We have read with great interest the article recently published by McDonald et al. (1) replicating the initial study of Owen et al. (2), which demonstrated that high-sensitivity C-reactive protein (hs-CRP) levels are lower in hepatocyte nuclear factor 1-α (HNF1A) maturity-onset diabetes of the young (MODY) patients in comparison with other forms of diabetes, including type 2 diabetes. Five years ago, we published that the presence of clinical and metabolic features related to the metabolic syndrome could be of help in discriminating HNF1A-MODY and type 2 diabetes diagnosed in young adults (3). Among them, we included hs-CRP (0.6 ± 0.2 vs. 1.7 ± 0.6 mg/dL, HNF1A-MODY, and type 2 diabetes, respectively; P < 0.001) interpreting that higher levels of hs-CRP in type 2 diabetes reflected the presence of low-grade inflammation associated with metabolic syndrome (4). We now know that we misinterpreted the significance of that observation. The CRP gene has HNF1A binding sites in its promoter, and it is downregulated in liver from mice lacking HNF1A (5), thus the association of hs-CRP levels and HNF1A gene mutations is not unexpected. Unfortunately, we did not measure hs-CRP in a group of subjects with type 1 diabetes or in a control group in order to discriminate between other subtypes of diabetes and normal conditions. It is possible that the combination of lower levels of hs-CRP in subjects with HNF1A-MODY caused by reduced CRP expression and higher levels in type 2 diabetes because of a low-grade inflammation state could contribute to enhance the difference observed in hs-CRP levels between both diseases.
In accordance with the two above-mentioned recent publications (1,2), we now know that lower levels of hs-CRP in HNF1A-MODY may be used as a biomarker to select patients for diagnostic HNF1A genetic testing. Its utilization may be of considerable value in improving diagnosis rates of MODY.
J.B. is the recipient of an “Emili Letang” grant from the Hospital Clínic i Universitari of Barcelona, Barcelona, Spain.
No potential conflicts of interest relevant to this article were reported.