Normoalbuminuric type 1 diabetic patients with retinopathy have an impaired tubular response to desmopressin: its relationship with plasma endothelin-1

J Clin Endocrinol Metab. 2009 Jun;94(6):2060-5. doi: 10.1210/jc.2008-2784. Epub 2009 Mar 17.

Abstract

Objective: The aim of the study was to evaluate whether normoalbuminuric type 1 diabetic patients with diabetic retinopathy (DR) have an impaired tubular response to desmopressin (dDAVP, a synthetic analog of vasopressin) administration, and its relationship with plasma and urine endothelin-1 (ET-1) levels.

Design: This was an interventional case-control study.

Setting: The study was conducted at a referral center.

Participants: Fifteen normoalbuminuric type 1 diabetic patients with DR were compared with 30 normoalbuminuric type 1 diabetic patients without DR. Both groups were matched by age, gender, body mass index, glycosylated hemoglobin, and the main laboratory markers of kidney function.

Intervention: After a 12-h period of water deprivation, dDAVP (0.3 microg/kg) was infused over 20 min. Urine was collected at baseline and 1, 2, and 3 h after dDAVP administration. ET-1 was assessed by ELISA.

Results: dDAVP induced a lower rise in urine osmolality in patients with DR (from 650 +/- 206 to 754 +/- 224 mosmol/kg; P = 0.02) than in diabetic patients without DR (from 714 +/- 194 to 905 +/- 163 mosmol/kg; P < 0.0001). In addition, fractional excretion of Na+ decreased in patients without DR (from 0.45 +/- 0.30 to 0.29 +/- 0.29%; P = 0.04) but not in the diabetic patients with DR (from 0.36 +/- 0.22 to 0.36 +/- 0.40%; P = 0.96). Plasma ET-1 levels were inversely correlated with the response of urinary osmolality after dDAVP administration (r = -0.62; P = 0.008).

Conclusions: Normoalbuminuric type 1 diabetic patients with DR have impaired renal response to dDAVP that is related to plasma ET-1 levels. Further studies are required to elucidate whether this tubular resistance to dDAVP might favor dehydration in these patients.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Albuminuria / complications
  • Creatinine / urine
  • Deamino Arginine Vasopressin / pharmacology*
  • Diabetes Mellitus, Type 1 / blood*
  • Diabetes Mellitus, Type 1 / complications
  • Diabetes Mellitus, Type 1 / physiopathology
  • Diabetes Mellitus, Type 1 / urine
  • Diabetic Retinopathy / blood*
  • Diabetic Retinopathy / physiopathology
  • Diabetic Retinopathy / urine
  • Endothelin-1 / blood*
  • Endothelin-1 / urine
  • Female
  • Humans
  • Kidney Tubules / drug effects*
  • Kidney Tubules / physiology
  • Male
  • Middle Aged
  • Osmolar Concentration
  • Young Adult

Substances

  • Endothelin-1
  • Creatinine
  • Deamino Arginine Vasopressin