scholarly journals The protean role of haptoglobin and haptoglobin genotypes on vascular complications in diabetes mellitus

2018 ◽  
Vol 25 (14) ◽  
pp. 1502-1519 ◽  
Author(s):  
Rinkoo Dalan ◽  
Goh Liuh Ling

Introduction and background Haptoglobin (Hp) is considered to be an antioxidant and protective against cardiovascular complications. Polymorphisms in the Hp gene interact with diabetes mellitus to affect the risk of vascular complications. Methods We review the updated literature about the protean role of Hp and Hp genotypes spanning genomics, molecular, translational and clinical studies. We searched Pubmed, SCOPUS and Google Scholar for all articles using the keywords: haptoglobin and/or haptoglobin polymorphism and diabetes. We review the diverse Hp genotypes, phenotypes and the impact on diabetes complications, including lessons from animal models and in vitro models. We describe the clinical studies on the associations of Hp genotypes with vascular complications in type 1 and type 2 diabetes comprehensively. We review the studies looking at vitamin E supplementation in a personalized manner in Hp2-2 diabetes individuals. Results and conclusion Hp genotypes have evolved as a result of deletions in the traditional Hp genes. The Hp genotypes have been associated with microvascular and macrovascular complications in type 1 diabetes mellitus but the association in type 2 diabetes is more consistent with cardiovascular complications. A preferential benefit of vitamin E and other antioxidants in the Hp2-2 genotype for cardiovascular complications in type 2 diabetes has been seen presumably secondary to interaction with high-density lipoprotein function. Hence, the Hp genotype can be used to personalize antioxidant therapeutics in diabetes patients. These results need to be corroborated in large, global, pragmatic, prospective, cardiovascular outcome trials in type 2 diabetes patients.

2020 ◽  
Vol 22 (12) ◽  
pp. 57-62
Author(s):  
Irina I. Kochergina ◽  

The article presents data on the prevalence of diabetes and prediabetes; the high compatibility of diabetes mellitus and cardiovascular pathology; high mortality among patients with diabetes mellitus and coronary heart disease, in the presence of both acute and chronic cardiovascular complications; on the important role of glucose- and lipotoxicity in the progression of carbohydrate metabolism from prediabetes to type 2 diabetes mellitus, the role of hyperglycemia in the deve-lopment of insulin resistance, atherosclerosis, hypertension, liver, kidney, endothelial dysfunction, the role of hyper- and hypoglycemia in the development of acute vascular complications – myocardial infarction, stroke, gangrene of the lower extremities; on the protective role of adiponectin – a predictor of type 2 diabetes mellitus, on the importance of glycemic control for the timely detection of early disorders of carbohydrate metabolism – impaired glucose tolerance and impaired fasting glucose; on the role of metformin in the prevention of progression of prediabetes to type 2 diabetes and cardiac pathology; on the gluco- and cardioprotective role of modern sugar-lowering drugs.


2020 ◽  
Author(s):  
Olurotimi O. Mesubi ◽  
Adam G. Rokita ◽  
Neha Abrol ◽  
Yuejin Wu ◽  
Biyi Chen ◽  
...  

AbstractDiabetes mellitus and atrial fibrillation (AF) are major unsolved public health problems, and diabetes is an independent risk factor for AF in patients. However, the mechanism(s) underlying this clinical association is unknown. Elevated protein O-GlcNAcylation (OGN) and reactive oxygen species (ROS) are increased in diabetic hearts, and calmodulin kinase II (CaMKII) is a proarrhythmic signal that may be activated by OGN (OGN-CaMKII) and ROS (ox-CaMKII). We induced type 1 (T1D) and type 2 diabetes (T2D) in a portfolio of genetic mouse models capable of dissecting the role of OGN and ROS at CaMKII and the type 2 ryanodine receptor (RyR2), an intracellular Ca2+ channel implicated as an important downstream mechanism of CaMKII- mediated arrhythmias. Here we show that T1D and T2D significantly increased AF, similar to observations in patients, and this increase required CaMKII. While T1D and T2D both require ox-CaMKII to increase AF, they respond differently to loss of OGN-CaMKII or OGN inhibition. Collectively, our data affirm CaMKII as a critical proarrhythmic signal in diabetic AF, and suggest ROS primarily promotes AF by ox-CaMKII, while OGN promotes AF by diverse mechanisms and targets, including CaMKII and RyR2. The proarrhythmic consequences of OGN- and ox-CaMKII differ between T1D and T2D. These results provide new and unanticipated insights into the mechanisms for increased AF in diabetes mellitus, and suggest successful future therapies will need to be different for AF in T1D and T2D.


2009 ◽  
Vol 12 (4) ◽  
pp. 90-92
Author(s):  
Elena Valer'evna Biryukova

This paper focuses on the approaches to target glycemic control in patients with type 2 diabetes mellitus. It is emphasized that timely onset of insulintherapy enhances glycemic control and reduces the risk of vascular complications. One way to achieve this goal is to use modern strategies of intensivehypoglycemic therapy with insulins having improved pharmacokinetic and pharmakodynamic properties, e.g. glargine (Lantus) and glulysine (Apidra).Results of international clinical studies confirm effi-ciency of basal and basal-plus insulin strategies allowing to achieve glycemic control in type 2diabetes without heightening the risk of hypoglycemia, development and progression of vascular complications.


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