目的研究甲状腺功能亢进与糖代谢紊乱、胰岛素β细胞功能异常、胰岛素抵抗的关系。方法选取我院2015年6月至2016年6月收治的48例甲状腺功能亢进患者为甲亢组,及同期在我院行健康体检的40例健康者作为对照组。检测并比较两组受检者的空...目的研究甲状腺功能亢进与糖代谢紊乱、胰岛素β细胞功能异常、胰岛素抵抗的关系。方法选取我院2015年6月至2016年6月收治的48例甲状腺功能亢进患者为甲亢组,及同期在我院行健康体检的40例健康者作为对照组。检测并比较两组受检者的空腹胰岛素(Fins)、餐后2 h胰岛素(2 h INS)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、游离甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平,并计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)、胰岛β细胞功能(HOMA-IS)。结果甲亢组患者出现糖耐量异常23例,占47.92%,10例糖耐量异常诊断达到糖尿病标准,占20.83%;甲亢组患者的FT3、FT4水平分别为(23.2±6.1)pmol/L、(61.2±20.4)pmol/L,均明显高于对照组,TSH水平为(0.21±0.11)u IU/m L,明显低于对照组,差异均有统计学意义(P<0.05);甲亢组患者的FPG、2 h PG、Hb Alc水平分别为(5.51±0.52)mmol/L、(8.92±1.77)mmol/L、(8.10±1.82)%,均明显高于对照组,差异均有统计学意义(P<0.05);甲亢组患者的2 h INS、HOMA-IR水平分别为(51.3±8.5)m U/L、(1.41±0.33),均较对照组显著升高,HOMA-IS、ISI水平分别为(1.41±0.33)、(-3.90±0.22),均较对照组显著降低,差异均有统计学意义(P<0.05);FT3与HOMA-IR呈正相关(r=0.908,P<0.05),FT4、TSH与HOMA-IR无显著相关性(r=-0.036、-58.755,P>0.05)。结论甲状腺功能亢进患者普遍存在糖代谢紊乱、胰岛β细胞损伤和胰岛素抵抗,且FT3与HOMA-IR有正相关性。展开更多
Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms ar...Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.展开更多
Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variant...Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.展开更多
文摘目的研究甲状腺功能亢进与糖代谢紊乱、胰岛素β细胞功能异常、胰岛素抵抗的关系。方法选取我院2015年6月至2016年6月收治的48例甲状腺功能亢进患者为甲亢组,及同期在我院行健康体检的40例健康者作为对照组。检测并比较两组受检者的空腹胰岛素(Fins)、餐后2 h胰岛素(2 h INS)、空腹血糖(FPG)、餐后2 h血糖(2 h PG)、糖化血红蛋白(Hb Alc)、游离甲状腺原氨酸(FT3)、游离甲状腺素(FT4)、促甲状腺激素(TSH)水平,并计算胰岛素抵抗指数(HOMA-IR)、胰岛素敏感指数(ISI)、胰岛β细胞功能(HOMA-IS)。结果甲亢组患者出现糖耐量异常23例,占47.92%,10例糖耐量异常诊断达到糖尿病标准,占20.83%;甲亢组患者的FT3、FT4水平分别为(23.2±6.1)pmol/L、(61.2±20.4)pmol/L,均明显高于对照组,TSH水平为(0.21±0.11)u IU/m L,明显低于对照组,差异均有统计学意义(P<0.05);甲亢组患者的FPG、2 h PG、Hb Alc水平分别为(5.51±0.52)mmol/L、(8.92±1.77)mmol/L、(8.10±1.82)%,均明显高于对照组,差异均有统计学意义(P<0.05);甲亢组患者的2 h INS、HOMA-IR水平分别为(51.3±8.5)m U/L、(1.41±0.33),均较对照组显著升高,HOMA-IS、ISI水平分别为(1.41±0.33)、(-3.90±0.22),均较对照组显著降低,差异均有统计学意义(P<0.05);FT3与HOMA-IR呈正相关(r=0.908,P<0.05),FT4、TSH与HOMA-IR无显著相关性(r=-0.036、-58.755,P>0.05)。结论甲状腺功能亢进患者普遍存在糖代谢紊乱、胰岛β细胞损伤和胰岛素抵抗,且FT3与HOMA-IR有正相关性。
基金This work was supported by grants from the National Natural Science Foundation of China （No. 30772142, 81070103, 81070102）, the National Key Basic Research Program （NKBRP） of China （No. 2006CB503806） and the Natural Science Foundation of Guangdong Province （No. 8251008004000001 and 9451008002003467）.
文摘Background The effect of impaired glucose tolerance （IGT） on cardiac function during the chronic prediabetes state is complicated and plays an important role in clinical outcome. However, the molecular mechanisms are not fully understood. This study was designed to observe cardiac dysfunction in prediabetic rats with IGT and to determine whether glucose metabolic abnormalities, inflammation and apoptosis are linked to it.Methods The IGT rat models were induced by streptozocin, and the heart functions were assessed by echocardiography. Myocardial glucose metabolism was analyzed by glycogen periodic acid-Schiff staining, and the pro-apoptotic effect of IGT was evaluated by TUNEL staining. Additionally, caspase-3 activation, macrophage migration inhibitory factor （MIF） and G-protein coupled receptor kinase 2 （GRK2） were detected by Western blotting in cardiac tissue lysates.Results Area-under-the-curve of blood glucose in rats injected with streptozotocin was higher than that in controls, increased by 16.28%, 38.60% and 38.61% at 2, 4 and 6 weeks respectively （F=15.370, P=0.003）. Abnormal cardiac functions and apoptotic cardiomyocytes were observed in the IGT rats, the ejection fraction （EF） being （68.594-6.62）% in IGT rats vs. （81.07±4.59）% in controls （t=4.020, P=0.002）. There was more glucose which was converted to glycogen in the myocardial tissues of IGT rats, especially in cardiac perivascular tissues. Compared to controls, the cleaved caspase-3, MIF and GRK2 were expressed at higher levels in the myocardial tissues of IGT rats.Conclusions IGT in the prediabetes period resulted in cardiac dysfunction linked to abnormal glycogen storage and apoptosis. Additionally, MIF and GRK2 may be involved in the pathogenesis of cardiac dysfunction in prediabetes and their regulation may contribute to the design of novel diagnostic and therapeutic strategies for those who have potential risks for diabetic cardiovascular complications.
基金Source of Support： This study was supported by grants from the Natural Sciences Foundation of Beijing （No. 5072042）, National Natural Science Foundation of China （No. 81170736）, National Key Program of Clinical Science. Conflict of Interest： None declared.
文摘Background： Fetal insulin hypothesis was proposed that the association between low birth weight and type 2 diabetes is principally genetically mediated. The aim of this study was to investigate whether common variants in genes CDKALI, HHEX, ADCY5, SRR, PTPRD that predisposed to type 2 diabetes were also associated with reduced birthweight in Chinese Han population.Methods： Twelve single nucleotide polymorphisms （rs7756992/rs10946398 in CDKAL1, rsl 111875 in HHEA; rs391300 in SRR, rs17584499 in PTPRD. rs1170806/rs9883204/rs4678017/rs9881942/rs7641344/rs6777397/rs6226243 in ADCY5） were genotyped in 1174 unrelated individuals born in Peking Union Medical College Hospital from 1921 to 1954 by TaqMan allelic discrimination assays, of which 645 had normal glucose tolerance, 181 had developed type 2 diabetes and 348 impaired glucose regulation. Associations of these 12 genetic variants with birthweight and glucose metabolism in later life were analyzed.Results： Birthweight was inversely associated with CDKAL 1-rs 10946398 （β = -41 g [95% confidence interval [CI]： -80, 3], P= 0.034）, common variants both associated with increased risk of impaired glucose metabolism and decreased insulin secretion index later in life. After adjusting for sex, gestational weeks, parity and maternal age, the risk allele of CDKAL1-rs7756992 was associated with reduced birthweight （β = 36 g [95% CI： -72, -0.2], P = 0.048）. The risk allele in SRR showed a trend toward a reduction ofbirthweight （P =0.085）. Conclusions： This study identified the association between type 2 diabetes risk variants in CDKAL 1 and birthweight in Chinese Hart individuals, and the carrier of risk allele within SRR had the trend of reduced birthweight. This demonstrates that there is a clear overlap between the genetics of type 2 diabetes and fetal growth, which proposes that lower birth weight and type 2 diabetes may be two phenotypes of one genotype.
