Hypoglycemic and Hyperglycemic Crises Among U.S. Adults With Diabetes and End-stage Kidney Disease: Population-Based Study, 2013–2017

<b>Objective</b>: We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (DM/ESKD). <p> </p> <p><b>Design</b>: Nationwide, retrospective study of adults (≥18 years) with DM/ESKD, from the United States Renal Data System registry, 2013 to 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1000 person-years. Adjusted event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen and U.S. region.</p> <p> </p> <p><b>Results</b>: Among 521,789 adults with DM/ESKD (median age 65 years [IQR 57-73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, the risks decreased with age and were lowest in older patients (≥75 vs 18-44 years: IRR 0.35 [95% CI 0.33-0.37] and 0.03 [0.02-0.03], women (IRR 1.09 [1.06-1.12] and 1.44 [1.35-1.54]), and with smoking (IRR 1.36 [1.28-1.43] and 1.71 [1.53-1.91]), substance abuse (IRR 1.27 [1.15-1.42] and 1.53 [1.23-1.9]), retinopathy (IRR 1.10 [1.06-1.15] and 1.36 [1.26-1.47]), and insulin therapy (vs. no therapy; IRR 0.60 [0.59-0.63] and 0.44 [0.39-0.48]), respectively. For hypoglycemia, specifically, additional risk was conferred by Black race (IRR 1.11 [1.08-1.15]) and amputation history (IRR 1.20 [1.13-1.27]).</p> <p> </p> <p><b>Conclusions</b>: In this nationwide study of patients with DM/ESKD, hypoglycemic crises were three-fold more common than hyperglycemic crises, greatly exceeding national reports in non-dialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected. </p>

Hypoglycemic and Hyperglycemic Crises Among U.S. Adults With Diabetes and End-stage Kidney Disease: Population-Based Study, 2013–2017

<b>Objective</b>: We characterized annual trends of severe hypoglycemic and hyperglycemic crises (diabetic ketoacidosis/hyperglycemic hyperosmolar state) in patients with diabetes and end-stage kidney disease (DM/ESKD). <p> </p> <p><b>Design</b>: Nationwide, retrospective study of adults (≥18 years) with DM/ESKD, from the United States Renal Data System registry, 2013 to 2017. Primary outcome was annual rates of emergency department visits or hospitalizations for hypoglycemic and hyperglycemic crises, reported as number of events/1000 person-years. Adjusted event rates and risk factors were adjusted for patient age, sex, race/ethnicity, dialysis modality, comorbidities, treatment regimen and U.S. region.</p> <p> </p> <p><b>Results</b>: Among 521,789 adults with DM/ESKD (median age 65 years [IQR 57-73], 56.1% male, and 46% White), overall adjusted rates of hypoglycemic and hyperglycemic crises were 53.64 and 18.24 per 1000 person-years, respectively. For both hypoglycemia and hyperglycemia crises, the risks decreased with age and were lowest in older patients (≥75 vs 18-44 years: IRR 0.35 [95% CI 0.33-0.37] and 0.03 [0.02-0.03], women (IRR 1.09 [1.06-1.12] and 1.44 [1.35-1.54]), and with smoking (IRR 1.36 [1.28-1.43] and 1.71 [1.53-1.91]), substance abuse (IRR 1.27 [1.15-1.42] and 1.53 [1.23-1.9]), retinopathy (IRR 1.10 [1.06-1.15] and 1.36 [1.26-1.47]), and insulin therapy (vs. no therapy; IRR 0.60 [0.59-0.63] and 0.44 [0.39-0.48]), respectively. For hypoglycemia, specifically, additional risk was conferred by Black race (IRR 1.11 [1.08-1.15]) and amputation history (IRR 1.20 [1.13-1.27]).</p> <p> </p> <p><b>Conclusions</b>: In this nationwide study of patients with DM/ESKD, hypoglycemic crises were three-fold more common than hyperglycemic crises, greatly exceeding national reports in non-dialysis patients with chronic kidney disease. Young, Black, and female patients were disproportionately affected. </p>

An extremely high blood glucose level in a child with hyperglycemic hyperosmolar state and type 1 diabetes

Objectives Hyperglycemic hyperosmolar state (HHS) is one of the most severe acute complications of diabetes mellitus (DM) characterized by severe hyperglycemia and hyperosmolality without significant ketosis and acidosis. What is new? Since HHS in the pediatric population is rare and potentially life-threatening, every reported case is very valuable for raising awareness among healthcare professionals. Case presentation A 7-year-old boy with previously diagnosed Joubert syndrome was admitted due to vomiting, polydipsia and polyuria started several days earlier. He was severely dehydrated, and the initial blood glucose level was 115 mmol/L. Based on clinical manifestations and laboratory results, he was diagnosed with T1DM and HHS. The treatment with intravenous fluid was started and insulin administration began later. He was discharged after 10 days without any complications related to HHS. Conclusions Since HHS has a high mortality rate, early recognition, and proper management are necessary for a better outcome.

Capecitabine-Induced Hyperosmolar Hyperglycemic State

Capecitabine is an orally administered prodrug of 5-fluorouracil (5-FU) which is often used for treatment of solid tumour cancers such as breast cancer and gastrointestinal tumours. Common adverse effects include nausea, diarrhea, anorexia and erythrodysthesia (hand-foot syndrome). However, there have been case reports of metabolic disturbances linked to capecitabine including hyperlipidemia, and less commonly, hyperglycemia. We report a case of a new diagnosis of persistent diabetes mellitus following an acute presentation of hyperosmolar hyperglycemic syndrome (HHS) subsequent to treatment with the chemotherapy agent, capecitabine. A 72 year old female with a history of metastatic breast cancer was admitted to hospital for management of hyperglycemic hyperosmolar state (HHS) after bloodwork from her family doctor revealed an elevated random blood glucose (40.2 mmol/L). Leading up to her presentation, the patient had completed 7 cycles of capecitabine treatment for her breast cancer. Prior to her capecitabine treatment, the patient did not have a history of diabetes mellitus. However, on admission, her hemoglobin A1C (HbA1C) was found to elevated into the diabetic range. Offending medications were considered and given the temporal dysglycemia following the patient’s chemotherapy regimen, capecitabine was thought to be a probable offending agent. The patient was acutely treated for HHS, and eventually transitioned to a basal-bolus insulin regimen at discharge. Her capecitabine was held pending review with her oncology team and she was closely followed up by her family doctor. The patient’s insulin regimen was ultimately titrated down to basal insulin only. Given the increasing use of capecitabine therapy in breast cancer, it is important to recognize the risk of hyperglycemia and hyperglycemic emergencies as a potential adverse effect of this treatment. It highlights the need to ensure that blood glucose is monitored throughout treatment to prevent hyperglycemic emergencies.

A Case Series of Hyperglycemic Hyperosmolar State During the Global COVID-19 Pandemic

Hyperglycemic hyperosmolar state (HHS) is rare in pediatrics, particularly in patients with antibody positive diabetes mellitus (DM). Recent literature has implicated COVID-19 in the reported increase in new-onset DM cases, as well as mixed diabetic ketoacidosis (DKA) and HHS cases, however a rise in HHS cases alone has not been well reported [1,2]. We noted an anecdotal increase in the frequency of HHS cases in our pediatric tertiary care center following the onset of the global COVID-19 pandemic. To investigate further, a retrospective chart review evaluating all patients with DM admitted in the first 6 months of 2019 and the first 6 months of 2020 was conducted. A diagnosis of HHS was defined as a blood glucose over 600 mg/dL with a serum osmolality (calculated or measured) greater than 320 mOsm/kg on initial laboratory evaluation. Patients with DKA, defined as a serum bicarbonate level less than 16 mmol/L with evidence of significant ketosis (serum ketones greater than 3 mmol/L), were excluded from the study. During the first 6 months of 2019, 1 patient met inclusion criteria. However, the diagnosis of HHS was complicated by a concurrent diagnosis of diabetes insipidus, which may have contributed to the hyperosmolar state, and a nonketotic lactic acidosis. Five HHS cases were noted in the first 6 months of 2020, 4 of which occurred in May and June. For the 2020 HHS cohort, the average patient age ± SD was 12 ± 3.34 years. The mean ± SD laboratory values included bicarbonate 18.2 ± 1.64 mmol/L, serum blood glucose 776.8 ± 30.75 mg/dL, calculated serum osmolality 328 ± 4.18 mOsm/kg, and HgA1C 12.72 ± 1.16%. All 5 patients in the 2020 cohort had new-onset DM, with 4 of the 5 patients having at least 1 positive DM antibody (GAD antibodies were positive in 3, ICA/IA-2 antibodies in 2, and Zinc Transporter 8 antibodies in 1). No patients displayed COVID-19 symptoms, and only 1 patient was tested for COVID-19 by PCR, which returned negative. However, SARS-CoV2 antibody testing was not available, and it is unknown if these patients had prior COVID-19 illness. In conclusion, we noted an increased incidence of HHS at our hospital, particularly among new-onset, antibody positive DM patients during the initial months of the COVID-19 pandemic. Further study and investigation are needed to determine the cause of this increased local incidence, and if infectious, social, or economic influences related to the COVID-19 pandemic contributed. References: [1] Chan, K.H., et al., Clinical characteristics and outcome in patients with combined diabetic ketoacidosis and hyperosmolar hyperglycemic state associated with COVID-19: A retrospective, hospital-based observational case series. Diabetes Res Clin Pract, 2020. 166: p. 108279. [2] Unsworth, R., et al., New-Onset Type 1 Diabetes in Children During COVID-19: Multicenter Regional Findings in the U.K. Diabetes Care, 2020.