The acute effect of clamped hyperglycemia on the urinary excretion of inflammatory cytokines/chemokines in uncomplicated type 1 diabetes: a pilot study.
OBJECTIVE
Acute glycemic variability contributes to diabetic complications potentially through induction of inflammation. Our objective was to determine whether acute hyperglycemia affects urinary secretion of inflammatory cytokines/chemokines in humans with uncomplicated type 1 diabetes.


METHODS
Blood pressure, renal hemodynamics (inulin and paraaminohippurate clearances), and urine samples were obtained after 6 h of clamped euglycemia (4-6 mmol/l) and hyperglycemia (9-11 mmol/l) on two consecutive days in subjects with type 1 diabetes (n = 25). Forty-two urinary cytokines/chemokines were measured using a Luminex platform.


RESULTS
Clamped hyperglycemia produced an expected increase in glomerular filtration rate (131 ± 4 to 148 ± 8 ml/min/1.73 m²). Clamped hyperglycemia was associated with significant increases in urinary eotaxin, fibroblast growth factor-2, granulocyte-macrophage colony-stimulating factor, interferon-α 2, interleukin-2 and -12, monocyte chemoattractant protein-3, macrophage-derived chemokine, macrophage inflammatory protein-1α, platelet-derived growth factor, tumor necrosis factor-α, and CD40 ligand (P < 0.05).


CONCLUSIONS
Acute hyperglycemia results in increased urinary excretion of inflammatory cytokines/chemokines in humans with uncomplicated type 1 diabetes, and this may contribute to kidney injury.
Cherney
David Z I
DZ
Division of Nephrology, Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada. david.cherney@uhn.on.ca
Scholey
James W
JW
Sochett
Etienne
E
Bradley
Timothy J
TJ
Reich
Heather N
HN
D000293:Adolescent; D000328:Adult; D054410:Chemokine CCL7 / Q000652:urine; D018925:Chemokines / Q000652:urine*; D016207:Cytokines / Q000652:urine*; D003922:Diabetes Mellitus, Type 1 / Q000652:urine*; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D006943:Hyperglycemia / Q000652:urine*; D016898:Interferon-alpha / Q000652:urine; D007376:Interleukin-2 / Q000652:urine; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000652:urine; D014409:Tumor Necrosis Factor-alpha / Q000652:urine; D055815:Young Adult
D054410:Chemokine CCL7; D018925:Chemokines; D016207:Cytokines; D016898:Interferon-alpha; D007376:Interleukin-2; D010982:Platelet-Derived Growth Factor; D014409:Tumor Necrosis Factor-alpha