Type 2 diabetes: epidemiologic trends, evolving pathogenic concepts, and recent changes in therapeutic approach.

Abstract: The prevalence of type 2 diabetes has assumed epidemic dimensions. Children are now vulnerable to a disease that was once the exclusive domain of adulthood. Increased body weight and sedentary behavior accelerate insulin resistance and [beta]-cell dysfunction, leading to the clinical manifestation of hyperglycemia. Other cardiovascular risk factors tend to cluster in this milieu, setting the stage for vastly increased macrovascular morbidity. Many more people have impaired glucose tolerance ('prediabetes'). They are not only at risk for frank diabetes but also for the recently recognized entity of 'metabolic syndrome,' which is further characterized by hypertension, dyslipidemia, and central adiposity. A multifactorial approach addressing these aspects in addition to intensive glycemic control is the most efficacious therapy, optimally achieved through a team effort comprising the clinician, diabetes nurse, dietitian, and other professionals. Early use of oral-agent combinations is gaining favor. Insulin is best utilized in a basal-bolus fashion to manage both fasting and postprandial glycemia, delivered with multiple-dose injections or continuously via the pump. In hospitalized patients, good diabetic control reduces mortality. Finally, recent trials show that optimal weight maintenance and regular exercise can prevent or delay type 2 diabetes. Such information can serve as the foundation for large-scale preventive endeavors at the community level.

Key Words: cardiovascular disease, insulin resistance, metabolic syndrome, pre-diabetes, type 2 diabetes

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The impact of diabetes on individuals and society is profound. Its devastating complications take a huge toll in terms of morbidity and overall mortality. The economic cost is enormous, and associated direct and indirect expenditures make diabetes the costliest chronic disease. To complicate this formidable problem, the prevalence of type 2 diabetes has been increasing at an alarming rate, concomitant with that of obesity. The disease has begun to make a significant impact in younger populations, especially in those belonging to minority groups. Although microvascular complications continue to be a cause of adverse outcomes, the link between type 2 diabetes and cardiovascular pathologies has emerged as a major determinant of early mortality. This association, under-recognized in the past, has been further highlighted by elucidation of the "metabolic syndrome," a condition characterized by insulin resistance and glucose intolerance coexisting with other cardiac risk factors. As a consolation for this gloomy outlook, data is accumulating that shows diabetes and its attendant syndromes and sequelae are preventable or modifiable through lifestyle changes and early, aggressive pharmacologic and nonpharmacologic interventions. In addition, clinicians are now better equipped to diagnose, monitor, and treat patients than ever before. The number of medications available for therapy has increased in recent years. More significant, however, is a change in overall treatment approach stemming from an improved cognizance of patho-physiological processes and clinical outcomes. This review summarizes the current knowledge and understanding in this arena, and is intended to give the practicing physician a brief update on some of the changes that are taking place in this important and burgeoning field.

Epidemiology

A public health epidemic and global burden

Diabetes has assumed epidemic proportions in the United States, with 18.2 million people having the disease, but only 13 million of them having been diagnosed. (1) Ninety percent of these individuals have type 2 diabetes. The incidence is increasing in every population segment and age group, but especially among minorities and the young. (2) This is fueled by the increase in obesity rates, and contributed to by sedentary lifestyles and dietary changes. It is estimated that one of every three persons born in the United States in the year 2000 will develop diabetes in their lifetime. (1)

Communities all over the world are reaping the benefits of advances in technology and urbanization. As an unintended consequence, we are in the midst of an unprecedented pandemic of obesity and type 2 diabetes. The latter takes a huge toll on public health, and is an economic drain on available resources. Due to the "Westernization" of societies around the globe, rates of type 2 diabetes and obesity are expected to increase exponentially. Worldwide, there are currently an estimated 194 million people with diabetes. This number is expected to increase to 221 million by the end of this decade, and continue on to 333 million by the year 2025. (3) This will pose an enormous global public health and community burden, one that local and international health agencies are ill-equipped to cope with. The focus will need to be shifted increasingly toward prevention of this pandemic through enhanced awareness and lifestyle modifications.

Economic Cost of Diabetes

In 2002, 92 billion dollars' worth of expenses in the United States (4) and 153 billion worldwide were directly attributable to diabetes. However, there are numerous indirect and "hidden" costs of the disorder; for example, the burden of its complications (dialysis, vision impairment, neuropathic ulceration, and amputations), days lost from work, and disability. Diabetes is a major risk factor for atherosclerosis, cardiovascular disease, and premature morbidity. Taken together, these aspects raised the calculated costs to $132 billion in the United States, more than any other chronic health condition. (4) Recent data show that in some countries diabetes already has a higher economic impact than acquired immunodeficiency syndrome (AIDS), and its cost burden will rise to an astounding $396 billion by 2025. (5) These figures underestimate the total burden of this disease because they do not take into account the intangible aspects like increased stress, pain, and suffering endured by people with diabetes.

Type 2 diabetes in children, adolescents, and younger adults

There has been an alarming increase in the incidence of diabetes and childhood obesity in the past decade. More children in their early teenage years are being diagnosed with type 2 diabetes, thus changing the demographics of the disease in this age group. (6,7) A shift from the traditional diagnosis of type 1 diabetes to type 2 diabetes is being observed, concomitant with a rise in obesity, sedentary habits, inappropriate diet, "fast food" intake, and possibly other unknown factors. Rural populations and minorities, especially African-American and Mexican-American youngsters, are over-represented in this epidemiologic change. This trend appears to continue unabated and shows no signs of slowing down. (8) Type 2 diabetes is manifesting earlier in young adults, for example, in the third and fourth decades of life. It is expected that this increase will continue to fuel the diabetes epidemic as these individuals age.

The metabolic syndrome and "prediabetes"

The pathophysiologic events leading to clinical manifestation and eventual diagnosis of type 2 diabetes are slow and insidious, being affected by a complex interplay of genetic and environmental factors. The onset is preceded, on average, by a decade of impaired glucose tolerance (2 h postprandial glucose between 140 and 200 mg/dL) or impaired fasting glucose (between 110 and 125 mg/dL) (Fig. 1). There are an estimated 47 million people with this abnormality in the United States, (9) and many will go on to develop type 2 diabetes. This stage of "prediabetes" is frequently associated with certain other characteristics like abdominal obesity, hypertension, and dyslipidemia, and this constellation has been recognized as "syndrome X" or the "insulin resistance syndrome." The National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) has designated guidelines (10) for the diagnosis of this "metabolic syndrome" if any three of five possible criteria (Table 1) are fulfilled. Hyperglycemia in the prediabetic or diabetic range is a common, though not necessary, component of this syndrome. The importance of this clustering of risk factors is a greater incidence of cardiovascular disease observed in patients with the metabolic syndrome. (11) This disorder, therefore, serves to identify a patient population at exaggerated risk for both diabetes and cardiovascular disease. It is now a recognized disease entity with its own ICD code (277.7), and can be diagnosed by clinicians in office practice. The diagnosis is meant to lend heightened cognizance of an individual's risk for diabetes (if not already present) and cardiovascular events. It mandates addressing the risk factors separately and lessening or reversing the impact of the syndrome through maintenance of weight loss and regular exercise.

[FIGURE 1 OMITTED]

Pathophysiology 

Insulin resistance

Tissue resistance to insulin-mediated glucose uptake is now recognized as a major pathophysiologic determinant of type 2 diabetes. (11) There has been an explosion of research that has established insulin resistance both as a clinical precursor of diabetes and a possible explanation for the associated injurious alterations in cardiovascular health. Although the cellular mechanisms are still being elucidated, there is mounting evidence pointing to elevated circulating levels of pro-inflammatory cytokines that trigger endothelial dysfunction and promote vascular abnormalities in association with an insulin-resistant state. (12) These pathophysiologic mechanisms are responsible for enhancing atherosclerosis and inducing a procoagulant tendency in diabetes, thus leading to the observed propensity for thrombotic events and macrovascular disease in diabetes. Medications that directly ameliorate insulin resistance and may beneficially impact this process have been marketed (the thiazolidinediones or "TZDs"). The clinical consequences of reduced insulin sensitivity are not limited to diabetes, however, and encompass other chronic pathologies, like dyslipidemia and hypertension. The best weapons to combat insulin resistance remain improvements in lifestyle, diet, and level of physical activity.

[beta]-cell function in type 2 diabetes

Islet-cell destruction leading to pancreatic insulin deficiency is classically described as the underlying etiology of type 1 diabetes, while insulin resistance is the hallmark of type 2 diabetes. However, the role of the [beta]-cell in the pathology of type 2 diabetes is being increasingly appreciated. It is the inability of the endocrine pancreas to compensate for peripheral insulin resistance that leads to hyperglycemia and the onset of clinical diabetes (Fig. 1). It is increasingly believed that this [beta]-cell failure is at least partly genetically preprogrammed, rather than driven by or a consequence of insulin resistance. The effect of various factors such as elevated glucose ("glucotoxicity"), free fatty acids ("lipotoxicity"), cytokines, and other inflammatory agents on pancreatic insulin production probably plays a role as well. (13) This concept of relative insulin insufficiency in type 2 diabetes leading to progressive deterioration in glycemic control was well demonstrated by the United Kingdom Prospective Diabetes Study (UKPDS). (14) Therefore, treatment strategies need to address this underlying mechanism of the disease. Early insulin therapy, alone or in combination with oral agents, is being advocated. (15) A recent focus has been the preservation of [beta]-cell insulin release by medications such as the thiazolidinediones (rosiglitazone and pioglitazone). This property of the insulin-sensitizing agents may be responsible for their observed long-term durability of glycemic control.

Type 2 diabetes is a cardiovascular disease

The connection between type 2 diabetes and macrovascular disease is so strong that the current NCEP guidelines have elevated diabetes to the level of a "cardiac risk equivalent." (10) This means that the presence of type 2 diabetes carries the same risk for a future cardiac event as established cardiovascular disease, a point demonstrated by Haffner et al (16) (Table 2). It also mandates that the target low-density lipoprotein level in diabetes be less than 100 mg/dL. It is felt that atherosclerotic disease and diabetes "spring from the same soil." Persons with diabetes have a two- to four-fold increased risk of myocardial infarction and stroke compared with those without diabetes. A predominant part of this increased risk is due to the common underlying problem of insulin resistance and clustering of cardiovascular risk factors in diabetes. Several observational studies have shown an association between level of glycemia and macrovascular events. (17,18) Evidence is also accumulating that sustained hyperglycemia may be a direct mediator of coronary and vascular complications, (19,20) as it is in the microvascular sequelae (retinopathy, nephropathy, and neuropathy). Therefore, the enormous burden of cardiovascular disease can be reduced by educating the public and health care providers, and taking practical measures to ameliorate the situation. In the clinical setting, this translates into increased vigilance, screening, treatment of comorbidities, and appropriate use of antiplatelet agents in patients with diabetes.

Shifts in treatment approach

Intensive glycemic control and multifactorial therapy

Landmark trials like the Diabetes Control and Complications Trial (DCCT), (21) the United Kingdom Prospective Diabetes Program, (14) and the Kumamoto Study (22) have proven beyond doubt that the degree of microvascular damage in diabetes is directly linked to the ambient level and duration of glycemia. "Tight" glycemic control is now the accepted standard of care to prevent or delay the onset and progression of complications. This is especially pertinent since diabetes is a leading cause of blindness, dialysis, and lower extremity amputations. Furthermore, increased emphasis on the importance of early diagnosis, proper self-management, improvements in monitoring, and availability of an expanded array of therapeutic regimens has made this task easier to attain in most patients. The blood glucose, glycosylated hemoglobin, blood pressure, and lipid goals in persons with diabetes advocated by the American Diabetes Association are shown in Table 3. An intensive, targeted, multifactorial intervention (treatment of hypertension, hyperglycemia, dyslipidemia, microalbuminuria, and use of angiotensin-converting enzyme inhibitors and aspirin) in type 2 diabetes was recently shown to confer a 53% reduction in all cardiovascular endpoints compared with conventional therapy. (23) It should be noted, however, that the level of aggressiveness of diabetic control should be tailored to the patient, and the benefits of intensive therapy should also be viewed from the perspective of cost, resource utilization, quality of life, and risk of hypoglycemia in individual subjects.

Team management and patient empowerment

A patient-centered approach is gaining importance as the most effective means of delivery of health care for diabetes. (24) Three main foci of this advance are: a multidisciplinary team care, the concept of disease management, and the empowerment of individuals to take responsibility for day-to-day self-management through education and a supportive, collaborative approach with health care providers. (25) It is recognized that treatment of diabetes is multifaceted and needs attention in the areas of nutrition, diet, physical activity, medications, sick-day management, and ongoing evaluation for the development of complications. This complex undertaking is a challenge beyond the single-handed effort of the lone clinician. The patient requires longitudinal guidance from a group of health-care professionals who have a consistent educational message for behavior change individualized to each patient's agenda. Members of the diabetes care team include the patient and a core of providers: the physician, nurse educator, and nutritionist. A schematic of this philosophy is presented in Figure 2. The services of other specialties like ophthalmology, podiatry, psychology, exercise physiology, etc may be called upon as needed. The primary goal is to educate the patient and provide tools for self-care and motivation in a partnership fashion rather than adopting a paternalistic, critical, and predominantly compliance-based atmosphere. Many diabetes educators with the required experience can now achieve certification through the certified diabetes educator (CDE) examination. Established diabetes education programs may also receive credentialing through the American Diabetes Association ("ADA-recognition"). Physicians caring for people with diabetes should make every effort to develop a working relationship with a diabetes education program in their area where patients can be referred. Lists of recognized programs and certified educators for patients, providers, consumers, insurers and payers and other interested parties are available from the ADA and the American Association of Diabetes Educators (AADE). However, the provision of these services is not uniformly available, which poses logistical hurdles in terms of access (especially in rural areas). Outreach programs have been used with some success in these settings.

[FIGURE 2 OMITTED]

Individualized nutrition therapy

There is no "one size fits all" ADA diet anymore. The American Diabetes Association Clinical Practice Guidelines recommend that "medical nutrition therapy for people with diabetes should be individualized, with consideration given to the individual's usual food and eating habits, metabolic profile, treatment goals and desired outcomes." (26) It is important to use an interdisciplinary approach and try to integrate nutrition into the overall treatment plan. Contrary to previous practices of labeling certain foods and food groups as taboo and banning them altogether, the current thinking emphasizes using different diet choices to achieve specific objectives. For example, calorie restriction should be used if the primary aim is weight loss, reduction of saturated fat and cholesterol if the patient has hyperlipidemia, protein restriction for nephropathy, and use of different combinations and timings of carbohydrate intake for glycemic spikes and postprandial elevations. Intake of fiber, fruits, vegetables, and low-fat dairy products may need to be enhanced to achieve a more balanced diet in some people with diabetes. It is obvious, therefore, that every patient with diabetes needs an individual consultation with the nutritionist for assessment of current dietary patterns, habits, and cultural influences, and to incorporate preferences and metabolic comorbidities into a modified plan for the future. Patients also require ongoing education and guidance in nutrition self-management over time so that dietary changes can be made as treatment aims change and new knowledge is acquired through additional research.

Combination oral therapy and early insulin use

Clinical evidence for the efficacy of a combination of oral antidiabetic agents with or without insulin use for optimal glycemic control is growing. (27) This premise is based on the following arguments: 1) there are multiple defects in the pathogenesis of type 2 diabetes--insulin resistance at the level of muscle and adipose tissue, relative insulinopenia due to [beta]-cell failure, and increased hepatic glucose output--which need to be addressed separately and simultaneously; 2) the inexorable progression of glycemic deterioration as seen in the UKPDS is probably due, at least in part, to an overly conservative approach with single agent use for a prolonged period; 3) early and aggressive control may favorably modulate this decline (by reducing glucotoxicity and preserving insulin production) in addition to minimizing long-term microvascular complications; 4) there is no evidence that exogenous insulin is harmful, and early institution of insulin alone or combined with oral agents is beneficial; 5) sequential oral agent treatment is a "failure-based" regimen, while early simultaneous multiple agent use maintains control and prevents relapse more effectively.

[FIGURE 3 OMITTED]

Typically, a regimen of medications that have different and complementary mechanisms of action (for example, a secretagogue like a sulfonylurea, and an insulin sensitizer like a thiazolidinedione or metformin) is employed, and a basal long-acting insulin is added if necessary. (28) Further titration of treatment may include adding pre-meal short-acting insulin doses while one or more of the oral agents is discontinued (see next section).

Basal-bolus concept

The healthy pancreas produces a constant amount of insulin to maintain normal glucose homeostasis ("basal" insulin) and releases extra increments at mealtimes to counteract postprandial hyperglycemia ("bolus" insulin). To mimic normal physiology, it makes sense to use therapeutic regimens designed to treat both fasting and post-meal glycemia (Fig. 3). Frequent pre- and post-meal glucose self-monitoring is necessary to identify patterns and implement this "basal-bolus" concept. (29) The use of a continuous glucose monitoring system (CGMS) (30) or noninvasive monitoring utilizing the Glucowatch (31) and analyzing downloaded data may assist in establishing a more accurate assessment of glycemic control. This regimen finds its best utility in multiple-dose insulin use in type 1 or insulin-requiring type 2 diabetes. A combination of long-acting (like neutral protamine Hagedorn [NPH] or glargine) and short-acting (like regular, lispro, or aspart) is used. The doses of the different insulins are titrated and fine-tuned based on the daily self-monitored glycemic data. The objective is to dovetail insulin to glucose levels to achieve a smooth profile and maintain an optimal HbA1c while minimizing glycemic variations and excursions.

Insulin pump use in type 2 diabetes

The basal-bolus insulin therapy is easier to implement when continuous short-acting insulin is given using an insulin pump. Traditionally, patients with type 1 diabetes who are young, motivated, relatively free of complications, and willing to put in the required extra effort have been considered candidates for this therapy. The pump delivers continuous insulin at a basal rate which is preprogrammed to account for variations in an individual's glycemic profile (for example, an increased rate may be set for the early morning hours to counteract the dawn phenomenon). Extra boluses of insulin can be delivered at meal or snack times by the patient to treat postprandial elevations (the amount given depends on the pre-meal glucose level and the carbohydrate content of the food). Current pump technology has become very user-friendly, with menu-driven features, built-in bolus calculations, and excellent back-up manufacturer support. Pump use has been shown to improve glycemic control, decrease the risk of serious hypoglycemia, and reduce cost of care by cutting down on emergency room visits and hospitalizations. (32)

In recent years this mode of insulin delivery has found useful application in type 2 diabetes as well. Encouraging experience with preliminary studies reveal that selected patients with insulin-requiring type 2 diabetes benefit greatly by using a pump, (33,34) especially if daily insulin requirements are high because of underlying insulin resistance. An advantage is that oral insulin sensitizers like metformin or the thiazolidinediones may be continued concomitantly, which aids in improving glycemic control, while the pump fulfills constant background as well as meal-associated insulin needs. Medicare has recently approved a set of guidelines for coverage of pump therapy in type 2 diabetes. (35) Further favorable data in this field is expected to emerge in the future.

Hospital management of diabetes

It is commonly accepted that hyperglycemia invites infection, retards healing, and worsens prognosis in general for inpatients with diabetes. (36) Clinicians have been wary of attempting intensive control in the inpatient setting because of various barriers (changes in usual routine, unpredictable oral intake, missed meals and medication doses due to procedures, acute illness, etc), fear of hypoglycemia, and the notion that a brief period of relative laxity in glycemic control would not impact outcomes. (37) It is the latter assumption that has been seriously challenged by recently published trials. The DIGAMI study (38) showed that good glycemic control in the phase immediately following myocardial infarction significantly improved survival. The Leuven trial (39) evaluated the effect of intensive glycemic control with insulin therapy in critically ill patients, whether or not they had known diabetes. It was hypothesized that hyperglycemia was a maladaptive response to severe illness which aggravated the usual intensive care complications and hastened death. The intensive therapy group received insulin infusion to maintain normoglycemia (serum glucose 80 to 110 mg/dL), while the control group was treated with the typical "sliding scale" insulin only if glucose levels exceeded 200 mg/dL. The intensive care unit and hospital mortality was reduced by 43% and 34% respectively in the intensive treatment group. Similar salutary effects of vigilant control have been noted in sepsis and stroke.

It is worthwhile to emphasize, therefore, that acute illness is a catabolic state due to release of counter-regulatory hormones and the stress response. Metabolic sequelae including hyperglycemia should be vigorously treated to prevent detrimental effects. In clinical practice, there should be a low threshold for using a titrated algorithm of insulin infusion to maintain normoglycemia in hospitalized patients. The 'insulin drip' is relatively easy to implement for nursing personnel. If 'sliding scale' insulin regimen is used, the information gathered should be employed for rational decision-making--persistently elevated glucose readings should be an indication to add, or adjust, basal long-acting insulin and meticulously explore the factors contributing to the hyperglycemia. The aim should be to prevent hyperglycemic spikes, rather than treat them retroactively with 'insulin coverage.'

Can Type 2 Diabetes Be Prevented?

Since the rise in the incidence of type 2 diabetes has definite and identifiable reasons, it follows that efforts aimed at reversing these underlying factors should help in stemming the tide of the disease. In fact, the Diabetes Prevention Project (DPP) (40) set out to investigate just that, and enrolled 3,234 subjects with an elevated risk for developing diabetes (impaired fasting glucose or increased post-load plasma glucose concentrations) and sedentary lifestyle. Participants were assigned in a random manner to metformin 850 mg twice daily, lifestyle intervention (7% reduction in weight and 150 minutes of weekly physical activity), or placebo. At 2.8 years of follow-up the incidence of diabetes was reduced 31% in the metformin group and 58% in the lifestyle intervention arm compared with the placebo group. Use of thiazolidinediones in high-risk subjects has also been shown to prevent the subsequent development of diabetes. The troglitazone in the prevention of diabetes (TRIPOD) study randomized women with a history of gestational diabetes to therapy with troglitazone or placebo. (41) The annual incidence of diabetes was 5.4% in the treatment group and 12.1% in the placebo arm after a mean follow-up of 30 months, reducing the onset of diabetes by 56% in the troglitazone-treated patients. Other observational as well as interventional studies have linked long-term maintenance of weight and regular exercise with a reduced propensity to develop type 2 diabetes. (42-44) Taken together, these data lend strong credence to the importance of lifestyle modification in the prevention of diabetes, and help explain the connection between diabetes, obesity, and physical inactivity.

Conclusion

Diabetes and its attendant comorbidities pose a significant and ever-growing health problem for populations in the United States and internationally, with the potential of assuming a massive health-care crisis in the foreseeable future. Type 2 diabetes, obesity, the metabolic syndrome, and cardiovascular problems are closely related. It behooves us as clinicians to be well-informed and optimally equipped with the resources available to deal with the ramifications of this epidemic. This will require a two-pronged strategy: a concerted effort at lifestyle change at the community level to promote healthy behaviors and thus prevent or delay disease onset, (45) and an aggressive, multifaceted treatment approach in the individual patient to minimize complications and disability. (23) Research needs to be continued at the genetic and molecular level to better understand diabetes and discover new pharmacologic therapies. It is important to keep in mind, however, that the rural population and young people represent the new face of diabetes. The challenge before us is how best to allocate resources, provide grassroots education, and improve access to quality diabetes care for future generations. This commitment will require a sustained, collaborative endeavor on the part of governmental agencies, private organizations, and individual members of society to give priority to counteracting an emergent health care dilemma.

One of the symptoms of an approaching nervous breakdown is the belief
that one's work is terribly important.
--Bertrand Russell

Table 1. Clinical diagnosis of the metabolic syndrome (if three or more
of the following are present) (a)

Risk factor                                 Defining level

1. Waist circumference (abdominal obesity)
   men                                      > 40 inches
   women                                    > 35 inches
2. Fasting glucose                          = or > 110 mg/dL
3. Blood pressure
   systolic                                 = or > 130 mm Hg
   diastolic                                = or > 85 mm Hg
4. Triglycerides                            = or > 150 mg/dL
5. HDL-C
   men                                      < 40 mg/dL
   women                                    < 50 mg/dL

(a) From the 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; 285:2486-97. Also available at
www.nhlbi.nih.gov/guidelines/cholesterol/atp_iii.

Table 2. Equivalent 7-year CAD mortality risk in subjects with type 2
diabetes without prior MI, and nondiabetic subjects with history of
prior MI (a,b)

                                 Hazards ratio for
                                 diabetic subjects  P
Variable                         (95% CI)           Value

Adjusted for age and sex         1.4 (0.7-2.6)      0.4
Adjusted for age, sex, smoking,  1.2 (0.6-2.4)      0.5
  hypertension, LDL, HDL and
  triglycerides

(a) CAD, coronary artery disease; MI, myocardial infarction; CI,
confidence interval; LDL, low-density lipoprotein; HDL, high-density
lipoprotein.
(b) Adapted with permission from Haffner et al. N Engl J Med. 1998;339
(4): 229-234.

Table 3. American Diabetes Association (ADA) recommendations for adults
with diabetes mellitus (a,b)

Glycemic control
  Hemoglobin A1c                 < 7.0%
  Pre-meal plasma glucose         90-130 mg/dL
  Postprandial plasma glucose  < 180 mg/mL
Blood pressure                 < 130/80 mm Hg
Lipid profile
  LDL                          < 100 mg/dL
  HDL                           > 40 mg/dL
  Triglycerides                < 150 mg/dL

Note: Goals should be individualized. Less intensive glycemic targets
may be indicated if there is frequent or severe hypoglycemia.
(a) LDL, low-density lipoproteins; HDL, high-density lipoproteins.
(b) Adapted with permission from The American Diabetes Association:
Clinical Practice Recommendations 2003. Standards of medical care for
patients with diabetes mellitus. Diabetes Care 2003; 26(supp. 1):S33-
S50.

Accepted January 8, 2004.

Please see Michael M. Bond and Scott W. Yates' editorial on page 1027 of this issue.

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RELATED ARTICLE: Key Points

* Type 2 diabetes is fast becoming a national and global epidemic secondary to the increasing prevalence of obesity and sedentary lifestyle.

* The entities of diabetes, prediabetes, and the metabolic syndrome are closely interlinked, and have over-lapping risk factors, common pathophysiology, and related adverse outcomes.

* Intensive glycemic control and an aggressive, targeted, multifactorial therapy for type 2 diabetes and its complications is the current standard of care, achieved through the concepts of multidisciplinary team management and patient empowerment.

* The cornerstones of an approach to the control of type 2 diabetes and its sequelae remain long-term behavior changes for patients and society with the goal of preventing, delaying the emergence, or reducing the impact of the disease.

Ali A. Rizvi, MD, FACP, FACE, CDE

From the Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of South Carolina School of Medicine, Columbia, SC.

Reprint requests to Ali A. Rizvi, MD, Department of Medicine, Two Medical Park, Suite 502, Columbia, SC 29203. Email: [e-mail]