Acute hyperglycaemia induces an inflammatory response in young patients with type 1 diabetes

Background. Patients with type 1 diabetes (T1D) are at a substantially increased risk of cardiovascular disease. Stress-induced hyperglycaemia in turn is shown to worsen the prognosis of patients suffering from an acute myocardial infarction. However, the mechanisms behind these findings are incompletely known. Aim. To investigate whether markers of chronic inflammation, and oxidative stress respond to acute hyperglycaemia in patients with T1D. Methods. The plasma glucose concentration was rapidly raised from 5 to 15 mmol/L in 35 males (22 men with T1D and 13 age-matched non-diabetic volunteers) and maintained for 2 h. All participants were young non-smokers without any signs of diabetic or other complications. Markers of chronic inflammation, and oxidative stress were analysed in serum/plasma samples drawn at base-line and after 120 min of hyperglycaemia. Results. Compared to normoglycaemia, acute hyperglycaemia increased the interleukin (IL)-6 concentrations by 39% in patients with T1D (P<0.01) and 26% in healthy volunteers (P<0.05). During hyperglycaemia the superoxide dismutase concentration was increased by 17% in the healthy volunteers (P<0.01) and 5% in the patients with type 1 diabetes (P=NS). The increase in tumour necrosis factor (TNF)-α was larger in patients with type 1 diabetes than in non-diabetic volunteers (35% versus −10%, P<0.05). Conclusions. This study shows that acute hyperglycaemia induces an inflammatory response in patients with type 1 diabetes.

[1]  C. Forsblom,et al.  Diabetic nephropathy is associated with low-grade inflammation in Type 1 diabetic patients , 2003, Diabetologia.

[2]  B. Zinman,et al.  Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. , 2005, The New England journal of medicine.

[3]  Y. Maor,et al.  Somatostatin inhibits pro‐inflammatory cytokine secretion from rat hepatic stellate cells , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[4]  L. Rand,et al.  Magnitude and determinants of coronary artery disease in juvenile-onset, insulin-dependent diabetes mellitus. , 1987, The American journal of cardiology.

[5]  F. Numano,et al.  Glucose-Dependent Interleukin 6 and Tumor Necrosis Factor Production by Human Peripheral Blood Monocytes In Vitro , 1996, Diabetes.

[6]  Merlin C. Thomas,et al.  Metabolic syndrome in type 1 diabetes: association with diabetic nephropathy and glycemic control (the FinnDiane study). , 2005, Diabetes care.

[7]  R. Marfella,et al.  Acute hyperglycemia induces an oxidative stress in healthy subjects. , 2001, The Journal of clinical investigation.

[8]  K. Williams,et al.  Atherosclerosis--an inflammatory disease. , 1999, The New England journal of medicine.

[9]  Norman Fleischer,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. , 1993 .

[10]  C. Richart,et al.  The tumour necrosis factor (TNF)-α system is activated in accordance with pulse pressure in normotensive subjects with type 1 diabetes mellitus , 2005 .

[11]  AntonioCeriello,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans , 2002 .

[12]  N. Chaturvedi,et al.  Vascular risk factors and markers of endothelial function as determinants of inflammatory markers in type 1 diabetes: the EURODIAB Prospective Complications Study. , 2003, Diabetes care.

[13]  S. Greene,et al.  Abnormal markers of endothelial cell activation and oxidative stress in children, adolescents and young adults with Type 1 diabetes with no clinical vascular disease , 1999, Diabetes/metabolism research and reviews.

[14]  D. Gordin,et al.  Acute hyperglycaemia disturbs cardiac repolarization in Type 1 diabetes , 2008, Diabetic medicine : a journal of the British Diabetic Association.

[15]  S. Anderson,et al.  Aortic Pulse-Wave Velocity and Its Relationship to Mortality in Diabetes and Glucose Intolerance: An Integrated Index of Vascular Function? , 2002, Circulation.

[16]  Sidney C. Smith,et al.  MARKERS OF INFLAMMATION AND CARDIOVASCULAR DISEASE: APPLICATION TO CLINICAL AND PUBLIC HEALTH PRACTICE: A STATEMENT FOR HEALTHCARE PROFESSIONALS FROM THE CENTERS FOR DISEASE CONTROL AND PREVENTION AND THE AMERICAN HEART ASSOCIATION , 2003 .

[17]  L. Kuller,et al.  The Pittsburgh Insulin-dependent Diabetes Mellitus (IDDM) Morbidity and Mortality Study: Mortality Results , 1984, Diabetes.

[18]  I. Wilkinson,et al.  Large artery stiffness and inflammation , 2005, Journal of Human Hypertension.

[19]  H. Gerstein,et al.  Stress hyperglycaemia and increased risk of death after myocardial infarction in patients with and without diabetes: a systematic overview , 2000, The Lancet.

[20]  Yasmin,et al.  C-Reactive Protein Is Associated With Arterial Stiffness in Apparently Healthy Individuals , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[21]  A. Goldfine,et al.  Ascorbate Restores Endothelium-Dependent Vasodilation Impaired by Acute Hyperglycemia in Humans , 2001, Circulation.

[22]  A. Ceriello.  Acute Hyperglycaemia and Oxidative Stress Generation , 1997, Diabetic medicine : a journal of the British Diabetic Association.

[23]  F. Numano,et al.  The Effect of Glucose and Advanced Glycosylation End Products on IL‐6 Production by Human Monocytes , 1994, Annals of the New York Academy of Sciences.

[24]  N. Mulvihill,et al.  Inflammation in acute coronary syndromes , 2002, Heart.

[25]  B. Pedersen,et al.  The role of IL-6 in mediating the anti-inflammatory effects of exercise. , 2006, Journal of physiology and pharmacology : an official journal of the Polish Physiological Society.

[26]  Aroon D. Hingorani,et al.  Acute Systemic Inflammation Impairs Endothelium-Dependent Dilatation in Humans , 1999, Circulation.

[27]  T. Tuomainen,et al.  Augmentation index and carotid intima–media thickness are differently related to age, C-reactive protein and oxidized low-density lipoprotein , 2007, Journal of hypertension.

[28]  M. Brownlee.  Biochemistry and molecular cell biology of diabetic complications , 2001, Nature.

[29]  R. Marfella,et al.  Inflammatory Cytokine Concentrations Are Acutely Increased by Hyperglycemia in Humans: Role of Oxidative Stress , 2002, Circulation.

[30]  K. Polonsky,et al.  Twenty-four-hour profiles and pulsatile patterns of insulin secretion in normal and obese subjects. , 1988, The Journal of clinical investigation.

[31]  V. Hiilesmaa,et al.  Pre-eclampsia but not pregnancy-induced hypertension is a risk factor for diabetic nephropathy in type 1 diabetic women , 2007, Diabetologia.

[32]  S. Coppack,et al.  C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[33]  P. Libby,et al.  Novel inflammatory markers of coronary risk: theory versus practice. , 1999, Circulation.

[34]  F. Santilli,et al.  Enhanced Lipid Peroxidation and Platelet Activation in the Early Phase of Type 1 Diabetes Mellitus: Role of Interleukin-6 and Disease Duration , 2003, Circulation.

[35]  M. Fisher,et al.  Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) , 2007 .

[36]  R. Sacco,et al.  Tumor Necrosis Factor Receptor Levels Are Associated With Carotid Atherosclerosis , 2002, Stroke.

[37]  B. Saltin,et al.  Production of interleukin‐6 in contracting human skeletal muscles can account for the exercise‐induced increase in plasma interleukin‐6 , 2000, The Journal of physiology.

[38]  P. Toutouzas,et al.  Assessment of aortic line of elasticity using polynomial regression analysis. , 2000, Circulation.

[39]  G. Chrousos,et al.  Somatostatin analogues suppress the inflammatory reaction in vivo. , 1994, The Journal of clinical investigation.

[40]  A. Schmidt,et al.  Advanced glycation endproducts interacting with their endothelial receptor induce expression of vascular cell adhesion molecule-1 (VCAM-1) in cultured human endothelial cells and in mice. A potential mechanism for the accelerated vasculopathy of diabetes. , 1995, The Journal of clinical investigation.

[41]  G. Paolisso,et al.  Circulating adhesion molecules in humans: role of hyperglycemia and hyperinsulinemia. , 2000, Circulation.

[42]  L. Lind.  Circulating markers of inflammation and atherosclerosis. , 2003, Atherosclerosis.

[43]  R. Marfella,et al.  Vascular effects of acute hyperglycemia in humans are reversed by L-arginine. Evidence for reduced availability of nitric oxide during hyperglycemia. , 1997, Circulation.

[44]  A. Krętowski,et al.  Serum levels of interleukin-18--a potential marker of cardiovascular death--could be determined by genetic predisposition. , 2003, Circulation.

[45]  Gary L Myers,et al.  Markers of inflammation and cardiovascular disease: application to clinical and public health practice: A statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. , 2003, Circulation.

[46]  S. Genuth,et al.  The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. , 1993, The New England journal of medicine.

[47]  J. Cockcroft,et al.  Diminished wave reflection in the aorta. A novel physiological action of insulin on large blood vessels. , 1999, Hypertension.

[48]  D. Gordin,et al.  Acute hyperglycaemia rapidly increases arterial stiffness in young patients with type 1 diabetes , 2007, Diabetologia.

[49]  R. Marfella,et al.  Acute hyperglycemia induces nitrotyrosine formation and apoptosis in perfused heart from rat. , 2002, Diabetes.