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Limb and patient outcomes in people with diabetic foot complications including diabetic foot ulcer (DFU) provided virtual triage and personalized video consultations during COVID-19 pandemic are not known. Patients with foot complications attending the diabetic foot clinic prior to lockdown who sought teleconsultations during COVID-19 lockdown underwent virtual triage to include clinical history, visual inspection of feet, domiciliary wound care (community nurse assisted dressings) and offloading instructions. The subsequent ulcer, limb and mortality outcomes during the following 24 weeks of COVID-19 lockdown (April-September 2020, group 1) were assessed and compared with those who attended foot clinic during the same period in 2019 (April-September, group 2). Group 1 included 561 participants with foot complications provided with teleconsultations, median age 57 (51 to 63) years and diabetes duration of 10 (5 to 16) years. Twelve patients with severe DFU were excluded and 549 patients [357 (65%) neuropathic foot, 104 (18.9%) ischemic foot and 88 (16%) chronic Charcot foot with deformities] were evaluated. There were 227 (41.3%) participants with active DFU at start of lockdown, 32 (5.8%) with new onset ulcer during lockdown (47.1%) and 290 patients without ulcers. Group 2 included 650 participants; active foot ulcer was present in 366 patients. Wound closed or reduced in area in 78.4% of participants of group 1 compared to 76.0% (p = 0.318) in group 2. Fourteen (5.4%) patients required amputations [3 major and 11 minor] in group 1 during the study period compared to 6.8% in group 2 (p = 0.191). Twenty-one (3.8%) and 28 (4.3%) patients died (p = 0.532) during 24 weeks of follow up in group 1 and 2, respectively. Targeted foot-care service through virtual triage and teleconsultations during COVID-19 pandemic for people with foot complications have similar ulcer and limb outcomes compared to face-to-face foot care delivery.

Purpose Both laparoscopic sleeve gastrectomy (LSG) and liraglutide cause a significant weight loss. We evaluated the effect of liraglutide in comparison with placebo on total weight loss (TWL) and excess body weight loss (EWL) and when added in initial weight loss period after LSG in obese individuals. Material and Methods Participants with BMI > 30 kg/m 2 undergoing LSG were randomised to receive either liraglutide (subcutaneous) in increasing does of 0.6 mg/day until maximum tolerated dose of 3.0 mg (L-L group) or placebo (L-P group) from 6 weeks post-operative until 6 months. Weight, BMI, %TWL, %EWL, HbA1c, fasting plasma glucose, HOMA-IR, resolution of type 2 diabetes mellitus, hypertension, dyslipidaemia, sleep apnea and quality of life were evaluated. Primary end point was %TWL and % EWL at post-operative 6 months. Results Thirty participants underwent LSG, and 23 were randomised to receive liraglutide ( n  = 12) or placebo ( n  = 11).The mean dose of liraglutide in L-L group was 1.41 ± 0.49 mg/day. Patients in L-L group had %TWL of 28.2 ± 5.7 and %EWL of 58.7 ± 14.3 as compared with 23.2 ± 6.2 ( p  = 0.116) and 44.5 ± 8.6 ( p  = 0.043) in L-P group at 24 weeks, respectively. BMI decreased by 11.7 ± 3.5 in L-L group compared with 9.5 ± 4.0 in L-P group ( p  = 0.287). All patients with diabetes or pre-diabetes had resolution of dysglycemia in the L-L group as compared with 50% in L-P group. However, there was no significant difference in resolution of other obesity-related comorbidities between two groups at 24-week follow-up. Conclusion Liraglutide added early after LSG significantly augments weight loss from LSG in obese individuals. Trial Registration The study protocol was registered at clinical trials.gov.in with NCT: 04325581.

Background and aimsCOVID-19 is likely to affect the lives of individuals with type 2 diabetes. However, the effect of COVID-19 lockdown on physical activity and glycemic control in such individuals is not known. We studied the physical activity and glycemic control during lockdown in comparison to pre-lockdown parameters in individuals with long-standing type 2 diabetes.MethodsThis prospective, observational study includes 2240 people with T2DM regularly attending diabetes clinic prior to lockdown. Glycemic record, HbA1c, and physical activity assessed with Global Physical Activity Questionnaire (GPAQ) as metabolic equivalents (MetS min/week) were obtained during lockdown (minimum duration of 3 months).ResultsA total of 422 out of 750 participants (nest) responded. The median (IQR) for age was 58 (52 to 64) years, duration of diabetes 11 (6 to 16) years, prevalent foot complications in 59.7%, and atherosclerotic cardiovascular disease in 21.3% of participants. There was a decrease in HbA1c from 7.8% (6.9 to 9.4) prior lockdown to 7.4% (6.6 to8.7) during lockdown [ΔHbA1c − 0.41 ± 0.27% (p = 0.005)] and postprandial blood glucose 200.0 mg/dl (152.0 to 252.0) to 158.0 (140.0 to 200.0) mg/dl (p < 0.001). The physical activity increased during lockdown from a GPAQ score 140 (0.0 to 1260) MetS to 840 (0.0 to 1680) MetS (p = 0.014). The improvement of glycemic control was observed in either gender and independent of the presence of foot complications or increase in physical activity.ConclusionsThere is an overall improvement of glycemic control during COVID-19 lockdown independent of increase in physical activity in people with long duration of diabetes.

This systematic review aimed to ascertain the diagnostic accuracy (sensitivity and specificity) of screening tests for early detection of type 2 diabetes and prediabetes in previously undiagnosed adults. This systematic review included published studies that included one or more index tests (random and fasting tests, HbA1c) for glucose detection, with 75-gram Oral Glucose Tolerance Test (or 2-hour post load glucose) as a reference standard (PROSPERO ID CRD42018102477). Seven databases were searched electronically (from their inception up to March 9, 2020) accompanied with bibliographic and website searches. Records were manually screened and full text were selected based on inclusion and exclusion criteria. Subsequently, data extraction was done using standardized form and quality assessment of studies using QUADAS-2 tool. Meta-analysis was done using bivariate model using Stata 14.0. Optimal cut offs in terms of sensitivity and specificity for the tests were analysed using R software. Of 7,151 records assessed by title and abstract, a total of 37 peer reviewed articles were included in this systematic review. The pooled sensitivity, specificity, positive (LR+) and negative likelihood ratio (LR-) for diagnosing diabetes with HbA1c (6.5%; venous sample; n = 17 studies) were 50% (95% CI: 42-59%), 97.3% (95% CI: 95.3-98.4), 18.32 (95% CI: 11.06-30.53) and 0.51 (95% CI: 0.43-0.60), respectively. However, the optimal cut-off for diagnosing diabetes in previously undiagnosed adults with HbA1c was estimated as 6.03% with pooled sensitivity of 73.9% (95% CI: 68-79.1%) and specificity of 87.2% (95% CI: 82-91%). The optimal cut-off for Fasting Plasma Glucose (FPG) was estimated as 104 milligram/dL (mg/dL) with a sensitivity of 82.3% (95% CI: 74.6-88.1%) and specificity of 89.4% (95% CI: 85.2-92.5%). Our findings suggest that at present recommended threshold of 6.5%, HbA1c is more specific and less sensitive in diagnosing the newly detected diabetes in undiagnosed population from community settings. Lowering of thresholds for HbA1c and FPG to 6.03% and 104 mg/dL for early detection in previously undiagnosed persons for screening purposes may be considered.

Inactivating germline mutations in the aryl hydrocarbon receptor interacting protein (AIP) gene are linked to pituitary adenoma predisposition. Here, we present the youngest known patient with AIP-related pituitary adenoma. The patient presented at the age of 4 years with pituitary apoplexy and left ptosis with severe visual loss following a 1-year history of abdominal pain, headaches, and rapid growth. His IGF-1 level was 5× the upper limit of normal, and his random GH level was 1200 ng/mL. MRI showed a 43 × 24 × 35‒mm adenoma with suprasellar extension invading the left cavernous sinus (Knosp grade 4). After transsphenoidal surgery, histology showed a grade 2A sparsely granulated somatotropinoma with negative O6-methylguanine-DNA methyltransferase and positive vascular endothelial growth factor staining. Genetic testing identified a heterozygous germline nonsense AIP mutation (p.Arg81Ter). Exome sequencing of the tumor revealed that it had lost the entire maternal chromosome-11, rendering it hemizygous for chromosome-11 and therefore lacking functional copies of AIP in the tumor. He was started on octreotide, but because the tumor rapidly regrew and IGF-1 levels were unchanged, temozolomide was initiated, and intensity-modulated radiotherapy was administered 5 months after surgery. Two months later, bevacizumab was added, resulting in excellent tumor response. Although these treatments stabilized tumor growth over 4 years, IGF-1 was normalized only after pegvisomant treatment, although access to this medication was intermittent. At 3.5 years of follow-up, gamma knife treatment was administered, and pegvisomant dose increase was indicated. Multimodal treatment with surgery, long-acting octreotide, radiotherapy, temozolomide, bevacizumab, and pegvisomant can control genetically driven, aggressive, childhood-onset somatotropinomas.

To study the pattern and prevalence of dyslipidemia in a large representative sample of four selected regions in India. Phase I of the Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study was conducted in a representative population of three states of India [Tamil Nadu, Maharashtra and Jharkhand] and one Union Territory [Chandigarh], and covered a population of 213 million people using stratified multistage sampling design to recruit individuals ≥20 years of age. All the study subjects (n = 16,607) underwent anthropometric measurements and oral glucose tolerance tests were done using capillary blood (except in self-reported diabetes). In addition, in every 5th subject (n = 2042), a fasting venous sample was collected and assayed for lipids. Dyslipidemia was diagnosed using National Cholesterol Education Programme (NCEP) guidelines. Of the subjects studied, 13.9% had hypercholesterolemia, 29.5% had hypertriglyceridemia, 72.3% had low HDL-C, 11.8% had high LDL-C levels and 79% had abnormalities in one of the lipid parameters. Regional disparity exists with the highest rates of hypercholesterolemia observed in Tamilnadu (18.3%), highest rates of hypertriglyceridemia in Chandigarh (38.6%), highest rates of low HDL-C in Jharkhand (76.8%) and highest rates of high LDL-C in Tamilnadu (15.8%). Except for low HDL-C and in the state of Maharashtra, in all other states, urban residents had the highest prevalence of lipid abnormalities compared to rural residents. Low HDL-C was the most common lipid abnormality (72.3%) in all the four regions studied; in 44.9% of subjects, it was present as an isolated abnormality. Common significant risk factors for dyslipidemia included obesity, diabetes, and dysglycemia. The prevalence of dyslipidemia is very high in India, which calls for urgent lifestyle intervention strategies to prevent and manage this important cardiovascular risk factor.

Abstract Background Corticotrophin-releasing hormone (CRH) is the major regulator of adrenocorticotrophic hormone (ACTH) secretion from the anterior pituitary and acts via CRH-1 receptors (CRH-1R). Corticotropinoma though autonomous, still retain their responsiveness to CRH and hence, we hypothesize that in vivo detection of CRH-1 receptors on pituitary adenoma using Gallium-68 (68Ga)-tagged CRH can indicate the functionality of adenoma, and combining it with positron emission tomography-computed tomography (PET-CT) can provide requisite anatomical information. Methods Subjects with ACTH-dependent Cushing’s syndrome (CS) (n = 27, 24 with Cushing’s disease [CD], 3 with ectopic CS [ECS]) underwent 68Ga CRH PET-CT. Two nuclear medicine physicians read these images for adenoma delineation and superimposed them on magnetic resonance imaging (MRI) sella. The information provided was used for intraoperative navigation and compared with operative and histopathological findings. Findings 68Ga CRH PET-CT correctly delineated corticotropinoma in all the 24 cases of CD, including the 10 cases with adenoma size < 6mm (4 cases were negative on MRI). Corticotropinoma location on 68Ga CRH PET fusion images with MRI were concordant with operative findings and were further confirmed on histopathology. There was no tracer uptake in the pituitary in 2 patients with ECS, while, in another, the diffuse uptake in pituitary suggested ectopic CRH production. Conclusion 68Ga CRH PET-CT represents a novel, noninvasive molecular imaging, targeting CRH receptors that not only delineate corticotropinoma and provides the surgeon with valuable information for intraoperative tumor navigation, but also helps in differentiating a pituitary from an extra-pituitary source of ACTH-dependent CS. Funding None.

Inflammatory osteolysis is sine-qua-non of active Charcot neuroarthropathy (CN) causing decreased foot bone mineral density (BMD) and fractures. We aimed to explore the effect of anti-inflammatory or anti-resorptive agents for effect on foot bone mineral content (BMC) and consequent long-term outcomes of foot deformities, fractures and amputation. Forty-three patients with active CN (temperature difference >2°C from normal foot) were evaluated. Patients were off-loaded with total contact cast and randomized to receive either methylprednisolone (1gm) (group A), zoledronate (5mg) (group B) or placebo (100ml normal saline) (group C) once monthly infusion for three consecutive months. Change in foot BMC was assessed at 6 months or at remission and followed subsequently up to 4 years for the incidence of new-onset fracture, deformities, or CN recurrence. Thirty-six participants (24 male, 12 female) were randomized (11 in group A, 12 group B, 13 group C). The mean age was 57.7± 9.9 years, duration of diabetes 12.3± 5.8 years and symptom duration 6.5± 2.8 weeks. BMC increased by 36% with zoledronate (p = 0.02) but reduced by 13% with methylprednisolone (p = 0.03) and 9% (p = 0.09) with placebo at remission. There were no incident foot fractures, however, two patients sustained ulcers, and 3 had new-onset or worsening deformities and none required amputation during 3.36 ± 0.89 years of follow-up. Bisphosphonate for active CN is associated with an increase in foot bone mineral content as compared to decrease with steroids or total contact cast but long-term outcomes of foot deformities, ulceration and amputation are similar. ClinicalTrials.gov: NCT03289338.

Aims/Introduction The study was carried out to assess the prevalence of diabetic peripheral neuropathy (DPN), compare the prevalence between known diabetes mellitus (KDM) and newly detected diabetes mellitus (NDDM), identify risk factors associated, its prevalence pattern and to assess if any sex‐specific differences are present. Materials and Methods A cross‐sectional study was carried out in a tertiary care hospital. Patients with duration of diabetes ≤6 months were considered to be NDDM. DPN was diagnosed by the combination of more than one abnormal result of 10‐g monofilament, pinprick sensations and ankle reflexes, and categorized according to the severity level using vibration perception threshold. The study included 1,637 KDM and 369 NDDM patients. Results A total of 586 participants were found to have DPN, accounting for 29.2% (95% confidence interval [CI] 27.2–31.2) prevalence. The higher prevalence was observed in KDM compared with NDDM 33.7% (95% CI 31.42–36.01) vs 9.2% (95% CI 6.3–12.2; P < 0.001). Prevalence of mild, moderate, and severe neuropathies was 8.06, 14.55 and 6.63%, respectively. Regression analysis showed age (P < 0.001), duration of diabetes (P < 0.001), dyslipidemia (P = 0.03), glycated hemoglobin (P < 0.001), the presence of other microvascular complications (P < 0.001), macrovascular complications (P = 0.003) and alcoholic status (P < 0.033) to be associated. No sex‐specific differences were observed in the mean age at diagnosis of diabetes, mean age at the diagnosis of neuropathy, and duration taken for the DPN development among females and males. Conclusions The study showed a high prevalence (29.2%) of DPN among north Indian type 2 diabetes mellitus patients. Thus, timely screening with earlier detection and intervention would be useful in preventing the progression of neuropathy.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes–associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10−9). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10−12) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D.