An Increase in Fat-Free Mass is Associated with Higher Appetite and Energy Intake in Older Adults: A Randomised Control Trial

Cross-sectional studies in younger adults have demonstrated a positive association between energy intake (EI) and fat-free mass (FFM), with this relationship seemingly mediated by resting metabolic rate (RMR). Establishing a causal effect longitudinally would be prudent in older adults suffering from loss of appetite. We investigated the effects of FFM on RMR, appetite and EI in 39 healthy older adults (age: 66 ± 4 years, BMI: 25.1 ± 3.5 kg∙m2) assigned to either 12-week resistance training + protein supplementation group (RT + PRO) or control group (CON). Body composition, subjective appetite, leptin, insulin, RMR and laboratory-measured ad libitum EI were measured at baseline, weeks 6 and 12 of the intervention, while daily EI at baseline and week 12. FFM (+1.2 kg; p = 0.002), postprandial subjective appetite (+8 mm; p = 0.027), ad libitum EI (+119 kcal; p = 0.012) and daily EI (+133 kcal; p = 0.010) increased from baseline to week 12 in the RT + PRO. RMR, fasted subjective appetite, leptin and insulin concentrations remained unchanged (all p > 0.05). The increases ad libitum EI correlated with increases in FFM (r = 0.527, p = 0.001), with 54% of the change in EI attributed to FFM changes. In conclusion, FFM increases were associated with an increased ad libitum EI and postprandial appetite in older adults

Omega-3 polyunsaturated fatty acid supplementation versus placebo on vascular health, glycaemic control, and metabolic parameters in people with type 1 diabetes: a randomised controlled preliminary trial

Background: The role of omega-3 polyunsaturated fatty acids (n-3PUFA), and the potential impact of n-3PUFA supplementation, in the treatment and management of type 1 diabetes (T1D) remains unclear and controversial. Therefore, this study aimed to examine the efficacy of daily high-dose-bolus n-3PUFA supplementation on vascular health, glycaemic control, and metabolic parameters in subjects with T1D. Methods: Twenty-seven adults with T1D were recruited to a 6-month randomised, double-blind, placebo-controlled trial. Subjects received either 3.3 g/day of encapsulated n-3PUFA or encapsulated 3.0 g/day corn oil placebo (PLA) for 6-months, with follow-up at 9-months after 3-month washout. Erythrocyte fatty acid composition was determined via gas chromatography. Endpoints included inflammation-associated endothelial biomarkers (vascular cell adhesion molecule-1 [VCAM-1], intercellular adhesion molecule-1 [ICAM-1], E-selectin, P-selectin, pentraxin-3, vascular endothelial growth factor [VEGF]), and their mediator tumor necrosis factor alpha [TNFα] analysed via immunoassay, vascular structure (carotid intima-media thickness [CIMT]) and function (brachial artery flow mediated dilation [FMD]) determined via ultrasound technique, blood pressure, glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG), and postprandial metabolism. Results: Twenty subjects completed the trial in full. In the n-3PUFA group, the mean ± SD baseline n-3PUFA index of 4.93 ± 0.94% increased to 7.67 ± 1.86% (P  0.05). Conclusions: This study indicates that daily high-dose-bolus of n-3PUFA supplementation for 6-months does not improve vascular health, glucose homeostasis, or metabolic parameters in subjects with T1D. The findings from this preliminary RCT do not support the use of therapeutic n-3PUFA supplementation in the treatment and management of T1D and its associated complications. Trial Registration ISRCTN, ISRCTN40811115. Registered 27 June 2017, http://www.isrctn.com/ISRCTN40811115

Associations between erythrocyte membrane fatty acid compositions and biomarkers of vascular health in adults with type 1 diabetes with and without insulin resistance: a cross-sectional analysis.

Purpose: The aim of this study was to assess the relationship between specific erythrocyte fatty acids levels and vascular health in type 1 diabetes (T1D) with and without insulin resistance (IR). Methods: We analysed baseline pretreatment data in a subset of 23 patients with T1D from a previously published randomised controlled trial consisting of comprehensive erythrocyte-derived fatty acid profiles and a panel of inflammation-associated endothelial markers. Estimated glucose disposal rate was used to identify and categorise patients with IR. We utilised principal component analysis (PCA) to cluster vascular biomarkers to compute a single ‘vascular signal’ and employed univariate linear regression models to investigate the association with IR and fatty acid profiles. Results: Subjects with IR displayed significantly higher levels of linoleic acid (p=0.001), lower levels of eicosapentaenoic acid (EPA) (p<0.001), lower total omega-3 polyunsaturated fatty acid (n-3PUFA) (p<0.006), and an increased n-6PUFA:n-3PUFA ratio (p=0.001). IR was associated with significantly higher linoleic acid levels, total n-6PUFA, and an increased ratio of n-6PUFA:n-3PUFA, and negatively associated with arachidonic and eicosapentaenoic acid levels, total saturated fatty acid, and total n-3PUFA. The PCA-derived vascular biomarker cluster was positively associated with linoleic acid, n-6PUFA:n-3PUFA ratio and inversely associated with EPA. Conclusion: Specific erythrocyte membrane fatty acid compositions are associated with impaired vascular health and IR in adults with T1D. These findings suggest that IR and risk of associated complications may be influenced by specific fatty acid profiles, and thus potentially modified by the selective targeting of dietary fatty acids

The impact of the Covid‐19 pandemic on glycaemic control in people with diabetes: a systematic review and meta‐analysis

Covid-19 pandemic and lock down (LD) has affected diabetes care. We aimed to identify, appraise and synthesise available evidence on the impact of the pandemic on glycaemic control in people with diabetes. Materials and Methods We searched multiple databases up to 02/02/2021 for studies reporting: glycated haemoglobin (HbA1c); time in range (TIR); average or fasting glucose; severe hypoglycaemia; diabetic ketoacidosis. Data were pooled using random-effects meta-analysis and presented as mean difference (MD) with 95% confidence intervals (CI). This review was pre-registered on PROSPERO (CRD42020179319). Results We include 59 studies; 44 (n=15,464) were included in quantitative syntheses and 15 were narratively synthesised. Pooled data were grouped by diabetes type. Results from 28 studies (n=5,048 T1D and combined diabetes participants) showed that TIR increased during LD compared to before LD (MD 2.74%, 95% CI 1.80 to 3.69). Data from 10 studies (n=1,294 T1D participants) showed TIR increased after LD compared to before LD (MD 5.14%, 95% CI 3.12 to 7.16). Pooled results from 12 studies (n= 4,810 T1D and T2D participants), resulted in average glucose decreasing after LD compared to before LD (MD -6.86 mg/dL, 95% CI -8.54 to -5.18). Results for other outcomes, including HbA1c, were not statistically significantly different. Conclusions The Covid-19 pandemic was associated with small improvements across multiple outcomes of glycaemic control, though there was insufficient evidence to suggest this led to changes in HbA1c. Most evidence came from people with access to diabetes technologies in high income countries; more research is needed in less advantaged populations

Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients

Bococizumab is a humanized monoclonal antibody that inhibits proprotein convertase subtilisin- kexin type 9 (PCSK9) and reduces levels of low-density lipoprotein (LDL) cholesterol. We sought to evaluate the efficacy of bococizumab in patients at high cardiovascular risk. METHODS In two parallel, multinational trials with different entry criteria for LDL cholesterol levels, we randomly assigned the 27,438 patients in the combined trials to receive bococizumab (at a dose of 150 mg) subcutaneously every 2 weeks or placebo. The primary end point was nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death; 93% of the patients were receiving statin therapy at baseline. The trials were stopped early after the sponsor elected to discontinue the development of bococizumab owing in part to the development of high rates of antidrug antibodies, as seen in data from other studies in the program. The median follow-up was 10 months. RESULTS At 14 weeks, patients in the combined trials had a mean change from baseline in LDL cholesterol levels of -56.0% in the bococizumab group and +2.9% in the placebo group, for a between-group difference of -59.0 percentage points (P<0.001) and a median reduction from baseline of 64.2% (P<0.001). In the lower-risk, shorter-duration trial (in which the patients had a baseline LDL cholesterol level of ≥70 mg per deciliter [1.8 mmol per liter] and the median follow-up was 7 months), major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group (hazard ratio, 0.99; 95% confidence interval [CI], 0.80 to 1.22; P = 0.94). In the higher-risk, longer-duration trial (in which the patients had a baseline LDL cholesterol level of ≥100 mg per deciliter [2.6 mmol per liter] and the median follow-up was 12 months), major cardiovascular events occurred in 179 and 224 patients, respectively (hazard ratio, 0.79; 95% CI, 0.65 to 0.97; P = 0.02). The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P = 0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001). CONCLUSIONS In two randomized trials comparing the PCSK9 inhibitor bococizumab with placebo, bococizumab had no benefit with respect to major adverse cardiovascular events in the trial involving lower-risk patients but did have a significant benefit in the trial involving higher-risk patients