Low HDL‐cholesterol is common in European Type 2 diabetic patients receiving treatment for dyslipidaemia: data from a pan‐European survey

Aims To measure the prevalence of low high‐density lipoprotein (HDL)‐cholesterol (men < 1.03 mmol/l; women < 1.29 mmol/l) in European Type 2 diabetic patients receiving treatment for dyslipidaemia. Methods The pan‐European Survey of HDL‐cholesterol measured lipids and other cardiovascular risk factors in 3866 patients with Type 2 diabetes and 4436 non‐diabetic patients undergoing treatment for dyslipidaemia in 11 European countries. Results Diabetic patients were more likely to be obese or hypertensive than non‐diabetic patients. Most patients received lifestyle interventions (87%) and/or a statin (89%); treatment patterns were similar between groups. Diabetic patients had [means (SD)] lower HDL‐cholesterol [1.22 (0.37) vs. 1.35 mmol/l (0.44) vs. non‐diabetic patients, P < 0.001] and higher triglycerides [2.32 (2.10) vs. 1.85 mmol/l (1.60), P < 0.001]. More diabetic vs. non‐diabetic patients had low HDL‐cholesterol (45% vs. 30%), high triglycerides (≥ 1.7 mmol/l; 57% vs. 42%) or both (32% vs. 19%). HDL‐cholesterol < 0.9 mmol/l was observed in 18% of diabetic and 12% of non‐diabetic subjects. Differences between diabetic and non‐diabetic groups were slightly greater for women. LDL‐ and total cholesterol were lower in the diabetic group [3.02 (1.05) vs. 3.30 mmol/l (1.14) and 5.12 (1.32) vs. 5.38 mmol/l (1.34), respectively, P < 0.001 for each]. Conclusions Low HDL‐cholesterol is common in diabetes: one in two diabetic women has low HDL‐cholesterol and one diabetic man in four has very low HDL‐cholesterol. Management strategies should include correction of low HDL‐cholesterol to optimize cardiovascular risk in diabetes.     

Serum triglycerides and HDL cholesterol -- major predictors of long-term survival after coronary surgery

The influence of pre-operative serum lipid levels on late clinicaloutcome after coronary artery bypass surgery was analysed in83 patients undergoing coronary bypass surgery for stable anginapectoris. The mean follow-up period for surviving patients was105±33 months (range 65–133). Twenty-two patients(27%) had died during follow-upt of whom 14 had sustained afatal myocardial infarction and four had succumbed to othercardiovascular causes. Thirty-one patients sustained 35 cardiacevents, defined as either fatal or non-fatal myocardial infarction,or reoperation, or PTCA during the follow-up period. With univariateanalysis, pre-operative serum levels of total cholesterol andtriglycerides were significantly related to cardiac events,P<0.05 and P<0.05, respectively. In a Cox proportionalanalysis, cardiac mortality and total mortality were relatedto serum triglycerides and HDL cholesterol (P<0.05 and P<0.01respectively). Eighty-five percent of the patients with triglycerides<2.0 mm. l^–1 survived for 10 years, while only 48%of patients with triglycerides >2.0 mM. 1^–1 remainedalive for that period. Figures were similar for subjects withHDL cholesterol >1.0mM. I^–1 or HDL cholesterol <1.0mM. I^–1, at 89 and 38%, respectively. Only 28% of the patients with the combination triglycerides>2.0 mM. I^–1 and HDL cholesterol <1.0 mM. I^–1were alive 10 years after surgery. These data suggest that dyslipidaemia,especially the combination of high serum triglycerides and lowHDL cholesterol, is an important factor influencing long-termclinical outcome after coronary bypass surgery.     

High-density lipoprotein cholesterol and coronary, cardiovascular and all cause mortality among middle-aged Norwegian men and women.

From 1977 to 1982 screening for cardiovascular disease was performed in three Norwegian counties. All those aged between 40 and 54 years were invited, of whom 23,690 men and 23,425 women (90%) attended. Smoking habits and previous cardiovascular disease were recorded; total cholesterol, high-density lipoprotein cholesterol (HDL cholesterol), triglycerides and blood pressure were measured. During subsequent follow-up (mean 6.8 years) 422 men and 54 women died from coronary heart disease, 514 and 114 from all cardiovascular diseases and 983 and 404 from all causes, men and women respectively. For men, mortality decreased with increasing HDL cholesterol, to a minimum of around 1.5 mmol.l-1 (58 mg.dl-1), whereafter mortality increased. This applies to coronary, cardiovascular and all causes of death, as well as to men with and without a history of disease. The association between mortality and HDL cholesterol in healthy men disappeared when total cholesterol was below 6.5 mmol.l-1 (251 mg.dl-1). The inverse association between mortality and HDL cholesterol in women was somewhat stronger than in men, both for coronary and cardiovascular diseases. The relative risks of coronary death, associated with an increase in HDL cholesterol of 0.5 mmol.l-1 (19 mg.dl-1), from the Cox proportional hazards regression, with other major cardiovascular risk factors as covariates, were 0.8 (95% confidence interval: 0.6, 1.0) and 0.8 (0.7, 1.0) for men with and without history of disease, respectively. Corresponding figures for women were 0.5 (0.3, 0.9) and 0.7 (0.4, 1.3).     

Risk factors for a major coronary event after myocardial infarction in the Scandinavian Simvastatin Survival Study (4S). Impact of predicted risk on the benefit of cholesterol-lowering treatment.

AIMS: To analyse (1) the prognostic importance of clinical findings and lipids in patients with a previous myocardial infarction and (2) the relative and absolute benefit of simvastatin in patients at low, medium and high predicted risk. METHODS: The 4S was a double-blind, randomized, clinical trial of long-term treatment with simvastatin or matching placebo in patients with myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol x l(-1), and serum triglycerides 相似文献   

Double-blind placebo-controlled study of the effects of bezafibrate on blood lipids, lipoproteins, and fibrinogen in hyperlipidaemic type 1 diabetes mellitus

The effects of bezafibrate 400 mg day-1 or placebo administered for 3 months, were compared in 36 patients with stable Type 1 diabetes and hypercholesterolaemia and/or hypertriglyceridaemia. Baseline characteristics of the 17 bezafibrate- and 19 placebo-treated patients were comparable in most respects with the exception of concentrations of fasting serum triglycerides and blood glucose which were lower (NS) and plasma fibrinogen which were higher (p less than 0.05), in those later treated with bezafibrate. Serum cholesterol concentrations decreased after 3 months bezafibrate treatment (from 7.1(0.2) (SE) to 6.3 (0.3) mmol l-1, p less than 0.05), predominantly due to a reduction in low density lipoprotein (LDL) cholesterol (from 4.8(0.3) to 4.2(0.3) mmol l-1, p less than 0.05). Over the same period bezafibrate reduced serum triglycerides from 1.78 (95% Cl 1.23-2.57) to 1.26(1.02-2.09) mmol l-1 (p less than 0.05), and plasma fibrinogen from 4.1(0.2) to 2.9(0.2) g l-1, p less than 0.001. Serum apolipoprotein B and apolipoprotein (a) showed no statistically significant changes. Overall there was no change in high density lipoprotein (HDL) cholesterol. However, in patients who were initially hypertriglyceridaemic there was significant increase in the cholesterol content of HDL and the HDL2-cholesterol subfraction (both p less than 0.05). After 3 months treatment with bezafibrate, fasting blood glucose levels were reduced from 8.5(1.1) to 6.4(0.7) mmol l-1, p less than 0.05, without any change in glycosylated haemoglobin (9.2(0.4) to 9.1(0.5)%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical significance of HbA<Subscript>1c</Subscript> as a marker of circulating lipids in male and female type 2 diabetic patients

Diabetic patients with accompanied (but often unnoticed) dyslipidemia are soft targets of cardiovascular deaths. An early intervention to normalize circulating lipids has been shown to reduce cardiovascular complications and mortality. Glycated hemoglobin (HbA_1c) is a routinely used marker for long-term glycemic control. This investigation is an attempt to evaluate the diagnostic value of HbA_1c in predicting diabetic dyslipidemia. Venous blood samples were collected from 2,220 type 2 diabetic patients (ages, 35–91 years; male/female ratio, 1.07). The sera were analyzed for HbA_1c, fasting blood glucose (FBG), total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL). The levels of HbA_1c did not differ significantly between males (8.33 ± 0.06%) and females (8.47 ± 0.07%), whereas female patients had significantly higher FBG (10.01 ± 0.13 mmol/l) than males (9.31 ± 0.11 mmol/l). HbA_1c showed direct and significant correlations with cholesterol, triglycerides and LDL and inverse correlation with HDL. Female diabetic patients had significantly higher levels of serum cholesterol (5.42 ± 0.03 vs. 5.18 ± 0.03 mmol/l) and HDL (1.32 ± 0.01 vs. 1.12 ± 0.01 mmol/l) as compared to males. There was no significant difference in triglycerides and LDL between the two genders. Older patients (>70 years) had significantly lower FBG, cholesterol, triglycerides and LDL. There was a linear and significant increase in triglycerides in the patients of both genders with impaired glycemic control. Both male and female patients with worse glycemic control (HbA_1c > 9%) had significantly high cholesterol and LDL levels. Serum HDL showed a significant and inverse relationship with uncontrolled hyperglycemia in females but not in males. These findings clearly suggest that HbA_1c can provide valuable supplementary information about the extent of circulating lipids besides its primary role in monitoring long-term glycemic control. Further studies are warranted to reinforce the potential of HbA_1c as a biomarker for screening of high-risk diabetic patients.     

Close correlation between high-density lipoprotein and triglycerides in normotriglyceridaemia.

The relationship between high-density-lipoprotein (HDL) particle size subclasses and the levels of the major lipoprotein lipids was studied in 74 men consecutively referred to the lipid clinic. HDL (density 1.070-1.21 kg l-1) was separated by polyacrylamide gradient gel electrophoresis (GGE) into five size-defined subclasses, in order of decreasing size as follows: HDL2b, HDL2a, HDL3a, HDL3b and HDL3c. Cholesterol and triglyceride concentrations in very-low-density (VLDL), low-density (LDL) and high-density (HDL) lipoproteins were determined. The level of VLDL triglycerides was negatively correlated with HDL2b (r = -0.66, P less than 0.0001), and positively correlated with HDL3b concentrations (r = 0.65, P less than 0.0001). Both correlations were restricted to subjects with VLDL triglyceride concentrations of less than 1.80 mmol l-1, i.e. those with normotriglyceridaemia. Patients with a history of myocardial infarction and/or angina pectoris (n = 18) had significantly lower HDL2b levels than subjects with asymptomatic hyperlipidaemia (n = 50), i.e. 0.16 vs. 0.22 mg protein ml-1 (P less than 0.05), despite essentially similar cholesterol and triglyceride levels in the VLDL, LDL and HDL fractions, including HDL2 and HDL3 cholesterol.     

The effect of acipimox in patients with type 2 diabetes and persistent hyperlipidaemia.

A placebo-controlled, double-blind study was performed to assess the effect of 12 weeks treatment with acipimox (250 mg three times per day) on lipoproteins and glycaemic control in patients with Type 2 diabetes. All patients studied had persistent hyperlipidaemia despite acceptable glycaemic control on treatment with diet alone or diet and oral hypoglycaemic agents, achieving glycosylated haemoglobin (HbA1) of less than 10.5% but with fasting total triglycerides greater than 2.5 mmol l-1 or total cholesterol greater than 6.5 mmol l-1. Forty-eight patients were randomized to treatment, 21 to acipimox and 27 to placebo; 43 completed the trial. All patients had been diabetic for at least 1 year. Total cholesterol fell by 6% and total triglycerides by 19% following 12 weeks of acipimox, compared to rises in the placebo group of 1% and 16%, respectively (p less than 0.05). There were no significant differences between acipimox and placebo in the change in low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, apolipoproteins AI, AII, or B, or in glycaemic control during the treatment period. Acipimox is effective in reducing fasting total cholesterol and total triglycerides in patients with Type 2 diabetes with acceptable blood glucose control but persistent hyperlipidaemia. Acipimox does not adversely affect glucose tolerance.     

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study

We report the results of a randomized single-centre study designedto assess the effects of simvastatin on blood lipids, bloodbiochemistry, haematology and other measures of safety and tolerabilityin preparation for a large-scale multicentre mortality study.Six hundred and twenty-one individuals considered to be at increasedrisk of coronary heart disease were randomized, following a2-month placebo ‘run-in’ period, to receive 40 mgdaily simvastatin, 20 mg daily simvastatin or matching placebo.Their mean age was 63 years, 85% were male, 62% had a historyof prior myocardial infarction (MI), and the mean baseline totalcholesterol was 7·0 mmol. 1^–1. Median follow-upin the present report is 3·4 years. Eight weeks after randomization, 40 mg daily simvastatin hadreduced non-fasting total cholesterol by 29·2% ±1·1 (2·03 ± 0·08 mmol. 1^–1)and20 mg daily simvastatin had reduced it by 26·8% ±1·0 (1·87 ± 0·07 mmol. 1^–1).Almost all of tile difference in total cholesterol at 8 weekswas due to the reduction in LDL cholesterol (40·8±1·6and 38·2%±1·4 among patients allocated40mg and 20mg of simvastatin daily respectively), but simvastatinalso reduced triglycerides substantially (19·0% and 17·3%)and produced a small increase in HDL cholesterol (6·4%and 4·8%). These effects were largely sustained overthe next 3 years, with 40 mg daily simvastatin producing a slightlygreater reduction in total cholesterol at 3 years (25·7%±1·9reduction) than did 20 mg daily simvastatin (22·2%±1·8). There were no differences between the treatment groups in thenumbers of reports of ‘possible adverse effects’of treatment or of a range of different symptoms or conditions(including those related to sleep or mood) recorded at regularclinic follow-up. Mean levels of alanine aminotransferase, aspartateaminotransferase and creatine kinase were slightly increasedby treatment, but there were no significant difference betweenthe treatment groups in the numbers of patients with significantlyelevated levels. A slightly lower platelet count in the simvasatingroup was the only haematological difference from placebo, withno difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced largesustained reductions in total cholesterol, LDL cholesterol andtriglyceride and small increases in HDL cholesterol. They werewell tolerated, with no evidence of serious side-effects duringthe first 3 years of this study. Consequently, simvastatin providesan opportunity to conduct large randomized studies that assessthe effects of cholesterol lowering on total mortality and oncause-spec mortality. Even with such an effective cholesterollowering treatment, however such mortality studies will stillneed to be prolonged and to involve some tens of thousands ofpatients at substantial risk of coronary heart disease if clearevidence is to emerge.     

Influence of baseline lipids on effectiveness of pravastatin in the CARE trial

Objectives. We sought to assess the influence of baseline lipid levels on coronary event rates and the effectiveness of pravastatin therapy in the Cholesterol And Recurrent Events (CARE) study.Background. The CARE study cohort provided a relatively unique opportunity to examine the relation between lipid levels and clinical events in a post–myocardial infarction (MI) population with relatively low cholesterol and low density lipoprotein (LDL) cholesterol values.Methods. There were 4,159 patients with a previous infarct and a total cholesterol level <240 mg/dl, LDL cholesterol level 115 to 174 mg/dl and triglyceride level <350 mg/dl randomly allocated to placebo (n = 2,078) or pravastatin 40 mg/day (n = 2,081). Time to either coronary death or nonfatal MI (primary end point) or to the secondary end point, which included undergoing a coronary revascularization procedure, was determined as a function of baseline lipids (total, LDL, high density lipoprotein [HDL] cholesterol and triglyceride levels).Results. Quartile analysis indicated important effects for LDL cholesterol, in which a higher LDL was associated with greater cardiac event rates (in the placebo group, every 25-mg/dl increment in LDL was associated with a 28% increased risk [5% to 56%, p = 0.015]) in the primary event. The differential event rates with respect to baseline LDL cholesterol for placebo and pravastatin groups reduced the difference in clinical outcomes at lower LDL cholesterol levels. In both the placebo and pravastatin groups, an inverse relation between baseline HDL cholesterol and cardiac events was observed (10 mg/dl lower baseline HDL cholesterol level was associated with a 10% [0% to 19%, p = 0.046] increase in coronary death or nonfatal MI).Conclusions. Within the LDL cholesterol levels in CARE (115 to 174 mg/dl), baseline values influenced both the risk of events in the placebo group as well as the clinical effectiveness of pravastatin therapy.     

The interaction between hyperuricemia and low-density lipoprotein cholesterol increases the risk of 1-year post-discharge all-cause mortality in ST-segment elevation myocardial infarction patients

Background and aimsHyperuricemia is a known risk factor for cardiovascular diseases, but little is known on whether the association between hyperuricemia and poor outcomes in ST-segment elevation myocardial infarction (STEMI) is modified by low-density lipoprotein cholesterol (LDL-c). This study aimed to investigate the effect of the interaction between hyperuricemia and LDL-c on the risk of 1-year post-discharge all-cause mortality in STEMI patients.Methods and resultsA total of 1396 STEMI patients were included. Cox proportional hazards models were used to determine the association between hyperuricemia and 1-year all-cause mortality in the overall population and subgroups stratified based on LDL-c levels (<3.0 mmol/L or ≥3.0 mmol/L). Multivariate analysis indicated that hyperuricemia was associated with 1-year mortality (HR: 2.66; 95% CI: 1.30–5.47; p = 0.008). However, the prognostic effect of hyperuricemia was only observed in patients with LDL-c level ≥3.0 mmol/L (HR: 12.90; 95% CI: 2.98–55.77; p < 0.001), but not in those with LDL-c level <3.0 mmol/L (HR: 0.91, 95% CI: 0.30–2.79, p = 0.875). The interaction between hyperuricemia and LDL-c levels had a significant effect on 1-year mortality.ConclusionHyperuricemia was associated with increased 1-year post-discharge mortality in patients with LDL-c level≥ 3.0 mmol/L, but not in those with LDL-c level< 3.0 mmol/L.     

Gemfibrozil treatment of the high triglyceride-low high-density lipoprotein cholesterol trait in men with established atherosclerosis

Abstract. Objective. To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the ‘high triglyceride-low high-density lipoprotein (HDL) cholesterol trait”. Design. Double-blind randomized placebo controlled prospective trial. Setting. Amsterdam Lipid Research Clinic at the Academic Medical Centre of the University of Amsterdam and the Slotervaart Training Hospital affiliated to the University of Amsterdam, Amsterdam, the Netherlands. Subjects. Thirty-five male patients, age 30–70, with established atherosclerosis and the high triglyceride-low HDL cholesterol trait. Main outcome measures. Plasma total cholesterol, triglycerides, lipoproteins, apolipoproteins A₁ and B₁₀₀, clinical and laboratory safety parameters. Results. Seventeen patients in the gemfibrozil group and 16 patients in the placebo group completed the study period. Compliance was considered adequate. Mean (± standard deviation) plasma HDL cholesterol levels increased 20.3% (±12.22) from 0.82 to 0.99 mmol L^?1 in the gemfibrozil group against 9.9% (±18.31) from 0.79 to 0.87 mmol L^?1 in the placebo group (P = 0.001). Mean plasma triglyceride level fell 49.5% (±14.27) from 3.65 to 1.82 mmol L^?1 in the gemfibrozil group against an increase of 13.6% (±40.31) from 3.62 to 4.01 mmol L^?1 in the placebo group (P < 0.001). Although plasma HDL cholesterol and triglyceride levels improved in all patients, normalization of these lipoproteins was only observed in approximately half of them. Plasma total and low-density lipoprotein (LDL) cholesterol levels, as well as plasma levels of apolipoprotein (apo) A₁, B₁₀₀ and lipoprotein [Lp(a)], did not show significant alterations compared to the placebo. All safety parameters were comparable between the two groups and remained within the reference limits. Gemfibrozil was well tolerated during treatment. Minor inconveniences were equally distributed between the two treatment groups. Conclusions. Gemfibrozil is an effective and safe drug in patients with coronary heart disease (CHD) and the high triglyceride-low HDL cholesterol trait.     

Placebo-controlled trial of the effects of guar gum and metformin on fasting blood glucose and serum lipids in obese, type 2 diabetic patients

Nineteen obese patients with Type 2 diabetes mellitus were treated for periods of 3 months with placebo, guar gum (5 g three times daily) and metformin (500 mg three times daily) in a randomized double-blind, double-placebo, cross-over study. Both active agents decreased fasting blood glucose from 11.4 +/- 3.7 mmol l-1 (mean +/- SD) to 8.6 +/- 2.8 mmol l-1 on metformin (p less than 0.001) and to 9.5 +/- 3.9 mmol l-1 on guar gum (p less than 0.01). Metformin significantly reduced the very low density lipoprotein (VLDL) cholesterol concentration from 0.62 (+0.73, -0.34) mmol l-1 (geometric mean (+SD, -SD)) to 0.43 (+0.58, -0.25) mmol l-1, (p less than 0.02), but unless hyperlipidaemia was present there were no changes in other serum lipid or lipoprotein levels. In patients with serum cholesterol greater than 6.5 mmol l-1 decreases in serum triglycerides from 3.29 (+3.27, -1.64) to 2.46 (+2.55, -1.25) mmol l-1 (p less than 0.02) occurred with metformin. In these patients guar gum produced a reduction in serum cholesterol (from 7.70 +/- 0.90 to 6.41 +/- 1.11 mmol l-1, p less than 0.01) due to an effect on low density lipoproteins. These differential effects may be important in planning therapy when hyperlipidaemia accompanies Type 2 diabetes.     

Effects of dietary cholesterol on plasma lipoproteins and their subclasses in IDDM patients

Summary To compare the effects of dietary cholesterol supplementation in insulin-dependent diabetic (IDDM) patients and normal subjects, 10 male IDDM patients in good glycaemic control (HbA_{1 c} 7.3 ± 0.9 %) (mean ± SD) and normal plasma lipid levels, and 11 control male subjects of similar age, body mass index and lipid plasma levels underwent a double blind, cross-over, sequential study. Cholesterol supplementation of 800 mg/day or placebo were given for consecutive periods of 3 weeks. The concentration of plasma total cholesterol increased significantly with the dietary cholesterol supplementation compared to placebo in IDDM patients by 6 % (p < 0.05) and in control subjects by 9 % (p < 0.05). No changes were observed in the concentration of plasma triglycerides in either group. The LDL cholesterol level increased by 12 % (p < 0.01) in patients and by 7 % (p < 0.05) in control subjects. In patients plasma HDL cholesterol concentration remained the same, while in control subjects it tended to increase after cholesterol supplementation (from 1.14 ± 0.26 to 1.23 ± 0.27 mmol/l, p = 0.06). During the cholesterol intake period the mean concentration of LDL1, LDL2 and LDL3 subclasses in patients showed a significant increase by 21.0 (p < 0.05), 20.4 (p < 0.001) and 11.1 % (p < 0.05), respectively, resulting in an 18.0 % increase in mean total LDL mass (p < 0.001) without major changes in LDL composition. In the control subjects the changes in the concentrations of LDL subclasses during cholesterol intake were less and not significant. In the IDDM patients the cholesterol intake did not affect the concentration or composition of HDL subclasses or total HDL mass. In contrast, in control subjects cholesterol intake increased the mean concentration of HDL2 a by 12.2.% (p < 0.05) and this increase was significantly different if compared to changes obtained in the patients. In conclusion, compared to normal subjects, in IDDM patients, dietary cholesterol intake increased the LDL particle mass significantly and had no positive effect on HDL. [Diabetologia (1998) 41: 193–200] Received: 4 July 1997 and in revised form: 12 September 1997     

我国血脂异常治疗现状的调查

目的 了解高脂血症患经过3个月以上恒定治疗后,各项血脂的变化及其达到规定目标水平的情况。方法 从北京,广州及上海17家医院10000例高脂血症患的病历中收集所需信息数据,进行整理分析。结果 患治疗前各项血脂平均值为总胆固醇6．55mmol/L,低密度脂蛋白胆固醇4．10mmol/L,甘油三酯2．89mmol/L,高密度脂蛋白胆固醇1．27mmol/L,治疗后分别为5．56,3．40,2．11和1．32mmol/L,前三有显降低。按我国“血脂异常防治建议”的目标,达到目标水平的百分率分别为总胆固醇27．4％,低密度脂蛋白胆固醇31．6％,甘油三酯42．9％,三项全部达标仅10．1％,所用调脂药物中他汀类占59．0％,贝特类23．7％,中成药11．4％,结论 目前在接受药物治疗的高脂血症患中,血脂水平大多数未达到要求的目标,今后应给以予足够剂量的已证明有效的药物,使患得到明确的临床效益。     

Variability of lipids in patients with Type 2 diabetes taking statin treatment: implications for target setting

Aims To determine the biological variability of lipids in patients with Type 2 diabetes (T2DM) who are on statin treatment and then to assess any implications for current lipid targets. Methods A cross‐over study of biological variation of lipids in 26 patients with T2DM taking either simvastatin 40 mg or atorvastatin 10 mg. After 3 months on one statin, fasting lipids were measured on 10 occasions over a 5‐week period. Following 3 months on the other statin, 10 further samples were taken over 5 weeks. The main outcome measures were biological variability of total cholesterol (TC), low‐density lipoprotein (LDL) cholesterol, high‐density lipoprotein (HDL) cholesterol and triglycerides. Results The coefficient of variation (CV) of TC, LDL, HDL and triglycerides on simvastatin was 8.17, 13.11, 7.95 and 12.06%, respectively, whereas the CV on atorvastatin was 6.92, 10.30, 5.13 and 19.71%, respectively, with no statistically significant differences between statins. Treating to sustain a target TC < 5.0 mmol/l or LDL < 3.0 mmol/l means needing to maintain a mean TC of 4.3–4.4 mmol/l or LDL of 2.4–2.5 mmol/l. Treating to consistently achieve an LDL < 2.0 mmol/l means aiming for a mean of only 1.5–1.6 mmol/l. Conclusion In patients with T2DM taking either simvastatin or atorvastatin, the mean TC and LDL concentrations needed to consistently remain below a target are much lower than the target value itself. This means that guideline target limits extrapolated from the mean values of patients participating in clinical studies may overestimate the lipid reductions required.     

Efficacy and safety of alirocumab in insulin‐treated individuals with type 1 or type 2 diabetes and high cardiovascular risk: The ODYSSEY DM‐INSULIN randomized trial

Aims

To investigate the efficacy and safety of alirocumab in participants with type 2 (T2D) or type 1 diabetes (T1D) treated with insulin who have elevated LDL cholesterol levels despite maximally tolerated statin therapy.

Methods

Participants at high cardiovascular risk with T2D (n = 441) or T1D (n = 76) and LDL cholesterol levels ≥1.8 mmol/L (≥70 mg/dL) were randomized 2:1 to alirocumab:placebo administered subcutaneously every 2 weeks, for 24 weeks' double‐blind treatment. Alirocumab‐treated participants received 75 mg every 2 weeks, with blinded dose increase to 150 mg every 2 weeks at week 12 if week 8 LDL cholesterol levels were ≥1.8 mmol/L. Primary endpoints were percentage change in calculated LDL cholesterol from baseline to week 24, and safety assessments.

Results

Alirocumab reduced LDL cholesterol from baseline to week 24 by a mean ± standard error of 49.0% ± 2.7% and 47.8% ± 6.5% vs placebo (both P < .0001) in participants with T2D and T1D, respectively. Significant reductions were observed in non‐HDL cholesterol (P < .0001), apolipoprotein B (P < .0001) and lipoprotein (a) (P ≤ .0039). At week 24, 76.4% and 70.2% of the alirocumab group achieved LDL cholesterol <1.8 mmol/L in the T2D and T1D populations (P < .0001), respectively. Glycated haemoglobin and fasting plasma glucose levels remained stable for the study duration. Treatment‐emergent adverse events were observed in 64.5% of alirocumab‐ vs 64.1% of placebo‐treated individuals (overall population).

Conclusions

Alirocumab produced significant LDL cholesterol reductions in participants with insulin‐treated diabetes regardless of diabetes type, and was generally well tolerated. Concomitant administration of alirocumab and insulin did not raise any safety concerns (NCT02585778).     

A long‐term comparison of pioglitazone and gliclazide in patients with Type 2 diabetes mellitus: a randomized,double‐blind,parallel‐group comparison trial

Aims This study compared the effects of pioglitazone and gliclazide on metabolic control in drug‐naïve patients with Type 2 diabetes mellitus. Methods A total of 1270 patients with Type 2 diabetes were randomized in a parallel‐group, double‐dummy, double‐blind study. Patients with poorly controlled Type 2 diabetes (HbA_1c 7.5–11%), despite dietary advice, received either pioglitazone up to 45 mg once daily or gliclazide up to 160 mg two times daily. Primary efficacy endpoint was change in HbA_1c from baseline to the end of the study. Secondary efficacy endpoints included change in fasting plasma glucose, fasting plasma insulin and plasma lipids. At selected centres, oral glucose tolerance tests were performed and C‐peptide and pro‐insulin levels were measured. Results Mean HbA_1c values decreased by the same amount in the two treatment groups from baseline to week 52 [pioglitazone: ?1.4%; gliclazide: ?1.4%; (90% CI: ?0.18 to 0.02)]. A significantly greater mean reduction in fasting plasma glucose was observed in the pioglitazone group (2.4 mmol/l) than in the gliclazide group [2.0 mmol/l; treatment difference ?0.4 mmol/l in favour of pioglitazone; P = 0.002; (95% CI: ?0.7 to ?0.1)]. Improvements in high‐density lipoprotein cholesterol (HDL‐C) and total cholesterol/HDL‐C were greater with pioglitazone than with gliclazide (P < 0.001). The frequencies of adverse events were comparable between the two treatment groups, but more hypoglycaemic events were reported for gliclazide, whereas twice as many patients reported oedema with pioglitazone than with gliclazide. Conclusions Pioglitazone monotherapy was equivalent to gliclazide in reducing HbA_1c, with specific differences between treatments in terms of mechanism of action, plasma lipids and adverse events.     

Effects of calcium supplementation on serum lipid concentrations in normal older women: a randomized controlled trial

PURPOSE: To determine the effect of supplementation with calcium citrate on circulating lipid concentrations in normal older women. SUBJECTS AND METHODS: As part of a study of the effects of calcium supplementation on fractures, we randomly assigned 223 postmenopausal women (mean [+/- SD] age, 72 +/- 4 years), who were not receiving therapy for hyperlipidemia or osteoporosis, to receive calcium (1 g/d, n = 111) or placebo (n = 112) for 1 year. Fasting serum lipid concentrations, including high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol, were obtained at baseline, and at 2, 6, and 12 months. RESULTS: After 12 months, HDL cholesterol levels and the HDL cholesterol to LDL cholesterol ratio had increased more in the calcium group than in the placebo group (mean between-group differences in change from baseline: for HDL cholesterol, 0.09 mmol/L (95% confidence interval [CI]: 0.02 to 0.17; P = 0.01); for HDL/LDL cholesterol ratio, 0.05 (95% CI: 0.02 to 0.08; P = 0.001). This was largely due to a 7% increase in HDL cholesterol levels in the calcium group, with a nonsignificant 6% decline in LDL cholesterol levels. There was no significant treatment effect on triglyceride level (P = 0.48). CONCLUSION: Calcium citrate supplementation causes beneficial changes in circulating lipids in postmenopausal women. This suggests that a reappraisal of the indications for calcium supplementation is necessary, and that its cost effectiveness may have been underestimated.     

Growth hormone treatment improves serum lipids and lipoproteins in adults with growth hormone deficiency

The effects of 6 months' treatment with recombinant human growth hormone (rhGH) on serum lipids and lipoproteins were assessed in 24 adult patients with GH deficiency in a double-blind, placebo-controlled trial. Compared with age-, weight-, and sex-matched controls, the patients had significantly higher serum concentrations of total cholesterol (P = .002), low-density lipoprotein (LDL) cholesterol (P < .001), apolipoprotein B ([apoB] P = .011), and triglyceride (P = .017), and lower concentrations of high-density lipoprotein (HDL) cholesterol (P < .001). The prevalence of elevated serum cholesterol, triglyceride, LDL cholesterol, and apo B levels was 39%, 26%, 39%, and 25%, respectively; 75% of patients had decreased concentrations of HDL cholesterol. Treatment with rhGH (0.07 U/kg daily) resulted in decreases in total cholesterol level (5.8 ± 0.3 to 5.1 ± 0.3 mmol · L⁻¹ over 6 months; P = .01 compared with placebo), LDL cholesterol level (4.22 ± 0.25 to 3.19 ± 0.23 mmol · L⁻¹; P = .0003), LDL:HDL cholesterol ratio (5.57 ± 0.47 to 3.29 ± 0.33; P = .03), apo B level (1.07 ± 0.06 to 0.84 ± 0.07 g · L⁻¹; P = .003), and apo B: A-1 ratio (0.73 ± 0.05 to 0.69 ± 0.05; P = .01). HDL cholesterol and apo A-1 levels did not change following rhGH treatment. The changes in lipid and lipoprotein levels were not significantly related to changes in insulin, thyroid hormones, insulin-like growth factor-1 (IGF-1), or indices of adiposity. The data suggest that (1) adults with GH deficiency may be at increased risk of cardiovascular (CVS) disease due to hyperlipidemia, and (2) long-term treatment with rhGH improves lipid and lipoprotein profiles. Alterations in CVS mortality following long-term rhGH treatment remain to be assessed.