Hormone replacement therapy is associated with increased C-reactive protein in women with Type 2 diabetes in the Diabetes Heart Study.

AIMS: Increased levels of inflammatory biomarkers, especially C-reactive protein (CRP), are associated with increased risk for cardiovascular disease (CVD) events, such as myocardial infarction, stroke, peripheral vascular disease, and sudden cardiac death. Medical interventions that increase CRP levels, such as hormone replacement therapy (HRT) in post-menopausal women, are under increasing scrutiny. The effect of HRT on CRP levels in women with Type 2 diabetes (T2DM) is not well documented, and conflicting conclusions have been reported. The aim of this study was to determine the influence of HRT on women with diabetes in a large cross-sectional study. METHODS: Three hundred and twenty-seven post-menopausal women with T2DM from the Diabetes Heart Study participated. Current use of HRT was determined and serum CRP levels were measured using a high-sensitivity ELISA kit. Generalized estimating equation methods were used to assess the relationship of multiple clinical and lifestyle (e.g. smoking) measures on CRP levels including differences between women taking HRT (HRT+) and not taking HRT (HRT-). RESULTS: Overall serum CRP levels were strongly associated with body mass index (P < 0.0001) and age (P < 0.0001). Of the women, 243 were not using HRT and 84 were using HRT. HRT+ and HRT- women did not differ significantly in measures of clinical traits, with the exception of higher mean low-density lipoprotein cholesterol in HRT- women (P = 0.004). In all models tested, HRT+ women had significantly higher circulating CRP levels, with P-values ranging from 0.0045 to 0.010. CONCLUSIONS: In this study of serum CRP concentration as a function of HRT in women with Type 2 diabetes, there was consistent evidence for increased circulating CRP levels in women receiving oestrogen-containing HRT. Whether HRT-induced increases in CRP can account for the adverse cardiovascular effects of HRT remains to be established; however, based on these data, there is little reason to believe that diabetic women would be spared from such an effect.     

Serum Sex Hormones,IGF-1, and IGFBP3 Exert a Sexually Dimorphic Effect on Lean Body Mass in Aging

BACKGROUND: Endogenous and exogenous sex hormones affect changes in body composition during aging via independent and dependent effects on the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and associated binding proteins (BP). METHODS: Fasting serum IGF-1, IGFBP3, testosterone, estrone, and sex hormone binding globulin were analyzed in 48 women on hormone replacement (HRT) (unopposed oral estrogen, HRT+, 74.0 +/- 6 years), 135 women not on HRT (HRT-, 77.3 +/- 7 years), and 128 healthy men (men, ). Total lean body mass (LBM) and total fat were measured by dual energy X-ray absorptiometry. RESULTS: Total LBM decreased with age in all groups (p = .05). LBM was greater, and IGF-1, IGFBP3, and testosterone were lower in HRT+ versus HRT- women (p = .02, p = .01, p = .04, and, respectively). LBM in men was positively related to IGF-1 (p = .02) and testosterone (p < .01), whereas LBM was associated with IGFBP3 (p = .04) and total fat (p < .001) in female HRT+ and total fat (p < .01) in HRT- women. IGF-1 decreased with age in men and HRT- women (p < .01) but did not decrease in HRT+ women. Total fat significantly decreased across age (p < .05). Controlling for age and HRT, the rate of decrease in fat was slower in men versus women (p = .02). IGFBP3 decreased in all groups across age (p < .01), and the ratio of IGF-1 to IGFBP3 decreased faster in men compared to HRT+ and HRT- women (p = .02). CONCLUSIONS: Our data indicate divergent influences of sex steroids, IGF-1, and IGFBP3 on age-related changes in LBM in healthy elderly men and women.     

Fasting insulin is a stronger cardiovascular risk factor in women than in men

Diabetes is a stronger risk factor for cardiovascular disease (CVD) in women than in men. It is not known whether there is also a sex difference in the association between hyperinsulinaemia, reflecting insulin resistance, and CVD. Fasting insulin was assessed with a specific assay in 6916 fasting, non-diabetic subjects of the PREVEND study without a prior history of CVD. Major Adverse Cardiovascular Events (MACE) (defined as CVD morbidity and CVD mortality) were prospectively recorded after the baseline survey. Cox-regression models were used to investigate the association of fasting insulin with subsequent development of MACE. Fasting insulin was 54 [38-77]pmol/l in women (age 48+/-12yrs) and 57 [40-88] pmol/l in men (age 49+/-13yrs). During follow-up for 7.5 [6.9-7.8]yrs, 98 cardiovascular events were recorded in 3626 women and 242 events in 3290 men. There was a significant (P<0.001) interaction between sex and fasting insulin for MACE, with the strongest association in women. In women, there was a logarithmic association for insulin with MACE, independent of age, alcohol consumption, and smoking (HR=1.50 [95% CI 1.17-1.91] per doubling of insulin, P=0.001). In men, for a similar multivariate model, there was a logarithmic association (HR=1.13 [95% CI [0.97-1.32] per doubling of insulin, P=0.1). Further adjustment for components of the insulin resistance syndrome weakened the association more in men than in women. With HOMA instead of insulin, results were essentially similar. In parallel with diabetes, fasting hyperinsulinaemia reflecting insulin resistance in non-diabetic subjects is associated with an increased risk for cardiovascular disease, which is more pronounced in women than in men.     

Proteinuria and metabolic syndrome as predictors of cardiovascular death in non-diabetic and type 2 diabetic men and women

Aims/hypothesis Proteinuria predicts cardiovascular disease (CVD), but it is unclear whether this is explained by the association of the metabolic syndrome with proteinuria. Therefore, we investigated proteinuria and the metabolic syndrome as independent predictors of CVD death in men and women. Methods The cohort comprised 574 non-diabetic men, 707 non-diabetic women, 371 diabetic men and 349 diabetic women, all free of CVD at baseline. Modified World Health Organization criteria were used to define the metabolic syndrome, and a urinary protein concentration of ≥0.1 g/l (or ≥0.2 g/l) to define proteinuria. The endpoint was CVD mortality during the 18-year follow-up. Results Among non-diabetic men, CVD mortality per 1,000 person-years was as follows: no metabolic syndrome, no urinary protein group: 5.3; no metabolic syndrome, positive for urinary protein: 8.9; positive for metabolic syndrome, no urinary protein: 13.3; and positive for metabolic syndrome and urinary protein: 14.9. For non-diabetic women the corresponding values were: 0.9, 2.3, 4.9 and 7.9, respectively. Among diabetic men, CVD mortality per 1,000 person-years was 15.2, 32.5, 23.6 and 42.0 for the respective groups. Among diabetic women it was 25.3, 38.0, 26.3 and 40.3 (urinary protein in all cases defined as ≥0.1 g/l). In multivariate Cox models including both urinary protein and metabolic syndrome, the hazard ratios (HRs, 95% CI) of proteinuria for CVD mortality were 1.5 (0.9–2.4) in non-diabetic men, 1.8 (0.8–4.2) in non-diabetic women, 1.6 (1.0–2.6) in diabetic men and 1.6 (1.1–2.3) in diabetic women. Urinary protein as a continuous variable was associated with CVD mortality in all groups. The corresponding HRs for metabolic syndrome were: 1.6 (0.9–2.7), 4.0 (1.7–9.7), 1.5 (1.1–2.0) and 1.1 (0.8–1.5). Conclusions/interpretation Proteinuria predicted CVD mortality independently of the presence of metabolic syndrome in non-diabetic and diabetic subjects. Metabolic syndrome predicted CVD mortality in non-diabetic women and in diabetic men, independently of the presence of proteinuria.     

Metabolic syndrome and gender differences in postprandial lipaemia.

BACKGROUND: Postprandial hyperlipidaemia may be a predictor of vascular risk. DESIGN: We evaluated postprandial lipaemia after an oral fat tolerance test (OFTT) in men (n=41) and women (n=21) with metabolic syndrome (MetS). METHODS: Triglyceride (TG) levels were measured before and 2, 4, 6 and 8 h after the fat load. RESULTS: Men showed a greater plasma TG response 8 h after the fat load (284+/-117 versus 224+/-126 mg/dl, P=0.029). Only fasting TG levels significantly predicted the TG area under the curve (AUC) and incremental AUC. CONCLUSIONS: Men had a more pronounced postprandial hypertriglyceridaemia and seem to have delayed TG clearance.     

餐后高甘油三酯血症与冠心病的关系

为探讨餐后高甘油三酯血症与冠心病的关系 ,6 1例研究对象被分为冠心病组 (n =30 )和对照组 (n =31)两组 ,均口服标准脂肪餐 (含脂肪 5 3.4g/m2 体表面积 ) ,分别测定其空腹及餐后 2、4、6、8及 10h的甘油三酯浓度及高密度脂蛋白胆固醇浓度。发现两组病人餐后甘油三酯浓度达高峰时间均为 6h ,冠心病组的高峰浓度 (6 .15±3.0 0mmol/L)及餐后甘油三酯代谢的曲线下面积 [2 5 .96± 14.33mmol/ (h·L) ]明显高于对照组 [4 .5 9± 2 .0 9mmol/L及 14.6 9± 6 .5 8mmol/ (h·L) ,P <0 .0 0 5 ]。Logistic多元回归分析提示 ,餐后甘油三酯代谢的曲线下面积是冠心病的独立危险因素。相关分析表明餐后甘油三酯代谢的曲线下面积与两组餐后 6h及 8h甘油三酯浓度存在明显的正相关关系。以上提示冠心病病人存在异常的餐后高甘油三酯血症 ,该异常是冠心病的独立危险因素。测定餐后 6h及 8h甘油三酯浓度可以代替餐后甘油三酯代谢的曲线下面积 ,从而简化脂肪餐负荷试验。     

Monocyte-derived macrophages from men and women with Type 2 diabetes mellitus differ in fatty acid composition compared with non-diabetic controls

We examined whether macrophages from men and women with Type 2 diabetes mellitus (T2DM) exhibited differences in expression of key genes involved in fatty acid metabolism and in fatty acid composition compared with macrophages from non-diabetic controls. Peripheral blood monocytes from subjects with T2DM (n=9) and non-diabetic controls (n=10) were differentiated into macrophages in 10% autologous serum and normal (5mM) or high (22mM) glucose. Levels of PPARalpha, PPARgamma, LXRalpha, SCD and ABCA1 mRNAs were similar in macrophages from subjects with T2DM and controls. At 5mM glucose, macrophage stearic acid (C18:0) was 12.6+/-1.0% of total fatty acids for T2DM compared with 18.1+/-2.0% for controls (p=0.03). Macrophage linoleic acid (C18:2) was 15.5+/-0.8% for T2DM and 9.3+/-2.0% for controls (p=0.005). The ratio of macrophage stearic acid (C18:0)/oleic acid (C18:1) was 0.29 [0.25,0.48] for T2DM versus 0.54 [0.36,0.82] for controls (p=0.04). Compared with non-diabetic controls, macrophages from men and women with T2DM had significantly different fatty acid profiles consistent with increased stearoyl-CoA desaturase (SCD) activity and increased C18:2 accumulation. This pattern of altered macrophage fatty acid composition may be relevant to diabetic atherogenesis.     

Effect of hormone replacement therapy on inflammation-sensitive proteins in post-menopausal women with Type 2 diabetes.

AIMS: To test the effect of oral hormone replacement therapy (HRT) on plasma C-reactive protein (CRP), soluble vascular cell adhesion molecule-1 (VCAM-1), soluble intercellular adhesion molecule-1 (ICAM-1) and IL-6 concentrations and leucocyte count in post-menopausal women with Type 2 diabetes. METHODS: Post-menopausal women with Type 2 diabetes (n = 61) were randomized in a double-blind fashion to receive either continuous combined hormone replacement therapy (n = 29) with conjugated equine oestrogen (0.625 mg/day) plus medroxyprogesterone acetate (2.5 mg/day) or placebo (n = 32) for 6 months. Study variables were measured at baseline and at the end of the study. RESULTS: Eight women randomized to hormone replacement therapy and four women assigned to placebo group dropped out of the study. Plasma CRP increased (2.2 mg/l, 95% confidence interval 0.3-4.1 mg/l) significantly (P = 0.02) in women treated with HRT (n = 21) compared with placebo (n = 29) taking baseline CRP, body mass index (BMI) and smoking status into account. Plasma levels of cell adhesion molecules, IL-6 and leucocyte count did not change significantly during the study. CONCLUSIONS: These findings indicate that oral HRT with conjugated equine oestrogen plus medroxyprogesterone acetate increases plasma CRP levels but not necessarily global inflammatory activity in post-menopausal diabetic women. An increase in plasma CRP may potentially increase risk of a cardiovascular event.     

Prevalence of diabetes and/or ischaemic heart disease in classes of increasing carotid artery atherosclerosis: an ultrasonographic study.

AIMS: To evaluate the prevalence of non-diabetic subjects and diabetic patients, with or without ischaemic heart disease (IHD), in different classes of increasing carotid atherosclerotic damage. METHODS: Using high-resolution B-mode ultrasound, we studied 598 subjects without known cardiovascular disease (CVD) or diabetes, 74 diabetic patients without CVD, 74 non-diabetic subjects with IHD and 36 patients with both diabetes and IHD. Carotid atherosclerosis was classified as: normal; thickened intima-media; non-stenotic plaque; stenotic plaque. RESULTS: Compared with subjects without diabetes or CVD, the frequency of patients with diabetes without known CVD increased significantly from 'normal' to 'stenotic plaque' (4.1%, 6.4%, 13%, 14.8% for normal, thickened intima-media, non-stenotic plaque and stenotic plaque, respectively; P = 0.0057). The same figures were 6%, 7.6%, 10.2%, 23.3% (P = 0.0007) for non-diabetic subjects with IHD, and 0%, 2%, 5.6%, 15.9% (P < 0.0001) for diabetic patients with IHD. No difference was found comparing subjects with diabetes without CVD with non-diabetic patients with IHD (P = 0.56). Using polychotomous logistic regression analysis, diabetic patients without CVD and non-diabetic subjects with IHD showed a similar association with the increasing degree of carotid atherosclerosis (P = 0.59), but significantly stronger compared with subjects without diabetes or CVD (P < 0.03 for both). CONCLUSIONS: Diabetic patients without known CVD show an advanced degree of carotid atherosclerotic damage similar to non-diabetic subjects with IHD and significantly higher compared with non-diabetic subjects without CVD. Our data support the need for an aggressive early prevention of CVD in diabetic subjects.     

Childhood risk factors predict cardiovascular disease, impaired fasting glucose plus type 2 diabetes mellitus, and high blood pressure 26 years later at a mean age of 38 years: the Princeton-lipid research clinics follow-up study

The objective was to assess whether pediatric risk factors predict cardiovascular disease (CVD), impaired fasting glucose (IFG) + type 2 diabetes mellitus (T2DM), and high blood pressure (HBP) in young adulthood. We performed a prospective follow-up of 909 public-parochial suburban schoolchildren first studied at ages 6 to 18 years and 26 years later at a mean age of 38 years. Pediatric triglycerides (TGs), blood pressure, low-density lipoprotein cholesterol, body mass index, and glucose above and high-density lipoprotein cholesterol below established pediatric cutoffs, along with race, cigarette smoking, family history of CVD, T2DM, and HBP, were assessed as determinants of young adult CVD, a composite variable including IFG + T2DM and HBP. By stepwise logistic regression, adult CVD (19 yes, 862 no) was associated with pediatric high TG (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.3-14.7). High TG in pediatric probands with young adult CVD was familial and was associated with early CVD in their high-TG parents. Adult IFG + T2DM (114 yes, 535 no) was associated with parental T2DM (OR, 2.2; 95% CI, 1.38-3.6), high childhood glucose (OR, 4.43; 95% CI, 2-9.7), and childhood cigarette smoking (OR, 1.64; 95% CI, 1.03-2.61). Adult HBP (133 yes, 475 no) was associated with pediatric high body mass index (OR, 2.7; 95% CI, 1.7-4.3) and HBP (OR, 2.5; 95% CI, 1.5-4.3). Pediatric risk factors are significantly, independently related to young adult CVD, IFG + T2DM, and HBP. Identification of pediatric risk factors for CVD, IFG + T2DM, and HBP facilitates initiation of primary prevention programs to reduce development of adult CVD, IFG + T2DM, and HBP.     

Fibrinolysis and lipoprotein(a) in women with coronary artery disease. Influence of hormone replacement therapy

BACKGROUND AND OBJECTIVES: The incidence of coronary artery disease (CAD) is higher in post-menopausal than in pre-menopausal women. Epidemiological studies suggest that hormone replacement therapy (HRT) decreases the risk of cardiovascular disease in post-menopausal women. HRT could modify the cardiovascular risk via several mechanisms, including modifications in the fibrinolytic system and lipoprotein (a) levels. Our study was aimed at investigating some of these modifications. DESIGN AND METHODS: In the cross-sectional part of the study we evaluated several components of the fibrinolytic system, coagulation inhibitors and lipid profile in premenopausal (n=15) and post-menopausal women (n=64) with CAD and compared these parameters with those of healthy pre-menopausal (n=31) and post-menopausal women (n=88). The prospective part of the study analyzed the effect of HRT with transdermal estrogen with or without progestogen in post-menopausal women with CAD. RESULTS: Pre- and postmenopausal women with CAD showed significant lower fibrinolytic activity and higher plasminogen activator inhibitor type 1 (PAI-1) levels than their control groups. Lp(a) levels were higher in premenopausal women with CAD than in healthy premenopausal women. In post-menopausal women with CAD, HRT induced a significant decrease in PAI-1 and Lp(a) levels. No significant differences were observed in any parameter studied between the groups treated with transdermal estrogen with and without progestogen. INTERPRETATION AND CONCLUSIONS: CAD is associated with a decrease in fibrinolytic activity, possibly due to an increase in PAI-1 levels. An increase in fibrinolytic activity and a decrease in PAI-1 and Lp(a) levels were observed in CAD women receiving transdermal HRT and these changes may have a favorable impact on the risk of new cardiovascular events in post-menopausal CAD women.     

Influence of aging and menopause on postprandial lipoprotein responses in healthy adult women

AIM: To analyze the influence of menopause and age on postprandial lipoprotein responses in healthy adult women. METHOD: Twenty-seven healthy young and middle-aged pre- and postmenopausal female volunteers aged 21-53 y were enrolled. They ingested OFTT cream(Jomo, Takasaki, Japan). Fasting and postprandial blood samples were obtained for up to 6 h, and serum concentrations of lipoproteins were analyzed. RESULTS: In the postprandial phase, serum triglycerides(TG), remnant-like particle(RLP)-TG(RLP-TG), RLP-cholesterol(RLP-C), and TG-rich lipoprotein-TG(TRL-TG)concentrations in all groups peaked after 2 h. After 4 h, the TG, RLP-C, RLP-TG and TRL-TG concentrations in the young women returned to the fasting concentrations. However, at 6 h, these parameters in the pre- and postmenopausal women had barely returned to the fasting concentrations. CONCLUSION: The present results suggest that:(1)the magnitude of postprandial TG concentrations is dependent on age, but not on menopause;(2)clearance of remnant lipoproteins is delayed with age in pre- and postmenopausal women compared to young women, and(3)menopause is associated with an increase of RLP-C, but may not influence LDL particle size.     

Moderate exercise, postprandial lipemia, and skeletal muscle lipoprotein lipase activity.

One mechanism by which prior exercise decreases the plasma triacylglycerol (TG) response to dietary fat may involve enhanced clearance of TG-rich lipoproteins. The purpose of the present study was to examine the influence of moderate intensity exercise on postprandial lipemia and muscle lipoprotein lipase (LPL) activity. Eight physically active, normolipidemic men aged 27.0 years (SD 4.2), body mass index 24.5 kg. m(-2) (SD 1.3), participated in 2 oral fat-tolerance tests with different preceding conditions. The afternoon before one test ( approximately 16 hours), subjects cycled for 90 minutes at 62.3% (SD 1.7%) of maximal oxygen uptake. Before the other test, subjects refrained from exercise. Samples of muscle, venous blood, and expired air were obtained in the fasted state. Subjects then consumed a high-fat meal (1.4 g fat, 1.2 g carbohydrate, 0.2 g protein, 73 kJ energy per kg body mass) before further blood and expired air samples were collected until 6 hours. The 6-hour areas under the TG concentration v time curves for plasma and for the chylomicron-rich fraction were lower (P <.05) after exercise (plasma, 7.91 [SE 1.09] v 5.72 [SE 0.47] mmol. L(-1). h; chylomicron-rich fraction, 1.98 [SE 0.51] v 0.92 [SE 0.16] mmol. L(-1). h). Muscle LPL activity was not significantly influenced by prior exercise, but the 4 subjects who had higher muscle LPL activity after exercise also had the most noticeable decreases in postprandial lipemia. The difference in lipemia between trials was inversely related to the difference in LPL activity (rho = -.79, P <.05). In the fasted state and postprandially, carbohydrate oxidation was lower after exercise (P <.05). Thus moderate exercise attenuates postprandial lipemia, possibly by altering muscle LPL activity.     

Association of serum levels of IGF-I and IGFBP-1 with renal function in patients with type 2 diabetes mellitus.

OBJECTIVE: Our aim was to determine whether serum Insulin-like growth factor-I (IGF-I) and Insulin-like growth factor binding protein-1 (IGFBP-1) levels were different between type 2 diabetic patients and non-diabetic control group. We also aimed to establish any relationship that might exist between the serum IGF-I and IGFBP-1 levels with the urinary albumin excretion (UAE), creatinine clearance and urinary N-acetyl-beta-D-glucosaminidase (NAG) excretion (as a marker of renal tubular dysfunction) and other parameters (such as age, duration of diabetes, treatment, etc.) in patients with type 2 diabetes mellitus (DM). DESIGN: Fifty-nine type 2 diabetic patients and thirty-one non-diabetic controls were included in this study. RESULTS: Mean serum IGF-I levels in diabetic patients were lower than the non-diabetic controls (158+/-12 vs. 287+/-26microg/l), (p<0.001). Serum IGFBP-1 levels were also higher in type 2 diabetic patients compared to the control group (67+/-5 vs. 35+/-4microg/l), (p<0.001). No relationship was obtained between IGF-I and IGFBP-1 levels with neither UAE nor urinary NAG excretion. A significant negative relationship was observed between creatinine clearance and serum IGFBP-1 level (r=-0.39, p=0.004). In multiple regression analysis IGF-I was independently and negatively associated with age and insulin treatment. On the other hand, IGFBP-1 was negatively related with creatinine clearance and positively related with the duration of diabetes. CONCLUSION: These results suggest that type 2 DM leads to a decrease in the IGF-I while elevating the IGFBP-1 levels. Further studies are needed to clarify a potential role of increased levels of IGFBP-1 in decreased creatinine clearance in type 2 DM.     

Cardiovascular disease in type 2 diabetes: challenge for treatment and prevention

Type 2 diabetes increases the risk of cardiovascular disease (CVD) two- to fourfold compared with the risk in non-diabetic subjects. Although type 2 diabetes is associated with a clustering of risk factors (small, dense low-density lipoprotein [LDL] particles, low high-density lipoprotein [HDL] cholesterol, high triglycerides, elevated blood pressure, obesity, central obesity, hyperinsulinaemia, hyperglycaemia, etc.), the cause for an excess risk of CVD remains unknown. Recent drug treatment trials have indicated that the lowering of total and LDL cholesterol and blood pressure is similarly beneficial in diabetic and non-diabetic subjects. The treatment of hyperglycaemia reduces micro- and macrovascular complications in type 2 diabetic patients. Beta-blocking agents, angiotensin-converting enzyme inhibitors, aspirin, and thrombolytic therapy are also effective in the treatment of CVD amongst diabetic patients.     

肺结核合并糖尿病患者自然杀伤T细胞的变化特点

目的 研究肺结核合并糖尿病患者自然杀伤T细胞(NKT细胞)的临床变化特点.方法 2008年1月至2010年6月,选取上海市肺科医院住院的肺结核患者40例为肺结核组,其中男26例,女14例,年龄19～65岁,平均(42±11)岁,平均体重指数(20.6±4.7)kg/m2;肺结核合并糖尿病患者40例为合并糖尿病组,其中男25例,女15例,年龄34～68岁,平均(47±10)岁,平均体重指数(21.3±1.9)kg/m2,采用流式细胞术检测外周血和BALF中表型为T细胞受体Vα24+Vβ11+的NKT细胞数量.同期选取门诊体检志愿者37例为对照组,其中男25例,女12例,年龄21～60岁,平均(42±12)岁,平均体重指数(21.9±5.4)kg/m2;门诊糖尿病患者38例为糖尿病组,其中男23例,女15例,年龄36～65岁,平均(44±8)岁,平均体重指数(20.5±3.2)kg/m2,检测外周血NKT细胞的数量[中位数(四分位间距)].计数资料比较采用t检验,组间两两比较采用SNK和LSD检验,采用双变量进行相关性分析.结果 肺结核组外周血NKT细胞[1.1%(0.8%～1.3%)]和合并糖尿病组[0.8%(0.5%～1.0%)]均明显高于对照组[0.4%(0.3%～0.7%)]和糖尿病组[0.3%(0.2%～0.5%)],均差异有统计学意义(q值为3.258～7.074,均P＜0.01);肺结核组与合并糖尿病组比较,差异有统计学意义(q=2.827,P＜0.01).肺结核组BALF中NKT细胞数[0.7%(0.3%～1.0%)]明显高于合并糖尿病组[0.3%(0.2%～0.6%)],差异有统计学意义(t=2.394,P＜0.05).BALF和外周血的NKT细胞数在轻度[0.9%(0.3%～1.3%)和1.0%(0.8%～1.3%)]、中度[0.4%(0.3%～0.9%)和1.0%(0.8%～1.3%)]和重度肺结核患者[0.3%(0.3%～0.5%)和0.7%(0.5%～1.1%)]中的分布差异均有统计学意义(F值分别为4.535和3.763,均P＜0.05),病情越重NKT细胞数越低.外周血与BALF中NKT细胞数量呈正相关(r=0.709,P＜0.01).结论 NKT细胞在抗MTB感染中发挥着重要作用.肺结核合并糖尿病患者体内复杂的微环境影响NKT细胞发挥其功能,使其保护性免疫力降低.

Abstract：

Objective To investigate the changes of NKT cells in pulmonary tuberculosis patients ( PTB ) complicated by diabetes mellitus ( DM ). Methods From January 2008 to June 2010, 40 cases of PTB patients without DM hospitalized in Shanghai Pulmonary Hospital were selected. There were 26 males and 14 females, aged from 19 -65 ( mean, 42 ± 11 ) years, with an average BMI ( 20.6 ±4.7 ) kg/m2.Forty cases of PTB complicated with DM were included as patient controls which consisted of 25 males and 15 females, aged from 34 -68 ( mean, 47 ± 10 )years, with an average BMI ( 21.3 ± 1.9 ) kg/m2. Thirtyseven healthy controls and 38 cases of non-TB DM in the outpatient department for physical examination were enrolled at the same period. There were 25 male and 12 female healthy controls, aged from 21 -60 ( mean,42 ± 12 ) years, with an average BMI ( 21.9 ±5.4 ) kg/m2. There were 23 males and 15 females in the nonTB DM volunteers, aged from 36 -65 ( mean, 44 ±8 ) years, with an average BMI ( 20. 5 ±3. 2 ) kg/m2.The percentages of NKT cells with the phenotype of TCRVα.24 + Vβ11 + in peripheral blood and bronchial alveolar lavage fluid ( BALF ) were tested by flow cytometry for all the patients. Continuous data were analyzed by t test. Multiple comparisons were performed by SNK and LSD test. Results The percentages of NKT cells in peripheral blood from non-diabetic PTB [ 1.1%( 0. 8% - 1.3% ) ] and diabetic PTB patients [0. 8% (0. 5% - 1.0% ) ] were all significantly higher as compared with healthy controls [0. 4% (0. 3% -0. 7% ) ] and DM patients without TB [ 0. 3% ( 0. 2% - 0. 5% ) ] ( q = 3. 258 - 7. 074, respectively, all P＜0. 01 ). The percentages of NKT cells in peripheral blood from non-diabetic PTB patients were also significantly higher as compared with diabetic PTB patients ( q = 2. 827, P ＜ 0. 01 ). The percentages of NKT cells in BALF from non-diabetic PTB patients [0. 7% (0. 3% - 1. 0% ) ] were significantly higher as compared with diabetic PTB patients [ 0. 3% ( 0. 2% - 0. 6% ) ] ( t = 2. 394, P ＜ 0. 05 ). The percentages of NKT cells from BALF in mild, moderate and severe PTB patients were [0. 9% (0. 3% - 1.3% ) ], [0. 4% (0. 3% -0. 9% ) ] and [0. 3% (0. 3% - 0. 5% ) ], respectively, which were significantly different ( F= 4. 535, P ＜0. 05 ). The percentages of NKT cells from peripheral blood in mild, moderate and severe PTB patients were[1.0%(0.8% -1.3%)], [1.0%(0.8% -1.3%)] and [0.7% (0.5% -1.1%)], respectively, which were also significantly different (F =3. 763, P ＜0. 05). The percentages of NKT cells from peripheral blood had a positive correlation with those from BALF ( r = 0. 709, P ＜ 0. 01 ). Conclusions NKT cells play an important role in TB infection. The complicated milieus in PTB patients with DM have adverse effects on NKT cells, resulting in their dysfunction.     

Failure of glucagon suppression contributes to postprandial hyperglycaemia in IDDM

Summary Carbohydrate ingestion results in a fall in glucagon concentration in non-diabetic but not in diabetic individuals. To determine if, and the mechanism by which, lack of postprandial suppression of glucagon contributes to hyperglycaemia, nine subjects with insulin-dependent diabetes mellitus (IDDM) ingested 50 g of glucose containing both [2-³H] glucose and [6-³H] glucose on two occasions. [6-¹⁴C] glucose, insulin and low-dose somatostatin were infused intravenously at the same rates on both occasions. A basal glucagon infusion was started either at the same time (constant glucagon) or 2 h following (suppressed glucagon) glucose ingestion. This resulted in lower (p<0.001) glucagon concentrations during the first 2 h of the suppressed than during the constant glucagon study days (63±1 vs 108±2 pg/ ml). Lack of suppression of glucagon led to higher (p<0.01) postprandial glucose concentrations (10.3±0.9 vs 8.1±0.7 mmol/l) and a greater (p<0.02) integrated glycaemic response. The excessive rise in glucose was due to higher (p<0.02) rates of postprandial hepatic glucose release during the constant than during the suppressed glucagon study days, whether measured using either [6-³H] glucose (2.6±0.2 vs 2.0±0.2 mmol·kg^–1 per 6 h) or [2-³H] glucose (3.0±0.3 vs 2.4±0.2 mmol·kg^–1 per 6 h) as the meal tracer. Glucose disappearance, initial splanchnic glucose clearance and hepatic glucose cycling did not differ on the two occasions. Thus, the present studies demonstrate that lack of postprandial suppression of glucagon, by increasing hepatic glucose release, contributes to hyperglycaemia in subjects with IDDM.Abbreviations IDDM Insulin-dependent diabetes mellitus     

HRT does not improve urinary albumin excretion in postmenopausal diabetic women

The effect of 6 months combined, continuous hormone replacement therapy (HRT) with conjugated equine oestrogen (0.625 mg) and medroxyprogesterone acetate (2.5 mg) on albumin/creatinine ratio (ACR) was determined in postmenopausal diabetic women in a randomised, controlled study. Mean (interquartile range) change in plasma ACR was not (P=0.96) different in women receiving HRT [2 (-11, 21) mg/g, n=20] compared with those randomised to placebo [2 (-1, 14) mg/g, n=27]. Also, the proportion of women with microalbuminuria did not change (P=0.75) during HRT (baseline, 0.45; end of study, 0.53). Furthermore, several risk factors for microalbuminuria including systolic blood pressure (SBP), fasting blood glucose, glycated haemoglobin (HbA1c) and adiposity did not vary significantly during HRT. These data suggest that 6 months HRT does not reverse microalbuminuria caused by prolonged hyperglycaemia and other risk factors that underlie leakage of albumin into the urine in postmenopausal women with type 2 diabetes.     

Increase in aortic pulse wave velocity is associated with abnormal postprandial triglyceride response

BACKGROUND: Aortic pulse wave velocity (aPWV), an index of aortic distensibility, and postprandial hypertriglyceridemia are recognized as independent cardiovascular risk factors. HYPOTHESIS: The aim of this study was to evaluate the relationship between postprandial hypertriglyceridemia and changes in aPWV. METHODS: We prospectively studied 45 patients (mean age 48 [14] years, 28.9% men), who were submitted to a standardized fat meal (FM) test. According to their triglyceride (TG) levels 2, 4, 6, and 8 h after the FM, the patients were divided into two groups: Group 1 (31 patients) with postprandial TG levels < or = 219 mg/dl, and Group 2 (14 patients) with TG levels > 219 mg/dl at one of the aforementioned time intervals. Before and 6 h after the FM, aPWV was measured noninvasively. RESULTS: Baseline characteristics in the two groups were similar, except for higher TG, pulse pressure, waist-to-hip ratio, percentage of patients who smoked or had arterial hypertension, and lower high-density lipoprotein cholesterol levels in Group 2. Postprandially, aPWV was higher in Group 2 [11.2(2.7) vs. 9.1(2.1) m/s, p = 0.004]. Changes in aPWV correlated with TG changes from baseline to 6 h after FM (r = 0.539, p < 0.001) and with the areas under the TG curve (r = 0.617, p < 0.001). A postprandial TG increase of 100 mg/dl resulted in a 0.88 m/s rise of aPWV. CONCLUSION: An increase in aPWV 6 h after an FM test correlates positively with abnormal postprandial hypertriglyceridemia. These relationships, reported here for the first time, could be of practical use for better evaluation of patient prognosis.     

Increased risk of cardiovascular disease in newly diagnosed type 2 diabetic patients in a primary health care center in Trinidad

The prevalence of cardiovascular diseases (CVD) has increased sharply in the developing countries and because Type 2 diabetic patients are at increased risk for CVD, we assessed CVD risk factors in newly diagnosed Type 2 diabetic patients presenting in a primary health care center in Trinidad. Fasting and 2 h postprandial blood samples were collected from 387 (269 females, 118 males) newly diagnosed Type 2 diabetic patients (mean age: 53.1+/-6.6 years) for the determination of plasma glucose, creatinine, cholesterol (chol), triglyceride (TG) and % glycated hemoglobin (HbA(1c)) concentrations. Blood pressure and anthropometric indices were also measured. There were high prevalence rates of obesity (37%), overweight (35%), hypertension (21%), hypercholesterolemia (25%) and hypertriglyceridemia (22.3%) among the patients and these were significantly higher in women than men (P<0.001). Patients of Indian descent had a significantly higher prevalence of diastolic hypertension and hypertriglyceridemia compared with patients of African origin or mixed race (P<0.001). In comparison with males, female diabetic patients were at greater risk of cardiovascular morbidity and mortality. Early detection of CVD risk factors and treatment, particularly in women, may be beneficial management strategy in all local diabetic clinics in Trinidad.