Clinico-radiological parameters, biochemical and molecular alterations predicting remission and recurrence after surgical treatment of corticotroph adenomas - Cushing's disease.

OBJECTIVES: Endonasal endoscopic transsphenoidal surgery (TSS) and resection of pituitary adenomas is considered to be the gold standard treatment for Cushing's Disease (CD). Even with various recent advances in management, disease persistence and recurrences are common in these patients. The remission rate in the global population after surgery has been reported to vary widely from 64 to 93%. This study aims to determine various clinical, biochemical, radiological and histological factors that correlate with persistence and recurrence in patients with CD. This study also aims to understand the clinicopathological significance of EGFR-MAPK, NF-kB and SHH pathway activation and to study the protein expression levels of activation markers of these pathways viz. c-Fos , c-Jun, GLI-1 , pMEK, NR4A1 and p44 in functioning corticotroph pituitary adenomas. METHODS: From January 2009 to September 2022, the clinical data of 167 patients who underwent surgical treatment (n=174 surgeries) for Cushing's disease was ambispectively analysed with a median follow up of 8.1 years (1-13.29 years). The preoperative clinical, biochemical, radiological features, operative findings, postoperative clinical and biochemical data, histopathological and molecular profile, were retrieved from electronic records. The patients were followed up to assess the remission status. RESULTS: Among the 174 surgeries performed, 140 were primary surgeries, 22 were revision surgeries, 24 surgeries were for paediatric patients and 12 surgeries were performed in patients with Nelson syndrome. In the primary surgery cohort, 74.3% were females and the average age was 28.73 years (SD 10.15). 75% of the patients experienced remission after primary surgery compared to 47.4% in revision surgery. The remission rate in paediatric patients was 55.5%. Post-operative day 1 plasma cortisol (p<0.001; AUC 0.8894 [0.8087-0.9701]) and ACTH (p<0.001; AUC 0.9 [0.7386-1]) levels were seen to be strong independent predictors of remission in the primary surgery cohort. Remission rates after Endoscopic TSS were more than that after microscopic TSS, in patients undergoing primary surgery (81.08% vs 57.14%; p=0.008). Presence of adenoma on histopathological examination (HPE) was also a strong predictor of disease remission (p=0.020). On categorising based on surgical approach and HPE, microscopically operated patients without histopathological evidence of adenoma had significantly higher odds of non-remission (OR 38.1 95% CI 4.2-348.3) compared to endoscopically operated patients with adenoma on HPE. Lower immune reactivity score (IRS) of NR4A1 was found to correlate with higher remission rates (p=0.074). However, none of the molecular markers studied viz. c-Fos , c-Jun, GLI-1, pMEK and p44 showed a significant correlation with the preoperative cortisol values. CONCLUSION: Remission rate after primary surgery is higher as compared to that after revision surgery, and that in paediatric patients is lower as compared to adults. Post-operative day 1 plasma cortisol and ACTH levels are strong independent predictors of remission in the primary surgery cohort. Endoscopic approach with histopathological evidence of adenoma is associated with a higher remission rate and thus endoscopy should be the approach of choice in these patients with the goal of identification of an adenoma on histopathological analysis.

Impact of Prevalent Dietary Pattern on Serum Vitamin B12 Status and Its Association With Inflammation Among Reproductive Age Women.

SCOPE: Association between vitamin B12 deficiency (VB12D) and dietary patterns being well documented has bearing on obstetrics and neonatal outcomes. However, relationship between VB12D and serum inflammatory markers (IMs), particularly in vegetarian diet and Polycystic ovary syndrome (PCOS), remains elusive. This cross-sectional study assesses VB12D and IMs among reproductive age women consuming different diets. METHODS AND RESULTS: Nonvegetarian (PCOS, n = 104; healthy, n = 148) and vegetarian women (PCOS n = 112; healthy, n = 186) are for evaluated clinical, biochemical, hormonal assessment, inflammatory, and four vitamin B 12 (VB12) markers. VB12D is defined by Fedosov's wellness quotient (4cB12). Using 4cB12, prevalence of VB12D is discerned in 54.4% (PCOS: 72.1%; healthy 36.5%) and 93.4% (PCOS: 95.9%; healthy: 91.9%) among nonvegetarians and vegetarians, respectively. Vegetarian PCOS women depict lowest median (interquartile range [IQR]) of serum B12 76.2(72.6) pg mL-1, holotranscobalamine (HTC) 37.9(11.3) and highest homocysteine (HCY) 40.32(6.0) µmol L-1, methylmalonic acid (MMA) 352.26(156.7) nmol L-1 with highest Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) and IMs (Monocyte chemoattractant protein 1 (MCP-1), High sensitivity C-reactive protein (hs-CRP), Tumour Necrosis Factor alpha (TNF-α) and Interleukin 6 (IL-6)). Significant correlation of serum hs-CRP, TNF-α, and IL-6 with VB12 markers is observed. CONCLUSION: The VB12D is rampant among reproductive age women that gets exacerbated by PCOS or vegetarian diet. It is directly correlated with magnitude of proinflammatory markers. The results carry substantial implications for public health policies aimed at improving preconception maternal VB12 status for better future pregnancy and offspring outcomes.

Postpartum diabetes and cardiometabolic outcomes among Indian (South Asian) women with early Gestational diabetes mellitus: Insights from the CHIP-F study.

Early GDM is associated with adverse pregnancy outcomes, however data on other outcomes are scarce. We evaluated women with early (n = 117) and classical (n = 412) GDM for long-term postpartum (median 32 months) glycemic and cardiometabolic outcomes and found a significantly higher prevalence of diabetes in the former [22.2 % vs. 12.6 %, p = 0.010].

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.

Longitudinal associations between ambient PM2.5 exposure and lipid levels in two Indian cities.

Background: Exposure to ambient PM2.5 is known to affect lipid metabolism through systemic inflammation and oxidative stress. Evidence from developing countries, such as India with high levels of ambient PM2.5 and distinct lipid profiles, is sparse. Methods: Longitudinal nonlinear mixed-effects analysis was conducted on >10,000 participants of Centre for cArdiometabolic Risk Reduction in South Asia (CARRS) cohort in Chennai and Delhi, India. We examined associations between 1-month and 1-year average ambient PM2.5 exposure derived from the spatiotemporal model and lipid levels (total cholesterol [TC], triglycerides [TRIG], high-density lipoprotein cholesterol [HDL-C], and low-density lipoprotein cholesterol [LDL-C]) measured longitudinally, adjusting for residential and neighborhood-level confounders. Results: The mean annual exposure in Chennai and Delhi was 40 and 102 µg/m3 respectively. Elevated ambient PM2.5 levels were associated with an increase in LDL-C and TC at levels up to 100 µg/m3 in both cities and beyond 125 µg/m3 in Delhi. TRIG levels in Chennai increased until 40 µg/m3 for both short- and long-term exposures, then stabilized or declined, while in Delhi, there was a consistent rise with increasing annual exposures. HDL-C showed an increase in both cities against monthly average exposure. HDL-C decreased slightly in Chennai with an increase in long-term exposure, whereas it decreased beyond 130 µg/m3 in Delhi. Conclusion: These findings demonstrate diverse associations between a wide range of ambient PM2.5 and lipid levels in an understudied South Asian population. Further research is needed to establish causality and develop targeted interventions to mitigate the impact of air pollution on lipid metabolism and cardiovascular health.

Validity of Montreal Cognitive Assessment to Detect Cognitive Impairment in Individuals with Type 2 Diabetes.

INTRODUCTION: Guidelines recommend screening older people (> 60-65 years) with type 2 diabetes (T2D) for cognitive impairment, as it has implications in the management of diabetes. The Montreal Cognitive Assessment (MoCA) is a sensitive test for the detection of mild cognitive impairment (MCI) in the general population, but its validity in T2D has not been established. METHODS: We administered MoCA to patients with T2D (age ≥ 60 years) and controls (no T2D), along with a culturally validated neuropsychological battery and functional activity questionnaire. MCI was defined as performance in one or more cognitive domains ≥ 1.0 SD below the control group (on two tests representing a cognitive domain), with preserved functional activities. The discriminant validity of MoCA for the diagnosis of MCI at different cut-offs was ascertained. RESULTS: We enrolled 267 patients with T2D and 120 controls; 39% of the participants with T2D met the diagnostic criteria for MCI on detailed neuropsychological testing. At the recommended cut-off on MoCA (< 26), the sensitivity (94.2%) was high, but the specificity was quite low (29.5%). The cut-off score of < 23 showed an optimal trade-off between sensitivity (69.2%), specificity (71.8%), and diagnostic accuracy (70.8%). The cut-off of < 21 exhibited the highest diagnostic accuracy (74.9%) with an excellent specificity (91.4%), a good positive and negative predictive value (78.5% and 73.7%, respectively). CONCLUSIONS: The recommended screening cut-off point on MoCA of < 26 has a suboptimal specificity and may increase the referral burden in memory clinics. A lower cut-off of < 21 on MoCA maximizes the diagnostic accuracy. Interactive Visual Abstract available for this article.

Type 2 diabetes (T2D) is a risk factor for cognitive dysfunction which potentially impacts diabetes self-management skills. Guidelines recommend screening older adults with diabetes for early detection of cognitive impairment. For screening cognitive impairment in busy endocrine clinics, we need a test that is easy and rapid to administer, sensitive enough to pick the cognitive deficits of T2D and at the same time gives less false-positive outcomes. The Montreal Cognitive Assessment (MoCA) scale is a widely available cognitive screening tool, but there are no studies evaluating its discriminant properties in people with diabetes. We evaluated the performance metrics of MoCA in this population. We found mild cognitive impairment in four out of ten participants with T2D at or above 60 years of age. At the recommended cut-off on MoCA (< 26), the sensitivity was high, but the specificity quite low. We found better diagnostic accuracy at lower cut-offs (20/21), with high specificity but a lower sensitivity. At this cut-off, approximately one out of five people screened using MoCA would require detailed neuropsychological testing, and four out of five who undergo detailed evaluation would have true cognitive impairment.

68 Ga-DOTANOC PET/CT in 2 Siblings With Von Hippel-Lindau Disease.

ABSTRACT: Von Hippel-Lindau disease is a rare multisystem disorder that shows autosomal dominant inheritance. It is a cancer syndrome that is characterized by the development of a variety of benign and malignant tumors-CNS hemangioblastomas, retinal angiomas, endolymphatic sac tumors, renal cysts and tumors, pancreatic cysts and tumors, adrenal pheochromocytomas, and epididymal cystadenomas. Here we present the 68 Ga-labeled DOTANOC scans of 2 siblings who show an interesting spectrum of findings consistent with Von Hippel-Lindau disease.

Natural History of Type 2 Diabetes in Indians: Time to Progression.

OBJECTIVE: To describe the natural history of diabetes in Indians. RESEARCH DESIGN AND METHODS: Data are from participants older than 20 years in the Centre for Cardiometabolic Risk Reduction in South Asia longitudinal study. Glycemic states were defined per American Diabetes Association criteria. Markov models were used to estimate annual transition probabilities and sojourn time through states. RESULTS: Among 2,714 diabetes-free participants, 641 had isolated impaired fasting glucose (iIFG), and 341 had impaired glucose tolerance (IGT). The annual transition to diabetes for those with IGT was 13.9% (95% CI 12.0, 15.9) versus 8.6% (7.3, 9.8) for iIFG. In the normoglycemia ↔ iIFG → diabetes model, mean sojourn time in normoglycemia was 40.3 (34.6, 48.2) years, and sojourn time in iIFG was 9.7 (8.4, 11.4) years. For the normoglycemia ↔ IGT → diabetes model, mean sojourn time in normoglycemia was 34.5 (29.5, 40.8) years, and sojourn time in IGT was 6.1 (5.3, 7.1) years. CONCLUSIONS: Individuals reside in normoglycemia for 35-40 years; however, progression from prediabetes to diabetes is rapid.

Association of pro-inflammatory cytokines, adipokines and hepatokine with incident diabetes in India: a nested case-control study within CARRS cohort.

AIMS: To study the association of pro-inflammatory markers with incident diabetes in India. METHODS: We did a nested case-control study within the CARRS (Centre for Ardiometabolic Risk Reduction in South Asia) cohort. Of the 5739 diabetes-free individuals at the baseline, 216 participants with incident diabetes and 432 age-, gender- and city-matched controls at 2-year follow-up were included. We measured high sensitive C-reactive protein (hsCRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 ( MCP-1), adiponectin, leptin and fetuin-A in the stored baseline blood samples. We did multivariate conditional logistic regression to estimate association of inflammatory markers (as quartiles) and incident diabetes. Covariates were baseline fasting plasma glucose (FPG) and lipids, body mass index (BMI), family history of diabetes, smoking and alcohol use. RESULTS: Baseline hsCRP and TNF-α were higher, and IL-6 and adiponectin were lower among cases vs. controls. In multivariate conditional logistic regression models, only quartile-3 (odds ratio [OR]: 2.96 [95% CI:1.39, 6.30]) and quartile-4 (OR: 2.58 [95% CI: 1.15, 5.79]) of TNF-α and quartile-4 of MCP-1 (OR: 2.55 [95% CI: 1.06, 6.16]) were positively associated with diabetes after adjusting for baseline FPG and BMI. These associations did not remain after adjusting for family history. High level (quartile-4) of IL-6 was negatively associated with diabetes after adjusting for all factors (OR: 0.18 [95% CI: 0.06, 0.55]). CONCLUSIONS: Higher TNF-α and MCP-1 levels and lower IL-6 were associated with higher risk of developing diabetes. Better understanding and potential methods of addressing these biomarkers, especially in relation to family history, are needed to address diabetes in South Asians.

Association of collaborative care intervention features with depression and metabolic outcomes in the INDEPENDENT study: A mixed methods study.

AIMS: The INtegrating DEPrEssioN and Diabetes treatmENT (INDEPENDENT) trial tested a collaborative care model including electronic clinical decision support (CDS) for treating diabetes and depression in India. We aimed to assess which features of this clinically and cost-effective intervention were associated with improvements in diabetes and depression measures. METHODS: Post-hoc analysis of the INDEPENDENT trial data (189 intervention participants) was conducted to determine each intervention feature's effect: 1. Collaborative case reviews between expert psychiatrists and the care team; 2. Patient care-coordinator contacts; and 3. Clinicians' CDS prompt modifications. Primary outcome was baseline-to-12-months improvements in diabetes control, blood pressure, cholesterol, and depression. Implementer interviews revealed barriers and facilitators of intervention success. Joint displays integrated mixed methods' results. RESULTS: High baseline HbA1c≥ 74.9 mmol/mol (9%) was associated with 5.72 fewer care-coordinator contacts than those with better baseline HbA1c (76.8 mmol/mol, 9.18%, p < 0.001). Prompt modification proportions varied from 38.3% (diabetes) to 1.3% (LDL). Interviews found that providers' and participants' visit frequencies were preference dependent. Qualitative data elucidated patient-level factors that influenced number of clinical contacts and prompt modifications explaining their lack of association with clinical outcomes. CONCLUSION: Our mixed methods approach underlines the importance of the complementarity of different intervention features. Qualitative findings further illuminate reasons for variations in fidelity from the core model.

Evaluating bias with loss to follow-up in a community-based cohort: empirical investigation from the CARRS Study.

BACKGROUND: Retention of participants is a challenge in community-based longitudinal cohort studies. We aim to evaluate the factors associated with loss to follow-up and estimate attrition bias. METHODS: Data are from an ongoing cohort study, Center for cArdiometabolic Risk Reduction in South Asia (CARRS) in India (Delhi and Chennai). Multinomial logistic regression analysis was used to identify sociodemographic factors associated with partial (at least one follow-up) or no follow-up (loss to follow-up). We also examined the impact of participant attrition on the magnitude of observed associations using relative ORs (RORs) of hypertension and diabetes (prevalent cases) with baseline sociodemographic factors. RESULTS: There were 12 270 CARRS cohort members enrolled in Chennai and Delhi at baseline in 2010, and subsequently six follow-ups were conducted between 2011 and 2022. The median follow-up time was 9.5 years (IQR: 9.3-9.8) and 1048 deaths occurred. Approximately 3.1% of participants had no follow-up after the baseline visit. Younger (relative risk ratio (RRR): 1.14; 1.04 to 1.24), unmarried participants (RRR: 1.75; 1.45 to 2.11) and those with low household assets (RRR: 1.63; 1.44 to 1.85) had higher odds of being lost to follow-up. The RORs of sociodemographic factors with diabetes and hypertension did not statistically differ between baseline and sixth follow-up, suggesting minimal potential for bias in inference at follow-up. CONCLUSION: In this representative cohort of urban Indians, we found low attrition and minimal bias due to the loss to follow-up. Our cohort's inconsistent participation bias shows our retention strategies like open communication, providing health profiles, etc have potential benefits.

Opportunistic screening for osteopathy with routine abdominal computed tomography scan in chronic pancreatitis.

BACKGROUND AND AIMS: Lumbar vertebral bone attenuation, measured in Hounsfield units (HU) can indirectly indicate the bone mineral density (BMD). The aim of this study is to determine the optimal HU threshold on abdominal computed tomography (CT) scans to detect osteopathy in patients with chronic pancreatitis (CP). METHODS: This cross-sectional study included patients with CP who underwent CT scans to measure HU at L1 to L4 vertebrae. The mean lumbar vertebral attenuation of female renal transplant donors, aged 20-30 years was utilized to calculate the T-scoreHU of all patients at each vertebral level. Receiver operator characteristic analysis was used to determine the HU and T-scoreHU for diagnosis of osteopathy in patients with CP. Dual-energy X-ray absorptiometry value was used to categorize osteopenia and osteoporosis. RESULTS: A total of 175 patients (mean age, 34.5 ± 10.9 years; 72 % males) and 33 female renal transplant donors (mean age, 28 ± 2.4 years) were included. A threshold HU value 212 or T scoreHU of -1.80 at L1 vertebra was found to have a 78 % sensitivity and 70 % specificity for differentiating between osteoporosis and non-osteoporosis (osteopenia and normal BMD). Similarly, a threshold HU value of 254 or a T-scoreHU of -0.46 at L1 vertebra had 78 % sensitivity and 71 % specificity for distinguishing between normal and low BMD (osteoporosis and osteopenia). CONCLUSION: Abdominal CT images, which are routinely performed in chronic pancreatitis, can be used for opportunistic screening of osteoporosis and osteopenia without additional cost or radiation exposure.

Burosumab: Current status and future prospects.

Hypophosphatemic rickets/osteomalacia caused by FGF23 excess is conventionally treated with multiple doses of inorganic phosphate salts and active vitamin D analogs. However, conventional therapy targets the consequences of elevated FGF23 and not the elevated FGF23 itself and is associated with poor adherence and long-term complications such as nephrocalcinosis and secondary/tertiary hyperparathyroidism. Burosumab is a fully human IgG1 monoclonal antibody that binds to and neutralises FGF-23, thereby leading to improvement in phosphate homeostasis and healing of rickets and osteomalacia. Data from phase 2 and 3 trials report overall safety and efficacy and Burosumab is now FDA approved for treatment of XLH and TIO in children and adults. Cost and absence of long-term data are major issues with Burosumab which should be addressed in near future. At present, experts recommend Burosumab use in patients with severe disease or those with mild-moderate disease and a failed response to a trial of conventional therapy.

Utility of Simple and Non-Invasive Strategies Alternative to Inferior Petrosal Sinus Sampling and Peripheral CRH Stimulation in Differential Diagnosis of ACTH-Dependent Cushing Syndrome.

We aimed to evaluate the utility of simple, cost-effective, and non-invasive strategies alternative to BIPSS and peripheral CRH stimulation in differential diagnosis of ACTH-dependent CS. First, we performed ROC analysis to evaluate the performance of various tests for differential diagnosis of ACTH-dependent CS in our cohort (CD, n=76 and EAS, n=23) and derived their optimal cut-offs. Subsequently, combining various demographic (gender), clinical (hypokalemia), biochemical (plasma ACTH, HDDST, peripheral CRH stimulation) and imaging (MRI pituitary) parameters, we derived non-invasive models with 100% PPV for CD. Patients with pituitary macroadenoma (n=14) were excluded from the analysis involving non-invasive models. Relative percent ACTH (AUC: 0.933) and cortisol (AUC: 0.975) increase on peripheral CRH stimulation demonstrated excellent accuracy in discriminating CD from EAS. Best cut-offs for CD were plasma ACTH<97.3 pg/ml, HDDST≥57% cortisol suppression, CRH stimulation≥77% ACTH increase and≥11% cortisol increase. We derived six models that provided 100% PPV for CD and precluded the need for BIPPS in 35/85 (41.2%) patients with ACTH-dependent CS and no macroadenoma (in whom BIPSS would have otherwise been recommended). The first three models included basic parameters and avoided both peripheral CRH stimulation and BIPSS in 19 (22.4%) patients, while the next three models included peripheral CRH stimulation and avoided BIPSS in another 16 (18.8%) patients. Using simple and non-invasive alternative strategies, BIPSS can be avoided in 41% and peripheral CRH stimulation in 22% of patients with ACTH-dependent CS and no macroadenoma; such patients can be directly referred for a pituitary surgery.

Metabolic Syndrome Among Adolescents Aged 10-19 Years in India: A Systematic Review and Meta-Analysis.

Metabolic syndrome (MetS) is a group of metabolic abnormalities that include disturbed glucose metabolism, dyslipidemia, abdominal obesity, and arterial hypertension. Nutritional and lifestyle modifications have increased the risk of cardiometabolic disorders among adolescents. Studies conducted in various parts of India have shown a wide range of prevalence among adolescents aged 10-19 years. The various criteria for defining MetS have led to controversial diagnoses, providing inconsistent findings. Additionally, there is a paucity of national-level estimates on the prevalence of MetS in India. Therefore, this systematic review and meta-analysis were conducted to estimate the prevalence of MetS among adolescents. A comprehensive search was conducted to identify studies that reported the prevalence of MetS among adolescents in India. The search was performed using several databases, including PubMed, Embase, ScienceDirect, Scopus, Medline, Web of Science, Google, and Google Scholar. Relevant data were extracted and assessed for quality using the Critical Appraisal Skills Programme (CASP) guidelines. To estimate the pooled prevalence and explore heterogeneity, a random effects model and I2 statistic were used. Subgroup analyses were conducted based on criteria for defining MetS, sex, study setting, and study site. Sensitivity analysis was performed, and publication bias was also explored. A sample size of 19044 adolescents from 16 studies was included in the meta-analysis. The pooled prevalence of Mets among adolescents using the International Diabetes Federation (IDF) criteria was 3.4% (95% CI: 1.1-6.6%, I2=97.1%) and the National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) criteria were 5.0% (95% CI: 3.3-6.9%, I2=95.9). The subgroup analyses did not reveal the reasons for heterogeneity, but sensitivity analysis showed a substantial change in the pooled estimate. Our study findings show that the prevalence of MetS among Indian adolescents is higher compared to other countries posing a challenge to address the necessity of intervention among adolescents. Standardizing the definition of MetS is necessary to avoid inconsistency in the estimates. The study findings highlight the need to strengthen existing adolescent programs through the encouragement of increased physical activity and the adoption of nutritious well-balanced diets to mitigate the burden of MetS among adolescents in India.

The Impact of a Collaborative Care Model on Health Trajectories among Patients with Co-Morbid Depression and Diabetes: The INDEPENDENT Study.

Context: Collaborative care models for depression have been successful in a variety of settings, but their success may differ by patient engagement. We conducted a post-hoc analysis of the INDEPENDENT trial to investigate the role of differential engagement of participants on health outcomes over 3 years. Settings and Design: INDEPENDENT study was a parallel, single-blinded, randomised clinical trial conducted at four socio-economically diverse clinics in India. Participants were randomised to receive either active collaborative care or usual care for 12 months and followed up for 24 months. Method: We grouped intervention participants by engagement, defined as moderate (≤7 visits) or high, (8 or more visits) and compared them with usual care participants. Improvements in composite measure (depressive symptoms and at least one of three cardio-metabolic) were the primary outcome. Statistical Analysis: Mean levels of depression and cardio-metabolic measures were analysed over time using computer package IBM SPSS Statistics 25. Results: The composite outcome was sustained the highest in the moderate engagers [27.5%, 95% confidence interval (CI): 19.5, 36.7] and the lowest in high engagers (15.8%, 95% CI: 8.1, 26.8). This pattern was observed for individual parameters - depressive symptoms and glycosylated haemoglobin. Progressive reductions in mean depressive symptom scores were observed for moderate engagers and usual care group from baseline to 36 months. However, in high engagers of collaborative care, mean depressive symptoms were higher at 36 months compared to 12 months. Conclusion: Sustained benefits of collaborative care were larger in participants with moderate engagement compared with high engagement, although a majority of participants relapsed on one or more outcome measures by 36 months. High engagers of collaborative care for co-morbid depression and diabetes may need light touch interventions for longer periods to maintain health and reduce depressive symptoms.

Incidence of Prediabetes/Diabetes among Women with Prior Gestational Diabetes and Non-Alcoholic Fatty Liver Disease: A Prospective Observational Study.

Background and Objectives: This prospective longitudinal study aims to evaluate and compare the incidence of prediabetes/diabetes among women stratified at the baseline postpartum visit according to the prior GDM and NAFLD status. Methods: Of the 309 women with baseline postpartum assessment at a median of 16 months following the index delivery, 200 (64.7%) [GDM: 137 (68.5%), normoglycaemia: 63 (31.5%)] were available for the follow-up analysis (performed at median of 54 months following the index delivery) and were participants for this study. We obtained relevant demographic, medical and obstetric details and performed a 75 g OGTT with glucose estimation at 0 and 120 min. NAFLD status was defined by ultrasonography at the baseline visit. Participants were divided into four groups: no NAFLD and no prior GDM (group 1), NAFLD but no prior GDM (group 2), prior GDM but no NAFLD (group 3), and NAFLD and prior GDM (group 4). Results: The mean age of study participants (n = 200) was 32.2 ± 5.1 years, and the mean interval between the two visits was 34.8 ± 5.5 months. A total of 74 (37%) women had progression to prediabetes/diabetes [incidence rate of 12.8/100 woman-years]. The incidence rates (per 100 woman-years) were 8.6, 8.9, 13.4 and 15.3 in groups 1, 2, 3 and 4, respectively. The adjusted hazard ratio for incident (new-onset) prediabetes/diabetes in group 4 (reference: group 1) was 1.99 (95% CI 0.80, 4.96, P = 0.140). Among women with baseline NAFLD (irrespective of GDM status), the risk of incident prediabetes/diabetes increased with an increase in the duration of follow-up (3.03-fold higher per year of follow-up, P = 0.029) and was significantly higher in women who were not employed (6.43, 95% CI 1.74, 23.7, P = 0.005) and in women with GDM requiring insulin/metformin during pregnancy (4.46, 95% CI 1.27, 15.64, P = 0.019). Conclusion: NAFLD and GDM increased the risk for glycaemic deterioration in young Indian women. Future studies should focus on evaluating the effectiveness of lifestyle and behavioural interventions in such high-risk women.

Docosahexaenoic Acid Supplementation in Lactating Women Increases Breast Milk and Erythrocyte Membrane Docosahexaenoic Acid Concentrations and Alters Infant n-6:n-3 Fatty Acid Ratio.

Background: Low concentrations of docosahexaenoic acid (DHA) or high n-6 (ω-6):n-3 ratio in pregnant women is associated with poor fetal growth velocity and suboptimal neurodevelopment. However, there is a lack of data on levels of important n-6 and n-3 fatty acids (FAs) at different time points during pregnancy and lactation from India. Data on how much DHA is transferred during actual supplementation are also scarce. Objectives: We report the concentrations of n-6 and n-3 FAs in maternal and infant blood and in breast milk following maternal supplementation with DHA or placebo. Methods: A total of 957 pregnant women (≤20 wk) from Belagavi, Karnataka, were randomly assigned to receive either 400 mg/d of algal DHA or placebo through 6 mo postpartum. Blood samples were collected from the mother at recruitment/baseline, delivery, and 6 mo postpartum and from the infant at birth (cord) and 12 mo (venous). Breast milk samples were collected from a subsample at delivery, 1 mo and 6 mo postpartum. The FA profile was analyzed using gas chromatography. Results: The concentration of DHA appeared to be higher in erythrocyte and breast milk samples of the DHA-supplemented group at all subsequent time points. The n-6:n-3 ratio was lower among women in the DHA group at delivery [DHA: 4.08 (1.79); placebo: 5.84 (3.57); P < 0.001] and at 6 mo postpartum [DHA: 5.34 (2.64); placebo: 7.69 (2.9); P < 0.001]. Infants of DHA-supplemented mothers also had a lower n-6:n-3 ratio at delivery and 12 mo. The n-6:n-3 ratio of breast milk increased from delivery through 1 to 6 mo but remained lower in the DHA-supplemented group than in the placebo. Conclusions: Maternal DHA supplementation with 400 mg/d from early pregnancy through 6 mo postpartum significantly increased circulating DHA in breast milk and infant erythrocyte, whereas decreased erythrocyte and breast milk n-6:n-3 ratio. However, maternal supplementation did not get the ratio to the recommended levels.

Hypertension Diagnosis, Treatment, and Control in India.

Importance: Hypertension is a major cause of morbidity and mortality worldwide. Previous efforts to characterize gaps in the hypertension care continuum-including diagnosis, treatment, and control-in India did not assess district-level variation. Local data are critical for planning, implementation, and monitoring efforts to curb the burden of hypertension. Objective: To examine the hypertension care continuum in India among individuals aged 18 to 98 years. Design, Setting, and Participants: The nationally representative Fifth National Family Health Survey study was conducted in 2 phases from June 17, 2019, to March 21, 2020, and from November 21, 2020, to April 30, 2021, among 1 895 297 individuals in 28 states, 8 union territories, and 707 districts of India. Exposures: District and state of residence, urban classification, age (18-39, 40-64, and ≥65 years), sex, and household wealth quintile. Main Outcomes and Measures: Hypertension was defined as a self-reported diagnosis or a newly measured blood pressure of 140/90 mm Hg or more. The proportion of individuals diagnosed (self-reported), the proportion of individuals treated among those diagnosed (self-reported medication use), and the proportion of individuals with blood pressure control among those treated (blood pressure <140/90 mm Hg [aged 18-79 years] or <150/90 mm Hg [aged ≥80 years]) were calculated based on national guidelines. Age-standardized estimates of treatment and control were also provided among the total with hypertension. To assess differences in the care continuum between or within states (ie, between districts), the variance was partitioned using generalized linear mixed models. Results: Of the 1 691 036 adult respondents (52.6% women; mean [SD] age, 41.6 [16.5] years), 28.1% (95% CI, 27.9%-28.3%) had hypertension, of whom 36.9% (95% CI, 36.4%-37.3%) received a diagnosis. Among those who received a diagnosis, 44.7% (95% CI, 44.1%-45.3%) reported taking medication (corresponding to 17.7% [95% CI, 17.5%-17.9%] of the total with hypertension). Among those treated, 52.5% (95% CI, 51.7%-53.4%) had blood pressure control (corresponding to 8.5% [95% CI, 8.3%-8.6%] of the total with hypertension). There were substantial variations across districts in blood pressure diagnosis (range, 6.3%-77.5%), treatment (range, 8.7%-97.1%), and control (range, 2.7%-76.6%). Large proportions of the variation in hypertension diagnosis (94.7%), treatment (93.6%), and control (97.3%) were within states, not just between states. Conclusions and Relevance: In this cross-sectional survey study of Indian adults, more than 1 in 4 people had hypertension, and of these, only 1 in 3 received a diagnosis, less than 1 in 5 were treated, and only 1 in 12 had blood pressure control. National mean values hide considerable state-level and district-level variation in the care continuum, suggesting the need for targeted, decentralized solutions to improve the hypertension care continuum in India.

PM2.5 exposure, glycemic markers and incidence of type 2 diabetes in two large Indian cities.

INTRODUCTION: Exposure to fine particulate matter has been associated with several cardiovascular and cardiometabolic diseases. However, such evidence mostly originates from low-pollution settings or cross-sectional studies, thus necessitating evidence from regions with high air pollution levels, such as India, where the burden of non-communicable diseases is high. RESEARCH DESIGN AND METHODS: We studied the associations between ambient PM2.5 levels and fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and incident type 2 diabetes mellitus (T2DM) among 12 064 participants in an adult cohort from urban Chennai and Delhi, India. A meta-analytic approach was used to combine estimates, obtained from mixed-effects models and proportional hazards models, from the two cities. RESULTS: We observed that 10 µg/m3 differences in monthly average exposure to PM2.5 was associated with a 0.40 mg/dL increase in FPG (95% CI 0.22 to 0.58) and 0.021 unit increase in HbA1c (95% CI 0.009 to 0.032). Further, 10 µg/m3 differences in annual average PM2.5 was associated with 1.22 (95% CI 1.09 to 1.36) times increased risk of incident T2DM, with non-linear exposure response. CONCLUSIONS: We observed evidence of temporal association between PM2.5 exposure, and higher FPG and incident T2DM in two urban environments in India, thus highlighting the potential for population-based mitigation policies to reduce the growing burden of diabetes.