Association Between Elevated Serum C-Reactive Protein and Triglyceride Levels in Young Subjects With Type 1 Diabetes

This sectional study included 45 consecutive young patients (26 boys) who fulfilled the inclusion criteria (diagnosed as type 1 diabetic, followed up at a public health assistance center, serum creatinine level <1.3 mg/dl, and normal thyroid-stimulating hormone values) and 30 healthy subjects (12 boys) matched by age (±3 years) and BMI. Exclusion criteria were hypertension, overweight or obesity, smoking, any infection having been diagnosed during the previous 3 months, and treatment for inflammatory or chronic infectious disease.

Measurements of pulse rate, blood pressure, height and weight, and specific clinical examination of throat, eyes, nose, ears, skin, and feet were performed. Laboratory data included fasting blood glucose, HbA_1c (A1C), total cholesterol, HDL and LDL cholesterol, triglycerides, serum creatinine, thyroid-stimulating hormone, and hs-CRP. Hs-CRP was determined by nephelometry.

Differences in the means were evaluated by the Student’s t test. The hs-CRP data were analyzed by the Mann-Whitney nonparametric test. Spearman’s correlation test was used when indicated. A P value <0.05 defined statistical significance.

The mean ages were 14.1 ± 4.6 years (95% CI 3–23) for the type 1 diabetic patients and 14.6 ± 3.9 years (6–22) for healthy subjects (P = 0.6). BMI was similar in the two groups (19.1 ± 2.6 vs. 19.6 ± 0.8 kg/m², P = 0.4). No differences were observed for systolic or diastolic blood pressure (106.3 ± 14.0 vs. 103.3 ± 11.3 mmHg, P = 0.3, and 66.6 ± 7.5 vs. 65.6 ± 7.6 mmHg, P = 0.4, respectively). Total cholesterol values were higher in diabetic patients than control subjects (173.7 ± 40.6 vs. 148.8 ± 32.6 mg/dl, P = 0.006); the other lipid variables were similar in the two groups. In the type 1 diabetic patients, age at diagnosis was 8.9 ± 4.9 years (0.5–18), and the duration of disease was 5.6 ± 4.1 years (0.9–17). Mean fasting blood glucose was 217.2 ± 127.7 mg/dl, and A1C was 10.2 ± 2.7%. None of the type 1 diabetic children were taking regular medications other than daily insulin. Microalbuminuria was positive in 10 of 35 patients (28.6%).

Type 1 diabetic patients had higher mean (1.7 ± 2.2 vs. 1.0 ± 1.6 mg/l, P = 0.012) and median (0.67 vs. 0.28 mg/l, P = 0.016) serum concentrations of hs-CRP than control subjects. In the diabetic patients, hs-CRP levels were positively correlated with triglycerides (r = 0.32, P = 0.03) and with the triglyceride-to-HDL ratio (r = 0.33, P = 0.03) (Fig. 1) but not with glycemic control, other lipid variables, or microalbuminuria. A positive correlation was also observed between hs-CRP and disease duration (r = 0.32, P = 0.028).

The present study compared young type 1 diabetic patients with nondiabetic control subjects, and it was shown that hs-CRP was higher in this diabetic population. In adult patients, hs-CRP did not show any significant difference between the diabetic and control subjects (9). In another study, type 1 diabetic patients had significantly higher hs-CRP levels than nondiabetic individuals, and this was correlated with the intima-media thickness of the carotid artery (7). It is interesting to note that in the present study, the diabetic group was younger than the groups in other studies (7,9,10) and had shorter disease duration. Furthermore, the positive correlation between hs-CRP levels and diabetes duration strongly suggests that information on inflammatory state, even in young diabetic patients with short disease duration, can be of clinical relevance because atherosclerosis and vascular damage begins in childhood (11).

In accordance with others (10), the present study demonstrated that hs-CRP levels were positively correlated with triglycerides and triglyceride-to-HDL ratio but not with the other lipid variables. These results are consistent with data in nondiabetic subjects (12,13) and in type 2 diabetic patients (14). The association between triglyceride-to-HDL ratio and hs-CRP level suggests that this unfavorable lipid profile may facilitate the formation of foam cells in the arterial wall, increasing the inflammatory activity in young type 1 diabetic subjects. Despite their size, triglyceride-rich remnants of VLDL and chylomicron metabolism are capable of penetrating the artery wall and the subintimal space, where they are ingested by macrophages and become proatherogenic foam cells (15). As the mass of circulating triglyceride rises, the average LDL and particle size is reduced (16), and these LDL particles would appear to be more susceptible to oxidation, a process that increases their atherogenicity. Available evidence also indicates that as triglyceride levels rise, the clearance rates of the major HDL proteins apoAI and apoAII are enhanced (17). This results in the generation of smaller and denser HDL, which is less capable of participating in the process of reverse cholesterol transport and is consequently less protective (18,19). Despite these plausible biological explanations, the association between lipid variables and CRP is not completely established, even in adult patients (20).

As in other studies (21), we found no correlation between hs-CRP and glycemic control. In addition, a recent study (22) failed to show a decrease in hs-CRP levels after intensive glycemic control in type 1 diabetic patients; in contrast, it showed increased concentrations of hs-CRP and tumor necrosis factor receptor 1 among those who gained weight. Indeed, the expression of hs-CRP as a marker of inflammatory activity is very complex and cannot only be explained by the hyperglycemic condition (10).

Somewhat unexpectedly, hs-CRP was not associated with microalbuminuria, an early marker of endothelial dysfunction, even in type 1 diabetes of short duration (23). The low frequency of individuals with positive microalbuminuria in this study and the skewed distribution of hs-CRP may explain this finding.

In conclusion, the present study has shown that hs-CRP levels are increased in very young type 1 diabetic patients, even with a relatively short disease duration. Plasma hs-CRP was correlated with triglycerides and triglyceride-to-HDL ratio, suggesting that strategies to decrease inflammatory activity should focus on the lipid profile as well. Moreover, the association of this inflammatory marker with lipid variables indicates an important linkage between type 1 diabetes and the risk of developing atherosclerosis.

E.S. was supported by the Research Foundation of Bahia (FAPESB), Bahia, Brazil.