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Biomedical subjects

J A Colwell

Publications and source records attributed to J A Colwell.

At least 55 records · Page 3Linked to original sources
PubMed1990

Hemostatic alterations with exercise conditioning in NIDDM.

Various parameters of coagulation and fibrinolysis were measured in 13 men (aged 54 +/- 3 yr) with non-insulin-dependent diabetes mellitus (NIDDM) before and after 12-14 wk of exercise training. Subjects exercised for 30 min 3 times/wk at 70% of maximum O2 consumption (VO2max). Training increased VO2max by 12.5% but did not alter body weight, relative body fat, blood pressure, cholesterol, triglycerides, or high-density lipoprotein cholesterol. Slight downward trends were apparent for fasting glucose and insulin, but glycosylated hemoglobin was unchanged. There were no changes in coagulation parameters of plasminogen, hematocrit, or alpha 2-antiplasmin. Plasma fibrinogen (303 +/- 24.2 vs. 256 +/- 12.3 mg/dl) and fibronectin (380 +/- 41.9 vs. 301 +/- 22.2 micrograms/ml) were significantly reduced (P less than 0.02) by exercise conditioning. Three assays of fibrinolytic activity (tissue plasminogen activator, euglobulin lysis time, and an isotopic measure of fibrinolysis) confirmed that neither basal fibrinolysis nor the fibrinolytic responses to venous occlusion and maximal exercise were significantly altered. Exercise conditioning may have antithrombotic effects in NIDDM by reducing plasma fibrinogen and fibronectin. Although the significance of the fall in fibronectin awaits further studies, the reduction in plasma fibrinogen gives a rationale for the use of exercise training in men with NIDDM.

Diabetes Mellitus, Type 2↗
PubMed1988

A review of the development of large-vessel disease in diabetes mellitus.

A review of certain aspects of the development of atherosclerosis in diabetes mellitus is presented. Emphasis is on work in the laboratories of the authors and their colleagues, which focused primarily on alterations of platelet and endothelial function and on lipoprotein-cell interactions. These findings are considered within the broad context of other factors that are of importance in the development of atherosclerosis in diabetes mellitus.

Animals↗
PubMed1988

Enhancement of platelet aggregation by low-density lipoproteins from IDDM patients.

Low-density lipoprotein (LDL) is known to enhance platelet sensitivity to some aggregating agents. In this study, we observed that LDL isolated from patients with insulin-dependent diabetes mellitus (IDDM) enhanced thrombin-induced platelet aggregation to a greater extent than LDL isolated from matched controls (P less than .01). Thromboxane B2 production during aggregation was also significantly more enhanced by LDL isolated from IDDM than by control LDL (P less than .01). There was no difference in the lipid composition (free and esterified cholesterol, total phospholipids, and triglycerides) of LDL isolated from diabetic and control subjects. In contrast, the extent of glycosylation of LDL isolated from diabetic patients was significantly greater than that observed in LDL from normal subjects (P less than .01), and a positive correlation (r = .605, P less than .01) between the degree of LDL glycosylation and the rate of platelet aggregation was observed. LDL glycosylated in vitro enhanced thrombin-, collagen-, and adenosine 5'-diphosphate-induced platelet aggregation to a greater extent than control LDL (P less than .01). Although LDL glycosylated in vitro was taken up by platelets to a greater extent than control LDL (P less than .05), the lipid composition (free cholesterol and phospholipid) of platelets was not significantly changed. We postulate that an increased degree of glycosylation of LDL may enhance its uptake by platelets and lead to increased platelet reactivity to aggregating agents, probably by altering the structure of the platelet membrane. The enhancement of platelet aggregation by LDL may contribute to the accelerated development of atherosclerosis in diabetes mellitus.

Adolescent↗
PubMed1986

Effects of exercise on platelet function, coagulation, and fibrinolysis.

Exercise and physical conditioning may reduce the subsequent risk of major vascular thrombotic events. In view of this, it may be important to examine the effects of exercise on the blood coagulation system. The present paper reviews the effects of physical exercise and conditioning on blood coagulation, platelet function, and fibrinolytic activity. A hypothetical scheme is developed, in which increased blood coagulability and activated platelet function is counterbalanced by increased fibrinolytic activity and endothelial prostacyclin release. Some consideration is given to how this sequence of events may be altered in vascular disease states.

Blood Coagulation↗
PubMed1986

Glycosylation of low density lipoprotein in patients with type 1 (insulin-dependent) diabetes: correlations with other parameters of glycaemic control.

Glycosylation of low density lipoproteins obtained from 16 patients with Type 1 (insulin-dependent) diabetes and from 16 age-, sex-, and race-matched controls, was determined. The diabetic patients were normolipaemic and were in good or fair glycaemic control. Eleven patients performed home blood glucose monitoring. Glycosylation of low density lipoproteins in the diabetic patients was significantly higher (p less than 0.001) than in the control subjects, and was significantly correlated with haemoglobin A1c, (p less than 0.01), glycosylation of plasma proteins, (p less than 0.001), and mean home blood glucose, (p less than 0.01). This study confirms that, in diabetic patients, increased glycosylation of low density lipoprotein occurs to an extent which correlates closely with other commonly used indices of glycaemic control.

Adult↗
PubMed1986

VA cooperative study on antiplatelet agents in diabetic patients after amputation for gangrene. IV. Issues in design, interpretation, and analysis.

This paper review some of the issues faced by the investigators involved in a VA Cooperative Study on Antiplatelet Agents in Diabetic Patients after Amputation for Gangrene. The study was a negative one, and some of the reasons for this are considered. In addition, suggestive results in two subgroups, cerebrovascular disease and unexpected, sudden, or unobserved deaths, were found. The implications and interpretation of these findings are discussed.

Amputation, Surgical↗
PubMed1985

Diabetic lipoprotein deficient serum: its effect in low density lipoprotein (LDL) uptake and degradation by fibroblasts.

Low density lipoproteins (LDL) isolated from poorly controlled diabetic patients are known to be taken up and degraded by fibroblasts at a lower rate than LDL isolated from normal subjects. This aberrant metabolic behavior has been attributed to a diabetic-related abnormality in LDL composition yet to be characterized. The studies reported in this article show that the decrease in uptake and intracellular degradation of LDL from diabetic patients is further enhanced when the cells are exposed to lipoprotein deficient serum (LPDS) isolated from the same poorly controlled diabetic patients. Comparative studies of the composition of LPDS obtained from normal donors and poorly controlled diabetic patients showed an increase in saturated and total unesterified fatty acids (UFA), lecithin, apolipoprotein A1, and immunoreactive insulin in the LPDS from diabetic patients. We postulate that exposure of cells to LPDS obtained from poorly controlled diabetic patients may induce changes in the composition of the fibroblast membrane and alter its fluidity, leading to further decrease in the uptake and degradation of LDL. During poor diabetic control, cell membrane changes, and modification of LDL composition are likely to act either additively or synergistically to induce an abnormal LDL-cell interaction. This abnormal interaction may be a relevant factor to explain the greater incidence of arteriosclerosis in diabetes mellitus.

Adolescent↗
PubMed1985

Insulin and arachidonic acid metabolism in diabetes mellitus.

The alterations in the metabolism of arachidonic acid to prostaglandin I2 (prostacyclin), a vasodilator antiaggregatory substance, and thromboxane A2, a vasoconstrictor proaggregatory substance, in diabetes mellitus are reviewed in this article. When tested in vitro, platelet aggregation is enhanced in some patients with diabetes mellitus. The synthesis of thromboxane B2, the stable metabolite of thromboxane A2, by platelets is increased in patients with diabetes mellitus compared with control subjects. This increased synthesis appears to play a role in the enhanced platelet aggregation since the latter can be reversed by aspirin treatment and in vitro by the thromboxane receptor-antagonist 13-azaprostanoic acid. Vascular prostacyclin synthesis is decreased in both patients and experimental animals with diabetes mellitus. Treatment of experimental animals with insulin reverses the decreased synthesis of prostacyclin. The etiology of the altered arachidonic acid metabolism remains uncertain but appears to be multifactorial and includes alterations in metabolic control and circulating immune complexes. The increased ratio of thromboxane A2 to prostacyclin, which favors an enhanced thrombotic state, may play a role in the accelerated vascular disease of diabetes mellitus.

Animals↗
PubMed1985

Platelet function during continuous insulin infusion treatment in insulin-dependent diabetic patients.

Patients with diabetes mellitus manifest increased in vitro platelet aggregation and increased synthesis of the proaggregant and vasoconstrictor, thromboxane A2 (TXA2). We studied the effects of continuous insulin infusion treatment on platelet aggregation and arachidonic acid (AA)-stimulated platelet TXA2 synthesis (15 and 30 s post-AA, 1 mM) in 16 type I diabetic patients. Strict glycemic control was induced with the Biostator for 2 days and maintained for 12-14 days with continuous subcutaneous insulin infusion (CSII). The average premeal plasma glucose level (4/day) fell from 184 +/- 15, before treatment, to 107 +/- 6 mg/dl on the final day (P less than 0.001). After control, platelet synthesis of TXA2, measured by radioimmunoassay of its stable metabolite, immunoreactive TXB2 (iTXB2), decreased in all patients (30 s: 276 +/- 31 versus 199 +/- 28 ng iTXB2/ml/5 X 10(5) platelets; P less than 0.05). The reduction in platelet iTXB2 synthesis (15 and 30 s) was greater in poorly controlled patients (HbA1c greater than 12%; N = 8), and for all patients the decrease in iTXB2 (15 and 30 s) was correlated with the prestudy HbA1c level (15 s: r = 0.6; P less than 0.01). In contrast, platelet aggregation responses did not improve during intensive insulin treatment. The ED50 for AA (dose producing 50% maximum aggregation at 1 min) was unchanged after 2 wk of treatment and the ED50 for aggregation induced by ADP fell significantly in patients with HbA1c greater than 12% (2.8 +/- 1.3 versus 1.2 +/- 0.6 microM; P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1985

V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: III. Definitions and review of design and baseline characteristics.

This report summarizes the major design features, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study. In eleven V.A. centers, 231 male diabetic patients who had either a recent amputation for gangrene (N = 207) or active gangrene (N = 24) were randomly assigned to a group which received aspirin (325 mg t.i.d.) plus dipyridamole (75 mg t.i.d.) (N = 110) or two placeboes t.i.d. (N = 121). Major end point were vascular death and amputation of the opposite extremity for gangrene. Forty-one percent of the 563 patients screened were enrolled during a 39 month period. Enrollment errors were found in 8.7%. Historically, the two groups were well matched regarding the following variables: age, duration of diabetes, insulin therapy, previous oral agent therapy, hypertension, myocardial infarction, congestive heart failure, renal disease, sensory neuropathy, and smoking. The drug therapy group had an increased frequency of a history of cerebrovascular disease (19% vs 7%, p = 0.01). The groups were well matched regarding amputation site, obesity, extent of lower extremity vascular disease, retinopathy, and neuropathy upon examination. Their baseline fasting values of glucose, cholesterol, triglycerides, and creatinine were also comparable. We conclude that this study should provide definitive data on the efficacy of these antiplatelet agents in preventing further vascular disease in this patient group. It should also provide new prospective data on the natural history of vascular disease, and the association of vascular risk factors with subsequent vascular events in this patient population.

Amputation, Surgical↗
PubMed1985

Effect of insulin treatment in streptozocin-induced diabetic rats on in vitro platelet function and plasma von Willebrand factor activity and factor VIII-related antigen.

Diabetes mellitus is associated with altered platelet function and endothelial damage, but their relationship remains unclear. We examined the effect of short-term metabolic control with insulin in 14- and 28-day streptozocin-induced diabetic rats on alterations in in vitro platelet aggregation and serotonin release. Endothelial damage was assessed by plasma concentrations of von Willebrand factor activity (VIIIR:WF) and factor VIII-related antigen (VIIIR:Ag). Insulin was administered for 5 or 7 days at 9 or 21 days, respectively, after streptozocin. Enhanced platelet aggregation responses to adenosine diphosphate (ADP) and thrombin occurred after both durations of diabetes. Insulin therapy returned ADP-induced, but not thrombin-induced, responses to normal. Enhanced thrombin-induced platelet release of serotonin occurred at both times. Collagen-induced platelet release was enhanced in 28-day diabetic rats. Insulin therapy returned these responses to normal. Plasma concentrations of VIIIR:WF and VIIIR:Ag were elevated in 28-day, but only VIIIR:WF was elevated in 14-day diabetic rats. Insulin therapy reduced the elevated levels of VIIIR:Ag in 28-day diabetic rats, but had little effect on either parameter after the shorter duration of diabetes. In summary, Enhanced platelet aggregation and increased release of serotonin occur shortly after the induction of diabetes by streptozocin in adult rats. These platelet changes precede alterations of endothelial function, as determined by plasma VIIIR:WF and VIIIR:Ag levels. Platelet changes respond more rapidly to insulin therapy than do endothelial changes in diabetic rats. The duration of diabetes before insulin therapy does not affect these relationships.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Reduced platelet-mediated and enhanced leukocyte-mediated fibrinolysis in experimentally induced diabetes in rats.

Studies of fibrinolytic activity in diabetes mellitus have produced conflicting results. This may be a result of methodologic insensitivity or of variable contributions of the different blood components to whole blood fibrinolysis. To explore these two possibilities, we used a sensitive solid-phase radiometric assay to examine the fibrinolytic activity of whole blood, platelet-rich plasma, leukocytes, and platelet- and leukocyte-poor plasma prepared from control rats and rats with streptozocin-induced diabetes at various times after induction of diabetes. Fibrinolytic activity of whole blood from diabetic rats after 7 days was significantly reduced, and remained reduced after longer durations of diabetes up to 28 days. Platelet-rich plasma from diabetic rats had decreased fibrinolytic activity, which followed the same time course of changes as in whole blood. The platelet contribution to whole blood fibrinolysis was further reduced in vivo after 14 days of diabetes by a reduced whole blood platelet count. In contrast, fibrinolytic activity of leukocytes from diabetic rats became enhanced after 7 days of diabetes. After 49 days of diabetes, the whole blood leukocyte count was reduced, and in vivo would offset the enhanced activity. Plasma fibrinolytic activity was small compared with that of whole blood and was unaltered in diabetic rats. We conclude that altered platelet function contributes to decreased fibrinolytic activity of whole blood in diabetic rats, and that this may be partially offset by enhanced leukocyte-mediated fibrinolysis.

Animals↗
PubMed1984

Platelet survival in streptozotocin-induced diabetic rats.

Platelet survival in diabetes mellitus may be decreased or normal, and it is not clear whether altered platelet survival is due to a platelet or to a non-platelet defect. Therefore, platelet survival studies were performed at intervals up to 28 days in streptozotocin-induced diabetic and normal rats, using washed platelets from diabetic or normal animals. When compared to platelets from control rats, there was a significant decrease in platelet survival when platelets from 7 and 14 day diabetic rats were injected into normal controls or into diabetic rats. After 28 days of diabetes, platelet survival in diabetic rats was significantly lengthened, whether the platelets came from control or diabetic rats. Conclusions. Shortened platelet survival in the diabetic rat is caused initially by a platelet defect. Later, non-platelet factors become dominant. These findings may help explain reported discrepancies in results of platelet survival in diabetes mellitus.

Animals↗
PubMed1984

V.A. Cooperative Study on antiplatelet agents in diabetic patients after amputation for gangrene: I. Design, methods, and baseline characteristics.

This report describes the experimental design, methods, and baseline characteristics of patients enrolled in a Veterans Administration Cooperative Study on the effect of aspirin (325 mg t.i.d.) and dipyridamole (75 mg t.i.d.) (110 patients), or placebo (121 patients) on major vascular outcome variables in noninsulin-dependent diabetic patients with either a recent amputation for gangrene (n = 207) or active gangrene (n = 24). It also describes the baseline characteristics of the patients. A total of 231 patients of 563 screened (41%) were enrolled at 11 participating V.A. Medical Centers during a 39 month period. The median age at entry was 60 years, the median duration of diabetes was 10 years, and weight was 110% of desirable. All patients were men. Sixty-eight percent were treated with insulin and 32% with diet alone. Only 42% were smokers at entry, 40% had retinopathy, 61% sensory neuropathy, 42% hypertension, and 29% had a history of myocardial infarction, angina, and/or congestive heart failure. Thirteen percent had a history of cerebrovascular disease. Despite randomization, the treatment group had an increased frequency of a history of cerebrovascular disease (p = 0.01), diagnosed as stroke (p = 0.03), a finding suggesting that the treatment group was at a slightly increased risk for vascular disease upon enrollment in the study. Other baseline variables did not differ significantly between the two groups. This study should provide definitive data on the efficacy of these doses of antiplatelet agents in preventing further vascular disease in diabetic men with gangrene or recent amputation for gangrene, using death due to vascular disease and subsequent amputation of the opposite extremity for gangrene as major outcome variables. It should also give useful information on the effect of antiplatelet therapy on vascular outcome variables such as same side amputations, myocardial infarction, stroke, transient ischemic attack, retinopathy, and renal failure. Finally, the study should provide useful data on the natural history and significance of risk factors in this patient population.

Amputation, Surgical↗
PubMed1984

Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control.

The renal kallikrein-kinin system is thought to be involved in vasoregulatory and epithelial ion-transporting processes. Renal kallikrein has not been studied in patients with diabetes mellitus, a disease in which abnormalities of renal hemodynamics and electrolyte handling occur. The urinary excretion of this kallikrein was measured in 20 type I diabetic patients and 10 normal subjects. On a 120-meq Na diet, daily kallikrein excretion, determined by both esterase activity and direct RIA, in 12 poorly controlled diabetic patients [hemoglobin A1c (HbA1c) = 14.2 +/- 0.5% (mean +/- SEM)] was significantly greater (P less than 0.05) than excretion in 8 diabetic patients in good to moderately good control (HbA1c = 9.4 +/- 0.5%) or in 10 normal subjects. In these groups, urinary esterase activities were 9.4 +/- 1.0, 6.1 +/- 1.4, and 6.7 +/- 0.5 esterase units/24 h, respectively. Corresponding excretion values of immunoreactive kallikrein were 171 +/- 14, 118 +/- 26, and 123 +/- 11 micrograms/24 h. Creatinine clearances were similar in the three groups. Urinary kallikrein was also measured in 8 diabetic and 8 normal subjects during 7 subsequent days of 10 meq Na intake. It increased less in diabetic patients than in normal subjects during Na depletion (P less than 0.02). The increase in urinary kallikrein in the diabetic patients was inversely related to their HbA1c levels (r = 0.88; P less than 0.01). The effect of glycemic control on urinary kallikrein excretion was determined in nine diabetic patients. Initial glycemic control was achieved using an artificial endocrine pancreas (Biostator) and was maintained by continuous sc insulin infusion with a portable pump. Before glycemic control, urinary kallikrein was 190 +/- 30 micrograms/24 h (by RIA). After 8-12 days of glycemic control, excretion fell to 144 +/- 23 micrograms/24 h (P less than 0.02). The abnormalities in kallikrein excretion in diabetic patients were not correlated with differences in water, electrolyte, protein, glucose, or aldosterone excretion in any of the studies. These results show that kallikrein excretion was increased in patients with poorly controlled insulin-dependent diabetes, and excretion rose less in diabetic subjects with low Na intake than in normal subjects. Strict glycemic control decreased urinary kallikrein excretion. These findings suggest that the renal kallikrein-kinin system is functioning abnormally in diabetes mellitus.

Adult↗