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

Early- and advanced non-enzymatic glycation in diabetic vascular complications: the search for therapeutics

Cardiovascular disease is a common complication of diabetes and the leading cause of death among people with diabetes. Because of the huge premature morbidity and mortality associated with diabetes, prevention of vascular complications is a key issue. Although the exact mechanism by which vascular damage occurs in diabetes in not fully understood, numerous studies support the hypothesis of a causal relationship of non-enzymatic glycation with vascular complications. In this review, data which point to an important role of Amadori-modified glycated proteins and advanced glycation endproducts in vascular disease are surveyed. Because of the potential role of early- and advanced non-enzymatic glycation in vascular complications, we also described recent developments of pharmacological inhibitors that inhibit the formation of these glycated products or the biological consequences of glycation and thereby retard the development of vascular complications in diabetes

What the radiologist needs to know about the diabetic patient

Diabetes mellitus (DM) is recognised as a major health problem. Ninety-nine percent of diabetics suffer from type 2 DM and 10% from type 1 and other types of DM. The number of diabetic patients worldwide is expected to reach 380 millions over the next 15 years. The duration of diabetes is an important factor in the pathogenesis of complications, but other factors frequently coexisting with type 2 DM, such as hypertension, obesity and dyslipidaemia, also contribute to the development of diabetic angiopathy. Microvascular complications include retinopathy, nephropathy and neuropathy. Macroangiopathy mainly affects coronary arteries, carotid arteries and arteries of the lower extremities. Eighty percent of deaths in the diabetic population result from cardiovascular incidents. DM is considered an equivalent of coronary heart disease (CHD). Stroke and peripheral artery disease (PAD) are other main manifestations of diabetic macroangiopathy. Diabetic cardiomyopathy (DC) represents another chronic complication that occurs independently of CHD and hypertension. The greater susceptibility of diabetic patients to infections completes the spectrum of the main consequences of DM. The serious complications of DM make it essential for physicians to be aware of the screening guidelines, allowing for earlier patient diagnosis and treatment

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Need for pathogenetically oriented therapy of neuropathy in diabetes mellitus

Peripheral and/or autonomous neuropathy is associated with increased cardiovascular risk in diabetes patients. One of the common pathogenetic factors is increased production of free oxygen radicals and their derivatives; a hyperglycaemic metabolism impairs endoneural blood perfusion, leading to neuronal cell damage as typical in diabetic neuropathy. The aim of pathogenetically oriented treatment is to slow down, stop, or reverse the progression of neuropathic damage, and clear indications show that benfotiamine and alpha-lipoic acid along with blood glucose optimization and risk factor management may have a positive effect on the processes involved in neuropathy. Benfotiamine inhibits pathways involved in developing neuropathy while stimulating pathways that play a role in improving neuropathy, such as the pentose-phosphate shunt. Alpha-lipoic acid - an effective antioxidant - may partly inhibit pathogenetic processes caused by oxidative stress. Both of these substances have been shown better tolerance profiles than drugs aimed at controlling symptoms, and should play a role in treating patients with diabetic neuropathy

Benfotiamine: Commentary and update on recent studies

The thiamine prodrug benfotiamine (S-benzoylthiamine-O-monophosphate) has been shown to prevent the formation of advanced glycation endproducts (AGEs), thus decreasing hyperglycaemia-induced damage and neuropathic sensory symptoms. However, recent studies have yielded contradictory results. Other studies emphasize the need for further research on the potential of benfotiamine in the treatment of vascular and diabetes complications. Currently, benfotiamine is considered to be a pathogenetic treatment in counteracting oxidative stress and hyperglycaemia-induced metabolic changes that lead to neuropathy

Perspectives in Diabetic Neuropathy: Update on Diagnostic Criteria and Treatment Options

Diabetic sensorimotor polyneuropathy (DSPN) is a common complication in patients with diabetes, >10 % of whom suffer from severe neuropathic pain. DSPN diagnosis remains challenging despite the breath of diagnostic tools; this is partly due to varying proficiency amongst examiners, but also variations in diagnostic criteria employed. Treatment options include pathogenesis-oriented and symptomatic approaches. Symptomatic pharmacotherapy in painful DSPN aims to ease neuropathic pain using analgesics such as the tricyclic antidepressants serotonin-noradrenaline reuptake inhibitors and alpha(2)delta ligands, but evidence points to pathogenesis-oriented treatments using alpha lipoic acid or benfotiamine. Combination therapy has also emerged as an important approach in DSPN treatment. In this review, we aim to update the current diagnostic and therapeutic options for DSPN