👤 Tina Costacou

We aimed to identify long-term HbA1c trajectories and examine associated characteristics in an observational, childhood-onset (<17 years) type 1 diabetes cohort. Data are from the Epidemiology of Diabetes Complications study, comprising 405 participants with ≥2 of seven possible HbA1c measurements over follow-up (1988-2013) and available DNA (baseline mean diabetes duration 21 years, 53% men). HbA1c trajectories were estimated using latent class growth models. Baseline and change in participant characteristics were compared across trajectories. Five HbA1c trajectories were identified: low (51%), intermediate stable (22%), improved (19%), high stable (6%), and worsened (2%; not included in analyses). Age, diabetes duration, diabetes onset age, and sex did not differ across trajectories. Characteristics did not differ significantly between intermediate stable and low trajectories at baseline, though albumin excretion rate (AER, p = 0.0002) and estimated glomerular filtration rate (eGFR, p = 0.001) worsened slightly more in intermediate stable over time. Improved and high stable trajectories had higher baseline LDL-c (p = 0.002 and 0.003, respectively). Improved trajectory increased median self-monitoring of blood glucose from <1 to 3.5 times/day (p < 0.0001) and had larger LDL-c improvement (p = 0.004) but greater worsening of AER (p < 0.0001) and eGFR (p < 0.0001) than low. The A allele of rs12970134 (near MC4R) was associated with improved (p = 0.0003) or high stable (p = 0.001) HbA1c trajectory, both patterns with high baseline HbA1c. Long-term HbA1c trajectories were primarily associated with modifiable factors in this type 1 diabetes cohort. The intermediate stable pattern had a risk factor profile that suggests some protection against adverse metabolic effects of chronic hyperglycaemia, warranting further study. Show less

To examine candidate insulin resistance single nucleotide polymorphisms (SNPs) for associations with glycemic control, insulin resistance, BMI, and complications in an observational type 1 diabetes (T1D) cohort: the Pittsburgh Epidemiology of Diabetes Complications (EDC) study. In 422 European-ancestry participants, we assessed associations using additive models between 15 candidate SNPs and 25-year mortality, cardiovascular disease, microalbuminuria, overt nephropathy and proliferative retinopathy, and 25-year mean HbA1c, estimated glucose disposal rate (eGDR, inverse measure of insulin resistance), and BMI. The A allele of rs12970134 was associated with higher mean HbA1c (β = +0.34 ± 0.09, p = 0.00009) and nominally associated with worse eGDR (p = 0.02). Further analyses suggest the HbA1c association may be modified by diabetes therapy regimen: rs12970134 AA genotype was associated with higher HbA1c under non-intensive therapy conditions (<3 insulin injections/day or monitoring blood glucose<3 times/day [p = 0.004]), but not under intensive therapy (≥3 injections/day or insulin pump and monitoring glucose≥3 times/day [p = 0.71]). There were no significant associations between any SNPs and BMI or complications. rs12970134, near MC4R, is strongly associated with HbA1c in this cohort. Further exploration of this genomic region is warranted, as it may hold promise for discovering new therapeutic targets to improve glycemic control in T1D. Show less