2型糖尿病短期胰岛素强化治疗对胰岛β细胞功能的影响

对50例新诊断T2DM病患者进行2周胰岛素强化治疗,然后随机分为2组,每组25例,一组改为口服降糖药强化治疗（OHA组）,一组继续胰岛素强化治疗（Ins组）,随访10周。结果治疗2周后,FPG、2hPG、HbA。c水平均有下降,而空腹C肽（FCP）及餐后2hC肽（2hCP）水平均升高。治疗12周后,FPG、2hPG、HbA1c水平进一步下降,而FCP及2hCP水平进一步升高;OHA组与Ins组之间血糖、糖化血红蛋白及胰岛功能差异均无统计学意义。结论早期胰岛素强化治疗能尽快解除高糖毒性,显著恢复胰岛β细胞功能,减轻胰岛素抵抗。     

早期强化治疗与常规治疗初诊2型糖尿病患者β细胞功能与胰岛素抵抗变化的比较

目的 探讨强化治疗与常规治疗对初诊T2DM患者胰岛β细胞功能和胰岛素抵抗(IR)的影响. 方法 初诊T2DM患者选用非胰岛素促泌药物治疗后,HbA_1c≤6.5%者53例,>6.5%者58例,对OGTT血糖、Ins、HOMA-β、HOMA-IR进行组间比较. 结果 与常规组比较,达标组OGTT的5个时点血糖均显著降低(P均<0.01);180min Ins明显降低(P<0.05),其他时点Ins也降低,但无统计学差异(P>0.05);HOMA-IR明显降低,HOMA-β明显升高(P均<0.05);葡萄糖处置指数显著升高(P<0.01);△I_(30)/△G_(30)和AUC_(Ins)组间差异无统计学意义(P>0.05). 结论 初诊T2DM患者早期血糖强化达标治疗比常规治疗更能有效改善高血糖状态,减轻IR程度,提高β细胞基础分泌功能.     

早期强化治疗对不同血糖水平新诊断2型糖尿病患者胰岛β细胞功能和预后的影响

目的 评价早期强化治疗对不同血糖水平新诊断2型糖尿病患者胰岛β细胞功能和预后的影响.方法 382例新诊断2型糖尿病患者随机给予持续皮下胰岛素输注(CSII)、每日多次胰岛素注射(MDI)及口服降糖药(OHA)短期强化治疗,治疗前后测血糖、血脂及游离脂肪酸(FFA)、空腹胰岛素原与空腹胰岛素比值(PI/I),行静脉葡萄糖耐量试验(IVGTT),评价胰岛素急性分泌时相(AIR),计算稳态模型母细胞功能指数(HOMA-β)和胰岛素抵抗指数(HOMA-IR).随访1年以上.根据入选时空腹血浆血糖(FPG)水平进行分层分析,A层:7.0 mmol/L≤FPG<11.1 mmol/L,B层:11.1 mmol/L≤ FPG≤16.7 mmol/L.结果 A层患者的治疗达标率更高(94.4%比89.8%),血糖达标时间更短,1年缓解率也更高(47.8%比35.7%,P<0.05);而B层患者治疗后血糖、血脂的改善和FFA的下降更明显,且HOMA-β增加更多,但A、B层患者间AIR、PI/I比值和HOMA-IR改善程度差异无统计学意义.而无论A层或B层,胰岛素治疗(CSII、MDI)较OHA组有更高的1年缓解率(A层:57.1%,51.8%比32.8%,P<0.05;B层:44.4%,38.7%比18.6%,P<0.05).结论 短期胰岛素强化治疗较口服药治疗不仅使FPG较高的2型糖尿病患者具有更高的1年缓解率,在FPG轻中度增高的患者中获益也较大.     

不同疗程胰岛素泵治疗对口服降糖药失效的糖尿病患者胰岛β细胞功能的保护作用

目的评价不同疗程持续皮下胰岛素注射（CSII）治疗对口服降糖药（OHA）治疗失效的2型糖尿病（T2DM）患者胰岛β细胞功能改善的作用。方法48例OHA治疗失败的T2DM患者按CSII疗程分成三组,7天组10例、14天组18例、28天组20例。结果14天组和28天组在疗程结束时,血糖达标的胰岛素基础用量和餐前日追加量均较治疗第一天减少;28天组平均胰岛素日用总量显著低于7天组;14和28天组第一时相胰岛素和C肽分泌显著改善;三组HbA1c均下降,以28天组最明显。P均〈0.05。1年后28天组60%单用口服降糖药即可有效控制血糖。结论CSII治疗4周更有利于OHA失效的T2DM患者胰岛β细胞功能的改善。     

短病程2型糖尿病患者持续皮下胰岛素输注及联合双胍类或噻唑烷二酮类药物的疗效对比

目的 比较持续皮下胰岛素输注 (CSII) 及联合二甲双胍或吡格列酮对短病程T2DM住院患者的疗效,探讨短病程T2DM强化治疗的优化方案.方法 73例的短病程T2DM住院患者随机分为CSII组(23例)、CSII联合二甲双胍(CSII+Met)组(26例)、CSII联合吡格列酮(CSII+Pio)组(24例).测定强化治疗2周前后各组患者FPG、Ins、C-P、hsC-RP及75g葡萄糖负荷后2hPG、Ins、C-P.应用稳态模型计算β细胞功能(HOMA-β) 和胰岛素抵抗指数(HOMA-IR),同时比较三组治疗前后各指标的变化及治疗费用.结果 强化治疗后CSII+Met组、CSII+Pio组与CSII组相比HOMA-β水平显著升高(P＜0.05),HOMA-IR水平显著下降(P＜0.05);CSII+Met组比CSII组、CSII+Pio组血糖达标时间显著缩短、胰岛素用量及治疗费用显著下降(P＜0.05).结论 CSII联合二甲双胍或联合吡格列酮较单纯CSII能更有效的改善T2DM患者的胰岛β细胞功能,减轻胰岛素抵抗;CSII联合二甲双胍能明显减少胰岛素用量和治疗费用.     

继发失效改用胰岛素强化治疗疗效观察

165例SFS的2型糖尿病(T2DM)患者停用口服降糖药,改用诺和灵强化治疗,维持血糖达标56天,结果各时相PG明显下降(P＜0.01),INS、C-P水平提高(P＜0.01),HbA1c下降(P＜0.01).结论胰岛素强化治疗可恢复部分胰岛β细胞功能,改善胰岛素抵抗,提高胰岛素敏感性.     

失效后短期应用胰岛素泵强化治疗的疗效观察

方法采用持续皮下胰岛素输注(CSⅡ)前后对照并随访一年,观察48例口服降糖药(OHA)治疗失败的2-DM患者血糖控制达标时间,IVGTT、C肽、胰岛素(P)、胰岛素原(PI)以及PI/P比值,HomaB、HomaIR等变化,血糖检测的远期疗效以及对HbA1c、体重、血脂等代谢的影响.结果不同时程CSⅡ治疗血糖均能3～5天内达标,停止CSII后25%的病人需联合胰岛素补充治疗,15%的病人仍需依靠胰岛素治疗,60%的病人恢复OHA有效,CSⅡ治疗前后对照及随访一年,部分病人胰岛素、C肽峰值、第一时相分泌尖峰,HomaB值均有提高,PI/P比值、HbA1c、血脂均有下降,以CSⅡ28天时程更为明显.结论对OHA失效的2-DM患者,短期CSⅡ强化治疗具有快速稳定检测血糖和改善胰岛B细胞功能的作用.     

胰岛素联合罗格列酮对初诊2型糖尿病患者胰岛β细胞功能的保护作用

目的探讨胰岛素与罗格列酮合用对初诊2型糖尿病(T2DM)患者胰岛β细胞功能和血糖控制的影响。方法新诊断的空腹血糖大于12 mmol/L的T2DM患者47例,随机分为胰岛素组(n=22)、胰岛素 罗格列酮组(n=25)治疗12 w,分别在治疗前后检测空腹血糖、胰岛素、糖化血红蛋白(HbA1 c)、高敏C反应蛋白(hs-CRP)和胰岛素敏感性指数(ISI)及Homa B胰岛素分泌指数,并随访胰岛素与罗格列酮合用对初诊T2DM患者长期血糖控制的影响。结果12 w后,胰岛素 罗格列酮组较胰岛素组hs-CRP及胰岛素日用量明显下降(P<0.05),ISI和Homa B治疗后较对照组明显升高(P<0.05)。随访12个月时,胰岛素 罗格列酮组有13例患者仅采用饮食控制,血糖就可达到理想水平,而对照组仅有5例。结论胰岛素联用罗格列酮可以明显恢复初诊T2DM患者的胰岛功能,改善胰岛素抵抗。     

罗格列酮与胰岛素治疗对2型糖尿病患者胰岛β细胞第一时相分泌功能的影响

目的罗格列酮（RGZ）与胰岛素治疗对2型糖尿病（T2DM）患者胰岛功能的影响。方法FPG）11．1mmol／L的患者随机分为胰岛素治疗（Ins）组和胰岛素＋罗格列酮治疗（Ins＋RGZ）组,两组年龄、病程、BMI均无统计学差异。血糖达标后再维持治疗3个月。治疗前后均作静脉糖耐量试验（IVGTT）,比较两组糖代谢和胰岛功能的变化。结果治疗后的FPG、2hPG、HbA1c、静脉葡萄糖曲线下面积（AUC-G0～60）均显著下降,HOMA—B改善（P〈0．01或P〈0．05）,两组间无统计学差异。两组IVGTT10min内胰岛素释放曲线下面积／60min内胰岛素释放曲线下面积（AUC-I0～10／AUC-I0～60）分别增加10％和12％（P=0．085,0．05）。Ins＋RGZ组I2、I5、I10及FC-P显著提高,Ins组增高无统计学意义。逐步回归分析显示,治疗后FPG和2hPG下降与负荷后胰岛素增值和血糖增值比值呈正相关（r=0．593,P=0．000;r=0．548,P=0．001）,表明治疗后胰岛素处理葡萄糖能力与血糖控制程度呈正相关。结论罗格列酮（而不是胰岛素）能恢复第一时相胰岛素分泌。T2DM患者早期联用RGZ,有利于保护胰岛β细胞功能。     

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。     

江苏省2型糖尿病患者血糖控制及治疗用药情况调查

目的了解江苏省2型糖尿病（T2DM）患者的血糖控制情况,分析治疗方法与血糖控制的关系。方法采用横断面研究方法,以调查问卷形式收集患者年龄、病程、降糖药物的使用情况等,留取血标本检测HbA1c。根据HbA1c水平将患者分为达标组（HbA1c〈6．5％）和未达标组（HbA1c≥6．5％）;根据降糖治疗情况分为胰岛素（Ins）组、胰岛素联用口服降糖药（Ins＋OA）组、口服降糖药（OA）组、生活方式干预（LS）组。结果入选T2DM患者2966例,年龄（56．4±11．2）岁,糖尿病平均病程（6．3±5．7）年,HbA1c值（7．2±1．6）％,HbA1c≥6．5％的患者占59．8％。（1）平均病程Ins组[（7．6±6．5）年]与Ins＋OA组[（8．2±6．2）年]均高于OA组C（5．3±5．0）年]（P〈0．01）。HbA1c均值及未达标比例Ins组[（7．4±1．6）％,未达标比例65．9％]与Ins＋OA组[（7．5±1．5）％,未达标比例77．9％]均高于OA组[（7．0±1．6）％,未达标比例52．4％]（P〈0．01）。（2）HbA1c达标组与未达标组病程分别为（4．8±4．9）年和（7．3±6．1）年（P〈0．01）,两组中胰岛素联合口服降糖药治疗者分别占11．5％和27．2％（P〈0．01）,单用胰岛素治疗者分别占17．0％和22．1％（P〈0．01）。结论江苏省T2DM患者血糖控制现状比3年前全国调查情况有所改善,但仍有相当比例的患者HbA1c水平没有达到IDF及《中国2型糖尿病防治指南》推荐标准。接受胰岛素治疗的患者HbA1c均值及不达标比例明显高于其他治疗组,表明由于病程延长及口服降糖药用药失效导致病情恶化后,再选择胰岛素治疗,血糖控制情况并不理想。     

Inhaled insulin provides improved glycemic control in patients with type 2 diabetes mellitus inadequately controlled with oral agents: a randomized controlled trial

BACKGROUND: The long-term benefits of good glycemic control are well established. The aim of this proof-of-concept study was to determine whether glycemic control can be improved in patients with type 2 diabetes mellitus with suboptimal glycemic control, despite therapeutic dosages of oral antihyperglycemic agents (OHAs), by the addition of preprandial inhaled insulin (INH). METHODS: Sixty-eight patients with inadequately controlled type 2 diabetes mellitus (glycosylated hemoglobin, 8.1%-11.9%), despite therapy with a sulfonylurea and/or metformin, were randomized to receive INH in addition to their prestudy OHA therapy (INH + OHA group, n = 32) or to continue taking their prestudy OHA alone for 12 weeks (OHA group, n = 36). Premeal INH doses were delivered in 1 to 2 inhalations of 1-mg or 3-mg doses (equivalent to 3 IU and 9 IU, respectively, of subcutaneously injected regular insulin). RESULTS: At week 12, there was a significantly greater reduction in glycosylated hemoglobin for the INH + OHA cohort (mean reduction, -2.3%) compared with the OHA-only cohort (mean reduction, -0.1%, P<.001). Eleven patients (34%) receiving INH + OHA achieved glycosylated hemoglobin values of less than 7%, compared with none taking OHAs only. Fasting plasma glucose improved significantly more in the INH + OHA group compared with the OHA-only group (-60.69 mg/dL (-3.37 mmol/L] greater reduction, P<.001), and the postprandial increase in glucose was significantly lower in those patients receiving INH + OHA (P =.02). There was 1 report of severe hypoglycemia in the INH + OHA group (home blood glucose, 54 mg/dL [3.0 mmol/L]) and a greater increase in body weight. Pulmonary function was unchanged in both groups. CONCLUSION: The addition of preprandial INH to existing OHAs improves glycemic control without the need for injections in patients with type 2 diabetes mellitus failing to achieve satisfactory control with OHAs alone.     

胰岛素泵强化治疗新诊断的2型糖尿病的疗效观察

目的 探讨短期胰岛素泵（CSII）联合动态血糖监测（CGMS）强化治疗对新诊断的T2DM患者的中远期疗效。方法随访观察36例新诊断的T2DM患者进行为期两周胰岛素泵强化治疗后的血糖控制及不服用药物血糖达标持续时间。结果CSII治疗3d后血糖达标率69．4％,7d血糖达标率88．9％．2周血糖达标率97．2%;缓解期超过3个月的患者共31例（86．1％）,超过6个月23例（63．9％）,超过12个月16例（44．4％）,超过18个月10例（27．8％）。结论联合CGMS,胰岛素泵强化治疗可迅速使新诊断的T2DM患者血糖达标,使残存胰岛8细胞得到一定程度恢复。     

Effects of the treatment with acarbose in elderly overweight type 2 diabetic patients in poor glycemic control with oral hypoglycemic agents or insulin

The aim of this study was to evaluate the efficacy of acarbose, an inhibitor of alpha-glucosidase, on glycemic control in elderly overweight type 2 diabetic patients poorly controlled by oral hypoglycemic agents (OHA) or insulin. Our study included 22 overweight patients, 60-75-years-old, treated with OHA and/or insulin who, after a period of 4 weeks of controlled diet, showed a poor metabolic control. They were divided into two groups: Group I (nine patients) on OHA treatment; Group II (13 patients) undergoing treatment with insulin alone or in combination with OHA. Acarbose was administered to all the patients (100 mg three times a day at meal times) for 6 months in addition to their previous treatment. The addition of acarbose caused a significant reduction in both groups with regard to fasting glycemia (after 3 and 6 months, respectively, 20.7 and 21.9%, P<0.04 in Group I; 19.1 and 21.8%, P<0.04 in Group II), and postprandial glycemia (after 3 and 6 months, respectively, 41.6 and 42.5%, P<0.0001 in Group I; 35.6 and 38%, P<0.0006 in Group II). There was also a significant reduction in the values of HBA(1c) in Group I after 6 months of treatment (24.3%, P<0.05) and in Group II after 3 and 6 months (respectively 13.4%, P<0.02 and 20.6%, P<0.01). Three months after treatment with acarbose ended, fasting and postprandial glycemia and HBA(1c) values returned to original baseline values. In conclusion, the addition of acarbose to the OHA in elderly overweight type 2 diabetic patients poorly controlled by OHA or insulin regimes improved metabolic control.     

Secondary failure of oral hypoglycaemic agents in lean patients with type 2 diabetes mellitus: insulin sensitivity, insulin response to different stimuli, and the role of cyclic-AMP.

The aim of this study was to evaluate the insulin (IRI) response to different stimuli and insulin sensitivity in Type 2 diabetic patients responsive to oral hypoglycaemic agents (OHA) and in Type 2 diabetic patients with secondary failure of OHA (SF), all patients being of normal body weight (relative body weight less than 120%), and the possible role of cyclic AMP in the reduced IRI release. SF patients, without islet cell antibodies (ICA), with hyperglycaemia lasting more than 3 months, underwent tests with i.v. tolbutamide (n = 21), i.v. glucose (n = 14), i.v. glucagon (n = 19), i.v. arginine infusion (n = 18); the arginine infusion was repeated in 12 patients during administration of aminophylline, an inhibitor of phosphodiesterase. The same tests were performed in groups of 8 to 15 OHA patients and in groups of 6 to 17 healthy subjects. During all the tests, blood glucose levels were higher in SF patients, than in OHA patients and in healthy subjects. Both SF patients and OHA patients had no IRI response to glucose; SF patients, in contrast to OHA patients, had a reduced IRI response to tolbutamide and to glucagon. The IRI response to arginine was not different in OHA, in SF patients and in healthy controls, but was significantly enhanced by aminophylline only in healthy controls. Insulin infusions (1.66 mU/Kg/min for 90 min) were performed in OHA patients and in SF patients at blood glucose levels of 150 and of 250 mg/dl: during the last 60 min, the amount of glucose metabolized (M), and the insulin sensitivity (M/I) index were greater in OHA than in SF patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Preprandial repaglinide decreases exogenous insulin requirements and HbA1c levels in type 2 diabetic patients taking intensive insulin treatment

Abstract In this study, we investigated the effects of combining preprandial repaglinide to the insulin therapy for reducing the exogenous insulin requirements and serum HbA_1c levels in type 2 diabetic patients whose blood glucose levels were previously regulated by multiple dose intensive insulin therapy. Fifty patients with type 2 diabetes who had been initially treated with oral antidiabetic agents without a satisfactory response were included in this study. After adequate glycemic control was achieved with intensive insulin therapy, the patients were divided into two subgroups. The first group continued with intensive insulin therapy. The second group received a combination of multiple insulin injections and oral repaglinide (1.5 mgr tid). The doses of insulin injections were gradually decreased accordingly in the second group. Both groups were followed-up for 3 months. Repaglinide was well tolerated and had no toxicity. A significant reduction regarding exogenous insulin requirements and serum HbA_1c levels were demonstrated in patients taking preprandial repaglinide (p<0.01). Combining repaglinide to intensive insulin therapy could be a safe and effective alternative to intensive insulin therapy alone for the glycemic control and for reducing exogenous insulin requirements in type 2 diabetic patients.     

Quantitation of forearm glucose and free fatty acid (FFA) disposal in normal subjects and type II diabetic patients: evidence against an essential role for FFA in the pathogenesis of insulin resistance

This study was designed to quantitate glucose and FFA disposal by muscle tissue in patients with type II diabetes and to investigate the relationship between FFA metabolism and insulin resistance. The forearm perfusion technique was used in six normal subjects and two groups of normal weight diabetic patients, i.e. untreated (n = 8) and insulin-treated (n = 6). The latter received 2 weeks of intensive insulin therapy before the study. Plasma insulin levels were raised acutely [950-1110 pmol/L) (130-150 microU/mL)], while the blood glucose concentration was clamped at its basal value [4.9 +/- 0.1 (+/- SE) mmol/L in the normal subjects, 5.7 +/- 0.5 in the insulin-treated diabetic patients, and 5.5 +/- 0.3 in the untreated diabetic patients] by a variable glucose infusion. During the control period, arterial FFA concentrations were similar in the three groups, and they decreased to a comparable extent (less than 0.1 mmol/L) in response to insulin infusion. During the control period, the mean forearm FFA uptake was 2.5 +/- 0.5 mumol/L.min in the normal subjects, 2.9 +/- 0.5 in the insulin-treated patients, and 2.1 +/- 0.5 in the untreated diabetic patients. During the insulin infusion, FFA uptake was profoundly suppressed to similar levels in the normal subjects (0.9 +/- 0.1 mumol/L.min), the insulin-treated diabetic patients (1.1 +/- 0.3), and the untreated diabetic patients (0.9 +/- 0.1; P less than 0.001). Forearm glucose uptake was similar in the three groups during the control period. It increased during the insulin infusion, but the response in both diabetic groups was less than that in the normal subjects. The total amounts of glucose taken up by the forearm during the study period were 5.2 +/- 0.7, 2.6 +/- 0.5, and 2.1 +/- 0.6 mmol/L.min in the normal subjects, the insulin-treated diabetic patients, and the untreated diabetic patients, respectively (P less than 0.01). We conclude that 1) insulin-mediated glucose uptake by forearm skeletal muscle is markedly impaired in type II diabetes and improves only marginally after 2 weeks of intensive insulin therapy; 2) in contrast, no appreciable abnormality in forearm FFA metabolism is demonstrable in insulin-treated type II diabetic patients; and 3) FFA do not contribute to the insulin-treated skeletal muscle insulin resistance that occurs in patients with type II diabetes mellitus.     

102例酮症倾向2型糖尿病患者的临床特征分析

目的探讨酮症倾向2型糖尿病的临床特征及治疗方法。方法102例酮症倾向2型糖尿病在胰岛素降糖治疗1个月后,停用胰岛素给予口服降糖药单用或联合治疗,接受至少1年的随访。根据最终的治疗方案,分为口服降糖药（OHA）组和胰岛素治疗（INS）组。结果（1）经过1年的随访,77．5％的患者通过口服药物可将血糖得到较满意的控制,22．5％的患者因严重高血糖或酮症需要再次接受胰岛素治疗。（2）酮症倾向的2型糖尿病具有普通2型糖尿病许多类似的临床特点和病理生理特征。（3）与INS组相比,OHA组起病时的血糖、HbA1c、胰岛素强化治疗达标时间、男性构成比较低,而BMI、甘油三酯、糖尿病家族史构成比较高（P〈0．05）。（4）在高血糖得到控制后,OHA组胰岛素分泌指数（MBCI）和MBCI的变化值均大于INS组（P〈0．05）。（5）多元回归分析发现,高血糖控制后的MBCI、：BMI为选择不同治疗方案（口服药治疗或胰岛素治疗）的主要参考因素。结论酮症倾向2型糖尿病可能是2型糖尿病的一个亚型。在短期胰岛素治疗后,大多数可以改用口服降糖药,高血糖控制后的MBCI、：BMI将有助于不同降糖方案的选择。     

非酒精性脂肪与胰岛素抵抗及糖代谢异常的关系

目的 探讨非酒精性脂肪肝（脂肪肝）与胰素抵抗及糖代谢异常之间的关系。方法 对４８例脂肪肝患者做胰岛素释放试验和葡萄糖耐量试验,计算胰岛素曲线下面积,血糖曲线下面积和胰岛素敏感性指标（血糖曲线下面积／胰岛素曲线下面积）,并以不嗜酒的正常人作为对照组。结果 脂肪肝组口服葡萄糖６０ｍｉｎ,１２０ｍｉｎ,１８０ｍｉｎ后胰岛素水平高于对照组且高峰后移;除１８０ｍｉｎ外脂肪肝组的各时点的血糖水平显著高于对照级