Association Between The Glucocorticoid-induce Glucose Metabolic Disorders And Plasma Corticosteroid Levels In The Patients With Renal Glomerular Disease

Objective: The patients with renal golmerular disease need a glucocorticoid therapy of larger daily doses and longer duration and that makes the incidence of glucose metabolic disorders and steroid diabetes (SD) more higher. Hyperglycemia or insulin resistance will in turn aggratate kidney damage. The development of SD undergoes a process from insulin resistance to isletβ-cells damage to glucose tolerance abnormal or diabetes as type 2 diabetics does. Derangement of pituitary-adrenal axis (HPA) function is observed in the patients with abnormal glucose tolerance and type 2 diabetics which may be one of the mechanisms that provokes the insulin resistance in early stage of type 2 diabetics.Renal glomerular disease is associated with dysimmunity and hypofunction of HPA is observed in nephrotic syndrome even before the glucocorticoid therapy.However,there are few studies analyzing the association between the functional changes of adrenal cortex and the development of glucose metabolic disorders.In our study,the function of adrenal cortex before glucocorticoid therapy and its subsequent relationship with the development of glucose metabolic disorders is analyzed in order to provide reference for the screening of high risk group and pristine treatment of SD.Methods: 63 patients (40 men; age:34.2±15.7 years; with renal glomerular disease who were confirmed by renal biopsy needing prednison therapy were recruited, 30 with nephrotic syndrome and 33 with chronic glomerulonephritis. No patients were suffered from diabetes;pancreatic,gall bladder or liver diseases;stess or took related drugs. All of them were follow up to end of February,2010. Before glucocorticoid therapy the following index were measured:①fasting plasma corticosteroid, ACTH at 8:00;2-hour postprandial plasma corticosteroid and ACTH;corticosteroid and ACTH at 16:00 (Chemiluminescence technique,IMMULITE,provided by American DBPC company).②pre-meal glucose and 2-hour post-meal glucose levels (finger-blood,Roche , GLUCORREND2);fasting and 2-hour postprandial plasma glucose,insulin.The glucose tolerance test was required if fasting plasma glucose is more than 6.0 mmol/L and/or 2-hour postprandial plasma glucose is more than 7.8 mmol/L.③HOMA-insulin resistance was calculated from the formula IR=fasting blood sugar×fasting insulin/22.5 (HOMA-IR,with venous blood).Patients were asked to monitor postprandial glucose at the first week and the first month after treatment.Results: Of the 63 patients (BMI 24.7±4.5 kg/m2;prednisone dosage 0.73±0.13 mg.kg-1.d-1;Scr 90.5±54.6μmol/L;Urine protein 4.1±2.4 g/d; seralbumin 9.2±19.3 g/L;triglyceride (TG) 2.6±2.4 mmol/L;cholesterol (TC) 7.3±3.1 mmol/L,high densitv lipoprotein (HDL) 1.5±0.4 mmol/L,low-density lipoprotein (LDL) 4.6±2.4 mmol/L),①Before prednisone treatment 23 patients were of impaired glucose tolerance among which 13 develop SD (incidence 56.5%) and it is much higher than the incidence (6 patients in 40,incidence 15.0%, p=0.001) of the normal glycometabolism group. The incidence of glucose metabolic disorders after corticosteroid therapy is 74.6% and SD is 30.2%.②The patients were divided into three groups :normal glucose regulation (NGT) 16 cases,impaired glucose tolerance (IGT) 12 cases and steroid diabetes (SD) 11 cases according to postprandial glucose . Age in NGR group was lower than that in the other two groups and Scr in SD group was higher than that in the other two groups (all p<0.05). Plasma corticosteroid, ACTH in three groups are of the normal range but show rhythm disturbance that the concentration at 16:00 exceeds half of that at 8:00 ;The concentration of 8:00 fasting plasma corticosteroid in SD group and IGT gruop is much higher than that of NGR group(p<0.05).③8:00 and postprandial corticosteroid were negatively correlated with TC, HDL and LDL levels (r=-0.361~-0.142,p=0.004~0.035). 8:00,16:00 corticosteroid were positively correlated with whether or not after taking corticosteroid (rs=0.365,0.293 and p=0.004,0.O25).The concentration of fasting plasma corticosteroid at 8:00 is the risk factors of occurrencing glucose metabolic disorders (χ2=5.374,p=0.020,RR=1.403) which means that with a 8:00 fasting plasma corticosteroid level more than 464.6 nmol/L,the risk of occurrencing glucose metabolic disorders is 1.4 times higher than that of less than that level.Conclusion: The incidence of glucocorticoid-induce glucose metabolic disorders is high in the derivative phase of renal glomerular disease. There is rhythm disturbance of the Pituitary-Adrenal Axis in more than half of the patients before glucocorticoid therapy.A higher level of 8:00 corticosteroid level is a risk factor for the development of SD.