0
We're unable to sign you in at this time. Please try again in a few minutes.
Retry
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
Retry
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Review Article |

Cardiovascular Disease in Type 2 Diabetes Mellitus:  Current Management Guidelines FREE

Arshag D. Mooradian, MD
[+] Author Affiliations

From the Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, St Louis University School of Medicine, St Louis, Mo.


Arch Intern Med. 2003;163(1):33-40. doi:10.1001/archinte.163.1.33.
Text Size: A A A
Published online

Cardiovascular disease is the most prevalent and detrimental complication of diabetes mellitus. The incidence of cardiovascular mortality in diabetic subjects without a clinical history of previous cardiac events is as high as the incidence in nondiabetic subjects with a history of myocardial infarction. This inordinate increase in the risk of coronary events in diabetic patients is attributed to multiple factors, including glycation and oxidation of proteins and increased prevalence of classic risk factors of coronary disease, such as hypertension, obesity, and dyslipidemia. Despite advances in the management of cardiovascular disease, a large proportion of diabetic subjects continue to have uncontrolled hyperglycemia, hypertension, and dyslipidemia. In addition, certain medical interventions with established efficacy in the general population do not appear to be appropriate for diabetic subjects. Recently published clinical trials of managing coronary risk factors indicate that more stringent goals of therapy should be set for diabetic patients. In this communication, some of these landmark studies are reviewed and some practical guidelines of management are suggested.

Figures in this Article

Cardiovascular disease (CVD) is the most prevalent complication of diabetes mellitus. It is estimated that 77% of hospitalizations in the United States for chronic complications of diabetes are attributable to CVD.1 The outcome of these hospitalizations is more often than not detrimental. The age-adjusted cardiovascular mortality is at least 2-fold higher in diabetic men than in nondiabetic subjects in the presence of any number of major risk factors.2 The survival after myocardial infarction is worse in diabetic men and women.3 The incidence of death from cardiovascular causes in diabetic subjects without a history of myocardial infarction during a 7-year follow-up was similar to the incidence observed in nondiabetic subjects with a history of myocardial infarction.4 These observations highlight the high prevalence of undiagnosed CVD in diabetes and the gravity of cardiovascular events in this population. The problem of undiagnosed disease is in part the result of lack of awareness by the patients of the strong association between diabetes and CVD. A recent survey commissioned by the American Diabetes Association and the American College of Cardiology found that almost 70% of people with diabetes do not realize that they are at increased risk of CVD and stroke (http://www.theheart.org HeartWire > News; February 20, 2002; accessed March 2002).

One of the most disconcerting observations is that, although the CVD mortality in nondiabetic men and women was reduced by 36.4% and 27.0%, respectively, during a decade of follow-up, the CVD mortality in diabetic men was reduced by only 13.1% and in diabetic women was actually increased by 23.0% during the same period of observation.5 The changes in diabetic subjects did not reach statistical significance. This suggests that certain interventions that have been useful in reducing the CVD mortality in the general population have been either less efficacious or sometimes detrimental in diabetic patients. An example of the latter is the finding that, for diabetic patients with multivessel disease, coronary artery bypass grafting is superior to percutaneous coronary angioplasty, while in nondiabetic subjects, the outcome of the 2 procedures is similar.68 It remains to be conclusively shown whether the advent of arterial stents and potent antiplatelet therapy will be equally beneficial in diabetic and nondiabetic subjects.9,10

Multiple factors contribute to the accelerated atherosclerosis in diabetes.11,12 These factors include excess prevalence of traditional risks such as obesity, hypertension, and dyslipidemia along with modifications of lipoproteins and other key proteins with glycation and oxidation, increased procoagulation, and possibly the state of insulin resistance. In this communication, the data from key clinical trials will be reviewed and some of the management guidelines developed in consensus conferences will be summarized.

Obesity is a common problem in diabetes and is estimated to account for approximately 60% of type 2 diabetes.1318 The central distribution of fat1921 and history of weight gain22,23 in addition to body mass are independent risks of developing diabetes. A recent statement from the American Heart Association acknowledges the importance of targeting obesity to prevent cardiovascular disease.24 Therefore, obesity is a rational target for the management of type 2 diabetes.25 The current dietary recommendations emphasize restriction of saturated fat to less than 7% of daily caloric intake and restriction of cholesterol to less than 200 mg/d.26,27 In addition, the use of dietary stanols and fish oil supplements may be considered in some patients. Although the optimal dietary composition is not well established, the benefits of modest caloric restriction are well recognized.2830 Recent clinical interventions with modest caloric restriction and increased physical activity have shown that the onset of diabetes can be significantly delayed and possibly prevented with modest weight loss.31,32 In the same study, the use of metformin was associated with 31.8% reduction in risk of type 2 diabetes.32 If lifestyle modifications are not sufficient to achieve at least 5% to 15% weight loss, then pharmacologic and possibly surgical interventions should be considered. The 2 antiobesity agents approved by the Food and Drug Administration in the United States, namely sibutramine hydrochloride and orlistat, have been used in patients with type 2 diabetes and have been found to be associated with amelioration of cardiovascular risk factors in this population.3336

The precise cause of increased cardiovascular morbidity and mortality in obesity is not known. Observational studies suggest that it may be related to insulin resistance and hyperinsulinemia.37 However, hyperinsulinemia induced by either exogenous insulin administration or the use of insulin secretagogues such as sulfonylureas does not appear to promote atherosclerosis.38 Future interventional trials using insulin sensitizers may uncover a possible pathogenetic role of insulin resistance in CVD.

Finally, patients should be counseled to avoid high-risk behaviors such as smoking and excessive alcohol consumption. However, some epidemiologic studies suggest that moderate alcohol consumption of 1 to 2 drinks per day may reduce the risk of diabetes as well as the risk of cardiovascular death.3944 However, alcohol consumption can aggravate hypertriglyceridemia and increase the risk of pancreatitis in susceptible individuals.

Although the value of tight glycemic control in the prevention of microvascular disease in type 1 and 2 diabetes is undisputable, its role in preventing macrovascular disease has been debated.38,4551 Two elegant studies, one in patients admitted with myocardial infarction52 and the other in critically ill patients after cardiac surgery,53 have clearly shown that intensive insulin therapy with the goal of normalizing blood glucose levels reduces hospitalization days and saves lives. The largest interventional trial in patients with type 2 diabetes showed that, although the reduction of glycosylated hemoglobin (HbA1c) from a mean of 7.9% to a mean of 7.0% was associated with 16% reduction in myocardial infarction, the change did not achieve statistical significance (P = .052).38 However, analysis of all the data points available in this trial showed a significant correlation between HbA1c achieved and the risk of cardiovascular deaths.54 A more recent epidemiologic study found a continuous relationship between all-cause mortality and HbA1c even for values in the nondiabetic range.55 Thus, 16% risk reduction for a modest change in HbA1c found in the United Kingdom Prospective Diabetes Study may well be biologically significant. Despite these uncertainties in the overall outcome of the study, in the subgroup of overweight patients randomized to the metformin arm of the study, there was 39% reduction in myocardial infarction, 42% reduction in diabetes-related deaths, and 36% reduction in all-cause mortality.48 These changes were statistically significant. The apparent increase in death related to diabetes in the subgroup of patients randomized to metformin-sulfonylurea combination was attributed to an unusually low mortality rate in the sulfonylurea arm of the study and short duration of follow-up, and because it could not be corroborated by the data from the overall population, the observation was considered to be a statistical fluke.

A role for postprandial hyperglycemia as an independent risk factor for CVD is now emerging.56,57 However, there are no universally accepted guidelines on how to target postprandial hyperglycemia. The American College of Endocrinology and the American Association of Clinical Endocrinologists Diabetes Mellitus Consensus Conference recommends a 2-hour postprandial glucose level of less than 140 mg/dL (7.8 mmol/L).58 On the basis of our clinical experience, we had earlier recommended a 1-hour postprandial glucose value of less than 160 mg/dL (8.9 mmol/L) as the target for achieving postprandial control and adjustment of medications.59 Since HbA1c is the gold standard for measurements of diabetes control, the principal goal of therapy should strive to achieve HbA1c levels as low as possible without increasing the hypoglycemia risk or compromising the patient's quality of life. Currently, the HbA1c goal recommended by the American Diabetes Association is less than 7.0%,60 while the American College of Endocrinologists and the European Diabetes Policy Group recommend an HbA1c goal of less than 6.5%.58,61

These observations taken together indicate that tight glycemic control, especially in the critically ill and high-risk patients, would decrease mortality. The initial choice of therapy depends on multiple factors, notably the clinical state of the patient, the degree of hyperglycemia, coexisting medical problems, and the cost of the medications.59 In overweight individuals, initiation of therapy with metformin or metformin-containing combination therapy is advisable unless there is a specific contraindication to metformin use.50 A suggested algorithm of drug therapy62 is shown in Figure 1. The response to drug therapy should be monitored with home blood glucose monitoring, and medications should be adjusted to keep the fasting as well as postprandial blood glucose values within the individualized targets. The main impediments to achieving glycemic targets include inaccessibility to medical care, difficulties in adherence to prescribed regimens, fear of hypoglycemia, and inordinate weight gain associated with some forms of therapy in a select group of patients. With the advent of a host of newer agents with diverse mechanisms of action, it will be feasible to achieve optimal blood glucose control in a larger number of subjects.

Place holder to copy figure label and caption
Figure 1.

A suggested algorithm for the initiation of drug therapy to control hyperglycemia in diabetes mellitus (DM) (adapted with permission from Chehade and Mooradian62; copyright 2001, John Wiley & Sons Limited). AGI indicates α-glucosidase inhibitors; FPG, fasting plasma glucose; PP, postprandial plasma glucose; SFU, sulfonylurea; and TZD, thiazolidinediones. To convert glucose levels to millimoles per liter, multiply by 0.0555.

Graphic Jump Location

Stratification of risk factors for coronary heart disease (CHD) in type 2 diabetes shows that low-density lipoprotein (LDL-C) and high-density lipoprotein cholesterol (HDL-C) are the best predictors of CHD.63 However, the prevalence of high LDL-C level in diabetic subjects is not different from the prevalence rate in the nondiabetic population.64 In contrast, the prevalence of hypertriglyceridemia and low HDL-C levels in diabetic subjects is approximately twice as high as in the nondiabetic groups.64 Thus, management should target all lipid abnormalities identified in diabetic subjects. Although at the present time there are no major clinical outcome trials in exclusively diabetic patients, many currently available trials have enrolled a subgroup of subjects with diabetes.6570 These trials indicate that cholesterol reduction with a statin is valuable in CHD risk reduction as both primary and secondary intervention. Of note is the recent demonstration that even those with normal or low cholesterol levels (ie, total cholesterol level <200 mg/dL [<5.2 mmol/L] or LDL-C level <120 mg/dL [<3.1 mmol/L]) will benefit from statin therapy.70,71 Because of the wealth of clinical experience with this class of agents, statins are the mainstay of therapy in diabetic dyslipidemia. However, 3 recent clinical trials with 3 different fibrates have also shown a therapeutic role of this class of agents in the prevention of CHD.6769

The choice of a particular agent depends on the baseline lipid profile achieved after 6 to 12 weeks of intense lifestyle changes and possible use of dietary supplements such as stanols. A simplified algorithm of drug therapy for dyslipidemia in diabetic subjects is shown in Figure 2. The values of the serum lipid profile are not intended to represent goals of therapy, but rather are suggested as trigger points for initiation or modification of drug choices. If the predominant lipid abnormality is hypertriglyceridemia with serum triglyceride concentration greater than 500 mg/dL (5.6 mmol/L), then fibrates would be considered the first choice of therapy. In subsequent follow-up, when LDL-C level is greater than 130 mg/dL (3.4 mmol/L), then a statin is added as a combination therapy. Other options to be used in combination with the fibrate could include niacin, bile acid–binding resin, or, when available, a cholesterol absorption inhibitor.72 On the other hand, if the serum triglyceride levels are less than 500 mg/dL (5.6 mmol/L) and the LDL-C values are greater than 130 mg/dL (3.4 mmol/L), then a statin would be the first drug of choice. The statin dose can be titrated up to achieve the therapeutic goal or, alternatively, a bile acid–binding resin is added if the serum triglyceride concentrations do not exceed 200 mg/dL (2.3 mmol/L). Otherwise, a fibrate, niacin, or, when available, a cholesterol absorption inhibitor would be considered. The use of a drug combination as first-line therapy is also an alternative; however, the clinical experience with this approach is limited. The combination of a statin with a fibrate or niacin increases the risk of rhabdomyolysis, and therefore a low dose of statins (10-20 mg) or a statin with the least drug interaction potential, such as pravastatin sodium, should be used.

Place holder to copy figure label and caption
Figure 2.

A suggested algorithm of drug therapy for dyslipidemia in diabetes mellitus. LDL-C indicates low-density lipoprotein cholesterol; TG, serum triglyceride concentration. To convert TG to millimoles per liter, multiply by 0.0113; LDL-C, by 0.0259.

Graphic Jump Location

The use of niacin to treat dyslipidemia in patients with type 2 diabetes has been discouraged because of the potential increase in insulin resistance.64 It appears that if the dose of niacin is limited to less than 2 g/d, the effect on insulin resistance is modest.73 Nevertheless, in an occasional patient with impaired glucose tolerance, the initiation of niacin treatment may precipitate overt diabetes. In addition, a substantial number of patients (up to 30%) may not tolerate the adverse effects associated with niacin therapy.

Some of the newly available insulin sensitizers, such as pioglitazone hydrochloride, have significant favorable effects on serum triglyceride and HDL-C levels, and these effects are independent of their effects on blood glucose control.74 Therefore, such agents may also be considered as adjunct therapy for diabetic dyslipidemia.

The goals of therapy were recently updated by the Adult Treatment Panel III of the National Cholesterol Education Program.26 This panel considers diabetes as a CHD risk equivalent and sets the LDL-C goal at less than 100 mg/dL (2.6 mmol/L). In addition, desirable serum triglyceride levels should be less than 150 mg/dL (1.7 mmol/L) and HDL-C, greater than 40 mg/dL (1.0 mmol/L). The Adult Treatment Panel III identifies non–HDL-C (ie, total cholesterol minus HDL-C) as a secondary target of therapy in patients with serum triglyceride levels equal to or greater than 200 mg/dL (2.3 mmol/L). In subjects with diabetes, the non–HDL-C goal is 130 mg/dL (3.4 mmol/L).26 Unfortunately, a substantial number of patients fail to achieve these goals.75 The task of achieving the lipid therapy goals in a larger number of patients will be greatly facilitated with the advent of more powerful agents that can be used safely in combination with other agents with distinct mechanisms of actions.

Hypertension awareness, treatment, and control are improving in the United States. However, of those with hypertension, 31.6% are still unaware that they have high blood pressure, only 27.4% are receiving antihypertensive medications and are under control, 26.2% are on medications but remain uncontrolled, and 14.8% are not taking any antihypertensive therapy at all.76 Overall, less than one third of hypertensive patients who are being treated for hypertension have their blood pressure under control despite the overwhelming evidence in favor of controlling hypertension.76 This is especially true for high-risk patients such as those with diabetes.

The results from United Kingdom Prospective Diabetes Study indicate that the risk of myocardial infarction and microvascular end points correlate with the blood pressure in patients with type 2 diabetes.77 In that study, the mean blood pressure achieved in the intensively treated subjects was 144/82 mm Hg, and in the conventional arm of the study, 154/87 mm Hg. Despite this modest difference in blood pressure, the risk of diabetes-related death was reduced by 32%; that of stroke, by 44%; and that of congestive heart failure, by 56%.77 The study also found that captopril and atenolol were equally safe and effective.77 However, this conclusion is debatable given that the design of the study was not optimal to detect drug-specific outcomes.

In the Systolic Hypertension in the Elderly Program, the effect of systolic blood pressure control with chlorthalidone with and without atenolol or reserpine on cardiovascular events was studied over 5 years. A 34% risk reduction was observed in diabetic patients (n = 583). This was similar in magnitude to the risk reduction seen in the nondiabetic group (n = 4149).78 The effect of systolic blood pressure control with nitrendipine was also studied in the Systolic Hypertension in Europe Trial.79 The diabetic group (n = 492) had 70% risk reduction, while the nondiabetic group (n = 4203) had 16% risk reduction.79 Primary prevention in diabetic patients was also observed in the study of ramipril on cardiovascular events.80 Finally, the Hypertension Optimal Treatment trial found that, in diabetic patients, targeting diastolic blood pressure to be less than 80 mm Hg is associated with greater risk reduction than the risk reduction observed in those who achieve diastolic blood pressure of less than 90 or 85 mm Hg.81

According to the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, the goal of blood pressure control should be 130/85 mm Hg.76 The goal of blood pressure control according to the American Diabetes Association is 130/80 mm Hg.60 Similarly, the National Kidney Foundation recommends a more stringent goal of 130/80 mm Hg, and, if proteinuria of more than 1 g/d is documented, then the goal is 125/75 mm Hg.82

The choice of the therapeutic agent depends on multiple variables. In general, angiotensin-converting enzyme inhibitors or angiotensin II blockers are recommended as first-line therapy if nephropathy is present.60,8387 The Heart Outcomes Prevention Evaluation study suggests that angiotensin-converting enzyme inhibitors may have the additional benefit of CVD and diabetes prevention.80,88 In those with established CVD, β-blockers are recommended unless the patient has hypoglycemia unawareness (ie, is unable to detect the early warning signs of hypoglycemia). Of note, some studies have found that the dihydropyridines are less effective in preventing the progression of renal disease, and, as such, they should be used only if other alternatives are not tolerated or ineffective.8893 A recent study found that irbesartan was more effective than amlodipine in reducing the progression of diabetic nephropathy when given with other drugs to control blood pressure.85 It is also noteworthy that the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) suggested that α-blockers may have less benefit in this population than diuretics and β-blockers.94 In the latter study, the α-blocker arm of the study was stopped by the data and safety monitoring committee because of increased incidence of heart failure.94 However, α-blockers may be useful in a subgroup of patients with symptoms of benign prostatic hypertrophy and in those in whom other antihypertensive agents are ineffective.

A subgroup of diabetic subjects who pose a therapeutic dilemma include those with supine hypertension and orthostatic hypotension. These patients may benefit from a trial of clonidine patch and judicious use of short-acting α-adrenergic agonists such as midodrine hydrochloride.9597 An alternative approach is bedtime use of short-acting agents such as oral clonidine or captopril. The availability of a wide variety of antihypertensive agents allows the physician to prescribe an agent with maximal efficacy and limited side effect profile. It is now possible to achieve the goals of blood pressure control in a large number of patients without compromising the quality of their lives.

Oxidative stress has been implicated in atherosclerosis.98 Since diabetes is considered a state of increased oxidative load, and some patients may have occasional micronutrient deficiencies,99101 it is tempting to speculate that supplementation with antioxidants may prevent CVD in diabetes. However, the relationship of antioxidants to atherosclerosis is moot. Whereas epidemiologic studies suggest a favorable role of dietary and possibly supplemental intake of antioxidants,102113 interventional trials by and large have failed to show beneficial results, and some studies have suggested that antioxidant supplementation may have deleterious effects on health.114119 One randomized study found that vitamin E supplementation at 400 mg/d but not at 800 mg/d is associated with reduced incidence of nonfatal myocardial infarctions.118 The overall mortality was not changed. However, a more recent trial of simvastatin with and without a cocktail of antioxidants including vitamins E and A and ascorbic acid found that use of antioxidants was associated with reduced efficacy of simvastatin in increasing HDL2 levels.120 Ongoing interventional trials may shed some additional light on this controversy. Meanwhile, it is prudent not to consume vitamins or minerals in excess of their recommended dietary intake limits.

Type 2 diabetes is a state of increased plasma coagulability.121 The platelet aggregability is increased and fibrinolytic capacity is reduced. Antiplatelet therapy, notably use of aspirin, has been shown to be effective in reducing CVD-related events.122 The recommended dose and frequency of administration is somewhat controversial. In most patients, 325 mg/d is recommended. If excess bruisability occurs, then a dose of 81 mg/d is advisable. Clopidogrel bisulfate, another antiplatelet agent with a different mechanism of action, is also an alternative. In one large trial, clopidogrel appeared to be more potent than aspirin in reducing cardiovascular events.123 In addition, in a recent trial in patients with acute myocardial infarction, clopidogrel therapy was associated with a significant reduction in event rate compared with aspirin alone.124 Thus, in diabetic patients who experience a cardiovascular event while taking aspirin therapy, clopidogrel therapy should be considered. The recent demonstration that a substantial number of people may have a relative resistance to antiplatelet effects of aspirin is of concern.125 Future studies are needed to address this confounding variable and to determine whether individualizing aspirin dose would enhance its cardioprotective properties.

It is generally accepted that only approximately 50% of myocardial infarctions can be attributed to the classic lipid risk factors. A host of lipid- and non–lipid-related risk factors have been studied. Of these risk factors, microalbuminuria is a major predictor of cardiovascular events.126 It is likely that the microalbuminuria is a marker of generalized endothelial dysfunction in diabetes. The beneficial role of angiotensin-converting enzyme inhibitors and angiotensin II blockers in patients with microalbuminuria is well established.60 Although there is no conclusive evidence, a case can be made for using these agents prophylactically to prevent the emergence of proteinuria in diabetic subjects.

The C-reactive protein level has emerged as another valuable independent predictor of cardiovascular disease both in men and in women.127,128 In addition, statin therapy is associated with reduced C-reactive protein levels independent of its effect on serum lipid levels.129131 Diabetic subjects tend to have higher C-reactive protein levels than nondiabetic control subjects, suggesting that an ongoing inflammatory response may be contributing to the accelerated atherosclerosis in diabetes.132

Another emerging risk factor is lipoprotein(a). Many studies have shown a correlation between lipoprotein(a) and coronary heart disease.133 The recent Atherosclerosis Risk in Communities Study reported that lipoprotein(a) added only modest predictive value to LDL-C, HDL-C, and total triglycerides.134

Finally, plasma homocysteine levels have been found to be associated with CVD in diabetic and nondiabetic subjects.135,136 However, this association was modest compared with the predictive role of C-reactive protein.135 It remains to be seen whether lowering plasma homocysteine levels with folic acid or cyanocobalamin supplementation would reduce risk of coronary heart disease.137

The prevalence of diabetes is increasing worldwide.138 The number of people with cardiovascular morbidity will also increase. Some of the mechanical interventions that have been helpful in the general population have not been found to be useful in diabetic subjects. In addition, the risk of sudden death in diabetic patients without known heart disease is as high as the rate seen in nondiabetic subjects with a history of myocardial infarction. Thus, it is imperative that the efforts at treating this disease emphasize preventive approaches. Early screening and identification of risk factors, including testing for microalbuminuria, should be instituted. Earlier and more rigorous control of blood pressure may well be the most important therapeutic strategy. The goals of therapy have to be individualized, taking into account the patient's coexisting medical problems and ability to adhere to prescribed regimens. Although screening for an underlying subclinical CVD is recommended for high-risk diabetic subjects planning to embark on a moderate- to high-intensity exercise program, in most patients the physician should use clinical judgment in recommending exercise or pharmacologic stress tests.139 Overall, it appears that diabetic subjects would benefit from a more aggressive preventive program that sets more stringent standards. It is likely that achieving these goals is a challenging task. Nevertheless, these measures are bound to reduce the incidence of cardiovascular morbidity and mortality in a very high-risk group of people.

Corresponding author and reprints: Arshag D. Mooradian, MD, Division of Endocrinology, St Louis University School of Medicine, St Louis, MO 63104 (e-mail: mooradad@slu.edu).

Accepted for publication April 22, 2002.

Wingard  DLBarrett-Connor  E Heart disease and diabetes. Diabetes in America, National Diabetes Data Group. 2nd ed. Bethesda, Md National Institutes of Health1995;429- 448NIH publication 95-1468.
Stamler  JVaccaro  ONeaton  JDWentworth  D Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16434- 444
Link to Article
Sprafka  JMBurke  GlFolsom  ARMcGovern  PGHahn  LP Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival: the Minnesota Heart Survey. Diabetes Care. 1991;14537- 543
Link to Article
Haffner  SMLehto  SRonnemaa  TPyorala  KLaakso  M Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior history of myocardial infarction. N Engl J Med. 1998;339229- 234
Link to Article
Gu  KCowie  CCHarris  MI Diabetes and decline in heart disease mortality in US adults. JAMA. 1999;2811291- 1297
Link to Article
Feit  FBrooks  MMSopko  G  et al. for the BARI Investigators, Long-term clinical outcome in the Bypass Angioplasty Revascularization Investigation Registry: comparison with the randomized trial. Circulation. 2000;1012795- 2802
Link to Article
Chaitman  BRRosen  ADWilliams  DO  et al.  Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial. Circulation. 1997;962162- 2170
Link to Article
Not Available, Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI). Circulation. 1997;961761- 1769
Link to Article
Abizaid  AKornowski  RMintz  GS  et al.  The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. J Am Coll Cardiol. 1998;32584- 589
Link to Article
Montalescot  GBarragan  PWittenberg  O  et al.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001;3441895- 1903
Link to Article
Mooradian  ADNowak  FV Diabetes mellitus and heart disease. Kaiser  FEMorley  JECoe  RMeds.Cardiovascular Disease in Older Persons. New York, NY Springer Verlag1997;53- 72
Mooradian  ADThurman  JE Glucotoxicity: potential mechanisms. Clin Geriatr Med. 1999;15255- 263
Mokdad  AHSerdula  MKDietz  WHBowman  BAMarks  JSKoplan  JP The spread of the obesity epidemic in the United States, 1991-1998. JAMA. 1999;2821519- 1522
Link to Article
Must  ASpadano  JCoakley  EHField  AEColditz  GDietz  WH The disease burden associated with overweight and obesity. JAMA. 1999;2821523- 1529
Link to Article
Morris  RDRimm  DLHartz  AJKalkhoff  RKRimm  AA Obesity and heredity in the etiology of non–insulin-dependent diabetes mellitus in 32,662 adult white women. Am J Epidemiol. 1989;130112- 121
Bray  GA Obesity increases risk for diabetes. Int J Obes Relat Metab Disord. 1992;16(suppl 4)S13- S17
Felber  JPAcheson  KJTappy  L From Obesity to Diabetes.  New York, NY John Wiley & Sons1993;
Knowler  WCPettitt  DJSavage  PJBennett  PH Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes. Am J Epidemiol. 1981;113144- 156
Ohlson  LOLarsson  BSvardsudd  K  et al.  The influence of body fat distribution on the incidence of diabetes mellitus: 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985;341055- 1058
Link to Article
Cassano  PARosner  BVokonas  PSWeiss  ST Obesity and body fat distribution in relation to the incidence of non–insulin-dependent diabetes mellitus: a prospective cohort study of men in the Normative Aging Study. Am J Epidemiol. 1992;1361474- 1486
Bosello  OZamboni  MArmellini  FTodesco  T Biological and clinical aspects of regional body fat distribution. Diabetes Nutr Metab. 1993;6163- 171
Colditz  GAWillett  WCRotnitzky  AManson  JE Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122481- 486
Link to Article
Chan  JMRimm  EBColditz  GAStampfer  JMWillett  WC Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17961- 969
Link to Article
Eckel  RHKrauss  RMfor the AHA Nutrition Committee, American Heart Association call to action: obesity as a major risk factor for coronary heart disease. Circulation. 1998;972099- 2100
Link to Article
Mooradian  AD Obesity: a rational target for managing diabetes mellitus. Growth Horm IGF Res. 2001;11(suppl A)S79- S83
Link to Article
Evaluation, Expert Panel on Detection and Treatment of High Blood Cholesterol in Adults, Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;2852486- 2497
Link to Article
American Diabetes Association, Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 2002;25202- 212
Link to Article
Wing  RRBlair  EHBononi  PMarcus  MDWatanabe  RBergman  RN Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care. 1994;1730- 36
Link to Article
Wing  RRKoeske  REpstein  LHNowalk  MPGooding  WBecker  D Long-term effects of modest weight loss in type II diabetic patients. Arch Intern Med. 1987;1471749- 1753
Link to Article
Heath  GWWilson  RHSmith  JLeonard  BE Community-based exercise and weight control: diabetes risk reduction and glycemic control in Zuni Indians. Am J Clin Nutr. 1991;53(suppl)1642S- 1646S
Uusitupa  MLouheranta  ALindstrom  J  et al.  The Finnish Diabetes Prevention Study. Br J Nutr. 2000;83(suppl 1)S137- S142
Link to Article
Knowler  WCBarrett-Connor  EFowler  SE  et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346393- 403
Link to Article
Gokcel  AKarakose  HErtorer  EMTanaci  NTutuncu  NBGuvener  N Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Diabetes Care. 2001;241957- 1960
Link to Article
Heath  MJChong  EWeinstein  SPSeaton  TB Sibutramine enhances weight loss and improves glycemic control and plasma lipid profile in obese patients with type 2 diabetes mellitus [abstract]. Diabetes. 1999;48(suppl)A308
Link to Article
Hollander  PAElbein  SCHirsch  IB  et al.  Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care. 1998;211288- 1294
Link to Article
Heymsfield  SBSegal  KRHauptman  J  et al.  Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000;1601321- 1326
Link to Article
Despres  J-PLamarche  BMauriege  P  et al.  Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334952- 957
Link to Article
UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352837- 853
Link to Article
Wannamethee  SGShaper  AG Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. Am J Public Health. 1999;89685- 690
Link to Article
Valmadrid  CTKlein  RMoss  SEKlein  BKCruickshanks  KJ Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus. JAMA. 1999;282239- 246
Link to Article
Solomon  CGHu  FBStampfer  MJ  et al.  Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus. Circulation. 2000;102494- 499
Link to Article
Ajani  UAHennekens  CHSpelsberg  AManson  JE Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians. Arch Intern Med. 2000;1601025- 1030
Link to Article
Tanasescu  MHu  FBWillett  WCStampfer  MJRimm  EB Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus. J Am Coll Cardiol. 2001;381836- 1842
Link to Article
Ajani  UAGaziano  MLotufo  PA  et al.  Alcohol consumption and risk of coronary heart disease by diabetes status. Circulation. 2000;102500- 505
Link to Article
Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329977- 986
Link to Article
Kuusisto  JMykkanen  LPyorala  KLaakso  M NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes. 1994;43960- 967
Link to Article
Ohkubo  YKishikawa  HAraki  E  et al.  Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non–insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28103- 117
Link to Article
Turner  RCCall  CAFrighi  VHolman  RR  Jrfor the UKPDS Group, Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;2812005- 2012
Link to Article
UK Prospective Diabetes Study (UKPDS) Group, Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352854- 865
Link to Article
Mooradian  ADChehade  J Implications of the UK Prospective Diabetes Study: questions answered and issues remaining. Drugs Aging. 2000;16159- 164
Link to Article
Abraira  CColwell  JANuttall  FQ  et al. for the Veterans Affairs Cooperative Study in Type II Diabetes, Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VACSDM): results of the feasibility trial. Diabetes Care. 1995;181113- 1123
Link to Article
Malmberg  Kfor the DIGAMI (Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group, Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;3141512- 1515
Link to Article
van den Berghe  GWouters  PWeekers  F  et al.  Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;3451359- 1367
Link to Article
Stratton  IMAdler  AINeil  HA  et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321405- 412
Link to Article
Khaw  KTWareham  NLuben  R  et al.  Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001;32215- 18
Link to Article
The DECODE Study Group, on behalf of the European Diabetes Epidemiology Group, Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161397- 405
Link to Article
Mooradian  ADThurman  JE Drug therapy of postprandial hyperglycaemia. Drugs. 1999;5719- 29
Link to Article
Not Available, ACE Consensus Conference on Guidelines for Glycemic Control. Endocr Pract. November/December2001;suppl2- 5
Chehade  JMMooradian  AD A rational approach to drug therapy of type 2 diabetes mellitus. Drugs. 2000;6095- 113
Link to Article
American Diabetes Association, Clinical practice recommendations 2002. Diabetes Care. 2002;25(suppl 1)S1- S147
Link to Article
European Diabetes Policy Group 1999, A desktop guide to type 2 diabetes mellitus. Diabet Med. 1999;16716- 730
Link to Article
Chehade  JMMooradian  AD Drug therapy: current and emerging agents. Sinclair  AJFinucane  Peds.Diabetes in Old Age. 2nd ed. Chichester, England John Wiley & Sons2001;199- 214
Turner  RCMillns  HNeil  HA  et al.  Risk factors for coronary artery disease in non–insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316823- 828
Link to Article
Garg  AGrundy  SM Management of dyslipidemia in NIDDM. Diabetes Care. 1990;13153- 169
Link to Article
Pyorala  KPedersen  TRKjekshus  JFaergeman  OOlsson  AGThorgeirsson  G Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997;20614- 620
Link to Article
Goldberg  RBMellies  MJSacks  FM  et al. for the CARE Investigators, Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation. 1998;982513- 2519
Link to Article
Rubins  HBRobins  SJCollins  D  et al. for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group, Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341410- 418
Link to Article
Elkeles  RSDiamond  JRPoulter  C  et al.  Cardiovascular outcomes in type 2 diabetes: a double-blind placebo-controlled of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. Diabetes Care. 1998;21641- 648
Link to Article
Not Available, Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study a randomised study. Lancet. 2001;357905- 910
Link to Article
Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;3607- 22
Link to Article
Downs  JRClearfield  MWeis  S  et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS: Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;2791615- 1622
Link to Article
Leitersdorf  E Cholesterol absorption inhibition: filling an unmet need in lipid-lowering management. Eur Heart J. 2001;3(suppl E)E17- E23
Link to Article
Elam  MBHunninghake  DBDavis  KB  et al. for the Arterial Disease Multiple Intervention Trial, Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. JAMA. 2000;2841263- 1270
Link to Article
Mooradian  ADChehade  JMThurman  JE The role of thiazolidenediones in the treatment of type 2 diabetes. Treat Endocrinol. 2002;113- 20
Link to Article
Pearson  TALaurora  IChu  HKfonek  S The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160459- 467
Link to Article
Not Available, The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997;1572413- 2446
Link to Article
Adler  AIStratton  IMNeil  HA  et al.  Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321412- 419
Link to Article
Curb  IDPressel  SLCutler  JA  et al. for the Systolic Hypertension in the Elderly Program Cooperative Research Group, Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA. 1996;2761886- 1892
Link to Article
Tuomilehto  JRastenyte  DBirkenhager  WH  et al. for the Systolic Hypertension in Europe Trial Investigators, Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. N Engl J Med. 1999;340677- 684
Link to Article
Heart Outcomes Prevention Evaluation Study Investigators, Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355253- 259
Link to Article
Hansson  LZanchetti  ACarruthers  SG  et al. for the HOT Study Group, Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;3511755- 1762
Link to Article
Bakris  GLWilliams  MDworkin  L  et al. for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group, Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000;36646- 661
Link to Article
Ravid  MSavin  HJutrin  IBental  TKatz  BLishner  M Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993;118577- 581
Link to Article
Lacourciere  YNadeau  APoirier  LTancrede  G Captopril or conventional therapy in hypertensive type II diabetics: three-year analysis. Hypertension. 1993;21786- 794
Link to Article
Lewis  EJHunsicker  LGClarke  WR  et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345851- 860
Link to Article
Brenner  BMCooper  MEde Zeeuw  D  et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345861- 869
Link to Article
Niskanen  LHedner  THansson  LLanke  JNiklason  A Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/β-blocker–based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care. 2001;242091- 2096
Link to Article
Yusuf  SGerstein  HHoogwerf  Bfor the HOPE Study Investigators, Ramipril and the development of diabetes. JAMA. 2001;2861882- 1885
Link to Article
Bakris  GLCopley  JBVicknair  NSadler  RLeurgans  S Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996;501641- 1650
Link to Article
Agodoa  LYAppel  LBakris  GL  et al.  Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001;2852719- 2728
Link to Article
Estacio  ROJeffers  BWHiatt  WRBiggerstaff  SLGifford  NSchrier  RW The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non–insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338645- 652
Link to Article
Tatti  PPahor  MByington  RP  et al.  Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998;21597- 603
Link to Article
Agardh  C-DGarcia-Puig  JCharbonnel  BAngelkort  BBarnett  AH Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine. J Hum Hypertens. 1996;10185- 192
Poulter  NWilliams  B Doxazosin for the management of hypertension: implications of the findings of the ALLHAT trial. Am J Hypertens. 2001;141170- 1172
Link to Article
Sowers  JR Hypertension in type II diabetes: update on therapy. J Clin Hypertens (Greenwich). 1999;141- 47
Brahmbhat  RBaggaley  PHockings  B Normalization of blood pressure in a patient with severe orthostatic hypotension and supine hypertension using clonidine [letter]. Hypertension. 2001;37E24
Link to Article
Cruz  DN Midodrine: a selective α-adrenergic agonist for orthostatic hypotension and dialysis hypotension. Expert Opin Pharmacother. 2000;1835- 840
Link to Article
Rosen  PNawroth  PPKing  GMoller  WTritschler  HJPacker  L The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev. 2001;17189- 212
Link to Article
Mooradian  AD Micronutrients in diabetes mellitus. Ioannides  CLewis  DFVeds.Drugs, Diet and Disease Mechanistic Approaches to Diabetes. New York, NY Ellis Horwood1995;2183- 200
Mooradian  ADFailla  MHoogwerf  BMaryniuk  MWylie-Rosett  J Selected vitamins and minerals in diabetes. Diabetes Care. 1994;17464- 479
Thurman  JMooradian  AD Vitamin supplementation therapy in the elderly. Drugs Aging. 1997;11433- 449
Link to Article
Klipstein-Grobusch  KGeleijnse  JMden Breeijen  JH  et al.  Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr. 1999;69261- 266
Will  JCFord  ESBowman  BA Serum vitamin C concentrations and diabetes: findings from the Third National Health and Nutrition Examination Survey 1988-1994. Am J Clin Nutr. 1999;7049- 52
Mayer-Davis  EJBell  KAReboussin  BARushing  JMarshall  JAHamman  RF Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study. Ophthalmology. 1998;1052264- 2270
Link to Article
Mayer-Davis  EJMonaco  JHMarshall  JARushing  JJuhaeri  Jfor the Insulin Resistance Atherosclerosis Study and the San Luis Valley Diabetes Study, Vitamin C intake and cardiovascular disease risk factors in persons with non–insulin-dependent diabetes mellitus. Prev Med. 1997;26277- 283
Link to Article
Hennekens  CHBuring  JEManson  JE  et al.  Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;3341145- 1149
Link to Article
Knekt  PJarvinen  RReunanen  AMaatela  J Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996;312478- 481
Link to Article
Kushi  LHFolsom  ARPrineas  RJMink  PJWu  YBostick  RM Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996;3341156- 1162
Link to Article
Losonczy  KGHarris  TBHavlik  RS Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Population for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64190- 196
Knekt  PReunanen  AJarvinen  RSeppanen  RHeliovaara  MAromaa  A Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994;1391180- 1189
Rimm  EBStampfer  MJAscherio  AGiovannucci  EColditz  GAWillett  WC Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;3281450- 1456
Link to Article
Stampfer  MJHennekens  CHManson  JEColditz  GARosner  BWillett  WC Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;3281444- 1449
Link to Article
Enstrom  JEKanim  LEKlein  MA Vitamin C intake and mortality among a sample of the United States population. Epidemiology. 1992;3194- 202
Link to Article
Christen  WGGaziano  JMHennekens  CH Design of Physicians' Health Study II: a randomized trial of beta carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol. 2000;10125- 134
Link to Article
Yusuf  SDagenais  GPogue  JBosch  JSleight  Pfor the Heart Outcomes Prevention Evaluation Study Investigators, Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med. 2000;342154- 160
Link to Article
GISSI-Prevenzione Investigators, Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione Trial. Lancet. 1999;354447- 455
Link to Article
Omenn  GSGoodman  GEThornquist  MD  et al.  Risk factors for lung cancer and for intervention effects in CARET: the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;881550- 1559
Link to Article
Stephens  NGParsons  ASchofield  PMKelly  FCheeseman  KMitchinson  MJ Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347781- 786
Link to Article
ATBC (Alpha-Tocopherol, Beta Carotene) Cancer Prevention Study Group, The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers: the Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994;3301029- 1035
Link to Article
Brown  BGZhao  X-QChait  A  et al.  Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;3451583- 1592
Link to Article
Colwell  JA Treatment for the procoagulant state in type 2 diabetes. Endocrinol Metab Clin North Am. 2001;301011- 1030
Link to Article
Antiplatelet Trialists' Collaboration, Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J (Clin Res Ed). 1988;296320- 331
Link to Article
CAPRIE Steering Committee, A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;3481329- 1339
Link to Article
Yusuf  SZhao  FMehta  SRChrolavicius  STognoni  GFox  KK Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345494- 502
Link to Article
Eikelboom  JWHirsh  JWeitz  JIJohnston  MYi  QYusuf  S Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002;1051650- 1655
Link to Article
Neil  AHawkins  MPotok  MThorogood  MCohen  DMann  J A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care. 1993;16996- 1003
Link to Article
Ridker  PMHennekens  CHBuring  JERifai  N C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342836- 843
Link to Article
Ridker  PMCushman  MStampfer  MJTracy  RPHennekens  CH Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336973- 979
Link to Article
Ridker  PMRifai  NClearfield  M  et al. for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators, Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;3441959- 1965
Link to Article
Ridker  PMRifai  NPfeffer  MASacks  FBraunwald  Efor the Cholesterol and Recurrent Events (CARE) Investigators, Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;100230- 235
Link to Article
Albert  MADanielson  ERifai  NRidker  PMfor the PRINCE Investigators, Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;28664- 70
Link to Article
Ford  ES Body mass index, diabetes, and C-reactive protein among US adults. Diabetes Care. 1999;221971- 1977
Link to Article
Scanu  AM The role of lipoprotein(a) in the pathogenesis of atherosclerotic disease and its utility as predictor of coronary heart disease events. Curr Cardiol Rep. 2001;3385- 390
Link to Article
Sharrett  ARBallantyne  CMCoady  SA  et al.  Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoprotein A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;1041108- 1113
Link to Article
Ridker  PMManson  JEBuring  JEShih  JMatias  MHennekens  CH Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA. 1999;2811817- 1821
Link to Article
Yeromenko  YLavie  LLevy  Y Homocysteine and cardiovascular risk in patients with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2001;11108- 116
Homocysteine Lowering Trialists' Collaboration, Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ. 1998;316894- 898
Link to Article
Kind  HAubert  REHerman  WH Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;211414- 1431
Link to Article
American Diabetes Association, Diabetes mellitus and exercise. Diabetes Care. 2002;25(suppl 1)S64- S68
Link to Article

Figures

Place holder to copy figure label and caption
Figure 1.

A suggested algorithm for the initiation of drug therapy to control hyperglycemia in diabetes mellitus (DM) (adapted with permission from Chehade and Mooradian62; copyright 2001, John Wiley & Sons Limited). AGI indicates α-glucosidase inhibitors; FPG, fasting plasma glucose; PP, postprandial plasma glucose; SFU, sulfonylurea; and TZD, thiazolidinediones. To convert glucose levels to millimoles per liter, multiply by 0.0555.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

A suggested algorithm of drug therapy for dyslipidemia in diabetes mellitus. LDL-C indicates low-density lipoprotein cholesterol; TG, serum triglyceride concentration. To convert TG to millimoles per liter, multiply by 0.0113; LDL-C, by 0.0259.

Graphic Jump Location

Tables

References

Wingard  DLBarrett-Connor  E Heart disease and diabetes. Diabetes in America, National Diabetes Data Group. 2nd ed. Bethesda, Md National Institutes of Health1995;429- 448NIH publication 95-1468.
Stamler  JVaccaro  ONeaton  JDWentworth  D Diabetes, other risk factors, and 12-yr cardiovascular mortality for men screened in the Multiple Risk Factor Intervention Trial. Diabetes Care. 1993;16434- 444
Link to Article
Sprafka  JMBurke  GlFolsom  ARMcGovern  PGHahn  LP Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival: the Minnesota Heart Survey. Diabetes Care. 1991;14537- 543
Link to Article
Haffner  SMLehto  SRonnemaa  TPyorala  KLaakso  M Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior history of myocardial infarction. N Engl J Med. 1998;339229- 234
Link to Article
Gu  KCowie  CCHarris  MI Diabetes and decline in heart disease mortality in US adults. JAMA. 1999;2811291- 1297
Link to Article
Feit  FBrooks  MMSopko  G  et al. for the BARI Investigators, Long-term clinical outcome in the Bypass Angioplasty Revascularization Investigation Registry: comparison with the randomized trial. Circulation. 2000;1012795- 2802
Link to Article
Chaitman  BRRosen  ADWilliams  DO  et al.  Myocardial infarction and cardiac mortality in the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial. Circulation. 1997;962162- 2170
Link to Article
Not Available, Influence of diabetes on 5-year mortality and morbidity in a randomized trial comparing CABG and PTCA in patients with multivessel disease: the Bypass Angioplasty Revascularization Investigation (BARI). Circulation. 1997;961761- 1769
Link to Article
Abizaid  AKornowski  RMintz  GS  et al.  The influence of diabetes mellitus on acute and late clinical outcomes following coronary stent implantation. J Am Coll Cardiol. 1998;32584- 589
Link to Article
Montalescot  GBarragan  PWittenberg  O  et al.  Platelet glycoprotein IIb/IIIa inhibition with coronary stenting for acute myocardial infarction. N Engl J Med. 2001;3441895- 1903
Link to Article
Mooradian  ADNowak  FV Diabetes mellitus and heart disease. Kaiser  FEMorley  JECoe  RMeds.Cardiovascular Disease in Older Persons. New York, NY Springer Verlag1997;53- 72
Mooradian  ADThurman  JE Glucotoxicity: potential mechanisms. Clin Geriatr Med. 1999;15255- 263
Mokdad  AHSerdula  MKDietz  WHBowman  BAMarks  JSKoplan  JP The spread of the obesity epidemic in the United States, 1991-1998. JAMA. 1999;2821519- 1522
Link to Article
Must  ASpadano  JCoakley  EHField  AEColditz  GDietz  WH The disease burden associated with overweight and obesity. JAMA. 1999;2821523- 1529
Link to Article
Morris  RDRimm  DLHartz  AJKalkhoff  RKRimm  AA Obesity and heredity in the etiology of non–insulin-dependent diabetes mellitus in 32,662 adult white women. Am J Epidemiol. 1989;130112- 121
Bray  GA Obesity increases risk for diabetes. Int J Obes Relat Metab Disord. 1992;16(suppl 4)S13- S17
Felber  JPAcheson  KJTappy  L From Obesity to Diabetes.  New York, NY John Wiley & Sons1993;
Knowler  WCPettitt  DJSavage  PJBennett  PH Diabetes incidence in Pima Indians: contributions of obesity and parental diabetes. Am J Epidemiol. 1981;113144- 156
Ohlson  LOLarsson  BSvardsudd  K  et al.  The influence of body fat distribution on the incidence of diabetes mellitus: 13.5 years of follow-up of the participants in the study of men born in 1913. Diabetes. 1985;341055- 1058
Link to Article
Cassano  PARosner  BVokonas  PSWeiss  ST Obesity and body fat distribution in relation to the incidence of non–insulin-dependent diabetes mellitus: a prospective cohort study of men in the Normative Aging Study. Am J Epidemiol. 1992;1361474- 1486
Bosello  OZamboni  MArmellini  FTodesco  T Biological and clinical aspects of regional body fat distribution. Diabetes Nutr Metab. 1993;6163- 171
Colditz  GAWillett  WCRotnitzky  AManson  JE Weight gain as a risk factor for clinical diabetes mellitus in women. Ann Intern Med. 1995;122481- 486
Link to Article
Chan  JMRimm  EBColditz  GAStampfer  JMWillett  WC Obesity, fat distribution, and weight gain as risk factors for clinical diabetes in men. Diabetes Care. 1994;17961- 969
Link to Article
Eckel  RHKrauss  RMfor the AHA Nutrition Committee, American Heart Association call to action: obesity as a major risk factor for coronary heart disease. Circulation. 1998;972099- 2100
Link to Article
Mooradian  AD Obesity: a rational target for managing diabetes mellitus. Growth Horm IGF Res. 2001;11(suppl A)S79- S83
Link to Article
Evaluation, Expert Panel on Detection and Treatment of High Blood Cholesterol in Adults, Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001;2852486- 2497
Link to Article
American Diabetes Association, Evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes and related complications. Diabetes Care. 2002;25202- 212
Link to Article
Wing  RRBlair  EHBononi  PMarcus  MDWatanabe  RBergman  RN Caloric restriction per se is a significant factor in improvements in glycemic control and insulin sensitivity during weight loss in obese NIDDM patients. Diabetes Care. 1994;1730- 36
Link to Article
Wing  RRKoeske  REpstein  LHNowalk  MPGooding  WBecker  D Long-term effects of modest weight loss in type II diabetic patients. Arch Intern Med. 1987;1471749- 1753
Link to Article
Heath  GWWilson  RHSmith  JLeonard  BE Community-based exercise and weight control: diabetes risk reduction and glycemic control in Zuni Indians. Am J Clin Nutr. 1991;53(suppl)1642S- 1646S
Uusitupa  MLouheranta  ALindstrom  J  et al.  The Finnish Diabetes Prevention Study. Br J Nutr. 2000;83(suppl 1)S137- S142
Link to Article
Knowler  WCBarrett-Connor  EFowler  SE  et al.  Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med. 2002;346393- 403
Link to Article
Gokcel  AKarakose  HErtorer  EMTanaci  NTutuncu  NBGuvener  N Effects of sibutramine in obese female subjects with type 2 diabetes and poor blood glucose control. Diabetes Care. 2001;241957- 1960
Link to Article
Heath  MJChong  EWeinstein  SPSeaton  TB Sibutramine enhances weight loss and improves glycemic control and plasma lipid profile in obese patients with type 2 diabetes mellitus [abstract]. Diabetes. 1999;48(suppl)A308
Link to Article
Hollander  PAElbein  SCHirsch  IB  et al.  Role of orlistat in the treatment of obese patients with type 2 diabetes: a 1-year randomized double-blind study. Diabetes Care. 1998;211288- 1294
Link to Article
Heymsfield  SBSegal  KRHauptman  J  et al.  Effects of weight loss with orlistat on glucose tolerance and progression to type 2 diabetes in obese adults. Arch Intern Med. 2000;1601321- 1326
Link to Article
Despres  J-PLamarche  BMauriege  P  et al.  Hyperinsulinemia as an independent risk factor for ischemic heart disease. N Engl J Med. 1996;334952- 957
Link to Article
UK Prospective Diabetes Study (UKPDS) Group, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet. 1998;352837- 853
Link to Article
Wannamethee  SGShaper  AG Type of alcoholic drink and risk of major coronary heart disease events and all-cause mortality. Am J Public Health. 1999;89685- 690
Link to Article
Valmadrid  CTKlein  RMoss  SEKlein  BKCruickshanks  KJ Alcohol intake and the risk of coronary heart disease mortality in persons with older-onset diabetes mellitus. JAMA. 1999;282239- 246
Link to Article
Solomon  CGHu  FBStampfer  MJ  et al.  Moderate alcohol consumption and risk of coronary heart disease among women with type 2 diabetes mellitus. Circulation. 2000;102494- 499
Link to Article
Ajani  UAHennekens  CHSpelsberg  AManson  JE Alcohol consumption and risk of type 2 diabetes mellitus among US male physicians. Arch Intern Med. 2000;1601025- 1030
Link to Article
Tanasescu  MHu  FBWillett  WCStampfer  MJRimm  EB Alcohol consumption and risk of coronary heart disease among men with type 2 diabetes mellitus. J Am Coll Cardiol. 2001;381836- 1842
Link to Article
Ajani  UAGaziano  MLotufo  PA  et al.  Alcohol consumption and risk of coronary heart disease by diabetes status. Circulation. 2000;102500- 505
Link to Article
Diabetes Control and Complications Trial Research Group, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329977- 986
Link to Article
Kuusisto  JMykkanen  LPyorala  KLaakso  M NIDDM and its metabolic control predict coronary heart disease in elderly subjects. Diabetes. 1994;43960- 967
Link to Article
Ohkubo  YKishikawa  HAraki  E  et al.  Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non–insulin-dependent diabetes mellitus: a randomized prospective 6-year study. Diabetes Res Clin Pract. 1995;28103- 117
Link to Article
Turner  RCCall  CAFrighi  VHolman  RR  Jrfor the UKPDS Group, Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;2812005- 2012
Link to Article
UK Prospective Diabetes Study (UKPDS) Group, Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). Lancet. 1998;352854- 865
Link to Article
Mooradian  ADChehade  J Implications of the UK Prospective Diabetes Study: questions answered and issues remaining. Drugs Aging. 2000;16159- 164
Link to Article
Abraira  CColwell  JANuttall  FQ  et al. for the Veterans Affairs Cooperative Study in Type II Diabetes, Veterans Affairs Cooperative Study on glycemic control and complications in type II diabetes (VACSDM): results of the feasibility trial. Diabetes Care. 1995;181113- 1123
Link to Article
Malmberg  Kfor the DIGAMI (Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction) Study Group, Prospective randomised study of intensive insulin treatment on long term survival after acute myocardial infarction in patients with diabetes mellitus. BMJ. 1997;3141512- 1515
Link to Article
van den Berghe  GWouters  PWeekers  F  et al.  Intensive insulin therapy in the critically ill patients. N Engl J Med. 2001;3451359- 1367
Link to Article
Stratton  IMAdler  AINeil  HA  et al.  Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study. BMJ. 2000;321405- 412
Link to Article
Khaw  KTWareham  NLuben  R  et al.  Glycated haemoglobin, diabetes, and mortality in men in Norfolk cohort of European prospective investigation of cancer and nutrition (EPIC-Norfolk). BMJ. 2001;32215- 18
Link to Article
The DECODE Study Group, on behalf of the European Diabetes Epidemiology Group, Glucose tolerance and cardiovascular mortality: comparison of fasting and 2-hour diagnostic criteria. Arch Intern Med. 2001;161397- 405
Link to Article
Mooradian  ADThurman  JE Drug therapy of postprandial hyperglycaemia. Drugs. 1999;5719- 29
Link to Article
Not Available, ACE Consensus Conference on Guidelines for Glycemic Control. Endocr Pract. November/December2001;suppl2- 5
Chehade  JMMooradian  AD A rational approach to drug therapy of type 2 diabetes mellitus. Drugs. 2000;6095- 113
Link to Article
American Diabetes Association, Clinical practice recommendations 2002. Diabetes Care. 2002;25(suppl 1)S1- S147
Link to Article
European Diabetes Policy Group 1999, A desktop guide to type 2 diabetes mellitus. Diabet Med. 1999;16716- 730
Link to Article
Chehade  JMMooradian  AD Drug therapy: current and emerging agents. Sinclair  AJFinucane  Peds.Diabetes in Old Age. 2nd ed. Chichester, England John Wiley & Sons2001;199- 214
Turner  RCMillns  HNeil  HA  et al.  Risk factors for coronary artery disease in non–insulin dependent diabetes mellitus: United Kingdom Prospective Diabetes Study (UKPDS: 23). BMJ. 1998;316823- 828
Link to Article
Garg  AGrundy  SM Management of dyslipidemia in NIDDM. Diabetes Care. 1990;13153- 169
Link to Article
Pyorala  KPedersen  TRKjekshus  JFaergeman  OOlsson  AGThorgeirsson  G Cholesterol lowering with simvastatin improves prognosis of diabetic patients with coronary heart disease: a subgroup analysis of the Scandinavian Simvastatin Survival Study (4S). Diabetes Care. 1997;20614- 620
Link to Article
Goldberg  RBMellies  MJSacks  FM  et al. for the CARE Investigators, Cardiovascular events and their reduction with pravastatin in diabetic and glucose-intolerant myocardial infarction survivors with average cholesterol levels: subgroup analyses in the cholesterol and recurrent events (CARE) trial. Circulation. 1998;982513- 2519
Link to Article
Rubins  HBRobins  SJCollins  D  et al. for the Veterans Affairs High-Density Lipoprotein Cholesterol Intervention Trial Study Group, Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med. 1999;341410- 418
Link to Article
Elkeles  RSDiamond  JRPoulter  C  et al.  Cardiovascular outcomes in type 2 diabetes: a double-blind placebo-controlled of bezafibrate: the St. Mary's, Ealing, Northwick Park Diabetes Cardiovascular Disease Prevention (SENDCAP) Study. Diabetes Care. 1998;21641- 648
Link to Article
Not Available, Effect of fenofibrate on progression of coronary-artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study a randomised study. Lancet. 2001;357905- 910
Link to Article
Heart Protection Study Collaborative Group, MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;3607- 22
Link to Article
Downs  JRClearfield  MWeis  S  et al.  Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS: Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;2791615- 1622
Link to Article
Leitersdorf  E Cholesterol absorption inhibition: filling an unmet need in lipid-lowering management. Eur Heart J. 2001;3(suppl E)E17- E23
Link to Article
Elam  MBHunninghake  DBDavis  KB  et al. for the Arterial Disease Multiple Intervention Trial, Effect of niacin on lipid and lipoprotein levels and glycemic control in patients with diabetes and peripheral arterial disease: the ADMIT study: a randomized trial. JAMA. 2000;2841263- 1270
Link to Article
Mooradian  ADChehade  JMThurman  JE The role of thiazolidenediones in the treatment of type 2 diabetes. Treat Endocrinol. 2002;113- 20
Link to Article
Pearson  TALaurora  IChu  HKfonek  S The Lipid Treatment Assessment Project (L-TAP): a multicenter survey to evaluate the percentages of dyslipidemic patients receiving lipid-lowering therapy and achieving low-density lipoprotein cholesterol goals. Arch Intern Med. 2000;160459- 467
Link to Article
Not Available, The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Arch Intern Med 1997;1572413- 2446
Link to Article
Adler  AIStratton  IMNeil  HA  et al.  Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000;321412- 419
Link to Article
Curb  IDPressel  SLCutler  JA  et al. for the Systolic Hypertension in the Elderly Program Cooperative Research Group, Effect of diuretic-based antihypertensive treatment on cardiovascular disease risk in older diabetic patients with isolated systolic hypertension. JAMA. 1996;2761886- 1892
Link to Article
Tuomilehto  JRastenyte  DBirkenhager  WH  et al. for the Systolic Hypertension in Europe Trial Investigators, Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. N Engl J Med. 1999;340677- 684
Link to Article
Heart Outcomes Prevention Evaluation Study Investigators, Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Lancet. 2000;355253- 259
Link to Article
Hansson  LZanchetti  ACarruthers  SG  et al. for the HOT Study Group, Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet. 1998;3511755- 1762
Link to Article
Bakris  GLWilliams  MDworkin  L  et al. for the National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group, Preserving renal function in adults with hypertension and diabetes: a consensus approach. Am J Kidney Dis. 2000;36646- 661
Link to Article
Ravid  MSavin  HJutrin  IBental  TKatz  BLishner  M Long-term stabilizing effect of angiotensin-converting enzyme inhibition on plasma creatinine and on proteinuria in normotensive type II diabetic patients. Ann Intern Med. 1993;118577- 581
Link to Article
Lacourciere  YNadeau  APoirier  LTancrede  G Captopril or conventional therapy in hypertensive type II diabetics: three-year analysis. Hypertension. 1993;21786- 794
Link to Article
Lewis  EJHunsicker  LGClarke  WR  et al.  Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med. 2001;345851- 860
Link to Article
Brenner  BMCooper  MEde Zeeuw  D  et al.  Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med. 2001;345861- 869
Link to Article
Niskanen  LHedner  THansson  LLanke  JNiklason  A Reduced cardiovascular morbidity and mortality in hypertensive diabetic patients on first-line therapy with an ACE inhibitor compared with a diuretic/β-blocker–based treatment regimen: a subanalysis of the Captopril Prevention Project. Diabetes Care. 2001;242091- 2096
Link to Article
Yusuf  SGerstein  HHoogwerf  Bfor the HOPE Study Investigators, Ramipril and the development of diabetes. JAMA. 2001;2861882- 1885
Link to Article
Bakris  GLCopley  JBVicknair  NSadler  RLeurgans  S Calcium channel blockers versus other antihypertensive therapies on progression of NIDDM associated nephropathy. Kidney Int. 1996;501641- 1650
Link to Article
Agodoa  LYAppel  LBakris  GL  et al.  Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial. JAMA. 2001;2852719- 2728
Link to Article
Estacio  ROJeffers  BWHiatt  WRBiggerstaff  SLGifford  NSchrier  RW The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non–insulin-dependent diabetes and hypertension. N Engl J Med. 1998;338645- 652
Link to Article
Tatti  PPahor  MByington  RP  et al.  Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998;21597- 603
Link to Article
Agardh  C-DGarcia-Puig  JCharbonnel  BAngelkort  BBarnett  AH Greater reduction of urinary albumin excretion in hypertensive type II diabetic patients with incipient nephropathy by lisinopril than by nifedipine. J Hum Hypertens. 1996;10185- 192
Poulter  NWilliams  B Doxazosin for the management of hypertension: implications of the findings of the ALLHAT trial. Am J Hypertens. 2001;141170- 1172
Link to Article
Sowers  JR Hypertension in type II diabetes: update on therapy. J Clin Hypertens (Greenwich). 1999;141- 47
Brahmbhat  RBaggaley  PHockings  B Normalization of blood pressure in a patient with severe orthostatic hypotension and supine hypertension using clonidine [letter]. Hypertension. 2001;37E24
Link to Article
Cruz  DN Midodrine: a selective α-adrenergic agonist for orthostatic hypotension and dialysis hypotension. Expert Opin Pharmacother. 2000;1835- 840
Link to Article
Rosen  PNawroth  PPKing  GMoller  WTritschler  HJPacker  L The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a Congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab Res Rev. 2001;17189- 212
Link to Article
Mooradian  AD Micronutrients in diabetes mellitus. Ioannides  CLewis  DFVeds.Drugs, Diet and Disease Mechanistic Approaches to Diabetes. New York, NY Ellis Horwood1995;2183- 200
Mooradian  ADFailla  MHoogwerf  BMaryniuk  MWylie-Rosett  J Selected vitamins and minerals in diabetes. Diabetes Care. 1994;17464- 479
Thurman  JMooradian  AD Vitamin supplementation therapy in the elderly. Drugs Aging. 1997;11433- 449
Link to Article
Klipstein-Grobusch  KGeleijnse  JMden Breeijen  JH  et al.  Dietary antioxidants and risk of myocardial infarction in the elderly: the Rotterdam Study. Am J Clin Nutr. 1999;69261- 266
Will  JCFord  ESBowman  BA Serum vitamin C concentrations and diabetes: findings from the Third National Health and Nutrition Examination Survey 1988-1994. Am J Clin Nutr. 1999;7049- 52
Mayer-Davis  EJBell  KAReboussin  BARushing  JMarshall  JAHamman  RF Antioxidant nutrient intake and diabetic retinopathy: the San Luis Valley Diabetes Study. Ophthalmology. 1998;1052264- 2270
Link to Article
Mayer-Davis  EJMonaco  JHMarshall  JARushing  JJuhaeri  Jfor the Insulin Resistance Atherosclerosis Study and the San Luis Valley Diabetes Study, Vitamin C intake and cardiovascular disease risk factors in persons with non–insulin-dependent diabetes mellitus. Prev Med. 1997;26277- 283
Link to Article
Hennekens  CHBuring  JEManson  JE  et al.  Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med. 1996;3341145- 1149
Link to Article
Knekt  PJarvinen  RReunanen  AMaatela  J Flavonoid intake and coronary mortality in Finland: a cohort study. BMJ. 1996;312478- 481
Link to Article
Kushi  LHFolsom  ARPrineas  RJMink  PJWu  YBostick  RM Dietary antioxidant vitamins and death from coronary heart disease in postmenopausal women. N Engl J Med. 1996;3341156- 1162
Link to Article
Losonczy  KGHarris  TBHavlik  RS Vitamin E and vitamin C supplement use and risk of all-cause and coronary heart disease mortality in older persons: the Established Population for Epidemiologic Studies of the Elderly. Am J Clin Nutr. 1996;64190- 196
Knekt  PReunanen  AJarvinen  RSeppanen  RHeliovaara  MAromaa  A Antioxidant vitamin intake and coronary mortality in a longitudinal population study. Am J Epidemiol. 1994;1391180- 1189
Rimm  EBStampfer  MJAscherio  AGiovannucci  EColditz  GAWillett  WC Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;3281450- 1456
Link to Article
Stampfer  MJHennekens  CHManson  JEColditz  GARosner  BWillett  WC Vitamin E consumption and the risk of coronary disease in women. N Engl J Med. 1993;3281444- 1449
Link to Article
Enstrom  JEKanim  LEKlein  MA Vitamin C intake and mortality among a sample of the United States population. Epidemiology. 1992;3194- 202
Link to Article
Christen  WGGaziano  JMHennekens  CH Design of Physicians' Health Study II: a randomized trial of beta carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol. 2000;10125- 134
Link to Article
Yusuf  SDagenais  GPogue  JBosch  JSleight  Pfor the Heart Outcomes Prevention Evaluation Study Investigators, Vitamin E supplementation and cardiovascular events in high-risk patients. N Engl J Med. 2000;342154- 160
Link to Article
GISSI-Prevenzione Investigators, Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione Trial. Lancet. 1999;354447- 455
Link to Article
Omenn  GSGoodman  GEThornquist  MD  et al.  Risk factors for lung cancer and for intervention effects in CARET: the Beta-Carotene and Retinol Efficacy Trial. J Natl Cancer Inst. 1996;881550- 1559
Link to Article
Stephens  NGParsons  ASchofield  PMKelly  FCheeseman  KMitchinson  MJ Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347781- 786
Link to Article
ATBC (Alpha-Tocopherol, Beta Carotene) Cancer Prevention Study Group, The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers: the Alpha Tocopherol, Beta Carotene Cancer Prevention Study Group. N Engl J Med. 1994;3301029- 1035
Link to Article
Brown  BGZhao  X-QChait  A  et al.  Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med. 2001;3451583- 1592
Link to Article
Colwell  JA Treatment for the procoagulant state in type 2 diabetes. Endocrinol Metab Clin North Am. 2001;301011- 1030
Link to Article
Antiplatelet Trialists' Collaboration, Secondary prevention of vascular disease by prolonged antiplatelet treatment. Br Med J (Clin Res Ed). 1988;296320- 331
Link to Article
CAPRIE Steering Committee, A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996;3481329- 1339
Link to Article
Yusuf  SZhao  FMehta  SRChrolavicius  STognoni  GFox  KK Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345494- 502
Link to Article
Eikelboom  JWHirsh  JWeitz  JIJohnston  MYi  QYusuf  S Aspirin-resistant thromboxane biosynthesis and the risk of myocardial infarction, stroke, or cardiovascular death in patients at high risk for cardiovascular events. Circulation. 2002;1051650- 1655
Link to Article
Neil  AHawkins  MPotok  MThorogood  MCohen  DMann  J A prospective population-based study of microalbuminuria as a predictor of mortality in NIDDM. Diabetes Care. 1993;16996- 1003
Link to Article
Ridker  PMHennekens  CHBuring  JERifai  N C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342836- 843
Link to Article
Ridker  PMCushman  MStampfer  MJTracy  RPHennekens  CH Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med. 1997;336973- 979
Link to Article
Ridker  PMRifai  NClearfield  M  et al. for the Air Force/Texas Coronary Atherosclerosis Prevention Study Investigators, Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events. N Engl J Med. 2001;3441959- 1965
Link to Article
Ridker  PMRifai  NPfeffer  MASacks  FBraunwald  Efor the Cholesterol and Recurrent Events (CARE) Investigators, Long-term effects of pravastatin on plasma concentration of C-reactive protein. Circulation. 1999;100230- 235
Link to Article
Albert  MADanielson  ERifai  NRidker  PMfor the PRINCE Investigators, Effect of statin therapy on C-reactive protein levels: the pravastatin inflammation/CRP evaluation (PRINCE): a randomized trial and cohort study. JAMA. 2001;28664- 70
Link to Article
Ford  ES Body mass index, diabetes, and C-reactive protein among US adults. Diabetes Care. 1999;221971- 1977
Link to Article
Scanu  AM The role of lipoprotein(a) in the pathogenesis of atherosclerotic disease and its utility as predictor of coronary heart disease events. Curr Cardiol Rep. 2001;3385- 390
Link to Article
Sharrett  ARBallantyne  CMCoady  SA  et al.  Coronary heart disease prediction from lipoprotein cholesterol levels, triglycerides, lipoprotein(a), apolipoprotein A-I and B, and HDL density subfractions: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2001;1041108- 1113
Link to Article
Ridker  PMManson  JEBuring  JEShih  JMatias  MHennekens  CH Homocysteine and risk of cardiovascular disease among postmenopausal women. JAMA. 1999;2811817- 1821
Link to Article
Yeromenko  YLavie  LLevy  Y Homocysteine and cardiovascular risk in patients with diabetes mellitus. Nutr Metab Cardiovasc Dis. 2001;11108- 116
Homocysteine Lowering Trialists' Collaboration, Lowering blood homocysteine with folic acid based supplements: meta-analysis of randomized trials. BMJ. 1998;316894- 898
Link to Article
Kind  HAubert  REHerman  WH Global burden of diabetes, 1995-2025: prevalence, numerical estimates, and projections. Diabetes Care. 1998;211414- 1431
Link to Article
American Diabetes Association, Diabetes mellitus and exercise. Diabetes Care. 2002;25(suppl 1)S64- S68
Link to Article

Correspondence

CME
Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment

Multimedia

Some tools below are only available to our subscribers or users with an online account.

Web of Science® Times Cited: 75

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles
JAMAevidence.com

The Rational Clinical Examination EDUCATION GUIDES
Clubbing