Abstract
We investigated whether metabolic biomarkers and single nucleotide polymorphisms (SNPs) improve diabetes prediction beyond age, anthropometry, and lifestyle risk factors. A case-cohort study within a prospective study was designed. We randomly selected a subcohort (n = 2,500) from 26,444 participants, of whom 1,962 were diabetes free at baseline. Of the 801 incident type 2 diabetes cases identified in the cohort during 7 years of follow-up, 579 remained for analyses after exclusions. Prediction models were compared by receiver operatoring characteristic (ROC) curve and integrated discrimination improvement. Case-control discrimination by the lifestyle characteristics (ROC-AUC: 0.8465) improved with plasma glucose (ROC-AUC: 0.8672, P < 0.001) and A1C (ROC-AUC: 0.8859, P < 0.001). ROC-AUC further improved with HDL cholesterol, triglycerides, gamma-glutamyltransferase, and alanine aminotransferase (0.9000, P = 0.002). Twenty SNPs did not improve discrimination beyond these characteristics (P = 0.69). Metabolic markers, but not genotyping for 20 diabetogenic SNPs, improve discrimination of incident type 2 diabetes beyond lifestyle risk factors.
MeSH Terms
Alanine Transaminase/blood
Area Under Curve
Biomarkers/blood
Blood Glucose/metabolism
Case-Control Studies
Cholesterol, HDL/blood
Cohort Studies
Diabetes Mellitus, Type 2/blood,epidemiology,genetics
Genetic Markers
Genotype
Germany
Glycated Hemoglobin A/metabolism
Humans
Polymorphism, Single Nucleotide
Predictive Value of Tests
Prospective Studies
ROC Curve
Risk Assessment
gamma-Glutamyltransferase/blood
Chemicals
Biomarkers
Blood Glucose
Cholesterol, HDL
Genetic Markers
Glycated Hemoglobin A
gamma-Glutamyltransferase
Alanine Transaminase
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Schulze Matthias B
Public Health Nutrition Unit, Technische Universität München, Freising, Germany.
[email protected]
Weikert Cornelia
Pischon Tobias
Bergmann Manuela M
Al-Hasani Hadi
Schleicher Erwin
Fritsche Andreas
Häring Hans-Ulrich
Boeing Heiner
Joost Hans-Georg
References (14)
14 references, click to expand
-
Prediction of incident diabetes mellitus in middle-aged adults: the Framingham Offspring Study.
Arch Intern Med. 2007 May 28;167(10):1068-74
PMID: 17533210
-
Identifying individuals at high risk for diabetes: The Atherosclerosis Risk in Communities study.
Diabetes Care. 2005 Aug;28(8):2013-8
PMID: 16043747
-
Joint effects of common genetic variants on the risk for type 2 diabetes in U.S. men and women of European ancestry.
Ann Intern Med. 2009 Apr 21;150(8):541-50
PMID: 19380854
-
Clinical risk factors, DNA variants, and the development of type 2 diabetes.
N Engl J Med. 2008 Nov 20;359(21):2220-32
PMID: 19020324
-
Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
Nat Genet. 2007 Aug;39(8):977-83
PMID: 17603485
-
Predicting type 2 diabetes based on polymorphisms from genome-wide association studies: a population-based study.
Diabetes. 2008 Nov;57(11):3122-8
PMID: 18694974
-
Genome-wide association analysis identifies loci for type 2 diabetes and triglyceride levels.
Science. 2007 Jun 1;316(5829):1331-6
PMID: 17463246
-
An accurate risk score based on anthropometric, dietary, and lifestyle factors to predict the development of type 2 diabetes.
Diabetes Care. 2007 Mar;30(3):510-5
PMID: 17327313
-
Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes.
Science. 2007 Jun 1;316(5829):1336-41
PMID: 17463249
-
Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.
Nat Genet. 2008 May;40(5):638-45
PMID: 18372903
-
Plasma fetuin-A levels and the risk of type 2 diabetes.
Diabetes. 2008 Oct;57(10):2762-7
PMID: 18633113
-
Evaluating the added predictive ability of a new marker: from area under the ROC curve to reclassification and beyond.
Stat Med. 2008 Jan 30;27(2):157-72; discussion 207-12
PMID: 17569110
-
Comparing the areas under two or more correlated receiver operating characteristic curves: a nonparametric approach.
Biometrics. 1988 Sep;44(3):837-45
PMID: 3203132
-
Genotype score in addition to common risk factors for prediction of type 2 diabetes.
N Engl J Med. 2008 Nov 20;359(21):2208-19
PMID: 19020323