The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes

Abstract

The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology of Type 2 diabetes have been debated extensively. The concept that a feedback loop governs the interaction of the insulin-sensitive tissues and the beta cell as well as the elucidation of the hyperbolic relationship between insulin sensitivity and insulin secretion explains why insulin-resistant subjects exhibit markedly increased insulin responses while those who are insulin-sensitive have low responses. Consideration of this hyperbolic relationship has helped identify the critical role of beta-cell dysfunction in the development of Type 2 diabetes and the demonstration of reduced beta-cell function in high risk subjects. Furthermore, assessments in a number of ethnic groups emphasise that beta-cell function is a major determinant of oral glucose tolerance in subjects with normal and reduced glucose tolerance and that in all populations the progression from normal to impaired glucose tolerance and subsequently to Type 2 diabetes is associated with declining insulin sensitivity and beta-cell function. The genetic and molecular basis for these reductions in insulin sensitivity and beta-cell function are not fully understood but it does seem that body-fat distribution and especially intra-abdominal fat are major determinants of insulin resistance while reductions in beta-cell mass contribute to beta-cell dysfunction. Based on our greater understanding of the relative roles of insulin resistance and beta-cell dysfunction in Type 2 diabetes, we can anticipate advances in the identification of genes contributing to the development of the disease as well as approaches to the treatment and prevention of Type 2 diabetes. [Diabetologia (2003) 46:3-19]

Low adiponectin concentration during pregnancy predicts postpartum insulin resistance, beta cell dysfunction and fasting glycaemia

“…However, direct measures (such as clamp studies) would be difficult to implement in a study of this size (n=487) given their cost, invasiveness and time requirements, which may be particularly burdensome for new mothers at 3 months postpartum. Moreover, both the IS OGTT index and insulinogenic index/HOMA-IR have been widely used in large clinical studies [19]. A second limitation is that the observational nature of these data cannot conclusively establish causality in the relationship between antepartum adiponectin and postpartum metabolic dysfunction.…”

“…The HOMA of insulin resistance (HOMA-IR) was calculated as described by Matthews et al [17]. Beta cell function was assessed by the insulinogenic index divided by HOMA-IR (insulinogenic index/HOMA-IR) [18,19].…”

Zinc and diabetes

“…It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].The links among Zn 2+ , diabetes and insulin were established in the 1930s, a decade after the discovery of the hormone, when a study showed crystallized insulin contains Zn 2+ and that Zn 2+ , along with other metal ions, could reversibly trigger insulin crystallization [3]. Zinc was later demonstrated to prolong insulin action when co-injected with the hormone [4].…”

“…It is characterized by high circulating glucose levels over a prolonged period of time which leads to long-term health complications [1]. Type 1 Diabetes (T1D) involves the autoimmune destruction of insulin-secreting β cells while Type 2 Diabetes (T2D) is linked to both a decrease of insulin release and deficient hormone action on targeted organs [2].…”

Chances and risks of SGLT2 inhibitors

“…During the course of the disease, pancreatic insulin production becomes decreased, and absolute insulin deficiency results (Kahn 2003). Based on these pathophysiological considerations, correcting the insulin resistance and substituting insulin is the current mainstay of diabetes therapy.…”