Proinflammatory cytokines, markers of cardiovascular risks, oxidative stress, and lipid peroxidation in patients with hyperglycemic crises.
Acute and chronic hyperglycemia are proinflammatory states, but the status of proinflammatory cytokines and markers of oxidative stress and cardiovascular risks is not known in hyperglycemic crises of diabetic ketoacidosis (DKA) and nonketotic hyperglycemia (NKH). We studied 20 lean and 28 obese patients with DKA, 10 patients with NKH, and 12 lean and 12 obese nondiabetic control subjects. We measured 1) proinflammatory cytokines (tumor necrosis factor-alpha, interleukin [IL]-6, IL1-beta, and IL-8), 2) markers of cardiovascular risk (C-reactive protein [CRP], homocysteine, and plasminogen activator inhibitor-1 [PAI-1]), 3) products of reactive oxygen species (ROS; thiobarbituric acid [TBA]-reacting material, and dichlorofluorescein [DCF]), and 4) cortisol, growth hormone (GH), and free fatty acids (FFAs) on admission (before insulin therapy) and after insulin therapy and resolution of hyperglycemia and/or ketoacidosis. Results were compared with lean and obese control subjects. Circulating levels of cytokines, TBA, DCF, PAI-1, FFAs, cortisol, and GH on admission were significantly increased two- to fourfold in patients with hyperglycemic crises compared with control subjects, and they returned to normal levels after insulin treatment and resolution of hyperglycemic crises. Changes in CRP and homocysteine in response to insulin therapy did not reach control levels after resolution of hyperglycemia. We conclude that DKA and NKH are associated with elevation of proinflammatory cytokines, ROS, and cardiovascular risk factors in the absence of obvious infection or cardiovascular pathology. Return of these values to normal levels with insulin therapy demonstrates a robust anti-inflammatory effect of insulin.
Stentz
Frankie B
FB
Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. fstentz@utmem.edu
Umpierrez
Guillermo E
GE
Cuervo
Ruben
R
Kitabchi
Abbas E
AE
D000328:Adult; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000032:analysis; D016207:Cytokines / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood*; D003925:Diabetic Angiopathies / Q000097:blood; D016883:Diabetic Ketoacidosis / Q000097:blood*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006943:Hyperglycemia / Q000097:blood*; D015227:Lipid Peroxidation / Q000502:physiology*; D008297:Male; D008875:Middle Aged; D009765:Obesity; D018384:Oxidative Stress / Q000502:physiology*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D012016:Reference Values
D015415:Biomarkers; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D017395:Plasminogen Activator Inhibitor 1; D006710:Homocysteine; D002097:C-Reactive Protein