Type 2 Diabetes Mellitus and Hypertension: An Update

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Key points

  • Patients with hypertension and type 2 diabetes are at increased risk of cardiovascular and chronic renal disease.

  • Factors involved in the pathogenesis of both hypertension and type 2 diabetes include inappropriate activation of the renin-angiotensin-aldosterone system, oxidative stress, inflammation, impaired insulin-mediated vasodilatation, augmented sympathetic nervous system activation, altered innate and adaptive immunity, and abnormal sodium processing by the kidney.

  • The

The burden

The National Health and Nutrition Examination Survey (NHANES) conducted from 2005 through 2008 estimated that HTN affects up to 65 million adults in the United States.9 Only 50% of hypertensive individuals have their blood pressure (BP) under control.10 The incidence of HTN is expected to increase further as the population ages and the frequency of obesity increases.10, 11 In a cross-sectional analysis of data from the Study to Help Improve Early Evaluation and Management of Risk Factors

Epidemiology

In nondiabetic individuals, the prevalence of HTN is higher in men than in women until the age of 64 years when the gap closes and prevalence in women reaches that of men.8 Women with impaired glucose tolerance (IGT) and DM have a higher incidence of HTN than men with equivalent impairment in glucose homeostasis.14 Diabetic women also have higher relative risk for death from CVD than diabetic men.15 The reason underlying the excess risk in diabetic women is still unclear. However, the increased

Pathophysiology: converging pathways in coexisting DM and HTN

DM and HTN share several pathophysiologic mechanisms including inappropriate activation of the renin-angiotensin-aldosterone system (RAAS), oxidative stress secondary to excessive production of reactive oxygen species (ROS), inflammation, impaired insulin-mediated vasodilatation, increased sympathetic nervous system (SNS) activation, dysfunctional innate and adaptive immune responses, and abnormal renal processing of sodium.2, 3 Obesity and increased visceral adiposity are key pathogenic

Role of oxidative stress

Increased oxidative stress is a key pathogenic factor in the development of insulin resistance, DM, and HTN.29 ROS can be produced in different vascular cell types, including endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) through activation of xanthine oxidase (XO), nitric oxide (NO) synthase, and the mitochondrial respiratory chain.30, 31, 32, 33 In turn, ROS can lead to impaired endothelial function by direct tissue injury, reduction of bioavailable NO, and impaired

Insulin resistance and hyperinsulinemia

Insulin resistance plays an important role in the development of both DM and HTN, as shown by approximately 50% of hypertensive patients manifesting systemic insulin resistance.3, 36, 37 Binding of insulin to the insulin receptor (IR) triggers 2 major pathways. A metabolic signaling pathway mediated by phosphatidylinositol 3-kinase (PI3K), downstream protein kinase B signaling, results in translocation of glucose transporter 4 (GLUT-4) to plasma membrane, thus resulting in increased

Impact of BP Control

High BP is a strong independent risk factor for CVD and chronic kidney disease (CKD), and, when HTN is associated with DM, the risk is increased even further.4, 52 Although controversy exists regarding the optimal target for BP reduction,3, 52, 53 consistent control of BP in patients with DM is important for preventing and delaying both microvascular and macrovascular complications.54, 55 Early data from landmark trials such as the United Kingdom Prospective Diabetes Study (UKPDS), Hypertension

Nonpharmacologic treatment: the role of therapeutic lifestyle intervention

Despite significant advances over the last several decades, the management of HTN is still not ideal, and about 50% of hypertensive patients are still not optimally controlled. The reasons underlying these results seem to be multiple and include deficiencies in current nonpharmacologic and pharmacologic management strategies. One of these issues, access to antihypertensive medications and BP control, was studied in the cross-sectional Reasons for Geographic And Racial Differences in Stroke

RAAS Blockade

Use of Ang II–converting enzyme inhibitors (ACEI) reduces the activity of Ang II, which results in vasodilatation, decreased BP, and improvement in the deleterious effects of Ang II on cardiac, vascular, and renal tissues.76, 77 The Heart Outcomes Prevention Evaluation (HOPE) study compared the effects of the ACE inhibitor ramipril versus placebo on cardiovascular complications and showed 25% risk reduction in MI, stroke, or cardiovascular death after a median follow-up period of 4.5 years.78 A

Incretin-based therapy and HTN: beyond glycemic control

A better understanding of the role of gut-derived hormones and their impact on carbohydrate homeostasis has been reached over the last decade, which has led to the development of incretin-based therapy. Glucagonlike peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide have been extensively studied in these regards, and are known to potentiate insulin secretion in a glucose-dependent manner in response to the presence of nutrients in the gut (ie, the incretin effect). In addition,

Combined pharmacologic therapy

Although treatment of HTN is often initiated with a single agent, most diabetic patients typically require combination therapy to control their BP. In a randomized, parallel-group, double-blind international trial comparing the once-daily single-pill combination of telmisartan 80 mg and amlodipine 10 mg (telmisartan/amlodipine; T/A) with once-daily amlodipine 10 mg (A) in patients with DM and HTN, T/A provided prompt and greater BP decreases compared with A monotherapy, with most patients

Telehealth

The treatment of HTN remains challenging and demands constant reshaping. Newer strategies are currently being tried for optimal control of HTN in diabetic patients, including the use of remote services like telehealth. Telehealth encompasses the use of medical information exchange remotely via electronic communications to improve a patient’s clinical health status. The use of telehealth for transmission of education and advice to the patient on an ongoing basis with close surveillance by nurses

Acknowledgments

The authors wish to thank Brenda Hunter for editorial assistance.

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References (123)

  • A. Fretheim

    VALUE: analysis of results

    Lancet

    (2004)
  • S. Julius et al.

    Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial

    Lancet

    (2004)
  • J.E. Campbell et al.

    Pharmacology, physiology, and mechanisms of incretin hormone action

    Cell Metab

    (2013)
  • J.R. Sowers et al.

    Diabetes, hypertension, and cardiovascular disease: an update

    Hypertension

    (2001)
  • J.R. Sowers et al.

    The role of overweight and obesity in the cardiorenal syndrome

    Cardiorenal Med

    (2011)
  • J.R. Sowers

    Diabetes mellitus and vascular disease

    Hypertension

    (2013)
  • J. Stamler et al.

    Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial

    Diabetes Care

    (1993)
  • G. Hu et al.

    Joint effects of history of hypertension at baseline and type 2 diabetes at baseline and during follow-up on the risk of coronary heart disease

    Eur Heart J

    (2007)
  • N. Sarwar et al.

    Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies

    Lancet

    (2010)
  • G. Chen et al.

    Cardiovascular outcomes in Framingham participants with diabetes: the importance of blood pressure

    Hypertension

    (2011)
  • B.M. Egan et al.

    US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008

    JAMA

    (2010)
  • J.D. Wright et al.

    Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001-2008

    Natl Health Stat Report

    (2011)
  • N.M. Kaplan et al.

    Hypertension in the population at large

  • A.J. Green et al.

    Quality of life, depression, and healthcare resource utilization among adults with type 2 diabetes mellitus and concomitant hypertension and obesity: a prospective survey

    Cardiol Res Pract

    (2012)
  • M.T. Eaddy et al.

    The burden of illness of hypertension and comorbid diabetes

    Curr Med Res Opin

    (2008)
  • S.M. Haffner et al.

    Greater effect of glycemia on incidence of hypertension in women than in men

    Diabetes Care

    (1992)
  • G. Hu et al.

    Gender difference in all-cause and cardiovascular mortality related to hyperglycaemia and newly-diagnosed diabetes

    Diabetologia

    (2003)
  • A.P. Carson et al.

    Ethnic differences in hypertension incidence among middle-aged and older adults: the multi-ethnic study of atherosclerosis

    Hypertension

    (2011)
  • A.R. Dyer et al.

    Ten-year incidence of elevated blood pressure and its predictors: the CARDIA Study, Coronary Artery Risk Development in (Young) Adults

    J Hum Hypertens

    (1999)
  • N. Etkin et al.

    Racial differences in hypertension-associated red cell sodium permeability

    Nature

    (1982)
  • X. Liu et al.

    Is the association of diabetes with uncontrolled blood pressure stronger in Mexican Americans and Blacks than in Whites among diagnosed hypertensive patients?

    Am J Hypertens

    (2013)
  • C.L. Ogden et al.

    Prevalence of obesity and trends in body mass index among US children and adolescents, 1999-2010

    JAMA

    (2012)
  • TODAY Study Group

    Rapid rise in hypertension and nephropathy in youth with type 2 diabetes: the TODAY clinical trial

    Diabetes Care

    (2013)
  • F. Massiera et al.

    Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation

    FASEB J

    (2001)
  • C.M. Boustany et al.

    Activation of the systemic and adipose renin-angiotensin system in rats with diet-induced obesity and hypertension

    Am J Physiol Regul Integr Comp Physiol

    (2004)
  • P.K. Mehta et al.

    Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system

    Am J Physiol Cell Physiol

    (2007)
  • J.S. Williams et al.

    50th anniversary of aldosterone

    J Clin Endocrinol Metab

    (2003)
  • M. Caprio et al.

    Pivotal role of the mineralocorticoid receptor in corticosteroid-induced adipogenesis

    FASEB J

    (2007)
  • J.H. Jeon et al.

    A novel adipokine CTRP1 stimulates aldosterone production

    FASEB J

    (2008)
  • S.A. Cooper et al.

    Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

    Am J Physiol Heart Circ Physiol

    (2007)
  • Y. Taniyama et al.

    Reactive oxygen species in the vasculature: molecular and cellular mechanisms

    Hypertension

    (2003)
  • N.R. Madamanchi et al.

    Oxidative stress and vascular disease

    Arterioscler Thromb Vasc Biol

    (2005)
  • W. Dröge

    Free radicals in the physiological control of cell function

    Physiol Rev

    (2002)
  • S. Johar et al.

    Aldosterone mediates angiotensin II-induced interstitial cardiac fibrosis via a Nox2-containing NADPH oxidase

    FASEB J

    (2006)
  • T. Barhoumi et al.

    T regulatory lymphocytes prevent angiotensin II-induced hypertension and vascular injury

    Hypertension

    (2011)
  • N.J. Brown

    Aldosterone and vascular inflammation

    Hypertension

    (2008)
  • E. Ferrannini et al.

    Insulin resistance in essential hypertension

    N Engl J Med

    (1987)
  • R. Muniyappa et al.

    Insulin action and insulin resistance in vascular endothelium

    Curr Opin Clin Nutr Metab Care

    (2007)
  • M.A. Vincent et al.

    Molecular and physiologic actions of insulin related to production of nitric oxide in vascular endothelium

    Curr Diab Rep

    (2003)
  • C.M. Taniguchi et al.

    Critical nodes in signalling pathways: insights into insulin action

    Nat Rev Mol Cell Biol

    (2006)
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    Disclosures: The authors have nothing to disclose.

    Funding Sources: Dr J.R. Sowers, NIH (R01 HL73101-01A1 and R01 HL107910-01), Veterans Affairs Merit System 0018.

    Conflict of Interest: Dr J.R. Sowers is on the Merck Pharmaceuticals Advisory Board.

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