Dapagliflozin for inpatient hyperglycemia in cardiac surgery patients with type 2 diabetes: randomised controlled trial (Dapa-Hospital trial).

AIMS: To examine the efficacy and safety of dapagliflozin in the treatment of hyperglycemia in cardiac surgery patients with type 2 diabetes (T2D). METHODS: Cardiac surgery patients with T2D (n = 250) were randomly assigned (1:1) to receive dapagliflozin plus basal-bolus insulin (DAPA group) or basal-bolus insulin alone (INSULIN group) in the early postoperative period. The primary outcome was mean difference in daily blood glucose (BG) concentrations between groups. The major safety outcomes were the occurrence of severe ketonemia/diabetic ketoacidosis (DKA) and hypoglycemia. All analyses were performed according to the intention-to-treat principle. RESULTS: The median age of the patients was 61 years (range, 55-61), and 219 (87.6%) were men. Overall, the randomization blood glucose was 165 mg/dL (SD, 37) and glycated hemoglobin was 7.7% (SD, 1.4). There were no differences in mean daily BG concentrations (149 vs. 150 mg/dL), mean percentage of readings within target BG of 70-180 mg/dL (82.7% vs. 82.5%), total daily insulin dose (mean, 39 vs. 40 units/day), number of daily insulin injections (median, 3.9 vs. 4), length of hospital stay (median, 10 vs. 10 days), or hospital complications (21.6% vs. 24.8%) between the DAPA and INSULIN groups. The mean plasma ketone levels were significantly higher in the DAPA group than in the INSULIN group at day 3 (0.71 vs. 0.30 mmol/L) and day 5 (0.42 vs. 0.19 mmol/L) of randomization. Six patients in the DAPA group developed severe ketonemia, but no patient developed DKA. There were no differences in the proportion of patients with BG < 70 mg/dL (9.6% vs. 7.2%) between the two groups. CONCLUSION: Dapagliflozin complementary to basal-bolus insulin does not improve glycemia further over and above the basal-bolus insulin alone in hospitalized cardiac surgery patients. Dapagliflozin significantly increases plasma ketones levels. Safety of dapagliflozin in hospitalized patients needs further investigation. Trial registration ClinicalTrials.gov NCT05457933.

Efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus undergoing coronary artery bypass graft surgery: A non-inferiority randomized trial.

AIMS: To compare the efficacy and safety of degludec U100 versus glargine U300 for the early postoperative management of patients with type 2 diabetes mellitus (T2D) undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 239 patients were randomly assigned (1:1) to receive a basal-bolus regimen in the early postoperative period using degludec U100 (n = 122) or glargine U300 (n = 117) as basal and glulisine before meals. The primary outcome was mean differences between groups in their daily BG concentrations. The major safety outcome was the occurrence of hypoglycemia. RESULTS: There were no differences in mean daily BG concentrations (157 vs. 162 mg/dl), mean percentage of readings within target BG of 70-180 mg/dl (74% vs. 73%), daily basal insulin dose (19 vs. 21 units/day), length of stay (median [IQR]: 9 vs. 9 days), or hospital complications (21.3% vs. 21.4%) between treatment groups. There were no differences in the proportion of patients with BG <70 mg/dl (15.6% vs. 23.1%) or <54 mg/dl (1.6% vs. 4.3%) between degludec-100 and glargine-300 groups. CONCLUSIONS: Treatment with degludec U100 is as effective and safe as glargine U300 for the early postoperative hospital management of patients with T2D undergoing CABG.

Non-alcoholic fatty liver disease-related fibrosis and sarcopenia: An altered liver-muscle crosstalk leading to increased mortality risk.

In the last few decades, the loss of skeletal muscle mass and function, known as sarcopenia, has significantly increased in prevalence, becoming a major global public health concern. On the other hand, the prevalence of non-alcoholic fatty liver disease (NAFLD) has also reached pandemic proportions, constituting the leading cause of hepatic fibrosis worldwide. Remarkably, while sarcopenia and NAFLD-related fibrosis are independently associated with all-cause mortality, the combination of both conditions entails a greater risk for all-cause and cardiac-specific mortality. Interestingly, both sarcopenia and NAFLD-related fibrosis share common pathophysiological pathways, including insulin resistance, chronic inflammation, hyperammonemia, alterations in the regulation of myokines, sex hormones and growth hormone/insulin-like growth factor-1 signaling, which may explain reciprocal connections between these two disorders. Additional contributing factors, such as the gut microbiome, may also play a role in this relationship. In skeletal muscle, phosphatidylinositol 3-kinase/Akt and myostatin signaling are the central anabolic and catabolic pathways, respectively, and the imbalance between them can lead to muscle wasting in patients with NAFLD-related fibrosis. In this review, we summarize the bidirectional influence between NAFLD-related fibrosis and sarcopenia, highlighting the main potential mechanisms involved in this complex crosstalk, and we discuss the synergistic effects of both conditions in overall and cardiovascular mortality.

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism.

Severe hypercalcemia is a medical emergency that requires immediate and aggressive management. Primary hyperparathyroidism (PHPT) often causes severe hypercalcemia. Volume resuscitation, parenteral salmon calcitonin, and administration of intravenous bisphosphonates are common measures used to stabilize patients. However, the use of these measures is inadequate in several patients and may even be contraindicated in individuals with renal insufficiency or severe systemic illness. This study demonstrated the efficacy and safety of denosumab in patients with severe hypercalcemia due to PHPT, when immediate surgery was not feasible. We present four patients with severe hypercalcemia due to PHPT. Immediate surgery was not feasible because the patients had severe systemic illness, such as seizures and altered sensorium (case 1); acute severe pancreatitis (cases 2 and 3); or coronavirus disease 2019 pneumonia (case 4). Intravenous normal saline and parenteral salmon calcitonin were inadequate for controlling hypercalcemia. Intravenous bisphosphonates were avoided because of severe systemic illness in all cases and impaired renal function in three cases. Denosumab was administered to control hypercalcemia and allow the stabilization of patients for definitive surgical management. Following denosumab administration, serum calcium levels normalized, and general condition improved in all patients. Three patients underwent parathyroidectomy after two weeks and another patient after eight weeks. The use of denosumab for the management of severe hypercalcemia due to PHPT is efficacious and safe in patients when immediate surgical management is not feasible due to severe systemic illness.

Prevalence of clinically relevant liver fibrosis due to nonalcoholic fatty liver disease in Indian individuals with type 2 diabetes.

BACKGROUND AND AIM: Type 2 diabetes (T2D) in associated with higher prevalence and worse outcomes of nonalcoholic fatty liver disease (NAFLD). However, data regarding the prevalence of clinically relevant liver fibrosis (CRLF) in Indian individuals with T2D are scarce. We investigated the prevalence of, and factors associated with, CRLF in Indians with T2D. METHODS: We conducted a prospective study of 601 consecutive adults with T2D. Steatosis was diagnosed using ultrasonography. Liver stiffness measurement (LSM) by transient elastography of ≥8.0 kPa was taken as cutoff suggesting CRLF. Individuals with LSM > 13.0 kPa underwent dynamic magnetic resonance imaging (MRI) of liver for detecting changes consistent with cirrhosis. RESULTS: The prevalence of steatosis was 84.2%. Higher body mass index (BMI, P = 0.022), alanine aminotransferase (ALT; P = 0.001), and lower high-density lipoprotein (HDL; P = 0.002) were independent factors associated with steatosis. The prevalence of CRLF was 28.2%. Higher BMI (P = 0.001), aspartate aminotransferase (AST; P < 0.0001), gamma-glutamyl transpeptidase (GGT; P < 0.0001), and concomitant hypertension (P = 0.03) were independent factors associated with CRLF. Elevated ALT and AST (≥40 units/L) levels were present in 70.6 and 51.6% individuals with CRLF, respectively. Thirty-one (7.2%) individuals had LSM > 13.0 kPa. Among them, 25 individuals underwent dynamic MRI of liver, which revealed features consistent with cirrhosis in 18 patients. CONCLUSION: CRLF, an established risk factor for cirrhosis and overall mortality, affects at least one out of four (25%) Indians with T2D. These results support screening of all patients with T2D and NAFLD for liver fibrosis.

Low skeletal muscle mass is associated with liver fibrosis in individuals with type 2 diabetes and nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Type 2 diabetes (T2D) and low skeletal muscle mass (SMM) are associated with increased risk of nonalcoholic fatty liver disease (NAFLD). However, data regarding the association between low SMM and NAFLD-related liver fibrosis in individuals with T2D are scarce. Therefore, we aimed to investigate the association between low SMM and liver fibrosis in individuals with T2D and NAFLD. METHODS: Controlled attenuation parameter (CAP) of ≥ 248 dB/m was taken as cutoff suggesting NAFLD. Clinically relevant liver fibrosis and advanced liver fibrosis were defined as liver stiffness measurement (LSM) by transient elastography (TE) of ≥ 8.0 and ≥ 9.6 kPa, respectively. SMM was measured using dual energy X-ray absorptiometry (DEXA). Low SMM was defined as appendicular SMM index of < 7.0 kg/m2 for men and < 5.4 kg/m2 for women. RESULTS: Of the 487 consecutive patients with T2D, 366 (75.1%) had NAFLD. Among individuals with NAFLD, 118 (32.2%) and 64 (17.5%) had clinically relevant liver fibrosis and advanced liver fibrosis, respectively. Low SMM was diagnosed in 78 (21.3%) individuals with NAFLD. Patients with low SMM were older (56.1 vs 52.8 years) and had longer duration of diabetes (10.3 vs 8.1 years). Low SMM was an independent risk factor associated with clinically relevant liver fibrosis (P = 0.002) and advanced liver fibrosis (P ≤ 0.0001). Associations between low SMM and clinically relevant- and advanced liver fibrosis were maintained even after sequential adjustment for confounding variables through the multivariate regression analysis. CONCLUSIONS: Low SMM is independently associated with liver fibrosis in individuals with T2D and NAFLD.

Decreased handgrip strength in patients with type 2 diabetes: A cross-sectional study in a tertiary care hospital in north India.

BACKGROUND AND AIMS: Type 2 diabetes mellitus (T2DM) has been associated with low muscle mass and strength. India has second highest number of diabetes cases worldwide. Till date, muscle mass and strength of Asian Indians with T2DM are not well studied. Aim of the study was to compare the skeletal muscle mass and muscle strength between individuals with and without T2DM. METHODS: This cross-sectional study, included subjects with T2DM, age 18-70 years and age and sex-matched individuals without diabetes (controls). Body composition was assessed using Inbody 570 body composition analyser. Hand grip strength (HGS) was measured using JAMAR's Hydraulic Hand Dynamometer. RESULTS: Total of 194 subjects (95 T2DM and 99 controls) were studied. Mean HGS (kg) was significantly lower both in men and women with diabetes compared with controls (32.4 ± 7.9 vs 37.9 ± 8.1, p = 0.001 in men and 20.6 ± 6.4 vs 23.1 ± 4.06, p = 0.02 in women). Significantly higher percentage of men and women with diabetes had sarcopenia compared with controls (44.4% vs 15.1% in men and 51% vs 20% in women). In multivariate logistic regression analysis, diabetes was an independent risk factor for low HGS in both men (OR = 6.6) and women (OR = 3.4) after adjusting for age, smoking, alcohol consumption, obesity, physical activity and dietary protein intake. CONCLUSION: HGS was significantly lower in subjects with T2DM compared with subjects without diabetes. Diabetes was an independent risk factor for low HGS.

Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis.

OBJECTIVES: To study the clinical profile and risk factors of cerebral edema and acute kidney injury in children with diabetic ketoacidosis. DESIGN: Retrospective review of medical records. PATIENTS: Fifty consecutive patients (age <18 years) admitted to our pediatric intensive care unit with a diagnosis of diabetic ketoacidosis over 5 years. MATERIALS AND METHODS: Retrospective analysis of medical records was done, and data including patients' age, sex, presenting features, biochemical profile including blood glucose, osmolality, urea, creatinine, and venous blood gas, electrolytes were recorded at admission, at 12 and 24 hours. Treatment details including fluid administration, rate of fall of glucose, time to resolution of diabetic ketoacidosis were noted. Complications such as cerebral edema and acute kidney injury were recorded. Patients with and without cerebral edema and acute kidney injury were compared. Variables that were significant on univariate analysis were entered in a multiple logistic regression analysis to determine the independent predictors for cerebral edema and acute kidney injury. Odds ratio and 95% confidence interval were calculated using SPSS version 22. MEASUREMENTS AND MAIN RESULTS: Between November 2015 and 2020, 48 patients were admitted for a total of 50 episodes of diabetic ketoacidosis. Two patients had recurrent diabetic ketoacidosis. Median age was 9.5 years (range 1-17). Thirty-one patients (62%) had new-onset type I diabetes mellitus. Twenty-two patients (44%) presented with severe diabetic ketoacidosis. Cerebral edema and acute kidney injury were seen in 11 (22%) and 15 (30%) patients, respectively. On multiple logistic regression analysis, higher blood urea level, lower serum bicarbonate level, and higher corrected sodium levels at admission were identified to be variables independently associated with risk of cerebral edema. CONCLUSIONS: Higher corrected sodium, higher urea level, and lower serum bicarbonate levels at admission are predictive of cerebral edema in patients presenting with diabetic ketoacidosis. The severity of dehydration and acidosis in DKA appears to be a common factor responsible for the development of dysfunction of both brain and kidney. HOW TO CITE THIS ARTICLE: Raghunathan V, Jevalikar G, Dhaliwal M, Singh D, Sethi SK, Kaur P, et al. Risk Factors for Cerebral Edema and Acute Kidney Injury in Children with Diabetic Ketoacidosis. Indian J Crit Care Med 2021;25(12):1446-1451.

Denosumab can be used successfully as a bridge to surgery in patients with severe hypercalcemia due to primary hyperparathyroidism

SUMMARY Severe hypercalcemia is a medical emergency that requires immediate and aggressive management. Primary hyperparathyroidism (PHPT) often causes severe hypercalcemia. Volume resuscitation, parenteral salmon calcitonin, and administration of intravenous bisphosphonates are common measures used to stabilize patients. However, the use of these measures is inadequate in several patients and may even be contraindicated in individuals with renal insufficiency or severe systemic illness. This study demonstrated the efficacy and safety of denosumab in patients with severe hypercalcemia due to PHPT, when immediate surgery was not feasible. We present four patients with severe hypercalcemia due to PHPT. Immediate surgery was not feasible because the patients had severe systemic illness, such as seizures and altered sensorium (case 1); acute severe pancreatitis (cases 2 and 3); or coronavirus disease 2019 pneumonia (case 4). Intravenous normal saline and parenteral salmon calcitonin were inadequate for controlling hypercalcemia. Intravenous bisphosphonates were avoided because of severe systemic illness in all cases and impaired renal function in three cases. Denosumab was administered to control hypercalcemia and allow the stabilization of patients for definitive surgical management. Following denosumab administration, serum calcium levels normalized, and general condition improved in all patients. Three patients underwent parathyroidectomy after two weeks and another patient after eight weeks. The use of denosumab for the management of severe hypercalcemia due to PHPT is efficacious and safe in patients when immediate surgical management is not feasible due to severe systemic illness.

Effect of dulaglutide on liver fat in patients with type 2 diabetes and NAFLD: randomised controlled trial (D-LIFT trial).

AIMS/HYPOTHESIS: Liraglutide, a daily injectable glucagon-like peptide-1 receptor (GLP-1r) agonist, has been shown to reduce liver fat content (LFC) in humans. Data regarding the effect of dulaglutide, a once-weekly GLP-1r agonist, on human LFC are scarce. This study examined the effect of dulaglutide on LFC in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). METHODS: Effect of dulaglutide on liver fat (D-LIFT) was a 24 week, open-label, parallel-group, randomised controlled trial to determine the effect of dulaglutide on liver fat at a tertiary care centre in India. Adults (n = 64), who had type 2 diabetes and MRI-derived proton density fat fraction-assessed LFC of ≥6.0% at baseline, were randomly assigned to receive dulaglutide weekly for 24 weeks (add-on to usual care) or usual care, based on a predefined computer-generated number with a 1:1 allocation that was concealed using serially numbered, opaque, sealed envelopes. The primary endpoint was the difference of the change in LFC from 0 (baseline) to 24 weeks between groups. The secondary outcome measures included the difference of the change in pancreatic fat content (PFC), change in liver stiffness measurement (LSM in kPa) measured by vibration-controlled transient elastography, and change in liver enzymes. RESULTS: Eighty-eight patients were screened; 32 were randomly assigned to the dulaglutide group and 32 to the control group. Overall, 52 participants were included for per-protocol analysis: those who had MRI-PDFF data at baseline and week 24. Dulaglutide treatment resulted in a control-corrected absolute change in LFC of -3.5% (95% CI -6.6, -0.4; p = 0.025) and relative change of -26.4% (-44.2, -8.6; p = 0.004), corresponding to a 2.6-fold greater reduction. Dulaglutide-treated participants also showed a significant reduction in γ-glutamyl transpeptidase (GGT) levels (mean between-group difference -13.1 U/l [95% CI -24.4, -1.8]; p = 0.025) and non-significant reductions in aspartate aminotransferase (AST) (-9.3 U/l [-19.5, 1.0]; p = 0.075) and alanine aminotransferase (ALT) levels (-13.1 U/l [-24.4, 2.5]; p = 0.10). Absolute changes in PFC (-1.4% [-3.2, 0.3]; p = 0.106) and LSM (-1.31 kPa [-2.99, 0.37]; p = 0.123) were not significant when comparing the two groups. There were no serious drug-related adverse events. CONCLUSIONS/INTERPRETATION: When included in the standard treatment for type 2 diabetes, dulaglutide significantly reduces LFC and improves GGT levels in participants with NAFLD. There were non-significant reductions in PFC, liver stiffness, serum AST and serum ALT levels. Dulaglutide could be considered for the early treatment of NAFLD in patients with type 2 diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03590626 FUNDING: The current study was supported by an investigator-initiated study grant from Medanta-The Medicity's departmental research fund and a grant from the Endocrine and Diabetes Foundation (EDF), India. Graphical abstract.

Anticancer Drug-induced Thyroid Dysfunction.

Cancer immunotherapy and targeted therapy, though less toxic than conventional chemotherapy, can increase the risk of thyroid dysfunction. Immune checkpoint inhibitors render the cancer cells susceptible to immune destruction, but also predispose to autoimmune disorders like primary hypothyroidism as well as central hypothyroidism secondary to hypophysitis. Tyrosine kinase inhibitors act by blocking vascular endothelial growth factor receptors and their downstream targets. Disruption of the vascular supply from the inhibition of endothelial proliferation damages not only cancer cells but also organs with high vascularity like the thyroid. Interferon-α, interleukin-2 and thalidomide analogues can cause thyroid dysfunction by immune modulation. Alemtuzumab, a monoclonal antibody directed against the cell surface glycoprotein CD52 causes Graves' disease during immune reconstitution. Metaiodobenzylguanidine, combined with 131-iodine, administered as a radiotherapeutic agent for tumours derived from neural crest cells, can cause primary hypothyroidism. Bexarotene can produce transient central hypothyroidism by altering the feedback effect of thyroid hormone on the pituitary gland. Thyroid dysfunction can be managed in the usual manner without a requirement for dose reduction or discontinuation of the implicated agent. This review aims to highlight the effect of various anticancer agents on thyroid function. Early recognition and appropriate management of thyroid disorders during cancer therapy will help to improve treatment outcomes.

Increased prevalence of self-reported fractures in Asian Indians with diabetes: Results from the ICMR-INDIAB population based cross-sectional study.

BACKGROUND: Diabetes mellitus (DM), has been associated with increased fracture risk. However, there are no data pertaining to the prevalence of fractures for patients with DM in India. The aim of this study was to determine the prevalence of fractures in Asian Indians with and without diabetes. METHODS: The study used the data of Indian Council of Medical Research-India Diabetes (ICMR-INDIAB) study, a community- based cross sectional survey conceived with the aim of obtaining the prevalence rates of diabetes in India as a whole. A community-based sample of 57,117 individuals aged ≥20 years was obtained. Diabetes was diagnosed by oral glucose tolerance test using capillary blood (except in self-reported diabetes). Fractures were self-reported. RESULTS: Fracture data were available in 54,093 subjects. Out of these, 1416 (2.6%) had fractures. Overall prevalence of diabetes and prediabetes was 7.1% and 10.5% respectively. Prevalence of fractures was significantly higher in diabetes group (4%) compared with non-diabetes group (2.5%). In multivariate logistic regression analysis, diabetes was associated with an increased risk (1) of any fracture (OR=1.28, 95% CI: 1.07-1.5) and (2) of low trauma fracture (hip and spine combined) (OR = 1.8, 95% CI:1.1-2.8). After gender stratification, diabetes was a risk factor for fracture only in women. Age (>40 years) in women, high waist circumference (>90 cm) in men, alcohol consumption and urban residence in both men and women were other significant contributors to fracture risk. CONCLUSION: Increased prevalence of self-reported fractures was seen in individuals with diabetes in this population-based study from India.

EFFECT OF GLUTEN-FREE DIET ON METABOLIC CONTROL AND ANTHROPOMETRIC PARAMETERS IN TYPE 1 DIABETES WITH SUBCLINICAL CELIAC DISEASE: A RANDOMIZED CONTROLLED TRIAL.

Objective: It is unclear whether the institution of gluten-free diet (GFD) is beneficial in patients with type 1 diabetes (T1DM) and subclinical celiac disease (CD). Our primary objective was to evaluate the effect of GFD on the frequency of hypoglycemia, in patients with T1DM and subclinical CD. Our secondary objective was to investigate the effect of GFD on height, weight, glycosylated hemoglobin (HbA1c), insulin dose requirement, and bone mineral homeostasis. Methods: We carried out a prospective open label randomized controlled trial (RCT). Patients with T1DM and subclinical CD were randomized to receive GFD or a normal diet for 1 year. The primary outcome was the frequency of hypoglycemic episodes (blood glucose <70 mg/dL) measured by self-monitoring of blood glucose (SMBG) at the sixth month of the study in the 2 groups. Results: Screening for CD was carried out in 320 T1DM patients. Thirty eligible patients were randomized to receive GFD (n = 15) or a normal diet (n = 15). The mean number of hypoglycemic episodes/month recorded by SMBG and the mean time spent in hypoglycemia measured by CGM (minutes) in the GFD group versus the non-GFD group at six months was 2.3 minutes versus 3.4 minutes (P = .5) and 124.1 minutes versus 356.9 minutes (P = .1), respectively. The mean number of hypoglycemic episodes/month significantly declined in the GFD group (3.5 episodes at baseline versus 2.3 episodes at the sixth month; P = .03). The mean HbA1c declined by 0.73% in the GFD group and rose by 0.99% in non-GFD group at study completion. Conclusion: This is the first RCT to assess the effect of GFD in T1DM and subclinical CD. A trend towards a decrease in hypoglycemic episodes and better glycemic control was seen in patients receiving GFD. Abbreviations: BMC = bone mineral content; BMI = body mass index; CD = celiac disease; CGM = continuous glucose monitoring; GFD = gluten-free diet; Hb = hemoglobin; HbA1c = glycosylated hemoglobin; iPTH = intact parathyroid hormone; RCT = randomized controlled trial; SMBG = self-monitoring of blood glucose; T1DM = type 1 diabetes mellitus; tTG-IgA = tissue transglutaminase immunoglobulin A.

Adverse Effect Profile and Effectiveness of Sodium Glucose Co-transporter 2 Inhibitors (SGLT2i) - A Prospective Real-world Setting Study.

BACKGROUND: Clinical trials have shown promising results in terms of glycemic control and weight reduction with the use of sodium glucose co-transporter 2 inhibitors (SGLT2i) in type 2 diabetes mellitus (T2DM). However, real-world evidence from standard clinical practice especially from Asia is still limited. The aim of this study was to evaluate the safety and effectiveness of SGLT2i in patients with T2DM in real-world setting. METHODS: This was a prospective observational longitudinal study involving consecutive patients with T2DM, initiated on SGLT2i from 1 April 2015 to 31 March 2016. The adverse effects and metabolic parameters were evaluated at 3 monthly intervals up to 1 year. RESULTS: Total 486 patients were initiated on SGLT2i. At baseline, mean age, glycosylated haemoglobin (HbA1c), and weight was 51.03 ± 9.82 years, 8.76 ± 1.59%, and 89.32 ± 16.04 kg, respectively. Data of 388 patients were available at 6 months of follow-up for analysis of adverse effects profile. About 38.6% patients experienced adverse effects. Genitourinary tract infection was the most common adverse effect (20.6%) followed by generalized weakness (10.5%). Significant reduction in mean weight and HbA1c reduction seen at 6 months (n = 202): 3.2 kg and 1.26%, respectively, and at 12 months (n = 104): 3.9 kg and 1.27%, respectively. CONCLUSION: In this real-world study of patients with T2DM living in hot climate, use of SGLT2i was associated with adverse effects in higher proportion of patients than those reported in clinical trials, but effectiveness was comparable. Patient guidance regarding adequate hydration and hygiene can maximize the benefits of this promising class of drugs.

Effect of Empagliflozin on Liver Fat in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease: A Randomized Controlled Trial (E-LIFT Trial).

OBJECTIVE: Sodium-glucose cotransporter 2 (SGLT-2) inhibitors have been shown to reduce liver fat in rodent models. Data regarding the effect of SGLT-2 inhibitors on human liver fat are scarce. This study examined the effect of empagliflozin (an SGLT-2 inhibitor) on liver fat in patients with type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) by using MRI-derived proton density fat fraction (MRI-PDFF). RESEARCH DESIGN AND METHODS: Fifty patients with type 2 diabetes and NAFLD were randomly assigned to either the empagliflozin group (standard treatment for type 2 diabetes plus empagliflozin 10 mg daily) or the control group (standard treatment without empagliflozin) for 20 weeks. Change in liver fat was measured by MRI-PDFF. Secondary outcome measures were change in alanine transaminase (ALT), aspartate transaminase (AST), and γ-glutamyl transferase (GGT) levels. RESULTS: When included in the standard treatment for type 2 diabetes, empagliflozin was significantly better at reducing liver fat (mean MRI-PDFF difference between the empagliflozin and control groups -4.0%; P < 0.0001). Compared with baseline, significant reduction was found in the end-of-treatment MRI-PDFF for the empagliflozin group (16.2% to 11.3%; P < 0.0001) and a nonsignificant change was found in the control group (16.4% to 15.5%; P = 0.057). The two groups showed a significant difference for change in serum ALT level (P = 0.005) and nonsignificant differences for AST (P = 0.212) and GGT (P = 0.057) levels. CONCLUSIONS: When included in the standard treatment for type 2 diabetes, empagliflozin reduces liver fat and improves ALT levels in patients with type 2 diabetes and NAFLD.

The changing profile of hypercalcemia in a tertiary care setting in North India: an 18-month retrospective study.

This retrospective study was undertaken to determine the profile of hypercalcemia in all patients who presented to Medanta-The Medicity, a tertiary care hospital in North India. A total of 255,830 patients presented to the hospital during 1st January 2014 till 30th June 2015 (18 months). Among them calcium measurement was done in 26,297 (10.2%) patients. A total of 552 patients was found to have hypercalcemia. Among them, 15 (2.7%) patients had transient hypercalcemia and 537 (97.3%) had sustained hypercalcemia. The incidence of hypercalcemia was 2.09%, being transient in 0.05% and sustained in 2.04%. The most common causes in the sustained group were malignancy (23.1%) followed by primary hyperparathyroidism (PHPT, 21.9%). Most cases of PHPT were asymptomatic. Interestingly, we found emergence of two unusual groups of hypercalcemia, namely hypercalcemia of advanced chronic liver disease (n = 34) and vitamin D toxicosis (n = 21) in the non-parathyroid group of hypercalcemia. This changing pattern of hypercalcemia should be kept in mind while evaluating a patient of hypercalcemia in a hospital setting.

Long-term efficacy of liraglutide in Indian patients with Type 2 diabetes in a real-world setting.

BACKGROUND: Long-term efficacy of liraglutide, a glucagon-like peptide-1 analog, on body weight and glycemic control has not been studied in Indian Type 2 diabetes mellitus (T2DM) subjects. AIM: To evaluate the effect of liraglutide on glycemic control and body weight for 1 year in Indian T2DM patients. METHODS: Liraglutide was prescribed to 96 obese patients with T2DM and followed up for 1 year. Clinical parameters were measured at baseline and 3, 6, 9, and 12 months. Dosage of liraglutide and other medications was adjusted according to clinical judgment. RESULTS: 1 year data were available for 74 patients. Mean age was 50.9 ± 9.6 years. Mean duration of diabetes was 11.6 ± 6.3 years. Glycosylated hemoglobin (HbA1c) significantly decreased from 8.9 ± 1.3% at baseline to 7.4 ± 1.2% at 1 year. Body weight significantly declined from 98.9 ± 16.0 kg at baseline to 93.8 ± 15.0 kg at 1 year. After an initial decline, subset of patients had an increase in mean HbA1c (n = 30/74) and mean body weight (n = 33/74) after 6 months of liraglutide initiation. Baseline HbA1c and baseline body weight were positively associated with a reduction of HbA1c and body weight at 1 year, respectively. No major side effects occurred. CONCLUSION: Liraglutide treatment resulted in a significant and sustained reduction in HbA1c and body weight over 1 year in Indian T2DM patients. Magnitude of reduction of HbA1c and body weight at 1 year was positively associated with baseline HbA1c and baseline weight, respectively.

Impact of preoperative imaging on surgical approach for primary hyperparathyroidism: Data from single institution in India.

CONTEXT: Preoperative localization of parathyroid adenoma is essential in deciding the surgical approach of parathyroidectomy. AIM: To describe clinical and biochemical profile, evaluate preoperative imaging modalities and surgical approach in patients with primary hyperparathyroidism (PHPT). METHODOLOGY: This was a retrospective study conducted at the single institution. All patients who underwent evaluation and surgery for PHPT from 2011 to 2015 were included in the study. RESULTS: A total of 100 patients underwent surgery for PHPT. Mean (standard deviation) age was 51.6 (15.9) years with female to male ratio of 1.7:1. Forty patients had severe symptoms, and sixty had mild to moderate symptoms. The sensitivity of technetium-99m hexakis (2-methoxyisobutylisonitrile) (MIBI) scan and ultrasonography (USG) neck in identifying abnormal parathyroid gland was 93% (93/100) and 98% (98/100), respectively. The MIBI scan results of 90/93 (96.7%) patients corresponded with their surgical findings whereas preoperative USG findings of 96/98 patients (98%) showed correlation with operative findings. Intraoperative intact parathyroid hormone (IOPTH) levels at 10 min postexcision were measured in forty patients (minimally invasive parathyroidectomy = 38, bilateral neck exploration = 1, and unilateral neck exploration = 1). All patients except two had <50% fall in IOPTH. Adenoma weight was positively correlated with preoperative intact PTH. CONCLUSION: We found that USG has higher sensitivity (98%) than MIBI scan (93%) in localizing abnormal parathyroid gland. Moreover, USG had a higher preoperative localization accuracy (93%) than MIBI scan (90%), allowing to choose an appropriate surgical approach. A higher proportion of patients (60%) had mild/asymptomatic form of PHPT.

Childhood and Youth Onset Diabetes: A Single Centre Experience.

OBJECTIVES: To identify proportion of various types of diabetes and differences between type 1 and type 2 diabetes in patients with youth onset diabetes (onset below 25 completed years of age). In addition, concurrent autoimmune diseases in type 1 diabetes were studied in a subset of patients. METHODS: A total of 577 patients (192 girls) with diabetes onset at median age of 14 y (range 1 mo-25 y) with median duration of 1 y (range day of diagnosis- 43 y) were included. Clinical details, investigations and complications were recorded in a proforma. Diabetes was classified using clinical criteria supported by laboratory tests of C peptide and anti GAD-65 antibody in a subset of patients. RESULTS: Type 1 diabetes accounted for 368/421 (87.4 %) patients with age of onset <18 y and 99/156 (63.5 %) of patients with onset between 19 and 25 y of age. Proportion of type 2 diabetes was 36/421 (8.5 %) and 41/156 (26.2 %) in these two groups. Older age at onset, diabetes in one or both parents, absence of ketosis /weight loss and presence of acanthosis were significant predictors of type 2 diabetes. Hypothyroidism (TSH >10) and biopsy proven celiac disease was found in 11.6 and 9.7 % of type 1 diabetes patients respectively. CONCLUSIONS: Type 1 diabetes is the most common type of diabetes in youth, however, a significant proportion of youth have type 2 diabetes. In these patients a combination of clinical factors, biochemical parameters and course over few months helps to guide the diagnosis.

Vitamin D toxicity resulting from overzealous correction of vitamin D deficiency.

BACKGROUND: Vitamin D toxicity, often considered rare, can be life-threatening and associated with substantial morbidity, if not identified promptly. OBJECTIVE: To describe clinical and biochemical features, risk factors and management of patients with vitamin D toxicity seen between January 2011 and January 2013. METHODOLOGY: Patients presenting with vitamin D toxicity, between January 2011 and January 2013, at single tertiary care centre in Delhi-NCR, India, were included. Evaluation included detailed clinical history and biochemical tests including serum calcium, phosphorus, creatinine, intact parathyroid hormone and 25-hydroxyvitamin D (25(OH)D). RESULTS: Sixteen patients with vitamin D toxicity could be identified. Clinical manifestations included nausea, vomiting, altered sensorium, constipation, pancreatitis, acute kidney injury and weight loss. Median (range) age was 64·5 (42-86) years. Median (range) serum 25(OH)D level and median (range) serum total serum calcium level were 371 (175-1161) ng/ml and 13·0 (11·1-15·7) mg/dl, respectively. Overdose of vitamin D caused by prescription of mega-doses of vitamin D was the cause of vitamin D toxicity in all cases. Median (range) cumulative vitamin D dose was 3,600,000 (2,220,000-6,360,000) IU. CONCLUSION: Our data demonstrate an emergence of vitamin D toxicity as an increasingly common cause of symptomatic hypercalcaemia. Irrational use of vitamin D in mega-doses resulted in vitamin D toxicity in all cases. Awareness among healthcare providers regarding the toxic potential of high doses of vitamin D and cautious use of vitamin D supplements is the key to prevent this condition.