The ORLIstat and CArdiovascular risk profile in patients with metabolic syndrome and type 2 DIAbetes (ORLICARDIA) Study.

BACKGROUND: Metabolic syndrome (MetSyn) is associated with a marked increase in the risk of cardiovascular disease, especially in patients with type 2 diabetes mellitus (DM). AIM: To investigate the effect of orlistat plus hypocaloric diet (HCD) vs HCD alone on the cardiovascular risk profile in patients with both MetSyn (National Cholesterol Educational Program--NCEP--Adult Treatment Panel III definition) and type 2 DM. METHODS: This was a prospective, multicentre, open-label, randomized, controlled study. One hundred and twenty-six patients, free of cardiovascular disease at baseline, were included in the final analysis. Ninety-four (73%) patients were treated with orlistat (360 mg/day) and HCD for a 6-month period, while 34 (27%) were on HCD alone. Analysis of covariance was used to assess differences between the treatment groups over time. MAIN OUTCOME MEASURES: Components of the MetSyn criteria assessed were: waist circumference; systolic and diastolic blood pressure; fasting glucose, triglycerides; high-density lipoprotein cholesterol (HDL-C) plus body mass index; glycosylated haemoglobin (HbA1C); homeostasis model for assessment of insulin resistance (HOMA) index; and total and low-density lipoprotein cholesterol (LDL-C). RESULTS: By protocol, all patients had MetSyn at baseline. After a 6 month treatment period there were significant differences between the orlistat plus HCD vs the HCD-alone groups in body weight (p = 0.0001), waist circumference (p < 0.0001), fasting glucose (p < 0.0001), HbA(1C) (p < 0.0001), systolic blood pressure (p = 0.024), total cholesterol (p < 0.0001), LDL-C (p = 0.034), and HOMA index (p = 0.022), while there were no significant differences in triglycerides and HDL-C. Orlistat was well tolerated. By the end of the study, 65% of the patients on orlistat plus HCD were still meeting the MetSyn criteria and 41% had four to five MetSyn components vs 91% (p < 0.0001) and 53% (p = 0.017), respectively, of those on HCD alone. CONCLUSIONS: Orlistat plus HCD favourably modified several cardiovascular risk factors in patients with both MetSyn and type 2 DM. These effects might partly offset the excess cardiovascular risk and improve outcome in this patient population.

Maximal post-prandial triglyceride increase reflects post-prandial hypertriglyceridaemia and is associated with the insulin resistance syndrome.

AIMS: To assess the value of maximal post-prandial triglyceride increase after a high fat, low carbohydrate (CHO) test meal, as index of post-prandial hypertriglyceridaemia and its relation with insulin resistance. METHODS: Fifty non-diabetic subjects, 22 male and 28 female, aged 52.1+/-4.5 and 56.9+/-3.8 years, were studied. Glucose, insulin and triglycerides were measured fasting and 1, 2, 3 and 4 h after a meal consisting of 40 g fat, 19 g protein and 10 g CHO. Insulin resistance was calculated according to the HOMA model. RESULTS: The maximal triglyceride increment occurred during the 4th hour. Its absolute value (delta-TG) and the per cent increase over the fasting value (PTI), were considered appropriate for the evaluation of the post-prandial triglyceride response. Both delta-TG and PTI were strongly correlated with triglycerides incremental area in males and females, r = 0.797 and r = 0.700, P<0.01 and r = 0.805 and r = 0.774, P<0.001, respectively, and thus they can be used as indices of the post-prandial triglyceride response. No correlation was found between fasting triglyceride and triglyceride incremental area or delta-TG. Thus, post-prandial hypertriglyceridaemia can occur irrespectively of the fasting triglyceride concentrations. A weak correlation was found between PTI and insulin resistance in females, r = 0.384, P<0.05, but not in males, r = 0.224, P>0.05. However further analysis by quartiles of PTI showed similar insulin resistance levels in the first three quartiles and a significant increase in the 4th, both for males and females, 4th vs. 3rd quartile 7.4+/-3.6 vs. 2.2+/-0.7 and 6.4+/-2.4 vs. 2.2+/-0.6, respectively. The 4th quartile corresponds to a PTI > or =80%. CONCLUSIONS: PTI after the high fat, low CHO test meal used, consistently reflects post-prandial hypertriglyceridaemia, is easily measured and it is not predicted by fasting triglycerides. A PTI > or = 80% is associated with a significant increase of insulin resistance, and might therefore be considered the cut-off point for an abnormal post-prandial hypertriglyceridaemic response, at least in relation with insulin resistance. Such response could be added to the abnormalities of the insulin resistance syndrome, as an independent parameter.

Influence of 5-fluorouracil on serum lipids.

The effect of the cytotoxic drug 5-fluorouracil (5-FU) on plasma lipid levels was studied in patients and animals. Seven patients with metastatic carcinoma of the colon and three with advanced breast cancer were treated with 5-FU monotherapy by i.v. push at a dose of 500 mg/m2/d for 3-5 consecutive days. The animal group comprised 9 rabbits treated with 5-FU by i.v. push at 12-18 mg/kg/d for 2 consecutive days. Measurements of serum lipid levels were performed before and 2 and 4 weeks after 5-FU administration. No obvious change of diet, body weight and bowel habits occurred during the study period. A significant reduction of total plasma cholesterol was observed in both patients and animals. The triglyceride levels were also reduced in the rabbits. Maximal cholesterol-lowering effect was observed in patients and rabbits with higher baseline cholesterol levels. The results suggest that 5-FU might interfere with lipid metabolism.

Insulin-specific IgE in serum of 67 diabetic patients against human insulin (Novo), porcine insulin, and bovine insulin. Four case reports.

We have investigated the binding of insulin-specific IgE (IgE1) to porcine, bovine, and human insulin (Novo), pancreatic polypeptide, and a-component in serum samples from type I diabetic patients treated with insulin preparations of different purity. Patients treated with porcine or mixed-species purified insulin (monocomponent) did not differ significantly from a nondiabetic control group. Hence, in these groups no IgE1 could be detected against any of the components investigated. Serum samples from patients treated with five-times recrystallized insulin preparations and patients with insulin allergy showed a significantly greater binding of IgE1 to the three species of insulin; IgE1 binding was greatest to bovine insulin and least to human insulin. The difference in binding was most significant in the allergic patients (P less than 0.001), probably due to differences in the affinity. It is concluded that conventional (recrystallized) insulin induces more IgE1 than monocomponent insulin. Data are presented on confirmed allergy in four diabetic patients whose allergy disappeared upon transfer to human insulin.