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Query: UMLS:C0011860 (type 2 diabetes)
 57,723 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metabolic abnormalities associated with the metabolic syndrome are also present in patients with type 2 diabetes mellitus and in those with familial combined hyperlipidemia (FCHL). These abnormalities include central obesity, insulin resistance with hyperinsulinemia, hypertension, increased plasma triglycerides, and decreased high-density lipoprotein cholesterol levels. Other characteristics associated with FCHL include the presence of small, dense low-density lipoprotein cholesterol and increased apolipoprotein B. Patients with these abnormalities are at an increased risk for premature coronary artery disease. Treatment of the dyslipidemia associated with type 2 diabetes and FCHL with a combination of a statin and a thiazolidinedione or niacin offers the most comprehensive modality to correct the various lipid abnormalities.
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PMID:Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. 1295 24

Available evidence clearly indicates a rapid progression in the prevalence of obesity worldwide. As a consequence, there has also been a marked increase in the prevalence of type 2 diabetes all over the world and this chronic metabolic disease is now considered as a coronary heart disease risk equivalent. However, even in the absence of the hyperglycaemic state which characterizes type 2 diabetic patients, non diabetic individuals with a specific form of obesity, named abdominal obesity, often show clustering metabolic abnormalities which include high triglyceride levels, increased apolipoprotein B, small dense low density lipoproteins and decreased high density lipoproteins-cholesterol levels, a hyperinsulinemic-insulin resistant state, alterations in coagulation factors as well as an inflammatory profile. This agglomeration of abnormalities has been referred to as the metabolic syndrome which can be identified by the presence of three of the five following variables: abdominal obesity, elevated triglyceride concentrations, low HDL-cholesterol levels, increased blood pressure and elevated fasting glucose. Post-mortem analyses of coronary arteries have indicated that obesity (associated with a high accumulation of abdominal fat measured at autopsy) was predictive of earlier and greater extent of large vessels atherosclerosis as well as increase of coronary fatty streaks. Metabolic syndrome linked to abdominal obesity is also predictive of recurrent coronary events both in post-myocardial infarction patients and among coronary artery disease men who underwent a revascularization procedures. It is suggested that until the epidemic progression of obesity is stopped and obesity prevented or at least properly managed, cardiologists will be confronted to an evolving contribution of risk factors where smoking, hypercholesterolemia and hypertension may be relatively less prevalent but at the expense of a much greater contribution of abdominal obesity and related features of the metabolic syndrome.
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PMID:[Obesity and cardiovascular disease]. 1461 4

The paradigm of obesity leading to insulin resistance and type 2 diabetes is examined in relation to dyslipidemia, which typically consists of high levels of triglycerides (TG) and low levels of high-density lipoprotein (HDL). Kinetic studies with stable isotope-labeled amino acid precursors have shown that the development of visceral obesity, as well as type 2 diabetes, leads to overproduction of the apolipoprotein B-100 and TG in very low-density lipoproteins. Elevated plasma levels or increased flux of albumin-bound free fatty acids to the liver appear to be underlying metabolic events in this process. Low levels of HDL are due to increased catabolism, which can be related to TG enrichment.
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PMID:Lipoprotein metabolism in obesity and diabetes: insights from stable isotope kinetic studies in humans. 1467 71

Patients with type 2 diabetes mellitus or the metabolic syndrome have a unique dyslipidemia characterized by hypertriglyceridemia; elevated blood levels of apolipoprotein B; small, dense low-density lipoprotein (LDL) cholesterol; and low levels of high-density lipoprotein (HDL) cholesterol, in particular HDL(2)-C. Treatment of the dyslipidemia associated with these disorders should focus on correcting the abnormal lipoprotein levels as well as LDL and HDL heterogeneity. Statins and fibrates are useful for treating elevated LDL in patients with and without diabetes or the metabolic syndrome. In addition, thiazolidinediones or niacin in combination with a statin show promise for correcting defects in LDL and HDL heterogeneity. The ultimate goal of treatment in this patient population is to prevent the development and progression of coronary artery disease.
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PMID:Dyslipidemia in the metabolic syndrome and type 2 diabetes mellitus. 1467 62

The dyslipidemia and insulin resistance of type 2 diabetes can be improved by aerobic exercise. The effect of 6 months supervised exercise on very low-density lipoprotein (VLDL) apolipoprotein B metabolism was investigated in patients with type 2 diabetes. Moderately obese patients (n = 18) were randomized into supervised (n = 9) and unsupervised (n = 9) exercise groups. All patients were given a training session and a personal exercise program and asked to exercise four times per week at 70% maximal oxygen uptake for 6 months. Patients in the supervised group had a weekly session with an exercise trainer. VLDL apolipoprotein (apo)B metabolism was measured with an infusion of 1-(13)C leucine before and after 6 months of the exercise program. Supervised exercise for 6 months resulted in a significant within-group decrease in percent hemoglobin A1c (P < 0.001), body fat (P < 0.004), nonesterified fatty acid (P < 0.04), and triglycerides (P < 0.05) and an increase in insulin sensitivity (P < 0.01). There was a decrease in VLDL apoB pool size (160.8 +/- 42.6 to 84.9 +/- 23.2 mg, P < 0.01) and VLDL apoB secretion rate (11.3 +/- 2.6 to 5.5 +/- 2.0 mg/kg.d, P < 0.05) with no change in fractional catabolic rate. In a between-group comparison, the decrease in VLDL apoB secretion rate in the supervised group did not achieve significance. This study demonstrates that in type 2 diabetes, a supervised exercise program reduces VLDL apoB pool size, which may be due to a decrease in VLDL apoB secretion rate.
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PMID:The effect of a six-month exercise program on very low-density lipoprotein apolipoprotein B secretion in type 2 diabetes. 1476 82

Triglyceride-rich lipoprotein (TRL) production was studied in Zucker diabetic fatty (ZDF) rats, a model of insulin-resistant type 2 diabetes progression. TRL production was measured in vivo by blocking catabolism with Triton WR-1339. Ten-week ZDF rats are hyperinsulinemic with increased TRL production [both triglyceride and apolipoprotein B (apoB)]. Twenty-week ZDF rats are insulinopenic, and TRL production is similar to lean controls. Insulin infusion suppresses glucose and free fatty acids in 10- and 20-wk ZDF rats. Increased TRL production is not reduced by insulin in 10-wk rats; however, at 20 wk, TRL production is suppressed by insulin. In vitro studies with hepatocytes derived from 10-wk ZDF rats showed minimal insulin dose effects on apoB secretion compared with the response and sensitivity of hepatocytes derived from 20-wk ZDF and control lean rats. Hepatic sterol regulatory-binding protein (SREBP)-1c mRNA levels are increased at 10 wk but return to control levels at 20 wk. ApoB mRNA levels are similar to lean controls at 10 and 20 wk. The following two mechanisms for hypertriglyceridemia associated with hyperinsulinemia are suggested: increased TRL synthesis and loss of TRL suppression. Increased triglyceride production in hyperinsulinemic rats likely relates to increased expression of SREBP-1c, whereas increased apoB production involves posttranscriptional processes.
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PMID:Altered triglyceride-rich lipoprotein production in Zucker diabetic fatty rats. 1497 3

Fluvastatin reduces atherogenic dense low-density lipoprotein (dLDL) in patients with type 2 diabetes mellitus (T2DM). dLDLs are associated with platelet-activating factor acetyl hydrolase (PAF-AH), an enzyme involved in inflammation and related to coronary artery disease (CAD). The association of preexisting CAD and PAF-AH and the effect of fluvastatin on enzyme activity is investigated in a placebo-controlled trial in patients with T2DM. A multicenter, double-blind, randomized comparison of fluvastatin XL (80 mg) (n = 42) and placebo (n = 47), each given once-daily for 8 wk, in 89 patients with T2DM, was conducted. At baseline and on treatment, lipoproteins, including lipoprotein (a) [Lp(a)] and LDL subfractions, and the activity of PAF-AH were measured. Increasing PAF-AH activity was significantly associated with a positive history of CAD (+0.7% per IU/liter PAH-AH; P = 0.010), the odds ratio estimate adjusted for age, gender, and body mass index of the highest quartile being 10.6 (P = 0.036). At baseline and at study end, PAF-AH activity was associated with the apolipoprotein B (apoB) content in dLDL (LDL-5 and LDL-6) (r = 0.447; P < 0.001 and r = 0.651; P < 0.001, respectively) and with non-HDL cholesterol at baseline (r = 0.485; P < 0.001). However, after additional adjustment for apoB in dLDL and non-HDL cholesterol at baseline, the odds ratio increment for CAD across PAF-AH quartiles was 2.09 (95% confidence interval, 1.02-4.29; P = 0.043). Fluvastatin treatment decreased the activity of PAF-AH by 22.8% compared with an increase of 0.4% in the placebo group (P < 0.001). This effect was independent of changes of Lp(a) concentrations. In patients with T2DM, PAF-AH activity is associated with a positive history of CAD. Fluvastatin not only decreases atherogenic dLDL but also PAF-AH activity, emphasizing the significance of fluvastatin treatment in T2DM. The antiatherogenic potential of fluvastatin in T2DM may thus be greater than expected from its effects on LDL-C and triglycerides alone.
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PMID:Fluvastatin slow-release lowers platelet-activating factor acetyl hydrolase activity: a placebo-controlled trial in patients with type 2 diabetes. 1500 1

The oxidative modification of low-density lipoprotein (LDL) plays a central role in the initiation and acceleration of atherosclerosis. Human serum paraoxonase (PON1) is associated with high-density lipoprotein (HDL) and has been shown to reduce the susceptibility of LDL to lipid peroxidation. We investigated whether circulating oxidized LDL (Ox-LDL) levels were associated with diabetic vascular complications, and whether the enzymatic activity and gene polymorphisms of PON1 influenced Ox-LDL concentrations in vivo. There was no difference in the plasma Ox-LDL concentrations between diabetic patients with and without macrovascular diseases. However, Ox-LDL concentrations corrected by LDL-cholesterol (OxLDL/LDL-C) or apolipoprotein B (apoB) concentrations (Ox-LDL/apoB), which probably reflect the proportion of oxidatively modified LDL to total LDL particles, were significantly higher in patients with macrovascular diseases than in those without. In addition, patients with peripheral neuropathy had a significantly higher Ox-LDL/apoB ratio than patients without this complication. The genotype TT of -108C/T polymorphism in the promoter region of the PON1 gene, which is associated with decreased PON1 expression, showed a significantly higher Ox-LDL/apoB ratio than genotypes TC or CC (TT: 0.60 +/- 0.15, CT + CC: 0.55 +/- 0.11, P =.02). Stepwise multiple regression analysis for Ox-LDL concentration revealed that the -108C/T polymorphism, subsequently to apoB concentration, was identified as a significant contributor. In summary, the Ox-LDL/apoB ratio was associated with macrovascular disease and peripheral neuropathy in Japanese patients with type 2 diabetes. Increased Ox-LDL/apoB may result, at least partly, from reduced serum antioxidant capacity in the diabetic state, including the attenuation of PON1 action. Increased Ox-LDL/apoB could be a significant marker for susceptibility to vascular complications in diabetic patients.
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PMID:Correlation of plasma oxidized low-density lipoprotein levels to vascular complications and human serum paraoxonase in patients with type 2 diabetes. 1501 40

Systemic lupus erythematosus (SLE) is a multifactorial polysystemic autoimmune disorder. Although life expectance in SLE has been improved by adequate immune suppressive therapy, the importance of chronic renal failure has not been reduced. Among late complications of the disease accelerated atherosclerosis attempts increasing attention. Dyslipoproteinemia and increased concentration of lipoproteins are important risk factors of atherosclerotic cardiovascular complication in SLE. Serum lipid parameters of 50 patients with lupus were examined in the present work. Thirty patients had histologically proven lupus nephritis (LN+), while the other group did not have renal involvement (LN-). Serum triglyceride, total cholesterol, LDL-C and apolipoprotein B (apoB) concentrations were significantly higher in the lupus nephritis (LN+) group. On the other hand, HDL-C and apoAI levels were also elevated in patients with LN. As a consequence of that, LDL-C/HDL-C and the apoB/apoAI ratios did not differ between patients with or without kidney involvement. This concluded the authors to measure the concentration of lipoprotein (a) in SLE patients, as Lp(a) is known to be an independent risk factor of atherosclerosis. Results indicated a significantly increased Lp(a) concentration in patients with lupus nephritis as compared to the LN- group. All but 2 patients without kidney involvement had lower than 100 mg/L Lp(a) concentration, while 27% of patients with lupus nephritis has an Lp(a) level between 100-300 mg/L. Further more, Lp(a) concentration was higher than 300 mg/L in 13% of the LN+ group. In a good correlation of these observations patients with nephritis suffered more frequently from deep venous thrombosis and ischaemic heart disease. The frequencies of hypertension and non-insulin dependent diabetes mellitus were slightly elevated in patients with nephritis. Present results suggest the importance of elevated lipoprotein (a) concentration in patients with lupus nephritis, further increasing the risk of athero-thrombotic cardiovascular complications.
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PMID:[Lipid profile in patients with systemic lupus erythematosus, with special focus on lipoprotein(a) in lupus nephritis]. 1502 32

Obesity is a risk factor for type 2 diabetes and cardiovascular diseases. The hypothesis that cytokines could play a role in the pathophysiology of obesity and insulin resistance is suggested in the last few years. We showed a positive correlation between circulating interleukin (IL-6) levels and obesity and insulin resistance suggesting that IL-6 could be involved in insulin resistance in humans. We showed a decrease of both circulating and adipose tissue IL-6 levels in non-diabetic obese subjects after a very low calorie diet program inducing weight loss. This suggests that adipose tissue could be involved in the regulation of circulating IL-6 levels in these subjects. Adipose tissue is also involved in lipodystrophies particularly in HIV patients on antiviral therapy. We showed an alteration of the SREBP-1 transcription step in subcutaneous abdominal adipose tissue from HIV patients. We found an inverse correlation between circulating adiponectin levels and both insulin resistance and cardiovascular risk factors such as CRP levels and apolipoprotein B/A1 ratio. These findings suggest that adipose tissue is involved in insulin resistance in humans particularly via adipocytokine secretion.
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PMID:[Insulin resistance and adipose tissue gene expression in humans]. 1504 87


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