scholarly journals O-GlcNAcylation, oxidation and CaMKII contribute to atrial fibrillation in type 1 and type 2 diabetes by distinct mechanisms

2020 ◽  
Author(s):  
Olurotimi O. Mesubi ◽  
Adam G. Rokita ◽  
Neha Abrol ◽  
Yuejin Wu ◽  
Biyi Chen ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Calmodulin Kinase ◽  
Elevated Protein ◽  
Intracellular Ca ◽  
Genetic Mouse Models

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.

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
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Vitamin E ◽  
Clinical Studies ◽  
Vascular Complications ◽  
Cardiovascular Complications ◽  
Diabetes Patients

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.

scholarly journals Role of CHA2DS2-VASc score in predicting new-onset atrial fibrillation in patients with type 2 diabetes mellitus with and without hyperosmolar hyperglycaemic state: real-world data from a nationwide cohort

BMJ Open ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. e020065 ◽  
Author(s):  
Wei-Syun Hu ◽  
Cheng-Li Lin
Keyword(s):  
Diabetes Mellitus ◽  
Atrial Fibrillation ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Predictive Ability ◽  
Type 2 Dm ◽  
History Of ◽  
New Onset

PurposeThe objective of the current study was to explore the role of CHA2DS2-VASc score in predicting incidence of atrial fibrillation (AF) in patients with type 2 diabetes mellitus (DM). Furthermore, the use of the CHA2DS2-VASc score for stratifying new-onset AF risk in patients with DM and with/without hyperosmolar hyperglycaemic state (HHS) was also compared.MethodsThe study subjects were identified from Longitudinal Health Insurance Database provided by the National Health Research Institutes. The patients with DM were divided into two groups based on a history of HHS or not. The predictive ability of CHA2DS2-VASc score for stratifying new-onset AF risk in the two groups was calculated using the area under the curve of receiver-operating characteristic (AUROC).ResultsThe present study involved a total of 69 530 patients with type 2 DM. Among them, 1558 patients had a history of HHS, whereas 67 972 patients did not. The AUROC of the CHA2DS2-VASc score as a predictor of incident AF in patients with DM and with/without HHS was 0.67 (95% CI 0.59 to 0.75) and 0.71 (95% CI 0.70 to 0.72), respectively.ConclusionsTo conclude, we reported for the first time on the assessment of CHA2DS2-VASc score for incident AF risk discrimination in patients with type 2 DM. We further found that the predictive ability of the CHA2DS2-VASc score was attenuated in patients with type 2 DM and with HHS in comparison with those without HHS.

6. Appetite, fat, and obesity

2014 ◽  
pp. 74-87
Author(s):  
Martin Luck
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 1 Diabetes ◽  
The Body ◽  
Storage Process ◽  
Lifestyle Disease ◽  
Energy Shortage

‘Appetite, fat, and obesity’ considers the role of insulin in the body’s fat storage process. In the condition diabetes mellitus, the sugar level in the blood rises uncontrollably so the kidneys cannot stop it leaking into the urine. Type 1 diabetes is an autoimmune disease in which a person’s immune system attacks the insulin-secreting β-cells of the pancreas. The only effective treatment is to inject the missing insulin. Type 2 diabetes is considered more of a lifestyle disease. But what exactly is the connection between obesity and poorly regulated blood glucose? The body has more hormones capable of responding to energy shortage than to energy abundance, which may be why keeping control of body weight can be difficult. The hormones affecting appetite are also discussed.

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