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)

Patients with type 1 (insulin-dependent) diabetes mellitus in good metabolic control usually have normal plasma lipid levels yet they have an increased incidence of vascular complications. Abnormalities in the distribution and composition of lipoprotein subfractions might in part be responsible for the macroangiopathy seen in type 1 diabetes mellitus. The plasma lipids, lipoproteins and apolipoproteins were studied in 9 type 1 diabetic patients during conventional insulin therapy and in 14 healthy controls. Plasma lipoproteins were analysed by ultracentrifugation in a zonal rotor to evaluate their concentrations and flotation properties and for compositional analysis. In diabetic patients the mean glycosylated haemoglobin (HbA1c) was 9.44 +/- 1.02% and the plasma lipid concentrations were not significantly different from healthy controls. The very low density lipoprotein (VLDL) subclass cholesterol concentrations were no different in diabetic patients and control subjects, but the VLDL cholesterol/triglyceride ratio was significantly lower in diabetic patients than in control subjects (0.43 +/- 0.05 vs 0.85 +/- 0.14; p < 0.05). The flotation rate LDL2, the major component of low density lipoprotein (LDL) was lower in the diabetic patients compared with the control subjects. The cholesterol concentrations of intermediate density lipoprotein and LDL3, the minor component of LDL, were significantly higher (0.17 +/- 0.03 and 0.83 +/- 0.14 mmol/l respectively) in diabetic patients than in control subjects (0.05 +/- 0.02 and 0.24 +/- 0.08 mmol/l). The flotation properties and cholesterol concentrations of the high density lipoprotein (HDL) subclass, and the protein-lipid composition of LDL2, HDL2 and HDL3, were no different in diabetic patients and control subjects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein compositional abnormalities in type 1 (insulin-dependent) diabetic patients. 832 25

In IDDM patients, serum high-density lipoprotein cholesterol concentrations have been reported to be normal or elevated. The spectrum of high-density lipoprotein particles is highly heterogeneous, but no data are available on the subpopulations of high-density lipoprotein in IDDM. We, therefore, studied the spectrum of high-density lipoprotein particles in 86 IDDM patients (51 men and 35 women) 37 +/- 10 yr of age and in 74 sex-, age-, and body mass index-matched healthy nondiabetic subjects. The concentrations of high-density lipoprotein and HDL2 cholesterol were higher in the IDDM group than in the control subjects (P < 0.01). The apoA-I-to-apoA-II ratio was higher in the IDDM patients than in the nondiabetic subjects (P < 0.001) because of an increased concentration of LpA-I particles (61 +/- 17 vs. 53 +/- 15, P < 0.01). LpA-I particles correlated positively with high-density lipoprotein and HDL2 cholesterol in the two groups. Postheparin plasma lipoprotein lipase activity was significantly higher in the IDDM group than in the control group (P < 0.001), whereas postheparin plasma hepatic lipase activities were similar in both groups. Plasma cholesteryl ester transfer protein activity was estimated in an in vitro isotopic assay using exogenous labeled donor (low-density) and acceptor (high-density) lipoproteins in the absence of native lipoproteins. We observed no difference in cholesteryl ester transfer protein activity between the groups, and no significant correlations existed between cholesteryl ester transfer protein activity and high-density lipoprotein subpopulations.(ABSTRACT TRUNCATED AT 250 WORDS)
Diabetes 1993 Sep
PMID:Regulation of apolipoprotein A-I-containing lipoproteins in IDDM. 834 39

Hyperlipidemia associated with non-insulin-dependent diabetes mellitus (NIDDM) and insulin resistance is characterized by high triglyceride levels; raised levels of total low-density lipoprotein (LDL), which is made up of small, dense, cholesterol-rich particles; low levels of high-density lipoprotein (HDL); and glycosylation of apolipoproteins. Optimal drug therapy for this lipid profile is controversial. To test whether a fibrinic acid derivative (gemfibrozil) or a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor (lovastatin) would produce better results in these patients, a crossover study was performed. Gemfibrozil 600 mg twice daily and, after a washout period, lovastatin 20 to 40 mg twice daily were administered to nine patients with NIDDM. Gemfibrozil significantly decreased triglyceride, very-low-density lipoprotein (VLDL), and intermediate-density lipoprotein (IDL) levels, the total cholesterol:HDL ratio, and the IDL plus VLDL;HDL ratio, and significantly increased levels of HDL, HDL2, and HDL3. Lovastatin significantly decreased levels of total cholesterol, calculated LDL, directly measured LDL, IDL, total triglycerides, VLDL, and the ratios of LDL:HDL, total cholesterol:HDL, and directly measured LDL:HDL and significantly increased total HDL and HDL3 levels. Gemfibrozil was significantly more effective than lovastatin in raising total HDL and HDL3 levels and in lowering the IDL plus VLDL:HDL ratio. Lovastatin was significantly more effective than gemfibrozil in lowering total cholesterol, LDL, directly measured LDL, and the LDL:HDL and directly measured LDL:HDL ratios. In the absence of malignant hypertriglyceridemia, an HMG-CoA reductase inhibitor, rather than a fibrinic acid derivative, is indicated for the treatment of patients with dyslipidemia associated with NIDDM and insulin resistance.
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PMID:A comparison of lovastatin, an HMG-CoA reductase inhibitor, with gemfibrozil, a fibrinic acid derivative, in the treatment of patients with diabetic dyslipidemia. 859 42

An analysis was undertaken to determine whether combined oral contraceptive (OC) use interacts with the effects of potential cardiovascular risk modifiers (age, body mass index, cigarette smoking, alcohol intake, exercise habit, family histories of heart disease or diabetes, number of pregnancies and duration of OC use) on blood pressure and lipid, lipoprotein, glucose and insulin risk markers for cardiovascular disease. Relationships between risk modifiers and risk markers were compared between non-users (n = 418) and users of low-estrogen dose OC (n = 925, categorised according to progestin content as monophasic levonorgestrel, triphasic levonorgestrel, norethindrone or desogestrel). OC use diminished the adverse effects of age on glucose tolerance. Aerobic exercise had a particularly beneficial effect on triglyceride levels and OGTT insulin response in OC users. The rise in HDL and HDL2 cholesterol concentrations with alcohol intake seen in non-users was diminished in OC users. Increasing duration of use of a desogestrel combination was associated with increasing HDL cholesterol concentrations. No adverse effects of risk modifiers on metabolic risk markers and blood pressure were augmented by OC use, and some were even diminished.
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PMID:Interaction of oral contraceptive use with the effects of age, exercise habits and other cardiovascular risk modifiers on metabolic risk markers. 863 Nov 92

While it is known that the transfer of cholesteryl ester (CE) from high density lipoprotein (HDL) to the apo B-containing lipoproteins is increased in patients with diabetes, the extent to which the various lipoprotein fractions engage in neutral lipid exchange and the magnitude to which triglyceride (TG) is translocated is not known. To examine in greater detail neutral lipid net mass transfer in diabetes, the HDL subfractions and the apo B-containing lipoproteins were separated, and the net mass transfer of CE and TG was compared to that of control subjects. In both groups, bidirectional transfer of CE from HDL3 to very low density lipoprotein (VLDL) + low density lipoprotein (LDL) and of TG from VLDL + LDL to HDL3, took place, but this process was significantly greater (P < .01) in insulin-dependent diabetes mellitus (IDDM). In contrast, CE and TG accumulated in HDL2 to a similar degree in normal and IDDM subjects. In recombination experiments with each of the apo B-containing lipoproteins, IDDM VLDL had a greater capacity to facilitate the exchange of core lipids from both IDDM and control HDL3: on the other hand, LDL from IDDM and control subjects both donated TG and CE to HDL2 and affected little change in HDL3. These findings indicate that all the major plasma fractions normally participate in the trafficking of CE and TG among the lipoproteins during neutral lipid transfer and show that the principal perturbation in cholesteryl ester transfer in IDDM involves altered interaction between VLDL and the HDL3 subfraction.
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PMID:Changes in high density lipoprotein subfraction lipids during neutral lipid transfer in healthy subjects and in patients with insulin-dependent diabetes mellitus. 864 26

Cholesterol metabolism is altered in diabetic states. Three main mechanisms seem to be involved in these alterations: a) an increased glycation of cholesterol-rich lipoproteins, b) an insulin-resistant state which is mainly present in overweight type 2 diabetic patients, and c) changes in insulin secretion which depends on the clinical type of diabetes. Insulin per se exerts beneficial effects on the metabolism of cholesterol binding lipoproteins. Despite insulin has a stimulatory influence on the endogenous cholesterol synthesis from Acetyl-CoA, this hormone tends to decrease the LDL cholesterol concentrations through two additional effects: a diminution in the ApoB VLDL synthesis and an increase in the LDL catabolism. In well controlled diabetic patients, plasma concentrations of cholesterol binding lipoproteins are generally found within the normal range. These patients exhibit usually a normal sensitivity to insulin in the liver and peripheral tissues. In this case, the VLDL production is generally decreased, the LDL catabolism is either increased or normal, and therefore the endogenous cholesterol synthesis from Acetyl-CoA remains setted at a normal level. In poorly controlled and/or in insulin resistant diabetic patients, both VLDL cholesterol production and cholesterogenesis are increased, mainly as a consequence of the insulin-resistant state. The excessive glycation of LDL results in a diminution of their catabolism and therefore in an increase of their plasma concentrations. The reverse cholesterol transport pathway is also altered, the modifications being characterized by a diminution in HDL cholesterol concentrations, especially in the HDL2 subfraction. All these changes are certainly involved in the accelerated development of cardio-vascular complications encountered in diabetic patients.
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PMID:[Insulin, diabetes and cholesterol metabolism]. 867 37

A detailed analysis of postprandial changes in the size, density, composition, and relative proportion of the major high-density lipoprotein (HDL) subfractions, HDL2 and HDL3, was performed in seven normolipidemic patients with insulin-dependent diabetes mellitus (IDDM) in moderate glycemic control and seven age-, sex-, and weight-matched healthy nondiabetic controls. IDDM subjects received an overnight insulin infusion to maintain euglycemia, with an incremental increase in the insulin infusion rate at the time of the test meal (containing 60 g fat/m2). Samples for detailed analysis of HDL by gradient density ultracentrifugation and nondenaturing gradient gel electrophoresis (GGE) were collected at 0, 4, Br, and 12 hours after the test meal. The composition of HDL, HDL2, and HDL3 was significantly altered in the postprandial state in IDDM subjects and controls with an increase in triglyceride content at 4 to 8 hours and a reciprocal decrease in cholesteryl ester, reflecting exchange of lipid constituents of HDL with triglyceride (TG)-rich lipoproteins. In addition, the phospholipid content of the particles increased at 8 hours after the meal. Peak density of HDL2 and HDL3 decreased slightly at 4 to 8 hours, reaching significance only in controls at 8 hours (P < .05), whereas the mean radius size of these subfractions did not change significantly. In controls and IDDM subjects, the ratio of HDL3 to HDL2 at 8 to 12 hours increased significantly (P < .005). Significant differences in the composition, size, density, or subfraction distribution of HDL between subjects with IDDM and controls were not observed following ingestion of the lipid-rich meal. We conclude from these data that in patients with IDDM in moderate glycemic control, there do not appear to be any significant gross abnormalities in postprandial HDL metabolism with respect to the size, density, or compositional changes of HDL particles.
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PMID:Postprandial changes in high-density lipoprotein composition and subfraction distribution are not altered in patients with insulin-dependent diabetes mellitus. 876 65

Although a strong genetic susceptibility has been established for NIDDM and a maternal transmission of the disease predominates in some populations, a relationship between parental diabetes status and metabolic abnormalities in nondiabetic offspring has not been shown in humans. To address this question, we studied 2,152 first-degree relatives of patients with NIDDM (FH+) and 528 age- and weight-matched spouses without a family history of NIDDM (FH-) in Western Finland (the Botnia study). A subset of the subjects underwent a euglycemic insulin clamp combined with indirect calorimetry to measure insulin sensitivity and energy expenditure. Despite similar amounts of total body fat, persons with a family history of NIDDM had a greater waist-to-hip ratio (WHR) than spouses without a family history of diabetes (P < 0.003). They also had a decreased resting metabolic rate (P = 0.005), but this difference disappeared when adjusted for the difference in WHR. Insulin-stimulated glucose metabolism (P = 0.002), particularly nonoxidative glucose metabolism (P = 0.009), was reduced in FH+ compared with FH- subjects, and this difference remained after adjustment for WHR. A parental history of NIDDM influenced the insulin response to the oral glucose load, with male offspring of diabetic mothers showing the lowest insulin values (P = 0.011). Moreover, a parental effect was also observed on HDL and HDL2 cholesterol concentrations with female offspring of diabetic mothers showing lower values than female offspring of diabetic fathers (both P < 0.002). We conclude that abdominal obesity, insulin resistance, and decreased resting metabolic rate are characteristic features of first-degree relatives of patients with NIDDM and that the decrease in resting metabolic rate is partially related to the degree of abdominal obesity. A sex-specific paternal effect was observed on insulin and HDL cholesterol concentrations. Therefore, one has to consider the possibility of unprecedented maternal or paternal inheritance of different NIDDM phenotypes.
Diabetes 1996 Nov
PMID:Metabolic consequences of a family history of NIDDM (the Botnia study): evidence for sex-specific parental effects. 886 65

Transfers or exchanges of cholesterol esters and triglycerides between lipoproteins are mediated by a specialized protein referred to as cholesteryl ester transfer protein (CETP), whereas those of phospholipids (PLs) are facilitated by both CETP and a specific phospholipid transfer protein (PLTP). In the present study, the authors compared phospholipid transfer (PLT) in normal subjects and in patients with non-insulin-dependent diabetes (NIDD), which is associated with an increased risk of atherosclerosis. PLT was measured in different recombination experiments using an isotopic assay in which the transfer of labelled PLs from very low-density lipoprotein (VLDLs) and low-density lipoproteins (LDLs) to high-density lipoproteins (HDLs) was determined. This allowed discrimination between the roles of VLDLs + LDLs, HDLs, and plasma PLT activity (PLTA). VLDL + LDL-dependent PLT, HDL-dependent PLT and PLTA were decreased in NIDD. VLDL + LDL-dependent PLT was found to be negatively correlated with the PL/apolipoprotein B ratio, whereas HDL-dependent PLT was positively correlated with the HDL2/HDL3 and PL/apolipoprotein A-I ratios and negatively correlated with the flow activation energy at the HDL surface. The HDL2/HDL3 ratio was positively correlated with PLTA but not with CETP, which confirms previous reports suggesting that PLTP might act as an HDL conversion factor. These data show that several abnormalities in PLT occur in NIDD and raise the question as to whether a lowered PLT might be a new characteristic of dis factors associated with an increased risk of atherosclerosis.
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PMID:Multiple abnormalities in the transfer of phospholipids from VLDL and LDL to HDL in non-insulin-dependent diabetes. 890 50

To determine whether insulin delivered into portal circulation by an implanted pump reversed abnormalities in lipoprotein composition in insulin-dependent diabetes mellitus, 10 well-controlled normolipidaemic patients were studied after conventional intensive sub-cutaneous (ISC) insulin management and then 3 and 6 months after intraperitoneal pump implantation (IP). Glycated haemoglobin (ISC: 6.9 +/- 1.7% vs. IP-3 months 6.3 +/- 0.7; IP-6 months 6.3 +/- 0.8; mean +/- S.D.), plasma triglyceride and cholesterol levels, and the cholesterol content of HDL2 and HDL3 were normal and not significantly changed during these treatments. Fasting free insulin concentrations measured before and after 6 months of IP fell by more than half (ISC 8.22 +/- 6.5 vs IP 2.77 +/- 2.4 mU/ml; p < 0.025). The plasma-free cholesterol/lecithin ratio, a potential new cardiovascular risk factor, was increased during ISC, declined progressively after 3 months of IP, and approached normal by 6 months (ISC 0.96 +/- 0.37 mol/mol vs. IP-3 months 0.91 +/- 0.34; IP 6 months 0.86 +/- 0.10; reference group 0.83 +/- 0.33). In all lipoprotein fractions, sphingomyelin concentrations tended to fall, and lecithin concentrations to rise progressively during IP. As a result, the sphingomyelin/lecithin ratio, an index of the surface rigidity of lipoproteins, declined. The fact that some of the compositional modifications associated with ISC were reversed when insulin was administered intraperitoneally suggests that they may have been iatrogenic and resulted from high systemic insulin levels.
Diabetes Metab 1996 Dec
PMID:Improved lipoprotein surface and core lipid composition following intraperitoneal insulin delivery in insulin-dependent diabetes mellitus. 898 50


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