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Copyright of Innere Medizin (2731-7080) is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Parasympathetic nervous system innervates peripheral organs including pancreas, hepatic portal system, and gastrointestinal tract. It thereby contributes to the regulation of whole-body glucose metabolism especially in the postprandial state when it promotes secretion of insulin and enhances its action in major target organs. We now aimed to evaluate the effect of parasympathetic modulation on human glucose metabolism. We used slow deep breathing maneuvers to activate the parasympathetic nervous system and tested for effects on metabolism during an oral glucose tolerance test in a randomized, controlled, cross-over trial in 15 healthy young men. We used projections towards the heart as a readout for parasympathetic activity. When analyzing heart rate variability, there was a significant increase of RMSSD (root mean square of successive differences) when participants performed slow deep breathing compared to the control condition, indicating a modulation of parasympathetic activity. However, no statistically significant effects on peripheral glucose metabolism or energy expenditure after the glucose tolerance test were detected. Of note, we detected a significant association between mean heart rate and serum insulin and C-peptide concentrations. While we did not find major effects of slow deep breathing on glucose metabolism, our correlational results suggest a link between the autonomic nervous system and insulin secretion after oral glucose intake. Future studies need to unravel involved mechanisms and develop potential novel treatment approaches for impaired insulin secretion in diabetes. [ABSTRACT FROM AUTHOR]

Purpose: Recent trials demonstrated remission of type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) following formula diet-induced weight loss. To improve the outreach for populations in need, many mobile health apps targeting weight loss have been developed with limited scientific evaluation of these apps. The present feasibility study investigated the effects of a novel approach incorporating a regular 'whole food-based' low-calorie diet combined with app-based digital education and behavioral change program on glucose metabolism and disease management. Methods: Twenty-four individuals with type 2 diabetes followed this approach supported by weekly coaching calls for 12 weeks. Phenotyping included bioimpedance analysis, mixed-meal tolerance test, magnetic resonance spectroscopy and transient elastography for assessing liver fat content and liver stiffness. Results: Over 12 weeks, participants reduced their body weight by 9% (97 ± 13 to 88 ± 12 kg), body mass index (BMI; 33 ± 5 to 29 ± 4 kg/m2), total fat mass (31 ± 10 to 27 ± 10%) (all p < 0.01) and liver fat by 50% alongside with decreased liver stiffness. Target HbA1c (< 6.5%) was achieved by 38% and resolution of NAFLD (liver fat content < 5.6%) was observed in 30% of the participants. Conclusion: This novel approach combining digital education with a low-calorie diet results in effective improvements of body weight, glycemic control and NAFLD and could complement existing care for patients with type 2 diabetes. Trial registration: NCT04509245 [ABSTRACT FROM AUTHOR]

The selection of carbohydrates or fat to generate intracellular energy is thought to be crucial for long-term metabolic health. While most studies assess fuel selection after a metabolic challenge, the determinants of substrate oxidation in the fasted state remain largely unexplored. We therefore assessed the respiratory quotient by indirect calorimetry as a read-out for substrate oxidation following an overnight fast. This cross-sectional analysis consisted of 192 (92 women, 100 men) either lean or obese participants. Following an overnight fast, the respiratory quotient (RQ) was assessed, after which a 5-point 75-g oral glucose tolerance test was performed. Unlike glucose and insulin, fasting free fatty acids (FFA) correlated negatively with fasting RQ (p < 0.0001). Participants with high levels of the ketone body β-hydroxybutyric acid had significantly lower RQ values. Fasting levels of glucose-dependent insulinotropic polypeptide (GIP) and glicentin were positively associated with fasting RQ (all p ≤ 0.03), whereas GLP-1 showed no significant association. Neither BMI, nor total body fat, nor body fat distribution correlated with fasting RQ. No relationship between the RQ and diabetes or the metabolic syndrome could be observed. In the fasting state, FFA concentrations were strongly linked to the preferentially oxidized substrate. Our data did not indicate any relationship between fasting substrate oxidation and metabolic diseases, including obesity, diabetes, and the metabolic syndrome. Since glicentin and GIP are linked to fuel selection in the fasting state, novel therapeutic approaches that target these hormones may have the potential to modulate substrate oxidation. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Lifestyle intervention is effective to prevent type 2 diabetes. However, a considerable long-term non-response occurs to a standard lifestyle intervention. We investigated which risk phenotypes at baseline and their changes during the lifestyle intervention predict long-term glycaemic non-response to the intervention. Methods: Of 300 participants at high risk for type 2 diabetes who participated in a 24 month lifestyle intervention with diet modification and increased physical activity, 190 participants could be re-examined after 8.7 ± 1.6 years. All individuals underwent a five-point 75 g OGTT and measurements of body fat compartments and liver fat content with MRI and spectroscopy at baseline, 9 and 24 months during the lifestyle intervention, and at long-term follow-up. Fasting proinsulin to insulin conversion (PI/I ratio) and insulin sensitivity and secretion were calculated from the OGTT. Non-response to lifestyle intervention was defined as no decrease in glycaemia, i.e. no decrease in AUC for glucose at 0-120 min during OGTT (AUCglucose). Results: Before the lifestyle intervention, 56% of participants had normal glucose regulation and 44% individuals had impaired fasting glucose and/or impaired glucose tolerance. At long-term follow-up, 11% had developed diabetes. Multivariable regression analysis with adjustment for age, sex, BMI and change in BMI during the lifestyle intervention revealed that baseline insulin secretion and insulin sensitivity, as well as change in insulin sensitivity during the lifestyle intervention, predicted long-term glycaemic control after 9 years. In addition, increased hepatic lipid content as well as impaired fasting proinsulin conversion at baseline were newly detected phenotypes that independently predicted long-term glycaemic control. Conclusions/interpretation: Increased hepatic lipid content and impaired proinsulin conversion are new predictors, independent of change in body weight, for non-response to lifestyle intervention in addition to the confirmed factors, impaired insulin secretion and insulin sensitivity. [ABSTRACT FROM AUTHOR]

Upstream transcription factor 1 (USF1) regulates the expression of many genes involved in lipid and glucose metabolism, among them genes regulating lipolysis. USF1 specifically regulates the expression of the hormone-sensitive lipase gene ( HSL) in adipocytes and the hepatic lipase gene ( LIPC) in the liver, which was found to be involved in liver fat accumulation. The usf1s1 C > T and usf1s2 G > A single-nucleotide polymorphisms (SNPs) in USF1 are associated with increased in vitro catecholamine-induced lipolysis in adipocytes. We investigated first whether SNPs in USF1 affect the lipolysis-suppressing action of insulin in vivo, and second, whether they interact with the −60C > G SNP in HSL on lipolysis and the −514C > T SNP in LIPC on liver fat. The usf1s1 C > T and usf1s2 G > A SNPs, together with the SNPs in HSL and LIPC, were determined in 407 Caucasians. Lipolysis was estimated as a change in free fatty acid (FFA) levels from baseline to 2 h of a 75-g oral glucose tolerance test (OGTT). Fifty-four subjects had data from a euglycemic hyperinsulinemic clamp with calculation of antilipolytic insulin sensitivity. Subjects carrying the minor alleles (T of usf1s1 and A of usf1s2) had lower 2 h FFA ( p = 0.01) and a larger decrease in FFA concentrations during the OGTT ( p = 0.02). Antilipolytic insulin sensitivity was higher in these individuals ( p = 0.03). No interaction of the usf1s1 C > T and usf1s2 G > A SNPs with the −60C > G SNP in HSL on antilipolytic insulin sensitivity was detected. Liver fat, measured by 1H magnetic resonance spectroscopy, was elevated only in subjects who were both homozygous for the major alleles of usf1s1 and usf1s2 and carriers of the T allele of the −514C > T SNP in LIPC ( p = 0.01). In conclusion, subjects carrying the T allele of SNP usf1s1 and the A allele of SNP usf1s2 have a higher antilipolytic insulin sensitivity. Moreover, both SNPs may interact with the −514C > T SNP in LIPC to determine liver fat. [ABSTRACT FROM AUTHOR]

Experimental evidence suggests a crucial role of the autonomic nervous system in whole body metabolism with major regulatory effects of the parasympathetic branch in postprandial adaptation. However, the relative contribution of this mechanism is still not fully clear in humans. We therefore compared the effects of transcutaneous auricular vagus nerve stimulation (taVNS, Cerbomed Nemos) with sham stimulation during an oral glucose tolerance test in a randomized, single-blind, cross-over design in 15 healthy lean men. Stimulation was performed for 150 min, 30 min before and during the entire oral glucose tolerance test with stimulation cycles of 30 s of on-phase and 30 s of off-phase and a 25 Hz impulse. Heart rate variability and plasma catecholamine levels were assessed as proxies of autonomic tone in the periphery. Neither analyzed heart rate variability parameters nor plasma catecholamine levels were significantly different between the two conditions. Plasma glucose, insulin sensitivity and insulin secretion were also comparable between conditions. Thus, the applied taVNS device or protocol was unable to achieve significant effects on autonomic innervation in peripheral organs. Accordingly, glucose metabolism remained unaltered. Therefore, alternative approaches are necessary to investigate the importance of the autonomic nervous system in postprandial human metabolism. [ABSTRACT FROM AUTHOR]

Niacin inhibits fatty acid flux from adipose tissue to liver, reduces hepatic triglyceride synthesis and increases hepatic lipid oxidation. Thus, niacin may have a role in the regulation of liver fat content in humans. We tested if dietary intake of niacin predicts change of liver fat content during a lifestyle intervention. To this end, we estimated the composition of diet from diaries of 202 healthy subjects at risk of type 2 diabetes undergoing lifestyle intervention comprising physical activity and diet counselling. Total-, subcutaneous- and visceral adipose tissue mass were measured by magnetic resonance (MR) tomography and liver fat content by 1H-MR spectroscopy at baseline and after 9 months of follow-up. Among fat compartments, liver fat content showed the largest decrease (−32%, p < 0.0001). High baseline niacin intake predicted a larger decrease of liver fat (p = 0.004). Subjects in the highest quartile of niacin intake at baseline also had the largest decrease of liver fat (1st:−10%; 2nd:−27%; 3rd:−35%; 4th:−37%). Among 58 subjects with nonalcoholic fatty liver disease (NAFLD) at baseline, NAFLD resolved in 23 subjects during the lifestyle intervention. For one standard deviation increase in niacin intake, the odds ratio for resolution of NAFLD was 1.77 (95% CI, 1.00-3.43). High dietary niacin intake may have a favorable effect on the reduction of liver fat during lifestyle intervention. [ABSTRACT FROM AUTHOR]