Coordinate Changes in Plasma Glucose and Pancreatic β-Cell Function in Latino Women at High Risk for Type 2 Diabetes

Abstract

The purpose of this study was to examine longitudinally the relationship among glucose levels, pancreatic ␤-cell function, and insulin resistance in women at high risk for type 2 diabetes. Oral glucose tolerance tests (OGTTs) and intravenous glucose tolerance tests (IVGTTs) were performed at 15-month intervals for up to 5 years or until fasting plasma glucose exceeded 140 mg/dl in Hispanic women with recent gestational diabetes. Data were analyzed 1) to compare changes in insulin sensitivity, ␤-cell function, and glucose levels between women who had diabetes at one or more visits and women who remained diabetes free and 2) to determine longitudinal patterns of change in glucose levels and acute ␤-cell compensation for insulin resistance. Seventy-one women provided data from a total of 280 paired OGTTs and IVGTTs during a median follow-up of 46 months. Compared with the 47 women who remained free of diabetes, the 24 who either had diabetes (n ‫؍‬ 9) or developed it during follow-up (n ‫؍‬ 15) had higher baseline glucose levels and lower acute ␤-cell compensation for insulin resistance. Baseline insulin sensitivity was low in both groups and did not change significantly during follow-up. Fasting and 2-h glucose levels increased more rapidly in the diabetic group despite a decline in acute ␤-cell compensation that was significantly slower than the decline in women who did not develop diabetes. This paradox was explained by an accelerated rise in glucose levels for any decline in ␤-cell compensation when ␤-cell compensation reached ϳ10% of normal, a level that was reached in the women who had or developed diabetes but not in the women who remained diabetes free. These findings define a pathogenesis for type 2 diabetes in one high-risk group that is characterized by a relatively long-term decline in acute ␤-cell compensation for chronic insulin resistance that is attended by slowly rising glucose levels. Only relatively late in this process do glucose levels rise rapidly and into the diabetic range. T ype 2 diabetes is defined by glucose levels in the diabetic range that are caused by inadequate pancreatic ␤-cell compensation for insulin resistance (1). Longitudinal studies indicate that insulin resistance precedes the development of diabetes by many years and may worsen during progression to diabetes (2-5). Inadequate insulin secretion is a less consistent finding long before diabetes develops, but declining function clearly occurs during the progression from normal glucose tolerance to diabetes (4) and during worsening of existing diabetes (6). At the present time, relatively little is known about the relationship among changes in insulin sensitivity (S I ), insulin secretion, and glucose levels during the development of type 2 diabetes. We have been performing serial measurements of S I , insulin secretion, and glucose tolerance in a cohort of Hispanic women at high risk for type 2 diabetes by virtue of a recent history of gestational diabetes mellitus (GDM). In the present report, we examine the relationship betw...

Simultaneous determination of cell aging and ATP release from erythrocytes and its implications in type 2 diabetes

“…[1][2][3][4] A vast amount of research involving diabetes and complications is focused on areas such as insulin secretion and resistance, pancreatic beta cells, and maintenance of blood glucose levels. 5,6 of this weakened antioxidant defense, the RBCs of these individuals are more prone to oxidant insult and are believed to be less deformable in comparison to RBCs obtained from healthy individuals.…”

Increased Skeletal Muscle Tumor Necrosis Factor-α and Impaired Insulin Signaling Persist in Obese Women With Gestational Diabetes Mellitus 1 Year Postpartum

“…Women with a history of GDM have up to a 60% chance of progressing to type 2 diabetes within 5 years after pregnancy (1,5), depending on advancing insulin resistance and deterioration of islet function (6,7). Subjects with a history of GDM tend to have a higher BMI (8), an athrogenic lipid profile (8 -10), and evidence of subclinical inflammation (11)(12)(13), all characteristics associated with a state of chronic insulin resistance.…”

Demographic and metabolic characteristics of individuals with progressive glucose tolerance

“…This result differs from that of population studies in lowincome Mexicans (5) and Fins from the Botnia Study (6), which showed that progressors initially present increased basal glucose and insulin levels. An intermediate result was reported by Xiang et al (18) in their non-population study of Hispanic women with a recent history of gestational diabetes mellitus, where progressors initially presented elevated fasting blood glucose but fasting insulinemia similar to non-progressors.…”

“…Our finding of elevated blood glucose in the second hour of the OGTT can be explained by the reduction in first-phase insulin secretion in the hyperglycemic clamp test. Previous studies (3,18,(28)(29)(30)(31), including ours involving Caucasian Americans (8), have reported that individuals with NGT and at risk for type 2 diabetes mellitus have an insufficient insulin response to intravenous glucose stimulation tests, suggesting that β cell dysfunction could be the first defect involved in type 2 diabetes mellitus pathogenesis.…”

“…For each insulin sensitivity index level in the progressor group, relative to the non-progressor group, there was a reduced response capacity from pancreatic β cells. This deficiency was the strongest metabolic predictor of the evolution to type 2 diabetes mellitus in Pima Indians (3), Fins in the Botnia Study (6), and Hispanic women with a recent history of gestational diabetes mellitus (18).…”