The primary analysis of the DIATOR trial did not find a significant effect of atorvastatin treatment on stimulated C-peptide concentrations at 18 months, although median C-peptide values were around 50% higher in the statin group compared to the placebo group 
. The underlying reason was a large range of C-peptide concentrations among patients at 18 months, varying from 0.1 to 2.3 nmol/l. Because of this apparent heterogeneity we investigated whether baseline patient parameters characterize those with good preservation of beta cell function when treated with atorvastatin from those with less preservation.
There was no association between atorvastatin treatment outcome and age or sex. Of the metabolic parameters analyzed, only liquid-mixed meal stimulated C-peptide levels at baseline was associated with outcome. I.e., patients with above median levels of stimulated C-peptide at baseline exhibited higher stimulated C-peptide levels at 18 months of statin treatment than patients with baseline levels below the median (p<0.031). The same association was observed in the placebo group, suggesting that the association of baseline stimulated C-peptide secretion with C-peptide outcome is independent of atorvastatin treatment. Indeed, it has been reported previously that there is a positive association between the level of C-peptide secretion at diagnosis of type 1 diabetes and residual beta cell function measured in later years 
Two major factors modulated by statin treatment are serum cholesterol and CRP. Both, total serum cholesterol and CRP concentrations were lowered significantly by atorvastatin treatment. Other lipid parameters such as LDL-cholesterol, HDL-cholesterol and triglyceride concentrations were also modulated by atorvastatin as expected 
and therefore were not analyzed separately. However, there was no association between baseline levels of total serum cholesterol and C-peptide outcome, and between the effect of atorvastatin treatment on cholesterol levels and C-peptide outcome.
The positive correlation between baseline CRP concentrations and C-peptide outcome in the patients of the statin group was not seen in those of the placebo group. At baseline, CRP concentrations ranged from 0.08 to 6.34 mg/l in patients of the statin group, and those patients with values above the median of 0.86 mg/l exhibited significantly higher stimulated C-peptide levels at 18 months than those with initially low CRP levels. Interestingly, there was no correlation between the extent of CRP level lowering by atorvastatin and C-peptide outcome. This suggests that increased CRP concentrations at baseline are a marker of responsiveness to atorvastatin treatment, but that the degree of CRP level lowering is not directly involved in the better preservation of beta cell function in response to atorvastatin. Interestingly, an anti-inflammatory CRP-lowering activity of atorvastatin was observed in a study of type 2 diabetes patients only for the subgroup with increased levels of CRP (>2 mg/l) 
Most pharmacological effects of statins are due to inhibiting hydroxyl-3-methylglutaryl-coenzyme A reductase. As a consequence, less mevalonate is available for the synthesis of cholesterol. An impaired mevalonate pathway causes lower production of farnesyl or geranylgeranyl pyrophosphates which can modify several transcription factors controlling cell growth, endothelial activity and immune gene expression 
. At the level of the immune system, statins decreased expression of several pro-inflammatory mediators and receptors 
. This is accompanied by dampening of aggressive Th1-type and promotion of more benign Th2-type T cell responses 
. Another relevant target is the endothelium where atorvastatin suppresses inflammatory reactivity and promotes NO bioavailability 
. It therefore was of interest to compare additional immune characteristics between the subgroup with “high” versus “low” baseline CRP levels. The comparison of serum concentrations of 13 immune mediators indicated significantly higher concentrations of IL-6, IL-1RA, sICAM-1 and E-selectin in the “high” CRP subgroup. For the 10 other pro- or anti-inflammatory immune mediators analyzed, no difference was found between the two subgroups. This indicates that there is no general immune activation in association with increased CRP levels.
Elevated concentrations of IL-6 in the “high” CRP subgroup represent a confirmatory finding because IL-6 is the major internal inductor of CRP production 
and a correlation between systemic CRP and IL-6 levels has been reported previously 
. Increased levels of IL-6, IL-1RA, sICAM-1 and E-selection in the “high” CRP group are reminiscent of subclinical systemic inflammation seen in obesity, metabolic syndrome or type 2 diabetes 
. Hence the “high” CRP subgroup may represent a subgroup among patients with type 1 diabetes which may share some features with type 2 diabetes. Such an interpretation is supported by the observation that patients with “high” CRP levels had a significantly higher BMI and fasting C-peptide concentrations. A positive association of CRP levels with BMI at diagnosis of type 1 diabetes was already noted in a previous study 
In conclusion, a higher than median level of plasma CRP at baseline is associated with better preservation of beta cell function in newly diagnosed patients with type 1 diabetes treated with atorvastatin while such an association is not seen in patients in the placebo group. Further analysis of this putative atorvastatin-response subgroup showed characteristics of systemic subclinical inflammation as seen in type 2 diabetes, increased BMI, higher levels of fasting C-peptide and, besides CRP, higher systemic concentrations of IL-6, IL-1RA, sICAM-1 and E-selectin.