Syndrome X, a clinical quartet of hyperinsulinemia, hypercholesterolemia, and hypertension with subsequent coronary artery disease (CAD), was initially described by Reaven¹ and has since been described by others.^2,3 Some⁴ consider obesity to be a component of Syndrome X, although obesity is not part of Reaven's original description. Recently, Syndrome X has been described in children⁵ and adolescents.⁶

The heralding defect in Syndrome X is believed by many to be hyperinsulinemia,⁷ and one could propose that reduction of insulin levels would improve the other symptomatology. Decreasing dietary fat intake improves cholesterol levels and weight loss in type II diabetics (noninsulin-dependent diabetes mellitus) and is associated with lower fasting insulin levels.⁸ Exercise promotes weight loss and improves insulin sensitivity.⁹ The purpose of this study was to describe the effects of diet or exercise on the clinical manifestations of Syndrome X in children.

METHODS

Subjects

Table 1. Subject Characteristics [View Table]

Description of Treatment Groups

The exercise group (E) participated in moderate aerobic exercise (to raise heart rate to 75 to 80% of maximum) for 1 hour three times per week at the University of Texas recreation center, under the guidance of an exercise physiologist. Compliance with exercise was encouraged by providing transportation to and from the sessions. The E group received additional measurement of maximal aerobic capacity (VO₂ max) at baseline and at the study's conclusion. The control group (C) received no intervention.

Study Measurements

At baseline and at the end of the study, after an 8- to 10-hour fast, each patient had blood drawn for the following laboratory analyses: fasting insulin, cholesterol, triglyceride, very low density lipoprotein, high density lipoprotein, and apolipoprotein A (ApoA).

In Vitro Methods

Statistical Analysis

RESULTS

The average pretreatment total cholesterol for all of the patients was 178 ± 34 mg/dL, which is considered moderately high for age.¹⁰ ApoA levels were high when compared with age-matched normal values.¹¹ In all patients, the average pretreatment SBP and DBP measurements were at the 75th to 95th percentile for age. The mean pretreatment fasting insulin level for all subjects was 50.5 ± 15 (normal, <20 µU/mL). Clearly the pretreatment data suggest that the clinical findings of these children is consistent with Syndrome X.

Dietary history was obtained from the D group only. We believe the pretreatment dietary history from this group is probably representative of the diets for most of our study children. As assessed from the pretreatment dietary history, the diet of these children is comprised as 38% fat, 12% protein, and 50% carbohydrate. The D group who successfully completed our study, shifted their dietary intake to 29% fat, 15% protein, and 56% carbohydrate.

After 6 weeks of treatment, there was no significant difference between the pretreatment and posttreatment values, or between the treatment groups for height, BMI, and percent ideal body weight. Likewise, SBP, DBP, and mean arterial pressure did not change with treatment in any group. All of the children who participated in the D group lost weight (0.7 to 2.2 kg); however, the mean group weight loss was not statistically significant. Posttreatment, total body cholesterol, and low density lipoprotein levels were not significantly different between any of the treatment groups; however, triglyceride levels significantly decreased in the D and E groups. ApoA levels decreased significantly in both the D and E groups, but did not change in the C group. The lipid profiles before and after treatment are listed in Table 2.

Table 2. Lipid Profiles [View Table]

The most significant finding of the study, is the marked decrease in the fasting insulin levels of the D and E groups after 6 weeks of treatment. These findings are illustrated by Fig 1.

DISCUSSION

The most significant limitation of our study is that we allowed the patients and/or their parents to select the treatment group. We accepted this limitation at the study's outset because we realized that families desired a particular treatment and to choose for them might adversely affect participation. Initially there were less children who selected the C group. Two of these patients did not return for the final blood work, thus the C group is slightly smaller than the D or E groups. Children who selected the D group tended to be the heaviest and had the worst lipid profiles.

The results from the D group suggest that even a modest reduction of fat intake for a short amount of time can result in decreased triglyceride and ApoA levels, as well as a small amount of weight loss, in children. Although these results are encouraging, the large percentage of drop-outs and noncompliant patients in this group tempers our enthusiasm. Our diet plan was aimed at reducing fat intake to age-recommended normal intake and therefore was not very restrictive. We also provided more contact and individualized dietary management than is often provided to obese patients. It is reasonable to hypothesize that even greater numbers of children would not follow a more restrictive, less-personalized diet plan. However, if our subjects continued the diet for a longer period of time, we may have seen greater improvement in the lipid profiles, or demonstrated significant weight loss.

Our exercise program was successful in part because we offered transportation, and in part, because the children who chose this treatment group were interested in exercise. Although the mean VO₂ max did not statistically improve for the group, all patients improved his/her VO₂ max during the 6 weeks of exercise. Both diet and exercise resulted in improved triglyceride and ApoA levels. High serum triglyceride levels are associated with coronary heart disease.¹² High ApoA levels have been found in Type II diabetes and are also associated with CAD.¹³ Reduction in triglyceride and ApoA levels with only 6 weeks of treatment suggests that children can improve their risk for both diabetes and CAD with small changes in lifestyle.

High fasting insulin levels are associated with insulin resistance,¹⁴ a hallmark of type II diabetes.¹⁵ High-fasting serum insulin levels is believed to be the underlying cause of many of the clinical problems noted in Syndrome X; for example, hypertriglyceridemia and CAD.⁷ Our study demonstrates that both diet and exercise successfully decrease high insulin levels in children. Some researchers believe hyperinsulinism is a result of obesity,¹⁶ yet our treatment groups successfully lowered fasting insulin levels without reducing body weight or BMI. Perhaps lower insulin levels precede the weight loss that occurs with diet or exercise. Although our study does not evaluate future development of disease, it seems plausible that sustained reduction of fasting insulin levels would lower the future risk for development of both diabetes and coronary heart disease.

In summary, results of this study suggest that Syndrome X is an entity that begins in childhood and can be treated by either diet or exercise. However, given the large percentage of the D group who were noncompliant, exercise is probably a better treatment choice in children. Prolonged diet or exercise may be necessary to unmask the full effect of these treatments in childhood Syndrome X.