Background: Non-alcoholic fatty liver disease (NAFLD) is a common metabolic disorder all over the world, mainly being associated with a sedentary lifestyle, adiposity, and nutrient imbalance. The increasing prevalence of NAFLD accommodates similar developments for type 2 diabetes and diabetes-related comorbidities and complications. Therefore, early detection of NAFLD is an utmost necessity. Potentially helpful tools for the prediction of NAFLD are liver fat indices. The fatty liver index (FLI) and the NAFLD-liver fat score (NAFLD-LFS) have been recently introduced for this aim. However, both indices have been shown to correlate with liver fat status, but there is neither sufficient data on the longitudinal representation of liver fat change, nor proof of a diet-independent correlation between actual liver fat change and change of index values. While few data sets on low-fat diets have been published recently, low-carb diets have not been yet assessed in this context. Aim: We aim to provide such data from a highly effective short-term intervention to reduce liver fat, comparing a low-fat and a low-carb diet in subjects with prediabetes. Methods: Anthropometric measurements, magnetic resonance (MR)-based intrahepatic lipid (IHL) content, and several serum markers for liver damage have been collected in 140 subjects, completing the diet phase in this trial. Area-under-the-responder-operator-curves (AUROC) calculations as well as cross-sectional and longitudinal Spearman correlations were used. Results: Both FLI and NAFLD-LFS predict liver fat with moderate accuracy at baseline (AUROC 0.775–0.786). These results are supported by correlation analyses. Changes in liver fat, achieved by the dietary intervention, correlate moderately with changes in FLI and NAFLD-LFS in the low-fat diet, but not in the low-carb diet. A correlation analysis between change of actual IHL content and change of single elements of the liver fat indices revealed diet-specific moderate to strong correlations between ΔIHL and changes of measures of obesity, ΔTG, and ΔALT (all low-fat, only) and between ΔIHL and ΔGGT (low-carb, only). With exception for a stronger decrease of triglycerides (TG) levels in the low-carb diet, there is no statistically significant difference in the effect of the diets on anthropometric or serum-based score parameters. Conclusion: While liver fat indices have proved useful in the early detection of NAFLD and may serve as a cost-saving substitute for expensive MR measurements in the cross-sectional evaluation of liver status, their capability to represent interventional changes of liver fat content appears to be diet-specific and lacks accuracy. Liver fat reduction by low-fat diets can be monitored with moderate precision, while low-carb diets require different measuring techniques to demonstrate the same dietary effect. Full article

Isosteviol (ISV), a diterpene molecule, is an isomer of the backbone structure of a group of substances with proven antidiabetic capabilities. The aim of this study was to investigate if ISV elicits dynamic insulin release from pancreatic islets and concomitantly is able to ameliorate gluco-, lipo-, and aminoacidotoxicity in clonal β-cell line (INS-1E) in relation to cell viability and insulin secretion. Isolated mice islets placed into perifusion chambers were perifused with 3.3 mM and 16.7 mM glucose with/without 10⁻⁷ M ISV. INS-1E cells were incubated for 72 h with either 30 mM glucose, 1 mM palmitate or 10 mM leucine with or without 10⁻⁷ M ISV. Cell viability was evaluated with a Cytotoxic Fluoro-test and insulin secretion was measured in Krebs-Ringer Buffer at 3.3 mM and 16.7 mM glucose. In the presence of 3.3 mM glucose, 10⁻⁷ M ISV did not change basal insulin secretion from perifused islets. However, at a high glucose level of 16.7 mM, 10⁻⁷ M ISV elicited a 2.5-fold increase (−ISV: 109.92 ± 18.64 ng/mL vs. +ISV: 280.15 ± 34.97 ng/mL; p < 0.01). After 72 h gluco-, lipo-, or aminoacidotoxicity in INS-1E cells, ISV treatment did not significantly affect cell viability (glucotoxicity, −ISV: 19.23 ± 0.83%, +ISV: 18.41 ± 0.90%; lipotoxicity, −ISV: 70.46 ± 3.15%, +ISV: 65.38 ± 2.81%; aminoacidotoxicity: −ISV: 8.12 ± 0.63%; +ISV: 7.75 ± 0.38%, all nonsignificant). ISV did not improve impaired insulin secretion (glucotoxicity, −ISV: 52.22 ± 2.90 ng/mL, +ISV: 47.24 ± 3.61 ng/mL; lipotoxicity, −ISV: 19.94 ± 4.10 ng/mL, +ISV: 22.12 ± 3.94 ng/mL; aminoacidotoxicity: −ISV: 32.13 ± 1.00 ng/mL; +ISV: 30.61 ± 1.54 ng/mL, all nonsignificant). In conclusion, ISV acutely stimulates insulin secretion at high but not at low glucose concentrations. However, ISV did not counteract cell viability or cell dysfunction during gluco-, lipo-, or aminoacidotoxicity in INS-1E cells. Full article

Diabetic dyslipidemia with elevated postprandial triglyceride (TG) responses is characteristic in type 2 diabetes (T2D). Diet and meal timing can modify postprandial lipemia (PPL). The impact of a pre-meal of whey proteins (WP) on lipid metabolism is unidentified. We determined whether a WP pre-meal prior to a fat-rich meal influences TG and apolipoprotein B-48 (ApoB-48) responses differentially in patients with and without T2D. Two matched groups of 12 subjects with and without T2D accomplished an acute, randomized, cross-over trial. A pre-meal of WP (20 g) or water (control) was consumed 15 min before a fat-rich meal (supplemented with 20 g WP in case of water pre-meal). Postprandial responses were examined during a 360-min period. A WP pre-meal significantly increased postprandial concentrations of insulin (P < 0.0001), glucagon (P < 0.0001) and glucose-dependent insulinotropic peptide (GIP) (P < 0.0001) in subjects with and without T2D. We detected no effects of the WP pre-meal on TG, ApoB-48, or non-esterified fatty acids (NEFA) responses to the fat-rich meal in either group. Paracetamol absorption i.e., gastric emptying was delayed by the WP pre-meal (P = 0.039). In conclusion, the WP pre-meal induced similar hormone and lipid responses in subjects with and without T2D. Thus, the WP pre-meal enhanced insulin, glucagon and GIP responses but did not influence lipid or glucose responses. In addition, we demonstrated that a WP pre-meal reduced gastric emptying in both groups. Full article

Since coffee may help to prevent the development of metabolic syndrome (MetS), we aimed to evaluate the short- and long-term effects of a coffee-based supplement on different features of diet-induced MetS. In this study, 24 Sprague Dawley rats were divided into control or nutraceuticals groups to receive a high-fat/high-fructose diet with or without a mixture of caffeic acid (30 mg/day), trigonelline (20 mg/day), and cafestol (1 mg/day) for 12 weeks. An additional 11 rats were assigned to an acute crossover study. In the chronic experiment, nutraceuticals did not alter body weight or glycemic control, but improved fed hyperinsulinemia (mean difference = 30.80 mU/L, p = 0.044) and homeostatic model assessment-insulin resistance (HOMA-IR) (mean difference = 15.29, p = 0.033), and plasma adiponectin levels (mean difference = −0.99 µg/mL, p = 0.048). The impact of nutraceuticals on post-prandial glycemia tended to be more pronounced after acute administration than at the end of the chronic study. Circulating (mean difference = 4.75 U/L, p = 0.014) and intrahepatocellular alanine transaminase activity was assessed by hyperpolarized-¹³C nuclear magnetic resonance NMR spectroscopy and found to be reduced by coffee nutraceuticals at endpoint. There was also a tendency towards lower liver triglyceride content and histological steatosis score in the intervention group. In conclusion, a mixture of coffee nutraceuticals improved insulin sensitivity and exhibited hepatoprotective effects in a rat model of MetS. Higher dosages with or without caffeine deserve to be studied in the future. Full article

There is evidence that vitamin D status is associated with type 2 diabetes. Many observational studies have been performed investigating the relationship of vitamin D status and circulating biomarkers of glycemic regulation. To find out whether this association holds, we conducted a systematic review and meta-analysis of cross sectional and longitudinal studies. We searched Pubmed, Medline and Embase, all through June 2017. The studies were selected to determine the effect of vitamin D on the parameters of glucose metabolism in diabetic and non-diabetic subjects. Correlation coefficients from all studies were pooled in a random effects meta-analysis. The risk of bias was assessed using Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We found significant inverse relationship of vitamin D status with glycemic level in both diabetic (r = −0.223, 95% CI = −0.184 to −0.261, p = 0.000) and non-diabetic (r = −0.073, 95% CI = −0.052 to −0.093, p = 0.000) subjects. This meta-analysis concludes that hypovitaminosis D is associated with increased risk of hyperglycemia both in diabetic and non-diabetic subjects. A future strategy for the prevention of impaired glycemic regulation could be individualized supplementation of vitamin D. Full article