Progression Of Atherosclerosis In Type Research Articles

Coronary artery calcium score as a predictor of atherosclerosis progression in type 2 diabetic patients after transfemoral amputation

Background and Aims: Coronary artery disease (CAD) and peripheral artery disease (PAD) are progressive atherosclerotic disorders. The aim of the study was to evaluate the dynamics of coronary artery calcium score (CACS) in symptomatic patients with type 2 diabetes (T2D) with/without diabetic nephropathy (DN).

Tofogliflozin does not delay progression of carotid atherosclerosis in patients with type 2 diabetes: a prospective, randomized, open-label, parallel-group comparative study

BackgroundThis study aimed to investigate the preventive effects of tofogliflozin, a selective sodium-glucose cotransporter 2 (SGLT2) inhibitor, on atherosclerosis progression in type 2 diabetes (T2DM) patients without apparent cardiovascular disease (CVD) by monitoring carotid intima-media thickness (IMT).MethodsThis prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study included 340 subjects with T2DM and no history of apparent CVD recruited at 24 clinical units. Subjects were randomly allocated to either the tofogliflozin treatment group (n = 169) or conventional treatment group using drugs other than SGLT2 inhibitors (n = 171). Primary outcomes were changes in mean and maximum common carotid IMT measured by echography during a 104-week treatment period.ResultsIn a mixed-effects model for repeated measures, the mean IMT of the common carotid artery (mean-IMT-CCA), along with the right and left maximum IMT of the CCA (max-IMT-CCA), significantly declined in both the tofogliflozin (− 0.132 mm, SE 0.007; − 0.163 mm, SE 0.013; − 0.170 mm, SE 0.020, respectively) and the control group (− 0.140 mm, SE 0.006; − 0.190 mm, SE 0.012; − 0.190 mm, SE 0.020, respectively). Furthermore, the tofogliflozin and the conventional treatment group did not significantly differ in the progression of the mean-IMT-CCA (mean change (95% CI) 0.008 (− 0.009, 0.025) mm, P = 0.34), along with the right (mean change (95% CI) 0.027 (− 0.005, 0.059) mm, P = 0.10) and the left max-IMT-CCA (mean change (95% CI) 0.020 (− 0.030, 0.070), P = 0.43). Similar findings were obtained even after adjusting for traditional CV risk factors and/or administration of drugs at baseline. Relative to the control treatment effects, tofogliflozin significantly reduced the HbA1c, blood glucose level, body weight/body mass index, abdominal circumference, and systolic blood pressure, and significantly increased the HDL-C. The total and serious adverse events incidences did not significantly vary between the treatment groups.Conclusions/interpretationNo IMT changes were observed between the tofogliflozin and the conventional treatment groups. However, tofogliflozin is a safe and effective treatment option for managing primary CVD risk factors in this population.Clinical Trial Registration UMIN000017607 (https://www.umin.ac.jp/icdr/index.html).

Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.

NADPH oxidase (NOX) 1 but not NOX4-dependent oxidative stress plays a role in diabetic vascular disease, including atherosclerosis. Endothelin (ET)-1 has been implicated in diabetes-induced vascular complications. We showed that crossing mice overexpressing human ET-1 selectively in endothelium (eET-1) with apolipoprotein E knockout (Apoe-/-) mice enhanced high-fat diet-induced atherosclerosis in part by increasing oxidative stress. We tested the hypothesis that ET-1 overexpression in the endothelium would worsen atherosclerosis in type 1 diabetes through a mechanism involving NOX1 but not NOX4. Six-week-old male Apoe-/- and eET-1/Apoe-/- mice with or without Nox1 (Nox1-/y) or Nox4 knockout (Nox4-/-) were injected intraperitoneally with either vehicle or streptozotocin (55 mg/kg/day) for 5 days to induce type 1 diabetes and were studied 14 weeks later. ET-1 overexpression increased 2.5-fold and five-fold the atherosclerotic lesion area in the aortic sinus and arch of diabetic Apoe-/- mice, respectively. Deletion of Nox1 reduced aortic arch plaque size by 60%; in contrast, Nox4 knockout increased lesion size by 1.5-fold. ET-1 overexpression decreased aortic sinus and arch plaque alpha smooth muscle cell content by ∼35% and ∼50%, respectively, which was blunted by Nox1 but not Nox4 knockout. Reactive oxygen species production was increased two-fold in aortic arch perivascular fat of diabetic eET-1/Apoe-/- and eET-1/Apoe-/-/Nox4-/- mice but not eET-1/Apoe-/-/Nox1y/- mice. ET-1 overexpression enhanced monocyte/macrophage and CD3+ T-cell infiltration ∼2.7-fold in the aortic arch perivascular fat of diabetic Apoe-/- mice. Both Nox1 and Nox4 knockout blunted CD3+ T-cell infiltration whereas only Nox1 knockout prevented the monocyte/macrophage infiltration in diabetic eET-1/Apoe-/- mice. Endothelium ET-1 overexpression enhances the progression of atherosclerosis in type 1 diabetes, perivascular oxidative stress, and inflammation through NOX1.

Effect of Tofogliflozin on Carotid Intima-Media Thickness in Patients with Type 2 Diabetes: Results from the Prospective, Randomized, Open-Label, Parallel-Group Comparative UTOPIA Trial

Effect of Tofogliflozin on Carotid Intima-Media Thickness in Patients with Type 2 Diabetes: Results from the Prospective, Randomized, Open-Label, Parallel-Group Comparative UTOPIA Trial

Liraglutide attenuates atherosclerosis via inhibiting ER-induced macrophage derived microvesicles production in T2DM rats

BackgroundWe investigated the effects of liraglutide on the formation and progression of atherosclerosis in type 2 diabetes mellitus (T2DM) rats.MethodsSprague–Dawley rats were divided into control group, diabetes group and liraglutide treated group. The T2DM rats model with atherosclerosis were induced by high fat diet followed small dosage streptozotocin injection. Body weight and blood glucose levels were monitored once a week for 3 months and then the rats were sacrificed.Peripheral blood and aorta tissues were collected for further biochemical and pathological estimation respectively. Moreover, immunohistochemistry staining was used to detect the infiltration of macrophages and cell apoptosis in tissue samples. The amount of microvesicles of atherosclerotic plaques was determined by ELISA. Western blot was applied to detect the protein expressions of CHOP, GRP78 and caspase-3 in tissue samples. The mRNA expressions of SREBP-1c and FAS were detected by RT-PCR.ResultsThe rat model of diabetic atherosclerosis was established successfully. Compared with the control group, glucose, triglycerides, total cholesterol, AST, ALT, BUN, fasting insulin and homeostatic model assessment insulin resistance levels in peripheral blood were significantly increased in the diabetes group. While, these indicators in the liraglutide group were significantly lower than that in the diabetes group. Moreover, the atherosclerotic plaques were observed in the rats of diabetes group but not remarkable in the liraglutide group. The ratio between aorta intima and media thickness was significantly greater in the diabetes group than that in the liraglutide group. Compared with the diabetes group, the infiltration and apoptosis of macrophages were milder in the liraglutide group. The expressions of CD68, caspase-3, CHOP and GRP78 in aorta tissue samples were significantly downregulated in the liraglutide group than that in the diabetes group. Furthermore, the microvesicles of aorta tissues in the liraglutide group were significantly decreased than that in the diabetes group. The mRNA expressions of SREBP-1c and FAS were lower in the liraglutide group than that in the diabetes group.ConclusionLiraglutide attenuates diabetic atherosclerosis by inhibition of ER stress and subsequent macrophage apoptosis and microvesicles production in T2DM rats.

Incretin treatment and atherosclerotic plaque stability: Role of adiponectin/APPL1 signaling pathway

AimsGlucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated. MethodsThe effect of incretin therapy in the regulation of adiponectin/APPL1 signaling was evaluated both on carotid plaques of asymptomatic diabetic (n=71) and non-diabetic patients (n=52), and through in vitro experiments on endothelial cell (EC). ResultsAtherosclerotic plaques of T2DM patients showed lower adiponectin and APPL1 levels compared with non-diabetic patients, along with higher oxidative stress, tumor necrosis factor-α (TNF-α), vimentin, and matrix metalloproteinase-9 (MMP-9) levels. Among T2DM subjects, current incretin-users presented higher APPL1 and adiponectin content compared with never incretin-users. Similarly, in vitro observations on endothelial cells co-treated with high-glucose (25mM) and GLP-1 (100nM) showed a greater APPL1 protein expression compared with high-glucose treatment alone. ConclusionsOur findings suggest a potential role of adiponectin/APPL1 signaling in mediating the effect of incretin in the prevention of atherosclerosis progression or plaque vulnerability in T2DM.

Atherosclerosis Is Associated with Neutrophil Lymphocyte Ratio As An Inflammatory Marker in Type 2 Diabetes Mellitus Patients with Coronary Artery Disease

Background: Increased neutrophil lymphocyte ratio is associated with major adverse outcomes of cardiac events in type 2 diabetes mellitus (DM) patients.Objective: To assess the NLR as an inflammatory marker in atherosclerosis in type 2 DM patients with coronary artery disease (CAD).Methods: This case control study was conducted in the Department of Clinical Pathology in collaboration with Department of Cardiology, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from March 2014 to February 2015. Total 134 patients were enrolled in this study who were waiting for coronary angiography in the Department of Cardiology, BSMMU; 84 cases were considered as Group I (DM with CAD) and 50 controls were Group II (DM without CAD). A 2 ml of blood was collected in EDTA tube from the patients prior to coronary angiogram for complete blood count (CBC) were measured by haematology autoanalyzer, rechecked manually and NLR was calculated in the Department of Clinical Pathology, BSMMU. Coronary artery disease with 50% coronary artery stenosis and more critical lesion that were diagnosed by coronary angiography were included in this study as cases. Coronary artery disease with less than 50% coronary artery stenosis that was diagnosed by coronary angiography was included in this study as control.Results: NLR was higher in CAD positive group compared to group without CAD negative in type 2 DM patients (2.76 (±0.74) vs. 1.56 (±0.15), p<0.001).Conclusion: With the help of neutrophil lymphocyte ratio we can take preventive measure and precaution to reduce the progression of atherosclerosis in type 2 diabetic patients with coronary artery disease.J Dhaka Medical College, Vol. 24, No.1, April, 2015, Page 24-29

The relationship of miR-146a gene polymorphism with carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus

ObjectiveAtherosclerosis (AS) is regarded as the major cause of disability and death in diabetic patients. However, its precise pathogenesis is not entirely clear. Recent genome-wide association studies (GWAS) have revealed AS is related to some epigenetic changes. This study aimed to investigate the possible associations of miR-146a and transcriptional coactivator p300 polymorphisms with carotid atherosclerosis in type 2 diabetes mellitus. MethodThis case–control study included 596 type 2 diabetes mellitus patients with carotid atherosclerosis and 379 patients without carotid atherosclerosis. Genotyping of miR-146a and p300 polymorphisms was performed by allelic discrimination assay with TaqMan-MGB probes. ResultsThe CC genotype of rs2910164 in miR-146a was found to be associated with an increased risk of carotid vulnerable plaque in the Chinese type 2 diabetes mellitus patients, but this association was not found in the type 2 diabetes mellitus patients with carotid atherosclerosis or in the plaque load group. In addition, no significant difference in transcriptional coactivator p300 genotype distribution was observed between the type 2 diabetes mellitus patients with and without carotid atherosclerosis, plaque stability or plaque load, respectively. Stratified analyses revealed that the miR-146aCC genotype was associated with an increased risk of vulnerable plaque in subjects who were older, females, those with diabetes duration of more than 10years, and those with hypertension. The gene-gene interactions between the miR-146a rs2910164 and p300 rs20551 polymorphisms were further analysed, but no combined effects of these two genes on enhancing the risk of carotid atherosclerosis, plaque stability, or plaque load were detected. ConclusionThe miR-146a rs2910164 polymorphism might be associated with carotid vulnerable plaque risk in Chinese type 2 diabetes mellitus patients, particularly in older patients, females, those with diabetes duration of more than 10years and those with hypertension. The transcriptional coactivator p300 rs20551 polymorphism may not be a risk factor for the development or progression of atherosclerosis in type 2 diabetes mellitus.

Arg399Gln Polymorphism of X-Ray Repair Cross-Complementing Group 1 Gene Is Associated with Angiographically Documented Coronary Artery Disease in South Indian Type 2 Diabetic Patients

DNA damage resulting from oxidative stress contributes significantly to the development and progression of atherosclerosis in type 2 diabetic (T2DM) individuals, thereby implicating polymorphisms in DNA repair genes in the modulation of DNA repair efficiency. Based on this premise, we explored the association between X-ray repair cross-complementing group 1 (XRCC1) gene Arg399Gln polymorphism, coronary artery disease (CAD), and myocardial infarction (MI) in type 2 diabetic patients. We screened 283 T2DM patients, inclusive of 160 with angiographically defined CAD, 73 with MI, 89 without MI, and 121 T2DM individuals with no evidence of CAD for XRCC1 Arg399Gln polymorphism. There appeared to be a significant difference in the distribution of genotype and allele frequencies of XRCC1 Arg399Gln polymorphism between T2DM groups with and without CAD (p=0.03), albeit no significant association with MI was observed (p=0.055). A further analysis revealed that the frequencies of the Arg/Gln, Gln/Gln genotypes and 399Gln allele were considerably higher in patients with triple vessel disease (TVD) as compared with those with the single and double vessel disease (p=0.03), thereby associating this polymorphism with severity of CAD in T2DM individuals. Multiple logistic regression analysis revealed a significant and independent association of XRCC1 Arg399Gln polymorphism and other putative risk factors with CAD/TVD in T2DM individuals. These findings reveal a significant association between XRCC1 gene Arg399Gln polymorphism, CAD/TVD, and coincident putative risk factors in T2DM individuals in the South Indian population.

Rationale, Design, and Baseline Characteristics of a Trial for the Prevention of Diabetic Atherosclerosis Using a DPP-4 Inhibitor: The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A)

Alogliptin, an efficacious inhibitor of DPP-4 that improves glycemic control, as well as the pancreatic beta-cell function, is now increasingly used to accomplish glycemic targets in type 2 diabetic patients. Interestingly, recent experimental studies have shown that alogliptin exerts anti-atherosclerotic effects in GLP-1-dependent and -independent manners. The aim of the present ongoing study is to investigate the preventive effects of alogliptin on the progression of atherosclerosis in type 2 diabetic subjects using the carotid intima-media thickness (IMT), an established marker of cardiovascular disease. The Study of Preventive Effects of Alogliptin on Diabetic Atherosclerosis (SPEAD-A) is a prospective, randomized, open-label, blinded-endpoint, multicenter, parallel-group, comparative study. Between March 2011 and March 2012, 341 participants were recruited at 11 clinical sites, and were randomly allocated either to an alogliptin treatment group (172 patients) or a conventional treatment group (169 patients). The primary outcomes are the changes in the maximum and mean IMT of the common carotid artery during a 24-month treatment period, as measured by carotid arterial echography. The secondary outcomes include the changes in glycemic control, parameters related to beta-cell function and diabetic nephropathy, the occurrence of cardiovascular events and adverse events and biochemical measurements reflecting vascular function. This is the first study to address the effects of DPP-4 inhibitors on the progression of changes in the carotid IMT, with the patients without DPP-4 inhibitor treatment serving as a control group. The results will be available soon, and these findings are expected to provide clinical data that will be helpful in the prevention of diabetic atherosclerosis and subsequent cardiovascular disease.

Proteomic profiling of high glucose primed monocytes identifies cyclophilin A as a potential secretory marker of inflammation in type 2 diabetes

Hyperglycemia is widely recognized to be a potent stimulator of monocyte activity, which is a crucial event in the pathogenesis of atherosclerosis. We analyzed the monocyte proteome for potential markers that would enhance the ability to screen for early inflammatory status in Type 2 diabetes mellitus (T2DM), using proteomic technologies. Monocytic cells (THP-1) were primed with high glucose (HG), their protein profiles were analyzed using 2DE and the downregulated differentially expressed spots were identified using MALDI TOF/MS. We selected five proteins that were secretory in function with the help of bioinformatic programs. A predominantly downregulated protein identified as cyclophilin A (sequence coverage 98%) was further validated by immunoblotting experiments. The cellular mRNA levels of cyclophilin A in various HG-primed cells were studied using qRT-PCR assays and it was observed to decrease in a dose-dependent manner. LC-ESI-MS was used to identify this protein in the conditioned media of HG-primed cells and confirmed by Western blotting as well as ELISA. Cyclophilin A was also detected in the plasma of patients with diabetes. We conclude that cyclophilin A is secreted by monocytes in response to HG. Given the paracrine and autocrine actions of cyclophilin A, the secreted immunophilin could be significant for progression of atherosclerosis in type 2 diabetes. Our study also provides evidence that analysis of monocyte secretome is a viable strategy for identifying candidate plasma markers in diabetes.

Is A1C Variability an Independent Predictor for the Progression of Atherosclerosis in Type 2 Diabetic Patients?

BackgroundLittle is known about the relative contribution of long-term glycemic variability to the risk of macrovascular complications in type 2 diabetes. This study was conducted to evaluate the effect of A1C variability on the progression of carotid artery intima-media thickness (IMT) in type 2 diabetic patients.MethodsAmong type 2 diabetic patients who visited Hallym University Sacred Heart Hospital from March 2007 to September 2009, 120 patients who had carotid artery IMT measured annually and A1C checked every three months for at least one year were analyzed. Individual A1C variability was defined as the standard deviation (SD) of five A1C levels taken every three months for approximately one year. Change in IMT was defined as an increase in IMT on follow-up measurement. The association between the SD of A1C and changes in IMT was evaluated.ResultsWith greater A1C variability, there was a greater increase in the mean IMT (r = 0.350, P < 0.001) of the carotid artery. After adjusting for confounding factors that may influence IMT, A1C variability was significantly associated with the progression of IMT (r = 0.222, P = 0.034). However, the SD of A1C was not a significant independent risk factor for the progression of IMT in multiple regression analysis (β = 0.158, P = 0.093).ConclusionHigher A1C variability is associated with IMT progression in type 2 diabetic patients; however, it is not an independent predictor of IMT progression. Overall glycemic control is the most important factor in the progression of IMT.

Carotid atherosclerosis mediated by visceral adiposity and adipocytokines in type 2 diabetic subjects

The aim of this study was to verify the possible association of visceral fat accumulation with carotid atherosclerosis in order to identify the practical and feasible determinants for each parameter of atherosclerosis in type 2 diabetic subjects. The subjects were 151 diabetic (DM) and age-matched 83 nondiabetic subjects (C), without atherosclerotic disease. Visceral fat area (VFA) on a CT scan at the umbilicus level was measured. Ambulatory 24-h blood pressure (BP) was recorded. Stiffness index β, intima–media thickness (IMT) and plaque formation of carotid arteries were measured by ultrasonography. Insulin sensitivity was estimated by homeostasis model assessment (HOMA). Serum levels of adiponectin and tumor necrosis factor (TNF)-α were determined. Male gender, HOMA, serum non-HDL-Cholesterol (Chol) and TNF-α/adiponectin ratio were higher, and VFA was larger in DM than in C. The IMT, stiffness index β and plaque formation in DM were more pronounced than in C, even after adjusting for age, sex and 24-h systolic BP (sBP). VFA was positively correlated with TNF-α/adiponectin ratio and serum non-HDL-Chol in DM. Furthermore, multiple regression analysis revealed that, in DM, serum non-HDL-Chol was associated with IMT, VFA probably via an increase in TNF-α/adiponectin ratio was associated with stiffness index β, and 24-h sBP, HOMA and VFA were associated with plaque formation independently of age and sex, respectively, although any association was not observed in C. Thus, we conclude that visceral fat-associated alterations in adipokines may be mediating the development and progression of atherosclerosis in type 2 diabetic subjects, compared with nondiabetic subjects.

Vessel Shrinkage as a Sign of Atherosclerosis Progression in Type 2 Diabetes

OBJECTIVE—The aim of this study was to determine the natural history of vascular remodeling of atherosclerotic plaques in patients with type 2 diabetes and the predictors of vessel shrinkage.RESEARCH DESIGN AND METHODS—In this serial intracoronary ultrasound (IVUS) study, 237 coronary segments from 45 patients enrolled in the DIABETES I, II, and III trials were included. Quantitative volumetric IVUS analyses (motorized pullbacks at 0.5 mm/s) were performed in the same coronary segment after the index procedure and at the 9-month follow-up. Nontreated mild lesions (angiographic stenosis <25%) with ≥0.5 mm plaque thickening and length of ≥5 mm assessed by IVUS were included. Vessel shrinkage was defined as a Δexternal elastic membrane area/Δplaque area < 0. Statistical adjustment by multiple segments and multiple lesions per patient was performed.RESULTS—Vessel shrinkage was identified in 37.1% of segments and was associated with a significant decrease in lumen area at 9 months (vessel shrinkage, 10 ± 4 mm2 vs. non–vessel shrinkage, 11 ± 4 mm2; P = 0.04). Independent predictors of vessel shrinkage were insulin requirements (odds ratio 4.6 [95% CI 1.40–15.10]; P = 0.01), glycated hemoglobin (1.5 [1.05–2.10]; P = 0.02), apolipoprotein B (0.96 [0.94–0.98]; P < 0.001), hypertension (3.7 [1.40–10.30]; P = 0.009), number of diseased vessels (5.6 [2.50–12.50]; P < 0.001), and prior revascularization (17.5 [6.50–46.90]; P < 0.001).CONCLUSIONS—This serial IVUS study suggests that progression of coronary artery disease in patients with type 2 diabetes may be mainly attributed to vessel shrinkage. Besides, vessel shrinkage is influenced by insulin requirements and metabolic control and is associated with more advanced coronary atherosclerosis.

Pro-Atherogenic Alterations in T-Lymphocyte Subpopulations Related to Acute Hyperglycaemia in Type 2 Diabetic Patients

T cells are among the earliest cells to infiltrate the arterial intima during the initial stages of atherosclerosis. Alterations in the peripheral blood lymphocyte distribution might be associated with intensive lymphocytes extravasation and stimulation of atherosclerotic plaque development. Epidemiological data reveal that short-term postprandial hyperglycemia is a significant risk factor for coronary heart disease. Using a parameter that indicates recently-past acute hyperglycemia, 1,5-anhydro-D-glucitol (1,5-AG), the aim of the present study was to elucidate which alterations in peripheral blood T-lymphocytes, if any, are associated with acute hyperglycemia in patients with type 2 diabetes mellitus (DM) and, thus, might be involved in the progression of atherosclerosis. Measurement of fasting glucose level, glycated hemoglobin A(1c), 1,5-AG, lipid profile and lymphocyte receptors expression (CD3+, CD4+, CD8+, CD8+28+, CD+28 -) was performed in 97 patients with type 2 DM, 23 patients with coronary heart disease, and 15 healthy controls. The mean CD3+, CD4+, CD8+28 - and CD8+28+ lymphocyte counts were significantly higher in the DM patients than in both control groups. Multiple regression analysis revealed that CD4+ and CD8+28- lymphocyte counts primarily were dependent on 1,5-anhydro-D-glucitol plasma levels. These results suggest that acute hyperglycemia results in the progression of atherosclerosis in type 2 DM, at least in part through changes in CD4+ and CD8+28- lymphocyte subsets.

Favorable Effects of Early Insulin Secretion by Nateglinide on Postprandial Hyperlipidemia in Patients With Type 2 Diabetes

Severe postprandial hyperlipidemia is observed in and substantially contributes to the progression of atherosclerosis in type 2 diabetic patients, especially those with insulin resistance and compensatory hyperinsulinemia (1–4). As with postprandial hyperglycemia, increased lipid levels in type 2 diabetic patients peak late, and the magnitude of the increase is greater than that seen in healthy people (2,4). To determine whether early insulin secretion by nateglinide can suppress postprandial hyperlipidemia in type 2 diabetic patients, 20 Japanese patients (10 men and 10 …

Favorable Effects of Early Insulin Secretion by Nateglinide on Postprandial Hyperlipidemia in Patients With Type 2 Diabetes

Severe postprandial hyperlipidemia is observed in and substantially contributes to the progression of atherosclerosis in type 2 diabetic patients, especially those with insulin resistance and compensatory hyperinsulinemia (1–4). As with postprandial hyperglycemia, increased lipid levels in type 2 diabetic patients peak late, and the magnitude of the increase is greater than that seen in healthy people (2,4). To determine whether early insulin secretion by nateglinide can suppress postprandial hyperlipidemia in type 2 diabetic patients, 20 Japanese patients (10 men and 10 …

We-P11:11 Relationship between circulating thrombomodulin levels and latent progression of atherosclerosis in type 2 diabetic patients

We-P11:11 Relationship between circulating thrombomodulin levels and latent progression of atherosclerosis in type 2 diabetic patients

Acid cholesteryl ester hydrolase activity of mononuclear leukocyte in type 2 (non-insulin-dependent) diabetic patients.

Acid cholesteryl ester hydrolase activity of mononuclear leukocytes was measured in 52 Type 2 (non-insulin-dependent) diabetic patients. Enzyme activity was significantly lower in the diabetic patients than in 14 age-matched control subjects (0.89 +/- 0.08 (mean +/- S.E.) vs. 2.20 +/- 0.17 nmol/mg protein/hr, p less than 0.01). In diabetic patients undergoing diet treatment only, the enzyme activity was significantly lower in poorly controlled patients than in well controlled patients (0.43 +/- 0.03 vs. 1.15 +/- 0.24 nmol/mg protein/hr, p less than 0.01). In the diabetic patients, there was a significant negative correlation between the enzyme activity and serum total cholesterol or low density lipoprotein cholesterol level (r = -0.361, p less than 0.01, n = 52 or r = -0.630, p less than 0.01, n = 28). These results suggest that a low level of acid cholesteryl ester hydrolase activity in mononuclear leukocyte might play an important role in the progression of atherosclerosis in Type 2 diabetes.