Obesity, Type 2 Diabetes and Beta Cell Failure: An Asian Perspective

Type 2 diabetes mellitus (T2DM) in children and adolescents is an important Public Health problem against the backdrop of the epidemic of childhood obesity. The clinical presentation of T2DM in youth is heterogeneous from minimal symptomatology to diabetic ketoacidosis. The increasing rates of youth T2DM have paralleled the escalating rates of obesity, which is the major risk factor impacting insulin sensitivity. Additional risk factors include minority race, family history of diabetes mellitus, maternal diabetes during pregnancy, pubertal age group and conditions associated with insulin resistance (IR) - such as polycystic ovary syndrome (PCOS). The pathophysiology of T2DM has been studied extensively in adults, and it is widely accepted that IR together with beta-cell failure are necessary for the development of clinical diabetes mellitus in adulthood. However, pathophysiologic studies in youth are limited and in some cases conflicting. Similar to adults, IR is a prerequisite, but beta-cell failure is necessary for progression from normal glucose tolerance to prediabetes and frank diabetes in youth. Even though rates of T2DM in youth are increasing, the overall prevalence remains low if compared with type 1 diabetes mellitus (T1DM). However, as youth with T1DM are becoming obese, the clinical distinction between T2DM and obese T1DM has become difficult, because of the overlapping clinical picture with evidence of islet cell autoimmunity in a significant proportion of clinically diagnosed youth with T2DM. The latter are most likely obese children with autoimmune T1DM who carry a misdiagnosis of T2DM. Further research is needed to probe the pathophysiological, immunological, and metabolic differences between these two groups in the hopes of assigning appropriate therapeutic regimens. These challenges combined with the evolving picture of youth T2DM and its future complications provide unending opportunities for acquisition of new knowledge in the field of childhood diabetes.

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Progressive beta cell failure in type 2 diabetes mellitus of youth

The Journal of Pediatrics ◽

10.1016/j.jpeds.2003.12.045 ◽

2004 ◽

Vol 144 (5) ◽

pp. 656-659 ◽

Cited By ~ 62

Author(s):

Neslihan Gungor ◽

Silva Arslanian

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Beta Cell ◽

Beta Cell Failure

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Beta‐cell failure in diabetes: common susceptibility and mechanisms shared between type 1 and type 2 diabetes

Journal of Diabetes Investigation ◽

10.1111/jdi.13576 ◽

2021 ◽

Author(s):

Hiroshi Ikegami ◽

Naru Babaya ◽

Shinsuke Noso

Keyword(s):

Type 2 Diabetes ◽

Beta Cell ◽

Beta Cell Failure

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Beta-cell Insufficiency

European Endocrinology ◽

10.17925/ee.2017.13.02.51 ◽

2017 ◽

Vol 13 (02) ◽

pp. 51 ◽

Cited By ~ 1

Author(s):

Sanjay Kalra ◽

Yashdeep Gupta ◽

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Keyword(s):

Type 2 Diabetes ◽

Decision Making ◽

Beta Cell ◽

Taxonomic Structure ◽

Therapeutic Decision ◽

Anatomy And Physiology ◽

Beta Cell Failure ◽

Three Phase ◽

Therapeutic Decision Making

‘B eta-cell failure’ is a frequently used term to describe the structural and functional inability of the cells to fulfil their metabolic responsibility. This editorial reviews the anatomy and physiology of the beta cell, and describes factors which regulate this. The authors focus on semantics, comparing the phrases ‘beta-cell failure’, ‘functional mass’, and ‘beta-cell insufficiency’. They suggest the use of ‘beta-cell insufficiency’, with descriptors such as ‘partial’ and ‘complete’, or ‘reversible’ and ‘irreversible’, to convey betacell dysfunction in type 2 diabetes. A three-phase taxonomic structure: beta-cell sufficiency, partial/reversible beta-cell insufficiency and complete/irreversible beta-cell insufficiency, is proposed as a tool to understand pathophysiology and facilitate therapeutic decision-making.

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Targeting type 2 diabetes: lessons from a knockout model of insulin receptor substrate 2

Canadian Journal of Physiology and Pharmacology ◽

10.1139/cjpp-2014-0114 ◽

2014 ◽

Vol 92 (8) ◽

pp. 613-620 ◽

Cited By ~ 21

Author(s):

Joana Moitinho Oliveira ◽

Sandra A. Rebuffat ◽

Rosa Gasa ◽

Ramon Gomis

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Beta Cell ◽

Insulin Receptor ◽

Beta Cells ◽

Pancreatic Beta Cells ◽

Mitogen Activated Protein Kinase ◽

Insulin Receptor Substrate ◽

Beta Cell Failure

Insulin receptor substrate 2 (IRS2) is a widely expressed protein that regulates crucial biological processes including glucose metabolism, protein synthesis, and cell survival. IRS2 is part of the insulin – insulin-like growth factor (IGF) signaling pathway and mediates the activation of the phosphotidylinositol 3-kinase (PI3K)–Akt and the Ras–mitogen-activated protein kinase (MAPK) cascades in insulin target tissues and in the pancreas. The best evidence of this is that systemic elimination of the Irs2 in mice (Irs2−/−) recapitulates the pathogenesis of type 2 diabetes (T2D), in that diabetes arises as a consequence of combined insulin resistance and beta-cell failure. Indeed, work using this knockout mouse has confirmed the importance of IRS2 in the control of glucose homeostasis and especially in the survival and function of pancreatic beta-cells. These studies have shown that IRS2 is critically required for beta-cell compensation in conditions of increased insulin demand. Importantly, islets isolated from T2D patients exhibit reduced IRS2 expression, which supports the likely contribution of altered IRS2-dependent signaling to beta-cell failure in human T2D. For all these reasons, the Irs2−/− mouse has been and will be essential for elucidating the inter-relationship between beta-cell function and insulin resistance, as well as to delineate therapeutic strategies to protect beta-cells during T2D progression.

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