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Issue 138 Item 15 Lowered Insulin Response May Predict Type 1 Diabetes

A lowered first-phase insulin response could occur early in pre-diabetes among young children at genetic and immunological risk for type 1 diabetes. This lowered response implies a rapid autoimmune destruction or loss of function of beta cells, say Finnish researchers. It also suggests possible metabolic compensation mechanisms, they added.

Although reduced insulin responses were considered a sign of well-advanced deterioration of beta-cell function during the development of type 1 diabetes, the researchers said, there were no data on these responses at the onset of diabetes-related autoimmunity.

In this study, newborns were screened for HLA-DQB1-associated genetic risk for Type 1 diabetes. Those found to be at increased risk were followed up for the emergence of islet-cell antibodies. If these were detected, autoantibodies to three other antigens (insulin, GAD65 and IA-2) were measured too.

Fifty two children (aged 1 to 5 years) who had recently seroconverted to islet-cell antibody positivity, underwent intravenous glucose tolerance tests in order to measure first-phase insulin responses to intravenous glucose.

The first-phase insulin response was subnormal in 22 of these children (42.3%). Statistical analysis showed that islet-cell antibody of more than 20 Juvenile Diabetes Foundation units, as well as insulin autoantibodies and an increasing number of positive autoantibodies, were independent predictors of low first-phase insulin response.

The researchers pointed out that 11 of the 22 high risk children remained non-diabetic for a long time despite low insulin responses. It was this, the researchers said, which suggested rapid autoimmune destruction, loss of beta cell function and possible metabolic compensation.
Diabetologia 2002;45:1639-1648