Prediabetes and Metabolic Syndrome: Current Trend

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It is estimated that up to 25% of the general nonobese, nondiabetic population has insulin resistance patterns similar to those seen in T2DM.10 These persons are at much higher risk for T2DM than are insulin-sensitive persons and also often have elevated plasma triglycerides, low levels of high-density lipoproteins (HDLs), and higher blood pressure. This clustering of metabolic risk factors is termed metabolic syndrome. The five criteria for metabolic syndrome are
• Large waistline or abdominal obesity
• High triglyceride level
• Low HDL cholesterol level High blood pressure
• High fasting blood sugar.11

Over time, the list of factors associated with the metabolic syndrome has been expanded to include small, dense, low-density lipoproteins (LDLs);12 hyperuricemia;13 prothrombotic state with increased levels of plasminogen activator inhibitor type 1;14 and proinflammatory states.14 These metabolic abnormalities significantly increase the risk for atherosclerotic disease.10

A number of health risks are associated with metabolic syndrome, including low-grade inflammation leading to bone loss in men, hypertension, hypertriglyceridemia, low LDL, abdominal obesity, xanthomas, heart disease, diabetes, fatty liver, cancers (including breast cancer), obstructive sleep apnea, and recurrent preeclampsia.11 Importantly, the risk for heart disease, diabetes, and stroke increases; patients with metabolic syndrome are two times more likely to develop heart disease and five times more likely to develop diabetes than those without it.15

A combination of factors contributes to the propensity for certain individuals to develop metabolic abnormalities. Nonmodifiable risk factors for metabolic syndrome include age, gender, ethnicity, and family history or genetic predisposition. Mexican Americans have the highest overall prevalence of metabolic syndrome at 31.9%.11 In general, the incidence is slightly higher in females; Hispanic and African American women are 1.5 times more likely to be affected than non-Hispanic Caucasian women.11

Some research suggests that criteria parameters should be adjusted for the nonmodifiable risk factors. For example, BMI, often used as a marker for obesity and a tool for predicting cardiometabolic risk, is much lower among Asian Americans compared with other ethnic groups, yet Asian Americans have a significantly higher prevalence of metabolic syndrome in all BMI categories compared with non-Hispanic Caucasians.16 This finding suggests that lower BMIs should be used for defining overweight/obesity in Asian Americans.16

Metabolic syndrome has been associated with an increased risk for hypertension as well as an increase in adverse cardiovascular events.10 The relationship between obesity and hypertension is also well established. With obesity, factors such as an increase in intravascular volume, elevated cardiac output, activation of the renin-angiotensin system, and elevated sympathetic outflow all can contribute to the development of hypertension. Weight control/reduction measures can result in lowered blood pressure.10

Weight gain and abdominal adiposity have been associated with increased prevalence and incidence of metabolic syndrome. While as much as a quarter of the general population meets the criteria for metabolic syndrome, the distribution in relation to weight reflects a prevalence of 4.6% in normal-weight individuals (BMI < 25), 22.4% in those who are overweight (BMI 25-29.9), and nearly 60% in those who are obese (BMI > 30).17

A longitudinal study of mean risk factors for metabolic syndrome demonstrated that young adults whose BMI increased over a 15-year period had steadily worsening levels of all metabolic components, regardless of their baseline BMI.18 Conversely, those with a stable or decreased BMI had no or only minimal worsening of risk factor levels, also independent from baseline.18 Thus, young adults who can maintain a stable BMI into middle age (when the incidence of metabolic syndrome peaks) may prevent the progression of other cardiovascular risk factors and the development of metabolic syndrome and T2DM, even if they are already overweight.

Screening for risk for macrovascular events
The original Framingham Heart Study (FHS) gave rise to a screening tool for identifying persons at risk for atherosclerotic cardiovascular disease (ASCVD) based on risk factors. These risk factors include ­hypertension, smoking, hyperlipidemia, and postmenopausal status. Nonmodifiable factors include male gender, increasing age, family history, and ­African American ethnicity. Contributing factors ­include obesity, T2DM, and stress.19 Although the risk assessment tool based on the FHS data was widely used for many years, cardiovascular events that were unexpected for given risk stratifications highlighted inconsistencies in the tool’s risk identification process.

To more accurately identify patients at risk for ASCVD and suggest preventive strategies, the American College of Cardiology (ACC) and American Heart Association (AHA) convened an expert panel in 2013 to develop new guidelines for screening and treatment of high cholesterol.20 These guidelines introduced a new screening tool for estimating risk for a cardiovascular event based on gender, age, race, total cholesterol, HDL cholesterol, systolic blood pressure, need for treatment for hypertension, presence of diabetes, and smoking status. The lifetime risk estimate tool is only appropriate for individuals ages 20 to 59 but can serve as an educational guideline for demonstrating how lifestyle factors can positively or negatively affect risk for a cardiovascular event. Based on the risk stratification generated by the ASCVD screening tool, clinicians can recommend and implement treatment strategies to lower the risk for a future event (see Figure).21

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