Study On The Therapeutic Effect Of GLP-1RAs Liraglutide On Type 2 Diabetes Mellitus With Psoriasis

ObjectiveTo clarify the therapeutic effect and safety of GLP-1 analogue liraglutide in psoriasis patients with type 2 diabetes,and to explore the related mechanism of its treatment.Method:In this study,included 7 psoriasis patients with type 2 diabetes who visited Fuzhou general hospital from December 2017 to June 2018.The clinical characteristics of patients（including age,gender,height,body weight,duration of disease,presence of familial history of psoriasis,and psoriatic arthritis）were collected.Under the guidance of the doctor,the patient was given subcutaneous injection of liraglutide 0.6mg every day before going to bed,and the dosage was increased to 1.2mg per day after 1 week,and then the maximum dosage was increased to 1.8mg.Assess respectively before and after 4 weeks treatment,treatment after 8weeks,12 weeks after treatment of physical characteristics,body mass index（BMI）,waist circumference,fasting blood sugar,2H postprandial blood glucose,fasting C-peptide,fasting insulin,glycosylated hemoglobin（HbA1c）,blood lipid levels,the Psoriasis Area and Severity Index（PASI）,the Dermatology Life Quality Index（DLQI）and immunological analyses of skin biopsies.PASI score has been used to quantify disease severity of erythema,infiltration or thickness,scaling and the extent of lesions in patients with widespread disease.Each patient’s BMI was calculated by dividing their weight（kg）by the square of their height（m）.The changes of psoriasis skin lesions were recorded with a nikon camera（Japan,D750）,and PASI was used to assess the improvement of the severity of psoriasis before and after treatment to evaluate the therapeutic effect of liraglutide.Scissoring the diameter of the damaged skin and the adjacent undamaged skin of the patient was 5mm,and the paraffin sections were made.The pathological changes of the skin of the psoriasis were observed under the light microscope by using hematoxylin staining.Results:1.Seven patients completed the trial,including 6 males（86%）and 1 female（14%）,with an average age of 60±8 years.The average PASI was 15.7±11.9,and the highest was 31.3,which met the criteria of severe psoriasis.The average duration of psoriasis in all patients was 6±2 years,and 10±5 years for type 2 diabetes.2.Physical characteristics:12 weeks after the use of liraglutide,the BMI decreased to 21±3kg m^-2（P<0.01）,and the waist circumference was also significantly improved to 83±1cm（P<0.05）.3.Glycometabolism,lipid metabolism,islet cell function and inflammation indicators:After 12 weeks of intervention,fasting blood glucose and postprandial blood glucose after 2H were significantly lower than before treatment,but did not reach statistical significance（P=0.3,P=0.08）.However,HbA1c was significantly improved after 12 weeks of treatment,falling to 6.4±0.8%（P=0.04）.In the islet function improved,compared with before treatment,the use of the liraglutide 4 weeks after treatment,the fasting C-peptide levels,HOMA-IR（insulin resistance index）get improved significantly,12 weeks after treatment,the fasting C-peptide levels increased to 1.9±0.5 ng/ml（P=0.006）,HOMA-IR fell to 1.6±0.6（P=0.03）,have obvious statistical significance.The values of LDL and hs-CRP decreased to 2.3±0.3mmol/L（P=0.14）and 3.3±2.4 mg/L（P=0.16）,respectively,compared with before treatment.4.PASI and DLQI:the average PASI decreased from 15.7（1.5-31.3）to 2.0（0.3-8.7）（P=0.03）,with 6 patients（86%）decreasing by more than 50%and 5patients（71%）decreasing by more than 75%.Similarly,the DLQI decreased from 22（8-27）to 4（0-10）（P=0.001）.5.Psoriasis skin tissue and pathological changes:Histopathological analysis was performed on the skin of the patients for HE staining.The pathological results of the normal skin showed that the skin layer of the patients was thicker than that of healthy people,although there was no pathological change of the skin of psoriasis.Before the treatment with liraglutide,skin pathology in psoriasis suggests extensive keratosis accompanied by edema exudation,hypertrophy of the spine layer,decreased epidermal granule layer,vasodilatation of the dermis,neutrophil infiltration with Munro microulcer formation.Injection liraglutide after 12 weeks,shearing again,comparing the same parts of the skin to the naked eye view shows typical psoriasis skin changes,not seen to normal skin view,controlling the thickness of epidermis layer to reduce the pathological results indicate,Munro micro ulcer and neutrophils disappear.Skin thickness（dermal and epidermal layers）was observed under an optical microscope,and the results suggested that the number of cell layers was significantly reduced after12 weeks of treatment with liraglutide compared with before treatment（P<0.05）.6.In terms of safety:During the treatment period,liraglutide was well tolerated,and 4 patients（57%）presented different degrees of nausea and vomiting at the initial stage of treatment.With the continued treatment of gastrointestinal adverse reactions,no severe adverse events such as hypoglycemia and serious complications occurred in all patients.Conclusions:1.GLP-1 analogue liraglutide plays an important role in protecting islet cells and improving insulin sensitivity at the same time as glycemic control.2.In this study,it was found that the effect on body weight and waist circumference was particularly significant after 12 weeks of the application of liraglutide.3.Liraglutide can improve the skin thickness and inflammation of T2DM patients with psoriasis,especially for the treatment of severe psoriasis with significant effect and good safety.4.Liraglutide effect of laluropeptide may be related to anti-inflammatory,auxiliary hypoglycemic and weight loss,the concrete mechanism of which remains to be further discussed and researched.