Abstract
Plasma lipid, glucose, and insulin levels were measured from 26 patients with Prader-Willi syndrome (16 with the chromosome 15q deletion and 10 with normal chromosomes) and 32 obese, normal individuals. The average percentage of ideal body weight (IBW) for the former group was 175.6 ± 68.0, compared to 150.3 ± 43.8 for the latter. Fasting plasma lipid, glucose, and insulin levels were not significantly different between the two groups. No significant correlations were found among the three measurements in patients with PWS (deletion or nondeletion) or obese individuals and either age or percentage of IBW. Both insulin and glucose levels were higher in the PWS group, while only insulin levels were higher in the obese group compared with normative laboratory standards. Our study supports previously reported lipid, glucose, and insulin data in PWS and obesity.
Keywords: glucose, insulin, lipids, obesity
In 1956 Prader et al.1 described a syndrome characterized by mental deficiency, obesity of early childhood onset, infantile hypotonia, short stature, small hands and feet, hypogonadism, and a characteristic combination of minor anomalies. Since then approximately 700 patients with the Prader-Willi syndrome (PWS) have been reported.2 It is the most common syndromal cause of marked human obesity, with many individuals weighing more than 200% of ideal body weight.3,4 While the basic cause of these features is not clearly understood, a chromosome abnormality, usually a deletion (15qll-13), has been found in about one-half of patients based on high-resolution chromosome analysis.
Despite obesity being a major feature of PWS, plasma levels of lipids, glucose, and insulin have been studied in only a few patients.5–13 The present study was undertaken to determine the effects of obesity on fasting plasma immunoreactive insulin, glucose, and lipid levels in a relatively large number of patients with PWS and to compare them with levels in obese individuals without PWS.
MATERIALS AND METHODS
Our subject population consisted of 26 patients with PWS (16 with the 15ql2 deletion, 10 with normal chromosomes) and 32 obese subjects, The inclusion criteria for patients with PWS were infantile hypotonia, hypogonadism, delayed psychomotor development with or without mental retardation, early childhood obesity, small hands and feet, and short stature. Obesity was defined as ideal body weight (IBW) greater than 130%. The clinical data of the patients with PWS and obese persons are shown in Table 1.
Table 1.
Clinical Data for Patients with FWS and Obese Individuals
| Group | N | Sex (M:F) |
Age (yrs) Mean ± SD (range) |
% IBW (mean ± SD) |
|---|---|---|---|---|
| PWS | 26 | 14:12 | 18.9 ± 7.0 (7.0–38.6) | 175.6 ± 68.0 |
| Obese | 32 | 6:26 | 23.6 ± 6.6 (8.4–33.0) | 150.3 ± 43.8 |
Fasting (6–12 hrs) blood samples from the two groups were anticoagulated with EDTA and the plasma was frozen at −70°C for assay at a later time. Total plasma cholesterol and triglyceride levels were measured by standard enzymatic assays using kits (Sigma Chemical Co., St. Louis, MO). High-density lipoprotein (HDL) cholesterol was measured by the enzymatic method after precipitation of very lowdensity lipoprotein (VLDL) and low-density lipoprotein (LDL) using Sigma HDL cholesterol reagent. The LDL cholesterol was estimated using the Fridewald equation.14
Fasting plasma glucose was measured by the oxidase method (Glucose Analyzer II, Beckman Instruments, Fullerton, CA). Plasma insulin levels were measured by double-antibody radioimmunoassay.15 Statistical analysis was undertaken on the laboratory data with the use of t tests and Pearson productmoment correlations.
RESULTS
Table 2 shows the plasma lipid, glucose, and insulin data for patients with PWS and obese individuals. Figures 1 and 2 show the data on all of the measurements for the two groups. No significant differences were found in the average triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels between patients with PWS and obese individuals. There also was no difference in these levels compared with age- and sex-matched standards published for triglycerides and cholesterol.16 Similarly, no significant correlations were found in lipid, insulin, or glucose levels in persons with PWS (deletion or nondeletion) or obese individuals and either age or IBW. The same held true for insulin and glucose levels. The average glucose level in patients with PWS was above the normal range established for our laboratory, but more variation was seen in this value in this group than in the obese group (Fig. 3). Four individuals with PWS had elevated fasting glucose levels greater than 105 mg/dl, or upper range of normal, while none of the obese persons had high levels. Conversely, five patients and three obese individuals had fasting glucose levels below 80 mg/di, the lower range of normal. The average insulin levels for both groups were above the normal range established for our laboratory.
Table 2.
Fasting Plasma Lipid, Glucose, and Insulin Data in Patients with PWS and Obese Individuals
| Laboratory Data | PWS Mean ± SD (N) |
Obese Mean ± SD (N) |
|---|---|---|
| Triglycerides (mg/dl) | 96.2 ± 67.0 (22) | 97.3 ± 61.8(32) |
| Total cholesterol (mg/dl) | 180.6 ± 46.5 (22) | 196.1 ± 53.9 (32) |
| HDL cholesterol (mg/dl) | 42.7 ± 12.9 (16) | 45.7 ± 14.2 (21) |
| LDL cholesterol (mg/dl) | 136.1 ± 32.6 (16) | 141.4 ± 62.1 (21) |
| Basal immunoreactive insulin (μU/ml) | 33.3 ± 35.7 (20)a | 24.9 ± 13.8 (17)a |
| Fasting glucose (mg/dl) | 113.6 ± 56.6 (11)a | 87.2 ± 7.4 (20) |
These values for both groups are outside the normative laboratory range. Three patients with PWS had fasting glucose levels greater than 150 mg/dl, while none of the obese individuals had values above 102 mg/dl.
Fig. 1.

Fasting plasma triglyceride, total cholesterol, HDL cholesterol, and LDL cholesterol levels for each group. Values are means ± standard deviation.
Fig. 2.

Fasting plasma glucose and immunoreactive insulin levels for each group. Values are means ± standard deviation.
Fig. 3.

Fasting plasma glucose and immunoreactive insulin levels plotted for 10 patients with PWS and 15 obese individuals. The regression lines are as follows: solid line, PWS; dashed line, non-PWS obese. A correlation of −0.35 for the patients and 0.22 for the obese persons were calculated but not significant.
DISCUSSION
Studies of fasting serum lipid, glucose, and insulin levels in patients with PWS and comparison of these values wjth those in obese individuals are limited. Serum cholesterol, triglyceride, and lipoprotein levels are generally within normal range in patients,7–9 although elevated levels of serum free fatty acid (FFA) and triglycerides were found in seven children with PWS.5 Parra et al.6 also found high fasting levels of FFA, which were similar to levels in obese children.
Consistent with the data of previous reports, our study revealed no differences in plasma cholesterol, triglyceride, LDL cholesterol, or HDL cholesterol levels between patients with PWS and obese individuals. We did not study plasma free fatty acid levels. It is also important to note that we found no differences comparing the plasma lipid values of patients with values from age- and sex-ma tch ed controls. Thus, we conclude that plasma lipid levels are not altered in PWS.
Fasting blood glucose levels are generally reported to be within normal range in patients with PWS6,8,13 although approximately 20% of these individuals reported in the literature have reduced glucose tolerance/diabetes mellitus.2 Recent data, however, suggest that glucose intolerance in PWS is related to obesity, while the frequency of diabetes mellitus is probably less than suggested in earlier reports.8 Our study showed that the average fasting glucose level was higher, but not significantly, in the PWS group compared with the obese group. Persons with PWS showed more variation in individual glucose levels than the obese group, which agrees with published data.
Fasting hyperinsulinemia has been reported in PWS, and the insulin levels may be comparable to normal values in obese persons.6,8,10–13 The high insulin levels in both obese and PWS groups apparently represent peripheral resistance to the metabolic actions of insulin and are not specific for PWS.6,8,10–13 Our data also indicate that basal insulin levels were higher than normal established by our laboratory but were comparable to the levels obtained in our obese subjects.
In summary, no significant differences were found in fasting plasma lipid, insulin, or glucose levels in a relatively large sample of obese individuals with or without PWS. Similarly, no significant correlations were found in these values in patients with PWS (deletion or nondeletion) or obese persons versus age or IBW.
ACKNOWLEDGMENTS
We thank Pam Phillips for expert preparation of the manuscript and Judy Haynes for technical assistance. This work was supported in part by grant DK 26657 from The National Institutes of Health.
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