The Natural Course of β-Cell Function in Nondiabetic and Diabetic Individuals

Abstract

Data from the UKPDS (U.K. Prospective Diabetes Study) indicate a continuous decline in ␤-cell function in patients with type 2 diabetes. We studied longitudinal changes in ␤-cell function (follow-up of 5.2 years) in subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes, using acute insulin response (AIR) and insulin sensitivity index (S i ) from a frequently sampled intravenous glucose tolerance test among African-American, Hispanic, and non-Hispanic white subjects aged 40 -69 years. At baseline, decreasing levels of both S i and AIR (either unadjusted or adjusted for S i ) mirrored deteriorating glucose tolerance status at baseline and at follow-up. A different pattern was found with respect to longitudinal changes; S i declined in each glucose tolerance category, ranging from ؊0.81 ؋10 ؊4 min ؊1 ⅐ U ؊1⅐ ml ؊1 in NGT at baseline and NGT at follow-up (NGT/NGT) to ؊1.06 ؋10 ؊4 in NGT/diabetes, whereas the directional change in AIR principally determined the glucose tolerance status at follow-up. In NGT/NGT S i decreased by 35% and AIR increased by 34%. Results were similar in each of the three ethnic groups. These data shed light on the natural course of ␤-cell function; over 5.2 years, mean insulin sensitivity declined in each glucose tolerance category. The change in AIR, however, principally determined glucose tolerance status at follow-up; NGT was maintained by a compensatory increase in insulin secretion. Failure to increase insulin secretion led to IGT, and a decrease in insulin secretion led to overt diabetes. This data may have important implications for the prevention and treatment of type 2 diabetes. Diabetes 55:1114 -1120, 2006 I mpaired insulin secretion and impaired insulin action (increased insulin resistance) are the two major components contributing to the pathophysiology of type 2 diabetes (1-3); their complex relationship has been mathematically described as a curvilinear relationship (4 -6). Longitudinal studies indicate that compromised ␤-cell function is detectable in pre-diabetic individuals long before the onset of actual type 2 diabetes (1,7). The natural course of ␤-cell function over time, however, is poorly understood, and published data are scarce. A longitudinal study in Pima Indians highlighted the importance of declining ␤-cell function in individuals transitioning from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) and IGT to diabetes, respectively (3). In the U.K. Prospective Diabetes Study (UKPDS), a continuous decline in ␤-cell function in patients with type 2 diabetes, irrespective of glucose-lowering treatment, was demonstrated (8). No data on the natural course of ␤-cell function is currently available in a large population, across different ethnic groups, and using a direct measure of insulin secretion. Therefore, we studied longitudinal changes in ␤-cell function over 5.2 years by acute insulin response (AIR) relative to insulin sensitivity index (S i ), as assessed from a frequently sampled intravenous gluco...

(How) Can We Prevent Type 2 Diabetes?

“…In type 2 diabetes, insufficient insulin supply occurs in a setting of increased insulin demands-chronic insulin resistance. Longitudinal studies of insulin secretion and insulin action in Pima Indians (8), Hispanic women with prior gestational diabetes (9), and Hispanic, white, and AfricanAmerican participants in the Insulin Resistance Atherosclerosis Study (10) reveal that abnormalities in insulin secretion and action are present long before type 2 diabetes develops. Moreover, both insulin resistance and failing insulin secretion are progressive over the course of years.…”

Métabolisme du cholestérol et function β-cellulaire

“…L'insulinorésistance est un événement précoce dans la physiopathologie du DT2, mais qui demeure relativement stable au cours de l'évolution de la maladie. À l'inverse, la capacité insulinosécrétrice de la cellule  pancréatique diminue au cours du temps et contribue de façon majoritaire à la détérioration progressive de l'équilibre glycémique chez les diabétiques de type 2 [1]. Étant donné que la carence fonctionnelle de la cellule  est potentiellement réversible, il apparaît important de développer des thérapeutiques visant à freiner cette insuffisance [2].…”

Meal composition affects insulin secretion in women with type 2 diabetes: a comparison with healthy controls. The Hoorn prandial study

“…Especially impairment of firstphase insulin secretion as measured by an intravenous glucose tolerance test has been shown to be predictive for the development of DM2 (Weyer et al, 1999;Festa et al, 2006). However, this first-phase insulin response and a biphasic shape are not identifiable in plasma samples of physiological circumstances (that is, following oral glucose ingestion or a meal) (Grodsky, 1972;Caumo and Luzi, 2004).…”

“…Insulin resistance and a decline in b-cell function contribute to the development of type 2 diabetes mellitus (DM2) (Weyer et al, 1999;Festa et al, 2006). Especially impairment of firstphase insulin secretion as measured by an intravenous glucose tolerance test has been shown to be predictive for the development of DM2 (Weyer et al, 1999;Festa et al, 2006).…”