Aim: Intermittent fasting, a dietary intervention of alternate eating and fasting, has gained popularity in people trying to lose weight. Intermittent fasting could provide an alternative to classic caloric restriction in people with type 2 diabetes mellitus. The aim of the study is to determine the impact of a 12‐week intermittent fasting regimen compared with usual care in people with type 2 diabetes mellitus receiving insulin therapy.Methods: This open, single‐centre, randomized controlled trial investigates participants with type 2 diabetes mellitus on insulin therapy and a glycated haemoglobin A1c (HbA1c) of ≥53 mmol/mol (≥7.0%) and a minimum insulin dose of 0.3 IU/kg body weight per day. Participants are randomized in a 1:1 ratio to either 12 weeks of intermittent fasting or the standard care group. All participants receive dietary counselling, continuous glucose monitoring, measurement of the resting metabolic rate, an oral glucose tolerance test, body composition measurement via dual‐energy X‐ray absorptiometry and stool samples for microbiome analyses at the beginning and at the end of the intervention. Two co‐primary outcomes (analysed in hierarchical order) were chosen for the study: (i) the difference in the change of HbA1c from baseline to 12 weeks and (ii) the difference in the number of participants achieving a combined end point encompassing a body weight reduction of at least 2%, an insulin dose reduction of at least 10% and an absolute HbA1c reduction of at least 3 mmol/mol (0.3%) between the two groups.

The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m²) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.

Metformin is a widely used and effective medication in type 2 diabetes (T2DM) as well as in polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) contribute to the occurrence of metformin side effects. The aim of the present study was to identify intronic genetic variants modifying the occurrence of metformin side effects and to replicate them in individuals with T2DM and in women with PCOS. We performed Next Generation Sequencing (Illumina Next Seq) of 115 SNPs in a discovery cohort of 120 metformin users and conducted a systematic literature review. Selected SNPs were analysed in two independent cohorts of individuals with either T2DM or PCOS, using 5′-3′exonucleaseassay. A total of 14 SNPs in the organic cation transporters (OCTs) showed associations with side effects in an unadjusted binary logistic regression model, with eight SNPs remaining significantly associated after appropriate adjustment in the discovery cohort. Five SNPs were confirmed in a combined analysis of both replication cohorts but showed different association patterns in subgroup analyses. In an unweighted polygenic risk score (PRS), the risk for metformin side effects increased with the number of risk alleles. Intronic SNPs in the OCT cluster contribute to the development of metformin side effects in individuals with T2DM and in women with PCOS and are therefore of interest for personalized therapy options.

To assess intermittently scanned continuous glucose monitoring (isCGM) performance for different rates of change in plasma glucose (RCPG) during glycemic challenges in type 1 diabetes (T1D). Nineteen people with T1D (7 females; age 35 ± 11 years; HbA_1c 7.3 ± 0.6% (56 ± 7 mmol/mol)) performing two glycemic challenges (OGTT) were included. During OGTTs, plasma glucose was compared against sensor glucose for timepoints 0 min (pre-OGTT), +15 min, +30 min, +60 min, +120 min, +180 min, and +240 min by means of median absolute (relative) difference (MARD and MAD) and Clarke Error Grid (CEG), then was stratified for RCPG and glycemic ranges. Overall, MARD was 8.3% (4.0–14.8) during hypoglycemia level 1 18.8% (15.8–22.0), euglycemia 9.5% (4.3–15.1), hyperglycemia level 1 9.4% (4.0–17.2), and hyperglycemia level 2 7.1% (3.3–11.9). The MARD was associated with the RCPG (p < 0.0001), detailing significant differences in comparison of low, moderate, high, and very high RCPG (p = 0.014). Overall, CEG resulted in 88% (212 values) of comparison points in zone A, 12% (29 values) in zone B, and 0.4% (1 value) in zone D. The isCGM system was accurate during OGTTs. Its performance was dependent on the RCPG and showed an overestimation of the actual reference glucose during hypoglycemia.

Background: C-peptide is produced in equimolar amounts with insulin from pancreatic beta cells, and thus is a fundamental biomarker for beta cell function. A non-invasive urinary C-peptide-to-creatinine ratio (UCPCR) has attracted attention as a biomarker for metabolic conditions. However, the UCPCR as an indicative risk predictor for prediabetes is still being investigated. Methods: We aimed to characterize UCPCRs in healthy people using American Diabetes Association (ADA) criteria and to evaluate their metabolic outcomes over time. A total of 1022 participants of the Biomarkers in Personalized Medicine cohort (BioPersMed) were screened for this study. Totals of 317 healthy with normal glucose metabolism, 87 prediabetic, and 43 diabetic subjects were included. Results: Prediabetic participants had a significantly higher UCPCR median value than healthy participants (p < 0.05). Dysglycaemia of healthy baseline participants was measured twice over 4.5 ± 0.9 years; 25% and 30% were detected with prediabetes during follow-ups, predicted by UCPCR both for the first (p < 0.05) and the second visit (p < 0.05), respectively. This is in good agreement with the negative predictive UCPCR value of 60.2% based on logistic regression. UCPCR levels were equal in both sexes. Conclusion: UCPCR measurements provide an indicative approach for metabolic risk, representing a potential use for prevention and monitoring of impaired glucose metabolism.

Background Metformin is a widely used and effective agent in type 2 diabetes mellitus (T2DM) and polycystic ovary syndrome (PCOS). Yet, the mechanisms of action and the occurrence of side effects (e.g. abdominal bloating and pain), are still poorly understood. Since organic cation transporters (OCTs) are responsible for the hepatic and renal transport of metformin, we investigated a series of short nucleotide polymorphisms (SNPs) in the OCT genes in PCOS and in T2DM patient samples from either our PCOS patient registry or the Graz Diabetes Registry for Biomarker Research (GIRO). Methods After DNA isolation from plasma in 181 PCOS samples and 44 T2DM samples followed by a subsequent polymerase chain reaction (PCR) with a combined TaqMan assay, we compared 17 SNPs (rs456598, rs461473, rs3798174, rs7766568, rs316007, rs3798167, rs662301, rs2048327, rs376563, rs622591, rs9295125, rs3798172, rs2197296, rs12208357, rs34059508, rs628031 and rs3777392) from OCT1 and OCT3 transporters. Results Data of the study participants were analyzed according to the presence or absence of documented metformin-induced side effects. The distributions of different genotypes of the rs2197296 locus in the SLC22A1 gene, the rs376563 locus in the SLC22A2 gene and the rs3798167 locus in the SLC22A3 gene were statistically significant between the two groups. The effect was shown by a higher minor allele frequency in the group with documented metformin associated side effects (χ⁽²⁾ = 3.953, P = 0.047, χ⁽²⁾ = 7.342, P = 0.025 and χ⁽²⁾ = 12.251, P = 0.002 respectively). Conclusion In conclusion, we found three specific allelic variants in OCT candidate genes with distinct associations for side effects in metformin users either in PCOS or in T2DM. Therefore, those variants can be further investigated to better understand the metformin-associated side effects.