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.

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.

Functional characterization of thyroid peroxidase missense variants causing thyroid dyshormonogenesis in Asian Indian population.

INTRODUCTION: Thyroid dyshormonogenesis (TDH) is a sub-group of congenital hypothyroidism with recessive inheritance resulting from disease causing variants in thyroid hormone biosynthesis pathway genes, like DUOX2, TG, TPO, SLC5A5, SLC26A4, IYD, DUOXA2, SLC26A7 and SECISBP2. Thyroid peroxidase (TPO) is a crucial enzyme involved in thyroid hormone biosynthesis and is one of the frequently mutated genes in patients with TDH. The purpose of the study is to describe the insilico and functional characterization of novel variants in TPO gene identified in patients with thyroid dyshormonogenesis. METHODS: We performed exome sequencing in Indian patients with TDH. In the current study, we describe the results of patients with TPO gene mutations. Exome sequencing results were further analysed by sanger sequencing, computational studies and invitro functional studies such as immunofluorescence and enzyme assay. RESULTS: We identified nine biallelic disease-causing variants in the TPO gene in twelve patients from nine unrelated Indian families. Eight of the nine variants were novel. No recurrent variants were identified. Computational analysis of six missense variants showed that these amino acid substitutions caused changes in non-covalent interactions with the adjacent residues that may affect the TPO protein structure and function. In-vitro experimental data using immunofluorescence assay showed that these variants did not affect the plasma membrane localization of the TPO protein but caused significant loss of TPO enzymatic activity compared to wild type. CONCLUSION: Our study revealed multiple novel pathogenic variants in TPO gene in Indian patients, thereby expanding the genotype spectrum. Functional studies helped us to reveal the pathogenicity of the missense variants.

Antenatal oral glucose tolerance test abnormalities in the prediction of future risk of postpartum diabetes in women with gestational diabetes: Results from the LIVING study.

OBJECTIVES: To explore associations between type and number of abnormal glucose values on antenatal oral glucose tolerance test (OGTT) with postpartum diabetes in South Asian women diagnosed with gestational diabetes (GDM) using International Association of the Diabetes and Pregnancy Study Groups criteria. METHODS: This post-hoc evaluation of the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, a randomized controlled trial, was conducted among women with GDM in the index pregnancy, across 19 centers in Bangladesh, India, and Sri Lanka. Postpartum diabetes (outcome) was defined on OGTT, using American Diabetes Association (ADA) criteria. RESULTS: We report data on 1468 women with GDM, aged 30.9 (5.0) years, and with median (interquartile range) follow-up period of 1.8 (1.4-2.4) years after childbirth following the index pregnancy. We found diabetes in 213 (14.5%) women with an incidence of 8.7 (7.6-10.0)/100 women-years. The lowest incidence rate was 3.8/100 women years, in those with an isolated fasting plasma glucose (FPG) abnormality, and highest was 19.0/100 women years in participants with three abnormal values. The adjusted hazard ratios for two and three abnormal values compared to one abnormal value were 1.73 (95% confidence interval [CI], 1.18-2.54; p = .005) and 3.56 (95% CI, 2.46-5.16; p < .001) respectively. The adjusted hazard ratio for the combined (combination of fasting and postglucose load) abnormalities was 2.61 (95% CI, 1.70-4.00; p < .001), compared to isolated abnormal FPG. CONCLUSIONS: Risk of diabetes varied significantly depending upon the type and number of abnormal values on antenatal OGTT. These data may inform future precision medicine approaches such as risk prediction models in identifying women at higher risk and may guide future targeted interventions.

Development of a risk prediction model for postpartum onset of type 2 diabetes mellitus, following gestational diabetes; the lifestyle InterVention in gestational diabetes (LIVING) study.

AIMS: This study aimed to develop a prediction model for identifying a woman with gestational diabetes mellitus (GDM) at high risk of type 2 diabetes (T2DM) post-birth. METHODS: Utilising data from 1299 women in the Lifestyle Intervention IN Gestational Diabetes (LIVING) study, two models were developed: one for pregnancy and another for postpartum. Key predictors included glucose test results, medical history, and biometric indicators. RESULTS: Of the initial cohort, 124 women developed T2DM within three years. The study identified seven predictors for the antenatal T2DM risk prediction model and four for the postnatal one. The models demonstrated good to excellent predictive ability, with Area under the ROC Curve (AUC) values of 0.76 (95% CI: 0.72 to 0.80) and 0.85 (95% CI: 0.81 to 0.88) for the antenatal and postnatal models, respectively. Both models underwent rigorous validation, showing minimal optimism in predictive capability. Antenatal model, considering the Youden index optimal cut-off point of 0.096, sensitivity, specificity, and accuracy were measured as 70.97%, 70.81%, and 70.82%, respectively. For the postnatal model, considering the cut-off point 0.086, sensitivity, specificity, and accuracy were measured as 81.40%, 75.60%, and 76.10%, respectively. CONCLUSIONS: These models are effective for predicting T2DM risk in women with GDM, although external validation is recommended before widespread application.

The incidence and risk factors of postpartum diabetes in women from Bangladesh, India and Sri Lanka (South Asia) with prior gestational diabetes mellitus: Results from the LIVING study.

AIM: To study, the incidence and risk factors for postpartum diabetes (DM), in women with gestational diabetes mellitus (GDM) from South Asia (Bangladesh, India and Sri Lanka), followed for nearly two years after delivery. METHODS: Women with prior GDM diagnosed using IADPSG criteria were invited at 19 centres across Bangladesh, India and Sri Lanka for an oral glucose tolerance test (OGTT) following childbirth, and were enrolled in a randomized controlled trial. The glycaemic category (outcome) was defined from an OGTT based on American Diabetes Association criteria. RESULTS: Participants (n = 1808) recruited had a mean ± SD age of 31.0 ± 5.0 years. Incident DM was identified, between childbirth and the last follow-up, in 310 (17.1 %) women [incidence 10.75/100 person years], with a median follow-up duration of 1.82 years after childbirth. Higher age, lower education status, higher prior pregnancy count, prior history of GDM, family history of DM, and postpartum overweight/obese status were significantly associated with incident DM. Women in Bangladesh had a higher cumulative incidence of DM [16.49/100 person years] than in Sri Lanka [12.74/100 person years] and India [7.21/100 person years]. CONCLUSIONS: A high incidence of DM was found in women with prior GDM in South Asia, with significant variation between countries. Women from Bangladesh had a significantly higher pregnancy count, family history of DM and overweight/obese status, despite having significantly lower age, which could be responsible for their higher rates of DM. Registration of this study: The study was registered with the Clinical Trials Registry of India (CTRI/2017/06/008744), Sri Lanka Clinical Trials Registry (SLCTR/2017/001), and ClinicalTrials.gov (NCT03305939).

Metabolic non-communicable disease health report of India: the ICMR-INDIAB national cross-sectional study (ICMR-INDIAB-17).

BACKGROUND: Non-communicable disease (NCD) rates are rapidly increasing in India with wide regional variations. We aimed to quantify the prevalence of metabolic NCDs in India and analyse interstate and inter-regional variations. METHODS: The Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a cross-sectional population-based survey, assessed a representative sample of individuals aged 20 years and older drawn from urban and rural areas of 31 states, union territories, and the National Capital Territory of India. We conducted the survey in multiple phases with a stratified multistage sampling design, using three-level stratification based on geography, population size, and socioeconomic status of each state. Diabetes and prediabetes were diagnosed using the WHO criteria, hypertension using the Eighth Joint National Committee guidelines, obesity (generalised and abdominal) using the WHO Asia Pacific guidelines, and dyslipidaemia using the National Cholesterol Education Program-Adult Treatment Panel III guidelines. FINDINGS: A total of 113 043 individuals (79 506 from rural areas and 33 537 from urban areas) participated in the ICMR-INDIAB study between Oct 18, 2008 and Dec 17, 2020. The overall weighted prevalence of diabetes was 11·4% (95% CI 10·2-12·5; 10 151 of 107 119 individuals), prediabetes 15·3% (13·9-16·6; 15 496 of 107 119 individuals), hypertension 35·5% (33·8-37·3; 35 172 of 111 439 individuals), generalised obesity 28·6% (26·9-30·3; 29 861 of 110 368 individuals), abdominal obesity 39·5% (37·7-41·4; 40 121 of 108 665 individuals), and dyslipidaemia 81·2% (77·9-84·5; 14 895 of 18 492 of 25 647). All metabolic NCDs except prediabetes were more frequent in urban than rural areas. In many states with a lower human development index, the ratio of diabetes to prediabetes was less than 1. INTERPRETATION: The prevalence of diabetes and other metabolic NCDs in India is considerably higher than previously estimated. While the diabetes epidemic is stabilising in the more developed states of the country, it is still increasing in most other states. Thus, there are serious implications for the nation, warranting urgent state-specific policies and interventions to arrest the rapidly rising epidemic of metabolic NCDs in India. FUNDING: Indian Council of Medical Research and Department of Health Research, Ministry of Health and Family Welfare, Government of India.

The evolution of thyroid function with puberty.

OBJECTIVE: This study was planned to describe thyroid functional status in different stages of puberty. STUDY DESIGN: We collected data from five schools across different geographical zones of Delhi. All children who consented were evaluated for anthropometry, pubertal stage, goitre status, serum free T3 (FT3), free T4 (FT4), TSH, anti-TPO (thyroid peroxidase) antibodies and thyroid ultrasound. From this sample, a disease- and risk-free or 'reference population' was obtained by excluding those with history of thyroid disease or use of thyroid medications, family history of thyroid disease, goitre, hypoechogenicity or nodularity on ultrasound or positive antithyroid antibodies. RESULTS: The 'total population' comprised 3722 children; the 'reference population' comprised 2134 subjects. The mean, median, 3rd and 97th percentiles of serum FT3, FT4 and TSH for each stage of puberty were obtained. In both boys and girls, FT3 increased with entry into puberty and either stayed constant or declined marginally after stage 3 of puberty. In contrast, in both genders, FT4 decreased with entry into puberty and stayed relatively constant after stage 3 of puberty. TSH levels declined through puberty in boys, but remained largely unchanged in girls. An increased conversion of T4 to T3 is the possible explanation for this finding. CONCLUSIONS: This large community-based study in school-age children using strict exclusion criteria provides data of thyroid function in the various stages of puberty. There is no evidence of 'thyroidarche' during or preceding puberty.

Thyroid status two decades after salt iodization: country-wide data in school children from India.

OBJECTIVE: Country-wide evaluation of thyroid disorders in school children following two decades of universal salt iodization (USI) has not been carried out till date. This study was planned with aim to assess thyroid status of school children two decades after the launch of USI programme. DESIGN: Population survey. PATIENTS: We collected data from 25 schools in 19 cities across five different geographical zones of India. Those children who were evaluated for anthropometry, and goitre status by palpation formed 'total population'. Children who consented to give blood samples were defined as 'study population'. MEASUREMENTS: Serum free T3, free T4, TSH, anti-TPO antibody and thyroid ultrasound. RESULTS: A total of 38,961 children aged 5-15 years formed total population. Goitre rate was 15.5% while thyroid hypoechogenicity was found in 4404 (11.3%) children. In the study population (13,790 children), 2258 (16.4%) had goitre, 505 (3.7%) had positive anti-TPO antibody titres, 1001 (7.3%) had hypothyroidism (TSH > 5.2 µIU/ml) and 41 (0.3%) had thyrotoxicosis (TSH < 0.1 µIU/ml). Among goitrous children, 203 (9.0%) had anti-TPO positivity, 365 (16.1%) had hypoechogenicity of thyroid and either of these were present in 488 (21.6%) children. CONCLUSIONS: Endemic goitre in school children persisted nationwide, despite more than two decades of USI programme. Thyroid autoimmunity only partially explains the increase in goitre prevalence.

Determinants of Waist-to-Height Ratio and Its Relation to Hypertension among School Children in India: A Multicenter Study.

OBJECTIVE: To study the factors associated with waist-to-height ratio (WHtR) among school children aged 5-15 y and its association with hypertension. METHODS: In this cross-sectional study, data on background characteristics, socioeconomic status (SES), anthropometric parameters, and blood pressure were obtained from school children from three states of India. WHtR ≥ 0.5 was defined as obesity and hypertensives were defined based on Fourth Report criteria. Descriptive statistics were applied and multiple linear regression was done to identify factors associated with WHtR. A receiver operating characteristics (ROC) analysis was used to evaluate the predictive ability of WHtR to predict hypertension RESULTS: The mean WHtR among the 12,068 students was 0.40 (± 0.05) and it showed a U-shaped distribution with age with trough at 10 y of age for both genders. Mean WHtR was higher among residents of Manipur, among boys and hypertensives. WHtR was positively associated with weight > 30 kg, male gender, schools with high SES, Manipur and Goa region, and negatively associated with age > 10 y. The area under the ROC curve of WHtR for diagnosis of hypertension was low 0.544 (95% CI 0.532, 0.556). CONCLUSION: There is a nonlinear relation between age, gender, and WHtR, which varies by geographical region and HT. This would need to be kept in mind while using it to identify obesity in children, though its discriminant value for hypertension is low.

A new FOXE1 homozygous frameshift variant expands the genotypic and phenotypic spectrum of Bamforth-Lazarus syndrome.

Bamforth-Lazarus syndrome is a rare autosomal recessive disease caused by biallelic loss-of-function variants in the FOXE1 gene. The condition is characterized by congenital hypothyroidism due to thyroid agenesis or thyroid hypoplasia, cleft palate, spiky hair, with or without choanal atresia, and bifid epiglottis. To date, seven pathogenic variants have been reported in the FOXE1 gene causing Bamforth-Lazarus syndrome. Here we report a novel homozygous loss-of-function variant in the FOXE1 gene NM_004473.4:c.141dupC:p.(Leu49Profs*75) leading to congenital hypothyroidism due to thyroid agenesis, scalp hair abnormalities, cleft palate, small areola, cafe-au-lait spots, mild bilateral hearing loss, skin abnormalities, and facial dysmorphism. We describe the evolving phenotype in the patient with age and review previous variants reported in FOXE1. This report further expands the clinical and molecular spectrum of Bamforth-Lazarus syndrome.

Effects of a Lifestyle Intervention to Prevent Deterioration in Glycemic Status Among South Asian Women With Recent Gestational Diabetes: A Randomized Clinical Trial.

Importance: Women with recent gestational diabetes (GDM) have increased risk of developing type 2 diabetes. Objective: To investigate whether a resource-appropriate and context-appropriate lifestyle intervention could prevent glycemic deterioration among women with recent GDM in South Asia. Design, Setting, and Participants: This randomized, participant-unblinded controlled trial investigated a 12-month lifestyle intervention vs usual care at 19 urban hospitals in India, Sri Lanka, and Bangladesh. Participants included women with recent diagnosis of GDM who did not have type 2 diabetes at an oral glucose tolerance test (OGTT) 3 to 18 months postpartum. They were enrolled from November 2017 to January 2020, and follow-up ended in January 2021. Data were analyzed from April to July 2021. Interventions: A 12-month lifestyle intervention focused on diet and physical activity involving group and individual sessions, as well as remote engagement, adapted to local context and resources. This was compared with usual care. Main Outcomes and Measures: The primary outcome was worsening category of glycemia based on OGTT using American Diabetes Association criteria: (1) normal glucose tolerance to prediabetes (ie, impaired fasting glucose or impaired glucose tolerance) or type 2 diabetes or (2) prediabetes to type 2 diabetes. The primary analysis consisted of a survival analysis of time to change in glycemic status at or prior to the final patient visit, which occurred at varying times after 12 months for each patient. Secondary outcomes included new-onset type 2 diabetes and change in body weight. Results: A total of 1823 women (baseline mean [SD] age, 30.9 [4.9] years and mean [SD] body mass index, 26.6 [4.6]) underwent OGTT at a median (IQR) 6.5 (4.8-8.2) months postpartum. After excluding 160 women (8.8%) with type 2 diabetes, 2 women (0.1%) who met other exclusion criteria, and 49 women (2.7%) who did not consent or were uncontactable, 1612 women were randomized. Subsequently, 11 randomized participants were identified as ineligible and excluded from the primary analysis, leaving 1601 women randomized (800 women randomized to the intervention group and 801 women randomized to usual care). These included 600 women (37.5%) with prediabetes and 1001 women (62.5%) with normoglycemia. Among participants randomized to the intervention, 644 women (80.5%) received all program content, although COVID-19 lockdowns impacted the delivery model (ie, among 644 participants who engaged in all group sessions, 476 women [73.9%] received some or all content through individual engagement, and 315 women [48.9%] received some or all content remotely). After a median (IQR) 14.1 (11.4-20.1) months of follow-up, 1308 participants (81.2%) had primary outcome data. The intervention, compared with usual care, did not reduce worsening glycemic status (204 women [25.5%] vs 217 women [27.1%]; hazard ratio, 0.92; [95% CI, 0.76-1.12]; P = .42) or improve any secondary outcome. Conclusions and Relevance: This study found that a large proportion of women in South Asian urban settings developed dysglycemia soon after a GDM-affected pregnancy and that a lifestyle intervention, modified owing to the COVID-19 pandemic, did not prevent subsequent glycemic deterioration. These findings suggest that alternate or additional approaches are needed, especially among high-risk individuals. Trial Registration: Clinical Trials Registry of India Identifier: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry Identifier: SLCTR/2017/001; and ClinicalTrials.gov Identifier: NCT03305939.

Effect of internal migration on diabetes and metabolic abnormalities in India - The ICMR-INDIAB study.

AIMS: To assess the effect of migration (rural-to-urban and vice versa) on prevalence of diabetes and metabolic disorders in Asian Indians participating in the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study. MATERIALS AND METHODS: The ICMR-INDIAB study is a national study on diabetes and associated cardiometabolic disorders in individuals aged ≥20 years from 28 states and 2 union territories of India. Individuals who moved to a different place from their place of birth and had resided in the new location for at least one year were considered as migrants. Anthropometric measurements, blood pressure estimation and a capillary oral glucose tolerance test were performed. RESULTS: Of the 113,043 participants, 66.4% were non-migrant rural dwellers, 19.4% non-migrant urban dwellers, 8.4% rural-urban migrants, 3.8% multiple migrants and 2.0% urban-rural migrants. Weighted prevalence of diabetes was highest in rural-urban migrants followed by urban dwellers, urban-rural migrants and rural dwellers [14.7%, 13.2%, 12.7% and 7.7% respectively (p < 0.001)]. Rural-urban migrants had highest prevalence of abdominal obesity (50.5%) compared to the other three groups. The risk for diabetes was 1.9 times higher in rural-urban migrants than among rural dwellers. Five risk factors [hypertension, abdominal and generalized obesity, physical inactivity and low fruit and vegetable intake] together explained 69.8% (partial population attributable risk) of diabetes among rural-urban migrants and 66.4% among non-migrant urban dwellers. CONCLUSIONS: Rural-to-urban migration is associated with increased risk of developing diabetes and other cardiometabolic abnormalities. Adoption of healthier lifestyle patterns among migrants could help prevent/delay onset of these abnormalities in this population.

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.

Comprehensive diabetes care: The Goa model.

Diabetes mellitus continues to increase in epidemic proportions globally as well as in India. Poor glycemic control in long-standing diabetes mellitus eventually leads to chronic complications such as retinopathy, nephropathy, neuropathy, and cardiovascular disease. Diabetic retinopathy is emerging as an important cause of avoidable visual impairment and blindness in India across all strata of society. Much of this vision loss can be prevented by improving control of known risk factors, annual fundus screening, with prompt treatment of individuals with sight-threatening retinopathy. The Queen Elizabeth Diamond Jubilee Trust has made a significant contribution by supporting such a program across India, including Goa. The newly established medical retina clinic at Goa Medical College now provides facilities for screening, a detailed evaluation of advanced retinopathy, and therapeutic modalities such as laser and intravitreal injections. The peripheral centers are equipped to screen all people with diabetes mellitus and refer those with sight-threatening retinopathy to the medical college. The provision of a foot scanner to evaluate the risk of foot ulcers and microalbuminuria assessment as part of the nephropathy screening would encompass the entire gamut of diabetic microvascular complications. The next decade would provide evidence if this initiative, with the enthusiastic partnership of the state government, results in reduction of blindness in the people of Goa and an overall reduction in diabetes-related morbidity and mortality.

Lifestyle InterVention IN Gestational diabetes (LIVING) in India, Bangladesh and Sri Lanka: protocol for process evaluation of a randomised controlled trial.

INTRODUCTION: The development of type 2 diabetes mellitus disproportionately affects South Asian women with prior gestational diabetes mellitus (GDM). The Lifestyle InterVention IN Gestational diabetes (LIVING) Study is a randomised controlled trial of a low-intensity lifestyle modification programme tailored to women with previous GDM, in India, Bangladesh and Sri Lanka, aimed at preventing diabetes/pre-diabetes. The aim of this process evaluation is to understand what worked, and why, during the LIVING intervention implementation, and to provide additional data that will assist in the interpretation of the LIVING Study results. The findings will also inform future scale-up efforts if the intervention is found to be effective. METHODS AND ANALYSIS: The Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) methodological approach informed the evaluation framework. Michie's Behaviour Change Theory and Normalisation Process Theory were used to guide the design of our qualitative evaluation tools within the overall RE-AIM evaluation framework. Mixed methods including qualitative interviews, focus groups and quantitative analyses will be used to evaluate the intervention from the perspectives of the women receiving the intervention, facilitators, site investigators and project management staff. The evaluation will use evaluation datasets, administratively collected process data accessed during monitoring visits, check lists and logs, quantitative participant evaluation surveys, semistructured interviews and focus group discussions. Interview participants will be recruited using maximum variation purposive sampling. We will undertake thematic analysis of all qualitative data, conducted contemporaneously with data collection until thematic saturation has been achieved. To triangulate data, the analysis team will engage in constant iterative comparison among data from various stakeholders. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the respective human research ethics committees of the All India Institute of Medical Sciences, New Delhi, India; University of Sydney, New South Wales, Australia; and site-specific approval at each local site in the three countries: India, Bangladesh and Sri Lanka. This includes approvals from the Institutional Ethics Committee at King Edwards Memorial Hospital, Maharaja Agrasen Hospital, Centre for Disease Control New Delhi, Goa Medical College, Jawaharlal Institute of Postgraduate Medical Education and Research, Madras Diabetes Research Foundation, Christian Medical College Vellore, Fernandez Hospital Foundation, Castle Street Hospital for Women, University of Kelaniya, Topiwala National Medical College and BYL Nair Charitable Hospital, Birdem General Hospital and the International Centre for Diarrhoeal Disease Research. Findings will be documented in academic publications, presentations at scientific meetings and stakeholder workshops. TRIAL REGISTRATION NUMBERS: Clinical Trials Registry of India (CTRI/2017/06/008744); Sri Lanka Clinical Trials Registry (SLCTR/2017/001) and ClinicalTrials.gov Registry (NCT03305939); Pre-results.

Lifestyle intervention programme for Indian women with history of gestational diabetes mellitus.

Aim: To evaluate the feasibility and potential effectiveness of a lifestyle intervention (diet and physical activity) among women with history of gestational diabetes mellitus (GDM), delivered by trained facilitators. Methods: Fifty-six normoglycaemic or prediabetic women with prior GDM were recruited at mean of 17 months postpartum. Socio-demographic, medical and anthropometric data were collected. Six sessions on lifestyle modification were delivered in groups (total four groups, with 12-15 women in each group). Pre and post intervention (6 months) weight, body mass index (BMI), waist circumference, 75 g oral glucose tolerance test, blood pressure (BP) and lipid parameters were compared. Results: The intervention was feasible, with 80% of women attending four or more sessions. Post-intervention analyses showed a significant mean reduction of 1.8 kg in weight, 0.6 kg/m2 in BMI and 2 cm in waist circumference. There was also a significant drop of 0.3 mmol/L in fasting plasma glucose, 0.9 mmol/L in 2 h post glucose load value of plasma glucose, 3.6 mmHg in systolic BP, and 0.15 mmol/L in triglyceride levels. Changes in total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol and diastolic BP were non-significant. Conclusions: This study showed feasibility of the lifestyle intervention delivered in group sessions to women with prior gestational diabetes.

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia.

BACKGROUND: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. METHODS/DESIGN: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. DISCUSSION: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01212328.

Reference range of thyroid hormones in normal Indian school-age children.

OBJECTIVE: There is an ongoing debate on narrowing the TSH reference range in adults. In view of the scarce data on normal values of thyroid function tests in children from India, we planned to establish a reference range for thyroid hormones in school-age children. DESIGN AND SUBJECTS: All children (N = 9527; 6-19 years) from six schools representing various zones of Delhi were evaluated for clinical evidence of goitre, thyroid ultrasound, serum free T3 (FT3), free T4 (FT4) and TSH and anti-thyroid peroxidase (anti-TPO) antibodies. From this sample, a reference population (N = 5122) was obtained by excluding those with a personal or family history of thyroid disease, use of thyroid medications, goitre, hypoechogenicity/nodularity on ultrasound or serum anti-TPO antibodies. MEASUREMENTS: Thyroid hormone (FT3, FT4 and TSH) reference ranges were established for each year of life for the total and reference populations. RESULTS: In the reference population, mean serum FT3 was in the range 4.19-4.84 pm/l for boys and 4.03-4.47 pm/l for girls, mean serum FT4 14.69-17.36 pm/l for boys and 14.32-15.88 pm/l for girls, and mean serum TSH 2.57-3.6 mIU/l for boys and 1.83-3.58 mIU/l for girls. For TSH, the 97th percentile was in the range 6.01-8.4 mIU/l for boys and 5.28-8.04 mIU/l for girls, suggesting that at least in children there may not be a need to reduce the upper limit of normal for serum TSH. CONCLUSIONS: This study provides mean reference intervals for FT3, FT4 and TSH for each year of life for both the sexes separately using strict exclusion criteria.