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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A single s.c. injection (10 mg/100 g bw of alloxan) was given to nonarteriosclerotic, virgin, Sprague--Dawley rats and to breeder rats with preexisting arteriosclerosis, hyperlipidemia and hyperglycemia. All of the animals promptly developed severe diabetes with ketosis, hyperglycemia, and hyperlipidemia. Insulin therapy was deliberately withheld. Mortality was high. Seven days later one group was subjected to hypophysectomy and 30 days later, all of the animals were autopsied. The diabetes + hypophysectomy animals maintained their body weight better, did not have hypertrophied adrenal glands, showed the least elevation of serum enzymes, e.g., CPK, SGOT, SGPT and LDH, less hyperlipidemia and hyperglycemia and reduced corticosterone production than the animals with untreated severe diabetes. Despite the relative amelioration of metabolic derangements prognostic of cardiovascular degenerative changes, the diabetes + hypophysectomy animals manifested extensive renovascular damage and the breeder rats with pre-existing arteriosclerosis showed definite exacerbation of their arterial disease in response to the severe alloxan diabetes regardless of hypophysectomy. It is suggested that although hypophysectomy may alleviate certain metabolic derangements attributed to growth hormone, ACTH and adrenal steroids, the angiopathic damage proceeds inexorably.
Atherosclerosis 1976 Oct
PMID:Effects of hypophysectomy on alloxan-diabetic, arteriosclerotic, breeder vs. non-arteriosclerotic, virgin rats. 98 94

Chronic insulinopenic diabetes was induced by i.v. streptozotocin in the non-human primate Macaca fuscata. Five diabetic monkeys were kept for 8-19 months and nine for 24-48 months without any insulin treatment. Hyperglycemia (241 +/- 22 mg/dl, M +/- SE less than or equal to 1 year) progressed to 376 +/- 34 mg/dl (greater than 2 years) and ketosis to 3.5 mM (greater than 2 years) during the course of diabetes; this was roughly inversely proportional to hypoinsulinemia (3.4 microU/ml, 2 years). Serum cholesterol increased from 184 +/- 11 (less than or equal to 1 year) to 328 +/- 66 mg/dl (greater than 2 years) with the major increase in LDL-cholesterol (2.7-fold over control, greater than 2 years). HDL-cholesterol did not change at all throughout the experimental period. TG increased from 144 +/- 25 (less than or equal to 1 year) to 676 +/- 116 (greater than 2 years) with a major increase in the VLDL fraction (15-fold over control, greater than 2 years). Serum levels of apo B increased to 141 +/- 16 (less than or equal to 2 years) and 223 +/- 8 mg/dl (greater than 2 years) in contrast to control, 73 +/- 2. Morphologically, lipid deposition in the intima and fatty streaks have been observed in the abdominal aorta of all the diabetic monkeys with duration of more than 2 years. In six of the diabetic monkeys atheromatous changes such as intimal and medial thickening with smooth muscle cell proliferation were observed with foam cell formation. Similar atherosclerotic lesions were observed in renal and coronary arteries in at least six of these monkeys. In diabetic monkeys with duration of less than 2 years, mild atherosclerotic lesions were observed in two out of five. The results indicate that long standing insulinopenia leads to metabolic derangements characterized by hyperglycemia, ketonemia and hyperlipidemia. Elevation of LDL-cholesterol and VLDL TG with an increase of apo B is a characteristic of lipoprotein disorder. Morphologically, early to moderately advanced lesions of atherosclerosis were observed in aorta, renal and coronary arteries as a result of metabolic derangement due to insulin deficiency.
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PMID:Hyperlipidemia and atherosclerosis in experimental insulinopenic diabetic monkeys. 142 36

Three labile diabetic patients had recurring episodes of altered sensorium. Each had severe cerebrovascular disease with superimposed metabolic derangements, including ketoacidosis, hyperglycemia without ketosis, mild uremia, and possibly cerebral edema. Two of the patients were examined postmortem. Severe leptomeningeal scarring, basal ganglial calcification and destruction of small intracerebral vessels without evidence of large vessel atherosclerosis were found unexpectedly in one patient, a rare occurrence in this country although recently reported from Europe. The other patient had large vessel atherosclerosis only. The clinical expression of the vascular disease was modified by concurrent abnormalities and reflected the sum total of the complexities which coexisted. The pathophysiology of the unconscious state necessarily depends on the inciting factors. Ketoacidotic coma is associated with depressed cerebral oxygen consumption. Spinal fluid pH is usually maintained during ketosis but is sometimes lowered inadvertently during bicarbonate therapy, with resultant coma. Other variables influencing the clinical expression, with or without ketosis, would include, among others, blood viscosity alterations, rapid decrements in blood sugar, and existing degrees of lactic acidosis. The increasing life-span of the juvenile diabetics, favorably influenced by improved management and recently by hemodialysis, may uncover vascular complications heretofore rarely seen and create additional diagnostic and therapeutic enigmas.
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PMID:Cerebral syndromes of diabetes mellitus. 579 97

Thirty-one insulin-dependent diabetic children were studied (11 boys and 20 girls; 22 whites, 6 mulattoes and 3 Negroes; age-range: 8-14 years; mean age 11.7 years). According to the quality of their metabolic control the children were divided into 3 groups: Group 1, children in good metabolic control; Group 2, children in poor metabolic control but without ketosis; Group 3, children in severe ketoacidosis; 15 normal children (Group 4) served as controls. No hypercholesterolemia was found. As to blood sugar and serum triglyceride levels, significant differences were found between the control group and the diabetic groups as well as between the diabetic groups. When evaluating the result of HDL-cholesterol determinations we found a significant difference between the control group and Groups 2 and 3, as well as between diabetics in good control (Group 1) compared to Groups 2 and 3. We also found a correlation in diabetics in good control between blood sugar values and high HDL-cholesterol levels, and in diabetics in poor control between high blood sugar values and low HDL-cholesterol levels. No correlation was found between HDL-cholesterol and triglycerides in diabetes in poor metabolic control. In view of these findings the importance of reaching an optimal metabolic control in insulin-dependent children is emphasized, and the role of normoglycemia in the prevention of atherosclerosis is stressed.
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PMID:High density lipoprotein cholesterol in insulin-dependent diabetic children. 666

Management of diabetes mellitus (DM) continues to undergo evolutionary changes with further refinements as a result of enhanced understanding of the pathophysiology, technologic advances in glucose monitoring techniques and equipment, and an abundance of new drugs and insulin administration devices. Clearly, the maintenance of near normal blood glucose levels remains the prime goal of therapy in both noninsulin-dependent diabetes mellitus (NIDDM) and insulin-dependent diabetes mellitus (IDDM) especially in the light of the recent diabetes control and complications trial. In addition, the data has always supported the role of sustained hyperglycemia in precipitating diabetic ketosis and hyperglycemic nonketotic state, as well as recurrent infections and changes in lipid levels leading to atherosclerosis in large-sized and medium-sized arteries. Basic therapeutic modalities to achieve euglycemia in NIDDM patients remain the diet, exercise, oral agents, and insulin. Optimal management of associated medical disorders, such as hypertension and obesity, also is important to prevent the onset or progress of angiopathic complications. Combination therapy with insulin and oral agents is a frequently used treatment strategy in the last decade to achieve optimal metabolic control in this population if the therapy with oral agents alone fails to achieve this objective. Furthermore, in patients with IDDM manifesting extreme excursion of diurnal glycemia, this approach deserves trial as suggested in recent studies. However, it is imperative to assess this modality in light of the knowledge of pathophysiology of DM.
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PMID:Combinations sulfonylurea and insulin therapy in diabetes mellitus. 878 38

The reason for the disproportionately higher level of vascular disease in patients with diabetes is not known. Oxidative modification of low-density lipoproteins has been implicated in impaired cholesterol uptake and its deposition in the arterial wall and atherosclerosis. The present study has examined the effects of hyperketonemia, glycemic control and duration of diabetes on the in vitro oxidative susceptibility to Cu++ of low-density lipoprotein (LDL) + very low-density lipoprotein (VLDL) from 34 Type-I diabetic patients without any clinical sign of vascular disease and 22 age-matched normal individuals. LDL + VLDL was isolated from plasma using a micro-affinity column. LDL + VLDL isolated from diabetic patients and age-matched normal individuals was treated with 25 mM CuCl2 for 1.5, 3 and 5 h. The ketone bodies acetoacetate (AA) and beta-hydroxybutyrate (BHB), as well as glycated hemoglobin (HbA1), were measured in the blood by standard methods. There was no difference in the in vitro oxidative susceptibility of LDL + VLDL at all time periods between Type-I diabetics (n = 34) and age-matched normal individuals (n = 22). However, among diabetics, when patients were separated into normoketonemic (NK) and hyperketonemic (HK) groups, in vitro oxidation of LDL + VLDL at 1.5 h from hyperketonemic diabetics was a 69% greater (p < .02) compared with that of normoketonemic diabetics and 80% greater (p < .02) compared with that of normal individuals. There was a significant correlation (r = 0.38, p < .03) between the in vitro oxidation of LDL + VLDL at 1.5 h and AA levels in diabetic patients. The level of in vitro oxidizability of LDL + VLDL did not have any correlation with levels of BHB (r = 0.20, p > .26), HbA1 (r = 0, p > .99), glucose (r = 0.06, p > .75) or duration of diabetes (r = 0.15, p > .40) in diabetic patients. In vitro incubation of normal plasma with AA resulted in an increase in the Cu + induced lipid peroxidation of LDL + VLDL. This study suggests that frequent episodes of ketosis and elevated levels of AA constitute a risk factor for the oxidative modification of low-density lipoproteins and development of vascular disease in diabetic patients.
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PMID:Hyperketonemia (acetoacetate) increases the oxidizability of LDL + VLDL in Type-I diabetic patients. 943 28

Chronic hyperglycemia has been implicated in a number of diabetes mellitus-related conditions in the human population, including retinopathy, neuropathy, nephropathy, and vasculopathy. However, it has been difficult to evaluate the effect of long-term hyperglycemia in a research setting because of the disease's slow progression. In this study, we used streptozotocin (30 mg/kg of body weight, intravenously) to induce a state of chronic hyperglycemia in eight cynomolgus monkeys, and compared these monkeys with a matched control group (n = 8). Seven of eight monkeys with streptozotocin-induced diabetes required insulin therapy to avoid ketosis. After disease induction, all diabetic monkeys had significantly higher preprandial plasma glucose and glycated hemoglobin values, compared with their baseline values or values for control monkeys. Diabetic monkeys also had abnormal responses to an intravenous glucose tolerance test. Consistent with the chronic hyperglycemic state and formation of advanced glycation end products, diabetic monkeys had a significant increase in skin fluorescence over the course of the 6-month study. Plasma triglyceride and cholesterol concentrations increased, but not significantly so, in the diabetic monkeys after disease induction and were not significantly different from concentrations in control monkeys. Six months after disease induction, monkeys were necropsied, and immunohistochemical staining for insulin in the pancreatic islets indicated that diabetic monkeys had a significantly decreased amount of staining for the hormone. The percentage of islet insulin staining was significantly correlated with physiologic responses to the postinduction intravenous glucose tolerance test in all monkeys. Because cynomolgus monkeys are well-characterized models of atherosclerosis, this model may be useful for determining mechanisms whereby diabetes mellitus increases cardiovascular disease.
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PMID:Streptozotocin-induced diabetes mellitus in cynomolgus monkeys: changes in carbohydrate metabolism, skin glycation, and pancreatic islets. 1009 9

Recent studies have proposed a role for a reduced number of circulating monocytes in the development of atherosclerosis and circulatory diseases in diabetes. Ketosis is frequently encountered in type-I diabetics. This study was undertaken to test the hypothesis that hyperketonemia can lower blood monocyte count in type-I diabetic patients. Blood monocyte count was significantly lower (p < 0.05) in diabetics (n = 27) compared with age-matched normal siblings (n = 22). Blood levels of acetoacetate (AA) and triglycerides were significantly higher in diabetics compared with normals. To examine whether hyperketonemia can directly alter the monocyte count in diabetics, we studied the effect of ketone bodies AA and beta-hydroxybutyrate (BHB) on U937 cells, a human-derived promonocytic cell line as an in vitro model. The cell culture studies showed a dose-dependent growth inhibition and induction of apoptosis as a result of treatment with AA in U937 cells. Furthermore, there was a significant decrease in GSH and increase in lipid peroxidation products in AA-treated U937 cells. Taken together, this study suggests that elevated levels of ketone body AA can result in oxidative damage, accelerated apoptosis, and inhibition of cell growth in monocytes, which in turn can lower monocyte count in the blood of type-I diabetic patients.
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PMID:Effect of hyperketonemia on blood monocytes in type-I diabetic patients and apoptosis in cultured U937 monocytes. 1122 48

An elevated blood level of tumor necrosis factor (TNF)-alpha is a validated marker of vascular inflammation, which can result in the development of vascular disease and atherosclerosis. This study examined the hypothesis that ketosis increases the TNF-alpha secretion, both in a cell culture model using U937 monocytes and in type 1 diabetic patients in vivo. U937 cells were cultured with ketone bodies (acetoacetate [AA] and beta-hydroxybutyrate [BHB]) in the presence or absence of high levels of glucose in medium at 37 degrees C for 24 h. This study demonstrates the following points. First, hyperketonemic diabetic patients have significantly higher levels of TNF-alpha than normoketonemic diabetic patients (P < 0.01) and normal control subjects (P < 0.01). There was a significant correlation (r = 0.36, P < 0.05; n = 34) between ketosis and oxidative stress as well as between oxidative stress and TNF-alpha levels (r = 0.47, P < 0.02; n = 34) in the blood of diabetic patients. Second, ketone body AA treatment increases TNF-alpha secretion, increases oxygen radicals production, and lowers cAMP levels in U937 cells. However, BHB did not have any effect on TNF-alpha secretion or oxygen radicals production in U937 cells. Third, exogenous addition of dibutyryl cAMP, endogenous stimulation of cAMP production by forskolin, and antioxidant N-acetylcysteine (NAC) prevented stimulation of TNF-alpha secretion caused by AA alone or with high glucose. Similarly, NAC prevented the elevation of TNF-alpha secretion and lowering of cAMP levels in H(2)O(2)-treated U937 cells. Fourth, the effect of AA on TNF-alpha secretion was inhibited by specific inhibitors of protein kinase A (H89), p38-mitogen-activated protein kinase (SB203580), and nuclear transcription factor (NF)kappaB (NFkappaB-SN50). This study demonstrates that hyperketonemia increases TNF-alpha secretion in cultured U937 monocytic cells and TNF-alpha levels in the blood of type 1 diabetic patients and is apparently mediated by AA-induced cellular oxidative stress and cAMP deficiency.
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PMID:Hyperketonemia increases tumor necrosis factor-alpha secretion in cultured U937 monocytes and Type 1 diabetic patients and is apparently mediated by oxidative stress and cAMP deficiency. 1208 62

Diabetic ketoacidosis (DKA) is life-threatening acute metabolic complication of diabetes mellitus (DM) that is characterized by acidosis, ketosis, and hyperglycemia, currently affecting mostly patients under 30 years of age with diabetes mellitus type 1. In both, DM and DKA, a pro-inflammatory state exists. This clinical entity occurs as a result of hyperglycemia-induced disturbances, resulting in an increased oxidative metabolism. For the latter reason, the use of vitamin C seems promising in DKA due to its antioxidant role in reducing the superoxide radicals that are consequence of the oxidative stress. This can decrease the pro-inflammatory state and avoids complications. Vitamin C, or also known as ascorbic acid, has been widely used in several illnesses, such as common cold, tissue healing, fertility, atherosclerosis, cancer prevention, immunity restoration, neuro-degenerative disease and also has been suggested to decrease the risk of DM, and this reason is giving place to believe that vitamin C can have an important role in treating diabetic complications such as DKA. In order to counteract these oxidative disturbances in DKA patients, we analyzed the current data regarding vitamin C and evaluate its role in any type treatment of this complication in the near future.
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PMID:Role of vitamin C in diabetic ketoacidosis: Is it ready for prime time? 3058 81


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