Plasma total homocysteine and carotid intima-media thickness in type 1 diabetes: A prospective study

- Plasma total homocysteine (tHcy) measured in 599 participants with type 1 diabetes.
- tHcy positively correlated with carotid IMT in cross-sectional analyses.
- tHcy correlated with age, diastolic blood pressure, renal dysfunction and smoking.
- tHcy not correlated with 6-year IMT progression after adjustment for CVD risk factors.

ObjectivePlasma total homocysteine (tHcy) has been positively associated with carotid intima-media thickness (IMT) in non-diabetic populations and in a few cross-sectional studies of diabetic patients. We investigated cross-sectional and prospective associations of a single measure of tHcy with common and internal carotid IMT over a 6-year period in type 1 diabetes.Research design and methodstHcy levels were measured once, in plasma obtained in 1997-1999 from patients (n = 599) in the Epidemiology of Diabetes Interventions and Complications (EDIC) study, the observational follow-up of the Diabetes Control and Complications Trial (DCCT). Common and internal carotid IMT were determined twice, in EDIC “Year 6” (1998-2000) and “Year 12” (2004-2006), using B-mode ultra-sonography.ResultsAfter adjustment, plasma tHcy [median (interquartile range): 6.2 (5.1, 7.5) μmol/L] was significantly correlated with age, diastolic blood pressure, renal dysfunction, and smoking (all p < 0.05). In an unadjusted model only, increasing quartiles of tHcy correlated with common and internal carotid IMT, again at both EDIC time-points (p < 0.01). However, multivariate logistic regression revealed no significant associations between increasing quartiles of tHcy and the 6-year change in common and internal carotid IMT (highest vs. lowest quintile) when adjusted for conventional risk factors.ConclusionsIn a type 1 diabetes cohort from the EDIC study, plasma tHcy measured in samples drawn in 1997-1999 was associated with measures of common and internal carotid IMT measured both one and seven years later, but not with IMT progression between the two time-points. The data do not support routine measurement of tHcy in people with Type 1 diabetes.

In a subset of 599 Type 1 diabetic patients from the DCCT/EDIC cohort, common (A) and internal (B) carotid intima-media thickness (IMT, medians and interquartile ranges), measured twice at EDIC 'Year 6' (1998-2000) and Year 12 (2004-2006), were related to quartiles of plasma total homocysteine (tHcy) measured in samples obtained in 1997-99. Quartile ranges for tHcy (μmol/L) were: Q1: 2.7-5.05; Q2: 5.06-6.15; Q3: 6.16-7.46; Q4: >7.46. Both common and internal carotid IMT increased significantly across tHcy quartiles at both time points (p < 0.001), and tHcy correlated significantly with age, diastolic blood pressure, renal function and smoking (p < 0.05). However, tHcy was not associated with the extent of progression of common or internal IMT between the two EDIC time points, and patients with 'high' values (>10 μmol/L) did not have significantly greater IMT or IMT progression. The current data do not support the utility of routine measurement of tHcy in people with T1DM, but future studies will relate tHcy to actual cardiovascular events.91