OBJECTIVEPhysical activity (PA) can improve cardiovascular risk in the general population and in patients with type 2 diabetes. Studies also indicate an HbA 1c -lowering effect in patients with type 2 diabetes. Since reports in patients with type 1 diabetes are scarce, this analysis aimed to investigate whether there is an association between PA and glycemic control or cardiovascular risk in subjects with type 1 diabetes. RESEARCH DESIGN AND METHODSA total of 18,028 adults ( ‡18 to <80 years of age) from Germany and Austria with type 1 diabetes from the Diabetes-Patienten-Verlaufsdokumentation (DPV) database were included. Patients were stratified according to their self-reported frequency of PA (PA0, inactive; PA1, one to two times per week; PA2, more than two times per week). Multivariable regression models were applied for glycemic control, diabetes-related comorbidities, and cardiovascular risk factors. Data were adjusted for sex, age, and diabetes duration. P values for trend were given. SAS 9.4 was used for statistical analysis. RESULTSAn inverse association between PA and HbA 1c , diabetic ketoacidosis, BMI, dyslipidemia (all P < 0.0001), and hypertension (P = 0.0150), as well as between PA and retinopathy or microalbuminuria (both P < 0.0001), was present. Severe hypoglycemia (assistance required) did not differ in PA groups (P = 0.8989), whereas severe hypoglycemia with coma was inversely associated with PA (P < 0.0001). CONCLUSIONSPA seemed to be beneficial with respect to glycemic control, diabetes-related comorbidities, and cardiovascular risk factors without an increase of adverse events. Hence, our data underscore the recommendation for subjects with type 1 diabetes to perform regular PA.

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.

Objective: Both a 1- to 4-week continuous or intermittent stay and moderate exercise in hypoxia versus normoxia can lead to weight loss. We examined the reproducibility and durability of added hypoxic exposure in a feasible health program of several months. Methods: 32 obese persons, randomly assigned to either a hypoxia (age 50.3 ± 10.3 years, BMI 37.9 ± 8.1 kg/m²) or a normoxia (age 52.4 ± 7.9 years, BMI 36.3 ± 4.0 kg/m²) group, completed 52 exercise sessions within 8 months. Participants exercised for 90 min (65-70% HR_peak) either at a simulated altitude of 3,500 m or in normoxia, and rested for further 90 min at 4,500 m or normoxia. Before, after 5 weeks, after 3 months, and after the intervention, body composition and exercise capacity were determined. Risk markers (e.g., blood pressure, cholesterol) were measured before, after 3 months, and after the intervention period. Results: Body weight, BMI, waist and hip circumference, P_peak and BP_sys improved over time (p < 0.05) but without group difference. Fat mass reductions correlated with HDL changes (r = -0.427; p < 0.05) in the entire group. Conclusion: Long-term, moderate intensity exercise and rest in hypoxia does not lead to higher reductions in body weight than normoxia alone. Therefore, for weight loss and metabolic markers hypoxic exposure does not add effects at least when stimuli (i.e., hypoxia dose, exercise intensity/duration) are unaltered throughout the intervention.

A famin was discovered in 1994 as the fourth member of the human albumin gene family, which includes human serum albumin, alfa-fetoprotein, and vitamin D-binding protein.1 All 4 genes map to the chromosomal region 4q11-q22. Afamin is also known as α-albumin or as α1T-glycoprotein.2,3 Afamin is a human plasma glycoprotein of 87 kDa with 15% carbohydrate content and 55% amino acid sequence similarity to albumin.Circulating plasma afamin is primarily of hepatic origin 1 ; brain, kidney, testes, and ovaries have been found as additional afamin-expressing tissues (www.proteinatlas.org). Abundant concentrations of afamin have been described in plasma and in other body fluids, such as follicular, cerebrospinal and seminal Background-Afamin is a human plasma vitamin E-binding glycoprotein primarily expressed in the liver and secreted into the bloodstream. Because little is known about (patho)-physiological functions of afamin, we decided to identify phenotypes associated with afamin by investigating transgenic mice overexpressing the human afamin gene and performing large-scale human epidemiological studies. Methods and Results-Transgenic mice overexpressing afamin revealed increased body weight and serum concentrations of lipids and glucose. We applied a random-effects meta-analysis using age-and sex-adjusted baseline and follow-up investigations in the population-based Bruneck (n=826), Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR; n=1499), and KOoperative Gesundheitsforschung in der Region Augsburg (KORA) F4 studies (n=3060 ). With the same afamin increment used at baseline, we observed an 8% gain in metabolic syndrome components between baseline and follow-up (incidence rate ratio=1.08; 95% CI, 1.06-1.10; P=8.87×10 −16 ). Afamin concentrations at baseline were highly significantly related to all individual metabolic syndrome components at baseline and at follow-up. This observation was most pronounced for elevated waist circumference (odds ratio, 1.79; 95% CI, 1.54-2.09; P=4.15×10 −14 at baseline and odds ratio, 1.46; 95% CI, 1.31-1.63; P=2.84×10 −11 for change during follow-up) and for elevated fasting glucose concentrations (odds ratio, 1.46; 95% CI, 1.40-1.52; P=1.87×10 −69 and odds ratio, 1.46; 95% CI, 1.24-1.71; P=5.13×10 −6 , respectively). Conclusions-This study in transgenic mice and >5000 participants in epidemiological studies shows that afamin is strongly associated with the prevalence and development of metabolic syndrome and all its components. (Circ Cardiovasc Genet. 2014;7:822-829.)Key Words: afamin protein, human ◼ epidemiology ◼ glucose ◼ lipoproteins ◼ metabolism ◼ metabolic syndrome X ◼ obesity © 2014 American Heart Association, Inc. Little is known about the physiological or pathophysiological functions of afamin. We previously demonstrated multiple vitamin E-binding sites of human afamin using a radioligand assay. Scatchard and Hill analyses showed binding affinity for both α-and γ-tocopherol. 5To deepen our understanding of possible functions of a...

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.

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.

Increases in relative telomere length were found after bariatric surgery in the long term, presumably due to amelioration of metabolic traits. This may overrule the influence of age and baseline telomere length and facilitate telomere protection in patients experiencing pronounced weight loss.

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