A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

Thanabalasingham, G; Shah, Nilpa; Vaxillaire, Martine; Hansen, Torben; Tuomi, Tiinamaija; Gašperíková, Daniela; Szopa, Magdalena; Tjora, Erling; James, Timothy; Kokko, Petra; Loiseleur, F.; Andersson, Ehm A.; Gaget, Stefan; Isomaa, Bo; Nowak, Natalia; Ræder, Helge; Staník, Juraj; Njølstad, Pål R.; Małecki, Maciej; Klimeš, I; Groop, Leif; Pedersen, Oluf; Froguel, Philippe; McCarthy, Mark I.; Gloyn, Anna L.; Owen, Katharine R.

doi:10.1007/s00125-011-2261-y

Cited by 103 publications

(86 citation statements)

References 28 publications

(40 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This occurred in spite of a more favorable lipid profile and lower CRP levels in these patients. This seemingly antiatherogenic lipid profile and low CRP level in HNF1A mutation carriers have been described earlier (18,19). The antiatherogenic profile of HNF1-MODY seems to be also associated with low sCD36, the scavenger protein that was shown to play a substantial role in the pathogenesis of atherosclerosis (20).…”

Section: Discussionsupporting

confidence: 56%

Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients

Szopa

Osmenda

Wilk

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

Objective: Mutations in the glucokinase (GCK) gene, along with hepatocyte nuclear factor 1A (HNF1A) gene mutations, are the most frequent cause of maturity-onset diabetes of the young (MODY). GCK-MODY patients are typically characterized by a moderate fasting hyperglycemia; however, little is known about atherosclerosis and intermediate-related phenotypes in these subjects. Design: To examine carotid artery intima-media thickness (IMT) and endothelial function assessed by brachial artery flow-mediated dilatation (FMD) in GCK gene mutations carriers and HNF1A-MODY. Methods: A total of 64 subjects with GCK gene mutations, and 52 HNF1A gene mutation carriers as well as 53 nondiabetic controls were examined. IMT and FMD were assessed by ultrasonography. Appropriate statistical tests were performed to assess differences between the groups, and multivariate linear regression was done for the association with IMT and FMD. Results: The clinical characteristics of all groups were similar with the mean age at examination of 35.1, 41.1, and 39.5 years for GCK, HNF1A and the control group respectively. The highest mean IMT value was in the HNF1A-MODY group: 7.0G1.4 mm, whereas it reached 6.3G1.4 mm in GCK mutation carriers and 6.3G1.3 mm in controls (PZ0.008). After adjustment for possible clinical and biochemical cofounders, IMT remained higher in HNF1A-MODY patients as compared with GCK-MODY patients (PZ0.02) and controls (PZ0.0003). FMD was significantly lower in HNF1A (9.9G4.6%) and GCK-MODY (11.1G4.6%) patients in comparison with controls (13.9G4.7%; PZ0.0001). After adjustment, FMD remained lower in HNF1A-MODY (PZ0.0005) and GCK-MODY patients (PZ0.01) as compared with controls. Conclusions: Both examined MODY groups demonstrated evidence of endothelial dysfunction. In addition, HNF1-MODY patients seem to be more prone to an early atherosclerotic phenotype.

show abstract

Section: Discussionsupporting

confidence: 56%

Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients

Szopa

Osmenda

Wilk

et al. 2015

European Journal of Endocrinology

View full text Add to dashboard Cite

show abstract

“…Recently, a new biomarker for HNF1A, high-sensitivity Creactive protein, has been reported [15,27]. Presently, this biomarker is not in routine use in our registry.…”

Section: Discussionmentioning

confidence: 98%

“…Studies indicate that lower levels of the biomarker high-sensitivity C-reactive protein (hs-CRP) can predict HNF1A-MODY patients for diagnostic genetic testing [15].…”

Section: Introductionmentioning

confidence: 99%

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry

et al. 2016

View full text Add to dashboard Cite

Aims/hypothesis MODY can be wrongly diagnosed as type 1 diabetes in children. We aimed to find the prevalence of MODY in a nationwide population-based registry of childhood diabetes. Methods Using next-generation sequencing, we screened the HNF1A, HNF4A, HNF1B, GCK and INS genes in all 469 children (12.1%) negative for both GAD and IA-2 autoantibodies and 469 antibody-positive matched controls selected from the Norwegian Childhood Diabetes Registry (3882 children). Variants were classified using clinical diagnostic criteria for pathogenicity ranging from class 1 (neutral) to class 5 (pathogenic). Results We identified 58 rare exonic and splice variants in cases and controls. Among antibody-negative patients, 6.5% had genetic variants of classes 3-5 (vs 2.4% in controls; p = 0.002). For the stricter classification (classes 4 and 5), the corresponding number was 4.1% (vs 0.2% in controls; p = 1.6 × 10 −5 ). HNF1A showed the strongest enrichment of class 3-5 variants, with 3.9% among antibody-negative patients (vs 0.4% in controls; p = 0.0002). Antibody-negative carriers of variants in class 3 had a similar phenotype to those carrying variants in classes 4 and 5. Conclusions/interpretation This is the first study screening for MODY in all antibody-negative children in a nationwide population-based registry. Our results suggest that the prevalence of MODY in antibody-negative childhood diabetes may reach 6.5%. One-third of these MODY cases had not been recognised by clinicians. Since a precise diagnosis is important Henrik U. Irgens, Janne Molnes and Paweł Sztromwasser contributed equally to the study. Stefan Johansson and Pål R. Njølstad share joint senior authorship.Electronic supplementary material The online version of this article

show abstract

“…We tested this theory initially in a small number of local patients with MODY 11 and then the results were replicated in two large European studies, 12,13 including nearly 700 cases of HNF1A-MODY. The results showed that levels of hsCRP were significantly lower in those with HNF1A mutations compared with those with all other forms of diabetes and also compared with those without diabetes.…”

Section: C-reactive Protein and Hnf1a-modymentioning

confidence: 99%

Monogenic diabetes: old and new approaches to diagnosis

Owen

2013

Clinical Medicine

View full text Add to dashboard Cite

-Up to 5% of young adults diagnosed with diabetes have a monogenic aetiology, the most common of which is maturity-onset diabetes of the young (MODY). A definitive molecular diagnosis is important, as this affects treatment, prognosis and family screening. Currently, however, rates of diagnosis are low due to a combination of lack of awareness of the benefits of making the diagnosis and the challenges of differentiating patients with MODY from those with common forms of diabetes. This article aims to introduce general physicians to the characteristics of monogenic diabetes and the clinical features that can be used to diagnose patients. Recently, genomewide association studies have resulted in the identification of C-reactive protein and glycan profile as specific biomarkers for the most common MODY subtype due to HNF1A mutations, and the potential translation of these findings are discussed.KEY WORDS: Aetiology of diabetes, glycolytic enzyme glucokinase (GCK), HNF1A, maturity-onset diabetes of the young (MODY), monogenic diabetes

show abstract

A large multi-centre European study validates high-sensitivity C-reactive protein (hsCRP) as a clinical biomarker for the diagnosis of diabetes subtypes

Cited by 103 publications

References 28 publications

Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients

Intima-media thickness and endothelial dysfunction in GCK and HNF1A-MODY patients

Targeted next-generation sequencing reveals MODY in up to 6.5% of antibody-negative diabetes cases listed in the Norwegian Childhood Diabetes Registry

Monogenic diabetes: old and new approaches to diagnosis

Contact Info

Product

Resources

About