Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

High density lipoprotein (HDL) kinetics were studied by infusing [5,5,5-2H3]-leucine in five subjects with normal glucose tolerance and eight patients with non-insulin-dependent diabetes mellitus (NIDDM) with poor metabolic control (HbA1c = 8.16 +/- 1.93%) (mean +/- SD). HDL were modelled as a single compartment since no kinetic differences were observed between HDL2 and HDL3 subclasses. Plasma apolipoprotein AI (apo AI) concentration was significantly lower in NIDDM patients (96.1 +/- 12.1 vs 124.4 +/- 13.1 mg.dl-1, p < 0.01). HDL composition was altered in NIDDM, as an increase in HDL-triglyceride and a decrease in HDL-cholesterol, negatively correlated (r = 0.780, p < 0.01). The mean fractional catabolic rate (FCR) of apo AI-HDL was significantly higher (0.39 +/- 0.16 vs 0.21 +/- 0.06 d-1, p < 0.05) while the apo AI-HDL absolute production rate was not significantly greater (13.6 +/- 5.1 vs 12.0 +/- 4.2 mg.kg-1.d-1) in diabetic patients compared to normal subjects. There were significant correlations between apo AI-HDL FCR and plasma apo AI concentration (r = -0.580, p < 0.05), plasma triglycerides (r = 0.839, p < 0.0001) or HDL-triglyceride levels (r = 0.597, p < 0.05). No correlation was observed between apo AI-HDL FCR and HbA1c or HDL-cholesterol level. These data support the view that the decrease in plasma apo AI level in patients with NIDDM is due to an increase of apo AI-HDL FCR, which may itself be related to changes in HDL composition.
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PMID:High density lipoprotein apolipoprotein AI kinetics in NIDDM: a stable isotope study. 916 27

Oestrogen replacement therapy is associated with a decreased risk of cardiovascular disease in postmenopausal women. Patients with non-insulin-dependent diabetes mellitus (NIDDM) have an increased cardiovascular risk. However, oestrogen replacement therapy is only reluctantly prescribed for patients with NIDDM. In a double blind randomized placebo controlled trial we assessed the effect of oral 17 beta-estradiol during 6 weeks in 40 postmenopausal women with NIDDM. Glycated haemoglobin (HbA1c), insulin sensitivity, suppressibility of hepatic glucose production, lipoprotein profile and parameters of fibrinolysis were determined. The oestrogen treated group demonstrated a significant decrease of HbA1c and in the normotriglyceridaemic group a significantly increased suppression of hepatic glucose production by insulin. Whole body glucose uptake and concentrations of non-esterified fatty acids did not change. LDL-cholesterol- and apolipoprotein B levels decreased, and HDL-cholesterol, its subfraction HDL2-cholesterol and apolipotrotein A1 increased. The plasma triglyceride level remained similar in both groups. Both the concentration of plasminogen activator inhibitor-1 antigen and its active subfraction decreased. Tissue type plasminogen activator activity increased significantly only in the normotriglyceridaemic group. Oestrogen replacement therapy improves insulin sensitivity in liver, glycaemic control, lipoprotein profile and fibrinolysis in postmenopausal women with NIDDM. For a definite answer as to whether oestrogens can be more liberally used in NIDDM patients, long term studies including the effect of progestogens are necessary.
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PMID:Short-term oestrogen replacement therapy improves insulin resistance, lipids and fibrinolysis in postmenopausal women with NIDDM. 924 7

This study evaluates the effects of insulin versus glibenclamide on lipoprotein metabolism at comparable levels of blood glucose control, in particular on the concentration and distribution of VLDL subfractions and lipolytic enzyme activities in nine NIDDM men (aged 56 +/- 3 years, BMI 26.5 +/- 0.9 kg/m2) (means +/- SE) participating in a crossover study. After a 3-week washout period, patients were randomly assigned to 2-month treatment periods (insulin or glibenclamide); thereafter, each patient crossed to the other treatment. At the end of each period, mean daily blood glucose (MDBG), HbA1e, plasma lipids, lipoproteins (VLDL, LDL, HDL), lipoprotein subfractions (VLDL1, 2, 3; HDL2, HDL3), and post-heparin lipase activities (lipoprotein lipase [LPL], hepatic lipase [HL]) were evaluated. Although glucose control was similar at the end of both periods (MDBG 8.3 +/- 0.3 vs. 7.9 +/- 0.3 mmol/l; HbA1c 7.4 +/- 0.3 vs. 7.0 +/- 0.2%, insulin versus glibenclamide), insulin compared with glibenclamide induced a significant reduction in plasma triglycerides (0.9 +/- 0.1 vs. 1.1 +/- 0.1 mmol/l, P < 0.05), VLDL triglycerides (50.1 +/- 12.2 vs. 63.6 +/- 12.3 mg/dl, P < 0.02), VLDL1 lipid concentration (24.9 +/- 7.5 vs. 39.9 +/- 9.5 mg/dl, P < 0.006), and increased HDL2 cholesterol (25.2 +/- 1.6 vs. 20.3 +/- 1.3 mg/dl, P < 0.03). In terms of VLDL percentage subfraction distribution, with insulin, there was a decrease in the larger subfractions (VLDL1 26.5 +/- 3.0 vs. 37.8 +/- 3.4%, P < 0.02) and an increase in the smallest (VLDL3 47.3 +/- 3.8 vs. 37.3 +/- 3.3%, P < 0.05). Moreover, HL activity was significantly lower after insulin than after glibenclamide (HL 247.2 +/- 22.3 vs. 263.5 +/- 22.6 mU/ml, P < 0.05). In conclusion, compared with glibenclamide, insulin treatment (independent of variations in glucose control) is able to decrease significantly plasma triglycerides, to increase HDL2 cholesterol, and to reduce only the concentration of the larger VLDL subfractions, with a consequent redistribution of their profile.
Diabetes 1997 Oct
PMID:Insulin and sulfonylurea therapy in NIDDM patients. Are the effects on lipoprotein metabolism different even with similar blood glucose control? 931 56

The influence of hGH and IGF-I levels on lipid-, lipoprotein metabolism and fibrinolysis were studied in 23 patients with active acromegaly (14 women and 9 men, mean age 49.8 +/- 2.1 years) compared to a sex, BMI and age-matched control group. Mean Lp(a) levels were significantly higher in acromegalics than in controls (469.8 +/- 140.1; n = 23 vs. 162.7 +/- 64.9 mg/l; n = 111; p < 0.01). We found elevated apolipoprotein A-I and Apo E-concentrations in acromegalic patients compared to controls (apo A-I: 1.79 +/- 0.06 vs. 1.46 +/- 0.04 g/l; p < 0.01; apo E: 98.35 +/- 6.4 vs. 72.53 +/- 3.38 mg/l; p < 0.05). 30% of the acromegalics showed increased plasminogen activator inhibitor activity (PAI) while 66% had increased tissue-type plasminogen activator (t-PA) concentrations. There was a correlation between hGH and Lp(a) (r = 0.414; p = 0.05), between hGH and PAI (r = -0.59; p < 0.005) and IGF-I and t-PA activity (r = -0.44; p < 0.05). In a subgroup of nine acromegalics Lp(a) was reduced by 32.2 +/- 6.7% (p < 0.05) after a six-month octreotide therapy and HDL2-cholesterol-concentration increased from 0.17 +/- 0.04 to 0.24 +/- 0.04 mmol/l (p < 0.05). In conclusion, our results demonstrate that elevated Lp(a)-concentrations and changes in fibrinolysis contribute to the cardiovascular complications and should therefore be controlled in acromegalic patients.
Exp Clin Endocrinol Diabetes 1997
PMID:Anomalies of lipoprotein pattern and fibrinolysis in acromegalic patients: relation to growth hormone levels and insulin-like growth factor I. 943 28

The objective of this study was to describe plasma and lipoprotein perturbations in gestational diabetes mellitus (GDM) compared to controls, and determine if alterations in lipids are related to gestational hormones and/or glucose control. Maternal HbA1c, free fatty acids (FFA), beta-estradiol, progesterone, prolactin, and plasma, very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL), high-density lipoprotein (HDL), HDL2 and HDL3 triglyceride (TG), cholesterol, and dietary intake were determined for women with diet-treated GDM and controls in a longitudinal design. Subjects (N = 25/group) were matched for age, race, and body-mass index (BMI). Women with GDM had significantly higher HbA1c than controls, although both groups were within the normal range (4%-6%). However, body weight gain was less for women with GDM. There was a trend for higher plasma FFAs at 37-38 weeks in GDM versus controls. Plasma and lipoprotein TG among the groups increased over the third trimester, and mean concentrations were greater for women with GDM. In GDM versus controls, VLDL and HDL3 TGs were higher at all times, HDL and HDL2 TGs at 33-34 and 37-38 weeks, and LDL TGs at 37-38 weeks. In VLDL, core lipids (TG + cholesterol) increased over gestation and were greater in GDM. In HDL, the TG/cholesterol ratio was greater in GDM. In GDM versus controls, plasma progesterone and prolactin were higher at all times; beta-estradiol was elevated at 37-38 weeks. HbA1c, progesterone, and prolactin correlated with all lipoprotein TG fractions. Exaggerated hypertriglyceridemia, particularly in the VLDL and HDL fractions, is a feature of GDM. The increase in VLDL TG is likely due to an increase in VLDL synthesis, whereas particle enrichment in TG is a plausible explanation for changes in HDL TG. Slight perturbations in glucose control and gestational hormones in diet-treated GDM may contribute to the observed increase in plasma and lipoprotein TG.
J Diabetes Complications
PMID:Elevated lipoprotein lipids and gestational hormones in women with diet-treated gestational diabetes mellitus compared to healthy pregnant controls. 944 8

To evaluate the inheritance of cardiovascular risk parameters in subjects with increased susceptibility for non-insulin-dependent diabetes mellitus, we compared 25 pairs of healthy twins who were offspring of diabetic parents with 25 pairs without a parental history for type 2 diabetes mellitus (12 monozygotic and 13 dizygotic in each group). Environmental factors were also evaluated to avoid bias in the assessment of concordance. No significant difference was found in concordance between monozygotic and dizygotic twins for physical activity, diet, smoking, alcohol intake and living together or apart. Genetic analysis revealed a substantial heritability for weight, body mass index, percentage of body fat, lipoprotein(a), high density lipoprotein (HDL)- and HDL2-cholesterol, without significant differences between the two groups. We conclude that heritability of several cardiovascular risk parameters is not increased in subjects with increased susceptibility to type 2 diabetes mellitus.
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PMID:Heritability of cardiovascular risk parameters in subjects with increased susceptibility to non-insulin-dependent diabetes mellitus. 945 73

Insulin Lispro (IL) is a short-acting insulin analog that better reproduces the physiological postprandial insulin profile. The aim of this study was to compare the effects of intensive insulin therapy on lipid metabolism using preprandial IL and regular insulin (RI) in 10 insulin-dependent diabetes mellitus (IDDM) subjects. The mean hemoglobin A1c (HbA1c) at baseline was 7.13% +/- 1.2% and did not change after both treatments. In IDDM patients, total cholesterol and triglyceride levels appeared lower after RI than after IL. The low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio significantly decreased only after RI (baseline, 2.01 +/- 0.6; IL, 1.88 +/- 0.6; RI, 1.71 +/- 0.5, P < .05). Although no very-low-density lipoprotein (VLDL) composition abnormalities were observed at baseline, the protein content was lower (P < .05) after IL (8.13% +/- 2.93%) than after RI (11.93% +/- 3.41%). Intermediate-density lipoprotein (IDL) protein depletion at baseline (6.14% +/- 6.84%) was normalized after both treatments (IL, 11.09% +/- 12.14%; RI, 10.38% +/- 16.68%, P < .05). LDL, HDL, HDL2, and HDL3 composition abnormalities were similar after both treatments and did not normalize. IDDM and control subjects showed similar LDL subfraction distribution at baseline and after both treatments. Two-hour postprandial VLDL composition alterations, although improved after RI, completely normalized after IL (P < .05). Lipoprotein lipase (LPL) and cholesteryl ester transfer protein (CETP) activities were similar to the control group and did not change after both treatments. Hepatic lipase (HL) activity was lower in diabetic patients (39.6 +/- 35.2 v 87.0 +/- 27.1 U/L, P < .01) and remained lower after both treatments. In conclusion, in IDDM patients, IL (injected immediately before the meal) may offer small different effects on lipoprotein metabolism versus RI (injected 30 minutes before the meal) that, taken together, do not seem relevant.
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PMID:Effects of a short-acting insulin analog (Insulin Lispro) versus regular insulin on lipid metabolism in insulin-dependent diabetes mellitus. 958 Feb 47

Serum lipid, apolipoprotein concentration, and lipoprotein composition were determined in maternal and umbilical venous cord blood at delivery by elective Cesarean section (CS) in 10 singleton, full-term pregnancies with maternal insulin-dependent diabetes mellitus (type I DM), which predated pregnancy, and in 22 nondiabetic pregnancies. The objectives of the study were to determine the influence of maternal type I DM, and hence potential fetal overnutrition on fetal lipid metabolism. There were no significant differences in gestational age, fetal weight, or fetal serum insulin concentration between the type I DM group and those with nondiabetic pregnancies, although fetal venous cord blood glucose was 3.4 mmol/L (3.0-4.5 mmol/L) (median and 25th-75th percentiles) and 2.9 mmol/L (2.0-3.4 mmol/L), respectively, and maternal Hemoglobin A1c [9.6% (8.2-10.7%) and 6.8% (6.3-7.8%), respectively], was significantly greater in the type I DM subjects (P < 0.02 and 0.002 respectively). Plasma nonesterified fatty acid (NEFA) concentrations were lower in the type I DM mothers [0.85 mmol/L (0.56-2.31 mmol/L) compared with 1.14 mmol/L (0.88-1.24 mmol/L] in nondiabetic pregnancies; P < 0.0001). Serum high-density lipoprotein phospholipids (HDL-PL) were increased in type I DM mothers because of elevated HDL2 phospholipid [0.39 mmol/L (0.27-0.48 mmol/L) compared with 0.12 mmol/L (0.06-0.21 mmol/L), respectively, P < 0.01). The maternal HDL cholesterol (C) concentration was not significantly different in the uncomplicated and type I DM pregnancies. However, in the umbilical venous cord blood, serum levels of NEFA [0.49 mmol/L (0.33-1.29 mmol/L) in type I DM compared with 0.13 mmol/L (0.06-0.33 mmol/L) in nondiabetics; P < 0.02)], total cholesterol (TC) [2.87 mmol/L (1.65-4.86 mmol/L) in type I DM compared with 1.65 mmol/L (1.46-1.87 mmol/L) in nondiabetics; P < 0.02]; free cholesterol (FC) [0.97 mmol/L (0.60-1.26 mmol/L) in type I DM compared with 0.62 mmol/L (0.37-0.75 mmol/L) in nondiabetics; P < 0.05), and cholesteryl ester (CE) [1.90 mmol/L (1.44-3.33 mmol/L) in type I DM compared with 1.01 mmol/L (0.83-1.24 mmol/L) in nondiabetics; P < 0.02), triglyceride (TG) (1.06 [0.50-1.91) mmol/L in type I DM compared with 0.29 [0.25-0.36] mmol/l in nondiabetics; P < 0.001), phospholipid (PL) (2.52 [1.73-3.03) mmol/L in type I DM compared with 1.34 [1.27-1.48] mmol/L in nondiabetics; P < 0.01], and the apolipoproteins A-I and B had significantly higher concentrations in type I DM. In umbilical venous cord blood, ratios of HDL-TC and HDL-PL to apo AI, reflecting the lipid content of HDL, were reduced when the mother had type I DM during pregnancy (P < 0.02 and P < 0.0001, respectively). These results indicate that maternal type I DM may lead to a fetal serum lipoprotein composition more closely resembling that seen in the adult. In type I DM, maternal TG and PL and fetal TC, TG, PL, CE, and FC were correlated to NEFA levels (P < 0.05), but not to glucose, insulin secretion, or maternal control of type I DM. These data suggest that the enhanced supply of NEFA to the fetus in type I DM pregnancies may drive the synthesis of cholesterol as well as TGs and PLs.
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PMID:Fetal and maternal lipoprotein metabolism in human pregnancy complicated by type I diabetes mellitus. 958 84

There is increasing evidence that high-density lipoprotein (HDL) and its subfractions are protective against atherosclerotic cardiovascular disease. Physical exercise, weight reduction, smoking cessation, diabetes mellitus control, and specific drugs, including niacin, fibrates, and estrogens, are effective methods to increase HDL levels. Niacin is the oldest and most powerful clinical agent for raising HDL levels. Niaspan, an extended-release niacin formulation, is as potent as immediate-release niacin in increasing levels of HDL cholesterol; subfractions HDL2 and HDL3; apolipoprotein A-I, the major protein of HDL, and its cardioprotective subfraction lipoprotein A-I. Recent research from our laboratory suggests a novel mechanism by which niacin inhibits hepatic removal of HDL-apoprotein A-I without interfering with the removal of cholesterol carried by HDL, thus augmenting reverse cholesterol transport. Other mechanistic studies indicate that fibrates and estrogens stimulate the synthesis and production of HDL-apoprotein A-I. Because niacin decreases HDL-apoprotein A-I removal, and fibrates and estrogens increase HDL-apoprotein A-I production, combinations of niacin with these agents may raise HDL levels more than fibrates or estrogens alone.
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PMID:Mechanistic studies of high-density lipoproteins. 991 62

The present study was designed to examine the effect of streptozotocin (STZ)-induced diabetes on the plasma lipoprotein profile and hepatic expression of the LDL receptor and HDL binding protein (HB2) in hypercholesterolemic Rico rats. The plasma level of HDL1 (density range 1.040-1.063), which is particularly high in this rat strain, decreased (-25%) 28 d after STZ administration (50 mg/kg). In contrast, the treatment increased (+54%) the plasma concentration of HDL2 (density range 1.063-1.210). These variations in the lipoprotein concentrations were associated with inverse changes in the hepatic protein levels of the LDL receptor (+118%) and HB2 (-46%). These results suggest that the hepatic expression of HB2, a putative HDL receptor, can influence the plasma level of apo Al-rich HDL as has already been shown for the LDL receptor for apo B/E containing lipoproteins.
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PMID:Effects of insulin deficiency on lipoproteins and their hepatic receptors in Rico rats. 992 81


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