Plasma Copeptin, Kidney Outcomes, Ischemic Heart Disease, and All-Cause Mortality in People With Long-standing Type 1 Diabetes

Diabetes Care. 2016 Dec;39(12):2288-2295. doi: 10.2337/dc16-1003. Epub 2016 Oct 11.

Abstract

Objective: Plasma copeptin, a surrogate for vasopressin, has been associated with a decline in renal function and albuminuria in population-based studies as well as with progression of diabetic nephropathy in people with type 2 diabetes. We assessed the risk of kidney and coronary events and all-cause mortality associated with plasma copeptin in people with type 1 diabetes.

Research design and methods: Plasma copeptin was measured in baseline samples of the GENEDIAB (n = 398; 56% male; mean ± SD age 45 ± 12 years and diabetes duration 28 ± 10 years) and GENESIS (n = 588; 52% male; age 42 ± 11 years; diabetes duration 27 ± 9 years) cohorts. Follow-up data were available for 218 GENEDIAB and 518 GENESIS participants. Median duration of follow-up was 10.2 and 5.0 years, respectively.

Results: Upper sex-specific tertiles of copeptin were associated with a higher incidence of end-stage renal disease (ESRD) during follow-up (hazard ratio [HR] for third vs. first tertile 26.5 [95% CI 8.0-163.3; P < 0.0001]; analysis in pooled cohorts adjusted for age, sex, duration of diabetes, and cohort membership). The highest tertile of copeptin was also associated with incidence of myocardial infarction or coronary revascularization (HR 2.2 [95% CI 1.2-4.0]; P = 0.01) and all-cause mortality (HR 3.3 [95% CI 1.8-6.5]; P < 0.0001) during follow-up.

Conclusions: Plasma copeptin is a predictor for the risk of ESRD, coronary heart disease, and all-cause mortality in people with type 1 diabetes. Results are consistent with data from experimental and epidemiological studies, suggesting that high circulating levels of vasopressin are deleterious to renal function.

MeSH terms

  • Adult
  • Albuminuria / blood
  • Albuminuria / complications
  • Albuminuria / diagnosis
  • Albuminuria / mortality
  • Cause of Death
  • Coronary Artery Disease / blood
  • Coronary Artery Disease / complications
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / mortality
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications*
  • Diabetes Mellitus, Type 1 / diagnosis
  • Diabetes Mellitus, Type 1 / mortality*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / mortality*
  • Disease Progression
  • Female
  • Glycopeptides / blood*
  • Humans
  • Incidence
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / diagnosis
  • Kidney Failure, Chronic / etiology
  • Kidney Failure, Chronic / mortality
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / complications
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / mortality
  • Myocardial Ischemia / blood
  • Myocardial Ischemia / diagnosis*
  • Myocardial Ischemia / mortality*
  • Prognosis
  • Time Factors

Substances

  • Glycopeptides
  • copeptins