Hypertriglyceridemic hyperapoB in type 2 diabetes

OBJECTIVES: Much less attention has been paid to LDL in type 2 diabetes than to VLDL or HDL. In particular, there are few data on apoB levels in these patients. Moreover, most reports have focused on mean lipoprotein levels and consequently there is little information on the frequencies of the various dyslipidemic phenotypes. RESEARCH DESIGN AND METHODS: Plasma and lipoprotein lipids, apoB and apoA1 were measured by standardized methods. LDL particle size was determined by PAGE. The total cohort was divided into phenotypes by two different methods. The first was based on triglycerides (> or = or <1.5 mmol/l) and LDL cholesterol (> or = or <4 mmol/l), whereas the second was based on triglycerides (> or = or <1.5 mmol/l) and apoB (> or = or <120 mg/dl). RESULTS: For the overall cohort, plasma triglycerides were elevated (2.13 +/- 1.6 mmol/l), total and LDL cholesterol were normal (5.34 +/- 1.1 and 3.28 +/- 0.88 mmol/l, respectively), and peak LDL size was reduced (252.9 +/- 5.8 A). HDL cholesterol was between the 25th and 50th percentiles of the general population (1.12 +/- 0.36 mmol/l). The average level of apoB was 114 +/- 29 mg/dl, a value that is between the 50th and 75th percentiles of the general population and is higher than that for LDL cholesterol, which was between the 25th and the 50th percentiles of the population. The results of the phenotyping analysis were as follows. Using the conventional approach, only 23% has abnormal LDL, i.e., an elevated LDL cholesterol level. Using the new approach, almost 40% has an elevated apoB and therefore an elevated LDL particle number. Only 12.8% has combined hyperlipidemia based on the conventional approach, whereas almost one-third had the equivalent, hypertriglyceridemic hyperapoB-based on the new algorithm. The severity of the dyslipoproteinemia in this group was noteworthy. Although the average LDL cholesterol was 3.91 mmol/l, a value just below the 75th percentile of the general population, the average apoB was 145 mg/dl, a value that approximates the 95th percentile of the population. CONCLUSIONS: The dyslipidemic profile of patients with type 2 diabetes is not uniform. A substantial group have normal lipids and normal LDL particle number and size whereas others have markedly abnormal profiles. Diagnosis based on triglycerides and apoB rather than triglycerides and LDL cholesterol revealed that more than one in five had hypertriglyceridemic hyperapoB, which is characterized by hypertriglyceridemia, marked elevation of LDL particle number, small dense LDL, and low HDL, a constellation of abnormalities that is associated with markedly accelerated atherogenesis and therefore justifies intensive medical therapy.     

Precipitation of LDL with sulphopolyanions: a comparison of two methods for LDL cholesterol determination

Two commercially available tests for the determination of LDL cholesterol were compared. The determination principle lies in the precipitation of LDL using heparin (Merck, Darmstadt test) or using polycyclic surface activated anions (bioMérieux test), as well as ascertaining LDL cholesterol by subtracting cholesterol in the supernatant from total cholesterol (Merck, Darmstadt test) or the direct determination of cholesterol in the redissolved precipitate (bioMérieux test). Regression analysis of the LDL cholesterol values obtained by precipitation and the LDL cholesterol values obtained by the combination of ultracentrifugation and HDL cholesterol determination (cholesterol in the d greater than 1.006 kg/l ultracentrifugation fraction- HDL cholesterol) resulted in a good correlation (precipitation using polycyclic surface activated anions: r = 0.95, y = 1.01x - 0.14, n = 34; heparin precipitation: r = 0.94, y = 0.86x + 0.10, n = 28). In sera containing triglycerides ranging from 2.28 mmol/l to 10.9 mmol/l there was an adequate agreement between the values obtained by precipitation with polycyclic surface activated anions and those of the reference method (r = 0.94, y = 0.9x + 0.47, n = 51), whereas the data obtained by heparin precipitation clearly deviated from the data of the reference method (r = 0.69, y = 0.75x + 0.003, n = 32).     

Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes

OBJECTIVE: Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT). RESEARCH DESIGN AND METHODS: Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal. RESULTS: Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002). CONCLUSIONS: Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.     

Pioglitazone reduces atherogenic dense LDL particles in nondiabetic patients with arterial hypertension: a double-blind,placebo-controlled study

OBJECTIVE: The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension. RESEARCH DESIGN AND METHODS: We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment. RESULTS: At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol. CONCLUSIONS: The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.     

Comparison of ultracentrifugation and a precipitation method for high-density lipoprotein cholesterol quantitation in insulin-dependent diabetic patients

We compared sodium phosphotungstic acid and magnesium chloride precipitation method for high-density lipoprotein (HDL) cholesterol quantitation with the ultracentrifugation method in 64 insulin-dependent diabetic patients with plasma triglyceride less than 3 mmol/l. The cholesterol content of HDL after precipitation of very-low-density lipoprotein (VLDL) and low-density lipoprotein (LDL) was 86% +/- 3% of the cholesterol content of HDL (q greater than 1.063) determined after ultracentrifugation at q = 1.063 (1.33 +/- 0.05 mmol/l vs 1.55 +/- 0.06 mmol/l; p less than 0.001). HDL cholesterol determined after precipitation closely correlated to HDL cholesterol determined after ultracentrifugation (r = 0.97; p less than 0.001). The absolute difference between the HDL cholesterol values obtained by the two methods was correlated to HDL cholesterol (ultracentrifugation) (r = 0.75; p less than 0.001), but it was not correlated to VLDL cholesterol, LDL cholesterol, triglyceride, HbA1c, blood glucose or serum albumin. LDL cholesterol calculated by use of Friedewald's formula was 108% +/- 4% of the cholesterol content of LDL (q = 1.019 to 1.063), determined after ultracentrifugation, but the calculated and the ultracentrifugally determined LDL cholesterol values were closely correlated (r = 0.98; p less than 0.001). These results suggest that during sodium phosphotungstic acid and magnesium chloride precipitation of plasma from diabetic patients, a constant fraction of HDL cholesterol is co-precipitated, resulting in a systematic difference in HDL cholesterol quantitation when compared with the ultracentrifugation method.     

Ratio of triglycerides to HDL cholesterol is an indicator of LDL particle size in patients with type 2 diabetes and normal HDL cholesterol levels

OBJECTIVE: In patients with type 2 diabetes, a normal HDL cholesterol level does not rule out that LDL particles may be small. Although techniques for analyzing LDL subfractions are not likely to be used in clinical practice, a prediction of LDL size based on a regular lipid profile may be useful for assessment of cardiovascular risk. RESEARCH DESIGN AND METHODS: Sixty patients with type 2 diabetes with acceptable glycemic control and an HDL cholesterol level > or = 1 mmol/l were recruited after cessation of lipid-altering treatments. LDL size was determined by 2-20% PAGE; patients having small LDL (n = 30) were compared with those having intermediate or large LDL (n = 30). RESULTS: Clinical characteristics, pharmacological therapies, lifestyle, and prevalence of diabetes-related complications were similar in both patient groups. LDL size correlated negatively with plasma triglycerides (TGs) (R2 = 0.52) and positively with HDL cholesterol (R2 = 0.14). However, an inverse correlation between the TG-to-HDL cholesterol molar ratio and LDL size was even stronger (R2 = 0.59). The ratio was > 1.33 in 90% of the patients with small LDL particles (95% CI 79.3-100) and 16.5% of those with larger LDL particles. A cutoff point of 1.33 for the TG-to-HDL cholesterol ratio distinguishes between patients having small LDL values better than TG cutoff of 1.70 and 1.45 mmol/l. CONCLUSIONS: The TG-to-HDL cholesterol ratio may be related to the processes involved in LDL size pathophysiology and relevant with regard to the risk of clinical vascular disease. It may be suitable for the selection of patients needing an earlier and aggressive treatment of lipid abnormalities.     

Serum lipids and apolipoproteins A-I, A-II and B in primary hypothyroidism before and during treatment

Serum lipids and apolipoproteins (apo) A-I, A-II, and B were measured in twenty-four patients with severe primary hypothyroidism (Thyrotropin above 40 mU/l), before and during 1-thyroxine treatment. Apo A-I, A-II, and B were assayed by immunonephelometry, using monospecific antisera. The serum levels of total cholesterol (TC), of low-density lipoprotein cholesterol (LDLc), and of the major LDL apoprotein, apo B, were markedly increased in the untreated hypothyroid patients compared to the values during therapy (TC: mean +/- SD, 8.87 +/- 2.9 v. 5.48 +/- 1.6 mmol/l; LDLc: 6.66 +/- 2.6 v. 3.78 +/- 1.4 mmol/l; apo B: 1.66 +/- 0.48 v. 1.14 +/- 0.37 g/l; P less than 0.00001 for all variables). High-density lipoprotein cholesterol (HDLc) was slightly higher before than during therapy (1.58 +/- 0.7 v. 1.31 +/- 0.4 mmol/l; P less than 0.05), while the main HDL apoprotein, apo A-I, was significantly elevated (1.49 +/- 0.42 v. 1.13 +/- 0.27 g/l; P less than 0.0002). The increase of the second major HDL apoprotein, apo A-II, was less pronounced (0.33 +/- 0.1 v. 0.30 +/- 0.08 g/l; P less than 0.022). The apo A-I to apo A-II ratio, which reflects the relative concentrations of the HDL subfractions HDL2 and HDL3, was significantly higher before than during treatment (P less than 0.0006). Serum triglyceride levels were moderately elevated in the untreated hypothyroid patients (1.34 +/- 0.6 v. 0.95 +/- 0.4 mmol/l; P less than 0.002). The small decrease in body weight during therapy did not correlate with the changes of the various lipid and apoprotein parameters.(ABSTRACT TRUNCATED AT 250 WORDS)     

Simvastatin and pravastatin equally improve flow-mediated dilation in males with hypercholesterolemia

BACKGROUND: Both simvastatin and pravastatin have been shown to improve endothelial function in patients with hypercholesterolemia. To our knowledge there has been no comparative study of these two HMG-CoA reductase inhibitors on endothelial dysfunction measured by flow-mediated dilation of the brachial artery in patients with hypercholesterolemia. METHODS: Fourteen middle-aged males with hypercholesterolemia (means +/- SD: total cholesterol 7.03 +/- 0.88 mmol/l, LDL cholesterol 5.02 +/- 0.63 mmol/l, HDL cholesterol 1.3 +/- 0.38 mmol/l and triglycerides 1.47 +/- 0.26 mmol/l) were randomised, after a 6 weeks' run-in phase with AHA step I diet treatment, to 12 weeks' treatment either with simvastatin or pravastatin. Both statins were given in a daily dose of 10 mg for 6 weeks, which was increased to 20 mg daily in patients who did not achieve an LDL-cholesterol goal of < 3.4 mmol/l. Endothelial dysfunction was measured as flow-mediated brachial artery dilation (FMD) using high resolution ultrasound. RESULTS: There were no significant differences between the drugs in reduction of total cholesterol, LDL cholesterol and triglycerides, or elevation of HDL cholesterol. FMD increased in the simvastatin group from 6.8 +/- 3.2 to 12.3 +/- 2.9% (p < 0.03) and in the pravastatin group from 6.3 +/- 4.8 to 13.3 +/- 4.7% (p = 0.001). The improvement in FMD was the same in both groups (p = 0.64) and did not correlate with changes of the lipid parameters measured. CONCLUSIONS: Both simvastatin and pravastatin reduce endothelial dysfunction to the same degree in patients with hypercholesterolemia, independently of changes in lipid parameters.     

Treatment with atorvastatin reduces serum adipocyte-fatty acid binding protein value in patients with hyperlipidaemia

BACKGROUND: Adipocyte-fatty acid binding protein (A-FABP) is a circulating protein expressed in adipocytes and macrophages. Several recent studies demonstrated that A-FABP might be involved in the pathogenesis of metabolic syndrome, particularly in dyslipidaemia, insulin resistance and atherosclerosis. The aim of this study was to investigate the influence of atorvastatin treatment (20 mg day(-1) for 3 months) on serum A-FABP value in subjects with hyperlipidaemia. MATERIALS AND METHODS: Anthropometric and serum analyses were performed for body mass index, A-FABP, triglycerides, total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, uric acid, alanine aminotransferase (ALT), aspartate aminotransferase (AST), high sensitive C-reactive protein (hs-CRP), creatine kinase (CK) and glucose on 26 subjects (BMI 30.3 +/- 6.0, mean age 62 +/- 10 years) with hyperlipidaemia who met the criteria: total cholesterol > 5.2 mmol L(-1), LDL cholesterol > 3.3 mmol L(-1) and triglycerides < 3 mmol L(-1). RESULTS: After the 3-month therapy, a significant reduction in total cholesterol (P < 0.001), LDL cholesterol (P < 0.001), glucose (P < 0.001), A-FABP (from 44.6 +/- 26.2 to 38.6 +/- 19.3 g L(-1), P < 0.01), uric acid (P < 0.05), AST (P < 0.05) and triglycerides (P < 0.05) values was observed. No difference was found in BMI, CK, ALT, hs-CRP, or HDL cholesterol values. A significant difference in the serum A-FABP value before and after the therapy remains after the correction for total cholesterol value (P < 0.001). A positive correlation between serum A-FABP and glucose was found (P < 0.05). CONCLUSIONS: In conclusion, our study confirmed in vivo that atorvastatin reduces serum A-FABP by a pleiotropic mechanism and supports the hypothesis that A-FABP is involved in atherosclerotic actions.     

Effects of peritoneal dialysis with an overnight icodextrin dwell on parameters of glucose and lipid metabolism.

OBJECTIVE: To examine whether a reduced daily glucose load by overnight application of the less-absorbed glucose polymer icodextrin would have favorable effects on lipid profiles of continuous ambulatory peritoneal dialysis (CAPD) patients. STUDY DESIGN: Randomized crossover study with two subsequent periods of 6 weeks. SETTING: Home PD unit of a secondary-care hospital. PATIENTS: Twenty-one nondiabetic CAPD patients (15 male, 6 female; mean age 50.3+/-11.8 years). INTERVENTION: Participants were randomly assigned to receive an overnight dwell with either standard glucose solution or with a 7.5% icodextrin-containing solution. MAIN OUTCOME MEASURES: Relation between reduction in the total amount of intraperitoneal infused glucose and parameters of glucose (plasma glucose, insulin, and HbA1C) and lipid metabolism [free fatty acids, plasma lipids, lipoproteins, and low density lipoprotein (LDL) subfraction profile]. RESULTS: After the icodextrin dwells, a reduction of plasma total cholesterol (from 5.43+/-0.85 to 4.86+/-0.70 mmol/L, p < 0.001) and LDL cholesterol (from 3.38+/-0.87 to 2.93+/-0.73 mmol/L, p = 0.001) was observed. Also, high density lipoprotein (HDL) cholesterol (from 0.95+/-0.27 to 0.90+/-0.24 mmol/L, p = 0.029) was reduced, but the plasma total cholesterol-to-HDL ratio remained similar. Plasma free fatty acids and triglyceride levels tended to decrease (from 0.16+/-0.10 to 0.13+/-0.08 mmol/L, p= 0.06, and from 2.14+/-1.96 to 1.92+/-1.03 mmol/L, respectively). Evaluation of LDL subfraction profiles after ultracentrifugation showed a more buoyant LDL subfraction profile with fewer dense LDL particles in 6 patients and no changes in 14 patients after icodextrin.The effects on lipids were not accompanied by a decrease in fasting plasma glucose (from 5.76+/-1.29 to 5.86+/-0.80 mmol/L) or insulin levels (from 19.5+/-14.4 to 20.3+/-13.0 mU/L). CONCLUSION: These results suggest a beneficial effect on lipid profiles of CAPD patients with the use of an overnight dwell with icodextrin.     

Factorial study of the effects of atorvastatin and fish oil on dyslipidaemia in visceral obesity

BACKGROUND: Dyslipidaemia may account for increased risk of cardiovascular disease in central obesity. Pharmacotherapy is often indicated in these patients, but the optimal approach remains unclear. We investigated the effects of atorvastatin and fish oil on plasma lipid and lipoprotein levels, including remnant-like particle-cholesterol and apolipoprotein C-III, in dyslipidaemic men with visceral obesity. METHODS: We carried out a 6-week randomized, placebo-controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg day(-1)) and fish oil (4 g day(-1)) on plasma lipids and lipoproteins in 52 obese men (age 53 +/- 1 years, BMI 33.7 +/- 0.55 kg m(-2)) with dyslipidaemia and insulin resistance. Treatment effects were analysed by general linear modelling. RESULTS: Atorvastatin had significant main effects in decreasing triglycerides (-0.38 +/- 0.02 mmol L(-1), P = 0.002), total cholesterol (-1.89 +/- 0.17 mmol L(-1), P = 0.001), LDL-cholesterol (-1.78 +/- 0.14 mmol L(-1), P = 0.001), remnant-like particle-cholesterol (-0.08 +/- 0.04 mmol L(-1), P = 0.035), apolipoprotein B (-49 +/- 4 mg dL(-1), P = 0.001), apolipoprotein C-III (-12.6 +/- 6.1 mg L(-1), P = 0.044) and in increasing HDL-cholesterol (+0.10 +/0- 0.04 mmol L(-1), P = 0.007). Fish oil had significant main effects in decreasing triglycerides (-0.38 +/- 0.11 mmol L(-1), P = 0.002) and in increasing HDL-cholesterol (+0.07 +/- 0.04 mmol L(-1), P = 0.041). There were no significant changes in weight or insulin resistance during the study. CONCLUSIONS: Atorvastatin and fish oil have independent and additive effects in correcting dyslipidaemia in viscerally obese men. Improvement in abnormalities in remnant lipoproteins may occur only with use of atorvastatin. Combination treatment with statin and fish oil may, however, offer an optimal therapeutic approach for globally correcting dyslipidaemia in obesity.     

Effects of dietary cholesterol and fasting on hamster plasma lipoprotein lipids

Hamsters are commonly utilized for comparative study of cholesterol metabolism. The present study was conducted to assess the effects of fasting on the plasma lipoprotein cholesterol concentrations of hamsters. Over a period of 3 weeks, adult male Golden Syrian hamsters (n = 32) were fed chow with or without the addition of 2 g/kg cholesterol. Half of the animals consuming each diet were fasted for 18 hours prior to blood sampling. Comparison of diets showed the following increases in those animals receiving cholesterol: total plasma cholesterol (180%) and triacylglycerols (75%), high density (75%), low density (250%), and very low density (560%) lipoprotein cholesterol. Compared with fasted animals, total plasma triacylglycerols were higher in both non-fasted diet groups. Compared with fasted hamsters that had received cholesterol, total plasma cholesterol (mean +/- SE mmol/l) was greater (6.36 +/- 0.18 vs 5.43 +/- 0.21; p less than or equal to 0.05) in the non-fasted group, due primarily to higher VLDL cholesterol (2.07 +/- 0.18 vs 1.58 +/- 0.18; p less than or equal to 0.05). There were no differences in HDL cholesterol (2.07 +/- 0.05 vs 2.17 +/- 0.08) or LDL cholesterol (1.29 +/- 0.08 vs 1.37 +/- 0.05) between fasted and non-fasted hamsters fed cholesterol. Fasting is not necessary for the study of the plasma HDL cholesterol and LDL cholesterol of hamsters fed cholesterol.     

Differing associations of lipid and lipoprotein disturbances with the macrovascular and microvascular complications of type 1 diabetes.

OBJECTIVE: Cardiovascular disease (CVD) is increased in patients with type 1 diabetes, but lipid and lipoprotein patterns remain favorable. In contrast, nephropathy is associated with an adverse distribution. We compared the associations and predictive power of lipid and lipoprotein disturbances with these complications. RESEARCH DESIGN AND METHODS: A nested case-control study from the EURODIAB cohort of 140 case subjects with evidence of at least one complication and 84 control subjects with no complications were analyzed. Conventional and unconventional lipid and lipoprotein fractions, including apolipoprotein (apo)-A1, lipoprotein (Lp)-A1, LpA1/A2, apoB, and LDL particle size were measured centrally. RESULTS: CVD was only associated with increased LDL cholesterol (3.6 vs. 3.0 mmol/l, P = 0.02). In contrast, albuminuria was associated with elevated cholesterol, triglyceride, LDL, and apoB and with diminished LDL particle size. No disturbances in HDL and related lipoproteins were noted. In normoalbuminuric patients, CVD was not associated with any significant changes in lipids. CVD in macroalbuminuric patients was associated with increased triglyceride level (2.37 vs. 1.07 mmol/l, P = 0.001; P = 0.02 for CVD/albuminuria interaction) and LDL cholesterol (5.4 vs. 3.3 mmol/l, P = 0.005; P = 0.004 for interaction). Independent associations were observed for total cholesterol and for LDL particle size and albuminuria. CONCLUSIONS: Abnormalities in lipid and lipoprotein disturbances are more closely related to albuminuria than to CVD in patients with type 1 diabetes. Measurement of conventional parameters provide sufficient risk information. ApoB and LDL particle size offer limited extra information. HDL metabolism remains undisturbed in the presence of complications. These changes reflect associations with glycemic control, which is the key to understanding lipid and lipoprotein disturbances.     

High protein diet complements resin therapy of familial hypercholesterolemia.

The intermediate-term effects on plasma lipoprotein lipids of substituting meat and dairy protein for carbohydrate in the diets of five subjects (three women, two men) with familial hypercholesterolemia receiving cholestyramine (mean dose, 18 g/d) were studied. Subjects were randomly allocated to either the high or low protein diets (mean 27 versus 10% of energy as protein, 25% as fat, and 48 versus 65% as carbohydrate) for 4 to 5 weeks and then switched to the other diet for another 4 to 5 weeks. Mean fasting plasma HDL cholesterol rose significantly by 17 +/- 3% (1.11 +/- 0.12 vs 0.95 +/- 0.11 mmol/L, p less than 0.005, n = 5), whereas total triglycerides fell by 23 +/- 2% (1.7 +/- 0.3 vs 2.2 +/- 0.3 mmol/L, p less than 0.005, n = 5), VLDL triglycerides fell by 28 +/- 5% (0.88 +/- 0.15 vs 1.18 +/- 0.19 mmol/L, p less than 0.02, n = 5), VLDL cholesterol fell by 32 +/- 7% (0.39 +/- 0.08 vs 0.56 +/- 0.09 mmol/L, p less than 0.01, n = 5), the ratio of LDL cholesterol: HDL cholesterol by 19 +/- 5% (4.7 +/- 0.7 vs 5.7 +/- 0.7, p less than 0.05) and that of total cholesterol: HDL cholesterol by 16 +/- 5% (6.6 +/- 0.5 vs 8.0 +/- 0.7, p less than 0.05) on the high versus low protein diet. Increasing dietary protein intake at the expense of carbohydrate may be useful in treating hypoalphalipoproteinemia and/or hypertriglyceridemia in patients with familial hypercholesterolemia.     

Treatment for dyslipidemias in patients with arterial hypertension

AIM: To evaluate a combination of the effects of non-drug measures and rozuvastatin on the lipid spectrum and blood pressure (BP) in patients with treated arterial hypertension (AH) concurrent with dyslipidemia. MATERIALS AND METHODS: The multicenter open-labeled prospective program included 299 patients from 19 cities and towns of Russia. Two hundred and eighty-eight patients completed phase 1 of the program; out of them 279 patients (149 males and 130 females) aged 58-80 years (56.7 +/- 8.7 years) with a mean AH history of 10.3 +/- 8.4 years. Phase 1 of the program involved 3 visits and it was over 12 weeks after rozuvastatin therapy. Phase 2 (including a visit 12 weeks following the termination of Phase 1) is being continued. RESULTS: Rozuvastatin therapy resulted in a reduction in the levels of total cholesterol (TC) by 2.5 +/- 0.8 mmol/l (p < 0.001), low-density lipoprotein (LDL) cholesterol by 2.2 +/- 0.8 mmol/l (p < 0.001), triglycerides (TG) by 0.8 +/- 0.9 mmol/l (p < 0.001), and atherogenicity index (AI) by 2.8 +/- 1.4 (p < 0.001) and an increase in the content of high-density lipoprotein (HDL) cholesterol by 0.2 +/- 0.2 mmol/l (p < 0.001), which produced the target levels of LDL cholesterol in 61% of the patients, HDL cholesterol in 70%, and TG in 73%. During unaltered antihypertensive therapy there were also decreases in body mass by 1.5 +/- 2.8 mmol/l (p < 0.001), body mass index by 0.5 +/- 1.0 kg/ m2 (p < 0.001), waist circumference by 1.0 +/- 3.2 cm (p < 0.001), and BP by 72 +/- 14.2/4.1 +/- 8.6 mm Hg (p < 0.001). There was an increase in the activity of aspartate aminotransferase and alanine aminotransferase, and creatine phosphokinase; however, this was clinically significant in none patients. CONCLUSION: Rozuvastatin significantly lowers the levels of TC, LDL cholesterol, TG, and AI and elevates the concentration of HDL cholesterol. In the majority (83%) of the patients, rozuvastatin used in a dose of 10 mg/day was sufficient to normalize the lipid profile, which makes it possible to recommend that rozuvastatin therapy should be started from this dose.     

Preclinical atherosclerosis and inflammation in 61-year-old men with newly diagnosed diabetes and established diabetes

OBJECTIVE: The aim of this study was to investigate the occurrence of subclinical atherosclerosis and underlying mechanisms in men with newly diagnosed diabetes and established diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: In a population-based study of 61-year-old Caucasian men (n = 271) with established diabetes (n = 50) and newly diagnosed diabetes (n = 24) and healthy control subjects (n = 197), standard risk factors and highly sensitive (hs) C-reactive protein (CRP) were measured. Ultrasound measurements of intima-media thickness (IMT) were performed bilaterally in the common carotid artery, and a composite measure was calculated from common carotid and carotid bulb IMT (composite IMT). The plaque status was assessed. RESULTS: Composite IMT and carotid plaque size increased gradually among the healthy control subjects, newly diagnosed diabetic patients, and established diabetic patients (P for trend < or =0.001, respectively). CRP was higher in newly and established diabetes (NS between diabetes groups) compared with healthy control subjects (P < 0.001). Total cholesterol levels were lower in newly diagnosed diabetes (5.51 +/- 1.13 mmol/l, P < 0.05) and established diabetes (5.45 +/- 1.15 mmol/l, P < 0.01) compared with those of healthy control subjects (5.77 +/- 1.03 mmol/l). In men with diabetes (n = 74), diabetes onset status (newly diagnosed versus established), waist-to-hip ratio (WHR), and serum triglycerides, but not CRP, explained 16% of the variance in composite IMT. CONCLUSIONS: This is the first study to show increased preclinical atherosclerotic changes (IMT and plaque size) and increased inflammation (hs-CRP) in men with newly diagnosed diabetes as well as in patients with established diabetes compared with healthy control subjects. WHR, diabetes onset status (newly diagnosed versus established), and triglycerides, but not CRP, were independent correlates of carotid artery IMT in men with diabetes.     

Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa

Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.     

HIV-positive patients treated with protease inhibitors have vascular changes resembling those observed in atherosclerotic cardiovascular disease

A metabolic syndrome associated with atherosclerosis and cardiovascular disease has been described in HIV-positive individuals. In the present study we investigated whether HIV-positive individuals and CAD (coronary artery disease) patients have similarities in their vascular function and structure. In a case-control study, we compared measurements of carotid artery IMT (intima-media thickness) and brachial artery FMD (flow-mediated vasodilation) in HIV-positive individuals with age- and sex-matched controls with similar risk factors and patients with established CAD. Seventy-one HIV patients, age 42+/-13.9 years (91% male), were compared with 29 CAD patients and 25 controls. HIV patients had higher IMT than controls and similar IMT to CAD patients (0.64+/-0.2 compared with 0.55+/-0.05 and 0.66+/-0.08 mm respectively; F=4.2, P=0.01). Patients taking protease inhibitors had higher IMT (0.69+/-0.2 compared with 0.57+/-0.15 mm; P=0.01), blood pressure, cholesterol and triacylglycerols than those not taking protease inhibtors (P<0.05). In multiple regression analyses, increasing blood pressure (beta: 0.37, P=0.001), glucose (beta: 0.26, P=0.016), cholesterol (beta: 0.24, P=0.033), duration of HIV disease (beta: 0.33, P=0.008) and use of protease inhibitors (beta: 0.27, P=0.04) were the most important determinants of IMT respectively. FMD was associated only with triacylglycerol measurements. Patients with HIV present arterial changes resembling those found in patients with atherosclerotic cardiovascular disease. These vascular changes are closely related to protease-inhibitor-induced changes of metabolic parameters. Thus intensive treatment of these metabolic parameters might retard atherosclerosis in HIV patients.     

Comparison of vildagliptin and rosiglitazone monotherapy in patients with type 2 diabetes: a 24-week, double-blind, randomized trial

OBJECTIVE: To compare the efficacy and tolerability of vildagliptin and rosiglitazone during a 24-week treatment in drug-na?ve patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: This was a double-blind, randomized, active-controlled, parallel-group, multicenter study of 24-week treatment with vildagliptin (100 mg daily, given as equally divided doses; n = 519) or rosiglitazone (8 mg daily, given as a once-daily dose; n = 267). RESULTS: Monotherapy with vildagliptin and rosiglitazone decreased A1C (baseline = 8.7%) to a similar extent during the 24-week treatment, with most of the A1C reduction achieved by weeks 12 and 16, respectively. At end point, vildagliptin was as effective as rosiglitazone, improving A1C by -1.1 +/- 0.1% (P < 0.001) and -1.3 +/- 0.1% (P < 0.001), respectively, meeting the statistical criterion for noninferiority (upper-limit 95% CI for between-treatment difference < or =0.4%). Fasting plasma glucose decreased more with rosiglitazone (-2.3 mmol/l) than with vildagliptin (-1.3 mmol/l). Body weight did not change in vildagliptin-treated patients (-0.3 +/- 0.2 kg) but increased in rosiglitazone-treated patients (+1.6 +/- 0.3 kg, P < 0.001 vs. vildagliptin). Relative to rosiglitazone, vildagliptin significantly decreased triglycerides, total cholesterol, and LDL, non-HDL, and total-to-HDL cholesterol (-9 to -16%, all P < or = 0.01) but produced a smaller increase in HDL cholesterol (+4 vs. +9%, P = 0.003). The proportion of patients experiencing an adverse event was 61.4 vs. 64.0% in patients receiving vildagliptin and rosiglitazone, respectively. Only one mild hypoglycemic episode was experienced by one patient in each treatment group, while the incidence of edema was greater with rosiglitazone (4.1%) than vildagliptin (2.1%). CONCLUSIONS: Vildagliptin is an effective and well-tolerated treatment option in patients with type 2 diabetes, demonstrating similar glycemic reductions as rosiglitazone but without weight gain.     

Clinical usefulness of different lipid measures for prediction of coronary heart disease in type 2 diabetes: a report from the Swedish National Diabetes Register

OBJECTIVE

We assessed the association between different blood lipid measures and risk of fatal/nonfatal coronary heart disease (CHD).

RESEARCH DESIGN AND METHODS

We conducted an observational study of patients with type 2 diabetes from the Swedish National Diabetes Register. Baseline LDL cholesterol, non-HDL cholesterol, ratio of non-HDL to HDL cholesterol (non-HDL:HDL), and ratio of triacylglycerol to HDL cholesterol (TG:HDL) was measured in 18,673 patients aged 30–70 years, followed for a mean of 4.8 years from 2003 to 2007.

RESULTS

Hazard ratios (HRs) for CHD per 1-SD increment in lipid measures were 1.23 with non-HDL:HDL, 1.20 with non-HDL cholesterol, 1.17 with LDL cholesterol, and 1.15 with TG:HDL (all P < 0.001 when adjusted for clinical characteristics and nonlipid risk factors). The best global model fit was found with non-HDL:HDL. When patients within the lowest tertile of a lipid measure were compared with those with all lipid measures within the highest tertile, the adjusted HR for CHD was 0.62 with non-HDL:HDL <3.5 mmol/L, 0.65 with non-HDL cholesterol <3.3 mmol/L, and 0.70 with LDL cholesterol <2.5 mmol/L (all P < 0.001). The lowest tertile of LDL and non-HDL cholesterol corresponded with treatment targets according to U.S. and European guidelines. HRs for CHD were 0.52, 0.62, and 0.66 with the lowest deciles of non-HDL:HDL, non-HDL cholesterol, and LDL cholesterol ≤1.8 mmol/L (all P < 0.001). Mean TG:HDL was considerably lower in patients within the lowest tertile of non-HDL:HDL, 0.82 ± 0.47, than in those within the lowest tertile of LDL cholesterol (<2.5 mmol/L), 1.49 ± 1.03.

CONCLUSIONS

Non-HDL:HDL had a stronger effect on CHD risk than LDL cholesterol, and low TG:HDL values were more often seen within the lowest non-HDL:HDL tertile than within the lowest LDL cholesterol tertile. LDL cholesterol was not the best predictor of CHD risk in type 2 diabetes.Randomized controlled clinical trials have established the clinical benefits of lowering LDL cholesterol levels for risk reduction of coronary heart disease (CHD) (1). The National Cholesterol Education Program Adult Treatment Panel (ATP) III (2) and the American Diabetes Association (3) have recommended LDL cholesterol <2.5 mmol/L as the primary treatment goal in patients with diabetes and hyperlipidemia.ATP III has also identified non-HDL cholesterol (the sum of LDL and VLDL) <3.3 mmol/L as a secondary treatment target in patients with triacylglycerol >2.3 mmol/L or HDL cholesterol <1.0 mmol/L (2). European guidelines recommend the same targets for LDL and non-HDL cholesterol (4,5), and these as well as those of the U.S. National Cholesterol Education Program (1) and the American Diabetes Association (3) have also recently underlined LDL cholesterol ≤1.8 mmol/L as an optional goal for patients with diabetes and overt cardiovascular disease (CVD).Against this background, we assessed the clinical usefulness of several lipid measures with regard to the risk of CHD in an observational study of 18,673 patients with type 2 diabetes in the Swedish National Diabetes Register (NDR). The main aim was to evaluate LDL cholesterol as a risk factor in comparison with the ratio of non-HDL cholesterol to HDL cholesterol (non-HDL:HDL).