Download PDF
Horm Metab Res 2020; 52(01): 39-48
DOI: 10.1055/a-0972-1302
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Endothelial and Autonomic Dysfunction at Early Stages of Glucose Intolerance and in Metabolic Syndrome

Rumyana Dimova
1   Department of Diabetology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
,
Tsvetalina Tankova
1   Department of Diabetology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
,
Georgi Kirilov
2   Department of Radioimmunology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
,
Nevena Chakarova
1   Department of Diabetology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
,
Greta Grozeva
1   Department of Diabetology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
,
Lilia Dakovska
1   Department of Diabetology, Clinical Centre of Endocrinology, Medical University, Sofia, Bulgaria
› Author Affiliations
Further Information

Publication History

received 24 June 2019

accepted 01 July 2019

Publication Date:
17 September 2019 (online)

Also available at
   Permissions and Reprints

Abstract

This study evaluated sE-selectin, Endothelin-1, and cardiovascular autonomic neuropathy (CAN) at early stages of glucose intolerance and in metabolic syndrome (MetS). A total of 87 subjects – 39 males, of mean age 45.7±11.6 years and mean BMI 31.4±6.6 kg/m2, divided according to glucose tolerance and the presence of MetS were enrolled. Glucose tolerance was studied during OGTT. Anthropometric indices, blood pressure, HbA1c, lipids, hsCRP, sE-selectin, Endothelin-1, and immunoreactive insulin were measured. Body composition was assessed by a bioimpedance method (InBody 720, BioSpace). Tissue AGEs accumulation was evaluated by skin autofluorescence (AGE-Reader, DiagnOpticsTM). CAN was assessed by ANX-3.0 technology. In the groups, according to glucose tolerance, the prevalence of CAN was 5.7% in normal glucose tolerance (NGT), 8.6% in prediabetes, and 23.5% in newly diagnosed type 2 diabetes (NDD). In the groups, according to the presence of MetS, the prevalence of CAN was 12.3% in those with MetS and 4.8% in those without MetS. Parasympathetic activity was diminished at rest (p=0.048, 0.015, respectively) in NDD as compared to prediabetes and NGT; and there was a numerically elevated heart rate at rest in NDD in comparison to NGT. There was a negative correlation between parasympathetic tone and waist circumference, BMI, and visceral and total fat. There was no difference in the measured endothelial function markers in the groups according to glucose tolerance and MetS. sE-selectin correlated with HOMA-IR (r=0.275, p=0.048). No association between Endothelin-1 levels and assessed metabolic parameters was observed. There is a high prevalence of CAN at early stages of glucose intolerance and in MetS, due to decreased parasympathetic activity. Slight elevation of glycemia and MetS probably do not affect endothelial function, since sE-selectin seems to be related to insulin resistance.

Key words

sE-selectin - Endothelin-1 - cardiovascular autonomic neuropathy - prediabetes - metabolic syndrome
 

  • References

  • 1 American Diabetes Association . Position statement. Standards of Medical Care in Diabetes. Diabetes Care 2010; 33 S1 11-61
    PubMedGoogle Scholar
  • 2 Definition and diagnosis of diabetes mellitus and intermediate hyperglycemia. Report of a WHO/IDF consultation. World Health Organization 2006
    PubMed
  • 3 Pop-Busui R, Evans GW, Gerstein HC. et al Action to Control Cardiovascular Risk in Diabetes Study Group Effects of cardiac autonomic dysfunction on mortality risk in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial. Diabetes Care 2010; 33: 1578-1584
    CrossrefPubMedGoogle Scholar
  • 4 Spallone V, Ziegler D, Freeman R. et al. Toronto Consensus Panel on Diabetic Neuropathy. Cardiovascular autonomic neuropathy in diabetes: Clinical impact, assessment, diagnosis, and management. Diabetes Metab Res Rev 2011; 27: 639-653
    CrossrefPubMedGoogle Scholar
  • 5 Vinik AI, Ziegler D. Diabetic cardiovascular autonomic neuropathy. Circulation 2007; 11: 387-397
    PubMedGoogle Scholar
  • 6 Ellenberg M. Diabetic neuropathy presenting as the initial clinical manifestation of diabetes. Ann Intern Med 1958; 49: 620-631
    PubMedGoogle Scholar
  • 7 Gaede P, Vedel P, Larsen N. et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003; 348: 383-393
    CrossrefPubMedGoogle Scholar
  • 8 Callaghan BC, Xia R, Banerjee M. et al. Metabolic syndrome components are associated with symptomatic polyneuropathy independent of glycemic status. Diabetes Care 2016; 39: 801-807
    CrossrefPubMedGoogle Scholar
  • 9 Campia U, Tesauro M, Di Daniele N. et al. The vascular endothelin system in obesity and type 2 diabetes: Pathophysiology and therapeutic implications. Life Sci 2014; 118: 149-155
    CrossrefPubMedGoogle Scholar
  • 10 Cusi K, Maezono K, Osman A. et al. Insulin resistance differentially affects the PI 3-kinase- and MAP kinase-mediated signaling in human muscle. J Clin Invest 2000; 105: 311-320
    CrossrefPubMedGoogle Scholar
  • 11 Kim JA, Montagnani M, Koh KK. et al. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms. Circulation 2006; 113: 1888-1904
    CrossrefPubMedGoogle Scholar
  • 12 Jiang ZY, Zhou QL, Chatterjee A. et al. Endothelin-1 modulates insulin signaling through phosphatidylinositol 3-kinase pathway in vascular smooth muscle cells. Diabetes 1999; 48: 1120-1130
    CrossrefPubMedGoogle Scholar
  • 13 Erbe DV, Wolitzky BA, Presta LG. et al. Identification of an E-selectin region critical for carbohydrate recognition and cell adhesion. J Cell Biol 1992; 119: 215-227
    CrossrefPubMedGoogle Scholar
  • 14 Taniguchi A, Fukushima M, Nakai Y. et al. Soluble E-selectin, leptin, triglycerides, and insulin resistance in nonobese Japanese type 2 diabetic patients. Metabolism 2005; 54: 376-380
    CrossrefPubMedGoogle Scholar
  • 15 Julia C, Czernichow S, Charnaux N. et al. Relationships between adipokines, biomarkers of endothelial function and inflammation and risk of type 2 diabetes. Diabetes Res Clin Pract 2014; 105: 231-238
    CrossrefPubMedGoogle Scholar
  • 16 Song Y, Manson JE, Tinker L. et al. Circulating levels of endothelial adhesion molecules and risk of diabetes in an ethnically diverse cohort of women. Diabetes 2007; 56: 1898-1904
    CrossrefPubMedGoogle Scholar
  • 17 Wu J, Liang Z, Zhou J. et al. Association of biomarkers of inflammation and endothelial dysfunction with fasting and postload glucose metabolism: A population-based prospective cohort study among inner Mongolians in China. Can J Diabetes 2016; 40: 509-514
    CrossrefPubMedGoogle Scholar
  • 18 Matsumoto K, Fujishima K, Moriuchi A. et al. Soluble adhesion molecule E-selectin predicts cardiovascular events in Japanese patients with type 2 diabetes mellitus. Metabolism 2010; 59: 320-324
    CrossrefPubMedGoogle Scholar
  • 19 Jude EB, Abbott CA, Young MJ. et al. The potential role of cell adhesion molecules in the pathogenesis of diabetic neuropathy. Diabetologia 1998; 41: 330-336
    CrossrefPubMedGoogle Scholar
  • 20 Albertini JP, Valensi P, Lormeau B. et al. Elevated concentrations of soluble E-selectin and vascular cell adhesion molecule-1 in NIDDM. Effect of intensive insulin treatment. Diabetes Care 1998; 21: 1008-1013
    CrossrefPubMedGoogle Scholar
  • 21 Tönjes A, Scholz M, Fasshauer M. et al. Beneficial effects of a 4-week exercise program on plasma concentrations of adhesion molecules. Diabetes Care 2007; 30: e1-e1
    CrossrefPubMedGoogle Scholar
  • 22 The International Diabetes Federation. The IDF Consensus Worldwide Definition of the Metabolic Syndrome Available at https://www.idf.org/webdata/docs/IDF_Metasyndrome_definition.pdf Accessed October 17 2005
    PubMed
  • 23 Mulder DJ, Water TV, Lutgers HL. et al. Skin autoflourescence, a novel marker for glycemic and oxidative stress-derived advanced glycation endproducts: An overview of current clinical studies, evidence, and limitations. Diabetes Technol Ther 2006; 8: 523-535
    CrossrefPubMedGoogle Scholar
  • 24 Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology . Heart rate variability, standards of measurement, physiological interpretation, and clinical use. Circulation 1996; 93: 1043-1065
    CrossrefPubMedGoogle Scholar
  • 25 Pop-Busui R, Boulton AJ, Feldman EL. et al. Diabetic neuropathy: A position statement by the american diabetes association. diabetes care 207 40 136-154
    PubMedGoogle Scholar
  • 26 Tesfaye S, Boulton AJ, Dyck PJ. et al. Diabetic neuropathies: Update on definitions, diagnostic criteria, estimation of severity, and treatments. Diabetes Care 2010; 33: 2285-2293
    CrossrefPubMedGoogle Scholar
  • 27 Dimova R, Tankova T, Guergueltcheva V. et al. Risk factors for autonomic and somatic nerve dysfunction in different stages of glucose tolerance. J Diabetes Complicat 2017; 31: 537-543
    CrossrefPubMedGoogle Scholar
  • 28 Dimova R, Tankova T, Chakarova N. et al. Cardio-metabolic profile of subjects with early stages of glucose intolerance and cardiovascular autonomic dysfunction. Diabetes Res Clin Pract 2017; 126: 115-121
    CrossrefPubMedGoogle Scholar
  • 29 DePace NL, Mears JP, Yayac M. et al. Cardiac autonomic testing and treating heart disease. A clinical perspective. Heart Int 2014; 9: 45-52
    PubMedGoogle Scholar
  • 30 Wu JS, Yang YC, Lin TS. et al. Epidemiological evidence of altered cardiac autonomic function in subjects with impaired glucose tolerance but not isolated fasting plasma glucose. J Clin Endocrinol Metab 2007; 92: 3885-3889
    CrossrefPubMedGoogle Scholar
  • 31 Ziegler D, Voss A, Rathmann W. et al. Increased prevalence of cardiac autonomic dysfunction at different degrees of glucose intolerance in the general population: The KORA S4 survey. Diabetologia 2015; 58: 1118-1128
    CrossrefPubMedGoogle Scholar
  • 32 Vinik AI, Aysin B, Colombo J. Differentiation of autonomic dysfunction by enhanced frequency domain analysis reveals additional stages in the progression of autonomic decline in diabetics. 5th Annual Diabetes Technology Meeting; San Francisco, CA: 10-12 November 2005
    Google Scholar
  • 33 Dimova R, Tankova T, Chakarova N. et al. Cardiovascular autonomic tone relation to metabolic parameters and hsCRP in normoglycemia and prediabetes. Diabetes Res Clin Pract 2015; 109: 262-270
    CrossrefPubMedGoogle Scholar
  • 34 Christou DD, Jones PP, Pimentel AE. et al. Increased abdominal-to-peripheral fat distribution contributes to altered autonomic-circulatory control with human aging. Am J Physiol 2004; 287: 1530-1537
    PubMedGoogle Scholar
  • 35 Koskinen T, Kähönen M, Jula A. et al. Metabolic syndrome and short-term heart rate variability in young adults: The cardiovascular risk in young Finns study. Diabetic Med 2009; 26: 354-361
    CrossrefPubMedGoogle Scholar
  • 36 Windham BG, Fumagalli S, Ble A et al. The Relationship between Heart Rate Variability and Adiposity Differs for Central and Overall Adiposity. J Obes 2012; 149516:
    PubMed
  • 37 Laitinen T, Lindström J, Eriksson J. et al. Cardiovascular autonomic dysfunction is associated with central obesity in persons with impaired glucose tolerance. Diabet Med 2011; 28: 699-704
    CrossrefPubMedGoogle Scholar
  • 38 Lindmark S, Lönn L, Wiklund U. et al. Dysregulation of the autonomic nervous system can be a link between visceral adiposity and insulin resistance. Obes Res 2005; 13: 717-728
    PubMedGoogle Scholar
  • 39 Laederach-Hofmann K, Mussgay L, Ruddel H. Autonomic cardiovascular regulation in obesity. J Endocrinol 2000; 164: 59-66
    CrossrefPubMedGoogle Scholar
  • 40 Piestrzeniewicz K, Luczak K, Lelonek M. et al. Obesity and heart rate variability in men with myocardial infarction. Cardiol J 2008; 15: 43-49
    PubMedGoogle Scholar
  • 41 Bray GA. Obesity, a disorder of nutrient partitioning: The MONA LISA hypothesis. J Nutr 1991; 121: 1146-1162
    CrossrefPubMedGoogle Scholar
  • 42 Peterson HR, Rothschild M, Weinberg CR. et al. Body fat and the activity of the autonomic nervous system. N Engl J Med 1988; 318: 1077-1083
    CrossrefPubMedGoogle Scholar
  • 43 Sztajzel J, Golay A, Makoundou V. et al. Impact of body fat mass extent on cardiac autonomic alterations in women. Eur J Clin Invest 2009; 39: 649-656
    CrossrefPubMedGoogle Scholar
  • 44 Chang C, Yang Y, Lu F. et al. Altered cardiac autonomic function may precede insulin resistance in metabolic syndrome. Am J Med 2010; 123: 432-438
    CrossrefPubMedGoogle Scholar
  • 45 Dekker JM, Schouten EG, Klootwijk P. et al. Heart rate variability from short electrocardiographic recordings predicts mortality from all causes in middle-aged and elderly men. The Zutphen Study. Am J Epidemiol 1997; 145: 899-908
    CrossrefPubMedGoogle Scholar
  • 46 Gerritsen J, Dekker JM. TenVoorde BJ et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: The Hoorn Study. Diabetes Care 2001; 24: 1793-1798
    CrossrefPubMedGoogle Scholar
  • 47 Liao D, Cai J, Brancati FL. et al. Association of vagal tone with serum insulin, glucose, and diabetes mellitus: The ARIC Study. Diabetes Res Clin Pract 1995; 30: 211-221
    CrossrefPubMedGoogle Scholar
  • 48 Singh JP, Larson MG, O'Donnell CJ. et al. Association of hyperglycemia with reduced heart rate variability (The Framingham Heart Study). Am J Cardiol 2000; 86: 309-312
    CrossrefPubMedGoogle Scholar
  • 49 Panzer C, Lauer MS, Brieke A. et al. Association of fasting plasma glucose with heart rate recovery in healthy adults: A population-based study. Diabetes 2002; 51: 803-807
    CrossrefPubMedGoogle Scholar
  • 50 DECODE Study Group . Glucose tolerance and cardio-vascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med 2001; 161: 397-405
    CrossrefPubMedGoogle Scholar
  • 51 Di Flaviani A, Picconi F, Di Stefano P. et al. Impact of glycemic and blood pressure variability on surrogate measures of cardiovascular outcomes in type 2 diabetic patients. Diabetes Care 2011; 34: 1605-1609
    CrossrefPubMedGoogle Scholar
  • 52 Fleischer J. Diabetic autonomic imbalance and glycemic variability. J Diabetes Sci Technol 2012; 6: 1207-1215
    CrossrefPubMedGoogle Scholar
  • 53 Franklin GM, Shetterly SM, Cohen JA. et al. Risk factors for distal symmetric neuropathy in NIDDM: The San Luis Valley Diabetes Study. Diabetes Care 1994; 17: 1172-1177
    CrossrefPubMedGoogle Scholar
  • 54 Lehtinen JM, Uusitupa M, Siitonen O. et al. Prevalence of neuropathy in newly diagnosed NIDDM and nondiabetic control subjects. Diabetes 1989; 3: 1308-1313
    PubMedGoogle Scholar
  • 55 Katon JG, Reiber GE, Nelson KM. Peripheral neuropathy defined by monofilament insensitivity and diabetes status: NHANES 1999–2004. Diabetes Care 2013; 36: 1604-1606
    CrossrefPubMedGoogle Scholar
  • 56 Meerwaldt R, Links TP, Graaff R. et al. Increased accumulation of skin advanced glycation end-products precedes and correlates with clinical manifestation of diabetic neuropathy. Diabetologia 2005; 48: 1637-1644
    CrossrefPubMedGoogle Scholar
  • 57 Anan F, Takahashi N, Nakagawa M. et al. High-sensitivity C-reactive protein is associated with insulin resistance and cardiovascular autonomic dysfunction in type 2 diabetic patients. Metabolism 2005; 54: 552-558
    CrossrefPubMedGoogle Scholar
  • 58 Thayer JF, Fischer JE. Heart rate variability, overnight urinary norepinephrine and C-reactive protein: Evidence for the cholinergic anti-inflammatory pathway in healthy human adults. J Intern Med 2009; 265: 439-447
    CrossrefPubMedGoogle Scholar
  • 59 Lieb D, Parson H, Mamikunian G. et al. Cardiac autonomic imbalance in newly diagnosed and established diabetes is associated with markers of adipose tissue inflammation. Exp Diabetes Res 2012; 1-8
    PubMedGoogle Scholar
  • 60 Gerritsen J, Dekker JM, TenVoorde BJ. et al. Impaired autonomic function is associated with increased mortality, especially in subjects with diabetes, hypertension, or a history of cardiovascular disease: The Hoorn Study. Diabetes Care 2001; 24: 1793-1798
    CrossrefPubMedGoogle Scholar
  • 61 Meyer C, Milat F, McGrath BP. et al. Vascular dysfunction and autonomic neuropathy in type 2 diabetes. Diabet Med 2004; 21: 746-751
    CrossrefPubMedGoogle Scholar
  • 62 Olausson J, Daka B, Hellgren MI. et al. Endothelin-1 as a predictor of impaired glucose tolerance and Type 2 diabetes – A longitudinal study in the Vara-Skövde Cohort. Diabetes Res Clin Pract 2016; 113: 33-37
    CrossrefPubMedGoogle Scholar
  • 63 Ferri C, Bellini C, Desideri G. et al. Circulating endothelin-1 levels in obese patients with the metabolic syndrome. Exp Clin Endocrinol Diabetes 1997; 105 (Suppl 2) 38-40
    Article in Thieme ConnectPubMedGoogle Scholar
  • 64 Wolpert HA, Steen SN, Istfan NW. et al. Insulin modulates circulating endothelin-1 levels in humans. Metabolism 1993; 42: 1027-1030
    CrossrefPubMedGoogle Scholar
  • 65 Hermans MP, Ahn SA, Gruson D. et al. The metabolic syndrome phenotype is associated with raised circulating Big endothelin-1 independently of coronary artery disease in type 2 diabetes. Diabetes Metab Syndr Clin Res Rev 2007; 1: 229-237
    CrossrefPubMedGoogle Scholar
  • 66 Caballero AE, Arora S, Saouaf R. et al. Microvascular and macrovascular reactivity is reduced in subjects at risk for type 2 diabetes. Diabetes 1999; 48: 1856-1862
    CrossrefPubMedGoogle Scholar
  • 67 Weil BR, Westby CM, Van Guilder GP. et al. Enhanced endothelin-1 system activity with overweight and obesity. Am J Physiol Heart Circ Physiol 2011; 301: H689-H695
    CrossrefPubMedGoogle Scholar
  • 68 Tesauro M, Schinzari F, Rovella V. et al. Ghrelin restores the endothelin 1/nitric oxide balance in patients with obesity-related metabolic syndrome. Hypertension 2009; 54: 995-1000
    CrossrefPubMedGoogle Scholar
  • 69 Rocha NG, Templeton DL, Greiner JJ. et al. Metabolic syndrome and endothelin-1 mediated vasoconstrictor tone in overweight/obese adults. Metabolism 2014; 63: 951-956
    CrossrefPubMedGoogle Scholar
  • 70 Diehl KJ, Templeton DL, Ma J. et al. Impaired fasting blood glucose is associated with increased endothelin-1 vasoconstrictor tone. Atherosclerosis 2013; 229: 130-133
    CrossrefPubMedGoogle Scholar
  • 71 Bertello P, Veglio F, Pinna G. et al. Plasma endothelin in NIDDM patients with and without complications. Diabetes Care 1994; 17: 574-577
    CrossrefPubMedGoogle Scholar
  • 72 De Mattia G, Bravi MC, Laurenti O. et al. Endothelial dysfunction and oxidative stress in type 1 and type 2 diabetic patients without clinical macrovascular complications. Diabetes Res Clin Pract 2008; 79: 337-342
    CrossrefPubMedGoogle Scholar
  • 73 Güvener N, Aytemir K, Aksöyek S. et al. Plasma endothelin-1 levels in non-insulin dependent diabetes mellitus patients with macrovascular disease. Coron Artery Dis 1997; 8: 253-258
    CrossrefPubMedGoogle Scholar
  • 74 Wagner OF, Christ G, Wojta J. et al. Polar secretion of endothelin-1 by cultured endothelial cells. J Biol Chem 1992; 267: 16066-16068
    CrossrefPubMedGoogle Scholar
  • 75 Cardillo C, Campia U, Bryant MB. et al. Increased activity of endogenous endothelin in patients with type II diabetes mellitus. Circulation 2002; 106: 1783-1787
    CrossrefPubMedGoogle Scholar
  • 76 Lteif A, Vaishnava P, Baron AD. et al. Endothelin limits insulin action in obese/insulin-resistant humans. Diabetes 2007; 56: 728-734
    CrossrefPubMedGoogle Scholar
  • 77 Ak G, Buyukberber S, Sevinc A. et al. The relation between plasma endothelin-1 levels and metabolic control, risk factors, treatment modalities, and diabetic microangiopathy in patients with type 2 diabetes mellitus. J Diabetes Complicat 2001; 15: 150-157
    CrossrefPubMedGoogle Scholar
  • 78 Blüher M, Unger R, Rassoul F. et al. Relation between glycaemic control, hyperinsulinaemia and plasma concentrations of soluble adhesion molecules in patients with impaired glucose tolerance or type II diabetes. Diabetologia 2002; 45: 210-216
    CrossrefPubMedGoogle Scholar
  • 79 Ferri C, Desideri G, Baldoncini R. et al. Early activation of vascular endothelium in nonobese, nondiabetic essential hypertensive patients with multiple metabolic abnormalities. Diabetes 1998; 47: 660-667
    CrossrefPubMedGoogle Scholar
  • 80 Adamska A, Karczewska-Kupczewska M, Nikołajuk A. et al. Relationships of serum soluble E-selectin concentration with insulin sensitivity and metabolic flexibility in lean and obese women. Endocrine 2014; 45: 422-429
    CrossrefPubMedGoogle Scholar
  • 81 Matsumoto K, Sera Y, Abe Y. et al. High serum concentrations of soluble E-selectin correlate with obesity but not fat distribution in patients with type 2 diabetes mellitus. Metabolism 2002; 51: 932-934
    CrossrefPubMedGoogle Scholar
  • 82 Zanni MV, Stanley TL, Makimura H. et al. Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulation. Clin Endocrinol (Oxf) 2010; 73: 48-54
    PubMedGoogle Scholar
  • 83 Pontiroli AE, Frigè F, Paganelli M. et al. In morbid obesity, metabolic abnormalities and adhesion molecules correlate with visceral fat, not with subcutaneous fat: Effect of weight loss through surgery. Obes Surg 2009; 19: 745-750
    CrossrefPubMedGoogle Scholar
  • 84 Targher G, Bonadonna RC, Alberiche M. et al. Relation between soluble adhesion molecules and insulin sensitivity in type 2 Diabetic individuals. Diabetes Care 2001; 24: 1961-1966
    CrossrefPubMedGoogle Scholar
  • 85 Fasching P, Veitl M, Rohac M. et al. Elevated concentrations of circulating adhesion molecules and their association with microvascular complications in insulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1996; 81: 4313-4317
    PubMedGoogle Scholar
  • 86 Kado S, Nagata N. Circulating intercellular adhesion molecule-1, vascular cell adhesion molecule-1, and E-selectin in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 1999; 46: 143-148
    CrossrefPubMedGoogle Scholar
  • 87 Matsumoto K, Miyake S, Yano M. et al. High serum concentrations of soluble E-selectin in patients with impaired glucose tolerance with hyperinsulinemia. Atherosclerosis 2000; 152: 415-420
    CrossrefPubMedGoogle Scholar
  • 88 Matsumoto K, Sera Y, Nakamura H. et al. Serum concentrations of soluble adhesion molecules are related to degree of hyperglycemia and insulin resistance in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2002; 55: 131-138
    CrossrefPubMedGoogle Scholar
  • 89 Petrie JR, Ueda S, Webb DJ. et al. Endothelial nitric oxide production and insulin sensitivity. A physiological link with implications for pathogenesis of cardiovascular disease. Circulation 1996; 93: 1331-1333
    CrossrefPubMedGoogle Scholar
  • 90 De Caterina R, Libby P, Peng HB. et al. Nitric oxide decreases cytokine-induced endothelial activation. Nitric oxide selectively reduces endothelial expression of adhesion molecules and proinflammatory cytokines. J Clin Invest 1995; 96: 60-68
    CrossrefPubMedGoogle Scholar
  • 91 Kowalska I, Straczkowski M, Szelachowska M. et al. Circulating E-Selectin, vascular cell adhesion molecule-1, and intercellular adhesion molecule-1 in men with coronary artery disease assessed by angiography and disturbances of carbohydrate metabolism. Metabolism 2002; 51: 733-736
    CrossrefPubMedGoogle Scholar
  • 92 Cominacini L, Fratta Pasini A, Garbin U. et al. Elevated levels of soluble E-selectin in patients with IDDM and NIDDM: relation to metabolic control. Diabetologia 1995; 38: 1122-1124
    CrossrefPubMedGoogle Scholar