A novel simple disposition index (SPINA-DI) from fasting insulin and glucose concentration as a robust measure of carbohydrate homeostasis.

AIMS: The widely used dynamic disposition index, derived from oral glucose tolerance testing, is an integrative measure of the homeostatic performance of the insulin-glucose feedback control. Its collection is, however, time consuming and expensive. We, therefore, pursued the question if such a measure can be calculated at baseline/fasting conditions using plasma concentrations of insulin and glucose. METHODS: A new fasting-based disposition index (structure parameter inference approach-disposition index [SPINA-DI]) was calculated as the product of the reconstructed insulin receptor gain (SPINA-GR) times the secretory capacity of pancreatic beta cells (SPINA-GBeta). The novel index was evaluated in computer simulations and in three independent, multiethnic cohorts. The objectives were distribution in various populations, diagnostic performance, reliability and correlation to established physiological biomarkers of carbohydrate metabolism. RESULTS: Mathematical and in-silico analysis demonstrated SPINA-DI to mirror the hyperbolic relationship between insulin sensitivity and beta-cell function and to represent an optimum of the homeostatic control. It significantly correlates to the oral glucose tolerance test based disposition index and other important physiological parameters. Furthermore, it revealed higher discriminatory power for the diagnosis of (pre)diabetes and superior retest reliability than other static and dynamic function tests of glucose homeostasis. CONCLUSIONS: SPINA-DI is a novel simple reliable and inexpensive marker of insulin-glucose homeostasis suitable for screening purposes and a wider clinical application.

Understanding the predictive accuracy of the InsuTAG index over other surrogate indices in normoglycaemic, non-obese males from Southern India.

We aimed to evaluate the predictive accuracy of InsuTAG index against M value of the hyperinsulinaemic-Euglycaemic clamp (HEC) procedure and fasting surrogate indices of insulin sensitivity/resistance in young, normoglycaemic, Asian Indian males. HEC studies were done in young (mean age 19.7 ± 1 years), non-obese (mean BMI 19.2 ± 2.6 kg/m2), normoglycemic Asian Indian males (n = 110) and the M value was calculated. Surrogate indices namely InsuTAG index, HOMA-IR, FG-IR, QUICKI and McAuley index were calculated. Pearson's correlation and ROC-AUC at 95% CI were applied. Significant negative correlation was observed for InsuTAG index with the M value (r - 0.23, p = 0.01), McAuley index (r - 0.65, p < 0.01), QUICKI (r - 0.34, p < 0.01) and FGIR (r - 0.35, p < 0.01). Significant positive correlations of InsuTAG index were observed for BMI and waist circumference. The ROC-AUC was higher for InsuTAG index (0.75) than FGIR (0.30), QUICKI (0.31), and McAuley index (0.20). The InsuTAG cut-off value ≥ 19.13 showed 66.7% sensitivity and 69.2% specificity in this study group.

Subacute thyroiditis following recovery from COVID-19 infection: novel clinical findings from an Eastern Indian cohort.

OBJECTIVE: Recent reports have suggested a link between COVID-19 infection and subacute thyroiditis (SAT). We aimed to describe variations in clinical and biochemical parameters in patients developing post-COVID SAT. DESIGN: Ours was a combined retrospective-prospective study on patients presenting with SAT within 3 months of recovery from COVID-19 infection, who were subsequently followed up for a further 6 months since diagnosis of SAT. RESULTS: Out of 670 patients with COVID-19, 11 patients presented with post-COVID-19 SAT (6.8%). Those with painless SAT (PLSAT, n = 5) presented earlier, had more severe thyrotoxic manifestations and exhibited higher C-reactive protein, interleukin 6 (IL-6), neutrophil-lymphocyte ratio and lower absolute lymphocyte count than those with painful SAT (PFSAT, n = 6). There were significant correlations of total and free T4 and total and free T3 levels with serum IL-6 levels (pall <0.04). No differences were observed between patients with post-COVID SAT presenting during the first and second waves. Oral glucocorticoids were needed for symptomatic relief in 66.67% of patients with PFSAT. At 6 months of follow-up, majority (n = 9, 82%) achieved euthyroidism, while subclinical and overt hypothyroidism were found in one patient each. CONCLUSIONS: Ours is the largest single-centre cohort of post-COVID-19 SAT reported until, demonstrating two distinct clinical presentations-without and with neck pain-depending on time elapsed since COVID-19 diagnosis. Persistent lymphopaenia during the immediate post-COVID recovery period could be a key driver of early,painless SAT. Close monitoring of thyroid functions for at least 6 months is warranted in all cases.

SPINA Carb: a simple mathematical model supporting fast in-vivo estimation of insulin sensitivity and beta cell function.

Modelling insulin-glucose homeostasis may provide novel functional insights. In particular, simple models are clinically useful if they yield diagnostic methods. Examples include the homeostasis model assessment (HOMA) and the quantitative insulin sensitivity check index (QUICKI). However, limitations of these approaches have been criticised. Moreover, recent advances in physiological and biochemical research prompt further refinement in this area. We have developed a nonlinear model based on fundamental physiological motifs, including saturation kinetics, non-competitive inhibition, and pharmacokinetics. This model explains the evolution of insulin and glucose concentrations from perturbation to steady-state. Additionally, it lays the foundation of a structure parameter inference approach (SPINA), providing novel biomarkers of carbohydrate homeostasis, namely the secretory capacity of beta-cells (SPINA-GBeta) and insulin receptor gain (SPINA-GR). These markers correlate with central parameters of glucose metabolism, including average glucose infusion rate in hyperinsulinemic glucose clamp studies, response to oral glucose tolerance testing and HbA1c. Moreover, they mirror multiple measures of body composition. Compared to normal controls, SPINA-GR is significantly reduced in subjects with diabetes and prediabetes. The new model explains important physiological phenomena of insulin-glucose homeostasis. Clinical validation suggests that it may provide an efficient biomarker panel for screening purposes and clinical research.

Comprehensive evaluation of patterns of hypoglycemia unawareness (HUA) and glycemic variability (GV) in patients with fibrocalculous pancreatic diabetes (FCPD): A cross-sectional study from South India.

OBJECTIVES: Hypoglycemia unawareness (HUA) in patients with FCPD is common with an unclear etiology. We evaluated the prevalence, characteristics of HUA, glycemic variability (GV), its possible association with pancreatic glucagon secretion & cardiac autonomic function in patients with FCPD. METHODS: A two-week ambulatory glucose profile (AGP) and cardiac autonomic function test was done in patients with FCPD (n = 60), and categorized into UNAWARE (n = 44) and AWARE (n = 16) groups based on the Hypoglycemia Unawareness Index (HUI) score. Glycaemic variability was assessed from the AGP data using Easy GV 9.0.2 software. A subset of patients from both the groups (n = 11) underwent a mixed-meal challenge test and were compared with healthy individuals (controls; n = 11). RESULTS: HUA was evidenced in 73% (44/60) of patients with FCPD. Significant hypoglycemia, nocturnal hypoglycemia, duration of hypoglycemia and poor cardiac autonomic functions (p = 0.01) were prominent in the UNAWARE group. The overall GV was greater in the UNAWARE group. In the UNAWARE group, significantly reduced fasting and post prandial glucagon levels negatively correlated with HUI (r = -0.74, p < 0.05) and GV-hypoglycemia indices (p < 0.05) In contrast, significantly higher post prandial glucagon levels in the AWARE group positively correlated with post prandial hyperglycemia (r = 0.61, p < 0.05). CONCLUSION: Heterogeneity in patterns of glucagon secretion were significantly associated with HUA and GV. Reduced glucagon levels contribute to greater risks of HUA, nocturnal hypoglycemia and greater GV, while hyperglucagonemia predisposes to postprandial hyperglycemia and hypoglycemia awareness in patients with FCPD.

Stress hyperglycemia ratio, rather than admission blood glucose, predicts in-hospital mortality and adverse outcomes in moderate-to severe COVID-19 patients, irrespective of pre-existing glycemic status.

AIM: To compare admission-blood-glucose (ABG) or stress-hyperglycemia-ratio (SHR) performs better in predicting mortality and worse outcomes in COVID-19 patients with (DM) and without known Type 2 Diabetes Mellitus (UDM). METHODS: ABG and SHR were tested for 451 patients with moderate-severe COVID-19 infection [DM = 216,47.9%; pre-diabetes = 48,10.6%, UDM = 187,41.4%],who were followed-up to look for in-hospital-mortality (primary outcome) and secondary outcomes (ICU stay or mechanical ventilation, hospital-acquired-sepsis and multiple organ dysfunction syndrome [MODS]). Those with and without SHR ≥ 1.14 were compared; logistic regression was done to identify predictors of outcomes, with subgroup analysis based on pre-existing DM status and COVID-19 severity. RESULTS: Those who died (n = 131) or developed ≥ 1 secondary outcomes (n = 218) had higher prevalence of SHR ≥ 1.14, ABG ≥ 180 mg/dl and higher median SHR (pall < 0.01). Those with SHR ≥ 1.14 had higher mortality (53.7%), higher incidence of ≥ 1 secondary outcomes (71.3%) irrespective of pre-existing diabetes status. SHR ≥ 1.14, but not ABG ≥ 180 was an independent predictor of mortality in the whole group (OR: 7.81,4.07-14.98), as also the DM (OR:10.51,4.34-25.45) and UDM (5.40 (1.57-18.55) subgroups. SHR ≥ 1.14 [OR: 4.41 (2.49-7.84)] but not ABG ≥ 180 could independently predict secondary outcomes AUROC of SHR in predicting mortality was significantly higher than ABG in all subgroups. CONCLUSION: SHR better predicts mortality and adverse outcomes than ABG in patients with COVID-19, irrespective of pre-existing chronic glycemic status.

An Atypical Form of Diabetes Among Individuals With Low BMI.

OBJECTIVE: Diabetes among individuals with low BMI (<19 kg/m2) has been recognized for >60 years as a prevalent entity in low- and middle-income countries (LMICs) and was formally classified as "malnutrition-related diabetes mellitus" by the World Health Organization (WHO) in 1985. Since the WHO withdrew this category in 1999, our objective was to define the metabolic characteristics of these individuals to establish that this is a distinct form of diabetes. RESEARCH DESIGN AND METHODS: State-of-the-art metabolic studies were used to characterize Indian individuals with "low BMI diabetes" (LD) in whom all known forms of diabetes were excluded by immunogenetic analysis. They were compared with demographically matched groups: a group with type 1 diabetes (T1D), a group with type 2 diabetes (T2D), and a group without diabetes. Insulin secretion was assessed by C-peptide deconvolution. Hepatic and peripheral insulin sensitivity were analyzed with stepped hyperinsulinemic-euglycemic pancreatic clamp studies. Hepatic and myocellular lipid contents were assessed with 1H-nuclear magnetic resonance spectroscopy. RESULTS: The total insulin secretory response was lower in the LD group in comparison with the lean group without diabetes and the T2D group. Endogenous glucose production was significantly lower in the LD group than the T2D group (mean ± SEM 0.50 ± 0.1 vs. 0.84 ± 0.1 mg/kg · min, respectively; P < 0.05). Glucose uptake was significantly higher in the LD group in comparison with the T2D group (10.1 ± 0.7 vs. 4.2 ± 0.5 mg/kg · min; P < 0.001). Visceral adipose tissue and hepatocellular lipids were significantly lower in LD than in T2D. CONCLUSIONS: These studies are the first to demonstrate that LD individuals in LMICs have a unique metabolic profile, suggesting that this is a distinct entity that warrants further investigation.

Differentials in dietary intake of macro and micronutrients in patients with type 2 diabetes and foot ulcers: Observations from a pilot study.

BACKGROUND AND AIM: The dietary profiles of patients with type 2 diabetes mellitus (T2DM) from Southern India have been infrequently studied. We aimed to study the differences in dietary intake of macro and micronutrients in elderly patients of Type 2 diabetes mellitus (T2DM), with and without foot ulcers. METHODS: Elderly patients with T2DM and foot ulcers (n = 79; mean age: 60.6 years) and those without foot ulcers (n = 59; mean age: 55.0 years) were studied. Biochemical evaluation for measures of glycemia, lipids and albumin were done and staging of foot ulcers was done using Wagner's scale. A 24-hour dietary recall was administered to quantify the mean daily intake (MDI) of macro, micronutrients and trace elements from portion sizes of food items consumed and compared to the recommended dietary allowance (RDA) for Indians aged 55 years and above. RESULTS: In patients with T2DM and foot ulcers, the MDI of carbohydrates, fats and phosphorus were significantly higher whereas the MDI of proteins and micronutrients namely zinc, folic acid, iron and carotene were lower than the RDA. Elderly patients with nephropathy and longer duration of T2DM have higher odds of developing foot ulcers, when compared to patients without foot ulcers. CONCLUSION: Elderly patients with T2DM and foot ulcers were deficient in dietary intake of proteins and micronutrients inclusive of carotene, folic acid, zinc, and Iron. Clinical care, regular monitoring of dietary intake and appropriate correction of nutritional deficiencies will aid in the management of diabetic foot ulcers.

Lipid accumulation product (LAP) as a potential index to predict risk of insulin resistance in young, non-obese Asian Indian males from Southern India: observations from hyperinsulinemic-euglycemic clamp studies.

INTRODUCTION: We aimed to compare the predictive accuracy of surrogate indices namely the lipid accumulation product (LAP) index, homeostatic model of assessment of insulin resistance (HOMA-IR), fasting glucose-insulin ratio (FG-IR) and the quantitative-insulin sensitivity check index (QUICKI), against the M value of hyperinsulinemic-euglycemic clamp (HEC), and to determine a cut-off value for the LAP index to predict risk of insulin resistance in non-obese (body mass index <21 kg/m2), normoglycemic, Asian Indian males from Southern India. RESEARCH DESIGN AND METHODS: Data of HEC studies performed in 108 non-obese, normoglycemic, Asian Indian males was obtained retrospectively and the M value (a measure of whole-body insulin sensitivity) was calculated. The M value is the rate of whole-body glucose metabolism at the hyperinsulinemic plateau (a measure of insulin sensitivity) and is calculated between 60 and 120 min after the start of the insulin infusion in the HEC procedure. The LAP index, the HOMA-IR, FG-IR and QUICKI were calculated. Spearman's correlation and logistic regression analysis were performed. Cut-off value for the LAP index was obtained using receiver operating characteristics with area under curve (AUC) analysis at 95% CI. P value <0.05 was considered to be statistically significant. RESULTS: Significant negative correlation was observed for the M value with LAP index (r=-0.39, p<0.001) while significant positive correlation was noted with FG-IR (r=0.25; p<0.01) and QUICKI (r=0.22; p<0.01). The LAP index cut-off value ≥33.4 showed 75% sensitivity and 75% specificity with AUC (0.72) to predict risk of insulin resistance in this cohort. CONCLUSION: The LAP index showed higher predictive accuracy for the risk of insulin resistance as compared with HOMA-IR, QUICKI and FG-IR in non-obese, normoglycemic Asian Indian males from Southern India.

Exocrine pancreatic insufficiency related fat malabsorption and its association with autonomic neuropathy in Asian Indians with type 2 diabetes mellitus.

BACKGROUND AND AIMS: We aimed to estimate the prevalence of exocrine pancreatic insufficiency (EPI) related fat malabsorption & to correlate it with measures of autonomic neuropathy in patients with T2DM from India. METHODS: Patients with T2DM (cases; n = 118) and normo-glycaemic individuals (controls; n = 82) underwent anthropometry and biochemical evaluation at baseline. The 72-hours fecal fat excretion was estimated by the Van de Kamer's titration method. Autonomic neuropathy was evaluated using an automated analyzer. RESULTS: The prevalence of EPI related fat malabsorption in cases was 45% (n = 53; 72 hours mean fecal fat level = 22.7 ± 5.6 g/day). Dysfunctions in the parasympathetic nervous system (PNS; 86.7%; p < 0.05), sympathetic nervous system (SNS; 92.4%; p < 0.05), and both; PNS + SNS (83.1%; p < 0.05) were significant. Amongst measures of PNS dysfunction, there was a significantly higher percentage of abnormal expiration: inspiration ratio (45.3%) and the 30:15 ratio (84.9%) (p < 0.05) in patients with T2DM and EPI related fat malabsorption. CONCLUSION: In this cross-sectional cohort of Asian Indian patients with T2DM (n = 118), EPI related fat malabsorption correlates significantly with autonomic dysfunction in patients with T2DM. However, these preliminary data need to confirmed in trials with more robust design.

Predictors of new-onset diabetic ketoacidosis in patients with moderate to severe COVID-19 receiving parenteral glucocorticoids: A prospective single-centre study among Indian type 2 diabetes patients.

BACKGROUND AND AIM: COVID-19 infection predisposes to diabetic ketoacidosis(DKA); whether glucocorticoids enhances this risk is unknown.We aimed to study the occurrence of DKA after initiating glucocorticoids in patients with type 2 diabetes mellitus(T2DM) and moderate-to-severe COVID-19, and identify predictors for it. METHODS: Patients with T2DM and moderate or severe COVID-19 infection were prospectively observed for development of new-onset DKA for one week following initiation of parenteral dexamethasone. Clinical and biochemical parameters were compared between those who developed DKA (Group A) and those who didnot (Group B). Logistic regression was done to identify independent risk-factors predicting DKA; ROC-curve analysis to determine cut-offs for the parameters in predicting DKA. RESULTS: Amongst 302 patients screened, n = 196 were finally included, of whom 13.2% (n = 26,Group A) developed DKA. Patients in Group A were younger, had lower BMI, increased severity of COVID-19 infection, higher HbA1c%, CRP, IL-6, D-dimer and procalcitonin at admission (pall < 0.02). Further, admission BMI (OR: 0.43, CI: 0.27-0.69), HbA1c % (OR: 1.68, CI: 1.16-2.43) and serum IL-6 (OR: 1.02, CI: 1.01-1.03) emerged as independent predictors for DKA. Out of these, IL-6 levels had the highest AUROC (0.93, CI: 0.89-0.98) with a cut-off of 50.95 pg/ml yielding a sensitivity of 88% and specificity of 85.2% in predicting DKA. CONCLUSION: There is significant incidence of new-onset DKA following parenteral glucocorticoids in T2DM patients with COVID-19, especially in those with BMI <25.56 kg/m2, HbA1c% >8.35% and IL-6 levels >50.95 pg/ml at admission.

Significance of single and multi-voxel 1H magnetic resonance spectroscopy in the quantification of myocellular lipid in young non-obese Asian Indian males.

To prospectively assess intramyocellular lipids (IMCL) and extramyocellular lipids (EMCL) using single voxel spectroscopy (SVS) and multi voxel magnetic resonance spectroscopy (MVS) in soleus muscle and correlate results with metabolic variables in non-obese (BMI < 23 kg/m2) Asian Indian males. Thirty one patients with diabetes (cases) and twelve normoglycaemic subjects (controls) underwent point resolved spectroscopy sequence (PRESS) of soleus muscle using SVS and MVS in a 3 T MRI scanner. Visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were measured from MRI images and body composition was measured from dual-energy x-ray absorptiometry (DXA). The mean IMCL from SVS and MVS were 1.6% and 2.6% in cases and 2.3% and 3.4% in controls respectively. The mean EMCL from SVS and MVS were 1.8% and 3% in cases and 1.5% and 3% respectively in controls. A significant correlation between IMCL and total fat mass (rho = 0.42, p < 0.01) and total body fat (rho = 0.46; p < 0.01) were observed in cases while using the SVS technique and no correlations were found in the MVS technique. The SVS showed significant correlations between total myocellular lipids with VAT and SAT in cases alone. Total myocellular lipids acquired using both techniques showed a significant correlation with BMI, waist circumference, total fat mass, total body fat and truncal fat in cases alone. Quantification of IMCL of soleus muscle using the SVS technique is useful in studying the relationship with metabolic markers in non-obese Asian Indians with diabetes.

Managing diabetic foot in times of COVID-19: time to put the best 'foot' forward.

INTRODUCTION: The COVID-19 pandemic has had an unparalleled impact on the socio-economic and healthcare structure of India. Due to our large populations of diabetic patients, who have an increased risk of worse outcomes with COVID-19 infection, it is of utmost public health importance to analyse the relationship between the two. The aim of our review was to analyse the possible relationship between COVID-19 infection and DFUs, which are a fairly common, yet serious complication in diabetic patients, as well as their management, under the given changing circumstances. METHODOLOGY: An extensive review of related educational articles was analysed from various databases. RESULTS: The two main pathogenic mechanisms described in COVID-19 infection are a cytokine storm (causing ARDS) as well as an acquired coagulopathy, with widespread thrombosis. DFUs are associated with an underlying peripheral neuropathy, a chronic low-grade inflammatory state and peripheral arterial disease, which lead to chronic non-healing ulcers. Similarities seen in the pathogenic mechanisms of these two conditions make a bidirectional relationship highly plausible. CONCLUSION: Due to the disruptions in the healthcare system brought on by the COVID-19 pandemic, changes in practice to a telehealth-driven approach, with emphasis on homecare and community clinics, need to be adopted, to ensure best possible care to patients with DFUs, in order to reduce their risk of DFU-related complications and need for hospitalization.

Platelet-Lymphocyte Ratio as a Novel Surrogate Marker to Differentiate Thyrotoxic Patients with Graves Disease from Subacute Thyroiditis: a Cross-Sectional Study from South India.

OBJECTIVE: Graves disease (GD) and the toxic phase of subacute thyroiditis (SAT) have similar clinical and biochemical presentations, and differentiating them requires sophisticated investigations. Since thyroid hormones have been noted to affect all hematologic cell lines, we have used the platelet lymphocyte ratio (PLR)-an index usually utilized in inflammatory or malignant disorders-to compare patients with and without thyrotoxicosis and to analyze its use in distinguishing between patients with GD and SAT prior to therapy. METHODS: This was a cross-sectional study conducted in the Department of Endocrinology, Christian Medical College, Vellore, India. During the study period, 800 patients with features of thyrotoxicosis visited the outpatient clinic. Those who had thyroid radioiodine (131I) uptake (RAIU) study and complete blood count (CBC) at diagnosis were included (N = 500). Based on the RAIU values, these were divided as GD (n = 354) and SAT (n = 146). Baseline characteristics, thyroid function tests, and components of the CBC and PLR were obtained. The data were compared with a group of 250 matched euthyroid controls. Analyses were performed using SPSS version 21.0 software. RESULTS: PLR showed significant reductions in both GD and SAT patients when compared to euthyroid controls (P = .01), with greater reductions seen in GD than SAT (74.5 ± 19 vs. 84.4 ± 26; P = .01). Using receiver operating characteristic analysis of PLR, an optimal PLR cut-off of 70.4 was found to differentiate GD from SAT with a sensitivity of 86% and specificity of 74%. CONCLUSION: PLR can be used as a novel surrogate marker to differentiate between patients with GD and SAT prior to therapy, especially in resource-limited settings.

An unusual cause of foot ulcer in a patient with diabetes mellitus.

A diabetic foot ulcer is the leading cause of nontraumatic amputation worldwide. The most important predisposing factor for diabetic foot ulcer is peripheral neuropathy. Rat bites are an uncommon but important cause of ulcer in patients with diabetes, especially in lower socioeconomic strata. A 56-year-old male from southern India, a known patient with type 2 diabetes for the past 15 years with severe peripheral neuropathy, presented to our center with multiple bite marks on bilateral feet and destroyed nails. He was initially managed with local measures and injection tetanus toxoid; however, he rapidly worsened over the next 5 days to develop bilateral cellulitis of the feet and right great toe osteomyelitis. His biochemistry showed uncontrolled diabetes (HbA1c: 9.9) and radiology confirmed right great toe osteomyelitis. He underwent transmetatarsal amputation of the right first toe along with intravenous antibiotics followed by oral antibiotics (amoxicillin with clavulanic acid) for a total duration of 6 weeks and optimization of glycemic control. He improved completely over the next 1 month. Rat bites are a rare but readily preventable cause of foot ulcer in diabetic patients. Primary care and family physician play a vital role in educating patients about preventive aspects such as avoidance of using vegetable oil as a moisturizer that may attract rodents and insects.

Clinical features, radiological characteristics and offloading modalities in stage 0 Acute Charcot's neuroarthropathy - A single centre experience from South India.

AIMS: Stage 0 Acute Charcot's Neuroarthropathy (ACN)in Type 2 Diabetes patients is a challenging diagnosis with subtle clinical features and normal appearing plain radiographs of the affected foot. Delay in diagnosis can lead to progression of disease and irreversible deformities. There is a paucity of data on Stage 0 ACN from India. The aim of this study was to assess clinical and radiological characteristics and treatment outcomes in Indian Type 2 Diabetes patients with Stage 0 ACN. MATERIALS AND METHODS: A comparative, case-control study was carried out amongst patients attending the Integrated Diabetes Foot Clinic at a tertiary care South Indian hospital. During the 3-year study period, a total of 1811 patients with Type 2 Diabetes Mellitus were screened. Of these, n = 10 patients with stage 0 ACN Charcot's arthropathy were identified based on clinical features and MRI imaging of the foot for confirmation of diagnosis. These were compared with an age and duration of diabetes-matched group of n = 50 patients without ACN as controls. RESULTS: Our study identified 10 patients (0.5%) with Stage 0 Acute charcot neuroarthropathy (ACN) in the study population. Those with ACN had higher BMI, poorer glycaemic control and greater degree of peripheral neuropathy (p < 0.05). Clinically relative lack of pain and infrared thermometric temperature difference >2 °C in the affected foot were the most significant findings, while MRI foot was useful in early detection of active and severe stage 0 disease. Total contact cast was the preferred initial offloading modality, with delay in initiating complete immobilization leading to worse outcomes. CONCLUSIONS: This is the first study to highlight the characteristic features of Stage 0 ACN in Indian Type 2 Diabetes patients. Thorough clinical evaluation, infrared thermometry and radiological findigs on MRI foot leads to early disease detection. Complete offloading, preferably with total contact casts can prevent disease progression and chronic deformities.

Longitudinal changes in bone mineral density and trabecular bone score following yearly zoledronic acid infusion in postmenopausal osteoporosis-a retrospective-prospective study from southern India.

This study from southern India showed that yearly administration of zoledronic acid demonstrated significant improvement in BMD at lumbar spine following two doses and no decline in BMD at femoral neck or hip and trabecular bone score (TBS) in postmenopausal women. PURPOSE: There is limited information available with regard to the impact of zoledronic acid treatment on bone mineral density (BMD) and trabecular bone score (TBS) in Indian postmenopausal women with osteoporosis. We studied the changes in BMD at femoral neck (FN), hip and lumbar spine (LS), and in TBS following yearly administration of zoledronic acid (ZA) in subjects with postmenopausal osteoporosis. MATERIAL AND METHODS: This was a prospective-retrospective study which included subjects on follow-up after administration of yearly zoledronic acid, over the past 6 years. Postmenopausal women with a T score of ≤ - 2.5 at any site, assessed by dual energy X-ray absorptiometry (DXA), were included. RESULTS: A total of 620 subjects had received ZA during the study period, 197 postmenopausal women were eligible, and follow-up data were available in 164 and 103 at 1st and 2nd follow-up yearly visits respectively. The mean (SD) age and BMI of the women were 63.2 (8.5) years and 25.6 (4.5) kg/m2 respectively. There was significant increment in LS BMD from baseline to the 1st and 2nd follow-up visits, respectively (mean (SD), 0.718 (0.116), 0.734 (0.104), 0.762 (0.127) g/cm2, p = 0.024). No decline in the BMD at FN and hip at first and second follow visit was found. The TBS scores (n = 90) on baseline and follow-up visits were 1.260 (±0.11), 1.256 (± 0.15), and 1.242 (± 0.17) (p value = 0.71). CONCLUSION: Lumbar spine BMD showed significant improvement with zoledronic acid treatment. No decline was noted in femoral neck BMD and TBS with treatment.

Arterial thrombosis as primary presentation of endogenous Cushing's syndrome.

Cushing's syndrome is known to present with a characteristic set of clinical manifestations and complications, well described in literature. However, hypercoagulability remains an under recognised entity in Cushing's syndrome. A 31-year-old woman from Southern India presented with history of fever, left upper quadrant pain and progressive breathing difficulty for 3 weeks. Clinical examination revealed discriminatory features of Cushing's syndrome. Laboratory investigations showed biochemical features of endogenous ACTH-dependent Cushing's syndrome. Imaging of the abdomen revealed splenic collection, left-sided empyema and extensive arterial thrombosis. Gadolinium enhanced dynamic MRI of the pituitary gland revealed no evidence of an adenoma while a Ga-68 DOTATATE positron emission tomography CT scan ruled out an ectopic Cushing's. A diagnosis of endogenous Cushing's syndrome causing a prothrombotic state with extensive arterial thrombosis was made. She was initiated on oral anticoagulation and oral ketoconazole for medical adrenal suppression. She subsequently underwent bilateral adrenalectomy and was well at follow-up.

Bioimpedance analysis with a novel predictive equation - A reliable technique to estimate fat free mass in birth weight based cohorts of Asian Indian males.

AIM: To validate bioimpedance based predictive equations for fat free mass (FFM) against DEXA and to derive a novel birth weight based predictive equation for FFM in a birth weight based cohort of healthy Asian Indian men. METHODOLOGY: Whole body composition was done using DEXA and bioimpedance in 117 young Asian Indian men, born of normal birth weight (n = 59, birth weight ≥2.5 kg) or low birth weight (n = 58, birth weight < 2.5 kg). Predictive accuracy of 11 different bioimpedance based equations for FFM was evaluated using Pearson's correlation analysis and the root of mean squared prediction error (RMSE) analysis. RESULTS: The mean FFM (on DEXA) and total lean mass & impedance index (on bioimpedance) were significantly higher in the low birth weight cohort. Significantly higher body fat percentage was noted on bioimpedance, for the normal birth weight cohort, but not on DEXA. In addition, the mean values of predicted FFM were significantly higher in the low birth weight cohort for 9 different predictive equations. Specifically, the mean FFM values obtained using the predictive equations of Schaefer et al., Hoot cooper et al. and Hughes et al. were in close agreement with the actual FFM values on DEXA. A novel predictive equation (CMC equation) for FFM based on birth weight was derived. FFM = 32.637 + (-0.222*age) + (-32.51*waist-to-hip ratio) + (0.33*body mass index) + (1.58 * 1 or 2 (1 = normal birth weight, 2 = low birth weight) + (0.510*waist circumference). CONCLUSIONS: Our study findings substantiate the validity of Bio-impedance analysis (BIA) as a reliable and noninvasive tool for estimating body composition measures in birth-weight based cohorts of Asian Indian males. Further, we have devised a novel BIA-based predictive equation that can be useful in larger epidemiological studies to look at alterations in body fat in this cohort.