Effect of flash glucose monitoring on ambulatory glucose profile in patients with type 2 diabetes mellitus / 中国医师进修杂志

Objective To investigate the effect of flash glucose monitoring (FGM) on ambulatory glucose profile of only oral antidiabetic drugs treated patients with type 2 diabetes mellitus. Methods Twenty-eight type 2 diabetic mellitus patients with only oral antidiabetic drugs treatment from August 2017 to January 2018 were enrolled. All the patients were exposed to FGM for 14 d without changing the original treatment and encouraged to manage self-behavior by adjusting diet and activity based on the blood glucose data obtained from the real-time scanning. The changes in glucose profile during the FGM period were observed, including estimated glycated hemoglobin (HbA1c), standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, time in range (blood glucose 3.9 to 10.0 mmol/L), area under the curve hyperglycemia (blood glucose> 10.0 mmol/L) and area under the curve hypoglycemia (blood glucose<3.9 mmol/L). The blood glucose levels on second day and thirteenth day were used as baseline and end point respectively. Results All of the 28 patients did not change their anti-diabetic drug therapy and there were no adverse events occurred. The estimated HbA1c was significantly lower than the baseline HbA1c: (6.90 ± 1.48)% vs. (7.57 ± 1.35)%, and there was statistical difference (P = 0.004). The standard deviation of blood glucose, variable coefficient of blood glucose, mean amplitude of glycemic excursions, area under the curve hyperglycemia and area under the curve hypoglycemia at end were significantly lower than those at baseline: (2.07 ± 0.86) mmol/L vs. (2.44 ± 0.86) mmol/L, 0.26 ± 0.11 vs. 0.30 ± 0.11, (5.32 ± 2.75) mmol/L vs. (6.76 ± 3.06) mmol/L, 265 (0, 1 310) vs. 351 (107, 2 177) and 0 (0, 0) vs. 0 (0, 19), the time in range at end was significantly higher than that at baseline: (1 069 ± 386) min vs. (921 ± 449) min, and there were statistical differences (P＜0.05 or＜0.01). The rate of scanning was (12.92 ± 4.87) times/d. Conclusions FGM could be applied by type 2 diabetic mellitus patients to make self-glycemic management without changing therapy, reduce the estimated HbA1c,and hypoglycemia, and improve the glucose fluctuations, which may result from real-time scanning to find abnormal glycemia and adjust daily behavior.

Clinical features and genetic characteristics of 33 patients with simple virilizing form of 21-hydroxylase deficiency / 中华内科杂志

Objective To analyze the clinical features and genotypes of adult patients with simple virilizing form of 21-hydroxylase deficiency (SV 21-OHD).Methods This is a retrospective study including 33 patients with SV 21-OHD from January 2015 to March 2018 in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine.Results The diagnostic age of the patients was (26.3± 6.5) years old.All patients presented with signs of masculinization,such as short stature (100％),clitoromegaly/microphallus (89.65％,26/29),undeveloped breasts (82.76％,24/29),deep voice (55.17％,16/29) and primary amenorrhea (89.65％,26/29).The serum levels of 17-hydroxyprogesterone (17-OHP),androstenedione (AD) and testosterone were significantly elevated in 90.9％,93.9％ and 91.2％ of the patients,respectively.Thirteen types of mutations were identified in CYP21A2 from these patients.Among them,I173N accounted for 40％ and I2 G accounted for 18.33％.Four patients were found with multiple mutations in CYP21A2.Conclusions Short stature,clitoromegaly/microphallus and primary amenorrhea are the most common clinical features in adult patients with SV 21-OHD.Serum levels of 17-OHP and AD are important indices for the diagnosis and monitoring of the patients.I173N and I2 G are the two most prevalent mutations in patients of the present study.Limitation of clinical recognition and delay in treatment contribute to the short stature of the SV 21-OHD patients.

Cross-sectional study of current situation of glucose metabolism with in-hospital type l diabetic patients / 中国医师进修杂志

Objective To analyze the present situation of glucose metabolism and the characteristics of blood glucose fluctuation in in-hospital type l diabetic patients (T1DM). Methods One hundred and forty-three hospitalized cases of T1DM patients from November 2012 to November 2016 were retrospectively analyzed.The percentage of adult-onset T1DM patients was 76.22%(109/143)and none adult-onset was 23.78%(34/143). The following data were collected: general information, the indexes of glucose metabolism and islet function.Seventy-two-hour continuous glucose monitoring(CGM) was carried on 40 patients as a subgroup.Results The average age was(40.29 ± 16.79)years.The onset age of diabetes was(33.57 ± 17.18)years.The disease duration was 4.0(1.0,10.0)years.The body mass index(BMI)was(20.68 ± 2.95)kg/m2.The fasting blood glucose(FBG)was(12.02 ± 5.40)mmol/L.The HbA1c was(9.80 ± 2.65)%.The fasting C-peptide was 0.08(0.01,0.38)nmol/L.The 2-hour postprandial C-peptide (C-P 2 h) was 0.12(0.01, 0.70) nmol/L. The anti-glutamic acid decarboxylase antibody was 12.08(8.16,20.56)μg/L.The islet-cell antibody was 4.85(2.66,12.07)μg/L.By using multivariate linear regression analysis, HbA1c were negatively related to the duration and BMI of T1DM. CGM: the mean blood glucose was (10.34 ± 2.97) mmol/L. The standard deviation of blood glucose was (2.89 ± 1.07) mmol/L. The mean amplitude glycemic excursions was (7.10 ± 3.09) mmol/L. The incidence of hypoglycemia was 10.00% (≤ 2.8 mmol/L) and 32.50% (≤ 3.9 mmol/L). Conclusions Adult-onset T1DM patients account for more than two-thirds. In-hospital T1DM patients have poor control of blood glucose, and they show the clinical characteristics of high blood glucose fluctuation and more hypoglycemia.

The association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients / 中华内科杂志

Objective To evaluate the association between vitamin D deficiency and diabetic nephropathy in type 2 diabetic patients.Methods A total of 594 patients with type 2 diabetes were enrolled from the inpatients of the Nanjing Medical University Affiliated Nanjing Hospital.Fasting serum lipid profile,25-hydroxycalciferol vitamin D and urinary albumin excretion rate were investigated.The relationship between nephropathy and vitamin D deficiency (＜ 20 μg/L) or insufficiency (20-＜ 30 μg/L) was analyzed.Results Nephropathy was found in 177 subjects (29.8％) with albuminuria in 141 and proteinuria in 36 subjects.Vitamin D deficiency was found in 180 subjects and insufficiency in 157 subjects.The proportion of vitamin D deficiency was higher in the individuals with nephropathy than those without nephropathy (36.2％ vs 27.8％,P ＜0.05).The urinary albumin excretion rate was significantly higher in the patients with vitamin D deficiency than those with normal vitamin D concentration [(123.0 ± 299.2)mg/24h vs (47.6 ±97.1) mg/24h,P ＜0.01].The prevalence of nephropathy was higher in the patientswith vitamin D deficiency than those with normal vitamin D concentration (35.6％ vs 26.1％,P ＜ 0.05),while the prevalence of proteinuria was higher in patients with vitamin D deficency (12.2％ vs 3.1％,P ＜0.01).Logistic regression analysis demonstrated that vitamin D deficiency was associated with nephropathy (OR 1.57,95％ CI 1.04-2.37),even after the adjustment for age,gender,hypertension,dyslipidemia,smoking status,use of angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (OR 1.78,95％ CI 1.12-2.81).The Vitamin D concentration was significantly negatively correlated with urinaryalbumin excretion rate (r =-1.783,P ＜ 0.001).Conclusions Type 2 diabetic patients have a high prevalence of vitamin D deficiency.Vitamin D deficiency is independently associated with diabetic nephropathy.

The single nucleotide polymorphisms in the intron 1 of TSHR gene were associated with Graves' disease / 中华内分泌代谢杂志

Objective To investigate the association between single nucleotide polymorphisms in the intron 1 of thyroid stimnulating hormone receptor gene (TSHR) and Graves' disease (GD) in the Chinese Han population from Linyi city,Shandong Province.Methods A total of 1759 GD patients and 1740 control subjects were recruited for genotyping in TSHR intron 1 with genome-wide association study (GWAS) and Taqman probe technique.At the same time,serum thyroid hormone and TSH receptor antibody (TRAb) levels of patients were determined.Results Five SNPs were selected for further replication.The rs12101261 _T was significantly associated with GD risk ( OR=1.257,95％CI 1.137-1.390,P =8.23 × 10-6 ). Logistic regression identified that rs12101261 was an independent susceptibility locus of GD ( P=1.61 × 10-3 ).Furthermore,rs12101261 _T was strongly associated with GD ( OR =1.317,95％ CI 1.171-1.481,P=4.14× 10-4 ) in TRAb positive patients,but no association in TRAb negative patients ( OR=1.056,95％ CI 0.892-1.251,P=0.524 ).Serum TRAb concentration showed remarkable difference among three genotype groups of rs12101261.Conclusions Five SNPs in TSHR intron 1 are associated with GD.rs12101261 contributes to increased GD risk independently and is associated with serum TRAb level.

TSHR gene intron 1 region polymorphism and its relationship with Graves' disease / 中华内分泌代谢杂志

Objective To investigate the association between the six single nucleotide polymorphisms ( SNP),named as rs179247,rsl2101261,rs2284722,rs4903964,rs2300525,rsl7111394 in the intron 1 of thyroid stimulating hormone receptor gene (TSHR) and Graves' disease (GD).MethodsThe genotypes of the six SNPs were genotyped by Taqman probe technique on Fluidigm EP1 platform in 618 GD patients and 646 control subjects.Meanwhile,TSH receptor antibodies (TRAb) of the patients were determined.ResultsAmong the six SNPs,five S NPs were strongly associated with GD,with the most signals at rs179247_G,rs12101261_C,rs4903964 _G (P=2.85×10-10,OR=1.73,95％CI1.46-2.05;P=1.74×10-10,OR=1.73,95％CI 1.46-2.05;P=2.24×10-10,OR=1.69,95％ CI 1.44-1.99 ).The results of logistic regression analysis indicated that rs12101261 and rs4903964 were main susceptibility loci of GD in the intron 1 of TSHR.rs179247_G,rs1210126 1_C,and rs4903964_G were associated with subset of the GD patients with positive TRAb (P=4.24× 10-13,p=5.48× 10-13,P =3.89×10-12 ).Conclusionrs179247,rs12101261,and rs4903964 in TSHR intron 1 were significantly associated with GD in the Chinese Han population from Bengbu city.rs12101261 and rs4903964 were the major susceptibility SNPs associated with GD.TSHR gene may play a main role of susceptibility gene in the subset of GD patients with persistent positive TRAb.

An unique exonic splicing mutation in the CYPI7AI gene as the cause of steroid 17α-hydroxylase deficiency / 中华内分泌代谢杂志

Objective To analyze CYP17A1 gene mutation in a patient with 46,XY disordered sex development and to explore the possible influence on the phenotype of the patient.Methods Eight exons of CYP17AI gene in the patient and her parents were amplified and directly sequenced.In order to construct Mini-gene system,PCR fragments containing wildtype and mutant splicing sites were inserted in expression vector,and then transfected into cells.RT-PCR was used to observe the influence of splicing site mutation.Wildtype and aberrant splicing CYP17A1 cDNA expression plasmids were constructed and transfected into cells respectively,and CYP17A1 enzyme activity was tested in vitro.Results Mutation analysis revealed compound heterozygous CYP17A1 mutations,with Y329fs in one allele and a synonymous substitution( c.1263G＞A:GCG＞GCA) in another allele.In vitro analysis showed that the synonymous substitution induced a novel splicing site,which resulted in aberrant splicing of CYP17A1 mRNA and lacked six or seven amino acids after 415 in splicing product.In vitro transfection and enzyme activity experiment showed that the aberrant splicing product abolished the enzyme activity completely.However,this mutation did not completely influence splicing.The patient also had a part of normal splicing product,which was a coincidence to the phenotype of the patient.Conclusion This is the first description of an exonic splicing mutation in CYP17A1 relevant to the 17ot-hydroxylase deficiency phenotype.The functional study of the aberrant splicing variant has been initiated.

Genetic diagnosis and weight loss surgery of a case of Prader-Willi syndrome / 中华内分泌代谢杂志

To investigate the clinical features, genetic diagnosis, and treatment of a patient with Prader-Willi syndrome(PWS). For a case with clinically suspected PWS, methylation specific PCR(MSPCR)amplification was applied to CpG islands of SNRPN(exon α)gene locus in the 15q11-q13. Furthermore, the diagnosis was comfirmed by the method of bisulfite sequencing PCR(BSPCR). Metabolic status before and after the operation of sleeve gastrectomy were compared. Absence of amplification of paternal allele on chromosome 15q11-q13 was detected in the case by MSPCR, different from the normal control. Results of BSPCR further proved a full methylation of CpG islands in the SNRPN gene locus. Four months after sleeve gastrectomy, systemic metabolic status and ventricular function were improved. MSPCR and BSPCR were both consistent with genetic diagnosis of PWS. Weight loss surgery is expected to be a major therapy of this disease.

Study on a pedigree with Leydig cell hypoplasia caused by novel mutation of luteinizing hormone receptor / 中华内分泌代谢杂志

Objective To investigate a Chinese pedigree suffering from Leydig cell hypoplasia ( LCH) based on clinical data and genetic diagnosis. Methods The patient was diagnosed by means of clinical data, hormone profiles, and human chorionic gonadotropin ( hCC) test. The luteinizing hormone/chorionic gonadotropin receptor(LHCGR) gene of the patient and family members was amplified and sequenced. Results The patient presented with male pseudohermaphroditism, low level of testosterone, which did not respond to hCG. Genetic analysis of the LHCGR revealed two novel mutations: a missense mutation located in exon 5, resulting in Ile replaced by Thr in the extracellular domain; and a splice site mutation in the 3' terminal of intron 6( IVS6-3 C→A). Proband's sister (46, XX) who lacked clinical manifestations showed the identical genotype with the patient. Conclusions A mutation in the consensus sequence of 3' splice site, in addition to a missense mutation (Ile 152Thr)in the extracellular ligand-binding domain is the cause of inactivation of the LHCGR gene in patient with Leydig cell hypoplasia.

Identification of steroid biosynthetic defects in genotype-proven heterozygote individuals with 17α-hydroxylase/17,20-lyase deficiency / 中华内分泌代谢杂志

Objective To investigate the adrenal steroidogenic function in genotype-proven heterozygotes carrying mutations in CYP17A1 gene in vivo. Methods Eight patients and 14 family members from 5 families with 17-hydroxylase/17,20-lyase deficiency (17OHD) were recruited. The mutations of the CYP17A1 gene in these individuals were screened by direct sequencing of PCR products. The hormonal response to ACTH was evaluated in the 14 genotype-proven carriers and 45 age- and sex-matched normal subjects. Results Three mutations were found in 5 unrelated families. 14 carriers with CYP17A1 mutation were identified, including 7 heterozygotes with D487_F489del, 6 with Y329fs, and 1 for H373L. Compared to the normal subjects, the carriers exhibited lower basal and ACTH-stimulated cortisol levels, but higher ACTH-stimulated corticosterone level. The ratios of corticosterone to cortisol in the genotype-proven heterozygotes were higher than those of normal individuals at baseline and following ACTH-stimulation. Similarly, progesterone level and ratios of progesterone to 17-hydroxyprogesterone in the male heterozygotes were also higher than that of normal individuals before and after stimulation. No significant differences were observed in the hormone levels between two genotypes (D487_F489del vs Y329fs). Conclusions Genotype-proven carriers of 17OHD without apparent clinical symptoms exhibit decreased enzyme activity,analogous to mildly impaired adrenal 21-hydroxylase activity in the carriers of CYP21 A2 gene mutation.