Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 136
Filtrar
2.
J Diabetes Investig ; 2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31605659

RESUMO

AIMS/INTRODUCTION: Neonatal diabetes mellitus is created by alterations in the genes responsible for beta-cell mass and/or function. The present study aimed to evaluate the genetic variants in the insulin gene (INS) in four Chinese infants aged <12 months with diabetes onset, and to explore the clinical and genetic characteristics of permanent neonatal diabetes mellitus caused by INS mutations. MATERIALS AND METHODS: The complete coding sequences of KCNJ11, ABCC8 and INS were detected using Sanger sequencing. The pathogenicity of the mutations was determined based on the American College of Medical Genetics and Genomics, and the structure of wild-type and mutant proteins was predicted using the web-based tool, Phyre2. RESULTS: One novel mutation (p.I99_C100insSI) and three previously reported variants (p.G32S, p.R89C and p.C96R) in INS were identified in four infants with early-onset diabetes. All the mutations in the four patients were de novo. Except for mutation R89C, which causes permanent neonatal diabetes mellitus through the addition of an additional cysteine residue at the cleavage site of the A chain and C-peptide, the other three mutations affected disulfide bonds. The patients had diabetes with marked hyperglycemia or diabetic ketoacidosis, and were then treated with exogenous insulin. Mutations in crucial regions of the INS might give rise to diabetes with varying severity. CONCLUSIONS: This study enriches our awareness of the mutant spectrum in INS, and suggests the important role of INS in the development of permanent neonatal diabetes mellitus.

3.
Artigo em Inglês | MEDLINE | ID: mdl-31622986

RESUMO

Fatty acids induced hepatic inflammation plays an important role in nonalcoholic fatty liver disease (NAFLD) pathogenesis. Hydrogen sulfide (H2S), an endogenous gasotransmitter, has been established to possess potent anti-inflammation in various human organs. However, the anti-inflammation property of H2S in the fatty liver is still needed to further elucidate. Hence, this study aimed to investigate whether exogenous H2S can protect hepatocytes against inflammation induced by palmitic acid (PA). HepG2 hepatocytes were exposed to PA for 24 h to induce free fatty acids-induced inflammation. The cells were pretreated with NaHS (a donor of H2S) before exposure to PA. Cell viability, inflammatory cytokines (TNF-α, IL-6 and IL-1ß), NLRP3 inflammasome and NF-κB were measured by a combination of MTT assay, ELISA, Western blot and Immunofluorescence. Here, we found that exogenous H2S dose-dependently inhibited the expression of pro-inflammatory cytokines, NLRP3 inflammasome and activation of NF-κB signaling in PA-induced HepG2 cells. Thus, H2S might be a candidate therapeutic agent against NAFLD.

4.
Food Funct ; 10(8): 4505-4521, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31348478

RESUMO

Adverse early-life exposures program an increased risk of chronic metabolic diseases in adulthood. However, the effects of genistein consumption in early life on metabolic health are unclear. Our objective was to investigate whether perinatal genistein intake could mitigate the deleterious effects of a high-fat diet (HF) on metabolism in dams and female offspring and to explore the role of the gut microbiota in mediating the transgenerational effects. C57BL/6 female mice were fed a HF, HF with genistein (0.6 g kg-1 diet) or normal control diet for 3 weeks before mating and throughout pregnancy and lactation. The offspring had free access to normal diet from weaning to 24 weeks of age. A glucose tolerance test was performed and the levels of serum insulin and lipid were measured. The cecal contents were collected for 16s rDNA sequencing. The results showed that perinatal genistein intake could not only significantly reduce blood glucose levels, insulin and free fatty acids (FFA) in dams, but also improve glucose tolerance, insulin sensitivity and serum lipid profiles in adult female offspring. Significant enrichment of short-chain fatty acid (mainly butyrate)-producing bacteria might play crucial roles in deciphering the metabolic benefits of perinatal genistein intake in dams. The obvious decrease in harmful microorganisms and increase in Erysipelotrichaceae_incertae_sedis were associated with the protective effects of maternal genistein intake on female offspring. In addition, Bifidobacterium might be an important factor for deciphering the metabolic improvement in both dams and female offspring by dietary genistein. Overall, perinatal genistein intake attenuated the harmful effects of HF on metabolism in both dams and female offspring, and the protective effects were associated with the alterations in the gut microbiota, which provides new evidence and targets for mitigating the poor effects of adverse early-life exposures on metabolic health in later life.

5.
Int J Obes (Lond) ; 43(8): 1556-1567, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31285522

RESUMO

BACKGROUND/OBJECTIVES: Short sleep is an obesity risk factor, however, little is known about its interplay with genetic predisposition and pathways involved in obesity pathogenesis, especially in the longitudinal setting. We aimed to investigate a possible sleep-gene interaction for childhood obesity risk, and whether the interaction in childhood longitudinally contributes to obesity risk at a 10-year follow-up and further to test if there is any mediation through the leptin pathway. SUBJECTS/METHODS: A total of 3211 children from China (6-18 years) at baseline and 848 participants at 10-year follow-up from the Beijing Child and Adolescent Metabolic Syndrome (BCAMS) cohort study were analyzed. Baseline leptin concentrations and 12 established adult body mass index (BMI) loci were examined for the associations with habitual sleep duration. RESULTS: After adjusting for covariates, including pubertal stages and behavioral factors, short sleep duration at baseline was significantly associated with increased overweight/obesity risk at both baseline and follow-up. Genetic predisposition scores (GPS), particularly consisting of leptin-related SNPs (GPSleptin), were robustly associated with baseline overweight/obesity in children who slept ≤8 h/day (P < 0.001), whereas the association was ablated in those who slept ≥10 h/day (P > 0.05). Comparable observations were made at follow-up. Mediation analysis revealed a modest direct effect of the GPSleptin-sleep interaction on BMI at baseline, while a significant indirect effect of this interaction was found to be mediated principally through elevated leptin (proportion: 52.6%); moreover, the mediation effect via leptin remained stable over 10 years. CONCLUSIONS: This study suggests that shorter sleep duration in children from China (< 8h/day), compared to longer sleep duration (≥10 h/day), has a long-term impact on the association of polygenic risk for obesity from childhood to young adulthood and leptin pathway explains a key mechanism via a modification effect. Therefore, adequate sleep duration during childhood is important for the early prevention of obesity, especially if there is a genetic predisposition to this trait.

6.
Int J Mol Med ; 44(2): 608-616, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31173188

RESUMO

Hypercholesterolemia is a key factor leading to ß­cell dysfunction, but its underlying mechanisms remain unclear. Secretagogin (Scgn), a Ca2+ sensor protein that is expressed at high levels in the islets, has been shown to play a key role in regulating insulin secretion through effects on the soluble N­ethylmaleimide­sensitive factor attachment receptor protein complexes. However, further studies are required to determine whether Scgn plays a role in hypercholesterolemia­associated ß­cell dysfunction. The present study investigated the involvement of a microRNA­24 (miR­24)­to­Scgn regulatory pathway in cholesterol­induced ß­cell dysfunction. In the present study, MIN6 cells were treated with increasing concentrations of cholesterol and then, the cellular functions and changes in the miR­24­to­Scgn signal pathway were observed. Excessive uptake of cholesterol in MIN6 cells increased the expression of miR­24, resulting in a reduction in Sp1 expression by directly targeting its 3' untranslated region. As a transcriptional activator of Scgn, downregulation of Sp1 decreased Scgn levels and subsequently decreased the phosphorylation of focal adhesion kinase and paxillin, which is regulated by Scgn. Therefore, the focal adhesions in insulin granules were impaired and insulin exocytosis was reduced. The present study concluded that a miR­24­to­Scgn pathway participates in the mechanism regulating cholesterol accumulation­induced ß­cell dysfunction.

7.
Diabetes Ther ; 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31214998

RESUMO

INTRODUCTION: Accurate diagnosis of maturity-onset diabetes of the young (MODY) is required in order to select appropriate treatment options and to assess prognosis. The aim of this study was to explore potential clinical indicators that could be used to differentiate MODY2, MODY3, and type 1 diabetes (T1D) in young subjects. METHODS: Twelve patients with MODY3 and 29 patients with MODY2 were characterized and compared to 26 patients with T1D. These three groups were matched for age and gender. Clinical profiles of the 67 patients were collected. Receiver operating characteristic (ROC) curves were used to identify the optimal cutoff values of clinical indicators. RESULTS: Compared to patients with T1D, subjects with MODY3 had higher fasting C-peptide levels (1.34 ± 1.51 vs. 0.29 ± 0.22 ng/mL; P < 0.001) and lower high-sensitivity C-reactive protein (hsCRP) levels (0.18 ± 0.15 vs. 1.22 ± 1.49 mg/L, P = 0.004); patients with MODY2 had lower hsCRP (0.37 ± 0.39 vs. 1.22 ± 1.49 mg/L; P = 0.003), total cholesterol (4.12 ± 0.68 vs. 4.61 ± 0.81 mmol/L, P = 0.034), and low-density lipoprotein cholesterol (LDL-C) (2.24 ± 0.68 vs. 2.67 ± 0.79 ng/L, P = 0.002) levels and higher fasting C-peptide levels (0.96 ± 0.42 vs. 0.29 ± 0.22 ng/mL, P = 0.002). The ROC-derived hsCRP values for discriminating MODY2 from T1D, MODY3 from T1D, and MODY3 from MODY2 were 0.675, 0.833, and 0.763, respectively. The ROC-derived fasting C-peptide levels for discriminating MODY2 from T1D and MODY3 from T1D were 0.951 and 0.975, respectively. The ROC-derived total cholesterol and LDL-C values for discriminating MODY2 from T1D were 0.670 and 0.662, respectively; the ROC-derived triglyceride value for discriminating MODY3 from MODY2 was 0.756. Additionally, a combination of indicators permitted better discrimination of MODY subtypes than any single parameter. CONCLUSION: Our findings suggest that fasting C-peptide, hsCRP, and lipid levels permit good discrimination among MODY2, MODY3, and T1D. These clinical indicators could be used as markers of MODY2 and MODY3 in young patients with diabetes.

8.
J Diabetes Investig ; 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31094068

RESUMO

AIMS/INTRODUCTION: The principal aim of this study was to investigate the clinical, genetic and functional characteristics of two cases of congenital hyperinsulinism (CHI) caused by glucokinase (GCK) mutations in young patients. MATERIALS AND METHODS: Novel mutations were detected by CHI next-generation sequencing, and the kinetic parameters and thermal stability of recombinant wild-type and mutant glucokinase were determined in vitro. In addition, 18 naturally occurring GCK-CHI mutations reported previously were also summarized. RESULTS: A de novo mutation (M197V) was found in a 17-year-old male with an epilepsy history, whereas an autosomal dominant mutation (K90R) was found in a 20-year-old female with inherited asymptomatic hypoglycemia. Kinetic analysis showed increased enzyme activity for both mutants (RAI 4.7 for M197V and 1.6 for K90R) and enhanced thermal stability for the M197V mutant. However, of all the GCK-CHI mutants, the increase in enzyme activity (RAI between 1.6 and 130) did not correlate strongly with the severity of hypoglycemia. The de novo group (7/19) showed distinctive phenotypes from the autosomal dominant group (12/19), such as a higher proportion of diazoxide unresponsiveness (28.6% vs 0%), a higher incidence of macrosomia (85.7% vs 40%) and a rarer incidence of adulthood onset (0% vs 25%). CONCLUSIONS: The clinical phenotypes of GCK-CHIs were highly heterogeneous. We have identified two novel GCK-CHI mutations in young patients and investigated their pathogenicity by enzyme kinetic analysis, which expanded the spectrum of this rare disease.

9.
J Clin Invest ; 129(6): 2266-2278, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-31033478

RESUMO

Chronic glucocorticoid therapy has serious side effects, including diabetes and fatty liver. However, the molecular mechanisms responsible for steroid-induced diabetes remain largely enigmatic. Here, we show that hepatic Krüppel-like factor 9 (Klf9) gene expression is induced by dexamethasone and fasting. The overexpression of Klf9 in primary hepatocytes strongly stimulated Pgc1a gene expression through direct binding to its promoter, thereby activating the gluconeogenic program. However, Klf9 mutation abolished the stimulatory effect of dexamethasone on cellular glucose output. Adenovirus-mediated overexpression of KLF9 in the mouse liver markedly increased blood glucose levels and impaired glucose tolerance. Conversely, both global Klf9-mutant mice and liver-specific Klf9-deleted mice displayed fasting hypoglycemia. Moreover, the knockdown of Klf9 in the liver in diabetic mouse models, including ob/ob and db/db mice, markedly lowered fasting blood glucose levels. Notably, hepatic Klf9 deficiency in mice alleviated hyperglycemia induced by chronic dexamethasone treatment. These results suggest a critical role for KLF9 in the regulation of hepatic glucose metabolism and identify hepatic induction of KLF9 as a mechanism underlying glucocorticoid therapy-induced diabetes.

10.
Diabetes Ther ; 2019 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-31028688

RESUMO

INTRODUCTION: Glycemic control in pregnant women with type 1 diabetes (T1D) is challenging with only insulin, and the incidence rate of adverse perinatal outcomes is high. Increasing data have indicated the safety and effect of metformin in pregnancy; however, no relevant data are available in pregnant women with T1D. We aimed to investigate glycemic control and perinatal outcomes in pregnant women with T1D in a Chinese population and explored the role of metformin in these patients. METHODS: We obtained data of 38 pregnant women with T1D who received regular antenatal care and delivered at Peking Union Medical College Hospital (PUMCH) between 1 January 2006 and 31 May 2018. The perinatal outcomes of T1D patients who added metformin as adjunct treatment and those who remained on insulin-alone therapy were compared retrospectively. RESULTS: Being overweight was common (35.1%) in pregnant women with T1D. On average, the insulin dose increased by 35.30 ± 22.60 unit/day during pregnancy. The cesarean delivery rate was high (65.8%), and fetal macrosomia was the main reason. The change of HbA1c in the metformin-insulin group was more prominent than in the insulin-only group (- 1.47 ± 1.17% vs. - 0.90 ± 1.13%, p = 0.05). There was no statistically significant difference in perinatal outcomes between the two groups. CONCLUSIONS: The incidence of adverse perinatal outcomes in pregnant women with T1D was high. This study innovatively suggested that metformin could be safe and could contribute to improving glucose management in pregnant women with T1D.

11.
Endocrine ; 65(1): 53-60, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028668

RESUMO

PURPOSE: Glucokinase-maturity onset diabetes of the young (GCK-MODY), also known as MODY2, is caused by heterozygous inactivating mutations in the GCK gene. The aim of this study is to investigate the relationship of birthweight and cardiometabolic characteristics in MODY2 patients. METHODS: Genetic screening for GCK mutations from 192 classical MODY families was performed, and birthweight and clinical profiles of 76 patients from 25 families with identified GCK mutations were collected. RESULTS: Mutations in GCK were identified in 25 (13%) of the 192 families. Four novel (c.1334 G > C, c.1289_1294delTGACGC, c.584 T > C, and c.30delC) and twenty-one previously reported mutations were identified and cosegregated with the clinical phenotypes of MODY2 within the pedigrees. MODY2 patients presented a mean birthweight of 3.11 ± 0.44 kg. Additionally, birthweight was negatively correlated with 2 h-postprandial glucose (r = -0.426, P = 0.006), glycated albumin (r = -0.462, P = 0.035), glycated hemoglobin (r = -0.529, P = 0.001), total cholesterol (r = -0.430, P = 0.016), and low-density lipoprotein cholesterol (LDL-C) (r = -0.383, P = 0.033) levels after adjustment for age, gender and BMI. Importantly, among the patients who inherited mutations from their mothers, 7 patients whose mothers were treated with insulin during pregnancy had particularly lower birthweight (2.83 ± 0.39 vs. 3.37 ± 0.39 kg; P = 0.003), higher total cholesterol (6.15 ± 0.43 vs. 4.06 ± 0.16 mmol/L; P = 0.002) and LDL-C (4.05 ± 0.35 vs. 2.21 ± 0.13 mmol/L; P = 0.001) levels compared to the other 21 patients whose mothers received no treatment. CONCLUSIONS: The correlations between birthweight and cardiometabolic indexes indicated that MODY2 patients with lower birthweight (<3.1 kg) should be monitored and treated more actively to prevent metabolic abnormalities, particularly dyslipidemia. Importantly, prenatal genic diagnosis is highly recommended to avoid inappropriate treatment in pregnancy leading to lower birthweight of offspring.

12.
Diabetes Metab Res Rev ; 35(5): e3148, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30838734

RESUMO

Excessive adiposity and metabolic inflammation are the key risk factors of type 2 diabetes mellitus (T2DM). Juxtaposed with another zinc finger gene 1 (JAZF1) has been identified as a novel transcriptional cofactor, with function of regulating glucose and lipid homeostasis and inflammation. JAZF1 is involved in metabolic process of T2DM via interaction with several nuclear receptors and protein kinases. Additionally, increasing evidence from genome-wide association studies (GWAS) has shown that JAZF1 polymorphisms are closely associated with T2DM. In this review, we have updated the latest research advances on JAZF1 and discussed its regulatory network in T2DM. The association between JAZF1 polymorphisms and T2DM is discussed as well. The information provided is of importance for guiding future studies as well as for the design of JAZF1-based T2DM therapy.

13.
Clin Chim Acta ; 494: 52-57, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30876855

RESUMO

BACKGROUD: CCN3 is a novel adipokine and has emerged as a potential metabolic regulator. However, information regarding the role of CCN3 in type 2 diabetes mellitus (T2DM) remains unclear. This study measured for the first time serum CCN3 levels in T2DM and explored the correlations between its serum levels and various metabolic parameters in humans. METHODS: A total of 219 newly diagnosed T2DM (nT2DM) patients and 205 healthy control subjects, matched for age and sex ratio, were enrolled. Circulating CCN3 and TNF-α, IL-6 and MCP-1 were measured by ELISA. The anthropometric assessment and biochemical evaluation were done in all subjects. OGTT were performed in 34 healthy individuals to investigate the association of CCN3 with glucose. RESULTS: Serum CCN3 levels were significantly higher in nT2DM patients compared to those of the healthy controls (6.71[4.88, 8.56] vs. 4.51[3.55, 5.99] ng/ml, P < 0.01). Serum CCN3 positively correlated with BMI, WC, FAT%, TG, FPG, 2 h-PG, HbA1c, FIns, HOMA-IR, hs-CRP and TNF-α, IL-6 and MCP-1, but negatively with HOMA-ß in all individuals (P < 0.05). Multiple linear regression analysis indicated that BMI, HOMA-IR, TNF-α and MCP-1 were independently associated with CCN3. Multivariate logistic regression analysis demonstrated that CCN3 was correlated with nT2DM. Finally, area under ROC curve of CCN3 (gender and age adjusted) for predicting the presence of nT2DM was 0.725(95% CI: 0.676-0.773). After an oral glucose challenge, there was no obvious change in the circulating levels of CCN3 as compared to 0 min (P > 0.05). CONCLUSIONS: Elevation of CCN3 in nT2DM supports the hypothesis that CCN3 may serve as a risk factor associated with the pathogenesis of T2DM.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Inflamação/sangue , Resistência à Insulina , Proteína Sobre-Expressa em Nefroblastoma/sangue , Obesidade/sangue , Adulto , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Humanos , Inflamação/complicações , Inflamação/metabolismo , Masculino , Proteína Sobre-Expressa em Nefroblastoma/metabolismo , Obesidade/complicações , Obesidade/metabolismo
15.
BMC Med Genet ; 20(1): 56, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30925902

RESUMO

BACKGROUND: PHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa). Elevated liver transaminase levels and liver enlargement are the most frequent phenotypes of GSD IXa. However, whether the phenotypes are applicable to Chinese patients remains unclear. CASE REPORT: A boy aged 2 years and 8 months with a history of episodic fatigue and weakness since he was 2 years old was referred to our endocrinology clinic. Apart from symptomatic ketotic hypoglycemic episodes (palpitation, hand shaking, sweating, etc.), no abnormalities of liver transaminase levels or liver size were found. To identify the aetiology of his clinically diagnosed hypoglycaemia, the proband and his parents were screened for PHKA2 gene mutations by next-generation sequencing. A heterozygous mutation (c.2972C > G, p.G991A) in PHKA2 was found in the proband and his mother. Twenty-one Chinese cases with GSD IXa have been reported in the literature to date, and elevated liver transaminase levels (95%) and liver enlargement (91%) are the most frequent phenotypes of GSD IXa in Chinese patients. Hypoglycaemia may be one of the early onset symptoms in infants with GSD IXa. CONCLUSIONS: This study enriches our knowledge of the PHKA2 gene mutation spectrum and provides further information about the phenotypic characteristics of Chinese GSD IXa patients.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Doença de Depósito de Glicogênio/genética , Hipoglicemia/complicações , Fosforilase Quinase/genética , Mutação Puntual , Pré-Escolar , Doença de Depósito de Glicogênio/etiologia , Doença de Depósito de Glicogênio/metabolismo , Doença de Depósito de Glicogênio/patologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hipoglicemia/genética , Fígado/enzimologia , Fígado/patologia , Masculino , Linhagem , Fenótipo , Análise de Sequência de DNA , Transaminases/metabolismo
16.
Diabetes Metab Res Rev ; 35(6): e3152, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30884108

RESUMO

Blood glucose monitoring is an important part of diabetes management. Continuous glucose monitoring (CGM) technology has become an effective complement to conventional blood glucose monitoring methods and has been widely applied in clinical practice. The indications for its use, the accuracy of the generated data, the interpretation of the CGM results, and the application of the results must be standardized. In December 2009, the Chinese Diabetes Society (CDS) drafted and published the first Chinese Clinical Guideline for Continuous Glucose Monitoring (2009 edition), providing a basis for the standardization of CGM in clinical application. Based on the updates of international guidelines and the increasing evidence of domestic studies, it is necessary to revise the latest CGM guidelines in China so that the recent clinical evidence can be effectively translated into clinical benefit for diabetic patients. To this end, the CDS revised the Chinese Clinical Guideline for Continuous Glucose Monitoring (2012 Edition) based on the most recent evidence from international and domestic studies.

17.
Diabetes Metab Res Rev ; 35(6): e3158, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30908791

RESUMO

The prevalence of diabetes in China has increased rapidly from 0.67% in 1980 to 10.4% in 2013, with the aging of the population and westernization of lifestyle. Since its foundation in 1991, the Chinese Diabetes Society (CDS) has been dedicated to improving academic exchange and the academic level of diabetes research in China. From 2003 to 2014, four versions of Chinese diabetes care guidelines have been published. The guidelines have played an important role in standardizing clinical practice and improving the status quo of diabetes prevention and control in China. Since September 2016, the CDS has invited experts in cardiovascular diseases, psychiatric diseases, nutrition, and traditional Chinese medicine to work with endocrinologists from the CDS to review the new clinical research evidence related to diabetes over the previous 4 years. Over a year of careful revision, this has resulted in the present, new version of guidelines for prevention and care of type 2 diabetes in China. The main contents include epidemiology of type 2 diabetes in China; diagnosis and classification of diabetes; primary, secondary, and tertiary diabetes prevention; diabetes education and management support; blood glucose monitoring; integrated control targets for type 2 diabetes and treatments for hyperglycaemia; medical nutrition therapy; exercise therapy for type 2 diabetes; smoking cessation; pharmacologic therapy for hyperglycaemia; metabolic surgery for type 2 diabetes; prevention and treatment of cardiovascular and cerebrovascular diseases in patients with type 2 diabetes; hypoglycaemia; chronic diabetic complications; special types of diabetes; metabolic syndrome; and diabetes and traditional Chinese medicine.

18.
J Diabetes Investig ; 2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30860651

RESUMO

We report a case of missed diagnosis of maturity-onset diabetes of the young type 5 uncovered during pregnancy with a previous diagnosis of type 1 diabetes. Maturity-onset diabetes of the young type 5 cannot be excluded in early-onset diabetes with positive islet-related autoantibodies and type 1 diabetes-prone human leukocyte antigen subtypes. Abdominal ultrasound should be used in all patients with pre-gestational diabetes, and maturity-onset diabetes of the young type 5 should be considered when renal abnormality is presented.

19.
BMC Endocr Disord ; 19(1): 12, 2019 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-30670019

RESUMO

BACKGROUND: Zinc-α2-glycoprotein (ZAG) is a recently novel lipolytic adipokine implicated in regulation of glucose and lipid metabolism in many metabolic disorders. In vitro and animal studies suggest that thyroid hormones (TH) up-regulates ZAG production in hepatocytes. However, there is no data evaluating the possible relationship between ZAG and TH in a human model of hyperthyroidism. The objective of the present study is to assess the association of serum ZAG levels with TH and lipid profile in patients with hyperthyroidism before and after methimazole treatment. METHODS: A total of 120 newly diagnosed overt hyperthyroidism and 122 healthy control subjects were recruited. Of them, 39 hyperthyroidism patients were assigned to receive methimazole treatment as follow-up study for 2 months. RESULTS: The clinical consequence showed that serum ZAG levels were elevated in patients with hyperthyroidism (P < 0.01). Adjust for age, gender and BMI, serum ZAG levels were positively related with serum free T3 (FT3), free T4 (FT4) levels and negatively correlated with serum total cholesterol (TC), low density lipoprotein cholesterol (LDLC) levels in hyperthyroidism subjects (all P < 0.01). After methimazole treatment, serum ZAG levels were decreased and the decline was associated with decreased FT3, FT4 and increased TC levels (all P < 0.001). CONCLUSION: We conclude that ZAG may be involved in the pathogenesis of lipid metabolism disorder in patients with hyperthyroidism. TRIAL REGISTRATION: ChiCTR-ROC-17012943 . Registered 11 October 2017, retrospectively registered.


Assuntos
Biomarcadores/sangue , Hipertireoidismo/sangue , Metimazol/uso terapêutico , Proteínas de Plasma Seminal/sangue , Hormônios Tireóideos/sangue , Adulto , Antitireóideos/uso terapêutico , Feminino , Seguimentos , Humanos , Hipertireoidismo/diagnóstico , Hipertireoidismo/tratamento farmacológico , Masculino , Prognóstico , Estudos Prospectivos
20.
BMC Med Genet ; 20(1): 8, 2019 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-30635042

RESUMO

BACKGROUND: Acanthosis nigricans (AN) is a clinical manifestation featured by velvety brown plaques in skin folds that occurs in some hereditary and syndromic disorders. Fibroblast growth factor receptor 3 (FGFR3) mutations have been identified as one of the genetic causes of inherited AN. CASE PRESENTATION: A 17-year-old Chinese female had presented generalized acanthosis nigricans since she was 4 years old. She yielded no family history of short stature or AN. Apart from a short stature, no skeletal defects, neurological defects or other abnormalities were found. To identify the aetiology of the clinically diagnosed AN, we screened the proband for genetic mutations using whole exome sequencing. A heterozygous mutation (c.1949A > C, p.Lys650Thr) in FGFR3 was found in the proband. To date, 26 cases of AN harbouring this specific gene mutation have been reported in the literature, and only one child carried a de novo mutation instead of inheriting the specific mutation from their parents. The present case is the first-reported Chinese patient with isolated AN with a de novo K650 T mutation in FGFR3. CONCLUSIONS: We reported a new case of AN caused by a heterozygous mutation (c.1949A > C, p.K650 T) in FGFR3, and review the past reports of AN with the same gene mutation. Sequencing of the FGFR3 gene is a feasible approach to identify the aetiology of AN, especially for early onset extensive AN.


Assuntos
Acantose Nigricans/genética , Predisposição Genética para Doença , Mutação , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Acantose Nigricans/diagnóstico , Acantose Nigricans/fisiopatologia , Adolescente , Grupo com Ancestrais do Continente Asiático , Análise Mutacional de DNA , Nanismo/genética , Éxons , Feminino , Heterozigoto , Humanos , Linhagem , Sequenciamento Completo do Exoma
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA