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Patients with hypertension and type 2 diabetes are at increased risk of cardiovascular and chronic renal disease.
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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.
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The
Type 2 Diabetes Mellitus and Hypertension: An Update
Section snippets
Key points
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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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.