Search

Introduction Hypoglycemia is a major limiting factor in achieving recommended glycemic targets for people with type 1 diabetes. Exposure to recurrent hypoglycemia results in blunted hormonal counter-regulatory and symptomatic responses to hypoglycemia. Limited data on metabolic adaptation to recurrent hypoglycemia are available. This study examined the acute metabolic responses to hypoglycemia and the effect of antecedent hypoglycemia on these responses in type 1 diabetes. Research design and methods Twenty-one outpatients with type 1 diabetes with normal or impaired awareness of hypoglycemia participated in a study assessing the response to hypoglycemia on 2 consecutive days by a hyperinsulinemic glucose clamp. Participants underwent a period of normoglycemia and a period of hypoglycemia during the hyperinsulinemic glucose clamp. Plasma samples were taken during normoglycemia and at the beginning and the end of the hypoglycemic period. Metabolomic analysis of the plasma samples was conducted using comprehensive two-dimensional gas chromatography with time-of-flight mass spectrometry. Results In total, 68 metabolites were studied. On day 1, concentrations of the branched-chain amino acids, leucine (p=3.8×10 -3) and isoleucine (p=2.2×10 -3), decreased during hypoglycemia. On day 2, during hypoglycemia, five amino acids (including leucine and isoleucine) significantly decreased, and two fatty acids (tetradecanoic and oleic acids) significantly increased (p<0.05). Although more metabolites responded to hypoglycemia on day 2, the responses of the single metabolites were not statistically significant between the 2 days. Conclusions In individuals with type 1 diabetes, one episode of hypoglycemia decreases leucine and isoleucine concentrations. Antecedent hypoglycemia results in the decrement of five amino acids and increases the concentrations of two fatty acids, suggesting an alteration between the two hypoglycemic episodes, which could indicate a possible adaptat

[Background] Non-alcoholic steatohepatitis (NASH) can adversely affect health-related quality of life (HRQoL)., [Aims] This double-blind, placebo-controlled, phase 2 trial aimed to report the effects of the glucagon-like peptide-1 receptor agonist, semaglutide, on HRQoL in patients with NASH as a secondary endpoint., [Methods] Adults with biopsy-proven NASH and stage 1–3 fibrosis were randomised (3:3:3:1:1:1) to once-daily subcutaneous semaglutide 0.1, 0.2 or 0.4 mg, or placebo, for 72 weeks. Patients were invited to complete the Short Form-36 version 2.0 questionnaire at weeks 0, 28, 52 and 72., [Results] Between January 2017 and September 2018, 320 patients were enrolled. At 72 weeks, semaglutide was associated with significant improvements in physical component summary (PCS) score (estimated treatment difference [ETD] 4.26; 95% confidence interval [CI]: 1.96–6.55; p = 0.0003); bodily pain (ETD 5.07; 95% CI: 2.15–7.99; p = 0.0007); physical functioning (ETD 3.51; 95% CI: 1.16–5.86; p = 0.0034); role limitations due to physical health problems (ETD 2.80; 95% CI: 0.28–5.33; p = 0.0294); social functioning (ETD 3.16; 95% CI: 0.53–5.78; p = 0.0183) and vitality (ETD 4.47; 95% CI: 1.63–7.32; p = 0.0021). There was no significant difference in the mental component summary score (ETD 1.02; 95% CI: −1.59 to 3.62; p = 0.4441). After 72 weeks, improvements in PCS scores were significantly greater in patients (pooled semaglutide and placebo) with NASH resolution than without (p = 0.014)., [Conclusions] Treatment with semaglutide is associated with improvements in the physical components of HRQoL in patients with biopsy-proven NASH and fibrosis compared with placebo. ClinicalTrials.gov: NCT02970942.

Purpose: Patients with epilepsy have a greatly increased risk of osteoporosis and fractures. The literature is diverse and contradictory when dealing with the underlying pathophysiological mechanisms. Consequently, the purpose of this review was to shed light on the multifactorial causes behind the increased occurrence of metabolic bone disease in patients with epilepsy and to identify areas for future research. Methods: A review of the literature was performed searching PubMed with relevant Medical Subject Headings MeSH terms. The results of the search were evaluated for relevance to the review based on the title and abstract of the publication. Publications in language other than English and publications pertaining only pediatric patients were excluded. For all studies, included reference lists were evaluated for further relevant publications. In total, 96 publications were included in this explorative review. Results: The high occurrence of metabolic bone disease in patients with epilepsy is multifactorial. The causes are the socioeconomic consequences of having a chronic neurological disease but also adverse effects to antiepileptic drug treatment ranging from interference with calcium and vitamin D metabolism to hyponatremia-induced osteoporosis. Conclusion: The literature supports the need for awareness of bone health in patients with epilepsy. The pathophysiological mechanisms are many and various wanting for further research in the less well-characterized areas. Furthermore, great responsibility rests on the healthcare professionals in implementing comprehensive patient care and in assuring bone protective measures in clinical practice to prevent bone loss in patients with epilepsy.

BACKGROUND: Recurrent hypoglycemia has been shown to blunt hypoglycemia symptom scores and counterregulatory hormonal responses during subsequent hypoglycemia. We therefore studied whether hypoglycemia-associated electroencephalogram (EEG) changes are affected by an antecedent episode of hypoglycemia.METHODS: Twenty-four patients with type 1 diabetes mellitus (10 with normal hypoglycemia awareness, 14 with hypoglycemia unawareness) were studied on 2 consecutive days by hyperinsulinemic glucose clamp at hypoglycemia (2.0-2.5 mmol/L) during a 1-h period. EEG was recorded, cognitive function assessed, and hypoglycemia symptom scores and counterregulatory hormonal responses were obtained.RESULTS: Twenty-one patients completed the study. Hypoglycemia-associated EEG changes were identified on both days with no differences in power or frequency distribution in the theta, alpha, or the combined theta-alpha band during hypoglycemia on the 2 days. Similar degree of cognitive dysfunction was also present during hypoglycemia on both days. When comparing the aware and unaware group, there were no differences in the hypoglycemia-associated EEG changes. There were very subtle differences in cognitive function between the two groups on day 2. The symptom response was higher in the aware group on both days, while only subtle differences were seen in the counterregulatory hormonal response.CONCLUSION: Antecedent hypoglycemia does not affect hypoglycemia-associated EEG changes in patients with type 1 diabetes mellitus.

OBJECTIVE: Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on the myocardial infarction size in a closed-chest pig model.DESIGN: 38 non-diabetic pigs were randomised to hypoglycaemic (1.8-2.2 mmol/l; n = 15), normoglycaemic (5-7 mmol/l; n = 12) or hyperglycaemic glucose clamping (22-23 mmol/l; n = 11). After 30 min within glucose target myocardial infarction was induced for 30 min followed by reperfusion for 120 min. Hereafter the heart was double-stained to delineate infarction from viable tissue within the area at risk.RESULTS: Mean infarction size was 201 ± 35 mm(2) (mean ± SEM) in the hypoglycaemic group, 154 ± 40 mm(2) in the normoglycaemic group and 134 ± 40 mm(2) in the hyperglycaemic group, with no differences in infarction size, infarct/area at risk ratio or troponin T levels between the groups. There was no difference in incidence of ventricular fibrillation or mortality between the groups.CONCLUSION: No statistically significant associations were observed between the acute glycaemic level and measures of myocardial infarction, rates of ventricular fibrillation and subsequent premature death in the setting of acute ischaemia and reperfusion.

AIMS: Carrying the D-allele of the angiotensin-converting enzyme (ACE) I/D polymorphism and high ACE activity are prognostic factors in diabetic nephropathy, which predicts mortality in type 1 diabetes. We studied the association between the ACE D-allele and ACE phenotype and long-term all-cause mortality in three single-institution outpatient cohorts.METHODS: Genotype-based analyses were performed in 269 patients from Hillerød Hospital (HIH) (follow-up: 12 years) and in 439 patients with diabetic nephropathy and 437 patients with persistent normoalbuminuria from the Steno Diabetes Center (SDC) (follow-up: 9.5 years). Patients not on renin-angiotensin system (RAS)-blocking treatment were included in analyses of serum ACE activity (HIH: n = 208) and plasma ACE concentration (SDC: n=269).RESULTS: In the HIH cohort, carrying a D-allele was associated with excess mortality (hazard ratio (HR) = 4.0 (95% confidence interval (CI) 1.0-16)), but not in the SDC cohorts. At HIH, serum ACE activity was associated with excess mortality (HR=1.04 (95% CI 1.0-1.1 per unit increase)), but in the SDC cohort plasma ACE concentration was not.CONCLUSION: In unselected patients with type 1 diabetes, carrying the ACE D-allele and high spontaneous serum ACE activity were associated with 12-year excess mortality. These findings could not be reproduced in two other cohorts with persistent normoalbuminuria or diabetic nephropathy.

INTRODUCTION: Recent studies show an association between hyponatremia and osteoporosis. We have previously reported a case of severe male osteoporosis due to chronic syndrome of inappropriate secretion of antidiuretic hormone (SIADH). Here, we provide a follow-up on this case after cure of the condition that further supports the causal relationship.THE CASE: A 38-year-old man had been diagnosed with severe osteoporosis most likely due to chronic SIADH. The SIADH was believed to be idiopathic. A magnetic resonance imaging scan, however, revealed a tumor in the sinus, and biopsies showed an esthesioneuroblastoma, immunohistochemically positive for antidiuretic hormone (ADH). After the tumor was removed, ADH and sodium levels normalized. A dual-energy x-ray absorptiometry scan performed 7 months after the patient's last surgery showed a significant spontaneous improvement in bone mineral density in the lumbar vertebrae.CONCLUSION: This case provides evidence for a causal relationship between SIADH and chronic hyponatremia and impaired bone metabolism that can lead to severe secondary osteoporosis. The effect on bone metabolism is at least partially reversible.