Rapid Decline in β-Cell Function and Increasing Adiposity Are Associated With Conversion to Type 2 Diabetes in At-Risk Latino Youth

Abstract

Youth-onset type 2 diabetes (T2D) is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Here, we describe findings from a longitudinal cohort study in 262 Latino children with overweight/obesity at risk of developing T2D with annual measures of oral and intravenous glucose tolerance (IVGTT), body composition, and fat distribution. Logistic binomial regression was used to identify significant predictors in those who developed T2D compared with matched control participants, and mixed-effects growth models were used to compare rates of change in metabolic versus adiposity measures between groups. Overall conversion rate to T2D at year 5 was 2% (n = 6). Rate of decline in disposition index (DI), measured with an IVGTT, over 5 years was three times higher in case patients (-341.7 units per year) compared with the extended cohort (-106.7 units per year) and 20 times higher compared with control participants (-15.2 units per year). Case patients had significantly higher annual increases in fasting glucose, hemoglobin A1c (HbA1c), waist circumference, and trunk fat, and there was an inverse correlation between rate of decline in DI and rates of increase in adiposity measures. T2D development in at-risk Latino youth is associated with a substantial and rapid decrease in DI that is directly correlated with increases in fasting glucose, HbA1c, and adiposity.

Article highlights: Youth-onset type 2 diabetes is becoming increasingly prevalent, especially among Latino youth, and there is limited information on its pathophysiology and causative factors. Overall conversion rate to type 2 diabetes over 5 years was 2%. In youth who converted to type 2 diabetes, disposition index decreased rapidly by 85% compared with that in patients who did not convert during the study period. There was an inverse correlation between rate of decline in disposition index and rates of increase in various adiposity measures.

Figure 1

Annual changes in DI (A), fasting glucose (B), fasting insulin (C), and HbA_1c fasting glucose (D) over 5 years in youth who converted to T2D (case patients; n = 6) compared with the extended cohort (n = 256) were examined by testing the interaction between diabetes status and time in the mixed-effects model. Analysis was performed on unadjusted data, as well as with adjustment for age, sex, BMI, and Tanner stage. In addition, adjustment for total fat, intra-abdominal adipose tissue, and other potential covariates was considered to examine whether and how much the differences in changes in insulin resistance, insulin secretion, and DI between diabetes status are mediated by changes in the covariates.

Figure 2

Change in DI over 5 years in youth who converted to T2D (case patients; n = 6) (A) compared with control participants (n = 30) (B) with mixed-effects growth models.

Figure 3

Change in DI over 5 years in youth who converted to T2D (case patients; n = 6) (A) compared with the extended cohort (n = 256) (B) with mixed-effects growth models.

Figure 4

Pearson correlation coefficient was used to evaluate the association between rate of change in DI and rate of change in BMI z score (A), WC (B), total fat mass (C), and intra-abdominal adipose tissue (D) for the entire cohort (n = 262).