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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Insulin-like growth factor-I (IGF-I) and insulin interact with related receptors to lower plasma glucose and to exert mitogenic effects. Recombinant human IGF-I (rhIGF-I) was recently shown to decrease serum levels of insulin and C-peptide in fasted normal subjects without affecting plasma glucose levels. In this study we have investigated in six healthy volunteers the responses of glucose, insulin, and C-peptide levels to intravenous rhIGF-I infusions (7 and 14 micrograms/kg.h) during standard oral glucose tolerance tests (oGTT) and meal tolerance tests (MTT), respectively. Glucose tolerance remained unchanged during the rhIGF-I infusions in the face of lowered insulin and C-peptide levels. The decreased insulin/glucose-ratio presumably is caused by an enhanced tissue sensitivity to insulin. The lowered area under the insulin curve during oGTT and MTT as a result of the administration of rhIGF-I were related to the fasting insulin levels during saline infusion (oGTT: r = 0.825, P less than 0.05; MTT: r = 0.895, P less than 0.02). RhIGF-I, however, did not alter the ratio between C-peptide and insulin, suggesting that the metabolic clearance of endogenous insulin remained unchanged. In conclusion, rhIGF-I increased glucose disposal and directly suppressed insulin secretion. RhIGF-I probably increased insulin sensitivity as a result of decreased insulin levels and suppressed growth hormone secretion. RhIGF-I, therefore, may be therapeutically useful in insulin resistance of type 2 diabetes, obesity, and hyperlipidemia.
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PMID:Effects of insulin-like growth factor-I on glucose tolerance, insulin levels, and insulin secretion. 160 98

Hepatobiliary characteristics of untreated obese patients and those of patients reducing weight through very-low-calorie diets (VLCDs) are reviewed. In untreated obesity, hepatobiliary abnormalities are prevalent. Fatty change is common and may be related to insulin resistance. Moreover, portal inflammation and fibrosis are prevalent findings, also in the absence of alcohol abuse. The liver plays a key role in the hyperinsulinism and hyperlipidemia, and hepatic drug metabolism is influenced by enhanced glucuronidation and sulphatation. Predisposition to gallstone formation can be ascribed to increased biliary cholesterol secretion in concert with changed nucleating factors and altered gallbladder motility. Weight loss by VLCD reduces fatty change but may induce slight portal inflammation and fibrosis. Insulin resistance and pharmacokinetic abnormalities regress. During VLCD the risk of gallstone formation is markedly increased. The deleterious effects described of a rapid weight loss should draw some attention to the liver and biliary tract during VLCD treatment.
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PMID:Liver and gallbladder disease before and after very-low-calorie diets. 161 89

Early screening for hypertension in diabetic patients and for glycoregulation abnormalities in hypertensives is justified by the additive cardiovascular risks when hypertension and diabetes co-exist and by the accelerated development of diabetic nephropathy and retinopathy if hypertension co-exists. In insulin-dependent diabetes, hypertension is generally preceded by microalbuminuria, known to be reduced by angiotensin converting enzyme inhibitors. The requirement for nephropathy prevention and the hemodynamic and/or tissular effects of this therapeutic class could justify their use at a blood pressure level less than that conventionally considered hypertensive. This strategy must be confirmed by prospective trials, already underway, evaluating the nephroprotective efficacy of this therapy. In non-insulin-dependent diabetes, hypertension is often present before the diabetes is diagnosed and antihypertensive therapy, especially thiazide diuretics, could play a demasking or favorizing role. The optimal blood pressure level to which these patients at high renal and coronary risk should be lowered still has to be determined. A prospective study, comparing the effects of strict (treated diastolic blood pressure less than 80 mmHg) and less strict (treated diastolic blood pressure between 90 and 100 mmHg) hypertensive control on coronary event prevention in essential hypertension, is in progress and will have important implications for hypertension treatment in diabetics. Appropriate treatment of other risk factors, such as hyperlipidaemia and smoking, contributes to coronary and renal prevention in all diabetic hypertensives.
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PMID:[Treatment of hypertension in diabetes: threshold of intervention and therapeutic options]. 163 6

Rainbow trout, Oncorhynchus mykiss, were used to evaluate the effects of carbohydrate loading on plasma levels of pancreatic hormones and associated changes in metabolic indexes in a carnivorous fish. Glucose (3,000 mg/dl, 10 microliters/g body wt) was injected intraperitoneally into fish (mean wt 54 +/- 5 g) that were killed 0.5-24 h after administration. Glucose injection resulted in hyperglycemia with maximum glucose levels of 306 +/- 13 mg/dl observed 60 min after injection. Glucose administration also resulted in hyperlipidemia. Plasma fatty acids increased twofold in glucose-injected animals. Alterations in plasma metabolites reflected changes in energy stores. Although total lipid concentration was unaffected by glucose injection, lipolytic enzyme activity in the liver was enhanced. Biosynthetic capacity, as indicated by NADPH production from glucose-6-phosphate dehydrogenase, was decreased by glucose injection. Liver glycogen content was reduced in glucose-injected animals 1 h after injection. Glucose injection was attended by increases in the plasma levels of gene II somatostatin-25 (predominant form of pancreatic somatostatin in salmonids) and of glucagon. Insulin levels were initially suppressed after glucose injection. These results indicate that metabolic adjustments caused by glucose administration can be related to the regulatory action of pancreatic hormones. Furthermore, these results suggest that the somatostatin-secreting cells of the trout are sensitive to glucose and that somatostatin-suppressed insulin secretion contributes to the glucose intolerance of trout.
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PMID:Insulin suppression is associated with hypersomatostatinemia and hyperglucagonemia in glucose-injected rainbow trout. 167 8

Intraperitoneal and subcutaneous routes of administration for diabetics on CAPD were compared. The comparison included: (1) Control of blood glucose concentration: both methods can provide satisfactory glycemic control for most patients. Changing the method of insulin administration is warranted when one method fails. (2) Effect on plasma insulin levels: intraperitoneal administration can produce a plasma insulin profile similar to the normal profile. This is unusual with subcutaneous administration. Consequences of hyperinsulinemia (hyperlipidemia, hypertension) seem, however, to be similar between the two methods of insulin administration. (3) Effect on peritoneal permeability: permeability characteristics are maintained unchanged, usually, with either method after long-term CAPD. However, insulin is mitogenic in vitro. Theoretically, intraperitoneal insulin could lead to peritoneal fibrosis. (4) Effect on infectious complications of CAPD: a difference in the rate of peritonitis or overall PD catheter-related infections has not been convincingly demonstrated between the two methods of insulin administration. Exit site and tunnel infections with staphylococcus aureus may be more frequent in diabetics receiving insulin subcutaneously. (5) Effect on hepatic structure and function: subcapsular hepatic steatosis was described in diabetics receiving insulin intraperitoneally. The clinical significance of this finding remains to be demonstrated. We conclude that both methods can be applied for insulin administration in diabetics on CAPD. The intraperitoneal method should be tried first in most instances. Prospective studies comparing the two methods are needed.
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PMID:Subcutaneous versus intraperitoneal insulin in the management of diabetics on CAPD: a review. 168 Apr 63

Short- and long-term effects of hyperlipidemia with elevated FFA on insulin secretion were investigated. Male Sprague-Dawley rats were fed ad libitum and additionally infused with Intralipid 10%, 1.0 ml/h. After 3 h of Intralipid the response to 27 mM glucose in isolated perfused pancreas was enhanced by 86%, P less than 0.02. After 6 h of Intralipid enhancement had subsided. After 48 h of Intralipid glucose-induced insulin release was inhibited by 49%, from 1950 +/- 177 microU/min after saline to 1003 +/- 232 microU/min after Intralipid, P less than 0.02. Inhibition was glucose-selective since responses to other secretagogues (1 mM 3-isobutyl-1 methylxanthine, 10 mM octanoate, or 5 mM alpha-ketoisocaproic acid) were unaffected as were pancreatic contents of insulin (2284 +/- 111 mU/pancreas after saline, 2566 +/- 131 mU/pancreas after Intralipid). In isolated islets from 48 h lipid infused rats production of [14-C]CO2 from D[U-14-C]glucose was decreased (P less than 0.02) in parallel with the insulin response to 27 mM glucose. Glucose-induced secretion was partially normalized by in vitro exposure to a carnitine palmitoyl-transferase I inhibitor (Etomoxir). Effects of a 48 h lipid infusion were also tested during hyperglycemia. Rats were infused with glucose, and hyperglycemia was enhanced by dexamethasone (25 micrograms/24 h). Hyperglycemia depressed glucose-induced secretion from perfused pancreas from 2072 +/- 22 microU/min after saline + dexamethasone to 1185 +/- 155 microU/min after glucose + dexamethasone, P less than 0.01). Intralipid, added to the latter protocol, further inhibited glucose-induced secretion to 437 +/- 87 microU/min, P less than 0.005. Hyperlipidemia is concluded to be associated with short term stimulation but long term inhibition of glucose-induced insulin secretion. Evidence indicates that inhibition depends on fatty acid oxidation, is coupled to decreased glucose oxidation and operates both during normo- and hyperglycemia.
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PMID:A 48-hour lipid infusion in the rat time-dependently inhibits glucose-induced insulin secretion and B cell oxidation through a process likely coupled to fatty acid oxidation. 169 43

Many lipoprotein abnormalities are seen in the untreated, hyperglycemic diabetic patient. The non-insulin-dependent diabetic (NIDDM) patient with mild fasting hyperglycemia commonly has mild hypertriglyceridemia due to overproduction of TG-rich lipoproteins in the liver, associated with decreased high-density lipoprotein (HDL) cholesterol levels. The more hyperglycemic untreated NIDDM and insulin-dependent diabetic (IDDM) patient have mild to moderate hypertriglyceridemia due to decreased adipose tissue and muscle lipoprotein lipase, (LPL) activity. These patients also have decreased HDL cholesterol levels associated with defective LPL catabolism of TG-rich lipoproteins. Treatment of diabetes with oral sulfonylureas or insulin corrects most of the hypertriglyceridemia and some of the decrease in HDL cholesterol. The abnormality in adipose tissue LPL activity corrects slowly over several months of therapy. The treated IDDM patient often has normal lipoprotein levels. The treated NIDDM patient may continue to have mild hypertriglyceridemia, increased intermediate-density lipoprotein levels, small dense low-density lipoproteins (LDL) with increased apoprotein B, and decreased HDL cholesterol levels. The central, abdominal distribution of adipose tissue in IDDM is associated with insulin resistance, hypertension, and the above lipoprotein abnormalities. Improvement in glucose control, in the absence of weight gain, leads to lower triglyceride and higher HDL cholesterol levels. In addition, the diabetic patient is prone to develop other defects that, in themselves, lead to hyperlipidemia, such as proteinuria, hypothyroidism, and hypertension, treated with thiazide diuretics and beta-adrenergic-blocking agents. When a diabetic patient independently inherits a common familial form of hypertriglyceridemia, he might develop the severe hypertriglyceridemia of the chylomicronemia syndrome.
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PMID:Pathophysiology of hyperlipidemia in diabetes mellitus. 171 Jul 39

The effects of a sustained-release preparation of bezafibrate (Bezalip Mono) 400 mg once daily and placebo administered for 3 months were compared in 36 patients with stable type 1 diabetes and hypercholesterolemia and/or hypertriglyceridemia. There was a significant decrease in fasting glucose levels with bezafibrate, but not in glycosylated hemoglobin. The serum cholesterol concentration decreased on bezafibrate [from 7.1 +/- 0.2 (mean +/- SEM) to 6.3 +/- 0.3 mmol/L; p less than 0.05] predominantly due to a reduction in low-density lipoprotein (LDL) cholesterol [from 4.8 +/- 0.3 to 4.2 +/- 0.3 mmol/L; p less than 0.05. There was also a decrease in fasting serum triglycerides with bezafibrate [1.82 to 1.26 mmol/L (geometric mean)] and in very-low-density lipoprotein (VLDL) cholesterol. Plasma fibrinogen decreased significantly with bezafibrate (from 4.1 +/- 0.2 to 2.9 +/- 0.2 g/L; p less than 0.001). Serum apolipoproteins B and A showed no statistically significant changes. Overall, there was no change in high-density lipoprotein (HDL). However, in patients who were initially hypertriglyceridemic, there was a significant increase in the cholesterol content of total HDL and the HDL2 subfraction (both p less than 0.05). It is concluded that in insulin-dependent diabetic patients with hyperlipidemia, bezafibrate is effective in lowering both serum VLDL and LDL. In addition, it has a potentially important action in decreasing plasma fibrinogen levels.
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PMID:Bezafibrate retard in patients with insulin-dependent diabetes: effect on serum lipoproteins, fibrinogen, and glycemic control. 171 Jul 43

There is evidence that hypertensive patients frequently have other metabolic disorders, such as hyperlipidemia and diabetes mellitus. It is also known that the reduction in high blood pressure alone, disregarding the other cardiovascular risk factors, is unable to reduce mortality to the level of the general population. Moreover, the occurrence of metabolic side effects with some antihypertensive drugs deserves particular attention in the treatment of hypertension. Calcium antagonists seem to be devoid of untoward metabolic effects. In particular, several studies have shown that nitrendipine does not deteriorate glucose tolerance. We have evaluated the effects of nitrendipine on insulin response to i.v. glucose load: no change was observed after 2 months of treatment in both serum insulin levels and glucose percent removal rate in comparison to pretreatment values. No unfavorable change was detectable in the studies aimed at investigating the effects of nitrendipine on lipid metabolism parameters. We observed a 22% increase of the percent removal rate of a lipid emulsion (Intralipid) after nitrendipine (3.11 +/- 1.0 vs. 3.80 +/- 1.0%/min, p less than 0.03). This finding suggests a favorable effect of nitrendipine on triglyceride catabolism, possibly mediated by an interference with lipoprotein lipase activity. The metabolic neutrality of nitrendipine, therefore, leads to considering the usefulness of this drug in an antihypertensive treatment that should not disregard the global risk profile.
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PMID:Metabolic neutrality in nitrendipine therapy. 172 52

The Japanese Mazindol study group investigated the action of an anorexiant, mazindol, and found that it reduced food intake by directly suppressing neurons in the lateral hypothalamus, inhibited gastric acid secretion, increased motor activity, decreased glucose absorption, and inhibited insulin secretion. It thus appears that the main effect of mazindol is to decrease food intake through suppressing feeding centers in the hypothalamus. A multicenter open study of mazindol in Japan revealed that loss of body weight and relative body weight in 14 wk were 4.6 kg and 9.2%, respectively, with suppression of appetite in the majority of obese patients. A multicenter double-blind study demonstrated that mazindol was superior to the placebo in the treatment of simple obesity. We also suggest that mazindol is effective in the maintenance of reduced body weight after obesity therapy and in the treatment of obesity-related diseases such as diabetes, hypertension, or hyperlipidemia.
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PMID:Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan. 172 34


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