吡格列酮联合利拉鲁肽治疗肥胖2型糖尿病的疗效及对胰岛功能 NLRP3炎性小体的影响

doi:10.3969/j.issn.1006-6233.2024.07.030

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Abstract Objective: To investigate the efficacy of pioglitazone combined with liraglutide in the treatment of obese type 2 diabetes mellitus (T2DM), and to analyze the effects of pioglitazone combined with liraglutide on islet function and the inflammasome of nucleotide-binding oligomerized domain-like receptor protein 3 (NLRP3). Methods: A retrospective study was conducted on 116 obese patients with type 2 diabetes mellitus (T2DM) from July 2021 to April 2023. The patients were randomly divided into a control group (liraglutide, 58 cases) and a study group (pioglitazone combined with liraglutide, 58 cases) according to a random number table method, and treated continuously for 3 months. The therapeutic efficacy of the two groups was compared. Blood samples were collected before and after treatment for 3 months in both groups, and the blood glucose and lipid metabolism were detected using an XC8001 automatic biochemical analyzer. The fasting insulin level was detected using immunochromatography (the kit was purchased from Shanghai Kanglang Biotechnology Co., Ltd.), and the insulin resistance index (HOMA-IR) and insulin beta cell function index (HOMA-β) were calculated. The level of NLRP3 inflammatory body index was detected using real-time quantitative polymerase chain reaction (qRT-PCR). The levels of serum interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were detected using ELISA before and after treatment in both groups. The adverse reactions of the two groups were compared. Results: The total effective rate in the study group was 94.83%, which was higher than the 81.03% in the control group (χ2=5.199, P=0.023). Three months after treatment, The levels of fasting blood glucose (FBG), 2 h postprandial glucose (2 hPG), glycated hemoglobin (HbA1c), total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C) in the study group were (4.82±0.56) mmol/L, (11.24±2.04) mmol/L and (5.47±0.61)%, (3.16±0.33) mmol/L, (1.31±0.30) mmol/L, (2.01±0.34) mmol/L, Were lower than (5.57±0.74) mmol/L, (13.07±2.16) mmol/L, (6.73±0.68)%, (3.89±0.54) mmol/L, (1.82±0.35) mmol/L, (2.39±0.42) mmol/L in control group (P<0.05). After 3 months of treatment, the level of high-density lipoprotein cholesterol (HDL-C) in the study group (1.38±0.22) mmol/L was higher than that in the control group (1.14±0.19) mmol/L (P<0.05). After 3 months of treatment, the insulin resistance index (HOMA-IR) of the study group (2.16±0.37) was lower than that of the control group (2.58±0.46), and the insulin beta cell function index (HOMA-β) of the study group (48.20±6.03) was higher than that of the control group [(42.81±5.54), (P<0.05)]. After 3 months of treatment, the expression levels of NLRP3 mRNA, apoptosis-related speck-like protein (ASC) mRNA and Caspase-1 mRNA in PBMC of the study group were (1.03±0.32), (1.11±0.28) and (1.09±0.41), respectively, lower than control group [(1.65±0.38), (1.57±0.30), (1.72±0.49), (P<0.05)]; Three months after treatment, Serum levels of interleukin-6 (IL-6), interleukin-β (IL-1β), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) in the study group were (8.55±2.13) pg/mL, (35.24±5.93) ng/L, (11.42±2.64) ng/L, (1.0 8±0.31 mg/L was lower than that of control group (11.47±2.68) pg/mL, (42.53±7.06) ng/L, (15.03±3.18) ng/L, (1.46±0.44) mg/L (P<0.05). There was no significant difference in adverse reactions between the two groups (P>0.05). Conclusion: Pioglitazone combined with liraglutide is effective and safe in the treatment of obese T2DM. It can correct the disorder of glucose and lipid metabolism, promote the improvement of islet function, and inhibit inflammatory response, which may be related to inhibiting the activation of NLRP3 inflammasome.

Key words： Type 2 diabetes mellitus Obesity Pioglitazone Liraglutide Curative effect Islet function Nucleotide-bound oligomerized domain-like receptor protein 3

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