二甲双胍对老年2型糖尿病患者血浆乳酸水平的影响

目的观察老年2型糖尿病(T2DM)患者二甲双胍治疗后血浆乳酸水平的变化。方法收集104例老年T2DM患者的资料,按有无使用二甲双胍分为两组:使用二甲双胍超过3个月者51例(老年双胍组);未使用二甲双胍者53例(老年对照组)。同时收集使用二甲双胍的中年T2DM患者91例作为中年双胍组。比较三组血浆乳酸水平。结果老年双胍组血浆乳酸水平较老年对照组(t=0.902,P=0.369)及中年双胍组(t=0.359,P=0.720)无显著差异;老年双胍组及对照组的内生肌酐清除率(Ccr)明显低于中年双胍组(t=8.924,P=0.000和t=2.865,P=0.005);老年T2DM患者二甲双胍的用量与中年患者无显著差异(t=0.686,P=0.494)。结论二甲双胍在一定剂量范围内用于治疗老年T2DM患者不会增加乳酸酸中毒的风险。     

二甲双胍治疗糖耐量减低者的疗效分析

2003年1月～2004年12月在浙江省东阳市横店镇集团医院就诊的IGT患者,口服二甲双胍片前后测定体重指数BMI及OGTT2h血糖值.结果治疗后的体重指数BMI及OGTT2h血糖值较治疗前有明显下降.结论二甲双胍干预治疗对糖耐量减低(IGT)患者有效.     

糖耐量减低者血清IL-6、hs-CRP的变化及二甲双胍的干预作用

目的观察不同血糖水平者血清IL-6、高敏C反应蛋白（hs-CRP）水平,并比较糖耐量减低（IGT）者二甲双胍干预治疗后IL-6、hs-CRP的变化。方法选择166例受试者,行口服75 g葡萄糖耐量试验（OGTT）,按糖耐量水平分正常糖耐量（NGT）组51例、IGT 70例、2型糖尿病（T2DM）组45例,同时将IGT患者分2组,分别予二甲双胍、安慰剂干预治疗,测定各组及干预治疗前后IL-6、hs-CRP水平。结果 NGT组、IGT组、T2DM组血清IL-6、hs-CRP水平逐渐升高（P〈0.01）;IL-6、hs-CRP水平与OGTT 2h PG、糖化血红蛋白、TC、TG、LDL-C呈正相关（P均〈0.01）。二甲双胍治疗组血清IL-6、hs-CRP水平治疗后显著降低（P〈0.05）,安慰剂组无明显变化,两组治疗后比较P〈0.05。结论血清IL-6、hs-CRP水平随着糖耐量受损加重逐渐升高。应用二甲双胍干预治疗后,随着糖脂代谢的改善,血清IL-6、hs-CRP水平也下降。     

老年糖耐量低减及新诊断2型糖尿病胰岛素抵抗及胰岛β细胞功能的研究

目的　了解老年糖耐量低减 (IGT)及新诊断的 2型糖尿病 (T2 DM)患者胰岛素抵抗 (IR)及 β细胞的功能状态。方法　对 32例口服葡萄糖耐量正常者 (NGT)、34例 IGT及 45例 T2 DM患者测定口服葡萄糖耐量试验 (OGTT)各点血糖、胰岛素等指标 ,计算 HOMA模型胰岛素抵抗指数 (HOMA- IR)、β细胞功能指数 (HOM- Aβ)、胰岛素敏感性指数 (ISI)并进行统计学比较。结果　 NGT、IGT、T2 DM组 HOMA- IR分别为 0 .74±0 .75、0 .84± 0 .90、1 .2 6± 0 .79,T2 DM与 NGT比较差异有显著性 (P=0 .0 33)。 NGT、IGT、T2 DM组 HOM- Aβ分别为 5.2 7± 0 .88、5.0 4± 0 .64、4.38± 0 .91 ,其中 T2 DM组与 NGT及 IGT组比较差异均有显著性 ,分别为 P=0 .0 0 1及 P=0 .0 2 2。在 OGTT试验中 IGT组 1 2 0 min胰岛素及 1 80min胰岛素显著高于 NGT组 ,分别为 1 2 8.3± 90 .0 m IU/ L,69.6± 49.3 m IU/ L,P=0 .0 1 9;62 .1± 70 .1 m IU/ L,2 7.1± 2 4 .8m IU/ L ,P=0 .0 30。结论　老年 T2 DM表现出显著的 IR及胰岛β细胞功能减退。老年 IGT作为 T2 DM的前期 ,表现出餐后的异常高胰岛素血症     

二甲双胍对糖耐量异常患者的治疗作用观察

目的观察二甲双胍对糖耐量减低（IGT）患者的治疗效果。方法98例IGT患者采用随机双盲法分成二甲双胍组和安慰剂组,观察两组二甲双胍和安慰剂干预治疗2a后空腹血糖（FPG）及葡萄糖耐量试验（OGTT）后2h血糖（2hPG）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL）、胰岛素抵抗指数、空腹胰岛素（FINS）和OGTT后2h胰岛素（2hPINS）水平的变化。结果干预治疗2a后,二甲双胍组与安慰剂组比较FPG、2hPG、TC、TG、LDL、FINS及2hPINS均明显下降（P〈0．05）;安慰剂组糖尿病的发病率为18．4％,二甲双胍组糖尿病的发病率为4．1％,两组比较差异有统计学意义（P〈0．05）。结论二甲双胍能够降低IGT人群糖尿病的发病率,减轻胰岛素抵抗的同时,可使IGT明显改善。     

改变服药方式对糖尿病代谢控制的影响

二甲双胍是超重的 2型糖尿病患者的首选口服降糖药 ,临床上常用的二甲双胍剂型为 0 .2 5 g/粒 ,服药方式通常为 0 .2 5～ 0 .5g口服 ,每日 3次。由于次数多 ,易漏服 ,不利于血糖的控制。我们观察了 5 8名患者 ,给予不同的服药方式 ,发现当二甲双胍用量为 0 .75 g时 ,每日口服 1次 ,腹胀、恶心等副作用较每日服药 3次组无增多 ,但依从性较好。对象与方法1.对象 :5 8例均为 2 0 0 0～ 2 0 0 1年在我院就诊的患者 ,其中男 3 6例 ,女 2 3例 ,按美国糖尿病学会 (ADA) 1997年糖尿病诊断标准经标准口服葡萄糖耐量试验 (OGTT)试验诊断为糖尿病 ,…     

二甲双胍对糖耐量减低患者血清C反应蛋白的影响

目的观察糖耐量减低(IGT)患者应用二甲双胍降糖治疗前后血清C反应蛋白(CRP)水平变化.方法口服75g葡萄糖耐量试验(OGTT)筛选出糖耐量正常(NGT)15例,IGT45例,对45例IGT患者进行为期20周的随机、双盲、安慰剂对照、二甲双胍(1.5g/d)干预治疗试验.血清CRP采用数率散射比浊法测定.结果(1)IGT患者血清CRP水平比NGT明显增高,分别为(5.89±0.52)和(4.72±0.65)mg/L(P＜0.01).(2)在IGT患者,应用二甲双胍治疗20周后,血清CRP水平从5.99±0.82mg/L下降到4.78+0.43mg/L(P＜0.05),对照组从5.92±0.85mg/L下降到5.72±0.68mg/L(P＞0.05).结论①糖耐量减低时,血清CRP水平已经开始升高;②在IGT患者,应用二甲双胍降糖治疗后,随着糖代谢的改善,血清CRP水平也下降.     

二甲双胍对初诊2型糖尿病患者脂餐后代谢的急性影响

目的　观察二甲双胍 1g顿服对 2型糖尿病 (T2DM)患者脂餐后代谢的急性影响 ,探讨其降糖机理及临床新用途。　方法　初诊T2DM、葡萄糖耐量低减 (IGT)患者共 30例 ,按胰岛素抵抗指数 (Homa IR) >2、Homa IR≤ 2分为A、B两组 ,观察服二甲双胍 +脂餐及对照脂餐后 8h内血糖、胰岛素 (INS)、血脂变化。　结果　在糖化血红蛋白 (HbA1c)、空腹、餐后血糖及体重指数 (BMI)相似情况下 ,A组显示高胰岛素血症 ,餐后长时间高甘油三酯 (TG)血症及胰岛素抵抗。二甲双胍 1g顿服显著抑制A组餐后 2h血糖、游离脂肪酸 (FFA) ,长达 8h的TG及 8h低密度脂蛋白 (LDL)水平(P均 <0 .0 5 )而不引起胰岛素变化 ,而B组未见显著改变。　结论　 1g二甲双胍在胰岛素抵抗的T2DM及IGT患者起了明显的胰岛素增敏作用 ,此作用是通过直接或间接促进TG的清除或利用实现的     

二甲双胍治疗糖耐量减低者的疗效分析

2003年1月～2004年12月在浙江省东阳市横店镇集团医院就诊的IGT患者，口服二甲双胍片前后测定体重指数BMI及OGTT2h血糖值。结果 治疗后的体重指数BMI及OGTT2h血糖值较治疗前有明显下降。结论 二甲双胍干预治疗对糖耐量减低（IGT）患者有效。     

阿卡波糖和二甲双胍对IGT人群糖尿病预防的效果--多中心3年前瞻性观察

目的 比较中国糖耐量低减（IGT）人群药物干预与非药物干预对糖尿病发病率的作用。方法 对以口服75克葡萄糖耐量试验（OGTT）筛查,按1985年WHO诊断标准判定的IGT321例（年龄＞25岁）进行了3年前瞻性研究。初访时按区域分成对照组、饮食加运动组、阿卡波糖（拜唐苹）组和二甲双胍组,每年进行OGTT复查,同时空腹状态测量身高、体重、血压、血脂等。对照组除进行一般糖尿病防治知识宣教外,不进行强化教育;饮良加运动组按个体情况安排饮食及运动方案,每年重复宣教饮食及运动的治疗意义;药物干预组每月定期发放口服药物,剂量为阿卡波糖50mg每日3次,二甲双胍0．25g每日3次。结果 初访时4组基线资料无统计学差异,3年末,对照组空腹血糖（FPG）及OGTT后2小时血糖（2hPG)均有上升,平均每年糖尿病发病率为11．6％;饮食加运动组FPG及2hPG均有显著下降,每年糖尿病发病率分别为2．0％和4．1％。药物组3年末平均FPG与对照组及2hPG均有显著下降,每年糖尿病发病率分别为2．0％和4．1％。药物组3年末平均FPG与对照组、饮食加运动给比较差异有显著性。多因素比例风险模型回归分析显示基线2hPG、体重指数与糖尿病呈独立正相关,阿卡波糖和二甲双胍组治疗与糖尿病发生呈独立负相关。结论 本研究资料显示,IGT人群每年糖尿病自然发病率为11．6％,一般饮食加运动干预治疗,每年糖尿病发病率为8．2％。阿卡波糖组和二甲双胍组每年糖尿病发病率分别下降至2．0％和4．1％,2组糖尿病发病危险性分别下降87．8％和76．8％。表明在IGT干预治疗中,小剂量药物干预治疗可达到显著地减少糖尿病发生的效果。     

Effect of metformin on patients with impaired glucose tolerance.

AIMS: To evaluate the effect of metformin on glucose metabolism, insulin sensitivity and rate of conversion diabetes in people with impaired glucose tolerance (IGT). METHODS: Seventy subjects with IGT were randomized under double-blind conditions to receive either placebo (n = 37) or metformin (n = 33) at a dosage of 250 mg three times daily for a duration of 12 months. Glycaemic control, plasma insulin and other biochemical indexes were assessed before and after 3, 6 and 12 months. RESULT: At 12 months the conversion rate to diabetes was 16.2% in the placebo group compared to 3.0% for the metformin group (P = 0.011). Of subjects treated with metformin for 12 months, 84.9% became normoglycaemic compared to 51.4% of those receiving the placebo. Significant improvements in fasting glucose, glucose tolerance and insulin sensitivity were found at 12 months and at intermediate clinic assessments. CONCLUSIONS: Metformin can improve glucose metabolism in IGT patients and may be a treatment option in their management of IGT subjects.     

Subscapular skinfold thickness distinguishes between transient and persistent impaired glucose tolerance: Study on Lifestyle-Intervention and Impaired Glucose Tolerance Maastricht (SLIM).

AIMS: To assess whether adding anthropometric measurements to an oral glucose tolerance test (OGTT) can help to distinguish between transient and persistent impaired glucose tolerance (IGT). METHODS: From the SLIM project (Study on Lifestyle-Intervention and IGT Maastricht), a study designed to evaluate whether diet and physical activity intervention can improve glucose tolerance in subjects at risk for diabetes, 108 subjects with IGT underwent a repeated OGTT 2-4 months after the initial OGTT. Following the second test, subjects were classified as transient IGT, or persistent IGT. Anthropometric measurements, including body mass index, waist and hip circumference, sagittal and transverse abdominal diameters and skinfold thickness measurements, were done during the second OGTT. RESULTS: Persistent IGT was diagnosed in 47 subjects (44%), transient IGT in 40 (37%), impaired fasting glucose in eight subjects (7%), and diabetes in 13 cases (12%). Two-hour blood glucose levels at the initial OGTT and subscapular skinfold thickness were significantly higher in subjects with persistent IGT (2-h blood glucose 9.8+/-0.1 mmol/l vs. 10.2+/-0.1 mmol/l for transient IGT and persistent IGT, respectively; subscapular skinfold thickness 25.4+/-1.4 mm vs. 29.8+/-1.2 mm for transient IGT and persistent IGT, respectively). After adjustment for age, sex and family history of diabetes mellitus, logistic regression indicated that 2-h blood glucose level during the initial OGTT represented the strongest predictor of persistent IGT (P<0.02), followed by subscapular skinfold thickness (P<0.05). After adjustment for 2-h blood glucose levels during the first OGTT, subscapular skinfold thickness remained significantly associated with persistent IGT (odds ratio 1.84; P<0.05). CONCLUSIONS: In addition to the 2-h blood glucose level, subscapular skinfold thickness was the best predictor of persistent IGT, suggesting that adding simple anthropometric measures to oral glucose tolerance testing may improve the distinction between persistent and transient glucose intolerance.     

Comparison of the effects of pioglitazone and metformin on insulin resistance and hormonal markers in patients with impaired glucose tolerance and early diabetes.

Impaired glucose tolerance (IGT) is associated with cardiovascular risk factors, but the effects of pioglitazone and metformin on IGT are not well described. We tested the hypothesis that each drug would exhibit antiatherogenic and anti-inflammatory effects in subjects with IGT and early diabetes. The study design was a prospective, randomized, open label, cross-over study. Blood tests, including a 75-g oral glucose tolerance test (OGTT), were performed at baseline and after each treatment. Pioglitazone 15 mg/day or metformin 500-750 mg/day was given for 3 months. Biochemical markers to assess insulin resistance as well as lipid, inflammatory, neurohumoral, and hemostatic factors were included. Twenty-five subjects (17 male, 8 female; age [mean+/-SD]: 61+/-9 years; 84% hypertensive) completed the protocol. Of 25 subjects, 14 were diagnosed as IGT and 11 as diabetes with 75-g OGTT. Pioglitazone significantly reduced fasting glucose (p<0.05), and homeostasis model assessment of insulin resistance (HOMA-IR) (p<0.05) and metformin (p<0.01) reduced cholesterol. Both drugs significantly reduced aldosterone (both p<0.05) and von Willebrand factor (vWF) (both p<0.05). Plasma adiponectin was increased only by pioglitazone (p<0.001). Neither drug affected BP levels. In conclusion, pioglitazone was superior to metformin for the improvement of insulin resistance and adiponectin, and both drugs were equally effective in reducing vWF and aldosterone in subjects with IGT and early diabetes. Early intervention with pioglitazone or metformin therapy may reduce the incidence of future cardiovascular disease in subjects with impaired glucose tolerance or early diabetes.     

Rosiglitazone improves insulin sensitivity, glucose tolerance and ambulatory blood pressure in subjects with impaired glucose tolerance.

AIMS: To determine the effects of rosiglitazone on insulin sensitivity, glucose tolerance and ambulatory blood pressure when administered to subjects with persistent impaired glucose tolerance (IGT). METHODS: Eighteen subjects with persistent IGT were randomized to receive rosiglitazone 4 mg twice daily or matching placebo for 12 weeks. Evaluation at baseline and at the end of treatment included measurement of whole body insulin sensitivity during a euglycaemic hyperinsulinaemic clamp and deriving an insulin sensitivity index. Changes in glucose and insulin concentration were determined after oral glucose tolerance test (OGTT) and mixed meal tolerance tests, and 24-h ambulatory blood pressure was monitored. RESULTS: Rosiglitazone significantly improved the insulin sensitivity index by 2.26 micro g/kg per min per pmol/l relative to placebo (P = 0.0003). Four of nine subjects receiving rosiglitazone reverted to normal glucose tolerance and 5/9 remained IGT, although four of these had improved 2-h glucose values. In the placebo group, 1/9 subjects progressed to Type 2 diabetes and 8/9 remained IGT. Following OGTT and meal tolerance test, glucose and insulin area under curve were reduced over 3 and 4 h, respectively. Compared with placebo, ambulatory blood pressure decreased significantly in the rosiglitazone group by 10 mmHg systolic (P = 0.0066) and 8 mmHg diastolic (P = 0.0126). CONCLUSIONS: Consistent with its effects in patients with Type 2 diabetes, rosiglitazone substantially improved whole body insulin sensitivity and the glycaemic and insulinaemic responses to an OGTT and meal tolerance test in subjects with persistent IGT. Furthermore, rosiglitazone reduced systolic and diastolic ambulatory blood pressure in these subjects.     

Relationship between insulin resistance and left ventricular diastolic dysfunction in patients with impaired glucose tolerance and type 2 diabetes

AIM: The aim of this study was to explore the relationship between insulin resistance (IR) and the left ventricular diastolic function in patients with type 2 diabetes and subjects with impaired glucose tolerance (IGT). METHODS: The study included 119 subjects who underwent oral glucose tolerance test (OGTT). IR was assessed using Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) and Quantitative Insulin Sensitivity Check Index (QUICKI). Left ventricular diastolic function was assessed using trans-thoracic Doppler echocardiography. RESULTS: Based on the OGTT results, 29 subjects had normal glucose tolerance (NGT), 20 subjects had impaired glucose tolerance (IGT), and 70 patients had type 2 diabetes. There were significant differences among the patients in groups with NGT, IGT and diabetes regarding HOMA-IR (4.20 +/- 1.20 vs. 6.45 +/- 3.83 vs. 8.70 +/- 6.26; P < 0.001) and QUICKI (0.54 +/- 0.11 vs. 0.49 +/- 0.08 vs. 0.47 +/- 0.08; P < 0.001). In subjects with NGT, IGT and patients with diabetes, the pulsed Doppler transmitral variables were: E-wave (0.72 +/- 0.16 cm/s vs. 0.62 +/- 0.13 cm/s vs. 0.58 +/- 0.17 cm/s; P < 0.001), A-wave (0.61 +/- 0.13 cm/s vs. 0.62 +/- 0.11 cm/s vs. 0.71+/- 0.14 cm/s; P = 0.006) and E/A ratio (1.22 +/- 0.33 vs. 1.02 +/- 0.24 vs. 0.85 +/- 0.26; p < 0.001). The proportion of subjects with an E/A ratio <1 was 27.6% in the group with NGT, 55% in the group with IGT and 75.7% in the group with diabetes (P < 0.001). The E/A ratio correlated with HOMA-IR (r = -0.30, p = 0.001) and QUICKI (r = 0.37, p < 0.0001). Multiple linear regression model showed that IR (assessed by QUICKI) was an independent correlate of diastolic dysfunction (P = 0.034). CONCLUSIONS: In subjects with impaired glucose tolerance and patients with type 2 diabetes, insulin resistance is associated with impaired diastolic function of the left ventricle.     

Long-term beneficial effects of glipizide treatment on glucose tolerance in subjects with impaired glucose tolerance

AIMS: To assess the efficacy and long-term effects of glipizide treatment on glucose and insulin metabolism in individuals with impaired glucose tolerance (IGT). METHODS: Thirty-seven first-degree relatives of patients with type 2 diabetes fulfilling WHO criteria for IGT were randomized to treatment with either glipizide 2.5 mg once daily or matching placebo for 6 months. A 75 g, 2-h oral (OGTT) and 60 min intravenous glucose tolerance test (IVGTT) were performed at baseline and after 6 months. The subjects were followed up for another 12 months after discontinuation of treatment and a repeat OGTT was performed at 18 months. RESULTS: Thirty-three subjects fulfilled the study. Markers of insulin sensitivity - i.e. fasting insulin and HOMA(IR)-index - improved in the glipizide group (P = 0.04 and 0.02 respectively) as well as HDL cholesterol (P = 0.05) compared with placebo group after 6 months. At 18 months, both fasting and 2 h glucose concentrations were significantly lower in the glipizide group compared with the placebo group (P = 0.04 and 0.03 respectively). The prevalence of type 2 diabetes was 29.4% in the placebo group and 5.9% in the glipizide group at 18 months. This equals an 80% relative risk reduction in the active treatment group. CONCLUSIONS: Short-term treatment with glipizide improves glucose and insulin metabolism in subjects with IGT primarily by improving insulin sensitivity mediated by lowering glucose toxicity, thereby providing the beta cells rest. Larger studies are needed to establish whether these effects are sufficient to prevent progression to manifest type 2 diabetes and associated cardiovascular morbidity in subjects at increased risk of developing type 2 diabetes.     

Metabolic effects of metformin in patients with impaired glucose tolerance.

AIMS: To assess the effect of metformin on insulin sensitivity, glucose tolerance and components of the metabolic syndrome in patients with impaired glucose tolerance (IGT). METHODS: Forty first-degree relatives of patients with Type 2 diabetes fulfilling WHO criteria for IGT and participating in the Botnia study in Finland were randomized to treatment with either metformin 500 mg b.i.d. or placebo for 6 months. An oral glucose tolerance test (OGTT) and a euglycaemic hyperinsulinaemic clamp in combination with indirect calorimetry was performed at 0 and 6 months. The patients were followed after stopping treatment for another 6 months in an open trial and a repeat OGTT was performed at 12 months. RESULTS: Metformin treatment resulted in a 20% improvement in insulin-stimulated glucose metabolism (from 28.7 +/- 13 to 34.4 +/- 10.7 micromol/kg fat-free mass (FFM)/min) compared with placebo (P = 0.01), which was primarily due to an increase in glucose oxidation (from 16.6 +/- 3.6 to 19.1 +/- 4.4 micromol/kg FFM; P = 0.03) These changes were associated with a minimal improvement in glucose tolerance, which was maintained after 12 months. CONCLUSIONS: Metformin improves insulin sensitivity in subjects with IGT primarily by reversal of the glucose fatty acid cycle. Obviously large multicentre studies are needed to establish whether these effects are sufficient to prevent progression to manifest Type 2 diabetes and associated cardiovascular morbidity and mortality. Diabet. Med. 18, 578-583 (2001)     

不同状态的糖调节受损患者胰岛素分泌和胰岛素敏感性的差异

目的评估初发的单纯空腹血糖受损（IFG）和单纯糖耐量受损（IGT）患者的胰岛素分泌以及胰岛素敏感性（IS）特征。方法北京市东城区既往无糖尿病史的2388名受试者行葡萄糖耐量试验,同时行胰岛素释放试验,本文纳入2244例,其中糖耐量正常（NGT）1608例,IFG240例,IGT243例,IFG＋IGT 153例。比较各组胰岛素抵抗指数（HOMA-IR）、IS指数（Matsudaindex）、B细胞功能指数（1相Stumvoll index、△I30／△G30）。结果与NGT组比较,其余三组HOMA-IR显著升高,Matsuda指数及B细胞功能指数均显著降低（P均〈0．01）;IFG组HOMA-IR及Matsuda指数均高于IGT组;IFG组△I30／△G30高于IGT组,而Stumvoll指数低于IGT组（P〈0．01）;与IFG组、IGT组比较,IFG＋IGT组HOMA-IR显著升高,Matsuda指数、1相Stumvoll指数显著降低（P均〈0．01）。结论糖尿病前期人群存在不同程度的胰岛素分泌缺陷和IR,IFG组肝IR较重,而IGT组肌肉IR较重。     

The G-250A promoter polymorphism of the hepatic lipase gene predicts the conversion from impaired glucose tolerance to type 2 diabetes mellitus: the Finnish Diabetes Prevention Study

In population-based studies, dyslipidemia related to insulin resistance (high triglyceride level and low high-density lipoprotein cholesterol level) is a risk factor for type 2 diabetes. Therefore, variants in genes regulating lipid and lipoprotein metabolism are potential candidate genes for diabetes. We investigated whether the G-250A polymorphism of the hepatic lipase gene (LIPC) predicts the conversion from impaired glucose tolerance (IGT) to type 2 diabetes in the Finnish Diabetes Prevention Study. This study randomized subjects to either the intervention group (lifestyle modification aimed at weight loss, such as changes in diet and increased physical exercise) or the control group. Genotyping at position -250 of the LIPC gene was performed with PCR amplification, DraI enzyme digestion, and gel electrophoresis in 490 subjects with IGT whose DNA was available. In the entire study population, the conversion rate to type 2 diabetes was 17.8% among subjects with the G-250G genotype and 10.7% among subjects with the -250A allele (P = 0.032). In univariate analysis, the odds ratio for the G-250G genotype to predict the conversion from IGT to type 2 diabetes was 1.80 (95% confidence interval, 1.05-3.10; P = 0.034). In multivariate logistic regression analysis, the G-250G genotype predicted the conversion to diabetes independently of the study group (control or intervention), gender, weight, waist circumference at baseline, and change in weight and waist circumference. In the intervention group, 13.0% of subjects with the G-250G genotype and 1.0% of the subjects with the -250A allele converted to diabetes (P = 0.001). We conclude that the G-250G genotype of the LIPC gene is a risk factor for type 2 diabetes. Therefore, genes regulating lipid and lipoprotein metabolism may be potential candidate genes for type 2 diabetes.     

不同糖耐量者血清游离脂肪酸与胰岛素抵抗的关系

以口服糖耐量试验(OGTT)确定受试者为正常人,糖耐量低减(IGT)和2型糖尿病,并测定空腹和OGTT 2h的游离脂肪酸(FFA)、血糖和胰岛素浓度,计算胰岛素敏感指数(IAI)。2型糖尿病和IGT患者的空腹和OGTT 2 h FFA、血糖和胰岛素浓度均明显高于正常组(均P<0.05),IAI均明显低于正常对照组(均P<0.01)。空腹及OGTT 2 h FFA与IAI之间呈显著负相关(分别为r=-0.38,P<0.01和r=-0.32,P<0.05),体重指数与IAI呈显著负相关(r=-0.39,P<0.05)。上述结果提示脂毒性在2型糖尿病的发病机制中有重要作用。