Mucosal insulin delivery systems based on complexation polymer hydrogels: effect of particle size on insulin enteral absorption.

Insulin-loaded polymer (ILP) microparticles composed of poly(methacrylic acid) and poly(ethylene glycol), which have pH-dependent complexation and mucoadhesive properties have been thought to be potential carriers for insulin via an oral route. Nevertheless, further optimization of the polymer delivery system is required to improve clinical application. Therefore, the effect of particle size of the ILP (L-ILP: 180-230 microm, S-ILP: 43-89 microm, SS-ILP: <43 microm) on insulin absorption was studied in the in situ loop system, hypothesizing smaller particle sizes of ILP could induce bigger hypoglycemic effects due to increase mucoadhesive capacity. To verify the hypothesis, the adhesive capacities of differently sized ILPs to the mucosal tissues were evaluated. Additionally, the intestinal site-specificity of ILP for insulin absorption was investigated. Intra- and inter-cellular integrity and/or damage were also examined by lactate dehydrogenase leakage and membrane electrical resistance change to ensure the safety of ILP as a carrier for oral route. As hypothesized, the smaller sized microparticles (SS-ILP) showed a rapid burst-type insulin release and higher insulin absorption compared with the microparticles having larger sizes, resulting in greater hypoglycemic effects without detectable mucosal damage. In fact, SS-ILP demonstrated higher mucoadhesive capacity to the jejunum and the ileum than those of L-ILP. Moreover, SS-ILP's enhancement effect of insulin mucosal absorption showed a site-specificity, demonstrating maximum effect at the ileal segment. These results imply that the particle size and delivery site are very important factors for ILP with respect to increasing the bioavailability of insulin following oral administration.     

Transdermal delivery of regular insulin to chronic diabetic rats: effect of skin preparation and electrical enhancement

The efficacy of passive transdermal versus electrically-enhanced, or iontophoretic delivery of insulin was studied. The effect of skin pre-treatment on iontophoretic delivery of insulin was also investigated. Rectangular pulses of 0.25 mA/cm² current amplitude, 2 kHz frequency, and 50% duty cycle were used as anodal stimulation for electrically enhanced transdermal delivery of insulin. Twenty (20) BB/Wor chronic diabetic adult male rats were shaved 48 h prior to the study, and some experimental groups had hair stubble removed with a depilatory lotion. The iontophoretic drug-containing electrode was filled with 3 ml of porcine regular insulin (100 IU/ml) which had been adjusted to an acidic pH of 3.68 using 0.1 M HCl. The iontophoretic electrodes were then adhered to the abdomen of the alert rat. Results of the iontophoretic procedure were quantified by monitoring changes in blood glucose levels. When insulin was placed on the shaved skin, blood glucose levels fell in the chronic diabetic rat. In general, glucose levels fell more quickly and more profoundly using an iontophoretic enhancement of transdermal insulin delivery. However, some skin preparations facilitated movement of insulin more efficiently. The most profound effect of lowered blood glucose occurred when a depilatory lotion was used on the day of the study in conjunction with iontophoresis, where blood glucose levels fell by 61% after 1 h of iontophoretic treatment. Results indicate that insulin was delivered passively at therapeutic levels when the skin had been treated with the depilatory lotion on the same day as the study, as measured through a reduction in blood glucose levels of 29% after 1 h of passive delivery. When the depilatory lotion was used 24 h prior to iontophoresis, blood glucose remained near initial blood glucose levels. In the groups that did not have the depilatory lotion applied, blood glucose levels fell by 8% after 1 h of iontophoretic insulin delivery. The experimental evidence indicates a substantial increase in the penetration of insulin with the same-day application of a depilatory lotion in conjunction with iontophoretic enhancement.     

吡格列酮对2型糖尿病患者血管内皮细胞功能及胰岛素抵抗的影响

目的观察吡格列酮(PIO)治疗糖尿病患者血管内皮细胞功能的变化及其对胰岛素抵抗(IR)的影响。方法随机选取2型糖尿病伴糖耐量减低(IGT)患者60例为观察组,正常对照组30例。观察组患者用PI0 30 mg/d治疗4个月。治疗前后分别检测反应性充血肱动脉内径增加程度(FMD),含服硝酸甘油后的血管舒张幅度(NID)指标,计算胰岛素敏感指数(ISI)、组织葡萄糖摄取率(GDR)和胰岛素抵抗指数(HOMA-IR)。结果 2型糖尿病糖耐量减低患者治疗前后比较,血糖指标(FBG、HbAlc、HOMA-IR)水平降低,ISI值升高;吡格列酮治疗组与常规治疗组比较,血清脂联素无差异(P>0.05);与正常对照组比较,FMD显著降低,NID无显著性变化;治疗组FMD较治疗前升高,而NID值治疗前后无显著性变化。结论吡格列酮能增加2型糖尿病并发心血管病患者血清脂联素水平,改善IR。     

诺和锐30强化治疗对初诊2型糖尿病患者的疗效及胰岛β细胞功能的影响

目的探讨门冬胰岛素30(诺和锐30)短期强化治疗对伴有明显高血糖的初诊2型糖尿病(T2DM)患者的疗效及胰岛功能的影响。方法对40例初诊2型糖尿病患者在饮食和运动治疗基础上给予诺和锐30强化治疗12周,分析比较治疗前后空腹血糖(FPG)、空腹胰岛素(FINS)、空腹C肽(F-C)、糖化血红蛋白(HbAlc)、总胆固醇(TC)、甘油三脂(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、体质指数(BMI)、餐后2小时血糖(2hPG)、餐后2小时胰岛素(2h-INS)、餐后2小时C肽(2h-C)、胰岛素分泌指数(HOMA-IS)、胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)和FINS/FPG比值的变化。结果40例患者血糖达标时间为(8.3±1.5)d,治疗后FPG、2hPG、HbAlc、TC、TG、LDL-C、HOMA-IR较治疗前均有显著下降(P<0.05),HDL、FINS、2h-INS、F-C、2h-C、HOMA-IS、ISI、FINS/FPG较治疗前明显升高(P<0.01),BMI稍有增高,但差别无统计学意义,治疗过程中无严重不良反应。结论对伴有明显高血糖的初诊T2DM患者,用诺和锐30强化降糖,可保护胰岛β细胞功能,间接改善血脂紊乱。     

胰岛素联合瑞易宁与单用胰岛素治疗继发性口服降糖药物失效的2型糖尿病的对比研究

目的 探讨胰岛素联合瑞易宁治疗与单用胰岛素控制稳定的继发性口服降糖药物失效的2型糖尿病的疗效及可能益处。方法 42例继发性药物失效的2型糖尿病患者用胰岛素控制糖代谢稳定至少2个月后 ,加用瑞易宁治疗 ,剂量从5mg/d开始 ,最大剂量20mg/d ,同时调整胰岛素用量 ,观察3个月。采用前后对比研究的方法 ,观察患者治疗前后的疗效和相关指标的变化。结果 胰岛素联合瑞易宁和单用胰岛素对继发性药物失效的2型糖尿病患者比较 ,空腹血糖(FBG)、糖基化血红蛋白(HbAlc)均能有效控制 ,餐后2h血糖(2hPG)的控制优于单用胰岛素治疗[(10.5±3.2)～(8.2±2.6)mmol/L,p<0.05],联合用药能明显减少胰岛素的用量[(45.2±10.6)u/d～(18.3±3.2)u/d,p<0.001] ,其中2例患者可以停用胰岛素治疗。(空腹C肽/空腹血糖)×100从(0.11±0.03)增加到(0.21±0.05)(p<0.05)。结论 胰岛素联合瑞易宁能控制继发口服降糖药物失效的2型糖尿病的糖代谢水平 ,可能避免对2型糖尿病大血管病变有关的高胰岛素血症。     

Comparison of continuous subcutaneous insulin infusion and multiple daily injection regimens using insulin lispro in type 1 diabetic patients on intensified treatment: a randomized study. The Study Group for the Development of Pump Therapy in Diabetes

OBJECTIVE: To compare the efficacy of 2 intensified insulin regimens, continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI), by using the short-acting insulin analog lispro in type 1 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 41 C-peptide-negative type 1 diabetic patients (age 43.5+/-10.3 years; 21 men and 20 women, BMI 24.0+/-2.4 kg/m2, diabetes duration 20.0+/-11.3 years) on intensified insulin therapy (MDI with regular insulin or lispro, n = 9, CSII with regular insulin, n = 32) were included in an open-label randomized crossover study comparing two 4-month periods of intensified insulin therapy with lispro: one period by MDI and the other by CSII. Blood glucose (BG) was monitored before and after each of the 3 meals each day. RESULTS: The basal insulin regimen had to be optimized in 75% of the patients during the MDI period (mean number of NPH injections per day = 2.65). HbA1c values were lower when lispro was used in CSII than in MDI (7.89+/-0.77 vs. 8.24+/-0.77%, P<0.001). BG levels were lower with CSII (165+/-27 vs. 175+/-33 mg/dl, P<0.05). The SD of all the BG values (73+/-15 vs. 82+/-18 mg/dl, P<0.01) was lower with CSII. The frequency of hypoglycemic events, defined as BG levels <60 mg/dl, did not differ significantly between the 2 modalities (CSII 3.9+/-4.2 per 14 days vs. MDI 4.3+/-3.9 per 14 days). Mean insulin doses were significantly lower with CSII than with MDI (38.5+/-9.8 vs. 47.3+/-14.9 U/day. respectively, P< 0.0001). CONCLUSIONS: When used with external pumps versus MDI, lispro provides better glycemic control and stability with much lower doses of insulin and does not increase the frequency of hypoglycemic episodes.     

Glycated albumin as an improved indicator of glycemic control in hemodialysis patients with type 2 diabetes based on fasting plasma glucose and oral glucose tolerance test

Aims

To compare glycated albumin (GA) with glycated hemoglobin (HbA1c) as an indicator of glycemic control in hemodialysis patients with diabetes mellitus (DM), based on relationships with plasma glucose (PG) after overnight fasting and during 75 g oral glucose tolerance test (OGTT).

Methods

GA, HbA1c, plasma glucose during 75 g OGTT, and serum pentosidine were determined in DM hemodialysis patients (n = 23, male/female 9/14).

Results

Significant positive correlations were found for GA and HbA1c with fasting PG (GA, r = .660, p = 0.0006; HbAlc r = 0.665, p = 0.0004), and with PG at 30, 60 and 120 min after initiation of 75 g OGTT (GA, r = 0.584, p = 0.0035; r = 0.624, p = 0.0015; r = 0.510, p = 0.0129, respectively; HbA1c, r = 0.669, p = 0.0004; r = 0.624, p = 0.0011; r = 0.509, p = 0.0112, respectively). The area under the curve for PG during 75 g OGTT showed strong correlations with GA (r = 0.625, p = 0.0008) and HbA1c (r = 0.671, p = 0.0003). GA and HbA1c also correlated positively with serum pentosidine, demonstrating that GA provides a no less significant assay than HbA1c as a reflection of glycemic control in DM hemodialysis patients. However, HbA1c was apparently reduced in DM hemodialysis patients, as reflected by an increase in the GA/HbA1c ratio to 3.58 ± 0.62 (mean ± SD), suggesting underestimation of glycemic control by HbA1c.

Conclusion

GA and HbA1c exhibited similar correlations with PG during a 75 g OGTT. The dependence of GA, in contrast to HbA1c, on PG does not differ in DM hemodialysis patients from that reported for subjects with normal renal function, suggesting GA as a better marker of glycemic control in DM hemodialysis patients.     

Effect of flaxseed (Linum usitatissimum) supplementation on glycemic control and insulin resistance in prediabetes and type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials

BackgroundPrediabetes and type 2 Diabetes Mellitus (T2DM) are characterized by increased blood sugar concentration and insulin resistance. Although there are only a few reports of potential benefits of flaxseed’s consumption on different metabolic parameters, there is no evidence of its effect among people with these conditions.ObjectivesThe present systematic review and meta-analysis aimed to assess the effect of flaxseed supplementation on glycemic control variables and insulin resistance in prediabetes and T2DM.MethodsA literature search was conducted through PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Science, to identify Randomized Control Trials (RCTs) that evaluated the effect of milled or ground flaxseed supplementation on fasting blood glucose, HbA1c, insulin concentrations, or HOMA-IR. The data were analyzed using Comprehensive Meta-Analysis (CMA) software version 3.3 in a fixed-effect model.ResultsSeven studies were included in the systematic review and the meta-analysis, the results showed a significant reduction on fasting blood sugar (SMD: −0.392, 95% CI: −0.596, −0.187, p = <0.001, I² = 64.81%) insulin concentrations, (SMD: −0.287, 95% CI: −0.534, −0.041, p = 0.022, I² = 32.53%), HbA1c (SMD: −0.442, 95% CI: −0.770, −0.114, p = 0.008, I² = 11.058%), and HOMA-IR (SMD: −0.284, 95% CI: −0.530, −0.038, p = 0.024, I² = 0.00%) after flaxseed supplementation.ConclusionsFlaxseed supplementation seems to improve glycemic control variables and insulin resistance in prediabetes and T2DM; however, more RCTs are needed to have more decisive evidence about doses, method of supplementation, and the possible effect of synergy with the dietetic treatment.