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Glucose Homeostasis and Cardiovascular Alterations in Diabetes

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ABSTRACT

Diabetes mellitus is an increasingly prevalent disease associated with a high morbidity and mortality burden. Many of the adverse outcomes secondary to diabetes occur as a result of the impaired glucose homeostasis and pathophysiological alterations to the cardiovascular system. The purpose of this overview is to broadly discuss many of the changes that occur in the context of diabetes that affect cardiovascular function. Following a brief introduction to the classification and etiologies of the various forms of diabetes, the mechanisms of impaired glucose homeostasis will be covered. Vascular endothelial dysfunction, which has been posited to play a major role in the development of target organ pathology, will be addressed, followed by a discussion of the effects of diabetes on the renal, cardiovascular, and pulmonary systems. © 2015 American Physiological Society. Compr Physiol 5:1815‐1839, 2015.

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Figure 1. Figure 1. Physiological alterations that occur in diabetes that contribute to hyperglycemia and hyperlipidemia. UCP‐2, uncoupling protein‐2; GLP‐1, glucagon‐like peptide‐1; ROS, reactive oxygen species.
Figure 2. Figure 2. Endocrine, neural, and inflammatory pathways contributing to stress hyperglycemia (stress diabetes) following major physical stress. SNA, sympathetic nerve activity; CRH, corticotropin‐releasing hormone; ACTH, adrenocorticotropic hormone.
Figure 3. Figure 3. Factors that contribute to the development of endothelial dysfunction in diabetes. eNOS, endothelial nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species; AGEs, advanced glycation end‐products; ALEs, advanced lipoxidation end‐products; ER stress, endoplasmic reticulum stress.
Figure 4. Figure 4. Mechanisms by which diabetes and hyperglycemia contribute to an upregulation in superoxide production. UCP, uncoupling protein; BH4, tetrahydrobiopterin; eNOS, endothelial nitric oxide synthase; NOX, NADPH oxidase; O2, superoxide; ΔΨ, electron gradient. The dashed line indicates an inhibitory effect.
Figure 5. Figure 5. Schematic depicting mitochondrial production of reactive oxygen species. SOD, superoxide dismutase; O2, superoxide; H2O2, hydrogen peroxide; NO, nitric oxide; ONOO, peroxynitrite; H+, hydrogen ion; ADP, adenosine diphosphate; ATP, adenosine triphosphate; UCP, uncoupling protein; ΔΨ, electron gradient; I‐V, electron transport complexes I‐V. The dashed line indicates an inhibitory effect.
Figure 6. Figure 6. Mechanisms by which diabetes and chronic hyperglycemia lead to impaired kidney function and the development of diabetic kidney disease. GFR, glomerular filtration rate; TGF, tubuloglomerular feedback.
Figure 7. Figure 7. Schematic showing how diabetes and associated pathophysiological changes contribute to cardiovascular dysfunction and disease. ROS, reactive oxygen species; NO, nitric oxide; AGEs, advanced glycation end‐products; ALEs, advanced lipoxidation end‐products; VO2, oxygen consumption; ATP, adenosine triphosphate. The + symbol indicates a potentiating effect.
Figure 8. Figure 8. Overall schematic depicting how acute and chronic hyperglycemia contribute to end‐organ disease and mortality. ROS, reactive oxygen species. The + symbol indicates a potentiating effect.


Figure 1. Physiological alterations that occur in diabetes that contribute to hyperglycemia and hyperlipidemia. UCP‐2, uncoupling protein‐2; GLP‐1, glucagon‐like peptide‐1; ROS, reactive oxygen species.


Figure 2. Endocrine, neural, and inflammatory pathways contributing to stress hyperglycemia (stress diabetes) following major physical stress. SNA, sympathetic nerve activity; CRH, corticotropin‐releasing hormone; ACTH, adrenocorticotropic hormone.


Figure 3. Factors that contribute to the development of endothelial dysfunction in diabetes. eNOS, endothelial nitric oxide synthase; NO, nitric oxide; ROS, reactive oxygen species; AGEs, advanced glycation end‐products; ALEs, advanced lipoxidation end‐products; ER stress, endoplasmic reticulum stress.


Figure 4. Mechanisms by which diabetes and hyperglycemia contribute to an upregulation in superoxide production. UCP, uncoupling protein; BH4, tetrahydrobiopterin; eNOS, endothelial nitric oxide synthase; NOX, NADPH oxidase; O2, superoxide; ΔΨ, electron gradient. The dashed line indicates an inhibitory effect.


Figure 5. Schematic depicting mitochondrial production of reactive oxygen species. SOD, superoxide dismutase; O2, superoxide; H2O2, hydrogen peroxide; NO, nitric oxide; ONOO, peroxynitrite; H+, hydrogen ion; ADP, adenosine diphosphate; ATP, adenosine triphosphate; UCP, uncoupling protein; ΔΨ, electron gradient; I‐V, electron transport complexes I‐V. The dashed line indicates an inhibitory effect.


Figure 6. Mechanisms by which diabetes and chronic hyperglycemia lead to impaired kidney function and the development of diabetic kidney disease. GFR, glomerular filtration rate; TGF, tubuloglomerular feedback.


Figure 7. Schematic showing how diabetes and associated pathophysiological changes contribute to cardiovascular dysfunction and disease. ROS, reactive oxygen species; NO, nitric oxide; AGEs, advanced glycation end‐products; ALEs, advanced lipoxidation end‐products; VO2, oxygen consumption; ATP, adenosine triphosphate. The + symbol indicates a potentiating effect.


Figure 8. Overall schematic depicting how acute and chronic hyperglycemia contribute to end‐organ disease and mortality. ROS, reactive oxygen species. The + symbol indicates a potentiating effect.
References
 1.Centers for Disease Control and Prevention, National Vital Statistics Reports www.cdc.gov/nchs/data/nvsr/nvsr61/nvsr61_06.pdf. [Accessed 28 Oct 2014]
 2.American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care 27(Suppl 1): S5‐S10, 2004.
 3.International Diabetes Federation, About Diabetes http://www.idf. org/about‐diabetes. [Accessed 5 Nov 2014].
 4.National Institute of Diabetes and Digestive and Kidney Diseases. Diagnosis of diabetes and prediabetes www.diabetes.niddk.nih.gov/dm/ pubs/diagnosis/ [Accessed 5 Nov 2014].
 5.World Health Organization. Fact Sheets, Diabetes http://www.who.int/ mediacentre/factsheets/fs312/en/ [Accessed 28 Oct 2014].
 6.Adeghate E. Molecular and cellular basis of the aetiology and management of diabetic cardiomyopathy: A short review. Mol Cell Biochem 261: 187‐191, 2004.
 7.Adeghate E, Kalasz H, Veress G, Teke K. Medicinal chemistry of drugs used in diabetic cardiomyopathy. Curr Med Chem 17: 517‐551, 2010.
 8.Agarwal R, Duffin KL, Laska DA, Voelker JR, Breyer MD, Mitchell PG. A prospective study of multiple protein biomarkers to predict progression in diabetic chronic kidney disease. Nephrol Dial Transplant 29: 2293‐2302, 2014.
 9.Al‐Biltagi M, Tolba OA, Rowisha MA, Mahfouz AE, Elewa MA. Speckle tracking and myocardial tissue imaging in infant of diabetic mother with gestational and pregestational diabetes. Pediatr Cardiol 36: 445‐453, 2014.
 10.Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15: 539‐553, 1998.
 11.Alexiewicz JM, Kumar D, Smogorzewski M, Klin M, Massry SG. Polymorphonuclear leukocytes in non‐insulin‐dependent diabetes mellitus: Abnormalities in metabolism and function. Ann Intern Med 123: 919‐924, 1995.
 12.Ali MO. Pulmonary complications in diabetes mellitus. Mymensingh Med J 23: 603‐605, 2014.
 13.Alp NJ, Channon KM. Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease. Arterioscler Thromb Vasc Biol 24: 413‐420, 2004.
 14.American Diabetes A. Economic costs of diabetes in the U.S. in 2012. Diabetes Care 36: 1033‐1046, 2013.
 15.Amori RE, Lau J, Pittas AG. Efficacy and safety of incretin therapy in type 2 diabetes: Systematic review and meta‐analysis. JAMA 298: 194‐206, 2007.
 16.An J, Muoio DM, Shiota M, Fujimoto Y, Cline GW, Shulman GI, Koves TR, Stevens R, Millington D, Newgard CB. Hepatic expression of malonyl‐CoA decarboxylase reverses muscle, liver and whole‐animal insulin resistance. Nat Med 10: 268‐274, 2004.
 17.Andresdottir G, Jensen ML, Carstensen B, Parving HH, Hovind P, Hansen TW, Rossing P. Improved prognosis of diabetic nephropathy in type 1 diabetes. Kidney Int 87: 417‐426, 2014.
 18.Andresdottir G, Jensen ML, Carstensen B, Parving HH, Rossing K, Hansen TW, Rossing P. Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors. Diabetes Care 37: 1660‐1667, 2014.
 19.Araki E, Oyadomari S, Mori M. Impact of endoplasmic reticulum stress pathway on pancreatic beta‐cells and diabetes mellitus. Exp Biol Med (Maywood) 228: 1213‐1217, 2003.
 20.Atkinson MA, Eisenbarth GS, Michels AW. Type 1 diabetes. Lancet 383: 69‐82, 2014.
 21.Axelrod S, Lishner M, Oz O, Bernheim J, Ravid M. Spectral analysis of fluctuations in heart rate: An objective evaluation of autonomic nervous control in chronic renal failure. Nephron 45: 202‐206, 1987.
 22.Ayala A, Munoz MF, Arguelles S. Lipid peroxidation: Production, metabolism, and signaling mechanisms of malondialdehyde and 4‐hydroxy‐2‐nonenal. Oxid Med Cell Longev 2014: 360438, 2014.
 23.Aye MM, Kilpatrick ES, Aburima A, Wraith KS, Magwenzi S, Spurgeon B, Rigby AS, Sandeman D, Naseem KM, Atkin SL. Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome. J Am Heart Assoc 3: e000706, 2014.
 24.Baggio LL, Drucker DJ. Biology of incretins: GLP‐1 and GIP. Gastroenterology 132: 2131‐2157, 2007.
 25.Bansal S, Siddarth M, Chawla D, Banerjee BD, Madhu SV, Tripathi AK. Advanced glycation end products enhance reactive oxygen and nitrogen species generation in neutrophils in vitro. Mol Cell Biochem 361: 289‐296, 2012.
 26.Barnett AH, Bain SC, Bouter P, Karlberg B, Madsbad S, Jervell J, Mustonen J. Angiotensin‐receptor blockade versus converting‐enzyme inhibition in type 2 diabetes and nephropathy. N Engl J Med 351: 1952‐1961, 2004.
 27.Baynes JW, Thorpe SR. Glycoxidation and lipoxidation in atherogenesis. Free Radic Biol Med 28: 1708‐1716, 2000.
 28.Belke DD, Swanson EA, Dillmann WH. Decreased sarcoplasmic reticulum activity and contractility in diabetic db/db mouse heart. Diabetes 53: 3201‐3208, 2004.
 29.Bella JN, Devereux RB, Roman MJ, Palmieri V, Liu JE, Paranicas M, Welty TK, Lee ET, Fabsitz RR, Howard BV. Separate and joint effects of systemic hypertension and diabetes mellitus on left ventricular structure and function in American Indians (the Strong Heart Study). Am J Cardiol 87: 1260‐1265, 2001.
 30.Benfield T, Jensen JS, Nordestgaard BG. Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia 50: 549‐554, 2007.
 31.Bertoni AG, Tsai A, Kasper EK, Brancati FL. Diabetes and idiopathic cardiomyopathy: A nationwide case‐control study. Diabetes Care 26: 2791‐2795, 2003.
 32.Betz B, Conway BR. Recent advances in animal models of diabetic nephropathy. Nephron Exp Nephrol 126: 191‐195, 2014.
 33.Bhatt DL, Fox KA, Hacke W, Berger PB, Black HR, Boden WE, Cacoub P, Cohen EA, Creager MA, Easton JD, Flather MD, Haffner SM, Hamm CW, Hankey GJ, Johnston SC, Mak KH, Mas JL, Montalescot G, Pearson TA, Steg PG, Steinhubl SR, Weber MA, Brennan DM, Fabry‐Ribaudo L, Booth J, Topol EJ. Clopidogrel and aspirin versus aspirin alone for the prevention of atherothrombotic events. N Engl J Med 354: 1706‐1717, 2006.
 34.Bjorntorp P, Rosmond R. Obesity and cortisol. Nutrition 16: 924‐936, 2000.
 35.Blantz RC, Singh P. Glomerular and tubular function in the diabetic kidney. Adv Chronic Kidney Dis 21: 297‐303, 2014.
 36.Boden G, Vaidyula VR, Homko C, Cheung P, Rao AK. Circulating tissue factor procoagulant activity and thrombin generation in patients with type 2 diabetes: Effects of insulin and glucose. J Clin Endocrinol Metab 92: 4352‐4358, 2007.
 37.Bolli G, de Feo P, Compagnucci P, Cartechini MG, Angeletti G, Santeusanio F, Brunetti P, Gerich JE. Abnormal glucose counterregulation in insulin‐dependent diabetes mellitus. Interaction of anti‐insulin antibodies and impaired glucagon and epinephrine secretion. Diabetes 32: 134‐141, 1983.
 38.Boudina S, Abel ED. Mitochondrial uncoupling: A key contributor to reduced cardiac efficiency in diabetes. Physiology (Bethesda) 21: 250‐258, 2006.
 39.Boudina S, Sena S, O'Neill BT, Tathireddy P, Young ME, Abel ED. Reduced mitochondrial oxidative capacity and increased mitochondrial uncoupling impair myocardial energetics in obesity. Circulation 112: 2686‐2695, 2005.
 40.Boulbou MS, Koukoulis GN, Makri ED, Petinaki EA, Gourgoulianis KI, Germenis AE. Circulating adhesion molecules levels in type 2 diabetes mellitus and hypertension. Int J Cardiol 98: 39‐44, 2005.
 41.Boyko EJ, Fihn SD, Scholes D, Abraham L, Monsey B. Risk of urinary tract infection and asymptomatic bacteriuria among diabetic and nondiabetic postmenopausal women. Am J Epidemiol 161: 557‐564, 2005.
 42.Brandt MM, Falvo AJ, Rubinfeld IS, Blyden D, Durrani NK, Horst HM. Renal dysfunction in trauma: Even a little costs a lot. J Trauma 62: 1362‐1364, 2007.
 43.Brassard P, Ferland A, Bogaty P, Desmeules M, Jobin J, Poirier P. Influence of glycemic control on pulmonary function and heart rate in response to exercise in subjects with type 2 diabetes mellitus. Metabolism 55: 1532‐1537, 2006.
 44.Brinkkoetter PT, Ising C, Benzing T. The role of the podocyte in albumin filtration. Nat Rev Nephrol 9: 328‐336, 2013.
 45.Brosius FC, Coward RJ. Podocytes, signaling pathways, and vascular factors in diabetic kidney disease. Adv Chronic Kidney Dis 21: 304‐310, 2014.
 46.Bruno A, Liebeskind D, Hao Q, Raychev R, Investigators US. Diabetes mellitus, acute hyperglycemia, and ischemic stroke. Curr Treat Options Neurol 12: 492‐503, 2010.
 47.Byrnes MC, McDaniel MD, Moore MB, Helmer SD, Smith RS. The effect of obesity on outcomes among injured patients. J Trauma 58: 232‐237, 2005.
 48.Cai D, Yuan M, Frantz DF, Melendez PA, Hansen L, Lee J, Shoelson SE. Local and systemic insulin resistance resulting from hepatic activation of IKK‐beta and NF‐kappaB. Nat Med 11: 183‐190, 2005.
 49.Cai H, Harrison DG. Endothelial dysfunction in cardiovascular diseases: The role of oxidant stress. Circ Res 87: 840‐844, 2000.
 50.Cai L, Kang YJ. Oxidative stress and diabetic cardiomyopathy: A brief review. Cardiovasc Toxicol 1: 181‐193, 2001.
 51.Cai L, Kang YJ. Cell death and diabetic cardiomyopathy. Cardiovasc Toxicol 3: 219‐228, 2003.
 52.Cai L, Wang Y, Zhou G, Chen T, Song Y, Li X, Kang YJ. Attenuation by metallothionein of early cardiac cell death via suppression of mitochondrial oxidative stress results in a prevention of diabetic cardiomyopathy. J Am Coll Cardiol 48: 1688‐1697, 2006.
 53.Calabia J, Torguet P, Garcia I, Martin N, Mate G, Marin A, Molina C, Valles M. The relationship between renal resistive index, arterial stiffness, and atherosclerotic burden: The link between macrocirculation and microcirculation. J Clin Hypertens (Greenwich) 16: 186‐191, 2014.
 54.Capes SE, Hunt D, Malmberg K, Pathak P, Gerstein HC. Stress hyperglycemia and prognosis of stroke in nondiabetic and diabetic patients: A systematic overview. Stroke 32: 2426‐2432, 2001.
 55.Cartin‐Ceba R, Kashiouris M, Plataki M, Kor DJ, Gajic O, Casey ET. Risk factors for development of acute kidney injury in critically ill patients: A systematic review and meta‐analysis of observational studies. Crit Care Res Pract 2012: 691013, 2012.
 56.Cesario DA, Brar R, Shivkumar K. Alterations in ion channel physiology in diabetic cardiomyopathy. Endocrinol Metab Clin North Am 35: 601‐610, ix‐x, 2006.
 57.Chade AR. Renal vascular structure and rarefaction. Compr Physiol 3: 817‐831, 2013.
 58.Charbonneau A, Marette A. Inducible nitric oxide synthase induction underlies lipid‐induced hepatic insulin resistance in mice: Potential role of tyrosine nitration of insulin signaling proteins. Diabetes 59: 861‐871, 2010.
 59.Chaudry IH, Sayeed MM, Baue AE. Insulin resistance in experimental shock. Arch Surg 109: 412‐415, 1974.
 60.Chawla LS, Kimmel PL. Acute kidney injury and chronic kidney disease: An integrated clinical syndrome. Kidney Int 82: 516‐524, 2012.
 61.Chen A, Mumick S, Zhang C, Lamb J, Dai H, Weingarth D, Mudgett J, Chen H, MacNeil DJ, Reitman ML, Qian S. Diet induction of monocyte chemoattractant protein‐1 and its impact on obesity. Obes Res 13: 1311‐1320, 2005.
 62.Chen J, Zhang Z, Cai L. Diabetic cardiomyopathy and its prevention by nrf2: Current status. Diabetes Metab J 38: 337‐345, 2014.
 63.Chen LH, Leung PS. Inhibition of the sodium glucose co‐transporter‐2: Its beneficial action and potential combination therapy for type 2 diabetes mellitus. Diabetes Obes Metab 15: 392‐402, 2013.
 64.Chen M, Robertson RP. Effects of prostaglandin synthesis inhibitors on human insulin secretion and carbohydrates tolerance. Prostaglandins 18: 557‐567, 1979.
 65.Chen Y, Liao WX, Roy AC, Loganath A, Ng SC. Mitochondrial gene mutations in gestational diabetes mellitus. Diabetes Res Clin Pract 48: 29‐35, 2000.
 66.Cheng J, Zhang W, Zhang X, Han F, Li X, He X, Li Q, Chen J. Effect of angiotensin‐converting enzyme inhibitors and angiotensin II receptor blockers on all‐cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: A meta‐analysis. JAMA Intern Med 174: 773‐785, 2014.
 67.Cherney DZ, Reich HN, Jiang S, Har R, Nasrallah R, Hebert RL, Lai V, Scholey JW, Sochett EB. Hyperfiltration and effect of nitric oxide inhibition on renal and endothelial function in humans with uncomplicated type 1 diabetes mellitus. Am J Physiol Regul Integr Comp Physiol 303: R710‐R718, 2012.
 68.Choban PS, Weireter LJ Jr., Maynes C. Obesity and increased mortality in blunt trauma. J Trauma 31: 1253‐1257, 1991.
 69.Chu SY, Callaghan WM, Kim SY, Schmid CH, Lau J, England LJ, Dietz PM. Maternal obesity and risk of gestational diabetes mellitus. Diabetes Care 30: 2070‐2076, 2007.
 70.Clementi E, Nisoli E. Nitric oxide and mitochondrial biogenesis: A key to long‐term regulation of cellular metabolism. Comp Biochem Physiol A Mol Integr Physiol 142: 102‐110, 2005.
 71.Clemmer J, Xiang L, Lu S, Mittwede P, Hester R. B2‐adrenergic regulation of stress hyperglycemia following hemorrhage in the obese Zucker rat. Physiol Rep 2: e12215, 2014.
 72.Cohen P. The twentieth century struggle to decipher insulin signalling. Nat Rev Mol Cell Biol 7: 867‐873, 2006.
 73.Coiro V, Volpi R, Capretti L, Speroni G, Caffarra P, Scaglioni A, Malvezzi L, Castelli A, Caffarri G, Rossi G, et al. Low‐dose ovine corticotropin‐releasing hormone stimulation test in diabetes mellitus with or without neuropathy. Metabolism 44: 538‐542, 1995.
 74.Coleman JW. Nitric oxide in immunity and inflammation. Int Immunopharmacol 1: 1397‐1406, 2001.
 75.Cosentino F, Luscher TF. Tetrahydrobiopterin and endothelial nitric oxide synthase activity. Cardiovasc Res 43: 274‐278, 1999.
 76.Coughlan MT, Thorburn DR, Penfold SA, Laskowski A, Harcourt BE, Sourris KC, Tan AL, Fukami K, Thallas‐Bonke V, Nawroth PP, Brownlee M, Bierhaus A, Cooper ME, Forbes JM. RAGE‐induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol 20: 742‐752, 2009.
 77.Coward RJ, Welsh GI, Yang J, Tasman C, Lennon R, Koziell A, Satchell S, Holman GD, Kerjaschki D, Tavare JM, Mathieson PW, Saleem MA. The human glomerular podocyte is a novel target for insulin action. Diabetes 54: 3095‐3102, 2005.
 78.Cox AJ, Hsu FC, Freedman BI, Herrington DM, Criqui MH, Carr JJ, Bowden DW. Contributors to mortality in high‐risk diabetic patients in the Diabetes Heart Study. Diabetes Care 37: 2798‐2803, 2014.
 79.Davidson NJ, Sowden JM, Fletcher J. Defective phagocytosis in insulin controlled diabetics: Evidence for a reaction between glucose and opsonising proteins. J Clin Pathol 37: 783‐786, 1984.
 80.Davidson SM, Duchen MR. Endothelial mitochondria: Contributing to vascular function and disease. Circ Res 100: 1128‐1141, 2007.
 81.Davis WA, Knuiman M, Kendall P, Grange V, Davis TM. Glycemic exposure is associated with reduced pulmonary function in type 2 diabetes: The Fremantle Diabetes Study. Diabetes Care 27: 752‐757, 2004.
 82.de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, Himmelfarb J. Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 305: 2532‐2539, 2011.
 83.Delamaire M, Maugendre D, Moreno M, Le Goff MC, Allannic H, Genetet B. Impaired leucocyte functions in diabetic patients. Diabet Med 14: 29‐34, 1997.
 84.Delbin MA, Davel AP, Couto GK, de Araujo GG, Rossoni LV, Antunes E, Zanesco A. Interaction between advanced glycation end products formation and vascular responses in femoral and coronary arteries from exercised diabetic rats. PLoS One 7: e53318, 2012.
 85.Di Carli MF, Hachamovitch R. Should we screen for occult coronary artery disease among asymptomatic patients with diabetes? J Am Coll Cardiol 45: 50‐53, 2005.
 86.Diener HC, Bogousslavsky J, Brass LM, Cimminiello C, Csiba L, Kaste M, Leys D, Matias‐Guiu J, Rupprecht HJ. Aspirin and clopidogrel compared with clopidogrel alone after recent ischaemic stroke or transient ischaemic attack in high‐risk patients (MATCH): randomised, double‐blind, placebo‐controlled trial. Lancet 364: 331‐337, 2004.
 87.Dooley KE, Chaisson RE. Tuberculosis and diabetes mellitus: Convergence of two epidemics. Lancet Infect Dis 9: 737‐746, 2009.
 88.Dornhorst A, Paterson CM, Nicholls JS, Wadsworth J, Chiu DC, Elkeles RS, Johnston DG, Beard RW. High prevalence of gestational diabetes in women from ethnic minority groups. Diabet Med 9: 820‐825, 1992.
 89.Drucker DJ, Nauck MA. The incretin system: Glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors in type 2 diabetes. Lancet 368: 1696‐1705, 2006.
 90.Duncan JG. Mitochondrial dysfunction in diabetic cardiomyopathy. Biochim Biophys Acta 1813: 1351‐1359, 2011.
 91.Duplain H, Burcelin R, Sartori C, Cook S, Egli M, Lepori M, Vollenweider P, Pedrazzini T, Nicod P, Thorens B, Scherrer U. Insulin resistance, hyperlipidemia, and hypertension in mice lacking endothelial nitric oxide synthase. Circulation 104: 342‐345, 2001.
 92.Dvorakova MC, Kruzliak P, Rabkin SW. Role of neuropeptides in cardiomyopathies. Peptides 61C: 1‐6, 2014.
 93.Eid AA, Gorin Y, Fagg BM, Maalouf R, Barnes JL, Block K, Abboud HE. Mechanisms of podocyte injury in diabetes: Role of cytochrome P450 and NADPH oxidases. Diabetes 58: 1201‐1211, 2009.
 94.Elmistekawy E, McDonald B, Hudson C, Ruel M, Mesana T, Chan V, Boodhwani M. Clinical impact of mild acute kidney injury after cardiac surgery. Ann Thorac Surg 98: 815‐822, 2014.
 95.Emre Y, Nubel T. Uncoupling protein UCP2: When mitochondrial activity meets immunity. FEBS Lett 584: 1437‐1442, 2010.
 96.Enomoto T, Usuki J, Azuma A, Nakagawa T, Kudoh S. Diabetes mellitus may increase risk for idiopathic pulmonary fibrosis. Chest 123: 2007‐2011, 2003.
 97.Erdmann J, Stark K, Esslinger UB, Rumpf PM, Koesling D, de Wit C, Kaiser FJ, Braunholz D, Medack A, Fischer M, Zimmermann ME, Tennstedt S, Graf E, Eck S, Aherrahrou Z, Nahrstaedt J, Willenborg C, Bruse P, Braenne I, Nothen MM, Hofmann P, Braund PS, Mergia E, Reinhard W, Burgdorf C, Schreiber S, Balmforth AJ, Hall AS, Bertram L, Steinhagen‐Thiessen E, Li SC, Marz W, Reilly M, Kathiresan S, McPherson R, Walter U, CARDIoGRAM, Ott J, Samani NJ, Strom TM, Meitinger T, Hengstenberg C, Schunkert H. Dysfunctional nitric oxide signalling increases risk of myocardial infarction. Nature 504: 432‐436, 2013.
 98.Ergul A. Endothelin‐1 and diabetic complications: Focus on the vasculature. Pharmacol Res 63: 477‐482, 2011.
 99.Eriksen BO, Ingebretsen OC. The progression of chronic kidney disease: A 10‐year population‐based study of the effects of gender and age. Kidney Int 69: 375‐382, 2006.
 100.Esper AM, Moss M, Martin GS. The effect of diabetes mellitus on organ dysfunction with sepsis: An epidemiological study. Crit Care 13: R18, 2009.
 101.Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: Role of oxidative stress. Circulation 106: 2067‐2072, 2002.
 102.Fadini GP, Sartore S, Agostini C, Avogaro A. Significance of endothelial progenitor cells in subjects with diabetes. Diabetes Care 30: 1305‐1313, 2007.
 103.Fadini GP, Sartore S, Albiero M, Baesso I, Murphy E, Menegolo M, Grego F, Vigili de Kreutzenberg S, Tiengo A, Agostini C, Avogaro A. Number and function of endothelial progenitor cells as a marker of severity for diabetic vasculopathy. Arterioscler Thromb Vasc Biol 26: 2140‐2146, 2006.
 104.Fang ZY, Prins JB, Marwick TH. Diabetic cardiomyopathy: Evidence, mechanisms, and therapeutic implications. Endocr Rev 25: 543‐567, 2004.
 105.Farina J, Furio V, Fernandez‐Acenero MJ, Muzas MA. Nodular fibrosis of the lung in diabetes mellitus. Virchows Arch 427: 61‐63, 1995.
 106.Fehm HL, Holl R, Spath‐Schwalbe E, Born J, Voigt KH. Ability of corticotropin releasing hormone to stimulate cortisol secretion independent from pituitary adrenocorticotropin. Life Sci 42: 679‐686, 1988.
 107.Fernandez‐Fernandez B, Ortiz A, Gomez‐Guerrero C, Egido J. Therapeutic approaches to diabetic nephropathy–beyond the RAS. Nat Rev Nephrol 10: 325‐346, 2014.
 108.Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, Kapoor WN. Prognosis and outcomes of patients with community‐acquired pneumonia. A meta‐analysis. JAMA 275: 134‐141, 1996.
 109.Fiordaliso F, Li B, Latini R, Sonnenblick EH, Anversa P, Leri A, Kajstura J. Myocyte death in streptozotocin‐induced diabetes in rats in angiotensin II‐ dependent. Lab Invest 80: 513‐527, 2000.
 110.Fitchett DH, Gupta M, Farkouh ME, Verma S. Cardiology Patient Page: Coronary artery revascularization in patients with diabetes mellitus. Circulation 130: e104‐e106, 2014.
 111.Flarsheim CE, Grupp IL, Matlib MA. Mitochondrial dysfunction accompanies diastolic dysfunction in diabetic rat heart. Am J Physiol 271: H192‐H202, 1996.
 112.Flynn ER, Lee J, Hutchens ZM Jr., Chade AR, and Maric‐Bilkan C. C‐peptide preserves the renal microvascular architecture in the streptozotocin‐induced diabetic rat. J Diabetes Complications 27: 538‐547, 2013.
 113.Fontana P, Zufferey A, Daali Y, Reny JL. Antiplatelet therapy: Targeting the TxA2 pathway. J Cardiovasc Transl Res 7: 29‐38, 2014.
 114.Frank JA, Nuckton TJ, Matthay MA. Diabetes mellitus: A negative predictor for the development of acute respiratory distress syndrome from septic shock. Crit Care Med 28: 2645‐2646, 2000.
 115.Franzen S, Friederich‐Persson M, Fasching A, Hansell P, Nangaku M, Palm F. Differences in susceptibility to develop parameters of diabetic nephropathy in four mouse strains with type 1 diabetes. Am J Physiol Renal Physiol 306: F1171‐F1178, 2014.
 116.Freidja ML, Vessieres E, Toutain B, Guihot AL, Custaud MA, Loufrani L, Fassot C, Henrion D. AGEs breaking and antioxidant treatment improves endothelium‐dependent dilation without effect on flow‐mediated remodeling of resistance arteries in old Zucker diabetic rats. Cardiovasc Diabetol 13: 55, 2014.
 117.Friederich‐Persson M, Thorn E, Hansell P, Nangaku M, Levin M, Palm F. Kidney hypoxia, attributable to increased oxygen consumption, induces nephropathy independently of hyperglycemia and oxidative stress. Hypertension 62: 914‐919, 2013.
 118.Frustaci A, Kajstura J, Chimenti C, Jakoniuk I, Leri A, Maseri A, Nadal‐Ginard B, Anversa P. Myocardial cell death in human diabetes. Circ Res 87: 1123‐1132, 2000.
 119.Fu J, Lee K, Chuang PY, Liu Z, He JC. Glomerular endothelial cell injury and crosstalk in diabetic kidney disease. Am J Physiol Renal Physiol 308: F287‐F297, 2014.
 120.Fu MX, Requena JR, Jenkins AJ, Lyons TJ, Baynes JW, Thorpe SR. The advanced glycation end product, Nepsilon‐(carboxymethyl)lysine, is a product of both lipid peroxidation and glycoxidation reactions. J Biol Chem 271: 9982‐9986, 1996.
 121.Fukami K, Yamagishi S, Okuda S. Role of AGEs‐RAGE system in cardiovascular disease. Curr Pharm Des 20: 2395‐2402, 2014.
 122.Gangadhariah MH, Luther JM, Garcia V, Paueksakon P, Zhang MZ, Hayward SW, Love HD, Falck JR, Manthati VL, Imig JD, Schwartzman ML, Zent R, Capdevila JH, Pozzi A. Hypertension is a major contributor to 20‐hydroxyeicosatetraenoic acid‐mediated kidney injury in diabetic nephropathy. J Am Soc Nephrol 26: 597‐610, 2014.
 123.Gao G, Zhang B, Ramesh G, Betterly D, Tadagavadi RK, Wang W, Reeves WB. TNF‐alpha mediates increased susceptibility to ischemic AKI in diabetes. Am J Physiol Renal Physiol 304: F515‐F521, 2013.
 124.Gargalovic PS, Gharavi NM, Clark MJ, Pagnon J, Yang WP, He A, Truong A, Baruch‐Oren T, Berliner JA, Kirchgessner TG, Lusis AJ. The unfolded protein response is an important regulator of inflammatory genes in endothelial cells. Arterioscler Thromb Vasc Biol 26: 2490‐2496, 2006.
 125.Gathercole LL, Stewart PM. Targeting the pre‐receptor metabolism of cortisol as a novel therapy in obesity and diabetes. J Steroid Biochem Mol Biol 122: 21‐27, 2010.
 126.Gilbert RE. The endothelium in diabetic nephropathy. Curr Atheroscler Rep 16: 410, 2014.
 127.Givertz MM, Sawyer DB, Colucci WS. Antioxidants and myocardial contractility: Illuminating the “Dark Side” of beta‐adrenergic receptor activation? Circulation 103: 782‐783, 2001.
 128.Golbidi S, Ebadi SA, Laher I. Antioxidants in the treatment of diabetes. Curr Diabetes Rev 7: 106‐125, 2011.
 129.Gong MN, Thompson BT, Williams P, Pothier L, Boyce PD, Christiani DC. Clinical predictors of and mortality in acute respiratory distress syndrome: Potential role of red cell transfusion. Crit Care Med 33: 1191‐1198, 2005.
 130.Goodwill AG, James ME, Frisbee JC. Increased vascular thromboxane generation impairs dilation of skeletal muscle arterioles of obese Zucker rats with reduced oxygen tension. Am J Physiol Heart Circ Physiol 295: H1522‐H1528, 2008.
 131.Gregg EW, Beckles GL, Williamson DF, Leveille SG, Langlois JA, Engelgau MM, Narayan KM. Diabetes and physical disability among older U.S. adults. Diabetes Care 23: 1272‐1277, 2000.
 132.Group DCaCTR. 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. N Engl J Med 329: 977‐986, 1993.
 133.Group DCaCTR. Effect of intensive diabetes treatment on the development and progression of long‐term complications in adolescents with insulin‐dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group. J Pediatr 125: 177‐188, 1994.
 134.Guazzi M, Brambilla R, De Vita S, Guazzi MD. Diabetes worsens pulmonary diffusion in heart failure, and insulin counteracts this effect. Am J Respir Crit Care Med 166: 978‐982, 2002.
 135.Guzman J, Jauregui AN, Merscher‐Gomez S, Maiguel D, Muresan C, Mitrofanova A, Diez‐Sampedro A, Szust J, Yoo TH, Villarreal R, Pedigo C, Molano RD, Johnson K, Kahn B, Hartleben B, Huber TB, Saha J, Burke GW, 3rd, Abel ED, Brosius FC, Fornoni A. Podocyte‐specific GLUT4‐deficient mice have fewer and larger podocytes and are protected from diabetic nephropathy. Diabetes 63: 701‐714, 2014.
 136.Gyurko R, Siqueira CC, Caldon N, Gao L, Kantarci A, Van Dyke TE. Chronic hyperglycemia predisposes to exaggerated inflammatory response and leukocyte dysfunction in Akita mice. J Immunol 177: 7250‐7256, 2006.
 137.Halter JB, Beard JC, Porte D Jr. Islet function and stress hyperglycemia: Plasma glucose and epinephrine interaction. Am J Physiol 247: E47‐E52, 1984.
 138.Hamasaki S, Higano ST, Suwaidi JA, Nishimura RA, Miyauchi K, Holmes DR Jr., Lerman A. Cholesterol‐lowering treatment is associated with improvement in coronary vascular remodeling and endothelial function in patients with normal or mildly diseased coronary arteries. Arterioscler Thromb Vasc Biol 20: 737‐743, 2000.
 139.Hansell P, Welch WJ, Blantz RC, Palm F. Determinants of kidney oxygen consumption and their relationship to tissue oxygen tension in diabetes and hypertension. Clin Exp Pharmacol Physiol 40: 123‐137, 2013.
 140.Har R, Scholey JW, Daneman D, Mahmud FH, Dekker R, Lai V, Elia Y, Fritzler ML, Sochett EB, Reich HN, Cherney DZ. The effect of renal hyperfiltration on urinary inflammatory cytokines/chemokines in patients with uncomplicated type 1 diabetes mellitus. Diabetologia 56: 1166‐1173, 2013.
 141.Harris DG, McCrone MP, Koo G, Weltz AS, Chiu WC, Scalea TM, Diaz JJ, Lissauer ME. Epidemiology and outcomes of acute kidney injury in critically ill surgical patients. J Crit Care 30: 102‐106, 2015.
 142.Havel PJ, Mundinger TO, Taborsky GJ Jr. Pancreatic sympathetic nerves contribute to increased glucagon secretion during severe hypoglycemia in dogs. Am J Physiol 270: E20‐E26, 1996.
 143.Havel PJ, Veith RC, Dunning BE, Taborsky GJ Jr. Pancreatic noradrenergic nerves are activated by neuroglucopenia but not by hypotension or hypoxia in the dog. Evidence for stress‐specific and regionally selective activation of the sympathetic nervous system. J Clin Invest 82: 1538‐1545, 1988.
 144.Hayat SA, Patel B, Khattar RS, Malik RA. Diabetic cardiomyopathy: Mechanisms, diagnosis and treatment. Clin Sci (Lond) 107: 539‐557, 2004.
 145.Heaberlin JR, Ma Y, Zhang J, Ahuja SS, Lindsey ML, Halade GV. Obese and diabetic KKAy mice show increased mortality but improved cardiac function following myocardial infarction. Cardiovasc Pathol 22: 481‐487, 2013.
 146.Helal I, Fick‐Brosnahan GM, Reed‐Gitomer B, Schrier RW. Glomerular hyperfiltration: Definitions, mechanisms and clinical implications. Nat Rev Nephrol 8: 293‐300, 2012.
 147.Herman‐Edelstein M, Thomas MC, Thallas‐Bonke V, Saleem M, Cooper ME, Kantharidis P. Dedifferentiation of immortalized human podocytes in response to transforming growth factor‐beta: A model for diabetic podocytopathy. Diabetes 60: 1779‐1788, 2011.
 148.Hirosumi J, Tuncman G, Chang L, Gorgun CZ, Uysal KT, Maeda K, Karin M, Hotamisligil GS. A central role for JNK in obesity and insulin resistance. Nature 420: 333‐336, 2002.
 149.Hishinuma T, Tsukamoto H, Suzuki K, Mizugaki M. Relationship between thromboxane/prostacyclin ratio and diabetic vascular complications. Prostaglandins Leukot Essent Fatty Acids 65: 191‐196, 2001.
 150.Hoeldtke RD, Boden G. Epinephrine secretion, hypoglycemia unawareness, and diabetic autonomic neuropathy. Ann Intern Med 120: 512‐517, 1994.
 151.Hoeldtke RD, Boden G, Shuman CR, Owen OE. Reduced epinephrine secretion and hypoglycemia unawareness in diabetic autonomic neuropathy. Ann Intern Med 96: 459‐462, 1982.
 152.Homko C, Sivan E, Chen X, Reece EA, Boden G. Insulin secretion during and after pregnancy in patients with gestational diabetes mellitus. J Clin Endocrinol Metab 86: 568‐573, 2001.
 153.Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS‐1‐mediated inhibition of insulin receptor tyrosine kinase activity in TNF‐alpha‐ and obesity‐induced insulin resistance. Science 271: 665‐668, 1996.
 154.Hu G, Sarti C, Jousilahti P, Peltonen M, Qiao Q, Antikainen R, Tuomilehto J. The impact of history of hypertension and type 2 diabetes at baseline on the incidence of stroke and stroke mortality. Stroke 36: 2538‐2543, 2005.
 155.Huang HC, Preisig PA. G1 kinases and transforming growth factor‐beta signaling are associated with a growth pattern switch in diabetes‐induced renal growth. Kidney Int 58: 162‐172, 2000.
 156.Hudson JI, Hudson MS, Rothschild AJ, Vignati L, Schatzberg AF, Melby JC. Abnormal results of dexamethasone suppression tests in nondepressed patients with diabetes mellitus. Arch Gen Psychiatry 41: 1086‐1089, 1984.
 157.Hur J, Sullivan KA, Schuyler AD, Hong Y, Pande M, States DJ, Jagadish HV, Feldman EL. Literature‐based discovery of diabetes‐ and ROS‐related targets. BMC Med Genomics 3: 49, 2010.
 158.Iqbal N, Seshadri P, Stern L, Loh J, Kundu S, Jafar T, Samaha FF. Serum resistin is not associated with obesity or insulin resistance in humans. Eur Rev Med Pharmacol Sci 9: 161‐165, 2005.
 159.Iwai‐Kanai E, Hasegawa K. Intracellular signaling pathways for norepinephrine‐ and endothelin‐1‐mediated regulation of myocardial cell apoptosis. Mol Cell Biochem 259: 163‐168, 2004.
 160.Jafar TH, Stark PC, Schmid CH, Landa M, Maschio G, de Jong PE, de Zeeuw D, Shahinfar S, Toto R, Levey AS. Progression of chronic kidney disease: The role of blood pressure control, proteinuria, and angiotensin‐converting enzyme inhibition: A patient‐level meta‐analysis. Ann Intern Med 139: 244‐252, 2003.
 161.Jesmin S, Zaedi S, Maeda S, Yamaguchi I, Goto K, Miyauchi T. Effects of a selective endothelin a receptor antagonist on the expressions of iNOS and eNOS in the heart of early streptozotocin‐induced diabetic rats. Exp Biol Med (Maywood) 231: 925‐931, 2006.
 162.Jha JC, Gray SP, Barit D, Okabe J, El‐Osta A, Namikoshi T, Thallas‐Bonke V, Wingler K, Szyndralewiez C, Heitz F, Touyz RM, Cooper ME, Schmidt HH, Jandeleit‐Dahm KA. Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long‐term diabetic nephropathy. J Am Soc Nephrol 25: 1237‐1254, 2014.
 163.Jha JC, Jandeleit‐Dahm KA, Cooper ME. New insights into the use of biomarkers of diabetic nephropathy. Adv Chronic Kidney Dis 21: 318‐326, 2014.
 164.John GW, Doxey JC, Walter DS, Reid JL. The role of alpha‐ and beta‐adrenoceptor subtypes in mediating the effects of catecholamines on fasting glucose and insulin concentrations in the rat. Br J Pharmacol 100: 699‐704, 1990.
 165.Jormsjo S, Ye S, Moritz J, Walter DH, Dimmeler S, Zeiher AM, Henney A, Hamsten A, Eriksson P. Allele‐specific regulation of matrix metalloproteinase‐12 gene activity is associated with coronary artery luminal dimensions in diabetic patients with manifest coronary artery disease. Circ Res 86: 998‐1003, 2000.
 166.Joseph JW, Koshkin V, Zhang CY, Wang J, Lowell BB, Chan CB, Wheeler MB. Uncoupling protein 2 knockout mice have enhanced insulin secretory capacity after a high‐fat diet. Diabetes 51: 3211‐3219, 2002.
 167.Jweied EE, McKinney RD, Walker LA, Brodsky I, Geha AS, Massad MG, Buttrick PM, de Tombe PP. Depressed cardiac myofilament function in human diabetes mellitus. Am J Physiol Heart Circ Physiol 289: H2478‐H2483, 2005.
 168.Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of type 2 diabetes: Perspectives on the past, present, and future. Lancet 383: 1068‐1083, 2014.
 169.Kanety H, Feinstein R, Papa MZ, Hemi R, Karasik A. Tumor necrosis factor alpha‐induced phosphorylation of insulin receptor substrate‐1 (IRS‐1). Possible mechanism for suppression of insulin‐stimulated tyrosine phosphorylation of IRS‐1. J Biol Chem 270: 23780‐23784, 1995.
 170.Kasznicki J, Kosmalski M, Sliwinska A, Mrowicka M, Stanczyk M, Majsterek I, Drzewoski J. Evaluation of oxidative stress markers in pathogenesis of diabetic neuropathy. Mol Biol Rep 39: 8669‐8678, 2012.
 171.Kato M, Natarajan R. Diabetic nephropathy–emerging epigenetic mechanisms. Nat Rev Nephrol 10: 517‐530, 2014.
 172.Kautzky‐Willer A, Krssak M, Winzer C, Pacini G, Tura A, Farhan S, Wagner O, Brabant G, Horn R, Stingl H, Schneider B, Waldhausl W, Roden M. Increased intramyocellular lipid concentration identifies impaired glucose metabolism in women with previous gestational diabetes. Diabetes 52: 244‐251, 2003.
 173.Kautzky‐Willer A, Prager R, Waldhausl W, Pacini G, Thomaseth K, Wagner OF, Ulm M, Streli C, Ludvik B. Pronounced insulin resistance and inadequate beta‐cell secretion characterize lean gestational diabetes during and after pregnancy. Diabetes Care 20: 1717‐1723, 1997.
 174.Kelly KJ, Burford JL, Dominguez JH. Postischemic inflammatory syndrome: A critical mechanism of progression in diabetic nephropathy. Am J Physiol Renal Physiol 297: F923‐F931, 2009.
 175.Khazim K, Gorin Y, Cavaglieri RC, Abboud HE, Fanti P. The antioxidant silybin prevents high glucose‐induced oxidative stress and podocyte injury in vitro and in vivo. Am J Physiol Renal Physiol 305: F691‐F700, 2013.
 176.Khoury JC, Kleindorfer D, Alwell K, Moomaw CJ, Woo D, Adeoye O, Flaherty ML, Khatri P, Ferioli S, Broderick JP, Kissela BM. Diabetes mellitus: A risk factor for ischemic stroke in a large biracial population. Stroke 44: 1500‐1504, 2013.
 177.Kido Y, Nakae J, Accili D. Clinical review 125: The insulin receptor and its cellular targets. J Clin Endocrinol Metab 86: 972‐979, 2001.
 178.Kim C, Berger DK, Chamany S. Recurrence of gestational diabetes mellitus: A systematic review. Diabetes Care 30: 1314‐1319, 2007.
 179.Kim C, Newton KM, Knopp RH. Gestational diabetes and the incidence of type 2 diabetes: A systematic review. Diabetes Care 25: 1862‐1868, 2002.
 180.Kim JA, Montagnani M, Koh KK, Quon MJ. Reciprocal relationships between insulin resistance and endothelial dysfunction: Molecular and pathophysiological mechanisms. Circulation 113: 1888‐1904, 2006.
 181.Kim JA, Wei Y, Sowers JR. Role of mitochondrial dysfunction in insulin resistance. Circ Res 102: 401‐414, 2008.
 182.Kjems LL, Holst JJ, Volund A, Madsbad S. The influence of GLP‐1 on glucose‐stimulated insulin secretion: Effects on beta‐cell sensitivity in type 2 and nondiabetic subjects. Diabetes 52: 380‐386, 2003.
 183.Knop FK, Vilsboll T, Hojberg PV, Larsen S, Madsbad S, Volund A, Holst JJ, Krarup T. Reduced incretin effect in type 2 diabetes: Cause or consequence of the diabetic state? Diabetes 56: 1951‐1959, 2007.
 184.Kobayashi S, Liang Q. Autophagy and mitophagy in diabetic cardiomyopathy. Biochim Biophys Acta 1852: 252‐261, 2014.
 185.Kodolova IM, Lysenko LV, Saltykov BB. [Changes in the lungs in diabetes mellitus]. Arkh Patol 44: 35‐40, 1982.
 186.Kornum JB, Thomsen RW, Riis A, Lervang HH, Schonheyder HC, Sorensen HT. Type 2 diabetes and pneumonia outcomes: A population‐based cohort study. Diabetes Care 30: 2251‐2257, 2007.
 187.Kornum JB, Thomsen RW, Riis A, Lervang HH, Schonheyder HC, Sorensen HT. Diabetes, glycemic control, and risk of hospitalization with pneumonia: A population‐based case‐control study. Diabetes Care 31: 1541‐1545, 2008.
 188.Kousta E, Ellard S, Allen LI, Saker PJ, Huxtable SJ, Hattersley AT, McCarthy MI. Glucokinase mutations in a phenotypically selected multiethnic group of women with a history of gestational diabetes. Diabet Med 18: 683‐684, 2001.
 189.Koves TR, Li P, An J, Akimoto T, Slentz D, Ilkayeva O, Dohm GL, Yan Z, Newgard CB, Muoio DM. Peroxisome proliferator‐activated receptor‐gamma co‐activator 1alpha‐mediated metabolic remodeling of skeletal myocytes mimics exercise training and reverses lipid‐induced mitochondrial inefficiency. J Biol Chem 280: 33588‐33598, 2005.
 190.Krankel N, Adams V, Linke A, Gielen S, Erbs S, Lenk K, Schuler G, Hambrecht R. Hyperglycemia reduces survival and impairs function of circulating blood‐derived progenitor cells. Arterioscler Thromb Vasc Biol 25: 698‐703, 2005.
 191.Krauss S, Zhang CY, Scorrano L, Dalgaard LT, St‐Pierre J, Grey ST, Lowell BB. Superoxide‐mediated activation of uncoupling protein 2 causes pancreatic beta cell dysfunction. J Clin Invest 112: 1831‐1842, 2003.
 192.Kumar PA, Brosius FC, III, Menon RK. The glomerular podocyte as a target of growth hormone action: Implications for the pathogenesis of diabetic nephropathy. Curr Diabetes Rev 7: 50‐55, 2011.
 193.Kumar R, Yong QC, Thomas CM, Baker KM. Intracardiac intracellular angiotensin system in diabetes. Am J Physiol Regul Integr Comp Physiol 302: R510‐R517, 2012.
 194.Laird AM, Miller PR, Kilgo PD, Meredith JW, Chang MC. Relationship of early hyperglycemia to mortality in trauma patients. J Trauma 56: 1058‐1062, 2004.
 195.Lautt WW, Martens ES, Legare DJ. Insulin and glucagon response during hemorrhage induced hyperglycemia. Can J Physiol Pharmacol 60: 1624‐1629, 1982.
 196.Laybutt DR, Sharma A, Sgroi DC, Gaudet J, Bonner‐Weir S, Weir GC. Genetic regulation of metabolic pathways in beta‐cells disrupted by hyperglycemia. J Biol Chem 277: 10912‐10921, 2002.
 197.Lenoir O, Milon M, Virsolvy A, Henique C, Schmitt A, Masse JM, Kotelevtsev Y, Yanagisawa M, Webb DJ, Richard S, Tharaux PL. Direct action of endothelin‐1 on podocytes promotes diabetic glomerulosclerosis. J Am Soc Nephrol 25: 1050‐1062, 2014.
 198.Levi M, van der Poll T, Buller HR. Bidirectional relation between inflammation and coagulation. Circulation 109: 2698‐2704, 2004.
 199.Li JM, Shah AM. Endothelial cell superoxide generation: Regulation and relevance for cardiovascular pathophysiology. Am J Physiol Regul Integr Comp Physiol 287: R1014‐R1030, 2004.
 200.Li SY, Huang PH, Yang AH, Tarng DC, Yang WC, Lin CC, Chen JW, Schmid‐Schonbein G, Lin SJ. Matrix metalloproteinase‐9 deficiency attenuates diabetic nephropathy by modulation of podocyte functions and dedifferentiation. Kidney Int 86: 358‐369, 2014.
 201.Lindsay TH, Halvorson KG, Peters CM, Ghilardi JR, Kuskowski MA, Wong GY, Mantyh PW. A quantitative analysis of the sensory and sympathetic innervation of the mouse pancreas. Neuroscience 137: 1417‐1426, 2006.
 202.Liu X, Suzuki H, Sethi R, Tappia PS, Takeda N, Dhalla NS. Blockade of the renin‐angiotensin system attenuates sarcolemma and sarcoplasmic reticulum remodeling in chronic diabetes. Ann N Y Acad Sci 1084: 141‐154, 2006.
 203.Lowell BB, Shulman GI. Mitochondrial dysfunction and type 2 diabetes. Science 307: 384‐387, 2005.
 204.Lu S, Xiang L, Clemmer JS, Mittwede PN, Hester RL. Oxidative stress increases pulmonary vascular permeability in diabetic rats through activation of transient receptor potential melastatin 2 channels. Microcirculation 21: 754‐760, 2014.
 205.Lu X, Guo X, Karathanasis SK, Zimmerman KM, Onyia JE, Peterson RG, Kassab GS. Rosiglitazone reverses endothelial dysfunction but not remodeling of femoral artery in Zucker diabetic fatty rats. Cardiovasc Diabetol 9: 19, 2010.
 206.Ma Y, Toth B, Keeton AB, Holland LT, Chaudry IH, Messina JL. Mechanisms of hemorrhage‐induced hepatic insulin resistance: Role of tumor necrosis factor‐alpha. Endocrinology 145: 5168‐5176, 2004.
 207.Maahs DM, West NA, Lawrence JM, Mayer‐Davis EJ. Epidemiology of type 1 diabetes. Endocrinol Metab Clin North Am 39: 481‐497, 2010.
 208.Maiese K. Turning up the pressure on vascular disease. Curr Neurovasc Res 11: 291‐293, 2014.
 209.Makarevich AE, Valevich VE, Pochtavtsev AU. Evaluation of pulmonary hypertension in COPD patients with diabetes. Adv Med Sci 52: 265‐272, 2007.
 210.Makino H, Okada S, Nagumo A, Sugisawa T, Miyamoto Y, Kishimoto I, Kikuchi‐Taura A, Soma T, Taguchi A, Yoshimasa Y. Decreased circulating CD34+ cells are associated with progression of diabetic nephropathy. Diabet Med 26: 171‐173, 2009.
 211.Malmberg K. Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. DIGAMI (Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group. BMJ 314: 1512‐1515, 1997.
 212.Malmberg K, Ryden L, Wedel H, Birkeland K, Bootsma A, Dickstein K, Efendic S, Fisher M, Hamsten A, Herlitz J, Hildebrandt P, MacLeod K, Laakso M, Torp‐Pedersen C, Waldenstrom A, Investigators D. Intense metabolic control by means of insulin in patients with diabetes mellitus and acute myocardial infarction (DIGAMI 2): effects on mortality and morbidity. Eur Heart J 26: 650‐661, 2005.
 213.Marchetti P, Bugliani M, Lupi R, Marselli L, Masini M, Boggi U, Filipponi F, Weir GC, Eizirik DL, Cnop M. The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients. Diabetologia 50: 2486‐2494, 2007.
 214.Marfella R, Esposito K, Giunta R, Coppola G, De Angelis L, Farzati B, Paolisso G, Giugliano D. Circulating adhesion molecules in humans: Role of hyperglycemia and hyperinsulinemia. Circulation 101: 2247‐2251, 2000.
 215.Marhoffer W, Stein M, Maeser E, Federlin K. Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes. Diabetes Care 15: 256‐260, 1992.
 216.Maric‐Bilkan C, Flynn ER, Chade AR. Microvascular disease precedes the decline in renal function in the streptozotocin‐induced diabetic rat. Am J Physiol Renal Physiol 302: F308‐F315, 2012.
 217.Marquez E, Riera M, Pascual J, Soler MJ. Renin angiotensin system within the diabetic podocyte. Am J Physiol Renal Physiol 308: F1‐F10, 2014.
 218.McAlpine CS, Bowes AJ, Werstuck GH. Diabetes, hyperglycemia and accelerated atherosclerosis: Evidence supporting a role for endoplasmic reticulum (ER) stress signaling. Cardiovasc Hematol Disord Drug Targets 10: 151‐157, 2010.
 219.McCance DR, Hanson RL, Charles MA, Jacobsson LT, Pettitt DJ, Bennett PH, Knowler WC. Comparison of tests for glycated haemoglobin and fasting and two hour plasma glucose concentrations as diagnostic methods for diabetes. BMJ 308: 1323‐1328, 1994.
 220.McCowen KC, Malhotra A, Bistrian BR. Stress‐induced hyperglycemia. Crit Care Clin 17: 107‐124, 2001.
 221.McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, Clark PM, Smith SA, Barnett AH, Kumar S. Resistin and type 2 diabetes: Regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 88: 6098‐6106, 2003.
 222.Mei Q, Mundinger TO, Lernmark A, Taborsky GJ Jr. Early, selective, and marked loss of sympathetic nerves from the islets of BioBreeder diabetic rats. Diabetes 51: 2997‐3002, 2002.
 223.Melsom T, Mathisen UD, Ingebretsen OC, Jenssen TG, Njolstad I, Solbu MD, Toft I, Eriksen BO. Impaired fasting glucose is associated with renal hyperfiltration in the general population. Diabetes Care 34: 1546‐1551, 2011.
 224.Mittwede PN, Xiang L, Lu S, Clemmer JS, Hester RL. Oxidative stress contributes to orthopedic trauma‐induced acute kidney injury in obese rats. Am J Physiol Renal Physiol 308: F157‐F163, 2015.
 225.Monami M, Nardini C, Mannucci E. Efficacy and safety of sodium glucose co‐transport‐2 inhibitors in type 2 diabetes: A meta‐analysis of randomized clinical trials. Diabetes Obes Metab 16: 457‐466, 2014.
 226.Montanari A, Biggi A, Cabassi A, Pelloni I, Pigazzani F, Pinelli S, Pela G, Musiari L, Cherney DZ. Renal hemodynamic response to L‐arginine in uncomplicated, type 1 diabetes mellitus: The role of buffering anions and tubuloglomerular feedback. Am J Physiol Renal Physiol 303: F648‐F658, 2012.
 227.Mora‐Fernandez C, Dominguez‐Pimentel V, de Fuentes MM, Gorriz JL, Martinez‐Castelao A, Navarro‐Gonzalez JF. Diabetic kidney disease: From physiology to therapeutics. J Physiol 592: 3997‐4012, 2014.
 228.Moratinos J, Carpene C, de Pablos I, Reverte M. Role of alpha 1‐ and alpha 2‐adrenoceptors in catecholamine‐induced hyperglycaemia, lipolysis and insulin secretion in conscious fasted rabbits. Br J Pharmacol 94: 299‐310, 1988.
 229.Morgan SA, Sherlock M, Gathercole LL, Lavery GG, Lenaghan C, Bujalska IJ, Laber D, Yu A, Convey G, Mayers R, Hegyi K, Sethi JK, Stewart PM, Smith DM, Tomlinson JW. 11beta‐hydroxysteroid dehydrogenase type 1 regulates glucocorticoid‐induced insulin resistance in skeletal muscle. Diabetes 58: 2506‐2515, 2009.
 230.Moriya T, Tsuchiya A, Okizaki S, Hayashi A, Tanaka K, Shichiri M. Glomerular hyperfiltration and increased glomerular filtration surface are associated with renal function decline in normo‐ and microalbuminuric type 2 diabetes. Kidney Int 81: 486‐493, 2012.
 231.Moss GS, Cerchio G, Siegel DC, Reed PC, Cochin A, Fresquez V. Decline in pancreatic insulin release during hemorrhagic shock in the baboon. Ann Surg 175: 210‐213, 1972.
 232.Moss M, Guidot DM, Steinberg KP, Duhon GF, Treece P, Wolken R, Hudson LD, Parsons PE. Diabetic patients have a decreased incidence of acute respiratory distress syndrome. Crit Care Med 28: 2187‐2192, 2000.
 233.Movahed MR, Hashemzadeh M, Jamal MM. The prevalence of pulmonary embolism and pulmonary hypertension in patients with type II diabetes mellitus. Chest 128: 3568‐3571, 2005.
 234.Muller WA, Faloona GR, Unger RH. Hyperglucagonemia in diabetic ketoacidosis. Its prevalence and significance. Am J Med 54: 52‐57, 1973.
 235.Muniyappa R, Iantorno M, Quon MJ. An integrated view of insulin resistance and endothelial dysfunction. Endocrinol Metab Clin North Am 37: 685‐711, ix‐x, 2008.
 236.Muoio DM, Newgard CB. Obesity‐related derangements in metabolic regulation. Annu Rev Biochem 75: 367‐401, 2006.
 237.Mustapha NM, Tarr JM, Kohner EM, Chibber R. NADPH oxidase versus mitochondria‐derived ROS in glucose‐induced apoptosis of pericytes in early diabetic retinopathy. J Ophthalmol 2010: 746978, 2010.
 238.Myint PK, Sinha S, Wareham NJ, Bingham SA, Luben RN, Welch AA, Khaw KT. Glycated hemoglobin and risk of stroke in people without known diabetes in the European Prospective Investigation into Cancer (EPIC)‐Norfolk prospective population study: A threshold relationship? Stroke 38: 271‐275, 2007.
 239.Nagaev I, Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 285: 561‐564, 2001.
 240.Nagareddy PR, Xia Z, McNeill JH, MacLeod KM. Increased expression of iNOS is associated with endothelial dysfunction and impaired pressor responsiveness in streptozotocin‐induced diabetes. Am J Physiol Heart Circ Physiol 289: H2144‐H2152, 2005.
 241.Nakagawa T, Tanabe K, Croker BP, Johnson RJ, Grant MB, Kosugi T, Li Q. Endothelial dysfunction as a potential contributor in diabetic nephropathy. Nat Rev Nephrol 7: 36‐44, 2011.
 242.Nakatani Y, Kaneto H, Kawamori D, Hatazaki M, Miyatsuka T, Matsuoka TA, Kajimoto Y, Matsuhisa M, Yamasaki Y, Hori M. Modulation of the JNK pathway in liver affects insulin resistance status. J Biol Chem 279: 45803‐45809, 2004.
 243.Nakazawa J, Isshiki K, Sugimoto T, Araki S, Kume S, Yokomaku Y, Chin‐Kanasaki M, Sakaguchi M, Koya D, Haneda M, Kashiwagi A, Uzu T. Renoprotective effects of asialoerythropoietin in diabetic mice against ischaemia‐reperfusion‐induced acute kidney injury. Nephrology (Carlton) 15: 93‐101, 2010.
 244.Navar LG. Intrarenal renin‐angiotensin system in regulation of glomerular function. Curr Opin Nephrol Hypertens 23: 38‐45, 2014.
 245.Navar LG, Kobori H, Prieto MC, Gonzalez‐Villalobos RA. Intratubular renin‐angiotensin system in hypertension. Hypertension 57: 355‐362, 2011.
 246.Navarro‐Gonzalez JF, Mora‐Fernandez C, Muros de Fuentes M, Garcia‐Perez J. Inflammatory molecules and pathways in the pathogenesis of diabetic nephropathy. Nat Rev Nephrol 7: 327‐340, 2011.
 247.Neville AL, Brown CV, Weng J, Demetriades D, Velmahos GC. Obesity is an independent risk factor of mortality in severely injured blunt trauma patients. Arch Surg 139: 983‐987, 2004.
 248.Nichols GA, Hillier TA, Erbey JR, Brown JB. Congestive heart failure in type 2 diabetes: Prevalence, incidence, and risk factors. Diabetes Care 24: 1614‐1619, 2001.
 249.Nishikawa T, Edelstein D, Du XL, Yamagishi S, Matsumura T, Kaneda Y, Yorek MA, Beebe D, Oates PJ, Hammes HP, Giardino I, Brownlee M. Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404: 787‐790, 2000.
 250.Nomura S. Dynamic role of microparticles in type 2 diabetes mellitus. Curr Diabetes Rev 5: 245‐251, 2009.
 251.Nordquist L, Friederich‐Persson M, Fasching A, Liss P, Shoji K, Nangaku M, Hansell P, Palm F. Activation of hypoxia‐inducible factors prevents diabetic nephropathy. J Am Soc Nephrol 26: 328‐338, 2015.
 252.O'Driscoll G, Green D, Rankin J, Stanton K, Taylor R. Improvement in endothelial function by angiotensin converting enzyme inhibition in insulin‐dependent diabetes mellitus. J Clin Invest 100: 678‐684, 1997.
 253.O'Toole JF, Sedor JR. Kidney disease: New technologies translate mechanisms to cure. J Clin Invest 124: 2294‐2298, 2014.
 254.Okada R, Yasuda Y, Tsushita K, Wakai K, Hamajima N, Matsuo S. Glomerular hyperfiltration in prediabetes and prehypertension. Nephrol Dial Transplant 27: 1821‐1825, 2012.
 255.Okapcova J, Gabor D. The levels of soluble adhesion molecules in diabetic and nondiabetic patients with combined hyperlipoproteinemia and the effect of ciprofibrate therapy. Angiology 55: 629‐639, 2004.
 256.Oliveira PJ, Seica R, Coxito PM, Rolo AP, Palmeira CM, Santos MS, Moreno AJ. Enhanced permeability transition explains the reduced calcium uptake in cardiac mitochondria from streptozotocin‐induced diabetic rats. FEBS Lett 554: 511‐514, 2003.
 257.Olver TD, Mattar L, Grise KN, Twynstra J, Noble EG, Lacefield JC, Shoemaker JK. Glucose‐stimulated insulin secretion causes an insulin‐dependent nitric oxide‐mediated vasodilation in the blood supply of the rat sciatic nerve. Am J Physiol Regul Integr Comp Physiol 305: R157‐R163, 2013.
 258.Palsson R, Patel UD. Cardiovascular complications of diabetic kidney disease. Adv Chronic Kidney Dis 21: 273‐280, 2014.
 259.Pant R, Marok R, Klein LW. Pathophysiology of coronary vascular remodeling: Relationship with traditional risk factors for coronary artery disease. Cardiol Rev 22: 13‐16, 2014.
 260.Paravicini TM, Touyz RM. NADPH oxidases, reactive oxygen species, and hypertension: Clinical implications and therapeutic possibilities. Diabetes Care 31(Suppl 2): S170‐180, 2008.
 261.Park M, Yoon E, Lim YH, Kim H, Choi J, Yoon HJ. Renal hyperfiltration as a novel marker of all‐cause mortality. J Am Soc Nephrol pii: ASN.2014010115, 2014.
 262.Patel DG. Role of parasympathetic nervous system in glucagon response to insulin‐induced hypoglycemia in normal and diabetic rats. Metabolism 33: 1123‐1127, 1984.
 263.Patinha D, Fasching A, Pinho D, Albino‐Teixeira A, Morato M, Palm F. Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors. Am J Physiol Renal Physiol 304: F614‐F622, 2013.
 264.Patti G, Proscia C, Di Sciascio G. Antiplatelet therapy in patients with diabetes mellitus and acute coronary syndrome. Circ J 78: 33‐41, 2014.
 265.Pautz A, Art J, Hahn S, Nowag S, Voss C, Kleinert H. Regulation of the expression of inducible nitric oxide synthase. Nitric Oxide 23: 75‐93, 2010.
 266.Peng J, Li X, Zhang D, Chen JK, Su Y, Smith SB, Dong Z. Hyperglycemia, p53, and mitochondrial pathway of apoptosis are involved in the susceptibility of diabetic models to ischemic acute kidney injury. Kidney Int 87: 137‐150, 2015.
 267.Peraldi P, Hotamisligil GS, Buurman WA, White MF, Spiegelman BM. Tumor necrosis factor (TNF)‐alpha inhibits insulin signaling through stimulation of the p55 TNF receptor and activation of sphingomyelinase. J Biol Chem 271: 13018‐13022, 1996.
 268.Persson P, Hansell P, Palm F. Tubular reabsorption and diabetes‐induced glomerular hyperfiltration. Acta Physiol (Oxf) 200: 3‐10, 2010.
 269.Persson P, Hansell P, Palm F. Reduced adenosine A receptor‐mediated efferent arteriolar vasodilation contributes to diabetes‐induced glomerular hyperfiltration. Kidney Int 109‐115, 2015.
 270.Pinkney JH, Stehouwer CD, Coppack SW, Yudkin JS. Endothelial dysfunction: Cause of the insulin resistance syndrome. Diabetes 46(Suppl 2): S9‐13, 1997.
 271.Pitocco D, Zaccardi F, Di Stasio E, Romitelli F, Santini SA, Zuppi C, Ghirlanda G. Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud 7: 15‐25, 2010.
 272.Ponchiardi C, Mauer M, Najafian B. Temporal profile of diabetic nephropathy pathologic changes. Curr Diab Rep 13: 592‐599, 2013.
 273.Pop‐Busui R, Kirkwood I, Schmid H, Marinescu V, Schroeder J, Larkin D, Yamada E, Raffel DM, Stevens MJ. Sympathetic dysfunction in type 1 diabetes: Association with impaired myocardial blood flow reserve and diastolic dysfunction. J Am Coll Cardiol 44: 2368‐2374, 2004.
 274.Pugliese G. Updating the natural history of diabetic nephropathy. Acta Diabetol 51: 905‐915, 2014.
 275.Puthanveetil P, Wang Y, Zhang D, Wang F, Kim MS, Innis S, Pulinilkunnil T, Abrahani A, Rodrigues B. Cardiac triglyceride accumulation following acute lipid excess occurs through activation of a FoxO1‐iNOS‐CD36 pathway. Free Radic Biol Med 51: 352‐363, 2011.
 276.Puthanveetil P, Zhang D, Wang Y, Wang F, Wan A, Abrahani A, Rodrigues B. Diabetes triggers a PARP1 mediated death pathway in the heart through participation of FoxO1. J Mol Cell Cardiol 53: 677‐686, 2012.
 277.Rajesh M, Mukhopadhyay P, Batkai S, Patel V, Saito K, Matsumoto S, Kashiwaya Y, Horvath B, Mukhopadhyay B, Becker L, Hasko G, Liaudet L, Wink DA, Veves A, Mechoulam R, Pacher P. Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy. J Am Coll Cardiol 56: 2115‐2125, 2010.
 278.Ramirez LC, Dal Nogare A, Hsia C, Arauz C, Butt I, Strowig SM, Schnurr‐Breen L, Raskin P. Relationship between diabetes control and pulmonary function in insulin‐dependent diabetes mellitus. Am J Med 91: 371‐376, 1991.
 279.Randriamboavonjy V, Fleming I. Insulin, insulin resistance, and platelet signaling in diabetes. Diabetes Care 32: 528‐530, 2009.
 280.Reece EA, Leguizamon G, Wiznitzer A. Gestational diabetes: The need for a common ground. Lancet 373: 1789‐1797, 2009.
 281.Rehman AU, Dugic E, Benham C, Lione L, Mackenzie LS. Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta. Redox Biol 2C: 61‐64, 2013.
 282.Ren J, Pulakat L, Whaley‐Connell A, Sowers JR. Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. J Mol Med (Berl) 88: 993‐1001, 2010.
 283.Retnakaran R, Hanley AJ, Raif N, Connelly PW, Sermer M, Zinman B. C‐reactive protein and gestational diabetes: The central role of maternal obesity. J Clin Endocrinol Metab 88: 3507‐3512, 2003.
 284.Riddell DR, Owen JS. Nitric oxide and platelet aggregation. Vitam Horm 57: 25‐48, 1999.
 285.Robitaille J, Grant AM. The genetics of gestational diabetes mellitus: Evidence for relationship with type 2 diabetes mellitus. Genet Med 10: 240‐250, 2008.
 286.Rochette L, Lorin J, Zeller M, Guilland JC, Lorgis L, Cottin Y, Vergely C. Nitric oxide synthase inhibition and oxidative stress in cardiovascular diseases: Possible therapeutic targets? Pharmacol Ther 140: 239‐257, 2013.
 287.Roe ND, Ren J. Nitric oxide synthase uncoupling: A therapeutic target in cardiovascular diseases. Vascul Pharmacol 57: 168‐172, 2012.
 288.Rollini F, Franchi F, Muniz‐Lozano A, Angiolillo DJ. Platelet function profiles in patients with diabetes mellitus. J Cardiovasc Transl Res 6: 329‐345, 2013.
 289.Roscioni SS, Heerspink HJ, de Zeeuw D. The effect of RAAS blockade on the progression of diabetic nephropathy. Nat Rev Nephrol 10: 77‐87, 2014.
 290.Roy MS, Roy A, Gallucci WT, Collier B, Young K, Kamilaris TC, Chrousos GP. The ovine corticotropin‐releasing hormone‐stimulation test in type I diabetic patients and controls: Suggestion of mild chronic hypercortisolism. Metabolism 42: 696‐700, 1993.
 291.Ruggenenti P, Porrini EL, Gaspari F, Motterlini N, Cannata A, Carrara F, Cella C, Ferrari S, Stucchi N, Parvanova A, Iliev I, Dodesini AR, Trevisan R, Bossi A, Zaletel J, Remuzzi G, Investigators GFRS. Glomerular hyperfiltration and renal disease progression in type 2 diabetes. Diabetes Care 35: 2061‐2068, 2012.
 292.Ruiz‐Hurtado G, Ruilope LM. Does cardiovascular protection translate into renal protection? Nat Rev Cardiol 11: 742‐746, 2014.
 293.Sacco RL, Benson RT, Kargman DE, Boden‐Albala B, Tuck C, Lin IF, Cheng JF, Paik MC, Shea S, Berglund L. High‐density lipoprotein cholesterol and ischemic stroke in the elderly: The Northern Manhattan Stroke Study. JAMA 285: 2729‐2735, 2001.
 294.Sadi G, Eryilmaz N, Tutuncuoglu E, Cingir S, Guray T. Changes in expression profiles of antioxidant enzymes in diabetic rat kidneys. Diabetes Metab Res Rev 28: 228‐235, 2012.
 295.Saito Y, Eraslan A, Lockard V, Hester RL. Role of venular endothelium in control of arteriolar diameter during functional hyperemia. Am J Physiol 267: H1227‐H1231, 1994.
 296.Sallstrom J, Eriksson T, Fredholm BB, Persson AE, Palm F. Inhibition of sodium‐linked glucose reabsorption normalizes diabetes‐induced glomerular hyperfiltration in conscious adenosine A ‐receptor deficient mice. Acta Physiol (Oxf) 210: 440‐445, 2013.
 297.Sandler M, Bunn AE, Stewart RI. Pulmonary function in young insulin‐dependent diabetic subjects. Chest 90: 670‐675, 1986.
 298.Sasaki N, Yamashita T, Takaya T, Shinohara M, Shiraki R, Takeda M, Emoto N, Fukatsu A, Hayashi T, Ikemoto K, Nomura T, Yokoyama M, Hirata K, Kawashima S. Augmentation of vascular remodeling by uncoupled endothelial nitric oxide synthase in a mouse model of diabetes mellitus. Arterioscler Thromb Vasc Biol 28: 1068‐1076, 2008.
 299.Satchell SC, Tooke JE. What is the mechanism of microalbuminuria in diabetes: A role for the glomerular endothelium? Diabetologia 51: 714‐725, 2008.
 300.Schlagowski AI, Singh F, Charles AL, Gali Ramamoorthy T, Favret F, Piquard F, Geny B, Zoll J. Mitochondrial uncoupling reduces exercise capacity despite several skeletal muscle metabolic adaptations. J Appl Physiol (1985) 116: 364‐375, 2014.
 301.Schrauwen P, Schrauwen‐Hinderling V, Hoeks J, Hesselink MK. Mitochondrial dysfunction and lipotoxicity. Biochim Biophys Acta 1801: 266‐271, 2010.
 302.Schuyler MR, Niewoehner DE, Inkley SR, Kohn R. Abnormal lung elasticity in juvenile diabetes mellitus. Am Rev Respir Dis 113: 37‐41, 1976.
 303.Schwartz TW, Holst JJ, Fahrenkrug J, Jensen SL, Nielsen OV, Rehfeld JF, de Muckadell OB, Stadil F. Vagal, cholinergic regulation of pancreatic polypeptide secretion. J Clin Invest 61: 781‐789, 1978.
 304.Seifi M, Fallah S, Firoozrai M. Influence of genetic polymorphism in matrix metalloproteinase‐3 on extent of coronary atherosclerosis and risk of coronary artery stenosis. Arch Med Res 40: 600‐604, 2009.
 305.Selvin E, Marinopoulos S, Berkenblit G, Rami T, Brancati FL, Powe NR, Golden SH. Meta‐analysis: Glycosylated hemoglobin and cardiovascular disease in diabetes mellitus. Ann Intern Med 141: 421‐431, 2004.
 306.Senn JJ, Klover PJ, Nowak IA, Mooney RA. Interleukin‐6 induces cellular insulin resistance in hepatocytes. Diabetes 51: 3391‐3399, 2002.
 307.Seyoum B, Estacio RO, Berhanu P, Schrier RW. Exercise capacity is a predictor of cardiovascular events in patients with type 2 diabetes mellitus. Diab Vasc Dis Res 3: 197‐201, 2006.
 308.Shafiee G, Mohajeri‐Tehrani M, Pajouhi M, Larijani B. The importance of hypoglycemia in diabetic patients. J Diabetes Metab Disord 11: 17, 2012.
 309.Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care 26: 510‐513, 2003.
 310.Sharma JN, Al‐Omran A, Parvathy SS. Role of nitric oxide in inflammatory diseases. Inflammopharmacology 15: 252‐259, 2007.
 311.Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87: 4‐14, 2010.
 312.Shi H, Patschan D, Epstein T, Goligorsky MS, Winaver J. Delayed recovery of renal regional blood flow in diabetic mice subjected to acute ischemic kidney injury. Am J Physiol Renal Physiol 293: F1512‐F1517, 2007.
 313.Siddiqi FS, Advani A. Endothelial‐podocyte crosstalk: The missing link between endothelial dysfunction and albuminuria in diabetes. Diabetes 62: 3647‐3655, 2013.
 314.Singh R, Singh AK, Leehey DJ. A novel mechanism for angiotensin II formation in streptozotocin‐diabetic rat glomeruli. Am J Physiol Renal Physiol 288: F1183‐F1190, 2005.
 315.Smyth LJ, Duffy S, Maxwell AP, McKnight AJ. Genetic and epigenetic factors influencing chronic kidney disease. Am J Physiol Renal Physiol 307: F757‐F776, 2014.
 316.Soskic SS, Dobutovic BD, Sudar EM, Obradovic MM, Nikolic DM, Djordjevic JD, Radak DJ, Mikhailidis DP, Isenovic ER. Regulation of Inducible Nitric Oxide Synthase (iNOS) and its potential role in insulin resistance, diabetes and heart failure. Open Cardiovasc Med J 5: 153‐163, 2011.
 317.Stanley WC, Chandler MP. Energy metabolism in the normal and failing heart: Potential for therapeutic interventions. Heart Fail Rev 7: 115‐130, 2002.
 318.Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA. The hormone resistin links obesity to diabetes. Nature 409: 307‐312, 2001.
 319.Stewart PM, Boulton A, Kumar S, Clark PM, Shackleton CH. Cortisol metabolism in human obesity: Impaired cortisone–>cortisol conversion in subjects with central adiposity. J Clin Endocrinol Metab 84: 1022‐1027, 1999.
 320.Strieter RM, Mehrad B. New mechanisms of pulmonary fibrosis. Chest 136: 1364‐1370, 2009.
 321.Sung J, Bochicchio GV, Joshi M, Bochicchio K, Tracy K, Scalea TM. Admission hyperglycemia is predictive of outcome in critically ill trauma patients. J Trauma 59: 80‐83, 2005.
 322.Susztak K, Raff AC, Schiffer M, Bottinger EP. Glucose‐induced reactive oxygen species cause apoptosis of podocytes and podocyte depletion at the onset of diabetic nephropathy. Diabetes 55: 225‐233, 2006.
 323.Taborsky GJ Jr., Mei Q, Hackney DJ, Figlewicz DP, LeBoeuf R, and Mundinger TO. Loss of islet sympathetic nerves and impairment of glucagon secretion in the NOD mouse: Relationship to invasive insulitis. Diabetologia 52: 2602‐2611, 2009.
 324.Taborsky GJ Jr., Mundinger TO. Minireview: The role of the autonomic nervous system in mediating the glucagon response to hypoglycemia. Endocrinology 153: 1055‐1062, 2012.
 325.Takenaka T, Inoue T, Ohno Y, Miyazaki T, Nishiyama A, Ishii N, Suzuki H. Elucidating mechanisms underlying altered renal autoregulation in diabetes. Am J Physiol Regul Integr Comp Physiol 303: R495‐R504, 2012.
 326.Tan RJ, Liu Y. Matrix metalloproteinases in kidney homeostasis and diseases. Am J Physiol Renal Physiol 302: F1351‐F1361, 2012.
 327.Tang SC, Lai KN. The pathogenic role of the renal proximal tubular cell in diabetic nephropathy. Nephrol Dial Transplant 27: 3049‐3056, 2012.
 328.Taniguchi CM, Emanuelli B, Kahn CR. Critical nodes in signalling pathways: Insights into insulin action. Nat Rev Mol Cell Biol 7: 85‐96, 2006.
 329.Taylor AJ, Burke AP, Farb A, Yousefi P, Malcom GT, Smialek J, Virmani R. Arterial remodeling in the left coronary system: The role of high‐density lipoprotein cholesterol. J Am Coll Cardiol 34: 760‐767, 1999.
 330.Taylor R. Type 2 diabetes: Etiology and reversibility. Diabetes Care 36: 1047‐1055, 2013.
 331.Tejada T, Catanuto P, Ijaz A, Santos JV, Xia X, Sanchez P, Sanabria N, Lenz O, Elliot SJ, Fornoni A. Failure to phosphorylate AKT in podocytes from mice with early diabetic nephropathy promotes cell death. Kidney Int 73: 1385‐1393, 2008.
 332.Thomas CM, Yong QC, Seqqat R, Chandel N, Feldman DL, Baker KM, Kumar R. Direct renin inhibition prevents cardiac dysfunction in a diabetic mouse model: Comparison with an angiotensin receptor antagonist and angiotensin‐converting enzyme inhibitor. Clin Sci (Lond) 124: 529‐541, 2013.
 333.Thomas G, Rojas MC, Epstein SK, Balk EM, Liangos O, Jaber BL. Insulin therapy and acute kidney injury in critically ill patients a systematic review. Nephrol Dial Transplant 22: 2849‐2855, 2007.
 334.Thompson LH, Kim HT, Ma Y, Kokorina NA, Messina JL. Acute, muscle‐type specific insulin resistance following injury. Mol Med 14: 715‐723, 2008.
 335.Thomsen RW, Hundborg HH, Lervang HH, Johnsen SP, Schonheyder HC, Sorensen HT. Risk of community‐acquired pneumococcal bacteremia in patients with diabetes: A population‐based case‐control study. Diabetes Care 27: 1143‐1147, 2004.
 336.Tiikkainen M, Tamminen M, Hakkinen AM, Bergholm R, Vehkavaara S, Halavaara J, Teramo K, Rissanen A, Yki‐Jarvinen H. Liver‐fat accumulation and insulin resistance in obese women with previous gestational diabetes. Obes Res 10: 859‐867, 2002.
 337.Toda N, Imamura T, Okamura T. Alteration of nitric oxide‐mediated blood flow regulation in diabetes mellitus. Pharmacol Ther 127: 189‐209, 2010.
 338.Toft‐Nielsen MB, Damholt MB, Madsbad S, Hilsted LM, Hughes TE, Michelsen BK, Holst JJ. Determinants of the impaired secretion of glucagon‐like peptide‐1 in type 2 diabetic patients. J Clin Endocrinol Metab 86: 3717‐3723, 2001.
 339.Touboul PJ, Labreuche J, Bruckert E, Schargrodsky H, Prati P, Tosetto A, Hernandez‐Hernandez R, Woo KS, Silva H, Vicaut E, Amarenco P. HDL‐C, triglycerides and carotid IMT: A meta‐analysis of 21,000 patients with automated edge detection IMT measurement. Atherosclerosis 232: 65‐71, 2014.
 340.Trost SU, Belke DD, Bluhm WF, Meyer M, Swanson E, Dillmann WH. Overexpression of the sarcoplasmic reticulum Ca(2+)‐ATPase improves myocardial contractility in diabetic cardiomyopathy. Diabetes 51: 1166‐1171, 2002.
 341.Tuomi T, Santoro N, Caprio S, Cai M, Weng J, Groop L. The many faces of diabetes: A disease with increasing heterogeneity. Lancet 383: 1084‐1094, 2014.
 342.Tuomilehto J, Rastenyte D, Birkenhager WH, Thijs L, Antikainen R, Bulpitt CJ, Fletcher AE, Forette F, Goldhaber A, Palatini P, Sarti C, Fagard R. Effects of calcium‐channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators. N Engl J Med 340: 677‐684, 1999.
 343.Tuttolomondo A, Pinto A, Salemi G, Di Raimondo D, Di Sciacca R, Fernandez P, Ragonese P, Savettieri G, Licata G. Diabetic and non‐diabetic subjects with ischemic stroke: Differences, subtype distribution and outcome. Nutr Metab Cardiovasc Dis 18: 152‐157, 2008.
 344.Vaidyula VR, Boden G, Rao AK. Platelet and monocyte activation by hyperglycemia and hyperinsulinemia in healthy subjects. Platelets 17: 577‐585, 2006.
 345.Vaidyula VR, Rao AK, Mozzoli M, Homko C, Cheung P, Boden G. Effects of hyperglycemia and hyperinsulinemia on circulating tissue factor procoagulant activity and platelet CD40 ligand. Diabetes 55: 202‐208, 2006.
 346.Valette X, Parienti JJ, Plaud B, Lehoux P, Samba D, Hanouz JL. Incidence, morbidity, and mortality of contrast‐induced acute kidney injury in a surgical intensive care unit: A prospective cohort study. J Crit Care 27: 322.e1‐e5, 2012.
 347.Vallon V, Gerasimova M, Rose MA, Masuda T, Satriano J, Mayoux E, Koepsell H, Thomson SC, Rieg T. SGLT2 inhibitor empagliflozin reduces renal growth and albuminuria in proportion to hyperglycemia and prevents glomerular hyperfiltration in diabetic Akita mice. Am J Physiol Renal Physiol 306: F194‐F204, 2014.
 348.Vallon V, Komers R. Pathophysiology of the diabetic kidney. Compr Physiol 1: 1175‐1232, 2011.
 349.Vallon V, Rose M, Gerasimova M, Satriano J, Platt KA, Koepsell H, Cunard R, Sharma K, Thomson SC, Rieg T. Knockout of Na‐glucose transporter SGLT2 attenuates hyperglycemia and glomerular hyperfiltration but not kidney growth or injury in diabetes mellitus. Am J Physiol Renal Physiol 304: F156‐F167, 2013.
 350.Vallon V, Thomson SC. Renal function in diabetic disease models: The tubular system in the pathophysiology of the diabetic kidney. Annu Rev Physiol 74: 351‐375, 2012.
 351.Valsamakis G, Anwar A, Tomlinson JW, Shackleton CH, McTernan PG, Chetty R, Wood PJ, Banerjee AK, Holder G, Barnett AH, Stewart PM, Kumar S. 11beta‐hydroxysteroid dehydrogenase type 1 activity in lean and obese males with type 2 diabetes mellitus. J Clin Endocrinol Metab 89: 4755‐4761, 2004.
 352.van Belle TL, Coppieters KT, von Herrath MG. Type 1 diabetes: Etiology, immunology, and therapeutic strategies. Physiol Rev 91: 79‐118, 2011.
 353.Van Buren PN, Toto R. Hypertension in diabetic nephropathy: Epidemiology, mechanisms, and management. Adv Chronic Kidney Dis 18: 28‐41, 2011.
 354.Viberti G. The need for tighter control of cardiovascular risk factors in diabetic patients. J Hypertens Suppl 21: S3‐S6, 2003.
 355.Vilsboll T, Krarup T, Deacon CF, Madsbad S, Holst JJ. Reduced postprandial concentrations of intact biologically active glucagon‐like peptide 1 in type 2 diabetic patients. Diabetes 50: 609‐613, 2001.
 356.Vilsboll T, Krarup T, Madsbad S, Holst JJ. Defective amplification of the late phase insulin response to glucose by GIP in obese Type II diabetic patients. Diabetologia 45: 1111‐1119, 2002.
 357.Vracko R, Thorning D, Huang TW. Basal lamina of alveolar epithelium and capillaries: Quantitative changes with aging and in diabetes mellitus. Am Rev Respir Dis 120: 973‐983, 1979.
 358.Wada J, Makino H. Inflammation and the pathogenesis of diabetic nephropathy. Clin Sci (Lond) 124: 139‐152, 2013.
 359.Wang H, Xu Y, Fu J, Huang L. Evaluation of the regional ventricular systolic function by two‐dimensional strain echocardiography in gestational diabetes mellitus (GDM) fetuses with good glycemic control. J Matern Fetal Neonatal Med 28: 1‐5, 2014.
 360.Weil EJ, Lemley KV, Mason CC, Yee B, Jones LI, Blouch K, Lovato T, Richardson M, Myers BD, Nelson RG. Podocyte detachment and reduced glomerular capillary endothelial fenestration promote kidney disease in type 2 diabetic nephropathy. Kidney Int 82: 1010‐1017, 2012.
 361.Weisbrod CJ, Eastwood PR, O'Driscoll G, Green DJ. Abnormal ventilatory responses to hypoxia in Type 2 diabetes. Diabet Med 22: 563‐568, 2005.
 362.Welsh GI, Hale LJ, Eremina V, Jeansson M, Maezawa Y, Lennon R, Pons DA, Owen RJ, Satchell SC, Miles MJ, Caunt CJ, McArdle CA, Pavenstadt H, Tavare JM, Herzenberg AM, Kahn CR, Mathieson PW, Quaggin SE, Saleem MA, Coward RJ. Insulin signaling to the glomerular podocyte is critical for normal kidney function. Cell Metab 12: 329‐340, 2010.
 363.Werner N, Nickenig G. Influence of cardiovascular risk factors on endothelial progenitor cells: Limitations for therapy? Arterioscler Thromb Vasc Biol 26: 257‐266, 2006.
 364.Weynand B, Jonckheere A, Frans A, Rahier J. Diabetes mellitus induces a thickening of the pulmonary basal lamina. Respiration 66: 14‐19, 1999.
 365.Whitehead JP, Clark SF, Urso B, James DE. Signalling through the insulin receptor. Curr Opin Cell Biol 12: 222‐228, 2000.
 366.Winkler G, Cseh K, Baranyi E, Melczer Z, Speer G, Hajos P, Salamon F, Turi Z, Kovacs M, Vargha P, Karadi I. Tumor necrosis factor system in insulin resistance in gestational diabetes. Diabetes Res Clin Pract 56: 93‐99, 2002.
 367.Winocour PD, Watala C, Perry DW, Kinlough‐Rathbone RL. Decreased platelet membrane fluidity due to glycation or acetylation of membrane proteins. Thromb Haemost 68: 577‐582, 1992.
 368.Winzell MS, Svensson H, Enerback S, Ravnskjaer K, Mandrup S, Esser V, Arner P, Alves‐Guerra MC, Miroux B, Sundler F, Ahren B, Holm C. Pancreatic beta‐cell lipotoxicity induced by overexpression of hormone‐sensitive lipase. Diabetes 52: 2057‐2065, 2003.
 369.Woo JS, Perez‐Rosendahl M, Haydel DM, Perens G, Fishbein MC. A novel association of biventricular cardiac non‐compaction and diabetic embryopathy: Case report and review of the literature. Pediatr Dev Pathol 18: 71‐75, 2015.
 370.Xiang L, Dearman J, Abram SR, Carter C, Hester RL. Insulin resistance and impaired functional vasodilation in obese Zucker rats. Am J Physiol Heart Circ Physiol 294: H1658‐H1666, 2008.
 371.Xiang L, Hester RL. Cardiovascular responses to exercise. In: Granger N, Granger J, editors. Integrated Systems Physiology: From Molecule to Function to Disease. Morgan and Claypool Life Sciences, 2011, pp. 1‐124.
 372.Xiang L, Lu S, Mittwede PN, Clemmer JS, Hester RL. Inhibition of NADPH oxidase prevents acute lung injury in obese rats following severe trauma. Am J Physiol Heart Circ Physiol 306: H684‐H689, 2014.
 373.Xiang L, Lu S, Mittwede PN, Clemmer JS, Husband GW, Hester RL. beta2‐Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats. Am J Physiol Heart Circ Physiol 307: H621‐H627, 2014.
 374.Xiang L, Naik JS, Abram SR, Hester RL. Chronic hyperglycemia impairs functional vasodilation via increasing thromboxane‐receptor‐mediated vasoconstriction. Am J Physiol Heart Circ Physiol 292: H231‐H236, 2007.
 375.Xiang L, Naik JS, Hodnett BL, Hester RL. Altered arachidonic acid metabolism impairs functional vasodilation in metabolic syndrome. Am J Physiol Regul Integr Comp Physiol 290: R134‐R138, 2006.
 376.Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity‐related insulin resistance. J Clin Invest 112: 1821‐1830, 2003.
 377.Xu J, Kim HT, Ma Y, Zhao L, Zhai L, Kokorina N, Wang P, Messina JL. Trauma and hemorrhage‐induced acute hepatic insulin resistance: Dominant role of tumor necrosis factor‐alpha. Endocrinology 149: 2369‐2382, 2008.
 378.Yamazaki KG, Gonzalez E, Zambon AC. Crosstalk between the renin‐angiotensin system and the advance glycation end product axis in the heart: Role of the cardiac fibroblast. J Cardiovasc Transl Res 5: 805‐813, 2012.
 379.Yamazaki S, Katada T, Ui M. Alpha 2‐adrenergic inhibition of insulin secretion via interference with cyclic AMP generation in rat pancreatic islets. Mol Pharmacol 21: 648‐653, 1982.
 380.Yang J, Pollock JS, Carmines PK. NADPH oxidase and PKC contribute to increased Na transport by the thick ascending limb during type 1 diabetes. Hypertension 59: 431‐436, 2012.
 381.Yeager MP, Pioli PA, Guyre PM. Cortisol exerts bi‐phasic regulation of inflammation in humans. Dose Response 9: 332‐347, 2011.
 382.Yendamuri S, Fulda GJ, Tinkoff GH. Admission hyperglycemia as a prognostic indicator in trauma. J Trauma 55: 33‐38, 2003.
 383.Yki‐Jarvinen H. Management of type 2 diabetes mellitus and cardiovascular risk: Lessons from intervention trials. Drugs 60: 975‐983, 2000.
 384.Yoneyama S, Arakawa K, Yonemura A, Isoda K, Nakamura H, Ohsuzu F. Oxidized low‐density lipoprotein and high‐density lipoprotein cholesterol modulate coronary arterial remodeling: An intravascular ultrasound study. Clin Cardiol 26: 31‐35, 2003.
 385.Zeng G, Nystrom FH, Ravichandran LV, Cong LN, Kirby M, Mostowski H, Quon MJ. Roles for insulin receptor, PI3‐kinase, and Akt in insulin‐signaling pathways related to production of nitric oxide in human vascular endothelial cells. Circulation 101: 1539‐1545, 2000.
 386.Zhang C, Meng Y, Liu Q, Xuan M, Zhang L, Deng B, Zhang K, Liu Z, Lei T. Injury to the endothelial surface layer induces glomerular hyperfiltration rats with early‐stage diabetes. J Diabetes Res 2014: 953740, 2014.
 387.Zhang C, Tobias DK, Chavarro JE, Bao W, Wang D, Ley SH, Hu FB. Adherence to healthy lifestyle and risk of gestational diabetes mellitus: Prospective cohort study. BMJ 349: g5450, 2014.
 388.Zhang CY, Baffy G, Perret P, Krauss S, Peroni O, Grujic D, Hagen T, Vidal‐Puig AJ, Boss O, Kim YB, Zheng XX, Wheeler MB, Shulman GI, Chan CB, Lowell BB. Uncoupling protein‐2 negatively regulates insulin secretion and is a major link between obesity, beta cell dysfunction, and type 2 diabetes. Cell 105: 745‐755, 2001.
 389.Zhang K, Kaufman RJ. From endoplasmic‐reticulum stress to the inflammatory response. Nature 454: 455‐462, 2008.
 390.Zhao Y, Ye W, Le TK, Boye KS, Holcombe JH, Swindle R. Comparing clinical and economic characteristics between commercially‐insured patients with diabetic neuropathy and demographically‐matched diabetic controls. Curr Med Res Opin 25: 585‐597, 2009.
 391.Zhuo JL, Li XC. Proximal nephron. Compr Physiol 3: 1079‐1123, 2013.
 392.Ziegler D, Dannehl K, Volksw D, Muhlen H, Spuler M, Gries FA. Prevalence of cardiovascular autonomic dysfunction assessed by spectral analysis and standard tests of heart‐rate variation in newly diagnosed IDDM patients. Diabetes Care 15: 908‐911, 1992.

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Lusha Xiang, Peter N. Mittwede, John S. Clemmer. Glucose Homeostasis and Cardiovascular Alterations in Diabetes. Compr Physiol 2015, 5: 1815-1839. doi: 10.1002/cphy.c150001