Insulin resistance and fasting plasma glucose in first degree relatives of patients with type 1 diabetes.

BACKGROUND

We analyzed the relationship between fasting plasma glucose (FPG), the presence of autoantibodies, first phase of insulin secretion and insulin resistance in the first degree relatives of patients with type 1 diabetes.

MATERIALS AND METHODS

The group studied consisted of 90 healthy relatives, divided into two groups: "high-normal" FPG group (≥88mg/dl) and "low-normal" FPG group (<88/mg/dl). All subjects underwent an intravenous glucose tolerance test, and the 1st phase insulin response (FPIR) and FPIR-to-HOMA-IR-ratio were calculated. Additionally, islet autoantibodies (GADA, IAA and IA-2A) were determined by radioimmunoassays.

RESULTS

The subjects with "high-normal" FPG were older (p=0.0009), had higher BMI (p<0.0001) and lower HOMA%B (p=0.0004), FPIR (p=0.006) and FPIR-to-HOMA-IR-ratio (p=0.004) in comparison with the "low-normal" FPG group. Autoantibodies were present in 40.9% and in 21.7% of the subjects with "high-normal" and "low-normal" FPG, respectively. In the "high-normal" FPG group, FPG correlated positively with GADA (r=0.31, p=0.04), and HOMA-IR (r=0.19, p=0.02), and negatively with HOMA%B (r=-0.36, p=0.001), whereas FPIR correlated positively with HOMA%B (r=0.55, p=0.0001) and BMI (r=0.30, p=0.04). After an adjustment for BMI, the difference in FPIR between the "high-normal" and "low-normal" FPG groups remained significant (p=0.025), whereas the difference in FPIR-to-HOMA-IR-ratio became insignificant.

CONCLUSIONS

Our results suggest that taking into account the impact of age and BMI on insulin sensitivity, it would be expected that the relatives of patients with type 1 diabetes with "high-normal" glucose levels would become gradually unable to compensate for increasing insulin resistance.