus. CONCLUSION: This article advocates adopting SGLT2 inhibitors as the primary treatment choice for treating patients with newly diagnosed T2D in India.

Subgroups of patients with young-onset type 2 diabetes in India reveal insulin deficiency as a major driver.

AIM/HYPOTHESIS: Five subgroups were described in European diabetes patients using a data driven machine learning approach on commonly measured variables. We aimed to test the applicability of this phenotyping in Indian individuals with young-onset type 2 diabetes. METHODS: We applied the European-derived centroids to Indian individuals with type 2 diabetes diagnosed before 45 years of age from the WellGen cohort (n = 1612). We also applied de novo k-means clustering to the WellGen cohort to validate the subgroups. We then compared clinical and metabolic-endocrine characteristics and the complication rates between the subgroups. We also compared characteristics of the WellGen subgroups with those of two young European cohorts, ANDIS (n = 962) and DIREVA (n = 420). Subgroups were also assessed in two other Indian cohorts, Ahmedabad (n = 187) and PHENOEINDY-2 (n = 205). RESULTS: Both Indian and European young-onset type 2 diabetes patients were predominantly classified into severe insulin-deficient (SIDD) and mild obesity-related (MOD) subgroups, while the severe insulin-resistant (SIRD) and mild age-related (MARD) subgroups were rare. In WellGen, SIDD (53%) was more common than MOD (38%), contrary to findings in Europeans (Swedish 26% vs 68%, Finnish 24% vs 71%, respectively). A higher proportion of SIDD compared with MOD was also seen in Ahmedabad (57% vs 33%) and in PHENOEINDY-2 (67% vs 23%). Both in Indians and Europeans, the SIDD subgroup was characterised by insulin deficiency and hyperglycaemia, MOD by obesity, SIRD by severe insulin resistance and MARD by mild metabolic-endocrine disturbances. In WellGen, nephropathy and retinopathy were more prevalent in SIDD compared with MOD while the latter had higher prevalence of neuropathy. CONCLUSIONS /INTERPRETATION: Our data identified insulin deficiency as the major driver of type 2 diabetes in young Indians, unlike in young European individuals in whom obesity and insulin resistance predominate. Our results provide useful clues to pathophysiological mechanisms and susceptibility to complications in type 2 diabetes in the young Indian population and suggest a need to review management strategies.

Combined associations of family history and self-management with age at diagnosis and cardiometabolic risk in 86,931 patients with type 2 diabetes: Joint Asia Diabetes Evaluation (JADE) Register from 11 countries.

BACKGROUND: Family history (FamH) of type 2 diabetes might indicate shared genotypes, environments, and/or behaviors. We hypothesize that FamH interacts with unhealthy behaviors to increase the risk of early onset of diabetes and poor cardiometabolic control. METHODS: In a cross-sectional analysis of the prospective Joint Asia Diabetes Evaluation Register including patients from 427 clinics in 11 Asian countries/regions in 2007-2021, we defined positive FamH as affected parents/siblings and self-management as (1) healthy lifestyles (balanced diet, non-use of alcohol and tobacco, regular physical activity) and (2) regular self-monitoring of blood glucose (SMBG). RESULTS: Among 86,931 patients with type 2 diabetes (mean±SD age: 56.6±11.6 years; age at diagnosis of diabetes: 49.8±10.5 years), the prevalence of FamH ranged from 39.1% to 85.3% in different areas with FamH affecting mother being most common (32.5%). The FamH group (n=51,705; 59.5%) was diagnosed 4.6 years earlier than the non-FamH group [mean (95% CI): 47.9 (47.8-48.0) vs. 52.5 (52.4-52.6), logrank p<0.001]. In the FamH group, patients with both parents affected had the earliest age at diagnosis [44.6 (44.5-44.8)], followed by affected single parent [47.7 (47.6-47.8)] and affected siblings only [51.5 (51.3-51.7), logrank p<0.001]. The FamH plus ≥2 healthy lifestyle group had similar age at diagnosis [48.2 (48.1-48.3)] as the non-FamH plus <2 healthy lifestyle group [50.1 (49.8-50.5)]. The FamH group with affected parents had higher odds of hyperglycemia, hypertension, and dyslipidemia than the FamH group with affected siblings, with the lowest odds in the non-FamH group. Self-management (healthy lifestyles plus SMBG) was associated with higher odds of attaining HbA1c<7%, blood pressure<130/80mmHg, and LDL-C<2.6 mmol/L especially in the FamH group (FamH×self-management, pinteraction=0.050-0.001). CONCLUSIONS: In Asia, FamH was common and associated with young age of diagnosis which might be delayed by healthy lifestyle while self management  was associated with better control of  cardiometabolic risk factors especially in those with FamH.

Effects of empagliflozin on proinflammatory cytokines and other coronary risk factors in patients with type 2 diabetes mellitus: A single-arm real-world observation.

OBJECTIVE: This single-arm real-world observation aims to examine the effects of empagliflozin (EMPA) on coronary risk factors among subjects with known diabetes. MATERIALS AND METHODS: Records of 63 subjects with type 2 diabetes mellitus, receiving EMPA were drawn for this study. Of 63 patients with diabetes, 6 were excluded, and the remaining 57 received EMPA (25 mg/day) for 24 weeks. Clinical data, dietary intakes, and physical activity were assessed by validated questionnaires. RESULTS: Treatment with EMPA was associated with significant decline in fasting and 2-hour post-prandial blood glucose and Hb1c indicating that this agent has potential antidiabetic effects. Pro-inflammatory cytokines; C-reactive protein, TNF-α, and interleukin-6 showed significant reduction after treatment with EMPA, compared to baseline levels. Apart from these changes, parameters of oxidative stress, thiobarbituric acid reactive substances, malondialdehyde, and diene conjugates as well as uric acid, showed a significant decline with an increase in antioxidant vitamins A, E, and C and beta-carotene as well as nitrite. There was a significant decline in serum uric acid, systolic and diastolic blood pressures, and angiotensin-converting enzyme (ACE), with a non-significant reduction in body weight and body mass index as well as in waist circumference of modest significance, after intervention of 12 weeks compared to baseline levels. Total cholesterol, VLDL cholesterol and triglycerides showed non-significant decline compared to baseline levels. CONCLUSION: It is possible that EMPA administration can cause a significant decline in pro-inflammatory cytokines along with blood glucose, Hb1c, oxidative stress, uric acid, blood pressures, and ACE with an increase in antioxidant vitamins and nitrite. Randomized, controlled intervention trials would be necessary to confirm our findings.

Evaluating Glycemic Control in Patients of South Asian Origin With Type 2 Diabetes Using a Digital Therapeutic Platform: Analysis of Real-World Data.

BACKGROUND: Digital therapeutics are evidence-based therapeutic interventions driven by high-quality software programs for the treatment, prevention, or management of a medical disorder or disease. Many studies in the western population have shown the effectiveness of mobile app-based digital therapeutics for improving glycemic control in patients with type 2 diabetes (T2D). However, few studies have assessed similar outcomes in the South Asian population. OBJECTIVE: This study aims to investigate the real-world effectiveness of the Wellthy CARE digital therapeutic for improving glycemic control among the South Asian population of Indian origin. METHODS: We analyzed deidentified data from 102 patients with T2D from India enrolled in a 16-week structured self-management program delivered using the Wellthy CARE mobile app. Patients recorded their meals, weight, physical activity, and blood sugar in the app, and they received lessons on self-care behaviors (healthy eating, being active, monitoring, medication adherence, problem solving, healthy coping, and reducing risks); feedback provided by an artificial intelligence-powered chatbot; and periodic interactions with certified diabetes educators via voice calls and chats. The primary outcome of the program was a change in glycated hemoglobin A1c (HbA1c). Secondary outcomes included the difference between preintervention and postintervention fasting blood glucose (FBG) and postprandial blood glucose (PPBG) levels; changes in BMI and weight at the completion of 16 weeks; and the association between program engagement and the changes in HbA1c, FBG, and PPBG levels. RESULTS: At the end of 16 weeks, the average change in HbA1c was -0.49% (n=102; 95% CI -0.73 to 0.25; P<.001). Of all the patients, 63.7% (65/102) had improved HbA1c levels, with a mean change of -1.16% (n=65; 95% CI -1.40 to -0.92; P<.001). The mean preintervention and postintervention FBG levels were 145 mg/dL (n=51; 95% CI 135-155) and 134 mg/dL (n=51; 95% CI 122-146; P=.02) and PPBG levels were 188 mg/dL (n=51; 95% CI 172-203) and 166 mg/dL (n=51; 95% CI 153-180; P=.03), respectively. The mean changes in BMI and weight were -0.47 kg/m2 (n=59; 95% CI -0.22 to -0.71; P<.001) and -1.32 kg (n=59; 95% CI -0.63 to -2.01; P<.001), respectively. There was a stepwise decrease in HbA1c, FBG, and PPBG levels as the program engagement increased. Patients in the highest tertile of program engagement had a significantly higher reduction in HbA1c (-0.84% vs -0.06%; P=.02), FBG (-21.4 mg/dL vs -0.18 mg/dL; P=.02), and PPBG levels (-22.03 mg/dL vs 2.35 mg/dL; P=.002) than those in the lowest tertile. CONCLUSIONS: The use of the Wellthy CARE digital therapeutic for patients with T2D showed a significant reduction in the levels of HbA1c, FBG, and PPBG after 16 weeks. A higher level of participation showed improved glycemic control, suggesting the potential of the Wellthy CARE platform for better management of the disease.

Real Time Flash Glucose Monitoring: Now a Reality in India.

Tight glycemic control has been recognised as the cornerstone of modern diabetes management. Until recently, glycated hemoglobin (HbA1c) was the only reliable tool for measuring glycemic control, but it is not an ideal metric as it is retrospective, unable to pick up hypo- and hyperglycemic excursions and prone to interference by conditions such as anemia and hemoglobinopathies. The advent of continuous glucose monitoring systems is a giant leap in diabetes management as it enables visualisation of glucose trends over periods of time, helping in identification of hypo- and hypoglycemic events and enabling appropriate treatment decisions to be made. The recent launch of the real-time patient CGM in India is a further step in the right direction as it will empower patients to take control of their diabetes by providing them information on their glucose levels and trends in real time.

New and Unique Clusters of Type 2 Diabetes Identified in Indians.

Type 2 diabetes (T2D), the most common form of diabetes, is recognized as being a heterogenous disorder, and presents a universal threat to health. In T2D, the pathophysiology and phenotype differ significantly by ethnicity, particularly among Asian Indians, who are known to have the 'Asian Indian phenotype', which makes them more susceptible to develop T2D than white Caucasians. The recent subclassification of T2D into different subtypes or clusters, which behave differently with respect to clinical presentation and risk of developing complications is a remarkable development. Five unique "clusters" of individuals with diabetes were described in the Scandinavian population [Severe Autoimmune Diabetes (SAID), Severe Insulin Deficient Diabetes (SIDD), Severe Insulin Resistant Diabetes (SIRD), Mild Obesity-related Diabetes (MOD) and Mild Age-Related Diabetes (MARD)]. For the first time in India, identification of clusters of diabetes was done on 19,084 individuals with T2D, using 8 clinically relevant variables (age at diagnosis, BMI, waist circumference, HbA1c, triglycerides, HDL cholesterol and fasting and stimulated C-peptide). Four replicable clusters were identified [SIDD, MARD, IROD (Insulin Resistant Obese Diabetes) and CIRDD (Combined Insulin Resistant and Deficient Diabetes)], two of which were unique to the Indian population (IROD and CIRDD). Clustering of T2D helps i) to accurately subclassify diabetes into different subtypes, ii) plan therapies based on the pathophysiology, iii) predict prognosis and prevent diabetic complications and iv) helps in our approach to precision diabetes. Further studies would help us to refine the usefulness of these clusters of T2D particularly in the Indian population, with respect to selection of appropriate therapies and hopefully in the prevention of complications of diabetes.