A total of 20 subjects with T1D who fulfilled the inclusion criteria were initially recruited after signing the informed consent. However, 8 subjects were excluded, 6 for not achieving the pre-defined target HbA1c at follow-up, and 2 who were lost to follow-up. For the remaining 12 subjects, all were assessed in the outpatient clinic within 7 days after the diagnosis of T1D.
Clinical and conventional lipid profile analysis in subjects with T1D
The clinical characteristics of the study T1D subjects are shown in Table 1. Optimization of glycemic control in subjects with T1D was shown by HbA1c levels of 6.2±0.5%, being the highest HbA1c value at follow-up 6.7%. Body mass index was increased after intensified optimization of glycemic control. Conventional biochemical profiles did not differ among groups, except for plasma glucose and HbA1c. Lipid parameters determined in subjects with onset T1D were within established normal ranges, except for a female with a TG concentration of 239 mg/dL and 2 males with lower baseline HDL-C (32 and 35 mg/dL, respectively) (Additional file 2). Overall, the conventional lipid profile normalized after the intensive management of glycemic control except in one subject who had a mild increase in the concentration of TG (163 mg/dL) (Additional file 2). The only meaningful change in the conventional lipid profile produced by intensively optimized glycemic control was a significant decrease in the LDL-C (-16%; p=0.011) (Table 1). ApoB was consistently lower at follow-up (-21%, p=0.002) in T1D (Additional file 3). Despite this, total cholesterol was just marginally reduced in subjects after achieving optimal glycemic control (p=0.054) compared with baseline concentrations (Table 1). Additionally, serum concentrations of both TG and NEFA did not significantly differ between baseline and follow-up (Table1, Additional file 3).
Of note, HbA1c values showed a close-to-significant trend to be increased (p=0.056) in T1D subjects (6.2%) compared with non-diabetic subjects (5.2%), even with intensified optimization of glycemic control (Additional file 1).
Advanced NMR analysis of the serum lipoprotein profile of subjects with T1D
Advanced 1H-NMR analysis yielded important changes in the lipoprotein profile in T1D subjects after intensive glycemic control (Table 2). Indeed, the serum concentration of non-HDL-P, which is representative of total ApoB-containing lipoproteins, was significantly decreased (-17%, p=0.005), as was the sum of atherogenic particles (-16%, p=0.006) (Additional file 4).
Total serum levels of VLDL-P did not change after glycemic optimization. However, the concentration of medium VLDL-P (representing about 10% of the three VLDL subclasses) was significantly reduced after achieving optimal glycemic control (-39.5%, p=0.033) (Table 3). This finding was accompanied by a concomitant decrease in the serum levels of total VLDL-TG and VLDL-C (-22%, p=0.021 and -23%, p=0.045, respectively) and in the IDL-C (-46%, p<0.001) and IDL-TG concentrations (-30%, p<0.001) (Table 2). Of note, the ratio IDL-C/IDL-TG was 23% lower in T1D subjects after glycemic control optimization (Additional file 5). Taken together, total circulating atherogenic remnants, which may be inferred by the sum of both VLDL and IDL classes, were favorably influenced (-35%, p=0.002) by optimization of glycemic control (Additional file 4).
Consistent with data from the conventional lipid profile (Table 1), serum concentrations of LDL-C were significantly lower (-16%, p=0.011) at follow-up (Table 2). In line with this, the serum concentration of atherogenic cholesterol was concomitantly lower (-19%, p=0.002) (Additional file 4). Similar results were found for serum LDL-TG levels at follow-up compared to the baseline (-36%, p<0.001) (Table 2). At follow-up, favorable reductions in circulating LDL lipids were further accompanied by concomitant decreases in the total LDL-P (-16%, p=0.007) which were mainly accounted for by a reduction in large- and medium-sized LDL-P subclasses concentrations (-12.9%, p=0.036 and -34%, p=0.007, respectively) (Table 3).
Regarding HDL, serum levels of HDL-TG were significantly decreased in T1D subjects (-18%, p=0.045) after reaching optimal glycemic control, but did not significantly influence serum concentrations of HDL-C (Table 2). In line with this, the HDL-TG-to-HDL-P ratio was concomitantly decreased after optimization (-39%, p=0.003) whereas that of HDL-C-to-HDL-TG increased compared with baseline values (Additional file 5).
Improved serum lipoprotein ratios calculated at follow-up in T1D subjects were mainly attributed to favorable reductions in the non-HDL component (LDL-P-to-HDL-P ratio: 0.82-fold, p=0.004; atherogenic particles (VLDL-P + LDL-P)-to-HDL-P ratio: 0.81-fold, p=0.004; atherogenic cholesterol-to-HDL-C ratio: 0.77-fold, p=0.002) (Additional file 4). Additionally, the ratio IDL-C-to-IDL-TG was significantly decreased in T1D subjects after intensive therapy (-23%, p=0.001) (Additional file 5).
Correlation between the changes produced after optimization of glycemic control on changes in serum lipid profile with anthropometric and clinical variables in subjects with T1D
Favorable changes of most VLDL characteristics, including concentrations and composition of circulating VLDL subclasses, were positively associated with improved HbA1c values (Additional file 6). Though moderately, the IDL lipids and circulating remnants (non-HDL-P) were also associated with favorable changes in HbA1c. Interestingly, large-sized (buoyant) LDL-P was inversely associated with leukocyte counts, a surrogate of inflammation. No additional significant relationships among lipoprotein characteristics and clinical or biochemical variables were seen, except for those between the HDL-C-to-HDL-TG ratio and liver gamma-glutamyl transferase.
Forest plot
This analysis showed changes in advanced lipoprotein characteristics during glycemic control in subjects with T1D (Additional file 7). Interestingly, the effect size of intensified glycemic control optimization was significantly larger in LDL and IDL than that observed in the VLDL.