Effects of dietary supplementation on progression to type 2 diabetes in subjects with prediabetes: a single center randomized double-blind placebo-controlled trial

Objectives: To examine the effect of dietary supplements on diabetic risk progression, blood glucose level, and lipid profiles.Methods: A randomized, double-blind, placebo-controlled study was conducted at Rajavithi hospital, Thailand. Participants with prediabetes were randomly allocated to three arms of dietary supplements: placebo (PL) or curcumin plus fish oil and vitamin D (CFD), or curcumin plus fish oil (CF) for 24 weeks. Primary outcomes were the progression of glycemic status and the progression to overt diabetes at 24-week and 36-week follow-ups. Secondary outcomes were changes in glycemic profiles (fasting plasma glucose, 75 g OGTT 2-h plasma glucose or HbA1C), body weight, BMI and lipid profiles.Results: A total of forty-seven participants (PL, n = 16; CFD, n = 15; CF, n = 16) were included in the study. At the 24-week follow-up, the participants with worsening glycemic status in the intervention groups were lower, CFD, CF and Placebo, 14.29%, 13.33% and 31.25%, respectively. However, the primary outcome, progression of glycemic status, was statistically different, with p - value = 0.046 (p < 0.05) when excluding previous diabetes in the study. As well as the incidence of type 2 diabetes at 24-week follow-up was not statistically different between the three groups, 14.29%, 13.33%, and 12.5%, p - value = 0.699 (p < 0.05) in CFD, CF, PL group, respectively. The secondary outcomes also failed to demonstrate the effect of dietary supplements on blood glucose, lipid profiles, weight, BMI and blood chemistry.Conclusion: The combined dietary supplements which contained curcumin-fish oil-vitamin D,could lower the glycemic status progression in prediabetes at six months follow-up and were well-tolerated among the participants

Effect on Vitamin D status of Breastfeeding Infants after Vitamin D3 Supplementation during Breastfeeding Lactation: A double-blind randomized controlled trial

Background: Vitamin D deficiency in pregnancy increases several risks of breastfed mothers. To prevent these adverse events, vitamin D supplementation during pregnancy and lactation is recommended, but suggested dose ranges vary. Objective: To determine whether vitamin D3 1,800 IU/d supplementation in lactating mothers improves the vitamin D status of their breastfed infants. Materials and Methods: A randomized, placebo–controlled trial with Thai pregnant women was conducted. Lactating mothers (n=72) and their breastfed infants with insufficient maternal 25 hydroxyvitamin D (25(OH)D) levels in the third trimester were randomly assigned to two groups, one of which received 1,800 IU/d vitamin D supplementation and the other a placebo. Maternal serum 25(OH)D during lactation, cord blood, and 6-week breastfed infant serum were measured using LC-MS/MS. Results: Mean maternal age (±SD) was 27±5 years, and pre-gestational BMI was 22.29±5 kg/m2. Maternal serum 25(OH)D at baseline was 22.29±7.15 nmol/L. At 6 weeks, both maternal 25(OH)D and infant 25 (OH)D levels had increased significantly in the vitamin D supplement group of mothers and infants (68.30±15.40, 40.40±12.56 nmol/L) compared to those in placebo groups (55.15±13.57, 24.28±17.20 nmol/L) (p <0.001, p<0.001). The changes in infant 25(OH)D levels increased substantially in the vitamin D supplement group but decreased in placebo(17.49±16.27 ng/ml compared to -1.34±19.23 nmol/L in the placebo group, p<0.001). The change of maternal 25(OH)D were positively correlation to the change of 25(OH)D level in breastmilk mothers and infants by r=0.697, p<0.001 and r=0.379, p=0.003 respectively. Conclusions: Vitamin D3 supplementation to breastfed mother during lactation can increase serum 25(OH)D level in Thai breastfed mother and infants. Further work is needed to determine the optimum duration of vitamin D supplementation to normalized breastfed infants with 25(OH)D level >75 nmol/L

A randomized study on the effect of vitamin D3 supplementation on skeletal muscle morphology and vitamin D receptor concentration in older women

Context:Studies examining whether vitamin D supplementation increases muscle mass or muscle-specific vitamin D receptor (VDR) concentration are lacking.Objective:To determine whether vitamin D3 4000 IU/d alters muscle fiber cross-sectional area (FCSA) and intramyonuclear VDR concentration over 4 months.Design and Setting:Randomized, double-blind, placebo-controlled study in a single center.Participants:21 mobility-limited women (aged ≥65 years) with serum 25-hydroxyvitamin D (25OHD) levels 22.5-60 nmol/L.Main Outcome Measures:Baseline and 4-month FCSA and intramyonuclear VDR were measured from vastus lateralis muscle cross-sections probed for muscle fiber type (I/IIa/IIx) and VDR using immunofluorescence.Results:At baseline, mean (±SD) age was 78±5 years; body mass index (BMI) was 27±5 kg/m(2); 25OHD was 46.3±9.5 nmol/L; and a short physical performance battery score was 7.95±1.57 out of 12. At 4 months, 25OHD level was 52.5±17.1 (placebo) vs. 80.0±11.5 nmol/L (VD; P<0.01) and change in 25OHD level was strongly associated with percent change in intramyonuclear VDR concentration independent of group (r=0.87, P<0.001). By treatment group, percent change in intramyonuclear VDR concentration was 7.8±18.2% (placebo) vs. 29.7±11.7% (VD; P=0.03) with a more pronounced group difference in type II vs. I fibers. Percent change in total (type I/II) FCSA was -7.4±18.9% (placebo) vs. 10.6±20.0% (VD; P=0.048).Conclusion:Vitamin D3 supplementation increased intramyonuclear VDR concentration by 30% and increased muscle fiber size by 10% in older, mobility-limited, vitamin D-insufficient women. Further work is needed to determine whether the observed effect of vitamin D on fiber size is mediated by the VDR and to identify which signaling pathways are involved

Multimerization of GPIHBP1 and Familial Chylomicronemia from a Serine-to-Cysteine Substitution in GPIHBP1's Ly6 Domain

GPIHBP1, a glycosylphosphatidylinositol-anchored glycoprotein of microvascular endothelial cells, binds lipoprotein lipase (LPL) within the interstitial spaces and transports it across endothelial cells to the capillary lumen. The ability of GPIHBP1 to bind LPL depends on the Ly6 domain, a three-fingered structure containing 10 cysteines and a conserved pattern of disulfide bond formation. Here, we report a patient with severe hypertriglyceridemia who was homozygous for a GPIHBP1 point mutation that converted a serine in the GPIHBP1 Ly6 domain (Ser-107) to a cysteine. Two hypertriglyceridemic siblings were homozygous for the same mutation. All three homozygotes had very low levels of LPL in the preheparin plasma. We suspected that the extra cysteine in GPIHBP1-S107C might prevent the trafficking of the protein to the cell surface, but this was not the case. However, nearly all of the GPIHBP1-S107C on the cell surface was in the form of disulfide-linked dimers and multimers, whereas wild-type GPIHBP1 was predominantly monomeric. An insect cell GPIHBP1 expression system confirmed the propensity of GPIHBP1-S107C to form disulfide-linked dimers and to form multimers. Functional studies showed that only GPIHBP1 monomers bind LPL. In keeping with that finding, there was no binding of LPL to GPIHBP1-S107C in either cell-based or cell-free binding assays. We conclude that an extra cysteine in the GPIHBP1 Ly6 motif results in multimerization of GPIHBP1, defective LPL binding, and severe hypertriglyceridemia