Risk prediction of major complications in individuals with diabetes: the Atherosclerosis Risk in Communities Study

Diabetes Obes Metab. 2016 Sep;18(9):899-906. doi: 10.1111/dom.12686. Epub 2016 Jun 14.

Abstract

Aims: To develop a prediction equation for 10-year risk of a combined endpoint (incident coronary heart disease, stroke, heart failure, chronic kidney disease, lower extremity hospitalizations) in people with diabetes, using demographic and clinical information, and a panel of traditional and non-traditional biomarkers.

Methods: We included in the study 654 participants in the Atherosclerosis Risk in Communities (ARIC) study, a prospective cohort study, with diagnosed diabetes (visit 2; 1990-1992). Models included self-reported variables (Model 1), clinical measurements (Model 2), and glycated haemoglobin (Model 3). Model 4 tested the addition of 12 blood-based biomarkers. We compared models using prediction and discrimination statistics.

Results: Successive stages of model development improved risk prediction. The C-statistics (95% confidence intervals) of models 1, 2, and 3 were 0.667 (0.64, 0.70), 0.683 (0.65, 0.71), and 0.694 (0.66, 0.72), respectively (p < 0.05 for differences). The addition of three traditional and non-traditional biomarkers [β-2 microglobulin, creatinine-based estimated glomerular filtration rate (eGFR), and cystatin C-based eGFR] to Model 3 significantly improved discrimination (C-statistic = 0.716; p = 0.003) and accuracy of 10-year risk prediction for major complications in people with diabetes (midpoint percentiles of lowest and highest deciles of predicted risk changed from 18-68% to 12-87%).

Conclusions: These biomarkers, particularly those of kidney filtration, may help distinguish between people at low versus high risk of long-term major complications.

Keywords: cardiovascular disease; diabetes complications; population study; type 2 diabetes.

MeSH terms

  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cohort Studies
  • Coronary Disease / epidemiology*
  • Creatinine / blood
  • Cystatin C / blood
  • Diabetes Complications / epidemiology*
  • Diabetes Mellitus / epidemiology*
  • Diabetes Mellitus / metabolism
  • Diabetic Angiopathies / epidemiology
  • Diabetic Nephropathies / epidemiology
  • Diabetic Nephropathies / metabolism
  • Female
  • Fructosamine / blood
  • Glomerular Filtration Rate
  • Glycated Hemoglobin / metabolism
  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Heart Failure / epidemiology*
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Peptide Fragments / blood
  • Prospective Studies
  • Renal Insufficiency, Chronic / epidemiology*
  • Renal Insufficiency, Chronic / metabolism
  • Risk Assessment
  • Self Report
  • Serum Albumin / metabolism
  • Stroke / epidemiology*
  • Troponin T / blood
  • beta 2-Microglobulin / blood
  • gamma-Glutamyltransferase / blood

Substances

  • Biomarkers
  • Cystatin C
  • Glycated Hemoglobin A
  • Glycation End Products, Advanced
  • Peptide Fragments
  • Serum Albumin
  • Troponin T
  • beta 2-Microglobulin
  • hemoglobin A1c protein, human
  • pro-brain natriuretic peptide (1-76)
  • Natriuretic Peptide, Brain
  • Fructosamine
  • C-Reactive Protein
  • Creatinine
  • gamma-Glutamyltransferase
  • Aspartate Aminotransferases
  • Alanine Transaminase
  • Glycated Serum Albumin