Incretin,insulinotropic and glucose-lowering effects of whey protein pre-load in type 2 diabetes: a randomised clinical trial

Aims/hypothesis

Since protein ingestion is known to stimulate the secretion of glucagon-like peptide-1 (GLP-1), we hypothesised that enhancing GLP-1 secretion to harness its insulinotropic/beta cell-stimulating activity with whey protein pre-load may have beneficial glucose-lowering effects in type 2 diabetes.

Methods

In a randomised, open-label crossover clinical trial, we studied 15 individuals with well-controlled type 2 diabetes who were not taking any medications except for sulfonylurea or metformin. These participants consumed, on two separate days, 50 g whey in 250 ml water or placebo (250 ml water) followed by a standardised high-glycaemic-index breakfast in a hospital setting. Participants were randomised using a coin flip. The primary endpoints of the study were plasma concentrations of glucose, intact GLP-1 and insulin during the 30 min following meal ingestion.

Results

In each group, 15 patients were analysed. The results showed that over the whole 180 min post-meal period, glucose levels were reduced by 28% after whey pre-load with a uniform reduction during both early and late phases. Insulin and C-peptide responses were both significantly higher (by 105% and 43%, respectively) with whey pre-load. Notably, the early insulin response was 96% higher after whey. Similarly, both total GLP-1 (tGLP-1) and intact GLP-1 (iGLP-1) levels were significantly higher (by 141% and 298%, respectively) with whey pre-load. Dipeptidyl peptidase 4 plasma activity did not display any significant difference after breakfast between the groups.

Conclusions/interpretation

In summary, consumption of whey protein shortly before a high-glycaemic-index breakfast increased the early prandial and late insulin secretion, augmented tGLP-1 and iGLP-1 responses and reduced postprandial glycaemia in type 2 diabetic patients. Whey protein may therefore represent a novel approach for enhancing glucose-lowering strategies in type 2 diabetes. Trial registration ClinicalTrials.gov NCT01571622 Funding The Israeli Ministry of Health and Milk Council funded the research.     

Systemic markers of microvascular disease and bone mineral density in older adults

Summary

Here we report that abnormal brain white matter and, to a lesser extent, albuminuria are associated with reduced bone mineral density in the hip, spine, and total body in men and women. These findings may explain the increased hip fracture risk reported in some studies in association with microvascular disorders.

Introduction

Markers of microvascular disease have been individually associated with increased risk of osteoporotic fractures in some studies. Here, we examine whether these markers are associated with reduced bone mineral density (BMD) individually and together.

Methods

BMD testing using dual x-ray absorptiometry of the hip, lumbar spine, and total body was performed in 1473 participants from the Cardiovascular Health Study (mean age ~ 78 years): 1215 were assessed for urinary albumin-creatinine ratio, 944 for abnormal white matter disease (AWMD) by brain MRI, and 541 for retinal vascular disease with fundus photographs. Linear regression models were used to evaluate the cross-sectional association of each marker with BMD accounting for potentially confounding factors.

Results

AWMD was associated with lower hip, spine, and total body BMD in women (β ?3.08 to ?4.53; p < 0.01 for all) and lower hip and total body BMD in men (β ?2.90 to ?4.24; p = 0.01–0.03). Albuminuria was associated with lower hip (β ?3.37; p = .05) and total body (β ?3.21; p = .02) BMD in men, but not in women. The associations of AWMD and albuminuria with BMD persisted with mutual adjustment and appeared to be additive to each other. Retinal vascular disease was not associated with BMD in men or women.

Conclusion

AWMD and, to a lesser extent, albuminuria were independently associated with lower BMD, suggesting that microvascular disease may play a role in the pathogenesis of reduced BMD. These findings need to be confirmed by longitudinal studies.

     

Safety of vaginal delivery in very low birthweight vertex singletons: a meta-analysis

Objective: The objective of this study is to assess the safety of vaginal delivery in VLBW singletons in the vertex presentation.

Methods: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science databases were searched for studies on mode of delivery and neonatal outcome in VLBW singletons in the vertex presentation. A total of 28 studies met our inclusion criteria.

Results: Vaginal delivery was not associated with an increase in overall neonatal mortality compared with cesarean delivery (OR 0.87, 95% CI 0.72–1.04). Vaginal delivery was associated with a significant decrease in mortality for the 1250–1500?g birthweight category (OR 0.57, 95% CI 0.36–0.92), while an increase in mortality in the 500–750?g category was not significant (OR 1.5, 95% CI 0.86–2.61). Severe intraventricular hemorrhage (IVH) was not associated with mode of delivery (OR 1.05, 95% CI 0.85–1.29), but the only two high quality study that assessed IVH of all grades found an increase in risk for IVH in vaginal delivery (OR 1.33, 95% CI 1.16–1.51).

Conclusions: Vaginal delivery does not appear to increase the risk for neonatal mortality. However, current available data on neonatal morbidity are limited. More high-quality studies are needed to assess the association between mode of delivery and neonatal morbidity.     

Seasonal changes of responses to gonadotropin-releasing hormone analog in expression of growth hormone/prolactin/somatolactin genes in the pituitary of masu salmon

Gonadotropin-releasing hormone (GnRH) is considered to stimulate secretion of growth hormone (GH), prolactin (PRL), and somatolactin (SL) at particular stages of growth and sexual maturation in teleost fishes. We therefore examined seasonal variation in the pituitary levels of GH/PRL/SL mRNAs, and tried to clarify seasonal changes of responses to GnRH in expression of GH/PRL/SL genes, in the pituitaries of growing and maturing masu salmon (Oncorhynchus masou). Pituitary samples were monthly collected one week after implantation with GnRH analog (GnRHa). The levels of mRNAs encoding GH, PRL, and SL precursors in single pituitaries were determined by a real-time polymerase chain reaction method. The fork lengths and body weights of control and GnRHa-implanted fish of both sexes gradually increased and peaked out in September of 2-year-old (2+) when fish spawned. GnRHa implantation did not stimulate somatic growth, nor elevate gonadosomatic index (GSI) of 1+ and 2+ males, whereas it significantly increased GSI of 2+ females in late August to early September. The GnRHa-implanted 1+ males had higher levels of GH and PRL mRNAs in July, and SL mRNA from June to August than the control males. The levels of GH, PRL, and SL mRNAs in the control and GnRHa-implanted 1+ females, however, did not show any significant changes. Afterward, the PRL mRNA levels elevated in the control 2+ fish of both sexes in spring. GnRHa elevated the GH mRNA levels in both males and females in 2+ winter, and the PRL mRNA levels in females in early spring. Regardless of sex and GnRHa-implantation, the SL mRNA levels increased during sexual maturation. In growing and maturing masu salmon, expression of genes encoding GH, PRL, and SL in the pituitary is thus sensitive to GnRH in particular seasons probably in relation to physiological roles of the hormones.     

The different faces of Creutzfeldt-Jacob Disease CJD in psychiatry

Objective

Creutzfeldt-Jacob Disease (CJD) is a rapidly progressive spongiform disease of the central nervous system. Psychiatric symptoms, though considered rare, can be the presenting symptoms of CJD and impose diagnosis difficulties. We reviewed prospectively our database to identify the frequency of psychiatric symptoms as identifying symptoms among our community.

Methods

We included all patients in Sheba Medical Center who were diagnosed with CJD between the years 2006 and 2012. Data were collected retrospectively.

Results

Twenty-three patients with CJD were admitted to our hospital during this 6-year period. Among them, 10 (44%) were diagnosed first as “psychiatric patients” due to psychiatric presenting symptoms.

Conclusion

In our series, the frequency of misleading psychiatric symptom was 44%. Clinicians should therefore include CJD in their differential diagnoses of new onset dementia, particularly when associated psychosis and depression symptoms persist and worsen, despite standard psychiatric treatments.