Prebiotic effect of inulin-type fructans on faecal microbiota and short-chain fatty acids in type 2 diabetes: a randomised controlled trial.

PURPOSE: Compared to a healthy population, the gut microbiota in type 2 diabetes presents with several unfavourable features that may impair glucose regulation. The aim of this study was to evaluate the prebiotic effect of inulin-type fructans on the faecal microbiota and short-chain fatty acids (SCFA) in patients with type 2 diabetes. METHODS: The study was a placebo controlled crossover study, where 25 patients (15 men) aged 41-71 years consumed 16 g of inulin-type fructans (a mixture of oligofructose and inulin) and 16-g placebo (maltodextrin) for 6 weeks in randomised order. A 4-week washout separated the 6 weeks treatments. The faecal microbiota was analysed by high-throughput 16S rRNA amplicon sequencing and SCFA in faeces were analysed using vacuum distillation followed by gas chromatography. RESULTS: Treatment with inulin-type fructans induced moderate changes in the faecal microbiota composition (1.5%, p = 0.045). A bifidogenic effect was most prominent, with highest positive effect on operational taxonomic units (OTUs) of Bifidobacterium adolescentis, followed by OTUs of Bacteroides. Significantly higher faecal concentrations of total SCFA, acetic acid and propionic acid were detected after prebiotic consumption compared to placebo. The prebiotic fibre had no effects on the concentration of butyric acid or on the overall microbial diversity. CONCLUSION: Six weeks supplementation with inulin-type fructans had a significant bifidogenic effect and induced increased concentrations of faecal SCFA, without changing faecal microbial diversity. Our findings suggest a moderate potential of inulin-type fructans to improve gut microbiota composition and to increase microbial fermentation in type 2 diabetes. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT02569684).

Effects of Vitamin D Supplementation on Insulin Sensitivity and Insulin Secretion in Subjects With Type 2 Diabetes and Vitamin D Deficiency: A Randomized Controlled Trial.

OBJECTIVE: In observational studies, low vitamin D levels are associated with type 2 diabetes (T2D), impaired glucose metabolism, insulin sensitivity, and insulin secretion. We evaluated the efficacy of vitamin D supplementation on insulin sensitivity and insulin secretion in subjects with T2D and low vitamin D (25-hydroxyvitamin D [25(OH)D] <50 nmol/L). RESEARCH DESIGN AND METHODS: Sixty-two men and women with T2D and vitamin D deficiency participated in a 6-month randomized, double-blind, placebo-controlled trial. Participants received a single dose of 400,000 IU oral vitamin D3 or placebo, and the vitamin D group received an additional 200,000 IU D3 if serum 25(OH)D was <100 nmol/L after 4 weeks. Primary end points were total Rd by euglycemic clamp with assessment of endogenous glucose production and first-phase insulin secretion by intravenous glucose tolerance test. RESULTS: In the vitamin D group, the mean ± SD baseline serum 25(OH)D of 38.0 ± 12.6 nmol/L increased to 96.9 ± 18.3 nmol/L after 4 weeks, 73.2 ± 13.7 nmol/L after 3 months, and 53.7 ± 9.2 nmol/L after 6 months. The total exposure to 25(OH)D during 6 months (area under the curve) was 1,870 ± 192 and 1,090 ± 377 nmol/L per week in the vitamin D and placebo groups, respectively (P < 0.001). Insulin sensitivity, endogenous glucose production, and glycemic control did not differ between or within groups after treatment (P = 0.52). First-phase insulin secretion did not change significantly after treatment (P = 0.10). CONCLUSIONS: Replenishment with a large dose of vitamin D3 to patients with T2D and vitamin D deficiency did not change insulin sensitivity or insulin secretion. These findings do not support such use of therapeutic vitamin D3 supplementation to improve glucose homeostasis in patients with T2D.

Vitamin D deficiency and supplementation in pregnancy in a multiethnic population-based cohort.

BACKGROUND: To investigate ethnic differences in vitamin D levels during pregnancy, assess risk factors for vitamin D deficiency and explore the effect of vitamin D supplementation in women with deficiency in early pregnancy. METHODS: This is a population-based, multiethnic cohort study of pregnant women attending Child Health Clinics for antenatal care in Oslo, Norway. Serum-25-hydroxyvitamin D [25(OH)D] was measured in 748 pregnant women (59% ethnic minorities) at gestational weeks (GW) 15 (SD:3.6) and 28 (1.4). Women with 25(OH)D <37 nmol/L at GW 15 were for ethical reasons recommended vitamin D3 supplementation. Main outcome measure was 25(OH)D, and linear regression models were performed. RESULTS: Severe deficiency (25(OH)D <25 nmol/L) was found at GW 15 in 45% of women from South Asia, 40% from the Middle East and 26% from Sub-Saharan Africa, compared to 2.5% in women from East Asia and 1.3% of women from Western Europe. Women from South Asia, the Middle East and Sub-Saharan Africa had mean values that were -28 (95 % CI:-33, -23), -24 (-29, -18) and -20 (-27, -13) nmol/L lower than in Western women, respectively. Ethnicity, education, season and intake of vitamin D were independently associated with 25(OH)D. At GW 28, the mean 25(OH)D had increased from 23 (SD:7.8) to 47 (27) nmol/L (p < 0.01) in women who were recommended vitamin D supplementation, with small or no change in women with sufficient vitamin D levels at baseline. CONCLUSIONS: Vitamin D deficiency was prevalent among South Asian, Middle Eastern and African women. The serum levels of 25(OH)D increased significantly from GW 15 to 28 in vitamin D deficient women who received a recommendation for supplementation. This recommendation of vitamin D supplementation increased vitamin D levels in deficient women.

The association of basal insulin glargine and/or n-3 fatty acids with incident cancers in patients with dysglycemia.

OBJECTIVE Epidemiologic studies linking insulin glargine and glucose-lowering therapies to cancers and n-3 fatty acids to cancer prevention have not been confirmed. We aimed to assess the effect of insulin glargine and n-3 fatty acids on incident cancers within the context of the ORIGIN (Outcome Reduction with Initial Glargine Intervention) trial. RESEARCH DESIGN AND METHODS The ORIGIN trial is an international, long-term, randomized two-by-two factorial study comparing insulin glargine with standard care and n-3 fatty acids with placebo (double blind) in people with dysglycemia at high risk for cardiovascular events. The primary outcome measure (cancer substudy) was the occurrence of any new or recurrent adjudicated cancer. Cancer mortality and cancer subtypes were also analyzed. RESULTS Among 12,537 people (mean age 63.5 years, SD 7.8; 4,388 females), 953 developed a cancer event during the median follow-up of 6.2 years. In the glargine and standard care groups, the incidence of cancers was 1.32 and 1.32 per 100 person-years, respectively (P = 0.97), and in the n-3 fatty acid and placebo groups, it was 1.28 and 1.36 per 100 person-years, respectively (P = 0.39). No difference in the effect of either intervention was noted within predefined subgroups (P for all interactions ≥0.17). Cancer-related mortality and cancer-specific outcomes also did not differ between groups. Postrandomization HbA1c levels, glucose-lowering therapies (including metformin), and BMI did not affect cancer outcomes. CONCLUSIONS Insulin glargine and n-3 fatty acids have a neutral association with overall and cancer-specific outcomes, including cancer-specific mortality. Exposure to glucose-lowering therapies, including metformin, and HbA1c level during the study did not alter cancer risk.

Vitamin D and the metabolic syndrome.

Vitamin D is essential in bone mineralization and calcium homeostasis, and an increasing body of evidence suggests that vitamin D may be important for maintaining extraskeletal health, including having beneficial effects on cardiometabolic outcomes. Vitamin D deficiency is widespread, but the role of vitamin D in the metabolic syndrome is not fully elucidated. In this review we summarize data from observational studies and randomized controlled trials on the relation between vitamin D and the metabolic syndrome and its components. A large number of observational studies suggest a relationship between low levels of 25(OH)D and the metabolic syndrome or its individual clinical features. Randomized controlled trials of vitamin D supplementation addressing aspects of the metabolic syndrome have yielded inconsistent results, and many studies suffer from methodological limitations. There is an urgent need for large, well-designed randomized controlled trials with relevant endpoints. Until definitive results from such studies are available, caution should be taken towards the use of vitamin D-supplementation for disorders other than musculoskeletal system. New molecular biological techniques elucidating the interaction between the active vitamin D derivatives and target genes represent a promising approach to more precise knowledge about new biomedical function, which also might shed light on the complex metabolic syndrome.

Dietary fat modifications and blood pressure in subjects with the metabolic syndrome in the LIPGENE dietary intervention study.

Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1.2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.

Vitamin status in morbidly obese patients: a cross-sectional study.

BACKGROUND: Morbid obesity is associated with low circulating concentrations of 25-hydroxyvitamin D. Few data on the concentrations of other vitamins in morbidly obese patients are available. OBJECTIVE: The objective was to compare serum and blood vitamin concentrations in morbidly obese patients with those in healthy subjects. DESIGN: In 2 public hospital departments (southeast Norway), we prospectively examined 110 consecutive patients (76 women) and 58 healthy controls (30 women) not taking multivitamin supplements. Patients and controls did not differ significantly in age or ethnicity. The mean (+/-SD) body mass index (in kg/m(2)) was 45 +/- 7 in the patients and was 24 +/- 3 in the controls. Patients with vitamin concentrations lower than 2 SD below the sex-specific mean in controls were considered to have inadequate vitamin status. RESULTS: The morbidly obese women and men had significantly lower concentrations of vitamin B-6, vitamin C, 25-hydroxyvitamin D, and lipid-standardized vitamin E than did the healthy controls (P < 0.01 for each). The status of these vitamins was inadequate in a substantial proportion of the patients (11-38%). The status of vitamins A, B-1, B-2, and B-12 and of folic acid was adequate in most of the patients (95-100%). A moderately elevated C-reactive protein concentration was associated with lower vitamin A, B-6, and C concentrations. In a multiple regression analysis, concentrations of alkaline phosphatase (inverse relation) and vitamin C were the strongest determinants of serum vitamin B-6 concentrations. CONCLUSIONS: Low concentrations of vitamin B-6, vitamin C, 25-hydroxyvitamin D, and vitamin E adjusted for lipids are prevalent in morbidly obese Norwegian patients seeking weight-loss treatment.