The growing number of trials that have highlighted the benefit of intensive lowering of total- and low density lipoprotein (LDL)-cholesterol levels especially with statins has created a need for more efficacious agents. Pitavastatin is a new synthetic 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor, which was developed, and has been available in Japan since July 2003. Metabolism of pitavastatin by the cytochrome P450 (CYP) system is minimal, principally through CYP 2C9, with little involvement of the CYP 3A4 isoenzyme, potentially reducing the risk of drug-drug interactions between pitavastatin and other drugs known to inhibit CYP enzymes. To date, human and animal studies have shown pitavastatin to be potentially as effective in lowering LDL-cholesterol levels as rosuvastatin; although, head-to-head studies are yet to be conducted.
OBJECTIVE -To compare effects of different oral hypoglycemic drugs as first-line therapy on lipoprotein subfractions in type 2 diabetes.RESEARCH DESIGN AND METHODS -Sixty overweight type 2 diabetic patients not on lipid-lowering therapy were randomized to metformin, pioglitazone, or gliclazide after a 3-month dietary run-in. Drug doses were uptitrated for 3 months to optimize glycemia and were kept fixed for a further 3 months. LDL subfractions (LDL 1 , LDL 2 , and LDL 3 ) were prepared by density gradient ultracentrifugation at randomization and study end. Triglycerides, cholesterol, total protein, and phospholipids were measured and mass of subfractions calculated. HDL subfractions were prepared by precipitation. The primary end point was change in proportion of LDL as LDL 3 .RESULTS -HbA 1c , triglycerides, glucose, and cholesterol were comparable across groups at baseline and over time. LDL 3 mass and the LDL 3 -to-LDL ratio fell with pioglitazone (LDL 3 mass 36.2 to 28.0 mg/dl, P Ͻ 0.01; LDL 3 -to-LDL 19.2:13.3%, P Ͻ 0.01) and metformin (42.7 to 31.5 mg/dl, P Ͻ 0.01; 21.3:16.2%, P Ͻ 0.01, respectively) with no change on gliclazide. LDL 3 reductions were associated with reciprocal LDL 1 increases. Changes were independent of BMI, glycemic control, and triglycerides. Total HDL cholesterol increased on pioglitazone (1.28 to 1.36 mmol/l, P ϭ 0.02) but not gliclazide (1.39 to 1.37 mmol/l, P ϭ NS) or metformin (1.26 to 1.18 mmol/l, P ϭ NS), largely due to an HDL 2 increase (0.3 to 0.4 mmol/l, P Ͻ 0.05). HDL 3 cholesterol fell on metformin (0.9 to 0.85 mmol/l, P Ͻ 0.01). On pioglitazone and metformin, the HDL 2 -to-HDL 3 ratio increased compared with no change on gliclazide.CONCLUSIONS -For the same improvement in glycemic control, pioglitazone and metformin produce favorable changes in HDL and LDL subfractions compared with gliclazide in overweight type 2 diabetic patients. Such changes may be associated with reduced atherosclerosis risk and may inform the choice of initial oral hypoglycemic agent. Diabetes Care 27:41-46, 2004P atients with type 2 diabetes are frequently overweight with associated hypertension and a characteristic dyslipidemia with raised triglycerides and low HDL cholesterol. This cluster of abnormalities partly explains their increased risk of macrovascular disease. Targeting and treating the hypertension and dyslipidemia improves long-term outcomes (1-3). However, despite intervention, these patients remain at increased risk, suggesting that other factors contribute.A proportion of the increased risk may be explained by qualitative changes in lipoprotein subfraction. Although LDL cholesterol may not be elevated in type 2 diabetes, the dyslipidemia is characterized by an increased proportion of LDL as small, dense LDL or LDL 3 (4). Increased LDL 3 has been shown to be associated with increased risk of myocardial infarction (5-7). Risk may also be increased by qualitative changes in HDL subfractions (8), with an increased proportion of HDL occurring as smaller, denser HDL 3 , which is believed t...
SUMMARY The influence of the type and size of solid particles on their emptying from the stomach was studied using isotopically labelled chicken liver and inert particles in normal subjects and in patients who had undergone gastric surgery. In normal subjects, initial emptying of the liver was slower than that of inert particles both for large liver cubes (1 cm) and small cubes (0.3 cm). Liver emptying subsequently accelerated to be faster than emptying of the inert particles. Overall emptying of the liver given as small cubes was faster than large cubes; 50% emptied in 50 minutes and 70 minutes respectively. In the postoperative subjects, emptying of the liver and of the inert particles was identical. The findings are consistent with the hypothesis that solid foods such as liver are ground down and 'liquefied' by the action of gastric peristalsis before being discharged to the duodenum. Ingested particle size appears to influence the rapidity of this process, which should be distinguished from the propulsive function of the stomach where small solid particles are concerned.After the ingestion of a mixed liquid and solid meal, the liquid component empties from the stomach more rapidly than the solid. Although there is still debate about the relative importance of the proximal stomach' and of gastric peristalsis2 in controlling the emptying of liquids, it is generally agreed that the emptying of solids is controlled by the distal stomach,3 where peristaltic activity also serves to grind and mix the gastric contents before their delivery to the duodenum. Recent interest in the gastric emptying of solids has led to the development of several radioisotopically labelled solid foods suitable for study by scintigraphic methods. Liver labelled with technetium 99m has been particularly favoured46 but emptying studies using bread7 and egg white,8 cellulose fibre,9 and bran'0 have also been described.We have previously reported studies of gastric emptying in man using small inert particles labelled with technetium 99m, which are added to a normal meal.11 These particles are emptied from the stomach in an approximately linear manner with time, corresponding to the pattern observed for solids which are normal dietary constituents. How-* Present address:
Levels of free anti-(xanthine oxidoreductase) (XOR) antibodies in the serum of normal healthy human subjects were determined, using both human and bovine enzyme as antigen, in an enzyme-linked immunosorbent assay (ELISA). Levels of IgM class anti-(human XOR) antibodies were found to be particularly high (mean values representing approximately 3% of total IgM) and to be significantly higher than levels of IgM anti-(bovine XOR) antibodies, indicating that endogenous XOR, rather than ingested bovine milk XOR, is the immunogen. IgM anti-XOR antibody levels were significantly higher in women under 50 years than in age-matched men, or in older women. Levels of IgG class anti-XOR antibodies were much lower and showed no correlation with gender or age. Affinity-purified anti-(human XOR) antibodies only partially inhibited enzymic activities of XOR. The majority of both IgM and IgG anti-(human XOR) antibodies in serum occurred as immune complexes, suggesting that the specific antibodies have a protective role in removing potentially damaging XOR from the circulation.
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