{"title":"Interactions amongst insulin, lipoproteins and haemostatic function relevant to coronary heart disease.","authors":"A Hamsten, F Karpe, P Båvenholm, A Silveira","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Interest has increased considerably in the past few years in the possible interactions amongst insulin, plasma lipoproteins and several components of the haemostatic system. There is now consistent epidemiological, clinical and experimental evidence that hypertriglyceridaemia, in particular, may represent a procoagulant state involving derangements of both blood coagulation and fibrinolysis. Imbalance in the haemostatic system secondary to increased clotting activity, impaired fibrinolytic function, or a combination thereof, should influence the growth and final size of evolving thrombi and predispose to arterial occlusion. This might be of particular significance in the coronary circulation, where a hypercoagulable state is likely to promote thrombosis at the site of a suddenly ruptured atherosclerotic plaque. In addition, there is accumulating experimental evidence that the haemostatic system plays a part in plaque formation and plaque growth. Basic research on the link between haemostasis and atherosclerosis should be given high priority, because modulation of haemostatic function will probably be a potent complementary approach to the prevention of coronary heart disease.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"75-88"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The epidemiology of coronary heart disease in glucose-intolerant and diabetic subjects.","authors":"E Eschwège, B Balkau, A Fontbonne","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes mellitus is usually recognized as a major risk factor for coronary heart disease (CHD) morbidity and mortality. As chronic hyperglycaemia defines diabetes mellitus, it is logical to think that hyperglycaemia itself is related to these complications. But, in diabetic patients, there appears to be no relation between CHD and the specific characteristics of diabetes, namely the duration of the disease and the level of blood glucose. Moreover, in the UGDP trial, the group of patients with the best-controlled glycaemia failed to demonstrate a reduction in CHD death, in comparison with the group with poor blood-glucose control. These results are reinforced by the data from 15 prospective studies, which failed to demonstrate a homogeneous and significant increase in CHD risk with asymptomatic hyperglycaemia. Coronary heart disease mortality depends on a constellation of risk factors which are interrelated to some extent; one of the risk factors, namely blood glucose, is not an independent risk factor, nor is diabetes mellitus. In patients with abnormal glucose tolerance, the factors contributing to CHD risk are hypertriglyceridaemia and also a central fat distribution. This central fat distribution could explain the low CHD risk in nondiabetic women, which contrasts with the high risk in diabetic women, who are characterized by central adiposity, as are diabetic men. Björntorp hypothesized that intra-abdominal fat, which has an exceedingly sensitive lipid mobilization capacity, could play a key role in the development of the cluster of metabolic abnormalities that are present in the plurimetabolic syndrome. Hyperglycaemia, one of the anomalies of the syndrome, could be an 'innocent bystander' rather than a 'partner in crime', in the manifestations of CHD.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"5-11"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dyslipidaemia and cardiovascular disease in non-insulin-dependent diabetic patient with and without diabetic nephropathy.","authors":"H H Parving, M A Gall, F S Nielsen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In 370 non-insulin-dependent diabetic (NIDDM) patients less than 66 years of age, we found the prevalence of albuminuria (> 300 mg 24 h-1) to be 13.8%. Males had a higher prevalence than females (19 vs. 5%). A kidney biopsy was performed in 35 patients. The biopsy revealed diabetic glomerulosclerosis in 77% of the cases and a variety of non-diabetic glomerulopathies in the remaining 23%. Fifty-six per cent of the patients with diabetic glomerulosclerosis had diabetic retinopathy, whereas none of the patients with non-diabetic glomerulopathies had signs of retinopathy. The presence of diabetic retinopathy strongly suggests that diabetic glomerulosclerosis is the cause of albuminuria. During a 5-year (range 1-7 years) prospective study, the course of kidney function was followed in 26 NIDDM patients with diabetic glomerulosclerosis. The glomerular filtration rate declined, and elevated systolic blood pressure was positively correlated to the rate of decline. The frequency of diabetic complications increased with increasing levels of urinary albumin excretion. In a cross-sectional study of 549 NIDDM patients, the prevalence of proliferative retinopathy was 2, 5 and 12%, the prevalence of hypertension 46, 68 and 85%, and the prevalence of ischaemic heart disease 22, 26 and 46% in normo-, micro-, and macroalbuminuria, respectively. The mortality from cardiovascular disease is increased ninefold in NIDDM patients with macroalbuminuria compared to the non-diabetic background population. The presence of the well-established risk factors cannot account for this finding alone.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"89-94"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
J Dallongeville, J C Fruchart, P Pfister, J M Bard
{"title":"Effect of fluvastatin on plasma apolipoprotein-B-containing particles, including lipoprotein(a). European Fluvastatin Study Group.","authors":"J Dallongeville, J C Fruchart, P Pfister, J M Bard","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Epidemiological studies have demonstrated an association between apolipoprotein-(apo)-B containing particles [lipoprotein (Lp) (a), LpE:B; LpC-III:B] and coronary heart disease (CHD). The effect of fluvastatin, a novel competitive inhibitor of HMG-CoA reductase, on these plasma lipoprotein levels was studied in patients with hypercholesterolaemia after 14 weeks of standard dietary therapy. The results of a placebo-controlled, dose-response study and of the combined data of the European double-blind, controlled studies on the effect of fluvastatin are presented. The patients were selected according to the following criteria of inclusion: plasma low-density-lipoprotein (LDL) cholesterol levels > 160 mg dL-1 and premature CHD and/or two associated risk factors, or LDL cholesterol > 190 mg dL-1 and no CHD, plus triglycerides < 300 mg dL-1. All measurements were performed at the Pasteur Institute Central Laboratory. Lp(a), LpE:B and LpC-III:B particles were measured by double-site ELISA. In the placebo-controlled, dose-response study, 429 subjects were randomly assigned to one of the following treatment groups: placebo, fluvastatin 2.5 mg q.p.m., 5 mg q.p.m., 10 mg q.p.m. and 20 mg q.p.m. Treatment with fluvastatin for 6 weeks was associated with a dose-dependent reduction of LDL cholesterol, apoB, LpE:B and LpCIII:B levels. In addition, treatment with fluvastatin 5 mg and 20 mg q.p.m. was associated with a significant reduction in median Lp(a) concentrations (3.2%, P < 0.05 and 6.4%, P < 0.05 respectively.(ABSTRACT TRUNCATED AT 250 WORDS)</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"95-101"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18981225","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Efficacy and safety of fluvastatin in hyperlipidaemic patients with non-insulin-dependent diabetes mellitus.","authors":"L A Jokubaitis, R H Knopp, J Frohlich","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In this preliminary report of a 20-week trial, 66 patients with non-insulin-dependent diabetes mellitus (NIDDM) and hyperlipidaemia who remained eligible after an 8-week dietary stabilization phase were randomly allocated to receive 20 mg of fluvastatin or placebo once daily for 6 weeks. Fluvastatin was subsequently increased to 20 mg twice daily and administered according to the same schedule, versus placebo, for a further 6 weeks. Both dosages of fluvastatin substantially improved serum lipid profiles compared with baseline and placebo. Both dosages of fluvastatin significantly reduced low-density- and very-low-density-lipoprotein (LDL, VLDL), cholesterol and triglyceride (TG) compared with placebo, and both dosages significantly elevated high-density-lipoprotein (HDL) cholesterol. The ratio of LDL to HDL was also significantly decreased. Amongst the 58 patients who completed the study, there was no evidence either of myopathy or of hepatotoxicity; mean creatine kinase values remained stable in the fluvastatin arm. Fasting glucose, glycosylated haemoglobin, and fructosamine levels were not markedly affected by active treatment. No serious adverse events attributable to the drug were reported. In conclusion, both dosages of fluvastatin appear to be effective and safe in the management of hyperlipidaemia in this outpatient, maturity-onset, diabetic population.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"103-7"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18981408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Polymorphisms of the lipoprotein lipase gene and premature atherosclerosis.","authors":"D J Galton, R K Mattu, J Cavanna","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Allelic frequencies of polymorphic variants at the lipoprotein lipase gene locus have been measured in subjects with premature coronary artery disease and dyslipidaemia. One of the polymorphic variants involves a termination codon in exon 9 that produces a truncated protein whose Michaelis constants for triolein or chylomicra are identical to the native enzyme but whose Vmax for both substrates may be increased. The other informative polymorphism is a HindIII site in intron 8 that shows marked assymetric allelic distribution in subjects with hypertriglyceridaemia/low HDL syndrome and in subjects with premature coronary artery disease. It is hoped that the marker may lead to the identification of an aetiological mutation in its vicinity to account for these disease associations.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"63-8"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Diabetic dyslipidaemia: treatment implications.","authors":"D J Betteridge","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes is associated with increased morbidity and mortality from cardiovascular disease in the absence of the major risk factors--cigarette smoking, hypertension and serum cholesterol concentration. When these risk factors are present, the attributable risk to each factor alone and to the combination of risk factors is higher in diabetic than in nondiabetic subjects. Thus, stringent measures to correct risk factors for cardiovascular disease have been advocated in diabetic patients. In addition to hypercholesterolaemia, other lipid and lipoprotein abnormalities collectively referred to as diabetic dyslipidaemia probably contribute to vascular risk. Hypertriglyceridaemia, often associated with low high-density-lipoprotein cholesterol, is common in NIDDM patients and is associated with insulin resistance. Recent information in diabetic patients, pointing to the association of hypertriglyceridaemia with accumulation of remnant particles and alterations in low-density-lipoprotein subfractions, helps to explain the strong relationship between hypertriglyceridaemia and vascular risk in these individuals. Although there are as yet no intervention trials with lipid-lowering diets or drugs in diabetic patients to judge the impact on vascular disease, national and international bodies have furnished guidelines for the identification and treatment of lipid disorders in diabetes in the hope of reducing the huge toll of vascular disease in these patients.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"47-52"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Modified lipoproteins in diabetes.","authors":"J P Deslypere","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The mechanisms by which diabetes leads to various manifestations of tissue damage are not yet fully understood; however, different recent studies suggest that some of them may be mediated by modified lipoproteins, although other lipid abnormalities also have been described in diabetes patients. Principally, the modification consists of an oxidation of the lipoprotein particle [mainly low-density lipoprotein (LDL)]. The oxidized LDL is then rapidly internalized by macrophages, converting them to cholesterol-loaded foam cells. In diabetic patients, oxidation occurs through two pathways: enzymatic (vascular inflammation) and nonenzymatic (polyunsaturated fatty acids) that can be blocked either by acetyl salicylic acid or by antioxidants. Moreover, in diabetes patients, higher glucose levels can also lead to a direct (stimulated by metals) or an indirect (by generation of glycosylated proteins) generation of free radicals, which will also damage proteins and collagen in particular. Clinically, lipid peroxide concentrations are higher in diabetic than in nondiabetic subjects, particularly in patients with vascular complications and with high triglyceride levels. These lipid peroxide levels can be decreased by antioxidants, whose concentrations are lower in diabetic patients. Preliminary data also indicate that HMG CoA reductase inhibitors can decrease lipid peroxide concentrations.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"69-74"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Genetic predisposition to hyperlipidaemia in diabetes: the end of the beginning?","authors":"D E Wilson, L K Kwong, S C Elbein, J M Lalouel","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Diabetes mellitus leads to disturbances in lipoprotein homeostasis particularly when there is poor glycaemic control. The resulting abnormalities in concentration and composition of the circulating lipoproteins are modified by inherited variation in the genes coding for apolipoproteins, for the lipoprotein-processing enzymes, and possibly for lipoprotein receptors. Thus, poorly controlled diabetes provides an opportunity to observe the phenotypic effects of recessive mutant alleles that would otherwise be silent. This phenomenon should be considered when one attempts to understand the pathogenesis of variant phenotypes, ones differing from those typical of diabetes mellitus alone. Our understanding of how genetic variation modulates the expression of hyperlipidaemia in diabetes is still rudimentary--it now seems probable that many other genetic conditions affecting lipoprotein metabolism in diabetes will eventually be brought to light.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"53-61"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18983304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hyperinsulinaemia and hypertriglyceridaemia.","authors":"G Steiner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Hyperinsulinaemia and hypertriglyceridaemia are frequently associated. This may be as a part of the syndrome of insulin resistance or in diabetes, particularly non-insulin-dependent diabetes (NIDDM). The importance of this association lies in the facts that atherosclerosis is the most frequent complication of diabetes, that hypertriglyceridaemia is a risk factor for coronary artery disease in diabetic populations and that hyperinsulinaemia also appears to be a risk factor for atherosclerosis. Hypertriglyceridaemia, even without obesity, is associated with resistance to insulin. This can result in compensatory hyperinsulinaemia. Chronic hyperinsulinaemia has been shown to increase the production of triglyceride (TG)-rich lipoproteins. The vast majority of particles in the TG-rich lipoprotein spectrum are in the intermediate-density-lipoprotein (IDL) range. Furthermore, increased levels of TG result primarily from increased numbers of these particles, rather than from increased particle size. This is important because, at least in nondiabetic individuals, increased levels of IDL are associated with increased atherosclerosis. Thus, there may be a vicious cycle of insulin resistance, hyperinsulinaemia, hypertriglyceridaemia and atherosclerosis. We have found that by reducing plasma TG levels alone, one can increase sensitivity to insulin and break this cycle.</p>","PeriodicalId":77556,"journal":{"name":"Journal of internal medicine. Supplement","volume":"736 ","pages":"23-6"},"PeriodicalIF":0.0,"publicationDate":"1994-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"18981410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}