Diabetes_in_Cardiovascular_Disease_-_A_C

381

quality is based on meeting one of four goals: (1) threshold eye examination, and foot examination. The proportion of 31
met; (2) appropriate clinical action taken (e.g., starting or diabetes patients undergoing annual testing of HbA1c has
increasing the dose of an appropriate medication); (3) been relatively stable over the past decade with a slight trend The Quality Chasm
longitudinal assessment with resolution without intervention; upward, in the high 80% range for most payers (Fig. 31-2).14
or (4) identification of an exception such as a contraindica-
tion to further therapy intensification (e.g., a very low diastolic In 2010, the National Diabetes Surveillance System
blood pressure) or maximal therapy already in use despite published self-reported data on several process measures
risk factor level without achievement of therapeutic target.6 (Fig. 31-3).15 According to self-reports, 68.5% of patients
With continued improvement of electronic health records had HbA1c measured at least twice per year, 62.8% received
(EHRs), clinical action measures may prove an important an annual eye examination, and 67.5% underwent an annual
way in which to measure quality, capturing provider action, foot examination.15 As discussed earlier, the past decade
patient preferences or attributes, and long-term effect. involved much effort toward improving process measures
as evidenced by the relatively high percentage of patients
SURVEY OF CURRENT QUALITY OF DIABETES undergoing HbA1c and LDL-C testing, blood pressure mea-
CARE IN THE UNITED STATES surement, and nephropathy screening.

The main process measures for quality of diabetes care In examining control process measures of quality care,
are (at least) annual measurement of HbA1c, lipids, blood metrics associated more closely with outcomes, the United
pressure, and body mass index (BMI), and preventative mea- States national data for diabetes present some positive obser-
sures including annual flu vaccine, testing for nephropathy, vations and some areas for improvement. The main control
process measures are good glucose control (as reflected by
100 HbA1c Screening HbA1c below 8%) as contrasted with poor glucose control (as
defined as HbA1c above 9%); good blood pressure control
90 (defined as blood pressure below 130/80 mm Hg); and
good LDL-C control (defined as LDL-C below 100 mg/dL).
80 In 2011, good HbA1c control (below 8%) averaged around
60% across multiple payers, ranging from 48% to 65%
70 (Fig. 31-4).14

60

50 INCENTIVIZATION OR PAY FOR
PERFORMANCE
40
Several major pay-for-performance (P4P) initiatives have
30 reported their results for patients with diabetes. Unfortu-
nately, the effect on quality from these initiatives remains
20 controversial. Many studies indicate that improvements in
measurements can be achieved; however, studies also indi-
10 cate two important points: (1) once the financial incentive is
removed, quality declines; and (2) once the quality targets
0 are achieved, little improvement occurs afterward.6 The
largest P4P initiative, also cited as the most aggressive, is
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 the U.K. Health System Quality and Outcomes Framework,

Commercial-HMO Commercial-PPO Medicaid Medicare-HMO Medicare-PPO

Data Source: National Committee For Quality Assurance (NCQA) The State of Healthcare Quality Report 2012

FIGURE 31-2 Rates of HbA1c testing among US adults with diabetes 1999-
2011, stratified by type of health care coverage. (Data from the National
Committee For Quality Assurance (NCQA) The State of Healthcare Quality Report
2012. Available at: http://www.ncqa.org./Portals/0/SOHC-web1.pdf.)

PERCENTAGE OF U.S. ADULTS AGED 18 YEARS WITH
DIABETES WHO REPORT RECEIVING PREVENTIVE CARE
PRACTICES, 2009–2010

Annual flu vaccine 50.1%
57.4%
Ever attended diabetes 68.5%
self-management class

Checked HbA1c Ն 2 times a year

Annual foot exam 67.5%

Daily self-monitor of blood glucose 63.6%

Annual eye exam 62.8%

0 20 40 60 80
Percentage

Data were age adjusted. See Technical Notes for more details.

FIGURE 31-3 Self-reported preventative care for patients with diabetes, 2009 and 2010. (Modified from National Diabetes Surveillance System, Behavioral Risk Factor
Surveillance System data.)

382

GOOD HbA1c CONTROL (HbA1c Ͻ 8.0%) the results of the quality measures decreased.6 Despite these
unintended consequences and difficulty with sustainability,
VI 100OTHER DIABETES-RELATED CARDIOVASCULAR CONSIDERATIONS Commercial HMO Medicare HMO these types of incentives continue to develop, including
90 Commercial PPO Medicare PPO value-based reimbursements. Time will tell how effective
they are or how they will need to be used to maintain the
80 Medicaid success and improvements sought.

70 EFFORTS TO IMPROVE CONTROL MEASURES

60 There have been many other initiatives focused on improve-
ment of control measures for patients with diabetes; unfor-
50 tunately, many of these efforts have failed. First, efforts to
improve patient adherence have been evaluated in seve-
40 ral studies.16–19 Although there were many different methods
used, such as diabetes education, home aides, or nurse-led
30 training, only a small effect was seen in improving some con-
trol measures.16,17 These efforts tended to be more associ-
20 ated with improvement in processes of care,18 consistent
with prior observations that treatment intensification has a
10 greater influence on achievement of control measures than
does targeting improved patient adherence.19 Specifically,
0 2010 2011 efforts aimed at improving treatment intensification have
2009 shown some short-term improvements in control measures
and may be a source of future focus.10,20,21 One area that
FIGURE 31-4 Proportion of United States patients with diabetes achieving has consistently produced improved achievement of control
good glucose control 2009-2011. HMO ¼ Health maintenance organization; measures is group-based training for self-management strat-
PPO ¼ preferred provider organization. (Modified from National Committee For egies. Several studies have demonstrated improved HbA1c,
Quality Assurance [NCQA]: The State of Healthcare Quality Report 2012.) diabetes knowledge, systolic blood pressure, and BMI and a
reduction in the need for medications with such group-
introduced in 2004 as part of the General Medical Services based intervention programs.22
contract. In this system, control of glucose improved dramat-
ically with the program for many years. However, rates of Recently, a promising new model was introduced aiming
quality for nonincentivized measures declined, and there to help identify more accurately the measurements needed
was little improvement beyond the targeted glycemic goals.6 to improve outcomes with accountability tied to the measures
In the United States, Kaiser Permanente is another system (Fig. 31-5).5,23 The model emphasizes areas of control and
that has initiated diabetes performance measures aligned the primary drivers that affect health outcomes. In this model,
with financial incentives. Diabetes eye examinations and ret- health care (high control) accounts for 20% of control of
inopathy screening were the focus of these measures. After improving health; health behaviors (shared between health
initiation of the surveillance program, screening rates care and patient) account for 30%; and socioeconomic and
increased from 85% to 88%.6 However, when the financial
incentive was removed, the rates fell to below 80% (worse
than baseline). More concerning are the findings of a
cluster-randomized trial done using EHR-based diabetes
clinical decision support to improve glucose and blood pres-
sure control through the use of real-time feedback and
incentives. In the trial, once the incentives and feedback
ceased, even though the clinical decision support remained,

Key Health Primary Alignment with
outcome determinant drivers mission, capabilities,
and degree of control
Health care Preventive services
(20%) Acute care • Central to mission
Chronic disease • Many capabilities
Improved Health behaviors End of life • High control
health (as (30%) Cross-cutting issues
measured by • Central to mission
a summary Socioeconomic Tobacco nonuse • Shared capabilities
measure of factors (40%) Activity • Shared control
Diet and nutrition
health) Alcohol use • Alignmed with mission
• Limited capabilities
Community-identified • Limited control
drivers (advocacy
Environmental and participation)
factors (10%)
Community identified
FIGURE 31-5 Framework of the drivers of health determinants. drivers (advocacy
and participation)

Communities Health care 383 The Quality Chasm
delivery
systems needed to improve these outcomes, holding accountable
those responsible for each part as well as continuing to 31
Government Ensuring the Employers and improve on diabetes quality measurements.
public health conditions for businesses
infrastructure population health References
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Academia The media 2. Institute of Medicine (IOM): Crossing the quality chasm: a new health system for the 21st century,
Washington DC, 2001, National Academies Press.
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DC, 2000, National Academy Press.
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counting what counts: workshop summary, Washington, DC, 2013, The National Academies Press.
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directions, Diabetes Care 34:1651–1659, July 2011.
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decade ago remain relevant for contemporary patients with cular outcomes in patients with diabetes? PLoS One 8(10):e78821, 2013.
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Physicians practicing within engaged health systems, cemic therapy in type 2 diabetes: translating research into action for diabetes (TRIAD), Diabetes
focused on improving processes, are continuing to struggle Care 32(6):971–976, 2009.
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outcomes.
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As illustrated in Figure 31-6, health is not defined simply BMJ Qual Saf 22:339–347, 2013.
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tem. There are many key stakeholders that need to be patient-centered approach: position statement of the American Diabetes Association (ADA) and
engaged, with health care systems playing a vital part.24,25 the European Association for the Study of Diabetes (EASD), Diabetes Care 35(6):1364–1379, 2012.
If the health care system is to improve the health of patients 12. Ryden L, Grant PJ, Anker SD, et al: ESC guidelines on diabetes, pre-diabetes, and cardiovascular
with diabetes, given the overwhelming rates of diabetes and diseases developed in collaboration with the EASD: the Task Force on diabetes, pre-diabetes, and
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(2):2005, CD003638.
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2002, National Academies Press.

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Index

Note: Page numbers followed by b indicate boxes, f indicate figures and t indicate tables.

A role of primary invasive strategy and revascularization in diabetic patients
with, 271–280
ABCD study. see Appropriate Blood Pressure Control in Diabetes (ABCD)
study summary and recommendations, 259–260
Acute Coronary Syndrome Israeli Survey (ACSIS), 181
Abciximab, 264t, 267, 268t Acute coronary thrombosis, 91
Abnormal circadian blood pressure pattern, cardiovascular autonomic Acute ischemic stroke

neuropathy and, 364 hyperglycemic damage mechanisms in, 352t
Acarbose, 64, 165–167 treatments, influence of diabetes on, 352–353
Acarbose Cardiovascular Evaluation (ACE) study, 161 Acute myocardial infarction
Accelerated atherosclerosis mortality rates of, 381f
prognosis after, in patients with pathologic glucose metabolism,
diabetes and, 99–107
mechanisms of, 95–97, 96f 83–84, 83t
scope and complexity of the problem, 99 Acute Myocardial Infarction Treated with Primary Angioplasty and

insulin resistance and hyperinsulinemia, 107–108 Intravenous Enoxaparin or Unfractionated Heparin to Lower
scope and complexity of the problem, 107 Ischemic and Bleeding Events at Short-and Long-term Follow-up
(ATOLL) trial, 268
ACCEPT-D study. see Aspirin and Simvastatin Combination for Acyl-CoA synthetase (ACSL1), 121–122
Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D) ADAMTS9, 11t
study Adaptive immune response, 27–28
ADDITION-Europe trial, 348
ACCOMPLISH trial. see Avoiding Cardiovascular Events through Adenosine monophosphate-activated protein kinase (AMPK), 295
Combination Therapy to Patients Living with Systolic Hypertension A Diabetes Outcome Prevention Trial (ADOPT) study, 163
Adipocytes, role of, in type 2 diabetes mellitus, 14–16, 15f
(ACCOMPLISH) trial Adipokines, 140, 295
ACCORD-Lipid trial, 194 Adiponectin, 16, 295
ACCORD trial. see Action to Control Cardiovascular Risk in Diabetes Adipose tissue, in insulin resistance, 17, 18f
Adiposity
(ACCORD) trial metabolic risk configuration, 344–345
Acetyl-CoA, 294 stroke risk, 343–345
ADMIT. see Arterial Disease Multiple Intervention Trial (ADMIT)
A chain, 26 ADVANCE trial. see Action in Diabetes and Vascular Disease: Preterax
ACSIS. see Acute Coronary Syndrome Israeli Survey (ACSIS) and Diamicron Modified Release Controlled Evaluation
ACSL1. see Acyl-CoA synthetase (ACSL1) (ADVANCE) trial
Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Advanced glycation endproducts (AGEs), 95–96, 103, 103f
ADVENT. see Assessment of Diabetes Control and Evaluation of the Efficacy
Release Controlled Evaluation (ADVANCE) trial, 159, 160f, 172–173, Niaspan Trial (ADVENT)
177f Aerobic exercise, type 2 diabetes treatment, 144
Action stage, transtheoretical model of lifestyle change, 149, 150t, 152t African-American Heart Failure Trial (A-HeFT), 320
Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial, 158–159, Agency for Healthcare Research and Quality (AHRQ), disparities in access
160f, 334, 347, 363 to care, 372
control of glycemia vs. standard regimen in type 2 diabetes, 100 AGEs. see Advanced glycation endproducts (AGEs)
Kaplan-Meier curves for, 178f A-HeFT. see African-American Heart Failure Trial (A-HeFT)
target BP levels with T2DM, 176, 177f AHRQ. see Agency for Healthcare Research and Quality (AHRQ)
Activated protein C (APC), 115 AIM-HIGH trial. see Atherothrombosis Intervention in Metabolic Syndrome
Activity pyramid, type 2 diabetes treatment, 146, 146f with Low HDL/High Triglycerides: Impact on Global Health
Actos Now for the Prevention of Diabetes (ACT NOW) study, and Outcomes (AIM-HIGH) trial
development of diabetes, 63–64 Albumin-to-creatinine ratios (ACR), 133, 133f
ACUITY trial. see Acute Catheterization and Urgent Intervention Triage Aldose reductase (AR), 100
Strategy (ACUITY) trial in atherosclerosis, 100, 101f
Aliskiren Trial on Acute Heart Failure Outcomes, direct renin inhibitors,
Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) 317–318
trial, 272 ALLHAT. see Antihypertensive and Lipid-Lowering Treatment to Prevent
Heart Attack Trial (ALLHAT)
Acute coronary syndrome (ACS), 251–261 Alpha2-antiplasmin, 116, 116t
antiplatelet and antithrombotic therapy in diabetic patients with, 262–270 Alpha-glucosidase inhibitors, 325
aspirin for, 206 Altered platelet function, in type 2 diabetes mellitus, 113–114, 114f
coronary calcification in, 95 Ambulatory blood pressure monitoring (ABPM), abnormal circadian BP
pattern on, 364
in diabetes American College of Cardiology/American Heart Association
epidemiology of, 239–250 (ACC/AHA)
randomized controlled trials of, 243–245, 244t, 245f, 245t, 246f, 246t, 247f Guidelines for the Treatment of Blood Cholesterol to Reduce
registry studies of, 245–246, 247f, 247t, 248f, 248t Atherosclerotic Cardiovascular Risk in Adults: Global Risk
Assessment for Primary Prevention, 197
dynamic changes in glucose levels, and mortality in, 253 practice guidelines on PAD management, 332
glucose control in stages of HF evolution and recommended therapy, 302–303, 303f

clinical trials of, 253–258
current patterns of, 259, 259f
glucose-insulin-potassium (GIK) therapy in, clinical trials of, 257t
hyperglycemia during, 251
non-ST-elevation see Non-ST-elevation acute coronary syndrome
oral antiplatelet agents and doses in patients with, 264t
prevalence of elevated glucose levels in, 251–252
prognostic importance of hypoglycemia in, 258–259
relationship between glucose levels and mortality in, 252–253, 252f
relationship between glucose variability and patient outcome

during, 258

385

INDEX 386 Aspirin for Asymptomatic Atherosclerosis (AAA) trial, 335
Assessment of Diabetes Control and Evaluation of the Efficacy Niaspan Trial
American Diabetes Association (ADA)
diagnostic criteria for diabetes and prediabetes, 2t (ADVENT), and development of diabetes, 62
dietary guidance for coronary heart disease with diabetes, 140–141 Assessment of Treatment with Lisinopril and Survival (ATLAS) trial,
in lipid management strategies to reduce cardiovascular risk, 188
in low-dose aspirin therapy, 205–206 angiotensin-converting enzyme inhibitors and, 313–314, 317f
PAD in diabetes, 331 A Study of Cardiovascular Events in Diabetes (ASCEND) trial, 206
type 1 diabetes and cardiovascular disease, 127 Atherogenesis, platelets and, 203
Atherosclerosis
American Heart Association (AHA)
guidelines for risk stratification and treatment in youth with diabetes, 129f accelerated see Accelerated atherosclerosis
metabolic syndrome according to, 38t clinical manifestations of, in prediabetes, metabolic syndrome, and type 2
type 1 diabetes and cardiovascular disease, 127
diabetes, 76–82
Amylin analogue, 166t coronary, in sudden death, 88–91, 89f, 90t
Android fat distribution, 14
Angiogenesis, in type 2 diabetes mellitus, 93–95, 94f diabetics vs. nondiabetics, 90t, 91t
Angiotensin-converting enzyme (ACE) inhibitors, 58, 131, 313–314, 315t, relationship of risk factors, to plaque characteristics, 91t
in diabetes
317f epidemiology of coronary/peripheral, 73–86
in coronary heart disease with type 2 diabetes mellitus, 172, 176 prevalence of impaired glucose metabolism in patients with manifest,
impact of, on diabetes incidence, 58t
Angiotensin II (Ang II), 293 73–74
in post-myocardial infarction prevention, 307 subclinical, 74–75, 75f
Angiotensin receptor blockers (ARBs), 58, 131 vascular biology of, 99–110, 111–126
in coronary heart disease with type 2 diabetes mellitus, 176 diabetic see Diabetic atherosclerosis
for heart failure with diabetes mellitus, 314–317, 315t, 317f diffuse coronary see Diffuse coronary atherosclerosis
for hypertension, 308 hyperinsulinemia in, 107–108
impact of, on diabetes incidence, 58t impaired regression of, diabetes and, 106–107
Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), hypertension and insulin resistance in, 107–108
protein kinase c in, 102
blood pressure-lowering drugs, 174–175 Atherosclerosis Risk in Communities (ARIC) study, 58–60, 77–79, 156, 282,
Ankle-brachial index (ABI), 329, 331, 331f
Antibody response, in type 1 diabetes, 28 282f, 283f, 344
Anticoagulants Atherothrombosis

endogenous, changes in, 115 diabetes-associated, 217, 218f
parenteral, for acute coronary syndrome, 268t platelets and, 203
Antidiabetic drugs, for diabetes with heart failure, 325–326 Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High
Antihyperglycemic drugs
adverse effects of, 168 Triglycerides: Impact on Global Health Outcomes (AIM-HIGH) trial,
risk associated with, 167–168 62, 193
and risk of heart failure, 309–311 ATLAS trial. see Assessment of Treatment with Lisinopril and Survival
Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack (ATLAS) trial
ATOLL trial. see Acute Myocardial Infarction Treated with Primary
Trial (ALLHAT), diabetes extension study, 61 Angioplasty and Intravenous Enoxaparin or Unfractionated Heparin
Antineoplastic agents, influence on glucose metabolism and diabetes to Lower Ischemic and Bleeding Events at Short-and Long-term
Follow-up (ATOLL) trial
development, 66 Atopaxar, 214
Antiobesity agents, influence on glucose metabolism and diabetes Atrial fibrillation, with diabetes, oral anticoagulation in, 348–349
Autoantigens, in type 1 diabetes, 26–27, 26t
development, 64–65 Autonomy, motivational interviewing, 150–151
Antiplatelet therapy Autophagy, 122, 296–297, 297f
Autophagy-related proteins (ATGs), 296–297
effect on coronary heart disease with diabetes mellitus, 203–216 Avoiding Cardiovascular Events through Combination Therapy to Patients
aspirin and, 203–207, 205f, 206t, 207t Living with Systolic Hypertension (ACCOMPLISH) trial, 175–176
future directions in, 214 Azilsartan, 177
protease-activated receptor 1 antagonists and, 213–214
P2Y12 receptor antagonists and, 207–213 B

for peripheral artery disease in diabetes mellitus, 334–335 Bare-metal stents, 219t
Antipsychotic medication, influence on glucose metabolism and diabetes versus drug-eluting stents, 220–221, 220t, 221f
with percutaneous coronary intervention, coronary artery bypass graft
development, 65 versus, 231
Antithrombotic Trialists' Collaboration (ATC), secondary prevention studies
BARI trial. see Bypass Angioplasty Revascularization Investigation (BARI)
of oral antiplatelet agents, 206–207 trial
Appropriate Blood Pressure Control in Diabetes (ABCD) study, PAD with
Bariatric surgery, 66–67
diabetes, 334 B chain, 26
ARBITER 6-HALTS trial, ezetimibe and, 191, 193 Behavior change, in diabetes prevention, 48–50, 49f
ARIC study. see Atherosclerosis Risk in Communities (ARIC) study Belfast Diet Study, on diabetes mellitus, 334
Arterial Disease Multiple Intervention Trial (ADMIT), and development of Beta-adrenergic blockers, in peripheral artery disease, 335–336
Beta blockers (BBs), 58–61
diabetes, 62
Arterial Revascularization Therapies Study (ARTS), 230t, 231 for heart failure with diabetes treatment, 315t, 318–319, 319f
Arterial stiffness, cardiovascular autonomic neuropathy and, 364 potential deleterious metabolic effects of, 60b
ARTS. see Arterial Revascularization Therapies Study (ARTS) Beta cells, 4, 4f
ASCEND trial. see A Study of Cardiovascular Events in Diabetes (ASCEND) dysfunction

trial diabetes prevention and, 46
ASCOT. see Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) in type 2 diabetes mellitus, 19–21
Asia Pacific Cohort Studies Collaboration, association between blood mass, in insulin resistance, 20
Bezafibrate Infarction Prevention (BIP) trial, and development of diabetes, 63
pressure and coronary heart disease with type 2 diabetes mellitus, Biguanide, 166t
171, 172f Bile acid sequestrants, 63
Aspirin Bioabsorbable scaffolding stents, 219t
in diabetes with acute coronary syndrome, 262–263, 264t Bioactive stents, 219t
effect on coronary heart disease with diabetes mellitus, 203–207, 205f Biomarker Study to Identify the Acute Risk of Coronary Syndrome 2
mechanism of action of, 264f
in primary prevention of cardiovascular events, 203–206, 206t, 207t (BIOMArCS-2) study, 256
in secondary prevention of cardiovascular events, 206–207
in stroke, 348
Aspirin and Simvastatin Combination for Cardiovascular Events Prevention
Trial in Diabetes (ACCEPT-D) study, 206

Biomarkers, screening with, in heart failure, 305–306 387 INDEX
BIP trial. see Bezafibrate Infarction Prevention (BIP) trial
Bivalirudin, 224–225, 264t, 268t, 269 epidemiological data of, 362–363
Blood pressure cardiovascular disorders associated with, 363–364, 363f
as predictor of cardiovascular morbidity and mortality, 363
cardiovascular disease in type 1 diabetes, 130–131 prevalence and correlates of, 362
management of, effect on coronary heart disease with type 2 diabetes,
management of, 366–367, 366t
171–180 Cardiovascular autonomic reflex tests (CARTs), for subclinical
efficacy of lifestyle interventions on, 171–172
renal sympathetic denervation on, 178 cardiovascular autonomic neuropathy, 364
Blood pressure-lowering drugs Cardiovascular consequences, disparities in, 369–375
based on different drug classes, 175f Cardiovascular disease
comparative efficacy of, 174–176
efficacy and safety of, on coronary heart disease with type 2 diabetes global burden of, 239–242, 240f, 241f, 241t, 242f, 242t, 243f
metabolic syndrome and, 37–38
mellitus, 172–177
guidelines for the use of, in type 2 diabetes mellitus, 173t common soil for, 40–41
legacy effects of, 177 intermediate markers of, 38–39
new drugs, 177 in patients with abnormal glucose tolerance, 39–40
and target blood pressure levels, 176–177, 176f in the population, 37–38
vs. placebo on the coronary heart disease with diabetes mellitus, 174f nonmodifiable risk factors of, 135
Blood Pressure Lowering Treatment Trialists' Collaboration in type 1 diabetes
age and, 128–129
(BPLTTC), 172 magnitude of clinical problem of, 127–129
Brain, in insulin resistance, 18 pathophysiology of, 129
Bromocriptine, 165–167 pros and cons of treatment of, 130t
Buflomedil, 336 rates of, 128
Bupropion, smoking cessation and, 333 risk factors in, 129–135
Bypass Angioplasty Revascularization Investigation 2 Diabetes (BARI 2D) vs. type 2 diabetes, 128–129, 130t
undiagnosed diabetes in, 247–249
trial, 163–164, 278 Cardiovascular Health Study (CHS)
Bypass Angioplasty Revascularization Investigation (BARI) trial, 229–231, diabetes mellitus and subclinical atherosclerosis, 74
heart failure and, 281, 306
230t, 278 Cardiovascular Inflammation Reduction Trial (CIRT), 123–124
Bypass surgery, percutaneous coronary intervention versus, 221–224, 223t, Cardiovascular Risk Reduction Trial, 124
CARE-HF study. see Cardiac Resynchronization in Heart Failure (CARE-HF)
224f
study
C Carotid artery disease, 87–88
Carotid artery stenting (CAS), in stroke with diabetes mellitus, 349–350
CABRI trial. see Coronary Angioplasty versus Bypass Revascularization Carotid endarterectomy (CEA), in stroke with diabetes mellitus, 349–350
Investigation (CABRI) trial Carotid Revascularization Endarterectomy Versus Stent Trial (CREST), 350,

CACTI study. see Coronary Artery Calcification in Type 1 Diabetes (CACTI) 350t
study Carotid ultrasound, for atherosclerosis, 75f
Carvedilol, 60
Calcification, coronary, 95 Carvedilol or Metoprolol European Trial (COMET), beta blockers and, 319
Calcium antagonists, in coronary heart disease with type 2 diabetes mellitus, Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS)

172 trial, beta blockers and, 315t, 318
Calcium channel blockers, 61 CD25, expression of, 31
Calpains, in altered platelet function, 113–114 CDC123, 11t
CAMK1D, 11t CDKAL1, 11t
Canakinumab, subcutaneous, 124 CDKN2A, 11t
Candesartan in Heart Failure: Assessment of Reduction in Mortality and CDKN2B, 11t
Ceramide production, 293
Morbidity (CHARM-Alternative), angiotensin receptor blockers, Cerebrovascular dementia, 341
314, 317f Cerebrovascular disease, with diabetes mellitus, 341–360
Candesartan in Heart Failure: Assessment of Reduction in Mortality and CHA2DS2-VASc score, stroke risk in atrial fibrillation, 348, 348t
Morbidity (CHARM) study, 58, 58t, 285, 335 CHARISMA trial. see Clopidogrel for High Atherothrombotic Risk and Ischemic
Cangrelor, 214, 267t
CANTOS trial, 124 Stabilization, Management, and Avoidance (CHARISMA) trial
CAPN10, 11t CHD. see Coronary heart disease (CHD)
CAPRIE trial. see Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Cholesterol, in cardiovascular disease in type 1 diabetes, 131–133
Events (CAPRIE) trial Cholesteryl ester transfer protein (CETP), 63, 193
CARDIA trial. see Coronary Artery Revascularization in Diabetes (CARDIA) inhibition, 193–194
trial Chromogranin A (ChgA), in type 1 diabetes, 27
Cardiac dysfunction, with diabetes, prevalence of, 283–284, 285f CIBIS II trial. see Cardiac Insufficiency Bisoprolol Study II (CIBIS II) trial
Cardiac function, 295 CILON-T trial. see Efficacy of Cilostazol on Ischemic Complications after
Cardiac Insufficiency Bisoprolol Study II (CIBIS II) trial, beta blockers and,
318 Drug-Eluting Stent Implantation (CILON-T) trial
Cardiac Resynchronization in Heart Failure (CARE-HF) study, in cardiac Cilostazol, 213, 336, 336f
resynchronization therapy, 321–322, 322f CIRT. see Cardiovascular Inflammation Reduction Trial (CIRT)
Cardiac resynchronization therapy (CRT), 315t, 321–322, 322f Claudication: Exercise Versus Endoluminal Revascularization (CLEVER)
Cardiac resynchronization therapy-defibrillator (CRT-D), 315t
Cardiac troponin, 305–306, 306f study, 336–337
CARDINAL trial. see Complement and Reduction of Infarct Size after Claudication, peripheral artery disease and
Angioplasty or Lytics (CARDINAL) trial
Cardiomyocytes, 292 pharmacologic agents for, 336
Cardiovascular autonomic neuropathy (CAN), 361–368 treatment of, 336–337, 336f
clinical context of, 365–366 CLEVER study. see Claudication: Exercise Versus Endoluminal
diagnosis of, 365–366
screening asymptomatic patients with, 366 Revascularization (CLEVER) study
detection of, 364–365, 364t Clinical Trial of Reviparin and Metabolic Modulation in Acute Myocardial
in clinical practice, 364–365
evaluation of vagosympathetic activity, 365 Infarction Treatment and Evaluation-Estudios Cardiológicos
staging of, 365, 366f LatinoAmérica (CREATE-ECLA), 256–257, 257t
standard tests of, 364–365, 365f Clopidogrel
for diabetes with acute coronary syndrome, 263–266, 264t, 267t
effect on coronary heart disease risk in diabetes mellitus, 207–210, 208f
for PAD, 335
relative benefit of, 209f

INDEX 388 risk
with diabetes, effect of lifestyle interventions on, 139–154, 140f
Clopidogrel (Continued) with metabolic syndrome, 77–79
response variability of, 210 with prediabetes, 76–77
versus ticagrelor, 212f
and stroke, comparison of vascular risk factors between, 342–343
Clopidogrel and Aspirin Optimal Dose Usage to Reduce Recurrent Events- with type 2 diabetes mellitus
Seventh Organization to Assess Strategies in Ischemic Syndromes
(CURRENT-OASIS 7) trial, 209, 262–263, 265t effect of blood pressure management on, 171–180
epidemiologic association between blood pressure and, 171, 172f
Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Coronary multivessel disease, diabetes with
Management, and Avoidance (CHARISMA) trial, 266, 335 Kaplan-Meier estimates of the composite primary outcome, 276f
primary composite outcome, 277f
aspirin and, 207 staged revascularization for, 278
use of dual antiplatelet therapy, 209, 209f Coronary stents, 219t
Clopidogrel for the Reduction of Events during Observation (CREDO) trial, CREDO trial. see Clopidogrel for the Reduction of Events during Observation

209 (CREDO) trial
Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial, CREST. see Carotid Revascularization Endarterectomy Versus Stent Trial

208, 265t, 266 (CREST)
Clopidogrel Versus Aspirin in Patients at Risk of Ischaemic Events (CAPRIE) CRUSADE quality improvement initiative, 245, 248t
CURE trial. see Clopidogrel in Unstable Angina to Prevent Recurrent Events
trial, 207–208, 266, 335
Coagulation factors, increased, in type 2 diabetes mellitus, 114–115 (CURE) trial
Coagulation inhibition, 268–269 CURRENT-OASIS 7 trial. see Clopidogrel and Aspirin Optimal Dose Usage to
Cognitive impairment
Reduce Recurrent Events-Seventh Organization to Assess Strategies
diabetes in, 355–358 in Ischemic Syndromes (CURRENT-OASIS 7) trial
role of hypoglycemia on, 357–358, 358t Cyclooxygenase-1 (COX-1) enzyme, inhibition of, 203, 204f
Colesevelam, 165–167 Cytokines, in type 1 diabetes, 28
Collaboration, motivational interviewing, 150 Cytotoxic T lymphocyte-associated 4 (CTLA-4), 25–26, 30
Collaborative Atorvastatin Diabetes Study (CARDS), lipids and stroke, 347
COMET. see Carvedilol or Metoprolol European Trial (COMET) D
COMPANION trial. see Comparison of Medical Therapy, Pacing, and
Da Qing IGT and Diabetes Study, 5
Defibrillation in Heart Failure (COMPANION) trial Da Qing Study, 45
Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure Dallas Heart Study, 74
DCCT. see Diabetes Control and Complications Trial (DCCT)
(COMPANION) trial, cardiac resynchronization therapy and, 315t, DECODE study. see Diabetes Epidemiology: Collaborative Analysis of
321–322
Complement and Reduction of Infarct Size after Angioplasty or Lytics Diagnostic Criteria in Europe (DECODE) study
(CARDINAL) trial, 253 Dementia
CONSENSUS trial. see Cooperative North Scandinavian Enalapril Survival
Study (CONSENSUS) trial cerebrovascular, 341
Contemplation stage, transtheoretical model of lifestyle change, 149, 150t, 152t diabetes-related see Diabetes-related dementia
Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS) mixed, 355
trial, angiotensin-converting enzyme inhibitors and, 313, 315t role of hypoglycemia on, 357–358, 358t
COPERNICUS trial. see Carvedilol Prospective Randomized Cumulative vascular risk factor for, 355–358
Survival (COPERNICUS) trial Dendritic cells, 28t, 29
Coronary angiography, for atherosclerosis, 75f Detection of Ischemia in Asymptomatic Diabetics (DIAD) trial, 363
Coronary Angioplasty versus Bypass Revascularization Investigation Diabetes and Insulin-Glucose in Acute Myocardial Infarction (DIGAMI) trial,
(CABRI) trial, 230–231, 230t
Coronary arterial remodeling, 93, 94f 233–234
Coronary artery bypass graft surgery (CABG) Diabetes Autoimmunity Study in the Young (DAISY), 26t, 27
in diabetic patients, 228–229 Diabetes Control and Complications Trial (DCCT), 99, 127, 131t, 346, 366
versus drug-eluting stents, 231–232 Diabetes Epidemiology: Collaborative Analysis of Diagnostic Criteria in
early outcomes of, 228
graft patency after, 229 Europe (DECODE) study, 77–79
in heart failure with diabetes mellitus, 315t, 322–323 Diabetes mellitus
hyperglycemia increases morbidity and mortality in, 233
insulin infusions in, favorable effects of, 233–234 accelerated atherosclerosis and, 99–107
late outcomes of, 229 acute coronary syndromes in
optimal target for serum glucose in, 234–235
percutaneous coronary intervention and, procedural aspects of, 276–278 epidemiology of, 239–250
versus percutaneous coronary intervention with bare metal stents, 231 randomized controlled trials of, 243–245, 244t, 245f, 245t, 246f, 246t, 247f
revascularization strategies registry studies of, 245–246, 247f, 247t, 248f, 248t
for diabetes mellitus, 229–233, 230t and acute stroke, 351–355
for ST-elevation myocardial infarction, 275 arterial wall in, 112f
risk profiles and comorbidities of, 228 association with incident heart failure, 281–283, 282t
role of, in diabetes and perioperative glucose management, 228–238 atherosclerosis in
Coronary artery calcification (CAC), 74 epidemiology of coronary/peripheral, 73–86
incidence of, 76f impaired regression of, 106–107
progression of, 133, 133f prevalence of impaired glucose metabolism in patients with manifest,
Coronary Artery Calcification in Type 1 Diabetes (CACTI) study, 128, 131,
131f, 132f 73–74
Coronary artery disease, 87–88 subclinical, 74–75, 75f
Coronary Artery Revascularization in Diabetes (CARDIA) trial, 230t, 231 atherosclerotic complications and, 85
Coronary CT, for atherosclerosis, 75f atherothrombosis and, specificities of, 217, 218f
Coronary Drug Project (CDP), 193 carotid artery interventions in, 349–350
Coronary heart disease (CHD) cerebrovascular disease in patients with, 341–360
with diabetes mellitus, 307 comorbidities
changing epidemiology of, 155 in racial and ethnic minorities, 369–372
common soil hypothesis of, 156f in women, 372
effect of glucose management on, 155–170 coronary artery disease (CAD) in sudden death with, 89f
in women, 84 coronary disease with, management of, 232f
epidemiologic relationship of glucose with, 155–157 coronary heart disease
HDL cholesterol levels associated with, 112–113 risk, 181–188
metabolic syndrome and, 39t in women, 84
and coronary heart disease, epidemiology of, 155
development of, pharmacologic treatment that influences glucose

metabolism and, 63–66

drug-eluting stents in, 222t 389 INDEX
endothelial function and dysfunction in, 116–120, 117t, 118f
global burden of, 239–242, 240f, 241f, 241t, 242f, 242t, 243f plaque morphology and inflammation in, 87–95
heart failure in receptor-dependent pathways in, 104–105, 105f, 106f
receptor-independent pathways in, 104
epidemiology of, 281–289 Diabetic atherosclerotic plaques, late progression of, mechanisms linked to
prevention of, 302–312
treatment of, 313–326, 314t, 315t early initiation versus, 109f
and hyperlipidemia, effect on macrophage infiltration and necrotic core Diabetic cardiomyopathy, 290–301, 291b

size, 93f cause of, 292f
impact in atherosclerosis, 101f current treatment strategies and potential therapeutic targets of, 297–299
epidemiological evidence of, 290–291
incidence, impact of angiotensin-converting enzyme inhibitors and metabolic events participating in, 294f
angiotensin receptor blockers, 58t natural history of, 291t
pathophysiology and molecular mechanisms of, 291–295, 292f
incident, in patients with heart failure, 285 scope of the problem, 290
invasive treatment to prevent/reverse, 66–67 Diabetic coronary arteries, inflammation in, 92f
ischemic stroke in, pathophysiology and subtypes of, 345–346, 346f Diabetic dyslipidemia, 111–113
in key statin trials, 189, 190t Diabetic retinopathy, 1
DIAD trial. see Detection of Ischemia in Asymptomatic Diabetics (DIAD) trial
lowering cardiovascular morbidity and mortality, 334 Diastolic blood pressure (DBP)
as a major risk factor in acute coronary syndromes, 271–272 association with coronary heart disease with type 2 diabetes mellitus, 171
metabolic syndrome and, 39t in patient with diabetes and hypertension, effect of blood pressure-

new-onset, 191 lowering treatment in, 177f
percutaneous coronary intervention in, 217–227 Diastolic dysfunction, 285f, 313–328
Diet
adjunctive pharmacologic treatment for, 224–225
bypass surgery versus, 221–224, 223t, 224f and cardiometabolic risk, 142
conservative strategy in, 218–219 cardiovascular disease in type 1 diabetes and, 134
methodologic considerations to, 217–218, 218f type 1 diabetes and, 31–32, 32t
strategies to improve, 225 type 2 diabetes mellitus and, 5
peripheral artery disease in, 84, 329–340 Dietary Approaches to Stop Hypertension (DASH) diet, 5, 142, 172
approach to the treatment of, 338 Dietary carbohydrate intake, 142
clinical presentation, diagnosis, and natural history of, 330–332 Dietary guidelines, associated with cardiovascular risk reduction, 141b
epidemiology and prognosis of, 329–330 Dietary n-3 polyunsaturated fatty acids, 142
revascularization for, 337–338 Diffuse coronary atherosclerosis, 89f, 91–92
risk factor identification, lifestyle modification, and pharmacotherapy DIGAMI-2 multicenter study, 254–255, 255t
DIGAMI trial. see Diabetes and Insulin-Glucose in Acute Myocardial
of, 332–337
quality of care and, 379–384 Infarction (DIGAMI) trial
Digitalis glycoside, 315t
assessing, 379–380 Digitalis Investigation Group (DIG) trial, digoxin and, 321
efforts to improve control measures, 382–383, 382f Digoxin
importance of physician-patient interface in achievement of high,
for heart failure with diabetes, 321
380–381 influence on glucose metabolism and diabetes development, 63
incentivization or pay for performance, 381–382 Dipeptidyl peptidase 4 (DPP-4) inhibitors, 165, 310
intermediate outcomes, 380 Dipyridamole, 213
Direct oral anticoagulants (DOACs), 349
measures, 380 advantages of, 349
survey of current, 381, 381f, 382f disadvantages of, 349
revascularization strategies for, 229–233, 230t Direct renin inhibitors, 317–318
risk, disparities in, 369, 370f Disability-adjusted life years (DALYs), type 2 diabetes mellitus and, 3
statin efficacy among patients with, 189–191, 198t Discrepancy, motivational interviewing, 151
stroke in Disparities in access to care, 372–373
epidemiology of, 341–345 age-related, 374–375
primary and secondary prevention of, 346–351 ethnic, 373–374
as stroke risk factor in younger patients, 343 gender, 373
and subclinical atherosclerosis, 74–75, 76f Diuretics
trials and substudies, baseline characteristics of, 186t for heart failure with diabetes mellitus, 321
trials with lipid intervention in patients with, 195–196 influence on glucose metabolism and diabetes development, 61
type 1 see Type 1 diabetes mellitus (T1DM) Dose-response effects, of lifestyle behavior in diabetes, 45f
type 2 see Type 2 diabetes mellitus (T2DM) DPP. see Diabetes Prevention Program (DPP)
Drug-eluting stents, 219t, 221, 222t
undiagnosed, with cardiovascular diseases and acute coronary bare-metal stents versus, 220–221, 220t
syndrome, 247–249, 248f, 249f coronary artery bypass graft versus, 231–232
percutaneous coronary intervention with, 278, 279f
as vascular risk factor for cognitive impairment and dementia, 355–358 Dual antiplatelet therapies, as adjunct to PCI, 224
autopsy studies in, 356–357 Dysfunctional visceral adipose tissue, 40
brain imaging studies in, 356 Dysglycemia, diabetes and, 39
clinical studies on, 355–356 Dyslipidemia
definition and epidemiology, 355, 355f atherogenic, drugs targeting, 194
in cardiovascular disease in type 1 diabetes, 131–133, 132f
vascular risk factors of
management of, 346–348 ADA recommendations for, 133t
multiplicative risk increase by, 343 coronary heart disease risk among patients with, 181–188
diabetic, 111–113
Diabetes Mellitus, Insulin Glucose Infusion in Acute Myocardial Infarction in peripheral artery disease, 332–333
(DIGAMI) trial, 165, 254, 255t
E
Diabetes Prevention Program (DPP), 64, 159–160
Diabetes Prevention Program Outcomes Study (DPPOS), 46 EARLY-ACS trial. see Early Glycoprotein IIb/IIIa Inhibition in Non-ST-
Segment Elevation Acute Coronary Syndrome (EARLY-ACS) trial
Diabetes Reduction Assessment with Ramipril and Rosiglitazone
Early Glycoprotein IIb/IIIa Inhibition in Non-ST-Segment Elevation Acute
Medication (DREAM) trial, and development of diabetes, 63 Coronary Syndrome (EARLY-ACS) trial, 248–249

Diabetes-related dementia

prevention and treatment of, 357
vascular and degenerative mechanisms in, 358, 358f

Diabetic atherosclerosis
additional mechanisms of, 105–106
glycation in, 103–105, 103f
inflammation as therapeutic target in, 122–124
pathology of, 87–98

INDEX 390 frequency, 147–148, 147t
intensity and duration, 146–147
Early Treatment Diabetic Retinopathy Study (ETDRS), 203 programming and prescription, 144–148
EAT CLEVER principle, 51t structured session, 148, 148b
Economic benefits, in diabetes prevention, 51 type of, 144–148
ECST. see European Carotid Surgery Trial (ECST) Exit stage, transtheoretical model of lifestyle change, 149, 150t, 152t
Ectopic fat depositions, insulin resistance and, 16 Extracellular newly identified RAGE-binding protein (EN-RAGE), 95–96
Efficacy of Cilostazol on Ischemic Complications after Drug-Eluting Stent Ezetimibe, 191
influence on glucose metabolism and diabetes development, 63
Implantation (CILON-T) trial, 213 mechanism of action of, 189f
EMERALD trial. see Enhanced Myocardial Efficacy and Removal by
F
Aspiration of Liberated Debris (EMERALD) trial
Emerging Risk Factors Collaboration (ERFC), 76–77 Factor VII, 115
Emory Angioplasty versus Surgery Trial (EAST), 230t Factor XIII, 115
Empathy, express, motivational interviewing, 151 Family history, type 2 diabetes mellitus and, 4
EMPHASIS-HF trial. see Eplerenone in Mild Patients Hospitalization and Fasting plasma glucose (FPG), 1

Survival Study in Heart Failure (EMPHASIS-HF) trial different levels of, stroke rates and, 344t
End-stage renal disease, with diabetes mellitus, 370–371, 371f “Fatty streaks”, 120
Endarterectomy Versus Angioplasty in Patients with Symptomatic Severe Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) study, 333
Fetuin-A, 18
Carotid Stenosis (EVA-3S), 350 Fibrates, 63, 112, 194, 195f
Endoplasmic reticulum, 28
general limitation of the available data, 194
stress response, 296f Fibric acid derivatives. see Fibrates
Endothelial cells, insulin receptor signaling and, 107 Fibrinogen, diabetes and, 115
Endothelial dysfunction Fibrinolysis, impaired, in diabetes, 115–116, 116t
Fibroatheromas, 90
adhesion and inflammation, 119–120 FIELD study. see Fenofibrate Intervention and Event Lowering in Diabetes
role of reactive oxygen species in, 119f
Endothelial lipase (EL), expression and activity of, 112–113 (FIELD) study
Endothelial progenitor cells (EPCs), diabetic atherosclerosis and, 107 Finnish Diabetes Prevention Study (DPS), 5–6, 7, 45
Endothelium, function and dysfunction, in diabetes, 116–120, 117t, 118f Finnish Diabetes Risk Score (FINDRISC) questionnaire, 46
Endovascular catheter technology, in hypertension, 178 Foam cells, 119–120
Energy balance, coronary heart disease risk in diabetes, 140–143 Fondaparinux, 264t, 268–269, 268t
Enhanced Myocardial Efficacy and Removal by Aspiration of Liberated Fontaine classification, of peripheral artery disease, 330–331, 331t
Forkhead transcription factors, 297–298, 298f
Debris (EMERALD) trial, 272 Formins, 105
Enoxaparin, 264t, 268t Fragmin and Fast Revascularization During Instability of Coronary Artery
ENPP1, 11t
Environmental factors, in type 1 diabetes, 31–33, 31t disease (FRISC II) trial, 243, 245f, 272–273
Epidemiology of Diabetes Complications (EDC) study, 128, 131t Framingham Heart Study
Epidemiology of Diabetes Interventions and Complications (EDIC) study,
cardiovascular consequences disparities, 369–370
99, 127, 131t, 346, 366 diabetes with heart failure in women, 286
Epigenetics diabetic cardiomyopathy, 290–291
screening strategies for heart failure prevention, 304
causal underpinnings of diabetes, 4–5 Free fatty acids, in insulin resistance and type 2 diabetes, 14–16
in type 1 diabetes, 31 FREEDOM RCT trial, 223, 224f
Eplerenone in Mild Patients Hospitalization and Survival Study in Heart FREEDOM trial. see Future Revascularization Evaluation in Patients with

Failure (EMPHASIS-HF) trial, 285, 315t, 319 Diabetes Mellitus: Optimal Management of Multivessel Disease
Eptifibatide, 264t, 267, 268t (FREEDOM) trial
Erythromycin, influence on glucose metabolism and diabetes development, FRISC II trial. see Fragmin and Fast Revascularization During Instability of
Coronary Artery disease (FRISC II) trial
65 FTO, 11t
ESPRIT. see European/Australasian Stroke Prevention in Reversible Future Revascularization Evaluation in Patients with Diabetes Mellitus:
Optimal Management of Multivessel Disease (FREEDOM) trial, 230t,
Ischaemia Trial (ESPRIT) 232, 276, 276f, 277f
Estimated glomerular filtration rate (eGFR), cardiovascular disease risk
G
factor, 133, 133f
Estrogen, influence on glucose metabolism and diabetes development, 65 GAD2, 27
Euro Heart Survey on Diabetes and the Heart, 73 GAPDH. see Glyceraldehyde phosphate dehydrogenase (GAPDH)
European Association for the Study of Diabetes (EASD) Gauging Responsiveness with a VerifyNow P2Y12 Assay-Impact on

ESC and, 248 Thrombosis and Safety (GRAVITAS) trial, 210
guidelines on diabetes, prediabetes, and cardiovascular diseases, GEMINI trial. see Glycemic Effects in Diabetes Mellitus: Carvedilol-

196–197 Metoprolol Comparison in Hypertensives (GEMINI) trial
European Atherosclerosis Society, guidelines for the management of Gene-environment interactions, in type 2 diabetes mellitus, 4–5
Genes, in type 2 diabetes mellitus, 4–5
dyslipidemias, 196 Genetics, in type 1 diabetes, 29–31
European/Australasian Stroke Prevention in Reversible Ischaemia Trial Ginkgo biloba, for claudication treatment, 336
GISSI-HF trial. see Gruppo Italiano per lo Studio della Sopravvivenza nell'
(ESPRIT), 213
European Carotid Surgery Trial (ECST), 349 Infarto Miocardico-Heart Failure (GISSI-HF) trial
European Diabetes Leadership Forum, diabetes prevention and, 44 GIST-UK. see Glucose Insulin in Stroke Trial (GIST-UK)
European Society of Cardiology guidelines Glinides, 166t
Global Registry of Acute Coronary Events (GRACE) study, 245, 271, 275f
aspirin and, 205–206 GLP-1, insulin resistance and, 20
on diabetes, prediabetes, and cardiovascular diseases, 196–197 Glucagon-like peptide 1 (GLP-1), 325
for the management of dyslipidemias, 196
European Stroke Prevention Study (ESPS), combination of aspirin and effect on autonomic activity, 361–362
Glucose
dipyridamole, 213
Evocation, motivational interviewing, 150 with coronary heart disease, epidemiologic relationship of,
Examination of Cardiovascular Outcomes with Alogliptin Versus Standard 155–157

of Care (EXAMINE) trial, 165, 167f, 310 homeostasis, 191
EXAMINE trial. see Examination of Cardiovascular Outcomes with Alogliptin

Versus Standard of Care (EXAMINE) trial
Exercise

cardioprotective effects of, 144, 145f
cardiovascular disease in type 1 diabetes and, 134
for claudication in PAD, 336–337, 337t
for heart failure with diabetes mellitus, 315t, 323
intolerance, cardiovascular autonomic neuropathy and, 364
in prevention and treatment of type 2 diabetes mellitus, 143–144

in insulin resistance 391 INDEX
toxicity, 20
transport, 14 HDL-Atherosclerosis Treatment Study (HATS), and development of
diabetes, 62
lowering of
and heart failure prevention, 309–311 Health, Aging, and Body Composition (Health ABC) study, screening
intensity of, for treatment of diabetes with heart failure, 326 strategies for heart failure prevention, 304, 305f

management of, effect on coronary heart disease (CHD) with diabetes, Health-related behavior change model, 148–149
155–170 Heart and Estrogen/Progestin Replacement Study (HERS), 65, 281
Heart and Soul Study, 281
implications for clinical practice, 168–169 Heart Failure Endpoint Evaluation of Angiotensin II Antagonist Losartan
and mortality in acute coronary syndrome
(HEAAL) trial, in angiotensin-converting enzyme inhibitors and,
dynamic changes in, 253 313–314
relationship between, 252–253, 252f Heart failure (HF), 290
perioperative management age-adjusted prevalence of, 284f
coronary artery bypass surgery in diabetes and, 228–238 antihyperglycemic agents and risk of, 309–311
in intensive care unit, 235b devices and surgery for, 321–323
in intraoperative period, 235b diabetes mellitus and
in preoperative period, 235b adverse outcomes in, 285–288
prevalence of elevated, in acute coronary syndrome, 251–252 prevalence of, 283–284, 285f, 314t
response, parameters associated with a normal, 58b treatment of, 313–323
Glucose-clamp technique, 12 etiology of, 287
Glucose control exercise prescription for, 323
in acute coronary syndrome hospitalization, 285, 286f
clinical trials of, 253–258, 255t identifying precursors of symptomatic, 302–304
current patterns, 259f incidence of, 282f, 282t, 283f, 283t
in cardiovascular disease in type 1 diabetes, 129–130 mortality of, 286, 286f, 287f, 287t
for prevention of stroke in diabetes, 346 pharmacologic therapy for, 313–321
Glucose Insulin in Stroke Trial (GIST-UK), 353–354, 354f post-myocardial infarction prevention of, 307–308, 307f
Glucose-insulin-potassium (GIK) therapy, in acute coronary syndrome, with preserved ejection fraction (HFpEF), 302
with preserved left ventricular ejection fraction, 288, 288f
clinical trials of, 257t prevention of
Glucose-lowering agents, 166t challenges in, 311
Glucose-lowering trials, 157–159, 160f glucose lowering and, 309–311
in patients with diabetes, 302–312
evidence for specific drugs and drug classes, 161–167 strategies in, 302
in prediabetes and early diabetes, 159–161 risk modification for, 306–311
Glucose metabolism screening for, 304–306
impaired, prevalence of, in patients with manifest atherosclerosis, 73–74 with biomarkers, 305–306
mechanisms by which statins may impair, 62b with clinical risk factors, 304
pharmacologic treatment that influences, 63–66 with imaging, 306
stage A, 303
cardiovascular, 58–63, 58b, 59f stage B, 303–304, 304b
Glucose tolerance, abnormal, cardiovascular disease and metabolic symptomatic, with reduced ejection fraction, randomized controlled
trials in, 315t
syndrome and, 39–40 Heart Outcomes Prevention Evaluation (HOPE) study, 58, 58t, 335
Glucosidase inhibitors, 166t Heart Protection Study 2-Treatment of HDL to Reduce the Incidence of
Glucotoxicity, and hyperglycemia, 292–293 Vascular Events (HPS2-THRIVE) study, 62, 193
Glutamic acid decarboxylase (GAD), in type 1 diabetes, 27 Hemodynamic forces, 120
Glycated hemoglobin Hemoglobin A1c (HbA1c), 129–130, 131f, 344
cardiovascular disease and, 155–156, 157f
heart failure prevention and, 309 diabetic atherosclerosis and, 87
for ischemic stroke, 344f stroke risk, 343–344, 344f
Glycation, in diabetic atherosclerosis, 103–105 Hemorrhage
Glycemic control in aortic atherosclerosis with and without diabetes, 95f
after intensive care unit, 236–237, 237b type 2 diabetes mellitus and, 93–95, 94f, 95f
impact on heart failure, 309 Heptokines, 17–18, 17t
in poststroke hyperglycemia, 354–355, 354f HERS. see Heart and Estrogen/Progestin Replacement Study (HERS)
role on cardiovascular autonomic neuropathy, 366–367 Hexosamine biosynthetic pathway (HBP), 102
Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in HHEX, 11t
HI-5 trial. see Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5)
Hypertensives (GEMINI) trial, and development of diabetes, 60 trial
Glycemic index, 142 High-density lipoprotein cholesterol (HDL-C), drugs targeting, 191–192
Glycemic load, 142 High-dose calcium channel blocker therapy, 61
Glyceraldehyde phosphate dehydrogenase (GAPDH), 292–293 High-mobility group box 1 (HMGB1), RAGE and, 104
Glycohemoglobin, multivariable analysis of, 90 Histone acetyltransferases (HATs), 106
Glycoprotein IIb/IIIa inhibitors, 267–268 Histone deacetylases (HDACs), 106
Glycosylated hemoglobin, 142 HLA genes, 29–30, 29t
Glyoxalase 1 (Glo1), 95–96, 104, 104f HNF18, 11t
GPIIb-IIIa inhibitors, 224–225 Homeostatic model assessment (HOMA), insulin resistance and, 12
G-protein-coupled receptor 40 (GPR40) agonists, 165–167 HORIZONS-AMI trial. see Harmonizing Outcomes with Revascularization
GRACE study. see Global Registry of Acute Coronary Events (GRACE) study and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial
Graft patency, after CABG, 229 Hp gene, and diabetes mellitus, 93–95
GRAVITAS trial. see Gauging Responsiveness with a VerifyNow P2Y12 Assay- HPS2-THRIVE study. see Heart Protection Study 2-Treatment of HDL to
Reduce the Incidence of Vascular Events (HPS2-THRIVE) study
Impact on Thrombosis and Safety (GRAVITAS) trial Human aldose reductase (hAR), role in atherosclerosis, 100
Group-based interventions, in diabetes prevention, 50 Human immunodeficiency virus, treatment, type 2 diabetes and, 65
Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico- Hydralazine, for heart failure with diabetes treatment, 320
Hydralazine and isosorbide dinitrate (H-ISDN), 315t
Heart Failure (GISSI-HF) trial, omega-3 polyunsaturated fatty acids 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors,
and, 315t, 320 189–191
Gynoid fat distribution, 14

H

Harmonizing Outcomes with Revascularization and Stents in Acute
Myocardial Infarction (HORIZONS-AMI) trial, 224–225, 272

Hazard ratios (HRs), for vascular outcomes in people with versus without
diabetes at baseline, 77f

INDEX 392 Ins2, 25
Insulin, 12, 57, 164–165, 166t
Hyperglycemia, 87–88, 251–261
-induced vascular damage, mechanisms of, 89f for acute coronary syndrome, 259f
during acute coronary syndrome, 251 for diabetes-related dementia, 357
atherosclerotic plaque with, 88 for diabetes with heart failure, 324–325
detrimental effects in diabetic myocardium and its reversal with insulin, effect on autonomic activity, 361–362
233–237 gene, 30
diabetic dyslipidemia and, 113 hyperglycemia reversal with, detrimental effects in diabetic myocardium,
and glucotoxicity, 292–293
increases morbidity and mortality, in coronary artery bypass graft, 233 233–237, 236f
in perioperative period, management of, 235–236 infusions
promoting atherogenesis, 96f
role of, in cardiovascular consequences in diabetes, 99–106 in diabetic coronary artery bypass graft, favorable effects of, 233–234
transition to subcutaneous insulin therapy, 236f
Hyperglycemia: Intensive Insulin Infusion in Infarction (HI-5) trial, 254, 255t and risk of heart failure, 310–311
Hyperinsulinemia secretion of
glucose-dependent, 19
in atherosclerosis, 107–108 pulsatility, 19
cardiovascular autonomic neuropathy and, 361–362 role in type 2 diabetes mellitus, 19
insulin resistance, and altered substrate metabolism, 293 in type 1 diabetes, 26
scope and complexity of the problem, 107 Insulin-dependent glucose transporter GLUT-4, 14, 15f
Hyperkalemia, mineralocorticoid receptor antagonists and, 320 Insulin-like growth factor 1 (IGF-1), 293
Hyperlipidemia Insulin receptor
and diabetes, effect on macrophage infiltration and necrotic core size, 93f in insulin resistance, 13–14
and lipotoxicity, 293 substrates, 13–14
Hypertension signaling
cardiovascular autonomic neuropathy and, 363 endothelial cells and, 107
in cardiovascular disease in type 1 diabetes, 130–131, 132f macrophages and, 108
diabetes and, 40 vascular smooth muscle cells and, 108
effect of blood pressure-lowering treatment in systolic and diastolic BP in Insulin receptor-mediated effects, 12f
Insulin resistance, 4, 10–23
patients with, 177f in atherosclerosis, 107–108
in peripheral artery disease, 333–334 cardiac lipotoxicity, 293
in strategies of risk modification of heart failure, 308 cardiovascular disease risk factor, 134
in stroke, 347, 347f cellular mechanisms of, 12–13
Hypertriglyceridemia, of diabetes, 111–112 diabetes prevention and, 46
Hypoglycemia glucose transport in, 14
with acute coronary syndrome, prognostic importance of, 258–259 hyperinsulinemia, and altered substrate metabolism, 293
beta blockers and, 319 metabolic risk configuration, 344
cardiovascular changes during, 366–367, 367f relationships between cardiac autonomic dysfunction, obesity and, 362f
with cardiovascular events, 158–159, 167–168, 168f role of vagosympathetic impairment in, 361
role on cognitive impairment and dementia, 357–358, 358t scope and complexity of the problem, 107
and stroke, 351 stroke risk, 343–345
tissue-and organ-specific contribution to, 16–18
I type A, 13–14
Insulin signaling
ICTUS trial. see Invasive Versus Conservative Treatment in Unstable in insulin resistance, 12–13, 13f
Coronary Syndromes (ICTUS) trial modulators of, 295
Insulinoma-associated protein 2 (IA-2), in type 1 diabetes, 27
IDF. see International Diabetes Federation (IDF) Insulitis, 27
IGF2BP2, 11t Intensive glucose therapy, 158–159
ILLUMINATE trial. see Investigation of Lipid Level Management to Interferon induced with helicase C domain 1 (IFIH1) gene, 30–31
INTERHEART study, 239
Understand Its Impact in Atherosclerotic Events (ILLUMINATE) trial Interleukin 2 receptor alpha subunit (IL2RA) gene, 31
IMAGE project (Development and Implementation of a European Guideline Intermittent claudication, 329
Internal mammary artery (IMA), graft patency of CABG, 229
and Training Standards for Diabetes Prevention), 50 International Diabetes Federation (IDF), 239
Immediate Myocardial Metabolic Enhancement During Initial Assessment metabolic syndrome according to, 38t
International Verapamil SR Trandolapril Study (INVEST)
and Treatment in Emergency Care (IMMEDIATE) trial, 257, 257t and development of diabetes, 61
IMMEDIATE trial. see Immediate Myocardial Metabolic Enhancement systolic blood pressure, 171
Intersectoral public health system, 383f
During Initial Assessment and Treatment in Emergency Care INTERSTROKE case-control study, 342–343
(IMMEDIATE) trial Intra-aortic balloon pump (IABP) placement, 228
Impaired contractility, cardiac lipotoxicity and, 293 Intracellular Ca2+ homeostasis, abnormalities in, 293–294
Impaired fasting glucose, stroke risk, 343–344, 344t Intracoronary atherothrombosis, 262
Impaired glucose tolerance (IGT), 45 Intramyocellular fat depositions, 16
stroke risk, 343–344 Intravascular ultrasound (IVUS), for atherosclerosis, 75f
Implantable cardioverter defibrillators (ICDs), 315t, 321 Invasive Versus Conservative Treatment in Unstable Coronary Syndromes
IMPROVE-IT study, ezetimibe and, 191
Incentivization, in quality of care for diabetes mellitus, 381–382 (ICTUS) trial, 272–273
Incretin, 123 INVEST. see International Verapamil SR Trandolapril Study (INVEST)
modulators, 166t, 325 Investigation of Lipid Level Management to Understand Its Impact in
and type 2 diabetes, 20
Incretin-based therapies, 165 Atherosclerotic Events (ILLUMINATE) trial, and development of
“Incretin effect”, 20 diabetes, 63
Infectious factors, in type 1 diabetes, 32–33, 33f IOM. see U.S. Institute of Medicine (IOM)
Inflammation Iron deposition, in diabetic coronary plaques, 94f
in aortic atherosclerosis with and without diabetes, 95f Islet-specific glucose-6-phosphatase catalytic subunit-related protein
in atherosclerosis with diabetes, 120–124 (IGRP), in type 1 diabetes, 27
cardiovascular disease risk factor, 134 Italian Longitudinal Study on Aging, 77–79
in diabetic coronary arteries, 92f Ivabradine, 320
in diabetic coronary plaques, 94f
as therapeutic target in diabetic atherosclerosis, 122–124
Inflammatory infiltrate, diabetics vs. nondiabetics, 92f
Innate immune cells, 28t
Innate immune system response, 28–29
Ins1, 25

J 393 INDEX

Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS), 195 Loss of tolerance, in type 1 diabetes, 25–26
Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes Low- and middle-income countries (LMICs), number of people with type 2

(JPAD) study, 204 diabetes mellitus in, 3
JAZF1, 11t Low-density lipoprotein cholesterol (LDL-C)
JELIS. see Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS)
JPAD study. see Japanese Primary Prevention of Atherosclerosis with Aspirin baseline characteristics of diabetes trials and substudies ranked by, 186t
drugs targeting, 188–191, 188f, 189f
for Diabetes (JPAD) study Low-density lipoproteins (LDLs), diabetic dyslipidemia and, 113
JUPITER trial. see Justification for the Use of Statins in Prevention: an Low-molecular-weight heparins (LMWHs), 268
Ludwigshafen Risk and Cardiovascular Health (LURIC) study, 73, 84
Intervention Trial Evaluating Rosuvastatin (JUPITER) LURIC study. see Ludwigshafen Risk and Cardiovascular Health (LURIC) study
Justification for the Use of Statins in Prevention: an Intervention Trial Lymphocytes, inflammation and, 122

Evaluating Rosuvastatin (JUPITER), 123 M

K Macrophage plaque area, in diabetes, 90–91
Macrophages, 28, 28t
KCNJ11, 11t
KCNQ1, 11t infiltration, effect of hyperlipidemia and diabetes on, 93f
Key statin trials, patients with diabetes in, 189, 190t inflammation and, 121–122
Kidney disease, cardiovascular disease risk factor, 133 insulin receptor signaling and, 108
KIHD study. see Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study MADIT-II. see Multicenter Automatic Defibrillator Implantation Trial II
Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study, 77–79, 78f
(MADIT-II)
L Magnetic resonance imaging (MRI), for atherosclerosis, 75f
Maintenance stage, transtheoretical model of lifestyle change, 149, 150t, 152t
LANCELOT program. see Lessons from Antagonizing the Cellular Effects of Malmo€ Feasibility Study, 45
Thrombin (LANCELOT) program Mammalian target of rapamycin (mTOR), 298
Meal replacement diets, 141
Lean body mass, 140 Medical nutritional therapy (MNT), 141
Left ventricular dysfunction, cardiovascular autonomic neuropathy and, 363 Mediterranean-style diet, 5
Left ventricular ejection fraction (LVEF), preserved MERIT-HF. see Metoprolol CR/XL Randomised Intervention Trial in
heart failure with, 288, 288f
“Legacy effect,” in diabetes, 106 Congestive Heart Failure (MERIT-HF)
Leptin, 295 MESA study. see Multi-Ethnic Study of Atherosclerosis (MESA)
Lessons from Antagonizing the Cellular Effects of Thrombin (LANCELOT) Metabolic imprinting, type 2 diabetes mellitus and, 4
Metabolic memory, 106
program, phase II, 214 Metabolic risk configurations, stroke risk in, 344–345
Leukocyte adhesion cascade, 117–118 Metabolic syndrome (MetS), 10–12, 37–43
Lifestyle
and cardiovascular disease, 37–38
change common soil for, 40–41
assessment of, 149–150 intermediate markers of, 38–39
psychosocial interventions to support, 148–152 in patients with abnormal glucose tolerance, 39–40
readiness for, 148–150, 150t, 152t in the population, 37–38
stages of transtheoretical model, 149, 149f
clinical manifestations of atherosclerosis in, 76–82
interventions coronary heart disease risk of patients with, 77–79, 78f, 79f
effect on coronary heart disease risk in patients with diabetes, 139–154 definitions of, 38t
efficacy on blood pressure levels and coronary heart disease risk in diseases and emerging risk factors related to, 42b
type 2 diabetes mellitus, 171–172 as guide for patient-centered treatment, 41–42
metabolic risk configuration, 344–345
physical activity, type 2 diabetes treatment, 146 pathogenesis of, 41f
type 2 diabetes mellitus and, 5–6, 5f phenotypes of, cardiovascular disease of, 40t, 41f
LIMB trial. see Limbs International Medicinal Buflomedil (LIMB) trial prevalence of, 39t
Limbs International Medicinal Buflomedil (LIMB) trial, 336
Lipid-lowering therapy in type 2 diabetes patients, 40t
clinical practice guidelines for, 196–199 stroke risk, 343–345
by numbers of diabetic patients at inclusion, trials of, 184t Metformin
policy, 197 for diabetes, 6
Lipid-lowering trials, primary outcome rates, baseline atherogenic lipids, for diabetes-related dementia, 357
as glucose-lowering agent, 162–163
and apo B from, 187t influence on glucose metabolism and diabetes development, 64
Lipid management, effect on coronary heart disease risk in patients with treatment of diabetes with heart failure, 323–324
for type 2 diabetes mellitus, 53
diabetes, 181–202 Methotrexate, 123–124
outcomes classification, 185t Methylglyoxal (MG) dicarbonyl, 104, 104f
reconciling discordance in the guidelines of, 197 Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart
strategies, 188–196
trials on, 182t Failure (MERIT-HF), beta blockers and, 315t, 318
unmet clinical needs and future directions in, 197–199 MicroRNAs
Lipid-modifying drugs, sites of action of, 188f
Lipids, in stroke, 347 diabetic atherosclerosis and, 105–106
Lipoprotein lipase (LPL), 112 diabetic cardiomyopathy and, 298–299
Lipotoxicity, 118 Mind-body therapies, evidenced-based, 152
hyperlipidemia and, 293 Mineralocorticoid receptor antagonists (MRAs), 315t, 319–320, 320f
in insulin resistance, 20–21 Minorities, racial and ethnic, diabetes comorbidities in, 369–372
Lisinopril miR-223, 299
effect on mortality and secondary endpoints in diabetic and nondiabetic Mitochondria, 28
Mitochondrial dysfunction, diabetic cardiomyopathy and, 294
patients with acute MI, 308f Mixed dementia, 355
vs. placebo, treatment of acute MI, 307f Molecular physiology, in prevention of type 2 diabetes mellitus, 53
Liver, in insulin resistance, 17–18, 18f Molecule diaphanous-1 (mDia1), 105, 105f, 106f
Look AHEAD (Action for Health in Diabetes) study, 141, 171–172 Monocyte, inflammation, 121–122
Losartan, for hypertension, 308 Motivational interviewing, 150–152, 152t
Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) change talk in, 152
principles of, 151
randomized trial, and development of diabetes, 58–60
Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) trial,

308, 308f, 335

INDEX 394 insulin-resistant state of, 40
in peripheral artery disease, 334
Motivational interviewing (Continued) in stroke, 345
skills and strategies of, 151–152 and type 2 diabetes mellitus, 5–6, 14–16, 48
spirit of, 150–151 Omega-3 fatty acids, 194–195
in type 1 diabetes, 32
MTNR1B, 11t Omega-3 polyunsaturated fatty acids, for heart failure with diabetes
Multi-Ethnic Study of Atherosclerosis (MESA), 74, 281
Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II), treatment, 315t, 320–321
Ongoing Telmisartan Alone and in Combination with Ramipril Global
implantable cardioverter defibrillators and, 321
Muscle, in insulin resistance, 16 Endpoint Trial (ONTARGET), 175
Myocardial infarction (MI) ONTARGET. see Ongoing Telmisartan Alone and in Combination with

acute, glucose normalization and survival during hospitalization Ramipril Global Endpoint Trial (ONTARGET)
for, 253f Optical coherence tomography (OCT), for atherosclerosis, 75f
OPTIMAAL trial. see Optimal Therapy in Myocardial Infarction with the
in diabetes, 243f
HbA1c and, 156, 158f Angiotensin II Antagonist Losartan (OPTIMAAL) trial
ST-elevation see ST-elevation myocardial infarction Optimal Therapy in Myocardial Infarction with the Angiotensin II Antagonist
in type 2 diabetes mellitus, 171
vascular risk factors on, 343t Losartan (OPTIMAAL) trial, angiotensin receptor blockers and, 317
Myocardium, diabetic, detrimental effects of hyperglycemia in, 233–237 Optimizing Antiplatelet Therapy in Diabetes Mellitus (OPTIMUS) trial, 210,

N 224
OPTIMUS trial. see Optimizing Antiplatelet Therapy in Diabetes Mellitus
Naftidrofuryl, 336
NASCET. see North American Symptomatic Carotid Endarterectomy Trial (OPTIMUS) trial
Oral anticoagulation, in atrial fibrillation with diabetes, 348–349
(NASCET) Oral glucose tolerance test (OGTT), 12, 19t, 247–248
Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Organization to Assess Strategies for Ischemic Syndromes (OASIS) trial,

Research (NAVIGATOR) trial, 161 79–80, 80f, 256–257
National Cholesterol Education Program-Adult Treatment Panel III (NCEP- Organokines, 16, 16t
ORIGIN trial. see Outcome Reduction with Initial Glargine Intervention
ATP-III), metabolic syndrome and, 39t
National Health and Nutrition Examination Survey (NHANES), 128, 304, 305f (ORIGIN) trial
Orthostatic hypotension (OH), management of, 367
Epidemiologic Follow-up Study, 281 Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial, 161,
prevalence of PAD, 329, 330f
National Health Interview Survey (NHIS), 369, 370f 195, 310, 324–325
National Health Service Health Check program, in diabetes prevention, Overweight, type 2 diabetes mellitus and, 5–6
Oxidative stress
54–55
National Healthcare Disparities, report in disparities in access to care, 372 atherosclerosis in diabetes and, 102–103
Natriuretic peptides, heart failure and, 305 sources of, in diabetes, 102–103
Natural killer cells, 28t, 29
NAVIGATOR trial. see Nateglinide and Valsartan in Impaired Glucose diabetic cardiomyopathy and, 294

Tolerance Outcomes Research (NAVIGATOR) trial P
NCEP-ATP-III. see National Cholesterol Education Program-Adult Treatment
PAI-1, impaired fibrinolysis in diabetes, 115–116, 116t
Panel III (NCEP-ATP-III) Pay for performance (P4P), in quality of care for diabetes mellitus, 381–382
Nebivolol, 60–61 PEACE clinical trial, 281
Necrotic core area, size of, effect of hyperlipidemia and diabetes on, 93f Pedometers, 146
Neovascularization, in aortic atherosclerosis with and without diabetes, 95f Pentoxifylline, for claudication, 336, 336f
New-onset diabetes, 191 Percent necrotic core area, 90
NHANES. see National Health and Nutrition Examination Survey (NHANES) Percutaneous coronary intervention (PCI), 219–224
NHIS. see National Health Interview Survey (NHIS)
NHLBI. see U.S. National Institutes of Health National Heart, Lung, and bypass surgery versus, 221–224, 223t, 224f
coronary artery bypass graft versus, 231
Blood Institute (NHLBI) in diabetes, 217–227, 218f
Niacin, 62, 192–193
methodologic considerations related to, 217–218
clinical trial results, 193 with drug-eluting stents, 278, 279f
mechanisms of action of, 192f future strategies to improve, 225
NIR fluorescence, for atherosclerosis, 75f history of, 219t
NIRS, for atherosclerosis, 75f procedural aspects of, 276–278
Nitrates, for heart failure with diabetes treatment, 320 Percutaneous transluminal angioplasty and stenting (PTAS), 350–351
Non-HLA genes, 30–31, 30t Peripheral artery disease (PAD), in diabetes mellitus, 84, 329–340
Non-ST-elevation acute coronary syndrome approach to the treatment of, 338, 338f
benefits of primary invasive strategy in, 272–273, 273f, 274f clinical classification schemes for, 331t
revascularization strategy for, 275–276 clinical presentation, diagnosis, and natural history of, 330–332
timing of intervention in, 273–275 epidemiology and prognosis of, 329–330
lowering cardiovascular morbidity and mortality, 332–336
suggested algorithm of, 275f prevalence and age, 330f
Nonalcoholic fatty liver disease (NAFLD), insulin resistance and revascularization for, 337–338
Nonalcoholic steatohepatosis (NASH), insulin resistance and, 17 risk factor identification, lifestyle modification, and pharmacotherapy of,
Noncommunicable diseases (NCDs), 3
Nonesterified fatty acids (NEFAs), 87–88 332–337
Nonsurgical duodenal exclusion, 67 treatment algorithm for, 338f
Nonvasodilating beta blockers, 60 Peroxisome proliferator-activated receptors (PPARs), in diabetic
Normoglycemia in Intensive Care Evaluation Survival Using Glucose
atherosclerosis, 122–123
Algorithm Regulation (NICE-SUGAR) trial, 258 Peroxynitrite, endothelial dysfunction in diabetes, 118
North American Symptomatic Carotid Endarterectomy Trial (NASCET), 349 PET, for atherosclerosis, 75f
NOTCH2, 11t Phenformin, 323
Nox, atherosclerosis and, 103 Physical activity See also Exercise

O cardiovascular disease in type 1 diabetes, 134
in diabetes prevention, 47–48, 48t
Obesity in prevention and treatment of type 2 diabetes mellitus, 143–144
in cardiovascular autonomic neuropathy, 361 Physician-patient interface, importance in achievement of high-quality care,
relationships between cardiac autonomic dysfunction, insulin
resistance and, 362f 380–381
cardiovascular disease risk factor, 134 Picotamide, 214
Pim-1 (proviral integration site for Moloney murine leukemia virus 1), 299

Pioglitazone, 63–64 395 INDEX
Pittsburgh Epidemiology of Diabetes Complications study, 364
PKB/AKT proteins, in insulin resistance, 13–14 Promiscuous gene expression, 25
Placebo-controlled trials Prospective Pioglitazone Clinical Trial in Macrovascular Events

versus blood pressure-lowering regimens, 174f (PRoACTIVE) study, 164, 164f
overall efficacy on coronary heart disease in type 2 diabetes mellitus, Prospective Pioglitazone Clinical Trial in Macrovascular Events

172–174 (PRoACTIVE) trial, 309
Platelet Inhibition and Patient Outcomes (PLATO) trial, 243–245, 246f, 246t, Prostaglandin H synthase 2 (PGH2), 262, 264f
Protease-activated receptor 1 antagonists, 213–214
247f Protein kinase C, in atherosclerosis, 102
Platelets Protein kinase RNA-like endoplasmic reticulum kinase (PERK), 296
Protein tyrosine phosphatase nonreceptor type 22 (PTPN22) gene, 30
activation of, 263f Prothrombotic state, in type 2 diabetes mellitus, 113–116
aggregation of, 262, 263f PROVET-TIMI22 trial. see Pravastatin or Atorvastatin Evaluation and

on dual antiplatelet therapy, 208f Infection Therapy-Thrombolysis in Myocardial Infarction 22
inhibition of, 262–268 (PROVEIT-TIMI22) trial
P2Y12 inhibitors, comparison of, 267t
in stroke, 347 P2Y1 receptor, 207
multiple ligands of, 204f P2Y12 receptor, 263
role in atherogenesis and atherothrombosis, 203 antagonists, 207–213
PLATO trial. see Study of Platelet Inhibition and Patient Outcomes (PLATO) inhibitor trials, 265t

trial Q

Plurimetabolic syndrome, 37 QT interval prolongation, cardiovascular autonomic neuropathy and,
Pol-GIK trial. see Poland Glucose-Insulin-Potassium (Pol-GIK) trial 363–364
Poland Glucose-Insulin-Potassium (Pol-GIK) trial, 257, 257t
Polycystic ovary syndrome, 64 Quality chasm, diabetes mellitus and, 379–384
Polyol pathway, 100–102, 101f Quality of care, diabetes mellitus and
Population attributable risk (PAR), in stroke and myocardial infarction, 343t
“Portland Protocol,” insulin infusion, 233–234 assessing, 379–380
Post-acute coronary syndrome, 313–328 measures, 380, 380f
Poststroke hyperglycemia (PSH), 351–355
R
causes of, 351–352
epidemiology and definition of, 351 RAAS. see Renin-angiotensin-aldosterone system (RAAS)
as global negative outcome predictor, 352, 353f RAGE. see Receptor for AGE (RAGE)
glucose-lowering treatment of, 353–355 RALES. see Randomized Aldactone Evaluation Study (RALES)
glycemic control in Rancho Bernardo Study, 77–79
Randomized Aldactone Evaluation Study (RALES), mineralocorticoid
feasibility of, 353–354
outcome in, 354–355 receptor antagonists and, 315t, 319–320
neurotoxicity in, 352 Randomized Evaluation of Long-Term Anticoagulation Therapy trial, 349
progression patterns of, 351t Randomized Intervention Trial of Unstable Angina (RITA 3), 272–273
PPARG, 11t Reactive oxygen species (ROSs), 27, 102–103, 104f
Prasugrel, 210–212, 224, 264t, 266, 267t
versus clopidogrel, 211f generation, cardiac lipotoxicity, 293
Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation Receptor for AGE (RAGE), 87, 95–96

and Aggregation-Thrombolysis in Myocardial Infarction 44 in human diabetic atherosclerosis, 104
(PRINCIPLE-TIMI 44) trial, 211 influence of, 104f
in receptor-dependent pathways, 104, 105f, 106f
Pravastatin, 62 soluble (sRAGE), 104–105
RECORD study. see Rosiglitazone Evaluated for Cardiovascular Outcomes in
Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis
in Myocardial Infarction 22 (PROVEIT-TIMI22) trial, 123 Oral Agent Combination Therapy for Type 2 Diabetes (RECORD)
study
Pre-diabetes, identification, screening, and prevention in high-risk groups, Reduced ejection fraction, prevalence of diabetes mellitus in key trials of
375–376 heart failure and, 314t
Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist
Precontemplation stage, transtheoretical model of lifestyle change, 149, Losartan (RENAAL) trial, 308, 308f
150t, 152t Relapse stage, transtheoretical model of lifestyle change, 149, 150t, 152t
RENAAL trial. see Reduction of Endpoints in NIDDM with the Angiotensin II
Prediabetes, 1, 343–344 Antagonist Losartan (RENAAL) trial
clinical manifestations of atherosclerosis in, 76–82 Renal sympathetic denervation, efficacy and safety of, on coronary heart
coronary heart disease risk of patients with, 76–77 disease with type 2 diabetes mellitus, 178
diagnostic criteria for, 2t Renin-angiotensin-aldosterone system (RAAS), overactivity of, 57
Renin angiotensin system
PREDICT study, 74 antagonism, additional benefits of, 335
Prepackaged meal replacements, 141 Renin-angiotensin system
Preparation stage, transtheoretical model of lifestyle change, 149, 150t, 152t dysregulation of, 295
Prevalence Researching Coronary Reduction by Appropriately Targeting Euglycemia
(RECREATE) trial, 255t, 256
of diabetes in patients with heart failure, 284–285 Resistance, motivational interviewing, 151
of heart failure and cardiac dysfunction in people with diabetes, 283–284 Resistance training, type 2 diabetes treatment, 145
Prevention of Events with Angiotensin Converting Enzyme Inhibition Resistin, 295
Resynchronization-Defibrillation for Ambulatory Heart Failure Trial (RAFT),
(PEACE) study, and development of diabetes, 58, 58t cardiac resynchronization therapy and, 315t, 322
Prevention of Progression of Arterial Disease and Diabetes (POPADAD) trial, Revascularization, 275–276
with diabetes mellitus, 229–233, 230t
204, 335 non-ST-elevation acute coronary syndromes, 275–276, 276f
in PAD with diabetes
Prevention with Ticagrelor of Secondary Thrombotic Events in High-Risk endovascular management in, 338
Patients with Prior Acute Coronary Syndrome-Thrombolysis in surgical management in, 338
Myocardial Infarction (PEGASUS-TIMI) 54 trial, 212–213 ST-elevation myocardial infarction, 275
Reye syndrome, aspirin and, 205–206
Primary Angioplasty in Myocardial Infarction (PAMI-2) study, 275 Rosiglitazone, 63, 161–162

Primary Prevention Project (PPP), aspirin and, 203
PRINCIPLE-TIMI 44 trial. see Prasugrel in Comparison to Clopidogrel for

Inhibition of Platelet Activation and Aggregation-Thrombolysis in
Myocardial Infarction 44 (PRINCIPLE-TIMI 44) trial

PRoACTIVE (Prospective Pioglitazone Clinical Trial in Microvascular
Events), 122–123

Proinsulin, 26
Proinsulin-to-insulin ratio, 19–20
Prolonging Dual Antiplatelet Treatment after Grading Stent-Induced Intimal

Hyperplasia Study (PRODIGY) trial, 209–210

INDEX 396 Steno-2 study
CHD risk among patients with diabetes and dyslipidemia, 181
Rosiglitazone Evaluated for Cardiovascular Outcomes in Oral Agent glycemic control measures, 100
Combination Therapy for Type 2 Diabetes (RECORD) study, 163, 309,
309f Stent-supported Percutaneous Angioplasty of the Carotid Artery Versus
Endarterectomy (SPACE) trial, 350
Rule of 2 and 3 miles per hour (mph), 145
Rutherford classification, of peripheral artery disease, 330–331, 331t Stenting and Aggressive Medical Management for Preventing Recurrent
Stroke in Intracranial Stenosis (SAMMPRIS) trial, 350–351
S
Stenting of Saphenous Vein Grafts (SOS) trial, 230t, 231
S100A12, 95–96 Stents
SAMMPRIS trial. see Stenting and Aggressive Medical Management for
coronary, 219t
Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) drug-eluting, 221, 222t
trial
San Antonio Heart Study versus bare-metal, 220–221, 220t, 221f
diabetes risk disparities, 369–370 STOP-NIDDM. see Study to Prevent Non-Insulin-Dependent Diabetes Mellitus
of insulin resistance, 107
San Luis Valley Diabetes Study, 371 (STOP-NIDDM)
SAVOR-TIMI 53 trial. see Saxagliptin Assessment of Vascular Outcomes Strategic Reperfusion Early after Myocardial Infarction (STREAM) study, 273
Recorded in Patients with Diabetes Mellitus-Thrombolysis in STREAM study. see Strategic Reperfusion Early after Myocardial Infarction
Myocardial Infarction 53 (SAVOR-TIMI 53) trial
Saxagliptin Assessment of Vascular Outcomes Recorded in Patients with (STREAM) study
Diabetes Mellitus-Thrombolysis in Myocardial Infarction 53 (SAVOR- Streptozotocin-induced diabetes, and aortic atherosclerosis, 96–97
TIMI 53) trial, 165, 167f, 310 Stroke, in diabetes mellitus
Scandinavian Simvastatin Survival Study (4S), 332
Scheduled basal/bolus insulin therapy, glycemic control with, 237 and coronary heart disease, vascular risk factors between, 342–343
SCOPE trial. see Study on Cognition and Prognosis in the Elderly (SCOPE) epidemiology of, 341–342, 342f
trial in fasting plasma glucose, 344t
SEARCH study, 3–4, 131f, 134 multifactor risk factor management of, 348, 348t
Second International Study of Infarct Survival (ISIS-2), aspirin and, 206 other risk factors for, 342–343, 343t
Self-delivered and Internet-based approaches, in diabetes prevention, 50 in prediabetes-and diabetes-associated metabolic risk configurations,
Self-efficacy, support, motivational interviewing, 151
SENIORS trial. see Study of Effects of Nebivolol Intervention on Outcomes 343–345
and Rehospitalization in Seniors with Heart Failure (SENIORS) trial risk according to CHA2DS2-VASc score, 348t
SERCA2a gene therapy, 299 vascular risk factors on, 343t
Serum glucose, optimal target for, in diabetic coronary artery bypass graft, Strong Heart Study, diabetes comorbidities in women, 372
234–235 Studies of Left Ventricular Dysfunction Prevention trial (SOLVD-Prevention)
Severe intracranial arterial stenosis, mechanical revascularization of,
350–351 trial, 307
SHARP trial, ezetimibe and, 191 Studies of Left Ventricular Dysfunction (SOLVD) trial, 58, 58t
SHEP trial. see Systolic Hypertension in the Elderly Program (SHEP) trial Study of Effects of Nebivolol Intervention on Outcomes and
Silent myocardial ischemia (SMI), cardiovascular autonomic neuropathy
and, 363 Rehospitalization in Seniors with Heart Failure (SENIORS) trial, 315t,
Simvastatin 318
for claudication in peripheral artery disease, 332, 332f Study of Platelet Inhibition and Patient Outcomes (PLATO) trial, 212, 212f,
plaques from, 87 224, 265t, 267, 267f
Single-nucleotide polymorphism (SNP), type 2 diabetes mellitus and, 10, 11t Study on Cognition and Prognosis in the Elderly (SCOPE) trial, 58, 58t
SIRT1, in endothelial cells, 106 Study to Prevent Non-Insulin-Dependent Diabetes Mellitus (STOP-NIDDM),
SLC30A8, 11t 64, 161
Sleep, type 2 diabetes mellitus and, 6 Subcutaneous insulin therapy, continuous insulin infusion to, 236f
Smoking Sudden death, coronary atherosclerosis in, 88–91, 89f
cardiovascular disease in type 1 diabetes and, 134 Sulfonylureas
cessation, 142–143 as glucose-lowering agent, 163, 166t
in peripheral artery disease, 333 treatment of diabetes with heart failure, 324
type 2 diabetes mellitus and, 6 Superficial erosion, 119–120
SOLVD-Prevention trial. see Studies of Left Ventricular Dysfunction Surgery, bypass, versus percutaneous coronary intervention, 221–224
Prevention trial (SOLVD-Prevention) trial Surgical Treatment for Ischemic Heart Failure (STICH) trial, coronary artery
SOLVD-Treatment. see Treatment arm of the Studies of Left Ventricular bypass grafting and, 315t, 322–323
Dysfunction (SOLVD-Treatment) Sympathetic nervous system (SNS), insulin and, 57
SOLVD trial. see Studies of Left Ventricular Dysfunction (SOLVD) trial Symplicity HTN-2 trial, 178
Sorbitol dehydrogenase (SDH), 100 Synergy between Percutaneous Coronary Intervention with Taxus and
SOS trial. see Stenting of Saphenous Vein Grafts (SOS) trial Cardiac Surgery (SYNTAX) study, 230t, 231, 276, 277f
SPACE trial. see Stent-supported Percutaneous Angioplasty of the Carotid SYNTAX RCT trial, 221–223, 224f
Artery Versus Endarterectomy (SPACE) trial SYNTAX study. see Synergy between Percutaneous Coronary Intervention
ST-elevation myocardial infarction with Taxus and Cardiac Surgery (SYNTAX) study
benefits of primary invasive strategy in, 272, 272f Systolic blood pressure (SBP)
revascularization strategy for, 275 association with coronary heart disease in type 2 diabetes mellitus, 171,
timing of intervention in, 273 172f
St Vincent's Screening to Prevent Heart Failure (STOP-HF) study, 305 in patient with diabetes and hypertension, effect of blood pressure-
Staff costs, in diabetes prevention, 50 lowering treatment in, 177f
Standardized recommendation, in diabetes prevention, 51 Systolic dysfunction, 313–328
Statin, 62–63, 123, 189–191 Systolic Hypertension in the Elderly Program (SHEP) trial, 61
efficacy
on coronary heart disease outcomes in patients with diabetes mellitus, T
198t
on diabetes mellitus patients, 189–191 T-cell infiltration, in diabetes, 90–91
impair glucose metabolism and, 62b T cell response, in type 1 diabetes, 27–28
mechanism of action of, 189f Tachycardia, management of, 367
therapy, 196–197 TAPAS. see Thrombus Aspiration During Percutaneous
use, 191
Coronary Intervention in Acute Myocardial Infarction Study (TAPAS)
Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically

Manage Acute Coronary Syndromes (TRILOGY ACS) trial, 211, 265t,
266
TCF7L2, 11t
TEDDY study, 31
THADA, 11t
Therapeutic lifestyle changes, to reduce cardiovascular risk in diabetic
patients, 188

Thiazolidinediones (TZDs), 283 397 INDEX
as glucose-lowering agent, 163–164, 166t
influence on glucose metabolism and diabetes development, Type 2 diabetes mellitus (T2DM)
63–64 angiogenesis in, 93, 94f
metabolic syndrome and, 42 beta cell dysfunction in, 19–21
and risk of heart failure, 304b, 309–310 causal underpinnings of, 4–6
treatment of diabetes with heart failure, 324 classification and detection of, 19t
clinical manifestations of atherosclerosis in, 76–82
Thienopyridines, 263–267 coronary heart disease risk, 79–82, 79f, 81f, 82f
Third National Health and Nutritional Examination Survey (NHANES III), effect of blood pressure management on, 171–180
definitions and outcomes of, 1–2
370–371 diabetic cardiomyopathy and, 290
Thrifty phenotype hypothesis, 4 diagnostic criteria for, 2t
Thrombin, 213–214 effect of SNPs in, 11t
Thrombin-activatable fibrinolysis inhibitor (TAFI), 116, 116t evidence for sustainable prevention of, 45–46
exercise and physical activity in prevention and treatment of, 143–144,
Thrombomodulin, 115 147t
genetic factors of, 10
Thrombosis, acute coronary, 91 global burden of, 3–4, 3t
Thromboxane A2 (TXA2), 203, 204f, 262, 263f global epidemic panorama of, 44–45
Thrombus, occlusive, acute plaque rupture with, 88f increased coagulation factors in, 114–115
lifestyle interventions for prevention of, 44–56
Thrombus Aspiration During Percutaneous Coronary Intervention in Acute major randomized controlled trials in, 162t
moving prevention into practice, 53–55
Myocardial Infarction Study (TAPAS), 275 availability of, 54
Ticagrelor, 212–213, 224, 264t, 266–267, 267t basic science in, 53
distribution of, 54
versus clopidogrel, 212f effectiveness in, 53–54
Ticlopidine, 207, 267t efficacy in, 53
TIMACS trial. see Timing of Intervention in Patients with Acute Coronary efficiency of, 54
fulfilling the National Diabetes Prevention Program, 55
Syndromes (TIMACS) trial national initiatives of, 54–55
steps in development of, 53–55
Timing of Intervention in Patients with Acute Coronary Syndromes pathogenesis of, 57
(TIMACS) trial, 274, 275f pharmacologic and surgical interventions that prevent/worsen, 57–72
platelet aggregation and, 262
Tirofiban, 264t, 267, 268t prevention elements of, 46–50
behavior change in, 48–50, 49f
Tissue factor pathway inhibitor (TFPI), 115 identifying people at risk in, 46–47
Tissue plasminogen activator (t-PA), 115–116, 116t intervention for person at risk, 48–50
Tissue-specific cleavage, 26 nutritional aspects of, 48
Toll-like receptors (TLRs), 119–120, 121–122 nutritional recommendations of, 48
TOMHS. see Treatment of Mild Hypertension Study (TOMHS) physical activity in, 47–48, 48t
“Toolkit for the Prevention of Type 2 Diabetes”, 50 prothrombotic state, 113–116
TRA-CER. see Trial to Assess the Effects of SCH 530348 in Preventing Heart recommendations for prevention practice of, 50–53, 51t
contents of Toolkit in, 50
Attack and Stroke in Patients with Acute Coronary Syndrome (TRA- cost and scarce resources in, 50–52
improving effectiveness in, 52–53
CER) nutrition and dietary guidance for, 52b
prevention managers in, 52–53
TRACE study, 307 research, future of, 6–7
risk factors for, 6
Transcription factor 7-like 2 (TCF7L2), type 2 diabetes mellitus and, 10 secondary complications of, 2f
Transmembrane insulin receptor, 12–13
Transthoracic echocardiography, 228 U
TRA2 P-TIMI50. see Trial to Assess the Effects of SCH 530348 in Preventing
UKPDS. see United Kingdom Prospective Diabetes Study (UKPDS)
Heart Attack and Stroke in Patients with Atherosclerosis (TRA2 P- Ulcers, in peripheral artery disease, 330, 330f
Unfolded protein response (UPR), 295–296, 296f
TIMI50) Unfractionated heparin (UFH), 264t, 268, 268t
United Kingdom Prospective Diabetes Study (UKPDS), 74, 99–100, 156,
Treatment arm of the Studies of Left Ventricular Dysfunction (SOLVD-
157–158, 158f, 160f, 171, 283, 308, 376
Treatment), 313 United Nations High-Level Meeting on Non-Communicable Diseases,
Treatment of Mild Hypertension Study (TOMHS), 333–334
Tregs, 25 diabetes and, 44
University Group Diabetes Program (UGDP) trial, 163
Trial to Assess Improvement in Therapeutic Outcomes by Optimizing U.S. Department of Veterans Affairs (VA), health care system, 373
U.S. Diabetes Prevention Program (DPP), 7, 45
Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial diabetes prevention, 6
Infarction 38 (TRITON-TIMI 38), 210, 224, 243–245, 246f, 246t, 247f, U.S. Food and Drug Administration (FDA), antipsychotic medication
265t, 266, 266f
Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and and, 65
U.S. Institute of Medicine (IOM), quality of care, 379
Stroke in Patients with Acute Coronary Syndrome (TRA-CER), 214 U.S. National Institutes of Health National Heart, Lung, and Blood Institute

Trial to Assess the Effects of SCH 530348 in Preventing Heart Attack and (NHLBI), metabolic syndrome according to, 38t

Stroke in Patients with Atherosclerosis (TRA2 P-TIMI50), 214 V

Triglycerides, drugs targeting, 194 VADT. see Veterans Affairs Diabetes Trial (VADT)
TRILOG ACS trial. see Targeted Platelet Inhibition to Clarify the Optimal Vagosympathetic imbalance

Strategy to Medically Manage Acute Coronary Syndromes (TRILOGY hemodynamic changes and, 362, 362f
pathophysiology of, 361–362, 362f
ACS) trial role in insulin resistance, 361
TRITON-TIMI 38 trial. see Trial to Assess Improvement in Therapeutic

Outcomes by Optimizing Platelet Inhibition with Prasugrel-

Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38)
TSPAN8/LGR5, 11t
Type 1 diabetes mellitus (T1DM), 24–36

autoimmunity of, 24–29
cardiovascular disease in, 127–138

considerations for, 128–129
history of, 127

pathophysiology in, 129
pros and cons of treatment of, 130t

rates of, 128
risk factors of, 129–135, 130t
diabetic cardiomyopathy and, 291–292
epidemiology of, 127–128
etiology of, 29–33
monocytes in, 121–122
natural history of, 26t
pathogenesis of, 24, 25f

INDEX 398 W

Val-HeFT. see Valsartan Heart Failure Trial (Val-HeFT) Walking
VALIANT trial. see Valsartan in Acute Myocardial Infarction brisk, 144, 145
for type 2 diabetes treatment, 144, 145
(VALIANT) trial
Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) trial, and Warfarin, 264t
Warfarin Antiplatelet Vascular Evaluation (WAVE) study, 335
development of diabetes, 58, 58t WAVE study. see Warfarin Antiplatelet Vascular Evaluation (WAVE) study
Valsartan Heart Failure Trial (Val-HeFT), angiotensin receptor blockers and, Weight

314, 315t loss, 140
Valsartan in Acute Myocardial Infarction (VALIANT) trial, angiotensin management, coronary heart disease risk in diabetes, 140–143
reduction, peripheral artery disease and, 334
receptor blockers and, 317 Weight-training, type 2 diabetes treatment, 145
VALUE trial. see Valsartan Antihypertensive Long-Term Use Evaluation WFS1, 11t
White matter hyperintensities (WMHs), 356
(VALUE) trial Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR), 128
Varenicline, smoking cessation and, 333 Women, diabetes mellitus comorbidities in, 372
Vascular dementia (VD), 341 World Health Organization (WHO), metabolic syndrome according
Vascular smooth muscle
to, 38t, 39t
cells, insulin receptor signaling and, 108
in inflammation, 122 X
Vasodilation, endothelial-dependent, 118f
Ventricular assist devices (VADs), and transplantation, for heart failure with XENDOS study. see Xenical in the Prevention of Diabetes in Obese Subjects
(XENDOS) study
diabetes treatment, 315t, 323
Veterans Affairs Diabetes Trial (VADT), 100, 159, 160f, 376 Xenical in the Prevention of Diabetes in Obese Subjects (XENDOS) study,
Virtual International Stroke Trials Archive (VISTA) registry, 353 and development of diabetes, 64
Visceral adiposity, 140
Visceral fat Z

mass, type 2 diabetes mellitus and, 53 ZnT8, in type 1 diabetes, 27
type 2 diabetes mellitus and, 5 Zopolrestat, for atherosclerosis in diabetes, 100
Visceral obesity, Type 2 diabetes mellitus and, 46
Vitamin D deficiency, in type 1 diabetes, 32
Von Willebrand factor, diabetes and, 115
Vorapaxar, 213–214