A STUDY OF LIPID PROFILE BEFORE AND AFTER CORONARY ARTERY BYPASS GRAFTING

SUMMARY This study was undertaken to establish the variability in the levels of total cholesterol (TC), total triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol before and after coronary artery bypass graft (CABG) surgery, in order to determine postoperatively when an accurate assessment can be made of the lipid status. During a prospective study over 4 months, fasting venous samples were taken pre- and postoperatively on day 5, and in the 4th, 8th and 12th weeks. Ninety-six patients admitted to the cardiothoracic and cardiac wards for CABG were recruited to the study. The mean preoperative levels were: TC 5.94 (± 0.1 mmol/l), LDL cholesterol 4.02 (± 0.09mmol/l) and HDL cholesterol 1.00 (± 0.03mmol/l). These were significantly different (p<0.01) from the levels on the 5th postoperative day when the mean level of TC was 4.14 (± 0.084mmol/l), LDL cholesterol was 2.45 (± 0.07mmol/l) and HDL cholesterol was 0.74 (±0.03mmol/l). By the 4th postoperative week, mean TC (5.73±0.13mmol/l), LDL cholesterol (3.79 ±0.14mmol/l) and HDL cholesterol (1.03 ± 0.04mmol/l) did not vary significantly from the mean preoperative values. There was no significant difference in the mean TG levels pre- and postoperatively. The mean TC, LDL cholesterol and HDL cholesterol rise to preoperative levels by the 4th week after CABG. Thus, an accurate assessment of patients' lipid status can be made from this period. An earlier postoperative assessment may be falsely reassuring.     

妊娠期糖尿病患者肝脏激酶B1 内含子380C ＞ T 基因多态性与糖脂代谢的关系及评估疾病易感性的价值

目的　探讨妊娠期糖尿病（gestational diabetes mellitus, GDM）患者肝脏激酶B1（liver kinase B1, LKB1）内含子380C ＞ T 基因多态性与糖脂代谢的关系及评估疾病易感性的价值。方法　选取2019 年1 月～ 2021 年4 月成都市双流区第一人民医院收治的92 例GDM 患者作为GDM 组,依据1∶1 对照设计原则,另选同期92 例正常孕妇作为对照组。比较两组一般资料: 糖脂代谢指标[ 空腹血糖（fasting plasma glucose,FPG）、糖化血红蛋白（hemoglobin A1c,HbA1c）]、低密度脂蛋白胆固醇（low density lipoprotein cholesterol,LDL-C）、高密度脂蛋白胆固醇（high densitylipoprotein cholesterol,HDL-C）、三酰甘油（triglyceride,TG）和总胆固醇（total cholesterol,TC）等水平以及LKB1内含子380C ＞ T 基因多态性, 分析糖脂代谢指标水平与基因型的关系及GDM 易感性的相关影响因素。结果　GDM 组有GDM 家族史者占比（18/92, 19.57%）明显高于对照组（3/92, 3.26%）,差异有统计学意义（χ2 =12.095,P ＜ 0.01）;GDM组FPG（6.14±0.67 mmol/L ）,HbA1c（6.87%±0.31%）,LDL-C（3.49±0.25 mmol/L）,TG（2.31±0.54 mmol/L）,TC（4.88±0.61 mmol/L）水平均明显高于对照组（4.52±0.33 mmol/L,5.09%±0.40%,3.05±0.27mmol/L,1.96±0.48mmol/L,4.39±0.72mmol/L）;HDL-C（1.06±0.19 mmol/L）水平明显低于对照组（1.33±0.22mmol/L）,差异均有统计学意义（t=20.805,33.737,11.469,4.647,4.981 和8.909,均P ＜ 0.01）;GDM 组与对照组LKB1 内含子380C ＞ T 基因型中CT（40.22%）,TT 基因型（18.48%）占比均明显高于对照组（27.17%,13.04%）,CC 基因型（41.30%）明显低于对照组（59.78%）,差异有统计学意义（χ2=6.292,P＜ 0.01）;LKB1内含子380C ＞T基因型TT患者HbA1c（7.13%±0.44%）水平高于基因型CT 患者（6.22%±0.39%）,基因型CT 患者HbA1c 水平高于基因型CC 患者（5.46%±0.36%）,差异有统计学意义（F=228.003,P ＜ 0.01）;且TT 和CT 基因型患者LDL-C 水平（3.59±0.37 mmol/L,3.45±0.32mmol/L）均明显高于CC 型患者LDL-C 水平（3.05±0.29mmol/L）,差异有统计学意义（F=48.151,P ＜ 0.01）;HbA1c 与基因型呈强正相关,LDL-C 与基因型呈弱正相关（r=0.815,0.366,均P ＜ 0.01）;有GDM 家族史及LKB1 内含子380C＞ T 基因型TT 均为GDM 易感性的独立危险因素（P ＜ 0.01）。结论　LKB1 内含子380C ＞ T 基因突变可引起机体发生糖脂代谢紊乱,从而增高GDM 易感性,是GDM 发生的危险因素之一。     

Reliability of the Reflotron in the determination of cholesterol

Measurements of total cholesterol in the field by means of the Reflotron dry-chemistry system (capillary blood) were compared to total cholesterol obtained by a standardized conventional wet-chemistry method in a clinico-chemical laboratory (serum). A total of 1200 people participated in the study. Two identical Reflotron machines were used. In the first period of the study an excellent agreement was found between Reflotron measurements of a reference serum provided by the manufacturer (mean, 4.99 mmol/l; CV, 1.8%) and the stated value (4.97 mmol/l). In the rest of the study higher values and greater variation were found with the Reflotron (mean, 5.32 mmol/l; CV 5.2%). Clearly the Reflotron measurements in the latter period of study were not reliable. In the period with stable instruments most of the values obtained at the two Reflotron machines differed from each other by less than 10%, with a mean difference of 0.08 mmol/l. Reflotron (both machines) and wet-chemistry measurements agreed well for the first 500 participants in the study (mean difference, Reflotron-wet-chemistry, -0.008 mmol/l; 95% confidence interval, -0.035 to 0.019 mmol/l; correlation, 0.967). In this period most Reflotron values differed from wet-chemistry values by less than 9% below to 9% above. With the next 200 participants the Reflotron gave on average slightly higher values than wet-chemistry measurements. The coefficients of variation for measurement variation were higher for Reflotron that for wet-chemistry even in the period with stable instruments. In all parts of the study period a lower HDL-cholesterol level was associated with larger differences between total cholesterol determined by Reflotron and wet-chemistry.     

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.     

Cholesterol screening in schools--initial results

Screening for cardiovascular risk factors was performed in November 1988 among 236 school children in S?lden (Tyrol/Austria). 77.5 per cent of the children had a raised blood cholesterol (greater than or equal to 160 mg/dl = 4.14 mmol/l), and 36.4 per cent a high cardiovascular risk (cholesterol greater than 190 mg/dl = 4.91 mmol/l). The mean cholesterol level for boys was 175.4 mg/dl (4.54 mmol/l), and for girls 186.9 mg/dl (4.83 mmol/l). All children with cholesterol greater than or equal to 160 mg/dl were sent to their general practitioner for follow up.     

Quality of care for patients with type 2 diabetes in primary care in Norway is improving: results of cross-sectional surveys of 33 general practices in 1995 and 2005

OBJECTIVE—To assess changes in the quality of care in Norway for patients with type 2 diabetes.RESEARCH DESIGN AND METHODS—Two cross-sectional surveys were examined that identified all patients (n = 1,470 in 1995 and n = 2,699 in 2005) with type 2 diabetes attending 33 general practices in 1995 and 2005.RESULTS—Between 1995 and 2005, there were significant improvements in the proportion of patients for whom important laboratory analyses, smoking habits, height, weight, and referral to eye examination were recorded. Mean A1C declined from 7.74 to 7.15%, systolic blood pressure from 150.0 to 140.4 mmHg, and cholesterol from 6.28 to 5.0 mmol/l (P < 0.001, age and sex adjusted). The 10-year risk of coronary heart disease for an average male patient declined from 42 to 29%.CONCLUSIONS—There have been substantial improvements in type 2 diabetes primary care in Norway that are potentially related to major improvements in health outcomes.Improving the quality of diabetes care has been a major focus of the Norwegian College of General Practice since the first diabetes guidelines for general practice were published in 1988. Guidelines were revised in 1995, 2000, and the late autumn of 2005 (1). Guideline targets for A1C ≤7.5% and serum cholesterol ≤5.0 mmol/l remained unchanged from 1995 to 2005, whereas target blood pressure was lowered from ≤140/90 to ≤140/85 mmHg in 2000. Our objective in this study was to assess changes in the quality of type 2 diabetes care in general practice from 1995 to 2005.     

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).     

Low LDL Cholesterol, Albuminuria, and Statins for the Risk of Cancer in Type 2 Diabetes: The Hong Kong Diabetes Registry

OBJECTIVE

LDL cholesterol <2.80 mmol/l was associated with increased cancer risk in type 2 diabetes. We explored the 1) interaction between low LDL cholesterol and albuminuria and 2) interaction between copresence of these two risk factors and statin use for cancer in type 2 diabetes.

RESEARCH DESIGN AND METHODS

We analyzed prospective data for 3,793 Chinese type 2 diabetic patients who remained naive for statin treatment and 1,483 patients in whom statin treatment was initiated during a median follow-up period of 5.24 years. All patients were free of cancer at baseline. Biological interactions were estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates biological interaction.

RESULTS

In 3,793 statin-naive type 2 diabetic patients, copresence of low LDL cholesterol and albuminuria increased cancer risk by 2.8-fold (hazard ratio 2.77 [95% CI 1.78–4.31]) with significant biological interactions (RERI 1.05 [0.04–2.06]; AP 0.38 [0.09–0.66]). In the whole cohort of 5,276 type 2 diabetic patients, there was interaction between nonuse of statins and copresence of low LDL cholesterol and albuminuria with increased cancer risk (RERI 2.87 [0.64–5.09] and AP 0.60 [0.29–0.90]). Statin nonusers with LDL cholesterol <2.80 mmol/l and albumunuria had a 4.9-fold risk of cancer compared with statin users with or without both risk factors.

CONCLUSIONS

In type 2 diabetes, there was interaction between low LDL cholesterol and albuminuria with increased cancer risks. The latter was attenuated in the presence of statin treatment.Type 2 diabetes predisposes patients to a variety of cancers (1–4). The prevalence of cancer in type 2 diabetic patients is one-third higher than that in the general population (5). Based on a prospective database, we reported that the association between LDL cholesterol and cancer risk in type 2 diabetes was V-shaped with a nadir at 3.28 mmol/l and that LDL cholesterol levels <2.80 mmol/l and ≥3.80 mmol/l were both associated with elevated cancer risks (5).Albuminuria is an early manifestation of generalized endothelial dysfunction (6). This urinary marker is closely associated with hyperglycemia, obesity, and hypertension (7). Using a prospective registry, we found possible biological interactions between albuminuria and hyperglycemia with increased risk of ischemic stroke (7). Given the intimate relationships between albuminuria, dyslipidemia, and cancer risk, we asked whether there are biological interactions between low LDL cholesterol (<2.80 mmol/l) and albuminuria for the risk of cancer in type 2 diabetes. Given the inconsistent findings for use of lipid-lowering drugs and cancer risks (8–10) and a paucity of such data in type 2 diabetes, we also explore the potential interaction (a second-order interaction) between use of statins and copresence of low LDL cholesterol and albuminuria on cancer risks.     

Renal hypouricaemia in insulin treated diabetes mellitus

Uric acid metabolism was investigated in 69 insulin-treated male diabetic outpatients and in 23 healthy male subjects, because of a reported coincidence between diabetes and gout. All subjects had normal serum creatinine concentrations and none received diuretic treatments.

Compared with normal, the diabetics had significantly lower mean serum uric acid concentrations (0.34 ± 0.08 (SD) mmol/l versus 0.23 ± 0.06 mmol/1, p < 0.001). 17% of the diabetic patients had serum concentrations below the normal mean—2 SD. In contrast, the diabetic patients had a 42% increase in renal uric acid excretion rate (p <0.01), and an 83% increase in the ratio of uric acid clearance/creatinine clearance (p < 0.001). These indices of renal uric acid excretion were both positively correlated to fasting blood glucose levels (r = 0.57, p < 0.001, and r = 0.50, p < 0.001, respectively), to the degree of glycosuria (r = 0.73, p < 0.001, and r = 0.63, p < 0.001, respectively), and to the magnitude of water diuresis (r = 0.60, p < 0.001, and r = 0.39, p < 0.01, respectively).

The hypouricaemia observed in these insulin-dependent diabetic male subjects may probably be caused by the increased renal excretion of uric acid in the presence of hyperglycaemia. The study gave no evidence of increased serum uric acid concentrations in insulin-dependent diabetics. It is therefore likely that any coincidence between gout and diabetes derives from other coexisting serum uric acid raising factors.     

Lipid-altering efficacy of ezetimibe/simvastatin 10/40 mg compared with doubling the statin dose in patients admitted to the hospital for a recent coronary event: the INFORCE study

Background: The aim of this study was to investigate the efficacy and safety profile of switching to ezetimibe/simvastatin (Eze/Simva) 10/40 mg compared with doubling the statin dose upon discharge in patients taking a statin and admitted to the hospital for the investigation of a coronary event. Design: This phase IV, multi‐centre, randomised, open‐label, active‐controlled, parallel group study enrolled 424 patients (aged ≥ 18 years) hospitalised for an acute coronary event and taking a stable dose of a statin (≥ 6 weeks) that could be doubled per the product label. Upon discharge from the hospital, patients were stratified by their statin dose/potency (high, medium and low) and randomised 1 : 1 to doubling of the statin dose (n = 211) or Eze/Simva 10/40 mg (n = 213) for 12 weeks. The primary efficacy variable was the absolute low‐density lipoprotein cholesterol (LDL‐C) value (mmol/l) at study end‐point. Results: Mean baseline LDL‐C for the two treatment groups were 2.48 and 2.31 mmol/l for the Eze/Simva and statin groups respectively. At study end‐point, least squares mean LDL‐C values were 1.74 mmol/l in the Eze/Simva group and 2.22 mmol/l in the statin group resulting in a significant between‐group difference of ?0.49 mmol/l (p ≤ 0.001). Eze/Simva 10/40 mg also produced significantly lower total cholesterol (?0.49 mmol/l), non‐high‐density lipoprotein cholesterol [(non‐HDL‐C); ?0.53 mmol/l] and apolipoprotein B (?0.14 mmol/l) values compared with doubling the statin dose (p ≤ 0.001 for all). Both treatments produced similar effects on triglycerides, C‐reactive protein and HDL‐C; the between treatment group differences were not significant (p ≥ 0.160). Significantly more patients achieved LDL‐C levels < 2.5 (< 100 mg/dl; 86% vs. 72%), < 2.0 (< 77 mg/dl; 70% vs. 42%) and < 1.8 mmol/l (< 70 mg/dl; 60% vs. 31%) with Eze/Simva than statin (all p ≤ 0.001). Eze/Simva was generally well tolerated, with a safety profile similar to statin. There were no differences in the incidences of liver transaminases ≥ 3 × upper limit of normal (ULN) or creatine kinase ≥ 10 × ULN between the groups. Conclusions: In patients taking a statin and admitted to the hospital for investigation of a coronary event, treatment with Eze/Simva 10/40 mg for 12 weeks produced greater improvements in lipids with a similar safety profile compared with doubling of the statin dose.