初诊2型糖尿病患者短期胰岛素强化治疗后超敏C-反应蛋白的变化

目的观察诺和锐强化治疗后超敏C-反应蛋白(hs-CRP)变化与胰岛素抵抗的关系。方法选择2005年6月至2007年2月在暨南大学医学院第五附属医院暨广东省清远市人民医院对30例初诊2型糖尿病(T2DM)患者进行14d的持续皮下诺和锐输注。分析比较治疗前后空腹(FPG)及餐后血糖(PPG),口服葡萄糖耐量试验时真胰岛素及C肽分泌和真胰岛素及C肽曲线下面积、胰岛素抵抗指数、胰岛素分泌指数、hs-CRP等指标的变化。结果短期诺和锐强化治疗后,FPG、PPG及葡萄糖曲线下面积均较治疗前明显下降(P<0.01);空腹及餐后真胰岛素和C肽的分泌、真胰岛素和C肽曲线下面积、胰岛素分泌指数均较治疗前明显升高(P<0.01)。胰岛素抵抗指数较治疗前明显下降(P<0.05)。hs-CRP明显下降。结论短期诺和锐强化治疗可以迅速降低血糖,改善胰岛B细胞功能,降低胰岛素抵抗,改善炎症,降低hs-CRP。     

胰岛素类似物强化治疗对新诊断2型糖尿病患者胰岛β细胞功能的影响

对22例新诊断T2DM患者进行为期2周的胰岛素类似物诺和锐强化治疗,分析比较治疗前后空腹血糖（FPG）及餐后2h血糖（2h PG）、糖化血红蛋白（HbA1c）、静脉葡萄糖耐量试验（IVGTT）时胰岛素及C肽分泌水平和胰岛素曲线下面积、胰岛素分泌指数（Homaβ）。结果FPG、2hPG和HbA1c均较治疗前显著降低（P〈0.01）;空腹及IVGTT时每一时间点的胰岛素和C肽浓度均较治疗前明显升高（P〈0.01）;胰岛素曲线下面积及Homaβ值均明显增加（P〈0.01）结论早期胰岛素类似物强化治疗可显著改善新诊断T2DM患者胰岛β细胞功能。     

诺和锐30强化治疗对初诊2型糖尿病患者第一时相胰岛素分泌的影响

目的探讨短期诺和锐30强化治疗对初诊2型糖尿病（T2DM）患者第一时相胰岛素分泌缺陷的作用。方法对30例初诊T2DM患者进行每日3次诺和锐30强化治疗2周,治疗前后分别行静脉葡萄糖耐量实验,测定0、3、4、5、8、10、120分钟血糖、胰岛素及C肽值,计算胰岛素和C肽曲线下面积（AUC）及稳态模型胰岛素抵抗指数（HOMA—IR）。结果患者治疗后血清胰岛素及C肽第一时相分泌明显增加,AUC0-10min均明显升高（P〈0．01）。HOMA-IR指数明显降低（P〈0．01）。结论短期每日3次诺和锐30强化治疗能明显改善初诊T2DM患者C肽的第一时相分泌及胰岛素敏感性。     

短期诺和锐强化治疗初诊2型糖尿病60例临床观察

对60例初诊T2DM患者进行为期四周的诺和锐强化治疗。结果治疗后，FPG、2hPG、HbA1c均较治疗前明显下降（P〈0．01）；Fins与FPG比值、胰岛素分泌指数、胰岛素敏感指数均较治疗前明显升高（P〈0．01）。胰岛素抵抗指数较治疗前明显下降（P〈0．01）。结论短期诺和锐强化治疗可显著改善初诊T2DM患者的胰岛素抵抗。     

短期诺和锐强化治疗初诊2型糖尿病60例临床观察

对60例初诊T2DM患者进行为期四周的诺和锐强化治疗。结果治疗后，FPG、2hPG、HbA1c均较治疗前明显下降（P〈0．01）；Fins与FPG比值、胰岛素分泌指数、胰岛素敏感指数均较治疗前明显升高（P〈0．01）。胰岛素抵抗指数较治疗前明显下降（P〈0．01）。结论短期诺和锐强化治疗可显著改善初诊T2DM患者的胰岛素抵抗。     

短期胰岛素强化治疗对2型糖尿病患者C肽的影响

对35例T2DM患者进行为期两周的胰岛素强化治疗,分析比较治疗前后FPG、（2hPG）、HbA1c、空腹及餐后1、2,3小时C肽分泌。结果胰岛素强化治疗后,FPG、2hPG、HbA1c均较治疗前明显下降（P〈0．01）;空腹及餐后1、2、3小时C肽均较治疗前明显升高。结论短期胰岛素强化治疗可显著改善T2DM患者C肽的释放。     

胰岛素泵强化治疗糖尿病疗效分析

对56例2型糖尿病(T2DM)病人进行为期2周的胰岛素泵强化治疗,分析比较治疗前后的空腹血糖(FPG)及餐后2h血糖(2hPG)、糖化血红蛋白(HbA1c)、空腹胰岛素(FINS)、体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)、胰岛素分泌指数(HOMA-β)、胰岛素敏感指数(ISI)、空腹胰岛素(FINS)与空腹血糖(FPG)的比值.结果胰岛素泵强化治疗后FPG、2hPG、HbAlc均较治疗前明显下降(P＜0.01)FINS与FPG比值、HOMA-β、ISI均较治疗前明显升高(P＜0.01)HOMA-IR较治疗前明显下降(P＜0.01).结论利用胰岛素泵对糖尿病进行强化治疗可以显著改善T2DM患者胰岛β细胞功能,具有胰岛素用量少、低血糖发病率低、控制血糖效果显著以及治疗时间短等特点,是治疗糖尿病最有效的方法之一.     

胰岛素强化治疗疗程与初诊2型糖尿病胰岛β细胞功能的关系

对110例初诊2型糖尿病（T2DM）患者,分为胰岛素强化治疗15 d组、30 d组、60 d组,检测3组治疗前后空腹血糖（FBG）、空腹胰岛素（FIns）,行标准口服馒头餐—胰岛素—C肽释放试验,分析比较3组患者治疗后血糖控制及胰岛β细胞功能恢复情况。发现3组患者治疗后血糖明显下降,胰岛β细胞功能明显改善;30 d组、60d组胰岛β细胞早时相分泌指标较15 d组改善更明显。可见适当延长胰岛素强化治疗疗程可进一步改善胰岛β细胞早时相分泌。     

诺和锐30治疗初诊2型糖尿病30例临床观察

目的探讨诺和锐30治疗初诊2型糖尿病疗效及对胰岛功能的影响。方法采用自身前后对照法对30例初诊2型糖尿病患者进行12周的诺和锐30治疗，观察治疗前后FPG及餐后2hPG、糖化血红蛋白、FINS、HOMA—βHOMA—IR。结果治疗后，FPG、2hPG、HbA1c、胰岛素抵抗指数均较治疗前下降（P〈0．05）。FINS、胰岛素分泌指数较治疗前明显升高（P〈0．01）。结论诺和锐30强化治疗能显著改善初诊2型糖尿病患者的血糖及胰岛功能。     

胰岛素强化治疗对初诊2型糖尿病患者胰岛β细胞功能和胰岛素抵抗的影响

目的探讨阶梯式胰岛素强化治疗对初诊2型糖尿病（T2DM）患者胰岛β细胞功能和胰岛素抵抗（IR）的影响及机制。方法初诊T2DM患者61例,进行为期2周的胰岛素强化治疗和后续10周的预混胰岛素治疗,比较治疗前后FPG、2hPG、HbA1c、Fins、2hIns、FC-P、2hC-P、TC、TG、胰岛β细胞分泌指数（HOMA-β）和胰岛素抵抗指数（HOMA-IR）的变化。结果治疗后患者FPG、2hPG、HbA1 c和HOMA-IR显著下降,而Fins、2hIns、FC-P、2hC-P和HOMA-β显著上升。结论对血糖明显升高的初诊T2DM患者,短期胰岛素强化治疗及后续数周预混胰岛素皮下注射治疗可有效控制血糖,明显改善胰岛8细胞功能并减轻IR。     

短期胰岛素强化治疗对初诊2型糖尿病患者胰岛素抵抗及血尿酸的影响

目的 探讨短期胰岛素强化治疗对初诊2型糖尿病患者胰岛素抵抗及血尿酸的影响.方法 对36例初诊2型糖尿病患者进行为期2周的胰岛素强化治疗,比较治疗前后血尿酸（UA）、空腹血糖（FPG）及餐后2h血糖（2hPG）、糖化血红蛋白（HbA1c）、空腹胰岛素（FINS）、胰岛素抵抗指数、胰岛素敏感指数.结果 经胰岛素强化治疗后,患者UA、FPG、2hPG、HbA1c、胰岛素抵抗指数均较治疗前明显下降（P均＜0.01）,胰岛素敏感指数明显升高（P＜0.01）.结论 短期胰岛素强化治疗可显著改善初诊2型糖尿病患者的胰岛素抵抗,降低血UA水平.     

不同糖耐量人群血浆载蛋白A5与胰岛B细胞第一时相胰岛素分泌关系研究

目的探讨不同糖耐量人群血浆载脂蛋白A5(apolipoprotein A5,apoA5)与胰岛B细胞第一时相胰岛素分泌的关系。方法选取2009年2月至9月重庆医科大学附院门诊35例新诊断的2型糖尿病(T2DM组),30例糖调节受损者(IGR组),35例正常对照(NGT组)。以葡萄糖刺激后3～5 min急性胰岛素反应(AIR3-5)来表示第一时相胰岛素分泌功能指数;测空腹apoA5、游离脂肪酸(FFA)及糖负荷后2hFFA(2hFFA);稳态模型评价胰岛素抵抗指数(HOMA-IR)及胰岛B细胞功能(HOMA-β)。探讨apoA5与AIR3-5、血脂、血糖、HOMA-B及HOMA-IR等关系。结果(1)T2DM组、IGR组的apoA5、AIR3-5、HDL-C、HOMA-B显著低于NGT组(P<0.05),且T2DM组显著低于IGR组(P<0.05);(2)T2DM组、IGR组TG、FFA、2hFFA、LDL-C、FPG、2hPG、FINS、BMI、WHR和HOMA-IR明显高于NGT组(P<0.05),T2DM组显著高于IGR组(P<0.05);(3)apoA5与AIR3-5、HOMA-B、HDL-C均呈正相关,与TG、FFA、2hFFA、LDL-C、FPG、2hPG、FINS、HOMA-IR、BMI、WHR均呈负相关;(4)多元逐步回归分析显示,AIR3-5、TG、FFA、WHR、HOMA-IR是apoA5的独立影响因素。结论从NGT到IGR到T2DM发病进程中,低apoA5血症可能通过升高FFA而导致高甘油三酯血症,使B细胞第一时相胰岛素分泌受损,故推测升高apoA5水平,可能会降低TG,从而改善和恢复第一时相胰岛素分泌,延缓T2DM的进程。     

Loss of beta cell function as fasting glucose increases in the non-diabetic range

Aims/hypothesis Our aim was to define the level of glycaemia at which pancreatic insulin secretion, particularly first-phase insulin release, begins to decline.Methods Plasma glucose and insulin concentrations were measured during an IVGTT in 553 men with non-diabetic fasting plasma glucose concentrations. In 466 of the men C-peptide was also estimated. IVGTT insulin secretion in first and late phases was assessed by: (i) the circulating insulin response; (ii) population parameter deconvolution analysis of plasma C-peptide concentrations; and (iii) a combined model utilising both insulin and C-peptide concentrations. Measurements of insulin sensitivity and elimination were also derived by modelling analysis.Results As fasting plasma glucose (FPG) increased, IVGTT first-phase insulin secretion declined by 73%, 71% and 68% for the three methods respectively. The FPG values at which this decline began, determined by change point regression, were 4.97, 5.16 and 5.42 mmol/l respectively. The sensitivity of late-phase insulin secretion to glucose declined at FPG concentrations above 6.0 mmol/l. Insulin elimination, but not insulin sensitivity, varied with FPG.Conclusions/interpretation The range of FPG over which progressive loss of the first-phase response begins may be as low as 5.0 to 5.4 mmol/l, with late-phase insulin responses declining at FPG concentrations above 6.0 mmol/l.Abbreviations f fractional hepatic insulin throughput - FPG fasting plasma glucose - FSD fractional standard deviation - k_c the plasma C-peptide elimination constant - k_i the plasma insulin elimination constant - MFG mean fasting glucose - SG minimal model glucose effectiveness - SI minimal model insulin sensitivity In the course of this work, our colleague and co-author James Jeffs died unexpectedly after a short illness. His contribution will be greatly missed.     

Insulin resistance, beta-cell function, and glucose tolerance in Brazilian adolescents with obesity or risk factors for type 2 diabetes mellitus

OBJECTIVE: To evaluate insulin resistance (IR), beta-cell function, and glucose tolerance in 119 Brazilian adolescents with obesity or risk factors (RF) for type 2 diabetes mellitus (T2DM). STUDY DESIGN: We analyzed weight (kg), height (m), body mass index (BMI; kg/m(2)), waist (W; cm), acanthosis nigricans (AN), systolic and diastolic blood pressure (SBP and DBP; mm Hg), fasting plasma glucose (FPG), and 2-h plasma glucose (2hPG) on oral glucose tolerance test (OGTT; 1.75 g of glucose/weight), lipid profile [total cholesterol (TC), fractions, and triglycerides (TGs)], fasting insulin (FI) and 2-h insulin on OGTT (2hI-RIA), HOMA-B (%; beta-cell function--HOMA program), HOMA-S (%; insulin sensitivity--HOMA program) and HOMA-IR [fasting plasma insulin (mU/ml)xfasting plasma glucose (mmol/L)/22.5]. Division according to number of RF-family history of T2DM (FHT2DM), obesity, hypertension, dyslipidemia, polycystic ovary syndrome (PCOS), and AN. G1: subjects with no or one RF; G2: subjects with two or more RFs. Statistical data were nonparametrical. RESULTS: Fasting plasma glucose (G2: 81.6+/-10.2 vs. G1: 79.8+/-9.9 mg/dl) and 2hPG (88.1+/-18.0 vs. 87.0+/-19.9 mg/dl) were not different between G2 (n=67) and G1 (n=52), and all adolescents had normal glucose tolerance (NGT). Fasting insulin (13.0+/-7.9 vs. 7.6+/-3.9 microIU/ml; P<.001) and 2hI (60.2+/-39.1 vs. 38.3+/-40.0 microIU/ml; P<.001), HOMA-B (169.1+/-131.6% vs. 106.1+/-39.9%; P<.001), and HOMA-IR (2.62+/-1.7 vs. 1.52+/-0.8; P<.001) were higher in G2. HOMA-S (92.5+/-59.5% vs. 152.2+/-100.5%; P<.001) was also lower in this latter group. CONCLUSION: Brazilian adolescents with two or more RFs for the development of T2DM have higher IR and beta-cell function and lower insulin sensitivity. However, adolescents with impaired glucose tolerance (IGT) or DM have not been found, differently from similar studies. Differences in ethnic background, environment, and lifestyle factors may account for this disparity.     

Relationship between beta-cell responsiveness and fasting plasma glucose in Caucasian subjects with newly presenting type 2 diabetes.

AIMS : beta-cell responsiveness was related to fasting plasma glucose to gain further understanding of pathophysiology of Type 2 diabetes. METHODS : An insulin secretion model gave fasting beta-cell responsiveness M0 (ability of fasting glucose to stimulate beta-cell) and postprandial beta-cell responsiveness MI (ability of postprandial glucose to stimulate beta-cell) by analysing glucose and C-peptide time-concentration curves sampled every 10-30 min over 240 min during a meal tolerance test (MTT; 75 g CHO, 500 kcal). Caucasian subjects with newly presenting Type 2 diabetes according to WHO criteria (N = 83, male/female: 65 : 18, age: 54 +/- 10 years, body mass index (BMI): 30.9 +/- 5.2 kg/m2, fasting plasma glucose (FPG): 11.0 +/- 3.2 mmol/L; mean +/- SD) and Caucasian healthy subjects (N = 54, m/f: 21 : 33, age: 48 +/- 9 years, BMI: 26.1 +/- 3.7 kg/m2, FPG: 5.1 +/- 0.4 mmol/L) were studied. RESULTS : A continuum inverse relationship between MI and FPG was observed. In the diabetes group, MI was closely related to FPG (rs = -0.74, P < 0.0001) and explained 60% intersubject FPG variability with the use of an exponential regression model. CONCLUSIONS : In newly presenting Type 2 diabetes in Caucasian subjects a close inverse association exists between postprandial beta-cell responsiveness and FPG.     

Associations of glucose control with insulin sensitivity and pancreatic beta-cell responsiveness in newly presenting type 2 diabetes.

We examined the ability of indices of insulin sensitivity and pancreatic beta-cell responsiveness to explain interindividual variability of clinical measures of glucose control in newly presenting type 2 diabetes. Subjects with newly presenting type 2 diabetes (n = 65; 53 males and 12 females; age, 54 +/- 1 yr; body mass index, 30.5 +/- 0.7 kg/m(2); mean +/- SE) underwent an insulin-modified iv glucose tolerance test to determine minimal model-derived insulin sensitivity (S(I)), glucose effectiveness, first-phase insulin secretion, and disposition index. Subjects also underwent a standard meal tolerance test (MTT) to measure fasting/basal (M(0)) and postprandial (M(I)) pancreatic beta-cell responsiveness. Stepwise linear regression used these indices to explain interindividual variability of fasting and postprandial plasma glucose and insulin concentrations and glycated hemoglobin (HbA(1C)). All measures of pancreatic beta-cell responsiveness (M(0), M(I), and first-phase insulin secretion) were negatively correlated with fasting plasma glucose (P < 0.01) and positively correlated with fasting plasma insulin (FPI) and insulin responses to MTT (P < 0.05). S(I) demonstrated negative correlation with FPI (P < 0.001) but failed to correlate with any glucose variable. M(I) followed by disposition index (composite index of insulin sensitivity and pancreatic beta-cell responsiveness) were most informative in explaining interindividual variability. It was possible to explain 70-80% interindividual variability of fasting plasma glucose, FPI, HbA(1C), and insulin responses to MTT, and only 25-40% interindividual variability of postprandial glucose. In conclusion, postprandial insulin deficiency is the most powerful explanatory factor of deteriorating glucose control in newly presenting type 2 diabetes. Indices of insulin sensitivity and pancreatic beta-cell responsiveness explain fasting glucose and HbA(1C) well but fail to explain postprandial glucose.     

Insulin action and insulin secretion in newly diagnosed type 2 diabetic patients

To clarify the insulin action and insulin secretion in newly diagnosed type 2 diabetic subjects, we investigated insulin and C-peptide response to an oral glucose tolerance test (OGTT) in 15 newly diagnosed type 2 diabetic patients and 17 healthy subjects. For insulin action, we found fasting hyperinsulinemia (8.4 +/- 0.8 vs. 6.0 +/- 0.5 microIU/ml, p = 0.014), higher insulin resistance by homeostasis model assessment (HOMA) (4.33 +/- 0.2 vs. 1.34 +/- 0.1 microIU/ml.mmol/l, p < 0.001), and lower insulin sensitivity index (ISI) (51.0 +/- 0.7 vs. 104.0 +/- 0.8, p < 0.001) in newly diagnosed diabetic patients compared to normal subjects. For insulin secretion, the increments of AUCI (area under curve of insulin) and AUCC-P (area under curve of C-peptide) (increment of AUCI: 26.1 +/- 1.4 vs. 82.8 +/- 4.5 microIU/ml.hour, p < 0.001; increment of AUCC-P: 3.9 +/- 0.2 vs. 11.4 +/- 0.6 ng/ml.hour, p < 0.001), insulin secretion by HOMA model (20.7 +/- 1.2 vs. 79.1 +/- 3.8 IU/mol, p < 0.001), and ratio of 30 min increment of fasting insulin to glucose during OGTT (1.14 +/- 0.1 vs. 13.1 +/- 0.5 IU/mol, p < 0.001) were significantly lower in the newly diagnosed diabetic patients than normal subjects. In addition, body mass index (BMI) in our type 2 diabetes is relatively lower (24 +/- 0.65 kg/m2) than those in western countries. These findings revealed poor insulin action and decreased insulin secretion in relatively less obese Taiwanese with newly diagnosed type 2 diabetes.     

Pancreatic beta-cell function and insulin sensitivity in japanese subjects with impaired glucose tolerance and newly diagnosed type 2 diabetes mellitus

To clarify whether pancreatic beta-cell function and/or insulin resistance contributes to development of glucose intolerance in Japanese subjects, we investigated 551 subjects who underwent a 75-g oral glucose tolerance test (OGTT). Subjects were divided into 3 groups: normal glucose tolerance (NGT, n = 238), impaired glucose tolerance (IGT, n = 211), and newly diagnosed type 2 diabetes mellitus (n = 102). The diabetics were subdivided into 3 subgroups as follows: diabetes with normal fasting glucose (fasting plasma glucose [FPG] < 110 mg/dL), diabetes with impaired fasting glucose (FPG 110 to 125 mg/dL), and diabetes with diabetic fasting glucose (FPG >or= 126 mg/dL). Insulinogenic index as early-phase insulin secretion, homeostasis model assessment (HOMA-beta and HOMA-resistance), and 4 different formulas of insulin sensitivity index were assessed by plasma glucose and insulin concentrations obtained at fasting or during a 75-g OGTT. Both early-phase insulin secretion and insulin sensitivity were low even in the IGT stage compared with NGT. The transition from IGT to diabetes was accompanied by a progressive deterioration of insulin reserve as well as insulin resistance. During the further progression in diabetes, insulinogenic index decreased additionally, whereas declines in insulin sensitivity were relatively small. In conclusion, both impaired insulin secretion and insulin resistance may contribute to the underlying mechanisms of glucose intolerance in Japanese subjects.