Objective To analyze the glucolipotoxicity effects of glucose combined with free fatty acid (FFA) on ketone production and ultrastructure of skeletal muscle, by exogenous elevating circulating glucose and FFA concentration. Methods Fifty Wistar rats were divided into high-fat-feed induced obesity group (OB group, n=40) and ordinary feed as normal control group (NC group, n=10). Circulating glucose and FFA levels were increased by infusion in high-fat-fed obese rats. The levels of serum lipid, plasma FFA and beta-hydroxybutyric acid were detected by the horizontal colorimetry, and the microstructure of skeletal muscle was observed by transmission electron microscopy, especially the changes of the mitochondrial structure. Euglycemic-hyperinsulinemic clamp with tracer infusion was performed to assess peripheral insulin sensitivity. Results The average weight and body fat ratio in the OB group was higher than that in the NC group (P<0.05). Insulin clamp test to assess peripheral insulin sensitivity showed that the steady-state glucose Infusion rate in the OB group during clamp test was significantly lower than that in the NC group [OB: (19.26±1.84) mg/(kg·min)vs. NC: (28.82±1.69) mg/(kg·min), P<0.05]. The mitochondrial denaturation of skeletal muscle in the OB group of rats was observed, and the swelling and crest permutation, the accumulation of lipid droplets and cavitation were formed, and hypertrophy of mitochondria were also seen after intralipid and glucose infusion, which was obvious in the combined infusion group. Conclusions By exogenous elevating circulating glucose and FFA concentration, the products of ketone body increases. The mitochondrial damage of skeletal muscle suggests that mitochondrial may be the potential target of glucoxicity and lipotocicity.
To compare the platelet enrichment ratio of platelet-rich plasma (PRP) prepared by different centrifuge methods and to compare the concentration of growth factors released from autologous platelet-rich gel (APG) with the whole blood. Methods Thirteen diabetic patients with refractory skin lesions were enrolled in APG treatment. ① Three kinds of centrifuge methods were selected for PRP by 11 diabetic patients: A(n=6): 529 × g for 4 minutes in the first centrifugeand 854 × g for 6 minutes in the second centrifuge; B (n=5): 313 × g for 4 minutes in the first centrifuge and 1 252 × g for 6 minutes in the second centrifuge; C (n=5): 176 × g for 5 minutes in the first centrifuge and 1 252 × g for 5 minutes in the second centrifuge. Platelet counted on the whole blood and PRP was determined. The APG, produced by combining the PRPwith thrombin and calcium gluconate (10 ∶ 1) was used by patients. ② PDGF-BB, TGF-β1, VEGF, EGF, and IGF-1 were measured in the APG and the whole blood using the enzyme-l inked immunosorbent assay method. Results ① The average platelet concentration was higher in group B [(1 363.80 ± 919.74) × 109/ L] than in groups A[(779.67 ± 352.39) × 109/ L)] and C[(765.00 ± 278.78) × 109/ L] and the platelet recovery rate was 75.2% ± 21.0% in group B. ② The concentration of growth factors all increased with the increasing platelet number. On average, for the whole blood as compared with APG, the PDGF-BB concentration increased from (145.94 ± 133.24) pg/mL to (503.81 ± 197.86) pg/mL (P lt; 0.05); TGF-β1 concentration increased from (3.31 ± 2.27) ng/mL to (5.67 ± 4.80) ng/mL (P lt; 0.05); IGF-1concentration increased from (14.54 ± 35.34) ng/mL to (110.56 ± 84.36) ng/mL (P lt; 0.05); and EGF concentration increased from (160.73 ± 71.10) pg/mL to (265.95 ± 138.43) pg/mL (P lt; 0.05). No increase was found for VEGF(P gt; 0.05). ③ There was positive correlation between the platelet concentration and PDGF-BB and TGF-β1 (r = 0.627, r = 0.437, P lt; 0.05). ④ Thirteen diabetic repractory dermal ulcers received APG treatment for 18 times, 9 ulcers (69.2%) and 10 sinuses (88.3%) were cured at the end of 12-week treatment. Conclusion The method ofgroup B is the best centrifuge method. A variety of growth factors are detected and released from the platelets at significant levels in APG. There is positive correlation between the platelet concentration and PDGF-BB and TGF-β1 .
【摘要】 目的 探讨胰岛素强化治疗对2型糖尿病（type 2 diabetes mellitus，T2DM）患者血清脂联素（adiponectin，APN）的影响。 方法 2007年7—12月，研究纳入连续使用胰岛素治疗至少3个月但血糖控制欠佳[6.5%≤糖化血红蛋白（hemoglobin A1c， HbA1c）≤11.0%]的T2DM患者40例，其中男18例，女22例；年龄29~〖JP2〗69岁；平均诊断T2DM病史11年。治疗方案为进行16周的胰岛素强化治疗，血糖控制目标为空腹血糖≤7 mmol/L，〖JP〗餐后2 h血糖≤8 mmol/L。分别于强化治疗前、强化治疗4周后及强化治疗16周后测定HbA1c以及血清APN水平。 结果 与强化治疗前相比，胰岛素治疗4周后空腹及三餐后2 h血糖明显下降（Plt;0.05），但HbA1c和血清APN水平差异无统计学意义（Pgt;0.05）；强化16周后，HbA1c水平明显低于治疗前和治疗4周后且差异具有统计学意义（Plt;0.05），APN水平高于治疗前和治疗4周后且差异有统计学意义（Plt;0.05）。体质量指数在强化治疗16周后明显增加且与强化治疗前和强化治疗后4周相比差异具有统计学意义（Plt;0.05）。APN与空腹血糖（b=-0.225，P=0.013）、早餐后2 h血糖（b=-0.229，P=0.012）呈负相关。 结论 胰岛素强化治疗可以提高T2DM患者血清APN水平。【Abstract】 Objective To investigate the effect of intensive insulin therapy on serum adiponectin (APN) level in patients with type 2 diabetes mellitus (T2DM). Methods Forty patients with T2DM who had undergone insulin therapy for at least three months but with their blood glucose poorly controlled [glycosylated hemoglobin Alc (HbA1c) level ranged from 6.5% to 10.0%] from July to December 2007 were enrolled in this study. There were 18 males and 22 females with their age ranged from 29 to 69 years. They had an average time of T2DM history of 11 years. Intensive insulin therapy was carried out for 16 weeks with a target of less than 7 mmol/L for fasting blood glucose and 8 mmol/L for postprandial blood glucose. HbA1c and serum adiponectin concentrations were detected at baseline, at week 4 after intensive therapy and at the end of the study. Results After 4 weeks of intensive blood glucose control, fasting and postprandial blood glucose levels decreased significantly (Plt;0.05), but the HbA1c and serum APN concentrations did not reduce remarkably (Pgt;0.05). After 16 weeks of treatment, the level of HbA1c was significantly lower than those at baseline and 4 weeks after treatment (Plt;0.05), and serum APN concentration increased significantly (Plt;0.05), compared with those two time points. However, an evident increase of body mass index (BMI) was found while compared with BMI at baseline and 4 weeks after treatment (Plt;0.05). The linear regression analysis indicated that APN was negatively associated with fasting blood glucose (b=-0.225,P=0.013) and blood glucose level 2 hours after breakfast (b=-0.229,P=0.012). Conclusion Intensive insulin therapy can improve serum adiponectin level in type-2 diabetic patients.
【摘要】 目的 调查成都地区2型糖尿病患者糖耐量正常一级亲属的代谢状态及与胰岛素抵抗、胰岛β细胞功能的相关性。 方法 2007年7-9月共纳入糖耐量正常的一级亲属312例（NGT-FDR组），无家族史的正常对照1 348例（NGT-C组）。测量两组血压、体重、腰围；检测口服葡萄糖耐量试验（OGTT）中0、0.5、2 h血糖、胰岛素水平；测定空腹血脂；计算体重指数、HOMA-胰岛素抵抗指数（HOMA-IR）、胰岛β细胞功能指数（HOMA-β），β细胞早相分泌功能指数（△I30/△G30），并比较两组间上述指标的差异和代谢综合征（MS）及其各组分的发病情况。 结果 ①NGT-FDR组MS发生率高于NGT-C组，发生MS的风险是后者的1.737倍。NGT-FDR组高甘油三酯血症（hypertriglyceridemia，HTG）、空腹血糖偏高（5.6~6.0 mmol/L）的发生率高于NGT-C组，合并4种及以上代谢异常的几率亦高于NGT-C组（Plt;0.05）；②年龄lt;40岁的NGT-FDR中心性肥胖、HTG、空腹血糖偏高和MS均高于同年龄对照；男性NGT-FDR空腹血糖偏高和MS发病率高于男性对照（Plt;0.05）；③腰围、收缩压（SBP）、空腹血糖（FBG）、甘油三酯（TG）及糖尿病家族史同HOMA-IR呈正相关。腰围、SBP、TG及糖尿病家族史同HOMA-β呈正相关，FBG则同HOMA-β呈负相关。 结论 2型糖尿病糖耐量正常一级亲属比无家族史的对照表现出更多的代谢异常，尤其是在年龄lt;40岁及男性中。各种代谢异常可加重胰岛素抵抗，影响胰岛基础分泌功能。故有必要对糖耐量正常的一级亲属进行各项代谢指标的监测和早期预防性干预。【Abstract】 Objective To investigate the metabolic status of the normal glucose-tolerant first-degree relatives (NGT-FDR) of type-2 diabetic patients and its relationship with insulin resistance (IR) and β-cell function in Chengdu area. Methods From July to September 2007, a total of 312 NGT-FDR of type-2 diabetic patients and 1 348 normal glucose tolerant controls without positive family history of diabetes (NGT-C) were enrolled in this study. Blood pressure, weight, waists, plasma glucose at hour 0, 1/2 and 2 in oral glucose tolerance test (OGTT), insulin levels and fasting blood lipids were measured. Body mass index (BMI), HOMA-IR, HOMA-β and the early insulin secreting index (△I30/△G30) were calculated. Then, we compared the above-mentioned data and the incidence of metabolic syndrome (MS) between the two groups. Results ①The incidence of MS, hypertriglyceridemia (HTG), higher fasting blood glucose (FBG) (5.6-6.0 mmol/L) in the NGT-FDR group were all significantly higher than those in the NGT-C group. The risk of developing MS in the NGT-FDR group was 1.737 times as high as that in the NGT-C group. Furthermore, the incidence of 4 or more than 4 co-existent metabolic disorders in the NGT-FDR group was also significantly higher than that in the NGT-C group (Plt;0.05); ②For subjects less than 40 years old, the incidence of central obesity, HTG, higher FBG and MS in the NGT-FDR group were all higher than those in the NGT-C group. In male subjects, the rates of higher FBG and MS were all significantly higher in the NGT-FDR group than those in the NGT-C group. (Plt;0.05); ③Waists, FBG, systolic blood pressure (SBP), triglycerides (TG) and diabetic family history were positively correlated with HOMA-IR. Waists, SBP, TG and diabetic family history were positively correlated with HOMA-β. Conclusion NGT-FDR present significantly increased metabolic disorders than NGT controls, especially in the less than 40-year-old and the male subjects. The metabolic disorders can aggravate insulin resistance and influence islet β-cell secretion function, so it is necessary to monitor the metabolic status of the NGT-FDR of type-2 diabetic patients and provide early preventive interventions.