Distinguishing the lipid profile of GCK-MODY patients and its correlation with hsCRP levels

Abstract

Aims: Glucokinase-maturity-onset diabetes of the young (GCK-MODY) is the most common monogenic diabetes in China. We have previously reported on the low levels of high-sensitivity C-reactive protein (hsCRP) in patients with GCK-MODY. In this study, we further explored the correlation between the serum lipid profiles and hsCRP levels of patients with different types of diabetes. We also proposed to determine the possible mechanism of macrovascular protection in GCK genetic variants.

Methods: The serum lipid profiles of the GCK-MODY group (n = 50) were compared with those of the hepatocyte nuclear factor-1 alpha (HNF1A)-MODY group (n = 19), the type 1 diabetes (T1D) group (n = 50), and the type 2 diabetes (T2D) group (n = 54). The associations between the lipid compositions and the hsCRP levels in each group were also explored.

Results: Elevated levels of high-density lipoprotein cholesterol (HDL-C) were found in the GCK-MODY group (1.5 ± 0.27) compared with the T1D (1.2 ± 0.47, p < 0.01) and T2D (1.3 ± 0.3, p < 0.01) groups. On the other hand, a significantly lower LDL-C level (2.4 ± 0.69) in the GCK-MODY group compared with the T1D (2.7 ± 0.72, p < 0.01) and T2D (2.9 ± 0.68, p < 0.01) groups was also noted. A lower ratio of triglyceride to HDL-C (TG/HDL) and a lower hsCRP level were also found in the GCK-MODY group [TG/HDL = 0.38 (0.25-0.52), hsCRP = 0.2 mg/L (0.16-0.37)] compared with the T1D group [(TG/HDL = 0.56 (0.39-1.29), hsCRP = 0.56 mg/L (0.39-1.29), p < 0.01] and the T2D group [(TG/HDL = 1.6 (1.1-2.68), hsCRP = 1.11 mg/L (0.66-2.34), p < 0.01]. Although patients with HNF1A-MODY showed similar hsCRP levels [0.17 (0.08-0.52), p > 0.05] compared with the patients in the GCK-MODY group, they had higher TG levels [1.01 (0.66-1.76), p < 0.05] and TG/HDL ratios [0.84 (0.56-1.31), p < 0.05]. Analysis of the correlations between the hsCRP levels and lipid profiles of each group confirmed that the LnhsCRP (natural logarithm-transformed hsCRP level) was positively correlated with the LnTG (natural logarithm-transformed TG) (r = 0.352, p = 0.011) and the Ln(TG/HDL) ratio (r = 0.283, p = 0.047) only in individuals with GCK-MODY.

Conclusions: Individuals harboring GCK variants have the characteristics of protective lipid profiles manifested as a higher level of HDL-C and a lower level of LDL-C compared with type 1 and 2 diabetes milletus (T1DM and T2DM, respectively) patients. In addition, lower ratios of TG/HDL were found to be associated with the inhibition of secretion of hsCRP, even when adjusted for the HbA1c levels in patients with GCK-MODY. It is suggested that the protective effect of macrovascular complications in GCK-MODY patients might partly be due to their unique lipid profiles associated with the suppression of inflammation.

Keywords: cardiovascular protection; glucokinase; high-sensitivity C-reactive protein; maturity-onset diabetes of the young; serum lipid profile.