Aims Impaired awareness of hypoglycemia (IAH) is a limiting factor in the treatment of type 1 diabetes (T1D) and is a challenging condition to reverse. The objective of this study was to test the hypothesis that naltrexone therapy in subjects with T1D and IAH will improve counterregulatory hormone response and recognition of hypoglycemia symptoms during hypoglycemia. Methods We performed a pilot randomized double blind trial of 4 weeks of naltrexone therapy (n=10) or placebo (n=12) given orally in subjects with T1D and IAH. Outcome measures included hypoglycemia symptom scores, counterregulatory hormone levels and thalamic activation as measured by cerebral blood flow using MRI during experimental hypoglycemia in all subjects before and after 4 weeks of intervention. Results After 4 weeks of therapy with naltrexone or placebo, no significant differences in response to hypoglycemia were seen in any outcomes of interest within each group. Conclusions In this small study, short-term treatment with naltrexone did not improve recognition of hypoglycemia symptoms or counterregulatory hormone response during experimental hypoglycemia in subjects with T1D and IAH. Whether this lack of effect is related to the small sample size or due to the dose, the advanced stage of study population or the drug itself should be the subject of future investigation.

Glucose transport kinetics in the hypothalamus of healthy humans with experimentally induced HAAF were not different from those measured without HAAF. Future studies of patients with diabetes and impaired awareness of hypoglycemia will be necessary to determine if the existence of the diabetes state is required for this adaptation to hypoglycemia to occur.

Supercompensated brain glycogen levels may contribute to the development of hypoglycemia-associated autonomic failure (HAAF) following recurrent hypoglycemia (RH) by providing energy for the brain during subsequent periods of hypoglycemia. To assess the role of glycogen supercompensation in the generation of HAAF, we estimated the level of brain glycogen following RH and acute hypoglycemia (AH). After undergoing 3 hyperinsulinemic, euglycemic and 3 hyperinsulinemic, hypoglycemic clamps (RH) on separate occasions at least 1 month apart, five healthy volunteers received [1-C]glucose intravenously over 80+ h while maintaining euglycemia. C-glycogen levels in the occipital lobe were measured byC magnetic resonance spectroscopy at ∼8, 20, 32, 44, 56, 68 and 80 h at 4 T and glycogen levels estimated by fitting the data with a biophysical model that takes into account the tiered glycogen structure. Similarly, prior C-glycogen data obtained following a single hypoglycemic episode (AH) were fitted with the same model. Glycogen levels did not significantly increase after RH relative to after euglycemia, while they increased by ∼16% after AH relative to after euglycemia. These data suggest that glycogen supercompensation may be blunted with repeated hypoglycemic episodes. A causal relationship between glycogen supercompensation and generation of HAAF remains to be established.

Introduction: Despite mounting evidence that increased frequency and duration of hemodialysis (HD) improves outcomes, less than 1% of HD patients worldwide receive nocturnal hemodialysis (NHD). Many perceived barriers exist to providing NHD and increasing its provision.Methods: A retrospective analysis of nocturnal therapy using a low-flow dialysate system in 4 European centers for a minimum of 12 months, with data collected on patient demographics, training times, safety features, medications, and biochemical parameters at baseline and at 6 and 12 months.Findings: Data were collected on 21 patients, with 12-month analysis available for 20 patients. Mean dialysis duration was 28 hours per week, with most dialysis on an alternate night regimen using 50-60 L of dialysate per session. All vascular access types were represented, and low molecular weight heparin was used as a bolus. All biochemical parameters met European standards, with a trend for improvement in standardized Kt/V, phosphate, hemoglobin, and albumin. There was a significant reduction in phosphate binder usage and a reduction in blood pressure medication. Training time was 9.6 sessions for independence at home, with 2 additional sessions to transition to NHD. Additional safety features included an alarmed drip tray under the cycler and moisture sensors under the venous needle (all patients used dual-cannulation technique). No patient safety events were reported.Discussion: These data support the use of a low-flow dialysate system for provision of NHD at home. Biochemical parameters were good, medication burden was reduced at 12 months, and all patients received more than double the duration of HD provided in standard in-center units. While patient numbers were small, low-flow dialysis in this cohort was both effective and safe. Use of this alternative HD system could reduce some of the barriers to NHD, increasing the uptake of therapy in Europe, and improving long-term patient outcomes.

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Background: The dialysis patient population in the United States continues to grow. Trends in rates of death and hospitalization among dialysis patients have important consequences for outpatient dialysis capacity and Medicare spending. Objectives: To estimate contemporary trends in rates of death and hospitalization among dialysis patients in the United States, overall and within subgroups. Methods: We used Medicare Limited Data Sets (100% sample) in 2014–2017 to estimate trends in rates of death and hospitalization among dialysis patients with Medicare Parts A and B enrollment. We used seasonal autoregressive integrated moving average models to identify secular trends in the incidence of outcomes. Results: There were 631,075 unique patients; 222,924 deaths; and 1,876,779 hospital admissions. Weekly risks of both death and hospitalization exhibited strong seasonality. However, overall weekly risks of death were 34.9, 35.4, 35.2, and 35.7 deaths per 10,000 patients in 2014–2017, respectively (p = 0.47, from a likelihood ratio test of secular trend). The overall weekly risk of hospitalization was 3.08, 3.05, 3.11, and 3.11% in 2014, 2015, 2016, and 2017, respectively (p = 0.30). There were significant secular trends in risk of death in subgroups defined by black race and residency in South Atlantic states (p < 0.05). There were also secular trends in risk of hospitalization in subgroups defined by age 20–44 years, concurrent enrollment in Medicaid, and residency in South Central states. Conclusion: For the first time since the beginning of this century, rates of both death and hospitalization among dialysis patients with Medicare fee-for-service coverage have stagnated. The reasons for this change are unknown and require detailed assessment. Persistent lack of change in clinical outcomes may alter the future expectations about dialysis patient population growth.

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At the 56th European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) Congress, held in June 2019 in Budapest, Hungary, physicians from the USA, UK, and Spain presented an educational symposium entitled ‘Survival After End-Stage Renal Failure: Preventing Cardiac Death in End-Stage Renal Disease Patients.’ During this symposium, physicians discussed concepts underlying dialysis as a chronic cardiovascular disease state; cardiovascular disease challenges with volume overload, hypertension, and heart failure; the challenge of fluid management in intermittent haemodialysis; and the effect of more frequent therapy on volume and symptom control. This review summarises the symposium.