| BackgroundType 2 diabetes is a complex disease with multiple subtypes.There are different clinical phenotypes and dynamic changes.Different pathological states are closely related to clinical treatment strategies.Clinical phenotype refers to a series of characteristics that can classify diseases into independent categories.We can classify different clinical phenotypes of type 2 diabetes based on BMI and fasting C-peptide levels.Sex hormone binding globulin(SHBG)is synthesized in liver cells and participates in the transport of sex hormones.It can also mediate the signal transduction of sex hormones and regulate its bioavailability.At the same time,the decrease in serum SHBG levels is the body’s insulin resistance,obesity and type 2 diabetes.One of the signs of a variety of metabolic abnormalities,SHBG levels are closely related to the prevalence and prognosis of type 2 diabetes.Therefore,it is necessary to explore how the serum SHBG level and its polymorphism change in different clinical phenotypes of type 2 diabetes,which is helpful for precise treatment.ObjectiveObjective to explore the correlation between different clinical phenotypes of type 2 diabetes and SHBG serum levels and gene polymorphism,so as to determine the clinical characteristics of different clinical phenotypes of type 2 diabetes,and further develop individualized treatment and prevention programs.MethodsAmong the 1,128 patients with type 2 diabetes who were diagnosed and treated by the Guangdong Provincial People’s Hospital from May 2018 to December 2019 and were managed by the National Metabolic Disease Standardized Metabolic Disease Management Center(MMC),those aged 18-75 years old were included 679 patients were used as research subjects,including 452 men and 227 postmenopausal women.Baseline data including BMI,glucose metabolism indicators,lipid metabolism indicators,sex hormone indicators were collected,and HOMA-IR,HOMA-β index and free testosterone index(FTI)were calculated.According to fasting C-peptide and BMI,patients with type 2 diabetes were divided into different clinical phenotypes,and then logistic regression analysis was used to determine whether each index is related to the clinical phenotype,and to clarify the characteristics of various clinical phenotypes.ResultsAccording to the SHBG tertiles,SHBG is divided into low value group,median value group and high value group.The logistic regression analysis of risk factors in non-NAFLD patients with type 2 diabetes shows that the higher value is higher for both men and postmenopausal women.BMI and fasting C-peptide levels are related risk factors for low serum SHBG levels in patients with type 2 diabetes.Then according to the fasting C peptide and BMI,the clinical phenotypes of type 2 diabetes patients were divided into four phenotypes:Phenotype 1:Fasting C peptide>0.3 nmol/L and BMI≤25(282 cases,41.53%,of which 174 were male),108 cases of postmenopausal women);Phenotype 2:Fasting C peptide>0.3nmol/L and BMI>25(252 cases,accounting for 37.11%,including 161 men and 91 postmenopausal women);Phenotype 3:Fasting C Peptide ≤0.3nmol/L and BMI≤25(117 cases,accounting for 17.23%,including 92 males and 25 postmenopausal women);Phenotype 4:Fasting C-peptide≤0.3nmol/L and BMI>25(28 cases,Accounted for 4.12%,including 25 males and 3 postmenopausal females).In type 2 diabetic patients,with "clinical phenotype" as the dependent variable,SHBG,age,course of diabetes,BMI,eGFR,glucose and lipid metabolism indicators(fasting blood glucose,HbAlc,HOMA-IR,HOMA-β,TG,TC,LDL),endogenous hormone indicators(T,FTI,E2,LH,FSH),and thyroid indicators(FT4,TSH)were independent variables for Logistic regression analysis.The results show that:In the logistic regression analysis of phenotype one and phenotype three,male patients with type 2 diabetes with phenotype three have higher levels of SHBG,eGFR,HbAlc,T,FTI,and FT4 than those with phenotype one(OR>1.P<0.05),and patients whose age,HOMA-IR,HOMA-β,and TG levels are lower than phenotype one(OR<1,P<0.05).After adjusting for age,diabetes course,fasting blood glucose and other factors,the levels of SHBG,eGFR,and HbA1c of phenotype three were still higher than those of patients with phenotype one(OR>1,P<0.05).In the logistics regression analysis of phenotype two and phenotype three,male type 2 diabetic patients with phenotype three have higher levels of SHBG,eGFR,HbAlc,T,and FTI than patients with phenotype one(OR>1,P<0.05),and patients whose age,HOMA-IR,HOMA-β,and TG levels were lower than phenotype one(OR<1,P<0.05).After adjusting for age,diabetes course,fasting blood glucose and other factors,the levels of SHBG,eGFR and HbAlc of phenotype 3 are still higher than those of phenotype 2(OR>1,P<0.05),and TG level is still lower than that of phenotype 2 patients(OR<1,P<0.05).In the logistic regression analysis of phenotype 1 and phenotype 2,postmenopausal women with phenotype 2 have type 2 diabetes patients whose SHBG,fasting blood glucose,and FT4 levels are lower than those of phenotype 1(OR<l,P<0.05).After adjusting for age,diabetes course,HbAlc and other factors,the levels of SHBG,fasting blood glucose and FT4 of phenotype 2 were still lower than those of phenotype 1(OR>1,P<0.05).In the logistic regression analysis of phenotype one and phenotype three,postmenopausal women with phenotype three had higher SHBG levels than those with phenotype one(OR>1,P<0.05),and Patients with fasting blood glucose,HOMA-IR,and TG levels lower than phenotype one(OR<1,P<0.05).After adjusting for age,diabetes course,HbAlc and other factors,the SHBG level of phenotype three was still higher than that of patients with phenotype one(OR>1,P<0.05).In the logistic regression analysis of phenotype two and phenotype three,the levels of SHBG,eGFR,HbAlc,and FT4 in postmenopausal women with phenotype three are higher than those with phenotype two(OR>1,P<0.05),and patients with HOMA-IR and TG levels lower than phenotype 2(OR<1,P<0.05).After adjusting for age,diabetes course,and fasting blood glucose,the levels of SHBG and HbAlc of phenotype 3 were still higher than those of phenotype 2(OR>1,P<0.05).Linear regression analysis was used to evaluate the correlation between the SNP locus of different clinical phenotypes of SHBG and ln(SHGB)levels.The analysis of each phenotype of male patients showed that the 4 SHBG genotypes studied were related to serum SHBG There is no correlation between levels.In the analysis of postmenopausal women,the genotype rs6259 of patients with phenotype three was negatively correlated with serum SHBG levels(Estimate=-0.382,P<0.05),and genotype rs858518(Estimate=0.670,P<0.01)was negatively correlated with serum SHBG levels.SHBG levels are positively correlated.ConclusionAmong the different clinical phenotypes of this group of type 2 diabetic patients,male type 2 diabetic phenotype 1(fasting C peptide>0.3nmol/L and BMI≤25)showed lower eGFR,lower HbAlc,low blood lipids,and SHBG level is lower,phenotype two(fasting C peptide>0.3nmol/L and BMI>25)is characterized by low SHBG level,low eGFR and low HbAlc,but higher TG level;phenotype three(fasting C peptide≤0.3nmol/L and BMI≤25)are manifested as higher SHBG levels,high eGFR,high HbAlc,low TG levels,and high CHOL levels.In postmenopausal women with type 2 diabetes,the phenotype group showed low SHBG levels and high fasting blood glucose;phenotype group two had low SHBG levels and low HbA 1 c,while phenotype group three showed high SHBG levels,low TG levels,and HbAlc high.According to the characteristics of different clinical phenotypes of type 2 diabetes,it will further guide the formulation of individualized treatment and prognosis programs for patients with type 2 diabetes. |
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