Insulin Resistance is a Risk Factor for Progression to Type 1 Diabetes

Fourlanos S, Narendran P, Byrnes GB, Colman PG, Harrison LC. Diabetologia. 2004;47:1661-1667.

Researchers have found that insulin resistance is a risk factor for type 1 diabetes, suggesting that reducing insulin resistance could delay the development of type 1 diabetes. In this prospective, longitudinal study, first-degree relatives (N=104) of type 1 diabetes probands who tested positive for 1 or more islet antibodies were followed for a median of 4.0 years; 43 subjects progressed to diabetes and 61 subjects did not.

Subjects who developed diabetes were found to have had higher baseline insulin resistance relative to insulin secretion compared with subjects who did not develop diabetes, independent of known risk factors. A number of parameters were found to be predictive of progression to diabetes. These include islet antibody number, first phase insulin response (FPIR), fasting plasma glucose, fasting serum insulin, homeostasis model assessment of insulin resistance (HOMA-R), and insulin resistance relative to insulin secretion (log [HOMA-R : FPIR]); however, the only variable independently associated with progression to diabetes was insulin resistance relative to insulin secretion.

This is the first prospective longitudinal study of the role of insulin secretion and insulin resistance in the development of type 1 diabetes, and although the physiological basis for the findings is unknown, they have important implications. Insulin resistance is another potential risk factor for type 1 diabetes and may help improve the identification of at-risk individuals both in the clinic setting and in the selection of study subjects. The findings also suggest the onset of type 1 diabetes can be delayed through decreased insulin resistance, which can be achieved through lifestyle modifications, such as diet and exercise, and pharmacological interventions, such as insulin sensitizing drugs.