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. RESEARCH DESIGN AND 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 m(2)). Clamped hyperglycemia was associated with significant increases in urinary eotaxin, fibroblast growth factor-2, granulocyte-macrophage colony-stimulating factor, interferon-alpha 2, interleukin-2 and -12, monocyte chemoattractant protein-3, macrophage-derived chemokine, macrophage inflammatory protein-l alpha, platelet-derived growth factor, tumor necrosis factor-alpha, 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.