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1.
Ars pharm ; 62(1): 52-65, ene.-mar. 2021. tab, graf
Artículo en Inglés | IBECS | ID: ibc-199700

RESUMEN

INTRODUCTION: The prevalence of diabetes type 2 is increasing worldwide, thus the search of novel alternative ther¬apies is needed. According to their traditional use, we selected five Bolivian plants Chenopodium quinoa (CQ) Ama¬ranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) and Smallanthus sonchifolius (SS) that are traditionally used to control glycemia. METHODS: The effect of a single oral administration of Ethanolic (EtOH), hydro-ethanolic (EtOH70) and aqueous (Aq) extracts from all plant species were tested for their effect on blood glucose in non-fasted mice and during the oral glucose tolerance test (OGTT). The effect on insulin secretion was evaluated in mice pancreatic islets. RESULTS: EtOH70 extracts of all the plants showed glucose-reducing effect at the highest dose evaluated (2000 mg/ kg b.w.). EtOH70 extracts improved the glucose tolerance evaluated by the OGTT in mice fasted for 12 hours. The extracts have different effects on glucose homeostasis since just extracts of AC, LM and CQ but not CP and SS in¬creased insulin secretion as shown on mice pancreatic islets. The phytochemical qualitative characterization of EtOH70 extracts detected phenolic acids and flavonoids in AC, CP and CQ; alkaloids in LM and anthocyanidins in SS. None of EtOH70 extracts tested showed in vitro or in vivo acute toxicity at concentrations where they exhibit glucose lowering effects. CONCLUSIONS: We report here that extracts from AC, CQ, CP, LM and SS exhibit glucose lowering effect while just AC, CQ and LM stimulate directly the insulin secretion


INTRODUCCIÓN: La prevalencia de diabetes tipo 2 está aumentando en todo el mundo, por lo que se necesita la búsqueda de nuevas terapias alternativas. Según su uso tradicional, seleccionamos cinco plantas bolivianas Chenopodium quinoa (CQ) Amaranthus caudatus (AC), Chenopodium pallidicaule (CP), Lupinus mutabilis (LM) y Smallanthus sonchifolius (SS) que se usan tradicionalmente para controlar la glucemia. MÉTODOS: Se evaluó el efecto de la administración oral única de extractos etanólicos (EtOH), hidroetanólicos (EtOH70) y acuosos (Aq) de las plantas mencionadas para determinar su efecto sobre la glucosa en sangre en ratones en o sin ayunas y durante la prueba de tolerancia a la glucosa oral (PTGO). El efecto sobre la secreción de insulina se evaluó en islotes pancreáticos de ratones. RESULTADOS: Los extractos de EtOH70 de todas las plantas disminuyeron la glucemia a la dosis más alta evaluada (2000 mg / kg b.w.). Los extractos de EtOH70 mejoraron la tolerancia a la glucosa evaluada mediante la PTGO en ratones con ayuno de 12 horas. Los extractos tienen diferentes efectos sobre la homeostasis de la glucosa, ya que solo los extractos de AC, LM y CQ pero no CP y SS aumentaron la secreción de insulina como se muestra en los islotes pancreáticos de los ratones. La caracterización cualitativa fitoquímica de extractos de EtOH70 detectó ácidos fenólicos y flavonoides en AC, CP y CQ, alcaloides en LM y antocianidinas en SS. Ninguno de los extractos de EtOH70 probados mostró toxicidad aguda in vitro o in vivo a concentraciones en las que exhiben efectos reductores de glucosa. CONCLUSIÓN: Los extractos de AC, CQ, CP, LM y SS exhiben un efecto reductor de la glucosa, mientras que solo AC, CQ y LM estimulan directamente la secreción de insulina


Asunto(s)
Animales , Masculino , Ratones , Glucemia/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Experimental/tratamiento farmacológico , Secreción de Insulina/efectos de los fármacos , Extractos Vegetales/farmacología , Suplementos Dietéticos , Chenopodium quinoa/química , Amaranthus/química , Chenopodium/química , Lupinus/química , Islotes Pancreáticos/efectos de los fármacos , Factores de Tiempo , Valores de Referencia , Reproducibilidad de los Resultados , Bolivia , Prueba de Tolerancia a la Glucosa
3.
Medicine (Baltimore) ; 100(10): e25100, 2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33725905

RESUMEN

BACKGROUND: Mitochondrial diabetes mellitus (MDM) is characterized by maternal inheritance, progressive neurosensory deafness, insulin secretory disorder, and progressive microvascular complications. Mitochondria are critical organelles that provide energy in the form of adenosine triphosphate (ATP). An impairment of ATP production in pancreatic ß cells is regarded as the main cause of the insulin secretory disorder in patients with MDM, and these patients require insulin replacement therapy early after the diagnosis. The amino acid 5-aminolevulinic acid (5-ALA), a precursor of heme metabolites, is a non-proteinogenic δ amino acid synthesized in mitochondria. An addition of ferrous iron to 5-ALA enhances heme biosynthesis and increases ATP production through an upregulation of the respiratory complex. Several studies have reported that the administration of 5-ALA and ferrous iron to existing treatment improved the glycemic control in both patients with prediabetes and those with type 2 diabetes mellitus. The additional administration of 5-ALA and ferrous iron to MDM patients on insulin therapy may improve their insulin secretory capacity and glycemic control by improving their mitochondrial function. The findings of this study are expected to provide new treatment options for MDM and improve the patients' glycemic control and prognosis. METHODS/DESIGN: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of treatment with 5-ALA plus sodium ferrous citrate (SFC) to patients with MDM on their glucose tolerance. A total of 5 patients with MDM will be administered 5-ALA/SFC (200 mg/d) for 24 weeks. We will perform a 75-g oral glucose tolerance test before and at 24 weeks after the start of this 5-ALA/SFC treatment to evaluate glucose-dependent insulin responses. DISCUSSION: To the best of our knowledge, this study will be the first assessment of the effects of 5-ALA/SFC in patients with MDM. This study will obtain an evidence regarding the effectiveness and safety of 5-ALA/SFC for patients with MDM. TRIAL REGISTRATION: This study was registered with the University Hospital Medical Information Network (UMIN000040581) on July 1, 2020 and with the Japan Registry of Clinical Trials (jRCTs071200025) on August 3, 2020.


Asunto(s)
Sordera/tratamiento farmacológico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Compuestos Ferrosos/administración & dosificación , Intolerancia a la Glucosa/tratamiento farmacológico , Insulina/administración & dosificación , Ácidos Levulínicos/administración & dosificación , Enfermedades Mitocondriales/tratamiento farmacológico , Adenosina Trifosfato/metabolismo , Adulto , Glucemia/análisis , Sordera/sangre , Sordera/diagnóstico , Sordera/patología , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Femenino , Compuestos Ferrosos/efectos adversos , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/diagnóstico , Intolerancia a la Glucosa/patología , Prueba de Tolerancia a la Glucosa , Humanos , Japón , Ácidos Levulínicos/efectos adversos , Masculino , Mitocondrias/efectos de los fármacos , Mitocondrias/patología , Enfermedades Mitocondriales/sangre , Enfermedades Mitocondriales/diagnóstico , Enfermedades Mitocondriales/patología , Proyectos Piloto , Resultado del Tratamiento
4.
Molecules ; 26(4)2021 Feb 17.
Artículo en Inglés | MEDLINE | ID: mdl-33671428

RESUMEN

The potential biological activities of Viburnum stellato-tomentosum (VS), a plant mainly found in Costa Rica, have yet to be reported. Supplementation of VS extract for 17 weeks significantly decreased body weight gain, fat weight, fasting glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), and triglyceride levels in high-fat diet (HFD)-fed C57BL/6J mice. The molecular mechanisms underlying the anti-obesity and glucose-lowering effects of VS extract were investigated. VS extract suppressed adipocyte hypertrophy by regulating lipogenesis-related CCAAT/enhancer-binding protein α (C/EBPα) and insulin sensitivity-related peroxisome proliferator-activated receptor γ (Pparg) expression in adipose tissue (AT) and hepatic steatosis by inhibiting C/EBPα and lipid transport-related fatty acid binding protein 4 (FABP4) expression. VS extract enhanced muscular fatty acid ß-oxidation-related AMP-activated protein kinase (AMPK) and PPARα expression with increasing Pparg levels. Furthermore, VS extract contained a much higher content of amentoflavone (AMF) (29.4 mg/g extract) compared to that in other Viburnum species. AMF administration decreased Cebpa and Fabp4 levels in the AT and liver, as well as improved insulin signaling-related insulin receptor substrate 1 (Irs1) and glucose transporter 1 (Glut1) levels in the muscle of HFD-fed mice. This study elucidated the in vivo molecular mechanisms of AMF for the first time. Therefore, VS extract effectively diminished obesity and hyperglycemia by suppressing C/EBPα-mediated lipogenesis in the AT and liver, enhancing PPARα-mediated fatty acid ß-oxidation in muscle, and PPARγ-mediated insulin sensitivity in AT and muscle.


Asunto(s)
Fármacos Antiobesidad/uso terapéutico , Dieta Alta en Grasa , Hiperglucemia/tratamiento farmacológico , Metabolismo de los Lípidos , Obesidad/tratamiento farmacológico , Obesidad/metabolismo , Extractos Vegetales/uso terapéutico , Viburnum/química , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/patología , Adipogénesis/efectos de los fármacos , Tejido Adiposo Blanco/patología , Animales , Fármacos Antiobesidad/farmacología , Biflavonoides/farmacología , Peso Corporal/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Hígado Graso/sangre , Hígado Graso/complicaciones , Hígado Graso/tratamiento farmacológico , Conducta Alimentaria , Glucosa/metabolismo , Prueba de Tolerancia a la Glucosa , Homeostasis/efectos de los fármacos , Hiperglucemia/sangre , Hiperglucemia/complicaciones , Hiperglucemia/metabolismo , Hipertrofia , Insulina/metabolismo , Resistencia a la Insulina , Metabolismo de los Lípidos/efectos de los fármacos , Ratones Endogámicos C57BL , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Obesidad/sangre , Obesidad/complicaciones , Tamaño de los Órganos/efectos de los fármacos , Oxidación-Reducción , Extractos Vegetales/farmacología , Transducción de Señal/efectos de los fármacos
5.
Medicine (Baltimore) ; 100(13): e25076, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33787590

RESUMEN

RATIONALE: Ectopic insulinomas are extremely rare and challenging to diagnose for clinicians. Precise preoperative localization is essential to successful treatment. PATIENT CONCERNS: A 23-year-old man presented with a 1-year history of recurrent hypoglycemia. DIAGNOSIS: Examinations in the local hospital did not reveal any pancreatic lesion. After admission, a fasting test and a 5-hour oral glucose tolerance test (OGTT) suggested a diagnosis of endogenous hyperinsulinemic hypoglycemia. Enhanced volume perfusion computed tomography (VPCT) revealed 2 nodules in the tail of the pancreas, a nodule in the gastric antrum, and a nodule in the hilum of the spleen. To differentiate which nodule was responsible for hypoglycemia, we performed 68Ga-Exendin-4 PET/CT and 68Ga-DOTATATE PET/CT which helped to make a conclusive diagnosis that the lesion in the gastric antrum was an ectopic insulinoma. INTERVENTIONS: The patient was cured with minimally invasive laparoscopic resection of the tumor. OUTCOMES: The symptoms were relieved and the blood glucose level remained normal after surgery. CONCLUSIONS: This case shows that 68Gallium-exendin-4 PET/CT is useful for precise localization and thereby successful treatment of insulinoma, especially for occult insulinomas and those derived from an ectopic pancreas.


Asunto(s)
Coristoma/diagnóstico por imagen , Insulinoma/diagnóstico por imagen , Neoplasias Pancreáticas/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias Gástricas/diagnóstico por imagen , Coristoma/complicaciones , Exenatida , Radioisótopos de Galio , Prueba de Tolerancia a la Glucosa , Humanos , Hipoglucemia/diagnóstico por imagen , Hipoglucemia/etiología , Insulinoma/complicaciones , Masculino , Compuestos Organometálicos , Páncreas , Antro Pilórico/diagnóstico por imagen , Radiofármacos , Recurrencia , Adulto Joven
6.
N Engl J Med ; 384(10): 895-904, 2021 03 11.
Artículo en Inglés | MEDLINE | ID: mdl-33704936

RESUMEN

BACKGROUND: Gestational diabetes mellitus is common and is associated with an increased risk of adverse maternal and perinatal outcomes. Although experts recommend universal screening for gestational diabetes, consensus is lacking about which of two recommended screening approaches should be used. METHODS: We performed a pragmatic, randomized trial comparing one-step screening (i.e., a glucose-tolerance test in which the blood glucose level was obtained after the oral administration of a 75-g glucose load in the fasting state) with two-step screening (a glucose challenge test in which the blood glucose level was obtained after the oral administration of a 50-g glucose load in the nonfasting state, followed, if positive, by an oral glucose-tolerance test with a 100-g glucose load in the fasting state) in all pregnant women who received care in two health systems. Guidelines for the treatment of gestational diabetes were consistent with the two screening approaches. The primary outcomes were a diagnosis of gestational diabetes, large-for-gestational-age infants, a perinatal composite outcome (stillbirth, neonatal death, shoulder dystocia, bone fracture, or any arm or hand nerve palsy related to birth injury), gestational hypertension or preeclampsia, and primary cesarean section. RESULTS: A total of 23,792 women underwent randomization; women with more than one pregnancy during the trial could have been assigned to more than one type of screening. A total of 66% of the women in the one-step group and 92% of those in the two-step group adhered to the assigned screening. Gestational diabetes was diagnosed in 16.5% of the women assigned to the one-step approach and in 8.5% of those assigned to the two-step approach (unadjusted relative risk, 1.94; 97.5% confidence interval [CI], 1.79 to 2.11). In intention-to-treat analyses, the respective incidences of the other primary outcomes were as follows: large-for-gestational-age infants, 8.9% and 9.2% (relative risk, 0.95; 97.5% CI, 0.87 to 1.05); perinatal composite outcome, 3.1% and 3.0% (relative risk, 1.04; 97.5% CI, 0.88 to 1.23); gestational hypertension or preeclampsia, 13.6% and 13.5% (relative risk, 1.00; 97.5% CI, 0.93 to 1.08); and primary cesarean section, 24.0% and 24.6% (relative risk, 0.98; 97.5% CI, 0.93 to 1.02). The results were materially unchanged in intention-to-treat analyses with inverse probability weighting to account for differential adherence to the screening approaches. CONCLUSIONS: Despite more diagnoses of gestational diabetes with the one-step approach than with the two-step approach, there were no significant between-group differences in the risks of the primary outcomes relating to perinatal and maternal complications. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ScreenR2GDM ClinicalTrials.gov number, NCT02266758.).


Asunto(s)
Diabetes Gestacional/diagnóstico , Prueba de Tolerancia a la Glucosa/métodos , Hiperglucemia/diagnóstico , Adulto , Glucemia/análisis , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Femenino , Macrosomía Fetal/epidemiología , Humanos , Hiperglucemia/sangre , Incidencia , Tamizaje Masivo , Embarazo , Resultado del Embarazo
7.
Nat Commun ; 12(1): 1064, 2021 02 16.
Artículo en Inglés | MEDLINE | ID: mdl-33594056

RESUMEN

Polycystic ovary syndrome (PCOS) is characterized by an oligo-anovulation, hyperandrogenism and polycystic ovarian morphology combined with major metabolic disturbances. However, despite the high prevalence and the human and economic consequences of this syndrome, its etiology remains unknown. In this study, we show that female Goto-Kakizaki (GK) rats, a type 2 diabetes mellitus model, encapsulate naturally all the reproductive and metabolic hallmarks of lean women with PCOS at puberty and in adulthood. The analysis of their gestation and of their fetuses demonstrates that this PCOS-like phenotype is developmentally programmed. GK rats also develop features of ovarian hyperstimulation syndrome. Lastly, a comparison between GK rats and a cohort of women with PCOS reveals a similar reproductive signature. Thus, this spontaneous rodent model of PCOS represents an original tool for the identification of the mechanisms involved in its pathogenesis and for the development of novel strategies for its treatment.


Asunto(s)
Síndrome del Ovario Poliquístico/patología , Adiposidad , Animales , Animales Recién Nacidos , Peso Corporal , Análisis Discriminante , Modelos Animales de Enfermedad , Dislipidemias/patología , Sistema Endocrino/patología , Ciclo Estral , Femenino , Prueba de Tolerancia a la Glucosa , Gonadotropinas/farmacología , Hormonas/sangre , Humanos , Secreción de Insulina , Análisis de los Mínimos Cuadrados , Lípidos/química , Masculino , Intercambio Materno-Fetal , Análisis Multivariante , Ovario/patología , Ovario/fisiopatología , Fenotipo , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/fisiopatología , Embarazo , Ratas Wistar , Reproducción , Maduración Sexual
8.
Nutrients ; 13(2)2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33567590

RESUMEN

Maternal metabolism and intrauterine conditions influence development of health and disease in offspring, leading to metabolic, physiologic, and/or epigenetic adaptation of the fetus. Maternal gestational diabetes (GDM) leads to higher incidence of obesity and type 2 diabetes in offspring. We have previously shown that fetuses of insulin-resistant mothers with GDM have a delayed reaction to auditory stimuli in the postprandial state, indicating a fetal central insulin resistance. We tested whether this effect could be influenced by a lifestyle intervention in mothers with GDM, including diet counselling and regular blood glucose measurements. We measured fetal brain activity over the course of a maternal glucose challenge, at two measurement time points (baseline at an average of 29 weeks of gestation and follow-up after 4 weeks) in mothers with GDM and mothers with normal glucose tolerance (NGT). Data from eight mothers were able to be included. Fetuses of GDM mothers showed longer latencies than those of NGT mothers postprandially at both measurement time points during the third trimester and did not show a difference in response patterns between baseline and after 4 weeks. Maternal postprandial blood glucose and insulin values did not change from baseline to follow-up either. While the overall intervention seems to have been effective, it does not appear to have influenced the fetal postprandial brain responses. This might have been because interventions for GDM take place relatively late in pregnancy. Future research should focus on maternal lifestyle interventions as early as possible during gestation, or even prenatally.


Asunto(s)
Encéfalo/embriología , Diabetes Gestacional/terapia , Feto/fisiopatología , Tercer Trimestre del Embarazo , Atención Prenatal/métodos , Adulto , Glucemia/metabolismo , Estudios de Cohortes , Diabetes Gestacional/sangre , Femenino , Feto/embriología , Edad Gestacional , Ganancia de Peso Gestacional , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Resistencia a la Insulina/fisiología , Estilo de Vida , Periodo Posprandial/fisiología , Embarazo
9.
Nutrients ; 13(2)2021 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-33561965

RESUMEN

The aim of this study was to investigate the underlying mechanism for the improvement of glucose tolerance following intake of high ß-glucan barley (HGB) in terms of intestinal metabolism. C57BL/6J male mice were fed a fatty diet supplemented with HGB corresponding to 5% of dietary fiber for 83 days. An oral glucose tolerance test was performed at the end of the experimental period. The concentration of short-chain fatty acids (SCFAs) in the cecum was analyzed by GC-MS (gas chromatography-mass spectrometry). The mRNA expression levels related to L cell function in the ileum were measured by real-time PCR. Glucagon-like peptide-1 (GLP-1) levels in the portal vein and cecal content were assessed by enzyme-linked immunosorbent assay. GLP-1-producing L cells of the ileum were quantified by immunohistochemistry. HGB intake improved glucose tolerance and increased the cecal levels of SCFAs, acetate, and propionate. The number of GLP-1-positive L cells in the HGB group was significantly higher than in the control group. GLP-1 levels in the portal vein and cecal GLP-1 pool size in the HGB group were significantly higher than the control group. In conclusion, we report improved glucose tolerance after HGB intake induced by an increase in L cell number and subsequent rise in GLP-1 secretion.


Asunto(s)
Suplementos Dietéticos , Péptido 1 Similar al Glucagón/metabolismo , Hordeum/química , Obesidad/dietoterapia , beta-Glucanos/administración & dosificación , Animales , Glucemia/metabolismo , Secreciones Corporales , Ciego/metabolismo , Dieta Alta en Grasa/efectos adversos , Ácidos Grasos Volátiles/metabolismo , Prueba de Tolerancia a la Glucosa , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/etiología , Obesidad/metabolismo
10.
Medicine (Baltimore) ; 100(5): e23955, 2021 Feb 05.
Artículo en Inglés | MEDLINE | ID: mdl-33592849

RESUMEN

BACKGROUND: Overweight before pregnancy is independent risk factor for diabetes mellitus. This randomized controlled trial was to investigate the long-term effects of regular exercise during pregnancy on overweight and obese gravidas. METHODS AND ANALYSIS: This single-center, prospective, randomized controlled test will be conducted in Wuhan Central Hospital, Tongji Medical College, Huazhong University of Science and Technology. Overweight and obese pregnant women will be included in our study and randomized into 2 groups: regular exercise and control groups. The informed consent will be acquired in each patient. Body weight, body fat, fasting and 2 h glucose level in 75 g oral glucose tolerance test (OGTT), insulin resistance index, and lipid profiles were compared. We also evaluated their physical activities with International Physical Activity Questionnaire (IPAQ), their dietary habits with modified Adult Dietary Behavior Assessment Scale, and depression condition with Postpartum Depression Screen Scale (PDSS). The significance level was defaulted as P < .05. RESULTS: Results will be published in relevant peer-reviewed journals. CONCLUSION: Our study aims to systematically assess the effects of regular exercise for overweight and obese gravidas, which will be provided clinical guidance for overweight and obese gravidas.


Asunto(s)
Terapia por Ejercicio/métodos , Ejercicio Físico/fisiología , Obesidad/terapia , Sobrepeso/terapia , Complicaciones del Embarazo/terapia , Adulto , Peso Corporal/fisiología , Dieta/estadística & datos numéricos , Ayuno/fisiología , Conducta Alimentaria/fisiología , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Resistencia a la Insulina , Lípidos/sangre , Obesidad/fisiopatología , Sobrepeso/fisiopatología , Embarazo , Complicaciones del Embarazo/fisiopatología , Atención Prenatal/métodos , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Adulto Joven
11.
Diabetes Res Clin Pract ; 173: 108683, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33607161

RESUMEN

AIM: There have been few reports regarding the association between 1 h-PG concentration and type 2 diabetes mellitus (T2DM) in the elderly. This study was performed to assess the efficacy of 1 h-PG and 2 h-PG values in predicting future risk of T2DM in elderly. METHODS: The study population consisted of 928 male volunteers ≥ 55 years old without diabetes who were involved in a retrospective-prospective cohort study over 20 years with a baseline fasting plasma glucose (FPG) and OGTT that included measurement of 1 h-PG and 2 h-PG. The predictive capabilities of FPG and 1 h-PG, 2 h-PG values obtained during OGTT alone and added to a clinical prediction model consisting of traditional diabetes risk factors were assessed. RESULTS: Overall, 577 of all the 928 study participants (62%) developed T2DM over the 20-year follow-up. 1 h-PG and 2 h-PG values predicted T2DM and remained independent predictors of T2DM after adjusting for various traditional risk factors [HR = 1.269 (95% CI = 1.214-1.327), P < 0.001; HR = 1.269 (95% CI = 1.179-1.366), P < 0.001, respectively]. C-statistics for 1-h PG (C-statistics 0.794 [95% CI 0.765-0.823]) was significantly greater than that for 2-h PG (C-statistic 0.747 [95% CI 0.716-0.779]) in models adjusting for various traditional risk factors. 1 h-PG had the greatest area under the ROC curve (AUC, 0.766), which was greater than that of 2 h-PG (0.719). CONCLUSIONS: 1 h-PG is useful as a predictor of future development of T2DM independently of traditional risk factors in an elderly Chinese male population.


Asunto(s)
Glucemia/metabolismo , Diabetes Mellitus Tipo 2/sangre , Prueba de Tolerancia a la Glucosa/métodos , Anciano , China , Humanos , Masculino , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Factores de Riesgo
13.
Biomed Environ Sci ; 34(1): 9-18, 2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33531103

RESUMEN

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion: An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.


Asunto(s)
Índice Glucémico , Ácido Úrico/sangre , Anciano , Grupo de Ascendencia Continental Asiática , Glucemia/análisis , China/epidemiología , Estudios de Cohortes , Diabetes Mellitus/sangre , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina A Glucada/análisis , Humanos , Masculino , Persona de Mediana Edad
14.
Nat Med ; 27(1): 49-57, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33398163

RESUMEN

The state of intermediate hyperglycemia is indicative of elevated risk of developing type 2 diabetes1. However, the current definition of prediabetes neither reflects subphenotypes of pathophysiology of type 2 diabetes nor is predictive of future metabolic trajectories. We used partitioning on variables derived from oral glucose tolerance tests, MRI-measured body fat distribution, liver fat content and genetic risk in a cohort of extensively phenotyped individuals who are at increased risk for type 2 diabetes2,3 to identify six distinct clusters of subphenotypes. Three of the identified subphenotypes have increased glycemia (clusters 3, 5 and 6), but only individuals in clusters 5 and 3 have imminent diabetes risks. By contrast, those in cluster 6 have moderate risk of type 2 diabetes, but an increased risk of kidney disease and all-cause mortality. Findings were replicated in an independent cohort using simple anthropomorphic and glycemic constructs4. This proof-of-concept study demonstrates that pathophysiological heterogeneity exists before diagnosis of type 2 diabetes and highlights a group of individuals who have an increased risk of complications without rapid progression to overt type 2 diabetes.


Asunto(s)
Diabetes Mellitus Tipo 2/fisiopatología , Fenotipo , Antropometría , Glucemia/metabolismo , Composición Corporal , Estudios de Cohortes , Progresión de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Insulina/sangre , Masculino , Persona de Mediana Edad
15.
Nature ; 590(7845): 326-331, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33505018

RESUMEN

Resistance to insulin and insulin-like growth factor 1 (IGF1) in pancreatic ß-cells causes overt diabetes in mice; thus, therapies that sensitize ß-cells to insulin may protect patients with diabetes against ß-cell failure1-3. Here we identify an inhibitor of insulin receptor (INSR) and IGF1 receptor (IGF1R) signalling in mouse ß-cells, which we name the insulin inhibitory receptor (inceptor; encoded by the gene Iir). Inceptor contains an extracellular cysteine-rich domain with similarities to INSR and IGF1R4, and a mannose 6-phosphate receptor domain that is also found in the IGF2 receptor (IGF2R)5. Knockout mice that lack inceptor (Iir-/-) exhibit signs of hyperinsulinaemia and hypoglycaemia, and die within a few hours of birth. Molecular and cellular analyses of embryonic and postnatal pancreases from Iir-/- mice showed an increase in the activation of INSR-IGF1R in Iir-/- pancreatic tissue, resulting in an increase in the proliferation and mass of ß-cells. Similarly, inducible ß-cell-specific Iir-/- knockout in adult mice and in ex vivo islets led to an increase in the activation of INSR-IGF1R and increased proliferation of ß-cells, resulting in improved glucose tolerance in vivo. Mechanistically, inceptor interacts with INSR-IGF1R to facilitate clathrin-mediated endocytosis for receptor desensitization. Blocking this physical interaction using monoclonal antibodies against the extracellular domain of inceptor resulted in the retention of inceptor and INSR at the plasma membrane to sustain the activation of INSR-IGF1R in ß-cells. Together, our findings show that inceptor shields insulin-producing ß-cells from constitutive pathway activation, and identify inceptor as a potential molecular target for INSR-IGF1R sensitization and diabetes therapy.


Asunto(s)
Glucemia/metabolismo , Antagonistas de Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Insulina/metabolismo , Proteínas de Neoplasias/metabolismo , Transducción de Señal , Animales , Glucemia/análisis , Línea Celular , Proliferación Celular/efectos de los fármacos , Tamaño de la Célula , Clatrina/metabolismo , Células Endocrinas/metabolismo , Endocitosis , Retículo Endoplásmico/metabolismo , Prueba de Tolerancia a la Glucosa , Aparato de Golgi/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismo , Células Secretoras de Insulina/citología , Células Secretoras de Insulina/efectos de los fármacos , Lisosomas/metabolismo , Masculino , Ratones , Proteínas de Neoplasias/química , Receptor de Insulina/metabolismo , Transducción de Señal/efectos de los fármacos , Tamoxifeno/farmacología
16.
Adv Ther ; 38(2): 1342-1351, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33474706

RESUMEN

INTRODUCTION: Our aim is to propose an evidence-based strategy for screening postpartum dysglycemia. METHODS: This study included adult non-pregnant women who were diagnosed with gestational diabetes (GDM) using International Association of Diabetes in Pregnancy Study Group (IADPSG) criteria during their index pregnancy (2012-2019). Eligible participants underwent a concurrent oral glucose tolerance test (OGTT) and glycated hemoglobin (HbA1c) test. A detailed questionnaire documenting relevant personal and medical history was filled, and the relevant anthropometric parameters were recorded. RESULTS: We evaluated data from 377 women at a mean (± SD) age of 32.1 ± 4.6 years and at a median duration of 15 (10-33) months following childbirth. Diabetes was diagnosed in 42 (11.1%) women. Use of a combination cutoff [fasting plasma glucose (FPG) ≥ 6.1 mmol/L or glycated hemoglobin (HbA1c) ≥ 6.0% (42 mmol/mol)] avoided OGTT in 80.9% of the study cohort, without missing the diagnosis of diabetes in any study subject. The diagnosis was missed in 2.4% of women with diabetes (and 0.3% of whole cohort) using only the FPG criterion (≥ 5.6 mmol/L) or HbA1c criterion [HbA1c ≥ 5.7% (39 mmol/mol)] alone. These tests avoided the need for an OGTT in 75.3% and 65.5% of women, respectively. CONCLUSIONS: The proposed strategies are likely to be both patient- and physician-friendly and have the potential to address several barriers for postpartum screening among women with prior GDM.


Asunto(s)
Diabetes Gestacional , Adulto , Glucemia , Diabetes Gestacional/diagnóstico , Ayuno , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina A Glucada/análisis , Humanos , Embarazo
17.
BMJ Case Rep ; 14(1)2021 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-33472798

RESUMEN

Maturity onset diabetes of the young defines a diabetes mellitus subtype, with no insulin resistance or autoimmune pancreatic ß-cells dysfunction, that occurs by mutation in a single gene. A 13-year-old girl hospitalised due to hyperglycemia plus glycosuria without ketosis, and with normal glycated haemoglobin of 6.8%. She started a sugar-free fast-absorption diet and no insulin therapy was required. Fasting glucose was normal, but 2 hours after lunch she presented hyperglycemia as after 2 hours of an oral glucose tolerance test, with 217 mg/dL. Family history was positive for type 2 diabetes mellitus with an autosomal dominant pattern. She was discharged with fast-absorption sugar-free diet and low-dose of sulfonylurea. A genetic test was performed detecting a mutation in heterozygosity of HNF1A gene, compatible with the diagnosis of maturity onset diabetes of the young 3 (MODY3), not reported in the literature. Early recognition of signs and symptoms increase awareness of MODY. Genetic test allows confirmation and leads to optimised treatment.


Asunto(s)
Diabetes Mellitus Tipo 2/genética , Factor Nuclear 1-alfa del Hepatocito/genética , Adolescente , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Ayuno/metabolismo , Femenino , Prueba de Tolerancia a la Glucosa , Gliburida/uso terapéutico , Hemoglobina A Glucada/metabolismo , Humanos , Hipoglucemiantes/uso terapéutico , Linaje , Periodo Posprandial , Eliminación de Secuencia
18.
Metabolism ; 114: 154415, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33137379

RESUMEN

BACKGROUND AND AIMS: The reduced action of incretin hormones in type 2 diabetes (T2D) is mainly attributed to GIP insensitivity, but efficacy estimates of GIP and GLP-1 differ among studies, and the negligible effects of pharmacological GIP doses remain unexplained. We aimed to characterize incretin action in vivo in subjects with normal glucose tolerance (NGT) or T2D and provide an explanation for the different insulinotropic activity of GIP and GLP-1 in T2D subjects. METHODS: We used in vivo data from ten studies employing hormone infusion or an oral glucose test (OGTT). To homogeneously interpret and compare the results of the studies we performed the analysis using a mathematical model of the ß-cell incorporating the effects of incretins on the triggering and amplifying pathways. The effect on the amplifying pathway was quantified by a time-dependent factor that is greater than one when insulin secretion (ISR) is amplified by incretins. To validate the model results for GIP in NGT subjects, we performed an extensive literature search of the available data. RESULTS: a) the stimulatory effects of GIP and GLP-1 differ markedly: ISR potentiation increases linearly with GLP-1 over the whole dose range, while with GIP infusion it reaches a plateau at ~100 pmol/L GIP, with ISR potentiation of ~2 fold; b) ISR potentiation in T2D is reduced by ~50% for GIP and by ~40% for GLP-1; c) the literature search of GIP in NGT subjects confirmed the saturative effect on insulin secretion. CONCLUSION: We show that incretin potentiation of ISR is reduced in T2D, but not abolished, and that the lack of effects of pharmacological GIP doses is due to saturation of the GIP effect more than insensitivity to GIP in T2D.


Asunto(s)
Diabetes Mellitus Tipo 2/tratamiento farmacológico , Polipéptido Inhibidor Gástrico/administración & dosificación , Péptido 1 Similar al Glucagón/administración & dosificación , Incretinas/administración & dosificación , Secreción de Insulina/efectos de los fármacos , Células Secretoras de Insulina/efectos de los fármacos , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Polipéptido Inhibidor Gástrico/uso terapéutico , Péptido 1 Similar al Glucagón/uso terapéutico , Prueba de Tolerancia a la Glucosa , Humanos , Incretinas/uso terapéutico , Células Secretoras de Insulina/metabolismo , Modelos Teóricos
19.
Diabetes Res Clin Pract ; 172: 108640, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33359083

RESUMEN

AIMS: To evaluate proposals considering HbA1c and fasting plasma glucose (FPG) measurement as a substitute for oral glucose tolerance test (OGTT) to diagnose hyperglycaemia in pregnancy (HIP) during COVID-19 pandemic. METHODS: Of the 7,334 women who underwent the OGTT between 22 and 30 weeks gestation, 966 had HIP (WHO diagnostic criteria, reference standard). The 467 women who had an available HbA1c were used for analysis. French-speaking Society of Diabetes (SFD) proposal to diagnose HIP during COVID-19 pandemic was retrospectively applied: HbA1c ≥5.7% (39 mmol/mol) and/or FPG level ≥5.1 mmol/l. SFD proposal sensitivity for HIP diagnosis and the occurrence of HIP-related events (preeclampsia, large for gestational age infant, shoulder dystocia or neonatal hypoglycaemia) in women with false negative (FN) and true positive (TP) HIP-diagnoses were evaluated. RESULTS: The sensitivity was 57% [95% confidence interval 52-62]. FN women had globally lower plasma glucose levels during OGTT, lower HbA1c and body mass index than those TP. The percentage of HIP-related events was similar in FN (who were cared) and TP cases, respectively 19.5 and 16.9% (p = 0.48). We observed similar results when women at high risk for HIP only were considered. CONCLUSION: The SFD proposal has a poor sensitivity to detect HIP. Furthermore, it fails to have any advantages in predicting adverse outcomes.


Asunto(s)
Glucemia/metabolismo , Ayuno/sangre , Hemoglobina A Glucada/metabolismo , Hiperglucemia/sangre , Complicaciones del Embarazo , Adulto , Comorbilidad , Femenino , Prueba de Tolerancia a la Glucosa , Humanos , Hiperglucemia/epidemiología , Recién Nacido , Pandemias , Embarazo , Pronóstico , Estudios Retrospectivos , Factores de Riesgo
20.
J Dairy Sci ; 104(2): 2422-2437, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33309361

RESUMEN

Circadian and metabolic systems are interlocked and reciprocally regulated. To determine if the circadian system regulates glucose homeostasis and mammary development, the function of the circadian system was disrupted by exposing cattle to chronic light-dark cycle phase shifts from 5 wk before expected calving (BEC) to parturition. Multiparous Holstein cows were exposed to 16 h of light and 8 h of dark (CON, n = 8) or phase shifting (PS, n = 8) the light cycle 6 h every 3 d beginning 35 d BEC. After calving, both treatments were exposed to CON lighting. Mammary biopsies were taken at 21 d BEC and 21 d in milk (DIM), and histological analysis indicated PS treatment decreased the ratio of lumen to alveolar area and percentage of proliferating epithelial cells in the prepartum period. Intravenous glucose tolerance test was performed at 14 d BEC and 7 DIM by administering 50% dextrose. Blood glucose, ß-hydroxybutyrate, insulin, and nonesterified fatty acids were consequently measured over 3 h. At 14 d BEC no treatment differences were observed in baseline glucose or insulin. Treatment had no effect on blood glucose or glucose area under the curve at 14 d BEC and 7 DIM. Insulin area under the curve was higher in PS versus CON at 14 d BEC and 7 DIM. The PS cows produced less milk than CON cows through 60 DIM (40.3 vs. 42.6 kg/d). Exposure to chronic light-dark PS in late gestation decreased mammary development and increased insulin resistance in periparturient cows, which may have caused subsequent lower milk yield.


Asunto(s)
Bovinos , Relojes Circadianos , Resistencia a la Insulina , Glándulas Mamarias Animales/crecimiento & desarrollo , Leche , Periodo Posparto , Ácido 3-Hidroxibutírico/sangre , Animales , Glucemia/metabolismo , Oscuridad , Ácidos Grasos no Esterificados/sangre , Femenino , Prueba de Tolerancia a la Glucosa/veterinaria , Insulina/sangre , Lactancia/fisiología , Luz , Parto , Embarazo
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