TYPE 2 DIABETES AND CARDIOVASCULAR DISEASE

CONTENTS

Preface xiDaniel Einhorn and Julio Rosenstock

Management of Diabetic Dyslipidemia 1Maria Del Pilar Solano and Ronald B. Goldberg

Identification and management of dyslipidemia is an importantelement in the multi-factorial approach to prevent coronary heartdisease. Diabetic dyslipidemia typically consists of elevated triglyc-eride, low high-density lipoprotein cholesterol, predominance ofsmall, dense low-density lipoprotein (LDL) particles, and averageLDL cholesterol (LDL-C). Lipid-lowering therapy has a beneficialeffect on cardiovascular outcomes. Statin treatment is beneficialin patients who are older than 40 years of age, irrespective of theLDL-C value. To achieve lipid targets, attention should be directedfirst toward nonpharmacologic therapeutic interventions, such asdiet, exercise, smoking cessation, weight loss, and improving glyce-mic control. Although statin therapy is recommended for most sub-jects, judicious use of combination therapy should be considered inthe highest risk subjects.

The Dyslipidemia of Diabetes Mellitus: Giving Triglyceridesand High-Density Lipoprotein Cholesterol a Higher Priority? 27David M. Kendall

Most excess mortality associated with diabetes mellitus results fromcardiovascular diseases, several risk factors of which are modifiablein diabetes mellitus patients, including dyslipidemia characterizedby increased levels of triglycerides (TGs), reduced high-density li-poprotein cholesterol (HDL-C) levels, and smaller, denser, moreatherogenic low-density lipoprotein cholesterol (LDL-C) particles.Lipid management focuses on reduction of LDL-C, with low levelsof HDL-C or high TGs receiving less attention. Given the prevalenceof this ‘‘dyslipidemia of diabetes,’’ therapeutic lifestyle changes andglucose control along with targeted drug therapy must be consid-ered. Emerging evidence and continuing clinical trials suggest that

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treatment of lipid disorders beyond those of LDL-C may be neces-sary to significantly reduce cardiovascular risk in the diabetesmellitus population.

Compensatory Hyperinsulinemia and the Development of anAtherogenic Lipoprotein Profile: The Price Paid to MaintainGlucose Homeostasis in Insulin-Resistant Individuals 49Gerald M. Reaven

The ability of insulin to stimulate glucose disposal varies six- toeightfold among apparently healthy individuals. The only way thatinsulin-resistant persons can prevent the development of type 2diabetes is by secreting the increased amount of insulin that is nec-essary to compensate for the resistance to insulin action. Thegreater the magnitude of muscle and adipose tissue insulin resis-tance, the more insulin must be secreted to maintain normal ornear-normal glucose tolerance. Although compensatory hyperinsu-linemia may prevent the development of fasting hyperglycemia ininsulin-resistant individuals, the price paid is the untoward physio-logic effects of increased circulating insulin concentrations on tis-sues that retain normal insulin sensitivity. This article focuseson the interplay between insulin resistance at the level of the mus-cle and adipose tissue and normal hepatic insulin sensitivity,which leads to the atherogenic lipoprotein profile characteristicof insulin-resistant individuals.

Hypertension Management in Type 2 Diabetes Mellitus:Recommendations of the Joint National Committee VII 63Adam Whaley-Connell and James R. Sowers

The Joint National Committee recently reconvened to prepare theirseventh report in an attempt to help clarify the guidelines for themanagement of hypertension (HTN) for clinicians. This was due,in large part, to recent reports of large, multi-center outcome trialswith new conclusions and the increasing recognition of widespreadunderuse of resources for HTN management. There is abundantevidence that combinations of two, three, or more antihypertensiveagents may be required to reach goal blood pressure of 130/80 mmHg in hypertensive patients who have diabetes. There are severalimportant implications for diabetic patients in the new guidelines;this article attempts to clarify them and provide clinicians with acurrent strategy for the management of HTN in patients who havediabetes.

Glycemic Management of Type 2 Diabetes: An Emerging Strategywith Oral Agents, Insulins, and Combinations 77Matthew C. Riddle

This article discusses glycemic management of type 2 diabetes,reviewing the characteristics, advantages, and limitations of thevarious treatment options. A broad strategy is proposed, with

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evidence-based standard tactics to be considered first, and indi-vidualized additional options reserved for situations in which thestandard approach is not sufficient.

Hospital Management of Diabetes 99Etie S. Moghissi and Irl B. Hirsch

Diabetes remains a major cause of death and disability and is agrowing global concern. Mounting observational and interven-tional evidence consistently indicates that hyperglycemia in thehospital setting is associated with increased mortality and morbid-ity and that meticulous glycemic control can improve clinical out-comes. The purpose of this article is to review the evidence, discussthe importance of striving for good glycemic control in the hospitalsetting, and emphasize the need for additional outcome researchstudies to further examine the currently recommended in-hospitalglycemic guidelines. This article concludes with a discussion ofstrategies for achieving tight glycemic targets.

Potential Cardiovascular Benefits of Insulin Sensitizers 117Biju P. Kunhiraman, Ali Jawa, and Vivian A. Fonseca

Patients who have diabetes have a greatly increased relative risk ofcardiovascular disease when compared with patients who do nothave diabetes. Much of this risk is related to insulin resistanceand is associated with traditional and nontraditional cardiovascu-lar risk factors. Metabolic syndrome is now recognized as a riskfactor for cardiovascular disease and recent studies show that thePPAR class of receptors are expressed in several tissues and mayhave implications in atherosclerosis and insulin resistance. Al-though still controversial, metformin is the only oral hypoglycemicagent shown to decrease cardiovascular events independent of gly-cemia. The thiazolidinediones (TZDs) directly improve insulinresistance, decrease plasma insulin concentration, and are increas-ingly proving to be beneficial in patients with insulin resistance. Anumber of studies have demonstrated that both classes of insulinsensitizers produce changes in several cardiovascular risk factorsassociated with the insulin resistance syndrome, including subtlelowering of blood pressure, impacting diabetic dyslipidemia, im-proving fibrinolysis, and decreasing carotid artery intima-medialthickness. Although TZDs raise low-density lipoprotein (LDL) cho-lesterol, they induce a favorable change in the LDL particle sizeand susceptibility to oxidation. Long-term outcome clinical trialsare being conducted to determine the impact that TZDs have oncardiovascular events in individuals who have type 2 diabetes.

Insulin Therapy in People Who Have Dysglycemia and Type 2Diabetes Mellitus: Can It Offer Both Cardiovascular Protectionand Beta-Cell Preservation? 137Hertzel C. Gerstein and Julio Rosenstock

Dysglycemia, an elevated glucose level that extends into the dia-betes mellitus range, is a recognized risk factor for cardiovascular

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disease. Glucose levels rise because of insufficient insulin causedby insulin resistance or insulin deficiency. Elevated glucose and in-sufficient insulin effects are implicated in the pathogenesis ofcardiovascular disease. Emerging data suggest that glucose lower-ing with insulin may reduce safely the risk for cardiovascular dis-ease and preserve beta-cell function. Large, controlled internationaltrials are testing the hypothesis that insulin therapy may havecardiovascular benefits.

Novel Pharmacologic Agents for Type 2 Diabetes 155Gabriel I. Uwaifo and Robert E. Ratner

The management of diabetes has undergone profound changes inthe last decade with the introduction of several new classes of oralhypoglycemic agents and insulin analogs. The next few yearspromise potentially more dramatic additions to the arsenal of anti-diabetic agents with several new agents like the glucagons-likepeptide-1 agonists and dipeptidyl peptidase IV inhibitors leadingthe way. Newer methods of insulin delivery and other insulin ana-logs also headline the prospects for improving diabetes pharma-cotherapy in the near future. The development of these and otheragents on the horizon hold the promise of enabling caregivers tobetter provide as near normal glycemic and metabolic control aspossible with reduced hypoglycemia so that so-called intensivediabetic therapy becomes standard therapy available to and attain-able by all patients who have diabetes.

The Prevention of Type 2 Diabetes Mellitus 199Silvio E. Inzucchi and Robert S. Sherwin

With aworldwide pandemic of type 2 diabetes upon us, it is impera-tive that effective and practical preventive strategies be developedfor this disease which, once established, carries with it excess mor-bidity and mortality. This article reviews recently published dataon the prevention of type 2 diabetes and compares the demonstratedeffectiveness of each strategy, including lifestyle modification andseveral pharmacologic agents. Although much new information isavailable, many translational questions remain that chiefly concernthe generalizability and applicability of these programs to clinicalpractice. Recent diabetes prevention guidelines are discussed, anda practical framework for their implementation is presented.

Prevention of Cardiovascular Outcomes in Type 2 DiabetesMellitus: Trials on the Horizon 221John B. Buse and Julio Rosenstock

This article focuses on the continuing clinical trials in patients whohave diabetes mellitus and pre�diabetes mellitus in which cardio-vascular disease outcomes—specifically, myocardial infarction,stroke, and cardiovascular death—are examined as primaryoutcomes.

Index 237

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