Serum lipoprotein(a) concentrations and apolipoprotein(a) phenotypes in the families of NIDDM patients

Summary We studied the quantitative and qualitative characteristics of lipoprotein(a) [Lp(a)] as a function of apolipoprotein(a) [apo(a)] phenotype in 87 members (42 males, 45 females) of 20 diabetic families, 26 of whom were diagnosed with non-insulin-dependent diabetes mellitus (NIDDM) with moderate glycaemic control (HbA_1c7.1±1.2%). Apo(a) phenotyping was performed by a sensitive, high-resolution technique using SDS-agarose/gradient PAGE (3–6%). To date, 26 different apo(a) phenotypes, including a null type, have been identified. Serum Lp(a) levels of NIDDM patients and non-diabetic members of the same family who had the same apo(a) phenotypes were compared, while case control subjects were chosen from high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups with the same apo(a) phenotypes in the same family. Serum Lp(a) levels were significantly higher in NIDDM patients than in non-diabetic subjects (39.8±33.3 vs 22.3±19.5 mg/dl, p<0.05). The difference in the mean Lp(a) level between the diabetic and non-diabetic groups was significantly (p<0.05) greater than that between the high-Lp(a) non-diabetic and low-Lp(a) non-diabetic groups. An analysis of covariance and a least square means comparison indicated that the regression line between serum Lp(a) levels [log Lp(a)] and apo(a) phenotypes in the diabetic patient group was significantly (p<0.01) elevated for each apo(a) phenotype, compared to the regression line of the control group. These data, together with our previous findings that serum Lp(a) levels are genetically controlled by apo(a) phenotypes, suggest that Lp(a) levels in diabetic patients are not regulated by smaller apo(a) isoforms, and that serum Lp(a) levels are greater in diabetic patients than in non-diabetic family members, even when they share the same apo(a) phenotypes.Abbreviations Lp(a) Lipoprotein(a) - apo(a) apolipoprotein(a) - NIDDM non-insulin-dependent diabetes mellitus - TC total cholesterol - LDL low density lipoprotein - TG triglycerides - HDL-C high density lipoprotein-cholesterol - LDL-C low density lipoprotein-cholesterol - PBS phosphate buffered saline The first two authors contributed equally to this work     

The relationship between lipoprotein(a) and the complications of diabetes mellitus

The risk of cardiovascular disease is increased approximately two- to four-fold in patients with diabetes mellitus compared with non-diabetic controls. The nature of this increased risk cannot be completely explained by the contribution of traditional risk factors. As such, there has been a great deal of interest in assessing the role of lipoprotein(a) (Lp(a)), an LDL-like lipoprotein, in the vascular complications of diabetes. Although numerous studies in the non-diabetic population have demonstrated an association between elevated plasma Lp(a) concentration and risk for atherosclerotic disorders, the contribution of Lp(a) to the enhanced risk of vascular disease in the diabetic population is not clearly defined. Herein we review the structure and potential functions of Lp(a), the determination of Lp(a) levels, and the epidemiological evidence supporting its role in coronary heart disease and address the following controversial questions regarding the role of Lp(a) in diabetes mellitus: (1) are plasma Lp(a) levels and phenotype distributions altered in type 1 (insulin-dependent) diabetes mellitus and type 2 (non-insulin-dependent) diabetes mellitus and does the degree of metabolic control influence Lp(a) levels in these patients; (2) what is the relationship between Lp(a) and renal disease in patients with diabetes mellitus; (3) do increased plasma Lp(a) concentrations in patients with diabetes contribute to the vascular complications of this disease; and (4) can the atherogenicity of Lp(a) in diabetes be enhanced in the absence of elevated levels of this lipoprotein due to biochemical modifications. Received: 11 January 2002 / Accepted in revised form: 9 December 2002 Correspondence to S.M. Marcovina     

Lipoprotein (a) and vascular disease in diabetic patients

Summary In order to assess the potential role of lipoprotein(a) as a risk factor for cardiovascular disease in diabetes mellitus, plasma concentrations were measured in a large group (n=500) of non-insulin-dependent (NIDDM, n=355) and insulin-dependent (IDDM, n=145) patients. Concentrations of lipoprotein (a) were compared in diabetic patients with (n=153) or without (347) documented vascular disease (ischaemic heart disease, peripheral vascular disease or macroangiopathy). They were significantly higher (p<0.05) in patients with ischaemic heart disease (mean [interquartile range] 15.5 (5.0–38.0) vs 9.0 (4.5–26.0) mg/dl) or macroangiopathy (13.0 (5.0–38.0) vs 9.0 (4.0–25.0) mg/dl) compared to patients without manifestations of vascular disease. In addition, stepwise logistic regression analysis identified lipoprotein (a) levels 30 mg/dl as being independently associated with the presence of cardiovascular disease. Lipoprotein (a) was an independent risk factor for ischaemic heart disease and macroangiopathy in this group of IDDM and NIDDM patients.Abbreviations Lp(a) lipoprotein (a) - LDL low density lipoproteins - CVD cardiovascular disease - IHD ischaemic heart disease - PVD peripheral vascular disease - HDL high density lipoproteins     

Correlation between serum lipoprotein (a) and angiographic coronary artery disease in non-insulin-dependent diabetes mellitus

Abstract. Comlekqi A, Biberoglu S, Kozan 0, Bahqeci 0, Ergene 0, Nazli C, Kinay 0, Guner G (Dokuz Eylul University, Medical School, Inciralti, Izmir, Turkey). Correlation between serum lipoprotein(a) and angio-graphic coronary artery disease in non-insulin-dependent diabetes mellitus. J Intern Med 1997; 242:449-54.
Objectives: To examine the impact of diabetic state on the concentrations of lipoprotein(a) [Lp(a)] in patients with non-insulin-dependent diabetes mellitus (NIDDM) and the correlation between angiographic coronary artery disease (CAD) and serum Lp(a) concentrations in NIDDM.
Design: In this cross-sectional study of 26 patients with NIDDM and 19 nondiabetic sex- and agematched patients who underwent coronary angiography, CAD was assessed visually using coronary artery score (CAS), and plasma Lp(a) was measured by an enzyme-linked immunosorbent assay.
Setting: The study was performed in an internal medicine clinic at a university hospital.
Subjects: Twenty-six age- and sex-matched patients with NIDDM and 19 control patients without diabetes.
Results: There was no significant difference between the Lp(a) concentrations of patientswith NIDDM and nondiabetic subjects (P > 0.05). When patients with NIDDM were stratified by absence or presence of CAD, patients with CAD had higher levels of Lp(a) (P < 0.05). However, there was no significant correlation between the concentrations of Lp(a) and CAS (P > 0.05).
Conclusions: Diabetic state does not have any impact on Lp(a) concentrations. Lp(a) excess seems to be atherogenic in patients with NIDDM as shown in nondiabetic patients in previous studies. Although diabetic patients with CAD have higher Lp(a) concentrations than the diabetic patients without CAD, Lp(a) levels were not correlated with CAS.     

Is apolipoprotein(a) a susceptibility gene for Type I diabetes mellitus and related to long-term survival?

Aims/hypothesis. High lipoprotein(a) [Lp(a)] plasma concentrations are a genetically determined risk factor for atherosclerotic complications. In healthy subjects Lp(a) concentrations are mostly controlled by the apolipoprotein(a) [apo(a)] gene locus which determines a size polymorphism with more than 30 alleles. Subjects with low molecular weight apo(a) phenotypes on average have higher Lp(a) concentrations than those with high molecular weight apo(a) phenotypes. There are many opinions about whether and why Lp(a) is raised in patients with Type I diabetes (insulin-dependent) mellitus. Methods. We investigated Lp(a) plasma concentrations and apo(a) phenotypes in 327 patients with Type I diabetes mellitus (disease duration 1–61 years) and in 200 control subjects matched for age and sex. Results. Patients with a disease duration of up to 15 years had significantly higher Lp(a) concentrations (24.3 ± 34.0 mg/dl vs 16.7 ± 22.6 mg/dl, p = 0.014) compared with control subjects. This increase can be explained by a considerably higher frequency of low molecular weight apo(a) phenotypes (38.9 % vs 23.5 %, p < 0.005). The frequency of low molecular weight apo(a) phenotypes decreased continuously with disease duration from 41.7 % in those with disease duration of up to 5 years to 18.2 % in those with the disease lasting more than 35 years. Conclusion/interpretation. Our data show that an increase of Lp(a) in Type I diabetic patients can only be observed in groups with short diabetes duration and that this elevation is genetically determined. Therefore, the apo(a) gene, located at 6q26–27, might be a susceptibility gene for Type I diabetes mellitus which is supported by recently published studies reporting evidence for linkage of this region (6q27) with Type I diabetes mellitus. Furthermore, the decreasing frequency of low molecular weight apo(a) phenotypes with disease duration suggests a survivor effect. [Diabetologia (1999) 42: 1021–1027] Received: 23 December 1998 and in revised form: 8 March 1999     

Cholesterol-lowering therapy may retard the progression of diabetic nephropathy

Summary There is experimental evidence to suggest that hypercholesterolaemia may play a pathogenetic role in progressive glomerular injury. We investigated the effect of cholesterol-lowering therapy on the progression of diabetic nephropathy in 34 patients with non-insulin-dependent diabetes mellitus. Patients were randomly assigned in a single-blind fashion to treatment with either lovastatin, an HMG CoA reductase inhibitor (n=16; mean dose 30.0±12.6 mg/day) or placebo (n=18) for 2 years. Renal function was assessed by serially measuring the serum creatinine, glomerular filtration rate (using Cr⁵¹-EDTA), and 24-h urinary protein excretion. Lovastatin treatment was associated with significant reductions in total cholesterol (p<0.001), LDL-cholesterol (p<0.001) and apo B (p<0.01), the reductions at 24 months being 26, 30 and 18%, respectively. Beneficial effects on serum triglyceride, HDL-cholesterol and apo A1 levels were also observed. Lp(a) showed no significant change in both groups. Glomerular filtration rate deteriorated significantly in the placebo group after 24 months (p<0.025) but showed no significant change in the lovastatin-treated patients. The increase in serum creatinine was statistically significant (p<0.02) in placebo-treated patients at 12 and 24 months, and in the lovastatin group after 24 months. Twenty-four hour urinary protein excretion increased in both groups (p<0.05). Lovastatin treatment was not associated with significant elevations in liver or muscle enzymes. We conclude that effective normalisation of hypercholesterolaemia may retard the progression of diabetic nephropathy.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - GFR glomerular filtration rate - Lp(a) lipoprotein(a) - apo apolipoprotein - LDL low-density lipoprotein - VLDL very low density lipoprotein - HDL high-density lipoprotein     

Urinary excretion of apo(a) fragments in NIDDM patients

Summary Lp(a), one of the most atherogenic lipoproteins, is believed to contribute significantly to vascular diseases in non-insulin-dependent diabetic (NIDDM) patients. Contradictive data have been published on these patients concerning plasma concentrations of Lp(a) and their relation to renal function. Since apo(a) fragments appear in urine, we measured urinary apo(a) in 134 NIDDM patients and 100 matched controls and related urinary apo(a) concentrations to plasma Lp(a) levels and kidney function. Plasma Lp(a) values were found to be significantly higher in NIDDM patients. NIDDM patients also secreted significantly more apo(a) into their urine as compared to control subjects. There was no correlation between creatinine clearance or albumin excretion and urinary apo(a) concentrations. Patients with macroalbuminuria exhibited a twofold higher apparent fractional excretion of apo(a) in comparison to patients with normal renal function. Urinary apo(a) values in both patients and control subjects were highly correlated to plasma Lp(a), yet no correlation was found with HbA_{1 c} or serum lipoproteins. It is concluded that urinary apo(a) excretion is correlated to plasma Lp(a) levels but not to creatinine clearance in patients suffering from NIDDM. [Diabetologia (1997) 40: 1455–1460] Received: 26 May 1997 and in revised form: 21 July 1997     

Elevated Lp(a) is the most frequent familial lipoprotein disorder leading to premature myocardial infarction in a country with low cholesterol levels

Disorders of the lipoprotein metabolism are an important cause of premature coronary artery disease and myocardial infarction. Of the genetic lipoprotein disorders, elevation of apoprotein (apo) B containing lipoproteins is the most frequent one in the western population. We aimed to define the prevalence of genetic lipoprotein disorders and other risk factors in a population from a country with a low average cholesterol levels. We examined 48 consecutive patients with premature myocardial infarction below age 55, their 78 siblings and age and body mass index matched controls for familial lipoprotein disorders. The patients with premature myocardial infarction had higher triglyceride, low-density lipoprotein, apo B, lipoprotein (Lp) (a) and lower apo A1 levels then controls (p<0.05). Of the nonlipid risk factors, 67% smoked, 8% had diabetes mellitus, 17% had hypertension and 58% a family history of premature coronary artery disease. Fifty percent of these patients with premature myocardial infarction had a familial lipoprotein disorder. Familial excess of Lp(a) was the most frequent lipoprotein abnormality present in 16% of the patients followed by familial combined hyperlipidemia. We conclude that, Lp(a) increase was the most frequent familial lipoprotein abnormality in this population. The frequency of familial lipoprotein disorders in this population emphasises the need to screen siblings of patients with premature myocardial infarction.     

Plasma lipoprotein (a) levels in Turkish NIDDM patients with and without vascular diabetic complications.

OBJECTIVE: Plasma concentrations of lipoprotein (a) [Lp(a)], an independent risk factor for atherosclerosis, were measured in 59 non-insulin-dependent diabetes mellitus (NIDDM) patients with and without vascular complications, and 21 non-diabetic healthy subjects. RESULTS: The plasma log Lp(a) levels were found to be significantly increased in the NIDDM patients (1.40 +/- 0.36) compared with the healthy subjects (1.02 +/- 0.53; p < 0.05). Plasma Lp(a) levels in NIDDM patients with diabetic vascular complications (1.51 +/- 0.27) were significantly higher than those of the NIDDM patients without diabetic vascular complications (1.23 +/- 0.43) and healthy subjects (p < 0.05). There were significant correlations between plasma log Lp(a) levels and apolipoprotein B (apo B) in all NIDDM patients (r: 0.68, p < 0.05). No correlation was observed between Lp(a) levels and age, sex, duration of diabetes, fasting blood glucose, haemoglobin Alc, the mode of treatment, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and apolipoprotein Al levels in all patients. CONCLUSIONS: It was concluded that Lp(a) was a risk factor for angiopathy in NIDDM patients and the patients who have a high plasma Lp(a) concentration should be kept under strict glycaemic control.     

老年2型糖尿病患者血清脂蛋白(a)水平与载脂蛋白(a)基因多态性分析

本文对老年 2型糖尿病患者血清脂蛋白 (a)水平及载脂蛋白 (a)多态性进行了分析 ,以探讨老年糖尿病与高脂蛋白 (a)血症的关系及其载脂蛋白 (a)遗传表型的分布特点 ,同时分析脂蛋白 (a)与糖尿病并发症的相关性。用酶联免疫吸附法测定脂蛋白 (a)水平 ,用十二烷基磺酸钠 -聚丙烯酰胺凝胶电泳和Westernblot技术测定脂蛋白(a)遗传表型。结果发现 :① 3组 (老年 2型糖尿病、非老年 2型糖尿病与老年健康对照组 )脂蛋白 (a)浓度差异无统计学意义 (P >0 .0 5 ) ,脂蛋白 (a)与血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇及其亚型、低密度脂蛋白胆固醇、载脂蛋白A和B水平无相关性 (P >0 .1) ;②老年 2型糖尿病组合并高血压、糖尿病性视网膜病变和糖尿病肾病者的血清脂蛋白 (a)浓度明显高于无合并相应疾病者 (P <0 .0 5或P <0 .0 0 1) ;③ 3组共检出 13种载脂蛋白 (a)基因型 ,在老年 2型糖尿病合并症患者中 ,低分子质量的S1和S2基因型明显多于其它组及无合并症者     

2型糖尿病患者血清脂蛋白(a)水平及其与冠心病的关系

目的　探讨 2型糖尿病患者血清脂蛋白 (a) [Lp(a) ]水平及其与冠心病的关系。方法　选择 90例 2型糖尿病及 6 8例健康对照者测定其血清Lp(a)、总胆固醇 (TC)、甘油三酯 (TG)、高密度脂蛋白胆固醇 (HDL C)水平 ;计算低密度脂蛋白胆固醇 (LDL C)水平及TC、TG、LDL C与HDL C比值。结果　 (1)糖尿病组血清Lp(a)水平与对照组比较差异无显著性意义 (P >0 .0 5 )。 (2 )将 2型糖尿病患者分为糖尿病伴冠心病和单纯糖尿病亚组后发现 :①糖尿病伴冠心病亚组血清Lp(a)水平明显高于单纯糖尿病亚组 [(2 3.78± 2 3.73)mg/dlvs (13.31± 10 .6 6 )mg/dl;P <0 .0 1]及对照组 [(2 3.78± 2 3.73)mg/dlvs (16 .2 8± 17.95 )mg/dl;P <0 .0 5 ];②糖尿病伴冠心病亚组血清Lp(a)水平与LDL C呈正相关关系 (r =0 .32 16 ,P <0 .0 5 )。结论　 2型糖尿病患者血清Lp(a)水平增高可能与冠心病发病有密切关系。     

Lipoprotein (a) in type 2 diabetes mellitus: Relation to LDL:HDL ratio and glycemic control

BACKGROUND:

Increased lipoprotein (a) [Lp (a)] concentrations are predictive of coronary artery disease (CAD). Type 2 diabetes mellitus also leads to dyslipidemia, like elevated triglyceride levels and low HDL levels, which are known risk factors for CAD. This study was designed to investigate the levels of Lp (a) in type 2 diabetic patients and their association with LDL: HDL ratio and glycemic control.

MATERIALS AND METHODS:

The study included 60 patients of type 2 diabetes and 50 age and sex matched controls. The Lp(a) levels in the diabetic group were compared with the control group and the relationship between the Lp(a) levels and LDL: HDL ratio was evaluated. Diabetic group was further divided into three subgroups according to levels of glycated hemoglobin. Lp(a) levels and glycated hemoglobin in controlled and uncontrolled diabetes mellitus were also compared to find out any correlation between them. Statistical analysis was done using the students ‘t’ test and Chi square test.

RESULTS:

Lp(a) levels were found to be significantly increased in the diabetic group as compared to the control group (P< 0.001). LDL: HDL ratio was also increased in the diabetic group as compared to the control group. Lp(a) levels showed no association with LDL: HDL ratio and degree of glycemic control in these patients.

CONCLUSIONS:

The results of the present study suggest that Lp(a) levels are increased in type 2 diabetic patients. The elevated Lp(a) levels do not reflect the glycemic status and are also independent of increase in LDL:HDL ratio suggesting different metabolic pathways and the genetic connection for LDL and Lp(a).     

Hypercoagulability and high lipoprotein(a) levels in patients with type II diabetes mellitus

Diabetes mellitus is associated with disturbances in hemostasis that could contribute to the development of diabetic vascular disease. We investigated the changes in parameters of blood coagulation and the fibrinolytic system and in plasma levels of lipoprotein(a) (Lp(a)) in 124 patients with type II diabetes mellitus and 44 healthy control subjects matched for age and body mass index (BMI) to determine whether hemostatic disturbances may lead to increased cardiovascular mortality. Median levels of fibrinogen (P < 0.0001), thrombin-antithrombin III complex (TAT) (P < 0.005), and plasminogen activator inhibitor-1 (PAI-1) activity (P < 0.05) in plasma were significantly elevated in diabetic patients compared with controls. The median concentration of Lp(a) was significantly higher in diabetic patients than in normal controls (18.2 vs. 12.6 mg/dl, P < 0.0005). Lp(a) levels tended to be elevated in patients with a prolonged history of diabetes. There was no evidence that Lp(a) levels were affected by metabolic control or by type of treatment. Twenty-two diabetics with coronary heart disease (CHD) had significantly higher levels of fibrinogen (P < 0.05), TAT (P < 0.05), and Lp(a) (24.7 vs. 13.7 mg/dl, P < 0.01) than the 51 patients without diabetic angiopathy. Our data indicate that impaired hemostatic balance in diabetes may cause hypercoagulability and may thus contribute to the increased cardiovascular mortality in diabetes.     

Apolipoprotein(a) size polymorphism is associated with coronary heart disease in polygenic hypercholesterolemia

BACKGROUND AND AIM: In addition to high serum cholesterol levels, various cardiovascular risk factors may be involved in the development of coronary heart disease (CHD) in hypercholesterolemic subjects. As the levels of lipoprotein(a) [Lp(a)], an important and independent cardiovascular risk factor, are high in polygenic hypercholesterolemia (PH), we investigated plasma Lp(a) levels and apolipoprotein(a) [apo(a)] phenotypes in relation to occurrence of CHD events in PH patients. METHODS AND RESULTS: Lp(a) levels and apo(a) isoforms were determined in 191 PH patients, 83 normocholesterolemic subjects with CHD, and 94 normocholesterolemic controls without CHD. Lp(a) levels were similar in the hypercholesterolemic subjects with (n=100) or without CHD (n=91): 21.4 (range 6.6-59.23) vs 18.5 (range 5.25-57.25) mg/dL (p=NS). Low molecular weight apo(a) isoforms were more prevalent (55%) in the PH patients with CHD, whereas high molecular weight apo(a) isoforms were more prevalent (62.6%) in those without CHD: this difference was significant (p<0.05). A stepwise multiple-discriminant analysis made in order to determine the independence of common cardiovascular risk factors, Lp(a) levels and low molecular weight apo(a) isoforms in predicting CHD among hypercholesterolemic subjects showed that the presence of a positive family history of CHD, smoking, age, and the presence of at least one apo(a) isoform of low molecular weight were independently associated with CHD. CONCLUSIONS: Despite high Lp(a) levels, our findings do not support the hypothesis that Lp(a) plays an independent role in determining clinical CHD in PH subjects. However, the presence of at least one low molecular weight apo(a) isoform is an independent genetic predictor of CHD in hypercholesterolemic subjects. Together with other cardiovascular risk factors, apo(a) phenotypes should be assessed to evaluate the overall CHD risk status of all subjects with high serum cholesterol levels.     

Lipoprotein(a): genotype-phenotype relationship and impact on atherogenic risk

In 2010, more than 45 years after the initial discovery of lipoprotein(a) [Lp(a)] by Kare Berg, an European Atherosclerosis Society Consensus Panel recommended screening for elevated Lp(a) in people at moderate to high risk of atherosclerotic cardiovascular disease (CVD). This recommendation was based on extensive epidemiological findings demonstrating a significant association between elevated plasma Lp(a) levels and coronary heart disease, myocardial infarction, and stroke. In addition to those patients considered to be at moderate to high risk of heart disease, statin-treated patients with recurrent heart disease were also identified as targeted for screening of elevated Lp(a) levels. Taken together, recent findings have significantly strengthened the notion of Lp(a) as a causal risk factor for CVD. It is well established that Lp(a) levels are largely determined by the size of the apolipoprotein a [apo(a)] gene; however, recent studies have identified several other LPA gene polymorphisms that have significant associations with an elevated Lp(a) level and a reduced copy number of K4 repeats. In addition, the contribution of other genes in regulating Lp(a) levels has been described. Besides the strong genetic regulation, new evidence has emerged regarding the impact of inflammation as a modulator of Lp(a) risk factor properties. Thus, oxidized phospholipids that possess a strong proinflammatory potential are preferentially carried on Lp(a) particles. Collectively, these findings point to the importance of both phenotypic and genotypic factors in influencing apo(a) proatherogenic properties. Therefore, studies taking both of these factors into account determining the amount of Lp(a) associated with each individual apo(a) size allele are valuable tools when assessing a risk factor role of Lp(a).     

Apolipoprotein (a) levels in type 1 and type 2 diabetes mellitus

Type 1 and type 2 diabetes mellitus are both characterized by increased cardiovascular mortality and morbidity. Since several reports have indicated that apolipoprotein (a) [apo (a)] levels are positively associated with an increased risk of macrovascular disease, we investigated whether apo (a) levels are elevated in both types of diabetes mellitus and may thus represent an independent risk factor for atherosclerotic disease. Apo(a) concentrations in type 1 diabetic patients were not significantly different from matched controls (276±78 vs 149±46 units/l). Type 2 diabetic patients had considerably higher levels of apo (a) than matched controls (471±89 vs 221±61 units/l,P=0.06), though the difference was not statistically significant. However, concentrations of apo (a) were above 300 units/l in 36% of type 1 and 67% of type 2 diabetic patients, but in only 14% and 25% respectively of matched control subjects. Plasma triglycerides were positively and independently correlated with apo (a) levels in both diabetic and non-diabetic subjects. On the other hand, no significant correlation was found between apo (a) levels and glycosylated haemoglobin, total cholesterol or high density lipoprotein cholesterol in any of the groups studied. In conclusion, apo (a) levels are not significantly elevated either in type 1 or type 2 diabetic patients without proteinuria and in moderate metabolic control; however, levels above 300 units/l were 2.6 times more frequent in both types of diabetes mellitus than in carefully age-, sex-, and weight-matched control subjects.     

Loss of abdominal fat and improvement of the cardiovascular risk profile by regular moderate exercise training in patients with NIDDM

Summary Non-insulin-dependent diabetes mellitus (NIDDM) is associated with an increased cardiovascular risk. Glycaemic control alone is often insufficient to control diabetic dyslipidaemia and other cardiovascular risk factors associated with NIDDM. The present trial was designed to evaluate the effects of physical activity as an adjunct to standard diabetes therapy on the lipid profile, blood pressure, glycaemic control, weight and body fat. Sixteen well-controlled (HbA_1c 7.5%) patients with NIDDM participated in a regular aerobic exercise training programme at 50–70% maximal effort over 3 months. Thirteen age- and sex-matched patients with NIDDM served as a control group. The 3-month intervention with an increase in physical activity from 92 (mean ± SD) ±79 to 246±112 min per week (p<0.001) by means of a structured activity programme resulted in significant improvement of plasma lipids with a 20% decrease in triglycerides (p<0.05), unchanged total cholesterol and increases in high-density lipoprotein and high-density lipoprotein-3 subfraction of 23% (p<0.001) and 26% (p<0.001), respectively. Systolic and diastolic blood pressure decreased significantly from 138±16 to 130±17 mm Hg (p<0.05) and 88±10 to 80±10 mmHg (p<0.001), respectively. Resting heart rate decreased from 81±13 to 74±14 beats per minute (p<0.001), waist-hip circumference ratio decreased from 0.96±0.11 to 0.92±0.10 (p<0.001) and body fat decreased from 35.3±7.2 to 33.0±8.0% (p<0.001). These effects occurred independently of changes in body weight and glycaemic control, which did not change during the study. This study shows that improvement in physical fitness by introducing regular physical exercise as part of the treatment programme in patients with NIDDM results in a significant amelioration of their cardiovascular risk profile.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - CHD coronary heart disease - HDL high density lipoprotein - BP blood pressure - bpm beats per minute - MAP mean arterial presssure - WHR waist-hip ratio - LPL lipoprotein lipase     

Serum lipids, lipoprotein(a) level, and apolipoprotein(a) isoforms as prognostic markers in patients with coronary heart disease

OBJECTIVE: Our objective was to study prognostic factors for death in patients with coronary heart disease (CHD), focusing on serum lipids and lipoproteins. DESIGN AND SUBJECTS: The study subjects were 964 patients with angina pectoris who underwent coronary angiography between 1985 and 1987. Follow-up, including survival and cause of death, was carried out in April 1998. RESULTS: A total of 363 patients died. Increasing age, diabetes and low levels of HDL cholesterol and of apolipoprotein (apo) AI were associated with increased risk of total mortality and cardiac mortality. In men, low levels of LDL cholesterol and of apoB were associated with increased risk of death, but not of cardiac death only; high levels of lipoprotein(a) [Lp(a)] were not associated with increased risk. In women, however, there was a trend towards increased risk with increasing Lp(a) levels (P = 0.054); the smallest isoform of apo(a) was associated with a twofold increase in risk. In women, but not in men, risk decreased with increasing molecular weight of the apo(a) isoforms. CONCLUSIONS: Amongst lipoprotein variables, low levels of HDL cholesterol and of apoAI and the presence of low-molecular weight isoforms of apo(a) are associated with increased risk of death in patients with CHD. Apo(a) isoforms and Lp(a) levels seem to be more important as risk factors amongst women. Low LDL cholesterol and apoB levels were associated with increased risk, but only in men. These findings demonstrate the importance of a gender-specific analysis of risk factors for CHD.     

Urinary excretion of apolipoprotein(a) fragments in type 1 diabetes mellitus patients

High levels of plasma lipoprotein(a) [Lp(a)] represent an independent risk factor for cardiovascular morbidity; however, Lp(a) has not yet been identified as a risk factor for type 1 diabetic patients. Results from the limited number of available studies on plasma Lp(a) levels in relation to renal function in type 1 diabetes mellitus are inconclusive. We hypothesized that only type 1 diabetes mellitus patients with impaired renal function show increased plasma Lp(a) levels, due to decreased urinary apolipoprotein(a) [apo(a)] excretion. We therefore measured urinary apo(a) levels in 52 type 1 diabetes mellitus patients and 52 matched controls, and related the urinary apo(a) concentration to the plasma Lp(a) level, kidney function, and metabolic control. Our findings indicate that patients with incipient diabetic nephropathy as evidenced by microalbuminuria (20 to 200 microg/min) exhibit significantly higher plasma Lp(a) levels (median, 15.6 mg/dL) in comparison to normoalbuminuric patients (median, 10.3 mg/dL) and healthy controls (median, 12.0 mg/dL). Urinary apo(a) normalized to creatinine excretion was significantly elevated in both normoalbuminuric (median, 22.3 microg/dL) and microalbuminuric type 1 diabetic patients (median, 29.1 microg/dL) compared with healthy subjects (median, 16.0 microg/dL) and correlated significantly with Lp(a) plasma levels in both patient and control groups (P < .003). No correlation existed between the Lp(a) plasma level or urinary apo(a) concentration and metabolic control in type 1 diabetes mellitus patients. From these studies, we conclude that urinary apo(a) excretion is significantly increased in type 1 diabetic patients and correlates with plasma Lp(a) levels, and only type 1 diabetic patients with microalbuminuria have higher plasma levels of Lp(a) compared with patients with normoalbuminuria and healthy controls.     

Lipoprotein(a) levels and apolipoprotein(a) polymorphism in type 1 diabetes mellitus: relationships to microvascular and neurological complications

To investigate plasma concentrations of lipoprotein(a) [Lp(a)] and apolipoprotein(a) [apo(a)] polymorphism in relation to the presence of microvascular and neurological complications in type 1 diabetes mellitus, 118 young diabetic patients and 127 age-matched controls were recruited. Lp(a) levels were higher in patients than in controls, but the apo(a) isoforms distribution did not differ between the two groups [higher prevalence of isoforms of high relative molecular mass (RMM) in both groups]. Microalbuminuric patients had Lp(a) levels significantly greater than normoalbuminuric patients, and normoalbuminuric patients showed higher Lp(a) levels than controls. Patients with retinopathy or neuropathy showed similar Lp(a) levels to those without retinopathy or neuropathy. No differences in apo(a) isoforms frequencies were observed between subgroups with and without complications (higher prevalence of isoforms of high RMM in every subgroup). However, among patients with retinopathy, those with proliferative retinopathy had higher Lp(a) levels and a different apo(a) isoforms distribution (higher prevalence of isoforms of low RMM) than those with non-proliferative and background retinopathy (higher prevalence of isoforms of high RMM). Our data suggest that young type 1 diabetic patients without microalbuminuria have Lp(a) levels higher than healthy subjects of the same age. Lp(a) levels are further increased in microalbuminuric patients. High Lp(a) levels and apo(a) isoforms of low RMM seem to be associated with the presence of proliferative retinopathy, but have no relation to neuropathy. Received: 23 June 1997 / Accepted in revised form: 27 November 1997