Plasma Lipoprotein Composition and Cholesteryl Ester Transfer from High Density Lipoproteins to Very Low Density and Low Density Lipoproteins in Patients with Non-insulin-dependent Diabetes Mellitus

We have examined cholesteryl ester transfer (CET) from HDL to low density and very low density lipoproteins (LDL and VLDL) and lecithin:cholesterol acyl transferase (LCAT) activity in plasma from 28 men with non-insulin-dependent diabetes mellitus (NIDDM) treated with diet alone or diet and sulphonylurea drugs and in 27 healthy non-diabetic controls. Patients and healthy subjects had similar LCAT activity, but CET was significantly higher in NIDDM 26.1 ± 11.5 μmol l⁻¹ h⁻¹) than in healthy men (17.8 ± 6.5 μmol l⁻¹ h⁻¹) (p = 0.001). Diabetic men also had higher CET compared to 15 healthy non-diabetic men (18.7 ± 5.6 μmol l⁻¹ h⁻¹) (p = 0.001) with similar serum lipids. CET activity was similar in patients treated with diet alone (24.8 ± μmol l⁻¹ h⁻¹) or with sulphonylureas (27.7 ± 15.8 μmol l⁻¹ h⁻¹). The Sf 0–12 fraction was significantly enriched with total cholesterol (p = 0.0001) and free cholesterol (p = 0.006) in diabetic subjects whether treated with diet alone or on sulphonylureas compared to the 15 non-diabetic controls matched for serum triglycerides. The free cholesterol/phospholipid, the free cholesterol/total protein and the free cholesterol/mass ratios were increased in the Sf 0–12 fraction in diabetic subjects (p < 0.01). These findings indicate that CET is accelerated in patients with NIDDM and that this may be due to the altered composition of acceptor lipoproteins.     

Serum Lipids and Apolipoproteins and Their Relationship with Macrovascular Disease in Type 1 Diabetes

In order to examine the relationship between serum lipids and apolipoproteins and macrovascular disease in patients with Type 1 diabetes mellitus, 50 patients with Type 1 diabetes mellitus attending the diabetic clinics at St Mary's and St Charles' Hospitals, London were recruited into a cross-sectional study. B-mode ultrasound was used to measure intima-media thickness and define an arterial ultrasound score for each patient as a non-invasive indicator of atherosclerotic change. Intima-medial (i-m) thickness was significantly higher in those subjects with clinical evidence of macrovascular disease compared to those without macrovascular disease (0.865 ± 0.191 vs 0.695 ± 0.162 mm, p = 0.0038). In the study group there were significant correlations between i-m thickness and age (r = 0.65, p < 0.01), total serum cholesterol (r = 0.32, p < 0.01), and serum fibrinogen (r = 0.43, p < 0.01) but no other lipid or apolipoprotein variable. When i-m thickness was corrected for age there were significant correlations with total cholesterol (r = 0.43, p < 0.01) and LDL-cholesterol (r = 0.42, p < 0.01). Whereas total and LDL-cholesterol and serum fibrinogen concentrations were related to the extent of atherosclerotic disease by ultrasound techniques, there was no relationship with high density lipoprotein (HDL) or subfraction cholesterol concentrations. HDL-cholesterol may not be a useful marker for cardiovascular disease in Type 1 diabetes.     

2型糖尿病患者颈动脉病变及其大血管并发症危险因素相关性研究

目的:分析2型糖尿病患者颈动脉内膜中层厚度与大血管并发症及危险因素相关性。方法:2型糖尿病伴发大血管病变组141例,2型糖尿病未伴发大血管病变组128例,正常对照组133例,检测其颈动脉内膜中层厚度及斑块,同时测定其血糖、血脂、C肽、体重指数及高敏C反应蛋白(hCRP)水平,比较3组间颈动脉内膜中层厚度及斑块发生率,分析其影响因素。结果:2型糖尿病伴发大血管病变组、2型糖尿病未伴发大血管病变组及正常对照组颈动脉内膜平均厚度分别为(1．09±0．22)mm、(O．89±0．23)mm、(0．66±0．13)mm,组间均有显著性差异(P<0．01);3组中斑块的发生率分别为63．1％、28．91％及0％,均有显著性差异(P<0．05)。在2型糖尿病患者合并大血管病变中,颈动脉内膜中层厚度与hCRP呈正相关(P<0．001)。结论:血清hCRP与2型糖尿病患者颈动脉内膜中层厚度显著相关,hCRP是2型糖尿病大血管病变的显著指标。     

Ⅱ型糖尿病患者的动态血压观察

对３１例Ⅱ型糖尿病患者（其中糖尿病肾病组１６例，糖尿病无肾病组１５例）进行２４ｈ动态血压观察。结果提示：Ⅱ型糖尿病不论有否合并肾病，２４ｈ平均收缩压（２４ｈＳＢＰ）、白昼平均收缩压（ｄＳＢＰ）、夜间平均收缩压（ｎＳＢＰ）均显著高于对照组（Ｐ均＜０．０１）；糖尿病肾病组的ｎＳＢＰ／ｄＳＢＰ和ｎＤＢＰ／ｄＤＢＰ均显著高于对照组（Ｐ均＜０．０１）；糖尿病肾病组的ｎＳＢＰ、ｎＳＢＰ／ｄＳＢＰ和ｎＤＢＰ／ｄＤＢｐ均显著高于糖尿病无肾病组（Ｐ均＜０．０５）。Ⅱ型糖尿病患者ＡＢＰＭ主要表现为收缩期血压增高，而且在糖尿病肾病患者中，夜间血压下降不明显，失去了血压的正常昼夜节律变化。结果提示血压超负荷时间延长可能是糖尿病肾病发生和发展的因素之一。     

Hormone Replacement Therapy and Cardiovascular Risk in Post-menopausal Women with NIDDM

Female patients with NIDDM have a high prevalence of, and mortality from, coronary heart disease (CHD). Hormone replacement therapy (HRT) may favourably influence several CHD risk factors in post-menopausal NIDDM patients, including dyslipidaemia, hypertension, prothrombotic changes, and endothelial dysfunction. Insulin resistance appears to have a central role in the pathogenesis of these abnormalities and can also be modified by HRT. However, the potentially beneficial effects of HRT in women with NIDDM have been extrapolated from the results of studies in non-diabetic females, as to date there have been few studies in NIDDM patients. In view of their excessive CHD mortality, further research is needed to investigate the effects of different HRT preparations on lipid and non-lipid risk factors in this high-risk population.     

对氧磷酶2基因311Cys/Ser多态性与2型糖尿病合并大血管病变的相关性

目的探讨对氧磷酶2基因311 Cys/Ser多态性与山东青岛地区2型糖尿病患者合并大血管病变的关系。方法通过抽提基因组DNA并应用聚合酶链反应扩增包含对氧磷酶2基因311位点的基因片段,然后应用聚合酶链反应限制片长多态性技术检测对氧磷酶2基因311 Cys/Ser多态性在2型糖尿病合并大血管病变组、单纯2型糖尿病组以及正常对照组的基因频率。结果山东青岛地区人群存在对氧磷酶2基因311 Cys/Ser多态性。2型糖尿病合并大血管病变组对氧磷酶2基因的3种基因型(CC、CS、SS)的构成比与单纯2型糖尿病组和正常对照组比较差异具有显著性(P<0.05或P<0.01),S等位基因频率较单纯2型糖尿病组和正常对照组显著增高(P<0.05或P<0.01);携带S等位基因的个体患糖尿病大血管病变的风险为非携带者的2.932倍;对氧磷酶2基因311 Cys/Ser多态性不同基因型亚组间血脂水平无明显差异。结论在山东青岛地区人群中,对氧磷酶2基因311 Cys/Ser多态性与2型糖尿病合并大血管病变具有相关性,其S等位基因可能是该地区2型糖尿病合并大血管病变的危险因素之一。     

Age and Cigarette Smoking are Independently Associated with the Cutaneous Vascular Response to Local Warming

Purpose : To investigate the relative impacts of age and cigarette smoking on cutaneous blood flow and flowmotion. Experimental Design : Skin blood flux was measured before and during the hyperaemic response to thermal warming of the skin to 43°C using laser Doppler fluximetry (LDF) in 28 habitual smokers (5.4 [11.4] (median [IQR]) pack years; pack years = packs/day X duration of smoking habit), aged between 18 and 63 years and their age, sex and body mass index. flowmotion was assessed using Fourier analysis of the LDF signal. Results : Mean and total hyperaemic (area under the flux curve, AUC₁₀) response during warming were reduced in smokers compared with their non‐smoking controls (P<0.05). Attenuation of the response to warming in smokers was associated with a reduction in relative spectral power around 0.01 Hz, reflecting a reduced endothelial/metabolic activity (P <0.04). In regression modelling with AUC₁₀ as the outcome, and smoking (yes/no), age, sex and BMI, as explanatory variables, age (P <0.0001) and smoking (P =0.018) were independently associated with the hyperaemic response and together accounted for 31% of the variance in AUC₁₀. Conclusions : Age and smoking are associated with approximately one‐third of the variance in the endothelium‐associated microvascular vasomotor activity in habitual smokers.     

Ⅱ型糖尿病病人的动态血压与胰岛素的关系

目的了解Ⅱ型糖尿病（ＮＩＤＤＭ）病人的动态血压与血中胰岛素的关系。方法对７２例ＮＩＤＤＭ病人行２４ｈ动态血压监测，根据监测结果，分为ＮＩＤＤＭ合并高血压组３６人，未合并高血压组３６人。所有病人行空腹血糖、胰岛素及血脂等检查，并经ｔ检验和多元回归分析。结果ＮＩＤＤＭ合并高血压组较未合并高血压组的空腹血胰岛素浓度显著增高（Ｐ＜０．００１），而且胰岛素浓度分别与２４ｈ平均收缩压和舒张压呈独立的相关性（Ｐ＜０．００１）。结论ＮＩＤＤＭ病人合并高血压较未合并高血压有更高的胰岛素血症，且在ＮＩＤＤＭ病人中高胰岛素血症是高血压的独立的危险因子。     

Smoking Habits in Patients with Inflammatory Bowel Disease

The proportion of smokers in this study was significantly lower among patients with ulcerative colitis (13%) than among patients with Crohn's disease (47%), the difference being significant for both sexes and for the age groups both below and above 40 years. The proportion of male ex-smokers among patients with ulcerative colitis (28%) was higher than among patients with Crohn's disease (8%), whereas the proportions of non-smokers differed less. Many of the patients with ulcerative colitis who had a late onset were male ex-smokers. The smoking patients with ulcerative colitis were mainly women. They smoked less than the smoking patients with Crohn's disease and less than the ex-smokers in each group. No smoking patient with ulcerative colitis smoked > 20 cigarettes/day. In the group of male ex-smokers with ulcerative colitis, there was an accumulation of onsets during the 4 years after the definitive smoking stop. The number of colectomies performed on patients with ulcerative colitis did not vary with smoking habits. In the group of ex-smokers the colectomy was performed after the smoking stop in 19 out of 20 patients.     

Myeloperoxidase is Independently Associated with Incident Heart Failure in Patients with Coronary Artery Disease and Kidney Disease

Chronic kidney disease (CKD) is associated with high cardiovascular risk and mortality. Myeloperoxidase (MPO) has been linked to adverse events in patients with mild-moderate CKD. We sought to investigate whether MPO levels are associated with adverse outcomes in patients with CKD. We studied participants with mild to moderate CKD in the prospective chronic renal insufficiency cohort (CRIC). We followed patients for incident heart failure (HF), death, and composite outcome (myocardial infarction, incident peripheral arterial disease, cerebrovascular accident and death). A total of 3872 patients were included (2702 without CVD, 1170 with CVD). After multiple adjustments, doubling of MPO in patients with prior CAD was associated with risk of HF (HR 1.15 [1.01-1.30], P = 0.032) and mortality (HR 1.16 [1.05-1.30], P = 0.005), and composite outcome of MI, PAD, CVA and death (HR 1.12 [1.01-1.25], P = 0.031). In this cohort of patients with mild to moderate CKD and CAD, MPO levels are independently associated with incident HF, all-cause mortality, and a composite outcome.     

NIDDM患者微量白蛋白尿与冠心病的关系

１０９例年龄≤６０岁的ＮＩＤＤＭ患者，其中４０例并有微量白蛋白尿或早期蛋白尿，６９例正常白蛋白尿，分析比较两组心血管疾病危险因素与心脏受损情况，结果发现微量白蛋白尿组与正常白蛋白尿组相比，缺血性心电图异常发生率较高（２５％比１５．９％），超声心动图左室舒张末期内径较大（４．８６±０．５４ｃｍ比４．６９±０．５５ｃｍ，Ｐ＜０．０５），表明微量白蛋白尿组有心脏受损较多的倾向，提示微量白蛋白尿是ＮＩＤＤＭ患者发生缺血性心脏病的危险信号。     

对氧磷酶1192Gln/Arg和对氧磷酶2311Cys/Ser多态性与2型糖尿病合并大血管病变的相关性

目的探讨对氧磷酶1基因192 Gln/Arg和对氧磷酶2基因311 Cys/Ser多态性与山东青岛地区2型糖尿病患者合并大血管病变的关系。方法通过抽提基因组DNA并应用聚合酶链反应检测对氧磷酶1 192 Gln/Arg和对氧磷酶2 311 Cys/Ser多态性在2型糖尿病合并大血管病变组、单纯2型糖尿病组以及正常对照组的基因频率。联合分析两种基因变异在2型糖尿病合并大血管病变的发病中有无协同效应。结果山东青岛地区人群存在对氧磷酶1 192 Gln/Arg和对氧磷酶2 311 Cys/Ser多态性。2型糖尿病合并大血管病变组与单纯2型糖尿病组和正常对照组比较对氧磷酶1的3种基因型(QQ、QR、RR)的构成比差异无显著性,而对氧磷酶2的3种基因型(CC、CS、SS)的构成比差异有显著性(P<0.05或P<0.01),S等位基因频率较其他两组显著增高(P<0.05或P<0.01)。联合分析发现对氧磷酶2 311 S等位基因是2型糖尿病合并大血管病变的独立危险因素,当对氧磷酶2 311 S等位基因与对氧磷酶1 192 R等位基因并存时,患2型糖尿病合并大血管病变的相对危险度明显增加(OR=49.494,95%CI为0.907~2701.872)。结论在山东青岛地区人群中,对氧磷酶2 311 Cys/Ser多态性与2型糖尿病合并大血管病变具有相关性,其S等位基因可能是该地区2型糖尿病合并大血管病变的危险因素之一。当同时检测出对氧磷酶1 192 R等位基因时对2型糖尿病合并大血管病变更具有预测或诊断价值。     

2型糖尿病患者动态血压及心率变异与肾病的相互关系

目的：探讨血压增高、血压昼夜节律异常和自主神经病变对糖尿病肾病的影响。方法：同步监测３５例糖尿病肾病患者、３５例糖尿病正常白蛋白尿患者和３５例正常对照组的动态血压和动态心电图。结果：糖尿病肾病组２４小时血压较正常白蛋白尿组和对照组明显增高,昼夜平均动脉压差值百分率下降（ｐ〈０．００１）;糖尿病正常白蛋白尿组虽然２４小时平均血压与对照组无明显差异,但却已存在夜间血压升高,昼夜平均动脉压差值百分率下降（ｐ〈０．０５～０．００１）;糖尿病肾病组ＨＲＶ指标较糖尿病正常白蛋白尿组和对照组显著减小（Ｐ〈０．０１～０．００１）;糖尿病正常白蛋白尿组ＨＲＶ各项指标也较对照组减小（Ｐ〈０．０１）。结论：糖尿病肾病的发生、发展与血压升高、血压昼夜节律异常和糖尿病自主神经病变有关。     

Evidence of higher insulin resistance in NIDDM patients with ischaemic heart disease

Summary Prospective studies have shown a relationship between hyperinsulinaemia, an indirect index of insulin resistance, and IHD in men with normal glucose tolerance. In NIDDM this association is less clear possibly due to the poor significance of insulin and C-peptide concentrations as an index of insulin resistance. Therefore, only a direct measurement of insulin sensitivity could clarify the possible relationship between insulin resistance and IHD in NIDDM. We have evaluated insulin sensitivity, by means of an ITT, and some risk factors for IHD in 72 men with NIDDM, 36 with and 36 without IHD, attending our out-patient Diabetic Clinic. The two groups were of similar age, duration of diabetes, glycaemic control and body composition. Subjects with IHD were more insulin resistant (K_ITT index 2.45±0.18 vs 3.12±0.13% per min, in patients with and without IHD, respectively, p<0.004), had higher total (p=0.011) and LDL serum cholesterol levels (p=0.010) and greater prevalence of hypertension (p=0.001) compared to subjects without IHD. Using step-wise logistic regression analysis, insulin resistance (odds ratio 2.57, 95% CI 1.87–3.28, p=0.008), hypertension (odds ratio 8.17, 95% CI 6.86–9.48, p=0.002), total serum cholesterol levels (odds ratio 1.02, 95% CI 1.005–1.035, p=0.015) and BMI (0.79, 95% CI 0.67–0.97, p=0.049) were independently associated with IHD. After adjustment for age and duration of diabetes, only insulin sensitivity was directly related to the age of onset of IHD, independently from other clinical and metabolic parameters (p<0.015). In conclusion: in NIDDM, patients with IHD are more insulin resistant compared to subjects without IHD. Insulin resistance is associated with IHD, independently from other cardiovascular risk factors. A higher insulin resistance seems to be related to an earlier clinical onset of IHD.Abbreviations NIDDM non-insulin-dependent diabetes mellitus - IHD ischaemic heart disease - ITT insulin tolerance test - CI confidence interval - ACE angiotensin-converting-enzyme     

Metabolic Abnormalities in Offspring of NIDDM Patients with a Family History of Diabetes Mellitus

NIDDM appears to be an inherited condition. Our aim was to identify early metabolic abnormalities in non-diabetic offspring with one NIDDM parent and with a strongly positive (n = 58, age 27.8 ± 7.0 years) or a negative family history (n = 38, age 27.4 ± 6.7 years) of diabetes. These were compared with 31 offspring of non-diabetic parents (age 26.9 ± 5.5 years). After an overnight fast, blood was taken for glucose, insulin, C-peptide, insulin receptors, and lipids. All the subjects underwent a 75 g oral glucose tolerance test. The positive family history group had significantly higher fasting levels of triglycerides (1.09 ± 0.24 vs control subjects: CS: 0.93 ± 0.16 mmol l⁻¹, p < 0.001), insulin (102.8 ± 46.4 vs CS: 77.5 ± 32.4 pmol l⁻¹, p < 0.01) and C-peptide (0.69 ± 0.22 vs CS: 0.61 ± 0.19 nmol l⁻¹, p < 0.05) and lower numbers of insulin receptors per red cell (9.1 × 10³ (4.5–18.1, 95 % confidence intervals) vs CS: (11.2 × 10³ (6.3–19.9)), p < 0.01, despite similar blood glucose levels. After a glucose challenge (120 min), the increases in both insulin and C-peptide concentrations were significantly greater in the positive family history group (289.2 ± 214.1 pmol l⁻¹, 2.23 ± 1.48 nmol l⁻¹), respectively, than in CS (192.4 ± 170.3 pmol l⁻¹, p < 0.05) (1.54 ± 0.99 nmol l⁻¹ p < 0.01), respectively. No significant differences were found in fasting and post-challenge glucose levels. The negative family history group had significantly lower numbers of insulin receptors 9.4 × 10³ (4.1–15.2) compared with CS (p < 0.05). Insulin sensitivity was significantly reduced in the positive family history group (41.6 %) compared with control subjects (51.9 %), p < 0.01. The results strongly support the familial basis of the disease.     

冠心病患者血脂、脂蛋白及载脂蛋白测定的临床意义

本文对48例冠心病患者及36例正常人的血脂、脂蛋白及载脂蛋白进行了对比分析。结果表明,冠心病患者血清甘油三酯水平高于正常对照组(P<0.001),血浆高密度脂蛋白(HDL—C)低于对照组(P<0.05)。载脂蛋白A(apoA)在冠心病组显著降低(P<0.01),总胆固醇、载脂蛋白B(apoB)两组无显著差异(P>0.05),冠心病组apoB/apoA比值高于正常对照组(P<0.05).