Table 5 Biomarkers studied as screening criteria for most common forms of MODY and their limitations for widespread clinical use
From: Update on clinical screening of maturity-onset diabetes of the young (MODY)
Biomarker | Rationale | Comments | Limitations | References |
|---|---|---|---|---|
High-sensitivity C-reactive protein (hsCRP) | Presence of HNF1A binding sites in the CRP gene promoter | hsCRP levels are lower in patients with HNF1A mutations | Intercurrent infection can elevate hsCRP level Inter-method and inter-laboratory variability | [78] |
C-peptide | Marker for endogenous insulin secretion Majority of patients with type 1 diabetes are severely insulin deficient within 2–3 years of diagnosis C-peptide persists in MODY. | Urinary C-peptide/creatinine ratio (UCPCR) and fasting C-peptide levels can distinguish patients with MODY from patients with T1DM Finding a UCPCR of ≥ 0.22 nmol/mmol suggests that a genetic test might be appropriate | C-peptide decline is highly variable between individuals Even after 5 years of diagnosis of type 1 diabetes, some patients have detectable C-peptide | [88] |
Apolipoprotein-M (ApoM) | Promoter region of ApoM contains a binding site for HNF1A ApoM is strongly transactivated by HNF1A in vitro Decreased HNF1A activity in humans leads to low plasma ApoM levels | No significant difference in ApoM concentration between HNF1A patients and type 2 diabetes patients was observed ApoM concentrations are lower in subjects with HNF1A-MODY than in those with Type 1 diabetes | Differences in methodology Limited availability of ApoM assay Low accuracy in the diagnosis of MODY | |
Cystatin-C | Cystatin-C is a marker of glomerular filtration rate (GFR) Levels are influenced by CRP, whose concentration is decreased in HNF1A-MODY | There are no differences in Cystatin-C between HNF1A-MODY and the other subgroups of diabetes, except HNF1B-MODY | Differences between Cystatin-C assays The hypothesis that Cystatin-C level is altered by HNF1A mutations was not confirmed | [121] |
Complement factors 5 (C5) and 8 (C8) | Transcription of genes C5 and C8 is regulated by transcription factors HNF1A and HNF4A | HNF4A- and HNF1A-MODY patients have reduced levels of C5 and C8 compared with type 2 diabetic patients | Inflammatory states are associated with increased expression of complement factors | [74] |
Transthyretin (TTR) | Transcription of the genes encoding TTR are regulated by HNF1A and HNF4A | Patients with HNF4A-MODY, but not those with HNF1A mutations, had decreased TTR compared with other types of diabetes | The effects of mutations on TTR is too modest to be detected by measuring TTR concentrations in serum | [74] |
1,5-anhydroglucitol (1,5-AG) | A low renal threshold for glucose results in lower serum 1,5-AG levels HNF1A mutations are characterized by low renal glucose threshold due to decreased expression of the high-affinity low-capacity sodium/glucose cotransporter 2 (SGLT2) | Plasma concentrations of 1,5-AG are lower in HNF1A-MODY compared with those in other types of diabetes at a similar HbA1c | Limited usefulness in pregnant women and patients with end-stage renal disease 1,5-AG is not a specific biomarker for patients with A1C > 9.0% Further investigation required in larger sets of patients and other subgroups of diabetes |