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.

Novel genomic variants related to visceral adiposity index (VAI) and body adiposity index (BAI) in Indian sib-pairs.

BACKGROUND: Obesity is among the leading public health threats globally. Over the last few years, visceral adiposity index (VAI), and body adiposity index (BAI), derived from anthropometric, and biochemical measures, have gained importance as a measure of obesity. However, unlike other common indices like body mass index, and waist circumference, the genetic predisposition of VAI, and BAI under-examined. METHODS: 2265 sib-pairs from Indian Migration Study were used for examining the association of genetic variants from the Cardio-Metabochip array with VAI, and BAI. Mixed linear regression models were run, and all inferences were based on the within-sib component of the Fulker's association models. Gene-environment/lifestyle interaction analyses were also undertaken. RESULTS: rs6659428 at LOC400796 | SEC16B (ß = 0.26, SE = 0.05), and rs7611535 at DRD3 | LOC645180 (ß = 0.18, SE = 0.04) were associated with VAI at suggestive significance value of <8.21 × 10-6. For BAI, rs73300702 at JAZF1-AS1 (ß = 0.27, SE = 0.06), was the top hit at p value < 8.21 × 10-6. Further, rs6659428 showed marginal effect modification with rural/urban location (ß = 0.26, SE = 0.13, p value = 0.047), and rs73300702 with physical activity (ß = -0.29,SE = 0.14, p value = 0.034). CONCLUSION: We report three novel genetic loci for VAI, and BAI in Indians that are important indicators of adiposity. These findings need to be replicated and validated with larger samples from different ethnicities. Further, functional studies for understanding the biological mechanisms of these adiposity indices need to be undertaken to understand the underlying pathophysiology.

Genetic architecture of adiposity measures among Asians: Findings from GWAS.

Adiposity has gradually become a global public threat over the years with drastic increase in the attributable deaths and disability adjusted life years (DALYs). Given an increased metabolic risk among Asians as compared to Europeans for any given body mass index (BMI) and considering the differences in genetic architecture between them, the present review aims to summarize the findings from genome-wide scans for various adiposity indices and related anthropometric measures from Asian populations. The search for related studies, published till February 2022, were made on PubMed and GWAS Catalog using search strategy built with relevant keywords joined by Boolean operators. It was recorded that out of a total of 47 identified studies, maximum studies are from Korean population (n = 14), followed by Chinese (n = 7), and Japanese (n = 6). Nearly 200 loci have been identified for BMI, 660 for height, 16 for weight, 28 for circumferences (waist and hip), 32 for ratios (waist hip ratio [WHR] and thoracic hip ratio [THR]), 5 for body fat, 16 for obesity, and 28 for adiposity-related blood markers among Asians. It was observed that though, most of the loci were unique for each trait, there were 3 loci in common to BMI and WHR. Apart from validation of variants identified in European setting, there were many novel loci discovered in Asian populations. Notably, 125 novel loci form Asian studies have been reported for BMI, 47 for height, 5 for waist circumference, and 2 for adiponectin level to the existing knowledge of the genetic framework of adiposity and related measures. It is necessary to examine more advanced adiposity measures, specifically of relevance to abdominal adiposity, a major risk factor for cardiometabolic disorders among Asians. Moreover, in spite of being one continent, there is diversity among different ethnicities across Asia in terms of lifestyle, climate, geography, genetic structure and consequently the phenotypic manifestations. Hence, it is also important to consider ethnic specific studies for identifying and validating reliable genetic variants of adiposity measures among Asians.

Alpha-ketoglutarate supplementation reduces inflammation and thrombosis in type 2 diabetes by suppressing leukocyte and platelet activation.

The interplay between platelets and leukocytes contributes to the pathogenesis of inflammation, thrombosis, and cardiovascular diseases (CVDs) in type 2 diabetes (T2D). Our recent studies described alpha-ketoglutarate (αKG), a Krebs cycle intermediate metabolite as an inhibitor to platelets and leukocytes activation by suppressing phosphorylated-Akt (pAkt) through augmentation of prolyl hydroxylase-2 (PHD2). Dietary supplementation with a pharmacological concentration of αKG significantly inhibited lung inflammation in mice with either SARS-CoV-2 infection or exposed to hypoxia treatment. We therefore investigated if αKG supplementation could suppress hyperactivation of these blood cells and reduce thromboinflammatory complications in T2D. Our study describes that dietary supplementation with αKG (8 mg/100 g body wt. daily) for 7 days significantly reduced the activation of platelets and leukocytes (neutrophils and monocytes), and accumulation of IL1ß, TNFα, and IL6 in peripheral blood of T2D mice. αKG also reduced the infiltration of platelets and leukocytes, and accumulation of inflammatory cytokines in lungs by suppressing pAkt and pP65 signaling. In a cross-sectional investigation, our study also described the elevated platelet-leukocyte aggregates and pro-inflammatory cytokines in circulation of T2D patients. T2D platelets and leukocytes showed an increased aggregation and thrombus formation in vitro. Interestingly, a pre-incubation of T2D blood samples with octyl αKG significantly suppressed the activation of these blood cells and ameliorated aggregate/thrombus formation in vitro. Thus, suggesting a potential therapeutic role of αKG against inflammation, thrombosis, and CVDs in T2D.

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.

Impact of Fluoro-Choline PET/CT in Reduction in Failed Parathyroid Localization in Primary Hyperparathyroidism.

INTRODUCTION: Accurate localization of the pathological parathyroid gland is a prerequisite for minimally invasive surgical management of hyperparathyroidism (HPT). Poor imaging or discordance in odd situations like ectopic adenomas, parathyroid hyperplasia, syndromic HPT results in localization dilemma thus causing failed parathyroidectomy. We studied the impact of Fluoro-Choline (FCH) PET/CT imaging in reduction in localization failure of parathyroid adenoma. MATERIALS AND METHODS: We did a retrospective observational study (2018-2021) of HPT among which 97 patients underwent focused parathyroidectomy (FP). All patients had undergone ultrasound imaging and 99mTc-sestaMIBI scan with early SPECT/CT (MIBI). When this preliminary imaging was doubtful or negative or multiple lesions were expected, FCH PET/CT was performed. We compared the localization accuracy of MIBI scan and FCH PET/CT with surgical outcomes as reference standard. RESULTS: MIBI scan showed overall lesion detection rate (LDR) of 88.65% in localization of pathological parathyroid gland in 97 patients. The addition of FCH PET/CT improved the overall lesion detection to 97.9%. The overall possible localization failure was reduced from 11.34 to 2.06% with the addition of FCH PET/CT (p < 0.05). Out of 97 patients of FP, 87 patients showed features of parathyroid adenoma. Single hyperplastic gland was seen in 7 patients, lipoadenoma was seen in 1 patient and 1 patient had features suggestive of parathyroiditis on histopathology. FCH PET/CT was a useful adjunct and showed significant reduction in localization failure of parathyroid adenoma.

Myoinositol versus metformin pretreatment in GnRH-antagonist cycle for women with PCOS undergoing IVF: a double-blinded randomized controlled study.

OBJECTIVE: To study the effects of myoinositol (Myo) in comparison to metformin (Met), in reducing the risk of OHSS and improving ART outcome in PCOS women undergoing IVF. DESIGN: Double-blinded randomized controlled trial (CTRI/2018/05/014196). SETTING: ART Clinic, AIIMS, New Delhi patients: 102 infertile PCOS women undergoing IVF cycles were enrolled after evaluating for eligibility and allotted as 50 in group 1 (Myo) and 52 in group 2 (Met) after randomization. INTERVENTIONS: Recruited patients received Myo 2 g twice daily (group 1) and Met 850 mg twice daily (group 2). Pre- and post-treatment clinical (menstrual pattern, BMI), hormonal profile (LH, FSH, testosterone, prolactin [PRL], and AMH), biochemical parameters (HOMA IR, fasting glucose, and insulin), ovarian with antral follicle count (AFC) and side effect profile were assessed. After 3 months of therapy, patients were recruited for IVF cycle by antagonist protocol was involving controlled ovarian stimulation, cycle monitoring, oocyte recovery, insemination of oocytes and follow up with fertilization, cleavage, transfer of good grade cleavage embryos, or blastocysts pregnancy outcomes and OHSS incidence and medications was continued until the day of OPU. MAIN OUTCOME MEASURES: Primary outcome was OHSS and clinical pregnancy rate including spontaneous, IVF, and cumulative pregnancy rate including FET. Secondary outcome was ART outcomes and the change in biochemistry and hormonal profile between groups and inter group after medications at 12 weeks. RESULTS: Incidence of OHSS (Myo 5 (10.0) (n = 50), Met 10 (20.0) (n = 50) p .07) was not statistically different between groups. Clinical pregnancy rate (Myo 18 (36.0) (n = 50), Met 9 (18.0) (n = 50) p .04) cumulative pregnancy rate including FET (Myo 16 (43.2) (n = 37) vs. Met 10) 22.7) (n = 44) p .05) and spontaneous conception (prior to IVF) Myo 13 (26.0) (n = 50), Met 6 (12.0) (n = 50) p .07) was significantly high in Myo group. No between group difference in ovarian stimulation outcomes including duration and dosage of gonadotropins, E2, P4 levels, number of follicles >14 mm on day of trigger. Number of oocytes retrieved and grade of maturity were similar between groups. Fertilization, cleavage and number of good grade embryos were significantly higher in Myo group. However, implantation rate and number of embryos for freezing were similar between groups. Myo had improvement in fasting insulin, HOMA, Sr.AMH, and SHBG suggesting decreased insulin resistance. CONCLUSIONS: Myo is equally beneficial as Met in reducing the risk of OHSS and has better ART outcome in PCOS women undergoing antagonist cycles.

Bone mass in newborns and its predictors.

OBJECTIVE: Optimal bone mass (a function of foetal programming and adequate intrauterine bone mineral accrual) is essential for prevention of osteoporosis. The present study was planned with the objectives to describe newborn bone mass (NBBM) and study the associated factors. DESIGN: Observational study Patients: Singleton pregnant women ≤16 weeks gestation. MEASUREMENTS: Maternal factors and antenatal events: Dietary assessment (3 days-24-h diet recalls at ≤16 and 32-34 weeks), fetal femoral volume (FFV) assessment at 19 and 34 weeks, serum 25 hydroxyvitamin D (S.25OHD) and placental weight. Newborn anthropometric parameters, cord S.25OHD & IGF-1 level and NBBM by DXA (whole-body bone mineral content (BMC), bone mineral density (BMD) and bone area). RESULTS: Total 224 subjects were studied: 198 full-term and 26 preterm. The mean BMC, BMD and bone area for term newborns was 46.5 g (95% confidence interval [CI]: 45.35-47.66), 0.209 g/cm2 (95% CI: 0.206-0.212) and 221.6 cm2 (95% CI: 218.52-224.62), respectively. The mean placental weight was 403.2 ± 75.01 g (n = 72) while FFV was 0.71 ± 0.28 ml (19 weeks; n = 59) and 4.4 ± 1.17 ml (34 weeks; n = 33). Factors significantly associated with NBBM -gestational age at delivery, gestational weight gain, FFV at 19 weeks, placental weight, third-trimester maternal serum albumin and newborn anthropometric parameters (univariable analysis) and newborn birth weight, placental weight and FFV at 19 weeks (multivariable analysis). CONCLUSION: This study described NBBM among term newborns and birth weight, second-trimester FFV and placental weight were the associated factors.

High prevalence and a long delay in the diagnosis of primary aldosteronism among patients with young-onset hypertension.

BACKGROUND: Despite being the most common cause of secondary hypertension, prevalence of primary aldosteronism (PA) among patients with young-onset hypertension (YH - age of hypertension onset <40 years) remains poorly studied. OBJECTIVE: We assessed the prevalence of PA in patients with YH referred for evaluation of secondary hypertension. DESIGN AND PATIENTS: In this prospective, cross-sectional study, 202 patients with YH, visiting endocrine and cardiology clinics of All India Institute of Medical Sciences, India, were evaluated. MEASUREMENTS: Primary aldosteronism was screened by measuring plasma aldosterone concentration (PAC) and direct renin concentration (DRC) and calculating aldosterone-to-renin ratio (ARR), followed by confirmatory saline infusion test (SIT) according to Endocrine Society Guideline. Those confirmed with post-SIT PAC >5 ng/dl underwent adrenal computed tomography (CT), followed by adrenal venous sampling (AVS). RESULTS: Of 202 YH patients, 38 (18.8%) screened positive, and PA was confirmed in 36 (17.8%). The mean age was 43.9 ± 10.9 years, and median duration of hypertension was 10.5 (3.5-18) years. The prevalence of PA increased with grade of hypertension (8.1% in grade 1 to 37.1% in grade 3), number of antihypertensive medications (2.5% in those taking ≤1 to 50% in those taking ≥4 medications) and severity of hypokalaemia (0% in potassium >5 to 85.7% in potassium <3.5 mmol/L). The prevalence of PA by age of hypertension onset was highest in age group 30-39 years (31.3%). CONCLUSIONS: There is a high prevalence and a long delay in diagnosis of PA among patients with YH, and YH should be considered as a separate high-risk category in PA screening algorithm.

Late effects in pediatric Hodgkin lymphoma survivors after uniform treatment with ABVD with or without radiotherapy.

PURPOSE: ABVD (doxorubicin, bleomycin,vinblastine, and dacarbazine) is not a standard regimen in children due to concerns regarding late effects. However, no studies have evaluated long-term toxicities of ABVD in children. METHODS: Total 154 pediatric Hodgkin lymphoma (HL) survivors uniformly treated with ABVD were clinically followed up as per institutional protocol. All participants were evaluated for cardiac, pulmonary, and thyroid function abnormalities by multigated acquisition scan (MUGA) scan, spirometry with diffusion capacity of lung for the uptake of carbon monoxide (DLCO), and thyroid profile test, respectively, at a single time point. Predictors of toxicity were also analyzed. RESULTS: The median duration of follow-up of the cohort was 10.3 years (6.04-16.8). No secondary malignant neoplasm (SMN) or symptomatic cardiac/pulmonary toxicities were detected. Nine patients (5.9%) had left ventricular ejection fraction (LVEF) <55%. Subclinical and overt hypothyroidism were observed in 78 (50.6%) and 16 (10.4%) survivors, respectively. Abnormal spirometry and reduced DLCO was observed in 43.2% and 42.0% survivors, respectively. Receiving neck radiation was significantly associated with thyroid dysfunction (odds ratio [OR] 16.04, p < .001); age ≥10 years predicted reduced DLCO (OR 4.12, p = .001). Sixty-three and 33 patients had one and two late adverse effects, respectively; receiving neck radiation predicted development of multiple late effects (proportional OR 4.72, p < 0.001). Cumulative dose of chemotherapy did not predict toxicity. CONCLUSIONS: Overall, ABVD appears safe in children at a relatively short follow-up. Long-term safety data are required before it can be adopted for treating pediatric HL patients. Children receiving neck radiation require close follow-up.

Response to single oral dose vitamin D in obese vs non-obese vitamin D-deficient children.

Obese individuals are prone to vitamin D deficiency because of sequestration of vitamin D in their body fat. We planned to evaluate the rise in serum 25(OH)D levels in vitamin D-deficient obese vs normal body mass index(BMI) children, after administration of identical single dose of vitamin D. Twenty-two obese and 22 normal BMI children with serum 25 (OH)D < 20 ng/mL were given single oral dose 150,000 IU vitamin D, and 25 (OH)D levels were measured at 1 week and 1 month post-intervention. Results show that rise in 25(OH)D level from baseline was about 2.2 times lesser in obese compared with children with normal BMI, both at 1 week and at 1 month. The rise in 25(OH)D from baseline to 1 month was inversely correlated to BMI (r = - 0.56, p = < 0.001), waist circumference (r = - 0.48, p = 0.001), total fat mass (r = - 0.58, p < 0.001), and fat mass index (r = - 0.59, p < 0.001).Conclusion: The obese children have a 2.2 times lower rise in serum vitamin D levels as compared with the normal BMI children for the same dose of vitamin D supplementation. What is Known: • The obese individuals are prone to vitamin D deficiency and may be given higher doses of vitamin D supplementation. What is New: • Our study demonstrates that obese children have 2.2 times lesser rise in serum 25(OH)D concentrations as compared with normal BMI children when administered similar oral dose vitamin D.

Impact of myoinositol with metformin and myoinositol alone in infertile PCOS women undergoing ovulation induction cycles - randomized controlled trial.

PURPOSE: To evaluate the benefits of myoinositol plus metformin versus myoinositol alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction cycles. MATERIALS AND METHODS: Total 116 infertile PCOS women were randomized: Group I (n = 57): metformin (1500 mg) plus myoinositol (4 g) per day; Group II (n=59): myoinositol 4 g per day. Subjects were advised to try for spontaneous conception. Those who did not conceive after three months were given three cycles of ovulation induction. Primary outcome was clinical pregnancy rate after 6 months. Secondary outcomes were improvement in metabolic and endocrine parameters, ongoing pregnancy, abortion and multiple pregnancy rate. RESULTS: Baseline demographic, metabolic and hormonal parameters were comparable in two groups. After 3 months of therapy, both study groups had comparable improvement in metabolic and hormonal parameters. After 6 months, clinical pregnancy rate was 42.0% in Group I and 45.5% Group II respectively (RR 0.92(95% CI:0.60-1.43) (p > .05). Side-effects (mainly gastrointestinal) were significantly higher in Group I than group II. CONCLUSIONS: Myoinositol (4 g) might be used alone as an insulin sensitizer to improve metabolic, hormonal and reproductive outcome in infertile PCOS women. Further studies with large numbers are warranted to confirm the role of myoinostiol as a sole insulin sensitizer.

Randomized Controlled Trial of A 12-Week Yoga-Based (Including Diet) Lifestyle vs. Dietary Intervention on Cardio-Metabolic Risk Factors and Continuous Risk Score in Indian Adults with Metabolic Syndrome.

Metabolic syndrome, a prediabetic and precardiovascular pathologic condition that begins early in life, tracks into adulthood and magnifies with age. Randomized controlled trials evaluating efficacy of yoga-based lifestyle vs. dietary intervention on metabolic syndrome are lacking. Here, the efficacy of a 12-week yoga-based lifestyle intervention vs. dietary intervention on cardio-metabolic risk factors and metabolic syndrome risk scores have been assessed in Indian adults with metabolic syndrome. In this two-arm, open label, parallel group, randomized controlled trial, 260 adults (20-45 years) diagnosed with metabolic syndrome as per joint interim statement, 2009 were randomized to yoga-based (including diet) lifestyle or dietary intervention alone (n = 130, each) for 12 weeks. Primary endpoints were the 12-week changes in cardio-metabolic risk factors and metabolic risk scores. The secondary endpoints were the 12-week changes in the proportion of subjects recovered from metabolic syndrome, dietary intake, and physical activity. Intent-to-treat analysis was performed including all the subjects with baseline data with imputed missing data. Treatment × time interaction showed yoga-based lifestyle intervention had a greater treatment effect over dietary intervention by significantly reducing waist circumference, continuous metabolic syndrome z-score, and dietary intake/day while significantly increasing physical activity. High-density lipoprotein cholesterol showed a significantly greater reduction following dietary intervention than yoga-based lifestyle intervention. A significantly greater proportion of subjects recovered from metabolic syndrome in yoga-based lifestyle (45.4%) vs. dietary intervention group (32.3%). A 12-week yoga-based lifestyle intervention is more efficacious than usual dietary intervention in improving cardio-metabolic risk factor and metabolic risk score in Indian adults with metabolic syndrome.

Pre-Basal Insulin Analog Era: Paving the Way for Modern Day Basal Insulins.

Prior to the discovery of insulins, diabetes was managed predominantly by dietary interventions. Discovery of insulin and its first human trial highlighted the need for higher purity insulin thereby steering the subsequent journey of insulin development. Considering the limitations of the early preparations like short duration of action and need for several injections per day, attempts at protracting the duration of insulin action were made. This led to the development of intermediate-acting Neutral Protamine Hagedorn (NPH) and the Lente family of insulins. This review provides insights into the discovery of insulins and the shortcomings of early protracted release preparations, which in turn, gave impetus to the search for a 'true' basal insulin, which could mimic the endogenous human basal insulin secretion.

Comparison of metformin plus myoinositol vs metformin alone in PCOS women undergoing ovulation induction cycles: randomized controlled trial.

The present study was planned to evaluate the benefit of synergetic effect of Metformin plus Myo-inositol versus Metformin alone in infertile polycystic ovarian syndrome (PCOS) women undergoing ovulation induction. One hundred and twenty infertile PCOS women were randomized: Group I (n = 60) received Metformin (500 mg) plus Myoinositol(600 mg) three times a day; Group II received Metformin 500 mg three times a day. Subjects were advised to try for spontaneous conception. Those who did not conceive after 3 months, were given three cycles of ovulation induction + intrauterine insemination. Hormonal and biochemical profile parameters were done at baseline and after 3 months of therapy. Primary outcome measure was live birth rate. Secondary outcomes were improvement in menstrual cycle, hormonal and biochemical parameters, spontaneous conception, abortions, multiple pregnancy, and ovarian hyperstimulation syndrome. Baseline demographic, hormonal and biochemical parameters were comparable in two groups. There was a significant improvement in menstrual cycles (cycle length and bleeding days) in Group I as compared to Group II. The improvement in biochemical and hormonal parameters were comparable in the two groups after 3 months. Live birth rate was significantly higher in the Group I as compared to Group II [55% (33/60); 26.67% (16/60); p = .002]. The study concluded significantly higher live birth rate in women receiving the combination as compared to metformin alone.

Primary hyperparathyroidism: insights from the Indian PHPT registry.

The presentation of primary hyperparathyroidism (PHPT) is variable throughout the world. The present study explored retrospective data submitted to the Indian PHPT registry ( http://www.indianphptregistry.com ) between July 2005 and June 2015 from 5 centres covering four different geographical regions. The clinical, biochemical, radiological and histopathological characteristics of PHPT patients across India were analysed for similarity and variability across the centres. A total of 464 subjects (137 men and 327 women) with histopathologically proven PHPT were analysed. The mean age was 41 ± 14 years with a female:male ratio of 2.4:1. The majority (95%) of patients were symptomatic. Common clinical manifestations among all the centres were weakness and fatigability (58.7%), bone pain (56%), renal stone disease (31%), pancreatitis (12.3%) and gallstone disease (11%). Mean serum calcium, parathyroid hormone and inorganic phosphorus levels were 11.9 ± 1.6 mg/dL, 752.4 ± 735.2 pg/mL and 2.8 ± 0.9 mg/dL, respectively. Sestamibi scanning had better sensitivity than ultrasonography in the localisation of parathyroid adenoma; however, when these two modalities were combined, 93% of the cases were correctly localised. Mean parathyroid adenoma weight was 5.6 ± 6.5 g (0.1-54 g). It was concluded that the majority of PHPT patients within India are still mainly symptomatic with >50% of patients presenting with bone disease and one-third with renal impairment. Compared to Western countries, Indian patients with PHPT are younger, biochemical abnormalities are more severe, and adenoma weight is higher. As our observation is largely derived from a tertiary care hospital (no routine screening of serum calcium level), the results do not reflect racial differences in susceptibility to PHPT.

Novel Heterozygous Genetic Variants in Patients with 46,XY Gonadal Dysgenesis.

46,XY gonadal dysgenesis (GD) constitutes a rare group of disorders characterized by the presence of dysfunctional testes in genotypic males. The molecular etiology is not known in about 2 thirds of instances. The aim of this study was to identify the genetic cause in patients with 46,XY gonadal dysgenesis. Based on clinical, cytogenetic, and biochemical screening, 10 patients with 46,XY GD were recruited. Direct sequencing of SRY, NR5A1, SOX9, DAX1, DHH, DMRT1 genes was carried out for molecular analysis. Among 10 patients, 5 were diagnosed with complete gonadal dysgenesis (CGD), 3 with partial gonadal dysgenesis (PGD), and 3 with testicular agenesis. Molecular analysis revealed 12 heterozygous genetic changes, 4 of which were novel. One (c.416T>A) was observed in evolutionary conserved region of DMRT1 gene in a patient with CGD and was found to be probably damaging on in silico analysis. Other 3 were identified in NR5A1 gene (c.990+22 C>A, c.1387+1403T>A and p.131P), but their association with gonadal dysgenesis is not evident from our study. These genetic changes were absent in parents and 50 healthy control samples, which were also studied. With targeted sequencing approach, a molecular diagnosis was made in only one patient with 46,XY GD. The application of new genomic technologies is required for the precise evaluation of these rare genetic defects.

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.

Somatostatin receptor based PET/CT imaging with 68Ga-DOTA-Nal3-octreotide for localization of clinically and biochemically suspected insulinoma.

BACKGROUND: Localization of primary tumor in insulinoma is often difficult. We evaluated the role of 68Ga-DOTA-Nal3-Octreotide (DOTANOC) PET/CT for localization of primary tumor in patients with clinical and biochemical suspicion of insulinoma. METHODS: Data of 35 patients (age: 38.4±16.5 years) who underwent 68Ga-DOTANOC PET/CT for clinical and biochemical suspicion of insulinoma (hypoglycemia, raised serum insulin and C-peptide levels) were retrospectively analyzed. PET/CT images were evaluated visually and semiquantitatively (SUV) by two experienced nuclear medicine physicians. A definite lesion in pancreas on non contrast CT showing increased 68Ga-DOTANOC was taken as positive. In the absence of CT lesion focal 68Ga-DOTANOC uptake in the pancreas more than liver was taken as positive. All patients had also undergone conventional imaging (CIM) (CT/MRI/endosonography) and their reports were retrieved for comparison. Histopathology and/or imaging/clinical/biochemical follow up (minimum 6 months) was used as reference standard. RESULTS: The mean serum insulin levels was 51.6±54 µIU/mL and C-peptide level was 6.9±7.3 ng/mL. 68Ga-DOTANOC PET/CT was interpreted as positive in 11 patients (31.5%) and negative in 24 (68.5%). PET/CT demonstrated total 16 pancreatic lesions in 11 patients. In two patients it also showed both liver and lymph nodal metastases. 68Ga-DOTANOC PET/CT was true positive in 8, true negative in 1, false positive in 3 and false negative in 23 patients. Per patient based sensitivity of PET/CT was 25.8% (95% CI: 11.8-44.6), specificity was 25% (95% CI: 0.6-80.5) and accuracy was 25.7%. The mean SUVmax of pancreatic lesions was 13.8±11.1. On comparison no significant difference was seen between CIM and PET/CT on patient based (P=1.00) or lesion based comparison (P=0.790). CONCLUSION: 68Ga-DOTANOC PET/CT has limited utility for localizing the primary tumor in patients with clinical and biochemical suspicion of insulinoma. However, it might be useful for differentiating benign and malignant insulinoma. Further prospective comparative studies are warranted.

Waist Circumference Rather than Body Mass Index is Better Indicator of Insulin Resistance in Type 2 Diabetes Mellitus in North Indian Population.

Obesity and insulin resistance (IR) are associated with type 2 diabetes mellitus (DM). Obesity can be quantified by body mass index (BMI) and waist circumference (WC). Similarly, IR is commonly quantified by fasting-plasma-insulin (FPI) and Homeostatic model assessment (HOMA-IR). We aimed our study to find correlation between obesity-parameters and IR especially in the Indian population where despite lower BMI there is more prevalence of type 2 DM. In 34 uncomplicated patients of type 2 DM weight and WC were measured and BMI was calculated. HOMA-IR and FPI level were estimated to assess IR. Significant correlation was found between HOMA-IR and WC (r = +0.368, P = 0.0324) but it was non-significant between HOMAIR and BMI. Correlations were also not significant between FPI and WC or BMI. In conclusion, HOMA-IR and WC are better measures of IR and obesity as compared to FPI and BMI, respectively in type 2 DM.