Plasma copeptin and the risk of diabetes mellitus.
BACKGROUND
Animal studies suggest that the arginine vasopressin system may play a role in glucose metabolism, but data from humans are limited.


RESULTS
We analyzed plasma copeptin (copeptin), a stable C-terminal fragment of the arginine vasopressin prohormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742; mean age, 58 years; 60% women) and multivariable logistic regression, we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes mellitus at baseline, insulin resistance (top quartile of fasting plasma insulin among nondiabetic subjects), and incident diabetes mellitus on long-term follow-up. New-onset diabetes mellitus was ascertained through 3 national and regional registers. All models were adjusted for clinical and anthropometric risk factors, cystatin C, and C-reactive protein. In cross-sectional analyses, increasing copeptin was associated with prevalent diabetes mellitus (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow-up, 174 subjects (4%) developed new-onset diabetes mellitus. The odds of developing diabetes mellitus increased across increasing quartiles of copeptin, even after additional adjustment for baseline fasting glucose and insulin (adjusted odds ratios, 1.0, 1.37, 1.79, and 2.09; P for trend=0.004). The association with incident diabetes mellitus remained significant in analyses restricted to subjects with fasting whole blood glucose <5.4 mmol/L at baseline (adjusted odds ratios, 1.0, 1.80, 1.92, and 3.48; P=0.001).


CONCLUSIONS
Elevated copeptin predicts increased risk for diabetes mellitus independently of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel antidiabetic treatments, and metabolic side effects from arginine vasopressin system modulation.
Enhörning
Sofia
S
Department of Clinical Sciences, Lund University, Clinical Research Center, Entrance 72, Bldg 91, Floor 12, Malmö University Hospital, SE 20502 Malmö, Sweden.
Wang
Thomas J
TJ
Nilsson
Peter M
PM
Almgren
Peter
P
Hedblad
Bo
B
Berglund
Göran
G
Struck
Joachim
J
Morgenthaler
Nils G
NG
Bergmann
Andreas
A
Lindholm
Eero
E
Groop
Leif
L
Lyssenko
Valeria
V
Orho-Melander
Marju
M
Newton-Cheh
Christopher
C
Melander
Olle
O
D001786:Blood Glucose / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006020:Glycopeptides / Q000097:blood*; D006801:Humans; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D011237:Predictive Value of Tests; D015995:Prevalence; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology
D001786:Blood Glucose; D006020:Glycopeptides; D007328:Insulin; C048197:copeptins