Insulin resistance in children and adolescents with type 1 diabetes mellitus: relation to obesity

In this issue, Reinehr et al. report on insulin resistance and its relationship to adiposity in children with type 1 diabetes (T1D). The total study population consisted of 8156 children aged 4—20 yr, but they focused on 4124 children with satisfactory glycemic control, defined by a hemoglobin A1c (HbA1c) of<8.0%. Insulin action was assumed to be related to the total daily insulin dose, which was calculated in three ways: dose per weight (ID/kg), dose per body surface area (ID/m), and dose per ideal body weight (ID/ideal kg). Adiposity was estimated as body mass index (BMI). The relationship between insulin resistance and adiposity was analyzed in three ways. First, children with satisfactory (HbA1c< 8.0%) and poor (HbA1c 8.0%) glycemic control were compared. The children with poor glycemic control had a higher BMI and daily insulin doses. Second, children with satisfactory glycemic control were divided into tertiles according to BMI; the highest tertile had a lower ID/kg but a higher ID/m compared to the lowest tertile. These findings were confirmed in a multivariate analysis, with BMI having a significant weak inverse correlation with ID/kg and a weak positive correlation to ID/m. Third, children with satisfactory glycemic control were categorized by daily insulin dose into insulin resistant (ID/ kg 1.0 units, n1⁄4 882) and insulin sensitive (ID/ kg< 1.0 unit, n1⁄4 3242) groups. BMI was not significantly different between the groups. The authors concluded that children with ‘‘T1D with insulin resistance based on ID/kg are not more overweight than insulinsensitive children with T1D’’ and ‘‘ID/m seems to reflect a better tool than ID/kg to describe the influence of overweight on insulin resistance in T1D’’. This is the first large-scale study attempting to address the relationship between insulin resistance and adiposity in establishedT1D. Its strengths include the large number of subjects and clearly outlined analyses of the different subgroups. The use of insulin dose as an estimate of insulin resistance is understandable because other simple indices such as fasting insulin or the homeostasis model assessment of insulin resistance (HOMA-R) are not applicable in people with endogenous insulin deficiency, and the gold-standard but, invasive, eugylcemic hyperinsulinemic clamp methodology is not feasible in a large study of children. Notwithstanding this limitation, we suggest that the following issues are pertinent. First, despite questioning the adequacy of ID/kg as a measure of insulin resistance, the authors go on to base their conclusions on this parameter. If they had used ID/m, which was directly related to BMI, they would have drawn the opposite conclusion. The difference between ID/kg and ID/m can be appreciated from the following example. Consider two children with T1D, each on 40 units of insulin per day. They both weigh 40kg but one is taller (150 cm) and theother shorter (130 cm). The ID/kg (1.0) is the same for both children, but the ID/m of the taller child (31.1) is less than that of the shorter child (32.9). This illustrates why ID/m should be a better reflection of adiposity than ID/kg and probably explains why BMI correlated positively with ID/m and not with ID/kg. Second, there was a selection bias in that children with poor glycemic control (HbA1c 8.0%) and higher BMI were excluded. Finally, BMI was the only marker of adiposity used and is likely to have a weaker association with insulin resistance than waist circumference or waist to hip ratio, which better reflect visceral adiposity (1). Pediatric Diabetes 2005: 6: 3—4 Copyright # Blackwell Munksgaard 2005 Printed in Denmark. All rights reserved Pediatric Diabetes