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1.
JAMA Netw Open ; 2(5): e193348, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31050781

RESUMO

Importance: Thyrotoxic periodic paralysis (TPP) is a potentially lethal complication of hyperthyroidism. However, only 1 specific susceptibility locus for TPP has been identified. Additional genetic determinants should be detected so that a prediction model can be constructed. Objective: To investigate the genetic architecture of TPP and distinguish TPP from Graves disease cohorts. Design, Setting, and Participants: This population-based case-control study used a 2-stage genome-wide association study to investigate the risk loci of TPP and weighted genetic risk score to construct a TPP prediction model with data from a Chinese Han population recruited in hospitals in China from March 2003 to December 2015. The analysis was conducted from November 2014 to August 2016. Main Outcomes and Measures: Loci specifically associated with TPP risk and those shared with Graves disease and prediction model of joint effects of TPP-specific loci. Results: A total of 537 patients with TPP (mean [SD] age, 35 [11] years; 458 male) 1519 patients with Graves disease and no history of TPP (mean [SD] age, 38 [13] years; 366 male), and 3249 healthy participants (mean [SD] age, 46 [10] years; 1648 male) were recruited from the Han population by hospitals throughout China. Two new TPP-specific susceptibility loci were identified: DCHS2 on 4q31.3 (rs1352714: odds ratio [OR], 1.58; 95% CI, 1.35-1.85; P = 1.24 × 10-8) and C11orf67 on 11q14.1 (rs2186564: OR, 1.50; 95% CI, 1.29-1.74; P = 2.80 × 10-7). One previously reported specific locus was confirmed on 17q24.3 near KCNJ2 (rs312729: OR, 2.08; 95% CI, 1.83-2.38; P = 8.02 × 10-29). Meanwhile, 2 risk loci (MHC and Xq21.1) were shared by Graves disease and TPP. After 2 years of treatment, the ratio of persistent thyrotropin receptor antibody positivity was higher in patients with TPP than in patients with Graves disease and no history of TPP (OR, 3.82; 95% CI, 2.04-7.16; P = 7.05 × 10-6). The prediction model using a weighted genetic risk score and 11 candidate TPP-specific single-nucleotide polymorphisms had an area under the curve of 0.80. Conclusions and Relevance: These findings provide evidence that TPP is a novel molecular subtype of Graves disease. The newly identified loci, along with other previously reported loci, demonstrate the growing complexity of the heritable contribution to TPP pathogenesis. A complete genetic architecture will be helpful to understand the pathophysiology of TPP, and a useful prediction model could prevent the onset of TPP.

2.
Endocr Connect ; 2019 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-30822273

RESUMO

OBJECTIVE: Thyroid nodules are usually accompanied by elevated thyroglobulin (Tg) level and autoimmune thyroid diseases (AITDs). However, the relationship between Tg and AITDs is not fully understood. Dysfunction of regulatory T cells (Tregs) plays important role in the development of AITDs. We aimed to evaluate the effects of Tg on the function of Tregs in patients with thyroid nodules. METHODS: Tg levels and the functions of Tregs in peripheral blood and thyroid tissues of patients with thyroid nodules from Nanjing First Hospital were evaluated. The effects of Tg on the function of Tregs from healthy donors were also assessed in vitro. The function of Tregs was defined as an inhibitory effect of Tregs on the effector T cell (CD4+ CD25- T cell) proliferation rate. RESULTS: The level of Tg in peripheral blood correlated negatively with the inhibitory function of Tregs (R = 0.398, P = 0.03), and Tregs function declined significantly in the high Tg group (Tg > 77 µg/L) compared with the normal Tg group (11.4 ± 3.9% vs. 27.5 ± 3.5%, P < 0.05). Compared with peripheral blood, the function of Tregs in thyroid declined significantly (P < 0.01), but the proportion of FOXP3+ Tregs in thyroid increased (P < 0.01). High concentration of Tg (100 µg/mL) inhibited the function of Tregs, and down-regulated FOXP3, TGF-ß, and IL-10 mRNA expression in Tregs in vitro. CONCLUSIONS: Elevated Tg level could impair the function of Tregs, which might increase the risk of AITDs in patient with thyroid nodules.

3.
Diabetes Res Clin Pract ; 150: 194-201, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30904742

RESUMO

AIMS: This study aimed to determine the association between lipoprotein-associated phospholipase A2 (Lp-PLA2), a marker for inflammation in the vessel wall and independently associated with atherosclerosis, and the incidence of diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). METHODS: A total of 1452 patients were enrolled in this retrospective cross­sectional study. We recruited patients with T2D who were tested for glycated hemoglobin, fasting and 2 h post-meal serum C-peptide, blood lipid profile, 24 h urine albumin excretion rate (UAER), blood creatine, blood albumin, uric acid, and Lp-PLA2. RESULTS: Among the patients with T2D, 40.3% were diagnosed with DKD and the correlation between DKD and Lp-PLA2 was the most significant one compared to other diabetic complications (odds ratio = 1.651, P < 0.001). Plasma Lp-PLA2 level in patients with DKD was significantly higher and increased Lp-PLA2 level was independently associated with the incidence of DKD after adjustment for age, gender, duration of diabetes, glycated hemoglobin, body mass index, blood lipids, blood pressure, presence of coronary heart disease and carotid plaque, and use of statins (odds ratio = 1.545, P = 0.013). Lp-PLA2 was found to be positively correlated with UAER (r = 0.123, P < 0.001) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.71, P = 0.009). CONCLUSIONS: Increased plasma level of Lp-PLA2 is associated with incidence and development of DKD in patients with T2D. Lp-PLA2 should be considered as a biomarker for early detection and follow-up of DKD. TRIAL REGISTRATION: clinicaltrials.gov, No. NCT03362112, Registered 30 November 2017, retrospectively registered.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , Biomarcadores/sangue , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/enzimologia , Nefropatias Diabéticas/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Endocrine ; 2018 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-30515677

RESUMO

PURPOSE: To observe the glycemic variation (GV) in uncontrolled Graves' disease (GD) patients with normal glucose metabolism measured by continuous glucose monitoring (CGM). METHODS: This was a single-center, open-label, observational study. From January 2017 to October 2017, 20 GD patients with normal glucose metabolism and 24 healthy control subjects were recruited. Serum samples were obtained at 0, 30, and 120 min after oral glucose loading for glucose, insulin, and C-peptide level measurements. Fasting plasma fasting free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone concentrations were also detected. All participants were subjected to a 3-day CGM after baseline data were collected. The primary endpoint was the difference in the mean amplitude of the glycemic excursions between the two groups. RESULTS: Compared with the healthy subjects, the GD patients had higher mean amplitude of glycemic excursions (MAGE) (P < 0.01). Multiple linear stepwise regression analysis showed that FT4 level was an independent factor for the MAGE. Interestingly, the GD patients had a significant prolongation in the time to peak glucose, especially after breakfast (P < 0.01), and the elevation in the incremental area under the curve of glucose after breakfast till 4 hours later. CONCLUSIONS: Uncontrolled GD patients with normal glucose metabolism had a greater GV, and the FT4 level may contributed to the increased GV.

5.
Arch. endocrinol. metab. (Online) ; 62(6): 585-590, Dec. 2018. tab
Artigo em Inglês | LILACS-Express | ID: biblio-983810

RESUMO

ABSTRACT Objective: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). Subjects and methods: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. Results: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. Conclusion: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.

6.
Sci Rep ; 8(1): 9713, 2018 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-29946148

RESUMO

To investigate whether metformin add-on to the continuous subcutaneous insulin infusion (Met + CSII) therapy leads to a significant reduction in insulin doses required by type 2 diabetes (T2D) patients to maintain glycemic control, and an improvement in glycemic variation (GV) compared to CSII only therapy. We analyzed data from our two randomized, controlled open-label trials. Newly diagnoses T2D patients were randomized assigned to receive either CSII therapy or Met + CSII therapy for 4 weeks. Subjects were subjected to a 4-day continuous glucose monitoring (CGM) at the endpoint. Insulin doses and GV profiles were analyzed. The primary endpoint was differences in insulin doses and GV between the two groups. A total of 188 subjects were admitted as inpatients. Subjects in metformin add-on therapy required significantly lower total, basal and bolus insulin doses than those of control group. CGM data showed that patients in Met + CSII group exhibited significant reduction in the 24-hr mean amplitude of glycemic excursions (MAGE), the standard deviation, and the coefficient of variation compared to those of control group. Our data suggest that metformin add-on to CSII therapy leads to a significant reduction in insulin doses required by T2D patients to control glycemic variations.

7.
Expert Rev Med Devices ; 15(6): 445-451, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29737214

RESUMO

BACKGROUND:  The blood glucose point-of-care testing (POCT) system is important in the decision-making process involving patients suspected of having hypoglycemia. To investigate the real world of the POCT system being used in teaching hospitals in China. METHODS: The survey was conducted by Hisend Research Group from May 2015 to July 2015 in four teaching hospitals in China. The survey questions were referred to the ISO 15197:2013 standard requirements for the use of the POCT system in a hospital setting. RESULTS: A total of 170 subjects were included from 4 hospitals, which included nursing staff, nurse unit managers, employees from the department of medical instruments, and staff members employed by the clinical laboratories in the Tianjin Metabolism Hospital, Nanjing First Hospital, First Affiliated Hospital of Dalian Medical University, and the First hospital affiliated with the Xi'an Transportation University. The average score for the four hospitals surveyed in this study was 66.6, which varied from 46.1 to 79.7. The main factors influencing the scores were the multiple choices of blood-glucose meters, and the quality control assessment. CONCLUSION: Our data indicates that the real world use of the POCT system in hospital settings in China needs more closer adherence to a quality management framework.


Assuntos
Glicemia/análise , Hospitais de Ensino , Testes Imediatos , China , Humanos , Inquéritos e Questionários
8.
Diabetes Res Clin Pract ; 141: 98-105, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29730390

RESUMO

AIMS: Considering the insulin sensitivity may increase by exercise particularly in patients with type 2 diabetes (T2D), glycemic variation during exercise needs to be studied when the patients are treated with insulin. This study aimed to explore the influence factors of the efficacy and safety of aerobic exercise in patients with T2D treated with Continuous Subcutaneous Insulin Infusion (CSII). METHODS: A total of 267 patients with T2D, treated with CSII, were included. Glycemic variations were assessed by continuous glucose monitoring (CGM). Patients were asked to complete 30 min aerobic exercise for at least one time during CGM. The patients were divided into effective and ineffective group by incremental glucose area under curve from 0 to 60 min after exercise (AUC0-60 min). RESULTS: The patients completed a total of 776 times of aerobic exercises. Blood glucose decreased fastest in the first 60 min of exercise. Pre-exercise blood glucose (PEBG) was negatively correlated with AUC0-60 min (standardized ß = -0.386, P < 0.001) and incremental AUC of blood glucose ≤ 4.4 mmol/L (standardized ß = -0.078, P = 0.034), and was significantly higher in effective group than in ineffective group (P < 0.001). The Δglucose AUC0-60 min during post-dinner was significantly higher than that during pre-lunch, post-lunch and pre-dinner (P < 0.05 for all). CONCLUSIONS: PEBG is positively correlated with efficacy of aerobic exercise. Aerobic exercise will not worsen hyperglycemia when the PEBG > 16.7 mmol/L. Post-dinner exercise decreases the blood glucose better than other periods of the day. CLINICAL TRIALS REGISTRATION: ChiCTR-ONC-17010400, www.chictr.org.cn.


Assuntos
Automonitorização da Glicemia/métodos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/terapia , Exercício/fisiologia , Infusões Subcutâneas/métodos , Sistemas de Infusão de Insulina/estatística & dados numéricos , Insulina/uso terapêutico , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
9.
Int J Endocrinol ; 2018: 2087960, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29780415

RESUMO

Objective: To compare the effect of the rapid-acting insulin analogues (RAIAs) aspart (NovoRapid) and lispro (Prandilin) on glycemic variations by continuous glucose monitoring system (CGMS) in patients within newly diagnosed type 2 diabetes mellitus (T2DM) receiving continuous subcutaneous insulin infusion (CSII) and metformin intensive therapy. Methods: This is a single-blind randomized controlled trial. A total of 110 patients with newly diagnosed T2DM and with hemoglobin A1c (HbA1c%) above 9% was hospitalized and randomly divided into two groups: group Asp (NovoRapid group) and group Lis (Prandilin group). They all received CSII and metformin therapy. Treatments were maintained for 2-3 weeks after the glycaemic target was reached. C-peptide and insulin and fructosamine were determined. CGMS was continuously applied for 4 days after reaching the glycemic target. Results: There were no significant differences in daily dosages of insulin, fasting plasma C-P and 2 h postprandial C-P and insulin, and fructosamine at the baseline and endpoint between the groups Asp and Lis. No significant differences were seen in the 24 h mean amplitude of glycemic excursions (MAGE), 24 h mean blood glucose (MBG), the standard deviation of the MBG (SDBG), fasting blood glucose, number of glycemic excursion (NGE), and the incidence of hypoglycemia between the two groups. Similarly, no significant differences were found in areas under the curve (AUC) of glucose above 10.0 mmol/L or the decremental area over the curve (AOC) of glucose below 3.9 mmol/L between the two groups. Conclusions: Lispro and aspart had the similar ability to control the glycemic variations in patients with newly diagnosed T2DM. This study was registered with ClinicalTrials.gov, number ChiCTR-IPR-17010338.

10.
Sci Rep ; 8(1): 5888, 2018 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-29651052

RESUMO

To compare the continuous subcutaneous insulin infusion (CSII) or insulin glargine based multiple injections (MDI) therapy on glycemic variations in diabetic patients receiving PN outside of intensive care settings. This was a single-center, randomized, open-label trial. Patients with type 2 diabetes (T2D) who were receiving parenteral nutrition (PN) were recruited. After baseline data were collected, recruited patients were then randomized 1:1 to a CSII group or a MDI group. All patients were subjected to a 4-day retrospective Continuous Glucose Monitoring (CGM). The primary endpoint was the differences of the 24-hrs mean amplitude of glycemic excursion (MAGE) in patients receiving the PN therapy between the two groups. A total of 102 patients with T2D receiving PN were recruited. Patients in the CSII group had a significantly decreased mean glucose level (MBG), the standard deviation of MG (SDBG), MAGE, and the coefficient of variation (CV%) compared to those in MDI group (all P < 0.01). Furthermore, we found that the patients who received a bolus insulin dose required maintaining euglycemic control was gradually decreased during the PN period in both groups at the endpoint. The administration of insulin via CSII led to a significant decrease in glycemic variations in patients receiving PN.

11.
Arch Endocrinol Metab ; 62(6): 585-590, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30624497

RESUMO

OBJECTIVE: The aim was to characterize blood glucose fluctuations in patients with fulminant type 1 diabetes (FT1DM) at the stable stage using continuous blood glucose monitoring systems (CGMSs). SUBJECTS AND METHODS: Ten patients with FT1DM and 20 patients with classic type 1 diabetes mellitus (T1DM) (the control group) were monitored using CGMSs for 72 hours. RESULTS: The CGMS data showed that the mean blood glucose (MBG), the standard deviation of the blood glucose (SDBG), the mean amplitude glycemic excursions (MAGE), the blood glucose areas and the percentages of blood glucose levels below 13.9 mmol/L were similar between the two groups. However, the percentage of blood glucose levels below 3.9 mmol/L was significantly higher in the FT1DM group compared to the T1DM group (p < 0.05). The minimum (Min) blood glucose level in the FT1DM group was significantly lower than that of the T1DM group (p < 0.05). Patients with FT1DM had severe dysfunction of the islet beta cells and alpha cells compared to patients with T1DM, as indicated by lower C-peptide values and higher glucagon/C-peptide values. CONCLUSION: In conclusion, patients with FT1DM at the stable stage were more prone to hypoglycemic episodes as recorded by CGMSs, and they had a greater association with severe dysfunction of both the beta and alpha islet cells compared to patients with T1DM.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 1/sangue , Adulto , Glicemia/metabolismo , Automonitorização da Glicemia/métodos , Peptídeo C/sangue , Estudos de Casos e Controles , Feminino , Glucagon/sangue , Humanos , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Valores de Referência , Estudos Retrospectivos , Estatísticas não Paramétricas
12.
Sci Rep ; 7(1): 16382, 2017 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-29180640

RESUMO

It is unknown whether YOD (young onset diabetes) and LOD (late onset diabetes) require similar insulin doses for intensive insulin therapy with a metformin add-on to achieve glycemic control. We analyzed data from our two previously performed randomized, controlled open-label trials. Patients were randomized to receive either continuous subcutaneous insulin infusion (CSII) therapy or CSII combined with metformin therapy for 4 weeks. The studies concentrated on the differences in the insulin doses used for the two groups. We included 36 YOD (age < 40 yrs) and 152 LOD (age > 40 yrs) patients. YOD patients who received metformin combined with CSII therapy required significantly lower insulin doses to maintain euglycemic control compared to patients with LOD. A multivariate analysis, controlled for gender and the fasting blood concentration, was performed to determine the significance of the differences between groups, particularly with respect to the total and basal insulin doses. There was a trend toward improvement in ß-cell function and insulin resistance in terms of ΔHOMA-B and ΔHOMA-IR in patients with YOD compared to those with LOD. Newly diagnosed T2D patients with YOD required significantly lower insulin doses, particularly basal insulin doses, to maintain glycemic control compared to the LOD patients.

13.
Sci Rep ; 7(1): 1583, 2017 05 08.
Artigo em Inglês | MEDLINE | ID: mdl-28484269

RESUMO

To define the features of glycemic variations in drug naïve type 2 diabetic (T2D) patients with different HbA1c values using continuous glucose monitoring (CGM), a total of 195 drug naïve T2D patients were admitted. The subjects were divided into the following groups: lower HbA1c values (≤8%), moderate HbA1c values (>8% and ≤10%), and higher HbA1c values (>10%). The patients underwent oral glucose tolerance tests and were then subjected to 3-day CGM. The primary endpoint was the differences in the 24-hr mean amplitude of glycemic excursions (MAGE) in patients with different HbA1c values. Patients with higher HbA1c values had larger MAGEs than those in the moderate and lower groups (7.44 ± 3.00 vs. 6.30 ± 2.38, P < 0.05, 7.44 ± 3.00 vs. 5.20 ± 2.35, P < 0.01, respectively). The 24-hr mean glucose concentrations increased incrementally in the patients with lower, moderate and higher HbA1c values. Moreover, the patients with higher HbA1c values exhibited higher peak glucose concentrations and prolongation in the time to peak glucose. Patients with higher HbA1c values had larger MAGE compared with those with lower and moderate HbA1c values. Our data indicated patients with higher HbA1c values should receive special therapy aimed at reducing the larger glycemic variations.

14.
J Diabetes Res ; 2017: 2740372, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28271075

RESUMO

Objectives. We performed continuous glucose monitoring (CGM) to define the features of patients with newly diagnosed type 2 diabetes (T2D) before and after Continuous Subcutaneous Insulin Infusion (CSII) therapy. Methods. This was a retrospective analysis. Newly diagnosed T2D patients (106) were admitted from eight centers in China. They were divided into a younger patient group (<60 years) and an older patient group (≥60 years). Each group was further divided into male and female patients. CSII therapy was maintained for 3 weeks after the glycemic target was reached. CGM was performed 2 times before and after completion of insulin treatment. Results. CGM data showed the expected significant improvement of mean amplitude glycemic excursion (MAGE) with CSII therapy. The older patients had lower hourly glucose concentrations from 0200 to 0700 o'clock compared to the younger patients at baseline. Surprisingly, in the older patient group, the male patients had a potential risk of hypoglycemia after CSII therapy, especially during periods from 2300 to 2400 and 0400 to 0600. Conclusions. Our data suggested that older male patients with newly diagnosed T2D may have lower nocturnal glucose concentrations. This may potentially increase the risk of nocturnal hypoglycemia during CSII therapy. This study was registered with Chinese Clinical Trial Registry, number CliCTR-TRC-11001218.


Assuntos
Glicemia/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Insulina/efeitos adversos , Adulto , Idoso , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Infusões Subcutâneas , Insulina/administração & dosagem , Insulina/uso terapêutico , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
15.
Diabetes Ther ; 7(4): 743-753, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27734321

RESUMO

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are widely used as second-option medications when metformin fails. Variance of the glycated hemoglobin (HbA1c) response to DPP-4 inhibitions in patients with type 2 diabetes mellitus (T2DM) has been observed, but the characteristics which predict the response to DPP-4 inhibitor therapy are unclear. The aim of this study was to investigate the characteristics of α- and ß-cell functions which might predict the efficacy of saxagliptin and facilitate personalization of treatment. METHODS: We studied 60 patients with T2DM who had inadequate glycemic control [HbA1c7.0-13.0% (53-119 mmol/mol)) with metformin alone. The patients were treated with saxagliptin (5 mg, daily) and metformin (1000-2000 mg as former) for 12 weeks. Oral glucose tolerance tests were carried out at baseline and endpoint to evaluate α- and ß-cell functions, and blood C-peptide, insulin, glucagon levels were tested. Blood glucose, HbA1c and weight were also observed. RESULTS: Significant reduction of weight, HbA1c and glucagon was observed after 12-week treatment, while C-peptide, insulin and homeostasis model assessment-ß increased (P < 0.05). Linear regression and receiver operating characteristic analysis showed that baseline HbA1c and 30 min-glucagon were correlated with the HbA1c response to saxagliptin, while the weight loss was correlated with gender, age and fasting-insulin level. Further analysis showed the 30 min-glucagon of 49.1 pmol/L was the optimal cutoff value to predict the efficacy of saxagliptin. CONCLUSIONS: Saxagliptin added to metformin significantly improved glycemic control and α- and ß-cell function. Blood glucagon level was a good predicting factor for the HbA1c response to saxagliptin, and it will help appropriate patient selection. TRIAL REGISTRATION: Chinese Clinical Trial Register identifier, ChiCTR-PPR-15007045.

16.
Arch Med Res ; 47(4): 310-4, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-27664492

RESUMO

BACKGROUND AND AIMS: To determine the relationship between thyroid stimulating hormone (TSH) and bone mineral density (BMD) in elderly women. METHODS: This is a retrospective cross-sectional population cohort study of women aged ≥65 years. All 1097 subjects had no overt thyroid dysfunction, 47 had subclinical hyperthyroidism and 100 had subclinical hypothyroidism. Overall, 167 had normal BMD, 594 had osteopenia and 336 had osteoporosis. RESULTS: The femoral neck (FN) BMD was lower in women with lower TSH, with a high prevalance of osteoporosis and osteopenia (p = 0.036).The prevalence of osteoporosis and osteopenia was significantly low in the lowest quartile compared with the third quartile (p = 0.023) and the fourth quartile (p = 0.002), and the second low quartile, compared with the fourth quartile (p = 0.028). The differences were not significant among subclinical hyperthyroid, subclinical hypothyroid and euthyroid women. Low TSH was related to low BMDs at FN by multiple logistic regression analysis corrected for age and BMI. TSH in the lower two quartiles were independently related to osteoporosis (OR: 1.960, p = 0.023 and OR: 1.800, p = 0.037) and osteopenia (OR: 2.108, p = 0.005 and OR: 1.723, p = 0.030). Low TSH quartile (ß: 0.007, p = 0.013) predicting low BMDs at FN. CONCLUSION: Low TSH was independently related to decreased BMDs at FN in elderly women without overt thyroid dysfunction.


Assuntos
Densidade Óssea , Colo do Fêmur/fisiopatologia , Hipotireoidismo/fisiopatologia , Tireotropina/sangue , Idoso , Doenças Ósseas Metabólicas/sangue , Doenças Ósseas Metabólicas/epidemiologia , Estudos Transversais , Feminino , Humanos , Hipotireoidismo/sangue , Osteoporose/sangue , Osteoporose/epidemiologia , Osteoporose/fisiopatologia , Prevalência , Estudos Retrospectivos
17.
Orthopedics ; 37(1): e24-8, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24683652

RESUMO

It is difficult to predict if and when the femoral head will collapse and whether the collapse can be minimized. This study examined the final outcome of early-stage osteonecrosis of the femoral head (ONFH) using magnetic resonance imaging to verify the relationship between preservation of the lateral pillar and collapse of the femoral head. A midcoronal section of the femoral head was divided into 3 pillars (medial, central, and lateral) on a T1-weighted image. According to the site of necrosis on the lateral pillar, the necrosis was divided into 3 types: I, the necrosis occupies the central and medial pillars, and the lateral pillar is preserved; II, the necrosis partially occupies the lateral pillar; and III, the necrosis totally occupies the lateral pillar. One group of 87 patients (127 hips) with Association for Research on Osseous Circulation (ARCO) stage I ONFH underwent nonoperative treatment and were followed for 3 to 8 years (average, 6.2 years). Another group of 42 patients (72 hips) with ARCO stage I ONFH underwent debridement and impacted bone graft and were followed for 5 to 9 years (average, 7.1 years). In both groups, the more preserved the lateral pillar, the less collapse occurred. The authors concluded that whether ONFH progressed to collapse is determined by preservation of the lateral pillar. The lateral pillar is the keystone for maintaining the sphere of the femoral head and its preservation.


Assuntos
Necrose da Cabeça do Fêmur/diagnóstico , Cabeça do Fêmur/patologia , Adulto , Progressão da Doença , Feminino , Necrose da Cabeça do Fêmur/patologia , Humanos , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto Jovem
18.
Eur J Endocrinol ; 170(1): 109-19, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24144966

RESUMO

BACKGROUND: Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population. OBJECTIVE: The aim of this study was to identify the causal variants for GD in the region encompassing TSHR by a refining association study. DESIGN AND METHODS: GD patients (1536) and 1516 sex-matched controls were recruited in the first stage, and an additional 3832 GD patients and 3426 sex-matched controls were recruited in the replication stage. Genotyping was performed using Illumina Human660-Quad BeadChips or TaqMan single nucleotide polymorphism (SNP) Genotyping Assays and the Fluidigm EP1 platform. RESULTS: When the results of regression analysis for 74 genotyped SNPs and 922 imputed SNPs in the first-stage cohort were combined, rs179243 and rs3783949 were the probable susceptibility SNPs associated with GD in TSHR. Eleven SNPs, including rs179243 and rs3783949, were selected to further refine the association in the replication study. Finally, rs12101261 and rs179243 were confirmed as independent GD susceptibility variants in the replication and combined populations. Further, we also found that the rate of persistent TSHR autoantibody positivity (pTRAb+) was significantly higher in the GD patients with the susceptible genotypes rs12101261 or rs179243 than in the GD patients carrying the protective genotypes, after the GD patients had been treated for more than 1 year. CONCLUSIONS: These findings indicate that rs12101261 and rs179243 are the possible causal SNPs for GD susceptibility in the TSHR gene and could serve as genetic markers to predict the outcome of pTRAb+ in GD patients.


Assuntos
Predisposição Genética para Doença , Doença de Graves/genética , Polimorfismo de Nucleotídeo Único , Receptores da Tireotropina/genética , Antitireóideos/uso terapêutico , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , China , Estudos de Coortes , Terapia Combinada , Resistência a Medicamentos , Feminino , Estudos de Associação Genética , Loci Gênicos , Doença de Graves/imunologia , Doença de Graves/metabolismo , Doença de Graves/terapia , Humanos , Imunoglobulinas Glândula Tireoide-Estimulantes/análise , Radioisótopos do Iodo/uso terapêutico , Masculino , Compostos Radiofarmacêuticos/uso terapêutico , Receptores da Tireotropina/antagonistas & inibidores , Receptores da Tireotropina/metabolismo , Reprodutibilidade dos Testes
19.
Hum Mol Genet ; 22(16): 3347-62, 2013 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-23612905

RESUMO

Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.


Assuntos
Predisposição Genética para Doença , Doença de Graves/genética , RNA não Traduzido/genética , Fatores de Necrose Tumoral/genética , Sistema do Grupo Sanguíneo ABO/genética , Adulto , Antígenos CD/genética , Sequência de Bases , Estudos de Casos e Controles , Colágeno , DNA Intergênico , Feminino , Loci Gênicos , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Masculino , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Receptores de Superfície Celular/genética , Receptores Acoplados a Proteínas-G/genética , Família de Moléculas de Sinalização da Ativação Linfocitária , Membro 1 da Família de Moléculas de Sinalização da Ativação Linfocitária
20.
PLoS One ; 8(3): e57758, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23505439

RESUMO

To pinpoint the exact location of the etiological variant/s present at 1q21.1 harboring FCRL1-5 and CD5L genes, we carried out a refined association study in the entire FCRL region in 1,536 patients with Graves' disease (GD) and 1,516 sex-matched controls by imputation analysis, logistic regression, and cis-eQTL analysis. Among 516 SNPs with P<0.05 in the initial GWAS scan, the strongest signals associated with GD and correlated to FCRL3 expression were located at a cluster of SNPs including rs7528684 and rs3761959. And the allele-specific effects for rs3761959 and rs7528684 on FCRL3 expression level revealed that the risk alleles A of rs3761959 and C of rs7528684 were correlated with the elevated expression level of FCRL3 whether in PBMCs or its subsets, especially in CD19(+) B cells and CD8(+) T subsets. Next, the combined analysis with 5,300 GD cases and 4,916 control individuals confirmed FCRL3 was a susceptibility gene of GD in Chinese Han populations, and rs3761959 and rs7528684 met the genome-wide association significance level (P(combined) = 2.27×10(-12) and 7.11×10(-13), respectively). Moreover, the haplotypes with the risk allele A of rs3761959 and risk allele C of rs7528684 were associated with GD risk. Finally, our epigenetic analysis suggested the disease-associated C allele of rs7528684 increased affinity for NF-KB transcription factor. Above data indicated that FCRL3 gene and its proxy SNP rs7528684 may be involved in the pathogenesis of GD by excessive inhibiting B cell receptor signaling and the impairment of suppressing function of Tregs.


Assuntos
Estudo de Associação Genômica Ampla , Doença de Graves/genética , Receptores Fc/genética , Cromossomos Humanos Par 1 , Epigênese Genética , Feminino , Perfilação da Expressão Gênica , Frequência do Gene , Haplótipos , Humanos , Desequilíbrio de Ligação , Masculino , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
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