The impact of cholecalciferol supplementation on the systemic inflammatory profile: a systematic review and meta-analysis of high-quality randomized controlled trials.

Causal links between vitamin D status [25(OH)D] and systemic inflammation were examined through a systematic review of randomized controlled trials (RCTs). Selected RCTs were ⩾12 weeks, conducted in adults free of acute inflammatory disease, and of high-quality (Jadad score ⩾3). Of 14 studies that met our criteria, 9 studies (15 study arms) permitted extraction of data. There was no effect on the weighted mean difference (WMD) of IL-6 (WMD (95% confidence interval)=0.1, (-0.166, 0.366) pg/ml, P=0.462) or C-reactive protein (CRP) (WMD=-0.324, (-1.007, 0.359) mg/l, P=0.352). Subgroup analyses of trials achieving ⩾80 nmol/l indicated a trend for lower CRP (WMD=-0.834, (-1.726, 0.058) mg/l, P=0.067), however heterogeneity was significant (I2=66.7%, P=0.017). Studies employing a low dose (<1000 IU/d) showed increased CRP (WMD=0.615, (0.132, 1.098), P=0.013). In contrast, ⩾1000 IU/d had a favourable effect on CRP (WMD=-0.939, (-1.805, -0.073), P=0.034) but heterogeneity was significant (I2=61.3%, P=0.017). Meta-regression indicated that older age predicted a significant decrease in IL-6 (ß=-0.02, (-0.034, -0.006) pg/ml, P=0.013) and CRP (ß=-0.06, (-0.103, -0.017), P=0.01), whereas a greater percentage of females (ß=0.027, (0.011, 0.044), P=0.004) and longer study duration independently predicted a higher WMD for CRP (ß=0.049, (0.018, 0.079), P=0.005). Available high-quality RCTs did not support a beneficial effect of cholecalciferol on systemic IL-6 and CRP. Future studies should consider the confounding effects of age, gender and study duration, while possibly targeting an achieved 25(OH)D ⩾80 nmol/l.

The bioenergetics of inflammation: insights into obesity and type 2 diabetes.

Diabetes mellitus is one of the most common chronic metabolic disorders worldwide, and its incidence in Asian countries is alarmingly high. Type 2 diabetes (T2DM) is closely associated with obesity, and the staggering rise in obesity is one of the primary factors related to the increased frequency of T2DM. Low-grade chronic inflammation is also accepted as an integral metabolic adaption in obesity and T2DM, and is believed to be a major player in the onset of insulin resistance. However, the exact mechanism(s) that cause a persistent chronic low-grade infiltration of leukocytes into insulin-target tissues such as adipose, skeletal muscle and liver are not entirely known. Recent developments in the understanding of leukocyte metabolism have revealed that the inflammatory polarization of immune cells, and consequently their immunological function, are strongly connected to their metabolic profile. Therefore, it is hypothesized that dysfunctional immune cell metabolism is a central cellular mechanism that prevents the resolution of inflammation in chronic metabolic conditions such as that observed in obesity and T2DM. The purpose of this review is to explore the metabolic demands of different immune cell types, and identify the molecular switches that control immune cell metabolism and ultimately function. Understanding of these concepts may allow the development of interventions that can correct immune function and may possibly decrease chronic low-grade inflammation in humans suffering from obesity and T2DM. We also review the latest clinical techniques used to measure metabolic flux in primary leukocytes isolated from obese and T2DM patients.

Nutrient regulation of ß-cell function: what do islet cell/animal studies tell us?

Diabetes mellitus is widely recognised as one of the most serious metabolic diseases worldwide, and its incidence in Asian countries is growing at an alarming rate. Type 2 diabetes (T2DM) is closely associated with age, sedentary lifestyle and poor diet. In T2DM, ß-cell dysfunction will occur before hyperglycaemia develops. Excessive levels of glucose, lipid and various inflammatory factors interact at the level of the pancreatic islet to promote ß-cell dysfunction. Pancreatic ß-cell lines have been widely utilised since the early 1980s and have contributed a large volume of important information regarding molecular, metabolic and genetic mechanisms that regulate insulin secretion. The purpose of this review is to describe the origin and characteristics of the most commonly used ß-cell lines and their contribution to discovery of fundamental regulatory processes that control insulin production and release. Pancreatic islets obtained from rodents as well as other animals have additionally provided information on the architecture and three-dimensional design of this endocrine tissue that allows precise regulation of hormone release. Understanding the nature of failure of physiologic and metabolic processes leading to insufficient insulin release and subsequent diabetes has allowed development of novel anti-diabetic therapeutics, now in common use, worldwide.

Vitamin D status and insulin sensitivity are novel predictors of resting metabolic rate: a cross-sectional analysis in Australian adults.

PURPOSE: Resting metabolic rate (RMR) accounts for two-thirds of the total energy expenditure in sedentary individuals. After accounting for traditional factors, there still remains a considerable unexplained variance in RMR. There is a pandemic of obesity and metabolic syndrome (MetS) which coexists with a high prevalence of vitamin D insufficiency. The aim of this study was to evaluate the potential effects of vitamin D status, insulin sensitivity (IS) and the metabolic syndrome (MetS) on RMR in Australian adults. METHODS: RMR, respiratory quotient (RQ), McAuley's insulin sensitivity index, fat mass (FM), fat-free mass (FFM) and vitamin D status were assessed in Australian adults. The presence of MetS was evaluated by current standard criteria. Predictors of RMR were examined through multiple linear regression based on stepwise and backward regression approaches with attention to multi-collinearity. All analyses were conducted on SPSS version 21. RESULTS: One hundred and twenty-seven participants (45 men, 82 women), aged 53.4 ± 11.7 years and BMI 31.9 ± 5.2 kg/m(2), were included. Forty-one subjects were insufficient in vitamin D status (<50 nmol/L), and 75 participants had the MetS. A parsimonious regression model explained 85.8 % of RMR and was given by: RMR (kJ/d) = 1931 + 83.5 × FFM (kg) + 29.5 × FM (kg) + 5.65 × 25(OH)D (nmol/L) - 17.6 × age (years) - 57.51 × IS. CONCLUSION: Vitamin D status and IS are novel independent predictors of RMR in adults. Future studies could validate a causal role for these factors in human energy metabolism.