Plasma Copeptin and the Risk of Diabetes Mellitus

Abstract

Background Animal studies suggest that the arginine vasopressin (AVP) system may play a role in glucose metabolism, but data from humans are limited. Methods and Results We analysed plasma copeptin (copeptin), a stable C-terminal fragment of the AVP pro-hormone. Using baseline and longitudinal data from a Swedish population-based sample (n=4742, mean age 58 years, 60% women), we examined the association of increasing quartiles of copeptin (lowest quartile as reference) with prevalent diabetes at baseline, insulin resistance (top quartile of fasting plasma insulin among non-diabetic subjects), and incident diabetes on long-term follow up using multivariable logistic regression. New-onset diabetes 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 (P=0.04) and insulin resistance (P<0.001). During 12.6 years of follow up 174 subjects (4%) developed new-onset diabetes. The odds of developing diabetes 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 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, independent of established clinical risk factors, including fasting glucose and insulin. These findings could have implications for risk assessment, novel anti-diabetic treatments, and metabolic side effects from AVP system modulation.

Sex differences in the association between plasma copeptin and incident type 2 diabetes: the Prevention of Renal and Vascular Endstage Disease (PREVEND) study

“…Likewise, all these conditions are known to be predictors for the risk of type 2 diabetes [13]. In an extension of these studies, two previous studies have investigated the association of copeptin with the risk of type 2 diabetes [6,32]. The Malmö Diet and Cancer (MDC) study showed that copeptin, independently of a wide range of clinical risk factors, predicts the risk of type 2 diabetes in the general population [6].…”

“…In an extension of these studies, two previous studies have investigated the association of copeptin with the risk of type 2 diabetes [6,32]. The Malmö Diet and Cancer (MDC) study showed that copeptin, independently of a wide range of clinical risk factors, predicts the risk of type 2 diabetes in the general population [6]. However, the FINRISK97 study could not find an independent association [32].…”

“…The fact that we found a stronger association between copeptin and the risk of type 2 diabetes in women than in men might partly be explained by differences in population characteristics compared with other studies. For example, the MDC study from a Swedish population-based cohort included 4,472 participants with 174 incident cases [6] who were older (mean age of 58 years) and contained around 60% women. In the MDC study, including a higher number of women who had comparable copeptin levels to those in our study, a potential sex-related effect on the association of copeptin with diabetes risk was not addressed.…”

“…One recent study found that high baseline levels of copeptin are associated with increased risk for development of type 2 diabetes [6]. The link between the AVP stress-adaptation system and type 2 diabetes may lie in stimulatory effects of AVP on hepatic glucose production [7], effects on insulin release from the pancreas [8], stimulation of endogenous cortisol secretion [9] and adverse effects on whole-body insulin resistance [10].…”

An obligatory role for neurotensin in high-fat-diet-induced obesity

“…Pro-NT was measured in stored fasting plasma specimens (all samples were assayed in 2010) that were immediately frozen to −80° C at the MDC-CC baseline examination using a chemiluminometric sandwich immunoassay to detect a pro-NT precursor fragment (pro-NT 1–117) as described previously 62 . Analyses of blood glucose and plasma insulin were carried out at the time of baseline examination at the Department of Clinical Chemistry, Malmö University Hospital, which is attached to a national standardization and quality control system 63 . Of the 4,626 subjects with baseline data on BMI and pro-NT, 2,900 subjects were re-examined with a new measurement of BMI after a mean follow-up of 16.5 ± 1.5 years.…”