Comparison of clustering and phenotyping approaches for subclassification of type 2 diabetes and its association with remission in Indian population.

Identification of novel subgroups of type 2 diabetes (T2D) has helped improve its management. Most classification techniques focus on clustering or subphenotyping but not on both. This study aimed to compare both these methods and examine the rate of T2D remission in these subgroups in the Indian population. K-means clustering (using age at onset, HbA1C, BMI, HOMA2 IR and HOMA2%B) and subphenotyping (using homeostatic model assessment (HOMA) estimates) analysis was done on the baseline data of 281 patients with recently diagnosed T2D who participated in a 1-year online diabetes management program. Cluster analysis revealed three distinct clusters: severe insulin-deficient diabetes (SIDD), severe insulin-resistant diabetes (SIRD), and mild obesity-related diabetes (MOD) while subphenotyping showed four distinct categories: hyperinsulinemic, insulinopenic, classical, and nascent T2D. Comparison of the two approaches revealed that the clusters aligned with phenotypes based on shared characteristics of insulin sensitivity (IS) and beta cell function (BCF). Clustering correctly identified individuals in nascent group (high IS and BCF) as having mild obesity related diabetes which subphenotyping did not. Post-one-year intervention, higher remission rates were observed in the MOD cluster (p = 0.383) and the nascent phenotype showing high IS and BCF (p = 0.061, Chi-Square test). In conclusion, clustering based on a comprehensive set of parameters appears to be a superior method for classifying T2D compared with pathophysiological subphenotyping. Personalized interventions may be highly effective for newly diagnosed individuals with high IS and BCF and may result in higher remission rates in these individuals. Further large-scale studies are required to validate these findings.

Interplay Between the American Diabetes Association's ABC Targets for Diabetes, Insulin Resistance Indices, and Dyslipidemia in Indian Type 2 Diabetes Patients.

Background The increasing incidence of type 2 diabetes (T2D) in India underscores the pressing need for effective management strategies. Meeting the American Diabetes Association (ADA) ABC targets for diabetes (glycated hemoglobin (HbA1c), blood pressure, and serum low-density lipoprotein cholesterol (LDL-C)) is crucial for effectively managing T2D, as it reflects the optimal control of key metabolic parameters. Insulin resistance (IR) and impaired beta cell function (BCF) have been found to have a significant impact on glycemic control, lipid metabolism, and hypertension, contributing to the complex cardiovascular risk profile of patients with T2D. This study aimed to explore the association between ABC targets for diabetes, IR, BCF, and dyslipidemia in a cross-sectional cohort of T2D patients. Methods This retrospective study examined data from 681 T2D patients with comorbid hypertension and dyslipidemia. The patients were part of a one-year online lifestyle intervention program for diabetes management at the Freedom from Diabetes Clinic in Pune, India, between January 2021 and December 2022. Baseline data (at the time of enrollment in the program) on medical history and anthropometric and biochemical parameters were retrospectively extracted from medical records and used to assess ABC targets and other clinical parameters. The ABC targets for diabetes include three goals: an HbA1c level of less than 7.0%, a blood pressure level of less than 140/90 mmHg, and an LDL-C level of less than 100 mg/dL. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), Homeostatic Model Assessment of Beta Cell Function (HOMA-B), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated using standard formulas. Results Cross-sectional analysis at baseline showed that 152 (22.3%) participants met all three ABC targets, 306 (45.0%) and 183 (26.8%) participants met two or one targets, respectively, and 40 (5.9%) did not meet any of the ABC targets. Participants meeting all three targets showed significantly lower IR, higher sensitivity (HOMA-IR, median 2.1; QUICKI, median 0.34), higher BCF (HOMA-B, median 62.9), and healthier lipid profiles (mg/dL) (total cholesterol, median 126; triglycerides, median 114; and non-high-density lipoprotein (HDL), median 84) than those who did not meet any of the ABC targets (HOMA-IR, median 3.4; QUICKI, median 0.31; HOMA-B, median 31.7; total cholesterol, median 221; triglycerides, median 187; and non-HDL, median 182) (p < 0.01). A significant association was observed between lower BMI (< 25 kg/m2), lower IR (HOMA-IR <2.5), and meeting all three ABC targets (p < 0.01). No significant association was observed between the duration of diabetes and ABC target status (p > 0.1). Lower IR was identified as a predictor of achievement of all three ABC targets (p < 0.01). Conclusion This study highlights the significance of meeting ABC targets for diabetes in relation to not only a better lipid profile but also lower IR and higher BCF. These preliminary findings provide novel insights into the interplay between IR, BCF, dyslipidemia, and meeting ABC targets in an Indian T2D population. These findings highlight the need for effective diabetes management strategies and improved patient outcomes, considering factors such as BMI and IR indices.

The Diabetes Remission in India (DiRemI) study: Protocol for a prospective matched-control trial.

BACKGROUND: The global rise in diabetes, particularly in India, poses a significant public health challenge, with factors such as limited awareness, financial strain, and cultural considerations hindering its effective management. Although lifestyle changes have shown promising results, their consistent implementation and maintenance continue to pose challenges. Most studies have focused primarily on dietary modifications, overlooking other essential aspects of lifestyle intervention. The DiRemI study aims to address these gaps by evaluating the efficacy of a comprehensive one-year program that combines diet, exercise, psychological support, and medical management to achieve weight loss, diabetes remission, and improved glycemic control among patients with type 2 diabetes (T2D) in India, while also considering the unique needs of the Indian population. METHODS: The DiRemI study is a prospective, open-label, matched-group trial aimed at assessing the impact of a one-year online integrated intensive lifestyle intervention (ILI) comprising dietary modifications, physical activity, psychological support, and medical management on weight loss and remission in adult T2D patients (aged 30-70 years), with a body mass index (BMI) between 25 and 35 kg/m2, and disease duration of <15 years. ILI will be compared with routine medical care (RMC). Participants will be recruited from three clinics: one providing ILI and two others providing RMC. The co-primary outcome will be weight loss and remission at 12 months, with a follow-up at 18 months. The proposed sample size is 360 participants (180 each in intervention and control group). DISCUSSION: The DiRemI study represents the first large-scale remission study in India to show the effectiveness of an integrated approach in the remission and management of T2D and its complications. The findings of this study hold the potential to report evidence-based strategies for managing T2D both in India and globally, thus alleviating the substantial burden of diabetes on public health systems. TRIAL REGISTRATION: Clinical Trials Registry, India (Registered Number: CTRI/2023/06/053885).

Oral glucose tolerance test clearance in type 2 diabetes patients who underwent remission following intense lifestyle modification: A quasi-experimental study.

Achieving diabetes remission (HbA1c<48mmol/mol without the use of anti-diabetic medication for 3 months) might not assure restoration of a normal glycemic profile [fasting blood sugar level <5.6 mmol/L and Post-Prandial (PP) blood glucose <7.8mmol/L]. The study investigates the factors associated with OGTT clearance in patients under type 2 diabetes remission. Four hundred participants who achieved remission during a one-year online structured lifestyle modification program, which included a plant-based diet, physical activity, psychological support, and medical management (between January 2021 and June 2022), and appeared for the OGTT were included in the study. OGTT clearance was defined by fasting blood glucose < 5.6 mmol/L and 2-hour post-prandial blood glucose <7.8 mmol/L post-consumption of 75g glucose solution. Of the 400 participants, 207 (52%) cleared OGTT and 175 (44%) had impaired glucose tolerance (IGT). A shorter diabetes duration (<5 years) was significantly associated with OGTT clearance (p<0.05). Pre-intervention use of glucose-lowering drugs showed no association with OGTT clearance (p<0.1). Post-intervention, the OGTT-cleared group showed significantly higher weight loss (p<0.05) and a decrease in HbA1c compared to the IGT group (p<0.05). Improvement in Insulin resistance and ß-cell function was also higher in the OGTT-cleared group compared to the IGT group (p<0.05). In conclusion, clearing the OGTT is a possibility for those achieving remission through lifestyle interventions. Higher weight loss, a shorter duration of diabetes, and improvement in insulin resistance were significantly associated with OGTT clearance in participants in remission. Future randomized controlled trials with longer follow-ups may help substantiate our findings.

Long-term remission of type 2 diabetes through intense lifestyle modification program - A case series.

Type 2 diabetes (T2D) remission is being widely accepted and documented as feasible through calorie restriction and bariatric surgery. Recent studies with lifestyle changes have also shown T2D remission; however, long-term remission through lifestyle modifications is not yet established. Though glycated hemoglobin (HbA1c) is a universally accepted indicator of glycemic status, oral glucose tolerance test (OGTT) would be a more robust marker in understanding whether the metabolic abnormalities in glucose metabolism have undergone complete remission as well. We present a case series of four patients enrolled in the Holistic Transformation Program, a lifestyle modification program, between 2016 and 2018. The intervention was a combination of a vegan diet, structured exercises, and stress management delivered over 12 months. All four patients successfully achieved T2D remission and cleared OGTT consecutively for a minimum period of 3 years. Our findings suggest that long-term T2D remission may be possible through lifestyle modification.

Type 2 Diabetes Remission Through Intense Lifestyle Modification with Three-Year Follow-Up of an Elderly Male on High Insulin Dosage: A Case Report.

An elderly obese male patient (60 yrs.) diagnosed Type 2 Diabetes (T2D) presented to our clinic. He was on 94 units of insulin and oral hypoglycemic agents during his initial consultation visit. After obtaining informed consent, he was enrolled into intense lifestyle modification program for a duration of six months, with a three-year follow-up after the intervention. The patient underwent complete remission losing 13 kg of body weight and also successfully clearing oral glucose tolerance tests (OGTT) for three consecutive years. We present three unique features in the current case report: (1) Elderly age of the patient (2) OGTT clearance along with normalisation of HbA1c, and (3) High initial insulin dosage at baseline. A few of the common positive predictors of T2D remission documented in earlier studies include younger age and minimal or low doses of insulin. The current case study shows that older age and higher dosage of insulin, it is possible to undergo complete T2D remission along with OGTT clearance through intense holistic lifestyle modification. Future experimental studies with adequate sample sizes would help substantiate our observation.

Low knowledge of osteoporosis and its risk factors in urban Indian adults from Pune city, India.

OBJECTIVE: To assess knowledge of osteoporosis and its risk factors and to explore associations between knowledge and various sociodemographic factors in Indian adults. DESIGN: Cross-sectional study. The Revised Osteoporosis Knowledge Test (OKT) was used to assess knowledge of osteoporosis. Four scores (OKT-total, range 0-32; OKT-exercise, range 0-20; OKT-nutrition, range 0-26; OKT-risk factors, range 0-14) were generated by giving 1 point to every correct answer and 0 points for incorrect or 'not known' answers. SETTING: Tertiary-care hospital in Pune city, India.ParticipantsAdults aged 40-75 years (n 477; 234 males) enrolled through voluntary routine health checks and health camps. RESULTS: Mean age of the study population was 54·6 (sd 9·5) years. Half the participants were aware of osteoporosis and could correctly define it. Women showed significantly higher median OKT-total and OKT-nutrition scores than men (P0·1). CONCLUSIONS: Understanding about osteoporosis and its risk factors is low in the present cohort of Indian men and women. There is need to create awareness programmes aimed at both men and women especially targeting those with lower education, lower socio-economic status and no previous exposure to osteoporosis.

Prevalence of Osteoporosis in Apparently Healthy Adults above 40 Years of Age in Pune City, India.

PURPOSE: The aim of study was to assess the prevalence of osteoporosis and changes in bone mass with increasing age and compare bone health status of apparently healthy men, premenopausal and postmenopausal women. METHODS: Data were collected on anthropometric and sociodemographic factors in 421 apparently healthy Indian adults (women = 228), 40-75 years of age, in a cross-sectional study in Pune city, India. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry at two sites-lumbar spine (LS) and left femur. Individuals were classified as having osteoporosis or osteopenia based on the World Health Organization criteria of T-scores. RESULTS: Mean age of study population was 53.3 ± 8.4 years. Of the total women, 44.3% were postmenopausal with 49.2 ± 3.5 years as mean age at menopause. Postmenopausal women showed a rapid decline in BMD with age till 50 years while men showed a gradual decline. Premenopausal women showed no significant decline in BMD with age (P > 0.1). Significantly lower T-scores were observed at LS in men compared to premenopausal (P < 0.05). At left femur, T-scores were lower in men compared to premenopausal women (P < 0.05) but not postmenopausal women (P > 0.1). The prevalence of osteoporosis in men at LS was lower than postmenopausal women but higher than premenopausal women. CONCLUSION: In Indian men, a low T-score compared to women indicates higher susceptibility to osteoporosis. In women, menopause causes a rapid decline in BMD. Therefore, both Indian men and postmenopausal women require adequate measures to prevent osteoporosis during later years in life.

Effect of micronutrient supplementation on height velocity of underprivileged girls in comparison with un-supplemented healthy controls.

The aim of this study was to investigate the effect of 1-year micronutrient supplementation on the height velocity of underprivileged premenarchal girls in comparison with the natural growth of apparently healthy girls from an affluent class. A 1-year cluster-randomisation intervention trial was conducted in 119 premenarchal girls (8-12 years) from two schools catering to the lower socioeconomic strata (LSES) in Pune, India. Three classes of age-matched girls were randomly allocated to any one of the three intervention groups: (i) Ca+MZn+D group (C1: zinc, 15 mg/day+multivitamins; calcium, 500 mg/day; vitamin D, 30,000 IU/3 months); (ii) Ca+D group (C2: calcium, 500 mg/day; vitamin D, 30,000 IU/3 months); and (iii) M+D group (C3: multivitamins; vitamin D, 30,000 IU/3 months). Height, weight, and Tanner stage were assessed at baseline and endline. A total of 119 age-matched, apparently healthy school girls from a higher socioeconomic group (HSES) were assessed for their growth after 1 year without any supplementation. At baseline, mean height-for-age Z-scores and weight-for-age Z-scores by Indian references were >-2 in 99% of HSES girls and 28% of LSES girls had height-for-age Z-scores <-2. Post-intervention, increase in height-for-age Z-scores adjusted for Tanner stage was significantly higher in the Ca+MZn+D group (0.32±0.06) than in the respective age-matched controls (C1 group) (-0.02±0.05) (p<0.05) as well as in both the Ca+D group (0.18±0.06) and the M+D group (0.14±0.04) (p<0.05). After adjusting for Tanner stage, height velocity was significantly higher for the Ca+MZn+D group (6.7±0.4 cm/year) than for the M+D group (6.1±0.2), Ca+D group (5.6±0.5) as well as age-matched controls (C1 group) (5.0±0.3) (p<0.05). Supplementation with calcium+vitamin D, zinc and multivitamins may be effective in improving stature in underprivileged Indian premenarchal girls.

Influence of micronutrient status and socioeconomic gradient on growth indices of 2-18-year-old Indian girls.

Micronutrient deficiencies are common consequences of the plant-based diet in children from developing countries which may affect their linear and ponderal growth. The aim of the study was to investigate the association between micronutrient status and growth indices in Indian girls. In cross-sectional studies (2006-2010), data on weight, height and diet were collected on 1302 girls (2-18 years) from Pune city, India. Fasting hemoglobin was measured on 1118 girls and serum zinc was measured on 695 girls. Height-for-age Z-scores (HAZ) and body mass index for age Z-score (BMIZ) were computed using contemporary Indian references. HAZ >-1 was observed in 54% girls, and 18.1% were short (HAZ <-2). BMIZ was within the reference range (-2-1 than in short girls even after adjusting for socioeconomic status (SES). The mean serum zinc level of thin girls (BMIZ <-2) was significantly lower than those of both normal and overweight girls after adjusting for SES. Micronutrient sufficiency is of paramount importance for adequate growth in Indian girls.

School-based calcium-vitamin D with micronutrient supplementation enhances bone mass in underprivileged Indian premenarchal girls.

Low adult bone mass is linked to osteoporosis and fractures and is dependent on the extent of childhood and adolescent bone mineralization. The aim of the study was to investigate the effect of 1-year supplementation of calcium, multivitamin with zinc along with vitamin-D on bone mass accrual of school-going premenarchal girls from low income groups in Pune, India. Double-blind, matched-pair, cluster, randomization study was carried out in 214 premenarchal girls (8-12 years) from 2 schools in Pune, India. The two schools together formed 3 classes with 3 clusters each of age-matched girls of which one cluster was allocated to either one of the intervention groups (Ca-group:500 mg/d calcium, Ca+MZ-group:500 mg/d calcium+multivitamin tablet containing 15 mg/d zinc) or control group (C-group: multivitamin tablet without any minerals); all subjects received vitamin-D supplementation. Anthropometry, biochemical parameters, total body bone mineral content (TBBMC) and bone mineral density (TBBMD) (Dual energy X-ray absorptiometry) were assessed at baseline and endline. Post supplementation, mean percent increase in TBBMC was significantly higher in Ca-group (22.3%) and Ca+MZ-group (20.8%) compared to C-group (17.6%) (p<0.05) with no significant differences observed between Ca+MZ and Ca groups (p>0.1). Improvement in TBBMC-for-age Z-scores was higher in the two calcium supplemented groups (13.6%-22%) compared to the C-group (no improvement). Calcium supplementation, with or without multivitamins and zinc, showed a promising improvement in bone health especially with regards to improvement in bone related Z-scores in our population of underprivileged premenarchal girls.

Poor bone health in underprivileged Indian girls: an effect of low bone mass accrual during puberty.

A socio-economic gradient exists for most reasons of morbidity and mortality including delayed puberty in lower (LSES) as compared to higher (HSES) socio-economic stratum and puberty is an important factor affecting bone status in children and adolescents. Thus, a cross-sectional study was conducted on 195 age-matched pairs of girls (8-17years) from LSES and HSES in Pune City, India to assess the hypothesis that socio-economic factors working through late puberty would have a negative association with bone status of adolescents. Height, weight and Tanner stage were assessed. Total body bone mineral content (TBBMC), total body bone area (TBBA), total body bone mineral density (TBBMD), lean body mass (LBM) and total body fat mass (TBFM) were measured using GE Lunar DPX Pro Pencil Beam DXA (Wisconsin, USA) scanner. Mean TBBMC (1172±434g), TBBA (1351±356cm(2)), TBBMD (0.846±0.104g/cm(2)), LBM (21,622±5306g) and TBFM (7746±5194g) in LSES girls were significantly lower than that of HSES girls [TBBMC (1483±525g), TBBA (1533±380cm(2)), TBBMD (0.942±0.119g/cm(2)), LBM (24,308±5829g) and TBFM (12,196±7404g)] (p<0.01). There was a significant effect of age and puberty on all bone parameters. The differences in TBBMC, TBBA, LBM and TBFM between the 2 socio-economic strata at Tanner stage I were not significant (p>0.1) whereas there were significant differences in these parameters from Tanner stages II to V (p<0.05). The percentage difference between LSES and HSES girls in TBBMC, TBBA, TBBMD, LBM and TBFM was 3.4%, 0%, 3.7%, 0.2% and 17.3% respectively at Tanner stage I which increased to 19.1%, 9.7%, 10.4%, 8.8% and 31.2% respectively at Tanner stage V. In conclusion, our results suggest that pubertal years may provide a window of opportunity to promote bone health in adolescent girls from the lower socio-economic stratum.

Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls.

Low adolescent peak bone mass is associated with bone problems in adulthood. Our aim was to assess underprivileged premenarchal Indian girls for low bone mineral content and to study the influence of anthropometric, lifestyle factors on bone health. Data on anthropometry, diet, lifestyle, total body bone mineral content (TBBMC), bone area, bone mineral density, and biochemical parameters [parathyroid hormone, vitamin D (25OH-D), calcium, and zinc] were assessed in 214 premenarchal girls (8-12 years). Compared with the Indian reference database, 15.6% girls had TBBMC for age Z-scores below -2 and 37.5% had Z-scores between -2 and -1. The TBBMC for total body bone area Z-scores were below -2 for one fifth of girls, indicating undermineralized bones. Mean rate of increase in TBBMC with age and Tanner stage was lower in our study population (11.6% and 20.7%, respectively) than reference database (14.2% and 33.4%, respectively). Low weight, 25OH-D, and intake of protein, calcium, and zinc adversely affected TBBMC (p < 0.05). Many underprivileged premenarchal Indian girls are at risk of achieving low bone mass. Steps to improve underweight, 25OH-D, intakes of protein, calcium, and zinc might improve bone health.

Low bone mass in urban Indian women above 40 years of age: prevalence and risk factors.

OBJECTIVE: To assess the prevalence and the relative importance of risk factors for low bone mass in Indian pre- and post-menopausal women. METHODS: Data were collected on anthropometry and lifestyle factors in apparently healthy 80 pre- and 92 post-menopausal (40-75 years) women. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. Fasting blood samples were analysed for Parathyroid hormone, vitamin D, calcium and zinc. RESULTS: BMD at all three sites was significantly lower in post-menopausal than the pre-menopausal women (p < 0.001). Prevalence of osteoporosis was highest at the lumbar spine (25.8%) in post-menopausal women, while prevalence of osteopenia was high in pre-menopausal women (44.3%). Vitamin D deficiency was seen in 54.5% pre and 41.8% post-menopausal women and significant correlation of serum 25(OH)D levels (r = 0.16) was obtained only for total hip Z-score (p < 0.05). Correlation between sun index and lumbar spine BMD was marginally significant (r = 0.14, p = 0.07). Generalised linear models revealed that after adjusting for age, weight and height, percent decrease of 2.1-4.5% in BMD may be attributed to menopause. CONCLUSION: Age, weight, height, menopause, low intakes of calcium and low 25(OH)D along with poor sunlight exposure are the major factors contributing to bone loss in Indian women above 40 years of age.

Variation in lumbar spine bone mineral content by age and gender in apparently healthy Indians.

The aim of this study was to assess variation in bone mass from childhood through later age and to examine bone health status of Indian males and females. Lumbar spine (LS) bone mineral content (BMC) was measured by dual energy X-ray absorptiometry of lumbar vertebrae (L1-L4) in 683 males and 858 females (5-70 years) from Pune, India and apparent bone mineral density (BMAD) was calculated. A cubic regression model was fitted to describe the change in bone mineral content (BMC) with age in males and females separately. Regression analysis revealed that peak LS BMC was achieved around 26 years (63.6 +/- 11.0 g) for males and 30 years (54.1 +/- 11.6 g) for females. After 50 years of age, BMC showed an average annual decrease of 2.7% in males and 4.1% in females. Males had 11-15% higher mean BMAD than females after 50 years of age. T scores of 19% males and 28% females above 50 years, were less than -2.5 and T scores of 36% males and 43% females were between -1.0 and -2.5 when compared with the Lunar reference database. Low peak bone mass at a young age and higher bone loss in adults are alarming features of apparently healthy Indians.