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.

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.

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.

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.

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.

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.

ASYMPTOMATIC PRIMARY HYPERPARATHYROIDISM EXISTS IN NORTH INDIA: RETROSPECTIVE DATA FROM 2 TERTIARY CARE CENTERS.

OBJECTIVE: Primary hyperparathyroidism (PHPT) has evolved into an asymptomatic disease in the west. In contrast, classic symptoms of PHPT have been reported to be common in the east. Here we describe clinical and biochemical profiles of patients diagnosed with PHPT between 2009 and 2012. METHODS: This was a retrospective study conducted at 2 tertiary care centers in north India. All patients who underwent evaluation and surgery for primary hyperparathyroidism (PHPT) from January 2009 to December 2012 were included. RESULTS: A total of 50 patients were studied between 2009 and 2012. Among them 31 (62%) were symptomatic and 19 (38%) were asymptomatic. The mean age (SD) was 48.3 (15.8) years, and the female to male ratio was 1.9:1. None of the patients had brown tumors or bone deformities. The asymptomatic group had significantly lower median adenoma weight (0.57 vs. 3.4 g, P<.05), a higher mean age (57.3 vs. 42.8 years, P<.05), and a lower median intact parathyroid hormone (iPTH) level (254.5 vs. 295 pg/mL, P<.05) compared to the symptomatic group. Adenoma weight was positively correlated with baseline serum calcium, iPTH, and alkaline phosphatase (ALP) levels. CONCLUSION: The asymptomatic form of PHPT was found in a significant percentage of north Indian patients in this study. Asymptomatic PHPT patients were older in age and had lower parathyroid adenoma weights and iPTH levels compared to symptomatic PHPT patients. Positive correlations were found between parathyroid adenoma weight and serum calcium, iPTH, and ALP levels.

Usage of pioglitazone at Medanta, the Medicity.

Pioglitazone improves glycemic control by acting as an insulin sensitizer and is used in the management of Type 2 diabetes mellitus. Pioglitazone has recently been at the center of a controversy with regards to its safety. There is no clear consensus on how, when and in what dose the drug should be used in the management of diabetes. We have summarized our strategy on pioglitazone use in Type 2 diabetes in a large private tertiary care center - Medanta, the Medicity- which may help in generating further thought about positioning of this anti-diabetic molecule. We use pioglitazone as the fourth in the pecking order of oral anti-diabetic agents. We typically use pioglitazone in a dose of 15 mg/day. We avoid using pioglitazone with insulin. We do not use pioglitazone under following situations: In the presence of significant or proven cardiac disease, in patients who are struggling with their weight or need to lose weight, in patients at high risk for osteoporotic fractures, in patients with macular edema, in patients with pre-existing bladder cancer and would discontinue in case hematuria or any other symptom of bladder cancer develops. We continue to use the drug in patients well controlled on it without any evident side-effects or contraindications.