Relationship between altered postprandial lipemia and insulin resistance in normolipidemic and normoglucose tolerant obese patients B Guerci 1 *, B Verge Ás 2 , V Durlach 3 , S Hadjadj 1 , P Drouin 1 and J-L Paul 4 1 Centre d'Investigation Clinique (CIC-Inserm=CHU de Nancy), Service de Diabe Âtologie, Maladies Me Âtaboliques et Maladies de la Nutrition, Ho à pital Jeanne d'Arc, 54201 Toul, France; 2 Service d'Endocrinologie, Diabe Âtologie et Maladies Me Âtaboliques, CHU de Dijon, 21000 Dijon, France; 3 Service d'Endocrinologie, Maladies Me Âtaboliques et Me Âdecine Interne, CHU de Reims, 51092 Reims, France; and 4 Laboratoire de Biochimie, Ho Ãpital Broussais, AP-HP, 75014 Paris, Faculte  de Pharmacie, Paris XI, 92296 Chatenay-Malabry, France OBJECTIVE: Although there are changes in the postprandial lipid responses of obese patients, these are closely associated with high fasting triglycerides (TG). This study of 17 normotriglyceridemic, normoglucose-tolerant android obese subjects (body mass index, BMI  34.3  3.1 kg=m 2 ) and 33 normal-weight controls (BMI  21.8  1.6 kg=m 2 ) was done to examine their postprandial responses to an oral fat loading test containing retinol (890 calories, 85% fat) and to evaluate the possible association between clinical and biological features of obesity and=or insulin resistance and postprandial lipemia. SUBJECTS AND MEASUREMENTS: Blood samples were taken before giving the fat load and at 2,3,4,5,6 and 8 h after it. Insulin sensitivity was assessed using HOMA, and TG and retinyl palmitate (RP) in the plasma, chylomicrons and non-chylomicron fractions were measured each time. RESULTS: The areas under the curves (AUC) of chylomicron TG for the obese and controls were not different, indicating adequate lipolytic activity. By contrast, the AUC for non-chylomicron TG was signi®cantly greater in the obese than in the controls (512  135 vs 429  141 mmol=l min, P < 0.01). In addition, the AUC for RP in this same fraction was signi®cantly lower in the obese than in the controls (103  55 vs 157  88 mg=l min, P < 0.05), suggesting that the TG from endogenous lipoproteins accounted for most of the increase in TG in the non chylomicron fraction. Parameters related to obesity showed no relationship with these postprandial abnormalities, whereas HOMA, which discriminated between the groups, partly explained (r 2  23%, P < 0.01) the signi®cant increase in non-chylomicron TG. CONCLUSIONS: Android obese patients with a fasting TG in the normal range and not different from the fasting TG of lean controls had an abnormal postprandial lipemia response, indicated by a signi®cantly greater TG in the non- chylomicron subfraction than in controls. These alterations may be partly due to postprandial changes in endogenous lipoproteins as a consequence of insulin resistance. International Journal of Obesity (2000) 24, 468±478 Keywords: postprandial lipemia; obesity; insulin resistance; oral fat load; retinyl palmitate; triglyceride-rich lipoproteins Introduction Atherosclerosis is a major cause of morbidity and death in af¯uent countries and postprandial lipopro- tein metabolism is likely to be involved in atherogen- esis, as ®rst suggested by Zilversmit. 1 Several studies have described abnormalities in postprandial metabo- lism in patients with coronary artery disease, 2±4 and shown that postprandial triglycerides (TG) are inde- pendent predictors of coronary artery disease in multi- variate analysis, 5 even after adjustment for fasting TG or HDL-cholesterol in normolipidemic men. 6 Obesity is associated with abnormal fasting lipid parameters such as increased fasting triglyceride and decreased HDL-cholesterol, 7 which could explain, at least in part, the greater development of cardiovas- cular disease in obese people. Nevertheless, obesity appears to be an independent risk factor for coronary artery disease, even in subjects with normal fasting plasma lipids and normal glucose tolerance. 8 Some studies have reported altered postprandial lipemia in obese patients, 9,10 but little is known about postpran- dial lipid metabolism in normolipidemic and normo- glucose tolerant obese patients. Liver-derived triglyceride-rich lipoproteins have recently been suggested to be important in the post- prandial lipemia alterations in patients with coronary heart disease. 11 In obese patients, these alterations could be due mainly to increased postprandial VLDL production 9,10 or to a defect in the clearance of intestinal or hepatic TG-rich lipoproteins. 12 The decreased insulin sensitivity commonly associated with obesity 13 and the abdominal distribution of fat 14 may well play an important part. Some published *Correspondence: B Guerci, Diabe  tologie, Maladies Me  taboliques et Maladies de la Nutrition, Centre d'Investigation Clinique-Inserm=CHU de Nancy, Ho à pital Jeanne d'Arc, BP 303, 54201 Toul, France. E-mail: b.guerci@chu-nancy.fr Received 20 May 1999; revised 14 October 1999; accepted 15 November 1999 International Journal of Obesity (2000) 24, 468±478 ß 2000 Macmillan Publishers Ltd All rights reserved 0307±0565/00 $15.00 www.nature.com/ijo