Effect of acute hyperglycaemia on selected plasma and urinary cytokine antagonists in Type 1 diabetes mellitus.
OBJECTIVE
Several cytokines have been implicated in the pathogenesis of diabetic nephropathy. Their ability to generate a biological response in vivo is modulated by specific antagonists and soluble receptors. The aims of the study were firstly, to measure the interleukin 1 receptor antagonist (IL-1ra) and tumour necrosis factor alpha soluble receptors p55 (TNFsr1) and p75 (TNFsr2) in plasma and urine, and secondly to test their response to acutely induced hyperglycaemia in Type 1 diabetes mellitus (DM 1).


METHODS
Plasma concentrations and urinary excretions of IL-1ra, TNFsr1 and TNFsr2 were measured in two 90-min periods of glycaemic clamp-induced normoglycaemia and hyperglycaemia (5 and 12 mmol/l; study 1) and during time-controlled normoglycaemia (5 and 5 mmol/l; study 2) in 20 Type 1 diabetic patients with normal albumin excretion and normal glomerular filtration rate, and in 11 weight-, age- and sex-matched healthy control subjects.


RESULTS
The plasma concentrations of IL-1ra, TNFsr1 and TNFsr2 were comparable in Type 1 diabetic patients and control subjects, and no significant changes during study 1 and study 2 were found. Urinary IL-1ra excretion measured during normoglycaemia was higher in Type 1 diabetic patients compared to control subjects ( p<0.05). In diabetic patients, it decreased in study 1 compared to study 2 ( p<0.05), while it did not change in control subjects. The urinary excretions of TNFsr1 and TNFsr2 during normoglycaemia were comparable in diabetic patients and controls. In diabetic patients, hyperglycaemia decreased TNFsr1 excretion (study 1 vs study 2; p<0.01), while TNFsr1 excretion did not change in control subjects. Hyperglycaemia did not affect TNFsr2 excretion in diabetic patients, while it led to an increase in TNFsr2 excretion in control subjects (study 1 vs study 2; p<0.05). Despite comparable renal haemodynamics, diabetic patients had lower fractional excretion of sodium compared to control subjects ( p<0.01). No significant relationships between cytokine antagonists and renal functions have been found.


CONCLUSIONS
Type 1 diabetic patients with normal renal haemodynamics are associated with impaired regulation of renal IL-1ra, TNFsr1 and TNFsr2 production with a potential impact on local control of cytokine activity in the kidneys.
Pelikánová
T
T
Diabetes Center, Institute for Clinical and Experimental Medicine, Vídenská 1958/9, 140 21, Prague, Czech Republic. terezie.pelikanova@medicon.cz
Simková
R
R
Tesar
V
V
Jirsa
M
M
D000328:Adult; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D005947:Glucose / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D006943:Hyperglycemia / Q000139:chemically induced / Q000503:physiopathology*; D007262:Infusions, Intravenous; D007328:Insulin / Q000008:administration & dosage / Q000493:pharmacokinetics; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D010446:Peptide Fragments / Q000097:blood* / Q000652:urine*; D012795:Sialoglycoproteins / Q000097:blood* / Q000652:urine*; D014409:Tumor Necrosis Factor-alpha / Q000652:urine*
C507763:IL1RN protein, human; D007328:Insulin; D053590:Interleukin 1 Receptor Antagonist Protein; D010446:Peptide Fragments; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha; C066650:tumor necrosis factor alpha (36-68); C112561:tumor necrosis factor alpha (70-80); D005947:Glucose