Effect of metformin adjunct therapy on cardiometabolic parameters in Indian adolescents with type 1 diabetes: a randomized controlled trial.

Introduction: Insulin resistance is being increasingly reported in type-1 Diabetes (T1D) and is known to accelerate microvascular complications. The Asian Indian population has a higher risk of double diabetes development compared to Caucasians. Hence, we studied the effect of adding Metformin to standard insulin therapy on glycemic control, insulin sensitivity (IS), cardiometabolic parameters and body composition in Indian adolescents with T1D. Methods: A Randomized controlled trial was conducted spanning 9 months (Registration number:CTRI/2019/11/022126). Inclusion: Age 10-19 years, T1D duration>1year, HbA1c>8% Exclusion: Uncontrolled vascular complications/comorbidities, Metformin intolerance, concomitant drugs affecting insulin sensitivity. Participants were randomized to Metformin/Placebo (n=41 each) groups and age, sex, duration-matched. Assessments were performed at baseline, 3 and 9 months. Results: 82 participants aged 14.7 ± 3years (40 females) were enrolled, with a mean diabetes duration of 5.2 ± 2.3 years. Over 9 months, HbA1c decreased significantly by 0.8 (95% confidence interval: -1.2 to -0.3) from 9.8 ± 1.8% to 9.1 ± 1.7% on Metformin but remained largely unchanged (difference of 0.2, 95% confidence interval: -0.7 to 0.2) i.e. 9.9 ± 1.6% and 9.7 ± 2.2% on placebo. HbA1c improvement correlated negatively with baseline IS (EGDR:r= -0.3;SEARCH:r = -0.24, p<0.05) implying better HbA1c-lowering in those with decreased initial IS. CGM-based glycemic variability (standard deviation) reduced by 6.3 mg/dL (95% confidence interval: -12.9 to 0.2) from 100.2 ± 19.1 mg/dL to 93.7 ± 19.9 mg/dL in those on Metformin (p=0.05) but not placebo (94.0 ± 20.5; 90.0 ± 22.6 mg/dL). Insulin sensitivity: CACTIexa & SEARCH scores demonstrated no change with Metformin but significant worsening on placebo. Significant increase in LDL-C(42%), total cholesterol(133.6 to 151.1 mg/dL), triglyceride (60.0 to 88.0 mg/dL) and carotid intima-media thickness was noted on placebo but not Metformin. Weight, BMI, fat Z-scores increased significantly on placebo but not Metformin. Adverse events (AE) were minor; AE, compliance and safety parameters were similar between the two groups. Conclusion: Metformin as an adjunct to insulin in Asian Indian adolescents with T1D demonstrated beneficial effect on glycemic control, glycemic variability, IS, lipid profile, vascular function, weight and body fat, with a good safety profile when administered for 9 months.

Weight Velocity Percentiles in Children Aged 4-17 Years from Pune During 2007-2013.

OBJECTIVE: To assess weight velocity and the age at peak weight velocity and to construct weight velocity percentiles in 4-17-year-old apparently healthy Indian children. METHOD: This longitudinal study enrolled 1045 children (588 boys) from Pune belonging to middle and upper socioeconomic class aged 4-17 years. The study parameters included annual height and weight measurements recorded longitudinally from 2007 to 2013. A total of 5225 weight velocity measurements (2940 on boys) were computed. Age- and gender-specific smoothened weight velocity percentiles (3rd, 10th, 25th, 50th, 75th, 90th and 97th) were constructed using LMS chart maker. RESULTS: The median weight velocity was low in boys and girls at 4 years, thereafter it increased to a peak of 4.6 kg/year at 13 years in boys, then declined to 1.1 kg/year at 17.5 years. In girls, median weight velocity peaked to 4.0 kg/year at 11 years, then declined to 0.8 kg/year at 17.5 years. Peak velocity-centred analysis revealed higher peak velocities of 7.5 kg/year at 13.1 years and 6.6 kg/year at 12 years in boys and girls respectively. CONCLUSION: Weight velocity percentiles are presented for 4-17-year-old apparently healthy Indian children.

Long term clinical follow up of four patients with Wolfram syndrome and urodynamic abnormalities.

OBJECTIVES: Wolfram syndrome is characterised by insulin-dependent diabetes (IDDM), diabetes insipidus (DI), optic atrophy, sensorineural deafness and neurocognitive disorders. The DIDMOAD acronym has been recently modified to DIDMOAUD suggesting the rising awareness of the prevalence of urinary tract dysfunction (UD). End stage renal disease is the commonest cause of mortality in Wolfram syndrome. We present a case series with main objective of long term follow up in four children having Wolfram syndrome with evaluation of their urodynamic profile. METHODS: A prospective follow up of four genetically proven children with Wolfram syndrome presenting to a tertiary care pediatric diabetes clinic in Pune, India was conducted. Their clinical, and urodynamic parameters were reviewed. RESULTS: IDDM, in the first decade, was the initial presentation in all the four children (three male and one female). Three children had persistent polyuria and polydipsia despite having optimum glycemic control; hence were diagnosed to have DI and treated with desmopressin. All four patients entered spontaneous puberty. All patients had homozygous mutation in WFS1 gene; three with exon 8 and one with exon 6 novel mutations. These children with symptoms of lower urinary tract malfunction were further evaluated with urodynamic studies; two of them had hypocontractile detrusor and another had sphincter-detrusor dyssynergia. Patients with hypocontractile bladder were taught clean intermittent catheterization and the use of overnight drain. CONCLUSIONS: We report a novel homozygous deletion in exon 6 of WFS-1 gene. The importance of evaluation of lower urinary tract malfunction is highlighted by our case series. The final bladder outcome in our cases was a poorly contractile bladder in three patients.

The automated Greulich and Pyle: a coming-of-age for segmental methods?

The well-known Greulich and Pyle (GP) method of bone age assessment (BAA) relies on comparing a hand X-ray against templates of discrete maturity classes collected in an atlas. Automated methods have recently shown great success with BAA, especially using deep learning. In this perspective, we first review the success and limitations of various automated BAA methods. We then offer a novel hypothesis: When networks predict bone age that is not aligned with a GP reference class, it is not simply statistical error (although there is that as well); they are picking up nuances in the hand X-ray that lie "outside that class." In other words, trained networks predict distributions around classes. This raises a natural question: How can we further understand the reasons for a prediction to deviate from the nominal class age? We claim that segmental aging, that is, ratings based on characteristic bone groups can be used to qualify predictions. This so-called segmental GP method has excellent properties: It can not only help identify differential maturity in the hand but also provide a systematic way to extend the use of the current GP atlas to various other populations.

Effect of Calcium and Vitamin D Supplementation (Dairy vs. Pharmacological) on Bone Health of Underprivileged Indian Children and Youth with Type-1 Diabetes: A Randomized Controlled Trial.

BACKGROUND: Bone health is affected by chronic childhood disorders including type-1 diabetes mellitus (T1DM). We conducted this randomized controlled trial with the objective of investigating the effect of 1-year supplementation of vitamin-D with milk or with pharmacological calcium on bone mass accrual in underprivileged Indian children and youth with T1DM. METHODS: 5 to 23year old (n = 203) underprivileged children and youth with T1DM were allocated to one of three groups: Milk (group A-received 200 ml milk + 1000 international unit (IU) vitamin-D3/day), Calcium supplement (group B-received 500 mg of calcium carbonate + 1000 IU of vitamin-D3/day) or standard of care/control (group C). Anthropometry, clinical details, biochemistry, diet (3-day 24-h recall), physical activity (questionnaires adapted for Indian children) and bone health parameters (using dual-energy X-ray absorptiometry and peripheral quantitative computed tomography- DXA and pQCT respectively) were evaluated at enrolment and end of 12 month intervention. RESULTS: Total body less head(TBLH) bone mineral content (BMC(g)) and bone mineral density (BMD(gm/cm2)) were significantly higher at end of study in girls in both supplemented groups (TBLHBMC-A-1011.8 ±â€¯307.8, B-983.2 ±â€¯352.9, C-792.8 ±â€¯346.8. TBLHBMD-A-± 0.2, B-0.8 ±â€¯0.2, C-0.6 ±â€¯0.2, p < 0.05). Z score of lumbar spine bone mineral apparent density of supplemented participants of both sexes was significantly higher than controls (Boys- A-0.7 ±â€¯1.1, B-0.6 ±â€¯1.4, C- -0.7 ±â€¯1.1; Girls- A-1.1 ±â€¯1.1, B-0.9 ±â€¯3.4, C- -1.7 ±â€¯1.3, p < 0.05). A significantly higher percentage increase was found in cortical thickness in girls in both supplemented groups (A-17.9 ±â€¯28.6, B-15.3 ±â€¯16.5, C-7.6 ±â€¯26.2); the differences remained after adjusting for confounders. CONCLUSION: Supplementation with milk or pharmacological calcium (+vitaminD3) improved bone outcomes-particularly geometry in children with T1DM with more pronounced effect in girls. Pharmacological calcium may be more cost effective in optimising bone health in T1DM in resource limited settings.

Development of a simplified new method of bone age estimation using three bones of the hand and wrist.

Though the Greulich and Pyle (GP) method is easy, inter-observer variability, differential maturation of hand bones influences ratings. The Tanner-Whitehouse (TW) method is more accurate, but cumbersome. A simpler method combining the above, such that it utilizes fewer bones without affecting accuracy, would be widely used and more applicable in clinical practice. OBJECTIVES: 1. Devising a simplified method utilizing three bones of the hand and wrist for bone age (BA) assessment. 2. Testing whether the 3 bone method gives comparable results to standard methods (GP,TW2,TW3) in Indian children. METHODS: Developmental stages and corresponding BA for radius, hamate, terminal phalanx (left middle finger) epiphyses combining stages from GP,TW3 atlases were described; BA were rated by two blinded observers. 3 bone method ratings were compared with the same dataset analyzed earlier using GP,TW2,TW3 (4 raters). RESULTS: Radiographs analysed:493 (Girls=226). Mean chronological age:9.4 ± 4.6 yrs, mean BA 3 bone:9.8 ± 4.8 yrs, GP:9.6 ± 4.8 yrs, TW3:9.3 ± 4.5 yrs, TW2:9.9 ± 5.0 yrs. The 3 bone method demonstrated no significant inter-observer variability (p = 0.3, mean difference = 0.02 ± 0.6 yrs); a strong positive correlation (p < 0.0001) with GP (r = 0.985), TW3 (r = 0.983) and TW2 (r = 0.982) was noted. Bland-Altman plots demonstrated good agreement; the root mean square errors between 3 bone and GP,TW3,TW2 ratings were 0.6,0.7,0.6 years; mean differences were 0.19,0.49,-0.14 years respectively. Greatest proportion of outliers (beyond ±1.96 SD of mean difference) was between 6 and 8 years age for difference in 3 bone and GP, and between 4-6 years for difference in 3 bone and TW3,TW2. CONCLUSION: The 3 bone method has multiple advantages; it is easier, tackles differential maturation of wrist and hand bones, has good reproducibility, without compromising on accuracy rendering it suitable for office practice.

Adaptation and validation of an artificial intelligence based digital radiogrammetry tool for assessing bone health of indian children and youth with type-1 diabetes.

BACKGROUND AND OBJECTIVES: BoneXpert (BX) is an artificial intelligence software used primarily for bone age assessment. Besides, it can also be used to screen for bone health using the digital radiogrammetry tool called bone health index (BHI) for which normative reference values available are calculated from healthy European children. Due to ethnic difference in bone geometry, in a previous study, we generated reference curves based on healthy Indian children. The objectives of this study were: 1) To assess and compare bone health of Indian children with Type 1 diabetes (T1D) using both European and Indian BHI SDS reference data and 2) To identify determinants of poor bone health in Indian children and youth with T1D by using BHI tool (based on BHI-SDS Indian reference data) of BX. METHOD: The BHI was assessed retrospectively in 1159 subjects with T1D using digitalised left-hand x-rays and SDS were computed using European and Indian data. The demographic, anthropometric, clinical, biochemistry, dual x-ray absorptiometry (DXA) data and peripheral quantitative computed tomography (pQCT) data collection were performed using standard protocols and were extracted from hospital records. RESULTS: The BHI correlated well with DXA and pQCT parameters in subjects with T1D. BHI-SDS calculated using Indian reference data had better correlation with height and DXA parameters. 8.6% study participants had low (less than -2) BHI-SDS (Indian), with height SDS having significant effect. Subjects with low BHI-SDS were older, shorter and had higher duration of diabetes. They also had lower IGF1 and vitamin D concentrations, bone mineral density, and trabecular density. Female gender, increased duration of illness, poor glycaemic control, and vitamin D deficiency/insufficiency were significant predictors of poor BHI-SDS. CONCLUSION: Our study highlights the utility of digital radiogrammetry AI tool to screen for bone health of children with T1D and demonstrates and highlights the necessity of interpretation using ethnicity specific normative data.

BoneXpert-derived bone health index reference curves constructed on healthy Indian children and adolescents.

BACKGROUND: Artificial intelligence (AI)-based applications for the assessment of the paediatric musculoskeletal system like BoneXpert are not only useful to assess bone age (BA) but also to provide a bone health index (BHI) and a standard deviation score (SDS) for both. This allows comparison of the BHI with age- and sex-matched healthy Caucasian children. OBJECTIVE: We conducted this study with the objective of generating BHI curves using BoneXpert in healthy Indian children with BA between 2 and 17 years. METHOD: We retrospectively reviewed anthropometric parameters, BHI, and BHI SDS data of digitalized left-hand radiographs (joint photographic experts group [jpg] format) of a cohort of 788 paediatric patients from a previous study to which they were recruited to compare various methods of BA assessment. The recruited children represented all age groups for both sexes. The corrected BHI for jpg images was calculated using the formula corrected BHI=BHI*(stature/(avL*50))^0.33333 where stature is height of subject and avL is average length of metacarpal bones. The reference Indian BHI curves and centiles were generated using the Lambda-Mu-Sigma method. RESULT: The mean BHI and BHI SDS of the study group were 4.02±0.57 and -1.73±1.09, respectively. The average increase in median BHI from each age group was between 2.5% and 3% in both sexes up to age of 14 years after which it increased to 4.5% to 5%. The mean BHI of Indian children was lower than that of Caucasian children with maximum differences noted in boys at 16 years (21.7%) and girls at 14 years (16%). We report 8.4% SD of BHI for our study sample. Reference percentile curves for BHI according to BA were derived separately for boys and girls. CONCLUSION: Reference data has been provided for the screening of bone health status of Indian children and adolescents.

A Cross-Sectional Multicentre Study to Validate Insulin Sensitivity Index Cut-Offs for Detection of Metabolic Syndrome in Indian Adolescents with Type-1 Diabetes.

Background: A previous study compared insulin sensitivity indices for the detection of double diabetes (DD) in Indian adolescents with type-1 diabetes (T1D) and derived a cut-off to predict future risk for the development of metabolic syndrome (MS) in adolescents with T1D. We conducted the current study with the aim to validate these cut-offs for detecting DD among Indian subjects with T1D from various geographical locations. Methods: This multicentric cross-sectional study included 161 Indian adolescents with T1D. Demographic, anthropometric, clinical, and biochemical data were collected using standard protocols. Insulin sensitivity (IS) was calculated using various equations developed to determine insulin sensitivity in subjects with T1D. Metabolic syndrome was diagnosed using International Diabetes Federation (IDF) Consensus Definition 2017. Results: We report 4.3% prevalence of MS in Indian adolescents with T1D with an additional 29.8% of study participants at risk of development of MS. Low High density lipoprotein (HDL) (23.6%) was the commonest abnormal component of the MS definition. Insulin sensitivity calculated by an equation derived by the SEARCH group was the most appropriate index to identify MS and metabolic risk in Indian adolescents with T1D. The proposed cut-off of 5.48 had high specificity, positive predictive value, and negative predictive value in identifying the risk of the development of DD. Conclusions: Insulin sensitivity calculated by the equation proposed by the SEARCH group together with cut-offs derived in earlier study may be used effectively to identify risk of development of MS/DD in Indian adolescents with T1D from various geographical locations.

Insulin Resistance in Adolescents and Youth With Type 1 Diabetes: A Review of Problems and Solutions.

Though insulin resistance (IR) was previously considered a feature of only type 2 Diabetes (T2DM), its development in type 1 Diabetes (T1DM) is not an uncommon occurrence, the causes of which are multifactorial (gender, pubertal status, diabetes duration, ethnicity, genetics, adiposity, glycemic control, chronic inflammation). Despite improvements in glucose, blood pressure and lipid profile, vascular complications (coronary artery disease and nephropathy) continue to remain common causes of morbidity and mortality in T1DM. Aggressive glycemic control reduces but does not eliminate the risk of IR. IR accelerates the development of micro and macrovascular complications, many of which can be potentially reversed if diagnosed and managed early. Lack of endogenous insulin production makes estimation of insulin sensitivity in T1DM difficult. As hyperinsulinemic-euglycemic clamp studies are cumbersome and invasive, the use of prediction equations for calculating estimated insulin sensitivity may prove to be useful. Along with intensive insulin therapy, dietary modifications and increasing physical activity, the role of Metformin in managing IR in T1DM is becoming increasingly popular. Metformin adjunct therapy in T1DM has been shown to improve insulin sensitivity, glycemic control, lipid profile, body composition, vascular smooth muscle function, thereby reducing the risk of vascular complications, as well as reversal of early vascular dysfunction. However, further studies to assess long-term efficacy and safety of Metformin use in adolescents and youth with T1DM are needed. This review aims at revisiting the pathophysiology of IR in T1DM and techniques of identifying those at risk so as to put into action various strategies for management of the same.

Assessment of pubertal onset and disorders of puberty in Indian children and youth with type-1 diabetes.

OBJECTIVES: Disorders of pubertal development are enlisted as associated conditions in children and adolescents with type-1 diabetes (T1D). We conducted this study with objective (1) To estimate the median age at onset of puberty and luteinizing hormone (LH) and sex-steroid concentrations in Indian adolescents with T1D and (2) To assess the impact of puberty on glycemic control and insulin resistance (IR). METHODS: This cross-sectional study included 399 children and youth aged 6-23 years with T1D. Demographic, anthropometric, biochemical and pelvic ultrasound data were collected using standard protocols. IR was calculated using estimated glucose disposal rate and puberty was assessed using Tanner staging. RESULTS: Median age at onset of thelarche, pubarche and menarche were 11.3, 11.4 and 12.8 years in girls and that of gonadarche and pubarche were 10.6 and 12.7 years for boys. The mean LH and sex-steroid concentrations of subjects with T1D were similar to healthy subjects at each stage of puberty. The cut-offs of LH and sex-steroids derived from healthy Indian children yielded high sensitivity and specificity in determining pubertal onset. The prevalence of precocity, delayed puberty, ovarian cysts and polycystic ovaries was 0.9 , 5.1, 5.1 and 8.6 %, respectively. Glycaemic control and insulin sensitivity was poor in pubertal subjects. CONCLUSIONS: The age at onset of puberty, LH, and sex-steroid concentrations in subjects with T1D were like otherwise healthy Indian children with poor glycemic control and IR in pubertal subjects. Although most complications of T1D are associated with poor glycemic control, pubertal disorders were significantly low despite the less-than-optimal glycemic control.

Adult Height in Indian Girls with Turner Syndrome Treated with Long-Term Growth Hormone Therapy - A Western India Tertiary Centre Experience.

Background and Objectives: Owing to paucity of data on adult height in Indian girls with Turner syndrome treated with growth hormone (GH), this study was conducted to assess improvement in height following GH therapy and adult height achieved with long-term GH therapy in Indian girls with Turner syndrome and to assess relationship between achieved and predicted height. Methodology: Retrospective analysis was performed on 12 girls with karyotype-proven Turner syndrome, who had attained adult height following mean duration of GH therapy of 4.8 years (range: 2.7-7.6). Adult height predictions were performed using index of responsiveness (IOR) and Ranke's prediction model. Results: Mean age at starting GH was 10.2 ± 1.9 years; Pubertal induction was between 11 and 15 years. Mean height gain was 29.3 ± 9.8 cm (range: 14-39.5) from onset of treatment to adult height. Significant improvement in height Z scores (IAP 2015 and Indian Turner reference data) following GH therapy (p = 0.002 and 0.012, respectively) was noted. Using Indian Turner reference data, the height Z score improved from pre-treatment 0.8 ± 0.8 to 2.0 ± 0.9 on stopping GH and adult height Z score of 1.3 ± 0.7. Using Ranke's equation for prediction of near adult height, predicted and achieved adult height showed a strong positive correlation (Spearman correlation coefficient = 0.827, significant at 0.01 level). Conclusion: At a dose in the lower range (40-50 mcg/kg/day) of recommendation and duration of 5 years, Indian girls with Turner syndrome can achieve adult height within the healthy Indian reference range. Dose individualization based on IOR would help in optimizing GH dosage and would turn out to be economically sustainable without compromising on height outcomes.

Nutritional Status of Underprivileged Indian Children and Youth with Type-1 Diabetes - A Multicentre Study.

Background: India has the highest number of prevalent type-1 diabetes (T1D) cases in the under-20-year age population. Data on the anthropometry of underprivileged Indian children with T1D are scarce. In economically disadvantaged countries like India, poor growth in patients with T1D is a major concern due to limited accessibility and affordability. Besides, due to the double burden of malnutrition, the prevalence of obesity is increasing mirroring the global trends, which may lead to the development of insulin resistance. Objectives: This study aims to assess the prevalence of malnutrition in Indian children and youth with T1D and to identify the determinants of short stature. Methods: A registry-based cross-sectional analysis of data collected from various centres across India enrolled in the Changing Diabetes in Children (CDiC) programme. Results: We observed that 6.4% were undernourished (3.4% severe undernutrition) and 17.7% (overweight 13.2%) had combined overweight/obesity. 21.2% of participants had short stature (adjusted for mid-parental height) with 7.4% cases of familial short stature. Longer duration of illness and insulin requirement were significant positive predictors of short stature while glycaemic control, insulin regimen and mid-parental height did not have a significant relationship with short stature. Participants on basal-bolus regimen had significantly higher insulin requirements and better glycaemic control than the ones on mixed-split regimen. Conclusion: We report that around one-fifth of children and youth with T1D were overweight/obese and around a fourth were stunted, especially those with longer duration of diabetes and higher insulin requirements. Close monitoring of anthropometric parameters is necessary for all children with T1D to optimize growth and nutrition.

A Pilot Study to Assess Effect of Metformin Therapy on Prevention of Double Diabetes in Indian Adolescents with Type-1 Diabetes.

Introduction: Increased prevalence of metabolic syndrome in Indian adolescents owing to the obesity epidemic leads to double diabetes (DD), which is associated with an increased risk of complications in type-1 diabetes (T1D). Metformin may be a useful intervention for the prevention and treatment of insulin resistance in T1D. We conducted this pilot randomized controlled trial with the objective of investigating the effect of metformin on insulin sensitivity in Indian adolescents with T1D. Method: This pilot randomized controlled trial was performed on 59 participants with T1D aged 10-19 years distributed uniformly by gender and puberty across two groups with a 3-month intervention period. The intervention group received metformin (weight less than 60 kg received 500 mg twice daily and more than 60 kg received 1 gm twice daily) and non-metformin group received standard of care for diabetes. Anthropometric, clinical details, biochemistry and insulin sensitivity indices (ISI) were evaluated using standard protocols at baseline and endline. Result: 22.2% of subjects from non-metformin group and 12.5% from metformin group were at the risk of the development of DD. The odds ratio and relative risk for the development of DD in non-metformin subjects were 2.0 and 1.4, respectively, as compared to participants in metformin group. The mean improvement in ISI ranged from 1.4% to 4.6% in participants on metformin as opposed to deterioration of -2% to -14.1% in non-metformin group. On performing the paired sample t-test, the reduction in ISI in non-metformin group was significant. Conclusion: Metformin may prevent deterioration in insulin sensitivity in Indian adolescents with T1D.

Adiponectin-leptin ratio as a marker of cardio-metabolic risk in Indian children and youth with type 1 diabetes.

OBJECTIVES: Adiponectin/leptin ratio (ALR) is a promising novel marker of cardio-metabolic risk in patients with metabolic syndrome. Our aim was to study the association of adiponectin-leptin ratio with markers of obesity and adiposity and also to assess its usefulness as a marker of increased cardiometabolic risk (CMR) in Indian children and youth with type 1 diabetes mellitus. METHODS: This observational study included 79 children and youth with type 1 diabetes (T1DM) (10-21 years) having disease duration>6 months. Demographic data and laboratory findings were obtained from patients' records. Patients with ALR<1 were categorised as having increased CMR and those with ALR>1 were categorised as having no CMR. RESULTS: ALR showed a significant negative correlation with body mass index (BMI), waist and hip circumference and body fat percentage (p<0.05). Body fat percentage was the single most important predictor of ALR. Children and youth with increased CMR had higher weight, BMI, waist and hip circumferences and body fat percentage as compared to those with no CMR (p<0.05). In T1DM children with dyslipidemia, ALR was significantly lower as compared to those without dyslipidemia (p<0.05). CONCLUSIONS: ALR may be a useful marker for adiposity and increased cardiometabolic risk in Indian children and youth with type 1 diabetes mellitus.

Utility of apolipoprotein ratio in predicting metabolic risk and microvascular complications in Indian children and young adults with type 1 diabetes mellitus.

OBJECTIVES: To assess the relationship of apolipoproteins with glycemic control and insulin resistance (IR) in Indian children and youth with type-1 diabetes (T1D) and to assess its utility in predicting metabolic risk (MR) and microvascular complications in these subjects. METHODS: This cross-sectional study included 152 participants aged 6-23 years with T1D. Demographic, anthropometric, clinical, biochemical and body composition data were obtained using standard protocols. IR was calculated using estimated glucose disposal rate (eGDR) and metabolic syndrome (MS) was diagnosed using the international diabetes federation consensus definition 2017. RESULTS: Apolipoprotein ratio in subjects with T1D had negative and positive correlation with eGDR and HbA1c respectively. Positive correlation of Apolipoproten B and apolipoprotein ratio with urinary albumin creatinine ratio is noted. The ratio had area under curve of 0.766 and 0.737 to predict MR and microvascular complications respectively. The ratio cut-off of 0.536 yielded 77.1 % sensitivity and 61 % specificity to predict MR. On adding the apolipoprotein ratio as a predictor to the regression model developed to predict MR, the R2 and accuracy improved. CONCLUSIONS: The apolipoprotein ratio had significant correlation with IR, microalbuminuria and glycaemic control. The ratio also predicts risk of development of microvascular complications and maybe used to predict MR in subjects with T1D.

Longitudinal trends in lipid profile in indian children and youth with type-1 diabetes: a 5-year follow up from a single centre.

INTRODUCTION: High prevalence of dyslipidaemia in children and adolescents with type-1 diabetes (T1D) places them at increased risk of developing atherosclerosis leading to mortality caused by cardiovascular disease(CVD). Thus, screening for fasting blood lipids when diabetes is stabilized in children aged 11 years and above is routinely recommended with follow-up every 5 years. OBJECTIVES: (1) To characterize the lipid profile of children and adolescents with respect to diabetes duration. (2) To describe longitudinal changes in lipid profile over a 5-year period in patients with T1D. METHODS: This longitudinal 5-year follow-up study included 112 patients with T1D aged 3-18 years. Demographic data, anthropometry and laboratory measurements were performed using standard protocols at baseline and endline. P value < 0.05 was considered significant. RESULTS: The prevalence of dyslipidaemia in our study was 49.5% with abnormal LDL as the most frequently deranged parameter. Duration of illness played a major role in deterioration of lipid profile mediated by triglyceride and VLDL. Duration of illness and fibre intake in diet significantly predicted the change in lipid profile which were driven by triglycerides and VLDL. Glycemic control, insulin sensitivity and serum TSH also significantly altered components of lipid profile with no impact on overall dyslipidaemia. A total of 6.5% subjects had LDL concentrations >130 mg/dl and the same proportion had non-HDL cholesterol concentrations >145 mg/dl at baseline while at endline, 11.9% subjects had LDL concentrations >130 mg/dl and 15.6% subjects had non-HDL cholesterol concentrations >145 mg/dl. 28.6% subjects with LDL > 130 mg/dl and non-HDL cholesterol >145 mg/dl at baseline had persistently elevated concentrations while 10.3% and 14.4% additional subjects developed elevated LDL and non-HDL cholesterol concentrations respectively during the study period. CONCLUSIONS: The deterioration of lipid profile in T1D, due to increase in disease duration was chiefly mediated by increase in serum triglyceride and VLDL concentrations which may be prevented by improving glycaemic control, insulin sensitivity and fibre intake in diet.

Response to sirolimus in a case of diffuse congenital hyperinsulinaemic hypoglycaemia due to homozygous KCNJ11 mutation.

We present a case of a male neonate with refractory and persistent neonatal hypoglycaemia not responding to octreotide. On evaluation for hypoglycaemia, his cortisol was within the reference range while the serum insulin concentrations were high. Gallium-68 dotatate scan (GA-68 DOTA) showed diffuse pancreatic involvement. Genetic diagnosis of congenital hyperinsulinaemic hypoglycaemia due to KCNJ11 mutation was made. He was started on tablet sirolimus, after which the child was off all other medication and was euglycaemic. However, he developed bilateral pneumonia leading to acute respiratory distress syndrome with refractory shock. Our case highlights the response to sirolimus in a case of congenital hyperinsulinaemia (CHI) due to KCNJ11 mutation and severe adverse event thereafter.

Vitamin D status and determinants in Indian children and adolescents: a multicentre study.

Studies performed on Indian children to assess vitamin-D status have been on small sample sizes, limited to specific geographical locations and used non-standard methods to measure 25(OH)D3. This multicentre study assessed 25(OH)D3 concentrations from dried blood spots (DBS) in 5-18-year-old Indian children and adolescents using a standardized protocol and identified factors contributing towards vitamin D deficiency. Cross-sectional, observational school-based study was conducted by multi-stage stratified random sampling. A city and nearby village were selected from 6 Indian states covering wide geographical areas. Demography, anthropometry, body-composition, dietary-intakes and DBS samples were collected. 25(OH)D3 was assessed from DBS using Liquid chromatography with tandem-mass spectrometry. Vitamin-D status was assessed in 2500 children; with additional data collected on a subset (n = 669) to assess predictors. Mean vitamin-D concentration was 45.8 ± 23.9 nmol/L, 36.8% of subjects had sufficient vitamin-D (> 50 nmol/L); rural subjects and boys had higher concentrations (p < 0.05). On regression analysis, younger age, female-gender, overweight and urban residence significantly contributed to deficiency. More than half the Indian children/adolescents were vitamin-D deficient or insufficient. Our study reinforces vitamin-D deficiency as a major public health problem and the need for supplementation, food fortification and educating the population as initiatives required to improve sufficiency status.