Apolipoprotein E polymorphism is associated with plasma cholesterol response in a 7-day hospitalization study for metabolic and dietary control in NIDDM.

OBJECTIVE

To investigate the effects of apolipoprotein E phenotype, which is an important genetic factor determining plasma cholesterol level, on plasma lipoprotein metabolism during a 7-day diet therapy of diabetes.

RESEARCH DESIGN AND METHODS

Diet therapy was performed in 242 subjects with NIDDM. Plasma lipid levels and apolipoprotein A-I, B, and E levels on hospital days 2 and 9 were compared in three phenotype groups, epsilon 2 (E2/2, and E2/3), epsilon 3 (E3/3), and epsilon 4 (E3/4 and E4/4).

RESULTS

No differences were observed in fasting blood glucose level, body mass index, age, duration of NIDDM, or medication among the three phenotype groups. Before starting the treatment, total plasma cholesterol did not vary by apolipoprotein E phenotype, although the mean plasma low-density lipoprotein cholesterol level in epsilon 4 patients was higher than in either epsilon 3 or epsilon 2 patients (epsilon 4, 145 +/- 42; epsilon 3, 131 +/- 34; epsilon 2, 128 +/- 36 mg/dl; P < 0.05). Changes in fasting blood glucose/body mass index after the 7-day treatment were not different among the apolipoprotein E phenotype groups, whereas the decrease in plasma cholesterol level after the treatment was significantly greater in epsilon 2 patients than in either epsilon 3 or epsilon 4 patients (epsilon 2, 10.3 +/- 14.2; epsilon 3, 6.1 +/- 11.0; epsilon 4, 3.8 +/- 9.6%; P < 0.05).

CONCLUSIONS

Total plasma cholesterol response to in-hospital diet therapy varies by apolipoprotein E phenotypes, with subjects with apolipoprotein E2 showing the greatest response, whereas those with apolipoprotein E4 show the least. We suggest that subjects with apolipoprotein E4 should be controlled more strictly than other subjects from a viewpoint of reducing plasma cholesterol levels.