Prevalence of carotid atherosclerosis in diabetic patients. Ultrasound high-resolution B-mode imaging on carotid arteries.

OBJECTIVE--To quantitatively assess atherosclerosis of the carotid artery in subjects with and without diabetes. RESEARCH DESIGN AND METHODS--Ultrasound high resolution B-mode imaging of carotid arteries was conducted on 71 nondiabetic subjects without hyperlipidemia or hypertension and 295 diabetic patients to determine IMT of the arterial wall. RESULTS--IMT was linearly related with age in nondiabetic (IMT = [0.0087 x age] + 0.3318) and diabetic subjects (IMT = [0.0155 x age] + 0.32450). The regression coefficient for age was significantly greater in diabetic than nondiabetic subjects. IMT (mean +/- SD) of diabetic subjects aged 20-29 was significantly greater than that of nondiabetic subjects aged 20-29 (0.73 +/- 0.27 vs. 0.52 +/- 0.07 mm, P less than 0.01). Multivariate regression analysis of 275 NIDDM patients indicated smoking, hyperlipidemia, duration of diabetes, hypertension, and age were factors determining thickness of the carotid arterial wall. CONCLUSIONS--Diabetes, along with age, hyperlipidemia, smoking, and hypertension, aggravates carotid atherosclerosis.     

Relationships of plasma interleukin-18 concentrations to hyperhomocysteinemia and carotid intimal-media wall thickness in patients with type 2 diabetes

OBJECTIVE: We compared plasma interleukin (IL)-18 concentrations in patients with type 2 diabetes with those in age-matched control subjects and investigated whether plasma IL-18 was associated with plasma total homocysteine (tHcy) concentration or carotid intimal-media wall thickness (IMT), an early marker of atherosclerosis, in these patients. RESEARCH DESIGN AND METHODS: We measured plasma IL-18 in 103 type 2 diabetic patients and 45 age-matched control subjects. We also measured patients' plasma tHcy and serum high-sensitivity C-reactive protein (hs-CRP). IMT was evaluated for both common carotid arteries. RESULTS: Plasma IL-18 was significantly higher in diabetic patients than in control subjects (203 +/- 153 vs. 118 +/- 37 pg/ml, P < 0.001). High IL-18 was defined as equaling or exceeding the mean + 2 SD of plasma IL-18 in control subjects (192 pg/ml). Patients with high IL-18 showed a greater carotid IMT than those with normal IL-18. Carotid plaques were more numerous in diabetic patients with high IL-18 than in those with normal IL-18. Plasma tHcy concentrations were significantly higher in patients with high IL-18 than in those with normal IL-18. Univariate and multivariate analyses showed a strong independent association between tHcy and IL-18. Plasma IL-18 also correlated positively with serum hs-CRP. CONCLUSIONS: In patients with type 2 diabetes, plasma IL-18 concentrations are greater than in nondiabetic subjects. Plasma IL-18 is an independent determinant of plasma tHcy, which is linked independently with atherosclerotic carotid wall thickening.     

Association of NAD(P)H oxidase p22 phox gene variation with advanced carotid atherosclerosis in Japanese type 2 diabetes

OBJECTIVE: To evaluate the association between the C242T polymorphism of the p22 phox gene, an essential component of NAD(P)H oxidase in the vasculature, with intima-media thickness (IMT) of the carotid artery and risk factors for atherosclerosis in type 2 diabetic subjects. RESEARCH DESIGN AND METHODS: C242T polymorphism of the p22 phox gene was detected by polymerase chain reaction-restriction fragment-length polymorphism in 200 Japanese type 2 diabetic subjects and 215 nondiabetic subjects. We examined the association with this mutation and carotid atherosclerosis as well as the patients' clinical characteristics and the level of 8-hydroxy-2'deoxyguanosine (8-OHdG) as an index of oxidative DNA damage. RESULTS: The diabetic subjects with the TC+TT genotypes displayed a significantly lower average IMT (1.13 +/- 0.31 vs. 1.31 +/- 0.34 mm; P = 0.0099) and a not significantly lower serum 8-OHdG level than those with the CC genotype, despite no difference in the risk factors. Stepwise multiple regression analysis showed that the risk factors for increased IMT in the diabetic subjects were systolic blood pressure (P = 0.0042) and p22 phox CC genotype (P = 0.0151). In nondiabetic subjects, the average IMT of the TC+TT group was not different from that of the CC group (0.85 +/- 0.14 vs. 0.94 +/- 0.30 mm, P = 0.417). Fasting plasma insulin concentration (41.4 +/- 15.6 vs. 64.2 +/- 59.4 pmol/l, P = 0.0098) and insulin resistance index of homeostasis model assessment (HOMA-R) (1.58 +/- 0.66 vs. 2.60 +/- 2.56, P = 0.0066) were significantly lower in the TC+TT group than in the CC group. CONCLUSIONS: These results show that the C242T mutation in the p22 phox gene is associated with progression of asymptomatic atherosclerosis in the subjects with type 2 diabetes and is also associated with insulin resistance in nondiabetic subjects.     

Decreased endogenous secretory advanced glycation end product receptor in type 1 diabetic patients: its possible association with diabetic vascular complications

OBJECTIVE: The binding of advanced glycation end products (AGEs) to their receptor (RAGE) plays an important role in the development of diabetic vascular complications. In the present study, we examined circulating endogenous secretory RAGE (esRAGE) levels in subjects with type 1 diabetes and explored the possible association between esRAGE levels and the severity of diabetic vascular complications. RESEARCH DESIGN AND METHODS: Circulating esRAGE levels in serum were examined in 67 Japanese type 1 diabetic patients (22 men and 45 women, age 24.0 +/- 4.4 years [means +/- SD]) and 23 age-matched healthy nondiabetic subjects (10 men and 13 women aged 24.9 +/- 1.4 years). Daily urinary albumin excretion, the presence of retinopathy, and intima-media thickness (IMT) of the carotid artery were also evaluated. We further explored the association between esRAGE levels and severity of diabetic vascular complications. RESULTS: Circulating esRAGE levels were significantly lower in subjects with type 1 diabetes than in nondiabetic subjects (0.266 +/- 0.089 vs. 0.436 +/- 0.121 ng/ml, respectively, P < 0.0001) and was inversely correlated with HbA(1c) (A1C) levels (r = -0.614, P < 0.0001). In addition, multivariate regression analysis demonstrated that A1C was an independent risk factor for a low esRAGE value. Furthermore, circulating esRAGE levels were inversely correlated with carotid IMT (r = -0.325, P = 0.0017) and was one of the independent risk factors for IMT thickening. Furthermore, there was a significant difference (P = 0.0124) in esRAGE levels between patients without retinopathy (0.286 +/- 0.092 ng/ml) and those with retinopathy (0.230 +/- 0.074 ng/ml). CONCLUSIONS: Circulating esRAGE levels were significantly lower in type 1 diabetic patients than in nondiabetic subjects and were inversely associated with the severity of some diabetic vascular complications.     

Preclinical atherosclerosis and inflammation in 61-year-old men with newly diagnosed diabetes and established diabetes

OBJECTIVE: The aim of this study was to investigate the occurrence of subclinical atherosclerosis and underlying mechanisms in men with newly diagnosed diabetes and established diabetes compared with healthy control subjects. RESEARCH DESIGN AND METHODS: In a population-based study of 61-year-old Caucasian men (n = 271) with established diabetes (n = 50) and newly diagnosed diabetes (n = 24) and healthy control subjects (n = 197), standard risk factors and highly sensitive (hs) C-reactive protein (CRP) were measured. Ultrasound measurements of intima-media thickness (IMT) were performed bilaterally in the common carotid artery, and a composite measure was calculated from common carotid and carotid bulb IMT (composite IMT). The plaque status was assessed. RESULTS: Composite IMT and carotid plaque size increased gradually among the healthy control subjects, newly diagnosed diabetic patients, and established diabetic patients (P for trend < or =0.001, respectively). CRP was higher in newly and established diabetes (NS between diabetes groups) compared with healthy control subjects (P < 0.001). Total cholesterol levels were lower in newly diagnosed diabetes (5.51 +/- 1.13 mmol/l, P < 0.05) and established diabetes (5.45 +/- 1.15 mmol/l, P < 0.01) compared with those of healthy control subjects (5.77 +/- 1.03 mmol/l). In men with diabetes (n = 74), diabetes onset status (newly diagnosed versus established), waist-to-hip ratio (WHR), and serum triglycerides, but not CRP, explained 16% of the variance in composite IMT. CONCLUSIONS: This is the first study to show increased preclinical atherosclerotic changes (IMT and plaque size) and increased inflammation (hs-CRP) in men with newly diagnosed diabetes as well as in patients with established diabetes compared with healthy control subjects. WHR, diabetes onset status (newly diagnosed versus established), and triglycerides, but not CRP, were independent correlates of carotid artery IMT in men with diabetes.     

Serum interleukin-18 levels are associated with nephropathy and atherosclerosis in Japanese patients with type 2 diabetes

OBJECTIVE: Interleukin (IL)-18 is a proinflammatory cytokine secreted from mononuclear cells. Serum concentration of IL-18 is a strong predictor of death in patients with cardiovascular diseases. Recent studies have shown that microinflammation is involved in the pathogenesis of diabetic nephropathy as well as of cardiovascular diseases. This study aimed to test the hypothesis that the serum level of IL-18 is a common predictor of nephropathy and atherosclerosis in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Eighty-two Japanese patients with type 2 diabetes and 55 age- and sex-matched healthy control subjects were enrolled. Patients with renal dysfunction (creatinine clearance <1 ml/s) were excluded. We assessed clinical parameters and measured serum and urinary IL-18 levels, serum IL-6 levels, carotid intima-media thickness (IMT), and brachial-ankle pulse wave velocity (baPWV) in all patients. Further, we evaluated changes of urinary albumin excretion rate (AER) after 6 months in 76 diabetic patients. RESULTS: Serum and urinary IL-18 levels were significantly elevated in patients with type 2 diabetes as compared with control subjects (serum IL-18 179 +/- 62 vs. 121 +/- 55 pg/ml, P < 0.001; urinary IL-18 97 +/- 159 vs. 47 +/- 54 pg/ml, P = 0.035). Univariate linear regression analysis showed significant positive correlations between serum IL-18 and AER (r [correlation coefficient] = 0.525, P < 0.001), HbA(1c) (r = 0.242, P = 0.029), high-sensitivity C-reactive protein (hs-CRP) (r = 0.240, P = 0.031), and urinary beta-2 microglobulin (r = 0.235, P = 0.036). Serum IL-18 levels also correlated positively with carotid IMT (r = 0.225, P = 0.042) and baPWV (r = 0.232, P = 0.040). We also found a significant correlation between urinary IL-18 and AER (r = 0.309, P = 0.005). Multivariate linear regression analysis showed that AER (standard correlation coefficients [B] = 0.405, P < 0.001) and hs-CRP (B = 0.207, P = 0.033) were independently associated with serum IL-18 levels. AER was also independently associated with urinary IL-18 levels (B = 0.295, P = 0.005). Moreover, serum and urinary IL-18 levels correlated positively with AER after 6 months (r = 0.489, P < 0.001 and r = 0.320, P = 0.005) and changes in AER during the follow-up period (r = 0.268, P = 0.018 and r = 0.234, P = 0.042). CONCLUSIONS: Serum levels of IL-18 might be a predictor of progression of diabetic nephropathy as well as cardiovascular diseases.     

Coronary artery disease and carotid artery intima-media thickness in Japanese type 2 diabetic patients

OBJECTIVE: To investigate the association between carotid atherosclerosis, measured as intima-media thickness (IMT), and cardiovascular morbidity in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: We investigated the relationship between IMT and coronary artery disease (CAD) in 40 type 2 diabetic patients and 40 control subjects. Diabetic patients with CAD determined by coronary angiography were consecutively recruited, whereas the control subjects were recruited from among diabetic outpatients without CAD at the same institution. IMT was measured in both carotid arteries using B-mode ultrasonography. RESULTS: Carotid IMT was significantly greater in the diabetic patients than in the control subjects (1.27 +/- 0.07 vs. 1.03 +/- 0.04 mm, P < 0.05). IMT was associated with CAD by logistic regression analysis using all independent variables (P = 0.062). When the 40 patients with CAD were divided into a group of 20 patients with coronary artery bypass grafting (CABG) and another 20 patients without CABG, the IMT was significantly greater in the CABG group than in the non-CABG group (1.47 +/- 0.11 vs. 1.07 +/- 0.07 mm, P < 0.05). CONCLUSIONS: These results indicate that the presence of carotid atherosclerosis implies a high probability of coronary involvement in Japanese nonobese subjects with type 2 diabetes.     

Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis

OBJECTIVES: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. METHODS AND RESULTS: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). CONCLUSION: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.     

Association between serum testosterone concentration and carotid atherosclerosis in men with type 2 diabetes

OBJECTIVE: There is evidence to suggest that low concentrations of testosterone are associated with an increased risk of cardiovascular disease in men. The aim of this study was to evaluate the relationship between serum testosterone concentration and carotid atherosclerosis as well as major cardiovascular risk factors in men with type 2 diabetes. RESEARCH DESIGN AND METHODS: Serum free and total testosterone concentrations were measured in 253 consecutive men with type 2 diabetes. The relationships between serum testosterone concentration and carotid atherosclerosis, determined by ultrasonographically evaluated intima-media thickness (IMT) and plaque score (PS) in a subgroup of 154 diabetic patients, as well as major cardiovascular risk factors, including age, blood pressure, and lipid concentrations, were evaluated. RESULTS: Inverse correlations were found between free testosterone (F-tes) concentration and IMT (r = -0.206, P = 0.0103) and between F-tes concentration and PS (r = -0.334, P < 0.001). The IMT and PS were significantly greater in patients with lower concentrations of F-tes (<10 pg/ml) than in patients with higher concentrations of F-tes (1.01 +/- 0.29 vs. 0.91 +/- 0.26 mm, P = 0.038; 4.5 +/- 3.8 vs. 2.4 +/- 3.2, P = 0.0003; respectively). An inverse correlation was found between serum F-tes concentration and age (r = -0.420, P < 0.0001). A positive correlation was found between serum F-tes and total cholesterol concentrations (r = 0.145, P = 0.0238). CONCLUSIONS: Serum F-tes concentration is inversely associated with carotid atherosclerosis determined by ultrasonographically evaluated IMT and PS in men with type 2 diabetes.     

Association of postprandial hypertriglyceridemia and carotid intima-media thickness in patients with type 2 diabetes

OBJECTIVE: Serum triglyceride levels are important in the development of atherosclerosis. Although triglyceride levels are generally increased in the postprandial periods, the association between postprandial triglyceride (pTG) levels and atherosclerosis has not been investigated in diabetic patients. To investigate the role of pTG levels in atherosclerosis, we examined the correlation between pTG levels and carotid intimal-medial thickness (IMT). RESEARCH DESIGN AND METHODS: Carotid IMT was measured by ultrasonography in 61 patients with type 2 diabetes. Plasma glucose (PG), insulin, total cholesterol, triglycerides, and HDL cholesterol levels were measured after overnight fasting and 4 h after a meal. RESULTS: Carotid IMT of the patients with fasting hypertriglyceridemia was greater than that of the patients with normal fasting triglyceride (fTG) levels (0.85+/-0.12 vs. 0.76+/-0.14 mm; P = 0.02). The carotid IMT was increased in the patients with pTG levels >2.27 mmol/l. The normo-normo (NN) and normo-hyper (NH) groups consisted of patients with normal fTG levels but with pTG levels <2.27 and >2.27 mmol/l, respectively. Patients with both hypertriglyceridemia and pTG levels >2.27 mmol/l formed the hyper-hyper (HH) group. Carotid IMT was significantly increased in the NH (0.86+/-0.13 mm) and HH (0.85+/-0.12 mm) groups compared with the NN group (0.73+/-0.13 mm; P<0.01). Although postprandial PG, pTG, and fasting LDL cholesterol levels were all independently correlated with carotid IMT, pTG levels had the strongest statistical influence (P = 0.002). CONCLUSIONS: Postprandial hypertriglyceridemia despite normal fTG levels may be an independent risk factor for early atherosclerosis in type 2 diabetes.     

Pancreas transplantation improves vascular disease in patients with type 1 diabetes

OBJECTIVE: Pancreas transplantation (PTX) normalizes glucose and improves microvascular complications, but its impact on macrovascular disease is still debated. RESEARCH DESIGN AND METHODS: Carotid intima-media thickness (IMT), shown to correlate with cardiovascular disease (CVD) risk and events, was determined prospectively by ultrasonography in successful pancreas transplant recipients to evaluate the effect of PTX on CVD risk. Carotid IMT and CVD risk factors of pancreas transplant recipients (n = 25) were compared with three groups: individuals with type 1 diabetes without significant nephropathy (n = 20), nondiabetic kidney transplant recipients (n = 16), and normal control subjects (n = 32). Mean age of pancreas transplant recipients at the time of transplantation was 42.4 +/- 1.2 years (mean +/- SE) and duration of diabetes was 25.9 +/- 1.4 years. RESULTS: After PTX, HbA(1c) level (P < 0.0001) decreased to normal and, whereas creatinine level (P = 0.0002) decreased, it remained elevated compared with normal control subjects (P < 0.05). Blood pressure, BMI, fasting lipid levels, smoking frequency, and use of hypolipidemic agents were unchanged. Mean carotid IMT was increased in pancreas transplant candidates but decreased by 1.8 +/- 0.1 year after PTX (P = 0.0068), no longer different from that in normal control subjects or patients with type 1 diabetes. CONCLUSIONS: Carotid IMT improves after successful PTX within 2 years of the procedure, with normalization of HbA(1c) and improved renal function, independent of changes in lipid levels, BMI, blood pressure, smoking, or use of hypolipidemic agents. This study suggests that CVD risk, future events, and mortality should improve after PTX in the absence of other significant, untreated CVD risk factors.     

糖尿病患者血清超敏C反应蛋白与动脉粥样硬化的关系

目的：探讨2型糖尿病（T2DM）患者血清超敏C反应蛋白（hs—CRP）水平与动脉粥样硬化之间的关系。方法：将141例T2DM患者具有大血管危险因素的数量分为三组，以颈动脉内膜中层厚度（IMT）反应动脉粥样硬化程度，并测定患者血清CRP、血脂水平和胰岛素抵抗相关指标。结果：具有3或4个危险因素即患者体重指数（BMI）、胰岛素抵抗指数（HOMA—IR）、血清甘油三酯（TG）和hs—CRP水平，较具有其中1或2个危险因素患者的水平高。随着危险因素增多，3个组颈动脉IMT依次为0．68mm、0．82mm、0．97mm；颈动脉斑块检出率依次为12．5％、24．1％、42．9％。颈动脉IMT随着危险因素的增加而显著增加，斑块检出率未见显著差异。颈动脉IMT与收缩压、HOMA—IR、hs—CRP呈显著正相关。CRP与HOMA—IR、BMI及TG呈显著正相关。经多元线形回归分析认为，hs—CRP和HOMA—IR是颈动脉IMT的独立危险因素。结论：T2DM患者血清hs—CRP水平与胰岛素抵抗和颈动脉IMT程度呈显著相关，hs-CRP是颈动脉IMT增厚的一个独立危险因素。     

老年2型糖尿病颈动脉粥样硬化与同型半胱氨酸、胱抑素C、超敏C反应蛋白的关系

目的观察老年2型糖尿病(T2DM)患者同型半胱氨酸(Hcy)、胱抑素C(Cys C)和超敏C反应蛋白(hs-CRP)浓度与颈动脉粥样硬化(CAS)的关系。方法将110例老年2型糖尿病(DM)患者作为T2DM组,根据颈动脉内膜中层厚度(IMT)分为IMT正常组和IMT增厚组,同时随机抽取同期健康体检者32例作为对照组。结果 (1)T2DM组Hcy、hs-CRP、Cys C、IMT、低密度脂蛋白胆固醇(LDL-C)、餐后2 h血糖(2h PP)、糖化血红蛋白(Hb A1c)、血脂(TG)、空腹血糖(FPG)显著高于对照组(均P0.05),叶酸(FA)、HDL-C低于对照组(P0.05);(2)IMT增厚组Hcy、hs-CRP、Cys C显著高于IMT正常组(均P0.01),FA水平低于IMT正常组(P0.05)。(3)相关分析显示IMT与Hcy、hs-CRP、Cys C、LDL-C、FPG、Hb A1c和2h PP正相关,与HDL-C负相关,与年龄、BMI、性别、血压、TC和TG无相关性。血浆Hcy与FA负相关,与维生素B12无相关。Cys C水平与hs-CRP、2h PP、Hb A1c相关。(4)Logistic回归分析Hcy、hs-CRP、Cys C是影响老年T2DM患者IMT的独立相关因素(OR=1.95、3.614、12.125,均P0.05)。结论血Cys C、Hcy、hs-CRP升高与老年2型糖尿病合并CAS的发生、发展密切相关。     

糖尿病患者心踝血管指数与颈动脉硬化的相关性及其危险因素分析

目的 探讨糖尿病患者心踝血管指数( CAVI)与颈动脉硬化的相关性及其危险因素.方法 入选60例2型糖尿病患者以及同期入院治疗的60例非糖尿病患者,对受试者进行病史采集,检测血糖、血脂等生化指标,行颈动脉彩色多普勒超声检查及CAVI测定,分析CAVI与颈动脉硬化的相关性;以CAVI为因变量,年龄、血压、体质量指数、血脂、空腹血糖、糖化血红蛋白(HbAlc)等指标为自变量进行多元线性回归分析.结果 糖尿病组患者体质量指数、甘油三酯、空腹血糖、HbAlc、颈动脉内膜中层厚度(IMT)、CAVI值及颈动脉斑块发生率均显著高于非糖尿病组[(27.6±3.6)、(25.3±3.3)kg/m2,(2.26±1.12)、(1.74±0.97) mmol/L,(8.86±2.64)、(5.26±0.92)mmol/L,(8.28±1.28)、(5.38±0.86),(1.16±0.16)、(0.86±0.14) mm,(9.55±1.13)、(8.54±0.94),46.7％ (28/60)与25.0％(15/60)],两组间差异均有统计学意义(t值分别为3.648、2.719、9.974、14.567、10.930、5.323,x2=6.125,P均＜0.05);CAVI与受试者颈动脉IMT呈正相关(r=0.435,P＜0.01);多元线性回归显示,CAVI与年龄(β=0.458,P＜0.01)、甘油三酯(β=0.058,P=0.012)、空腹血糖(β=0.168,P=0.002)、HbAlc(β =0.228,P=0.003)存在显著正相关.结论 CAVI与糖尿病患者颈动脉IMT呈正相关,糖尿病患者年龄、甘油三酯、空腹血糖及HbAlc是动脉僵硬的独立危险因素.     

Impact of physical fitness and glycemic control on in vivo insulin action in adolescents with IDDM

The relationship of in vivo insulin-mediated glucose utilization to the state of physical fitness and the degree of glycemic control was examined in 27 adolescents with insulin-dependent diabetes mellitus (IDDM) compared with 10 nondiabetic adolescent control subjects. In vivo total-body insulin-mediated glucose metabolism was evaluated by the hyperinsulinemic-euglycemic clamp. Physical fitness was assessed by maximal oxygen consumption (VO2 max) during cycle ergometry. Patients and control subjects had similar levels of VO2 max (34.9 +/- 8.6 vs. 38.6 +/- 9.9 ml.kg-1.min-1, P = 0.3). Patients had lower total-body insulin-mediated glucose metabolism compared with control subjects (33.9 +/- 14.3 vs. 63.8 +/- 17.2 mumol.kg-1.min-1, P = 0.0002). Among the patients, females had lower total-body insulin-mediated glucose metabolism compared with males (24.2 +/- 2.8 vs. 40.7 +/- 3.4 mumol.kg-1.min-1, P less than 0.001); however, this difference disappeared after correcting for sex differences in fitness levels. Insulin-mediated glucose metabolism correlated with VO2 max in patients and control subjects (r = 0.83, r = 0.81, P less than 0.05). The regression of total-body insulin-mediated glucose metabolism on VO2 max for patients was -2.84 +/- 0.255 VO2 max and for control subjects was 7.12 +/- 0.143 VO2 max, indicating that for similar degrees of physical fitness patients have lower total body insulin-mediated glucose metabolism levels than control subjects. In patients, total-body insulin-mediated glucose metabolism correlated with the degree of glycemic control as assessed by the level of glycosylated hemoglobin (r = -0.63, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

辛伐他汀联合非洛地平对高血压并发2型糖尿病患者颈动脉粥样硬化的影响

目的探讨辛伐他汀与非洛地平单用及联合对高血压并发2型糖尿病患者颈动脉粥样硬化的疗效。方法原发高血压并发2型糖尿病颈动脉粥样硬化患者92例,随机分组为2组,实验组口服辛伐他汀20mg,每晚一次和非洛地平5—10mg,1次／d;对照组口服其他类型降压药及辛伐他汀20mg,每晚一次。采用彩色多普勒超声检测颈动脉,记录颈动脉内膜一中层厚度（IMT）、颈动脉斑块积分、斑块发生率。并分别监控血压、血糖变化及于人院后和6个月时检测血浆hs．CRP、总胆固醇（Tc）、低密度脂蛋白胆固醇（LDL-C）、糖化血红蛋白（HbAlc）。结果实验组治疗后hs—CRP[（9．2±1．5）比治疗后（6．5±1．6）]mg／L下降（P〈0．05）,且下降幅度较对照组大（P〈0．05）、IMT（1．25±0．13）比治疗后（0．97±0．15）mm下降（P〈0．05）,且下降幅度较对照组大（P〈0．05）、颈动脉斑块积分（6．21±0．50）比治疗后（5．05-t-O．39）mill下降（P〈0．05）,且下降幅度较对照组大（P〈0．05）,斑块检出率（84．5％）比治疗后（67．5％）下降（P〈0．05）,且下降幅度较对照组大（P〈0．05）。相关分析表明hs-CRP下降程度与颈动脉粥样指标改善程度成正相关关系。结论辛伐他汀联合非洛地平治疗可改善合并2型糖尿病高血压患者颈动脉粥样硬化病变及炎性反应程度。     

Effect of peroxisome proliferator-activated receptor gamma agonist treatment on subclinical atherosclerosis in patients with insulin-requiring type 2 diabetes

OBJECTIVE: To determine the effect of thiazolidinedione treatment on subclinical atherosclerosis progression in insulin-requiring patients with clinical characteristics suggesting type 2 diabetes. RESEARCH DESIGN AND METHODS: Eligible participants (n = 299) were randomized within strata of baseline common carotid artery (CCA) intima-media thickness (IMT) (<0.8 mm, >or=0.8 mm) to 400 mg troglitazone daily or placebo for 2 years. A general linear mixed-effects model was used to compare the rate of change in CCA-IMT between treatment groups. RESULTS: Overall, average rates of CCA-IMT change were not significantly different between troglitazone- and placebo-treated subjects (0.0030 +/- 0.021 vs. 0.0066 +/- 0.021 mm/year; P = 0.17). In the stratum of subjects with CCA-IMT >or=0.8 mm, troglitazone significantly reduced the progression of CCA-IMT relative to placebo (0.0013 +/- 0.022 vs. 0.0084 +/- 0.023 mm/year; P = 0.03). Fasting glucose, insulin, and HbA(1c) were significantly lower in troglitazone- versus placebo-treated subjects (P < 0.01). Whereas blood pressure significantly differed between treatment groups in the >or=0.8-mm stratum, there was no difference between treatment groups in the <0.8-mm stratum. CONCLUSIONS: Insulin sensitization and reduction in blood pressure may be contributory mechanisms by which troglitazone reduced subclinical atherosclerosis progression in this cohort of well-controlled insulin-dependent patients with clinical characteristics suggesting type 2 diabetes.     

2型糖尿病患者动脉粥样硬化与超敏C反应蛋白及糖化血红蛋白的相关性研究

目的 探讨2型糖尿病(T2DM)患者动脉粥样硬化与超敏C反应蛋白(hs-CRP)及糖化血红蛋白(HbA1C)的关系.方法 选取T2DM患者405例,使用彩色多普勒超声测定受试者的颈动脉内膜中层厚度(IMT),按颈动脉IMT分为颈动脉IMT增厚组(IMT＞0.9mm)200例及颈动脉IMT正常组(IMT＜0.9mm)205例,分别测定hs-CRP、FBG、HbA1C.结果 IMT增厚组hs-CRP、HbA1C显著高于IMT正常组(P＜0.01、P＜0.01);T2DM患者hs-CRP、HBA1C与IMT具有相关性(P ＜0.01、P＜0.01),且hs-CRP与HbA1C也具有相关性(P＜0.01).结论 hs-CRP及HbA1C与T2DM患者早期动脉粥样硬化可能有密切关系,在临床上可以作为2型糖尿病患者早期动脉粥样硬化的预测指标.     

Serum levels of advanced glycation end products are increased in patients with type 2 diabetes and coronary heart disease.

OBJECTIVE: To investigate whether serum levels of advanced glycation end products (AGEs) and the glycoxidation product Nepsilon-(carboxymethyl)lysine (CML) are increased in patients with type 2 diabetes compared with nondiabetic control subjects and whether levels of AGEs and/or CML differ in patients with type 2 diabetes with or without coronary heart disease (CHD). RESEARCH DESIGN AND METHODS: Serum levels of AGEs and CML were measured with an immunoassay in 32 men and 21 women aged 59.3+/-6.2 years (means +/- SD) with type 2 diabetes for 7.3 + 3.1 years and in 17 men and 17 women aged 56.2+/-4.2 years without diabetes. Of the patients with diabetes, 18 had CHD. RESULTS: The serum levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects (median [5th-95th percentile]: AGEs 7.4 [4.4-10.9] vs. 4.2 [1.6-6.4] U/ml, P < 0.0001; CML 15.6 [5.6-29.9] vs. 8.6 [4.4-25.9] U/ml, P < 0.0001). The median level of AGEs but not CML was significantly increased in patients with type 2 diabetes and CHD compared with patients without CHD (8.1 [6.4-10.9] vs. 7.1 [3.5-9.8] U/ml, P = 0.03). There were significant positive correlations between serum levels of AGEs and CML in both patients and control subjects. CONCLUSIONS: Levels of AGEs and CML were significantly increased in patients with type 2 diabetes compared with nondiabetic control subjects, and levels of AGEs but not CML were significantly higher in patients with type 2 diabetes and CHD than in patients without diabetes. These results may indicate a role for non-CML AGEs in the development of macrovascular disease in patients with type 2 diabetes.     

Association of angiotensin II type 1 receptor gene polymorphism with carotid atherosclerosis.

BACKGROUND: Polymorphisms of the angiotensin II type 1 receptor (AGTR1) gene are associated with essential hypertension and cardiovascular disease, but the correlation between AGTR1 A1166C polymorphism and carotid intima-media thickness (IMT) remains unclear. We sought to demonstrate correlation between AGTR1 gene polymorphism and carotid atherosclerosis in a Chinese population. METHOD: A total of 150 patients diagnosed with essential hypertension were included in this study. The AGTR1 A1166C polymorphism was detected by restriction analysis of the polymerase chain reaction product with Ddel digestion. Carotid IMT was measured by B-mode ultrasonography. RESULTS: The AC genotype frequency and the C1166 allele frequency of the AGTR1 gene in essential hypertensive patients were significantly higher than in controls (22.00% vs. 6.00% for AC, p < 0.01; 18.67% vs. 8.00% for the C allele, p < 0.05). Hypertensive subjects with the AC genotype had increased carotid artery IMT and IMT/D (common carotid artery diameter) ratio compared with the AA genotype (IMT 1.14 +/- 0.39 vs. 0.88 +/- 0.16, p < 0.05; IMT/D 14.08 +/- 2.88 vs. 10.51 +/- 1.94, p < 0.01). CONCLUSION: These results suggest that the AGTR1 A1166C polymorphism is associated with essential hypertension and carotid atherosclerosis in a Chinese population.