Diabetes and atherosclerosis ? The role of insulin

Stout, Robert W.

doi:10.1007/bf01219790

Cited by 222 publications

(84 citation statements)

References 101 publications

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“…24 ' M This hyperinsulinemia may predispose to vascular disease. 26 Our finding of a correlation of PA-inhibitor activity and BMI therefore strengthens the hypothesis recently formulated by Vague et al, 19 which states that the relative hyperinsulinism In obese Individuals, through its effects on PA-inhibltor activity, results in lower fibrlnotysls and thus enhanced development of vascular disease. In insulin-treated IDDM patients, who are also in a state of therapeutic" hyperinsulinism, the same mechanism might be operative as suggested by the correlation of insulin dose and PA-inhibltor activity (r = 0.4, p<0.05).…”

Section: Discussionsupporting

confidence: 76%

Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus.

et al. 1988

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Parameters of flbrlnolysls, Including euglobulln fibrlnolytlc activity, tissue-type plasminogen activator (t-PA) antigen, plasminogen activator Inhibitor (PA-lnhlbltor) activity, and plasmln-aj-antlplasmln complex (PAP) were studied In 62 patients (35 women and 27 men; ages 53 ± 16 years) with either Insulin-dependent (IDDM) or nonlnsulln-dependent (NIDDM) diabetes mellKus. Compared to a control group of similar age (n = 57), the diabetic patients had a significantly lower mean euglobulln fibrlnolytlc activity (1.2 ±0.7 vs. 1.7 ±1.1 ng/ml, p<0.01) but significantly higher mean t-PA antigen (15.7 ± 8.4 vs. 6.6 ± 2.9 ng/ml, p < 0.001) and PA-lnhlbltor activity (2.6 ± 1.3 vs. 1.5 ± 0.7 lU/ml, p<0.001) levels. Significant unlvarlate correlations were observed between PA-lnhlbttor activity and age (r=0.32, p<0.05), dlastollc blood pressure (r = 0.42, p < 0.01) and euglobulin fibrlnolytlc activity (r = -0.40, p < 0.01). In multlvariate analysis, only body mass Index (positively) and euglobulin fibrlnolytlc activity (negatively) remained significantly related to PA-lnhlbltor activity In the total diabetic population as well as In the NIDDM group. The only parameter In the IDDM group significantly related to PA-lnhlbltor activity was dlastollc blood pressure. These results suggest that PA-lnhibltor plays a role In the regulation of flbrlnolysls In diabetes patients and that factors like obesity and hypertension may be related to reduced flbrlnolysls via PA-lnhlbltor levels. (Arteriosclerosis 8:68-72, January/February 1988) D iabetes patients are predisposed to cardiovascular complications, which occur earlier and more frequently than in comparable nondiabetic patients. Abnormalities in both lipid metabolism and hemostasis contribute to the development of vascular damage.1 In diabetes patients, spontaneous fibrinolytic activity is reported to be normal or low, 2 -6 while release of plasminogen activator from the vascular endothelium is abnormal in some cases. 59 recently demonstrated that elevated tissue-type plasminogen activator (t-PA) antigen levels in poorly controlled diabetics could be decreased by insulin administration. These authors argued that a decrease of t-PA antigen in hyperinsulinemic, insulin-treated diabetics could hamper the fibrinolytic capacity and thereby favor the development of atherosclerosis.In the present study we have evaluated t-PA antigen and plasminogen activator inhibitor (PA-inhibitor) activity by both univariate and multtvariate analysis in a well-defined group of moderately controlled diabetic patients, including both insulin-dependent and noninsulin-dependent subjects. MethodsSixty-two diabetic patients (35 women and 27 men) ages 16 to 79 years (53 ± 16 years, mean ± SD) were

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Section: Discussionsupporting

confidence: 76%

Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus.

et al. 1988

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“…1). Dies hat unter anderem zu Überlegungen über den Zusammenhang zwischen Hyperjnsulinämie und Makroangiopathie geführt (97 Normalpersonen (9) Nprmalpersonen (9) Altersdiabetiker (11) Altersdiabetiker (11) Normalpersonen (14) Normalpersoneri (14) Insulinpflichtige Diabetiker vor Insulin-Behandlung (10) Insulinpflichtige Diabetiker vor Insulin-Behandlung (10) Altersdiabetiker (9) Altersdiabetiker (9) Normalpersonen (24) Normälpersonen (24) juvenile Diabet. (17) juvenile Diabet.…”

Section: Die Periphere Resistenzlageunclassified

Pankreatische B-Zellen-Peptide: Kinetik und Konzentration von Proinsulin, Insulin und C-Peptid in Plasma und Urin, Probleme der Meßmethoden, klinische Aussage und Literaturübersicht

Gerbitz¹

1980

CCLM

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Zusammenfassung: Kinetik und Konzentrationen der in Plasma und Urin meßbaren B-Zellen-Peptide werden anhand einer Übersicht der bisher in der Literatur mitgeteilten Daten erläutert und die möglichen Anwendungsgebiete sowie die klinische Aussagekraft der Methoden diskutiert. Allgemeine Probleme der Meßmethoden für freies und antikörper-gebundenes Insulin, Proinsulin und C-Peptid und die möglichen Anwendungsgebiete vor allem im Hinblick auf Diagnostik und Therapie insulinpflichtiger Diabetiker werden dargelegt. Pancreatic B cell peptides: Kinetic behaviour and concentrations ofproinsulin, insulin and C-peptide in plasma and urine, problems of assay methods, clinical significance and literature reviewSummary: The kinetics and the concentrations of B-cell peptides in plasma and urine are reviewed. Methodical problems in the determination of proinsulin, free and antibody-bound insulin and C-peptide are discussed, together with the possible application of these methods in the control of insulin-dependent diabetics. Einführung

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“…25 " 8 In attempts to elucidate atherogenic mechanisms associated with diabetes, most work has centered around characterization of alterations in lipid catabolism and associated changes in circulating lipoprotein patterns.…”

mentioning

confidence: 99%

Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes.

Orlidge¹,

Hollis²

1982

Arteriosclerosis

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We studied histamine metabolism, i.e., histldine decarboxylase (HD)-mediated synthesis and hlstamlnase-mediated catabollsm, in relation to intracellular histamine content in both aortic endothelial and subjacent smooth muscle cells of control and diabetic rats. Diabetes was Induced by a single jugular vein Injection of streptozotocln (55 mg/kg in acidified saline, pH 4.5), and animals were held for either 2 or 4 weeks following overt manifestation of diabetes. An additional 4-week diabetic group received Insulin (lletln NPH, 10 U per 24 hour) during the last week. With respect to control values, the histamine content of aortic endothelial cells increased 138%, HD activity Increased 250%, and histaminase activity decreased 50% over the 4-week period. In subjacent smooth muscle cells, the histamine content Increased In excess of 150%, HD activity Increased more than 300%, and histaminase activity decreased in excess of 30%. Insulin treatment for the last week resulted In complete reversal of all these changes. These results support the concept that a large vessel response similar to the microclrculatory prolonged phase of inflammation occurs In experimental diabetes, a change similar to that occurring in experimental atherosclerosis. They also Indicate that both synthetic and catabollc changes occur In histamine metabolism under these conditions, changes that alter arterlai wall histamine pools, and suggest that Insulin administration under conditions of experlmentai diabetes may modulate aortic histamine metabolism and the resultant Intraaortlc histamine pools.

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Diabetes and atherosclerosis ? The role of insulin

Cited by 222 publications

References 101 publications

Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus.

Tissue-type plasminogen activator antigen and plasminogen activator inhibitor in diabetes mellitus.

Pankreatische B-Zellen-Peptide: Kinetik und Konzentration von Proinsulin, Insulin und C-Peptid in Plasma und Urin, Probleme der Meßmethoden, klinische Aussage und Literaturübersicht

Aortic endothelial and smooth muscle histamine metabolism in experimental diabetes.

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