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Integration of the peaks corresponding to each injection and correction for the baseline were done using Origin-based software provided by the manufacturer.
Correlations between the biomarkers and known microvascular predictors (AER, triglycerides, HbA1c percentage, serum creatinine, HDL-C, LDL-cholesterol [LDL-C], age ate) at DCCT baseline were done using Spearman correlation coefficients.
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The assessment of functional mobility at baseline was done using the "Timed Up & Go" (TUG) test [ 11].
Recruitment at baseline was done using random digit dialling [ 13], selecting a single person over 17 years old in each of the identified households.
Comparison between the groups at baseline was done using Student's t-test and between baseline and phases 1 and 2 were done by repeated-measures analysis of variance in both the groups.
Baseline comparisons were done using univariate analyses of variance for continuous variables.
Cross-sectional analyses of MRI measures were done using baseline measurements.
Comparisons between baseline and follow up scores were done using paired t-test for continuous scores (WHOQOL-BREF and Health and Well-being Questionnande) and McNamara Chi-square test for categorical variables (GHQ12).
Comparisons of the baseline characteristics among DM/CHD groups were done using ANOVA or χ2 test and we used t-test or χ2 test to compare any group with the DM-/CHD+ group considering Bonferroni correction for multiple comparisons.
The baseline correction was done using a calibrated sample of barium sulfate as reference.
A baseline spirometry was done using portable spirometer (Superspiro MK2 Micro Medical Ltd, UK).
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