初发2型糖尿病患者GLP-1水平变化对胰高血糖素及早相胰岛素分泌的影响

目的探讨初发2型糖尿病（T2DM）患者血胰高血糖素样肽-1（GLP-1）对胰高血糖素及早相胰岛素分泌的影响。方法以新发T2DM患者（T2DM组）、健康体检者（对照组）为研究对象,采用标准馒头餐试验,观察空腹、进餐后30 min、120 min静脉血浆GLP-1动态变化及对血浆葡萄糖、胰高血糖素、胰岛素分泌的影响。结果初发T2DM组患者馒头餐各时点GLP-1水平均分别较对照组显著降低,差异有统计学意义（P〈0.05）,馒头餐后30 min、120 min胰岛素水平显著降低（P〈0.05）,但空腹胰岛素无明显差异（P〉0.05）;而胰高血糖素则较对照组各时点显著升高,差异有统计学意义（P〈0.05）。初发T2DM组早相胰岛素分泌指数（ΔFINS30/ΔG30）显著低于对照组,差异有统计学意义（P〈0.05）。结论初发T2DM患者存在GLP-1分泌减少,GLP-1缺乏可能是T2DM患者胰岛β细胞分泌缺乏及胰高血糖素分泌过多的重要因素。     

2型糖尿病患者胰高血糖素及生长抑素功能变化分析

目的检测2型糖尿病患者（T2DM组）及健康人（NC组）的胰岛素（INS）、C肽（C-P）、胰高血糖素（GLC）、生长抑素（SS）的水平,探讨2型糖尿病患者胰岛功能受损可能的机制。方法 T2DM组40例和NC组19名均行口服75g葡萄糖耐量试验（OGTT）,于0、30、120min采静脉血,分别测定空腹及口服葡萄糖后30、120min血糖及INS、C-P、GLC、SS。结果 （1）与NC组比较,T2DM组INS、C-P明显降低（P〈0.01）;（2）T2DM组各时间点GLC较NC组显著升高（P〈0.01）。（3）T2DM组口服葡萄糖后30min、120min的SS水平均较0min显著升高,30min较NC组低（P〈0.05）,120min较NC组高（P〈0.01）。结论 T2DM患者INS、C-P分泌水平较正常人显著下降;GLC分泌亢进;SS分泌紊乱。     

146例结直肠癌患者糖代谢紊乱的初步调查分析

目的了解结直肠癌患者糖代谢异常发生情况,为干预提供依据。方法检测46例结直肠癌患者空腹及服糖后60、120、180 min时血糖、血清胰岛素和C肽的水平,并选择30例健康体检者作为对照。结果结直肠癌患者空腹及服糖后60、120、180 min时的血糖、胰岛素与C肽水平均高于对照组（P〈0.05）,且以120 min时最为显著（P〈0.01）。结论结直肠癌患者存在糖代谢紊乱,主要表现为血糖升高、糖耐量异常。     

2型糖尿病患者垂体细胞分泌功能研究

通过葡萄糖耐量试验,观察垂体细胞分泌促甲状腺素和B细胞分泌胰岛素的动态变化。和对照组比较,分析T2DM患者胰腺β细胞和胰腺外垂体细胞的分泌功能,分析2型糖尿病发病机理。结果：葡萄糖刺激后,胰岛素分泌异常。空腹值较对照组高、30分钟较对照组低（P〈0．05）,对照组高峰值在60分钟,T2DM组高峰值在120分钟。120分钟,垂体细胞分泌促甲状腺素明显低于空腹水平（P〈0．01）,也低于对照组同期分泌水平。结论：T2DM患者对葡萄糖刺激反应缓慢,胰岛素分泌、释放异常,胰腺β细胞分泌功能障碍。T2DM患者分泌促甲状腺素异常,垂体细胞分泌功能障碍。T2DM存在多种机体细胞功能障碍,与T2DM发病机理密切相关。     

空腹高血糖对初发2型糖尿病患者口服葡萄糖激发胰岛素释放试验的影响分析

目的观察胰岛素释放和初发2型糖尿病(T2DM)空腹血糖(FPG)水平的关系,分析解葡萄糖毒性对胰岛B细胞分泌功能的影响。方法选取该院2010年2月—2013年2月期间收治的初发T2DM患者120例,给予口服葡萄糖耐量试验(OGTT)和胰岛素释放试验(IRT),对比较初发T2DM患者在不同FPG水平胰岛素分泌不足检出率的差异。结果①为IR伴胰岛素分泌不足是初发2型糖尿病主要表现;②当FPG>11.0 mmo/L时,初发T2DM患者中口服葡萄糖刺激后胰岛素分泌明显不足。结论葡萄糖毒性对胰岛B细胞分泌功能的判断产生干扰,初发2型糖尿病患者的)空腹血糖控制在11.0 mmol/L以下,进行口服葡萄糖耐量试验,可较为准确地反映胰岛B细胞功能。     

地特胰岛素（诺和平）联合阿卡波糖和诺和灵30R治疗2型糖尿病临床观察

52例口服降糖药血糖控制不良的T2DM患者随机分为地特组26例,预混30R组26例,地特组三餐前服阿卡波糖,30R组中餐前加服阿卡波糖,根据血糖水平调整胰岛素用量,观察8周。结果：两组治疗后血糖及HbA1c较治疗前明显下降,C肽分泌改善,地特组空腹血糖下降更明显,空腹达标时间缩短,低血糖发生率低,并且体重无明显改变。     

胰岛素治疗与胰岛B细胞休息的相关性研究

目的　探讨短期胰岛素强化治疗对2型糖尿病(T2DM)患者胰岛B细胞功能的影响。方法　2003-11~2004-09在中国医科大学第一临床学院收治T2DM患者,应用化学免疫发光法测定强化治疗前后T2DM患者血清胰岛素和C肽水平。结果　强化治疗后的T2DM患者OGTT试验中0、30、60、120、180min血清胰岛素和C肽水平均较治疗前明显升高。结论　短期胰岛素强化治疗可使胰岛素分泌减低的T2DM患者胰岛B细胞得到休息,从而促其功能部分恢复。     

冠心病患者胰岛素抵抗及胰岛β细胞功能检测临床意义的研究

目的:通过口服葡萄糖耐量试验研究空腹血糖正常的冠心病患者胰岛素抵抗状态、胰岛β细胞分泌功能及其临床意义。方法:对冠心病组(35例)及对照组(30例)按空腹及服糖后30、60、120和180min进行糖耐量、胰岛素释放实验,测量各时点血糖值及胰岛素值。同时测量其血压、身高、体重、总胆固醇、甘油三酯,并计算出体重指数(BMI)=体重(kg)/身高2(m2)。按照稳态模型胰岛素抵抗指数(HOMA-IR)=空腹胰岛素(FINS)×空腹血糖(FPG)/22.5;胰岛β细胞分泌指数(HBCI)=20×空腹胰岛素/(空腹血糖-3.5);早期胰岛素分泌指数(△I30/△G30)=口服葡萄糖耐量试验30min胰岛素增量与葡萄糖增量的比值;李氏β细胞胰岛素分泌指数(MBCI)=(空腹胰岛素×空腹血糖)/(血糖2h 血糖1h-2×空腹血糖)公式计算稳态模型胰岛素抵抗指数、胰岛β细胞分泌指数、△I30/△G30及李氏β细胞胰岛素分泌指数值。结果:空腹血糖正常的冠心病患者糖代谢异常(120min血糖≥7.8mmol/L)的发生率为43%,明显高于对照组23%,仅用空腹血糖这些患者将不能被诊断;冠心病组空腹及服糖后120min、180min胰岛素水平、稳态模型胰岛素抵抗指数显著高于对照组[(11.4±9.4)vs(5.3±3.1)mU/L,(71.6±48.5)vs(31.2±22.0)mU/L,(42.7±35.4)vs(8.6±6.9)mU/L,(0.62±0.32)vs(0.47±0.21),P<0.01],△I30/△G30、李氏β细胞胰岛素分泌指数低于对照组[(1.13±0.65)vs(1.42±0.57),(1.03±0.35)vs(1.36±0.37),P<0.01],差异有显著性;Logistic回归分析显示稳态模型胰岛素抵抗指数、120min胰岛素水平、总胆固醇与冠心病的发生显著相关(OR值分别为1.432、0.644、1.116,P<0.05)。结论:空腹血糖正常的冠心病患者糖代谢异常发病率明显高于对照组,简易口服葡萄糖耐量试验可揭示血糖代谢状态,应常规用于冠心病患者血糖代谢异常的诊断。冠心病患者存在胰岛素抵抗及胰岛β细胞分泌功能缺陷。     

糖调节受损结直肠癌患者临床干预研究

目的了解糖调节受损结直肠癌(CRC)患者化疗期间临床干预对其糖调节受损及预后的影响。方法分别检测糖调节受损CRC患者干预组与非干预组化疗后空腹及服糖后60、120、180 min时血糖、胰岛素和C肽的水平。结果糖调节受损CRC患者干预组化疗后空腹及服糖后60、120、180 min时的血糖、胰岛素与C肽水平均低于非干预组(P<0.05或<0.01);随访截止2011年6月31日,糖调节受损CRC患者临床干预组生存率高于非干预组(χ2=5.47,P<0.05)。结论临床干预可能改善糖调节受损CRC患者的糖代谢,并且可能改善预后。     

血糖、胰岛素水平与冠心病病变程度关系的探讨

目的:探讨血糖、胰岛素水平与冠心病病变程度的关系。方法:以入选53例血压正常,经冠状动脉造影证实的冠心病患者为冠心病组,22例血压和冠状动脉造影均正常的人为正常组。测定所有对象的血脂,空腹血糖,口服葡萄糖后血糖及胰岛素分泌水平。结果:冠心病组空腹血糖,口服葡萄糖后120min的血糖,口服葡萄糖后30min,60min,120min,180min的胰岛素水平明显的高于正常组(P<0.05～<0.01);多支病变组的血糖、胰岛素水平明显高于单支病变组(P<0.05～<0.01),冠脉评分≥3分组的血糖、胰岛素水平明显高于≤2分组(P<0.05～<0.01)。结论:血糖、血胰岛素水平可反映冠脉病变的严重性。     

Oral glucose load inhibits circulating ghrelin levels to the same extent in normal and obese children

OBJECTIVE: The presence of both the GH secretagogue (GHS) receptor and ghrelin in the pancreas indicates an involvement of this hormone in glucose metabolism. Ghrelin secretion is increased by fasting and energy restriction, decreased by food intake, glucose load, insulin and somatostatin in normal adults; however, food intake is not able to inhibit circulating ghrelin levels in children, suggesting that the profile of ghrelin secretion in children is different from that in adults. Moreover, how ghrelin secretion is regulated in childhood as a function of fat mass is still unclear. DESIGN AND SUBJECTS: We studied the effect of oral glucose load (75 g solution orally) on circulating total ghrelin levels in 14 obese children (group A, four boys and 10 girls, aged 9.3 +/- 2.3 years) and 10 lean children (group B, five boys and five girls, aged 9.7 +/- 3.8 years). MEASUREMENTS: In all the sessions, blood samples were collected every 30 min from 0 up to +120 min. GH, insulin and glucose levels were assayed at each time point. RESULTS: Glucose peaks following an oral glucose tolerance test (OGTT) in groups A and B were similar; however, both basal and OGTT-stimulated insulin levels in group A were higher than in group B (P < 0.05). Basal total ghrelin levels in group A (281.3 +/- 29.5 pg/ml) were lower (P < 0.0005) than in group B (563.4 +/- 81.5 pg/ml). In both groups A and B, the OGTT inhibited total ghrelin levels (P < 0.005). In terms of absolute values, total ghrelin levels in group A were lower (P < 0.0005) than those in group B at each time point after glucose load. The percentage nadir in total ghrelin levels recorded in group A (-25% at 90 min) was similar to that recorded in group B (-31% at 120 min). Total ghrelin levels were negatively associated with BMI (r = 0.5, P < 0.005) but not with glucose or insulin levels. CONCLUSION: Ghrelin secretion is reduced in obese children. It is, however, equally sensitive in both obese and lean children to the inhibitory effect of oral glucose load.     

乙型肝炎病毒相关的肝源性糖尿病糖代谢异常的临床分析

目的 探讨HBV相关的肝源性糖尿病糖代谢的临床特点及其发生机制.方法 患者分为2型糖尿病组、慢性乙型肝炎合并肝源性糖尿病组(简称慢肝组)及乙型肝炎肝硬化合并肝源性糖尿病组(简称肝硬化组),所有研究对象均行口服葡萄糖耐量试验(OGTT)联合胰岛素、C肽释放试验,并测定糖化血红蛋白(HbAlc)水平.结果 肝硬化组空腹血糖、30min、60min血糖分别为(6.98±2.75)mmol/L、(11.93±2.98)mmol/L、(15.37±3.67)mmol/L,均明显低于慢肝组、糖尿病组(P＜0.01),后两组间差异无统计学意义;肝硬化组120min血糖低于糖尿病组(P＜0.01).各时间点三组之间C-肽水平差异无统计学意义,峰值出现的时间基本一致(120min),均呈低峰延迟曲线.各时间点肝硬化组和慢肝组胰岛素水平的对数值均与糖尿病组存在统计学差异(P＜0.01),前两组水平高于糖尿病组,但两组间差异无统计学意义.峰值出现的时间基本一致(120min).三组之间HbAlc差异有统计学意义(P＜0.05),肝硬化组最低,糖尿病组最高.结论 HBV相关的肝硬化患者推荐行OGTT作为糖尿病筛查指标.     

Effect of oral glucose administration on ghrelin levels in obese children

OBJECTIVE: Coexpression of GH secretagogue receptor and ghrelin in the pancreas suggests that this peptide is involved in glucose metabolism. Previous reports in adult humans have demonstrated that plasma ghrelin levels decrease after oral glucose administration. However, no data are available in children. Therefore, the aim of this study was to analyze the response of plasma ghrelin levels in obese children after oral glucose administration. SUBJECTS AND METHODS: Twenty-eight obese children ranging from Tanner I to Tanner V were studied. All subjects were given 0.75 g/kg (maximum 75 g) glucose solution after overnight fasting. Ghrelin, insulin, glucose and IGF-binding-protein-1 were determined at 0, 30, 60 and 120 min of the oral glucose tolerance test (OGTT). RESULTS: Basal plasma ghrelin levels were significantly lower than in the respective control groups. These levels decreased significantly during OGTT in obese children, reaching a nadir of 28+/-9% at 60 min in parallel with the maximum increase in glucose levels and previous to maximum insulin levels. CONCLUSION: The rapid fall in plasma ghrelin concentration in obese children after glucose load suggests a mechanism for the control of appetite after food intake.     

Changes of ghrelin following oral glucose tolerance test in obese children with insulin resistance

AIM： To characterize changes in ghrelin levels in response to oral glucose tolerance test （OGTT） and to correlate changes in ghrelin levels with changes in insulin and glucose following OGTT in Chinese obese children of Tanner Ⅰ and Ⅱ stage with insulin resistance. METHODS： 22 obese children with insulin resistance state were divided into four groups according to their Tanner stage and gender： boys of Tanner Ⅰ （fir- Ⅰ ）, boys of Tanner Ⅱ（BT-Ⅱ ）, girls of Tanner Ⅰ （GT- Ⅰ ）, girls of Tanner Ⅱ （GT-Ⅱ）. Ghrelin, insulin and glucose were measured at 0, 30, 60 and 120 rain following OGTT. The control children with normal BMI were divided into control boys of Tanner Ⅰ （CBT- Ⅰ, n = 6）, control boys of Tanner Ⅱ （CBT-Ⅱ, n = 5）, control girls of Tanner Ⅰ （CGT- Ⅰ, n = 6）, control girls of Tanner Ⅱ （CGT-Ⅱ, n = 5）. Fasting serum ghrelin levels were analyzed. RESULTS： Ghrelin levels were lower in obese groups. Ghrelin levels of control group decreased in Tanner Ⅱ stage （CGT- Ⅰ vs CGT-Ⅱ t = -4.703, P = 0.001; CBT- Ⅰ vs CBT- Ⅱ t = -4.794, P = 0.001）. Basal ghrelin levels in fir-Ⅱ decreased more significantly than that in BT- Ⅰ group （t = 2.547, P = 0.029）. Ghrelin levels expressed a downward trend after OGTT among obese children. The decrease in ghrelin levels at 60 min with respect to basal values was 56.9% in BT- Ⅰ. Ghrelin concentrations at 0 min correlated directly with glucose level at 0 min in fir- Ⅰ （r = 0.898, P = 0.015）. There wasn＇t a significant correlation of ghrelin changes with glucose changes and insulin changes during OGTT in obese children with insulin resistance. CONCLUSION： In conclusion, in obese children with insulin resistance, ghrelin levels decreased with advancing pubertal stage. Ghrelin secretion suppression following OGTT was influenced by gender and pubertal stage. Baseline ghrelin levels and ghrelin suppression after OGTT did not significantly correlate with the degree of insulin resistance     

Acute plasma glucose increase, but not early insulin response, regulates plasma ghrelin

OBJECTIVE: The independent role of glucose and insulin in ghrelin regulation is still controversial; this is also because in healthy subjects it is difficult to isolate the increase of glucose from that of insulin. The aim of this study was to discriminate the effect of glucose increase alone and early insulin response on plasma ghrelin, comparing ghrelin variation after i.v. glucose between healthy subjects and type 2 diabetic (T2DM) subjects, in whom the early insulin response to i.v. glucose is abolished. METHODS: Plasma glucose, insulin and ghrelin levels were measured 0, 3, 5, 10, 30, 45 and 60 min after a 5 g glucose i.v. bolus in seven healthy control subjects and eight T2DM subjects. RESULTS: There were no significant differences in body mass index, basal insulin and basal ghrelin between T2DM and healthy subjects. Basal glucose levels were higher in T2DM subjects than in controls. After i.v. glucose administration, plasma glucose increased significantly in both groups and the glucose peak was higher in T2DM subjects than in controls (9.67+/-1.25 (s.d.) vs 6.88+/-1.00 mmol/l, P<0.01). Insulin increased rapidly in controls, while in T2DM subjects, plasma insulin did not rise in the first 10 min. After the glucose bolus, plasma ghrelin showed a significant reduction both in controls and in T2DM subjects after 5 min. CONCLUSION: These findings indicate that a low-dose i.v. glucose bolus reduces ghrelin both in controls and in T2DM subjects and therefore that early insulin response does not affect plasma ghrelin.     

Plasma ghrelin levels of gastrectomized and vagotomized patients are not affected by glucose administration

BACKGROUND: Ghrelin is a brain-gut peptide with GH-releasing and appetite-inducing activities, secreted mainly by the stomach. Circulating ghrelin concentrations fall rapidly after nutrient ingestion as well as after oral and intravenous glucose challenge. A number of gut hormones including ghrelin require an intact vagal system, which has been hypothesized to have a major role in initiating the postprandial fall in ghrelin levels. AIM: We aimed to investigate the effect of oral glucose challenge on ghrelin secretion in gastrectomized (GASTRX) and vagotomized patients. DESIGN: Interventional study. PATIENTS: Six GASTRX-vagotomized patients and 11 healthy sex- and body mass index (BMI)-matched subjects. METHODS: An oral glucose tolerance test (OGTT) was performed in all subjects. At baseline, circulating plasma total ghrelin, serum glucose, insulin and GH levels were measured. Serum glucose, insulin, GH and plasma ghrelin levels were determined every 30 min for 2 h. RESULTS: Plasma ghrelin levels at baseline were reduced by 55% in GASTRX-vagotomized patients compared to the control group (P < 0.01). In control subjects, plasma ghrelin levels decreased significantly during the OGTT whereas in GASTRX-vagotomized patients no reduction was registered (26.4 +/- 2.8% vs. 5.5 +/- 3.4%). The OGTT revealed a significantly greater increase in circulating glucose levels and serum insulin levels while GH response was not different in GASTRX-vagotomized patients compared to control subjects. CONCLUSIONS: Our data show that circulating ghrelin levels in GASTRX and vagotomized patients were not suppressed after oral glucose administration, unlike control subjects, suggesting that this effect could be due, at least in part, to the lack of contribution of the vagal nervous system to the regulation of ghrelin.     

LncRNA MALAT1在2型糖尿病患者中的表达及临床意义

目的探讨LncRNA MALAT1在2型糖尿病患者中的表达及临床意义。方法收集正常健康体检者25例,糖尿病患者69例,Real-time PCR法(qPCR)测定两组血清白细胞中LncRNA MALAT1的表达。结果糖尿病组血清白细胞中LncRNA MALAT1表达水平较对照组明显升高(P<0.05)。二元回归分析显示LncRNA MALAT1及超氧化物歧化酶(SOD)是2型糖尿病发病的危险因素。Spearman相关分析提示LncRNA MALAT1表达与糖化血红蛋白、SOD、口服葡萄糖耐量试验(OGTT)中胰岛素分泌(60 min)及血糖(60、120、180 min)存在相关性。受试者工作特征(ROC)曲线结果显示ROC曲线下面积(AUC)为0.807,敏感度为78.3%,特异度为84.0%。结论LncRNA MALAT1在2型糖尿病患者中高表达,可作为糖尿病诊断的潜在生物标志物。     

Potential correlation between plasma total GIP levels and body mass index in Japanese patients with types 1 or 2 diabetes mellitus

Glucose-dependent insulinotropic polypeptide (GIP) secretion in diabetic Europeans with type 1 (T1DM) and type 2 (T2DM) following test meal (TM) has been shown to be normal. In Japanese patients with T2DM, GIP secretion was also normal. We determined whether GIP secretin is influenced by various factors. Plasma glucose (PG), serum insulin (s-IRI), serum C-peptide (s-CPR), and plasma total GIP (p-total GIP) levels were measured at 0, 30, and 60 minutes after TM (560 kcal) in patients with T1DM (n = 15, group 1) and T2DM (n = 29, group 2) treated with various medications. HbA1c was also measured. At baseline, means of age, BMI, HbA1c, PG, s-CPR, SUIT (secretory unit in transplantation) and p-total GIP were significantly lower in group 1 than in group 2. Each mean of postprandial p-total GIP levels after TM in all patients was more dramatically increased than other factors. The area under the curve (AUC) of p-total GIP levels in early-phase (0 to 30 min) was significantly positively correlated with BMI in group 2 but not in group 1, and not with other factors. These results indicate that the GIP secretion after TM in diabetic Japanese patients was dramatically increased, and the AUC of GIP secretion in early-phase was positively correlated with BMI in non-obese and obese patients with T2DM, but not with T1DM. The increase was not influenced by gender, age, glycemic control, duration of disease, micro- or macro-vascular disturbances, or oral drugs.