Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human serum paraoxonase is physically associated with HDL and has been implicated in the detoxification of organophosphates and possibly in the prevention of LDL lipid peroxidation. We investigated the serum activity and concentration of paraoxonase in 78 patients with type 1 diabetes mellitus, 92 with type 2 diabetes, and 82 nondiabetic control subjects. Paraoxonase activity was generally lower in diabetics than in control subjects. This decrease was unrelated to differences in paraoxonase phenotype distribution or its serum concentration. Rather, the difference in paraoxonase activity was explained by its specific activity, which was lower in diabetics, indicating either the presence of a circulating inhibitor or disturbance of the interaction of paraoxonase with HDL affecting its activity. Paraoxonase specific activity was lowest in patients with peripheral neuropathy, suggesting an association of paraoxonase with neuropathy. In control subjects but not patients with diabetes, paraoxonase correlated with HDL cholesterol and apolipoprotein A-1. Our results indicate that the low paraoxonase activity in diabetes is due to decreased specific activity. In other studies low serum paraoxonase activity has been associated with increased susceptibility to atherosclerosis, and the present results also suggest an association with peripheral neuropathy, which could be due to reduced capacity to detoxify lipid peroxides in diabetes.
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PMID:Serum paraoxonase activity, concentration, and phenotype distribution in diabetes mellitus and its relationship to serum lipids and lipoproteins. 758 60

We tested the ability of remnant-like particles (RLP) from NIDDM patients to stimulate cholesteryl ester synthesis in human monocyte-derived macrophages. Six NIDDM patients were studied together with 7 non-diabetic subjects. All had apolipoprotein (apo) E3/3 phenotype. RLP were isolated using an immunoaffinity gel mixture of anti apo B-100 and anti apo A-1 monoclonal antibodies coupled to Sepharose 4B. Plasma levels of triglyceride, total cholesterol (chol) and high density lipoprotein-chol were not statistically different, but plasma levels of RLP-chol were significantly (p < 0.05) higher in NIDDM patients (10.5 +/- 2.2 mg/dl) than in non-diabetic controls (5.0 +/- 1.7 mg/dl). The effects of RLP from NIDDM patients on macrophage cholesteryl ester synthesis were estimated. 14C-oleate incorporation into cholesteryl esters in macrophages was significantly (p < 0.01) higher in NIDDM patients with apo E3/3 (0.326 +/- 0.037 nmole/mg cell protein) than in non-diabetic controls with apo E3/3 (0.181 +/- 0.011 nmole/ mg cell protein). It is suggested that RLP from NIDDM play a role in the accumulation of cholesteryl esters and are one of the risk factors for the acceleration of atherosclerosis in NIDDM.
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PMID:Remnant-like particles (RLP) from NIDDM patients with apolipoprotein E3/3 phenotype stimulate cholesteryl ester synthesis in human monocyte-derived macrophages. 889 73

In hypertriglyceridemic states, triglyceride enrichment of high-density lipoprotein (HDL) may play an important role in decreasing the HDL cholesterol and apolipoprotein (apo) A-1 plasma concentration. We have shown previously that HDL particles are transformed into small HDLs when lipolysis is stimulated in vivo or in vitro, and this process is more marked if the HDL is triglyceride-rich. The present study was conducted to determine whether the susceptibility of HDL to transformation can be altered by triglyceride-lowering therapy in humans. Seventeen moderately hypertriglyceridemic individuals (nine with type II diabetes mellitus and eight moderately hypertriglyceridemic nondiabetic subjects) were studied before and after 3 months of triglyceride-lowering therapy with gemfibrozil. Since no significant differences in postprandial and postheparin HDL metabolism were detected between type II diabetic and nondiabetic subjects, results are reported for the two groups combined (N = 17). Fasting HDL was triglyceride-rich with a preponderance of HDL3, and became more enriched with triglycerides postprandially. Heparin administration resulted in a rapid decrease in plasma and HDL triglycerides and an increase in plasma and HDL free fatty acids (FFAs). Postheparin, there was a reduction in HDL size and an increase in the proportion of small (HDL3c) HDL particles (HDL3c constituted 7.1% +/- 1.8% of total HDL preheparin and 26.6% +/- 3.8% postheparin, P < .001). Triglyceride-lowering treatment resulted in a decrease in fasting triglycerides (-54%, P < .001) and HDL triglyceride content (-36%, P = .002), an increase in fasting HDL cholesterol (19%, P = .004), and proportionately fewer (13.2% +/- 2.1%, P < .001) HDL3c particles formed postheparin. Postheparin HDL size correlated inversely with the fasting triglyceride level (r = -.55, P < .001) and HDL triglyceride concentration (r = -.34, P = .02). These results show that the postprandial increase in triglyceride levels in hypertriglyceridemic subjects is associated with increased production of small HDL particles when lipolysis is stimulated, and that lipid-lowering therapy can contribute to favorably reduce this postprandial production of small HDL particles. Further studies are needed to clarify how these abnormalities ultimately lead to a decrease of plasma HDL cholesterol and apo A-1 in hypertriglyceridemic states.
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PMID:Production of small high-density lipoprotein particles after stimulation of in vivo lipolysis in hypertriglyceridemic individuals: studies before and after triglyceride-lowering therapy. 947 77

About 15% of the adult Kuwaiti population has type 2 diabetes and over 50% are hyperlipidaemic by current diagnostic criteria. Not surprisingly, coronary heart disease (CHD) is the leading cause of death in Kuwait. Reports from coronary care units in Kuwait suggest that 40-80% of the CHD patients were diabetic and 50-80% hyperlipidaemic. The pattern worldwide is similar. International guidelines have therefore consistently recognised diabetes as a major risk factor for CHD. In our Lipid Clinic population in Kuwait, about 30% are diabetic. The commonest lipid abnormalities seen in Kuwaiti diabetic patients, as elsewhere, are hypertriglyceridaemia with low HDL levels and variable LDL levels. About 75% of the subjects had either mixed hyperlipidaemia or predominant hypertriglyceridaemia. There are possibly some compositional changes in LDL in the diabetic subjects in that there were important differences in the statistical relationships between LDL and HDL and their respective apolipoproteins - apo B and apo A-1 in diabetic as compared to non-diabetic subjects. Other important observations made in diabetic subjects in Kuwait are: (i) similar serum Lp (a) levels and pattern of apo(a) polymorphism with non-diabetic subjects, with no demonstrable relationship between serum levels of Lp(a) and insulin/insulin sensitivity, although with CHD, Lp(a) levels were increased; (ii) diabetic hyperlipidaemic subjects had elevated PAI-1 levels with significant correlations between blood PAI-1 and insulin levels suggesting underlying insulin resistance (syndrome X). Various landmark trials of cholesterol-lowering therapies in the prevention of CHD have consistently demonstrated near-normalization of the increased CHD risk in diabetes. Our experience in Kuwait suggests that diabetic patients and others with mixed hyperlipidaemia benefit from tight glycaemic control, appropriate advice on diet and exercise with regular reinforcement by continuing contact with professional dietitians and regular availability of drugs where prescribed. Often, it is the regular compliance with medication that is important, rather than the specific medication used particularly where HMG CoA reductase inhibitors (statin drugs) are not always available. A useful guideline for management of dyslipidaemia in diabetes is suggested.
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PMID:Diabetic dyslipidaemia in Kuwait. 1244 10

It has been estimated that 92% of individuals with type 2 diabetes, without cardiovascular disease (CVD), have a dyslipidaemic profile. Several guidelines on cardiovascular risk now recommend that patients with diabetes should be considered at high risk of CVD and should thus receive lipid-lowering therapy to reduce low-density lipoprotein cholesterol (LDL-C) to below 2.5 mmol/L. Since their introduction in 1987, statins have revolutionized the management of CVD. The most recent statin to be introduced, rosuvastatin, has been shown to be the most effective at lowering LDL-C, as well as consistently raising HDL-C across the 10-40 mg dose range. This has been confirmed by many studies, including the Measuring Effective Reductions in Cholesterol Using Rosuvastatin Therapy (MERCURY I) study in which rosuvastatin 10 mg was shown to be more effective than commonly used doses of other statins, both for LDL-C reduction and achieving treatment target goals. The effectiveness of rosuvastatin has also been studied in type 2 diabetes patients in three studies: the URANUS (Use of Rosuvastatin vs. Atorvastatin iN type 2 diabetes mellitUS), ANDROMEDA (A raNdomized, Double-blind study to compare Rosuvastatin [10 & 20 mg] and atOrvastatin [10 & 20 Mg] in patiEnts with type II DiAbetes) and CORALL (COmpare Rosuvastatin [10-40 mg] with Atorvastatin [20-80 mg] on apo B/apo A-1 ratio in patients with type 2 diabetes meLLitus and dyslipidaemia) studies. URANUS and ANDROMEDA showed rosuvastatin to be more effective than atorvastatin at reducing LDL-C and achieving treatment target goals. CORALL demonstrated rosuvastatin 10, 20 and 40 mg to be more effective at lowering LDL-C than 20, 40 and 80 mg of atorvastatin, respectively. Ongoing studies will evaluate whether these properties of rosuvastatin translate into beneficial effects on atherosclerosis and significant reductions in cardiovascular events.
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PMID:A review of the efficacy of rosuvastatin in patients with type 2 diabetes. 1603 94

Specific retinoid X receptor (RXR) agonists, such as LG100268 (LG268), and the thiazolidinedione (TZD) PPARgamma agonists, such as rosiglitazone, produce insulin sensitization in rodent models of insulin resistance and type 2 diabetes. In sharp contrast to the TZDs that produce significant increases in body weight gain, RXR agonists reduce body weight gain and food consumption. Unfortunately, RXR agonists also suppress the thyroid hormone axis and generally produce hypertriglyceridemia. Heterodimer-selective RXR modulators have been identified that, in rodents, retain the metabolic benefits of RXR agonists with reduced side effects. These modulators bind specifically to RXR with high affinity and are RXR homodimer partial agonists. Although RXR agonists activate many heterodimer partners, these modulators selectively activate RXR:PPARalpha and RXR:PPARgamma, but not RXR:RARalpha, RXR:LXRalpha, RXR:LXRbeta, or RXR:FXRalpha. We report the in vivo characterization of one RXR modulator, LG101506 (LG1506). In Zucker fatty (fa/fa) rats, LG1506 is a potent insulin sensitizer that also enhances the insulin-sensitizing activities of rosiglitazone. Administration of LG1506 reduces both body weight gain and food consumption and blocks the TZD-induced weight gain when coadministered with rosiglitazone. LG1506 does not significantly suppress the thyroid hormone axis in rats, nor does it elevate triglycerides in Sprague Dawley rats. However, LG1506 produces a unique pattern of triglycerides elevation in Zucker rats. LG1506 elevates high-density lipoprotein cholesterol in humanized apolipoprotein A-1-transgenic mice. Therefore, selective RXR modulators are a promising approach for developing improved therapies for type 2 diabetes, although additional studies are needed to understand the strain-specific effects on triglycerides.
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PMID:Biological characterization of a heterodimer-selective retinoid X receptor modulator: potential benefits for the treatment of type 2 diabetes. 1626 50

Hyperlipidemia is commonly observed in patients with type 2 diabetes and is an independent risk factor for cardiovascular disease. The authors tested the effect of atorvastatin (10 mg/d) on 110 hyperlipidemic type 2 diabetes patients with low-density lipoprotein cholesterol (LDL-C) levels exceeding 130 mg/d. The primary efficacy end point was the percentage change in LDL-C and high-density lipoprotein cholesterol (HDL-C), and secondary efficacy included the percentage change in apolipoproteins at weeks 6, 12, and 24. The tertiary goal was percentage change in free radical scavenger enzymes and oxidative stress. LDL-C was reduced by 25%, 39.3%, and 49.2%. A similar trend was observed in total cholesterol, triglyceride, non-HDL-C, and apolipoprotein (apo) B-100. HDL-C was raised by 3.2%, 6%, and 8.2%. A similar trend was seen in apo A-1. Copper zinc-superoxide dismutase and glutathione were raised significantly (P < .001); however, changes in glutathione-S-transferase and glutathione peroxidase activities were nonsignificant. Malondialdehyde was decreased significantly (P < .001). Atorvastatin improves the lipoprotein profile and oxidative status in patients with type 2 diabetes.
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PMID:Effect of atorvastatin on type 2 diabetic dyslipidemia. 1722 Apr 73

Therapeutic modulation of low-density lipoprotein (LDL) size could be of benefit in reducing the risk of cardiovascular events in diabetic patients. This study evaluated the efficacy of L-carnitine on the size of LDL particles in type 2 diabetes mellitus patients treated with simvastatin. Eighty diabetic patients were randomly assigned to 1 of 2 treatment groups for 3 months. The 2 groups received either simvastatin monotherapy 20 mg (n = 40) or L-carnitine 2 g/d and simvastatin 20 mg (n = 40). The following variables were assessed at baseline; after washout; and at 1, 2, and 3 months of treatment: body mass index, fasting plasma glucose, glycosylated hemoglobin, total cholesterol, LDL cholesterol, LDL subclasses, LDL size, high-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1, and apolipoprotein B-100. After 12 weeks, comparing the 2 groups, we observed a decrease in fasting plasma glucose (1.45 vs 0.61 mmol/L, P < .001) and an increase in glycosylated hemoglobin (0.2% vs 0.4%, P < .05). Moreover, there was a decrease in total cholesterol (2.07 vs 1.45 mmol/L, P < .001), LDL (1.65 vs 1.29 mmol/L, P < .001), triglycerides (1.36 vs 0.41 mmol/L, P < .001), apo B-100 (49 vs 9 g/L, P < .001), and small-sized LDL proportion (10.8% vs 4.9%, P < .001), whereas LDL particle size increased (6 vs 3 A, P < .001) and HDL increased (0.2 vs 0.11 mmol/L, P < .001). We observed that patients treated with carnitine and simvastatin showed a reduction in small-sized LDL proportion and an increase in LDL particle size.
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PMID:Effect of L-carnitine on the size of low-density lipoprotein particles in type 2 diabetes mellitus patients treated with simvastatin. 1960 23

Apolipoprotein B to A-1 (apo B/A-1) ratio is reportedly a better predictor of atherosclerotic vascular disease than low-density lipoprotein cholesterol (LDL-C). The aim of this study was to assess the association of serum apo B/A-1 ratio with insulin resistance and adiponectin in patients with different grades of glucose intolerance. Patients were divided according to glucose tolerance into 3 groups: normal glucose tolerance without metabolic syndrome (n = 229), impaired fasting glucose (subjects with fasting plasma glucose level between 100 and 125 mg/dL, n = 658), and type 2 diabetes mellitus (n = 381). Serum concentrations of apo B, apo A-1, glucose, total cholesterol (TC), triglycerides, and high-density lipoprotein cholesterol (HDL-C) and adiponectin were measured. Insulin resistance was estimated by the homeostasis model assessment of insulin resistance index (HOMA-IR). There were significant differences in metabolic parameters among the groups, including waist circumference, insulin, HOMA-IR, and apo B/A-1 ratio, which increased sequentially with glucose intolerance, whereas adiponectin level decreased with increasing severity of glucose intolerance. The apo B/A-1 ratio was significantly correlated with TC, triglycerides, LDL-C, HDL-C, adiponectin, and HOMA-IR in normal glucose tolerance, impaired fasting glucose, and type 2 diabetes mellitus. Multiple regression analysis showed that apo B/A-1 ratio was significantly associated with TC, LDL-C, HDL-C, and adiponectin. In conclusion, apo B/A-1 ratio was significantly associated with insulin resistance according to glucose intolerance; and serum adiponectin was an important independent factor associated with apo B/A-1 ratio in Koreans.
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PMID:Adiponectin is independently associated with apolipoprotein B to A-1 ratio in Koreans. 1991 67

Thiazolidinediones (TZD), which are widely used as insulin sensitizers, and fibrates, which are lipid-lowering drugs, are used in the treatment of dyslipidemia that commonly accompanies diabetes. Several reports suggest elevated levels of high-density lipoprotein (HDL) cholesterol, but the paradoxical reduction of HDL cholesterol level during single or combined TZD and fibrate therapies has been occasionally reported. Herein, we report a case of paradoxical decrease in HDL cholesterol and apolipoprotein A-1 levels during rosiglitazone and fenofibrate treatment for the first time in Korea. The patient was a 56-yr-old man presenting with type 2 diabetes mellitus and dyslipidemia. His HDL cholesterol and apolipoprotein A-1 levels returned to normal after the cessation of fenofibrate therapy. Since diabetes is an established risk factor of cardiovascular diseases, low HDL cholesterol can be a key cause of concern for patients with diabetes. Therefore, HDL cholesterol level should be determined before and after starting TZD and/or fibrate therapy in diabetic patients.
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PMID:[HDL cholesterol reduction during rosiglitazone and fenofibrate treatment in a type 2 diabetes mellitus patient with dyslipidemia]. 2019 17


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