Supplementation-induced change in muscle carnosine is paralleled by changes in muscle metabolism, protein glycation and reactive carbonyl species sequestering.

Carnosine is a performance-enhancing food supplement with a potential to modulate muscle energy metabolism and toxic metabolites disposal. In this study we explored interrelations between carnosine supplementation (2 g/day, 12 weeks) induced effects on carnosine muscle loading and parallel changes in (i) muscle energy metabolism, (ii) serum albumin glycation and (iii) reactive carbonyl species sequestering in twelve (M/F=10/2) sedentary, overweight-to-obese (BMI: 30.0+/-2.7 kg/m2) adults (40.1+/-6.2 years). Muscle carnosine concentration (Proton Magnetic Resonance Spectroscopy; 1H-MRS), dynamics of muscle energy metabolism (Phosphorus Magnetic Resonance Spectroscopy; 31P-MRS), body composition (Magnetic Resonance Imaging; MRI), resting energy expenditure (indirect calorimetry), glucose tolerance (oGTT), habitual physical activity (accelerometers), serum carnosine and carnosinase-1 content/activity (ELISA), albumin glycation, urinary carnosine and carnosine-propanal concentration (mass spectrometry) were measured. Supplementation-induced increase in muscle carnosine was paralleled by improved dynamics of muscle post-exercise phosphocreatine recovery, decreased serum albumin glycation and enhanced urinary carnosine-propanal excretion (all p<0.05). Magnitude of supplementation-induced muscle carnosine accumulation was higher in individuals with lower baseline muscle carnosine, who had lower BMI, higher physical activity level, lower resting intramuscular pH, but similar muscle mass and dietary protein preference. Level of supplementation-induced increase in muscle carnosine correlated with reduction of protein glycation, increase in reactive carbonyl species sequestering, and acceleration of muscle post-exercise phosphocreatine recovery.

Vitamin D and cardiometabolic disorders: a review of current evidence, genetic determinants and pathomechanisms.

Vitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1-α-hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.

Younger people with Type 2 diabetes have poorer self-care practices compared with older people: results from the Australian National Diabetes Audit.

AIM: This cross-sectional study compares the self-care practices of younger and older people with Type 2 diabetes. METHODS: Data were analysed from the Australian National Diabetes Audit (ANDA) including 2552 adults with Type 2 diabetes from Australian Diabetes Centres. Pre-specified demographic and clinical variables were obtained. Self-care variables (physical activity, following dietary recommendations, medication adherence and monitoring blood glucose levels) were compared in people ≤ 64 and > 64 years of age. RESULTS: Mean age (± sd) of participants was 63 ± 13 years overall, 53 ± 9 years for the younger group and 73 ± 6 years for the older group. A greater proportion of younger people had HbA1c levels > 53 mmol/mol (> 7.0%) (76% vs. 68%), reported difficulty following dietary recommendations (50% vs. 32%) and forgetting medications (37% vs. 22%) compared with older people (all P-values <0.001). A smaller proportion of younger compared with older people reported monitoring their blood glucose levels as often as recommended (60% vs. 70%, P < 0.001). Similar proportions of people aged ≤ 64 and > 64 years required insulin therapy (59% vs. 57%, P = 0.200). Younger age was associated with a twofold increase in the odds of not following the recommended self-care practices after adjustment for gender, smoking, insulin therapy, depression and allied health attendance (all P < 0.001). CONCLUSIONS: Despite shorter diabetes duration, younger age was associated with worse glycaemic control and poorer diabetes self-care practices among people with Type 2 diabetes. Targeted strategies are required to optimize diabetes self-care practices and thereby glycaemic control.

Emergency treatment of hypoglycaemia: a guideline and evidence review.

AIM: To examine the current treatment guidelines for the emergency management of hypoglycaemia and the evidence underpinning recommendations. METHODS: International diabetes agencies were searched for hypoglycaemia treatment guidelines. Guidelines were assessed using the Appraisal of Guidelines Research and Evaluation II (AGREE II) instrument. An electronic database search was conducted for evidence regarding emergency treatment of hypoglycaemia in adults, and relevant articles were critically appraised. RESULTS: Of the international diabetes agencies, six sets of guidelines were deemed relevant and of sufficient detail for appraisal by AGREE II. The evidence search returned 2649 articles, of which 17 pertaining to the emergency management of hypoglycaemia were included. High-quality evidence for the management of hypoglycaemia was lacking, limiting treatment recommendations. In general, guidelines and studies were somewhat concordant and recommended 15-20 g of oral glucose or sucrose, repeated after 10-15 min for treatment of the responsive adult, and 10% intravenous dextrose or 1 mg intramuscular glucagon for treatment of the unresponsive adult. No evidence was found for other treatment approaches. CONCLUSION: Evidence for the emergency treatment of hypoglycaemia in adults is limited, is often low grade and mostly pre-dates contemporary management of diabetes. Guideline recommendations are limited by the lack of randomized trials. Further high-quality studies are required to inform the optimum management of this frequently occurring emergency condition.

Salsalate has no effect on insulin secretion but decreases insulin clearance: a randomized, placebo-controlled trial in subjects without diabetes.

To elucidate whether increased insulin concentration after salsalate treatment (3 g/day for 7 days) is attributable to an increased insulin secretion rate (ISR) or to reduced metabolic clearance of endogenous insulin (MCI) during stepped glucose infusion (SGI). The analysis was performed in obese subjects who participated in a randomized double-blind, parallel, placebo-controlled clinical trial. A total of 27 participants (16 on salsalate, 11 on placebo) completed baseline and follow-up SGI. During SGI in the salsalate group, C-peptide concentrations were reduced by 11%, while plasma insulin concentrations were increased by 30%, corresponding to a 30% reduction in MCI (p < 0.0001). At molar increments of glucose, insulin concentrations were increased by 27% (p = 0.02), but ISR was unchanged. Salsalate did not alter insulin secretion, but lowered MCI, indicating that a reduction in insulin clearance is the principal mechanism for increased insulin levels after salsalate administration.

Vitamin D and cardiometabolic risk factors and diseases.

Obesity, type 2 diabetes, and cardiovascular disease (CVD) are the most common preventable causes of morbidity and mortality worldwide. Insulin resistance, which is a shared feature in these conditions, is also strongly linked to the development of polycystic ovary syndrome (PCOS), which is the most common endocrine disease in women of reproductive age and a major cause of infertility. Vitamin D deficiency has reached epidemic proportions worldwide, primarily due to the shift to sedentary, indoor lifestyles and sun avoidance behaviours to protect against skin cancer. In recent years, vitamin D deficiency has been implicated in the aetiology of type 2 diabetes, PCOS and CVD, and has been shown to be associated with their risk factors including obesity, insulin resistance, hypertension, as well as chronic low-grade inflammation. Treating vitamin D deficiency may offer a feasible and cost-effective means of reducing cardiometabolic risk factors at a population level in order to prevent the development of type 2 diabetes and CVD. However, not all intervention studies show that vitamin D supplementation alleviates these risk factors. Importantly, there is significant heterogeneity in existing studies with regards to doses and drug regimens used, populations studied (i.e. vitamin D deficient or sufficient), and the lengths of supplementation, and only few studies have directly examined the effect of vitamin D on insulin secretion and resistance with the use of clamp methods. Therefore, there is a need for well-designed large scale trials to clarify the role of vitamin D supplementation in the prevention of type 2 diabetes, PCOS, and CVD.

Obesity and polycystic ovary syndrome.

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

The effect of salsalate on insulin action and glucose tolerance in obese non-diabetic patients: results of a randomised double-blind placebo-controlled study.

AIM/HYPOTHESIS: Low-grade inflammation may contribute to obesity-related insulin resistance and has been associated with increased risk of type 2 diabetes mellitus. The present study evaluated whether treatment with salsalate, a traditional anti-inflammatory medication, would improve insulin action in obese non-diabetic individuals. METHODS: The study was a randomised, double-blind, placebo-controlled, parallel trial conducted at the inpatient clinical research unit of the NIDKK (Phoenix, AZ, USA). Participants were 54 adults (18 to 45 years of age) with BMI >or= 30 kg/m(2). The intervention was salsalate (3 g/day, n = 28) or identical placebo (n = 26) for 7 days. The allocation was kept concealed by giving the investigator only a number corresponding to a vial of placebo or salsalate sequentially randomised in blocks by sex. Main outcomes were changes in insulin action assessed as rate of glucose disposal (R (d)) by euglycaemic-hyperinsulinaemic clamp (insulin infusion rate 40 mU m(-2) min(-1)) and glucose tolerance by 75 g OGTT. RESULTS: The study was completed by 47 participants, of which 40 were analysed (salsalate n = 22, placebo n = 18). Salsalate treatment resulted in decreased fasting plasma glucose concentration (mean [SD]; 4.83 [0.28] vs 5.11 [0.33] mmol/l, p = 0.001) and glucose AUC during the OGTT (p = 0.01), and in increased R (d) (20 [8] vs 18 [6] micromol [kg estimated metabolic body size](-1) min(-1), p = 0.002), while there was no significant change in these variables with placebo (p > 0.3 for all). The effect of salsalate on R (d) disappeared (p = 0.9) after normalising to increased insulin concentrations (701 [285] vs 535 [201] pmol/l, p < 0.0001) measured during the clamp. No side effects of salsalate were observed during the study. CONCLUSIONS/INTERPRETATION: The glucose-lowering potential of salicylates appears to be due to effects on insulin concentration rather than improved insulin action. Salicylate-based compounds may be useful for the treatment and prevention of type 2 diabetes.