Urinary retinol binding protein and β 2-microglobulin were associated with urinary albumin to creatinine ratio and renal function in hospitalized diabetic patients / 中华内科杂志

Objective:To explore the associations of urinary retinol binding protein (RBP) and β 2-microglobulin (β 2-MG) with urinary albumin to creatinine ratio (UACR) and renal function in hospitalized patients with type 2 diabetes mellitus (T2DM). Methods:A total of 1 030 Chinese patients with T2DM were included in this study. The subjects were divided into the UACR normal group (<30 mg/g), microalbuminuria group (30-300 mg/g) and macroalbuminuria group (>300 mg/g). Patients with normal UACR were further divided into two groups according to the estimated glomerular filtration rate (eGFR): the eGFR low group (<90 ml·min -1·1.73m -2) and the normal eGFR group (≥90 ml·min -1·1.73m -2). Urine RBP and β 2-MG levels among the groups were compared. Multiple linear regression analyses were applied to evaluate risk factors of urine RBP and β 2-MG. Results:In all patients ( n=1 030), urine RBP and β 2-MG increased gradually with the increase of UACR across the three groups, the proportions of abnormal urine RBP (>0.7 mg/L) and β 2-MG (>370 μg/L) in these groups were 3.8%, 8.5%, 39.0% ( P<0.001), and 12.9%, 26.7%, 46.8% ( P<0.001), respectively. In the UACR normal group ( n=788), 12.2% of the patients were with eGFR<90 ml·min -1·1.73m -2. The proportion of abnormal β 2-MG (>370 μg/L) was higher in the eGFR low group than that in the eGFR normal group (29.2% vs. 10.7%, P<0.001). Multivariate linear stepwise regression analyses were performed using natural logarithm of urine RBP or β 2-MG as dependent variable, and showed that urine RBP was independently associated with UACR ( β=0.0005, P<0.001), serum creatinine ( β=0.006, P<0.001) and glycosylated hemoglobin A1c ( β=0.050, P=0.001), and β 2-MG was independently correlated with UACR ( β=0.000 4, P<0.001), serum creatinine ( β=0.011, P<0.001), systolic blood pressure ( β=0.005, P=0.031) and fasting blood-glucose ( β=0.027, P=0.046). Conclusions:Urine RBP and β 2-MG are positively associated with high UACR and impaired renal function in T2DM patients, and these changes could occur before UACR and eGFR turned out to be abnormal. It is recommended that urine RBP and β 2-MG be detected as early as possible to identify diabetic kidney disease in patients with normal UACR and eGFR.

Application of the superior thyroid artery peak systolic velocity in differentiating Graves′ disease from autoimmune thyroiditis / 中华内科杂志

Objective@#To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis.@*Methods@#A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People′s Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves′ disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD.@*Results@#STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95%CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT4) (β=0.371, 95%CI 0.005-0.010, P<0.001) and TRAb (β=0.138, 95%CI 0.001-0.014, P=0.035) were positively associated with STA-PSV.@*Conclusions@#The STA-PSV is positively associated with FT4 and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

Application of the superior thyroid artery peak systolic velocity in differentiating Graves′ disease from autoimmune thyroiditis / 中华内科杂志

Objective:To evaluate the clinical value of the superior thyroid artery peak systolic velocity (STA-PSV) for the differential diagnosis of autoimmune thyrotoxicosis.Methods:A total of 301 patients with newly diagnosed thyrotoxicosis and without any anti-thyroid drug intervention were collected from the Department of Endocrinology and Metabolism, Peking University People′s Hospital from Jan. 2015 to Oct. 2018. Among them, 241 patients were with Graves′ disease (GD) and 60 patients were with autoimmune thyroiditis (AIT). STA-PSV, thyroid function and thyrotropin receptor antibody (TRAb) were determined. A multiple linear regression was used to identify factors associated with STA-PSV. A receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the discriminating ability of STA-PSV to GD.Results:STA-PSV leves in GD group were significantly higher than those in AIT group [61.00 (41.00, 86.50) cm/s vs. 34.50 (25.25, 46.00) cm/s, P<0.001]. The ROC curve analysis showed that the AUC was 0.790 (95 %CI 0.734-0.845), and 49.5cm/s was the optimal cutoff point for the diagnosis of GD, in which the sensitivity was 64.3% and the specificity was 83.3%. In all patients with thyrotoxicosis, multiple linear regression analyses showed free thyroxine (FT 4) (β=0.371, 95 %CI 0.005-0.010, P<0.001) and TRAb (β=0.138, 95 %CI 0.001-0.014, P=0.035) were positively associated with STA-PSV. Conclusions:The STA-PSV is positively associated with FT 4 and TRAb levels, and it is a helpful marker in differential diagnosis between GD and AIT.

Research on Metformin pharmacogenomics in the treatment of type 2 diabetes / 中国糖尿病杂志

Metformin is a first-line therapy for type 2 diabetes mellitus.Individual variation in response to metformin exists in clinical practice,which is associated with genetic background.Current researches focus on elucidating the relationship between the polymorphisms of genes and the absorption,transportation,metabolism,and excretion of metformin,and also pharmacogenomics of metformin treatment.Pharmacogenomics also provides theoretical basis for individualized therapy.Here,we reviewed the literature progress for metformin pharmacogenomics.

Impaired early-phase insulin secretion is the major risk factor for glucose metabolism deterioration in the population with normal glucose tolerance / 中华内分泌代谢杂志

Objective To evaluate the effect of early-phase insulin secretion and insulin resistance in the pathogenesis of type 2 diabetes, and to analysis the risk factors of glucose tolerance deterioration. Methods Oral glucose tolerance test (OGTT) was performed in subjects over 30 years old coming from 78 families with type 2 diabetes. A total of 118 subjects with normal glucose tolerance (NGT) [fasting plasma glucose (FPG)<6.1 mmol/L and 2h postprandial glucose (2hPG)<7.8 mmol/L] were enrolled. Another OGTT was performed in them to define the glucose tolerance status at the end of the 4-7 years follow-up. AINS30/APG30, the ratio of the increment of insulin to that of plasma glucose at 30 min after the glucose load, was used to assess the early phase insulin secretion. HOMA-IR and HOMA-β were calculated to assess the insulin resistance and β-cell function respectively. Results After 4-7 years follow-up, 66 of 118 subjects still remained NGT, while 52 became either diabetic (n=11)or pre-diabetic (n=41). Using the median of HOMA-IR and AINS30/APG30 as the cutoff points, all subjects were divided into four groups: subjects with good early phase insulin secretion and no insulin resistance, subjects with good early insulin secretion but relative insulin resistance, subjects with impaired early phase insulin secretion but no insulin resistance, subjects with impaired early phase insulin secretion and also relative insulin resistance. The incidences of abnormal glucose tolerance among these four groups were 23.1%, 36.4%, 45.5% and 73.1% respectively. There was a statistical difference between the former three groups and the last one (P<0.05). Log/st/c regression analysis showed that only the early phase insulin secretion was the risk factor of glucose tolerance deterioration, while age, gender, insulin resistance or β-cell function were not. Conclusion Impaired early phase insulin secretion is a major risk factor for the disturbance of glucose metabolism in the population with NGT.

The clinical characteristics of the familial early onset type 2 diabetes mellitus / 中国糖尿病杂志

Objective To investigate the clinical characteristics of the familial early onset type 2 diabetes（T2DM）,and the factors affecting the age at diagnosis. Methods 190 probands from early onset T2DM pedigrees （diagnosed before 40 years old） and 103 probands from late onset T2DM （pedigrees） （all patients were diagnosed after 40 years old）were included in this study. The homeostasis model assessment of insulin resistance （HOMA-IR）was used to estimate insulin resistance, HOMA-β cell was used to evaluate basal insulin secretion. The ratio of the incremental insulin (ΔI30) over （incremental） glucose(ΔG30) was calculated after intake of a steamed bread made of 100g flour to （evaluate） the early insulin secretion. Body mass index（BMI）and serum lipid levels were also （determined.） （Results） （1）The early onset group had significantly higher fasting serum insulin （（natural） logarithm transformed, 2.6±0.6 vs 2.4±0.5 μU/ml, P<0.05）, triglycerid （TG, 1.7±2.0 vs 1.4±2.0 mmol/L,P<0.05）,HOMA-IR（natural logarithm transformed, 1.6±0.8 vs 1.3±0.6, P<0.01）and lower high density lipoprotein （HDL-C, 1.2±0.3 vs 1.3±0.3mmol/L,P<0.05） than those in late onset group.（2）Linear regression analyses showed that HOMA-IR, HOMA-β were （independent） risk factors predicting early age of onset. （3）In the early onset type 2 diabetic patients, the subgroup with BMI more than 25 kg/m2 had significant earlier diagnosis age （32±7 vs 34±5 y, P<0.05）, lower level of serum HDL-C （1.1±0.3 vs 1.3±0.3 mmol/L, P<0.01）, higher FIns （（natural） logarithm transformed, 2.8±0.6 vs 2.4±0.6, P<0.01）, higher HOMA-IR （natural （logarithm） transformed, 4.3±0.9 vs 3.9±1.0, P<0.01）and higher TG （1.9±2.0 vs 1.5±2.1 mmol/L, P<0.01）than those with BMI less than 25 kg/m2. Conclusion Compared with late onset familial type 2 diabetic patients,more severe insulin resistance and relative β cell function defect are the important clinical （features） in early onset familial type 2 diabetic patients. The interaction between （insulin resistance） and （β-cell） dysfunction are probably the determinants of onset age of T2DM.

Cross-sectional study of the pathophysiologic and clinical features in the first-degree relatives of type 2 diabetic patients / 北京大学学报(医学版)

Objective: To explore the pathophysiologic and clinical features and investigate the roles of insulin resistance and insulin secretion in the pathogenesis of type 2 diabetes mellitus. Methods:A total of 888 first-degree relatives without glucose intolerance history underwent an oral glucose test (OGTT) and their level of HbA1c, insulin concentration and lipid levels were determined. The homeostasis model assessment was used to estimate insulin resistance (HOMA IR ) and ?-cell function (HOMA-?). The ratio of incremental glucose (?G30) and insulin (?I30) response was used to evaluate the early insulin secretion.?I30/?G30/HOMA IR was used to evaluate the glucose disposition index (DI). Results: In the subjects, 167 were diagnosed with diabetes, 180 with impaired glucose tolerance or/and impaired fasting glucose (impared glucose regulation), 457 with normal glucose tolerance and normal HbA1c, and 84 with normal glucose tolerance and high HbA1c. From normal glucose tolerance through impared glucose regulation to diabetes mellitus, the HOMA IR , body mass index (BMI), waist/hip ratio (WHR) and serum triglyceride (TG) progressively increased, HOMA-? cell 、?I30/?G30 、 DI and high density liproprotein (HDL) progressively decreased. Subjects with normal glucose tolerance were divided into three tertile subgroups (1/3, 2/3 and 3/3 groups) with different area under the curve of OGTT glucose, after being adjusted by sex, age, BMI, the 3/3 group was found having higher HOMA IR , and lower HOMA-?, ?I30/?G30/, and DI than the 1/3 group. Conclusion: Both insulin resistance and impaired ? cell function are important pathophysiologic changes contributing to the onset and development of type 2 diabetes. These changes and lipid profile have occurred before a patient is diagnosed with abnormal glucose tolerance.

Contribution of MODY2 gene to the pathogenesis of Chinese early onset familial type 2 diabetes / 北京大学学报(医学版)

T polymorphism and early onset familial type 2 diabetes,the frequency of allele T of early onset familial type 2 diabetes population was significantly lower ,and the frequency of allele C significantly higher, than those of control subjects(PT polymorphism at MODY2 gene, intron 9 or nearby genes was associated with early onset familial type 2 diabetes .

Stydy of relationship of sulfonylurea receptor-1 gene polymorphism with high insulin secretion levels in non-diabetes Chinese / 中国糖尿病杂志

Objective　A recent study has shown the association between a sulfonylurea receptor gene-1 (SUR1) variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group,supporting the hypothesis that the primary insulin hypersecretion may be an antecedent of type 2 diabetes.Methods　To test this hypothesis in Chinese population,we studied the allele and genotype distribution of the polymorphism at -3 position of intron 24 in SUR1 by PCR-RFLP technique in 206 unrelated normal glucose tolerant subjects with strong family history of type 2 diabetes (group A) and 110 normal individuals without family history of diabetes (group B).Results　The frequency of “-3c” allele and “-3cc” genotype of intron 24 in group A was significantly higher than that in group B (64% vs 54%，P=0.004 and 38% vs 24%，P=0.002 respectively).Moreover,in group A, those carrying “cc” genetype had a higher BMI (27.27±6.37 vs 24.99±3.43kg/m2，P＜0.05；27.27±6.37 vs 25.28±2.78kg/m2，P＜0.05),fasting insulin (15.52±10.72 vs 9.27±5.03U/ml,P＜0.01；15.52±10.72 vs 10.79±7.80U/ml,P＜0.05) and 2h insulin levels (76.41±54.02 vs 55.43±49.60U/ml,P＜0.01；76.41±54.02 vs 55.71±40.39, P＜0.05) as well as lower insulin sensitivity ［HOMA(Ri］: 4.00±3.09 vs 2.79±1.32, P＜0.01； 4.00±3.09 vs 2.82±2.94, P＜0.01) as compared with that in carriers of other genotypes (“ct” and “tt”).Conclusion　This study suggested the possibility that the defect in SUR1 gene might contribute to the insulin hypersecretion which might be the cause of subsequent increased body weight and decreased insulin sensitivity.

Prevalence and clinical characteristics of mitochondrial mutations in Chinese patients with type 2 diabetes / 中国糖尿病杂志

Objective To assess the prevalence of the A to G mutation at position 3243 of the mitochondrial tRNALeu(UUR) gene in type 2 diabetes in a Chinese population. Methods We screened 716 randomly selected, unrelated patients with type 2 diabetes for the mutation with a PCR-RFLP technique. Results Three individuals with this mutation were identified, representing approximately 0. 4％ of the type 2 patients screened. Further screening of first degree relatives of these 3 patients identified another 4 affected carriers. In comparison with type 2 diabetic patients without the mutation, these 7 carriers of the mt3243 mutation had:①an earlier onset of diabetes (38. 0±10.1 yr vs 53. 4±10.0 yr, P ＜0. 001) ;②lower BMI (19.5±2.0 vs 24. 9±10. 9, P ＜0. 0001) ;and ③ lower post-challenge insulin levels (Area under the curve of insulin levels during the OGTT, 2946± 1647.2 vs 7469±6647.7, P ＜ 0. 01). In addition, we screened the same 716 patients with type 2 diabetes, as well as 181 controls with normal glucose tolerance,for a newly described mt 3316 G→A mutation. This mutation was found in 16 patients with type 2 diabetes (2.20％) and 5 controls (2.7％). Therefore, the frequency of the mutation was not different between patients and controls.Moreover, clinical characteristics such as age of onset of diabetes, BMI, and insulin levels were not different between diabetic patients with the mt3316 mutation and those without it. Concision The mt3316 G→ A mutation is a polymorphism unrelated to diabetes.

The role of apoptosis of ?-cells in the pathogenesis of Diabetis in OLETF, of obese type 2 diabetes rats / 中国糖尿病杂志

Objective To determine whether the ? cells apoptosis exits in the obesity associated type 2 diabetic rats OLETF and the relationship between the apoptosis and development of type 2 diabetes. Methods Twenty OLETFs and twenty LETOs as control were used. HE staining and TUNE were the way to examine apoptotic ? cell in pancreatic sections. Results (1) The incidence of diabetes in OLETF rats was 95%. None of diabetic rat was found among LETO rats. (2) Apoptotic cells only appeared in pancreatic sections from OLETF rats. (3) The percentage of islet ? cell apoptosis in OLETF rats was higher than that in LETO rats (P=1.26?10 -17 ). (4) In OLETF rats, the percentage of islet ? cells apoptosis was higher in the ages of 4 weeks after the onset of diabetes than that in the ages of four weeks before the onset of diabetes. Conclusion There was a high level of ? cell apoptosis in OLETF rats prior to the onset of diabetes and a further increase of apoptosis after diabetes.

The role of calpain10 gene polymorphism in the genetic susceptibility to type 2 diabetes in Chinese population / 中国糖尿病杂志

Objective To test the hypothesis that calpain 10 gene (CAPN 10) contributes to the genetic susceptibility to type 2 diabetes in Chinese population.Methods Case control study. PCR RFLP method was used to determine the distribution of allele and genotype frequencies of SNP43 polymorphism (G/A) and SNP 19 polymorphism (1/2) in the intron 3 of calpain 10 gene in 211 type 2 diabetes patients and 127 normal control subjects. Results The frequency of "G" allele of the SNP43 in type 2 diabetes patients was significantly increased as compared with that in the control subjects (91.9% vs 85.8%, P =0.01). The distribution of allele and genotype frequency of the SNP19 (1/2) polymorphism were equal in diabetes and control groups.In addition, we also observed the association between GG genotype and increased body mass index and waist to hip ratio in the control group.Conclusion This study suggested that calpain 10 gene may contribute to the genetic susceptibility of type 2 diabetes in Chinese population.

Stydy of relationship of sulfonylurea receptor-1 gene polymorphism with high insulin secretion levels in non-diabetes Chinese / 中国糖尿病杂志

Objective A recent study has shown the association between a sulfonylurea receptor gene 1 (SUR1) variant and hyperinsulinemia in normal individuals from a high diabetes risk ethnic group,supporting the hypothesis that the primary insulin hypersecretion may be an antecedent of type 2 diabetes.Methods To test this hypothesis in Chinese population,we studied the allele and genotype distribution of the polymorphism at -3 position of intron 24 in SUR1 by PCR RFLP technique in 206 unrelated normal glucose tolerant subjects with strong family history of type 2 diabetes (group A) and 110 normal individuals without family history of diabetes (group B).Results The frequency of “-3c” allele and “-3cc” genotype of intron 24 in group A was significantly higher than that in group B (64% vs 54%, P =0 004 and 38% vs 24%, P =0.002 respectively).Moreover,in group A, those carrying “cc” genetype had a higher BMI (27 27?6 37 vs 24.99?3.43kg/m 2, P