Blood pressure control and inflammatory markers in type 2 diabetic patients treated with pioglitazone or rosiglitazone and metformin.

The aim of the study was to assess the effects of the combination of metformin plus pioglitazone or rosiglitazone on glucose and blood pressure in type 2 diabetic patients with metabolic syndrome, as well as its tolerability in those patients. In this 12-month, multicentric, double-blind, randomized, controlled, parallel-group trial, all patients began with metformin. Patients were randomized for self-administration of either pioglitazone or rosiglitazone for 12 months. We assessed body mass index (BMI), glycemic control (glycosylated hemoglobin [HbA(1c)], fasting and postprandial plasma glucose and insulin levels [FPG, PPG, FPI and PPI, respectively] and homeostasis model assessment [HOMA] index) and systolic and diastolic blood pressure (SBP and DBP, respectively), at baseline and at 3, 6, 9 and 12 months of treatment, as well as high-sensitivity C-reactive protein (hs-CRP), nitrites/nitrates and adiponectin (ADN) at baseline and at 12 months of treatment. Significant HbA(1c) decreases were obtained after 9 (p<0.05) and 12 (p<0.01) months in both groups. After 9 and 12 months, mean FPG and PPG levels were decreased in both groups (p<0.05 and p<0.01, respectively). We observed decreases in FPI and PPI at 9 and 12 months (p<0.05 and p<0.01, respectively) compared to the baseline values in both groups. Furthermore, HOMA index improvement over the baseline value was obtained only at 12 months (p<0.05) in both groups. SBP and DBP improved significantly (p<0.05, for each) in both groups after 12 months. hs-CRP decreased significantly (p<0.05) in both groups after 12 months; nitrites/nitrates and ADN increased significantly (p<0.05, for each) in both groups after 12 months. The combination of thiazolinediones and metformin is associated with a slight but significant improvement in the long-term blood pressure control of these patients, and with an improvement in the anti-inflammatory state, both of which are related to a similar reduction in insulin-resistance.     

Thiazolidinedione effects on blood pressure in diabetic patients with metabolic syndrome treated with glimepiride.

The aim of our study was to compare the long-term effect of pioglitazone and rosiglitazone on blood pressure control of diabetic patients with metabolic syndrome treated with glimepiride. We evaluated 91 type 2 diabetic patients with metabolic syndrome. All were required to have been diagnosed as diabetic for at least 6 months, and to have failed to achieve glycemic control by dietary changes and the maximum tolerated dose of the oral hypoglycemic agents sulfonylureas or metformin. All patients took a fixed dose of 4 mg/day glimepiride. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) for 12 months in a randomized, double-blind fashion, and evaluated body mass index (BMI), glycemic control, blood pressure and heart rate (HR) throughout the treatment period. A total of 87 patients completed the study and were randomized to receive double-blind treatment with pioglitazone or rosiglitazone. An increase in BMI was observed after 12 months (p < 0.05) in both groups. After 9 and 12 months, there were significant decreases in glycated hemoglobin (HbA(1c)), mean fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), and postprandial plasma insulin (PPI) in both treatment groups (p < 0.05 at 9 months and p < 0.01 at 12 months for all parameters). Furthermore, homeostasis model assessment index (HOMA index) improvement was obtained at 9 and 12 months (p < 0.05 and p < 0.01, respectively) in both groups. Significant systolic blood pressure (SBP) and diastolic blood pressure (DBP) improvement (p < 0.05, respectively) was observed in both groups after 12 months. There were no significant changes in transaminases at any point during the study. We can conclude that the association of a thiazolinedione to the glimepiride treatment of type 2 diabetic subjects with metabolic syndrome is associated to a significant improvement in the long-term blood pressure control, related to a reduction in insulin-resistance.     

A comparison of the effects of pioglitazone and rosiglitazone combined with glimepiride on prothrombotic state in type 2 diabetic patients with the metabolic syndrome

OBJECTIVE: To compare the effects of glimepiride plus pioglitazone or plus rosiglitazone in diabetic patients with the metabolic syndrome on coagulation and fibrinolysis parameters. STUDY DESIGN AND METHODS: 91 type 2 diabetic patients with the metabolic syndrome participated. All patients took a fixed dose of glimepiride, 4 mg/day. We administered pioglitazone (15 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We compared body mass index (BMI), glycemic control, coagulation and fibrinolysis parameters, and heart rate (HR) during 12 months of this treatment. RESULTS: A total of 87 completed the study (pioglitazone n=45 or rosiglitazone n=42). Body mass index increased after 12 months compared to baseline (p<0.05) in both groups. A significant decrease in glycated haemoglobin (HbA(1c)) was observed after 9 (p<0.05), and 12 (p<0.01) months in both groups. After 9 and 12 months, mean fasting plasma glucose (FPG) and postprandial plasma glucose (PPG) levels were lower in both groups (p<0.05 and 0.01, respectively), as were fasting plasma insulin (FPI) and postprandial plasma insulin (PPI) (p<0.05 and p<0.01, respectively). An improvement in the homeostasis model assessment index (HOMA index) was seen at 9 and 12 months (p<0.05 and 0.01, respectively) compared to the baseline value in both groups. Plasminogen activator inhibitor 1 (PAI-1) was significant lower (p<0.05) in both groups after 12 months compared to the baseline values. No changes in tissue-plasminogen activator (t-PA) and fibrinogen (Fg) were seen during the study nor were there any changes in transaminases. CONCLUSIONS: We conclude that the addition of a thiazolinedione to glimepiride treatment in type 2 diabetic subjects with the metabolic syndrome is associated with a slight but significant reduction of PAI-1 value, related to a similar reduction in insulinresistance.     

Evaluation of metalloproteinase 2 and 9 levels and their inhibitors in diabetic and healthy subjects

OBJECTIVES: We hypothesized that molecules active in vascular remodeling (i.e. MMPs and their TIMPs) could be modified in diabetic patients, as indirect markers of the diabetes related generalized abnormality of vascular activity. To test this hypothesis, we measured the plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 in type 2 diabetic patients and in healthy subjects. METHODS: We enrolled 181 diabetic patients and 165 controls. We measured body mass index (BMI), glycosylated hemoglobin (HbA(1c)), fasting plasma glucose (FPG), fasting plasma insulin (FPI), homeostasis model assessment index (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), lipoprotein(a) [Lp(a)], plasminogen activator inhibitor-1 (PAI-1), homocysteine (Hct) fibrinogen (Fg), high sensitivity C-reactive protein (hs-CRP), and plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2. RESULTS: A significant increase (P<0.0001) of BMI, HbA(1c), FPG, FPI, HOMA index, SBP, DBP, TC, LDL-C, Tg, Lp(a), PAI-1, Hct, Fg, and hs-CRP was present in the diabetic group, with a significant decrease (P<0.0001) of HDL-C levels compared to healthy subjects. MMP-2 and MMP-9 levels were significantly higher (P<0.0001) in diabetic patients. Significant TIMP-1, and TIMP-2 increase was also observed (P<0.0001) in the diabetic group. CONCLUSION: Plasma levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 are increased in diabetic patients which may reflect abnormal extracellular matrix (ECM) metabolism.     

Sibutramine effect on metabolic control of obese patients with type 2 diabetes mellitus treated with pioglitazone

Thiazolidinediones are supposed to be the pharmacologic agents that more physiologically fight the insulin resistance, but a possible adverse effect may be a weight increase. The aim of the study was to test the efficacy and tolerability of sibutramine on the metabolic effect of pioglitazone in obese patients with type 2 diabetes mellitus. All enrolled patients were required to have been diagnosed as being diabetic for at least 6 months and did not have glycemic control with diet and oral hypoglycemic agents such as sulfonylureas or metformin, both to the maximum tolerated dose. After a run-in period in which the eligible patients took a fixed dose of pioglitazone (30 mg/d), the patients were randomized to receive also sibutramine (10 mg/d) or placebo for 6 months. We assessed body mass index, hemoglobin A_1c (HbA_1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), lipid profile, lipoprotein parameters, and lipoprotein (a) at baseline and after 3 and 6 months. No body mass index change was observed after 3 and 6 months in the pioglitazone + placebo (pp) group. Significant decrease was present in the pioglitazone + sibutramine (ps) group after 3 (P < .05) and 6 months (P < .01) compared with the baseline values, and this variation was significant (P < .05) between groups. A significant HbA_1c decrease was observed after 3 (P < .05) and 6 months (P < .01) in both groups with respect to the baseline values. There was no difference in HbA_1c value between the 2 groups. No FPG, PPG, FPI, PPI, and homeostasis model assessment index change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in FPG, PPG, FPI, PPI, and homeostasis model assessment index value between the pp and ps groups. No significant low-density lipoprotein cholesterol change was observed at 3 months, whereas a significant decrease was present after 6 months (P < .05), in both groups with respect to the baseline values. There was no difference in low-density lipoprotein cholesterol value between the pp and ps groups. No triglyceride variation was present at 3 and 6 months in the pp group and at 3 months in the ps group, whereas a significant decrease was observed at 6 months (P < .05) in the ps group with respect to the baseline values. There was no difference in triglyceride value between both groups. No high-density lipoprotein cholesterol, apolipoprotein A-I, apolipoprotein B, and lipoprotein (a) changes were present in both groups with respect to the baseline values. Sibutramine appears to be a tolerable and efficacious drug when added to pioglitazone for the global management of obese diabetic patients.     

The effects of irbesartan and telmisartan on metabolic parameters and blood pressure in obese, insulin resistant, hypertensive patients

Obesity, hypertension, dyslipidemia and glucose intolerance cluster in the insulin resistance syndrome. Angiotensin II receptor blockers (ARB) are able to reduce insulin resistance. Furthermore, among ARB, telmisartan displays the property of stimulating PPARgamma. The aim of the study was to examine if and to what extent treatment with irbesartan and telmisartan induces variations in metabolic parameters in insulin resistant, hypertensive subjects. Forty-six non diabetic, obese, insulin-resistant, hypertensive patients took part in the study. They were divided into 2 groups. Group A (23) was submitted to irbesartan 150 mg/day, Group B (23) to telmisartan 80 mg/day for 6 months. Adiponectin, glucose, cholesterol, triglycerides, free fatty acids (FFA), steady-state plasma insulin and glucose (SSPG), 24-hBP were determined at the beginning and at the end of the study. Both irbesartan or telmisartan reduced blood pressure and ameliorated the insulin sensitivity, with increased adiponectin values; in Group B, the amelioration of metabolic parameters was greater than in Group A and the reduction of blood pressure was related with variation of adiponectin levels. Data obtained showed that the antihypertensive action of telmisartan and irbesartan is associated with the amelioration of the metabolic picture. The greater impact on the improvement of the metabolic profile showed by telmisartan and the inverse correlation between adiponectin levels and blood pressure may be partly due to the action as partial PPARgamma agonist displayed by telmisartan.     

比较替米沙坦与卡托普利对有高血压的代谢综合征患者颈动脉内膜中层厚度及脂联素水平的影响

目的探讨瞥米沙坦对有高血压的代谢综合征患者动脉粥样硬化进展及血脂联素水平的影响。方法入选84例有高血压的代谢综合征患者,随机分为替米沙坦组和卡托普利组,两组患者接受十日应药物治疗6个月,对比两组患者在用药前后颈动脉内膜中层厚度、血脂联素水平等指标的变化情况。结果药物治疗6个月后替米沙坦组患者血脂联素水平[（2．8±0．7）mg／L]明湿高于卡托背利组患者[（0．8±0．6）mg／L,P=0．033],同时与卡托普利比较,替米沙坦在降低颈动脉内膜中层厚度方面显示更为有效的趋势[（0．06±0．07）mm,（0．03±0．06）mm]。结论与卡托普利比较,替米沙埘能史有效地提高有商血压的代谢综合征患者血脂联素的水平,抑制动脉粥样硬化的进展。     

罗格列酮对多囊卵巢综合征的疗效观察

目的　探讨噻唑烷二酮类药物罗格列酮对多囊卵巢综合征 (PCOS)患者的代谢和性激素紊乱的作用。方法　48名PCOS患者按体重指数(BMI)分为非肥胖组和肥胖组。每位患者每天空腹口服 4mg罗格列酮,共 12周。测定治疗前后BMI、腰臀比(WHR)、胰岛素、胰岛素原 (PI)、血浆纤溶酶原激活物抑制物 1(PAI 1)、血脂、血压、肝功能、肾功能、稳态模型胰岛素抵抗指数 (HOMA IR)、FSH、LH、睾酮 (T),观察月经、卵泡发育情况(阴式或腹式B超 )。结果　罗格列酮治疗前,与非肥胖组相比,肥胖组收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、FPI、FINS、FPG、PAI 1、T均升高,差异有统计学意义 (均P<0. 05)。非肥胖组罗格列酮治疗后,FPI、FINS、HOMA IR、PAI 1、LH水平与治疗前相比均下降,差异有统计学意义(均P<0. 05)。肥胖组罗格列酮治疗后,SBP、TG、TC、FPI、FINS、HOMA IR、FPG、PAI 1、T、LH水平与治疗前相比均下降差异有统计学意义(均P<0. 05 )。结论　罗格列酮可降低PCOS患者的FINS、FPI、PAI 1、TG等水平,起到有效治疗及预防PCOS患者并发糖尿病,高血压,心血管疾病等代谢并发症的作用;罗格列酮可降低LH、T,调整生殖内分泌紊乱,调节月经周期,促进优势卵泡发育,治疗不孕症。     

Potential effect of insulin resistance and cardiovascular risk factors on metabolic syndrome in subjects with normal fasting plasma glucose levels

The prevalence of metabolic syndrome has progressively increased with increasing fasting plasma glucose (FPG) levels. This study aimed to investigate the influence of insulin resistance and cardiovascular risk factors on metabolic syndrome in individuals with normal FPG. Study subjects with FPG levels below 100 mg/dL were divided into 5 groups depending on the exact FPG levels. We then evaluated the association of metabolic syndrome with insulin resistance and total cholesterol/ high density lipoprotein-cholesterol ratio (TC/HDL ratio). The odds ratio of insulin resistance in the level of HOMA-IR above 2.34 group [3.483(95 % CI, 1.110?～?10.932)] was significantly increased in the group of FPG level from 93 mg/dL to 99 mg/dL compared to the group below 80 mg/dL. The odds ratio of metabolic syndrome in the group of FPG level from 89 mg/dL to 92 mg/dL [2.459, (95%CI, 1.275?～?4.741)] and 93 mg/dL to 99 mg/dL [2.079, (95%CI, 1.052?～?4.110)] was significantly increased compared to the group below 80 mg/dL after adjusting age, sex, smoking status, physical activity, heavy drinking, TC/HDL ratio. Higher FPG levels within the normoglycemic range may constitute a risk of insulin resistance and is associated more strongly with the risks of metabolic syndrome.     

Differential effect of glimepiride and rosiglitazone on metabolic control of type 2 diabetic patients treated with metformin: a randomized, double-blind, clinical trial

AIM: Accumulating evidence suggests that combination therapy using oral antidiabetic agents with different mechanisms of action may be highly effective in achieving and maintaining target blood glucose levels. The aim of our study is to evaluate the differential effect on glucose and lipid parameters of the association between glimepiride plus metformin and rosiglitazone plus metformin in patients affected by type 2 diabetes and metabolic syndrome. METHODS: Patients were enroled, evaluated and followed at two Italian centres. We evaluated 99 type 2 diabetic patients with metabolic syndrome (48 males and 47 females; 23 males and 24 females, aged 52 +/- 5 with glimepiride; 25 males and 23 females, aged 54 +/- 4 with cglitazone). All were required to have been diagnosed as being diabetic for at least 6 months and did not have glycaemic control with diet and oral hypoglycaemic agents such as sulphonylureas or metformin, both to the maximum tolerated dose. All patients took a fixed dose of metformin, 1500 mg/day. We administered glimepiride (2 mg/day) or rosiglitazone (4 mg/day) in a randomized, controlled, double-blind clinical study. We evaluated body mass index (BMI), glycaemic control, lipid profile [total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol and triglycerides] and lipoprotein parameters [apolipoprotein A-I and apolipoprotein B (Apo B)] during 12 months of this treatment. RESULTS: A total of 95 patients completed the study. Significant BMI decrease was observed at 12 months in glimepiride and rosiglitazone group (p < 0.05 and p < 0.01 respectively) as well as of glycated haemoglobin decrease (p < 0.05 and p < 0.01 respectively), mean fasting plasma glucose and postprandial plasma glucose levels (p < 0.05 and p < 0.01 respectively). A decrease in fasting plasma insulin and postprandial plasma insulin at 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group was observed. Furthermore, homeostasis model assessment index improvement was obtained only at 9 and 12 months (p < 0.05 and p < 0.01 respectively) compared with the baseline value in rosiglitazone group. Significant TC, LDL-C and Apo B improvement (p < 0.05 respectively) was present in glimepiride group after 12 months compared with the baseline values, and these variations were significant (p < 0.05) between groups. Of the 95 patients who completed the study, 8.5% of patients in glimepiride group and 12.5% of patients in rosiglitazone group had side-effects (p = not significant). Four patients had transient side-effects in glimepiride group and six patients in rosiglitazone group. Altogether, we did not have statistically significant changes in transaminases. CONCLUSIONS: The rosiglitazone-metformin association significantly improve the long-term control of all insulin-resistance-related parameters in comparison with the glimepiride-metformin-treated group. On the other side, glimepiride treatment is associated to a slight improvement in cholesterolaemia, not observed in the rosiglitazone-treated patients.     

罗格列酮联合阿司匹林治疗对糖尿病代谢综合征患者胰岛素抵抗的影响

目的探讨罗格列酮（RGZ）联合阿司匹林（Asp）治疗对糖尿病代谢综合征（MS）患者胰岛素抵抗（IR）的影响。方法126例MS患者按随机区组设计法分为基础治疗组（31例）,Asp组（31例）,RGZ组（32例）,RGZ联合Asp组（32例）,观察各组治疗前后FPG、2hPG、HbA1c、Ins、C-P、C—RP、纤维蛋白原水平及HOMA—IR等的变化。结果RGZ联合Asp组FPG、2hPG、Ins、HOMA—IR、炎症因子水平均较其他三组下降。结论RGZ联合Asp应用可协同改善糖尿病MS患者IR,并具有抗炎作用。     

替米沙坦对老年高血压不稳定性心绞痛患者脂联素及C反应蛋白的影响

目的探讨过氧化物酶体增殖物活化受体γ(PPARγ)激动剂替米沙坦对伴有高血压的老年不稳定性心绞痛患者血清脂联素及C反应蛋白的影响。方法用随机方法(分层抽样法)将120例伴有高血压的老年不稳定性心绞痛患者分为替米沙坦组(60例)和培垛普利组(60例),分别用酶联免疫吸附法及酶标多克隆抗体夹心法测定患者在治疗前和治疗后6个月的血清脂联素、高敏C反应蛋白(hs-CRP)浓度,并观察血糖、胰岛素敏感性指数(ISI)及血脂水平的改变。结果用培垛普利及替米沙坦治疗6个月后,平均血压显著下降〔(126±16)至(104±11)mmHg及(125±14)至(103±12)mmHg,均为P<0.05〕,血清脂联素浓度及ISI明显升高〔(5.8±2.7)至(6.3±2.5)mg/L,(5.9±2.9)至(8.4±3.1)mg/L及0.0075±0.0015至0.0088±0.0019,0.0069±0.0013至0.0137±0.0037,P<0.05及P<0.01〕,而hs-CRP明显下降〔(0.79±0.13)至(0.54±0.09)mg/L及(0.80±0.12)至(0.38±0.06)mg/L,P<0.05及P<0.01)〕,尤以替米沙坦组较甚。替米沙坦组治疗6个月后,心血管事件发生率显著下降(P<0.01)。结论与培垛普利相比,替米沙坦能够明显升高伴有高血压的老年不稳定性心绞痛患者血清脂联素浓度及显著降低其血浆hs-CRP水平和心血管事件发生率。     

Effects of sitagliptin or metformin added to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients

The aim of the study was to compare the effects of the addition of sitagliptin or metformin to pioglitazone monotherapy in poorly controlled type 2 diabetes mellitus patients on body weight, glycemic control, β-cell function, insulin resistance, and inflammatory state parameters. One hundred fifty-one patients with uncontrolled type 2 diabetes mellitus (glycated hemoglobin [HbA_1c] >7.5%) in therapy with pioglitazone 30 mg/d were enrolled in this study. We randomized patients to take pioglitazone 30 mg plus sitagliptin 100 mg once a day, or pioglitazone 15 mg plus metformin 850 mg twice a day. We evaluated at baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index, HbA_1c, fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment β-cell function index, fasting plasma proinsulin (Pr), Pr/FPI ratio, adiponectin, resistin (R), tumor necrosis factor-α (TNF-α), and high-sensitivity C-reactive protein. A decrease of body weight and body mass index was observed with metformin, but not with sitagliptin, at the end of the study. We observed a comparable significant decrease of HbA_1c, FPG, and PPG and a significant increase of homeostasis model assessment β-cell function index compared with baseline in both groups without any significant differences between the 2 groups. Fasting plasma insulin, fasting plasma Pr, Pr/FPI ratio, and HOMA-IR values were decreased in both groups even if the values obtained with metformin were significantly lower than the values obtained with sitagliptin. There were no significant variations of ADN, R, or TNF-α with sitagliptin, whereas a significant increase of ADN and a significant decrease of R and TNF-α values were recorded with metformin. A significant decrease of high-sensitivity C-reactive protein value was obtained in both groups without any significant differences between the 2 groups. There was a significant correlation between HOMA-IR decrease and ADN increase, and between HOMA-IR decrease and R and TNF-α decrease in pioglitazone plus metformin group after the treatment. The addition of both sitagliptin or metformin to pioglitazone gave an improvement of HbA_1c, FPG, and PPG; but metformin led also to a decrease of body weight and to a faster and better improvement of insulin resistance and inflammatory state parameters, even if sitagliptin produced a better protection of β-cell function.     

Association of insulin resistance and nocturnal fall of blood pressure in GH-deficient adults during GH replacement

The GH deficiency syndrome in adults is characterized by changes in body composition, metabolic, cardiovascular and psychological profile. Such alterations fit the metabolic syndrome. Changes of blood pressure (BP) levels related to the presence of insulin resistance (IR) may be present in the GH-deficient adult prior to or after therapy with recombinant GH (hGH). The purpose of the study was to assess the relationship between BP and IR in GH-deficient adults after 24 months of replacement with hGH. Thirteen GH-deficient adults were studied [7 men and 6 women, with an average age of 38.6+/-14.14 yr body mass index (BMI) 25.83+/-2.26 kg/m2]. The BP was assessed by means of ambulatory monitoring of BP (AMBP), prior to the treatment and 12 and 24 months after replacement with hGH. Glucose metabolism was assessed by the homeostatic model assessment (HOMA), during the same periods. The average dosage of hGH utilized was 0.67+/-0.15 mg/day. In the analysis of BP levels, we observed a decrease of the diurnal systolic BP (SB P) (p=0.043) and a reduction of the diurnal systolic (p=0.002) and diastolic pressure loads (p=0.038). During the night there were no changes in BP levels. We observed an increase in the percentage of patients with a non-physiological nocturnal fall (non dippers) after replacement with hGH (61.53%). The mean HOMA, insulin and glucose in the fasting state did not present any statistically significant changes. Although the patients within the nondipper group had higher HOMA and insulin levels throughout the study, there were no changes in any of these parameters after GH replacement. All patients with HOMA >2.5 were within the non-dipper group, whereas all dippers had HOMA <2.5. In conclusion, 24 months of therapy with hGH do not seem to have affected glucose homeostasis, and since there is no relationship with the increase of the percentage of non-physiological nocturnal fall, we will need a longer observation time to discover the effects of this finding.     

替米沙坦对肥胖高血压患者胰岛素抵抗和血清视黄醇结合蛋白4水平的影响

目的: 观察替米沙坦对伴超重或肥胖的高血压患者血压、糖脂代谢指标和血清视黄醇结合蛋白4（RBP4）水平的影响。方法: 将45例门诊超重或肥胖的原发性高血压患者随机分为替米沙坦组(n=23)和氯沙坦组(n=22),分别给予替米沙坦80 mg(qd)或氯沙坦100 mg(qd),必要时加用长效钙拮抗剂,治疗16周。观察用药前后腰围、腰臀比、体质量指数、血压、空腹血糖、胰岛素、血脂和血清RBP4含量的变化。采用稳态模式法计算胰岛素抵抗指数（HOMA-IR）。结果: 两组治疗后,收缩压及舒张压与治疗前比较均明显下降,替米沙坦组分别降低20.5 mmHg和14.8mmHg,氯沙坦组分别降低18.3 mmH和14.2 mmHg,下降幅度组间比较无差异;替米沙坦组HOMA-IR和血清RBP4的含量明显下降,分别由7.24±1.82下降至6.02±2.16（P<0.05）和(46.9±15.0)mg/L下降至(39.8±14.8)mg/L（P<0.05）。结论: 替米沙坦可改善肥胖伴高血压患者的胰岛素敏感性、降低血清RBP4的水平。     

Effect of antidiabetic medications on microalbuminuria in patients with type 2 diabetes

The progression of diabetes and hypertension complications is associated with microalbuminuria. Intensive glycemic control prevents or retards microalbuminuria in patients with type 2 diabetes, but little is known about the respective benefits of different antidiabetic drugs. We studied the effect of gliclazide and pioglitazone on microalbuminuria in patients with type 2 diabetes. We excluded patients with very poor glycemic control (glycated hemoglobin [HbA(1c)] >10%), impaired liver function, nondiabetic renal diseases, and those whose urine contained red blood cells, hemoglobin, or casts. Each patient received the designated drug for 12 weeks and their body weight, blood pressure (BP), fasting plasma glucose (FPG), HbA(1c), lipids (triglycerides [TG], total, and high-density lipoprotein-cholesterol [HDL-C]), 1,5 anhidroglucitol (1,5-AG), immunoreactive insulin (IRI), and urinary albumin to creatinine ratio (UACR) were measured every month. The effects of the drugs were analyzed using 2-way repeated measures analysis of variance (ANOVA). The 2 groups of patients were well matched for age, duration of diabetes, retinal status, blood pressure, body mass index (BMI), IRI, FPG, HBA(1c), 1,5-AG, lipids, and UACR, as well as the use of antihypertensive drugs. After treatment, no significant differences were seen in drug efficacy between the 2 groups. Gliclazide and pioglitazone significantly reduced FPG (F = 26.0, P <.0001), HBA(1c) (F = 48.1, P <.0001), and total cholesterol (TC) levels (F = 3.5, P <.05). Decrements in these metabolic parameters were comparable between the groups. 1,5-AG increased in both groups (F = 27.5, P <.0001), and the increment was comparable in both groups. Gliclazide and pioglitazone significantly reduced UACR (F = 15.7, P <.0001) with a comparable decrement in both groups. No other variables changed significantly throughout the 12-week treatment. These results suggest that 12 weeks of treatment with gliclazide or pioglitazone are equally effective in reducing microalbuminuria with similar improvements in blood glucose and cholesterol levels, independent of their mechanisms of actions.     

藏族人群代谢综合征对早期动脉粥样硬化的影响

目的:探讨藏族人群代谢综合征对早期动脉粥样硬化的影响。方法:在查体的藏族人群中筛选代谢综合征(MS)患者。记录身高、体重、腰围、血压,测定空腹血糖(FPG)、空腹胰岛素(FINS)、甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白-胆固醇(LDL-C)。超声检查颈动脉内中膜(IMT)厚度。结果:总共1187人参加筛选,其中MS患者206人。分为MS组和对照组。MS组的体重指数、收缩压、舒张压、TC、TG、FPG、FINS、胰岛素抵抗指数(HOMA指数)均显著高于对照组(P<0.01)。MS组的IMT较对照组增厚(P<0.001)。多元回归分析结果显示FPG、收缩压、舒张压、TG、HDL-C、腰围和HOMA指数均为颈动脉IMT的危险因子(P<0.05)。结论:藏族人群代谢综合征对早期动脉粥样硬化的形成有不利影响。     

Influence of glucose control and improvement of insulin resistance on microvascular blood flow and endothelial function in patients with diabetes mellitus type 2

OBJECTIVE: The study was performed to investigate the effect of improving metabolic control with pioglitazone in comparison to glimepiride on microvascular function in patients with diabetes mellitus type 2. METHODS: A total of 179 patients were recruited and randomly assigned to one treatment group. Metabolic control (HbA1c), insulin resistance (HOMA index), and microvascular function (laser Doppler fluxmetry) were observed at baseline and after 3 and 6 months. RESULTS: HbA1c improved in both treatment arms (pioglitazone: 7.52 +/- 0.85% to 6.71 +/- 0.89%, p < .0001; glimepiride: 7.44 +/- 0.89% to 6.83 +/- 0.85%, p < .0001). Insulin-resistance decreased significantly in the pioglitazone group (6.15 +/- 4.05 to 3.85 +/- 1.92, p < .0001) and remained unchanged in the glimepiride group. The microvascular response to heat significantly improved in both treatment groups (pioglitazone 48.5 [15.2; 91.8] to 88.8 [57.6; 124.1] arbitrary units [AU], p < .0001; glimepiride 53.7 [14.1; 91.9] to 87.9 [52.9, 131.0] AU, p < .0001, median [lower and upper quartile]). Endothelial function as measured with the acetylcholine response improved in the pioglitazone group (38.5 [22.2; 68.0] to 60.2 [36.9; 82.8], p = .0427) and remained unchanged in the glimepiride group. CONCLUSIONS: Improving metabolic control has beneficial effects in microvascular function in type 2 diabetic patients. Treatment of type 2 diabetic patients with pioglitazone exerts additional effects on endothelial function beyond metabolic control.     

以钙拮抗剂为基础的联合降压对高血压患者中心动脉压和脉搏波传导速度的对比研究

目的探讨氨氯地平联合复方阿米洛利或联合替米沙坦对高血压患者中心动脉压(CAP)和脉搏波传导速度(PWV)的影响。方法采用随机抽样方法选取2008-03-2011-02济南4个社区查体人群中高血压患者275例,年龄50～79岁。随机分为氨氯地平联合复方阿米洛利组(A组,134例)或联合替米沙坦组(B组,141例)。排除68例应用调脂药物的患者后,对207例(A组,102例;B组,105例)患者进行分析。在基线、治疗12、24月,分别应用动脉脉搏波分析仪测量CAP和增强指数,应用PWV测定仪测定颈桡动脉PWV(crPWV)。结果两组治疗12月后,中心动脉收缩压、舒张压、脉压,增强指数及crPWV均明显降低。24月时,B组crPWV较12月时进一步降低[(8.9±2.0)比(9.5±2.2)m/s,P<0.05],然而A组患者的crPWV并未随着时间的延长进一步改善(P>0.05)。治疗12和24月后,B组crPWV下降幅度[12月(-3.5±2.1)m/s,24月(-4.1±2.3)m/s]均较A组[12月(-2.3±1.6)m/s,24月(-2.5±1.8)m/s]更明显(均P<0.01)。结论以钙拮抗剂氨氯地平为基础,联合替米沙坦或复方阿米洛利均能够降低CAP、增强指数和改善大动脉顺应性,其中氨氯地平联合替米沙坦改善动脉弹性更明显,并且随着治疗时间的延长,效果更佳。     

Tumor necrosis factor-alpha is a marker of familial combined hyperlipidemia, independently of metabolic syndrome

It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.