Is the association of serum sodium with mortality in patients with type 2 diabetes explained by copeptin or NT-proBNP? (ZODIAC-46)

- Hyponatremia has been associated with an increased mortality risk.
- Patients with DM2 are predisposed to elevated levels of AVP and heart failure.
- Both elevated AVP and heart failure are common causes of hyponatremia.
- Low serum sodium, high copeptin and NT-proBNP are associated with mortality in DM2.
- Low serum sodium is associated with mortality independent of copeptin and NT-proBNP.

Background and aimsHyponatremia has been associated with an increased mortality risk in the general population. Diabetes is a condition predisposing for elevated levels of arginine vasopressin (AVP) and heart failure, both common causes of hyponatremia. These factors, however, are also associated with an increased mortality risk. We aimed to investigate whether serum sodium is associated with cardiovascular and all-cause mortality in type 2 diabetes and whether these associations could be explained by copeptin, a surrogate for AVP, or NT-proBNP, a marker for heart failure.MethodsPatients with type 2 diabetes participating in the observational ZODIAC study were included. Cox regression analyses were used to investigate the association of serum sodium with mortality.ResultsWe included 1068 patients (age 67 ± 12 years, 45% male, serum sodium 142 ± 3 mmol/L). After 15 years of follow-up, 519 patients (49%) died, with 225 cardiovascular deaths (21%). In univariable analyses, serum sodium, copeptin, and NT-proBNP were all significantly associated with cardiovascular and all-cause mortality. These associations remained significant after combination of these markers in a multivariable model. Serum sodium and NT-proBNP remained significantly associated with mortality after further adjustment for potential confounders, whereas copeptin lost significance after adjustment for SCr and ACR.ConclusionLow serum sodium was associated with an increased risk of cardiovascular and all-cause mortality in type 2 diabetes. Moreover, these associations were not explained by copeptin and NT-proBNP. Whether low serum sodium itself leads to poor outcome or is a marker for (unidentified) co-morbidity severity or use of specific medications remains to be elucidated.