Abstract
Aims: While cytokines play a role in the etiology of type 1 diabetes, cytokines later in
the disease are less understood. We therefore investigated associations of pro-inflammatory
tumor necrosis factor-α levels measured at prolonged disease duration with C-peptide
at diagnosis, long-term glycemic control, diabetes duration, clinical factors, and
health behaviors.
Methods: Data and blood were collected during an ancillary study to the longitudinal Wisconsin
Diabetes Registry, a population-based cohort followed since diagnosis of type 1 diabetes.
The ancillary study was conducted at 13–18 years diabetes duration, and enrolled premenopausal
women age 18–45 years (n=87).
Results: Higher tumor necrosis factor-α levels at 13–18 years diabetes duration were independently
associated with longer duration (p=0.0004) and worse current renal function (p=0.02).
Additionally, diabetes duration modified both of the positive associations of tumor
necrosis factor-α levels (both interactions p≤0.01) with mean glycemic control during
the previous 10 years (significant only in women with longer durations) and current
daily caffeine intake (significant only in women with shorter durations). In women
with C-peptide measured at diagnosis (n=50), higher tumor necrosis factor-α levels
at 13–18 years duration were associated with lower C-peptide (p=0.01), independent
of glycemic control during the previous 10 years.
Conclusions: Lower residual C-peptide at diagnosis and poor long-term glycemic control independently
predicted higher pro-inflammatory tumor necrosis factor-α levels years later. The
novel relationship with C-peptide needs confirmation in a larger cohort. Given the
association between tumor necrosis factor-α and diabetes complications, further longitudinal
studies may help clarify the potentially complex associations between glycemic control,
inflammatory cytokines, and complications.
Key words
diabetes type 1 - C-peptide - TNF-α - young women
