Beta-Cell Fragility As a Common Underlying Risk Factor in Type 1 and Type 2 Diabetes

: Chronic hyperglycemia is an established risk factor for the development of complications in both type 1 and type 2 diabetes, but glycemic variability has emerged as a possible independent risk factor for diabetes complications, possibly throughout oxidative stress. In this review we discuss methods to access glycemic variability and oxidative stress, as well as their correlations. We also debate non-pharmacological and pharmacological strategies to achieve a better glycemic control, not only by HbA1c target, but also with reduced glycemic fluctuations, possibly minimizing the risk of diabetes complications.

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Next steps in the identification of gene targets for type 1 diabetes

Diabetologia ◽

10.1007/s00125-020-05248-8 ◽

2020 ◽

Vol 63 (11) ◽

pp. 2260-2269 ◽

Cited By ~ 1

Author(s):

Struan F. A. Grant ◽

Andrew D. Wells ◽

Stephen S. Rich

Keyword(s):

Type 2 Diabetes ◽

Type 1 Diabetes ◽

Beta Cell ◽

Genetic Risk ◽

Genetic Risk Score ◽

Cell Types ◽

Total Risk ◽

Chromosome Conformation

Abstract The purpose of this review is to provide a view of the future of genomics and other omics approaches in defining the genetic contribution to all stages of risk of type 1 diabetes and the functional impact and clinical implementations of the associated variants. From the recognition nearly 50 years ago that genetics (in the form of HLA) distinguishes risk of type 1 diabetes from type 2 diabetes, advances in technology and sample acquisition through collaboration have identified over 60 loci harbouring SNPs associated with type 1 diabetes risk. Coupled with HLA region genes, these variants account for the majority of the genetic risk (~50% of the total risk); however, relatively few variants are located in coding regions of genes exerting a predicted protein change. The vast majority of genetic risk in type 1 diabetes appears to be attributed to regions of the genome involved in gene regulation, but the target effectors of those genetic variants are not readily identifiable. Although past genetic studies clearly implicated immune-relevant cell types involved in risk, the target organ (the beta cell) was left untouched. Through emergent technologies, using combinations of genetics, gene expression, epigenetics, chromosome conformation and gene editing, novel landscapes of how SNPs regulate genes have emerged. Furthermore, both the immune system and the beta cell and their biological pathways have been implicated in a context-specific manner. The use of variants from immune and beta cell studies distinguish type 1 diabetes from type 2 diabetes and, when they are combined in a genetic risk score, open new avenues for prediction and treatment.

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Oral administration of bacterial Beta cell expansion factor A (BefA) alleviates diabetes in mice with Type 1 and Type 2 diabetes

10.1101/2021.10.22.465460 ◽

2021 ◽

Author(s):

Huan Wang ◽

Jing Wei ◽

Hong Hu ◽

Fuyin Le ◽

Heng Wu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Beta Cell ◽

Cell Expansion ◽

Dependent Manner ◽

Expansion Factor ◽

Concentration Dependent Manner ◽

Protective Function

Diabetes mellitus (DM) is a group of metabolic diseases, which is of urgent need to develop new therapeutic DM oral drugs with less side effects and sound therapeutic efficacy. In this study, a Beta cell expansion factor A (BefA) production strain of Escherichia Coli BL21-pet 28C-BefA was constructed, and the anti-diabetes effect of BefAwas evaluated using type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) mice models. The T1DM mice results indicated that BefA significantly reduced the blood glucose level, exerted protective function of islet β cell morphology, down-regulated the TLR-4, p-NFκB/NFκB, Bax/Bcl-2 expressions and the secretion level of IL-1β, TNF-α, increased the expression of PDX-1 protein and insulin secretion in a concentration-dependent manner, and restored the disturbed microbial diversity to normal level. Similar with the T1DM mice, BefA obviously increased islet β cells, reduced inflammatory reaction and apoptosis in T2DM mice, and also improved liver lipid metabolism by down-regulating the expression of CEBP-α, ACC, Fasn and inhibiting the synthesis of triglyceride and induce Cpt-1, Hmgcs2, Pparα in a concentration-dependent manner. In the present study, we verified therapeutic effect and potential mechanisms of BefA in mammal for the first time, providing basic data for its clinical application.

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