Background: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. Methods: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. Results: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: − 0.10, (95% CI − 0.17, − 0.03); p = 0.007], VLDL (ES: − 0.26 (− 0.51, − 0.01); p = 0.044], triglycerides (ES: − 0.39 (− 0.55, − 0.24; p ≤ 0.001] and HbA1c (ES: − 0.27 (− 0.48, − 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: − 0.59 (− 1.17, − 0.01); p = 0.045] and IL-6 (ES: − 1.67 (− 3.14, − 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). Conclusions: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Introduction Evening-time exercise is a frequent cause of severe hypoglycemia in type 1 diabetes, fear of which deters participation in regular exercise. Recommendations for normalizing glycemia around exercise consist of prandial adjustments to bolus insulin therapy and food composition, but this carries only short-lasting protection from hypoglycemia. Therefore, this study aimed to examine the impact of a combined basal-bolus insulin dose reduction and carbohydrate feeding strategy on glycemia and metabolic parameters following evening exercise in type 1 diabetes. Methods Ten male participants (glycated hemoglobin: 52.4±2.2 mmol/mol), treated with multiple daily injections, completed two randomized study-days, whereby administration of total daily basal insulin dose was unchanged (100%), or reduced by 20% (80%). Participants attended the laboratory at ∼08:00 h for a fasted blood sample, before returning in the evening. On arrival (∼17:00 h), participants consumed a carbohydrate meal and administered a 75% reduced rapid-acting insulin dose and 60 min later performed 45 min of treadmill running. At 60 min postexercise, participants consumed a low glycemic index (LGI) meal and administered a 50% reduced rapid-acting insulin dose, before returning home. At ∼23:00 h, participants consumed a LGI bedtime snack and returned to the laboratory the following morning (∼08:00 h) for a fasted blood sample. Venous blood samples were analyzed for glucose, glucoregulatory hormones, non-esterified fatty acids, β-hydroxybutyrate, interleukin 6, and tumor necrosis factor α. Interstitial glucose was monitored for 24 h pre-exercise and postexercise. Results Glycemia was similar until 6 h postexercise, with no hypoglycemic episodes. Beyond 6 h glucose levels fell during 100%, and nine participants experienced nocturnal hypoglycemia. Conversely, all participants during 80% were protected from nocturnal hypoglycemia, and remained protected for 24 h postexercise. All metabolic parameters were similar. Conclusions Reducing basal insulin dose with reduced prandial bolus insulin and LGI carbohydrate feeding provides protection from hypoglycemia during and for 24 h following evening exercise. This strategy is not associated with hyperglycemia, or adverse metabolic disturbances. Clinical trials number NCT02204839, ClinicalTrials.gov.

OBJECTIVE To examine the acute and 24-h glycemic responses to reductions in postexercise rapid-acting insulin dose in type 1 diabetic patients. RESEARCH DESIGN AND METHODS After preliminary testing, 11 male patients (24 ± 2 years, HbA_1c 7.7 ± 0.3%; 61 ± 3.4 mmol/mol) attended the laboratory on three mornings. Patients consumed a standardized breakfast (1 g carbohydrate ⋅ kg⁻¹ BM; 380 ± 10 kcal) and self-administered a 25% rapid-acting insulin dose 60 min prior to performing 45 min of treadmill running at 72.5 ± 0.9% VO_2peak. At 60 min postexercise, patients ingested a meal (1 g carbohydrate ⋅ kg⁻¹ BM; 660 ± 21 kcal) and administered a Full, 75%, or 50% rapid-acting insulin dose. Blood glucose concentrations were measured for 3 h postmeal. Interstitial glucose was recorded for 20 h after leaving the laboratory using a continuous glucose monitoring system. RESULTS All glycemic responses were similar across conditions up to 60 min postexercise. After the postexercise meal, blood glucose was preserved under 50%, but declined under Full and 75%. Thence at 3 h, blood glucose was highest under 50% (50% [10.4 ± 1.2] vs. Full [6.2 ± 0.7] and 75% [7.6 ± 1.2 mmol ⋅ L⁻¹], P = 0.029); throughout this period, all patients were protected against hypoglycemia under 50% (blood glucose ≤3.9; Full, n = 5; 75%, n = 2; 50%, n = 0). Fifty percent continued to protect patients against hypoglycemia for a further 4 h under free-living conditions. However, late-evening and nocturnal glycemia were similar; as a consequence, late-onset hypoglycemia was experienced under all conditions. CONCLUSIONS A 25% pre-exercise and 50% postexercise rapid-acting insulin dose preserves glycemia and protects patients against early-onset hypoglycemia (≤8 h). However, this strategy does not protect against late-onset postexercise hypoglycemia.

Large doses of whey protein consumed as a preload before single high–glycemic load meals has been shown to improve postprandial glycemia in type 2 diabetes. It is unclear if this effect remains with smaller doses of whey co-ingested at consecutive mixed-macronutrient meals. Moreover, whether hydrolyzed whey offers further benefit under these conditions is unclear. The aim of this study was to investigate postprandial glycemic and appetite responses after small doses of intact and hydrolyzed whey protein co-ingested with mixed-nutrient breakfast and lunch meals in men with type 2 diabetes. In a randomized, single-blind crossover design, 11 men with type 2 diabetes [mean ± SD age: 54.9 ± 2.3 y; glycated hemoglobin: 6.8% ± 0.3% (51.3 ± 3.4 mmol/mol)] attended the laboratory on 3 mornings and consumed 1) intact whey protein (15 g), 2) hydrolyzed whey protein (15 g), or 3) placebo (control) immediately before mixed-macronutrient breakfast and lunch meals, separated by 3 h. Blood samples were collected periodically and were processed for insulin, intact glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), leptin, peptide tyrosine tyrosine (PYY_3–36), and amino acid concentrations. Interstitial glucose was measured during and for 24 h after each trial. Subjective appetite was assessed with the use of visual analog scales. Total postprandial glycemia area under the curve was reduced by 13% ± 3% after breakfast following the intact whey protein when compared with control (P < 0.05). Hydrolyzed whey attenuated early glucose after breakfast when compared with control (P < 0.05). Glycemia was improved postlunch after the intact whey protein only when compared with control (P < 0.05). Greater satiety was observed after the intact whey protein only after both meals when compared with control (P < 0.05). Insulin concentrations increased after both the intact and hydrolyzed whey protein, showing strong positive correlations with increases in valine and isoleucine (P < 0.05). Incretin and appetite regulatory hormone responses were similar across trials (P > 0.05). The consumption of a small 15-g dose of intact whey protein immediately before consecutive mixed-macronutrient meals improves postprandial glycemia, stimulates insulin release, and increases satiety in men with type 2 diabetes. This trial was registered at www.clinicialtrials.gov as NCT02903199.

Magnesium (Mg²⁺) has many physiological functions within the body. These include important roles in maintaining cardiovascular functioning, where it contributes to the regulation of cardiac excitation–contraction coupling, endothelial functioning and haemostasis. The haemostatic roles of Mg²⁺ impact upon both the protein and cellular arms of coagulation. In this review, we examine how Mg²⁺ homeostasis is maintained within the body and highlight the various molecular roles attributed to Mg²⁺ in the cardiovascular system. In addition, we describe how nutritional and/or disease-associated magnesium deficiency, seen in some metabolic conditions, has the potential to influence cardiac and vascular outcomes. Finally, we also examine the potential for magnesium supplements to be employed in the prevention and treatment of cardiovascular disorders and in the management of cardiometabolic health.