Why insulin resistance causes metabolic disturbances that can ultimately increase the risk for heart disease and diabetes and how you help.
You may have heard it called metabolic syndrome or just plain old syndrome X. Regardless of the moniker, more and more research is emerging about this condition, which affects an individual’s insulin sensitivity, metabolic function and utilization of energy nutrients.
Current estimates show that almost 1 in 4 U.S. adults now has metabolic syndrome and the prevalence is growing (Ford, Giles & Dietz 2002). Even more alarming are reports that a burgeoning number of obese children are likely to contract the syndrome before they reach the age of 20 (Weiss et al. 2004).
Because metabolic syndrome is thought to be related to obesity and a sedentary lifestyle, fitness professionals are in a good position to help clients who face the risk of developing this condition. Moreover, efforts we take today can pave the way for new generations of children and adolescents to steer clear of behaviors that ultimately lead to the syndrome.
Gerald Reaven, MD, was one of the first people to describe the condition in 1988, coining the term syndrome X (Reaven 1988). The syndrome has since been studied by many different investigators, who now favor the term metabolic syndrome, as it more accurately reflects the serious disturbances in metabolism and utilization of energy nutrients that occur in individuals who have this cluster of risk factors.
There is no universally accepted definition of metabolic syndrome (also referred to as insulin resistance syndrome). However, losing sensitivity to insulin, which results in the pancreas releasing extra insulin to handle daily glucose loads, is considered the underlying cause. Actually, the syndrome is really not one particular condition; instead it is a whole group of risk factors for heart disease and diabetes. The principal risk factors associated with the syndrome are
- abdominal obesity (i.e., an apple-shaped body with fat clustered around the waist)
- high blood pressure
- low levels of (the “good”) high-density cholesterol (HDL-C)
- high levels of blood triglycerides
In 2001, the U.S. National Cholesterol Education Panel (NCEP) established specific criteria for officially diagnosing the condition (see “Identifying Metabolic Syndrome” on page 51). To be diagnosed with metabolic syndrome, individuals need to display at least three of these criteria (NCEP 2001). Using the criteria, national data collected from 1988 to 1994 showed that 24% of adults over age 20 had the condition and that prevalence was higher in Hispanics (32%) (Ford, Giles & Diez 2002). More recent worldwide estimates indicate that these numbers are on the rise, especially among older age groups (Cameron, Shaw & Zimmet 2004). It is likely that increased obesity with age contributes to the higher prevalence observed in older individuals.
Sadly, it is also likely that the obesity epidemic will continue to cause the prevalence of metabolic syndrome to rise. Research indicates that obesity is clearly associated with the syndrome, especially in children and young adults. Weiss et al. (2004) found that the prevalence of metabolic syndrome was 0% in normal-weight and overweight children and adolescents, but it increased to 39% in those who were moderately obese and reached 50% in severely obese young people.
Lack of physical activity is also associated with metabolic syndrome. In a cross-sectional study of adults 45–68 years old, those who were sedentary had a 100% chance of developing the syndrome, compared to a 78% chance among those who engaged in regular moderate activity and a 52% risk among those who reported vigorous activity (Rennie et al. 2003).
Put simply, developing metabolic syndrome increases the probability that an individual will suffer a heart attack or stroke or be diagnosed with diabetes. Many studies have shown that the risk for heart disease is as much as 1.5 to 3 times higher for those who have the syndrome than for those who do not (Bloomgarden 2004b).
In addition to cardiovascular and diabetes risks, the syndrome has been associated with an increased incidence of cancer, thought to be caused by the hyperinsulinemia (excess insulin in the blood) that is a consequence of insulin resistance (Bloomgarden 2004b). The adult chronic illnesses most frequently associated with metabolic syndrome are listed on page 54. It is predicted that children who acquire the syndrome in adolescence will experience the onset of these debilitating conditions in early adulthood. This makes metabolic syndrome one of the most urgent public-health problems in the U.S. and other developed nations.
No one knows for sure what causes this cluster of different metabolic abnormalities to develop in one person. The predominant theory among researchers is that a loss of insulin sensitivity underlies the metabolic abnormalities. Reaven (1988) hypothesized that insulin resistance (and the compensatory increase in insulin circulating in the blood) was the primary cause of all the separate abnormalities. Other scientists have since provided substantial evidence that the high levels of circulating insulin that accompany insulin resistance play a role in elevating blood pressure and altering cholesterol and triglyceride levels (Wilkin & Voss 2004).
Genetic susceptibility and lifestyle are also known to play a role in insulin sensitivity. Genetics are thought to be at the root of 50% of cases of insulin sensitivity, whereas obesity and lack of physical fitness may each account for about 25% of cases (Bloomgarden 2004a).
Metabolic syndrome is related to obesity, especially abdominal obesity, although not everyone who has the condition is obese (Bloomgarden 2004a). One theory is that people who are able to expand their adipose tissue by making new fat cells tend to maintain insulin sensitivity (Danforth 2000). Under this hypothesis, adipose tissue is thought to be protective by keeping fat stored and away from tissue where fat deposits can cause harm. The idea that fat causes insulin resistance when it accumulates in muscle or beta cells in the pancreas is known as lipotoxicity. Lipotoxicity may also destroy insulin-secreting beta cells in the pancreas, causing metabolic syndrome to progress to type 2 diabetes (McGarry & Dobbins 1999). In other words, only when the adipose fat cells, or adipocytes, are filled to capacity and no new adipocytes are being developed do metabolic problems begin.
Stress may also play a role in metabolic syndrome. Research has shown that increased levels of the hormone cortisol, perhaps caused by everyday stress in genetically susceptible individuals, can lead to the development of the syndrome by increasing the accumulation of abdominal fat (Björntorp 2001). One study found higher levels of stress (distress) and abdominal obesity and more cases of metabolic syndrome among workers in lower economic positions than among those in higher brackets (Brunner et al. 1997). Data from a subgroup of males from the same cohort showed changes in levels of cortisol and epinephrine, which suggests a greater activation of the stress pathways in those who had metabolic syndrome compared with those who did not (Brunner et al. 2002).
There is also evidence that elevated levels of cortisol, especially when accompanied by emotional stress, lead to greater accumulation of fat in abdominal adipose tissue, which contains elevated cortisol receptors (Björntorp 1996). In turn, enlarged adipocytes that are filled to capacity with fat lose their insulin sensitivity (Danforth 2000). Enlarged, insulin-resistant adipocytes don’t remove glucose or dietary fat from the bloodstream very well after a meal, so fat remains in the blood for a longer period. This excess fat in the bloodstream causes glucose transport to malfunction, leading to insulin resistance in liver and muscle (Seppälä-Lindroos et al. 2002; Lowell & Schulman 2005).
Another theory to explain the loss of insulin sensitivity points to the body’s inability to oxidize fat properly. When the mitochondria in muscles and liver lose their natural ability to oxidize fatty acids, the result is an accumulation of intracellular fat, followed by insulin resistance (Lowell & Schulman 2005). This may explain why some individuals who are not obese can still develop metabolic syndrome. This theory is supported by study findings in which healthy, older adults who were not obese were markedly insulin resistant (but not diabetic) compared to younger subjects who were similar in other respects (Petersen et al. 2003). The investigators speculated that the loss of insulin sensitivity in the older subjects was due to reduced mitochondrial function caused by aging.
Other research indicates that the hormones leptin and adiponectin may be important in preventing metabolic syndrome (Unger 2003). Leptin appears to have a direct effect on the muscles and liver by enhancing fat oxidation and diminishing lipid accumulation in these tissues. Research indicates that abdominal obesity is associated with the syndrome to a greater extent than subcutaneous obesity because abdominal adipocytes undersecrete leptin and therefore cannot promote sufficient oxidation to prevent lipotoxicity in liver, muscle and pancreatic beta cells (Wajchenberg et al. 2002).
Despite the lack of certainty as to the causes of insulin resistance, there are known ways clients can maintain insulin sensitivity or regain sensitivity that has been lost, which should improve other indicators of the syndrome. The two major ways to increase insulin sensitivity are to engage in regular physical activity and to lose weight. Physical activity and modest weight loss have both been found to have independent and additive effects on insulin sensitivity (Cox et al. 2004).
The good news is that regular physical activity can improve insulin sensitivity and enhance removal of blood glucose—even without weight loss (Boule et al. 2005). Moreover, regular physical activity can improve the ability to remove glucose from the blood—independently of any changes in insulin sensitivity—because the production of glucose transporter proteins and glycogen-synthesizing enzymes increases in trained muscle fiber. Research has shown that exercised muscle removes glucose from the blood more easily and stores it as glycogen in trained muscle fiber, independently of the effects of insulin (Christ-Roberts et al. 2004).
Clients will be even more encouraged to learn that exercise has an immediately positive effect on insulin sensitivity. In fact, studies have shown that a subject’s very first bout of endurance exercise has a protective effect, and each subsequent bout is more protective as adaptive mechanisms to regular exercise become established (Borghouts & Keizer 2000). Resistance exercise training also improves insulin sensitivity, although fewer scientific data are available regarding the underlying mechanisms of action (Krisan et al. 2004).
One of the most effective ways to keep adipocytes sensitive to insulin is to keep them only partially full; this can be achieved either by preventing weight gain or by losing weight. Weight loss has been consistently found to improve insulin sensitivity, whether it is achieved by undergoing gastric bypass surgery (Dixon et al. 2004) or by maintaining a low-calorie diet (Reaven 2005).
Clients will be happy to hear that losing even a small amount of weight is helpful in improving metabolic syndrome. A loss of even 5% of body weight can improve insulin sensitivity and decrease fasting blood glucose levels in many individuals (Reaven 2005). The research is also promising when it comes to improving insulin sensitivity in overweight children. In a 1-year trial involving obese children, those who decreased their body mass index (BMI) showed improved insulin sensitivity, whereas those who gained greater weight than height (thus increasing their BMI) had worse insulin resistance at the end of the study period (Reinehr et al. 2004).
Because metabolic syndrome is really a constellation of different abnormalities that in themselves are all risk factors for heart disease and diabetes, medications are often prescribed for each abnormality. Consequently, individuals may be treated with multiple drugs.
Although no one drug is approved for abdominal obesity in particular, the Federal Drug Administration has approved two drugs for long-term weight control, one that suppresses appetite (sibutramine) and one that blocks fat absorption (orlistat). Each has been shown to result in modest weight loss that can be maintained as long as the drug is in use (Ryan & Stewart 2004).
High triglycerides and low HDL-C levels can both be treated with pharmacological doses of niacin and fibrates, which are often effective in reversing these blood imbalances (Birjmohun et al. 2005). Blood pressure can be controlled using a variety of medications, while other drugs are typically prescribed for elevated blood glucose. One insulin-sensitizing drug (metformin) reduced the incidence of type 2 diabetes by 31% in high-risk adults over 3 years during the Diabetes Prevention Program Group clinical trial (Knowler et al. 2002). However, in the same study, a lifestyle intervention consisting of 150 minutes of regular exercise per week plus a 7% weight loss proved to be almost twice as effective (58%) as the drug in reducing the onset of diabetes.
The take-home message for clients at risk of developing metabolic syndrome? Regular exercise and weight loss are incredibly effective in addressing many of the abnormalities associated with metabolic syndrome. Share the successful strategies that follow with your clients.
Some individuals are genetically predisposed to storing fat in their abdominal area. Overall weight loss can reduce abdominal fat, as well as subcutaneous fat; this can improve insulin sensitivity (Laaksonen et al. 2003). In some studies, exercise appears to cause a preferential loss of abdominal fat during modest weight loss, especially in men (Mayo, Grantham & Balasekaran 2003). Research has also demonstrated that eating slightly higher levels of protein (about 25% of total calories) causes preferential loss of abdominal fat for a given loss in body weight, especially in women (Due et al. 2004; Parker et al. 2002). Finally, increasing levels of dietary calcium, particularly from low-fat, dairy-rich products, has been shown to enhance loss of abdominal fat during weight loss (Zemel et al. 2005).
Restricting calories to lose weight has been consistently shown to improve or normalize blood lipids in overweight individuals (Dattilo & Kris-Etherton 1992). Regular exercise is consistently associated with small beneficial changes in blood lipid levels, particularly triglycerides and HDL-C (Kelley, Kelly & Tran 2004; Halbert et al. 1999). Clients can make small alterations in their diets by simply substituting monounsaturated fats for saturated fat; for example, using canola oil in place of shortening or margarine and dipping bread in olive oil instead of spreading on butter are simple ways to make a difference. Eating fatty fish (e.g., salmon) containing omega-3 fatty acids can also decrease fasting triglyceride levels and curb the usual rise in triglycerides that occurs after eating. Studies have shown that it takes 1–2 grams (g) of omega-3 fatty acids per day (or about the amount in a 3-ounce serving of salmon, trout or sardines) to reduce fasting triglycerides by about 25% (Calder 2004). Moderate alcohol consumption (1 drink per day) is associated with modest improvements in blood lipids, even in severely obese individuals (Djousse et al. 2004).
Weight loss is remarkably effective at lowering blood pressure in many mildly hypertensive individuals. Studies have shown that systolic blood pressure can be reduced by as much as 5–20 milliliters of mercury (mm Hg) per 10 kilograms of body weight lost (Franco, Oparil & Carretero 2004). To lower blood pressure, 30 minutes of moderate-intensity aerobic exercise per day on most days of the week is recommended (Pescatello et al. 2004).
Diet is also effective in reducing blood pressure. The successful diet used in the Dietary Approaches to Stop Hypertension (DASH) trial is rich in fruits, vegetables, whole grains and low-fat dairy products. The DASH diet has consistently lowered blood pressure in several trials and is even more effective when sodium is restricted to 1,200 milligrams per day, normalizing blood pressure without medication in 77% of participants (Svetkey et al. 2004).
Very limited research suggests that certain nutrients (e.g., potassium, magnesium, calcium, vitamin D, chromium and fiber) may be important for maintaining insulin sensitivity and low fasting blood glucose. One clinical trial found that a diet rich in fruits, vegetables, whole grains and low-fat dairy products that provided approximately 30 g of fiber per day was effective in improving insulin sensitivity when accompanied by other lifestyle changes, such as weight loss and regular physical activity (Ard et al. 2004). However, this is an emerging area of study with inadequate or inconsistent data available. For now, regular physical activity and weight loss are likely to be the best interventions for lowering fasting blood glucose and improving insulin sensitivity.
Clearly, regular endurance exercise is the most effective way for both normal-weight and overweight clients to improve their insulin sensitivity and reduce their chances of developing metabolic syndrome. Resistance training may also be beneficial. Physical activity has a favorable impact on all of the other abnormalities associated with the syndrome as well. The best news is that even modest weight loss can improve metabolic syndrome. Overweight clients who lose as little as 5% of their body weight can improve their insulin sensitivity and positively affect other associated metabolic abnormalities. Just 30 minutes of moderate activity each day can reduce dangerous deposits of abdominal fat.
Eating nutrient-rich foods, like those featured in the DASH diet, can lower blood pressure and lipid levels and may also improve insulin sensitivity. Monunsaturated fats and omega-3 fats are especially beneficial in altering the high triglycerides and low HDL-C levels that are hallmarks of insulin resistance.
These beneficial lifestyle choices preserve insulin sensitivity, protect against the abnormalities that make up metabolic syndrome and prevent the chronic illnesses associated with long-term insulin resistance.
According to the National Cholesterol Education Program (NCEP), metabolic syndrome is identified by the presence of three or more of these metabolic abnormalities:
waist circumference greater than 35 inches
equal to or greater than 150 mg/dl
less than 50 mg/dl
equal to or greater than 130/85 mm Hg
equal to or greater than 110 mg/dl
fasting blood triglycerides
fasting blood glucose
waist circumference greater than 40 inches
equal to or greater than 150 mg/dl
less than 40 mg/dl
equal to or greater than 130/85 mm Hg
equal to or greater than 110 mg/dl
mg/dl = milligrams per deciliter; mm Hg = millimeters of mercury
For more information on metabolic syndrome, check out these helpful websites:
- American Diabetes Association, www.diabetes.org/weightloss-and -exercise/weightloss/metabolic syndrome.jsp. Provides an official description of metabolic syndrome.
- Centers for Disease Control and Prevention, www.cdc.gov/nccdphp /dnpa/obesity/trend/metabolic .htm. Outlines prevalence data for metabolic syndrome.
- National Institutes of Health, www.nih.gov/news/pr/apr97/Dash .htm. Gives details of the DASH diet plus sample menus.
- type 2 diabetes
- cardiovascular disease (e.g., heart attack, hypertension, stroke)
- nonalcoholic fatty-liver disease
- breast and colon cancer
- sleep apnea
- polycystic ovarian syndrome
- erectile dysfunction and female sexual dysfunction