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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Compositional changes of apoproteins and lipids in lipoproteins influence their affinities for receptors and enzymes. Decrease of apo C proteins and increase of apo E in chylomicron and very low density lipoproteins (VLDL) during their catabolism might promote the binding to remnant receptor. On the other hand, the affinity for lipoprotein lipase (LPL) gradually decreases and that for hepatic lipase increases. However, the responsiveness of VLDL to LPL might be under the control of triglyceride (TG)/surface component ratios but not of the apoprotein ratios in ordinary circumstances judging from the results of the releases of fatty acids from VLDL by LPL in vitro. Responses of VLDL from diabetic patients to LPL significantly decreased compared with those from non-diabetic subjects. Glycation of VLDL in vitro impaired their responses to LPL. Therefore, delayed catabolism of VLDL in diabetes might partially depend upon glycation of VLDL besides the decreased LPL activity. Low density lipoproteins (LDL), apoproteins of which consist mostly of apo B protein and had a low TG level, showed a high affinity to the LDL receptor. However, LDL from hypertriglyceridemic subjects, in which the TG contents was increased, had a low affinity to the receptor. Since high density lipoproteins (HDL) from patients in acute phases contain a large amount of serum amyloid A protein (SAA), the percentages of apo A proteins markedly decreased. When SAA-rich HDL were incubated with leucocytes, SAA were degraded rapidly, although other apoproteins remained to be unchanged. Therefore, such HDL become unstable, and this might induce low HDL levels in the acute phase.
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PMID:[Metabolic disorders of lipoproteins--influences of compositional changes of lipoproteins upon their metabolic behavior]. 188 Sep 36

The relative effects of obesity, alone or in combination with insulin resistance and hyperinsulinemia (with or without diabetes), on lipoprotein concentrations, blood pressure, and other risk factors for cardiovascular disease were investigated in 28 men (mean age, 63 years). Special attention was given to lipoprotein lipase (LPL) activity in tissues and to postheparin plasma LPL activity and hepatic lipase activity and their relation to insulin resistance. The 28 men fulfilled the entrance criteria of the study so that they could be allocated to one of the four groups (seven in each group): 1) normal body weight, normal fasting insulin level, and normal glucose tolerance (controls); 2) the same as in group 1 but with moderate obesity; 3) the same as in group 2 but with fasting hyperinsulinemia; 4) the same as in group 3 but with non-insulin-dependent diabetes mellitus. Glucose infusion rate for the control group was 8.1 +/- 2.1 mg/kg body wt/min (mean +/- SD) at an insulin infusion rate of 56 milliunits/m2/min. The average values in groups 2, 3, and 4 were 6.0 +/- 0.7, 3.2 +/- 0.5, and 1.9 +/- 1.0 mg/kg body wt/min, respectively. Concentrations of very low density lipoproteins as well as blood pressure and urate concentrations were highest and those of high density lipoproteins were lowest in the two hyperinsulinemic groups (groups 3 and 4). Skeletal muscle LPL activity was 46 +/- 23, 41 +/- 25, 23 +/- 6, and 31 +/- 13 milliunits/g wet wt (mean +/- SD) in the four groups, respectively. There was a positive correlation between glucose infusion rate and muscle LPL activity (r = 0.58, p less than 0.0001). The hepatic lipase activity was positively correlated with the insulin area under the curve of the intravenous glucose tolerance test (r = 0.35, p = 0.02). Furthermore, blood pressure, free fatty acid concentration, liver enzymes, and urate concentrations were significantly correlated with glucose infusion rate at the clamp test. These data give further support for insulin resistance as an important factor behind the observed lipoprotein abnormalities and blood pressure elevations as part of the insulin resistance syndrome characteristic for obese and diabetic patients.
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PMID:Lipoprotein lipase activity in skeletal muscle is related to insulin sensitivity. 191 6

Abnormalities of plasma lipid and lipoprotein concentrations are common in both insulin-dependent (IDDM) and non-insulin-dependent (NIDDM) diabetes mellitus. In general, individuals with IDDM who are untreated or inadequately treated have elevations in both postprandial and fasting triglyceride levels in association with reduced activity of lipoprotein lipase. Low-density lipoprotein (LDL) cholesterol levels can rise when insulin deficiency impacts on LDL-receptor function. When patients with IDDM are treated and plasma glucose levels well controlled, plasma very-low-density lipoprotein (VLDL) triglyceride and LDL cholesterol levels are usually normal. In addition, plasma high-density lipoprotein (HDL) cholesterol levels are normal or elevated in well-controlled IDDM subjects. In NIDDM, increased VLDL triglyceride and reduced HDL cholesterol concentrations are common and are only partially related to glycemic control. Overproduction of VLDL leads to hypertriglyceridemia, which can be exacerbated if lipoprotein lipase activity is also reduced. The regulation of LDL levels is complex; catabolism can be reduced if significant insulin deficiency exists or increased if significant hypertriglyceridemia is present. The reduced levels of HDL cholesterol in NIDDM appear to be related to increased exchange of HDL cholesteryl esters for VLDL triglycerides, although other mechanisms may exist. The roles of insulin resistance, obesity, and independently inherited abnormalities of lipoprotein metabolism in the etiology of dyslipidemia of NIDDM are complex and require further investigation. Finally, the effects of diabetes on glycosylation of apoproteins; on other lipid enzymes, particularly hepatic triglyceride lipase; on lipoprotein surface lipids; and on hepatic uptake of remnants have only just begun to be defined. In view of the marked increase in atherosclerotic cardiovascular disease in individuals with diabetes mellitus, prompt attention to and aggressive therapy for dyslipidemia should be a central component of care for these patients.
Diabetes Care 1991 Sep
PMID:Lipoprotein physiology in nondiabetic and diabetic states. Relationship to atherogenesis. 195 76

Previous studies demonstrated that administration of tumor necrosis factor (TNF) to diabetic rats rapidly increases serum triglyceride levels and stimulates hepatic lipogenesis without affecting the activity of adipose tissue lipoprotein lipase or serum insulin levels. The purpose of this study was to determine the mechanism by which TNF increases serum triglyceride levels and stimulates hepatic fatty acid synthesis in diabetic animals. The maximal increase (approximately 2-fold) in serum triglyceride levels in diabetic rats is seen with a dose of 10 micrograms TNF/200 g body wt, and the half-maximal effect is observed with 5 micrograms TNF/200 g body wt. The clearance of labeled triglyceride-rich lipoproteins from the circulation is not affected by TNF administration (triglyceride t 1/2; diabetic vs. TNF-administered diabetic, 3.5 +/- 0.7 vs. 4.0 +/- 0.6 min, respectively; NS). The production of triglyceride, measured by the Triton WR-1339 technique, is increased twofold in diabetic animals after TNF administration. These results indicate that the rapid increase in serum triglyceride levels after TNF treatment is accounted for by increased hepatic lipoprotein secretion. TNF administration did not alter either the amount or activation state of hepatic acetyl-CoA carboxylase, a key regulatory enzyme in fatty acid synthesis. There was also no change in the hepatic levels of fatty acyl-CoA, an allosteric inhibitor of acetyl-CoA carboxylase. However, there was a 71% increase in hepatic citrate concentrations. Citrate is an allosteric activator of acetyl-CoA carboxylase, and changes in hepatic citrate concentrations have been shown to mediate changes in the rates of fatty acid synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1990 Dec
PMID:Tumor necrosis factor-increased hepatic very-low-density lipoprotein production and increased serum triglyceride levels in diabetic rats. 197 29

Dysbetalipoproteinaemia is a genetic disorder characterized by accumulation of lipoprotein remnant particles in the plasma, accelerated atherosclerosis, and the abnormal apoprotein E2. Uncontrolled diabetes mellitus can aggravate the hyperlipidaemia associated with this disorder, presumably by increasing triglyceride synthesis and reducing very low density lipoprotein catabolism by lipoprotein lipase. This report documents the gradual amelioration of dysbetalipoproteinaemia in uncontrolled diabetes mellitus following therapy with exogenous insulin alone. Although the beneficial effects of insulin therapy in this patient may include inhibition of triglyceride synthesis and improved triglyceride catabolism, we propose that insulin may also stimulate clearance of atherogenic remnant lipoprotein particles.
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PMID:Potential role of insulin in the clearance of remnant lipoproteins in dysbetalipoproteinaemia. 199 70

Factors contributing to fasting hypertriglyceridaemia were studied in 20 patients with non-insulin-dependent diabetes--nine with normal triglyceride concentrations [fasting triglyceride 0.94 (range 0.58-1.23) mmol l-1] and eleven with mild fasting hypertriglyceridaemia [fasting triglyceride 2.4 (1.82-4.0) mmol l-1]. The patients with hypertriglyceridaemia were more obese [body mass index 29.0 (24.6-33.8) vs. 25.7 (21.9-30.1) kg m-2, P less than 0.05] and demonstrated impaired glucose disposal in response to exogenous insulin at isoglycaemia [insulin sensitivity index, SIp 0.7 (0.27-2.5) vs. 2.4 (0.62-5.1) ml m-2 min per mU l-1, P less than 0.001]. Basal non-esterified fatty acid (NEFA) and glycerol concentrations were higher and were suppressed to a lesser extent during isoglycaemic hyperinsulinaemia. Fasting glucose and apolipoprotein B concentrations were higher in the hypertriglyceridaemic patients, but lipoprotein lipase activities were similar in the two groups. When the effect of obesity was removed (by weight-matching six normotriglyceridaemic with seven hypertriglyceridaemic patients) basal NEFA and glycerol concentrations and the suppression of NEFA in response to insulin remained significantly different between the two groups. We propose that defects in both the glucoregulatory and antilipolytic actions of insulin contribute to mild fasting hypertriglyceridaemia in NIDDM, and that these defects cannot be attributed solely to obesity. These disorders of insulin action may also have important implications for the postprandial metabolism of triglyceride-rich lipoproteins and hence atherogenesis.
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PMID:Determinants of mild fasting hypertriglyceridaemia in non-insulin-dependent diabetes. 200 44

The relation between obesity and noninsulin-dependent diabetes mellitus is established. The weak association between obesity and cardiovascular disease or stroke might be attributable to a risk present only in a subgroup of obesity patients. Recent prospective studies have shown such a group to be characterized by abdominal localization of adipose tissue, reviving old empiric observations of such links. The sex-linked adipose tissue distribution is probably dependent on a balance between glucocorticoids and sex steroid hormones. The former are active mainly on intraabdominal adipose tissues through the high density of a specific receptor expressing lipoprotein lipase activity. This effect is counteracted by female sex steroid hormones, mainly progesterone, which promote fat deposition in the gluteal-femoral regions, utilized mainly during pregnancy and lactation. Testosterone stimulates lipid mobilization through transcriptional expression of beta-adrenergic receptors via a specific androgen receptor and also inhibits lipoprotein lipase activity. Intraabdominal adipose tissues, drained by the portal vein, have a very sensitive lipolytic system in men, based on an increased beta-adrenoceptor activity. This is probably a testosterone effect via the mechanisms mentioned. With testosterone deficiency, these mechanisms are less active, permitting accumulation of fat that can be reversed by testosterone substitution. Abdominal distribution of fat in men thus is probably a sign of relative testosterone deficiency.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Classification of obese patients and complications related to the distribution of surplus fat. 213 24

Recent studies have shown the predictive power of abdominal distribution of adipose tissue for the development of cardiovascular disease, stroke, diabetes as well as strong associations to the previously known risk factors for these endpoints. The reason for the accumulation of abdominal fat might be due to an imbalance between cortisol and sex steroid hormones. Cortisol receptor density seems to be particularly high in abdominal adipose tissue, leading to expression of lipoprotein lipase activity primarily here. Progesterone and testosterone seems to counteract this, the former perhaps through competition with the cortisol receptor. Accumulation of intraabdominal fat, particularly in the tissues drained by the portal circulation, probably leads to high free fatty acid concentrations in the portal vein, because of the high lipolytic sensitivity of these tissues. This in turn seems to inhibit hepatic clearance of portal insulin, leading to peripheral hyperinsulinemia, insulin resistance, perhaps hypertension as well as hyperlipidemia via drive by free fatty acids of lipoprotein synthesis in the liver. These are risk factors for diabetes, cardiovascular disease and stroke. It is of interest that subjects with abdominal adipose tissue have several factors leading to increased cortisol and low sex steroid hormone secretion, including stress, high alcohol consumption and smoking. This might provide some of the background to this syndrome.
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PMID:Obesity and adipose tissue distribution as risk factors for the development of disease. A review. 214 Jan 8

Non-insulin-dependent diabetic (NIDDM) subjects exhibit abnormalities in their plasma lipid and lipoprotein profiles that increase the risk of ischemic heart disease. This study was designed to examine the metabolic behavior of very-low-density (VLDL), intermediate-density (IDL), and low-density (LDL) lipoproteins in NIDDM patients before treatment and after 4 wk of insulin therapy. Basal turnover studies of 131I-labeled VLDL1 (svedberg units [Sf] 60-400) and 131I-labeled VLDL2 (Sf 20-60) apolipoprotein B (apoB) were conducted in a group of seven NIDDM patients who had been off oral therapy for 1 wk. The subjects exhibited higher than normal transport rates for VLDL1 and a diminished input of apoB into the VLDL2 density range. These observations are concordant with the hypothesis that NIDDM patients overproduce VLDL triglyceride but not apoB. VLDL1 and VLDL2 were converted to IDL and ultimately to LDL at approximately normal rates, although the delipidation pathway by which apoB-containing particles were processed exhibited different properties from that seen in control subjects. Insulin therapy reduced plasma triglyceride by 38%, and this was associated with a 41% fall in VLDL1 mass (P less than 0.01). VLDL2 was less affected (19% reduction, P less than 0.05), IDL was unchanged, and LDL fell 17% (P less than 0.05). Repeat metabolic studies revealed that the major effects of insulin were to reduce VLDL1-apoB transport (from 811 to 488 mg/day) and increase the direct input of VLDL2 into the plasma (from 182 to 533 mg/day, P less than 0.05). These alterations in VLDL production led to normalization of apoB kinetics in IDL and LDL. The fractional catabolic rate of LDL increased 19% (P less than 0.05), whereas direct input into this fraction, which had been high before treatment, was reduced. Postheparin plasma lipoprotein lipase (LPL) and hepatic lipase levels were unaffected by insulin, although the hormone did increase LPL in adipose tissue. This lack of effect on lipase activities correlated well with the observation that the rates of catabolism of apoB in VLDL1, VLDL2, and IDL were not significantly affected by insulin therapy.
Diabetes 1990 Sep
PMID:Effect of insulin therapy on metabolic fate of apolipoprotein B-containing lipoproteins in NIDDM. 220 Jul 27

Dyslipidemias are frequent in diabetic subjects: they increase the risk for atherosclerosis, in addition to the risk of diabetes mellitus per se. The pathogenesis of dyslipidemias differs between type I and type II diabetes: untreated type I diabetic subjects demonstrate frequently increased triglyceride concentrations due to diminished removal of triglyceride-containing particles, as a result of diminished activity of lipoprotein lipase. In addition, more triglycerides are produced due to increased lipolysis and increased free fatty acid supply to the liver. Type II diabetic subjects demonstrate very low density lipoprotein (VLDL) over-production due to obesity, insulin resistance and caloric overconsumption. In addition, triglyceride removal may be diminished due to diminished lipoprotein lipase activity when diabetes mellitus is poorly controlled. In addition, high density lipoprotein (HDL) is frequently lowered. During decompensation low density lipoprotein (LDL) concentrations may also increase. LDL particle composition is frequently abnormal. A severe dyslipidemia in diabetes mellitus is frequently a combined effect of diabetes mellitus and a congenital lipoprotein abnormality. The evaluation and treatment of dyslipidemias in diabetic subjects should be performed similarly to non-diabetics according to the guidelines published recently by the Working Group 'Lipids' of the Swiss Foundation of Cardiology. Additional accents in diabetic subjects are necessary. It is recommended that serum cholesterol, triglycerides and HDL are determined in every patient when diabetes mellitus is diagnosed. If serum cholesterol is greater than 6.5 mmol/l and the cholesterol/HDL-ratio is greater 6.5, dietary treatment should be reinforced; if its effect is insufficient, drug therapy should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Dyslipidemia in diabetes mellitus: significance, diagnosis and treatment]. 223 46


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