达格列净对2型糖尿病合并代谢相关脂肪性肝病患者代谢指标及自主神经功能的影响

张真真; 张耀颐; 王凯; 田晨光

doi:10.3969/j.issn.1001-5256.2021.12.023

达格列净对2型糖尿病合并代谢相关脂肪性肝病患者代谢指标及自主神经功能的影响

DOI: 10.3969/j.issn.1001-5256.2021.12.023

郑州大学第二附属医院内分泌科，郑州 450000

基金项目:

河南省科技厅科技攻关项目 (182102310596)

详细信息

通信作者:
田晨光，tcg90123@163.com

中图分类号: R575.5
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出版历程
- 收稿日期: 2021-05-07
- 录用日期: 2021-06-25
- 出版日期: 2021-12-20

Effect of dapagliflozin on metabolic markers and autonomic function in patients with type 2 diabetes mellitus and metabolic associated fatty liver disease

Department of Endocrinology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou 450000, China

Research funding:

Science and Technique Foundation of He'nan (182102310596)

摘要

摘要: 目的探讨达格列净对2型糖尿病(T2DM)合并代谢相关脂肪性肝病(MAFLD)患者代谢指标、肝脂肪含量及自主神经功能的影响。方法选取2019年10月—2020年10月在郑州大学第二附属医院收治的T2DM合并MAFLD患者90例，随机分为对照组(Con组)和达格列净组(Dap组)，各45例。患者入组前均已进行常规治疗，Con组继续给予原有常规降糖方案治疗，Dap组在此基础上加用达格列净，治疗周期为24周。收集两组患者治疗前后一般资料，比较治疗前后BMI、糖化血红蛋白(HbA1c)、空腹血糖(FPG)、血脂、血尿酸(SUA)、胰岛素抵抗指数(HOMA-IR)、肝功能、肝脂肪含量、心率变异性指标的变化。正态分布的计量资料组内比较采用配对t检验，两组间比较采用独立样本t检验; 非正态分布的计量资料组内比较采用Wilcoxon秩和检验，两组间比较采用Mann- Whitney U检验。计数资料两组间比较采用χ²检验。结果 Dap组和Con组各有43例、40例患者完成研究。治疗24周后，与治疗前相比，Dap组BMI、HbA1c、FPG、TG、SUA、ALT、AST、HOMA-IR、肝脂肪含量降低(t值分别为8.781、8.765、8.813、3.485、6.199、5.694、3.428、6.492、4.925，P值均＜0.05)，HDL-C、SDNN、SDANN、RMSSD、pNN50、HF、LF升高(t值分别为-2.055、-6.307、-7.696、-3.388、-7.928;Z值分别为-3.339、-3.309，P值均＜0.05);Con组HbA1c、FPG、HOMA-IR降低(t值分别为9.220、7.214、3.340，P值均＜0.05)。治疗后，Dap组BMI、HbA1c、TG、SUA、HOMA-IR、ALT、AST、肝脂肪含量低于Con组(t值分别为-4.055、-2.670、-2.056、-2.496、-3.976、-3.703、-2.123、-5.184，P值均＜0.05)，SDNN、SDANN、pNN50、LF、HF高于Con组(t值分别为4.136、5.433、5.971;Z值分别为-2.333、-2.010，P值均＜0.05)。结论达格列净可以降低T2DM合并MAFLD患者BMI、HbA1c、TG、SUA、肝脂肪含量，改善胰岛素抵抗和肝功能，并且可以降低交感神经活性，具有调节自主神经的功能。
- 糖尿病, 2型 /
- 代谢相关脂肪性肝病 /
- 自主神经系统
Abstract: Objective To investigate the effect of dapagliflozin on metabolic markers, hepatic fat content, and autonomic nervous function in patients with type 2 diabetes mellitus (T2DM) and metabolic associated fatty liver disease (MAFLD). Methods A total of 90 patients with T2DM and MAFLD who were admitted to The Second Affiliated Hospital of Zhengzhou University from October 2019 to October 2020 were enrolled and randomly divided into control group and dapagliflozin group, with 45 patients in each group. All patients were given conventional treatment before enrollment; the patients in the control group were treated with the original hypoglycemic regimen, and those in the dapagliflozin group were given dapagliflozin in addition to the treatment in the control group. The treatment cycle was 24 weeks. General information was collected before and after treatment, and the two groups were compared in terms of the changes in body mass index (BMI), glycosylated hemoglobin (HbA1c), fasting blood glucose (FPG), blood lipids, serum uric acid (SUA), Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), liver function, liver fat content, and heart rate variability after treatment. The paired t-test was used for comparison of normally distributed continuous data within each group, and the independent samples t-test was used for comparison between groups; the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data within each group, and the Mann-Whitney U test was used for comparison between groups. The Chi-square test was used for comparison of categorical data between two groups. Results A total of 43 patients in the dapagliflozin group and 40 patients in the control group completed the study. After 24 weeks of treatment, the dapagliflozin group had significant reductions in BMI, HbA1c, FBG, triglyceride (TG), SUA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), HOMA-IR, and liver fat content (t=8.781, 8.765, 8.813, 3.485, 6.199, 5.694, 3.428, 6.492, and 4.925, all P < 0.05) and significant increases in high-density lipoprotein cholesterol, standard deviation of all normal R-R intervals (SDNN), standard deviation of average NN intervals (SDANN), root mean square of successive differences, percent of the number whose difference between adjacent NN interval are more than 50 ms (pNN50), high frequency (HF), and low frequency (LF) (t=-2.055, -6.307, -7.696, -3.388, and -7.928, Z=-3.339 and -3.309, all P < 0.05), while the control group had significant reductions in HbA1c, FBG, and HOMA-IR (t=9.220, 7.214, and 3.340, all P < 0.05). Compared with the control group after treatment, the dapagliflozin group had significantly lower levels of BMI, HbA1c, TG, SUA, HOMA-IR, ALT, AST, and liver fat content (t=-4.055, -2.670, -2.056, -2.496, -3.976, -3.703, -2.123, and -5.184, all P < 0.05) and significantly higher levels of SDNN, SDANN, pNN50, LF, and HF (t=4.136, 5.433, and 5.971, Z=-2.333 and -2.010, all P < 0.05). Conclusion For patients with T2DM and MAFLD, dapagliflozin can reduce BMI, HbA1c, TG, SUA, and liver fat content, improve insulin resistance and liver function, reduce the activity of sympathetic nerve, and regulate autonomic nerve function.
- Diabetes Mellitus, Type 2 /
- Metabolic Associated Fatty Liver /
- Autonomic Nervous System

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表 1 两组患者一般资料比较

指标	Con组(n=40)	Dap组(n=43)	统计值	P值
男/女(例)	18/22	19/24	χ²=0.006	0.941
年龄(岁)	60.5±6.6	59.0±10.1	t=-0.790	0.432
病程(年)	10.4±3.3	10.8±4.1	t=0.585	0.560
收缩压(mmHg)	133.4±5.1	131.4±5.9	t=-1.587	0.116
舒张压(mmHg)	82.0±8.7	79.5±9.1	t=-1.273	0.207

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表 2 两组治疗前后代谢指标及肝脂肪含量变化

指标	Con组(n=40)	Dap组(n=43)	t值	P值
BMI(kg/m²)
治疗前	26.8±1.6	26.3±1.5	-1.312	0.193
治疗后	26.6±1.4	25.3±1.5	-4.055	＜0.001
HbA1c(%)
治疗前	8.1±0.7	8.0±0.9	-0.695	0.489
治疗后	7.4±0.8	6.9±0.9	-2.670	0.009
FPG(mmol/L)
治疗前	8.6±2.0	8.6±1.5	0.062	0.951
治疗后	7.1±1.2	6.9±0.9	-0.868	0.388
TC(mmol/L)
治疗前	5.0±0.7	5.0±0.8	-0.050	0.960
治疗后	4.9±0.6	4.9±1.0	0.353	0.725
TG(mmol/L)
治疗前	2.0±0.5	2.1±0.6	0.682	0.497
治疗后	1.9±0.5	1.7±0.6	-2.056	0.043
HDL-C(mmol/L)
治疗前	1.2±0.3	1.2±0.3	0.371	0.712
治疗后	1.3±0.3	1.4±0.2	1.906	0.062
LDL-C(mmol/L)
治疗前	2.3±0.7	2.3±0.5	-0.232	0.817
治疗后	2.3±0.8	2.2±0.3	-0.505	0.616
ALT(U/L)
治疗前	44.3±7.0	44.6±7.7	0.172	0.864
治疗后	42.6±4.4	38.7±5.3	-3.703	＜0.001
AST(U/L)
治疗前	36.4±6.2	36.4±5.4	-0.002	0.998
治疗后	35.5±5.9	33.6±5.1	-2.123	0.037
SUA(mg/g)
治疗前	356.7±87.8	351.5±87.0	-0.270	0.788
治疗后	340.7±74.5	302.4±65.3	-2.496	0.015
HOMA-IR
治疗前	5.2±1.5	5.5±1.4	0.898	0.372
治疗后	4.5±0.9	3.5±1.3	-3.976	＜0.001
肝脂肪含量(%)
治疗前	16.2±1.5	15.8±1.8	-0.974	0.333
治疗后	16.0±1.4	14.1±1.8	-5.184	＜0.001

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表 3 两组治疗前后HRV相关指标变化

指标	Con组(n=40)	Dap组(n=43)	统计值	P值
SDNN(ms)
治疗前	96.3±26.6	95.7±25.3	t=-0.106	0.916
治疗后	99.0±21.7	122.1±28.8	t=4.136	＜0.001
SDANN(ms)
治疗前	88.5±25.1	88.3±24.0	t=-0.032	0.974
治疗后	90.0±23.3	117.8±23.3	t=5.433	＜0.001
RMSSD(ms)
治疗前	19.0±5.6	18.7±5.6	t=-0.226	0.822
治疗后	20.4±4.6	22.8±7.7	t=1.807	0.075
pNN50(%)
治疗前	3.9±2.2	3.3±2.0	t=-1.241	0.218
治疗后	4.3±2.5	11.1±6.9	t=5.971	＜0.001
LF(ms²)
治疗前	717.0(663.4~799.8)	738.5(639.8~800.1)	Z=-0.246	0.806
治疗后	723.8(637.8~799.7)	812.4(698.5~987.5)	Z=-2.333	0.020
HF(ms²)
治疗前	457.8(331.4~690.9)	389.2(292.4~634.0)	Z=-0.861	0.389
治疗后	504.5(401.2~595.6)	583.7(453.2~734.9)	Z=-2.010	0.044

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