Insulin resistance is an important component of type 1 diabetes (2
). To our knowledge, this is the first study to show that racial/ethnic differences in insulin resistance, as measured by eGDR, exist in this group. Furthermore, this variation was observed in a sample of young individuals with short diabetes duration and normal adiposity, suggesting that racial/ethnic differences are present early in the disease course.
The current results are consistent with previous research in healthy individuals and in those with type 2 diabetes of whom nonwhite groups were generally more insulin resistant. Specifically, nondiabetic African American and Hispanic adults were more insulin resistant than nondiabetic NHW adults, using a frequently sampled intravenous glucose tolerance test with minimal model analysis (8
). For adults with type 2 diabetes, African Americans, but not Hispanics, were more insulin resistant than NHW (1
). The picture may be more complicated in adolescence, because puberty is an insulin-resistant state (10
). One study demonstrated that Mexican American, but not black, children were more insulin-resistant than NHW youth as measured by homeostasis model assessment (9
), whereas another study using the clamp method found that insulin resistance was increased in black but not white participants between 11 and 19 years of age (10
Our results demonstrating trends for racial/ethnic differences in the eGDR components are also consistent with the literature, with minorities demonstrating poorer outcomes. For example, African American children with type 1 diabetes have worse glycemic control than white children with diabetes (18
). With regard to adiposity, a higher percentage of Mexican-American and black adolescents are overweight/obese compared with NHW adolescents (9
). The National Health and Nutrition Examination Survey III also found that African American adult women with type 2 diabetes have a higher BMI than NHW women with diabetes (19
). Last, hypertension is more prevalent in African American adults than in NHW and Mexican American adults, both with and without type 2 diabetes (20
Several clinical characteristics are associated with insulin resistance in type 1 diabetes. For example, higher insulin resistance is related to older age and longer disease duration (6
). The authors found similar relationships, but the association with age was stronger and duration was no longer significant after adjustment for age. Family history of type 2 diabetes has been shown to be associated with greater insulin resistance in those with type 1 diabetes (5
). In the current study, there was no association with parental history of diabetes, which was based on self-report. However, parental obesity and parental insulin resistance, which were directly measured in the current study and are risk factors for diabetes, were related to greater proband age-adjusted insulin resistance. This association was independent of the probands' adiposity, indicating that other familial characteristics in addition to factors affecting probands' body composition (e.g., genetic predisposition) may influence their insulin resistance.
As may be expected, acanthosis nigricans was related to greater insulin resistance. Lower levels of SHBG were also significantly associated with greater insulin resistance in age-adjusted analysis. This finding is consistent with basic science (21
) and clinical research (22
) demonstrating a negative association between insulin and SHBG levels, such that the greater the level of insulin resistance in an individual with type 1 diabetes is, the higher is the insulin dose required to meet physiological requirements and the lower the hepatic production of SHBG. These results suggest that the derived measure of insulin resistance, eGDR, is indeed measuring insulin resistance in those with type 1 diabetes.
The risk of micro-and macrovascular complications is elevated for individuals with type 1 diabetes who have insulin resistance. For example, greater insulin resistance is associated with the development of nephropathy (3
), neuropathy (7
), and elevated lipids (6
). In the current study, higher insulin resistance was associated with prevalent dyslipidemia and nephropathy. It could be argued that these relationships may be capturing the well-established associations of diabetes complications with the components used to calculate eGDR, specifically suboptimal glycemic control and/or hypertension. However, previous research in NHW adults with long-standing type 1 diabetes showed that insulin resistance as measured by eGDR more strongly predicted overt diabetic nephropathy than did glycemia or blood pressure (23
). There were no differences in insulin resistance by prevalent neuropathy.
eGDR is a derived measure of insulin resistance, and clamp techniques are needed to confirm our results. However, because eGDR is noninvasive and strongly correlated with clamp-measured insulin resistance, it is useful for population-based studies, similar to the numerous surrogate measures of insulin resistance that are commonly used in studies of type 2 diabetic and nondiabetic groups. We demonstrated for the first time associations of proband insulin resistance with parental obesity and parental insulin resistance, although there may have been limited power to confirm the associations in the multivariable model. Limited sample size may also explain the lack of a significant difference in insulin resistance by neuropathy status, although the magnitude of the difference was small. Last, because we combined nonwhite groups owing to small sample sizes and similar eGDR, we may have limited the ability to detect interactions by race/ethnicity. The research had a number of strengths, most importantly that it is the first study of type 1 diabetes, to our knowledge, to examine insulin resistance using a racially/ethnically diverse sample. We were also able to evaluate and adjust for confounders in the multivariable model to estimate the independent association of race/ethnicity with insulin resistance.
The greater insulin resistance observed in nonwhites with type 1 diabetes may help clarify the well-documented gaps in diabetes outcomes for underserved minorities. Insulin resistance is associated with a spectrum of poor health outcomes; thus, the greater insulin resistance in minorities with type 1 diabetes may explain their higher incidence of diabetes-related complications compared with NHW (24
). Future research is needed to determine which factors contribute to racial/ethnic differences in insulin resistance in this group, such as disparities in diabetes care, differences in behaviors, environmental factors, or physiological processes, or simply residual confounding. Understanding which modifiable factors prevent insulin resistance and then targeting interventions to those groups most at risk will help address the public health burden of type 1 diabetes and its complications in minority populations.
In summary, insulin resistance as estimated by eGDR was greater in minorities with type 1 diabetes than in NHW probands. Because there exists a strong association between insulin resistance and poor health outcomes in diabetes, the search for effective interventions to improve insulin resistance in minorities with type 1 diabetes must become a priority.