Aims/hypothesis Insoluble cereal fibres have been shown in large prospective cohort studies to be highly effective in preventing type 2 diabetes, but there is a lack of interventional data. Our 2 year randomised double-blind prospective intervention study compared the effect of an insoluble oat fibre extract with that of placebo on glucose metabolism and incidence of diabetes. Methods A total of 180 participants with impaired glucose tolerance underwent a modified version of the 1 year lifestyle training programme PREvention of DIAbetes Self-management (PREDIAS) and were randomised to receive a fibre supplement (n = 89; 7.5 g of insoluble fibre per serving) or placebo (n = 91; 0.8 g of insoluble fibre per serving) twice daily for 2 years. Eligible participants were men and women, were at least 18 years old and did not report corticosteroid or other intensive anti-inflammatory treatment, fibre intolerance or any of the following disorders: overt diabetes, chronic or malignant disease, or severe cardiopulmonary, endocrine, psychiatric, gastrointestinal, autoimmune or eating disorder. Participants were recruited at two clinical wards in Berlin and Nuthetal. The allocation was blinded to participants and study caregivers (physicians, dietitians, study nurses). Randomisation was conducted by non-clinical staff, providing neutrally numbered supplement tins. Both supplements were similar in their visual, olfactory and gustatory appearance. Intention-to-treat analysis was applied to all individuals. Results After 1 year, 2 h OGTT levels decreased significantly in both groups but without a significant difference between the groups (fibre −0.78 ± 1.88 mmol/l [p ≤ 0.001] vs placebo −0.46 ± 1.80 mmol/l [p = 0.020]; total difference 0.32 ± 0.29 mmol/l; Caroline Honsek and Stefan Kabisch contributed equally to this publication.Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00125-018-4582-6) contains peer-reviewed but unedited supplementary material, which is available to authorised users. not significant). The 2 year incidence of diabetes was 9/89 (fibre group) compared with 16/91 (placebo group; difference not significant). As secondary outcomes, the change in HbA 1c level was significantly different between the two groups (−0.2 ± 4.6 mmol/mol [−0.0 ± 0.0%; not significant] vs +1.2 ± 5.2 mmol/mol [+0.1 ± 0.0%; not significant]; total difference 1.4 ± 0.7 mmol/mol [0.1 + 0.0%]); p = 0.018); insulin sensitivity and hepatic insulin clearance increased in both groups. After 2 years, improved insulin sensitivity was still present in both groups, although the effect size had diminished. Separate analysis of the sexes revealed a significantly greater reduction in 2 h glucose levels for women in the fibre group (−0.88 ± 1.59 mmol/l [p ≤ 0.001] vs −0.22 ± 1.52 mmol/l [p = 0.311]; total difference 0.67 ± 0.31 mmol/l; p = 0.015). Levels of fasting glucose, adipokines and inflammatory markers remained unchanged in the two groups. Significantly increased fibre intake was restricted ...

Background: High intake of cereal fibre is associated with reduced risk for type 2 diabetes and long-term complications. Within the first long-term randomized controlled trial specifically targeting cereal fibre, the Optimal Fibre Trial (OptiFiT), intake of insoluble oat fibre was shown to significantly reduce glycaemia. Previous studies suggested that this effect might be limited to subjects with impaired fasting glucose (IFG). Aim: We stratified the OptiFiT cohort for normal and impaired fasting glucose (NFG, IFG) and conducted a secondary analysis comparing the effects of fibre supplementation between these subgroups. Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomized to twice-a-day fibre or placebo supplementation for 2 years (n = 89 and 91, respectively), while assuring double-blinded intervention. Fasting blood sampling, oral glucose tolerance test and full anthropometry were assessed annually. At baseline, out of 136 subjects completing the first year of intervention, 72 (54%) showed IFG and IGT, while 64 subjects had IGT only (labelled “NFG”). Based on these two groups, we performed a stratified per-protocol analysis of glycometabolic and secondary effects during the first year of intervention. Results: The NFG group did not show significant differences between fibre and placebo group concerning anthropometric, glycometabolic, or other biochemical parameters. Within the IFG stratum, 2-h glucose, HbA1c, and gamma-glutamyl transferase levels decreased more in the fibre group, with a significant supplement x IFG interaction effect for HbA1c. Compared to NFG subjects, IFG subjects had larger benefits from fibre supplementation with respect to fasting glucose levels. Results were robust against adjustment for weight change and sex. An ITT analysis did not reveal any differences from the per-protocol analysis. Conclusions: Although stratification resulted in relatively small subgroups, we were able to pinpoint our previous findings from the entire cohort to the IFG subgroup. Cereal fibre can beneficially affect glycemic metabolism, with most pronounced or even isolated effectiveness in subjects with impaired fasting glucose.

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.

Obesity does not modulate the glycometabolic benefit of insoluble cereal fibre in subjects with prediabetes—a stratified post hoc analysis of the Optimal Fibre Trial (OptiFiT). Background: OptiFiT demonstrated the beneficial effect of insoluble oat fibres on dysglycemia in prediabetes. Recent analyses of OptiFiT and other randomised controlled trials (RCTs) indicated that this effect might be specific for the subgroup of patients with impaired fasting glucose (IFG). As subjects with IFG are more often obese, there is a need to clarify if the effect modulation is actually driven by glycemic state or body mass index (BMI). Aim: We conducted a stratified post hoc analysis of OptiFiT based on the presence or absence of obesity. Methods: 180 Caucasian participants with impaired glucose tolerance (IGT) were randomised in a double-blinded fashion to either twice-a-day fibre or placebo supplementation for 2 years (n = 89 and 91, respectively). Once a year, they underwent fasting blood sampling, an oral glucose tolerance test (oGTT) and full anthropometry. At baseline, out of 136 subjects who completed the first year of intervention, 87 (62%) were classified as OBESE (BMI >30) and 49 subjects were NONOBESE. We performed a stratified per-protocol analysis of the primary glycemic and secondary metabolic effects attributable to dietary fibre supplementation after 1 year of intervention. Results: Neither the NONOBESE nor the OBESE subgroup showed significant differences between the respective fibre and placebo groups in metabolic, anthropometric or inflammatory outcomes. None of the four subgroups showed a significant improvement in either fasting glucose or glycated haemoglobin (HbA1c) after 1 year of intervention and only OBESE fibre subjects improved 2 h glucose. Within the NONOBESE stratum, there were no significant differences in the change of primary or secondary metabolic parameters between the fibre and placebo arms. We found a significant interaction effect for leukocyte count (time × supplement × obesity status). Within the OBESE stratum, leukocyte count and gamma-glutamyl transferase (GGT) levels decreased more in the fibre group compared with placebo (adjusted for change in body weight). Comparison of both fibre groups revealed that OBESE subjects had a significantly stronger benefit with respect to leukocyte count and fasting C-peptide levels than NONOBESE participants. Only the effect on leukocyte count survived correction for multiple comparisons. In contrast, under placebo conditions, NONOBESE subjects managed to decrease their body fat content significantly more than OBESE ones. Intention-to-treat (ITT) analysis resulted in similar outcomes. Conclusions: The state of obesity does not relevantly modulate the beneficial effect of cereal fibre on major glycometabolic parameters by fibre supplementation, but leukocyte levels may be affected. Hence, BMI is not a suitable parameter to stratify this cohort with respect to diabetes risk or responsiveness to cereal fibre, but obesity needs to be accounted for when asse...

Some individuals develop T2DM despite significant metabolic improvements through lifestyle intervention. We tested the hypotheses that IGF1 and its binding proteins 1 and 2 a) predict the onset of T2DM in prediabetes patients, b) determine the capacity for metabolic regeneration. Design We measured fasting serum IGF1, IGFBP1 and IGFBP2 in 3 randomized controlled lifestyle intervention trials, covering at least 1 year of intervention period and 1 year of additional follow-up. Methods Within a sample of 414 high-risk prediabetes patients (58% women; 28-80 years), we analyzed fasting serum concentrations of IGF1, IGFBP1 and IGFBP2 in relation to diabetes incidence and metabolic parameters over 2 years. 345 subjects finished the first year of intervention. Results The interventions significantly improved body weight (BMI: -3.24%, p<0.001), liver fat (-36.8%, p<0.001), IS (HOMA-IR: -6.3%, p<0.001) and insulin secretion (Disposition index: +35%, p <0.001) in the cohort. 14 % developed T2DM within 2 years. Mean IGFBP1 levels at baseline were lower in prediabetes compared to a healthy population. Also, prediabetes patients with obesity and NAFLD had lower IGFBP1. Those with impaired glucose tolerance had higher IGFBP1 compared to those with only impaired fasting glucose. Baseline IGF1 was lower (122.5 vs. 146.6 µg/L) and IGFBP1 higher (3.32 vs. 2.09 µg/L) in subjects who developed T2DM (n=57), resulting in a significant prediction of diabetes incidence (HR IGF1 0.991 µg/L, p=0.003; HR IGFBP1 1.061 µg/L, p=0.002). This translates into a 20% and 9% difference in T2DM incidence for IGF1 and IGFBP1, respectively. Despite reduced weight, visceral and hepatic fat as response to one year of lifestyle intervention, those who developed T2DM had not improved insulin sensitivity, glucose tolerance or IGFBP1. Conclusions Lower IGF1 and higher IGFBP1 in prediabetes predicted the incidence of T2DM, indicating an impairment of beta-cell function, which explains the unresponsiveness to lifestyle intervention.