Factors influencing diabetes treatment satisfaction in the INtegrating DEPrEssioN and Diabetes treatmENT randomized clinical trial: A multilevel model analysis.

AIMS: Patient satisfaction is associated with positive diabetes outcomes. However, there are no identified studies that evaluate both patient- and clinic-level predictors influencing diabetes care satisfaction longitudinally. METHODS: Data from the INtegrating DEPrEssioN and Diabetes treatmENT trial was used to perform the analysis. We used fixed and random effects models to assess whether and how changes in patient-level predictors (treatment assignment, depression symptom severity, systolic blood pressure, body mass index, LDL cholesterol, and haemoglobin A1C) from 0 to 24 months and clinic-level predictors (visit frequency, visit cost, number of specialists, wait time, time spent with healthcare provider, and receiving verbal reminders) measured at 24 months influence diabetes care satisfaction from 0 to 24 months. RESULTS: Model 1 (patient-level predictors) accounted for 7% of the change in diabetes satisfaction and there was a significant negative relationship between change in depressive symptoms and care satisfaction (ß = -0.23, SE = 0.12, p < 0.05). Within Model 1, 2% of the variance was explained by clinic-level predictors. Model 2 included both patient- and clinic-level predictors and accounted for 18% of the change in diabetes care satisfaction. Within Model 2, 9% of the variance was attributed to clinic-level predictors. There was also a cross-level interaction where the change in depression had less of an impact on the change in satisfaction for those who received a verbal reminder (ß = -0.11, SE = 0.21, p = 0.34) compared with those who did not receive a reminder (ß = -0.62, SE = 0.08, p < 0.01). CONCLUSIONS: Increased burden of depressive symptoms influences diabetes care satisfaction. Clinic-level predictors also significantly influence diabetes care satisfaction and can reduce dissatisfaction in primary care, specifically, reminder calls from clinic staff.

COVID-19 and tobacco cessation: lessons from India.

OBJECTIVES: The Government of India prohibited the sale of tobacco products during the COVID-19 lockdown to prevent the spread of the SARS-CoV-2 virus. This study assessed the tobacco cessation behaviour and its predictors among adult tobacco users during the initial COVID-19 lockdown period in India. METHODS: A cross-sectional study was conducted with 801 adult tobacco users (both smoking and smokeless tobacco) in two urban metropolitan cities of India over a 2-month period (July to August 2020). The study assessed complete tobacco cessation and quit attempts during the lockdown period. Logistic and negative binomial regression models were used to study the correlates of tobacco cessation and quit attempts, respectively. RESULTS: In total, 90 (11.3%) tobacco users reported that they had quit using tobacco after the COVID-19 lockdown period. Overall, a median of two quit attempts (interquartile range 0-6) was made by tobacco users. Participants with good knowledge on the harmful effects of tobacco use and COVID-19 were significantly more likely to quit tobacco use (odds ratio [OR] 2.2; 95% confidence interval [CI] 1.2-4.0) and reported more quit attempts (incidence risk ratio 5.7; 95% CI 2.8-11.8) compared to those with poor knowledge. Participants who had access to tobacco products were less likely to quit tobacco use compared to those who had no access (OR 0.3; 95% CI 0.2-0.5]. CONCLUSIONS: Access restrictions and correct knowledge on the harmful effects of tobacco use and COVID-19 can play an important role in creating a conducive environment for tobacco cessation among users.

A unique case of light chain (AL) amyloidosis masquerading as hypophosphatemic osteomalacia.

Light chain (AL) amyloidosis is the result of a clonal plasma cell disorder which causes organ damage by deposition of misfolded light chains. Kidney is a common site of amyloid deposition. Proteinuria, usually in nephrotic range and unexplained renal insufficiency are the main manifestations of renal injury. We report a unique case of renal involvement by AL amyloidosis masquerading as metabolic bone disease. 38 year old male patient presented with progressively increasing diffuse bony pains, low backache and proximal weakness of both lower limbs since two years. On investigation, he was detected to have hypophosphatemic osteomalacia due to renal phosphate loss which was fibroblast growth factor 23 (FGF23)- independent. He also had nephrotic range low molecular weight proteinuria. Renal biopsy to ascertain the aetiology revealed deposition of amyloid fibrils in the glomerular mesangium on electron microscopy. Its characterization by immunofluorescence (IF) was consistent with immunoglobulin light chain (AL) amyloidosis. In the absence of a demonstrable plasma cell clone on bone marrow biopsy, we made a diagnosis of monoclonal gammopathy of renal significance (MGRS). He was treated with chemotherapy following which there was symptomatic improvement and reduction in phosphaturia. This case describes a unique presentation of renal injury due to AL amyloidosis masquerading as hypophosphatemic osteomalacia. The aim of this report is to highlight that hypophosphatemia in adults is usually acquired and treatment of underlying etiology results in cure, unlike in children where genetic counseling and phosphate replacement is the mainstay of treatment.

High burden of cardiometabolic risk factors in spouses of Indian women with hyperglycaemia in pregnancy.

AIM: To evaluate the burden and association of cardiometabolic risk factors in the spouses of women with and without hyperglycaemia in pregnancy. METHODS: Women with (n = 204) and without (n = 197) hyperglycaemia in pregnancy, along with their spouses, participated in this cross-sectional study. The hyperglycaemia in pregnancy group included women with gestational diabetes and diabetes in pregnancy. A detailed questionnaire was completed for all participants (men and women), documenting relevant personal and medical history, along with biochemical investigations (men). RESULTS: A total of 401 couples were evaluated at the time point during the pregnancy of 24.7 ± 5.2 gestational weeks (mean ± sd). Dysglycaemia (prediabetes or diabetes), overweight/obesity (BMI ≥25 kg/m2 ) and metabolic syndrome were detected in 120 (58.9%), 123 (60.3%) and 98 spouses (48.3%) of women with hyperglycaemia in pregnancy, respectively. In the fully adjusted model, an increased risk of dysglycaemia [odds ratio 1.43 (95% CI 0.95-2.17); P = 0.088], overweight/obesity [odds ratio 1.49 (95% CI 0.98-2.27); P = 0.064] and metabolic syndrome [odds ratio 2.00 (95% CI 1.30-3.07); P = 0.001] was seen in the spouses of women with hyperglycaemia in pregnancy. The prevalence of these metabolic conditions was higher in spouses of women with diabetes in pregnancy compared to spouses of women with gestational diabetes mellitus. CONCLUSIONS: A high burden of cardiometabolic risk factors was observed in the spouses of women with hyperglycaemia in pregnancy. The opportunity provided by pregnancy could be used by the healthcare system not only to improve the health of the woman and her offspring, but also her spouse.

Effect of a multicomponent intervention on achievement and improvements in quality-of-care indices among people with Type 2 diabetes in South Asia: the CARRS trial.

AIMS: To evaluate whether and what combinations of diabetes quality metrics were achieved in a multicentre trial in South Asia evaluating a multicomponent quality improvement intervention that included non-physician care coordinators to promote adherence and clinical decision-support software to enhance physician practices, in comparision with usual care. METHODS: Using data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, we evaluated the proportions of trial participants achieving specific and combinations of five diabetes care targets (HbA1c <53 mmol/mol [7%], blood pressure <130/80 mmHg, LDL cholesterol <2.6 mmol/L, non-smoking status, and aspirin use). Additionally, we examined the proportions of participants achieving the following risk factor improvements from baseline: ≥11-mmol/mol (1%) reduction in HbA1c , ≥10-mmHg reduction in systolic blood pressure, and/or ≥0.26-mmol/l reduction in LDL cholesterol. RESULTS: Baseline characteristics were similar in the intervention and usual care arms. Overall, 12.3%, 29.4%, 36.5%, 19.5% and 2.2% of participants in the intervention group and 16.2%, 38.3%, 31.6%, 11.3% and 0.8% of participants in the usual care group achieved any one, two, three, four or five targets, respectively. We noted sizeable improvements in HbA1c , blood pressure and cholesterol, and found that participants in the intervention group were twice as likely to achieve improvements in all three indices at 12 months that were sustained over 28 months of the study [relative risk 2.1 (95% CI 1.5,2.8) and 1.8 (95% CI 1.5,2.3), respectively]. CONCLUSIONS: The intervention was associated with significantly higher achievement of and greater improvements in composite diabetes quality care goals. However, among these higher-risk participants, very small proportions achieved the complete group of targets, which suggests that achievement of multiple quality-of-care goals is challenging and that other methods may be needed in closing care gaps.

A lifestyle intervention programme for the prevention of Type 2 diabetes mellitus among South Asian women with gestational diabetes mellitus [LIVING study]: protocol for a randomized trial.

AIM: This study aims to determine whether a resource- and culturally appropriate lifestyle intervention programme in South Asian countries, provided to women with gestational diabetes (GDM) after childbirth, will reduce the incidence of worsening of glycaemic status in a manner that is affordable, acceptable and scalable. METHODS: Women with GDM (diagnosed by oral glucose tolerance test using the International Association of the Diabetes and Pregnancy Study Groups criteria) will be recruited from 16 hospitals in India, Sri Lanka and Bangladesh. Participants will undergo a repeat oral glucose tolerance test at 6 ± 3 months postpartum and those without Type 2 diabetes, a total sample size of 1414, will be randomly allocated to the intervention or usual care. The intervention will consist of four group sessions, 84 SMS or voice messages and review phone calls over the first year. Participants requiring intensification of the intervention will receive two additional individual sessions over the latter half of the first year. Median follow-up will be 2 years. The primary outcome is the proportion of women with a change in glycaemic category, using the American Diabetes Association criteria: (i) normal glucose tolerance to impaired fasting glucose, or impaired glucose tolerance, or Type 2 diabetes; or (ii) impaired fasting glucose or impaired glucose tolerance to Type 2 diabetes. Process evaluation will explore barriers and facilitators of implementation of the intervention in each local context, while trial-based and modelled economic evaluations will assess cost-effectiveness. DISCUSSION: The study will generate important new evidence about a potential strategy to address the long-term sequelae of GDM, a major and growing problem among women in South Asia. (Clinical Trials Registry of India No: CTRI/2017/06/008744; Sri Lanka Clinical Trials Registry No: SLCTR/2017/001; and ClinicalTrials.gov Identifier No: NCT03305939).

Acceptability of a decision-support electronic health record system and its impact on diabetes care goals in South Asia: a mixed-methods evaluation of the CARRS trial.

AIMS: To describe physicians' acceptance of decision-support electronic health record system and its impact on diabetes care goals among people with Type 2 diabetes. METHODS: We analysed data from participants in the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) trial, who received the study intervention (care coordinators and use of a decision-support electronic health record system; n=575) using generalized estimating equations to estimate the association between acceptance/rejection of decision-support system prompts and outcomes (mean changes in HbA1c , blood pressure and LDL cholesterol) considering repeated measures across all time points available. We conducted in-depth interviews with physicians to understand the benefits, challenges and value of the decision-support electronic health record system and analysed physicians' interviews using Rogers' diffusion of innovation theory. RESULTS: At end-of-trial, participants with diabetes for whom glycaemic, systolic blood pressure, diastolic blood pressure and LDL cholesterol decision-support electronic health record prompts were accepted vs rejected, experienced no reduction in HbA1c [mean difference: -0.05 mmol/mol (95% CI -0.22, 0.13); P=0.599], but statistically significant improvements were observed for systolic blood pressure [mean difference: -11.6 mmHg (95% CI -13.9, -9.3); P ≤ 0.001], diastolic blood pressure [mean difference: -5.2 mmHg (95% CI -6.5, -3.8); P ≤ 0.001] and LDL cholesterol [mean difference: -0.7 mmol/l (95% CI -0.6, -0.8); P ≤0.001], respectively. The relative advantages and compatibility of the decision-support electronic health record system with existing clinic set-ups influenced physicians' acceptance of it. Software complexities and data entry challenges could be overcome by task-sharing. CONCLUSION: Wider adherence to decision-support electronic health record prompts could potentially improve diabetes goal achievement, particularly when accompanied by assistance from a non-physician health worker.

Prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents from rural and urban localities and its relationship with various anthropometric indices: a cross-sectional study.

BACKGROUND: Micronutrient deficiency is a global health burden, especially among developing countries. The present cross-sectional study aimed to determine the prevalence of vitamin B12 deficiency in healthy Indian school-going adolescents, based on area of residence, sex and body mass index (BMI). Furthermore, the relationship of serum B12 concentration with dietary vitamin B12 intake and anthropometric indices was assessed among adolescents from rural and urban India. METHODS: A total of 2403 school-going adolescents (11-17 years) from National Capital Region and rural areas of Haryana, India were selected. Serum B12 concentrations were estimated using an electrochemiluminescence immunoassay. Dietary assessments were conducted on 65% of total participants (n = 1556) by two 24-h diet recalls. RESULTS: The prevalence of vitamin B12 deficiency in the total study population was 32.4% (rural: 43.9% versus urban: 30.1%, P < 0.001; male: 34.4% versus female: 31.0%, P < 0.05; normal weight: 28.1%, versus overweight: 39.8%, versus obese: 51.2%, P < 0.001). More than half (51.2%) of obese adolescents were vitamin B12 deficient. On multiple linear regression analysis, serum B12 in rural adolescents was associated with age (ß = -0.12, P < 0.05). Among urban adolescents, serum B12 was associated with BMI (ß = -0.08, P < 0.05) and adjusted dietary vitamin B12 intake (ß = 0.14, P < 0.001). Serum vitamin B12 levels were found to be lower in rural females (ß = -0.12, P = 0.030) and urban males (ß: 0.11, P < 0.001) compared to their respective contemporaries. CONCLUSIONS: Vitamin B12 deficiency was higher among rural school-going adolescents. Boys had a higher B12 deficiency than girls. Inverse associations of serum B12 with adiposity indices were observed. Serum B12 levels were positively associated with dietary vitamin B12 intake.

Conversion of gestational diabetes mellitus to future Type 2 diabetes mellitus and the predictive value of HbA1c in an Indian cohort.

AIM: To investigate the distribution of and risk factors for dysglycaemia (Type 2 diabetes and prediabetes) in women with previous gestational diabetes mellitus in India. METHODS: All women (n = 989) from two obstetric units in New Delhi and Hyderabad with a history of gestational diabetes were invited to participate, of whom 366 (37%) agreed. Sociodemographic, medical and anthropometric data were collected and 75-g oral glucose tolerance test were carried out. RESULTS: Within 5 years (median 14 months) of the pregnancy in which they were diagnosed with gestational diabetes, 263 (72%) women were dysglycaemic, including 119 (32%) and 144 (40%) with Type 2 diabetes and prediabetes, respectively. A higher BMI [odds ratio 1.16 per 1-kg/m2 greater BMI (95% CI 1.10, 1.28)], presence of acanthosis nigricans [odds ratio 3.10, 95% CI (1.64, 5.87)], postpartum screening interval [odds ratio 1.02 per 1 month greater screening interval 95% CI (1.01, 1.04)] and age [odds ratio 1.10 per 1-year older age 95% CI (1.04, 1.16)] had a higher likelihood of having dysglycaemia. The American Diabetes Association-recommended threshold HbA1c value of ≥ 48 mmol/mol (6.5%) had a sensitivity and specificity of 81.4 and 90.7%, respectively, for determining the presence of Type 2 diabetes postpartum. CONCLUSION: The high post-pregnancy conversion rates of gestational diabetes to diabetes reported in the present study reinforce the need for mandatory postpartum screening and identification of strategies for preventing progression to Type 2 diabetes. Use of the American Diabetes Association-recommended HbA1c threshold for diabetes may lead to significant under-diagnosis.

Evolving management of insulinoma: Experience at a tertiary care centre.

BACKGROUND & OBJECTIVES: Since our previous study in 2006, several new modalities for localization of cause of endogenous hyperinsulinemic hypoglycaemia such as multiphasic computed tomography (CT), multiphasic magnetic resonance imaging (MRI), endoscopic ultrasound (EUS), intraoperative ultrasound, and intra-arterial calcium infusion with arterial stimulation venous sampling (ASVS) have become available. Therefore, to evaluate the relative usefulness of various imaging modalities to guide future management in terms of diagnosis and patient care, we analyzed presentation and management of patients of endogenous hyperinsulinemic hypoglycaemia. METHODS: In this retrospective study, medical records of patients admitted with endogenous hyperinsulinemic hypoglycaemia were retrieved. Data pertaining to clinical features, diagnosis, imaging, surgery and patient outcome were extracted. The localization of insulinoma by preoperative imaging techniques was compared with the findings at surgery to assess the accuracy of localization. RESULTS: Fasting hypoglycaemia was present in all, and post-prandial hypoglycaemia (plasma glucose ≤50 mg/dl within four hours of meal) in 25.8 per cent. Mean duration of symptoms before reaching a diagnosis of hyperinsulinemic hypoglycaemia was 3.9 years. Mean duration of provocative fast was 21.8 h (range 6-48 h). Among the currently used imaging modalities, the sensitivity of localizing tumour was 79.3 per cent for multiphasic CT, 85 per cent for multiphasic MRI and 95 per cent for EUS. EUS detected tumour missed by both CT and MRI. All, except one of the operated patients, were cured by surgery. INTERPRETATION & CONCLUSIONS: Our results suggest that patients with insulinoma have a varied presentation. Multiphasic contrast-enhanced MRI/CT scan, EUS and ASVS may be complimentary in pre-operative localization.

Pituitary volume and clinical trajectory in young relatives at risk for schizophrenia.

BACKGROUND: Stress and vulnerability likely interact to play a major role in psychosis. While much has been written about the neural diathesis-stress model in psychosis and its clinical risk states, little is known about HPA axis biomarkers in non-help-seeking individuals at familial high risk (FHR). We sought to prospectively measure pituitary volume (PV) in adolescents and young adults at FHR for schizophrenia and to follow their emerging sub-clinical psychotic symptoms and clinical trajectories. METHOD: Forty healthy controls and 38 relatives of patients with schizophrenia or schizoaffective disorder were identified in Pittsburgh, USA. PV was derived from baseline 1.5 T magnetic resonance imaging. Chapman's schizotypy scales were acquired at baseline, and structured clinical interviews for DSM-IV-TR Axis I diagnoses were attempted annually for up to 3 years. RESULTS: Seven individuals converted to psychosis. PV did not differ between FHR and control groups overall. Within the FHR group, PV was positively correlated with Chapman's positive schizotypy (Magical Ideation and Perceptual Aberration) scores, and there was a significant group × PV interaction with schizotypy. PV was significantly higher in FHR subjects carrying any baseline Axis I diagnosis (p = 0.004), and higher still in individuals who went on to convert to psychosis (p = 0.0007). CONCLUSIONS: Increased PV is a correlate of early positive schizotypy, and may predict trait vulnerability to subsequent psychosis in FHR relatives. These preliminary findings support a model of stress-vulnerability and HPA axis activation in the early phases of psychosis.

CTLA4+49G allele associates with early onset of type 1 diabetes in North Indians.

Type 1 diabetes (T1D) is a complex autoimmune disease with strong genetic influence. In this study, we investigated +49A/G SNP (rs 231775) in exon 1 of cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) by PCR-RFLP and its influence as a risk factor for the disease in the North Indian population. This polymorphism at codon 17 results in an amino acid substitution (Thr/Ala) in the leader peptide of the molecule. The study included 232 patients with T1D (age at onset of disease (AOD): 0.5-37 years) and 305 ethnically matched healthy controls. The DNA obtained from these 537 individuals was amplified using a set of specific primers followed by restriction enzyme digestion with Fnu4HI. The +49G allele as well as its homozygous genotype G/G was observed to be significantly higher in patients as compared to the healthy controls {(37.3% vs. 25.6%, P = 4.96E(-05) , OR = 1.73; 95%CI = 1.33-2.25) (15.52% vs. 6.6%, P = 0.001, OR = 2.62; 95% CI = 1.48-4.63) respectively}. The frequency of G/G genotype was significantly higher in patients with early age at onset of disease (AOD:<12 years) as compared to that in the late-onset patients with AOD: ≥12 years (21.1% vs. 10.6%, P = 0.042, OR = 2.26; 95% CI = 1.09-4.67) as well as to that in the healthy controls (21.1% vs. 6.6%, P = 0.00004, OR = 3.8; 95% CI = 2.01-7.2). Further analysis revealed that the median AOD significantly reduced (P = 0.049) from 14 years in patients with A/A genotype to 11 and 10 years in those with A/G and G/G genotypes, respectively. These results suggest that CTLA4+49G allele, particularly in homozygous G/G condition, associates with early onset of T1D.

Surface-based mixed effects multilevel analysis of grouped human electrocorticography.

Electrocorticography (ECoG) in humans yields data with unmatched spatio-temporal resolution that provides novel insights into cognitive operations. However, the broader application of ECoG has been confounded by difficulties in accurately depicting individual data and performing statistically valid population-level analyses. To overcome these limitations, we developed methods for accurately registering ECoG data to individual cortical topology. We integrated this technique with surface-based co-registration and a mixed-effects multilevel analysis (MEMA) to control for variable cortical surface anatomy and sparse coverage across patients, as well as intra- and inter-subject variability. We applied this surface-based MEMA (SB-MEMA) technique to a face-recognition task dataset (n=22). Compared against existing techniques, SB-MEMA yielded results much more consistent with individual data and with meta-analyses of face-specific activation studies. We anticipate that SB-MEMA will greatly expand the role of ECoG in studies of human cognition, and will enable the generation of population-level brain activity maps and accurate multimodal comparisons.

The relationship between serum 25-hydroxy vitamin D, parathormone and bone mineral density in Indian population.

OBJECTIVES: Vitamin D deficiency (VDD) is a global problem. Not all patients with VDD have clinical manifestations or secondary hyperparathyroidism. We studied the interaction between serum 25-hydroxy vitamin D (25OHD), parathormone (PTH) and bone mineral density (BMD) in Indian adolescents and adults. DESIGN: Population survey. PATIENTS: A total of 1829 adolescents and 1346 adults aged 50 years and above were analysed in this study. MEASUREMENTS: Serum biochemistry, 25OHD, PTH and BMD were estimated. Subjects were grouped according to quartiles of serum PTH. VDD was defined as severe (25OHD ≤ 5 ng/ml), moderate (25OHD ≤ 10 ng/ml) and mild (25OHD ≤ 20 ng/ml) and secondary hyperparathyroidism (SHPT) when serum PTH levels >65 pg/ml. RESULTS: Only 30-40% of subjects with moderate and severe VDD, respectively, had SHPT. BMD decreased from Quartile 1 to Quartile 4 of PTH at all sites among adolescents and adults, with only a marginal decline in serum 25OHD levels between these quartiles. Further, within each PTH quartile, there was no difference in BMD according to categories of VDD. Analysing BMD in the different PTH quartiles, the PTH cut-offs beyond which BMD showed a significant decline, was 35 pg/ml in adolescents and 53 pg/ml in adults. CONCLUSIONS: Less than half of the subjects with VDD have SHPT. BMD levels start to decline at PTH values currently considered to be normal. These data suggest the need to redefine SHPT in different age groups keeping in mind the relationship between PTH and BMD. This may also influence the decision to supplement subjects with VDD.

Association of PTPN22+1858C/T polymorphism with Type 1 diabetes in the North Indian population.

A nonsynonymous SNP +1858C/T (rs2476601) in the protein tyrosine phosphatase, nonreceptor type 22(PTPN22) gene leading to Arg 620 Trp substitution is known to be associated with susceptibility to type 1 diabetes (T1D) and several other autoimmune diseases. We studied this polymorphism in 145 T1D patients and 210 healthy controls from North India. The minor allele +1858T was observed to be significantly increased among patients as compared to healthy controls (2.76% vs 0.5%, P = 0.027, OR = 5.93; 95% CI = 1.4-24.8). The association was also observed at the level of heterozygous C/T genotype (5.5% vs 0.95%, P = 0.026, OR = 6.07; 95% CI = 1.43-25.6). The T allele and C/T genotype were predominantly found among patients who were positive for both glutamic acid decarboxylase 65 (GAD65) and insulin antigen 2 (IA2) autoantibodies and showed significantly increased frequencies (10%, P = 0.034, OR = 11.67; 95% CI = 1.58-84.1 and 20%, P = 0.031, OR = 13.0; 95% CI = 1.66-97.5, respectively) as compared to patients negative for these autoantibodies (0.95% and 1.9%, respectively). The results suggest that the PTPN22+1858T allele is positively associated with T1D in the North Indian population.

Glutamic acid decarboxylase (anti-GAD) & tissue transglutaminase (anti-TTG) antibodies in patients with thyroid autoimmunity.

BACKGROUND & OBJECTIVES: Several autoimmune disorders have been reported to be associated with autoimmune thyroiditis and may coexist with other organ-specific autoantibodies. The aim of the present study was to evaluate the presence of tissue transglutaminase (anti-TTG) and glutamic acid decarboxylase (anti-GAD) antibodies in patients suffering from autoimmune thyroiditis as diagnosed by anti-thyroid peroxidase (anti-TPO) antibodies, which may indicate high risk for developing celiac disease or type 1 diabetes mellitus. METHODS: Five thousand children and 2800 adults were screening as part of a general health examination done on a voluntary basis in four different parts of Delhi. A total of 577 subjects positive for anti-TPO antibody constituted the cases. Equal number of age and sex matched anti-TPO antibody negative controls were randomly selected from the same cohort to form paired case control study. The cases and controls were further divided into two groups as follows: group-1 (children and adolescent <18 yr), group-2 (adults >18 yr). Serum samples of cases and controls were analysed for thyroid function test (FT3, FT4, and TSH), anti-TTG and anti-GAD antibodies. RESULTS: A total of 1154 subjects (577 cases and 577 controls) were included in this study. Hypothyroidism was present in 40.2 per cent (232) cases compared to only 4.7 per cent (27) in controls (P<0.001). Anti-TTG and anti-GAD antibodies were present in 6.9 and 12.5 per cent subjects among cases compared to 3.5 per cent (P=0.015) and 4.3 per cent (P=0.001) in controls, respectively. Only anti-GAD antibody were significantly positive in cases among children and adolescents (P =0.0044) and adult (P=0.001) compared to controls. Levels of anti-TTG and anti-GAD antibodies increased with increasing titre of anti-TPO antibody. INTERPRETATION & CONCLUSIONS: Our findings showed high positivity of anti-GAD and anti-TTG antibodies among subjects with thyroid autoimmunity. It is, therefore, important to have high clinical index of suspicion for celiac disease or type 1 diabetes mellitus in patients with autoimmune thyroiditis.

Major histocompatibility complex class I chain related gene-A microsatellite polymorphism shows secondary association with type 1 diabetes and celiac disease in North Indians.

Microsatellite polymorphism in exon 5 of major histocompatibility complex class I chain related gene-A (MIC-A) has been implicated in the etiology of autoimmune diseases including type 1 diabetes (T1D) and celiac disease (CD). In this study on North Indian population, the MIC-A5.1 allele, carrying a premature termination codon in transmembrane region, was observed with increased frequency in T1D (29.6%, odds ratio OR = 2.1, P = 0.00017) and CD patients (40.3%, OR = 3.37, P = 1.67E-05) than in controls (16.7%). When the MIC-A5.1 association was adjusted for linkage with human leukocyte antigen (HLA)-DR3, the statistical significance of the association was abolished. This implies that the observed association of MIC-A5.1 is due to its linkage disequilibrium (D' = 0.94) with HLA-B8-DR3-DQ2 haplotype and is secondary to the overall association with DR3 positive MHC haplotypes.

Growth from birth to adulthood and peak bone mass and density data from the New Delhi Birth Cohort.

UNLABELLED: Growth in early life may predict adult bone health. Our data showed that greater height and body mass index (BMI) gain in utero and infancy are associated with higher peak bone mass, and greater BMI gain in childhood/adolescence with higher peak bone density. These associations are mediated by attained adult height and BMI. INTRODUCTION: To study the relationship of height and BMI during childhood with adult bone mineral content (BMC), areal density (aBMD) and apparent density (BMAD, estimated volumetric density). METHODS: Participants comprised 565 men and women aged 33-39 years from the New Delhi Birth Cohort, India, whose weight and height were recorded at birth and annually during infancy (0-2 years), childhood (2-11 years) and adolescence (11 years-adult). Lumbar spine, femoral neck and forearm BMC and aBMD were measured using dual X-ray absorptiometry; lumbar spine and femoral neck BMAD were calculated. RESULTS: Birth length, and height and height gain during infancy, childhood and adolescence were positively correlated with adult BMC (p≤0.01 all sites except birth length with femoral neck). Correlations increased with height from birth to 6 years, then remained constant for later height measurements. There were no associations with BMAD. BMI at birth, and during childhood and adolescence was also positively correlated with BMC (p < 0.01 all sites). BMI at 11 years, and BMI gain in childhood and adolescence, were correlated with aBMD and BMAD (p < 0.001 for all); these correlations strengthened with increasing age of BMI measurement. The associations with height and BMI in early life became non-significant after adjustment for adult height and BMI. CONCLUSIONS: Greater skeletal growth and BMI gain in utero and during infancy are associated with higher peak BMC, and greater BMI gain in childhood and adolescence is associated with higher peak aBMD and BMAD. These associations are mediated by the attainment of adult height and BMI, respectively.

Bone health in healthy Indian population aged 50 years and above.

UNLABELLED: One thousand six hundred healthy subjects aged more than 50 years, residing in Delhi, were evaluated for bone mineral metabolic parameters. High prevalence of osteoporosis (35.1% subjects) was observed in this population. Bone mineral density (BMD) correlated positively with body mass index (BMI) and negatively with PTH levels. No correlation was observed with serum 25(OH)D levels. INTRODUCTION: To assess the bone health status in elderly Indians and compare peripheral DXA (pDXA) with central DXA in evaluation of osteoporosis. METHODS: The study involved 1,600 healthy subjects more than 50 years of age residing in Delhi, India, who underwent anthropometric, biochemical, and hormonal evaluation. BMD was measured by DXA at lumbar spine, hip, and distal radius; and by pDXA at forearm and calcaneum. RESULTS: Seven hundred ninety-two males and 808 postmenopausal females, with a mean age of 57.67 ± 9.46 years were evaluated. Osteoporosis was present in 35.1% subjects (M-24.6%, F-42.5%) and osteopenia in 49.5% (M-54.3%, F-44.9%). Prevalence of osteoporosis increased with age in females, but not in males. BMD at all sites, except distal radius, was positively correlated with BMI (r=0.037, p=0.14). Total body BMD was negatively correlated with alkaline phosphatase (r= -0.184, p<0.00001) and PTH levels (r= -0.099, p<0.00001), respectively. No significant correlation was observed between serum 25(OH)D levels and BMD at any site. BMD at forearm and calcaneum, measured using pDXA, showed strong positive correlation with BMD measured by central DXA. pDXA had sensitivity of 88%, specificity of 55%, and negative and positive predictive values of 89% and 52%, respectively, at T-score -2.5 at peripheral sites compared to central DXA. CONCLUSIONS: A high prevalence of osteoporosis was observed in elderly Indian subjects. pDXA has high negative predictive value, making it a useful tool in population screening for osteoporosis.

Liraglutide provides similar glycaemic control as glimepiride (both in combination with metformin) and reduces body weight and systolic blood pressure in Asian population with type 2 diabetes from China, South Korea and India: a 16-week, randomized, double-blind, active control trial(*).

AIM: To assess and compare the efficacy and safety of liraglutide with those of glimepiride, both in combination with metformin for the treatment of type 2 diabetes in Asian population from China, South Korea and India. METHODS: A 16-week, randomized, double-blind, double-dummy, four-arm, active control trial was carried out. In total, 929 subjects with type 2 diabetes with a mean (±s.d.) age of 53.3 ± 9.5 years, HbA1(c) of 8.6 ± 1.0% and body weight of 68.1 ± 11.7 kg were randomized (liraglutide 0.6, 1.2 or 1.8 mg once daily or glimepiride 4 mg once daily all in combination with metformin: 1 : 1 : 1 : 1). One subject withdrew immediately after randomization and before exposure. RESULTS: HbA1(c) was significantly reduced in all groups compared with baseline. Treatment with liraglutide 1.2 and 1.8 mg was non-inferior to glimepiride (mean HbA1(c) reduction: 1.36% points, 1.45% points and 1.39% points, respectively). No significant difference was shown in the percentage of subjects reaching American Diabetes Association HbA1(c) target <7% or American Association of Clinical Endocrinologists target ≤6.5% between liraglutide 1.2 and 1.8 mg and glimepiride. Liraglutide was associated with a 1.8-2.4 kg mean weight reduction, compared with a 0.1 kg mean weight gain with glimepiride. Liraglutide led to a significantly greater reduction in systolic blood pressure (SBP) compared with glimepiride. Two subjects in the glimepiride group reported major hypoglycaemia while none in the liraglutide groups. Liraglutide was associated with about 10-fold lower incidence of minor hypoglycaemia than glimepiride. Gastrointestinal disorders were the most common adverse events (AEs) for liraglutide, but were transient and resulted in few withdrawals. CONCLUSIONS: In Asian subjects with type 2 diabetes, once-daily liraglutide led to improvement in glycaemic control similar to that with glimepiride but with less frequent major and minor hypoglycaemia. Liraglutide also induced a significant weight loss and reduced SBP and was generally well tolerated. The most frequently reported AE was transient nausea. The effect of liraglutide in this Asian population is comparable to the effects seen in Caucasian, African American and Hispanic populations in global liraglutide phase 3 trials.