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1.
Nat Commun ; 11(1): 4458, 2020 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895383

RESUMO

In rodent models of type 2 diabetes (T2D), sustained remission of hyperglycemia can be induced by a single intracerebroventricular (icv) injection of fibroblast growth factor 1 (FGF1), and the mediobasal hypothalamus (MBH) was recently implicated as the brain area responsible for this effect. To better understand the cellular response to FGF1 in the MBH, we sequenced >79,000 single-cell transcriptomes from the hypothalamus of diabetic Lepob/ob mice obtained on Days 1 and 5 after icv injection of either FGF1 or vehicle. A wide range of transcriptional responses to FGF1 was observed across diverse hypothalamic cell types, with glial cell types responding much more robustly than neurons at both time points. Tanycytes and ependymal cells were the most FGF1-responsive cell type at Day 1, but astrocytes and oligodendrocyte lineage cells subsequently became more responsive. Based on histochemical and ultrastructural evidence of enhanced cell-cell interactions between astrocytes and Agrp neurons (key components of the melanocortin system), we performed a series of studies showing that intact melanocortin signaling is required for the sustained antidiabetic action of FGF1. These data collectively suggest that hypothalamic glial cells are leading targets for the effects of FGF1 and that sustained diabetes remission is dependent on intact melanocortin signaling.


Assuntos
Diabetes Mellitus Experimental/dietoterapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Fator 1 de Crescimento de Fibroblastos/administração & dosagem , Hipoglicemiantes/administração & dosagem , Hipotálamo/efeitos dos fármacos , Proteínas Recombinantes/administração & dosagem , Proteína Relacionada com Agouti/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Glicemia/análise , Comunicação Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica/efeitos adversos , Sacarose na Dieta/administração & dosagem , Sacarose na Dieta/efeitos adversos , Humanos , Hipotálamo/citologia , Hipotálamo/patologia , Injeções Intraventriculares , Leptina/genética , Masculino , Melanocortinas/metabolismo , Hormônios Estimuladores de Melanócitos/administração & dosagem , Camundongos , Camundongos Knockout , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Oligodendroglia/efeitos dos fármacos , Oligodendroglia/metabolismo , RNA-Seq , Receptor Tipo 4 de Melanocortina/genética , Receptores de Melanocortina/antagonistas & inibidores , Receptores de Melanocortina/metabolismo , Indução de Remissão/métodos , Transdução de Sinais/efeitos dos fármacos , Análise de Célula Única , Técnicas Estereotáxicas , Transcriptoma/efeitos dos fármacos
2.
PLoS One ; 15(7): e0235637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32628710

RESUMO

BACKGROUND: The high risk of cardiovascular disease is well recognized in rheumatoid arthritis. Type 2 diabetes also attributes to this increase in risk. Rheumatoid arthritis is a chronic inflammatory condition, which aggravates insulin resistance, placing the patients at a higher risk of type 2 diabetes and subsequent cardiovascular outcomes. Methotrexate treatment, as a gold standard anti-inflammatory drug in the treatment of rheumatoid arthritis has shown beneficial effects on cardiovascular health. However, its impact on type 2 diabetes is still unknown. OBJECTIVE: To assess the strength of the association between exposure to methotrexate and the rate of development of type 2 diabetes in rheumatoid arthritis patients. METHODS: All rheumatoid arthritis studies reporting the use of methotrexate as an exposure and type 2 diabetes as an outcome were searched until March 2020 using MEDLINE, Cochrane and Scopus databases. Studies were included if the diagnosis of rheumatoid arthritis was made according to current guidelines or by a rheumatologist, and if there was information about methotrexate exposure and the type 2 diabetes outcome. The author and an independent assessor evaluated the articles for eligibility. Meta-analyses combined relative risk estimates from each study where raw counts were available. RESULTS: Sixteen studies reporting sufficient data for inclusion in the meta-analyses were identified. Methotrexate showed a promising effect on the risk of type 2 diabetes as this risk decreased in rheumatoid arthritis patients using methotrexate (Relative risk 0.48, 95% CI 0.16, 1.43). CONCLUSION: Rheumatoid arthritis patients on methotrexate treatment had a lower risk of developing type 2 diabetes compared to rheumatoid arthritis patients not exposed to methotrexate. This finding highlights the need for future, randomized control trials to confirm the beneficial effect of methotrexate on type 2 diabetes in the rheumatoid arthritis population.


Assuntos
Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Metotrexato/uso terapêutico , Fatores Etários , Antirreumáticos/efeitos adversos , Artrite Reumatoide/patologia , Diabetes Mellitus Tipo 2/etiologia , Humanos , Metotrexato/efeitos adversos , Risco , Índice de Gravidade de Doença
3.
PLoS Med ; 17(7): e1003206, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32722673

RESUMO

BACKGROUND: Previous clinical trials and institutional studies have demonstrated that surgery for the treatment of obesity (termed bariatric or metabolic surgery) reduces all-cause mortality and the development of obesity-related diseases such as type 2 diabetes mellitus (T2DM), hypertension, and dyslipidaemia. The current study analysed large-scale population studies to assess the association of bariatric surgery with long-term mortality and incidence of new-onset obesity-related disease at a national level. METHODS AND FINDINGS: A systematic literature search of Medline (via PubMed), Embase, and Web of Science was performed. Articles were included if they were national or regional administrative database cohort studies reporting comparative risk of long-term mortality or incident obesity-related diseases for patients who have undergone any form of bariatric surgery compared with an appropriate control group with a minimum follow-up period of 18 months. Meta-analysis of hazard ratios (HRs) was performed for mortality risk, and pooled odds ratios (PORs) were calculated for discrete variables relating to incident disease. Eighteen studies were identified as suitable for inclusion. There were 1,539,904 patients included in the analysis, with 269,818 receiving bariatric surgery and 1,270,086 control patients. Bariatric surgery was associated with a reduced rate of all-cause mortality (POR 0.62, 95% CI 0.55 to 0.69, p < 0.001) and cardiovascular mortality (POR 0.50, 95% CI 0.35 to 0.71, p < 0.001). Bariatric surgery was strongly associated with reduced incidence of T2DM (POR 0.39, 95% CI 0.18 to 0.83, p = 0.010), hypertension (POR 0.36, 95% CI 0.32 to 0.40, p < 0.001), dyslipidaemia (POR 0.33, 95% CI 0.14 to 0.80, p = 0.010), and ischemic heart disease (POR 0.46, 95% CI 0.29 to 0.73, p = 0.001). Limitations of the study include that it was not possible to account for unmeasured variables, which may not have been equally distributed between patient groups given the non-randomised design of the studies included. There was also heterogeneity between studies in the nature of the control group utilised, and potential adverse outcomes related to bariatric surgery were not specifically examined due to a lack of available data. CONCLUSIONS: This pooled analysis suggests that bariatric surgery is associated with reduced long-term all-cause mortality and incidence of obesity-related disease in patients with obesity for the whole operated population. The results suggest that broader access to bariatric surgery for people with obesity may reduce the long-term sequelae of this disease and provide population-level benefits.


Assuntos
Cirurgia Bariátrica , Doenças Cardiovasculares/mortalidade , Diabetes Mellitus Tipo 2/epidemiologia , Hipertensão/epidemiologia , Obesidade/cirurgia , Adulto , Cirurgia Bariátrica/métodos , Cirurgia Bariátrica/estatística & dados numéricos , Doenças Cardiovasculares/etiologia , Comorbidade , Diabetes Mellitus Tipo 2/etiologia , Dislipidemias/epidemiologia , Dislipidemias/etiologia , Humanos , Hipertensão/etiologia , Incidência , Pessoa de Meia-Idade , Mortalidade , Isquemia Miocárdica/epidemiologia , Isquemia Miocárdica/etiologia , Obesidade/complicações , Obesidade/mortalidade , Síndromes da Apneia do Sono/epidemiologia , Síndromes da Apneia do Sono/etiologia , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
4.
Medicine (Baltimore) ; 99(29): e21123, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702863

RESUMO

INTRODUCTION: Gitelman syndrome (GS) is an autosomal-recessive disease caused by SLC12A3 gene mutations. It is characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Recently, patients with GS are found at an increased risk for developing type 2 diabetes mellitus (T2DM). However, diagnosis of hyperglycemia in GS patients has not been thoroughly investigated, and family studies on SLC12A3 mutations and glucose metabolism are rare. Whether treatment including potassium and magnesium supplements, and spironolactone can ameliorate impaired glucose tolerance in GS patients, also needs to be investigated. PATIENT CONCERNS: We examined a 55-year-old Chinese male with intermittent fatigue and persistent hypokalemia for 17 years. DIAGNOSES: Based on the results of the clinical data, including electrolytes, oral glucose tolerance test (OGTT), and genetic analysis of the SLC12A3 gene, GS and T2DM were newly diagnosed in the patient. Two mutations of the SLC12A3 gene were found in the patient, one was a missense mutation p.N359K in exon 8, and the other was a novel insert mutation p.I262delinsIIGVVSV in exon 6. SLC12A3 genetic analysis and OGTT of 9 other family members within 3 generations were also performed. Older brother, youngest sister, and son of the patient carried the p.N359K mutation in exon 8. The older brother and the youngest sister were diagnosed with T2DM and impaired glucose tolerance by OGTT, respectively. INTERVENTIONS: The patient was prescribed potassium and magnesium (potassium magnesium aspartate, potassium chloride) oral supplements and spironolactone. The patient was also suggested to maintain a high potassium diet. Acarbose was used to maintain the blood glucose levels. OUTCOMES: The electrolyte imbalance including hypokalemia and hypomagnesemia, and hyperglycemia were improved with a remission of the clinical manifestations. CONCLUSION: GS is one of the causes for manifestation of hypokalemia. SLC12A3 genetic analysis plays an important role in diagnosis of GS. Chinese male GS patients characterized with heterozygous SLC12A3 mutation should be careful toward occurrence of T2DM. Moreover, the patients with only 1 SLC12A3 mutant allele should pay regular attention to blood potassium and glucose levels. GS treatment with potassium and magnesium supplements, and spironolactone can improve impaired glucose metabolism.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Síndrome de Gitelman/complicações , Hipopotassemia/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Fadiga/etiologia , Síndrome de Gitelman/fisiopatologia , Humanos , Hipopotassemia/fisiopatologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Membro 3 da Família 12 de Carreador de Soluto/genética
5.
Metabolism ; 110: 154304, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32599081

RESUMO

The loss of beta-cell functional mass is a necessary and early condition in the development of type 2 diabetes (T2D). In T2D patients, beta-cell function is already reduced by about 50% at diagnosis and further declines thereafter. Beta-cell mass is also reduced in subjects with T2D, and islets from diabetic donors are smaller compared to non-diabetic donors. Thus, beta-cell regeneration and/or preservation of the functional islet integrity should be highly considered for T2D treatment and possibly cure. To date, the available anti-diabetes drugs have been developed as "symptomatic" medications since they act to primarily reduce elevated blood glucose levels. However, a truly efficient anti-diabetes medication, capable to prevent the onset and progression of T2D, should stop beta-cell loss and/or promote the restoration of fully functional beta-cell mass, independently of reducing hyperglycemia and ameliorating glucotoxicity on the pancreatic islets. This review provides a view of the experimental and clinical evidence on the ability of available anti-diabetes drugs to exert protective effects on beta-cells, with a specific focus on human pancreatic islets and clinical trials. Potential explanations for the lack of concordance between evidence of beta-cell protection in vitro and of persistent amelioration of beta-cell function in vivo are also discussed.


Assuntos
Diabetes Mellitus Tipo 2/fisiopatologia , Ilhotas Pancreáticas/fisiopatologia , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Humanos , Hipoglicemiantes/uso terapêutico , Células Secretoras de Insulina/efeitos dos fármacos , Ilhotas Pancreáticas/patologia
6.
J Pharmacol Sci ; 143(4): 307-314, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32536591

RESUMO

Rutaecarpine, an indolopyridoquinazoline alkaloid, attracted attentions because of possessing various biological activities. The objective of this study was to investigate the effect of rutaecarpine on glucose and lipid metabolism in high fat diet-multiple low dose streptozotocin induced type 2 diabetic (HFD-db) mice and to understand the mechanism of action. HFD-db mice showed impaired glucose metabolism and lipid profile. Oral administration of rutaecarpine reduced the blood glucose levels, decreased blood hemoglobin A1c (HbA1c) levels, improved glucose tolerance and restored insulin sensitivity in HFD-db mice. Rutaecarpine also decreased body weight gain, water intake and visceral fat gain in HFD-db mice. Total cholesterol, triglycerides, very low density lipoprotein and low density lipoprotein were reduced and high density lipoprotein level was augmented in rutaecarpine treated HFD-db mice. Rutaecarpine also reduced the elevated levels of serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, urea and creatinine in HFD-db mice. Rutaecarpine significantly promoted the rate of glucose consumption, glucose uptake and glycolysis in C2C12 myotubes. Western blotting results showed that rutaecarpine augmented p-GSK-3ß and p-AMPK expression, and suppressed G6Pase expression in HepG2 cells. These results suggest that rutaecarpine might be having therapeutic importance to fight against type 2 diabetes mellitus associated with dyslipidemia.


Assuntos
Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta Hiperlipídica/efeitos adversos , Glucose/metabolismo , Homeostase/efeitos dos fármacos , Hipoglicemiantes , Alcaloides Indólicos/farmacologia , Fígado/metabolismo , Quinazolinas/farmacologia , Animais , Diabetes Mellitus Experimental/etiologia , Diabetes Mellitus Tipo 2/etiologia , Modelos Animais de Doenças , Alcaloides Indólicos/uso terapêutico , Masculino , Camundongos Endogâmicos C57BL , Quinazolinas/uso terapêutico
7.
Am J Clin Nutr ; 112(3): 512-518, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32520324

RESUMO

BACKGROUND: Yogurt consumption and low-fat dairy consumption have been associated with reduced incidence of type 2 diabetes (T2D) in some studies. OBJECTIVE: We assessed the relation of yogurt and other dairy consumption to incidence of T2D in black women, a population group with a disproportionately high incidence of T2D. METHODS: The Black Women's Health Study has followed 59,000 US black women since 1995 through biennial questionnaires which update health information. Each questionnaire inquired about doctor-diagnosed diabetes in the previous 2 y. FFQs completed by participants in 1995 and 2001 provided information on yogurt and other dietary intake. HRs with 95% CIs for yogurt (nonfrozen or frozen) and other dairy consumption in relation to incident T2D (n = 8061 cases) were estimated with Cox proportional hazards regression, controlling for risk factors for T2D. RESULTS: The HR for consumption of ≥1 serving of yogurt/d relative to <1 serving/mo was 0.99 (95% CI: 0.87, 1.13, P trend = 0.65) after control for dietary and nondietary risk factors for T2D. The multivariable HR was 0.97 (95% CI: 0.75, 1.27; P trend = 0.74) for 2 or more servings/d of low-fat dairy other than yogurt relative to <1 serving/mo and 1.06 (95% CI: 0.91, 1.25, P trend = 0.36) for 2 or more servings/d of regular dairy relative to <1 serving/mo. CONCLUSION: Results from this study do not support an inverse association of yogurt consumption or other dairy consumption with T2D risk in black women.


Assuntos
Laticínios , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Dieta/efeitos adversos , Adulto , Grupo com Ancestrais do Continente Africano , Glicemia , Feminino , Hemoglobina A Glicada , Humanos , Incidência , Pessoa de Meia-Idade , Estudos Prospectivos , Estados Unidos/epidemiologia
8.
Ann Biol Clin (Paris) ; 78(3): 243-252, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540813

RESUMO

Adiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.


Assuntos
Adiponectina/fisiologia , Animais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia
9.
PLoS One ; 15(6): e0234465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544194

RESUMO

Obesity leads a crucial importance in metabolic disorders, as well as type 2 diabetes mellitus. Our present study was designed to assess the potential role of irisin, adiponectin, leptin and gene polymorphism of PNPLA3, leptin and adiponectin as predictive markers of diabetes associated with obesity. One hundred eighty subjects were distributed to three groups including; healthy non-diabetic non obese volunteers as a control group, diabetic non obese group, and diabetic obese group (n = 60 for each group). Fasting blood samples of all groups were collected to determine fasting blood glucose, insulin levels, insulin resistance, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triacylglycerol, irisin, adiponectin, leptin; as well as, polymorphism of PNPLA3, adiponectin and leptin. The results showed that glucose, insulin resistance, total cholesterol, irisin, leptin, LDL-C, triacylglycerol concentrations were significantly increased, however, insulin, HDL-C, adiponectin were significantly decreased in diabetic obese patients in relation to diabetic non-obese patients as well as in healthy volunteers. The polymorphism of PNPLA3 rs738409 was linearly related to irisin and leptin but was not related with circulating concentrations of adiponectin. We concluded that increased irisin and leptin levels can predict the insulin resistance in obese patients. Moreover, patients who have mutant genotype of PNPLA3 I148 gene (rs738409) C>G, ADIPOQ gene (rs266729) G>C and LEP gene (rs2167270) G>A showed a significant higher susceptibility rate for DM in obese people than those with wild type. This could be considered as an adjustable retort to counter the impact of obesity on glucose homeostasis.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/etiologia , Predisposição Genética para Doença , Resistência à Insulina/genética , Leptina/genética , Lipase/genética , Proteínas de Membrana/genética , Obesidade/complicações , Obesidade/genética , Adiponectina/sangue , Adulto , Feminino , Fibronectinas/sangue , Fibronectinas/genética , Marcadores Genéticos , Humanos , Leptina/sangue , Lipase/sangue , Masculino , Proteínas de Membrana/sangue , Polimorfismo Genético , Adulto Jovem
10.
PLoS One ; 15(6): e0234768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555694

RESUMO

BACKGROUND: There is a growing interest in the life course approach for the prevention, early detection and subsequent management of morbidity in women of reproductive age to ensure optimal health and nutrition when they enter pregnancy. Reliable estimates of such morbidities are lacking. We report the prevalence of health or nutrition-related morbidities, specifically, anemia, undernutrition, overweight and obesity, sexually transmitted infections (STIs) or reproductive tract infections (RTIs), diabetes or prediabetes, hypothyroidism, hypertension, and depressive symptoms, during the preconception period among women aged 18 to 30 years. METHODS: A cross-sectional study was conducted among 2000 nonpregnant married women aged 18 to 30 years with no or one child who wished to have more children in two low- to middle-income urban neighborhoods in Delhi, India, in the context of a randomized controlled trial. STIs and RTIs were measured by symptoms and signs, blood pressure by a digital device, height by stadiometer and weight by a digital weighing scale. A blood specimen was taken to screen for anemia, diabetes, thyroid disorders and syphilis. Maternal depressive symptoms were assessed using the Patient Health Questionnaire-9 (PHQ-9). Multivariable logistic regression analysis was performed to identify sociodemographic factors associated with individual morbidity. RESULTS: Overall, 58.7% of women were anemic; 16.5%, undernourished; 26%, overweight or obese; 13.2%, hypothyroid; and 10.5% with both symptoms and signs of STIs/RTIs. There was an increased risk of RTI/STI symptoms and signs in undernourished women and an increased risk of diabetes or prediabetes in overweight or obese women. An increased risk of undernutrition was also observed in women from lower categories of wealth quintiles. A decreased risk of moderate to severe anemia was seen in overweight women and those who completed at least secondary education. CONCLUSIONS: Our findings show a high burden of undernutrition, anemia, RTIs, hypothyroidism and prediabetes among women in the study. This information will aid policymakers in planning special programs for women of reproductive age.


Assuntos
Infecções do Sistema Genital/patologia , Doenças Sexualmente Transmissíveis/patologia , Adolescente , Adulto , Anemia/complicações , Anemia/patologia , Estudos Transversais , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Hipotireoidismo/patologia , Índia/epidemiologia , Morbidade , Obesidade/complicações , Obesidade/patologia , Prevalência , Infecções do Sistema Genital/epidemiologia , Fatores de Risco , Índice de Gravidade de Doença , Doenças Sexualmente Transmissíveis/epidemiologia , Adulto Jovem
11.
Chronobiol Int ; 37(6): 804-808, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32516020

RESUMO

COVID-19 and metabolic syndrome are devastating pandemics. Effective control of metabolic parameters and their dysfunction may help prevent or minimize the acute and devastating effects of SARS-CoV-2 by reducing the local inflammatory response and blocking the entry of the virus into cells. With such consideration in mind, we gathered data from dietary surveys conducted in nine European countries to explore the relationship between actual clock hour of the large dinner meal and also interval in minutes between it and sunset in the respective countries and death rate above the median rate of per one million people as an index of mortality due to COVID-19 infection. Clock time of the dinner meal varied between 16:00 and 21:00 h across the European counties sampled, and the correlation between dinner mealtime and death rate was strongly correlated, R = 0.7991 (two-tailed p = 0.0098), with R 2 explaining 63% of the variation within the data. This strong linear positive correlation indicates that the later the clock time of the dinner meal, the higher is the death rate (and vice versa). The relationship between meal timing in reference to sunset, utilized as a gross surrogate marker of the activity/rest synchronizer of circadian rhythms, and death rate was negative and even slightly stronger, R = -0.8025 (two-tailed p = 0.0092), with R 2 explaining 64% of the variation within the data. This strong linear negative correlation indicates that the shorter the interval between the dinner meal and sunset, i.e., the closer the time of the largest meal of the day to bedtime, the greater is the death rate (and vice versa). Our preliminary approach to nighttime eating, in terms of the day's largest caloric intake, as a risk factor for the predisposing conditions of obesity, metabolic syndrome, type 2 diabetes, and other commonly associated comorbidities of being overweight, and death from COVID-19 infection reveals strong correlation with the time of the dinner meal, both in terms of its actual clock and circadian time.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/etiologia , Diabetes Mellitus Tipo 2/etiologia , Refeições/fisiologia , Pneumonia Viral/etiologia , Ritmo Circadiano/fisiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/mortalidade , Diabetes Mellitus Tipo 2/complicações , Ingestão de Alimentos/fisiologia , Ingestão de Energia/fisiologia , Comportamento Alimentar/fisiologia , Humanos , Obesidade/etiologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/mortalidade , Tempo
12.
Life Sci ; 256: 117913, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32526287

RESUMO

The growing evidence has been tried to explain and characterize C1q/TNF- related proteins (CTRPs) family as the potential diagnostic or therapeutic targets of obesity-related metabolic disorders such as insulin resistance, type 2 diabetes (T2D), and cardiovascular disorders. However, the underlying mechanism is still obscure. Unraveling the signaling pathways downstream of CTRP family members is of great interest and could certainly be beneficial for finding new insights into therapeutic strategies for improving metabolic abnormalities. This review focused on the role of CTRP members in the initiation and development of obesity-related metabolic disorders with a focus on T2D and cardiovascular diseases. Here we summarize and discuss the role of CTRPs in the regulation of insulin signaling, inflammatory pathways, and energy metabolism, and other signaling pathways pertinent to the pathogenesis of T2D and cardiovascular diseases. We also review available clinical studies to better elucidate the roles of these potential molecules in the initiation and development of the afore-mentioned disorders.


Assuntos
Doenças Cardiovasculares/etiologia , Complemento C1q/metabolismo , Diabetes Mellitus Tipo 2/etiologia , Obesidade/complicações , Fator de Necrose Tumoral alfa/metabolismo , Animais , Doenças Cardiovasculares/metabolismo , Complemento C1q/genética , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético , Regulação da Expressão Gênica , Humanos , Inflamação/metabolismo , Resistência à Insulina , RNA Mensageiro , Transdução de Sinais , Fator de Necrose Tumoral alfa/genética
13.
Lancet Diabetes Endocrinol ; 8(7): 616-627, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32559477

RESUMO

An increase in fat mass is considered to be an important risk factor for the worldwide increase in type 2 diabetes and cardiovascular disease. However, for a given fat mass, there is a large variability in the risk prediction of these cardiometabolic diseases. For example, some lean people unexpectedly have a risk of type 2 diabetes and cardiovascular disease that is similar to the increased risk that is observed in most people who have obesity. What both of these phenotypes have in common is a very characteristic fat distribution. As a result, much focus has been given on the strong predictive power of increased visceral fat mass. However, an analysis of the causes of type 2 diabetes and cardiovascular disease, as well as comparisons to rare diseases such as lipodystrophy and studying genetically determined fat distribution in the general population, suggest that an impaired ability to expand subcutaneous fat in the lower part of the body is also important for predicting the incidence of these cardiometabolic diseases. This Review, first, addresses the identification of distinct fat distribution phenotypes and their risk of cardiometabolic diseases by discussing findings from published studies that have applied precise quantification of different fat depots. Second, this Review provides support for the theory that a lower amount of lower-body fat mass is equally important to a high amount of visceral fat mass as a determinant of cardiometabolic diseases. Third, this Review discusses the genetic and lifestyle-related causes of metabolically healthy and unhealthy fat distribution. Finally, this Review summarises and appraises the effectiveness of lifestyle-related interventions and pharmacological interventions for reducing visceral adiposity and maintaining lower-body fat mass to prevent and treat cardiometabolic diseases.


Assuntos
Tecido Adiposo/patologia , Distribuição da Gordura Corporal , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Resistência à Insulina , Obesidade/complicações , Doenças Cardiovasculares/patologia , Diabetes Mellitus Tipo 2/patologia , Humanos , Fatores de Risco
14.
Am J Clin Nutr ; 112(3): 619-630, 2020 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-32453379

RESUMO

BACKGROUND: Whether egg consumption is associated with the risk of type 2 diabetes (T2D) remains unsettled. OBJECTIVES: We evaluated the association between egg consumption and T2D risk in 3 large US prospective cohorts, and performed a systematic review and meta-analysis of prospective cohort studies. METHODS: We followed 82,750 women from the Nurses' Health Study (NHS; 1980-2012), 89,636 women from the NHS II (1991-2017), and 41,412 men from the Health Professionals Follow-up Study (HPFS; 1986-2016) who were free of T2D, cardiovascular disease, and cancer at baseline. Egg consumption was assessed every 2-4 y using a validated FFQ. We used Cox proportional hazard models to estimate HRs and 95% CIs. RESULTS: During a total of 5,529,959 person-years of follow-up, we documented 20,514 incident cases of T2D in the NHS, NHS II, and HPFS. In the pooled multivariable model adjusted for updated BMI, lifestyle, and dietary confounders, a 1-egg/d increase was associated with a 14% (95% CI: 7%, 20%) higher T2D risk. In random-effects meta-analysis of 16 prospective cohort studies (589,559 participants; 41,248 incident T2D cases), for each 1 egg/d, the pooled RR of T2D was 1.07 (95% CI: 0.99, 1.15; I2 = 69.8%). There were, however, significant differences by geographic region (P for interaction = 0.01). Each 1 egg/d was associated with higher T2D risk among US studies (RR: 1.18; 95% CI: 1.10, 1.27; I2 = 51.3%), but not among European (RR: 0.99; 95% CI: 0.85, 1.15; I2 = 73.5%) or Asian (RR: 0.82; 95% CI: 0.62, 1.09; I2 = 59.1%) studies. CONCLUSIONS: Results from the updated meta-analysis show no overall association between moderate egg consumption and risk of T2D. Whether the heterogeneity of the associations among US, European, and Asian cohorts reflects differences in egg consumption habits warrants further investigation.This systematic review was registered at www.crd.york.ac.uk/prospero as CRD42019127860.


Assuntos
Diabetes Mellitus Tipo 2/etiologia , Dieta , Ovos , Ásia/epidemiologia , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/prevenção & controle , Ovos/efeitos adversos , Europa (Continente)/epidemiologia , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Medição de Risco , Estados Unidos/epidemiologia
15.
Nat Rev Endocrinol ; 16(7): 349-362, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32398822

RESUMO

Loss of functional ß-cell mass is the key mechanism leading to the two main forms of diabetes mellitus - type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Understanding the mechanisms behind ß-cell failure is critical to prevent or revert disease. Basic pathogenic differences exist in the two forms of diabetes mellitus; T1DM is immune mediated and T2DM is mediated by metabolic mechanisms. These mechanisms differentially affect early ß-cell dysfunction and eventual fate. Over the past decade, major advances have been made in the field, mostly delivered by studies on ß-cells in human disease. These advances include studies of islet morphology and human ß-cell gene expression in T1DM and T2DM, the identification and characterization of the role of T1DM and T2DM candidate genes at the ß-cell level and the endoplasmic reticulum stress signalling that contributes to ß-cell failure in T1DM (mostly IRE1 driven) and T2DM (mostly PERK-eIF2α dependent). Here, we review these new findings, focusing on studies performed on human ß-cells or on samples obtained from patients with diabetes mellitus.


Assuntos
Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/fisiopatologia , Insuficiência Pancreática Exócrina/etiologia , Células Secretoras de Insulina/fisiologia , Animais , Diabetes Mellitus Tipo 1/etiologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/patologia , Insuficiência Pancreática Exócrina/fisiopatologia , Humanos , Células Secretoras de Insulina/patologia , Transdução de Sinais/fisiologia
16.
Medicine (Baltimore) ; 99(18): e11005, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358339

RESUMO

INTRODUCTION: Cardamom possesses antioxidant, anti-inflammation, and blood pressure lowering properties, which might improve endothelial function in type 2 diabetic patients. However, no study has examined the effect of cardamom on diabetic patients. The present study aimed to examine the effects of 10-week green cardamom intake on blood pressure, concentrations of inflammatory and endothelial function biomarkers in type 2 diabetes mellitus patients, and its potential mechanisms. METHODS AND ANALYSIS DESIGN: Eighty overweight or obese patients with type 2 diabetes mellitus (aged 30-60 years) will be recruited into the trial and will assign to receive either cardamom (3 g/day, 6 capsules) or placebo (rusk powder, 6 capsules) for a period of 10 weeks. Systolic blood pressure and diastolic blood pressure, asymmetric dimethylarginine, and nitric oxide will be measured. Serum inflammatory markers namely interleukin 6, tumor necrosis factor-α, high-sensitivity C-reactive protein, and factors related to endothelial function including intercellular adhesion molecule-1, vascular cell adhesion molecule 1, CD62 antigen-like family member E, and cluster of differentiation 163 will be measured at baseline and at the end of the trial. Sociodemographic, International Physical Activity Questionnaire, and three 24-hour dietary recall questionnaires will be collected for each participant. ETHICS AND DISSEMINATION: The study has been approved by The Ethics Committee of Tehran University of Medical Sciences (IR.TUMS.REC.1395.2700). Each participant will sign a written informed consent at the beginning of the study. At the end of the study, results will be published timely manner. TRIAL REGISTRATION NUMBER: (http://www.irct.ir, identifier: IRCT-2016042717254N5) Date of registration: 2016-11-23.


Assuntos
Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/terapia , Suplementos Nutricionais , Elettaria , Endotélio/efeitos dos fármacos , Adulto , Biomarcadores/sangue , Determinação da Pressão Arterial , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Irã (Geográfico) , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Sobrepeso/complicações , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
17.
Med Sci (Paris) ; 36(5): 497-503, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-32452372

RESUMO

In healthy subjects, the balance between glucose production and its usage is precisely controlled. When circulating glucose reaches a critical threshold, pancreatic ß-cells secrete insulin, which has two major actions: lowering circulating glucose concentrations by facilitating its uptake mainly in skeletal muscles and the liver, and inhibiting glucose production. Triglycerides are the main source of fatty acids to meet the energy needs of oxidative tissues and any excess is stored in adipocytes. Thus, adipose tissue acts as a trap for excess fatty acids released from plasma triglycerides. When the buffering action of adipose tissue to store fatty acids is impaired, they accumulate in other tissues where they are metabolized in several lipid species, including sphingolipid derivatives such as ceramides. Numerous studies have shown that ceramides are among the most active lipid second messengers to inhibit insulin signalling. This review describes the major role played by ceramides in the development of insulin resistance in peripheral tissues.


Assuntos
Ceramidas/fisiologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Tecido Adiposo/metabolismo , Animais , Humanos , Metabolismo dos Lipídeos/fisiologia , Transdução de Sinais/fisiologia
18.
Obesity (Silver Spring) ; 28(6): 1149-1156, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32379398

RESUMO

OBJECTIVE: People with diabetes show great variability in weight gain and duration of obesity at the time of diagnosis. BMI trajectories and other cardiometabolic risk factors prior to type 2 diabetes were investigated. METHODS: A total of 6,223 participants from the Rotterdam Study cohort were included. BMI patterns before diagnosis of diabetes were identified through latent class trajectories. RESULTS: During a mean follow-up of 13.7 years, 565 participants developed type 2 diabetes. Three distinct trajectories of BMI were identified, including the "progressive overweight" group (n = 481, 85.1%), "progressive weight loss" group (n = 59, 10.4%), and "persistently high BMI" group (n = 25, 4.4%). The majority, the progressive overweight group, was characterized by a steady increase of BMI in the overweight range 10 years before diabetes diagnosis. The progressive weight loss group had fluctuations of glucose and marked beta cell function loss. The persistently high BMI group was characterized by a slight increase in insulin levels and sharp increase of insulin resistance accompanied by a rapid decrease of beta cell function. CONCLUSIONS: Heterogeneity of BMI changes prior to type 2 diabetes was found in a middle-aged and elderly white population. Prevention strategies should be tailored rather than focusing only on high-risk individuals.


Assuntos
Índice de Massa Corporal , Diabetes Mellitus Tipo 2/etiologia , Obesidade/classificação , Sobrepeso/classificação , Adulto , Idoso , Estudos de Coortes , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Análise de Classes Latentes , Masculino , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Fatores de Risco , Ganho de Peso , Perda de Peso
19.
BMJ ; 369: m1361, 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32404325

RESUMO

OBJECTIVE: To estimate and compare progression rates to type 2 diabetes mellitus (T2DM) in women with gestational diabetes mellitus (GDM) and healthy controls. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Medline and Embase between January 2000 and December 2019, studies published in English and conducted on humans. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies investigating progression to T2DM. Inclusion criteria were postpartum follow-up for at least 12 months, incident physician based diagnosis of diabetes, T2DM reported as a separate outcome rather than combined with impaired fasting glucose or impaired glucose tolerance, and studies with both a group of patients with GDM and a control group. RESULTS: This meta-analysis of 20 studies assessed a total of 1 332 373 individuals (67 956 women with GDM and 1 264 417 controls). Data were pooled by random effects meta-analysis models, and heterogeneity was assessed by use of the I2 statistic. The pooled relative risk for the incidence of T2DM between participants with GDM and controls was estimated. Reasons for heterogeneity between studies were investigated by prespecified subgroup and meta-regression analyses. Publication bias was assessed by funnel plots and, overall, studies were deemed to have a low risk of bias (P=0.58 and P=0.90). The overall relative risk for T2DM was almost 10 times higher in women with previous GDM than in healthy controls (9.51, 95% confidence interval 7.14 to 12.67, P<0.001). In populations of women with previous GDM, the cumulative incidence of T2DM was 16.46% (95% confidence interval 16.16% to 16.77%) in women of mixed ethnicity, 15.58% (13.30% to 17.86%) in a predominantly non-white population, and 9.91% (9.39% to 10.42%) in a white population. These differences were not statistically significant between subgroups (white v mixed populations, P=0.26; white v non-white populations, P=0.54). Meta-regression analyses showed that the study effect size was not significantly associated with mean study age, body mass index, publication year, and length of follow-up. CONCLUSIONS: Women with a history of GDM appear to have a nearly 10-fold higher risk of developing T2DM than those with a normoglycaemic pregnancy. The magnitude of this risk highlights the importance of intervening to prevent the onset of T2DM, particularly in the early years after pregnancy. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42019123079.


Assuntos
Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/fisiopatologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Gestacional/etiologia , Progressão da Doença , Feminino , Humanos , Incidência , Período Pós-Parto , Gravidez , Fatores de Risco
20.
BMC Public Health ; 20(1): 452, 2020 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-32252701

RESUMO

BACKGROUND: Body composition is a crucial factor associated with the incidence of type 2 diabetes mellitus. However, no study on this relationship has been performed in the Chinese population. This study aimed to investigate the relationship between body composition indicators and risk of type 2 diabetes mellitus among Chinese adults undergoing medical examination. METHODS: Between January 2018 and July 2018, a retrospective cross-sectional study was performed on 3367 (2307 male and 1060 female) participants aged ≥18 years undergoing medical examination in Zhengzhou. Logistic regression analysis was performed to explore the relationship between body composition indicators and risk of type 2 diabetes mellitus. A receiver operating characteristic curve was used to calculate cutoff points and the predictive power of each indicator. RESULTS: Among the 3367 participants, 12.53% were diagnosed with type 2 diabetes mellitus. Multivariate logistic analysis indicated that male participants (odds ratio [OR] = 1.68, 95% confidence interval [CI]: 1.29-2.19), older participants (OR = 1.05, 95% CI: 1.04-1.06), participants with a waist-to-hip ratio above the reference value (OR = 1.56, 95% CI: 1.18-2.07), participants with body fat percentage above the reference value (OR = 1.62, 95% CI: 1.01-2.68), and participant with a large visceral fat area (OR = 1.01, 95% CI: 1.01-1.02) had a high risk of type 2 diabetes mellitus. Waist-to-hip ratio, body fat percentage, and visceral fat area were the best indicators of type 2 diabetes mellitus (P < 0.001) with cutoff values of 0.90, 25.02%, and 92.00 cm2, respectively. CONCLUSION: This study suggests a predictive relationship between type 2 diabetes mellitus and body composition indicators of waist-to-hip ratio, body fat percentage, and visceral fat area, which are valuable for screening diabetes and providing effective health education and behavioral intervention for high-risk populations.


Assuntos
Tecido Adiposo , Composição Corporal , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Relação Cintura-Quadril , Adolescente , Adulto , Idoso , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Humanos , Incidência , Gordura Intra-Abdominal , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Curva ROC , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
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