Radioimmunoassay May Overestimate Insulin in Non‐insulin‐dependent Diabetics

Temple, Rosemary; Clark, P. M. S.; Nagi, Dinesh; Schneider, A; Yudkin, John; Hales, C. N.

doi:10.1111/j.1365-2265.1990.tb00915.x

Cited by 120 publications

(56 citation statements)

References 12 publications

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“…This observation has implications for considerations of pathophysiology, for if a variable is regulated by insulin resistance but the measure being employed to assess it is such a poor indicator of insulin resistance, then one might have to postulate other explanations for the associations. Some years ago, it was shown that the standard insulin immunoassays cross-reacted with the biologically less active insulin precursor molecules proinsulin and its split products [32]. This observation, and emerging assays that permitted specific measures of both insulin and these proinsulin-like molecules, led to studies that found that the correlations of concentrations of these molecules were stronger than those for insulin itself [33], despite their having little biological activity.…”

Section: New Members Of the Metabolic Syndrome And Their Pathophysiologymentioning

confidence: 99%

Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology

Yudkin

2007

Diabetologia

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The clustering of dyslipidaemia, hypertension and glucose intolerance, predominantly in overweight individuals, has been ascribed many names, including syndrome X and the metabolic syndrome. In Reaven's original description of syndrome X, a central aetiological role was attributed to insulin resistance, and this assumption has remained as the dominant paradigm for the metabolic syndrome. There are a number of conceptual problems in such a model, particularly those arising from observations that several novel markers, including measures of endothelial dysfunction and of low-grade inflammation, are as closely related to insulin resistance as are the classic components of the syndrome. Because it is difficult to envisage how these traits might develop as a consequence of insulin resistance, such observations indicate the need for a new paradigm to explain the mechanisms of association better. It has been proposed that a state of low-grade inflammation, consequent upon the production of adipocytokines, particularly from truncal fat, explains the observed relationships between insulin resistance and endothelial dysfunction better than does a model revolving around insulin resistance. Furthermore, the inflammatory cytokines generated from adipose tissue may influence vessel endothelial function without elevations in circulating concentrations. This review alludes to several problems inherent in the epidemiological method in understanding disease mechanisms. These include crude biological measures, the use of venous systemic fasting samples, imprecision of assays, naive physiological models, simplistic statistical approaches and, without clinical trials, an inability to test causation. Integrated systems biology needs more complex approaches to investigate disease mechanisms, involving cell, organ, whole organism and population studies.

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Section: New Members Of the Metabolic Syndrome And Their Pathophysiologymentioning

confidence: 99%

Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology

Yudkin

2007

Diabetologia

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“…The beta cell is also unable to oscillate in concert with the fluctuations in plasma glucose induced by an oscillating glucose 6 S. Kahn: The relative contributions of insulin resistance and beta-cell dysfunction to the pathophysiology infusion [76]. Finally, inefficient proinsulin processing to insulin [77,78,79,80,81,82,83] and a reduction in the release of islet amyloid polypeptide (IAPP), known also as amylin [84,85,86,87], have been observed in established Type 2 diabetes. These alterations in beta-cell function have been observed in Type 2 diabetic subjects, typically following the administration of intravenous stimuli.…”

Section: Beta-cell Dysfunction In Type 2 Diabetesmentioning

confidence: 99%

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

2003

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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]

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“…15 Initially this may be masked by excess production of proinsulins. 47 The rise in proinsulin represents increased insulin demand in T2D, causing depletion of mature insulin-rich granules with mobilisation of immature granules rich in proinsulin.…”

Section: Beta-cell Dysfunction In T2dmentioning

confidence: 99%

Targeting beta-cell preservation in the management of type 2 diabetes

2017

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Type 2 diabetes (T2D) is widely considered a chronic and progressive disease without cure. As beta-cell function progressively declines over time, blood glucose rises. Current management of T2D involves incremental introduction of dietary and drug therapies to achieve normoglycaemia. However, recent studies have demonstrated remission of T2D following bariatric surgery, very low calorie diet or intensive insulin therapy, raising the possibility that the declining beta-cell function in T2D may be arrested or even reversed. The point at which such interventions are introduced in the course of T2D is key for clinical benefit. Future treatment strategies should be revised to target early betacell preservation and thus disease remission. This article reviews the pathogenesis of beta-cell dysfunction and evidence for the clinical benefit of preserving beta-cell function in T2D, and discusses the evidence for beta-cell preservation of current glucose-lowering therapies with particular reference to their effect when initiated at the time of diagnosis of T2D. Br J Diabetes 2017;17:134-144

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Radioimmunoassay May Overestimate Insulin in Non‐insulin‐dependent Diabetics

Cited by 120 publications

References 12 publications

Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology

Insulin resistance and the metabolic syndrome—or the pitfalls of epidemiology

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

Targeting beta-cell preservation in the management of type 2 diabetes

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