吡格列酮与二甲双胍对初诊肥胖2型糖尿病患者血清内脏脂肪素影响的研究

目的观察吡格列酮与二甲双胍对初诊肥胖T2DM患者血清内脏脂肪素（visfatin）水平的影响,探讨visfatin与T2DM发病的关系和药物的治疗机制。方法100例初诊肥胖T2DM患者随机分为吡格列酮组50例,每日口服盐酸吡格列酮片30mg,二甲双胍组50例,每日早晚口服二甲双胍缓释片500mg,疗程24周。结果吡格列酮组空腹血清visfatin、IR、TG较用药前明显降低,B细胞功能有改善（P〈0．05或P〈0．01）。二甲双胍组血清visfatin、TG无统计学改变。两组治疗后比较,吡格列酮组的visfatin、IR、TG降低明显,差异有统计学意义（P〈0．05或〈0．01）,但二甲双胍组的BMI较吡格列酮组下降更明显（P〈0．05）。结论对初诊肥胖T2DM患者吡格列酮与二甲双胍均能较好地控制血糖,吡格列酮还能明显降低血清visfatin的水平,提示吡格列酮通过下调visfatin水平发挥抗炎作用。     

双时相门冬胰岛素30联合二甲双胍治疗基础胰岛素控制不佳的2型糖尿病患者:疗效及安全性评价

目的 评价既往基础胰岛素联合口服降糖药物(OAD)治疗血糖控制不佳的2型糖尿病患者转用双时相门冬胰岛素30(BIAsp30)联合二甲双胍治疗的疗效及安全性.方法 本试验为多中心、非随机、开放、单组治疗达标研究,包括2周筛选期、4周导入期和16周治疗期.既往使用基础胰岛素联合OAD治疗血糖控制不佳的2型糖尿病患者转用每日两次BIAsp30注射联合口服二甲双胍治疗.收集疗效及安全性数据进行统计学分析.结果 共293例患者(男154,女139)入选,平均年龄(54.0±9.6)岁,平均糖尿病病程(8.54±5.49)年,平均体重指数(24.89±3.28)kg/m2,HbA1c 8.16%±0.89%,122例既往使用基础胰岛素类似物,169例使用人中效胰岛素.经16周的治疗,平均HbA1C降幅达1.30%±0.96%(P＜0.01);HbA1C达到＜7.0%和≤6.5%的患者比例分别为60.4%和38.9%.患者8点血糖谱各点血糖值均有显著降低(P＜0.01),8点血糖均值由基线时的(10.53±2.58)mmol/L降至(7.79±1.58)mmol/L(P＜0.01),降幅为2.76 mmol/L.早餐和晚餐后血糖增幅显著下降,分别下降了1.73 mmol/L(P＜0.01)和1.28 mmol/L(P＜0.01),而午餐后的血糖增幅未发现显著性降低(-0.09 mmol/L,P=0.734 5).研究治疗中无严重不良事件和重度低血糖事件报告,总体低血糖发生率为2.68例/患者年;患者体重平均增加(0.76±0.14)kg(P＜0.01).结论 BIAsp30联合二甲双胍可显著改善基础胰岛素联合OAD血糖控制不佳的2型糖尿病患者的血糖控制,并具有良好的安全性.     

吡格列酮和二甲双胍对2型糖尿病胰岛素抵抗的影响

目的　观察吡格列酮和二甲双胍治疗对 2型糖尿病患者胰岛素抵抗 (IR)的影响。方法 5 0例血糖控制不良的 2型糖尿病患者在原治疗方案下 ,随机给予盐酸吡格列酮片 3 0mg(2片 ) 1次 /日和模拟二甲双胍片 (1片 ) 2次 /日 ,即吡格列酮组 ;或随机给予盐酸二甲双胍片 5 0 0mg(1片 ) 2次 /日和模拟吡格列酮片 (2片 ) 1次 /日 ,即二甲双胍组 ,所有治疗疗程 12周。结果　在两组患者取得相当降糖疗效基础上 ,二甲双胍组和吡格列酮组在治疗后空腹和馒头餐后C肽水平均较用药前有明显降低、IR稍有降低 ,β细胞功能明显改善。吡格列酮在减低餐后胰岛素、改善IR方面优于二甲双胍。两种药物治疗前后血游离脂肪酸水平则差异未见显著性。结论　吡格列酮和二甲双胍均能有效地降低IR和改善 β细胞功能。在改善IR方面 ,吡格列酮稍优于二甲双胍。     

2型糖尿病血清瘦素质量浓度与胰岛素抵抗的关系

目的探讨2型糖尿病人群血清瘦素水平与胰岛素抵抗的关系。方法2001-102002-08对河北医科大学第三医院的196例受试者(2型糖尿病者118例、对照者78名)用放射免疫法测定空腹血清瘦素水平,同时测量身高、体重、腰围、臀围。结果糖化血红蛋白(HbA1c)、收缩压(SBP)、甘油三酯(TG)和瘦素(Leptin)是影响胰岛素敏感性的因素;2型糖尿病组瘦素质量浓度高于对照组;肥胖者瘦素质量浓度显著升高,而2型糖尿病组内肥胖与非肥胖者之间瘦素质量浓度差异无显著性。结论肥胖者大多存在胰岛素抵抗;2型糖尿病人无论肥胖与否均存在一定程度的胰岛素抵抗。     

甘精胰岛素联合口服降糖药治疗肥胖2型糖尿病患者的疗效观察

目的 观察甘精胰岛素联合阿卡波糖和(或)二甲双胍治疗肥胖T2DM临床疗效.方法 32例肥胖T2DM患者,在注射预混Ins一段时间后血糖控制不理想情况下,改用甘精胰岛素联合阿卡波糖和(或)二甲双胍,疗程3个月,观察治疗前后BP、FPG、HbA_1c、TC、TG、HDL-C、LDL-C、UA、C-P、UAER变化情况,计算HOMA-IR、HOMA-β.结果 治疗后BMI、FPG、HOMA-IR低于治疗前,而C-P、HOMA-β高于治疗前(P＜0.05).结论 甘精胰岛素联合阿卡波糖和(或)二甲双胍治疗肥胖T2DM,不仅成功控制血糖,且明显改善IR,治疗中无明显体重增加等不良反应.     

地特胰岛素联合低剂量二甲双胍、阿卡波糖治疗老年2型糖尿病超重与肥胖患者疗效及安全性的观察

目的 探讨老年T2DM超重、肥胖患者在口服降糖药基础上加用每日一次地特胰岛素（Det）治疗的临床疗效及安全性. 方法 93例老年T2DM超重、肥胖患者随机分为A、B组.A组口服二甲双胍＋阿卡波糖（Met＋ Acarbose）;B组二甲双胍＋阿卡波糖＋Det （Met＋ Acarbose＋ Det）,疗程24周.观察两组治疗前后FPG、2hPG、BMI、HbA1c及低血糖发生率等情况. 结果 24周后,B组FPG、2hPG、HbA1 c、BMI较基线及A组降低（P＜0.05）,且无夜间低血糖发生. 结论 Det联合低剂量二甲双胍＋阿卡波糖可有效控制老年T2DM超重、肥胖患者血糖,优于单纯口服给药,并能控制体重,且无夜间低血糖发生.     

地特胰岛素对2型糖尿病肥胖及非肥胖患者血糖及体重的影响

目的观察地特胰岛素治疗24周对2型糖尿病（T2DM）肥胖及非肥胖患者血糖及体重的影响。方法选取既往未接受过胰岛素治疗的T2DM患者54例,根据BMI分为肥胖（Ob）组24例和非肥胖（NOb）组30例,检测治疗前后体重、FBG、HbA1C,计算BMI、胰岛素用量等。结果地特胰岛素治疗24周后,Ob组和NOb组FBGE（7．3±1．2）mmol／L、（6．7±1．5）mmol／L]、HbA1C[（7．3±0．9）％、（6．5±0．8）％]均较基线值{FBGE（9．4±2．5）mmol／L、（8．1±1．7）mmol／L]、HbA1cE（8．2±1．1）％、（7．6±1．9）％]}明显下降（P〈0．05）;Ob组治疗前后BMI变化[（-1．51±1．10）kg／m2]与NOb组[（0．15±1．00）kg／m2]比较,差异有统计学意义（P〈0．05）。结论地特胰岛素治疗可有效降低肥胖和非肥胖T2DM患者血糖,且无明显体重增加效应。     

血浆脂联素与2型糖尿病胰岛素抵抗关系的研究

目的　测定 2型糖尿病患者血浆脂联素的水平 ,并分析它与体重指数、血糖、胰岛素、血脂和胰岛素抵抗的关系 ,从而探讨脂联素在糖尿病发病中的作用。方法　健康对照组 2 8例 ,2型糖尿病组 60例 ,根据体重指数又将糖尿病组分为非肥胖糖尿病组 3 0例 (BMI <2 5kg/m2 )和肥胖糖尿病组 3 0例 (BMI >2 5kg/m2 )。用ELISA方法检测空腹血浆脂联素浓度 ,同时测定各组的空腹血糖、胰岛素、血脂的水平 ;根据HOMA模型提出的公式 ,计算分析胰岛素抵抗指数 ,并分析各指标间的相关性。结果　 (1)糖尿病各组血浆脂联素的水平明显低于正常对照组 ,且肥胖糖尿病组脂联素的水平低于非肥胖组 ,差异均有显著性 (P 0 .0 1) ;(2 )血浆脂联素浓度与体重指数、空腹胰岛素、胰岛素抵抗指数 (IR)、甘油三酯呈显著负相关。结论　脂联素参与了胰岛素抵抗的发生过程 ,与糖尿病的发生发展密切相关 ;脂联素可作为评价胰岛素抵抗程度的一种新的敏感指标     

Effects of pioglitazone and metformin on NEFA-induced insulin resistance in type 2 diabetes

Aims/hypothesis  We sought to determine whether pioglitazone and metformin alter NEFA-induced insulin resistance in type 2 diabetes and, if so, the mechanism whereby this is effected. Methods  Euglycaemic–hyperinsulinaemic clamps (glucose ∼5.3 mmol/l, insulin ∼200 pmol/l) were performed in the presence of Intralipid–heparin (IL/H) or glycerol before and after 4 months of treatment with pioglitazone (n = 11) or metformin (n = 9) in diabetic participants. Hormone secretion was inhibited with somatostatin in all participants. Results  Pioglitazone increased insulin-stimulated glucose disappearance (p < 0.01) and increased insulin-induced suppression of glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) during IL/H. However, glucose disappearance remained lower (p < 0.05) whereas glucose production (p < 0.01), gluconeogenesis (p < 0.05) and glycogenolysis (p < 0.05) were higher on the IL/H study day than on the glycerol study day, indicating persistence of NEFA-induced insulin resistance. Metformin increased (p < 0.001) glucose disappearance during IL/H to rates present during glycerol treatment, indicating protection against NEFA-induced insulin resistance in extrahepatic tissues. However, glucose production and gluconeogenesis (but not glycogenolysis) were higher (p < 0.01) during IL/H than during glycerol treatment with metformin, indicating persistence of NEFA-induced hepatic insulin resistance. Conclusions/interpretation  We conclude that pioglitazone improves both the hepatic and the extrahepatic action of insulin but does not prevent NEFA-induced insulin resistance. In contrast, whereas metformin prevents NEFA-induced extrahepatic insulin resistance, it does not protect against NEFA-induced hepatic insulin resistance. B. R. Landau died after the completion of this study.     

Comparison of insulin monotherapy and combination therapy with insulin and metformin or insulin and rosiglitazone or insulin and acarbose in type 2 diabetes

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6 months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7 units/day in insulin alone group, decreased to 4.7 units/day in insulin plus rosiglitazone group, to 4.2 units/day in insulin plus metformin group, and to 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). No significant change in lipid levels—except serum triglycerides—was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.     

中国汉族肥胖人群IRS-2 G1057D多态性筛查

目的筛查肥胖人群IRS2G1057D多态性并探讨其意义。方法选取辽宁汉族肥胖者225例,其中2型糖尿病(T2DM)组112例,健康对照组113例。用PCRRFLP方法检测IRS2G1057D多态性,结合T2DM发病机制相关的胰岛素分泌和胰岛素作用简易指标的变化探讨其意义。结果(1)IRS2G1057D变异频率在肥胖总研究人群中为28.7%,T2DM组和对照组分别为33.5%和23.9%(P=0.025)。(2)T2DM组DD基因型频率显著高于对照组,分别为13.4%和5.3%(P=0.041)。Logistic回归分析结果显示:GD和DD基因型的OR值分别为1.246和3.991。(3)在T2DM组,DD基因型的腰臀比(WHR)、HOMAIR及OGTT后2h的血糖、胰岛素和C肽均显著高于同组GG基因型,HOMAβ显著低于同组GG基因型。(4)在肥胖对照组,DD基因型的WHR、2h胰岛素、HOMAIR及HOMAβ也分别高于及低于同组GG基因型(均P<0.05)。(5)T2DM组GD、DD基因型的WHR较对照组均有升高趋势,但差异无统计学意义(P>0.05)。结论肥胖尤其是中心性肥胖的DD基因型携带者T2DM患病风险增大。     

Meta-analysis: metformin treatment in persons at risk for diabetes mellitus

Purpose

We performed a meta-analysis of randomized controlled trials to assess the effect of metformin on metabolic parameters and the incidence of new-onset diabetes in persons at risk for diabetes.

Methods

We performed comprehensive English- and non-English-language searches of EMBASE, MEDLINE, and CINAHL databases from 1966 to November of 2006 and scanned selected references. We included randomized trials of at least 8 weeks duration that compared metformin with placebo or no treatment in persons without diabetes and evaluated body mass index, fasting glucose, fasting insulin, calculated insulin resistance, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, and the incidence of new-onset diabetes.

Results

Pooled results of 31 trials with 4570 participants followed for 8267 patient-years showed that metformin reduced body mass index (−5.3%, 95% confidence interval [CI], −6.7-−4.0), fasting glucose (−4.5%, CI, −6.0-−3.0), fasting insulin (−14.4%, CI, −19.9-−8.9), calculated insulin resistance (−22.6%, CI, −27.3-−18.0), triglycerides (−5.3%, CI, −10.5-−0.03), and low-density lipoprotein cholesterol (−5.6%, CI, −8.3-−3.0%), and increased high-density lipoprotein cholesterol (5.0%, CI, 1.6-8.3) compared with placebo or no treatment. The incidence of new-onset diabetes was reduced by 40% (odds ratio 0.6; CI, 0.5-0.8), with an absolute risk reduction of 6% (CI, 4-8) during a mean trial duration of 1.8 years.

Conclusion

Metformin treatment in persons at risk for diabetes improves weight, lipid profiles, and insulin resistance, and reduces new-onset diabetes by 40%. The long-term effect on morbidity and mortality should be assessed in future trials.     

利拉鲁肽联合二甲双胍治疗2型糖尿病合并肥胖症的临床疗效探讨

目的探讨应用利拉鲁肽联合二甲双胍治疗2型糖尿病合并肥胖症患者的临床效果及安全性。方法选取2013-06~2015-05收治的2型糖尿病合并肥胖症患者62例为研究对象,通过随机数字表法分为观察组和对照组,每组31例。对照组给予二甲双胍治疗,观察组在对照组基础上加用利拉鲁肽,治疗12周。观察两组患者血糖、体重控制情况及不良反应发生情况。结果治疗前两组患者各项指标差异均无统计学意义(P均0.05),治疗后观察组空腹血糖(FPG)、餐后2 h血糖(2h PG)、糖化血红蛋白、腰臀比及体质量指数(BMI)均明显低于对照组,差异有统计学意义(P均0.05)。观察组和对照组治疗期间不良反应发生率分别为9.68%和6.45%,差异无统计学意义(P0.05),均未出现严重不良反应。结论 2型糖尿病合并肥胖症患者给予利拉鲁肽联合二甲双胍治疗,能有效控制血糖,改善体质量,且安全性高,值得推广。     

Combinational therapy with metformin and sodium-glucose cotransporter inhibitors in management of type 2 diabetes: Systematic review and meta-analyses

Aims

In search of add-on treatments to metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors are potential candidates. This meta-analysis examines the potential use of SGLT-2 inhibitors in combination with metformin as a therapeutic option for type 2 diabetes management in patients with inadequate control with metformin.

Methods

A literature search was made in several databases for randomized controlled trials (RCTs) utilizing metformin therapy combined with SGLT-2 inhibitors or placebo. Heterogeneity was estimated with I² statistics and random effect model was chosen for the meta-analyses of mean differences in changes from baseline in both SGLT-2 inhibitor treated and control groups.

Results

Seven RCTs were selected for the meta-analysis. In comparison with placebo-MET, the SGLT-2 inhibitor–MET combination therapy resulted in significant HbA1c decline in 12–24 week duration, to less extent after 1 year (−0.37 [−0.77, 0.03]; P = 0.07) but not by 2 year (−0.41 [−1.09, 0.28]; P = 0.24) duration. SGLT-2 inhibitor–MET significantly lowered FPG and body weight after 24 weeks, 1 year, and 2 years. Systolic and diastolic blood pressure declined only in the short-term (12–24 weeks). After 2 years, neither systolic (−1.80 [−6.18, 2.58]; P = 0.42) nor diastolic blood pressure (−0.20 [−2.94, 2.54]; P = 0.89) declined significantly more than control. Incidence of suspected genital infections was slightly more in SGLT-2 inhibitor–MET group.

Conclusion

SGLT-2 inhibition in combination with metformin is a potential therapeutic option based on its effects on glycemic control, body weight, and blood pressure, but further trials are required to refine this evidence.     

The interplay of insulin resistance and beta-cell dysfunction involves the development of type 2 diabetes in Chinese obeses

Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder characterized by defects in insulin secretion and action and obesity plays an important role in the deterioration of glucose metabolism. In the present study we evaluated the degree of insulin resistance and first-phase insulin secretion of β-cell in obese subjects with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM in Chinese. A total of 220 subjects underwent standard 75 g oral glucose tolerance test (OGTT) and insulin-modified frequently sampled intravenous glucose tolerance test (FSIGT). Insulin sensitivity index (S _I) was assessed by the reduced sample number (n = 12) of Bergman’s minimal model method with FSIGT. Insulin secretion capacities were determined by the insulinogenic index (I _{30 min} − I _{0 min})/(G _{30 min} − G _{0 min}) in OGTT and the acute insulin response to glucose (AIR) in FSIGT. The disposition index (DI), the product of AIR and S _I was used to determine whether AIR was adequate to compensate for insulin resistance. The S _I in healthy lean control group was significantly higher than that in NGT, IGT, and T2DM group, but there was no significant difference among NGT, IGT, and T2DM group. The AIR in NGT group was significantly greater than that in control group, but then it was progressively decreased in IGT and T2DM group. The value of DI in control group was significantly higher than that in those three abnormal groups, and was decreased from NGT to IGT and T2DM group with significant difference. It indicates that obese subjects with different glucose tolerances have a similar degree of insulin resistance but differ in insulin secretion in Chinese Han population.     

利拉鲁肽和西格列汀对超重和肥胖2型糖尿病患者的疗效和安全性比较

目的 比较利拉鲁肽和西格列汀与二甲双胍联合应用时对超重和肥胖的2型糖尿病患者疗效和安全性.方法 选取2012年4月至10月住院的体质指数（BMI）＞25 kg/m2的2型糖尿病患者86例,按随机数字表法分为利拉鲁肽治疗组（40例）和西格列汀治疗组（46例）,于用药前、用药4周、12周和24周后分别测定患者的空腹静脉血糖（FPG）、餐后2h血糖（PPG）、糖化血红蛋白（HbA1c）、体重、腰围、血压、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）、肝功能、肾功能、24 h尿微量白蛋白（UMA）.记录用药期间的低血糖发生情况和其他不良反应.采用t检验和重复测量资料方差分析进行数据分析.结果 （1）两组患者的血糖和HbA1c在治疗后均出现下降,但两组间差别无统计学意义（均P＞0.05）.（2）利拉鲁肽组患者用药24周后体重较用药前下降[（80±7）比（85 ±8）kg,t=2.9,P＜0.05],西格列汀组患者用药24周后体重较用药前下降[（82±7）比（84±7） kg,t =2.78,P＜0.05];用药24周后两组间差别有统计学意义[（80±7）比（82 ±7） kg,t=-3.5,P＜0.05].（3）利拉鲁肽组患者用药24周后较用药前腰围下降[分别为（101±7）比（106±8）cm,t =13.35,P＜0.05],西格列汀组用药24周后腰围较用药前减少[分别为（102 ±6）比（105 ±6） cm,t =3.3,P＜0.05],用药24周后两组间差别有统计学意义[（101±7）比（102±6）cm,t=-3.1,P＜0.05].（4）利拉鲁肽组患者用药24周后收缩压较用药前下降[（138±7）比（143±6） mmHg,1 mmHg=0.133 kPa,=3.69,P＜0.05],西格列汀组用药24周后较用药前收缩压下降[（139±4）比（141 ±5） mmHg,t=2.8,P＜0.05],用药24周后两组间差异有统计学意义[（138±7）比（139 ±4） mm Hg,t=-3.0,P＜0.05];利拉鲁肽组患者用药4周后较用药前舒张压下降[（89±2）比（93±2）mmHg,t=2.6,P＜0.05],西格列汀组用药24周后较用药前舒张压下降[（89±3）比（92±3）mmHg,t=3.5,P＜0.05],两组间差异无统计学意义（P＞0.05）.（5）利拉鲁肽组患者的上消化道不良反应多于西格列汀组,差异具有统计学意义（30.0％比4.3％,t=2.86,P＜0.05）.结论 利拉鲁肽联合二甲双胍与西格列汀联合二甲双胍降低超重和肥胖的2型糖尿病患者的即时血糖和HbA1c的能力相同,利拉鲁肽能够更有效地降低患者体重、腰围和血压,西格列汀具有良好的安全性.     

二甲双胍对2型糖尿病合并结直肠癌患者预后的影响

目的 探讨T2DM合并结直肠癌患者的临床病理特征和二甲双胍对肿瘤分化程度及转移的影响.方法 检测研究对象FPG、血白蛋白（Alb）、BUN、血肌酐（Scr）、血尿酸（SUA）、TG、TC、HDL-C、LDL-C和极低密度脂蛋白胆固醇（VLDL-C）水平,观察结直肠癌病理分级、结直肠癌淋巴结及远处转移情况. 结果 按照患者诊断结直肠癌时是否服用二甲双胍进行分组后发现,二甲双胍组低分化腺癌比例及远处转移率均低于无二甲双胍组（P＜0.05）. 结论 T2DM合并结直肠癌患者口服二甲双胍降糖,其肿瘤预后较好.     

2型糖尿病血浆抵抗素水平与胰岛素敏感性相关因素的研究

2型糖尿病患者血浆抵抗素水平明显高于正常人；在糖尿病患者中血浆抵抗素水平肥胖者明显高于非肥胖者，且与胰岛素敏感指数（ISI）呈负相关，与FPG、血脂、年龄、性别，WHR无相关性。     

Low dose metformin in the treatment of type II non-insulin-dependent diabetes: Clinical and metabolic evaluations

Summary Low doses of metformin (500 mg twice daily) were administered to 20 diabetic patients, combined with the original sulfonylurea treatment which had become ineffective even at full dosage. After 1 and 5 weeks, the effects of the drug on glycemic control, blood intermediate metabolites and monocyte insulin receptors were monitored. Metformin clearly improved glycemic control by reducing both fasting blood glucose from 189.88±21.11 mg/dl to 131.12±16.02 mg/dl after 1 week and to 130.11±13.29 mg/dl after 5 weeks (p<0.025 both after 1 and 5 weeks); the diurnal blood glucose average fell from 235.33±24.11 mg/dl to 174.66±23.45 mg/dl (p<0.0025) after 1 week and to 177.65±21.71 mg/dl (p<0.0005) after 5 weeks. Consequently both blood glycosylated hemoglobin (p=n.s. after 1 week, p<0.025 after 5 weeks) and serum fructosamine (p<0.0025 after both 1 and 5 weeks) also decreased after metformin treatment. No change in plasma insulin and C-peptide levels was reported and no modification in diurnal rhythms of blood lactate, pyruvate, alanine glycerol and β-OH-butyrate was detected at any time during metformin treatment. All the changes documented in the binding values were already complete at the end of the first week: insulin binding to monocytes increased slightly but significantly (p<0.05) and the number of receptors per cell rose (p<0.05) but could not be correlated to any index of glycemic control. These data suggest that the antidiabetic action of metformin is neither related to its lactate-increasing activity nor does it depend upon its inducing an increase in insulin binding values. This metformin-related hypoglycemic effect might be the result, at least in part, of a reduced oxidative phosphorylation without inhibition of hepatic guconeogenesis and/or of decreased hepatic glucose output. Moreover, our data are also consistent with the hypothesis that metformin might affect insulin action at a post-receptor level.     

Ⅱ型糖尿病患者中胰岛素抵抗与胆石症的关系

采用病例对照研究的方法，观察40例Ⅱ型糖尿病伴胆石症和40例Ⅱ型糖尿病不伴胆石症患者的胰岛素敏感指数（ISI）、血清脂质和载脂蛋白（Apo）的变化及其相互关系。Ⅱ型糖尿病伴胆石症组与不伴胆石症组相比，ISI明显降低，甘油三酯（TG）、ApoAⅠ、B、CⅡ和E明显增高，总胆固醇（TC）、高密度脂蛋白-胆固醇（HDL-C）、ApoAⅡ和CⅢ则无显著变化。而且ISI与TG、ApoB、CⅡ和E呈负相关，与HDL-C呈正相关。多元回归分析显示胆石症与ISI呈负相关。上述结果表明胰岛素抵抗可能是Ⅱ型糖尿病患者中胆石形成的危险因素。