Abstract
Abstract
Aim
Cerebral small-vessel disease (SVD) is prevalent in type 1 diabetes and has been associated with the haptoglobin variant allele Hp1. Contrarily, the Hp2-allele has been linked to cardiovascular disease and the role of haptoglobin-genotype in asymptomatic SVD is unknown. We, therefore, aimed to evaluate the alleles’ association with SVD.
Methods
This cross-sectional study included 179 neurologically asymptomatic adults with type 1 diabetes (women 53%, mean age 39 ± 7 years, diabetes duration 23 ± 10 years, HbA1c 8.1 ± 3.2% [65 ± 12 mmol/mol]). Examinations included genotyping (genotypes Hp1-1, Hp2-1, Hp2-2) by polymerase chain reaction, clinical investigation, and magnetic resonance brain images assessed for SVD manifestations (white matter hyperintensities, cerebral microbleeds, and lacunar infarcts).
Results
SVD prevalence was 34.6%. Haptoglobin genotype frequencies were 15.6% (Hp1-1), 43.6% (Hp1-2), and 40.8% (Hp2-2). Only diastolic blood pressure differed between the genotypes Hp1-1, Hp1-2, and Hp2-2 (81 [74–83], 75 [70–80], and 75 [72–81] mmHg, p = 0.019). Haptoglobin genotype frequencies by presence versus absence of SVD were 16.1%; 46.8%; 37.1% versus 15.4%; 41.9%; 42.7% (p = 0.758). Minor allele frequencies were 39.5% versus 36.3% (p = 0.553). Hp1 homozygotes and Hp2 carriers displayed equal proportions of SVD (35.7% vs 34.4%, p > 0.999) and SVD manifestations (white matter hyperintensities 14.3% vs 17.9%, p = 0.790; microbleeds 25.0% vs 21.9%, p = 0.904; lacunar infarcts 0% vs 3.6%, p > 0.999). Hp1-1 was not associated with SVD (OR 1.19, 95% CI 0.46–2.94, p = 0.712) when adjusting for age, blood pressure, and diabetic retinopathy.
Conclusions
Although the SVD prevalence was high, we detected no significant association between SVD and haptoglobin-genotype.
Funder
Folkhälsanin Tutkimussäätiö
Academy of Finland
Wilhelm och Else Stockmanns Stiftelse
Medicinska Understödsföreningen Liv och Hälsa
Novo Nordisk Fonden
Sigrid Juséliuksen Säätiö
Finska Läkaresällskapet
Otto A. Malm Lahjoitusrahasto
Biomedicum Helsinki-säätiö
Päivikki ja Sakari Sohlbergin Säätiö
Sydäntutkimussäätiö
Finnish governmental EVO grant
Helsingin Yliopisto
Diabetestutkimussäätiö
Diabetes Wellness Suomi Säätiö
Suomen Lääketieteen Säätiö
University of Helsinki including Helsinki University Central Hospital
Publisher
Springer Science and Business Media LLC
Subject
Endocrinology,General Medicine,Endocrinology, Diabetes and Metabolism,Internal Medicine