2型糖尿病患者空腹血清真胰岛素水平和胰岛素抵抗与血脂的关系

目的　探讨 2型糖尿病 (T2DM )患者空腹血清真胰岛素水平、胰岛素抵抗与血脂的关系。　方法　应用BA ELISA法测定正常糖耐量 (NC)组 96例、T2DM组 132例和T2DM伴原发性高血压 (T2DM EH)组 14 8例的空腹血清真胰岛素 (TI)水平 ,酶法检测血脂 ,计算胰岛素抵抗指数(HOMA IR)、β细胞功能指数 (HOMA β)。 　结果　T2DM组及T2DM EH组的甘油三酯 (TG)、HOMA IR高于NC组 ,高密度脂蛋白胆固醇 (HDL C)和HOMA β低于NC组 ,差异均有显著意义 (P<0 0 5 )。T2DM EH组HOMA IR高于T2DM组 ,差异有显著意义 (P <0 0 5 )。T2DM组及T2DM EH组的TG与TI、HOMA IR呈正相关 (P <0 0 1) ,HDL C与TI、HOMA IR呈负相关 (P <0 0 5 )。　结论　T2DM患者空腹血清TI水平与脂代谢异常相关 ,血清TI水平的升高和 (或 )IR的加重均会引起TG升高和HDL C降低。IR与脂代谢异常及高血压的关系较高TI血症更密切。     

SIRT1 mRNA在新诊断的2型糖尿病患者脂肪组织的表达及意义

目的探讨新诊断的2型糖尿病（T2DM）患者脂肪组织SIRT1 mRNA表达水平及其与体质指数（BMI）、腰臀比（WHR）、血糖、血浆胰岛素、胰岛素抵抗指数（HOMA—IR）关系。方法采用RT—PCR方法检测了40例对照组和40例T2DM患者脂肪组织SIRT1 mRNA水平,并分析了SIRT1水平与BMI、WHR、血脂、HbA1C、血糖、血浆胰岛素和HOMA—IR等的关系。结果新诊断的T2DM患者SIRT1 mRNA水平显著低于对照组（1．49±0．47VS1．12±0．32,P〈0．01）;线性相关分析表明,SIRT1与Fins、HOMA—IR呈显著负相关（r=-0．421,P〈0．01和r=-0．511,P〈0．01）。以SIRT1为因变量,年龄、WHR、BMI、TG、TC、LDL—C、HDL—C、HbA1C、FPG、Fins和HOMA—IR为自变量,进行多元线性逐步回归分析,结果表明HOMA—IR是影响SIRT1的独立相关因素。Logistic回归分析表明控制性别、年龄、WHR、BMI、TC、TG、HDL—C、LDL—C后,发现SIRT1与T2DM发病呈负相关,OR〈1。结论脂肪组织中SIRT1 mRNA水平的变化与IR和T2DM相关。     

家族性早发2型糖尿病的病理生理和临床特征

目的　探讨早发家族性2型糖尿病(T2DM)的病理生理、临床特征和影响发病年龄的因素。　方法　190个早发(在40岁前诊断)和103 个晚发T2DM家系(家系中所有患者均在40 岁后诊断)的先证者参加了本研究。用稳态模型胰岛素抵抗指数(HOMA-IR)评估胰岛素抵抗, 胰岛β细胞功能指数(HOMA β)评估β细胞胰岛素基础分泌,用空腹和进食100 g馒头30 min胰岛素血糖差值的比值(ΔI30/ΔG30)评价胰岛素早期分泌,同时测血脂和体质指数(BMI)。　结果　(1)早发T2DM先证者的甘油三酯、空腹胰岛素(FIns)、HOMA IR显著高于晚发患者,而高密度脂蛋白胆固醇(HDL-C)则低于晚发的T2DM患者(P<0.05)。(2)多元逐步回归分析显示HOMA IR、HOMA β是诊断年龄的独立预测因素。(3)在早发T2DM患者中,肥胖组(BMI≥25 kg/m2 )的诊断年龄和HDL C均低于非肥胖组(BMI<25 kg/m2)(P<0.05, P<0.01),而TG、FIns、HOMA IR高于非肥胖组(P<0.05, P<0.01)。　结论　更严重的胰岛素抵抗和相对β细胞功能缺陷是早发家族性T2DM重要的病理生理改变, 两者的共同作用与糖尿病的提前发生有关。     

2型糖尿病合并痛风患者胰岛素抵抗与红细胞膜胰岛素受体的关系

目的 探讨2型糖尿病(T2DM)合并痛风患者胰岛素抵抗(IR)与红细胞膜胰岛素受体之间的关系。方法 30例T2DM合并痛风患者(T2DM Gout)、30例无痛风的T2DM患者、30例痛风患者(Gout)、26名正常人作对照(NC)，进行空腹血糖(FPG)、胰岛素(Fins)及口服葡萄糖耐量试验(OGTT)后2h血糖(2hPG)、胰岛素(2hlns)及胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)、血尿酸(UA)的测定，同时检测高、低亲和力红细胞膜胰岛素受体数目(R1、R2)和高、低亲和力常数(K1、K2)，并以稳态模型(HOMA)计算胰岛素抵抗指数(HOMA-IR)为应变量，Fins、年龄、体质指数(BMI)、TG、TC、LDI～HDL、收缩压(SBP)、舒张压(DBP)、UA、R1、R2、K1、K2为自变量，进行多元逐步回归分析，分析T2DM合并痛风患者IR与红细胞膜胰岛素受体变化的关系。结果 T2DM合并痛风较无痛风的T2DM患者LDL明显升高，HDL降低，HOMA-IR显著升高，且R1、R2、K2明显减少，有统计学意义。多元逐步回归分析结果示：在α-0．05水平，进入回归方程的因素有Fins、BMI、R2、K1，有统计学意义。结论 T2DM合并痛风较无痛风的T2DM患者存在明显IR，且与红细胞膜胰岛素受体数目和亲和力密切相关。     

2型糖尿病病人的非糖尿病一级亲属胰岛β细胞功能和胰岛素抵抗的研究

目的　研究 2型糖尿病 (T2DM )及 2型糖尿病病人的非糖尿病一级亲属胰岛 β细胞功能、胰岛素抵抗 (IR)及早期胰岛素分泌功能 ,探讨其在糖尿病发生发展中的作用。方法　选取 59例正常对照组、58例T2DM病人糖耐量正常的T2DM病人一级亲属及 38例T2DM ,他们的体重指数 (BMI)均 <2 5kg/m2 ,计算并比较三组的血清胰岛素、血糖及稳态模型胰岛素抵抗指数 (HOMA IR)、β细胞功能指数 (HOMA β)及胰岛早期分泌指数 (△I30 /△G30 )。结果　非肥胖的糖耐量正常的一级亲属组的HOMA IR均高于正常对照 (P <0 0 5) ,但低于T2DM组 ;而HOMA βTI一级亲属组低于对照组 (P <0 0 5) ,但高于T2DM组 (P <0 0 1 ) ;△I30 /△G30 显示一级亲属组低于对照组 (P <0 0 5)。结论　非肥胖 2型糖尿病一级亲属在糖耐量正常时就已经存在胰岛β细胞功能的受损、胰岛素抵抗及胰岛素早期分泌指数减低 ;IR并非继发于肥胖和高血糖症。     

糖尿病病人LMNA1908C/T基因多态性与胰岛素抵抗和血脂的关系

目的　研究大连地区 2 型糖尿病(DM)病人细胞核框架蛋白 lamin 基因(LMNA)1908C/T基因多态性与血脂紊乱的关系。　方法　以121例非糖尿病(NDM)者为对照组,平均年龄(61±9)岁。154例DM病人,平均年龄(63±13)岁。检测空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)和高密度脂蛋白胆固醇(HDL-C)、空腹胰岛素(FIns)和 C肽等。采用聚合酶链反应 限制性内切酶长度多态性技术分析LMNA1098C/T基因型。　结果　LMNA1908CT TT基因型在 DM病人和NDM者中分布差异有统计学意义(P<0.05)。在 NDM组 CT TT基因型携带者的体质指数(BMI)、FIns、C肽和胰岛素抵抗指数(IRI)均高于 CC基因型携带者(P<0.01),在 DM组 CT TT基因型携带者BMI和腰围高于CC基因型携带者(P<0.01)。无论是 DM还是 NDM有无血脂紊乱者,其CT TT频率差异均有统计学意义(P<0.01)。NDM有血脂紊乱者的 LMNA1908CC TT基因型频率高于DM病人,但差异无统计学意义。LMNA1908C/T基因型者的 TC、TG水平均高于CC型携带者(P<0.01);DM病人 CT TT型携带者的 TC水平高于 CC型携带者,HDL C水平低于CC型携带者(P<0.01)。　结论　LMNA1908C/T多态性与 IR及 DM发病可能相关;无论在DM还是NDM个体LMNA1908C/T多态性与血脂紊乱均密切相关。     

成人隐匿性自身免疫性糖尿病与经典1型糖尿病比较

对50例LADA患者4,0例经典(速发性)T1DM患者进行了身高、体重、血糖、空腹和餐后2h C肽、糖化血红蛋白(HbA1c)、甘油三酯(TG)、胆固醇(TC)测定,并计算体重指数(BMI)、胰岛素抵抗指数(HOMA-IR)。结果 LADA组HOMA–IR明显高于T1DM组,空腹C肽与T1DM组近似;餐后2h C肽明显高于T1DM组。结论 LADA患者存在相当程度的胰岛素抵抗,但又有胰岛B细胞功能不足。     

短期胰岛素强化治疗对初诊老年2型糖尿病患者糖毒性及脂毒性作用的影响

目的探讨短期胰岛素强化治疗对初诊老年2型糖尿病（T2DM）患者高血糖毒性及脂毒性作用的改善情况。方法对空腹血糖〉11．1mmol／L的30例初诊老年2型糖尿病患者进行短期（1～30d）胰岛素强化治疗，观察治疗前后空腹血糖（FBG）、甘油三酯（TG）、总胆固醇（TC）、低密度脂蛋白胆固醇（LDL—C）、高密度脂蛋白胆固醇（HDL-C）、糖化血红蛋白（HbA1C）、胰岛β细胞功能（以HOMA β反映）和胰岛素抵抗（IR）（用HOMA IR表示）等指标的改善情况。结果短期胰岛素强化治疗后，患者的FBG，餐后2h血糖（P2hBG），HbA1C，（TG），LDL—C，TC，IR（HOMA IR）等指标较治疗前明显降低。HDL—C、HOMAβ较治疗前明显提高。随访3个月后66．7％的患者可以不需使用口服降糖药及胰岛素治疗就可维持血糖值达标。结论对伴明显高血糖的初诊老年T21DM患者，短期胰岛素强化治疗可以显著改善高血糖毒性和脂毒性对胰岛β细胞功能以及胰岛素敏感性的损害作用。     

胰岛素抵抗与2型糖尿病合并非酒精性脂肪肝关系的研究

研究胰岛素抵抗与2型糖尿病（T2DM）合并非酒精性脂肪肝（NAFL）的关系,发现T2DM伴有脂肪肝组BMI、WHR、TC、TG、血尿酸、丙氨酸氨基转移酶、γ-谷氨酰转移酶和HOMA-IR较T2DM不伴脂肪肝组升高（P均〈0．01）;Logistic回归分析表明,HOMA—IR、TC、TG、WHR是NAFL形成的独立危险因素。     

原发性高血压伴微量蛋白尿患者胰岛素抵抗性研究

目的 :研究原发性高血压 (EH)并发微量蛋白尿患者的胰岛素抵抗 (IR)状态。方法 :根据尿白蛋白排泄率将EH患者分为两组 :微量蛋白尿阳性组 (4 0例 )和微量蛋白尿阴性组 (35例 ) ,计算体重指数 (BMI)、腰臀比值 (WHR) ,空腹采血测血糖 (FBG)、三酰甘油、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇和空腹胰岛素(FINR)水平。按HOMA模型计算胰岛素抵抗指数 (HOMA IR) ,HOMA IR =(FBG×FINR) / 2 2 .5 ,再取其自然对数。两组进行比较。结果 :患者年龄、性别比例、高血压病程、血压水平和FBG、血脂水平在两组间差异均无显著性意义 (P >0 .0 5 ) ,但BMI、WHR、FINR和HOMA IR在微量蛋白尿阳性组显著高于阴性组 (P <0 .0 5 )。结论 :EH微量蛋白尿阳性患者存在明显的IR ,高血压肾病的发生与EH患者的胰岛素敏感状态密切相关。BMI、WHR可作为IR的初筛指标     

Clinical utility of insulin and insulin analogs

Diabetes is a pandemic disease characterized by autoimmune, genetic and metabolic abnormalities. While insulin deficiency manifested as hyperglycemia is a common sequel of both Type-1 and Type-2 diabetes (T1DM and T2DM), it does not result from a single genetic defect—rather insulin deficiency results from the functional loss of pancreatic β cells due to multifactorial mechanisms. Since pancreatic β cells of patients with T1DM are destroyed by autoimmune reaction, these patients require daily insulin injections. Insulin resistance followed by β cell dysfunction and β cell loss is the characteristics of T2DM. Therefore, most patients with T2DM will require insulin treatment due to eventual loss of insulin secretion. Despite the evidence of early insulin treatment lowering macrovascular (coronary artery disease, peripheral arterial disease and stroke) and microvascular (diabetic nephropathy, neuropathy and retinopathy) complications of T2DM, controversy exists among physicians on how to initiate and intensify insulin therapy. The slow acting nature of regular human insulin makes its use ineffective in counteracting postprandial hyperglycemia. Instead, recombinant insulin analogs have been generated with a variable degree of specificity and action. Due to the metabolic variability among individuals, optimum blood glucose management is a formidable task to accomplish despite the presence of novel insulin analogs. In this article, we present a recent update on insulin analog structure and function with an overview of the evidence on the various insulin regimens clinically used to treat diabetes.     

Precipitin reactions between insulin,proinsulin, insulin chains and insulin antibody

Summary Insulin antibody was produced in guinea pigs and the precipitins tested by double diffusion in agarose gel. Pork, beef and monocomponent insulin produced precipitin lines. Proinsulin also produced a precipitin line with these antisera but no lines appeared with either the A-chain or the B-chain of insulin. There was good correlation between the precipitin titre and the radioimmunoassay titre.     

免疫原性与特异性胰岛素检测对胰岛β细胞功能评估的比较

在不同糖耐量者同时检测免疫原性胰岛素(IRI)与特异性胰岛素,发现虽然数值不同,但两种测定方法对于评估不同糖耐量者胰岛β细胞分泌功能及胰岛素敏感性的效果是一致的,提示测定IRI仍有临床实用价值.     

Measurement of insulin absorption and insulin action

For the practical implementation of every type of insulin therapy it is necessary to know both the time course of action of therapeutically used short- and long-acting insulin preparations and the factors influencing such time-action profiles. The only reliable way to obtain the required quantitative information about the pharmacokinetic and glucodynamic properties of insulin preparations has been the use of the euglycemic glucose clamp technique. The first studies with each new insulin formulation or insulin application technique should be performed with healthy subjects in order to have the most comparable study conditions. Thereafter, results from such clinical-experimental studies should be verified in similar studies with patients with diabetes. Earlier investigational approaches, which either had been limited to the determination of the pharmacokinetic properties of insulin preparations or had used the quantitative decrease of the blood glucose level as a measure of the pharmacodynamic properties, do not provide valid quantitative results. The proposed glucose clamp technique makes possible the quantitative study of the pharmacokinetic and pharmacodynamic properties of insulin preparations under comparative and reproducible conditions.     

Variability of insulin absorption and insulin action

Subcutaneous (s.c.) injections of identical insulin doses may lead to considerable intra- and inter-individual differences in the current metabolic control of patients with diabetes mellitus. This well-known variability of the metabolic effect of insulin hampers practical insulin therapy considerably. The aim of this review is to summarize the knowledge about this topic, with a special focus on the variability of insulin action after pulmonary administration of insulin. A number of studies have been published describing the variability of insulin absorption from the s.c. depot. Only in a few published studies has the variability of insulin action after s.c. administration been quantified. Under controlled experimental conditions s.c. injections of regular insulins result in an intra-individual coefficient of variation (CV) of 15-25% of certain pharmacodynamic summary measures--which characterize the metabolic effect of the applied insulin--in healthy subjects. The inter-individual variability was approximately 10% higher than the intra-individual variability. Subcutaneously injected intermediate- and long-acting insulin preparations were described to have an even greater variability (> 50%) than subcutaneously injected regular insulin. However, in a glucose clamp study s.c. application of NPH insulin led to an intra-individual CV in the range of 12-45% in healthy subjects. The reason for this discrepancy might be that the NPH insulin suspension was sufficiently shaken prior to drawing up the dose. Compared with conventional insulin formulations, rapid- and long-acting insulin analogues appear to have a similar variability, which means that, unfortunately, no considerable advantages in terms of variability were achieved by the invention of these novel insulin preparations. There are no appropriate studies available investigating the variability of the metabolic effect after s.c. insulin administration in patients with diabetes. The inhalation of insulin is a novel form of insulin administration that is currently under clinical development. The variability of the metabolic effect induced by the inhalation of insulin has up to now only been investigated in a small number of (published) studies. In a glucose-clamp study with healthy subjects the inhalation of an identical insulin dose on three study days led to an intra-individual variability that was comparable to that after s.c. injection of regular insulin. In a dose-response study with patients with type 1 diabetes the intra-individual CV was 34% for the area under the curve of the glucose infusion rate for 0-10 h. Studies with patients with type 2 diabetes have shown that the intra-individual CVs were within the range seen after s.c. insulin administration or even lower. In summary, the intra-individual variability of the metabolic effect observed after insulin application, be it subcutaneously injected or be it inhaled, is considerable and, therefore, hampers practical diabetes therapy. To date no means have been found that could lead to a clinically relevant reduction in the variable metabolic effect.     

Mechanism of action of insulin and insulin analogues

Summary A [¹⁴C]-glucose tracer infusion method was used to compare the effects of insulin infusion on glucose metabolism with the effects of infusion of three semisynthetic modified insulins and of proinsulin. Insulin produced hypoglycaemia in the anaesthetised dog by decreasing hepatic glucose production and increasing peripheral glucose utilisation. Compensatory antihypoglycaemic mechanisms eventually modified these responses. A₁ B₂₉-Diacetyl insulin exerted an hypoglycaemic effect entirely by stimulation of peripheral glucose uptake. A₁-B₂₉ crosslinked insulins and proinsulin produced hypoglycaemia almost entirely by decreasing hepatic glucose production and had little effect on tissue uptake. These observations suggest that insulin analogues may have actions in vivo that are qualitatively different from those of native insulin and suggest that certain analogues have a predominant action on the liver. This has important therapeutic implications concerning the development of semisynthetic insulins for clinical use.     

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.