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The individual components of the metabolic syndrome such as central obesity, dyslipidemia with increased triglycerides and decreased HDL-cholesterol, hyperuricemia, hypertension and progressive glucose intolerance are markers for an increased risk of atheroma and type 2 (non-insulin-dependent) diabetes. All components, with the exception of hyperuricemia, are associated with skeletal muscle insulin resistance, leading to compensatory chronic hyperinsulinemia. Insulin resistance/hyperinsulinemia, in turn, is associated with a series of hypertensiogenic and atherogenic side effects, aggravating the individual components of the metabolic syndrome. From a more pathophysiologically orientated point of view, early identification of individuals obviously at risk for atheroma and type 2 diabetes, as well as early intervention aimed at the improvement of reduced insulin action may play a central role in an integrated life-style approach of primary prevention of atherosclerosis and type 2 diabetes.
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PMID:[The metabolic syndrome. Pathophysiologic causes, diagnosis, therapy]. 784 93

The objectives of this research were to determine the prevalence of essential and borderline hypertension in a population of blood donors and their families and to determine if there is a correlation between blood pressure and lifestyle and/or other cardiovascular risk factors. The study was comprised of 1976 individuals, of whom 1290 were men and 686 were women, aged 18-65 years. The prevalence of essential hypertension was 15.1% for males and 12.5% for females: the prevalence of borderline hypertension was 22.3% for males and 15.7% for females. The population was divided into two groups: the first group included only subjects (1170 men, 543 women) who did not regularly use drugs that could modify the blood pressure and the heart rate, the second group included the entire population. In the first group, the multiple regression analysis indicated, in order of importance: age, BMI (body mass index), and heart rate. These variables were important in determining the systolic blood pressure in both sexes, uricemia for males and glycemia for females. The diastolic blood pressure was dependent on BMI, heart rate, and alcohol in both sexes, and glycemia, LDL cholesterol, and uricemia in the men. In the second group, primary and borderline hypertension are significantly correlated with age, BMI, and uricemia in both sexes and glycemia in females. A program of health and nutritional education could modify some factors related to blood pressure, such as obesity and alcohol consumption. The result would be a reduction of the prevalence not only of essential and borderline hypertension, but also of metabolic diseases such as dyslipidaemias, diabetes and hyperuricemia, with a global reduction of the cardiovascular risk.
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PMID:[Arterial hypertension in relation to life style and other cardiovascular risk factors. Epidemiologic study of a population of blood donors. Project AVIS]. 802 51

In this review the independent risk factors of hypertension, diabetes mellitus type II and large vessel disease are discussed. Hyperinsulinemia as the most important factor is associated with obesity, dyslipoproteinemia, alcohol drinking, physical inactivity, hyperfibrinogenemia, smoking (among men), microalbuminuria and hyperuricemia, which are sometimes partially related. If one factor occurs, the other associated factors have to be searched for in order to initiate an adequate treatment. To improve the acceptance of adequate advice, the knowledge of risk reduction should influence the health education.
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PMID:[Hypertension, Type II diabetes mellitus and macroangiopathy: risk factors and their association]. 812 58

Metabolic disorders including diabetes mellitus, glucose intolerance, dyslipidemias, hyperuricemia, and hypervitaminosis A have often been mentioned in association with diffuse idiopathic skeletal hyperostosis (DISH). Production of bone under the influence of insulin or retinol has been suggested as a possible mechanism for this disease. We prospectively studied metabolic disorders in 25 patients with DISH and 25 controls matched for age, sex, and body mass index. Correlations between simultaneously evaluated parameters were looked for. Obesity was prevalent in both groups. Serum levels of glucose, insulin, glycated hemoglobin, total cholesterol, HDL cholesterol, triglycerides, uric acid, retinol, and retinol binding protein were similar in the two groups. A positive correlation was found between body mass index and serum insulin. We found no correlation between serum levels of insulin and retinol. None of the metabolic parameters studied showed alterations likely to explain the development of hyperostosis. Other growth factors such as retinoic acid or insulin-like growth factor 1, perhaps produced on a paracrine basis, may be the cause of increased bone at enthesis production.
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PMID:[Forestier disease and metabolism disorders. A prospective controlled study of 25 cases]. 816 24

From 1970 to 1990, 57 patients 50 years old or younger were treated for hypertension caused by atherosclerotic renal artery disease. Predisposing factors for atherosclerosis included smoking in 43 cases, hyperlipidemia in 15, diabetes in 8 and hyperuricemia in 8. Of the patients 47 had a family history of atherosclerotic vascular disease or a significant related disorder. Evidence of generalized atherosclerosis was present in 55 patients. Atherosclerotic renal artery disease was present unilaterally in 16 cases, bilaterally in 39 and in a solitary kidney in 2. Of the patients 34 were treated surgically, 20 medically and 2 by percutaneous angioplasty. Surgically treated patients experienced significant postoperative improvement in blood pressure (p = 0.001) and renal function (p = 0.05). Medically treated patients experienced significant improvement in blood pressure (p = 0.03) but renal function deteriorated. Younger patients with atherosclerotic renal artery disease suffer from a more severe and accelerated form of atherosclerosis than older patients. Although blood pressure control can be achieved with medical treatment, surgical revascularization offers the best opportunity for stabilization or improvement of renal function.
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PMID:Management of atherosclerotic renal artery disease in younger patients. 825 82

Hyperinsulinemia is very much in the spotlight. Debate rages as to its significance and role in the etiology not only of NIDDM, but also other morphological and metabolic risk factors for atherosclerotic cardiovascular disease, including upper-body obesity, dyslipidemia, hypertension, and hyperuricemia. Epidemiological data support a key role for hyperinsulinemia in these disorders but it is far from conclusive except for the fact that hyperinsulinemia and insulin resistance may be present many years before the onset of impaired glucose tolerance and NIDDM, and clearly play a role in their etiology. The thrifty genotype hypothesis provides a plausible basis for a better understanding of how hyperinsulinemia and insulin resistance could lead to glucose intolerance and atherosclerotic cardiovascular disease, but the detailed biochemical mechanisms remain elusive. A role for increased sympathetic nervous system activity, resulting from hypothalamic stimulation as a primary event causing hyperinsulinemia, cannot be excluded as a cause of hyperinsulinemia. The current focus on hyperinsulinemia also has resulted in closer examination of the therapy of diabetes and hypertension, emphasizing the need to avoid hyperinsulinemia in both IDDM and NIDDM individuals because of the putative risk of atherosclerotic cardiovascular disease and hypertension. There is still a paucity of epidemiological data to support a role for hyperinsulinemia in the etiology of hypertension. However, clinical practice already is being influenced by the fact that ACE inhibitors have been shown to reduce insulin resistance in clinical research studies. The research reviewed here, particularly that relating to hyperinsulinemia, insulin resistance, and cardiovascular disease risk factors, has opened new vistas for the treatment and prevention of NIDDM and atherosclerotic cardiovascular disease. Appropriate exercise clearly is associated with improved insulin sensitivity, modification of CVD risk factors, and lower prevalence of NIDDM. Upper-body obesity, the latest culprit in the field, can also be reduced by exercise. Hyperinsulinemia and insulin resistance can be detected in children, adolescents, and young adults. NIDDM can be prevented, but clearly, intervention needs to commence in childhood, and intensive risk factor intervention in subjects with NIDDM can reduce the risk of atherosclerotic cardiovascular disease. It seems paradoxical that prevention of NIDDM and atherosclerotic cardiovascular disease are now possible even though the biochemical and molecular basis of these disorders is not fully understood.
Diabetes Care 1993 Dec
PMID:Hyperinsulinemia--how innocent a bystander? 829 79

It has been found that polycystic kidney (ADPKD) is often associated with gout. On the other hand, there are reports describing that the hyperuricemia (HU) seen in ADPKD corresponds to a reduction in renal function. We investigated the uric acid metabolism in 44 patients with ADPKD (age, 50 +/- 12.8 years; CCR, 50.5 +/- 41.1 ml/min) at our hospital. From among these 44 patients, 14 with a CCR of 80 ml/min were selected. Their data for uric acid metabolism were compared against those from the previous year's studies on various disease types (114 normal subjects, 70 with membranous nephropathy, 175 with IgA nephritis, 122 with gout, 137 with asymptomatic hyperuricemia, and 42 with diabetes mellitus). Among the 44 patients with ADPKD, the serum uric acid (SUA) was 7.7 +/- 1.9 mg/dl and HU affected 28 (63.6%). The incidence of gouty arthritis was also high (6 patients, 13.6%), revealing a positive correlation between SUA and CCR. Compared with membranous nephropathy and IgA nephritis, ADPKD exhibited an accentuated increase in SUA associated with a reduction in CCR. It is believed that this represents a factor for a high incidence of complications of hyperuricemia and gouty arthritis in ADPKD in contrast to other diseases. However, no increase in the production of uric acid was noted in ADPKD.
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PMID:A study of uric acid metabolism and gouty arthritis in patients with polycystic kidney. 833 99

The history and laboratory examination of the parents of six families with a history of biliary showed that five mothers and one father had cholelithiasis. Two of the mothers also had exogenous obesity and diabetes mellitus, and one mother also had lipid abnormalities. Among the 21 children of the same families, one son had cholelithiasis; 5 children (4 women and one man) had cholelithiasis and exogenous obesity; 10 (9 women and one man) had cholelithiasis, exogenous obesity and diabetes mellitus; two (one man and one woman) had cholelithiasis, exogenous obesity and lipid abnormalities; one son had cholelithiasis and diabetes mellitus, and one son had cholelithiasis and lipid abnormality. Among the 18 grandchildren of these families, 3 (2 women and one man) had cholelithiasis; 5 granddaughters had cholelithiasis and exogenous obesity; 2 grandsons had cholelithiasis, exogenous obesity and diabetes mellitus; 2 grandsons had cholelithiasis and lipid abnormality; one grandson had cholelithiasis, diabetes mellitus and hyperuricemia; one grandson had cholelithiasis, exogenous obesity, lipid abnormalities and hyperuricemia, and one grandson had exogenous obesity and diabetes mellitus. Finally, of the greatgrandchildren, one girl had cholelithiasis.
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PMID:[Familial calculous cholecystopathy]. 847 36

Patients who develop diabetic nephropathy, one of the leading causes of end-stage renal diseases in Western communities, have an increased red cell Li+/Na+ countertransport (CT). Li+/Na+ CT is a membrane function which exchanges intracellular Li for extracellular Na in vitro. High Li+/Na+ CT reflects abnormal kinetic properties of red cell membrane Na/H exchange. A widespread abnormality of Na/H exchange could play a major role in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases since Na/H exchange is involved in the regulation of cell pH and cell volume; in the cellular response to hormones, mitogens, and growth factors; and in the renal reabsorption of Na and bicarbonate. Li+/Na+ CT is under genetic control and raised in a subgroup of patients with essential hypertension. Among these patients, high Li+/Na+ CT is associated with increased glomerular filtration rate, filtration fraction, proximal fractional Na reabsorption, microalbuminuria, plasma renin activity, and kidney and cardiac volume. Increased Li+/Na+ CT is often associated with hyperlipidemia, hyperuricemia, reduced insulin sensitivity, and obesity. The whole of these observations may explain why patients with diabetes or essential hypertension and increased Li/Na CT are at risk of early renal and cardiac impairment.
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PMID:Red blood cell Li+/Na+ exchange in patients with diabetic nephropathy and essential hypertension: therapeutic implications. 851 86

The insertion/deletion DNA polymorphism of the gene coding human angiotensin converting enzyme (ACE) was examined in 109 patients with coronary artery disease (CAD) and 93 non-coronary subjects (NCS) living in a northern part of Japan. The presence of risk factors including age, hypertension, hypercholesterolemia, tobacco use, diabetes mellitus and hyperuricemia were also examined. An insertion (I) / deletion (D) polymorphism of the ACE gene was determined by the polymerase chain reaction with oligonucleotide primers encompassing the polymorphic region in intron 16. The template DNA was isolated from peripheral blood leukocytes of patients. The frequency of the D-allele in NCS was 0.27, significantly lower than that reported in Caucasians or in Japanese living in the Osaka area. The frequency of the D-allele in patients with myocardial infarction (MI) and angina pectoris was 0.39 and was higher than that in NCS. The frequencies of genotypes DD, ID, and II were 17.8, 43.3 and 38.9%, respectively, in CAD except in young patients (below 40 years of age) with MI and AP groups, and 6.5, 40.9 and 52.7%, respectively in NCS (p < 0.05 between CAD and NCS). Young MI showed similar frequencies in ACE gene polymorphisms to those in NCS, a pattern which differed from that seen in subjects with CAD (p < 0.05). The numbers of risk factors did not alter the frequency of ACE gene genotype among patients with CAD, however, in normotensives, the odds ratio of DD-genotype was significantly increased to 3.4. Accordingly, ACE gene polymorphism may be associated with morbidity from CAD in Japanese living in northern Japan as has been noted in Caucasians, despite the lower frequencies of the D-allele in the Japanese population.
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PMID:Association of ACE gene polymorphisms with coronary artery disease in a northern area of Japan. 855 60


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