Decreased active GLP-1 response following large test meal in patients with type 1 diabetes using bolus insulin analogues

Postprandial plasma immunoreactive active glucagon-like peptide-1 (p-active GLP-1) levels in type 1 diabetic patients who did not use bolus insulin responded normally following ingestion of test meal, while a small response of p-active GLP-1 levels was seen in type 2 diabetic patients. To determine whether p-active GLP-1 levels are affected by ingestion of test meal in type 1 diabetic Japanese patients who used bolus rapid-acting insulin analogues, plasma glucose (PG), serum immunoreactive insulin (s-IRI), serum immunoreactive C-peptide (s-CPR), and p-active GLP-1 levels were measured 0, 30, and 60 min after ingestion of test meal in Japanese patients without diabetic complications (n=10, group 1) and control subjects with normal glucose tolerance (n=15, group 2). HbA1c levels were also measured in these groups. The patients in group 1 were treated with multiple daily injections or CSII using injections of bolus rapid-acting insulin analogues before ingestion of test meal. There was no significant difference in mean of sex, age, or BMI between groups. Means of HbA1c, basal and postprandial PG, and postprandial s-IRI levels with integrated areas under curves (0-60 min) (AUC) in group 1 were significantly higher than those in group 2. Means of basal and postprandial s-CPR, and postprandial p-active GLP-1 levels with AUCs were significantly lower in group 1 than in group 2. These results indicated that postprandial p-active GLP-1 levels following ingestion of test meal in type 1 diabetic Japanese patients using bolus rapid-acting insulin analogues were decreased relative to those in controls.     

Comparison of annual variability in HbA1c and glycated albumin in patients with type 1 vs. type 2 diabetes mellitus

ObjectiveIt has been suggested that plasma glucose (PG) levels per se and long-term variations in PG levels are associated with diabetic vascular complications. Glycated albumin (GA) reflects shorter-term glycemic control, as well as postprandial PG levels, as compared to HbA1c. In this study, we hypothesized that GA more strongly reflects long-term variations in PG levels than HbA1c, and compared the variability of HbA1c and that of GA in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM).MethodsThis study included 8 T1DM patients and 48 T2DM patients. Over a 1-year period, HbA1c and GA were measured every month and the mean values and coefficients of variation (CV) for each patient were calculated.ResultsIn both T1DM and T2DM patients, the CV of GA was significantly higher than the CV of HbA1c. Both the CV of HbA1c and the CV of GA were significantly higher in the T1DM patients than in the T2DM patients.ConclusionThe annual variability in GA was greater than that in HbA1c. In addition, the annual variability in HbA1c and that in GA in the T1DM patients were greater than in the T2DM patients. Our findings suggest that GA more accurately reflects long-term variations in PG levels than HbA1c.     

2型糖尿病合并高尿酸血症患者动脉粥样硬化的影响因素

目的研究2型糖尿病合并高尿酸血症(HUADM)患者颈动脉内膜中层厚度(IMT)与脂联素、C反应蛋白(CRP)的关系。方法选择2型糖尿病患者85例,按血尿酸水平分为:HUADM组43例、血尿酸正常糖尿病(NUADM)组42例,分析2组空腹血糖(FPG)、空腹胰岛素(FINS)、脂联素、CRP、糖化血红蛋白(HbA1c)及餐后2h血糖、餐后2h胰岛素,IMT,计算胰岛素抵抗指数(HOMA-IR),并且进行多元逐步回归分析。结果与NUADM组比较,HUADM组患者FPG、餐后2h血糖、FINS、餐后2h胰岛素、HbA1c、IMT、尿酸和lgHOMA-IR均明显升高,脂联素明显降低(P0.05,P0.01)。HUADM组患者IMT与HOMA-IR、TG、LDL-C和CRP呈正相关,与脂联素呈负相关。结论 HUADM患者存在更明显的代谢紊乱和胰岛素抵抗,且血清脂联素水平降低,CRP水平升高,提示更容易发生动脉粥样硬化。     

T2DM酮症患者血清脂联素水平变化及其与血脂的关系

目的探讨2型糖尿病（T2DM）酮症患者血清脂联素（APN）水平的变化，以及其与血脂等因素的相关性。方法选择T2DM酮症患者（酮症组）52例，无酮症患者（非酮症组）58例；另选健康个体54例为正常对照（NC）组。分别测身高、体重、空腹血清APN、血糖、HbA1c、血脂。结果两组患者血清APN水平明显低于NC组（P〈0.01）。酮症组APN水平明显低于非酮症组（P〈0.01）。血清APN水平与HbA1c、TC、TG呈负相关，与HDL-C呈正相关，酮症组患者酮症纠正后APN水平与非酮症患者相比，差异无统计学意义。结论糖尿病酮症期间APN水平明显降低，酮症纠正后恢复。     

初诊2型糖尿病患者血清25-羟维生素D3水平与胰岛β细胞功能和胰岛素抵抗的相关性

目的 评估初诊2型糖尿病患者低维生素D血症发生率,探讨血清25-羟维生素D3与胰岛β细胞功能和胰岛素抵抗的关系.方法 入选2008年4至7月在四川省人民医院就诊的初诊2型糖尿病患者97例（糖尿病组）,其中男57例,女40例,年龄（52±10）岁.以同期健康体检者69名为对照组,其中男40名,女29名,年龄（50±11）岁.采用高压液相色谱法测定2组参试者空腹血清25-羟维生素D3水平.根据25-羟维生素D3是否＜37.5 nmol/L将糖尿病组分为低25-羟维生素D3亚组（n=61）和非低25-羟维生素D3亚组（n=36）,比较糖化血红蛋白、稳态模型胰岛素抵抗指数、胰岛β细胞功能指数、早期相胰岛素分泌指数、葡萄糖曲线下面积、胰岛素曲线下面积.采用多元逐步回归分析评价血清25-羟维生素D3与性别、年龄、体质指数、腰臀比、血压、血脂、糖化血红蛋白、胰岛素抵抗及胰岛β细胞功能的相关性.结果 糖尿病组血清25-羟维生素D3水平显著低于对照组[（36±19）nmol/L vs（80±26）nmol/L,t=-13.00,P＜0.01].糖尿病组低25-羟维生素D3的发生率为62.9%（61/97）.与非低25-羟维生素D3亚组比较,低25-羟维生素D3亚组糖化血红蛋白、葡萄糖曲线下面积较高[（10.1±3.0）% vs （7.7±2.6）%,（32±7）h·mmol-1·L-1 vs （25±7）h·mmol-1·L-1,t值分别为4.44、4.45,均P＜0.01],胰岛β细胞功能指数、早期相胰岛素分泌指数、胰岛素曲线下面积较低[21±16 vs 75±64,1.9±1.9 vs 8.3±7.7,（30±21）h·mU-1·L-1vs（104±80）h·mU-1·L-1,t值分别为-5.68、-6.81、-7.69,均P＜0.01].多元逐步回归分析显示,2型糖尿病患者早期相胰岛素分泌指数、胰岛素曲线下面积与25-羟维生素D3独立正相关（t值分别为2.21、4.67,均P＜0.01）.结论部分初诊2型糖尿病患者存在25-羟维生素D3缺乏,缺乏程度与血糖升高程度有关;25-羟维生素D3缺乏与早期相胰岛素分泌和总体胰岛素分泌下降有关.     

2型糖尿病患者腹部脂肪分布与糖尿病并发症的相关性研究

目的探讨2型糖尿病患者腹部脂肪分布与糖脂代谢及糖尿病并发症的关系。方法选本院内分泌科住院的2型糖尿病患者357例,定量CT测量内脏脂肪(VAT)和皮下脂肪(SAT)面积,同时检查患者糖尿病肾病、视网膜病变、周围神经病变、外周动脉粥样硬化、心脑血管疾病的患病情况。根据VAT的值以三分位数法分为3组:T1组(VAT<162.0 cm^2)、T2组(162.0≤VAT<221.1 cm^2)、T3组(VAT≥221.1 cm^2)。结果T1组HbA1C水平高于T3组(P<0.05);T1组高密度脂蛋白胆固醇(HDL-C)、肾小球滤过率(eGFR)高于T2、T3组(P<0.05);T2、T3组男性比例、年龄、体重指数(BMI)、收缩压、舒张压、三酰甘油(TG)、24h尿白蛋白、糖尿病肾病和外周动脉粥样硬化的比例高于T1组(P<0.05);T3组空腹C肽(FCP)、改良稳态模型评估的胰岛素抵抗指数(HOMA-IR)高于T1、T2组(P<0.01)。Spearman相关分析显示,VAT、SAT与BMI、FCP、HOMA-IR呈正相关(P<0.01),VAT与年龄、收缩压、舒张压、TG、24h尿白蛋白、糖尿病肾病、外周动脉粥样硬化、心脑血管疾病呈正相关(P<0.05),与HbA1C、HDL-C、eGFR呈负相关(P<0.05),SAT与总胆固醇、低密度脂蛋白胆固醇呈正相关(P<0.01),与外周动脉粥样硬化呈负相关(P<0.01)。多因素相关分析显示,校正年龄、BMI、收缩压、空腹血糖等因素后,VAT仍是发生糖尿病肾病的危险因素(P=0.013)。结论VAT、SAT均与血脂和胰岛素抵抗相关,VAT可能是2型糖尿病患者发生糖尿病肾病的危险因素。     

Factors responsible for deteriorating glucose tolerance in newly diagnosed type 2 diabetes in Japanese men

Hyperglycemia frequently continues to worsen even after the diagnosis of overt diabetes. The aim of this study is to evaluate the factors contributing to increasing glucose intolerance after onset of type 2 diabetes in Japanese subjects. Five hundred fifty newly diagnosed type 2 diabetic patients were classified into 3 degrees of hyperglycemia based on plasma glucose levels estimated by 75-g oral glucose tolerance test: diabetes mellitus with isolated fasting hyperglycemia (DM/IFH), DM with isolated postchallenge hyperglycemia (DM/IPH), and DM with fasting and postchallenge hyperglycemia (DM/FPH). In addition, the DM/IFH and DM/IPH groups were subdivided to clarify the determinants of fasting and postchallenge hyperglycemia. Insulin secretion was evaluated by insulinogenic index, and insulin sensitivity was evaluated by composite index of insulin sensitivity (ISI composite). The insulinogenic index in DM/IFH was highest of the 3 groups (P < .0001). The insulinogenic index in DM/IPH was higher than in DM/FPH (P < .0001). The international sensitivity index composite in DM/IPH was highest of the 3 groups (P < .05). Although impaired early-phase insulin secretion plays the crucial role in deterioration from DM/IFH to DM/FPH in Japanese subjects, impaired early-phase insulin secretion and decreased insulin sensitivity both are factors in deterioration from DM/IPH to DM/FPH. In addition, comparison of subgroups of DM/IFH and DM/IPH shows that although decreased early-phase insulin secretion plays the more significant role in postchallenge hyperglycemia in Japanese subjects, insulin sensitivity is the more important factor in fasting hyperglycemia.     

老年2型糖尿病发生骨质疏松的临床多因素分析

目的 探讨老年2型糖尿病(T2DM)患者发生骨质疏松的影响因素. 方法 根据患者的骨密度值将患者分为骨量正常(NOP)组、低骨量(LBMD)组、骨质疏松(OP)组,对比3组在年龄、糖尿病病程、体质量指数(BMI)、胱抑素C(Cys C)、经皮氧分压检查(TcPO2)、糖化血红蛋白(HbA1c)、尿C肽(U-CP)等指标之间的差异,并进行相关性分析. 结果 (1)与NOP组相比,LBMD及OP组年龄、病程显著性升高,U-CP显著性下降;(2)OP组BMI、Cys C显著低于NOP组;(3)OP组年龄显著高于LBMD组,而BMI显著低于LBMD组(P＜0.05或P＜0.01).老年T2DM患者的BMD与年龄、病程呈负相关,与BMI、U-CP呈正相关.逐步多元回归分析显示U-CP是BMD的正性预测因子. 结论 老年T2DM患者并发骨质疏松与多因素有关,包括高龄、低体质量、病程长、胰岛功能差等.     

血尿酸和细胞间黏附分子1对2型糖尿病颈动脉内膜中层厚度的影响

目的探讨2型糖尿病合并颈动脉粥样硬化(CA)患者血尿酸、细胞间黏附分子1(ICAM-1)与颈动脉内膜中层厚度(IMT)的关系。方法选择2型糖尿病患者80例,根据诊断分为糖尿病合并颈动脉粥样硬化组(CA组)40例和单纯糖尿病组(对照组)40例,检测分析2组患者血尿酸、ICAM-1、收缩压、舒张压、空腹血糖、空腹胰岛素、糖化血红蛋白、餐后2 h血糖、餐后2 h胰岛素、HDL-C、LDL-C、TC、TG等糖、脂代谢指标及颈动脉IMT的水平差异。同时计算体重指数、胰岛素抵抗指数(HOMA-IR)。结果 CA组颈动脉IMT、血尿酸、ICAM-1、收缩压、体重指数、TG、TC、LDL-C、糖化血红蛋白、空腹血糖、餐后2 h血糖、空腹胰岛素、餐后2 h胰岛素、HOMA-IR均明显高于对照组(P<0.05,P<0.01)。血尿酸、ICAM-1与颈动脉IMT密切相关(P<0.01),作为CA的主要独立影响因素最先进入多元逐步回归方程。结论 2型糖尿病合并CA患者较无CA的糖尿病患者存在更明显的代谢紊乱、胰岛素抵抗、血管内皮功能障碍及炎性反应,早期联合检测血尿酸、ICAM-1有助于对糖尿病人群发生血管病变进行预测。     

Insulin secretion and insulin sensitivity at different stages of glucose tolerance: a cross-sectional study of Japanese type 2 diabetes

To evaluate the factors causing glucose intolerance in type 2 diabetes in Japan, insulin secretion and insulin sensitivity were compared across the range of glucose tolerance. Subjects were divided into 3 groups: normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes (DM) according to the criteria of the World Health Organization (WHO). We examined insulin secretion and insulin sensitivity using fasting blood glucose and insulin levels and 75 g oral glucose tolerance test (OGTT). We used homeostasis model assessment (HOMA) beta-cell and insulinogenic index (30 minutes) to estimate insulin secretion and HOMA-insulin resistance (IR) and insulin sensitivity index (ISI) composite for insulin sensitivity. Although insulin resistance plays an important role in the development of diabetes in many ethnic populations, the differences in insulin sensitivity between NGT and IGT and between IGT and DM are small in Japanese patients. On the other hand, as glucose intolerance increases, insulin secretion decreases most remarkably both between NGT and IGT and between IGT and DM in Japanese patients. Decreasing insulin secretion and decreasing insulin sensitivity both occur in developing type 2 diabetes in Japanese patients, but decreased basal and early-phase insulin secretion had more pronounced contribution to glucose tolerance than the indices of insulin sensitivity. Japanese type 2 diabetic patients are characterized by a larger decrease in insulin secretion and show less attribution of insulin resistance.     

褪黑素对2型糖尿病患者血管内皮功能的影响

目的:探讨褪黑素对2型糖尿病患者血管内皮功能的影响。方法:选择早期无大血管并发症的2型糖尿病患者60例,随机分为试药组和对照组各30例,对照组采用饮食、运动、胰岛素治疗,试药组加用褪黑素（MLT）胶囊6 mg,每晚口服,共治疗6个月。同期选择28例健康个体为正常对照组。治疗前后检测血压、空腹血糖（FPG）、餐后2 h血糖（2hPG）、糖化血红蛋白（HbA1c）、三酰甘油（TG）、低密度脂蛋白胆固醇（LDL-C）、高密度脂蛋白胆固醇（HDL-C）,计算体质量指数（BMI）。用高分辨率超声检测、计算肱动脉血流介导的内皮依赖性血管舒张功能(FMD)和硝酸甘油介导的内皮非依赖性血管舒张功能(NMD)。结果:①与正常对照组比较,糖尿病组治疗前FPG、2hPG、HbA1c、TG、LDL-C明显增高(均P<0.01),HDL-C明显降低(P<0.05)。 治疗半年后糖尿病组TG、LDL-C略下降,BMI、HDL C略升高但均无统计学差异,FBG、2hPG、HbA1c无明显变化。②与正常对照组比较, 糖尿病组治疗前肱动脉基础内径、NMD无显著差异,FMD明显降低（均P<0.01）。治疗半年后糖尿病各组肱动脉基础内径、NMD无明显变化;FMD明显升高（P<0.05或P<0.01）,试药组FMD明显高于对照组（P<0.05）。结论:2型糖尿病患者早期出现血管内皮舒张功能降低,褪黑素明显改善2型糖尿病早期患者受损血管内皮功能。     

2型糖尿病患者胰岛β细胞功能与泌汗功能的相关性

目的探讨2型糖尿病(T2DM)患者胰岛β细胞功能与泌汗功能的关系。方法选取2016年3月至2018年5月于东部战区总医院内分泌科住院的385例T2DM患者为研究对象,根据SUDOSCAN仪测得的手和足电化学传导率[双手平均电化学传导率(HESC)、双足平均电化学传导率(FESC)]将患者分为泌汗功能正常组(262例)和泌汗功能异常组(123例)。采用稳态模型评估胰岛β细胞功能指数(HOMA-β)评估基础胰岛素分泌;采用糖负荷30 min净增C肽与葡萄糖比值(ΔC-P30/ΔG30)和净增胰岛素与葡萄糖比值(ΔI30/ΔG30)评估早相胰岛素分泌功能;采用120 min血糖曲线下面积(AUC)校正后的C肽和胰岛素AUC(C-PAUC/GAUC、IAUC/GAUC)评估总的β细胞分泌功能。相关分析采用Spearman线性相关分析及多元逐步线性回归分析。结果(1)与泌汗功能正常组相比,泌汗功能异常组患者ΔC-P30/ΔG30和ΔI30/ΔG30均更低[分别为0.19(0.08,0.30)比0.30(0.19,0.53)和1.47(0.67,3.28)比2.26(1.28,4.65),Z=-5.495、-3.897;P均<0.05],C-PAUC/GAUC和IAUC/GAUC也更低[分别为0.07(0.04,0.16)比0.12(0.06,0.25)和2.79(0.76,6.35)比3.30(1.35,8.32),Z=-3.894、-2.092;P均<0.05]。(2)ΔC-P30/ΔG30、ΔI30/ΔG30与HESC(分别为r=0.306、0.272,P均<0.05)、FESC(分别为r=0.304、0.233,P均<0.05)均呈正相关。(3)多元逐步线性回归分析显示,ΔC-P30/ΔG30、病程、年龄、糖化血红蛋白以及血尿酸是泌汗功能的独立影响因素。结论T2DM患者早相胰岛素分泌功能受损与泌汗功能障碍独立正相关;对于早相胰岛素分泌功能受损的患者应尽早评估泌汗功能,以便早期筛查糖尿病周围神经病变。     

Plasma gastric inhibitory polypeptide and glucagon‐like peptide‐1 levels after glucose loading are associated with different factors in Japanese subjects

Aims/Introduction: Gastric inhibitory polypeptide (GIP) and glucagon‐like peptide‐1 (GLP‐1) are major incretins that potentiate insulin secretion from pancreatic β‐cells. The factors responsible for incretin secretion have been reported in Caucasian subjects, but have not been thoroughly evaluated in Japanese subjects. We evaluated the factors associated with incretin secretion during oral glucose tolerance test (OGTT) in Japanese subjects with normal glucose tolerance (NGT). Materials and Methods: We measured plasma GIP and GLP‐1 levels during OGTT in 17 Japanese NGT subjects and evaluated the factors associated with GIP and GLP‐1 secretion using simple and multiple regression analyses. Results: GIP secretion (AUC‐GIP) was positively associated with body mass index (P < 0.05), and area under the curve (AUC) of C‐peptide (P < 0.05) and glucagon (P < 0.01), whereas GLP‐1 secretion (AUC‐GLP‐1) was negatively associated with AUC of plasma glucose (P < 0.05). The insulinogenic index was most strongly associated with GIP secretion (P < 0.05); homeostasis model assessment β‐cell was the most the strongly associated factor in GLP‐1 secretion (P < 0.05) among the four indices of insulin secretion and insulin sensitivity. Conclusions: Several distinct factors might be associated with GIP and GLP‐1 secretion during OGTT in Japanese subjects. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00078.x, 2011)     

Association between body mass index and core components of metabolic syndrome in 1486 patients with type 1 diabetes mellitus in Japan (JDDM 13)

There is no recent study on the prevalence of overweight and obesity in patients with type 1 diabetes mellitus (T1DM) in Japan. Being overweight has a significant effect on the metabolic condition and glycemic control of such patients. In the present cross-sectional study, we investigated the effects of body mass index (BMI) on lipid profile, blood pressure, and glycemic control in patients with T1DM. In total, 1486 patients with T1DM (including 401 patients with early onset T1DM who were <20 years of age at diagnosis) were included. Patients were divided into four groups according to their BMI, and glycosylated hemoglobin (HbA1c), daily insulin dose per kg body weight, lipid profile, and blood pressure were compared between groups. We found that 15.7% of all patients were overweight (BMI >or= 25.0 kg/m(2)) and 2.0% were obese (BMI >or= 30.0 kg/m(2)), compared with 17.5% and 2.0%, respectively, in the early onset T1DM subgroup. Significant changes in lipid profiles and blood pressure were found with increasing BMI in both the entire population and the early onset T1DM subgroup. In the entire study population HbA1c and the body weight-adjusted daily insulin dose were significantly higher in patients with a BMI >or= 23 kg/m(2) compared with those with a BMI<23 kg/m(2); however, this was not the case in the early onset T1DM subgroup. This difference may be due to the relatively small number of patients in that subgroup. In conclusion, the prevalence of overweight and obesity in patients with T1DM was less than that in the normal Japanese population. For patients with T1DM, being overweight was associated with higher blood pressure and dyslipidemia. Furthermore, we cannot exclude an association between being overweight and the need for higher daily doses of insulin.     

2型糖尿病并发非酒精性脂肪肝患者的临床特征及影响因素分析

目的分析并发非酒精性脂肪肝(NAFLD)的2型糖尿病(T2DM)患者的临床特征,探讨T2DM患者发生NAFLD的影响因素。方法选取T2DM患者167例,收集患者性别、年龄、糖尿病病程、身高、体质量等一般资料,采集空腹血糖(FPG)、TG、TC、LDL-C、HDL-C、糖化血红蛋白(HbA1c)、ALT、AST、空腹胰岛素、空腹-C肽(FCP)等实验室检查指标。于空腹状态下行腹部肝脏多普勒超声检查,根据检查结果诊断是否存在NAFLD。比较有、无并发NAFLD的T2DM患者的一般资料、实验室检查指标;比较不同HbA1c、TG、TC、BMI水平分层的T2DM患者的NAFLD发生率;分析T2DM患者并发NAFLD的相关危险因素。结果根据B超检查结果,分为单纯T2DM患者86例、T2DM并发NAFLD患者81例。T2DM并发NAFLD患者的HbA1c、TG、TC、BMI、ALT、FCP均高于单纯T2DM患者,糖尿病病程小于单纯T2DM患者(P均<0.05)。HbA1c>8.9%、TG>1.7 mmol/L、BMI>23.43 kg/m²的T2DM患者并发NAFLD的发生率较高(P均<0.05)。以是否并发NAFLD为因变量,临床指标为自变量进行logistic回归分析示,FCP(OR=0.737,P=0.009)、BMI(OR=0.786,P=0.003)、HbA1c(OR=0.996,P<0.001)是导致T2DM患者并发NAFLD的独立危险因素。结论血糖控制不佳、血脂水平较高、病程短的T2DM患者更易出现NAFLD。FCP、BMI、HbA1c是导致T2DM患者发生NAFLD的独立危险因素。建议对BMI超过23.43 kg/m²、高脂血症的T2DM人群进行肝脏彩超筛查,及时预防NAFLD发生。     

Determinants of insulin secretion and sensitivity in bangladeshi type 2 diabetic subjects

Background: The relative contribution of insulin secretion and sensitivity in the development of type 2 diabetes mellitus (T2DM) vary from population to population due to the heterogeneous nature of the disease. The study was undertaken to evaluate the insulin secretory capacity and sensitivity in a Bangladeshi type 2 diabetic population and to explore the association of some of the anthropometric (BMI, WHR, MBP) and biochemical factors (glucose, lipids, HbA(1c)) known to modulate B-cell function and insulin action. Methods: Ninety three T2DM and 70 age-matched control subjects were studied for their fasting glucose, lipids, HbA(1c) (by HPLC) and C-peptide (by ELISA). Insulin secretion (HOMA B) and insulin sensitivity (HOMA S) were calculated by homeostasis model assessment (HOMA). Results: Both insulin secretion and sensitivity were significantly reduced in diabetic as compared to control subjects (HOMA B%, geometric M +/- SD, 34.67 +/- 1.73 vs 104.71 +/- 1.34, p < 0.001; HOMA S%, 67.60 +/- 1.69 vs 85.11 +/- 1.54, p < 0.01). However, the discriminant function coefficient for HOMA B (1.142) was about 1.5 times higher than that for HOMA S (0.731). In T2DM, HOMA B had positive correlation with BMI (r = 0.362, p < 0.001) and inverse correlation with plasma glucose (r = - 0.701, p < 0.001) and HbA1c (r = - 0.612, p < 0.001). HOMA S was inversely correlated to BMI (r = - 0.274, p < 0.01), WHR (r = - 0.252, p < 0.05), plasma total cholesterol (r = - 0.240, p < 0.05) and triglycerides (r = 0.301, p < 0.01). Conclusions: Both insulin secretory dysfunction and insulin resistance are present in Bangladeshi T2DM subjects, but B-cell dysfunction seems to be the predominant defect. BMI, plasma glucose and insulin are the major determinants of insulin secretory capacity; and generalized as well as central obesity, plasma glucose, total cholesterol, triglycerides and insulin are among the major determinants of insulin sensitivity in this population.     

利拉鲁肽对2型糖尿病合并阻塞性睡眠呼吸暂停低通气综合征患者睡眠呼吸紊乱及微血管病变的影响

目的探讨胰高糖素样肽-1(GLP-1)类似物对2型糖尿病(T2DM)合并阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者睡眠呼吸紊乱及微血管病变的影响。方法选取2017年1月至2018年12月河南省人民医院内分泌科及睡眠中心239例T2DM住院患者为研究对象,进行多导睡眠图(PSG)监测及糖尿病微血管病变筛查,纳入患糖尿病微血管病变的T2DM合并OSAHS患者93例,其中利拉鲁肽治疗患者50例作为治疗组,常规降糖治疗患者43例作为对照组,比较两组治疗6个月前后体质指数(BMI)、腰围、糖化血红蛋白(HbA1c)、血压、血脂、尿酸、呼吸暂停低通气指数(AHI)等指标的变化及糖尿病微血管病变改善情况。两组间比较采用t检验、非参数秩和检验或χ2检验,评价各指标与AHI变化值的相关性采用偏相关分析、协方差分析,利拉鲁肽与糖尿病微血管病变改善的相关性采用Logistic回归分析。结果治疗后利拉鲁肽治疗组较对照组BMI、腰围、HbA1c、收缩压、AHI下降更显著[分别为(-1.85±2.46)比(0.02±0.46)kg/m2、(-3.24±10.34)比(-0.07±0.88)cm、(-0.83±0.55)%比(-0.06±0.40)%、(-7.92±14.16)比(-0.56±16.16)mmHg(1 mmHg=0.133 kPa)、(-3.16±3.52)比(0.5±1.54)次/h,t=2.159~7.703,均P<0.05],糖尿病周围神经病变改善比例更高[26.0%(13/50)比9.3%(4/43),χ2=4.315,P<0.05]。治疗后AHI变化值与BMI变化值、腰围变化值、HbA1c变化值呈正相关(r=0.238、0.232、0.317,均P<0.05),与年龄呈负相关(r=-0.21,P<0.05)。调整年龄、糖尿病病程、BMI、腰围、收缩压、HbA1c等因素后,利拉鲁肽与AHI变化值水平有关(F=8.155,P=0.005)。调整年龄、糖尿病病程、BMI、腰围、HbA1c、收缩压、AHI等因素后,多因素Logistic回归分析显示利拉鲁肽对糖尿病周围神经病变有改善作用(OR=3.426,95%CI:1.024~11.46,P=0.046)。结论利拉鲁肽治疗可能有改善T2DM合并OSAHS患者睡眠呼吸紊乱及糖尿病周围神经病变的作用,对糖尿病肾脏病变、糖尿病视网膜病变无影响。     

Effect of acute reduction of free fatty acids by acipimox on growth hormone-releasing hormone-induced GH secretion in type 1 diabetic patients

BACKGROUND: In type 1 diabetes mellitus (DM1), high GH basal levels and exaggerated responses to several stimuli have been described. Acipimox is an antilipolytic drug that produces an acute reduction of free fatty acids (FFA). The aim of this study was to evaluate the effect of the reduction of plasma FFA with acipimox, alone or in combination with GHRH, on GH secretion in DM1. METHODS: Six type 1 diabetic patients were studied (three women, three men), mean age of 30 +/- 2.1 years, body mass index (BMI) 23.1 +/- 1.5 kg/m2. As a control group, six normal healthy subjects of similar age, sex and weight were studied. Each patient and control received GHRH [1 microg/kg intravenously (i.v.) at min 180], acipimox (250 mg orally at min 0 and 120) and GHRH plus acipimox on three separated days. Subjects served as their own control. Blood samples were taken at appropriate intervals for determination of GH, FFA and glucose. RESULT: In control subjects, the GH area under the curve (AUC; microg/l x 120 min) was for acipimox-treated 1339 +/- 292 and 1528 +/- 330 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 3031 +/- 669, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). In diabetic patients, the GH AUC was for acipimox-treated 2516 +/- 606 and 1821 +/- 311 for GHRH-induced secretion. The GH AUC after the administration of GHRH plus acipimox was 7311 +/- 1154, significantly greater than the response after acipimox alone (P<0.05) or GHRH alone (P<0.05). The GH response after acipimox was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 1339 +/- 292 and 2515 +/- 606 for normal subjects and diabetic patients, respectively. The GH response after acipimox plus GHRH was increased in diabetic when compared with normal (P<0.05), with a GH AUC of 3031 +/- 669 and 7311 +/- 1154 for normal subjects and diabetic patients, respectively. The administration of acipimox induced a FFA reduction during the entire test. CONCLUSIONS: Reduction of free fatty acids with acipimox is a stimulus for GH secretion in DM1. The combined administration of GHRH plus acipimox induces a markedly increased GH secretion in type 1 diabetic patients when compared with normal subjects. These data suggest that patients with DM1 exhibit a greater GH secretory capacity than control subjects, despite the fact that endogenous FFA levels seems to exert a greater inhibitory effect on GH secretion in these patients.     

The addition of metformin in type 1 diabetes improves insulin sensitivity, diabetic control, body composition and patient well-being

AIM: As many overweight people with T1DM are insulin resistant, adjuvant therapy with insulin sensitising agents, such as metformin, may be beneficial. This study evaluated the effect of adjuvant metformin in T1DM on insulin sensitivity, diabetic control, body composition, quality of life (QOL) and treatment satisfaction. MATERIALS AND METHODS: A 3-month prospective open-labelled pilot study of 16 patients aged 18-40 with T1DM and body mass index (BMI) >25 kg/m(2) was performed. The patients received 500-850 mg metformin twice daily. Insulin sensitivity, assessed by a frequently sampled intravenous glucose tolerance test [n=5], body composition, HbA(1c) and quality of life (QOL) were measured before and after treatment. A retrospective review of 30 patients with T1DM treated with metformin for at least 4 months was also performed. BMI, HbA(1c) and insulin requirements during metformin treatment was compared to pre-metformin data, and to patients treated with insulin only. RESULTS: In the pilot study, insulin sensitivity increased significantly from 0.86 +/- 0.33 x 10(-4)/min/(microU/ml) to 1.17 +/- 0.48 x 10(-4)/min/(microU/ml) after 3 months adjuvant therapy (p = 0.043). This was associated with a decreased insulin requirement and mean daily blood glucose. There were no significant changes in HbA(1c) or body composition. QOL significantly improved (p < 0.002). The retrospective review revealed an initial reduction in HbA(1c) (0.8 +/- 1.4%, p = 0.001). This effect diminished with prolonged treatment. BMI decreased in patients remaining on metformin for a 2-year period (0.5 +/- 0.5kg/m(2), p = 0.042). CONCLUSION: Adjuvant metformin can improve QOL, insulin sensitivity and glycaemic control in overweight adults with T1DM.     

2型糖尿病血清脂联素与心血管相关标志物相关性的研究

目的检测老年糖尿病(DM)患者血清脂联素(APN)与3个心血管相关标志物水平并探讨二者之间的相关关系。方法将70例老年受试者分为3组:正常对照组、老年DM未合并大血管病变组(DM1)和老年DM合并大血管病变组(DM2),检测血清APN与心血管相关标志物-血浆C反应蛋白(c-reactive protein,CRP)、Ⅰ型血浆纤溶酶原活化抑制剂(plasminogen activator inhibitor type-1,PAI-1)和血清基质金属蛋白酶-9(matrx metalloproteinase-9,MMP-9)的水平变化。结果从正常对照组、DM1到DM2组血清APN水平依次下降,各组间差别均具有显著意义(均P<0.01)从正常对照组、DM1到DM2组,CRP、PAI-1、MMP-9的水平逐渐升高,CRP、PAI-1升高在各组间均具有显著性(均P<0.05),MMP-9在DM2组开始出现显著升高(P<0.01),DM1组较正常对照组升高没有显著意义。APN水平与CRP、PAI-1、腰围、BMI、WHR及FBG、2h PBG、HbA1C、TG呈显著负相关。多元逐步回归分析显示APN与CRP(r2=0.18)、PAI-1(r2=0.16)、WHR(r2=0.21)及HbA1C(r2=0.19)具有高度的相关性(均P<0.05)结论APN可能是老年DM动脉粥样硬化发生发展中的保护因素。