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23-12-2009 | Diabetes | Article

Beta cell failure is main determinant of impaired glucose tolerance


Free abstract

MedWire News: Progressive loss of beta cell function is the main determinant of progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT), a US study has found.

Glucose intolerance is a continuum and declines progressively throughout the entire range of NGT and IGT, say R DeFronzo, from the University of Texas Health Science Center in San Antonio, USA.

They note that there has been a lack of large studies characterizing the pathophysiological disturbances responsible for IGT and employing sophisticated measures of beta cell function and insulin sensitivity.

For their study, the researchers examined the determinants of oral glucose tolerance in 602 people with IGT who participated in the Actos Now for Prevention of Diabetes (ACT NOW) study, along with 115 people with NGT and 50 with impaired fasting glucose (IFG) who were identified during screening. Insulin secretion and insulin sensitivity indices were derived from plasma glucose and insulin during an oral glucose tolerance test (OGTT).

At baseline, fasting plasma glucose, 2-hour postprandial glucose (OGTT) and hemoglobin A1c were, on average, 5.8 μmmol/l, 10.5 μmmol/l and 5.5%, respectively, in participants with IGT.

IGT was associated with defects in early and total insulin secretion and in insulin sensitivity. IGT patients who had a 2-hour plasma glucose level of 7.8–8.3 mmol/l, had a 63% decrease in scores on the insulin sensitivity/insulin resistance index compared with NGT participants. Moreover, this defect worsened progressively as 2-hour plasma glucose levels rose, with a 73% decrease in those with levels of 8.9–9.94 mmol/l and an 80% decrease in those with levels of 10.0–11.05 mmol/l.

The Matsuda insulin sensitivity index was significantly reduced by 40% in IGT compared with NGT participants. In multivariate analysis, beta cell function was the primary determinant of glucose area under the curve during OGTT, explaining 62% of the variance.

Writing in the journal Diabetologia, the researchers conclude: “The two major pathophysiological disturbances – insulin resistance and beta cell dysfunction – declined progressively over the range of NGT and IGT. Participants in the upper tertile of IGT lost approximately 80% of their beta cell function compared with participants with NGT.”

They comment: “The establishment of defined glucose cut-off points for the diagnosis of IGT and Type 2 diabetes is somewhat arbitrary and needs to be re-evaluated.”

MedWire ( is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2009

By Joel Levy