正常范围内轻度升高的丙氨酸转氨酶与2型糖尿病患者夜间血糖升高的相关性
|
摘要
目的探讨在正常范围内轻度升高的丙氨酸转氨酶(ALT)水平与2型糖尿病患者夜间血糖之间的关系。方法将185例ALT在正常范围内的2型糖尿病患者分为低ALT组(ALT<17 U/L)82例和高ALT组(ALT≥17 U/L)103例。全部患者接受72 h动态血糖监测,比较两组间空腹血糖、糖化血红蛋白(HbA_(1c))、24 h平均血糖、日间(06:00-20:00之前)平均血糖、夜间(20:00-06:00之前)平均血糖、夜间最低血糖和平均血糖波动幅度的差异。采用Pearson相关性分析和多元线性回归评估夜间血糖的相关因素。结果高ALT组患者的夜间平均血糖为(7.6±1.4) mmol/L,夜间最低血糖为(6.4±1.4) mmol/L,分别显著高于低ALT组的(7.1±1.5)和(6.0±1.4) mmol/L(P值均<0.05)。两组间HbA_(1c)、空腹血糖、平均血糖波动幅度、24 h平均血糖和日间平均血糖的差异均无统计学意义(P值均>0.05)。Pearson相关性分析显示,血清ALT与夜间平均血糖(r=0.206,P=0.005)、夜间最低血糖(r=0.215,P=0.003)和胰岛素抵抗指数(r=0.200,P=0.006)均相关。多元线性回归分析显示,ALT是夜间血糖的独立影响因素(标准化β=0.041,P=0.003)。结论正常范围内轻度升高的血清ALT水平与糖尿病患者夜间血糖升高有关,但与日间血糖无关。
Objective To investigate the relationship between mildly elevated alanine aminotransferase(ALT) and nocturnal glucose in patients with type 2 diabetes. Methods A total of 185 type 2 diabetic patients whose ALT was in normal range were divided into two groups according to serum ALT level: low ALT group(n=82,ALT<17 U/L) and high ALT group(n=103,ALT≥17 U/L). All the patients received 72-hour continuous glucose monitoring. The fasting blood-glucose, glycosylated hemoglobin(HbA_(1 c)), mean glucose with in 24 h, diurnal(06:00-20:00) mean glucose, nocturnal(20:00-06:00) mean glucose, nocturnal nadir glucose and mean amplitude of glycemic excursions were compared between two groups. Pearson correlation analysis and multiple linear regression were applied to detect correlative factors of the nocturnal mean glucose. Results The nocturnal mean glucose and nocturnal nadir glucose in the high ALT group was(7.6±1.4) mmol/L and(6.4±1.4) mmol/L respectively, which were significantly higher than those in the low ALT group([7.1±1.5] mmol/L,[6.0±1.4] mmol/L, both P<0.05). There was no significant difference in the HbA_(1 c), fasting glucose, mean amplitude of glycemic excursions, 24-hour mean glucose, or diurnal mean glucose between two groups(all P>0.05). ALT was positively correlated with nocturnal mean glucose(r=0.206, P=0.005), nocturnal nadir glucose(r=0.215, P=0.003) and insulin resistance index(r=0.200, P=0.006). ALT was an independent influence factor of nocturnal mean glucose(standardized β=0.041, P=0.003). Conclusion Mildly elevated ALT(still in normal range) is correlated with increased nocturnal glucose, but not with diurnal glucose in diabetic patients.(Shanghai Med J, 2019, 42: 193-197)
Objective To investigate the relationship between mildly elevated alanine aminotransferase(ALT) and nocturnal glucose in patients with type 2 diabetes. Methods A total of 185 type 2 diabetic patients whose ALT was in normal range were divided into two groups according to serum ALT level: low ALT group(n=82,ALT<17 U/L) and high ALT group(n=103,ALT≥17 U/L). All the patients received 72-hour continuous glucose monitoring. The fasting blood-glucose, glycosylated hemoglobin(HbA_(1 c)), mean glucose with in 24 h, diurnal(06:00-20:00) mean glucose, nocturnal(20:00-06:00) mean glucose, nocturnal nadir glucose and mean amplitude of glycemic excursions were compared between two groups. Pearson correlation analysis and multiple linear regression were applied to detect correlative factors of the nocturnal mean glucose. Results The nocturnal mean glucose and nocturnal nadir glucose in the high ALT group was(7.6±1.4) mmol/L and(6.4±1.4) mmol/L respectively, which were significantly higher than those in the low ALT group([7.1±1.5] mmol/L,[6.0±1.4] mmol/L, both P<0.05). There was no significant difference in the HbA_(1 c), fasting glucose, mean amplitude of glycemic excursions, 24-hour mean glucose, or diurnal mean glucose between two groups(all P>0.05). ALT was positively correlated with nocturnal mean glucose(r=0.206, P=0.005), nocturnal nadir glucose(r=0.215, P=0.003) and insulin resistance index(r=0.200, P=0.006). ALT was an independent influence factor of nocturnal mean glucose(standardized β=0.041, P=0.003). Conclusion Mildly elevated ALT(still in normal range) is correlated with increased nocturnal glucose, but not with diurnal glucose in diabetic patients.(Shanghai Med J, 2019, 42: 193-197)
引文
[1]YI M,CHEN R P,YANG R,et al.Increased prevalence and risk of non-alcoholic fatty liver disease in overweight and obese patients with type 2 diabetes in South China[J].Diabet Med,2017,34(4):505-513.
[2]LALLUKKA S,YKI-JRVINEN H.Non-alcoholic fatty liver disease and risk of type 2diabetes[J].Best Pract Res Clin Endocrinol Metab,2016,30(3):385-395.
[3]TOKITA Y,MAEJIMA Y,SHIMOMURA K,et al.Nonalcoholic fatty liver disease is a risk factor for type 2diabetes in middle-aged Japanese men and women[J].Intern Med,2017,56(7):763-771.
[4]NANNIPIERI M,GONZALES C,BALDI S,et al.Liver enzymes,the metabolic syndrome,and incident diabetes:the Mexico City diabetes study[J].Diabetes Care,2005,28(7):1757-1762.
[5]FRASER A,EBRAHIM S,SMITH G D,et al.Acomparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose,fasting insulin,and glycated hemoglobin in women with and without diabetes[J].Hepatology,2007,46(1):158-165.
[6]FRASER A,HARRIS R,SATTAR N,et al.Alanine aminotransferase,gamma-glutamyltransferase,and incident diabetes:the British Women’s Heart and Health Study and meta-analysis[J].Diabetes Care,2009,32(4):741-750.
[7]SUH S Y,CHOI S E,AHN H Y,et al.The association between normal alanine aminotransferase levels and the metabolic syndrome:2005 Korean National Health and Nutrition Examination Survey[J].Metabolism,2009,58(12):1731-1736.
[8]YUN K E,SHIN C Y,YOON Y S,et al.Elevated alanine aminotransferase levels predict mortality from cardiovascular disease and diabetes in Koreans[J].Atherosclerosis,2009,205(2):533-537.
[9]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中华糖尿病杂志,2014,6(7):447-498.
[10]ZHOU J,MO Y,LI H,et al.Alanine aminotransferase is associated with an adverse nocturnal blood glucose profile in individuals with normal glucose regulation[J/OL].PLoSOne,2013,8(2):e56072[2018-11-10].https:∥doi.org/10.1371/journal.pone.0056072.
[11]TAO M,ZHOU J,ZHU J,et al.Continuous glucose monitoring reveals abnormal features of postprandial glycemic excursions in women with polycystic ovarian syndrome[J].Postgrad Med,2011,123(2):185-190.
[12]LI X,XIA M,MA H,et al.Liver fatcontent,evaluated through semi-quantitative ultrasound measurement,isassociated with impaired glucose profiles:a communitybased study in Chinese[J/OL].PLoS One,2013,8(7):e65210[2013-07-02].https:∥doi.org/10.1371/journal.pone.0065210.
[13]肖海英,郑雪莲,汪安江.非酒精性脂肪性肝病治疗进展[J].中国实用内科杂志,2017,37(12):1069-1073.
[14]RODRGUEZ-HERNNDEZ H,SIMENTAL-MENDA LE,BERMU′DEZ-PEA C,et al.Elevated alanine aminotransferase levels are associated with impaired fasting glucose and type 2 diabetes in obese women[J].Ann Hepatol,2012,11(6):966.
[15]YUEH C Y,CHEN J H,LEE L W,et al.Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2diabetes mellitus[J].Diabetes Res Clin Pract,2011,94(1):64-70.
[16]LIU A,CHEN S,GUO X,et al.Relationship between alanine aminotransferase levels and type 2diabetes mellitus in the general Chinese population[J].J Diabetes,2017,9(12):1120-1123.
[17]ATIQ M,SAFA M.Recurrent hypoglycemia associated with poorly differentiated carcinoma of the liver[J].Am JClin Oncol,2007,30(2):213-214.
[18]MONNIER L,COLETTE C,DEJAGER S,et al.Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes:is this of concern?[J].Diabetes Care,2013,36(12):4057-4062.
[19]BONNET F,DUCLUZEAU P H,GASTALDELLI A,et al.Liver enzymes are associated with hepatic insulin resistance,insulin secretion,and glucagon concentration in healthy men and women[J].Diabetes,2011,60(6):1660-1667.
[20]BIAN H,YAN H,ZENG M,et al.Increased liver fatcontent and unfavorable glucose profiles in subjects without diabetes[J].Diabetes Technol Ther,2011,13(2):149-155.
[21]KIDA K,NISHIO T,YOKOZAWA T,et al.The circadian change of gluconeogenesis in the liver in vivoin fed rats[J].J Biochem,1980,88(4):1009-1013.
[22]ANDO H,USHIJIMA K,SHIMBA S,et al.Daily fasting blood glucose rhythmin male mice:a role of the circadian clock in the liver[J].Endocrinology,2016,157(2):463-469.
[23]BODEN G,RUIZ J,URBAIN J L,et al.Evidence for a circadian rhythm of insulin secretion[J].Am J Physiol,1996,271(2Pt 1):E246-E252.
[24]BODEN G,CHEN X,URBAIN J L.Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production[J].Diabetes,1996,45(8):1044-1050.
[2]LALLUKKA S,YKI-JRVINEN H.Non-alcoholic fatty liver disease and risk of type 2diabetes[J].Best Pract Res Clin Endocrinol Metab,2016,30(3):385-395.
[3]TOKITA Y,MAEJIMA Y,SHIMOMURA K,et al.Nonalcoholic fatty liver disease is a risk factor for type 2diabetes in middle-aged Japanese men and women[J].Intern Med,2017,56(7):763-771.
[4]NANNIPIERI M,GONZALES C,BALDI S,et al.Liver enzymes,the metabolic syndrome,and incident diabetes:the Mexico City diabetes study[J].Diabetes Care,2005,28(7):1757-1762.
[5]FRASER A,EBRAHIM S,SMITH G D,et al.Acomparison of associations of alanine aminotransferase and gamma-glutamyltransferase with fasting glucose,fasting insulin,and glycated hemoglobin in women with and without diabetes[J].Hepatology,2007,46(1):158-165.
[6]FRASER A,HARRIS R,SATTAR N,et al.Alanine aminotransferase,gamma-glutamyltransferase,and incident diabetes:the British Women’s Heart and Health Study and meta-analysis[J].Diabetes Care,2009,32(4):741-750.
[7]SUH S Y,CHOI S E,AHN H Y,et al.The association between normal alanine aminotransferase levels and the metabolic syndrome:2005 Korean National Health and Nutrition Examination Survey[J].Metabolism,2009,58(12):1731-1736.
[8]YUN K E,SHIN C Y,YOON Y S,et al.Elevated alanine aminotransferase levels predict mortality from cardiovascular disease and diabetes in Koreans[J].Atherosclerosis,2009,205(2):533-537.
[9]中华医学会糖尿病学分会.中国2型糖尿病防治指南(2013年版)[J].中华糖尿病杂志,2014,6(7):447-498.
[10]ZHOU J,MO Y,LI H,et al.Alanine aminotransferase is associated with an adverse nocturnal blood glucose profile in individuals with normal glucose regulation[J/OL].PLoSOne,2013,8(2):e56072[2018-11-10].https:∥doi.org/10.1371/journal.pone.0056072.
[11]TAO M,ZHOU J,ZHU J,et al.Continuous glucose monitoring reveals abnormal features of postprandial glycemic excursions in women with polycystic ovarian syndrome[J].Postgrad Med,2011,123(2):185-190.
[12]LI X,XIA M,MA H,et al.Liver fatcontent,evaluated through semi-quantitative ultrasound measurement,isassociated with impaired glucose profiles:a communitybased study in Chinese[J/OL].PLoS One,2013,8(7):e65210[2013-07-02].https:∥doi.org/10.1371/journal.pone.0065210.
[13]肖海英,郑雪莲,汪安江.非酒精性脂肪性肝病治疗进展[J].中国实用内科杂志,2017,37(12):1069-1073.
[14]RODRGUEZ-HERNNDEZ H,SIMENTAL-MENDA LE,BERMU′DEZ-PEA C,et al.Elevated alanine aminotransferase levels are associated with impaired fasting glucose and type 2 diabetes in obese women[J].Ann Hepatol,2012,11(6):966.
[15]YUEH C Y,CHEN J H,LEE L W,et al.Elevated alanine aminotransferase is associated with metabolic syndrome but not consistently associated with impaired fasting glucose or type 2diabetes mellitus[J].Diabetes Res Clin Pract,2011,94(1):64-70.
[16]LIU A,CHEN S,GUO X,et al.Relationship between alanine aminotransferase levels and type 2diabetes mellitus in the general Chinese population[J].J Diabetes,2017,9(12):1120-1123.
[17]ATIQ M,SAFA M.Recurrent hypoglycemia associated with poorly differentiated carcinoma of the liver[J].Am JClin Oncol,2007,30(2):213-214.
[18]MONNIER L,COLETTE C,DEJAGER S,et al.Magnitude of the dawn phenomenon and its impact on the overall glucose exposure in type 2 diabetes:is this of concern?[J].Diabetes Care,2013,36(12):4057-4062.
[19]BONNET F,DUCLUZEAU P H,GASTALDELLI A,et al.Liver enzymes are associated with hepatic insulin resistance,insulin secretion,and glucagon concentration in healthy men and women[J].Diabetes,2011,60(6):1660-1667.
[20]BIAN H,YAN H,ZENG M,et al.Increased liver fatcontent and unfavorable glucose profiles in subjects without diabetes[J].Diabetes Technol Ther,2011,13(2):149-155.
[21]KIDA K,NISHIO T,YOKOZAWA T,et al.The circadian change of gluconeogenesis in the liver in vivoin fed rats[J].J Biochem,1980,88(4):1009-1013.
[22]ANDO H,USHIJIMA K,SHIMBA S,et al.Daily fasting blood glucose rhythmin male mice:a role of the circadian clock in the liver[J].Endocrinology,2016,157(2):463-469.
[23]BODEN G,RUIZ J,URBAIN J L,et al.Evidence for a circadian rhythm of insulin secretion[J].Am J Physiol,1996,271(2Pt 1):E246-E252.
[24]BODEN G,CHEN X,URBAIN J L.Evidence for a circadian rhythm of insulin sensitivity in patients with NIDDM caused by cyclic changes in hepatic glucose production[J].Diabetes,1996,45(8):1044-1050.