Is islet autoimmunity related to insulin sensitivity or body weight in children of parents with type 1 diabetes?

Abstract

Aims/hypothesis It has been suggested that metabolic demand and insulin resistance play a role in the development of type 1 diabetes, including the onset of autoimmunity. The aim of the present study was to determine whether insulin demand is increased in children with islet autoantibodies. Methods BMI standard deviation score (BMI-SDS) was measured from 2 years of age in 1,650 prospectively followed children of mothers or fathers with type 1 diabetes, including 135 who developed persistent islet autoantibodies. HOMA of insulin resistance (HOMA-IR) was determined using fasting samples from 777 of the children starting from age 5 years. Results An increased HOMA-IR was associated with female sex (p=0.0004), older age (p<0.0001) and increased BMI-SDS (p<0.0001). Children with islet autoantibodies did not have an increased HOMA-IR compared with agematched islet autoantibody-negative children (age 8 years: mean 0.61 vs mean 0.72, respectively, p=0.21; age 11 years: mean 0.96 vs mean 1.21, respectively, p=0.07). Furthermore, after correction for age and sex, autoantibody positivity was associated with decreased HOMA-IR values (p=0.01). BMI-SDS was similar between islet autoantibodypositive and -negative children at age 2 (mean 0.07 vs mean 0.16, respectively), 5 (mean 0.06 vs 0.08, respectively), 8 (mean −0.09 vs mean 0.02, respectively), and 11 years (mean 0.22 vs mean 0.16, respectively) and similar to that of national reference values. Conclusions/interpretation Islet autoantibody-positive children in the BABYDIAB cohort are not insulin resistant and do not have an increased BMI around and early after islet autoantibody seroconversion. These findings are inconsistent with the notion that insulin resistance is a risk factor for islet autoimmunity.

Hyperglycaemic clamp test for diabetes risk assessment in IA-2-antibody-positive relatives of type 1 diabetic patients

“…However, this requires confirmation in larger ongoing studies. The clamp test also allowed estimation of insulin sensitivity in FDRs and HVs, but in line with previous publications [29,30] it failed to detect differences in biological measures of insulin sensitivity according to clinical outcome.…”

“…The increase in concentration between time 0 and 30 min was determined for glucose (Δglucose 30 ) and C-peptide (ΔCP 30 ). The incremental response was defined as ΔCP 30 /Δglu-cose 30 as previously described [20]. The disposition index (DI) [21] was computed by multiplying ISI from the clamp with the OGTT-derived AUC 0-120 for C-peptide.…”

BMI is an important driver of β-cell loss in type 1 diabetes upon diagnosis in 10 to 18-year-old children

“…Finally, several studies indicate that in individuals at risk for the development of type 1 diabetes, insulin resistance is an independent risk factor for disease development (17,18,19,20), and in studies of identical twins the co-twin who goes on to develop type 1 diabetes is more insulin resistant than the twin who does not (21). However it is important to add that other studies question these findings, and hence the theory is controversial (22).…”

The Enlarging List of Phenotypic Characteristics That Might Allow the Clinical Identification of Families at Risk for Type 1 Diabetes

“…Metabolic demand and insulin resistance have been suggested to be involved in the development of type 1 diabetes (Evertsen et al, 2009;Wilkin, 2009), but the evidence is not consistent across the studies. In 1650 prospectively followed children of mothers or fathers with type 1 diabetes (BABYDIAB cohort), islet autoantibodies-positive children were not insulin resistant (based on homeostasis model assessment of insulin resistance, HOMA-IR) and did not have increased BMI around and early after seroconversion (Winkler at al., 2009). In this study, of 777 children with HOMA-IR measurements, 84 developed islet antibodies during the study: analysis of HOMA-IR by age showed no significant difference between islet autoantibody-positive and islet autoantibody-negative children, with a tendency towards a lower HOMA-IR in the antibody-positive children compared with the antibody-negative children.…”