Intravenous calcitriol normalizes insulin sensitivity in uremic patients

Intravenous calcitriol normalizes insulin sensitivity in uremic patients. Recent studies suggest that secondary hyperparathyroidism and/or vitamin D deficiency are responsible for the insulin resistance in chronic renal failure. We investigated the effect of a 12-week intravenous treatment with 1,25 dihydroxycholecalciferol on glucose metabolism in 10 hemodialysis patients compared with 10 healthy control subjects by the frequently-sampled intravenous glucose tolerance test, analyzed with the minimal model technique. Compared to control subjects, the uremic patients featured elevated levels of parathyroid hormone (432 ± 60 vs. 41 ± 4 ng/liter, P < 0.001), insulin resistance (insulin sensitivity index, SI: 4.9 ± 0.8 vs. 9.5 ± 0.9 MIN-1/(µ/m1), P < 0.002), increased posthepatic insulin delivery (6.48 ± 2.48 vs. 2.73 ± 3.14 nmol/liter in 4 hr, P < 0.001) and a reduced C-peptide fractional clearance (0.033 ± 0.004 vs. 0.085 ± 0.009 min-1, P < 0.0002). Following treatment with 1,25 dihydroxycholecalciferol, the parathyroid hormone levels decreased significantly to 237 ± 30 ng/liter (P < 0.05), the insulin sensitivity index (SI: 9.6 ± 2.2, P < 0.05) reached a value similar to that of control subjects, and posthepatic insulin delivery decreased to 4.63 ± 0.83 nmol/liter in 4 hr (P < 0.01), while all the other parameters remained unchanged. In summary, uremic patients with secondary hyperparathyroidism were found to be severely insulin resistant and hyperinsulinemic. Intravenous vitamin D treatment led to a significant reduction of parathyroid hormone levels and to a complete normalization of insulin sensitivity in the hemodialysis patients. Thus, intravenous 1,25 dihydroxycholecalciferol improves insulin resistance in uremic patients, acting per se or by reducing secondary hyperparathyroidism

Dulaglutide as add-on therapy to SGLT-2 inhibitors in patients with inadequately controlled type 2 diabetes (AWARD-10): a 24-week, randomised , double-blind, placebo-controlled trial

BACKGROUND: The safety and efficacy of the once-weekly GLP-1 receptor agonist dulaglutide, added to an ongoing treatment regimen in patients inadequately controlled with SGLT2 inhibitors, with or without metformin was investigated. METHODS: This was a phase 3b, double-blind, placebo-controlled, 24-week study. Patients (≥18yrs), HbA1c ≥7.0% [53mmol/mol] and ≤9.5% [80mmol/mol]), BMI ≤45 kg/m2, stable doses of an SGLT2 inhibitor (±metformin) were randomly assigned (1:1:1) to dulaglutide 1.5 mg, dulaglutide 0.75 mg, or placebo. Patients and investigators were masked to treatment assignment (those assessing outcomes to study drug assignment). The primary objective was to test for the superiority of dulaglutide (1.5 mg or 0.75 mg) vs placebo for change in HbA1c from baseline to 24 weeks. RESULTS: 423 patients were randomly assigned to dulaglutide 1.5 mg (n=142), dulaglutide 0.75 mg (n=141), and placebo (n=140). Greater reduction in HbA1c at 24 weeks was seen in patients receiving dulaglutide (1.5 mg -1.34% [SE 0.06]/14.7 mmol/mol [0.6]; 0.75 mg -1.21% [0.06]/-13.2 mmol/mol [0.6]) than in patients receiving placebo (-0.54% [0.06]/-5.9 mmol/mol [0.6]; p<0.0001 for both groups vs placebo). Serious adverse events were reported for five patients in the dulaglutide 1.5 mg group, three in the dulaglutide 0.75 mg group, and five in the placebo group. Treatment-emergent adverse events were more common in patients treated with dulaglutide: nausea (21 [15%] patients in the dulaglutide 1.5 mg group vs seven [5%] in the dulaglutide 0.75 mg group vs five [4%] in the placebo group), diarrhoea (eight [6%] vs 14 [10%] vs four [3%]), and vomiting (five [4%] vs four [3%] vs one [1%]). One episode of severe hypoglycaemia was reported in the dulaglutide 0.75 mg group. CONCLUSIONS: Dulaglutide as add-on treatment to SGLT2 inhibitors (±metformin) resulted in significant and clinically relevant improvements in glycaemic control, with acceptable tolerability consistent with the established safety profile of dulaglutide

Differences in serum magnesium levels in diabetic and non-diabetic patients following one-anastomosis gastric bypass

Patients with obesity and type 2 diabetes mellitus (T2DM) are regarded to have reduced serum magnesium (Mg) concentrations. We aimed to assess the changes in serum Mg concentrations at 12-month follow-up in patients, with and without T2DM, who underwent one anastomosis gastric bypass surgery. Overall, 50 patients (80% female, age 42.2 (12.5) years) with morbid obesity (mean baseline BMI 43.8 (4.3) kg/m2) were included in the analysis. Half of the included patients had T2DM diagnosed at baseline, and these patients showed lower serum Mg concentration (0.78 (0.07)) vs. 0.83 (0.05) mmol/L; p = 0.006), higher blood glucose levels (129.9 (41.3) vs. 87.6 (8.1) mg/dL; p < 0.001) as well as HbA1c concentrations (6.7 (1.4) vs. 5.3 (0.5)%; p < 0.001). During follow-up, BMI and glucose levels showed a decrease; however, serum Mg levels remained stable. At baseline 42% of patients were found to be Mg deficient, which was reduced to 33% at six months and to 30% at 12 months follow-up. Moreover, patients with T2DM had an odds ratio of 9.5 (95% CI = 3.0–29.7; p < 0.001) for magnesium deficiency when compared to patients without T2DM. Further research into the role of Mg and its role in T2DM and other obesity-related comorbidities are needed

Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes

Aims: Data on the impact of hypoglycaemia on patients' daily lives and diabetes self-management, particularly in developing countries, are lacking. The aim of this study was to assess fear of, and responses to, hypoglycaemia experienced by patients globally. Materials and methods: This non-interventional, multicentre, 4-week prospective study using self-assessment questionnaires and patient diaries consisted of 27,585 patients, >= 18 years, with type 1 diabetes (n = 8022) or type 2 diabetes (n = 19,563) treated with insulin for > 12 months, at 2004 sites in 24 countries worldwide. Results: Increased blood glucose monitoring (69.7%) and seeking medical assistance (62.0%) were the most common responses in the 4 weeks following hypoglycaemic events for patients with type 1 diabetes and type 2 diabetes, respectively. Approximately 44% of patients with type 1 diabetes or type 2 diabetes increased calorie intake in response to a hypoglycaemic episode. Following hypoglycaemia, 3.9% (type 1 diabetes) and 6.2% (type 2 diabetes) of patients took leave from work or study. Regional differences in fear of, and responses to, hypoglycaemia were evident - in particular, a lower level of hypoglycaemic fear and utilisation of healthcare resources in Northern Europe and Canada. Conclusions: Hypoglycaemia has a major impact on patients and their behaviour. These global data for the first time reveal regional variations in response to hypoglycaemia and highlight the importance of patient education and management strategies. (C) 2017 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under thePeer reviewe

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background: Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods: In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings: The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p&lt;0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p&lt;0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation: In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding: Novo Nordisk, Denmark

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Erfolgsstrategien zur Stabilisierung des reduzierten Körpergewichts. Erste Follow-up-Ergebnisse der Lean-Habits-Studie

[in Aktuelle Ernährungsmedizin, 24, 209