CE/CME

Prediabetes and Metabolic Syndrome: Current Trend

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References

MANAGEMENT OF PREDIABETES AND METABOLIC SYNDROME
Lifestyle interventions
Early intervention in prediabetes will delay and even prevent diabetes. Only 11.1% of American adults with prediabetes are aware of their diagnosis.22 Therefore, the initial step in the management of prediabetes is increasing patient awareness.23 Lifestyle changes improve insulin sensitivity and preserve β-cell function and therefore must be the cornerstone of any diabetes prevention program.6,24

According to AACE, weight loss is essential for the management of prediabetes.9 Intensive lifestyle interventions such as dietary changes, exercise, and weight loss can reduce the rate of conversion to T2DM by approximately 58% after three years.8 In addition, lifestyle modification is recommended as a firstline measure before pharmacologic therapies are started and should be continued throughout the process of any hypertension treatment plan.25

Activity level. Physical inactivity is a major risk factor for metabolic syndrome. As such, physical activity can become a therapeutic strategy to reduce body weight and increase fitness in adults with metabolic syndrome.26 Obesity incidence has increased globally, largely due to a combination of poor dietary habits and a sedentary lifestyle.

The clinical benefits of physical activity and exercise programs include weight loss, increased insulin sensitivity, improved glycemic control, and a reduction in all-cause mortality risk.26 When an exercise intervention is maintained, there is also an improvement in the lipid profile and a decrease in mean arterial blood pressure.26 Even when not combined with dietary restrictions, endurance-type exercise reduces body weight, waist circumference, and visceral adipose tissue mass in obese individuals, although the reductions are less than those seen with diet–­exercise interventions.26

There is a strong relationship between visceral obesity and risk for CVD, but individuals with visceral obesity who are physically active have a 24% lower mortality risk than their sedentary counterparts.27 Exercise interventions for metabolic syndrome also improve insulin sensitivity and decrease blood A1C, which in turn leads to a reduced risk for microvascular and macrovascular disease and premature death.26

The goals for individuals with prediabetes should include a 7% weight loss and at least 30 min/d of walking at least five times per week, or participation in other moderate-intensity exercise for a minimum of 150 min/wk.8,28 Many guidelines recommend exercising three to five times per week, but few studies demonstrate the level of activity necessary to generate adventitious effects. Hansen and colleagues conducted a literature review focusing on the effects of exercise interventions on metabolic syndrome and related conditions and found that prolonged low-intensity exercise sessions are at least as effective as high-intensity exercise performed for a shorter duration in persons with known metabolic syndrome.26

Dietary considerations. Dietary education should include instruction regarding portion control and use of the glycemic index.29 Maintenance of a food and exercise diary, with regular review by an educator or primary care provider, may encourage compliance in at-risk individuals. Many different diet types have been studied, and the therapeutic efficacy of certain diets has been demonstrated for multiple components of metabolic syndrome.

The Dietary Approaches to Stop Hypertension (DASH) diet has been shown to be the most effective diet for lowering blood pressure. The DASH recommendations include consuming a diet that emphasizes high intake of vegetables, fruits, whole grains, low-fat dairy products, poultry, nontropical vegetable oils, nuts, fish, and legumes.30 The DASH diet limits the intake of sweets, sugar-sweetened beverages, and red meats and also limits sodium intake to a desirable level of 1,500 mg/d.

Numerous studies have demonstrated the effects of “heart healthy” diets in reducing metabolic risk factors, with recommendations for low-fat, low-carbohydrate, and low-sugar meals, but relatively few studies have evaluated specific dietary alterations. Dhingra and colleagues examined the link between the obesity epidemic and the rising consumption of soft drinks and found a more than 50% higher incidence of metabolic syndrome among persons who drank at least one regular or diet soft drink per day as compared with those who drank less than one soft drink per week.31 High-fructose corn syrup, the primary added sweetener in soft drinks, contains approximately 55% fructose and can lead to weight gain, increased insulin resistance, a decrease in HDL cholesterol, and an increase in triglycerides.31 In this study, however, both regular and diet soft drinks led to similar metabolic derangements, suggesting that additional factors may be involved.31

Geographic studies of metabolic syndrome have given rise to research in regional diets and their beneficial effects. The low incidence of coronary heart disease in Mediterranean countries drove the research for the PREDIMED trial, which compared the effects of two Mediterranean-style diets with a typical low-fat diet. The term “low fat” is often misleading, because it suggests that all fats are bad for the body. While the general principles of Mediterranean-type diets include eating more fruits, vegetables, whole grains, legumes, and nuts, their main component is the use of olive oil in place of butter. Olive oil is a rich source of monounsaturated fatty acids, which have proven beneficial effects on cardiovascular risk factors, obesity, and diabetes.32

In the PREDIMED trial, the participating high-risk individuals on all three diet interventions experienced a decrease in body weight and adiposity measurements, with no observed differences in outcomes for subgroups defined by age, sex, ethnicity, baseline weight, or activity level.32 Compared with the low-fat diet group, participants in the Mediterranean diet groups had decreased systolic and diastolic blood pressures, improved lipid profiles, decreased insulin resistance, and reduced concentrations of inflammatory molecules.32 Since low-fat diets tend to lower both LDL and HDL cholesterol, a fat-rich Mediterranean diet may be more appropriate for high-risk individuals because it decreases LDL cholesterol, triglycerides, and total cholesterol while increasing HDL cholesterol.32 These findings challenge the efficacy of low-fat diets centered on carbohydrate intake by demonstrating greater benefits through carbohydrate replacement with dietary fats.

Pharmacologic interventions
Diabetes. Many studies have shown that pharmacologic intervention can delay the onset of T2DM in those at high risk. Several classes of medications have been studied to evaluate their effectiveness in diabetes prevention. In the Diabetes Prevention Program study, metformin reduced the incidence of T2DM by 31% when compared with placebo; lifestyle intervention reduced the incidence by 58%.24 Metformin reduces the risk for diabetes by inhibiting glucose production in the liver while improving peripheral muscle tissue sensitivity to insulin.6

Other oral agents, such as thiazolidinediones, α-glucosidase inhibitors, and the lipase inhibitor orlistat, have been shown to decrease the incidence of T2DM. However, because studies have demonstrated that medications such as metformin are not as effective as diet and exercise in delaying the onset of diabetes, their use must be limited to high-risk individuals, such as those with a history of GDM, those who are extremely obese, and/or those with uncontrolled hyperglycemia.8

Dyslipidemia. Persons with prediabetes are prone to progression to T2DM and experience cardiovascular events.33 Dyslipidemias—or abnormal blood cholesterol levels—commonly occur in persons with prediabetes and are strongly associated with macrovascular events such as MI or CVD.

The 2013 ACC/AHA guidelines for lowering cholesterol to reduce ASCVD risk in adults are unlike previous guidelines in that they do not provide hard and fast rules about reducing the LDL cholesterol (LDL-C) level to a specific number.20 Instead, the guidelines focus on using statins to reduce the risk for primary and secondary cardiovascular events in those most likely to benefit.20 The panel described four groups who would most likely benefit from statin therapy:
• Persons who have clinical ASCVD
• Persons with LDL-C levels ≥ 190 mg/dL
• Persons ages 40 to 75 with diabetes and LDL-C levels of 70-189 mg/dL
• And (most pertinent to those with prediabetes) persons ages 40 to 75 who do not have clinical ASCVD or diabetes but have LDL-C levels of 70-189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher.20

Based on risk stratification, treatment strategies such as statins are recommended to lower an individual’s risk for a future event. High-intensity statin therapy should be initiated in persons with a lifetime risk of 7.5% or higher.20

Hypertension. Metabolic syndrome has a strong relationship with the development of hypertension.10 Pharmacologic intervention for hypertension may be appropriate if lifestyle changes alone do not provide adequate control of blood pressure. Evidence-based guidelines for hypertension management were released in 2014 by the panel members appointed to the Eighth Joint National Committee (JNC 8).25 The JNC 8 guidelines include new, specific recommendations aimed at managing high blood pressure in adults.

For individuals ages 60 and older, pharmacologic therapy should be initiated at a blood pressure of 150/90 mm Hg or higher. For adults younger than 60 or those with comorbidities such as diabetes and chronic kidney disease, the guidelines recommend initiating pharmacologic therapy at a blood pressure of 140/90 mm Hg or higher.

Firstline drug recommendations vary among individuals. For nonblack adults, even those with diabetes, the recommended initial medications include a thiazide-type diuretic, calcium channel blocker, ACE inhibitor, or angiotensin receptor blocker. For the general black population, including those with diabetes, initial treatment with either a thiazide-type diuretic or calcium channel blocker is preferred.25

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