High-sensitivity CRP discriminates HNF1A-MODY from other subtypes of diabetes

OBJECTIVE

Maturity-onset diabetes of the young (MODY) as a result of mutations in hepatocyte nuclear factor 1-α (HNF1A) is often misdiagnosed as type 1 diabetes or type 2 diabetes. Recent work has shown that high-sensitivity C-reactive protein (hs-CRP) levels are lower in HNF1A-MODY than type 1 diabetes, type 2 diabetes, or glucokinase (GCK)-MODY. We aim to replicate these findings in larger numbers and other MODY subtypes.

RESEARCH DESIGN AND METHODS

hs-CRP levels were assessed in 750 patients (220 HNF1A, 245 GCK, 54 HNF4-α [HNF4A], 21 HNF1-β (HNF1B), 53 type 1 diabetes, and 157 type 2 diabetes).

RESULTS

hs-CRP was lower in HNF1A-MODY (median [IQR] 0.3 [0.1–0.6] mg/L) than type 2 diabetes (1.40 [0.60–3.45] mg/L; P < 0.001) and type 1 diabetes (1.10 [0.50–1.85] mg/L; P < 0.001), HNF4A-MODY (1.45 [0.46–2.88] mg/L; P < 0.001), GCK-MODY (0.60 [0.30–1.80] mg/L; P < 0.001), and HNF1B-MODY (0.60 [0.10–2.8] mg/L; P = 0.07). hs-CRP discriminated HNF1A-MODY from type 2 diabetes with hs-CRP <0.75 mg/L showing 79% sensitivity and 70% specificity (receiver operating characteristic area under the curve = 0.84).

CONCLUSIONS

hs-CRP levels are lower in HNF1A-MODY than other forms of diabetes and may be used as a biomarker to select patients for diagnostic HNF1A genetic testing.Maturity-onset diabetes of the young (MODY) is a rare monogenic form of diabetes and is often misdiagnosed as type 1 diabetes or type 2 diabetes (1,2). A correct genetic diagnosis of MODY is important for predicting the clinical course of disease, risk to relatives, and optimizing treatment. Therefore, cheap and novel biomarkers that help identify these patients are desirable.The CRP gene has hepatocyte nuclear factor 1-α (HNF1A) binding sites in its promoter, and common variants in and around HNF1A are associated with circulating high-sensitivity C-reactive protein (hs-CRP) levels (3,4). Recently, Owen et al. (5) demonstrated that hs-CRP levels were reduced in 31 HNF1A-MODY patients compared with type 1 diabetes, type 2 diabetes, glucokinase (GCK) MODY, and normal control subjects, making it potentially a useful clinical test.We aim to replicate this initial study in a larger cohort of patients and assess whether the reduction in hs-CRP is also seen in patients with mutations of other genes encoding hepatic nuclear factors (hepatocyte nuclear factor 4-α [HNF4A] and hepatocyte nuclear factor 4-β [HNF1B]).