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Hypertension in Children with Type 2 Diabetes or the Metabolic Syndrome

  • Grace J. KimEmail author
  • Craig E. Taplin
  • Joseph T. Flynn
Reference work entry

Abstract

The childhood obesity epidemic has been accompanied by an increase in complications of obesity such as the metabolic syndrome and type 2 diabetes. Obese youth with the metabolic syndrome are frequently hypertensive and may present with clinically significant evidence of hypertensive target-organ damage. There are important considerations in the approach to treating hypertension in young patients with the metabolic syndrome or type 2 diabetes, which include the primacy of lifestyle approaches to effect substantial weight loss, increases in exercise, and reduced caloric and salt intake. The cardiovascular effects of oral hypoglycemic agents, and the potentially diabetogenic effects of certain antihypertensive medications must also be considered. A comprehensive approach, including nonpharmacologic measures, the use of hypoglycemic and antihypertensive medications, and perhaps even bariatric surgery in selected patients, is indicated in order to reduce future cardiovascular risk.

Keywords

Pediatric hypertension Metabolic syndrome Type 2 diabetes 

References

  1. Abbasi F, Chu JW, McLaughlin T et al (2004) Effect of metformin treatment on multiple cardiovascular disease risk factors in patients with type 2 diabetes mellitus. Metabolism 53:159–164PubMedGoogle Scholar
  2. Aghamohammadzadeh R, Heagerty AM (2012) Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue. Ann Med 44(Suppl 1):S74–S84PubMedGoogle Scholar
  3. Anderson EA, Hoffman RP, Balon TW et al (1991) Hyperinsulinemia produces both sympathetic neural activation and vasodilation in normal humans. J Clin Invest 87:2246–2252PubMedPubMedCentralGoogle Scholar
  4. Appel LJ, Moore TJ, Obarzanek E et al (1997) A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med 336:1117–1124Google Scholar
  5. Appel LJ, Brands MW, Daniels SR et al (2006) Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association. Hypertension 47:296–308Google Scholar
  6. Asfaha S, Padwal R (2005) Antihypertensive drugs and incidence of type 2 diabetes: evidence and implications for clinical practice. Curr Hypertens Rep 7:314–322PubMedGoogle Scholar
  7. Beltran-Sanchez H, Harhay MO, Harhay MM et al (2013) Prevalence and trends of metabolic syndrome in the adult U.S. population, 1999–2010. J Am Coll Cardiol 62:697–703PubMedPubMedCentralGoogle Scholar
  8. Ben Ounis O, Elloumi M, Ben Chiekh I et al (2008) Effects of two-month physical-endurance and diet-restriction programmes on lipid profiles and insulin resistance in obese adolescent boys. Diabetes Metab 34:595–600PubMedGoogle Scholar
  9. Berenson GS, Srinivasan SR, Bao W et al (1998) Association between multiple cardiovascular risk factors and atherosclerosis in children and young adults. The Bogalusa Heart Study N Engl J Med 338:1650–1656PubMedGoogle Scholar
  10. Brown NJ (2012) Cardiovascular effects of antidiabetic agents: focus on blood pressure effects of incretin-based therapies. J Am Soc Hypertens 6:163–168PubMedPubMedCentralGoogle Scholar
  11. Chiasson JL (2006) Acarbose for the prevention of diabetes, hypertension, and cardiovascular disease in subjects with impaired glucose tolerance: the Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM) Trial. Endocr Pract 12(Suppl 1):25–30PubMedGoogle Scholar
  12. Chobanian AV, Bakris GL, Black HR et al (2003) The seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA 289:2560–2572PubMedGoogle Scholar
  13. Cook S, Weitzman M, Auinger P et al (2003) Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988–1994. Arch Pediatr Adolesc Med 157:821–827PubMedPubMedCentralGoogle Scholar
  14. Copeland KC, Zeitler P, Geffner M et al (2011) Characteristics of adolescents and youth with recent-onset type 2 diabetes: the TODAY cohort at baseline. J Clin Endocrinol Metab 96:159–167PubMedGoogle Scholar
  15. Cosenso-Martin LN, Giollo-Junior LT, Vilela-Martin JF (2015) DPP-4 inhibitor reduces central blood pressure in a diabetic and hypertensive patient: a case report. Medicine (Baltimore) 94:e1068Google Scholar
  16. Couch SC, Saelens BE, Levin L et al (2008) The efficacy of a clinic-based behavioral nutrition intervention emphasizing a DASH-type diet for adolescents with elevated blood pressure. J Pediatr 152:494–501PubMedGoogle Scholar
  17. Daniels SR, Arnett DK, Eckel RH et al (2005) Overweight in children and adolescents: pathophysiology, consequences, prevention, and treatment. Circulation 111:1999–2012PubMedGoogle Scholar
  18. Derosa G, Cicero AF, Gaddi AV et al (2005) Long-term effects of glimepiride or rosiglitazone in combination with metformin on blood pressure control in type 2 diabetic patients affected by the metabolic syndrome: a 12-month, double-blind, randomized clinical trial. Clin Ther 27:1383–1391PubMedGoogle Scholar
  19. Eckel RH, Alberti KG, Grundy SM et al (2010) The metabolic syndrome. Lancet 375:181–183PubMedGoogle Scholar
  20. Eppens MC, Craig ME, Cusumano J et al (2006a) Prevalence of diabetes complications in adolescents with type 2 compared with type 1 diabetes. Diabetes Care 29:1300–1306PubMedGoogle Scholar
  21. Eppens MC, Craig ME, Jones TW et al (2006b) Type 2 diabetes in youth from the Western Pacific region: glycaemic control, diabetes care and complications. Curr Med Res Opin 22:1013–1020PubMedGoogle Scholar
  22. Esler M, Rumantir M, Wiesner G et al (2001) Sympathetic nervous system and insulin resistance: from obesity to diabetes. Am J Hypertens 14:304S–309SPubMedGoogle Scholar
  23. Ettinger LM, Freeman K, Dimartino-Nardi JR et al (2005) Microalbuminuria and abnormal ambulatory blood pressure in adolescents with type 2 diabetes mellitus. J Pediatr 147:67–73PubMedGoogle Scholar
  24. Falkner B, Kushner H (2008) Treatment with metoprolol succinate, a selective beta adrenergic blocker, lowers blood pressure without altering insulin sensitivity in diabetic patients. J Clin Hypertens (Greenwich) 10:51–57Google Scholar
  25. Falkner B, Michel S (1997) Blood pressure response to sodium in children and adolescents. Am J Clin Nutr 65:618S–621SPubMedGoogle Scholar
  26. Farpour-Lambert NJ, Aggoun Y, Marchand LM et al (2009) Physical activity reduces systemic blood pressure and improves early markers of atherosclerosis in pre-pubertal obese children. J Am Coll Cardiol 54:2396–2406PubMedGoogle Scholar
  27. Flynn JT, Alderman MH (2005) Characteristics of children with primary hypertension seen at a referral center. Pediatr Nephrol 20:961–966Google Scholar
  28. Flynn JT, Kaelber DC, Baker-Smith CM et al (2017) Clinical practice guideline for screening and management of high blood pressure in children and adolescents. Pediatrics 140(3):e20171904Google Scholar
  29. Ford ES, Giles WH, Dietz WH (2002) Prevalence of the metabolic syndrome among US adults: findings from the third National Health and Nutrition Examination Survey. JAMA 287:356–359PubMedGoogle Scholar
  30. Gillespie EL, White CM, Kardas M, Lindberg M, Coleman CI (2005) The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes. Diabetes Care 28:2261–2266PubMedGoogle Scholar
  31. Giorda C, Appendino M, Mason MG et al (1995) Alpha 1-blocker doxazosin improves peripheral insulin sensitivity in diabetic hypertensive patients. Metabolism 44:673–676PubMedGoogle Scholar
  32. Goodman E, Daniels SR, Meigs JB et al (2007) Instability in the diagnosis of metabolic syndrome in adolescents. Circulation 115:2316–2322PubMedPubMedCentralGoogle Scholar
  33. Hall JE (2003) The kidney, hypertension, and obesity. Hypertension 41:625–633PubMedGoogle Scholar
  34. Harano Y, Kageyama A, Hirose J et al (1995) Improvement of insulin sensitivity for glucose metabolism with the long-acting Ca-channel blocker amlodipine in essential hypertensive subjects. Metabolism 44:315–319PubMedGoogle Scholar
  35. Hypertension in Diabetes Study (HDS) (1993) Hypertension in Diabetes Study (HDS): I. Prevalence of hypertension in newly presenting type 2 diabetic patients and the association with risk factors for cardiovascular and diabetic complications. Journal of Hypertension 11:309–17Google Scholar
  36. Inge TH, Courcoulas AP, Jenkins TM et al (2016) Weight loss and health status 3 years after bariatric surgery in adolescents. N Engl J Med 374:113–123PubMedGoogle Scholar
  37. Ingelfinger JR (2011) Bariatric surgery in adolescents. N Engl J Med 365:1365–1367PubMedGoogle Scholar
  38. Inukai T, Inukai Y, Matsutomo R et al (2004) Clinical usefulness of doxazosin in patients with type 2 diabetes complicated by hypertension: effects on glucose and lipid metabolism. J Int Med Res 32:206–213PubMedGoogle Scholar
  39. Izzedine H, Launay-Vacher V, Deybach C et al (2005) Drug-induced diabetes mellitus. Expert Opin Drug Saf 4:1097–1109PubMedGoogle Scholar
  40. James PA, Oparil S, Carter BL et al (2014) 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth Joint National Committee (JNC 8). JAMA 311:507–520PubMedPubMedCentralGoogle Scholar
  41. Kahn SE, Hull RL, Utzschneider KM (2006) Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444:840–846PubMedGoogle Scholar
  42. Kamide K, Hori MT, Zhu JH et al (2000) Insulin and insulin-like growth factor-I promotes angiotensinogen production and growth in vascular smooth muscle cells. J Hypertens 18:1051–1056PubMedGoogle Scholar
  43. Kit BK, Kuklina E, Carroll MD et al (2015) Prevalence of and trends in dyslipidemia and blood pressure among US children and adolescents, 1999–2012. JAMA Pediatr 169:272–279PubMedGoogle Scholar
  44. Knowler WC, Barrett-Connor E, Fowler SE et al (2002) Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346:393–403Google Scholar
  45. Koyama Y, Kodama K, Suzuki M et al (2002) Improvement of insulin sensitivity by a long-acting nifedipine preparation (nifedipine-CR) in patients with essential hypertension. Am J Hypertens 15:927–931PubMedGoogle Scholar
  46. Laakso M, Edelman SV, Brechtel G et al (1990) Decreased effect of insulin to stimulate skeletal muscle blood flow in obese man. A novel mechanism for insulin resistance. J Clin Invest 85:1844–1852PubMedPubMedCentralGoogle Scholar
  47. Landsberg L (2001) Insulin-mediated sympathetic stimulation: role in the pathogenesis of obesity-related hypertension (or, how insulin affects blood pressure, and why). J Hypertens 19:523–528PubMedGoogle Scholar
  48. Lawrence JM, Mayer-Davis EJ, Reynolds K et al (2009) Diabetes in Hispanic American youth: prevalence, incidence, demographics, and clinical characteristics: the SEARCH for diabetes in youth study. Diabetes Care 32(Suppl 2):S123–S132PubMedPubMedCentralGoogle Scholar
  49. Lee S, Bacha F, Arslanian SA (2006) Waist circumference, blood pressure, and lipid components of the metabolic syndrome. J Pediatr 149:809–816PubMedGoogle Scholar
  50. Liska D, Dufour S, Zern TL et al (2007) Interethnic differences in muscle, liver and abdominal fat partitioning in obese adolescents. PLoS One 2:e569PubMedPubMedCentralGoogle Scholar
  51. Love-Osborne K, Sheeder J, Zeitler P (2008) Addition of metformin to a lifestyle modification program in adolescents with insulin resistance. J Pediatr 152:817–822PubMedPubMedCentralGoogle Scholar
  52. Lurbe E, Agabiti-Rosei E, Cruickshank JK et al (2016) 2016 European Society of Hypertension guidelines for the management of high blood pressure in children and adolescents. J Hypertens 34:1887–1920Google Scholar
  53. Majithiya JB, Balaraman R (2006) Metformin reduces blood pressure and restores endothelial function in aorta of streptozotocin-induced diabetic rats. Life Sci 78:2615–2624PubMedGoogle Scholar
  54. Manzella D, Grella R, Esposito K et al (2004) Blood pressure and cardiac autonomic nervous system in obese type 2 diabetic patients: effect of metformin administration. Am J Hypertens 17:223–227PubMedGoogle Scholar
  55. Marney A, Kunchakarra S, Byrne L et al (2010) Interactive hemodynamic effects of dipeptidyl peptidase-IV inhibition and angiotensin-converting enzyme inhibition in humans. Hypertension 56:728–733PubMedPubMedCentralGoogle Scholar
  56. Mason JM, Dickinson HO, Nicolson DJ et al (2005) The diabetogenic potential of thiazide-type diuretic and beta-blocker combinations in patients with hypertension. J Hypertens 23:1777–1781PubMedGoogle Scholar
  57. Mu JJ, Liu ZQ, Liu WM et al (2005) Reduction of blood pressure with calcium and potassium supplementation in children with salt sensitivity: a 2-year double-blinded placebo-controlled trial. J Hum Hypertens 19:479–483PubMedGoogle Scholar
  58. Mugo MN, Link D, Stump CS, Sowers JR (2007) Comprehensive hypertension. Mosby, Inc., PhiladelphiaGoogle Scholar
  59. National High Blood Pressure Education Program Working Group on High Blood Pressure in, C. & Adolescents (2004) The fourth report on the diagnosis, evaluation, and treatment of high blood pressure in children and adolescents. Pediatrics 114:555–576Google Scholar
  60. Negro R, Dazzi D, Hassan H et al (2004) Pioglitazone reduces blood pressure in non-dipping diabetic patients. Minerva Endocrinol 29:11–17PubMedGoogle Scholar
  61. Negro R, Mangieri T, Dazzi D et al (2005) Rosiglitazone effects on blood pressure and metabolic parameters in nondipper diabetic patients. Diabetes Res Clin Pract 70:20–25PubMedGoogle Scholar
  62. Officers A, Coordinators for the, A. C. R. G. T. A. & Lipid-Lowering Treatment to Prevent Heart Attack, T (2002) Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 288:2981–2997Google Scholar
  63. Okerson T, Yan P, Stonehouse A et al (2010) Effects of exenatide on systolic blood pressure in subjects with type 2 diabetes. Am J Hypertens 23:334–339PubMedGoogle Scholar
  64. Olza J, Gil-Campos M, Leis R et al (2011) Presence of the metabolic syndrome in obese children at prepubertal age. Ann Nutr Metab 58:343–350PubMedGoogle Scholar
  65. Pershadsingh HA (2006) Treating the metabolic syndrome using angiotensin receptor antagonists that selectively modulate peroxisome proliferator-activated receptor-gamma. Int J Biochem Cell Biol 38:766–781PubMedGoogle Scholar
  66. Preiss D, Lloyd SM, Ford I et al (2014) Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. Lancet Diabetes Endocrinol 2:116–124PubMedGoogle Scholar
  67. Punzi HA, Punzi CF, Antihypertensive, Lipid-Lowering Heart Attack Trial, S. & Trinity Hypertension Research, I (2004) Metabolic issues in the Antihypertensive and Lipid-Lowering Heart Attack Trial Study. Curr Hypertens Rep 6:106–110PubMedGoogle Scholar
  68. Rachmani R, Bar-Dayan Y, Ronen Z et al (2004) The effect of acarbose on insulin resistance in obese hypertensive subjects with normal glucose tolerance: a randomized controlled study. Diabetes Obes Metab 6:63–68PubMedGoogle Scholar
  69. Reaven GM, Lithell H, Landsberg L (1996) Hypertension and associated metabolic abnormalities – the role of insulin resistance and the sympathoadrenal system. N Engl J Med 334:374–381Google Scholar
  70. Redon J, Cifkova R, Laurent S et al (2009) Mechanisms of hypertension in the cardiometabolic syndrome. J Hypertens 27:441–451PubMedGoogle Scholar
  71. Reinehr T, Andler W (2004) Changes in the atherogenic risk factor profile according to degree of weight loss. Arch Dis Child 89:419–422PubMedPubMedCentralGoogle Scholar
  72. Reinehr T, Wunsch R, De Sousa G et al (2008) Relationship between metabolic syndrome definitions for children and adolescents and intima-media thickness. Atherosclerosis 199:193–200PubMedGoogle Scholar
  73. Ribeiro MM, Silva AG, Santos NS et al (2005) Diet and exercise training restore blood pressure and vasodilatory responses during physiological maneuvers in obese children. Circulation 111:1915–1923PubMedGoogle Scholar
  74. Ritz E, Dikow R (2006) Hypertension and antihypertensive treatment of diabetic nephropathy. Nat Clin Pract Nephrol 2:562–567PubMedGoogle Scholar
  75. Rocchini AP (2002) Obesity hypertension. Am J Hypertens 15:50S–52SPubMedGoogle Scholar
  76. Rocchini AP, Katch V, Anderson J et al (1988) Blood pressure in obese adolescents: effect of weight loss. Pediatrics 82:16–23PubMedGoogle Scholar
  77. Rocchini AP, Key J, Bondie D et al (1989) The effect of weight loss on the sensitivity of blood pressure to sodium in obese adolescents. N Engl J Med 321:580–585Google Scholar
  78. Rodriguez BL, Fujimoto WY, Mayer-Davis EJ et al (2006) Prevalence of cardiovascular disease risk factors in U.S. children and adolescents with diabetes: the SEARCH for diabetes in youth study. Diabetes Care 29:1891–1896PubMedGoogle Scholar
  79. Rodriguez BL, Dabelea D, Liese AD et al (2010) Prevalence and correlates of elevated blood pressure in youth with diabetes mellitus: the SEARCH for diabetes in youth study. J Pediatr 157(2):245–251 e1Google Scholar
  80. Ryan MJ, Didion SP, Mathur S et al (2004) PPAR(gamma) agonist rosiglitazone improves vascular function and lowers blood pressure in hypertensive transgenic mice. Hypertension 43:661–666PubMedGoogle Scholar
  81. Sarafidis PA, Lasaridis AN, Nilsson PM et al (2004) Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase. J Hypertens 22:1769–1777PubMedGoogle Scholar
  82. Scheen AJ (2004) Renin-angiotensin system inhibition prevents type 2 diabetes mellitus. Part 2. Overview of physiological and biochemical mechanisms. Diabetes Metab 30:498–505PubMedGoogle Scholar
  83. Scherrer U, Randin D, Vollenweider P et al (1994) Nitric oxide release accounts for insulin's vascular effects in humans. J Clin Invest 94:2511–2515PubMedPubMedCentralGoogle Scholar
  84. Schillaci G, Pirro M, Vaudo G et al (2004) Prognostic value of the metabolic syndrome in essential hypertension. J Am Coll Cardiol 43:1817–1822PubMedGoogle Scholar
  85. Schulman IH, Zhou MS (2009) Vascular insulin resistance: a potential link between cardiovascular and metabolic diseases. Curr Hypertens Rep 11:48–55PubMedPubMedCentralGoogle Scholar
  86. SEARCH for Diabetes Group (2006) The burden of diabetes mellitus among US youth: prevalence estimates from the SEARCH for diabetes in youth study. Pediatrics 118:1510–1518Google Scholar
  87. Sha S, Polidori D, Heise T et al (2014) Effect of the sodium glucose co-transporter 2 inhibitor canagliflozin on plasma volume in patients with type 2 diabetes mellitus. Diabetes Obes Metab 16:1087–1095PubMedGoogle Scholar
  88. Shatat IF, Flynn JT (2011) Relationships between renin, aldosterone, and 24-hour ambulatory blood pressure in obese adolescents. Pediatr Res 69:336–340PubMedGoogle Scholar
  89. Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116:1793–1801PubMedPubMedCentralGoogle Scholar
  90. Silva GM, Osorio A, Pereira F et al (2012) Effect of laparoscopic adjustable gastric banding on modifiable cardiovascular risk factors in extremely obese adolescents. Obes Surg 22:991–994PubMedGoogle Scholar
  91. Sinaiko AR, Gomez-Marin O, Prineas RJ (1997) Relation of fasting insulin to blood pressure and lipids in adolescents and parents. Hypertension 30:1554–1559PubMedGoogle Scholar
  92. Sinaiko AR, Steinberger J, Moran A et al (2002) Relation of insulin resistance to blood pressure in childhood. J Hypertens 20:509–517Google Scholar
  93. Stakos DA, Schuster DP, Sparks EA et al (2005) Long term cardiovascular effects of oral antidiabetic agents in non-diabetic patients with insulin resistance: double blind, prospective, randomised study. Heart 91:589–594PubMedPubMedCentralGoogle Scholar
  94. Stears AJ, Woods SH, Watts MM et al (2012) A double-blind, placebo-controlled, crossover trial comparing the effects of amiloride and hydrochlorothiazide on glucose tolerance in patients with essential hypertension. Hypertension 59:934–942PubMedGoogle Scholar
  95. Steinberger J, Daniels SR, Eckel RH et al (2009) Progress and challenges in metabolic syndrome in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in the Young Committee of the Council on Cardiovascular Disease in the Young; Council on Cardiovascular Nursing; and Council on Nutrition, Physical Activity, and Metabolism. Circulation 119:628–647PubMedGoogle Scholar
  96. Suh DC, Kim CM, Choi IS et al (2009) Trends in blood pressure control and treatment among type 2 diabetes with comorbid hypertension in the United States: 1988–2004. J Hypertens 27:1908–1916PubMedGoogle Scholar
  97. Sun SS, Grave GD, Siervogel RM et al (2007) Systolic blood pressure in childhood predicts hypertension and metabolic syndrome later in life. Pediatrics 119:237–246PubMedGoogle Scholar
  98. Tentolouris N, Liatis S, Katsilambros N (2006) Sympathetic system activity in obesity and metabolic syndrome. Ann N Y Acad Sci 1083:129–152PubMedGoogle Scholar
  99. TODAY Study Group (2012) A clinical trial to maintain glycemic control in youth with type 2 diabetes. N Engl J Med 366:2247–2256PubMedCentralGoogle Scholar
  100. TODAY Study Group (2013) Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial. Diabetes Care 36:1735–1741PubMedCentralGoogle Scholar
  101. Togashi K, Masuda H, Rankinen T et al (2002) A 12-year follow-up study of treated obese children in Japan. Int J Obes Relat Metab Disord 26:770–777PubMedGoogle Scholar
  102. Torrance B, McGuire KA, Lewanczuk R et al (2007) Overweight, physical activity and high blood pressure in children: a review of the literature. Vasc Health Risk Manag 3:139–149PubMedPubMedCentralGoogle Scholar
  103. Urbina E, Alpert B, Flynn J et al (2008) Ambulatory blood pressure monitoring in children and adolescents: recommendations for standard assessment: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee of the Council on Cardiovascular Disease in the Young and the Council for High Blood Pressure Research. Hypertension 52:433–451Google Scholar
  104. Urbina EM, Kimball TR, McCoy CE et al (2009) Youth with obesity and obesity-related type 2 diabetes mellitus demonstrate abnormalities in carotid structure and function. Circulation 119:2913–2919PubMedPubMedCentralGoogle Scholar
  105. Uzunlulu M, Oguz A, Yorulmaz E (2006) The effect of carvedilol on metabolic parameters in patients with metabolic syndrome. Int Heart J 47:421–430PubMedGoogle Scholar
  106. Vague P (2003) Is metformin more than an oral hypoglycaemic agent? Diabetes Metab 29:6S5–6S7PubMedGoogle Scholar
  107. Van Gaal LF, De Block CE (2012) Bariatric surgery to treat type 2 diabetes: what is the recent evidence? Curr Opin Endocrinol Diabetes Obes 19:352–358PubMedGoogle Scholar
  108. Verdecchia P, Angeli F, Reboldi GP et al (2005) New-onset diabetes in treated hypertensive patients. Curr Hypertens Rep 7:174–179PubMedGoogle Scholar
  109. Weber MA, Bakris GL, Jamerson K et al (2010) Cardiovascular events during differing hypertension therapies in patients with diabetes. J Am Coll Cardiol 56:77–85PubMedGoogle Scholar
  110. Weiss R, Dziura J, Burgert TS et al (2004) Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 350:2362–2374Google Scholar
  111. Wellington K (2005) Rosiglitazone/Metformin. Drugs 65:1581–1592. discussion 1593–4PubMedGoogle Scholar
  112. Williams CL, Hayman LL, Daniels SR et al (2002) Cardiovascular health in childhood: a statement for health professionals from the Committee on Atherosclerosis, Hypertension, and Obesity in the Young (AHOY) of the Council on Cardiovascular Disease in the Young, American Heart Association. Circulation 106:143–160PubMedGoogle Scholar
  113. Zhou MS, Schulman IH, Raij L (2010) Vascular inflammation, insulin resistance, and endothelial dysfunction in salt-sensitive hypertension: role of nuclear factor kappa B activation. J Hypertens 28:527–535PubMedGoogle Scholar
  114. Zimmet P, Alberti G, Kaufman F et al (2007a) The metabolic syndrome in children and adolescents. Lancet 369:2059–2061PubMedGoogle Scholar
  115. Zimmet P, Alberti KG, Kaufman F et al (2007b) The metabolic syndrome in children and adolescents – an IDF consensus report. Pediatr Diabetes 8:299–306PubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Grace J. Kim
    • 1
    • 2
    Email author
  • Craig E. Taplin
    • 1
    • 2
  • Joseph T. Flynn
    • 3
  1. 1.Division of Endocrinology and DiabetesSeattle Children’s HospitalSeattleUSA
  2. 2.Department of PediatricsUniversity of Washington School of MedicineSeattleUSA
  3. 3.University of Washington School of MedicineDepartment of Pediatrics and Seattle Children’s Hospital, Division of NephrologySeattleUSA

Section editors and affiliations

  • Joseph T. Flynn
    • 1
    • 2
  1. 1.Department of PediatricsUniversity of Washington School of MedicineSeattleUSA
  2. 2.Division of NephrologySeattle Children’s HospitalSeattleUSA

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