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1.
Medicine (Baltimore) ; 103(26): e38583, 2024 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-38941365

RESUMO

The aspartate to alanine transaminase (AST/ALT) ratio indicates oxidative stress and inflammatory reactions related to the occurrence of diabetic retinopathy (DR). Currently, there are no reports on the correlation between AST/ALT ratio and DR. Hence, this study aimed to explore the relationship between AST/ALT ratio and DR. This cross-sectional study utilized data from the Metabolic Management Center of the First People's Hospital in City. In total, 1365 patients with type 2 diabetes mellitus (T2DM) participated in the study, including 244 patients with DR and 1121 patients without DR. We collected the results of fundus photography, liver function, and other research data and grouped them according to tertiles of AST/ALT ratios. DR prevalence was the highest in the group with the highest AST/ALT ratio (22.12%, P = .004). Both univariate (OR = 2.25, 95% CI: 1.51-3.34, P < .001) and multivariable logistic regression analyses (adjusted for confounding factors) showed that the risk of DR increased by 36% when the AST/ALT ratio increased by 1 standard deviation (SD) (OR = 1.36, 95% CI: 1.16-1.59, P < .001), and 29.3% was mediated by the duration of diabetes. A sensitivity analysis confirmed the stability of the results. This study showed that an increase in AST/ALT ratio is an independent risk factor for DR.


Assuntos
Alanina Transaminase , Aspartato Aminotransferases , Diabetes Mellitus Tipo 2 , Retinopatia Diabética , Humanos , Retinopatia Diabética/epidemiologia , Retinopatia Diabética/sangue , Retinopatia Diabética/etiologia , Estudos Transversais , Masculino , Feminino , Pessoa de Meia-Idade , Fatores de Risco , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Idoso , Prevalência , Biomarcadores/sangue
2.
Diabetol Metab Syndr ; 16(1): 123, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840161

RESUMO

BACKGROUND: Few studies have compared the correlation between visceral fat area (VFA) and abdominal subcutaneous fat area (SFA) with arterial stiffness (AS) in patients with type 2 diabetes (T2D). In addition, there is currently controversy regarding the correlation between VFA and SFA with AS. We aimed to investigate the relationship between VFA and SFA with AS in patients with T2D. METHODS: In this cross-sectional study, 1475 Chinese T2D patients with an average age of 52.32 ± 10.96 years were included. VFA and SFA were determined by a dual bioelectrical impedance analyzer, and AS was determined by measurement of brachial-ankle pulse wave conduction velocity (baPWV). Atherosclerosis was deemed present in study participants with baPWV values higher than 75th percentile (1781 cm/s). Independent correlations of logVFA and logSFA with AS were assessed using multiple linear regression and multivariate logistic regression. RESULTS: The baPWV was linked with VFA, waist circumference, and women's SFA in a general linear correlation study (P < 0.05), but not with body mass index (P = 0.3783) or men's SFA (P = 0.1899). In both men and women, VFA and SFA were positively correlated with AS, according to the generalized additive model (GAM). After fully adjusting for confounders, multiple linear regression analyses showed that for every 1-unit increase in logVFA, the beta coefficient of baPWV increased by 63.1 cm/s (95% CI: 18.4, 107.8) (P < 0.05). logSFA did not correlate significantly with baPWV (P = 0.125). In the multiple logistic regression analysis, the odds ratio (OR) of elevated baPWV was 1.8 (95% CI: 1.1, 3.1) (P = 0.019) per 1-unit increase in logVFA. logSFA did not correlate significantly with AS (P = 0.091). In the subgroup analysis, the correlation between logVFA and baPWV did not interact across subgroups (P-interaction > 0.05). CONCLUSIONS: Compared with SFA, VFA had a stronger independent positive correlation with AS in Chinese T2D patients. Patients with T2D should pay more attention to monitoring VFA and lowering it to minimize cardiovascular events.

3.
Diabetes Care ; 47(1): 160-168, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-37943529

RESUMO

OBJECTIVE: We conducted a randomized, double-blind, placebo-controlled phase 2 trial to evaluate the efficacy and safety of mazdutide, a once-weekly glucagon-like peptide 1 and glucagon receptor dual agonist, in Chinese patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Adults with type 2 diabetes inadequately controlled with diet and exercise alone or with stable metformin (glycated hemoglobin A1c [HbA1c] 7.0-10.5% [53-91 mmol/mol]) were randomly assigned to receive 3 mg mazdutide (n = 51), 4.5 mg mazdutide (n = 49), 6 mg mazdutide (n = 49), 1.5 mg open-label dulaglutide (n = 50), or placebo (n = 51) subcutaneously for 20 weeks. The primary outcome was change in HbA1c from baseline to week 20. RESULTS: Mean changes in HbA1c from baseline to week 20 ranged from -1.41% to -1.67% with mazdutide (-1.35% with dulaglutide and 0.03% with placebo; all P < 0.0001 vs. placebo). Mean percent changes in body weight from baseline to week 20 were dose dependent and up to -7.1% with mazdutide (-2.7% with dulaglutide and -1.4% with placebo). At week 20, participants receiving mazdutide were more likely to achieve HbA1c targets of <7.0% (53 mmol/mol) and ≤6.5% (48 mmol/mol) and body weight loss from baseline of ≥5% and ≥10% compared with placebo-treated participants. The most common adverse events with mazdutide included diarrhea (36%), decreased appetite (29%), nausea (23%), vomiting (14%), and hypoglycemia (10% [8% with placebo]). CONCLUSIONS: In Chinese patients with type 2 diabetes, mazdutide dosed up to 6 mg was generally safe and demonstrated clinically meaningful HbA1c and body weight reductions.


Assuntos
Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Hipoglicemiantes/efeitos adversos , Hemoglobinas Glicadas , Peptídeo 1 Semelhante ao Glucagon/uso terapêutico , Peptídeos Semelhantes ao Glucagon/efeitos adversos , Peso Corporal , Método Duplo-Cego , China , Resultado do Tratamento , Quimioterapia Combinada
4.
Front Endocrinol (Lausanne) ; 14: 1277162, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075069

RESUMO

Background: Many studies have confirmed that lipid accumulation products (LAP) predict arterial stiffness (AS) in hypertensive patients. But there is little research on the use of LAP in identifying early atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to determine the relationship between the LAP index and brachial-ankle pulse wave velocity (baPWV) in Chinese patients with T2DM. Methods: A total of 1471 Chinese participants with T2DM, ranging in age from 18 to 80, were included in this cross-sectional study. BaPWV measurements were used to calculate the AS. A baPWV greater than the 75th percentile (1700 cm/s) was defined as indicating increased AS. The LAP index was calculated from the combination of waist circumference (WC) and triglycerides (TG). Results: According to the quartiles of the LAP index, baPWV tended to increase after adjusting for sex and age. Multiple linear regression analysis showed that the beta coefficient (ß) of baPWV increased by 31.0 cm/s for each unit of lnLAP that was increased, and the 95% confidence interval (CI) was (6.5, 55.5) cm/s. In multivariate logistic regression analyses, after fully adjusting for confounders, the risk of elevated baPWV increased with each unit increase in lnLAP, with an odds ratio (OR) of 1.3 (95% CI: 1.0, 1.8). According to the generalized additive model (GAM), we found that lnLAP was positively correlated with baPWV and baPWV elevation. The results were the same for males and females. Subgroup analyses showed that the positive correlation between lnLAP and elevated baPWV did not interact across all subgroups. Conclusions: In Chinese patients with T2DM, LAP was strongly and positively correlated with baPWV and elevated baPWV.


Assuntos
Diabetes Mellitus Tipo 2 , Produto da Acumulação Lipídica , Rigidez Vascular , Masculino , Feminino , Humanos , Índice Tornozelo-Braço , Fatores de Risco , Estudos Transversais , Análise de Onda de Pulso , China/epidemiologia
5.
Front Endocrinol (Lausanne) ; 14: 1248614, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37854188

RESUMO

Purpose: The prevalence of metabolic syndrome (MetS) is increasing globally and has become a global and national public health problem that cannot be ignored as an independent predictor of cardiovascular events, cancer and all-cause mortality. γ-glutamyl transferase (GGT) and high-density lipoprotein cholesterol (HDL-C) are associated with insulin resistance, dyslipidemia and oxidative stress. This study was designed to explore the relationship and predictive performance between γ-glutamyl transferase high-density lipoprotein cholesterol ratio (GGT/HDL-C) and MetS. Methods: This was a cross-sectional study. MetS was diagnosed from biochemical and anthropometric data in subjects with T2DM. Multivariate logistic regression was used to analyses the relationship between GGT/HDL-C ratio, TyG index and HOMA-IR and MetS in subjects with T2DM. Receiver operating characteristic (ROC) curve was drawn and the areas under the curve (AUC) were used to assess the ability of these indexes in screening MetS in subjects with T2DM. Statistical differences between the AUC values of these indexes were compared. In addition, we performed subgroup analyses and interactions. Results: 769 (70.55%) patients with T2DM were defined as having MetS. patients with MetS had higher anthropometric values and biochemical indicators compared to those without MetS. Multivariate logistic regression analysis of GGT/HDL-C ratio was an independent risk factor for MetS (Per 1 SD increase, OR = 2.49, 95% CI: 1.51, 4.10). According to ROC curve analysis, the value of GGT/HDL-C ratio in predicting MetS in subjects with T2DM was superior to that of TyG index and HOMA-IR. The best cut-off value for GGT/HDL-C prediction was 19.94. Conclusions: GGT/HDL-C ratio may be an important predictor of MetS in subjects with T2DM, and its predictive power is stronger than that of TyG index and HOMA-IR. The risk of MetS in subjects with T2DM is increased in the presence of a higher GGT/HDL-C ratio.


Assuntos
HDL-Colesterol , Diabetes Mellitus Tipo 2 , Síndrome Metabólica , gama-Glutamiltransferase , Humanos , Glicemia/análise , HDL-Colesterol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , gama-Glutamiltransferase/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Triglicerídeos/sangue , Resistência à Insulina
6.
Diabetes Obes Metab ; 25(10): 2878-2887, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37385967

RESUMO

AIM: To investigate the post-treatment effect of dorzagliatin in drug-naïve patients with type 2 diabetes (T2D) regarding the achievement of stable glycaemic control and drug-free diabetes remission. MATERIALS AND METHODS: Patients who completed dorzagliatin treatment in the SEED trial and achieved stable glycaemic control were enrolled in this 52-week study without any antidiabetic medication. The primary endpoint was the diabetes remission probability at week 52 using the Kaplan-Meier method. The potential factors that contribute to stable glycaemic control and diabetes remission based on the characteristics of patients before and after treatment with dorzagliatin were analysed. A post hoc sensitivity analysis of diabetes remission probability using the American Diabetes Association (ADA) definition was conducted. RESULTS: The Kaplan-Meier remission probability was 65.2% (95% CI: 52.0%, 75.6%) at week 52. Based on the ADA definition, the remission probability was 52.0% (95% CI: 31.2%, 69.2%) at week 12. The significant improvements in the insulin secretion index ΔC30/ΔG30 (41.46 ± 77.68, P = .0238), disposition index (1.22 ± 1.65, P = .0030), and steady-state variables of HOMA2-ß (11.49 ± 14.58, P < .0001) and HOMA2-IR (-0.16 ± 0.36, P = .0130) during the SEED trial were important factors in achieving drug-free remission. A significant improvement in time in range (TIR), a measure of glucose homeostasis, in the SEED trial from 60% to more than 80% (estimated treatment difference, 23.8%; 95% CI: 7.3%, 40.2%; P = .0084) was observed. CONCLUSIONS: In drug-naïve patients with T2D, dorzagliatin treatment leads to stable glycaemic control and drug-free diabetes remission. Improvements in ß-cell function and TIR in these patients are important contributors to diabetes remission.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/induzido quimicamente , Estudos Prospectivos , Hemoglobinas Glicadas , Hipoglicemiantes/uso terapêutico , Glicemia
7.
Int J Gen Med ; 16: 2271-2283, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37304903

RESUMO

Purpose: To explore the correlation between Chinese visceral adipose index (CVAI) and urinary microalbumin/creatinine ratio (UACR) and urinary albumin, and whether there is any difference in correlation between Han and Tujia ethnicity. Methods: This cross-sectional study was conducted in Changde, Hunan, China from May 2021 to December 2021. Biochemical indicators including anthropometric parameters, blood pressure, blood glucose, blood lipids, and UACR of the participants were measured. Univariate analysis, multivariate analyses and multinomial logistic regression analysis were carried out to assess the association between CVAI and albuminuria. In addition, curve fitting and threshold effect analysis were used to explore the nonlinear association between CVAI and albuminuria, and to observe whether there were ethnic differences in this association. Results: A total of 2026 adult residents were enrolled in this study, 500 of whom had albuminuria. Population-standardized prevalence of albuminuria is 19.06%. In the multivariable model adjusted for confounding factors, the odds ratio (OR) of albuminuria for pre-unit increase of CVAI and pre-SD increase of CVAI were 1.007 (1.003-1.010) and 1.298 (1.127-1.496), respectively. Multinomial logistic regression analysis confirmed the robustness and consistency of the results.The generalized additive model showed that CVAI and albuminuria had a nonlinear relationship with inflection point at 97.201 using the threshold effect. Compared with Han ethnic groups, the threshold between CVAI and albuminuria in Tujia people moved backward. The thresholds were 159.785 and 98.527, respectively. Conclusion: There was a positive nonlinear dose-response relationship between increased CVAI and higher levels of albuminuria. Maintaining appropriate CVAI levels may be important for the prevention of albuminuria.

8.
Diabetes Metab Syndr Obes ; 16: 505-514, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36852179

RESUMO

Purpose: The best predictors and cut points for metabolic syndrome (MetS) in Chinese patients with type 2 diabetes (T2DM) were determined by comparing six anthropometric measures: body mass index (BMI), triglyceride-glucose (TyG), the product of TyG and waist-to-hip ratio (TyG-WHpR), the product of TyG and waist-to-height ratio (TyG-WHtR), the product of TyG and waist circumference (TyG-WC), and the product of TyG and body mass index (TyG-BMI). Patients and Methods: Sixteen hundred and sixty-five adult patients with T2DM were collected, and the ability and cut points of each index to predict MetS were compared by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC) values. Then, logistic regression analysis was used to adjust for confounders, including adjustment for menopause in women, to obtain the odds ratio (OR) and 95% confidence interval (CI). Results: MetS was present in 71.60% of T2DM patients, 75.00% of men, and 67.02% of women. BMI was the best predictor of MetS in men with T2DM (AUC = 0.8646, 95% CI: 0.8379-0.8912), with a cut point of 24.5500 kg/m2 (specificity: 0.7714; sensitivity: 0.7533), and TyG-WC was the best predictor of MetS in women with T2DM (AUC = 0.8362, 95% CI: 0.8034-0.8690), with a cut point of 154.1548 (specificity: 0.7455; sensitivity: 0.8076). Conclusion: The best predictor of MetS in adults with T2DM is BMI with a cut point of 24.5500 kg/m2 for men and TyG-WC with a cut point of 154.1548 for women.

9.
Front Endocrinol (Lausanne) ; 13: 972785, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36204109

RESUMO

Aims: The comorbidity of metabolic syndrome (MetS) and type 1 diabetes mellitus (T1DM) is an obstacle to glucose control in patients with T1DM. We compared glycemic profiles using continuous glucose monitoring (CGM) systems in patients with T1DM with or without MetS. Methods: This was a multicenter cross-sectional study of patients with T1DM (N = 207) with or without MetS. CGM data were collected from study enrollment until discharge during a 1-week study session. We analyzed baseline HbA1c, average glucose, estimated HbA1c, time in range (TIR), time above range (TAR), time below range (TBR), coefficient of variation (CV), postprandial glucose excursions (PPGE) and other glycemic variability (GV) metrics. Logistic regression was developed to investigate the association between MetS and CGM metrics. Results: The results showed higher average baseline HbA1c levels, and a higher percentage of patients with baseline HbA1c levels ≥7.5%, in the T1DM with MetS group. Furthermore, MetS was associated with GV, which indicated a higher CV in patients with T1DM with MetS. However, our results showed that TAR, TIR, TBR and other GV metrics were comparable between the two groups. The T1DM with MetS group also had a higher proportion of patients with high CV (≥ 36%) than the group without MetS. In multivariable logistic regression analysis, the presence of MetS was a risk factor for high CV (≥ 36%) in our study participants. Conclusions: T1DM patients with MetS in our study had better ß-cell function. However, MetS was associated with worse glycemic control characterized by higher GV and HbA1c levels. Efforts should be expanded to improve treatment of MetS in patients with T1DM to achieve better glycemic control.


Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Síndrome Metabólica , Glicemia/análise , Automonitorização da Glicemia , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Hemoglobinas Glicadas/análise , Humanos , Hiperglicemia/complicações , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia
10.
Nat Med ; 28(5): 974-981, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35551292

RESUMO

Metformin, the first-line therapy for type 2 diabetes (T2D), decreases hepatic glucose production and reduces fasting plasma glucose levels. Dorzagliatin, a dual-acting orally bioavailable glucokinase activator targeting both the pancreas and liver glucokinase, decreases postprandial glucose in patients with T2D. In this randomized, double-blind, placebo-controlled phase 3 trial, the efficacy and safety of dorzagliatin as an add-on therapy to metformin were assessed in patients with T2D who had inadequate glycemic control using metformin alone. Eligible patients with T2D (n = 767) were randomly assigned to receive dorzagliatin or placebo (1:1 ratio) as an add-on to metformin (1,500 mg per day) for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin (HbA1c) levels from baseline to week 24, and safety was assessed throughout the trial. At week 24, the least-squares mean change from baseline in HbA1c (95% confidence interval (CI)) was -1.02% (-1.11, -0.93) in the dorzagliatin group and -0.36% (-0.45, -0.26) in the placebo group (estimated treatment difference, -0.66%; 95% CI: -0.79, -0.53; P < 0.0001). The incidence of adverse events was similar between groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin and metformin combined therapy group. In patients with T2D who experienced inadequate glycemic control with metformin alone, dorzagliatin resulted in effective glycemic control with good tolerability and safety profile ( NCT03141073 ).


Assuntos
Diabetes Mellitus Tipo 2 , Metformina , Glicemia , Método Duplo-Cego , Quimioterapia Combinada , Glucoquinase , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/uso terapêutico , Humanos , Hipoglicemiantes/efeitos adversos , Pirazóis , Resultado do Tratamento
11.
Nat Med ; 28(5): 965-973, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35551294

RESUMO

Improving glucose sensitivity remains an unmet medical need in treating type 2 diabetes (T2D). Dorzagliatin is a dual-acting, orally bioavailable glucokinase activator that enhances glucokinase activity in a glucose-dependent manner, improves glucose-stimulated insulin secretion and demonstrates effects on glycemic control in patients with T2D. We report the findings of a randomized, double-blind, placebo-controlled phase 3 clinical trial to evaluate the efficacy and safety of dorzagliatin in patients with T2D. Eligible drug-naïve patients with T2D (n = 463) were randomly assigned to the dorzagliatin or placebo group at a ratio of 2:1 for 24 weeks of double-blind treatment, followed by 28 weeks of open-label treatment with dorzagliatin for all patients. The primary efficacy endpoint was the change in glycated hemoglobin from baseline to week 24. Safety was assessed throughout the trial. At week 24, the least-squares mean change in glycated hemoglobin from baseline (95% confidence interval) was -1.07% (-1.19%, -0.95%) in the dorzagliatin group and -0.50% (-0.68%, -0.32%) in the placebo group (estimated treatment difference, -0.57%; 95% confidence interval: -0.79%, -0.36%; P < 0.001). The incidence of adverse events was similar between the two groups. There were no severe hypoglycemia events or drug-related serious adverse events in the dorzagliatin group. In summary, dorzagliatin improved glycemic control in drug-naïve patients with T2D and showed a good tolerability and safety profile.


Assuntos
Diabetes Mellitus Tipo 2 , Glicemia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Método Duplo-Cego , Quimioterapia Combinada , Glucoquinase , Glucose , Hemoglobinas Glicadas/análise , Hemoglobinas Glicadas/uso terapêutico , Humanos , Hipoglicemiantes , Pirazóis , Resultado do Tratamento
12.
Medicine (Baltimore) ; 101(49): e32266, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36626508

RESUMO

RATIONALE: Severe insulin receptor gene (INSR)-related insulin resistance syndromes (SIR) include Donohue syndrome (DS), Rabson-Mendenhall syndrome (RMS), and type A insulin resistance. The incidence of DS is about 1 in 4 million births. We identified novel INSR mutations (c.2246delG and c.2646 + 5G > A) in a patient with SIR, which expanded the variant spectrum and helped to improve the understanding of the diagnosis and treatment of this condition. PATIENT CONCERNS: A 10-year-old Chinese boy was admitted to the hospital for deepening skin color. He presented with growth retardation, peculiar facial features, acanthosis nigricans, hypertrichosis, extremely high insulin levels, fasting hypoglycemia, and postprandial hyperglycemia, Whole-exome gene testing suggested compound heterozygous mutations in INSR (c.2246delG and c.2646 + 5G > A). DIAGNOSIS: The diagnosis was SIR. What's more, based on the phenotypic and biographical results, this child did not present typical RMS and DS but rather an intermediate phenotype between the 2 conditions. INTERVENTIONS: On the basis of a sensible diet and exercise, the patient was prescribed metformin (250 mg) at breakfast and lunch, which was increased to 500 mg after 1 month. OUTCOMES: After 2 months of treatment, the patient's glycated hemoglobin (HbA1c) levels decreased to 6% but his insulin resistance did not improve significantly. LESSONS: In children who are not obese but with severe insulin resistance, growth retardation, hirsutism, and hyperglycemia, genetic testing should be performed for early diagnosis, active treatment, and follow-up.


Assuntos
Síndrome de Donohue , Resistência à Insulina , Síndrome Metabólica , Humanos , Masculino , Antígenos CD/genética , Síndrome de Donohue/genética , Síndrome de Donohue/diagnóstico , População do Leste Asiático , Transtornos do Crescimento , Resistência à Insulina/genética , Mutação , Receptor de Insulina/genética , Criança
13.
Medicine (Baltimore) ; 101(52): e32510, 2022 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-36595986

RESUMO

RATIONALE: Glycogen storage disease (GSD) is a glycogen metabolism disorder caused by congenital enzyme defects, with type I being the most common. Owing to the rarity of glycogen storage disease type Ia (GSD Ia) and the involvement of diverse systems, patients are prone to delayed diagnosis and inappropriate treatment. Additional studies are required to standardize the diagnosis and treatment of GSD Ia. PATIENT CONCERNS: We report 2 cases of GSD Ia that occurred in 2 sisters. The elder sister also had recurrent pancreatitis, and the pancreatic pseudocyst rupture resulted in sepsis, portal hypertension, and splenic infarction. The younger sister had the same mutation site, but the clinical phenotypes were not identical. DIAGNOSIS: Abdominal computed tomography and laboratory examinations revealed regional portal hypertension, splenic infarction, and sepsis in the elder sister; diagnosis was confirmed by whole exome sequencing. Sanger sequencing was used to confirm that the younger sister and their parents also had the mutation site. INTERVENTIONS: The elder sister was treated with corn starch therapy, and medication for antiinfection and reducing hypertriglyceridemia, inhibiting trypsin activity, relieving hyperuricemia. The younger sister was treated with raw cornstarch-based nutritional therapy and sodium bicarbonate. OUTCOMES: The elder sister's infection was controlled and she gradually returned to a normal diet. After discharge, hyperlipidemia was not controlled satisfactorily, but hypoglycemia, hyperuricemia, hyperlactatemia, and anemia improved. LESSONS: GSD should be considered in childhood patients with hypoglycemia, hypertriglyceridemia, hyperuricemia, and hyperlactatemia. Gene sequencing can enable quick identification of GSD subtypes. This case report highlights the common clinical manifestations can be linked to rare diseases. Clinical work requires careful observation of the correlations between patient history, physical examinations, and laboratory examinations.


Assuntos
Hiperlactatemia , Hipertrigliceridemia , Hiperuricemia , Hipoglicemia , Pancreatite Crônica , Sepse , Infarto do Baço , Feminino , Humanos , Mutação
14.
Lancet Diabetes Endocrinol ; 6(8): 627-636, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29735394

RESUMO

BACKGROUND: Glucokinase acts as a glucose sensor in the pancreas and a glucose processor in the liver, and has a central role in glucose homoeostasis. Dorzagliatin is a new, dual-acting, allosteric glucokinase activator that targets both pancreatic and hepatic glucokinases. Dorzagliatin has good pharmacokinetic and pharmacodynamic properties in humans, and provides effective 24-h glycaemic control and improves glucose sensitivity in patients with type 2 diabetes. We aimed to assess the efficacy and safety of dorzagliatin monotherapy at different doses in Chinese patients with type 2 diabetes. METHODS: In this multicentre, randomised, double-blind, placebo-controlled, phase 2 study, we randomly assigned (1:1:1:1:1) patients to receive oral placebo or one of four doses of oral dorzagliatin (75 mg once a day, 100 mg once a day, 50 mg twice a day, or 75 mg twice a day) using permuted-block randomisation, with a block size of ten and without stratification. Eligible patients were men or non-fertile women (aged 40-75 years) with type 2 diabetes who had a BMI of 19·0-30·0 kg/m2, were on a diet and exercise regimen, and were previously untreated or treated with metformin or α-glucosidase inhibitor monotherapy. The study started with a 4-week placebo run-in period followed by a 12-week treatment period. The primary endpoint was the change in HbA1c from baseline to week 12, which was assessed in all patients who received at least one dose of study drug and had both baseline and at least one post-baseline HbA1c value. Safety was assessed in all patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, number NCT02561338. FINDINGS: Between Sept 29, 2015, and Aug 17, 2016, we randomly assigned 258 patients to one of the five study groups. At the end of 12 weeks, the least squares mean change in HbA1c from baseline was -0·35% (95% CI -0·60 to -0·10) in the placebo group, -0·39% (-0·64 to -0·14) in the 75 mg once daily group, -0·65% (-0·92 to -0·38) in the 100 mg once daily group, -0·79% (-1·06 to -0·52) in the 50 mg twice daily group, and -1·12% (-1·39 to -0·86) in the 75 mg twice daily group. Compared with the placebo group, the change in HbA1c between baseline and 12 weeks was significant in the 50 mg twice daily (p=0·0104) and the 75 mg twice daily (p<0·0001) groups. The number of adverse events was similar between the treatment groups and the placebo group. There were no reports of drug-related serious adverse events or severe hypoglycaemia. INTERPRETATION: Dorzagliatin had a beneficial effect on glycaemic control and was safe and well tolerated over 12 weeks in Chinese patients with type 2 diabetes. FUNDING: Hua Medicine, National Major Scientific and Technological Special Project for Significant New Drugs Development, Shanghai Science and Technology Innovation Action Project, Shanghai Pudong District Science and Technology Innovation Action Project, and Shanghai Municipal Commission of Economy and Informatisation Innovation Action Project.


Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Pirazóis/uso terapêutico , Adulto , Idoso , Povo Asiático , Glicemia/análise , Método Duplo-Cego , Ativadores de Enzimas/uso terapêutico , Feminino , Seguimentos , Hemoglobinas Glicadas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
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