Using Clinical Indices to Distinguish MODY2 (GCK Mutation) and MODY3 (HNF1A Mutation) from Type 1 Diabetes in a Young Chinese Population

Abstract

Introduction Accurate diagnosis of maturity-onset diabetes of the young (MODY) is required in order to select appropriate treatment options and to assess prognosis. The aim of this study was to explore potential clinical indicators that could be used to differentiate MODY2, MODY3, and type 1 diabetes (T1D) in young subjects. Methods Twelve patients with MODY3 and 29 patients with MODY2 were characterized and compared to 26 patients with T1D. These three groups were matched for age and gender. Clinical profiles of the 67 patients were collected. Receiver operating characteristic (ROC) curves were used to identify the optimal cutoff values of clinical indicators. Results Compared to patients with T1D, subjects with MODY3 had higher fasting C-peptide levels (1.34 ± 1.51 vs. 0.29 ± 0.22 ng/mL; P < 0.001) and lower high-sensitivity C-reactive protein (hsCRP) levels (0.18 ± 0.15 vs. 1.22 ± 1.49 mg/L, P = 0.004); patients with MODY2 had lower hsCRP (0.37 ± 0.39 vs. 1.22 ± 1.49 mg/L; P = 0.003), total cholesterol (4.12 ± 0.68 vs. 4.61 ± 0.81 mmol/L, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) (2.24 ± 0.68 vs. 2.67 ± 0.79 ng/L, P = 0.002) levels and higher fasting C-peptide levels (0.96 ± 0.42 vs. 0.29 ± 0.22 ng/mL, P = 0.002). The ROC-derived hsCRP values for discriminating MODY2 from T1D, MODY3 from T1D, and MODY3 from MODY2 were 0.675, 0.833, and 0.763, respectively. The ROC-derived fasting C-peptide levels for discriminating MODY2 from T1D and MODY3 from T1D were 0.951 and 0.975, respectively. The ROC-derived total cholesterol and LDL-C values for discriminating MODY2 from T1D were 0.670 and 0.662, respectively; the ROC-derived triglyceride value for discriminating MODY3 from MODY2 was 0.756. Additionally, a combination of indicators permitted better discrimination of MODY subtypes than any single parameter. Conclusion Our findings suggest that fasting C-peptide, hsCRP, and lipid levels permit good discrimination among MODY2, MODY3, and T1D. These clinical indicators could be used as markers of MODY2 and MODY3 in young patients with diabetes. Electronic Supplementary Material The online version of this article (10.1007/s13300-019-0647-x) contains supplementary material, which is available to authorized users.

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

“…Even though patients with MODY were found to differ from T1DM patients in several clinical predictors, such as C-peptide concentration [ 114 ], hsCRP [ 115 , 116 , 117 ], lipid levels, polyuria or age at diagnosis, still around 38% of the MODY patients are misdiagnosed with T1DM or T2DM [ 27 , 87 , 118 , 119 , 120 ]. In 2013 Steele et al reported that age-related glycated haemoglobin (HbA1c) reference ranges can be used as diagnostic criteria for GCK-MODY discriminator [ 121 ].…”

Localized increases in CEPT1 and ATGL elevate plasmalogen phosphatidylcholines in HDLs contributing to atheroprotective lipid profiles in hyperglycemic GCK-MODY

“…In particular, GCK-MODY is characterized by strongly cardioprotective lipid profiles of high-density lipoproteins (HDLs) subpopulations, with significantly elevated levels of large HDLs and lower levels of intermediate and small (potentially atherogenic) HDLs compared to controls [ 15 ]. Our previous work also shown GCK-MODY exhibited lower total cholesterol (TC) and low-density lipoprotein cholesterol compared to T1D [ 16 ]. A lipid-centric investigation of serum metabolic alterations accompanying perturbed glucose homeostasis in GCK-MODY, in comparison to type 2 diabetes, may thus reveal new therapeutic targets of vascular protection under concurrent hyperglycemia.…”

Detection and analysis of glucose metabolism‑related genes in childhood diabetes using targeted next‑generation sequencing: In pediatric population‑a hospital‑based study

“…Of which 32 cases with autoantibody-negative diabetes (male, 16 cases; female, 16 cases) were screened for ICA, GAD antibody (GADA), IA-2 and ZnT8 at diagnosis. Having at least one positive antibody and a fasting C peptide of ≥0.3 ng/ml at initial diagnosis was considered positive autoimmunity (8)(9)(10). Peripheral blood DNA was extracted from the 32 patients with autoantibody-negative diabetes and their parents for high-throughput sequencing of glucose metabolism-related genes.…”