Association between microfibrillar-associated protein 4 (MFAP4) and micro- and macrovascular complications in long-term type 1 diabetes mellitus

Acta Diabetol. 2017 Apr;54(4):367-372. doi: 10.1007/s00592-016-0953-y. Epub 2016 Dec 30.

Abstract

Aims: To evaluate microfibrillar-associated protein 4 (MFAP4) as a marker of micro- and macrovascular complications in patients with type 1 diabetes.

Methods: This cross-sectional study included 203 persons with a long duration of type 1 diabetes from a population-based cohort ascertained in the former Funen County, Denmark. Detection of plasma-MFAP4 (pMFAP4) was performed by the AlphaLISA Technique. Diabetic retinopathy (DR) was graded in accordance with the Early Treatment Diabetic Retinopathy Study adaptation of the modified Airlie House classification. A monofilament test was used to test for neuropathy, and nephropathy was evaluated in a single spot urine sample. Data describing macrovascular disease were obtained from the Danish National Patient Register.

Results: Median age and duration of diabetes were 58.7 and 43 years, respectively, and 61% were males. High levels of pMFAP4 were found in participants of old age, in women and in non-smokers (p < 0.05). In a multiple logistic regression model, patients with high levels of pMFAP4 were more likely to have diabetic neuropathy (OR 2.47 for quartile 4 versus quartile 1, 95% CI 1.01-6.03). No association was found between pMFAP4 and proliferative diabetic retinopathy, nephropathy or macrovascular disease.

Conclusions: No association between pMFAP4 and macrovascular vascular complications was found. However, high levels of pMFAP4 correlated independently with diabetic neuropathy. Further studies on the predictive value of increased circulating MFAP4 in diabetic neuropathy are warranted.

Keywords: Complications; Microfibrillar-associated protein 4 (MFAP4); Pathophysiology; Type 1 diabetes mellitus.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / diagnosis
  • Carrier Proteins / blood*
  • Cross-Sectional Studies
  • Denmark
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetic Angiopathies / blood*
  • Diabetic Angiopathies / diagnosis
  • Diabetic Neuropathies / blood
  • Diabetic Neuropathies / complications
  • Diabetic Neuropathies / diagnosis
  • Diabetic Retinopathy / blood
  • Diabetic Retinopathy / complications
  • Diabetic Retinopathy / diagnosis
  • Extracellular Matrix Proteins / blood*
  • Female
  • Glycoproteins / blood*
  • Humans
  • Male
  • Middle Aged
  • Predictive Value of Tests
  • Risk Factors

Substances

  • Biomarkers
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • Glycoproteins
  • MFAP4 protein, human