Abstract

RESEARCH DESIGN AND METHODS

The analysis included data from 96 (29 female and 67 male; Tanner stages 1 and 2) overweight (BMI 26.7 ± 4.6 kg/m²; BMI percentile 96.9 ± 4.1) children who are part of the University of Southern California Study of Latino Adolescents at Risk (USC SOLAR) diabetes project, a longitudinal study that examines the development of type 2 diabetes in at-risk Hispanic youth. The subsample was chosen from a larger cohort (n = 222) based on Tanner stage and the completeness of their measures from four consecutive annual visits. Insulin sensitivity, acute insulin response, and disposition index were assessed annually with a frequently sampled intravenous glucose tolerance test (FSIVGTT). The FSIVGTT was performed in the morning after an overnight fast as previously described (6). Body composition was determined annually with a whole-body dual-energy X-ray absorptiometry scan using a Hologic QDR 4500W. Intra-abdominal and subcutaneous abdominal adipose tissue were determined by magnetic resonance imaging using a GE 1.5 Signa LX-Ecospeed with a GE 1.5 Tesla magnet and a single slice at the level of the umbilicus.

Included in the study were healthy children of Hispanic ethnicity and a BMI that was at or above the 85th percentile for age and sex (7).

A detailed description of the methods and the study protocol for the USC SOLAR study have been previously published (8).

RESULTS

S_i decreased significantly over the period of 3 years from 2.4 ± 1.4 ([×10⁻⁴ min⁻¹/(μU/ml)]³ at baseline to 1.5 ± 0.79 [(×10⁻⁴ min⁻¹/(μU/ml)]³ at the fourth consecutive annual assessment (P < 0.05), while fat mass increased from 21.8 ± 8.7 to 28.9 ± 10 kg (P < 0.05). For the whole group, the change in S_i during the first study year was a significant predictor of further fat mass development (P < 0.05), independent of fat-free mass, change in S_i, age, Tanner stage, and sex. In return, the change in fat mass between baseline and the first follow-up was not related to a change in S_i over the following 2 years.

When comparing a subgroup that significantly increased their S_i during the initial study year (n = 17) with a group that decreased in S_i (n = 79) during that time, the change in S_i was a strong predictor for further fat mass development only in the group that decreased their S_i (P < 0.05), not in the group that increased in S_i during the first year. Fat mass increased from 21.3 ± 7.5 to 26.2 ± 10.9 kg in the group that increased in S_i and from 21.9 ± 8.9 to 29.4 ± 9.9 kg in the group that decreased in S_i during the initial study year. Baseline S_i, age, fat mass, lean body mass, and specific fat compartments (intra-abdominal and subcutaneous abdominal adipose tissue) were not different between the two groups.

CONCLUSIONS

The main finding of the analysis is that the first-year change in S_i was an independent predictor of subsequent gain in fat mass over the next 2 years, specifically in those who decreased in S_i. The result was independent of fat-free mass, sex, age, and Tanner stage and is in accordance with a recently published study reporting preteen insulin resistance as a predictor for weight gain (5).

While a decrease in insulin sensitivity traditionally has been looked at as a consequence of increased body adiposity, the present study shows that insulin resistance in turn might also be a cause of increased body adiposity. Hispanic youths are more likely to be insulin resistant than their Caucasian peers, independent of body adiposity (2), predisposing them to an even higher disease risk. We can only speculate on the possible mechanisms behind that relationship, but among other possibilities it very well might involve the effects of insulin resistance on the brain. Insulin receptors have been located in areas that are important for the motivational regulation of food intake (9). Recently, evidence emerged that insulin resistance in the brain might co-occur with insulin resistance in the periphery (10). Sufficient insulin supply, transport, and reception in the brain are thus essential for the maintenance of energy balance. Considering this evidence, the present study might be supportive of the idea that the natural defense against excessive weight gain through adiposity signaling can be undermined by acquired resistance to adiposity-regulating hormones (11,12). The results of the present study show that the change in insulin sensitivity at an early age is an important independent predictor for further weight gain and emphasize the importance of insulin sensitivity as a primary target for long-term obesity prevention in addition to it being a secondary target to weight loss.

Acknowledgments

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