Improvement in Visceral Adipose Tissue and LDL Cholesterol by High PUFA Intake: 1-Year Results of the NutriAct Trial.

We assessed the effect of a dietary pattern rich in unsaturated fatty acids (UFA), protein and fibers, without emphasizing energy restriction, on visceral adipose tissue (VAT) and cardiometabolic risk profile. Within the 36-months randomized controlled NutriAct trial, we randomly assigned 502 participants (50-80 years) to an intervention or control group (IG, CG). The dietary pattern of the IG includes high intake of mono-/polyunsaturated fatty acids (MUFA/PUFA 15-20% E/10-15% E), predominantly plant protein (15-25% E) and fiber (≥30 g/day). The CG followed usual care with intake of 30% E fat, 55% E carbohydrates and 15% E protein. Here, we analyzed VAT in a subgroup of 300 participants via MRI at baseline and after 12 months, and performed further metabolic phenotyping. A small but comparable BMI reduction was seen in both groups (mean difference IG vs. CG: -0.216 kg/m2 [-0.477; 0.045], partial η2 = 0.009, p = 0.105). VAT significantly decreased in the IG but remained unchanged in the CG (mean difference IG vs. CG: -0.162 L [-0.314; -0.011], partial η2 = 0.015, p = 0.036). Change in VAT was mediated by an increase in PUFA intake (ß = -0.03, p = 0.005) and induced a decline in LDL cholesterol (ß = 0.11, p = 0.038). The NutriAct dietary pattern, particularly due to high PUFA content, effectively reduces VAT and cardiometabolic risk markers, independent of body weight loss.

Implication of sugar, protein and incretins in excessive glucagon secretion in type 2 diabetes after mixed meals.

AIMS: Amino acids powerfully release glucagon but their contribution to postprandial hyperglucagonemia in type 2 diabetes remains unclear. Exogenously applied GIP stimulates, while GLP-1 inhibits, glucagon secretion in humans. However, their role in mixed meals is unclear, which we therefore characterized. METHODS: In three experiments, participants with type 2 diabetes and obese controls randomly received different loads of sugars and/or proteins. In the first experiment, participants ingested the rapidly cleaved saccharose (SAC) or slowly cleaved isomaltulose (ISO) which is known to elicit opposite profiles of GIP and GLP-1 secretion. In the second one participants received test meals which contained saccharose or isomaltulose in combination with milk protein. The third set of participants underwent randomized oral protein tests with whey protein or casein. Incretins, glucagon, C-peptide, and insulin were profiled by specific immunological assays. RESULTS: 50 g of the sugars alone suppressed glucagon in controls but slightly less in type 2 diabetes patients. Participants with type 2 diabetes showed excessive glucagon responses within 15 min and lasting over 3 h, while the obese controls showed small initial and delayed greater glucagon responses to mixed meals. The release of GIP was significantly faster and greater with SAC compared to ISO, while GLP-1 showed an inverse pattern. The glucagon responses to whey or casein were only moderately increased in type 2 diabetes patients without a left shift of the dose response curve. CONCLUSIONS: The rapid hypersecretion of glucagon after mixed meals in type 2 diabetes patients compared to controls is unaffected by endogenous incretins. The defective suppression of glucagon by glucose combined with hypersecretion to protein is required for the exaggerated response. CLINICAL TRIALS NUMBERS: NCT03806920, NCT02219295, NCT04564391.

Effects of Insoluble Cereal Fibre on Body Fat Distribution in the Optimal Fibre Trial.

SCOPE: The Optimal Fibre Trial (OptiFiT) investigates metabolic effects of insoluble cereal fibre in subjects with impaired glucose tolerance (IGT), showing moderate glycemic and anti-inflammatory benefits, especially in subjects with an obesity-related phenotype. An OptiFiT sub-group is analysed for effects on body fat distribution. METHODS AND RESULTS: 180 participants with IGT receive a blinded, randomized supplementation with insoluble cereal fibre or placebo for 2 years. Once a year, all subjects undergo fasting blood sampling, oral glucose tolerance test, and anthropometric measurements. A subgroup (n=47) also received magnetic resonance imaging and spectroscopy for quantification of adipose tissue distribution and liver fat content. We compared MR, metabolic and inflammatory outcomes between fibre and placebo group metabolism and inflammation. Visceral and non-visceral fat, fasting glucose, HbA1c, fasting insulin, insulin resistance, and uric acid decrease only in the fibre group, mirroring effects of the entire cohort. However, after adjustment for weight loss, there are no significant between-group differences. There is a statistical trend for fibre-driven liver fat reduction in subjects with confirmed non-alcoholic fatty liver disease (NAFLD; n = 19). CONCLUSIONS: Data and evidence on beneficial effects of insoluble cereal fibre on visceral and hepatic fatstorage is limited, but warrants further research. Targeted trials are required.

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).

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 assessing anti-inflammatory effects of fibre treatments. Targeted diabetes prevention should focus on the actual metabolic state rather than on mere obesity.