Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

Effects of home-based exergaming on cardio-metabolic and cognitive health in physically inactive individuals.

AIMS: To examine the effects of a home-based exergame training over 6 weeks on cardio-metabolic and cognitive health, as well as training adherence, in physically inactive individuals. MATERIALS AND METHODS: Twenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks. Exercise duration increased biweekly until 75 min of vigorous exercise were performed in Weeks 5 and 6. Maximum oxygen uptake (VO2max), cardio-metabolic profiling, and neuro-cognitive tests were performed at baseline and study end. Additionally, training adherence was assessed via training diaries. RESULTS: After 6 weeks of home-based exergaming, VO2max increased significantly, while there was a significant decrease in heart rate (resting and maximum), blood pressure (systolic, diastolic and mean), and low-density lipoprotein cholesterol. Dynamic balance and reaction time improved after 6 weeks of exergaming. Training adherence was 88.4%. CONCLUSIONS: Home-based exergaming induced a clinically relevant increase in VO2max, a determinant of cardiovascular health, accompanied by further improvements in cardiovascular, metabolic and neuro-cognitive parameters. Exergaming may, therefore, offer an innovative approach to increasing regular physical activity, improving metabolic risk profile, and preventing chronic diseases.

Afamin predicts the prevalence and incidence of nonalcoholic fatty liver disease.

OBJECTIVES: In the general population, increased afamin concentrations are associated with the prevalence and incidence of metabolic syndrome as well as type 2 diabetes. Although metabolic syndrome is commonly associated with nonalcoholic fatty liver disease (NAFLD), there exist no information on afamin and NAFLD. METHODS: Afamin concentrations were cross-sectionally measured in 146 Austrian patients with NAFLD, in 45 patients without NAFLD, and in 292 age- and sex-matched healthy controls. Furthermore, the feasibility of afamin to predict incident NAFLD was evaluated in 1,434 adult participants in the population-based Cardiovascular Risk in Young Finns Study during a 10-year follow-up. RESULTS: Median afamin concentrations were significantly higher in NAFLD patients (83.6 mg/L) than in patients without NAFLD (61.6 mg/L, p<0.0001) or in healthy controls (63.9 mg/L, p<0.0001). In age- and sex-adjusted logistic regression analyses a 10 mg/L increase of afamin was associated with a 1.5-fold increase of having NAFLD as compared with patients without NAFLD and the risk was even two-fold when compared with healthy controls. In the population-based cohort, afamin concentrations at baseline were significantly lower in participants without NAFLD (n=1,195) than in 239 participants who developed NAFLD (56.5 vs. 66.9 mg/L, p<0.0001) during the 10-year follow up, with highest afamin values observed in individuals developing severe forms of NAFLD. After adjustment for several potentially confounding parameters, afamin remained an independent predictor for the development of NAFLD (OR=1.37 [95% CI 1.23-1.54] per 10 mg/L increase, p<0.0001). CONCLUSIONS: Afamin concentrations are increased in patients with NAFLD and independently predict the development of NAFLD in a population-based cohort.

[Closed-loop systems - Update 2020]. / Closed-loop-Systeme ­ Update 2020.

Closed-loop systems - Update 2020 Abstract. The artificial pancreas (also referred to as a Closed-loop system) represents the latest development in diabetes therapy. Closed-loop systems autonomously direct subcutaneous insulin infusion via a control algorithm based on real-time continuous glucose monitoring. Closed-loop systems have been tested in clinical studies since 2011, and were shown to improve glucose control by reducing hyper- and hypoglycaemia as well as glucose variability when compared with conventional insulin pump therapy. In 2016, the US regulatory authority approved the first hybrid-closed-loop system for the treatment of type 1 diabetes. Hybrid-closed loop systems are not yet fully automated and still require the user to be actively involved for insulin dosing at mealtimes. In spite of the remarkable progress, the delayed action profile of subcutaneously administered insulin and the need to wear multiple devices on the body remain challenging. The present review article summarizes the current state of the art of closed-loop systems in diabetes care and will address technical aspects, evidence from clinical studies as well as future developments in the field.

Glycaemic control in individuals with type 1 diabetes using an open source artificial pancreas system (OpenAPS).

Open source artificial pancreas systems (OpenAPS) have gained considerable interest in the diabetes community. We analyzed continuous glucose monitoring (CGM) records of 80 OpenAPS users with type 1 diabetes (T1D). A total of 19 495 days (53.4 years) of CGM records were available. Mean glucose was 7.6 ± 1.1 mmol/L, time in range 3.9-10 mmol/L was 77.5 ± 10.5%, <3.9 mmol/L was 4.3 ± 3.6%, <3.0 mmol/L was 1.3 ± 1.9%, >10 mmol/L was 18.2 ± 11.0% and > 13.9 mmol/L was 4.1 ± 4.0%, respectively. In 34 OpenAPS users, additional CGM records were obtained while using sensor-augmented pump therapy (SAP). After changing from SAP to OpenAPS, lower mean glucose (-0.6 ± 0.7; P < 0.0001), lower estimated HbA1c (-0.4 ± 0.5%; P < 0.0001), higher time in range 3.9-10 mmol/L (+9.3 ± 9.5%; P < 0.0001), less time < 3.0 mmol/L (-0.7 ± 2.2%; P = 0.0171), lower coefficient of variation (-2.4 ± 5.8; P = 0.0198) and lower mean of daily differences (-0.6 ± 0.9 mmol/L; P = 0.0005) was observed. Glycaemic control using OpenAPS was comparable with results of more rigorously developed and tested AP systems. However, OpenAPS was used by a highly selective, motivated and technology-adept cohort, despite not being approved for the treatment of individuals with T1D.

Supervised Short-term High-intensity Training on Plasma Irisin Concentrations in Type 2 Diabetic Patients.

Irisin is a myokine involved in adipocyte transformation. Its main beneficial effects arise from increased energy expenditure. Irisin production is particularly stimulated by physical exercise. The present study investigates the changes of plasma irisin in type 2 diabetic patients performing 2 different training modalities. Fourteen type 2 diabetic patients underwent 4 week of supervised high-intensity interval training (HIT; n=8) or continuous moderate-intensity training (CMT; n=6), with equivalent total amounts of work required. Plasma samples were collected in the resting state atbaseline and one day after the exercise intervention to analyse resting plasma irisin, blood lipids, blood glucose, hsCRP, Adiponectin, Leptin and TNF-α concentrations. In addition, body composition and VO2peak were determined Resting plasma irisin increased after HIT (p=0.049) and correlated significantly with plasma fasting glucose at follow-up (r=0.763; p=0.006). CMT did not significantly change the amount of plasma irisin, although follow-up values of plasma irisin correlated negatively with fat-free mass (r=-0.827, p=0.002) and with fasting plasma glucose (r = - 0.934, p=0.006). Plasma irisin was found to increase with higher training intensity, confirming the assumption that exercise intensity, in addition to the type of exercise, may play an important role in the stimulation of the irisin response.

Short-term effects of dapagliflozin on insulin sensitivity, postprandial glucose excursion and ketogenesis in type 1 diabetes mellitus: A randomized, placebo-controlled, double blind, cross-over pilot study.

We investigated the short-term effects of dapagliflozin as adjunct to insulin on insulin sensitivity, postprandial glucose excursions and ketone body production in type 1 diabetes mellitus (T1DM). A total of seven male patients completed the randomized, double-blind, placebo-controlled cross-over trial, receiving 10 mg of dapagliflozin daily for 3 days, followed by placebo, or the reverse. At Day 3, hyperinsulinaemic, euglycaemic clamps and oral glucose tolerance test clamps with repeated blood sampling were performed. Required glucose infusion and blood glucose excursions did not differ significantly between dapagliflozin treatment and placebo (P = 0.491; P = 0.342). Prior to oral glucose, total ketone bodies showed a higher trend following dapagliflozin treatment (P = 0.051). Following oral glucose, total ketone bodies decreased while concentrations of total GLP-1 were higher following dapagliflozin (P = 0.009). Non-esterified free fatty acids did not differ between dapagliflozin treatment and placebo and ketonuria was absent under both conditions. In T1DM, short-term addition of dapagliflozin to insulin influenced neither postprandial glucose excursions nor insulin sensitivity. Following oral glucose, total ketone bodies decreased in parallel with an increase in GLP-1 concentrations, which were higher under dapagliflozin treatment as compared with placebo.

The Effects of 3 Weeks of Uphill and Downhill Walking on Blood Lipids and Glucose Metabolism in Pre-Diabetic Men: A Pilot Study.

The prevention of type 2 diabetes in persons at risk for diabetes is of utmost importance. Physical activity in general and even exercises at moderate intensities such as walking significantly reduce the risk of the development of type 2 diabetes. However, it is still a matter of debate whether lipids and glucose metabolism are differently affected by regular concentric (e.g., uphill walking) and eccentric (e.g., downhill walking) endurance exercise. The aim of this study was to investigate the effects of short-term (3 weeks) uphill and downhill walking on glucose metabolism and blood lipids in pre-diabetic middle-aged men in a real world setting. The study was designed as an investigator-initiated 2 group random selection pre-test post-test trial. Sixteen pre-diabetic men (age: 56.9 ± 5.1 years; BMI: 28.1 ± 2.3 kg·m-2) performed 9 uphill (n = 8) or 9 downhill (n = 8) walking sessions within 3 weeks. The primary outcomes were the markers of glucose metabolism and blood lipids measured before and after the training period. After uphill walking glucose tolerance (area under the curve of the oral glucose tolerance test: -43.25 ± 53.12 mg·dl-1; p = 0.05; effect size: 0.81), triglycerides (-48.75 ± 54.49 mg·dl-1; p = 0.036; effect size: 0.89), HDL-C (+7.86 ± 9.54 mg·dl-1; p = 0.05; effect size: 0.82) and total cholesterol/HDL-C ratio (-0.58 ± 0.41; p = 0.012; effect size: 1.39) had significantly improved. No significant metabolic adaptations were found after downhill walking. However, when adjusted for estimated energy expenditure, uphill and downhill walking had equal effects on almost all metabolic parameters. Moreover, the magnitude of the baseline impairments of glucose tolerance was significantly related to the extent of change in both groups. Depending on the fitness level and individual preferences both types of exercise may be useful for the prevention of type 2 diabetes and disorders in lipid metabolism.

Loss of dermatan sulfate epimerase (DSE) function results in musculocontractural Ehlers-Danlos syndrome.

The sulfated polysaccharide dermatan sulfate (DS) forms proteoglycans with a number of distinct core proteins. Iduronic acid-containing domains in DS have a key role in mediating the functions of DS proteoglycans. Two tissue-specific DS epimerases, encoded by DSE and DSEL, and a GalNAc-4-O-sulfotransferase encoded by CHST14 are necessary for the formation of these domains. CHST14 mutations were previously identified for patients with the musculocontractural type of Ehlers-Danlos syndrome (MCEDS). We now identified a homozygous DSE missense mutation (c.803C>T, p.S268L) by the positional candidate approach in a male child with MCEDS, who was born to consanguineous parents. Heterologous expression of mutant full-length and soluble recombinant DSE proteins showed a loss of activity towards partially desulfated DS. Patient-derived fibroblasts also showed a significant reduction in epimerase activity. The amount of DS disaccharides was markedly decreased in the conditioned medium and the cell fraction from cultured fibroblasts of the patient when compared with a healthy control subject, whereas no apparent difference was observed in the chondroitin sulfate (CS) chains from the conditioned media. However, the total amount of CS disaccharides in the cell fraction from the patient was increased ∼1.5-fold, indicating an increased synthesis or a reduced conversion of CS chains in the cell fraction. Stable transfection of patient fibroblasts with a DSE expression vector increased the amount of secreted DS disaccharides. DSE deficiency represents a specific defect of DS biosynthesis. We demonstrate locus heterogeneity in MCEDS and provide evidence for the importance of DS in human development and extracellular matrix maintenance.

Plasma concentrations of the vitamin E-binding protein afamin are associated with overall and progression-free survival and platinum sensitivity in serous ovarian cancer--a study by the OVCAD consortium.

OBJECTIVE: Comparative proteomics identified the plasma protein afamin as potential biomarker for ovarian cancer (OC). Significantly decreased afamin plasma concentrations in pre-therapeutic OC patients reconstituted to control values after successful tumor surgery. This study evaluates the association of afamin with survival and response to therapy in serous OC patients within the OVCAD consortium project. METHODS: We measured afamin in 215 pre-therapeutic plasma samples, 246 tumor lysates and 109 plasma samples taken 6months after finishing platinum-based chemotherapy. Differences in afamin plasma concentrations among FIGO stages were tested by Kruskal-Wallis test; association of afamin concentrations with overall and progression-free survival was evaluated using Kaplan-Meier survival plots and multivariate adjusted COX regression analysis. RESULTS: Pre-therapeutic afamin correlated significantly with FIGO stages (p=0.012) and was lower in the presence of metastases (p=0.013) and poorly differentiated OC in patients responding to therapy (p=0.016). Afamin ≥48.0mg/L was also associated with a lower hazard ratio for recurrent disease as compared to afamin <48.0mg/L (p=0.007). Post-therapeutic afamin ≥48mg/L was positively correlated with overall (p<0.001) and progression-free (p=0.012) survival and was lower in non-responders than in responders (p=0.048). Thus, afamin returned post-therapeutically to values of healthy controls in responders (p<0.001) but not in non-responders (p=0.114). Afamin in tumor lysates was lower in poorly differentiated OC than in G 1+2 tumors (p=0.041). Higher afamin concentrations in tumor lysates were associated with increased overall survival (p=0.003). CONCLUSION: These data indicate that afamin is associated with therapy response and survival rate in advanced OC patients.

Analysis of diabetes attitudes, wishes and needs in Switzerland, the Swiss DAWN2™ Study.

AIMS OF THE STUDY: Swiss DAWN2™ aimed to evaluate the difficulties and unmet needs of individuals with diabetes and stakeholders, based on the assessments of diabetes care and self-management: the individual burden of disease, the perception of the quality of medical care, and the treatment satisfaction of individuals with diabetes living in the Canton of Bern. The results of the Swiss cohort were analysed and compared with the global DAWN2™ results. METHODS: 239 adult individuals with diabetes were enrolled in a cross-sectional study at the Department of Diabetes, Endocrinology, Nutritional Medicine and Metabolism at the University Hospital of Bern between 2015 and 2017. The participants completed validated online questionnaires regarding health-related quality of life (EQ-5D-3L) and emotional distress (PAID-5), diabetes self-care activities (SDSCA-6), treatment satisfaction (PACIC-DSF), and health-related wellbeing (WHO-5). Eligibility criteria were as follows: participants were aged >18 years, had a diagnosis of diabetes type 1 or 2 since at least 12 months and gave written informed for the participation in the present study. RESULTS: When compared globally, the Swiss cohort reported a higher quality of life (77.28 ± 16.73 vs. 69.3 ± 17.9 EQ-5D-3L score, p <0.001) and lower emotional distress (22.28 ± 20.94 vs. 35.2 ± 24.2 PAID-5 score, p = 0.027). Higher frequencies of self-measurement of blood glucose (6.43 ± 1.68 vs. 3.4 ± 2.8 SDSCA-6 score, p <0.001) and physical activity (4.40 ± 2.04 vs. 3.8 ± 2.7 SDSCA-6 score, p = 0.05) were reported. PACIC-DSF revealed higher satisfaction concerning organisational aspects of patient care (60.3 ± 1.51 vs. 47.3 ± 24.3, p<0.001) and higher health-related well-being as compared to the global score (71.38 ± 23.31 vs. 58 ± 13.8 WHO-5 Well-Being Index, p <0.001). HbA1c >7% correlated to emotional distress (PAID-5, 26.08 ± 23.37 vs. 18.80 ± 17.49, p = 0.024), unfavourable eating habits (4.28 ± 2.22 vs. 4.99 ± 2.15, p = 0.034) and decreased physical activity (3.95 ± 2.16 vs. 4.72 ± 1.92, p = 0.014). Sleeping problems were most commonly reported (35.6%). In total, 28.8% of respondents completed diabetes-related educational programs. CONCLUSION: In global comparison, Swiss DAWN2™ showed a lower burden of disease and yet a higher level of treatment satisfaction in patients who were treated in Switzerland. Further studies are required to assess the quality of diabetes treatment and unmet needs in patients treated outside of a tertiary care center.

Performance of the Dexcom G6 Continuous Glucose Monitoring System During Cardiac Surgery Using Hypothermic Extracorporeal Circulation.

OBJECTIVE: Continuous glucose monitoring (CGM) may be challenged by extreme conditions during cardiac surgery using hypothermic extracorporeal circulation (ECC). RESEARCH DESIGN AND METHODS: We evaluated the Dexcom G6 sensor in 16 subjects undergoing cardiac surgery with hypothermic ECC, of whom 11 received deep hypothermic circulatory arrest (DHCA). Arterial blood glucose, quantified by the Accu-Chek Inform II meter, served as reference. RESULTS: Intrasurgery mean absolute relative difference (MARD) of 256 paired CGM/reference values was 23.8%. MARD was 29.1% during ECC (154 pairs) and 41.6% immediately after DHCA (10 pairs), with a negative bias (signed relative difference: -13.7%, -26.6%, and -41.6%). During surgery, 86.3% pairs were in Clarke error grid zones A or B and 41.0% of sensor readings fulfilled the International Organization for Standardization (ISO) 15197:2013 norm. Postsurgery, MARD was 15.0%. CONCLUSIONS: Cardiac surgery using hypothermic ECC challenges the accuracy of the Dexcom G6 CGM although recovery appears to occur thereafter.

Bariatric surgery prevents carotid wall thickness progression.

BACKGROUND: Bariatric surgery is a treatment option for patients with severe obesity and improves parameters of cardiovascular and/or metabolic disease. Carotid intima media thickness (C-IMT) is a surrogate measure of subclinical atherosclerosis. Previous studies showed short to mid-term arrest and even regression of C­IMT progression following bariatric surgery. We aimed to investigate the long-term effect of weight loss on C­IMT progression 10 years after bariatric surgery in comparison to a population-based control cohort. METHODS: In total, 21 eligible patients were examined preoperatively, at 5 and 10 years after bariatric surgery. Anthropometric parameters, plasma triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), insulin, and glucose were assessed at all three study visits. C­IMT was measured via B­mode scans of the common carotid artery. C­IMT progression was measured in an age-matched and BMI-matched cohort selected from the population-based Bruneck study to compare with changes in C­IMT progression after bariatric surgery. RESULTS: C­IMT remained stable over the 10-year observation period after bariatric surgery. The control cohort showed a significant C­IMT progression over 10 years. The difference in C­IMT progression over 10 years was significant (p < 0.01) between both cohorts. CONCLUSION: Weight loss induced by bariatric surgery halts the natural progression of C­IMT over a 10-year observation period.

Randomized, Double-Blind, Placebo-Controlled Crossover Trial of Once Daily Empagliflozin 25 mg for the Treatment of Postprandial Hypoglycemia After Roux-en-Y Gastric Bypass.

Aims: To investigate the effect of empagliflozin on glucose dynamics in individuals suffering from postbariatric hypoglycemia (PBH) after Roux-en-Y gastric bypass (RYGB). Methods: Twenty-two adults with PBH after RYGB were randomized to empagliflozin 25 mg or placebo once daily over 20 days in a randomized, double-blind, placebo-controlled, crossover trial. The primary efficacy outcome was the amplitude of plasma glucose excursion (peak to nadir) during a mixed-meal tolerance test (MMTT). Outcomes of the outpatient period were assessed using continuous glucose monitoring (CGM) and an event-tracking app. Results: The amplitude of glucose excursion during the MMTT was 8.1 ± 2.4 mmol/L with empagliflozin versus 8.1 ± 2.6 mmol/L with placebo (mean ± standard deviation, P = 0.807). CGM-based mean amplitude of glucose excursion during the 20-day period was lower with empagliflozin than placebo (4.8 ± 1.3 vs. 5.2 ± 1.6. P = 0.028). Empagliflozin reduced the time spent with CGM values >10.0 mmol/L (3.8 ± 3.5% vs. 4.7 ± 3.8%, P = 0.009), but not the time spent with CGM values <3.0 mmol/L (1.7 ± 1.6% vs. 1.5 ± 1.5%, P = 0.457). No significant difference was observed in the quantity and quality of recorded symptoms. Eleven adverse events occurred with empagliflozin (three drug-related) and six with placebo. Conclusions: Empagliflozin 25 mg reduces glucose excursions but not hypoglycemia in individuals with PBH. Clinical Trial Registration: Clinicaltrials.gov: NCT05057819.

Study protocol for a randomised, double-blind, placebo-controlled crossover trial assessing the impact of the SGLT2 inhibitor empagliflozin on postprandial hypoglycaemia after gastric bypass.

INTRODUCTION: Postprandial hypoglycaemia after gastric bypass surgery (also known as postbariatric hypoglycaemia or PBH) is an increasingly encountered clinical problem. PBH is characterised by meal-induced rapid spikes and consequent falls in glycaemia, resulting in both hypoglycaemia burden and high glycaemic variability. Despite its frequency, there is currently no approved pharmacotherapy. The purpose of this investigation is to evaluate efficacy and safety of empagliflozin 25 mg, a sodium-glucose cotransporter 2-inhibitor, to reduce glucose excursions and hypoglycaemia burden in patients with PBH after gastric bypass surgery. METHODS AND ANALYSIS: In a prospective, single-centre, randomised, double-blind, placebo-controlled, crossover trial, we plan to enrol 22 adults (≥18 years) with PBH after Roux-en-Y gastric bypass surgery (plasma or sensor glucose <3.0 mmol/L). Eligible patients will be randomised to receive empagliflozin 25 mg and placebo once daily, each for 20 days, in random order. Study periods will be separated by a 2-6 weeks wash-out period. The primary efficacy outcome will be the amplitude of plasma glucose excursion (peak to nadir) during a mixed meal tolerance test. Results will be presented as paired-differences±SD plus 95% CIs with p values and hypothesis testing for primary and secondary outcomes according to intention-to-treat. Secondary outcomes include continuous glucose monitoring-based outcomes, further metabolic measures and safety. ETHICS AND DISSEMINATION: The DEEP-EMPA trial (original protocol title: Randomized, double-blind, placebo-controlled crossover trialassessing the impact of the SGLT2 inhibitor empagliflozin onpostprandial hypoglycaemia after gastric bypass) was approved by the Bern Ethics Committee (ID 2021-01187) and Swissmedic (Ref. Number: 102663190) in October and November 2021, respectively. First results are expected in the first quarter of 2023 and will be disseminated via peer-reviewed publications and presented at national and international conferences. The acronym DEEP was derived from an overarching project title (DEciphering the Enigma of Postprandial Hyperinsulinaemic Hypoglycaemia after Bariatric Surgery), the term EMPA stands for the drug empagliflozin. TRIAL REGISTRATION NUMBER: NCT05057819.

Type 1 diabetes mellitus and SARS-CoV-2 in pediatric and adult patients - Data from the DPV network.

BACKGROUND: Data on patients with type 1 diabetes mellitus (T1DM) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are sparse. This study aimed to investigate the association between SARS-CoV-2 infection and T1DM. METHODS: Data from the Prospective Diabetes Follow-up (DPV) Registry were analyzed for diabetes patients tested for SARS-CoV-2 by polymerase chain reaction (PCR) in Germany, Austria, Switzerland, and Luxembourg during January 2020-June 2021, using Wilcoxon rank-sum and chi-square tests for continuous and dichotomous variables, adjusted for multiple testing. RESULTS: Data analysis of 1855 pediatric T1DM patients revealed no differences between asymptomatic/symptomatic infected and SARS-CoV-2 negative/positive patients regarding age, new-onset diabetes, diabetes duration, and body mass index. Glycated hemoglobin A1c (HbA1c) and diabetic ketoacidosis (DKA) rate were not elevated in SARS-CoV-2-positive vs. -negative patients. The COVID-19 manifestation index was 37.5% in individuals with known T1DM, but 57.1% in individuals with new-onset diabetes. 68.8% of positively tested patients were managed as outpatients/telemedically. Data analysis of 240 adult T1MD patients revealed no differences between positively and negatively tested patients except lower HbA1c. Of these patients, 83.3% had symptomatic infections; 35.7% of positively tested patients were hospitalized. CONCLUSIONS: Our results indicate low morbidity in SARS-CoV-2-infected pediatric T1DM patients. Most patients with known T1DM and SARS-CoV-2 infections could be managed as outpatients. However, SARS-CoV-2 infection was usually symptomatic if it coincided with new-onset diabetes. In adult patients, symptomatic SARS-CoV-2 infection and hospitalization were associated with age.

[Diagnosis, Prevention and Treatment of Cardiovascular Disease in People with Diabetes and Prediabetes]. / Diagnose, Prävention und Behandlung kardiovaskulärer Ereignisse bei Menschen mit Diabetes und Prädiabetes.

Diagnosis, Prevention and Treatment of Cardiovascular Disease in People with Diabetes and Prediabetes Abstract. Diabetes is associated with an increased cardiovascular risk. In addition to optimizing glycemia, timely diagnosis and stringent control of cardiovascular risk factors is essential for individuals with diabetes. Therapeutic options include lifestyle-optimization, individualized drug therapy and targeted treatment of concomitant or secondary cardiovascular disease. Cardiovascular disease occurs more often in individuals with diabetes and includes heart failure, atrial fibrillation, coronary heart disease and sudden cardiac death. The correct choice of antidiabetic drugs and interventions can control cardiovascular risk factors, reduce cardiovascular risk and treat concomitant or secondary diseases in a targeted manner. This review is intended to provide guidance on diagnosis, treatment and choice of therapy for individuals with type 2 diabetes without and with concomitant or secondary cardiovascular disease.

Differences in insulin dosing in women with type 1 diabetes before and after the menopause.

The menstrual cycle increases insulin requirements in a subset of women with type 1 diabetes as a result of reduced insulin action through sexual hormones. If exposure to sexual hormones declines during the menopause, adaptions of insulin dosing may be required. However, there are no validated recommendations available on how to adapt insulin treatment in postmenopausal women with type 1 diabetes. The present study compared insulin dosing profiles of 630 premenopausal and 548 postmenopausal women, who had long-term type 1 diabetes and used continuous subcutaneous insulin infusion. Data were extracted from the German "Diabetes-Patienten- Verlaufsdokumentation". It was found that total daily insulin (p <0.0001), daily insulin per kilogram bodyweight (p <0.0001), total daily basal insulin (p <0.0001), daily basal insulin per kilogram bodyweight (p <0.0001) and estimated glomerular filtration rate (eGFR) (p <0.0001) were lower in postmenopausal women. Total daily bolus insulin, daily bolus insulin per kilogram, glycated haemoglobin A1, body mass index and the incidence of severe hypoglycaemic events were similar in both cohorts.Postmenopausal women with type 1 diabetes used lower insulin doses as compared with premenopausal women, whereas glycaemic control and body mass index were comparable. This observation might be explained by lower exposure to sexual hormones and lower eGFR, even though the contribution of other factors such as body composition and eating habits requires further investigation.