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.