Cross-sectional and longitudinal relationships of body mass index with glycemic control in children and adolescents with type 1 diabetes mellitus

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Abstract

Aims

Weight gain is an oft-cited outcome of improved glycemic control in adults with type 1 diabetes, though few studies have investigated this in youth. The purpose of this paper was to examine cross-sectional and longitudinal associations of body mass index (BMI, kg/m2) with glycemic control in youth with type 1 diabetes (n = 340, 12.5 ± 1.7 year, 49% female, duration ≥1 year) participating in a 2-year multi-center intervention study targeting family diabetes management.

Methods

BMI was calculated from height and weight measured at clinic visits. Glycohemoglobin (HbA1c) at each visit was assayed centrally. Cross-sectional associations of baseline BMI with glycemic control, and of change in BMI and HbA1c with baseline values, were examined. Longitudinal associations of time-varying BMI and HbA1c were examined using a multilevel linear mixed effects model controlling for time-varying time (months), insulin dose (units/kg/day), regimen, Tanner stage, and time invariant baseline diabetes duration, BMI, treatment group and sociodemographic characteristics.

Results

Baseline HbA1c was unrelated to baseline BMI, but was related positively to subsequent BMI change (p = 0.04) and inversely to HbA1c change (p = 0.002). Baseline BMI was inversely related to BMI change (p = 0.01) and unrelated to HbA1c change. In multilevel regression, BMI was related inversely to HbA1c (%) (β ± SE = −0.11 ± 0.02, p < 0.001) and positively to insulin dose (0.23 ± 0.07, p = 0.001). In the treatment group only, BMI was positively related to pump regimen (0.18 ± 0.08, p = 0.02).

Conclusions

Increased insulin administered to improve glycemic control may contribute to increased BMI in youth with type 1 diabetes, indicating the importance of determining ways to minimize weight gain while optimizing glycemic control.

Introduction

Cardiometabolic risk is a primary concern for patients with type 1 diabetes mellitus [1]. Despite improvements in glycemic control and reduced microvascular complications demonstrated with intensive insulin therapy [2], [3], weight gain is a frequently noted side-effect [4], [5], [6] that may contribute to increased cardiometabolic risk [7], [8], [9]. Weight gain occurring as a result of intensive insulin therapy in patients with type 1 diabetes has been attributed to improved energy utilization and decreased glycosuria [5], [10], increased insulin administration [7], [11], and increased dietary flexibility [12]. Reported health consequences of this weight gain include increased blood pressure and dyslipidemia [7], [8], [9], which increase risk of adverse micro- and macrovascular outcomes [13]. Cardiovascular disease is the major cause of mortality in adults over 30 years of age with type 1 diabetes [13]. Evidence suggests atherosclerosis begins during adolescence, with elevated risk of adult cardiovascular disease in adolescents with known risk factors [14], [15], underscoring the importance of elucidating influences on risk factor development in this population.

Findings are mixed regarding the relationship between BMI and glycemic control, with studies in youth and adults showing positive [9], [16], inverse [7], [17], and no associations [18], [19]. Previous studies were conducted in samples on earlier insulin regimens, and none in the US. The mixed findings observed may be attributable to the limitations in data collection and analytic methods. Prospective studies are important both for confirming the cross-sectional association between glycemic control and BMI as well as for assessing the direction of causality. Appropriate analytic methods must be applied in order to maximize the informative value of repeated measures on subjects in a prospective study design while also accounting for within-subject correlation. Further, multivariable methods are necessary in order to assess the possibility of confounding in bivariate associations.

The objective of this study was to examine the cross-sectional and longitudinal associations of glycemic control with BMI in a sample of children and adolescents with type 1 diabetes assessed at multiple times over 2 years. We first examine bivariate baseline associations between BMI and glycemic control, and the association of baseline values of BMI and glycemic control with subsequent change in each. We then examine the longitudinal relationship of BMI with glycemic control using a multilevel linear regression model controlling for insulin dose, insulin regimen, treatment group, and other diabetes-related and sociodemographic covariates.

Section snippets

Subjects

Data for this analysis come from a multicenter randomized controlled trial testing the impact of a family-based behavioral intervention on glycemic control and adherence conducted from January 2006 to March 2009 at four pediatric endocrinology clinics located in the United States (Massachusetts, Florida, Illinois, Texas). The intervention focused on enhancing parent–child teamwork and problem-solving skills for diabetes management. BMI was not a primary or secondary outcome of the study, and

Materials and methods

Families were enrolled in the study for 2 years; data were collected at routine clinic visits occurring approximately every 3–4 months. There was 92% retention at the 2-year follow-up. Child sex, diabetes duration, race/ethnicity, parent income and parent education were assessed at baseline; insulin regimen and insulin dose were assessed at each visit. Frequency of blood glucose monitoring was obtained at each visit by blood glucose meter download. Tanner stage (1–5) was assessed as per each

Baseline characteristics

The sample was predominantly White (76%), was highly educated (59% college graduate or above) and represented a wide income range (Table 1). Nearly forty percent of the sample had baseline HbA1c  8.0% (64 mmol/mol) (Table 2). Subjects with more optimal glycemic control at baseline had shorter diabetes duration (p = 0.03), were more likely to be on pump regimen (p = 0.03), and exhibited more frequent blood glucose monitoring (p < 0.0001) than those with poorer glycemic control. Approximately one-third

Discussion

The present study describes cross-sectional and longitudinal relationships of BMI with glycemic control in a large, multisite sample of children and adolescents with type 1 diabetes in the United States. We observed no significant baseline associations between weight category and HbA1c, and no significant differences in subsequent change in HbA1c by baseline weight category. However, subjects with higher baseline HbA1c demonstrated a larger subsequent increase in BMI and a smaller subsequent

Financial disclosure

This research was supported by the Intramural Research Program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development.

Conflict of interest

The authors declare no conflicts of interest.

Acknowledgements

The authors wish to acknowledge the contributions of the research staff at the participating clinical sites and the families who participated in the study. This research was funded by the intramural research program of the NIH, Eunice Kennedy Shriver National Institute of Child Health and Human Development, contract #s N01-HD-3-3360, James Bell Associated; N01-HD-4-3363, Children's Memorial Hospital, Chicago, Illinois; N01-HD-4-3362, Texas Children's Hospital, Houston, Texas; N01-HD-4-3361,

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