An Investigation Of Urinary Protein Excretion In Hospitalized Patients With Type 2 Diabetes Mellitus

Objective:? This study was performed to clear the basic characteristics and the incidence of cardiovascular disease and dyslipidemia in hospitalized patients with type 2 diabetes mellitus(T2DM).? Further analysis was performed to study the clinical characteristics and urinary protiens excretions of patients with or without diabetic kidney disease(DKD).Thyroid hormone levels and thyroid dysfunction were also investigated in T2 DM patients with DKD.Urinary excretions of various glomerular or tubular proteins in different conditions of thyroid function were also evaluated.? The risk factors for the development of DKD were also analyzed in this study.Methods:1)The Electronic Patient Record was used to define the cohort of hospitalized patients diagnosed T2 DM from May 2008 to February 2016 in the Department of Endocrinology of Anhui Provincial Hospital Affiliated to Anhui Medical University.Demographic information,history,lab test reports and medical examinations were obtained from 4116 hospitalized patients with T2 DM.2)Bloodspecimen detection.Overnight blood samples were collected for testing of hemoglobin A1c(Hb A1c),renal function,serum lipid and thyroid hormone levels.Hb A1 c was detected by high performance liquid chromatography.The SCr,BUN and blood lipid were determined using the automatic biochemical analyzer and HITACHI original kit.Free triiodothyronine(FT3),free thyroxine(FT4)and sensitive thyrotropin hormone(s TSH)were tested by chemiluminescence immunoassay.The modified MDRD fomular for Chinese was used to calculate e GFR.3)Urine specimen detection method.Morning urine was collected to detect the urine protein,including albuminuria(ALB),transferrin(TRF),immunoglobulin G(Ig G),Tamm-Horsfall protein(THP)and retinol binding protein(RBP).Urinary ALB,Ig G and THP were determined by radioimmunoassay.The urinary creatinine was detected by enzymatic method.Urine albumin creatinine ratio was calculated.Urinary TRF and RBP were detected by enzyme-linked immunoassay.Results:? The basic characteristics of patients of T2DM: Durations ranged from newly diagnosed to 40 years;age distributed from 18 y to 80 y and 49.83% were elders exceeding 60y;24.83% of the inpatients had a hemoglobin A1 c below 7%.27.55% of patients had a history of smoking.41.16% of patients presented as overweight and18.56% presented as obesity.The incidences of high blood pressure present,cardiovascular and stroke were 55.13%,15.38% and 20.41%,respectively.65.67% of patients presented dyslipidemia.57.68% of them had hypercholesterolemia and 24.76%hypertriglyceridemia.Average hemoglobin A1 c was 9.04±2.53%.Mean serum creatinine level was 79.31±55.19?mol/L and mean blood urea nitrogen level was 6.47±3.06mmo/L.Compared to male,femalepatients had a lower smoking rate(P<0.05),higher ratio of overweight or obesity,and also higher incidences of cardiovascular disease and dyslipidemia(P<0.05).? The clinical characteristics of DKD in T2 DM patients: After removing the missing values,2278 patients were consisted in final analysis.39.29% of T2 DM patients was diagnosed DKD.Patients in the group of DKD had older age,longer duration,a higher ratio of female,higher incidences of high blood pressure,coronary heart disease,hypercholesteremia and hypertriglyceridemia,and also higher systolic pressures,blood cholesterol,low density lipoprotein cholesterol,serum creatinine,blood urea nitrogen and sensitive thyrotropin hormone(s TSH)(P < 0.05).However,the free triiodothyronine(FT3)and free thyroxine(FT4)were much lower in patients with DKD(P<0.05).? The clinical characteristics of T2 DM patients according to the urinary albumin to creatinine ratio(UACR): Compared to nomoalbuminuria group,patients of microalbuminuria had higherincidences of high blood pressure,coronary heart disease and hypercholesteremia,and also higher level of serum creatinine.The patients in macroalbuminuria had longer duration,higherincidences of high blood pressure,coronary heart disease and hypercholesteremia,as well as higher blood cholesterol,low density lipoprotein cholesterol,serum creatinine and blood urea nitrogen than those of patiens with nomoalbuminuria(P<0.0167).Incidences of high blood pressure and hypercholesteremia,total cholesterol,low density lipoprotein cholesterol,serum creatinine,blood urea nitrogen were higher and hemoglobin A1 c was lower in macroalbuminuria group than those in microalbuminuria group(P<0.0167).The proportion of T2 DM patients with e GFR <60ml·min-1·1.73m2 was much higher in albuminuria groups and was the highest in macroalbuminuria group(P<0.0167).? The clinical characteristics of T2 DM patients according to estimated glomerular filtration rate(e GFR): Among three groups,patients in low filtration group had the oldest age,the highest female ratio,incidences of high blood pressure and coronary heart disease,as well as total cholesterol,serum creatinine and blood urea nitrogen,but the lowest smoking rate,hemoglobin A1 c and high density lipoprotein cholesterol(P<0.0167).Compared to normal filtration group,patients in hyperfiltration group had younger age,shorter duration,lower female ratio,incidences of high blood pressure andstroke and hypercholesteremia,and also serum creatinine level,but had higher smoking rate,hemoglobin A1 c and high density lipoprotein cholesterol(P<0.0167).Patients in low filtration group also had older age,longer duration,higher female ratio,incidences of CVD,hemoglobin A1 c,serum creatinine level and blood urea nitrogen than those indexes of patients in hyperfiltration group(P<0.0167).The proportion of albuminuria was highest in T2 DM patients with low filtration.?Diagnosis test performed by UACR and Scr to detect e GFR<60ml·min-1·1.73m2:When e GFR<60ml·min-1·1.73m2 was considered as a standard,SCr had the best consistency with e GFR.Combination of ACR and Scr was superior to assess the consistency than UACR alone.Although the sensitivities of UACR?30 mg/g Cr alone or with SCr?120?mol/L were not bad to detect an e GFR< 60ml·min-1·1.73m2,neither of them had a good specificity.All the Diagnosis indexes had good negative predictive rate to assess an e GFR<60ml·min-1·1.73m2.? The determination of urinary protein excretion showed that patients with microalbuminuria and macroalbuminuria had higher urinary excretions of transferrin(TRF),immunoglobulin G(Ig G)and retinol binding protein(RBP)and urinary excretion of lower Tamm-Horsfall protein(THP)than those of patients with nomoalbuminuria(P<0.0167).Urinary excretions of TRF,Ig G and RBP were the highest and urinary excretion of THP was lowest in macroalbuminuria group(P<0.0167).More proportions of higher urinary TRF,Ig G and RBP and lower urinary THP were in albuminuria groups,especially in macroalbuminuria group.In low filtration group,urinary excretions of TRF,Ig G and RBP were the highest and urinary excretion of THP was the lowest(P<0.0167).Urinary TRF and RBP excretions were lower and urinary THP excretion was higher in hyperfiltration group than those in normal filtration group(P<0.0167).Urinary Ig G excretion had no different between hyperfiltration group and normal filtration group(P>0.0167).The proportions of high urinary TRF,Ig G and RBP,as well as the low urianry THP,were highest in low filtration group(P<0.0167).? The incidences of thyroid dysfunction in patients with or without DKD: Mean levels of FT3 and FT4 levels were the lowest,whereas s TSH level was the highest both in macroalbuminuira group and low filtration group(P<0.0167).There was no significant difference of thyroid hormone between normoalbuminuria and microalbuminuria(P>0.0167).Also,Thyroid hormone levels had no significant difference between normal filtration group and hyperfiltration group(P > 0.0167).In patients with DKD,proportions of normal thyroid function,clinical hypothyroidism,subclinical hypothyroidism,subclinical hyperthyroidism and clinical hyperthyroidism presented as81.57%,2.01%,14.41%,1.23% and 0.78%,respectively.The incidences of subclinical hypothyroidism in DKD group was higher than non-DKD group(?2=16.33,P<0.0125).There were no significant differences in the incidences of clinical hypothyroidism,subclinical hyperthyroidism and clinical hyperthyroidism between two groups(?2=2.196,0.92 and 0.05,P>0.0125).The incidence of subclinical hypothyroidism was thehighest both in macroalbuminuria group and low filtration group(21.22% and21.40% respectively).? The effects of thyroid dysfunction on urinary proteins excretion: Among three groups,UACR and urinary excretion of TRF were the highest,whereas urinary THP excretion was the lowest in T2 DM with hypothyroidism(vs.normal thyroid function group or hyperthyroidism group,P<0.0167).UACR and urinary TRF excretion were the lowest in patients with hyperthyroidism among three groups(P<0.0167),but not lower than patients with normal thyroid function(P>0.0167).Urinary excretions of Ig G and RBP had no differences among the three groups(P>0.0167).? Logistic regression showed that hypothyroidism and increased duration andsystolic pressures were associated with increased UACR.Both hypothyroidism and subclinical hypothyroidism,and also increased age,systolic pressures were associated with declined eGFR as well as decreased high density lipoprotein cholesterol in the model.Conclusions:1.The control of blood glucose and body weightis seriously poor and the incidences of dyslipidemia and cardiovascular disease are high in hospitalized patients with T2 DM.2.Combination of e GFR,UACR and SCr may increase the diagnosis of DKD.Further combined examination of various urinary proteins is morehelpful to the diagnosis of DKD in the early stage and monitoring of the therapy effect.3.Subclinical hypothyroidism is more prevalent in T2 DM Patients with DKD.Hypothyroidism has a significant association with DKD,which may cause renal damage both in glomerulus and tubule.