The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults.

The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors.

The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

https://www.lipidcenter.com/pdf/metabolic.pdf

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement.

The metabolic syndrome

Metabolic syndrome is associated with abdominal obesity, blood lipid disorders, inflammation, insulin resistance or full-blown diabetes, and increased risk of developing cardiovascular disease. Proposed criteria for identifying patients with metabolic syndrome have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial. The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity - the most prevalent manifestation of metabolic syndrome - is a marker of 'dysfunctional adipose tissue', and is of central importance in clinical diagnosis. Better risk assessment algorithms are needed to quantify diabetes and cardiovascular disease risk on a global scale.

Abdominal obesity and metabolic syndrome

Numerous studies have reported increased risks of hip, spine, and other fractures among people who had previous clinically diagnosed fractures, or who have radiographic evidence of vertebral fractures. However, there is some variability in the magnitudes of associations among studies. We summarized the literature and performed a statistical synthesis of the risk of future fracture, given a history of prior fracture. The strongest associations were observed between prior and subsequent vertebral fractures; women with preexisting vertebral fractures (identified at baseline by vertebral morphometry) had approximately 4 times greater risk of subsequent vertebral fractures than those without prior fractures. This risk increases with the number of prior vertebral fractures. Most studies reported relative risks of approximately 2 for other combinations of prior and future fracture sites (hip, spine, wrist, or any site). The confidence profile method was used to derive a single pooled estimate from the studies that provided sufficient data for other combinations of prior and subsequent fracture sites. Studies of peri- and postmenopausal women with prior fractures had 2.0 (95 % CI = 1.8, 2.1) times the risk of subsequent fracture compared with women without prior fractures. For other studies (including men and women of all ages), the risk was increased by 2.2 (1.9, 2.6) times. We conclude that history of prior fracture at any site is an important risk factor for future fractures. Patients with a history of prior fracture, therefore, should receive further evaluation for osteoporosis and fracture risk.

http://www.prevrefrat.org/Patients%20with%20Prior%20Fractures%20Have%20an%20Increased%20Risk%20of%20Future%20Fractures.pdf

Patients with Prior Fractures Have an Increased Risk of Future Fractures: A Summary of the Literature and Statistical Synthesis

Although the individual components of the metabolic syndrome are clearly associated with increased risk for coronary heart disease (CHD), we wanted to quantify the increased prevalence of CHD among people with metabolic syndrome. The Third National Health and Nutrition Examination Survey (NHANES III) was used to categorize adults over 50 years of age by presence of metabolic syndrome (National Cholesterol Education Program [NCEP] definition) with or without diabetes. Demographic and risk factor information was determined for each group, as well as the proportion of each group meeting specific criteria for metabolic syndrome. The prevalence of CHD for each group was then determined. Metabolic syndrome is very common, with approximately 44% of the U.S. population over 50 years of age meeting the NCEP criteria. In contrast, diabetes without metabolic syndrome is uncommon (13% of those with diabetes). Older Americans over 50 years of age without metabolic syndrome regardless of diabetes status had the lowest CHD prevalence (8.7% without diabetes, 7.5% with diabetes). Compared with those with metabolic syndrome, people with diabetes without metabolic syndrome did not have an increase in CHD prevalence. Those with metabolic syndrome without diabetes had higher CHD prevalence (13.9%), and those with both metabolic syndrome and diabetes had the highest prevalence of CHD (19.2%) compared with those with neither. Metabolic syndrome was a significant univariate predictor of prevalent CHD (OR 2.07, 95% CI 1.66-2.59). However, blood pressure, HDL cholesterol, and diabetes, but not presence of metabolic syndrome, were significant multivariate predictors of prevalent CHD. The prevalence of CHD markedly increased with the presence of metabolic syndrome. Among people with diabetes, the prevalence of metabolic syndrome was very high, and those with diabetes and metabolic syndrome had the highest prevalence of CHD. Among all individuals with diabetes, prevalence of CHD was increased compared with those with metabolic syndrome without diabetes. However, individuals with diabetes without metabolic syndrome had no greater prevalence of CHD compared with those with neither.

https://diabetes.diabetesjournals.org/content/diabetes/52/5/1210.full.pdf

NCEP-Defined Metabolic Syndrome, Diabetes, and Prevalence of Coronary Heart Disease Among NHANES III Participants Age 50 Years and Older

ContextMany health plans have instituted more cost sharing to discourage use
of more expensive pharmaceuticals and to reduce drug spending.ObjectiveTo determine how changes in cost sharing affect use of the most commonly
used drug classes among the privately insured and the chronically ill.Design, Setting, and ParticipantsRetrospective US study conducted from 1997 to 2000, examining linked
pharmacy claims data with health plan benefit designs from 30 employers and
52 health plans. Participants were 528 969 privately insured beneficiaries
aged 18 to 64 years and enrolled from 1 to 4 years (960 791 person-years).Main Outcome MeasureRelative change in drug days supplied (per member, per year) when co-payments
doubled in a prototypical drug benefit plan.ResultsDoubling co-payments was associated with reductions in use of 8 therapeutic
classes. The largest decreases occurred for nonsteroidal anti-inflammatory
drugs (NSAIDs) (45%) and antihistamines (44%). Reductions in overall days
supplied of antihyperlipidemics (34%), antiulcerants (33%), antiasthmatics
(32%), antihypertensives (26%), antidepressants (26%), and antidiabetics (25%)
were also observed. Among patients diagnosed as having a chronic illness and
receiving ongoing care, use was less responsive to co-payment changes. Use
of antidepressants by depressed patients declined by 8%; use of antihypertensives
by hypertensive patients decreased by 10%. Larger reductions were observed
for arthritis patients taking NSAIDs (27%) and allergy patients taking antihistamines
(31%). Patients with diabetes reduced their use of antidiabetes drugs by 23%.ConclusionsThe use of medications such as antihistamines and NSAIDs, which are
taken intermittently to treat symptoms, was sensitive to co-payment changes.
Other medications—antihypertensive, antiasthmatic, antidepressant, antihyperlipidemic,
antiulcerant, and antidiabetic agents—also demonstrated significant
price responsiveness. The reduction in use of medications for individuals
in ongoing care was more modest. Still, significant increases in co-payments
raise concern about adverse health consequences because of the large price
effects, especially among diabetic patients.

https://jamanetwork.com/journals/jama/articlepdf/198761/JOC40033.pdf

Pharmacy Benefits and the Use of Drugs by the Chronically Ill

Patients with diabetes mellitus (DM), both diagnosed (history of) and undiagnosed (by fasting glucose [FG] only), as well as impaired FG have an increased risk of coronary heart disease (CHD), compared with those with normal FG. Elevations in FG levels, even in normoglycemic subjects ( or =65 years had increased prevalence compared with those <50 years old (rate ratios for IFG, DM-FG, and history of DM were 3.5, 4.8, and 10.8, respectively). Glycosylated hemoglobin levels were increased by glucose status. The frequency of known CHD risk factors also increased with worsening glucose status. Age-adjusted CHD prevalence was increased with impaired FG (rate ratio 1.47), DM-FG (rate ratio 1.56), and history of DM (rate ratio 1.72), compared with normal FG. Adjusting for age and other CHD risk factors, hyperglycemia was no longer significantly associated with CHD prevalence. Lipid values, especially high-density lipoprotein cholesterol, hypertension, and other CHD risk factors were more strongly associated with CHD than glucose status. Thus, patients with impaired FG, DM-FG, and history of DM should be considered at higher risk for CHD morbidity and mortality. However, hyperglycemia, per se, does not explain the excess risk. In addition to glucose, lipid profiles and blood pressure should be periodically monitored and appropriate treatment provided to reduce morbidity and mortality from CHD.

Diabetes mellitus, impaired fasting glucose, atherosclerotic risk factors, and prevalence of coronary heart disease.

OBJECTIVE To estimate responsiveness of prescription demand within 9 therapeutic classes to increased cost-sharing compared with constant cost-sharing. STUDY DESIGN Retrospective prescription claims analysis. METHODS Between 1999 and 2001, 3 benefit plans changed from a 2-tier to a 3-tier design (cases); 1 plan kept a 2-tier design (controls). Study subjects needed 24 months of continuous coverage and a prescription filled < OR = 3 months before the benefit change for a nonsteroidal anti-inflammatory agent (NSAID), a cyclooxygenase (COX-2) inhibitor, a selective serotonin reuptake inhibitor (SSRI), a tricyclic antidepressant (TCA), an angiotensin-converting enzyme (ACE) inhibitor, a calcium-channel blocker (CCB), an angiotensin-receptor blocker (ARB), a statin, or a triptan. Changes in use were compared with the Wilcoxon signed rank test. Elasticity of demand among cases was calculated. RESULTS Generally, medication possession ratios decreased for cases and increased for controls between 1999 and 2000. Switch rates increased for cases and decreased for controls for all classes but CCBs. Switches to lower copayments for ACE inhibitors, statins, and triptans occurred more often for cases. Discontinuation-rate changes for cases were 2 to 8 times those for controls. Generic-substitution rates depended on availability and initial generic utilization. Elasticity of demand for drugs was generally low, -0.16 to -0.10, for asymptomatic conditions (ACE inhibitors, ARBs, CCBs, statins), and moderate, -0.60 to -0.24, for symptomatic conditions (COX-2 inhibitors, NSAIDs, triptans, SSRIs). CONCLUSION Use of retail prescription medications within 9 specific therapeutic classes decreased as copayment increased. Demand for pharmaceuticals was relatively inelastic with these copayment increases.

Pamela B. Landsman

Papers

Patients with Prior Fractures Have an Increased Risk of Future Fractures: A Summary of the Literature and Statistical Synthesis

NCEP-Defined Metabolic Syndrome, Diabetes, and Prevalence of Coronary Heart Disease Among NHANES III Participants Age 50 Years and Older

Pharmacy Benefits and the Use of Drugs by the Chronically Ill

Diabetes mellitus, impaired fasting glucose, atherosclerotic risk factors, and prevalence of coronary heart disease.

Impact of 3-tier pharmacy benefit design and increased consumer cost-sharing on drug utilization.