Blood letting in high-ferritin type 2 diabetes -: Effects on insulin sensitivity and β-cell function
Blood letting in high-ferritin type 2 diabetes -: Effects on insulin sensitivity and β-cell function
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DOI：
10.2337/diabetes.51.4.1000
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发表时间：
2002-04-01
期刊：
影响因子：
7.7
通讯作者：
Ricart, W
中科院分区：
文献类型：
--
作者：
Fernández-Real, JM;Peñarroja, G;Ricart, W
铁相关的胰岛素抵抗可以通过铁消耗或铁螯合剂治疗来改善。本研究的目的是评估高铁蛋白2型糖尿病患者放血后的胰岛素敏感性和胰岛素分泌，这些患者随机接受放血（3次抽血[500 ml血液]，间隔2周，组1）或观察组（组2）。在基线和4个月及12个月后检测胰岛素分泌和敏感性。两组在年龄、BMI、药物治疗和慢性糖尿病并发症方面相匹配。所有患者均为遗传性血色病C282 Y突变阴性。基线糖化血红蛋白（6.27 +/- 0.9% vs. 6.39 +/- 1.2%胰岛素敏感性（2.75 +/- 1.8 vs. 3.2 +/- 2.1 mg（.）dl（-1）min（-1））和C肽曲线下面积（AUC（C）.（肽）; 38.7 +/- 11.6 vs. 37.6 +/- 14.1 ng（.）ml（-1）min（-1））在两组患者之间无显著差异。体重、血压、血细胞比容水平和药物治疗在研究期间基本保持不变。正如预期的那样，血清铁蛋白，转铁蛋白饱和指数，和血液血红蛋白在4个月时显着下降，只有接受放血的患者。与此变化平行，仅第1组受试者的血HbA（1c）显著降低（平均差异，-0.61; 95% CI，-0.17至-1.048; P = 0.01）。AUC（C）。（肽），放血后下降-10.2 +/-6.3%。相比之下，AUC（C）增加10.4 +/- 6.4%。第2组受试者在4个月时观察到（肽）（P = 0.032）。12个月时，AUC（C）。在两组受试者中，（肽）恢复到与基线无显著差异的值。4个月时，两组胰岛素敏感性较基线的变化存在显著差异（第1组和第2组分别为80.6 +/- 43.2% vs. -8.6 +/- 9.9%，P = 0.049）。在12个月时，两组之间的差异更加显著（55.5 +/- 24.8% vs. -26.8 +/- 9.9%; P = 0.005）。当分析仅限于完成随访至12个月的受试者时，除胰岛素敏感性外，与4个月时观察到的变化相比，结果未显示差异。在放血组中观察到胰岛素敏感性的统计学显著增加（从2.30 +/- 1.81至3.08 +/- 2.55 mg（.）dl（-1）（.）min（-1），4个月时为3.16 +/- 1.85 mg（.）dl（-1）（.）min（-1）12个月; P = 0.045）与F组2受试者（从3.24 +/- 1.9至3.26 +/- 2.05 mg（.）dl（-1 .）min（-1），4个月时降至2.31 +/- 1.35 mg（.）dl（-1）（.）12个月时min（-1））。总之，放血同时导致血液HbA（1c）水平降低以及胰岛素分泌和胰岛素抵抗的变化，这些变化与高铁蛋白2型糖尿病受试者的匹配观察组中观察到的结果显著不同。放血后外周胰岛素敏感性改善的机制有待进一步研究。
Iron-related insulin-resistance is improved by iron depletion or treatment with iron chelators. The aim of this study was to evaluate insulin sensitivity and insulin secretion after blood letting in patients who had high-ferritin type 2 diabetes and were randomized to blood letting (three phlebotomies [500 ml of blood] at 2-week intervals, group 1) or to observation (group 2). Insulin secretion and sensitivity were tested at baseline and 4 and 12 months thereafter. The two groups were matched for age, BMI, pharmacologic treatment, and chronic diabetic complications. All patients were negative for C282Y mutation of hereditary hemochromatosis. Baseline glycated hemoglobin (6.27 +/- 0.9% vs. 6.39 +/- 1.2% insulin sensitivity (2.75 +/- 1.8 vs. 3.2 +/- 2.1 mg(.)dl(-1) min(-1)), and area under the curve for C-peptide (AUC(C).(peptide); 38.7 +/- 11.6 vs. 37.6 +/- 14.1 ng (.) ml(-1) min(-1)) were not significantly different between the two groups of patients. Body weight, blood pressure, blood hematocrit levels, and drug treatment remained essentially unchanged during the study period. As expected, serum ferritin, transferrin saturation index, and blood hemoglobin decreased significantly at 4 months only in patients who received blood letting. In parallel to this changes, blood HbA(1c), decreased significantly only in group 1 subjects (mean differences, -0.61; 95% CI, -0.17 to -1.048; P = 0.01). AUC(C).(peptide), decreased by -10.2 +/- 6.3% after blood letting. In contrast, a 10.4 +/- 6.4% increase in AUC(C).(peptide) was noted in group 2 subjects at 4 months (P = 0.032). At 12 months, AUC(C).(peptide) returned to values not significantly different from baseline in the two groups of subjects. At 4 months, the change in insulin sensitivity from baseline was significantly different between the two groups (80.6 +/- 43.2% vs. -8.6 +/- 9.9% in groups 1 and 2, respectively, P = 0.049). At 12 months, the differences between the two groups were even more marked (55.5 +/- 24.8% vs. -26.8 +/- 9.9%; P = 0.005). When the analysis was restricted to those subjects who completed the follow-up until 12 months, results did not show differences compared with the changes observed at 4 months, except for insulin sensitivity. A statistically significant increase in insulin sensitivity was observed in the blood-letting group (from 2.30 +/- 1.81 to 3.08 +/- 2.55 mg (.) dl(-1) (.) min(-1) at 4 months, to 3.16 +/- 1.85 mg (.) dl(-1) (.) min(-1) 12 months; P = 0,045) in contrast with F roup 2 subjects (from 3.24 +/- 1.9 to 3.26 +/- 2.05 mg (.) dl(-1 .) min(-1) at 4 months, to 2.31 +/- 1.35 mg (.) dl(-1) (.) min(-1) at 12 months). In summary, blood letting led simultaneously to decreased blood HbA(1c), levels and to changes in insulin secretion and insulin resistance that were significantly different from those observed in a matched observational group of subjects with high-ferritin type 2 diabetes. The mechanisms for improvement in peripheral insulin sensitivity after blood letting should be investigated further.