Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus

• Published in: American journal of physiology: endocrinology and metabolism Vol. 279; no. 1; p. E155
• Main Authors: McKenna, K, Morris, A D, Ryan, M, Newton, R W, Frier, B M, Baylis, P H, Saito, T, Ishikawa, S, Thompson, C J
• Format: Journal Article
• Language: English
• Published: United States 01-07-2000
• Subjects: Adolescent; Adult; Aquaporin 2; Aquaporin 6; Aquaporins - urine; Arginine Vasopressin - pharmacology; Blood Glucose - analysis; Creatinine - urine; Diabetes Mellitus, Type 1 - blood; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 1 - urine; Drug Resistance; Glycated Hemoglobin A - analysis; Humans; Hypoglycemic Agents - therapeutic use; Insulin - therapeutic use; Kidney - drug effects; Kidney - physiopathology; Kidney Concentrating Ability - drug effects; Osmolar Concentration; Renal Agents; Urine - physiology; Vasopressins - physiology
• ISSN: 0193-1849
• DOI: 10.1152/ajpendo.2000.279.1.E155

To investigate the hypothesis that diabetes induces nephrogenic diabetes insipidus, we studied the urine-concentrating ability in response to vasopressin (AVP) in 12 patients with insulin-dependent diabetes mellitus (IDDM) and 12 nondiabetic controls. Subjects were euglycemic-clamped, and after oral water loading, AVP was infused intravenously for 150 min. AVP induced a greater (P<0.001) rise in urine osmolality in controls (67.6+/-10.7 to 720+/-31.1 mosmol/kg, P<0.001) than in IDDM patients (64.3+/-21.6 to 516.7+/-89.3 mosmol/kg, P<0.001). Urinary aquaporin-2 concentrations after AVP infusion were higher in controls (611.8+/-105.6 fmol/mg creatinine) than in IDDM (462.0+/-94.9 fmol/mg creatinine, P = 0. 003). Maximum urine osmolality in IDDM was inversely related to chronic blood glucose control, as indicated by Hb A(Ic) (r = -0.87, P = 0.002). To test the hypothesis that improved glycemic control could reverse resistance to AVP, 10 IDDM subjects with poor glycemic control (Hb A(Ic) >9%) were studied before (B) and after (A) intensified glycemic control. Maximum urine osmolality in response to AVP increased with improved glycemic control (B, 443.8+/-49.0; A, 640.0+/-137.2 mosmol/kg, P<0.001), and urinary aquaporin-2 concentrations after AVP increased from 112.7 +/-69 to 375+/-280 fmol/mg creatinine (P = 0.006), with improved glycemic control. Poorly controlled IDDM is associated with reversible renal resistance to AVP.