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Background and Aims: Non‐alcoholic fatty liver disease (NAFLD) has been linked to type 2 diabetes (T2D), but also to hypothyroidism. Nevertheless, the relationship between thyroid function and NAFLD in diabetes is less clear. This study investigated associations between free thyroxine (fT4) or thyroid‐stimulating hormone (TSH) and NAFLD in recent‐onset diabetes. Methods: Participants with recent‐onset type 1 diabetes (T1D, n = 358), T2D (n = 596) or without diabetes (CON, n = 175) of the German Diabetes Study (GDS), a prospective longitudinal cohort study, underwent Botnia clamp tests and assessment of fT4, TSH, fatty liver index (FLI) and in a representative subcohort 1H‐magnetic resonance spectroscopy. Results: First, fT4 levels were similar between T1D and T2D (p =.55), but higher than in CON (T1D: p <.01; T2D: p <.001), while TSH concentrations were not different between all groups. Next, fT4 correlated negatively with FLI and positively with insulin sensitivity only in T2D (ß = −.110, p <.01; ß =.126, p <.05), specifically in males (ß = −.117, p <.05; ß =.162; p <.01) upon adjustments for age, sex and BMI. However, correlations between fT4 and FLI lost statistical significance after adjustment for insulin sensitivity (T2D: ß = −.021, p = 0.67; males with T2D: ß = −.033; p =.56). TSH was associated positively with FLI only in male T2D before (ß =.116, p <.05), but not after adjustments for age and BMI (ß =.052; p =.30). Conclusions: Steatosis risk correlates with lower thyroid function in T2D, which is mediated by insulin resistance and body mass, specifically in men, whereas no such relationship is present in T1D. [ABSTRACT FROM AUTHOR]

Background: Diabetes distress is increasingly considered one of the most important psychosocial issues in the care of people with type 1 diabetes (T1D). We analyse whether diabetes distress and depression screening results of emerging adults are associated with the age at T1D onset. Methods: Data were taken from two cohort studies conducted at the German Diabetes Center, Düsseldorf, Germany. The 18–30-year-old participants had an age at onset either before the age of 5 years (childhood-onset long-term T1D study group, N = 749) or during adulthood (adult-onset short-term T1D study group from the German Diabetes Study (GDS), N = 163). Diabetes distress and depression screening were analysed by means of the 20-item Problem Areas in Diabetes (PAID-20) scale and the nine-item depression module from the Patient Health Questionnaire (PHQ-9). The average causal effect of age at onset was estimated by a doubly robust causal inference method. Results: The PAID-20 total scores were increased in the adult-onset study group [potential outcome mean (POM) 32.1 (95% confidence interval 28.0; 36.1) points] compared to the childhood-onset study group [POM 21.0 (19.6; 22.4) points, difference 11.1 (6.9; 15.3) points, p<0.001] adjusted for age, sex and haemoglobin A1c (HbA1c) levels. Moreover, more participants in the adult-onset group [POM 34.5 (24.9; 44.2) %] than in the childhood-onset group [POM 16.3 (13.3; 19.2) %] screened positive for diabetes distress [adjusted difference 18.3 (8.3; 28.2) %, p<0.001]. The PHQ-9 total score [difference 0.3 (-1.1; 1.7) points, p=0.660] and the proportion of participants with a positive screening result for depression [difference 0.0 (-12.7; 12.8) %, p=0.994] did not differ between the groups in the adjusted analyses. Conclusions: Emerging adults with short-term type 1 diabetes screened positive for diabetes distress more often than adults with type 1 diabetes onset during early childhood when age, sex and HbA1c values were considered confounding factors. Accounting for age at onset or the duration of diabetes may help explain the heterogeneity in the data when psychological factors are examined. [ABSTRACT FROM AUTHOR]

Background: Application of mixed meal tolerance tests (MMTT) to measure beta-cell function in long-term studies is limited by modification of the commercial products occurring over time. This study assessed the intra-individual reliability of MMTTs and compared the effects of liquid meals differing in macronutrient composition on the estimation of beta-cell function in type 2 diabetes (T2DM). Methods: To test the reliability of MMTTs, 10 people with T2DM (age 58 ± 11 years, body mass index 30.0 ± 4.9 kg/m2) received Boost®high Protein 20 g protein three times. For comparing different meals, another 10 persons with T2DM (58 ± 5 years, 31.9 ± 5.3 kg/m2) ingested either Boost®high Protein 20 g protein or the isocaloric Boost®high Protein 15 g protein containing 35% less protein and 18% more carbohydrates. C-peptide, insulin and glucose release were assessed from the incremental area under the concentration time curve (iAUC) and the intra- and inter-individual variation of these parameters from the coefficients of variations (CV). Results: Repetitive ingestion of one meal revealed intra-individual CVs for the iAUCs of C-peptide, insulin and glucose, which were at least 3-times lower than the inter-individual variation of these parameters (18.2%, 19.7% and 18.9% vs. 74.2%, 70.5% and 207.7%) indicating a good reliability. Ingestion of two different meals resulted in comparable intra-individual CVs of the iAUCs of C-peptide and insulin (16.9%, 20.5%). Conclusion: MMTTs provide reliable estimation of beta-cell function in people with T2DM. Furthermore, moderate differences in the protein and carbohydrate contents in a standardized liquid meal do not result in relevant changes of C-peptide and insulin responses. Trial registration: Clinicaltrials.gov, Identifier number: NCT01055093. Registered 22 January 2010 – Retrospectively registered, https://www.clinicaltrials.gov/ct2/show/study/NCT01055093 [ABSTRACT FROM AUTHOR]

Diabetes mellitus has been associated with impaired cognitive performance, particularly in verbal memory. Mediterranean diets (MedD) may lead to improvements in overall and single cognitive functions. We hypothesised that adherence to MedD associates with better performance in verbal memory in patients with type 1 or type 2 diabetes. Thus, we performed a cross-sectional analysis including patients with recently diagnosed type 1 (n = 75) or type 2 diabetes (n = 118), metabolically healthy individuals (n = 41) and individuals with type 1 (n = 44) or type 2 diabetes (n = 62) of at least five years after diagnosis. Participants underwent comprehensive metabolic phenotyping and cognitive testing. Adherence to the Modified Mediterranean diet scale (MMDS) was computed from a food frequency questionnaire. Among patients with type 2 diabetes with a known diabetes duration ≥5 years, closer adherence to the MMDS was associated with higher score in verbal memory after adjustment for potential confounders (P = 0.043). Adherence to the MMDS did not relate to verbal memory in recently diagnosed type 2 diabetes (P = 0.275), recently diagnosed or longer-standing type 1 diabetes (P = 0.215 and P = 0.626, respectively) or metabolically healthy individuals (P = 0.666). In conclusion, closer adherence to MedD may exert beneficial effects on cognitive performance in the course of type 2 diabetes. [ABSTRACT FROM AUTHOR]

For treatment of type 1 diabetes mellitus, a combination of immune-based interventions and medication to promote beta-cell survival and proliferation has been proposed. Dextromethorphan (DXM) is an N -methyl-D-aspartate receptor antagonist with a good safety profile, and to date, preclinical and clinical evidence for blood glucose-lowering and islet-cell-protective effects of DXM have only been provided for animals and individuals with type 2 diabetes mellitus. Here, we assessed the potential anti-diabetic effects of DXM in the non-obese diabetic mouse model of type 1 diabetes. More specifically, we showed that DXM treatment led to five-fold higher numbers of pancreatic islets and more than two-fold larger alpha- and beta-cell areas compared to untreated mice. Further, DXM treatment improved glucose homeostasis and reduced diabetes incidence by 50%. Our data highlight DXM as a novel candidate for adjunct treatment of preclinical or recent-onset type 1 diabetes., Competing Interests: A.W., T.M., E.M. and E.L. declare the following competing financial interests: these authors are inventors of the US patent 10,464,904 entitled “Dextrorphan-derivatives with suppressed central nervous activity”; and T.M. and E.L. are inventors of the US patent 9,370,511 entitled “Morphinan-derivatives for treating diabetes and related disorders.”, (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Outer dense fibres are located on the outside of the axoneme in the midpiece and principal piece of the mammalian sperm tail and may help to maintain the passive elastic structures and elastic recoil of the sperm tail. Here we describe the isolation and genomic organization of a rat gene encoding a cysteine-proline-rich outer dense fibre protein. The cDNA sequence of rts 5/1 and its expression pattern have already been published [Burfeind, P. & Hoyer-Fender, S. (1991) Dev. Biol. 148, 195-204]. There exist two different genes in the rat genome, rts 5/1 major and rts 5/1 minor. Rts 5/1 major consists of two exons interrupted by one intron of about 3.8 kb. Exon 1 and rts 5/1 minor contains a deletion of 120 bp, without destroying the open reading frame, which is flanked by short direct repeats, 15 bp in length. The first two nucleotides of the intronic sequence were identified as GA and, therefore, do not agree with the donor consensus sequence. From the analysis of mouse x rat cell hybrids, the rts 5/1 major gene has been assigned to chromosome 7. By immunoblotting and immunocytochemistry, it was demonstrated that the isolated gene encodes a major protein of rat sperm outer dense fibres.