Renal resistance to vasopressin in poorly controlled type 1 diabetes mellitus.
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.
McKenna
K
K
Beaumont Hospital, Dublin 9, Republic of Ireland.
Morris
A D
AD
Ryan
M
M
Newton
R W
RW
Frier
B M
BM
Baylis
P H
PH
Saito
T
T
Ishikawa
S
S
Thompson
C J
CJ
D000293:Adolescent; D000328:Adult; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins / Q000652:urine; D001127:Arginine Vasopressin / Q000494:pharmacology; D001786:Blood Glucose / Q000032:analysis; D003404:Creatinine / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology* / Q000652:urine; D004351:Drug Resistance; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000187:drug effects / Q000503:physiopathology*; D007671:Kidney Concentrating Ability / Q000187:drug effects; D009994:Osmolar Concentration; D012076:Renal Agents; D014556:Urine / Q000502:physiology; D014667:Vasopressins / Q000502:physiology*
D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D001127:Arginine Vasopressin; D001786:Blood Glucose; D003404:Creatinine; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D012076:Renal Agents; D014667:Vasopressins; C496023:AQP2 protein, human