Background: Regular consumption of nϪ3 fatty acids of marine origin can improve serum lipids and reduce cardiovascular risk. Objective: This study aimed to determine whether eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids have differential effects on serum lipids and lipoproteins, glucose, and insulin in humans. Design: In a double-blind, placebo-controlled trial of parallel design, 59 overweight, nonsmoking, mildly hyperlipidemic men were randomly assigned to receive 4 g purified EPA, DHA, or olive oil (placebo) daily while continuing their usual diets for 6 wk. Results: Fifty-six men aged 48.8 ± 1.1 y completed the study. Relative to those in the olive oil group, triacylglycerols fell by 0.45 ± 0.15 mmol/L (Ϸ20%; P = 0.003) in the DHA group and by 0.37 ± 0.14 mmol/L (Ϸ18%; P = 0.012) in the EPA group. Neither EPA nor DHA had any effect on total cholesterol. LDL, HDL, and HDL 2 cholesterol were not affected significantly by EPA, but HDL 3 cholesterol decreased significantly (6.7%; P = 0.032). Although HDL cholesterol was not significantly increased by DHA (3.1%), HDL 2 cholesterol increased by Ϸ29% (P = 0.004). DHA increased LDL cholesterol by 8% (P = 0.019). Adjusted LDL particle size increased by 0.25 ± 0.08 nm (P = 0.002) with DHA but not with EPA. EPA supplementation increased plasma and platelet phospholipid EPA but reduced DHA. DHA supplementation increased DHA and EPA in plasma and platelet phospholipids. Both EPA and DHA increased fasting insulin significantly. EPA, but not DHA, tended to increase fasting glucose, but not significantly so. Conclusions: EPA and DHA had differential effects on lipids, fatty acids, and glucose metabolism in overweight men with mild hyperlipidemia.Am J Clin Nutr 2000;71:1085-94. KEY WORDSEicosapentaenoic acid, docosahexaenoic acid, EPA, DHA, hyperlipidemia, fish oil, nϪ3 fatty acids, lipids, LDL particle size, glucose metabolism, insulin metabolism, men INTRODUCTIONThere is considerable evidence to support a protective effect of dietary nϪ3 polyunsaturated fatty acids against atherosclerotic heart disease (1). The 2 principal nϪ3 fatty acids in marine oils, eicosapentaenoic acid (EPA; 20:5nϪ3) and docosahexaenoic acid (DHA; 22:6nϪ3), have a wide range of biological effects (1-3). Those relevant to heart disease include influences on lipoprotein metabolism (4, 5), platelet and endothelial function, vascular reactivity, neutrophil and monocyte cytokine production, coagulation, fibrinolysis, and blood pressure (1-3, 6, 7). In addition, the effect of nϪ3 fatty acids may be dependent, to some extent, on the presence of underlying disorders such as dyslipidemia, hypertension, diabetes mellitus, and vascular disease.nϪ3 Fatty acid supplementation in animals and humans results in substantial increases in plasma and tissue EPA and DHA as well as variable incorporation in different phospholipid classes in different tissues (8-10). These differences may be important to the subsequent utilization and metabolism of EPA and DHA. Although both fatty acids are considered to ...

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SummaryBackground-Metformin might reduce insulin requirement and improve glycaemia in patients with type 1 diabetes, but whether it has cardiovascular benefits is unknown. We aimed to investigate whether metformin treatment (added to titrated insulin therapy) reduced atherosclerosis, as measured by progression of common carotid artery intima-media thickness (cIMT), in adults with type 1 diabetes at increased risk for cardiovascular disease.

This study evaluated the long-term safety and efficacy of dapagliflozin as an adjunct to adjustable insulin in patients with type 1 diabetes and inadequate glycemic control. RESEARCH DESIGN AND METHODS DEPICT-1 (Dapagliflozin Evaluation in Patients With Inadequately Controlled Type 1 Diabetes) was a randomized (1:1:1), double-blind, placebo-controlled phase 3 study of dapagliflozin 5 mg and 10 mg in patients with type 1 diabetes (HbA 1c 7.5-10.5% [58-91 mmol/mol]) (NCT02268214). The results of the 52-week study, consisting of the 24-week short-term and 28-week extension period, are reported here. RESULTS Of the 833 patients randomized into the study, 708 (85%) completed the 52-week study. Over 52 weeks, dapagliflozin 5 mg and 10 mg led to clinically significant reductions in HbA 1c (difference vs. placebo [95% CI] 20.

Aims/hypothesis The objective of this study was to assess the impact of patient-led sensor-guided pump management on glycaemic control, and compare the effect with that of standard insulin pump therapy. Methods An open multicentre parallel randomised controlled trial was conducted at five tertiary diabetes centres. Participants aged 13.0-40.0 years with well-controlled type 1 diabetes were randomised 1:1 to either study group for 3 months. Randomisation was carried out using a central computer-generated schedule. Participants in the intervention group used sensor-guided pump management; no instructive guidelines in interpreting real-time data were provided ('patient-led' use). Participants in the control group continued their original insulin pump regimen. Continuous glucose monitoring (CGM) and HbA 1c level were used to assess outcomes. The primary outcome was the difference in the proportion of time in the target glycaemic range during the 3 month study period (derived from CGM, target range 4-10 mmol/l). Secondary outcomes were difference in HbA 1c , time in hypoglycaemic (≤3.9 mmol/l) and hyperglycaemic (≥10.1 mmol/l) ranges and glycaemic variability. Results Sixty-two participants were recruited and randomised; 5/31 and 2/31 withdrew from intervention and control groups, respectively, leaving 26/31 and 29/31 for the intention-to-treat analyses. When adjusted for baseline values, the mean end-of-study HbA 1c was 0.43% lower in the intervention group compared with the control group (95% CI 0.19 to 0.75%; p=0.009). No difference was observed in CGM-derived time in target (measured difference 1.72; 95% CI −5.37 to 8.81), hypoglycaemic (0.54; 95% CI −3.48 to 4.55) or hyperglycaemic (−2.18; 95% CI −10.0 to 5.69) range or in glycaemic variability (−0.29; 95% CI −0.34 to 0.28). Within the intervention group, HbA 1c was 0.51% lower in participants with sensor use ≥70% compared with participants with sensor use <70% (95% CI −0.98 to −0.04, p=0.04). Five episodes of device malfunction occurred. Conclusions/interpretation Individuals established on insulin pump therapy can employ sensor-guided pump management to improve glycaemic control. An apparent dose-dependent effect of sensor usage was noted; however, Diabetologia

■ AbstractThere is a global diabetes epidemic correlating with an increase in obesity. This coincidence may lead to a rise in the prevalence of type 2 diabetes. There is also an as yet unexplained increase in the incidence of type 1 diabetes, which is not related to adiposity. Whilst improved diabetes care has substantially improved diabetes outcomes, the disease remains a common cause of working age adult-onset blindness. Diabetic retinopathy is the most frequently occurring complication of diabetes; it is greatly feared by many diabetes patients. There are multiple risk factors and markers for the onset and progression of diabetic retinopathy, yet residual risk remains. Screening for diabetic retinopathy is recommended to facilitate early detection and treatment. Common biomarkers of diabetic retinopathy and its risk in clinical practice today relate to the visualization of the retinal vasculature and measures of glycemia, lipids, blood pressure, body weight, smoking, and pregnancy status. Greater knowledge of novel biomarkers and mediators of diabetic retinopathy, such as those related to inflammation and angiogenesis, has contributed to the development of additional therapeutics, in particular for late-stage retinopathy, including intra-ocular corticosteroids and intravitreal vascular endothelial growth factor inhibitors ('anti-VEGFs') agents. Unfortunately, in spite of a range of treatments (including laser photocoagulation, intraocular steroids, and anti-VEGF agents, and more recently oral fenofibrate, a PPAR-alpha agonist lipid-lowering drug), many patients with diabetic retinopathy do not respond well to current therapeutics. Therefore, more effective treatments for diabetic retinopathy are necessary. New analytical techniques, in particular those related to molecular markers, are accelerating progress in diabetic retinopathy research. Given the increasing incidence and prevalence of diabetes, and the limited capacity of healthcare systems to screen and treat diabetic retinopathy, there is need to reliably identify and triage people with diabetes. Biomarkers may facilitate a better understanding of diabetic retinopathy, and contribute to the development of novel treatments and new clinical strategies to prevent vision loss in people with diabetes. This article reviews key aspects related to biomarker research, and focuses on some specific biomarkers relevant to diabetic retinopathy.

Research on and commercial development of the artificial pancreas (AP) continue to progress rapidly, and the AP promises to become a part of clinical care. In this report, members of the JDRF Artificial Pancreas Project Consortium in collaboration with the wider AP community 1) advocate for the use of continuous glucose monitoring glucose metrics as outcome measures in AP trials, in addition to HbA1c, and 2) identify a short set of basic, easily interpreted outcome measures to be reported in AP studies whenever feasible. Consensus on a broader range of measures remains challenging; therefore, reporting of additional metrics is encouraged as appropriate for individual AP studies or study groups. Greater consistency in reporting of basic outcome measures may facilitate the interpretation of study results by investigators, regulatory bodies, health care providers, payers, and patients themselves, thereby accelerating the widespread adoption of AP technology to improve the lives of people with type 1 diabetes.

Background The role of adiponectin, tumour necrosis factor α (TNFα), leptin and C-reactive protein in the insulin resistance of pregnancy is not clear. We measured their levels in women with gestational diabetes (GDM) and in controls, during and after pregnancy, and related them to insulin secretion and action.