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1.
Medicine (Baltimore) ; 99(31): e21438, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756155

RESUMO

RATIONALE: Mutations in the hepatocyte nuclear factor-1-beta (HNF1B) gene result in a very variable presentation, including maturity onset diabetes of the young (MODY), renal cysts, renal dysplasia, and autosomal dominant tubulointerstitial kidney disease (ADTKD), which is characterized by tubular damage, renal fibrosis, and progressive renal dysfunction. PATIENT CONCERNS: A 22-year-old man came to the hospital presenting with hyperglycemia, hyperuricemia and elevated serum creatinine. His urine protein was within the normal range. The ultrasound examination revealed shrunken kidneys with renal cysts. The patient's mother was diagnosed with diabetes mellitus when she was 25 years old. Her laboratory results showed elevated serum creatinine. Her ultrasonography revealed shrunken kidneys with renal cysts and hydronephrosis without kidney stones. The next-generation sequencing revealed that the proband and his mother held the same heterozygous missense mutation (c.530G>A, NM_000458, p.R177Q) in the HNF1B gene. Bioinformatic analyses predicted that the mutation was likely pathogenic. DIAGNOSIS: The patient and his mother were diagnosed as ADTKD and MODY5 due to HNF1B mutation. INTERVENTION: The proband was administered metformin at a dose of 500 mg/day. OUTCOMES: The patient had well-controlled blood glucose levels and a stable renal function at his 12-month follow-up. LESSONS: We should take into account the diagnoses of ADTKD and MODY5 if patients present with early onset diabetes and multiple renal cysts or evidence of renal tubulointerstitial dysplasia, especially those with negative proteinuria results. Genetic testing helps detect the HNF1B gene mutations.


Assuntos
Doenças do Sistema Nervoso Central/genética , Esmalte Dentário/anormalidades , Diabetes Mellitus Tipo 2/genética , Fator 1-beta Nuclear de Hepatócito/genética , Doenças Renais Císticas/genética , Nefrite Intersticial/genética , Assistência ao Convalescente , Doenças do Sistema Nervoso Central/complicações , Doenças do Sistema Nervoso Central/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Heterozigoto , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Hiperglicemia/etiologia , Hiperuricemia/etiologia , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Rim/diagnóstico por imagem , Rim/patologia , Rim/fisiopatologia , Doenças Renais Císticas/complicações , Doenças Renais Císticas/tratamento farmacológico , Doenças Renais Císticas/patologia , Masculino , Metformina/administração & dosagem , Metformina/uso terapêutico , Mutação de Sentido Incorreto , Nefrite Intersticial/complicações , Nefrite Intersticial/patologia , Linhagem , Ultrassonografia/métodos , Adulto Jovem
2.
Life Sci ; 260: 118339, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32841660

RESUMO

AIMS: To design and screen a potent GLP-1/GIP/Gcg receptors triagonist with therapeutic potential in rodent animals with diabetes and obesity. MAIN METHODS: First, we obtained a 12-mer dual GIP/Gcg receptor agonist from a large combinatorial peptide library via high-throughput screening technique and then fused to the Exendin (9-39) to generate a potent GLP-1/GIP/Gcg triagonist. Further site fatty chain modification was performed to improve the druggability via enhancing in vivo stability and cyclic half-life. In vitro signaling and functional assays in cell lines expressing each receptor and in vivo efficacy evaluation in rodent model animals with hyperglycemia and obesity were all carefully performed. KEY FINDINGS: We screened and obtained a potent GLP-1/GIP/Gcg triagonist, termed XFL0, which promotes in vitro GLP-1, GIP, Gcg receptor activation comparable to native GLP-1, GIP and glucagon, respectively. Site-specific fatty acid modification significantly enhanced plasma stability of XFL0 and exhibited no obvious impact on receptor activation. The selected XFL0 conjugates termed XFL6, showed glucose-dependent insulin secretion and improved glucose tolerance by acting on all GLP-1, GIP and Gcg receptors in gene-deficient mice of which the effects were all significantly greater than any single receptor agonist. After chronic treatment in rodent animals with diabetes and obesity, XFL6 potently decreased body weight and food intake, ameliorated the hyperglycemia and hemoglobin A1c levels as well as the lipid metabolism and diabetic nephropathy related disorders. SIGNIFICANCE: XFL6, as a novel GLP-1/GIP/Gcg receptor triagonist, held potential to deliver outstanding improvement in correcting hyperglycemia, obesity and diabetic nephropathy.


Assuntos
Nefropatias Diabéticas/prevenção & controle , Desenho de Fármacos , Polipeptídeo Inibidor Gástrico/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucagon/agonistas , Hiperglicemia/prevenção & controle , Obesidade/prevenção & controle , Animais , Diabetes Mellitus Experimental/fisiopatologia , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Polipeptídeo Inibidor Gástrico/fisiologia , Glucagon/fisiologia , Receptor do Peptídeo Semelhante ao Glucagon 1/fisiologia , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/patologia
3.
Diabetes ; 69(10): 2048-2053, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32778570

RESUMO

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this virus. Although the information continues to emerge, here we provide our perspective on initial outcomes observed in hospitalized patients with diabetes and the potential role played by the proinflammatory metabolic state in these patients that promotes fertile ground for the virus' inflammatory surge, resulting in severe insulin resistance and severe hyperglycemia. The rapidly evolving renal failure, hypotension, pressor and steroid use, and variable nutritional support further complicates their management. Thus, timely implementation of glucose management protocols addressing these complex scenarios while also following COVID-19-related trajectories in inflammatory biomarkers and being cognizant of the health care provider exposure may substantially affect morbidity and mortality.


Assuntos
Betacoronavirus , Infecções por Coronavirus/complicações , Hiperglicemia/terapia , Pneumonia Viral/complicações , Glicemia/análise , Humanos , Hiperglicemia/etiologia , Unidades de Terapia Intensiva , Pandemias
5.
Diabetes Metab Syndr ; 14(4): 513-517, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388331

RESUMO

BACKGROUND AND AIMS: Diabetes mellitus is associated with poor prognosis in patients with COVID-19. On the other hand, COVID-19 contributes to worsening of dysglycemia in people with diabetes mellitus over and above that contributed by stress hyperglycemia. Herein, we have reviewed the two-way interactions between COVID-19 and diabetes mellitus. METHODS: We have performed an extensive literature search for articles in PubMed, EMBASE and Google Scholar databases till April 25, 2020, with the following keywords: "COVID-19", "SARS-CoV-2", "diabetes", "diabetes mellitus", "SARS", "infection" and "management of diabetes mellitus" with interposition of the Boolean operator "AND". RESULTS: Compromised innate immunity, pro-inflammatory cytokine milieu, reduced expression of ACE2 and use of renin-angiotensin-aldosterone system antagonists in people with diabetes mellitus contribute to poor prognosis in COVID-19. On the contrary, direct ß-cell damage, cytokine-induced insulin resistance, hypokalemia and drugs used in the treatment of COVID-19 (like corticosteroids, lopinavir/ritonavir) can contribute to worsening of glucose control in people with diabetes mellitus. CONCLUSIONS: The two-way interaction between COVID-19 and diabetes mellitus sets up a vicious cycle wherein COVID-19 leads to worsening of dysglycemia and diabetes mellitus, in turn, exacerbates the severity of COVID-19. Thus, it is imperative that people with diabetes mellitus take all necessary precautions and ensure good glycemic control amid the ongoing pandemic.


Assuntos
Betacoronavirus/patogenicidade , Infecções por Coronavirus/complicações , Diabetes Mellitus/fisiopatologia , Hiperglicemia/patologia , Hipoglicemia/patologia , Pneumonia Viral/complicações , Índice de Gravidade de Doença , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/transmissão , Infecções por Coronavirus/virologia , Diabetes Mellitus/tratamento farmacológico , Humanos , Hiperglicemia/etiologia , Hipoglicemia/etiologia , Pandemias , Pneumonia Viral/transmissão , Pneumonia Viral/virologia
6.
Diabetes Metab Syndr ; 14(4): 519-520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32388332

RESUMO

BACKGROUND AND AIMS: Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. METHODS: We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. RESULTS: SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. CONCLUSIONS: Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.


Assuntos
Corticosteroides/farmacologia , Infecções por Coronavirus/complicações , Diabetes Mellitus/fisiopatologia , Hiperglicemia/patologia , Hipoglicemia/patologia , Pneumonia Viral/complicações , Complicações Infecciosas na Gravidez/patologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/virologia , Feminino , Homeostase , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hipoglicemia/etiologia , Hipoglicemia/metabolismo , Secreção de Insulina/efeitos dos fármacos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/virologia , Gravidez , Complicações Infecciosas na Gravidez/etiologia , Complicações Infecciosas na Gravidez/metabolismo
7.
Mol Cell ; 79(1): 43-53.e4, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32464093

RESUMO

The physiological role of immune cells in the regulation of postprandial glucose metabolism has not been fully elucidated. We have found that adipose tissue macrophages produce interleukin-10 (IL-10) upon feeding, which suppresses hepatic glucose production in cooperation with insulin. Both elevated insulin and gut-microbiome-derived lipopolysaccharide in response to feeding are required for IL-10 production via the Akt/mammalian target of rapamycin (mTOR) pathway. Indeed, myeloid-specific knockout of the insulin receptor or bone marrow transplantation of mutant TLR4 marrow cells results in increased expression of gluconeogenic genes and impaired glucose tolerance. Furthermore, myeloid-specific Akt1 and Akt2 knockout results in similar phenotypes that are rescued by additional knockout of TSC2, an inhibitor of mTOR. In obesity, IL-10 production is impaired due to insulin resistance in macrophages, whereas adenovirus-mediated expression of IL-10 ameliorates postprandial hyperglycemia. Thus, the orchestrated response of the endogenous hormone and gut environment to feeding is a key regulator of postprandial glycemia.


Assuntos
Tecido Adiposo/efeitos dos fármacos , Hiperglicemia/patologia , Insulina/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/fisiologia , Serina-Treonina Quinases TOR/metabolismo , Tecido Adiposo/metabolismo , Animais , Glicemia/análise , Gluconeogênese/genética , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hipoglicemiantes/farmacologia , Resistência à Insulina , Interleucina-10/fisiologia , Macrófagos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C3H , Camundongos Knockout , Período Pós-Prandial , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Proteína 2 do Complexo Esclerose Tuberosa/fisiologia
8.
Eur J Clin Invest ; 50(7): e13262, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32383239

RESUMO

The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.


Assuntos
Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hiperglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Pneumonia Viral/terapia , Insuficiência Adrenal/complicações , Insuficiência Adrenal/tratamento farmacológico , Bélgica , Betacoronavirus , Glicemia/metabolismo , Infecções por Coronavirus/complicações , Infecções por Coronavirus/metabolismo , Complicações do Diabetes , Diabetes Insípido/complicações , Diabetes Insípido/terapia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Gerenciamento Clínico , Hemoglobina A Glicada/metabolismo , Unidades Hospitalares , Hospitalização , Humanos , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/metabolismo
9.
Medicine (Baltimore) ; 99(18): e19964, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358368

RESUMO

RATIONALE: Holocarboxylase synthetase (HCLS) deficiency, especially the late-onset type, is a rare disease. Affected patients can present with irreversible metabolic acidosis and may be misdiagnosed with a glucose metabolic disorder. Prompt and correct diagnosis and treatment can reduce mortality to a great extent. PATIENT CONCERNS: We report 2 Chinese patients who were diagnosed with late-onset HCLS deficiency. The age of onset of the 2 patients was approximately 8 months. The 2 patients had skin lesions, severe profound metabolic acidosis, dyspnea, and hyperglycemia. DIAGNOSES: The results of urinary and blood organic acid analysis with gas chromatography/mass spectrometry revealed multiple carboxylase deficiency. Maple syrup urine disease and diabetic ketoacidosis could not be excluded. This finding is different from those of hypoglycemic complications reported in previous reports. Human genetic analysis eventually provided a definite diagnosis. INTERVENTIONS: Prompt oral treatment with biotin dramatically corrected the metabolic imbalances of the 2 patients, and continued oral biotin therapy was essential to the improvement of their prognoses. OUTCOMES: Their metabolic disorders were corrected within 48 hours. During long-term follow-up, the patients achieved developmental milestones. LESSONS: Late-onset HCLS deficiency may present with obvious hyperglycemia. Human genetic analysis eventually provided a definite diagnosis. Prompt treatment with biotin is vital to correct metabolic imbalances, and continued therapy is essential to the improving long-term prognoses. Their mutations were p.R508W and c.1088T > A, and these mutations might represent hot-spot genes in Chinese populations with HCLS deficiency. The variants c.1484T > G(p.L495*) and c.835G > T(p.E279x) are likely pathogenic, and more studies are needed to confirm these results.


Assuntos
Deficiência de Holocarboxilase Sintetase/diagnóstico , Deficiência de Holocarboxilase Sintetase/fisiopatologia , Acidose/etiologia , Biotina/uso terapêutico , China , Dispneia/etiologia , Feminino , Deficiência de Holocarboxilase Sintetase/complicações , Deficiência de Holocarboxilase Sintetase/tratamento farmacológico , Humanos , Hiperglicemia/etiologia , Lactente , Masculino
10.
BMJ Case Rep ; 13(4)2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32300036

RESUMO

Hyperglycaemia is one of the most common metabolic disturbances encountered in clinical practice, with an important differential diagnosis. We report a case of a 72-year-old woman referred to diabetes services with rapidly increasing blood glucose and weight loss despite oral hypoglycaemic therapy. She reported mild upper abdominal discomfort and liver function tests were deranged, prompting further investigation. Abdominal imaging demonstrated a diffusely enlarged pancreas and subsequent investigations noted a markedly raised serum IgG4. She was diagnosed with IgG4-related pancreatitis and swiftly responded to steroid therapy. Secondary causes of diabetes should be considered in people with atypical presentation such as weight loss or rapid progression to insulin use. While IgG4-related disease is rare, its varied clinical presentation as a result of its multiorgan involvement requires a high index of suspicion. This case highlights the importance of a detailed diagnostic work-up and describes an unusual clinical presentation of this increasingly recognised multisystem disease.


Assuntos
Pancreatite Autoimune/etiologia , Hiperglicemia/etiologia , Doença Relacionada a Imunoglobulina G4/complicações , Idoso , Diagnóstico Diferencial , Feminino , Humanos , Perda de Peso
11.
Proc Natl Acad Sci U S A ; 117(14): 8166-8176, 2020 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-32188779

RESUMO

Multiple insulin-regulated enzymes participate in hepatic glycogen synthesis, and the rate-controlling step responsible for insulin stimulation of glycogen synthesis is unknown. We demonstrate that glucokinase (GCK)-mediated glucose phosphorylation is the rate-controlling step in insulin-stimulated hepatic glycogen synthesis in vivo, by use of the somatostatin pancreatic clamp technique using [13C6]glucose with metabolic control analysis (MCA) in three rat models: 1) regular chow (RC)-fed male rats (control), 2) high fat diet (HFD)-fed rats, and 3) RC-fed rats with portal vein glucose delivery at a glucose infusion rate matched to the control. During hyperinsulinemia, hyperglycemia dose-dependently increased hepatic glycogen synthesis. At similar levels of hyperinsulinemia and hyperglycemia, HFD-fed rats exhibited a decrease and portal delivery rats exhibited an increase in hepatic glycogen synthesis via the direct pathway compared with controls. However, the strong correlation between liver glucose-6-phosphate concentration and net hepatic glycogen synthetic rate was nearly identical in these three groups, suggesting that the main difference between models is the activation of GCK. MCA yielded a high control coefficient for GCK in all three groups. We confirmed these findings in studies of hepatic GCK knockdown using an antisense oligonucleotide. Reduced liver glycogen synthesis in lipid-induced hepatic insulin resistance and increased glycogen synthesis during portal glucose infusion were explained by concordant changes in translocation of GCK. Taken together, these data indicate that the rate of insulin-stimulated hepatic glycogen synthesis is controlled chiefly through GCK translocation.


Assuntos
Fígado Gorduroso/patologia , Glucoquinase/metabolismo , Glucose/metabolismo , Glicogênio Hepático/biossíntese , Fígado/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Técnicas de Silenciamento de Genes , Glucoquinase/genética , Glucose/administração & dosagem , Glucose-6-Fosfato/análise , Glucose-6-Fosfato/metabolismo , Humanos , Hiperglicemia/etiologia , Hiperglicemia/patologia , Hiperinsulinismo/etiologia , Hiperinsulinismo/patologia , Insulina/metabolismo , Resistência à Insulina , Fígado/patologia , Masculino , Metabolômica , Fosforilação , Ratos
12.
Exp Anim ; 69(3): 326-335, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-32188837

RESUMO

High fat diet (HFD) treated mouse is widely used as experimental animal model for hyperlipidemia and hyperglycemia study. Many factors contribute to establish animal model that meant to simulate high fat and glucose diet induced phenotypes. In the present study, four strains of experiment mouse treated by HFD were used to explore the impact of mouse strain on lipid profile, glucose level, and major inflammation cytokines. HFD fed Kunming and ICR mouse gained significantly higher body weight than control which was not shown by C57BL/6 and BALB/c mouse. All four strains fed by HFD has heavier liver and adipose tissue than control ones. Obvious fat droplets and enlarged adipose cells were observed in obese mouse of four strains. Additionally, obese mouse showed typical response to glucose and insulin load in OGTT and ITT. Serum TC, LDL-c, and TC/HDL-c ratio, but not TG, increased in all four strains. Major inflammatory cytokines and insulin level showed little changes in obese mouse as well (P<0.05) The present study could provide basic information for diet induced obesity developed by four commonly used experimental mouse strains.


Assuntos
Dieta Hiperlipídica , Modelos Animais de Doenças , Obesidade , Animais , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/etiologia , Hiperlipidemias/etiologia , Metabolismo dos Lipídeos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Obesidade/etiologia
13.
Cleve Clin J Med ; 87(2): 100-108, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32015063

RESUMO

The classification of diabetes mellitus in 2020 still starts with 2 major types, ie, type 1 and type 2, but each of these now includes a few uncommon variants. Understanding the many faces of the diabetes syndrome can make a difference in how clinicians select glucose-lowering therapy.


Assuntos
Autoanticorpos/sangue , Peptídeo C/sangue , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 2/diagnóstico , Hiperglicemia/etiologia , Diabetes Autoimune Latente em Adultos/diagnóstico , Biomarcadores/sangue , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Hiperglicemia/diagnóstico , Diabetes Autoimune Latente em Adultos/sangue , Fenótipo
15.
Nutrients ; 12(1)2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31947853

RESUMO

Hyperglycemia is linked to impaired arterial endothelial function (EF), an early sign of cardiovascular disease. We compared the efficacy of low-glycemic index isomaltulose (Palatinose™) with that of sucrose in modulating EF, as assessed by flow-mediated dilation (FMD). In this double-blinded cross-over study, 80 overweight mildly hypertensive subjects were randomized to receive 50 g of either isomaltulose or sucrose. On two non-consecutive days, brachial artery ultrasound FMD scans were obtained prior to and hourly (T0-T3) after carbohydrate load. Blood was drawn immediately after scanning. Glucose and insulin levels were analyzed. Overall, the FMD decrease was attenuated by isomaltulose compared to sucrose (ΔFMD = -0.003% and -0.151%; p > 0.05 for the interaction treatment x period). At T2, FMD was significantly higher after isomaltulose administration compared to that after sucrose administration (FMD = 5.9 ± 2.9% and 5.4 ± 2.6%, p = 0.047). Pearson correlations between FMD and blood glucose showed a trend for a negative association at T0 and T2 independently of the carbohydrate (r-range = -0.20 to -0.23, p < 0.1). Sub-analysis suggested a lower FMD in insulin-resistant (IR) compared to insulin-sensitive subjects. Isomaltulose attenuated the postprandial decline of FMD, particularly in IR persons. These data support the potential of isomaltulose to preserve the endothelial function postprandially and consequently play a favorable role in cardiovascular health.


Assuntos
Sacarose na Dieta/administração & dosagem , Endotélio Vascular/efeitos dos fármacos , Hemorreologia/efeitos dos fármacos , Isomaltose/análogos & derivados , Sobrepeso/fisiopatologia , Adulto , Glicemia/análise , Artéria Braquial/diagnóstico por imagem , Artéria Braquial/fisiopatologia , Estudos Cross-Over , Método Duplo-Cego , Endotélio Vascular/diagnóstico por imagem , Feminino , Índice Glicêmico , Humanos , Hiperglicemia/etiologia , Insulina/sangue , Isomaltose/administração & dosagem , Masculino , Pessoa de Meia-Idade , Sobrepeso/sangue , Sobrepeso/complicações , Período Pós-Prandial , Ultrassonografia
16.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-31974550

RESUMO

CONTEXT: Chronic pancreatitis (CP), is a long-term inflammation of the pancreatic parenchyma, and might increase risk of a hyperglycemia crisis or hypoglycemia in patients with diabetes mellitus (DM); however, the relationship has not been previously investigated. OBJECTIVE: To investigate the risk of diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), hypoglycemia, and long-term outcomes in DM patients with CP. DESIGN: A population-based cohort study. SETTING AND PARTICIPANTS: Tapping Taiwan's National Health Insurance Research Database, we identified 506 DM patients with newly diagnosed CP from 1999 to 2010 and created a control cohort consisting of 5060 age- and sex-matched DM patients without CP from the same time period. We followed those 2 cohorts from the index date to occurrence of outcomes, the date of death or 31 December 2012. MAIN OUTCOME MEASURES: DKA, HHS, hypoglycemia and mortality. RESULTS: DM patients with CP, who were predominantly male (88%) and younger (60% < 45 years old), had a 9.5-, 5.0-, and 3.0-fold higher risk for DKA (95% confidence interval [CI]: 6.51-13.91), HHS (95% CI: 2.85-8.62), and hypoglycemia (95% CI: 2.23-4.08), respectively. They also had lower 1-, 5-, and 10-year cumulative survival rates (98.4% vs 99.0%, 87.7% vs 96.6%, and 78.7% vs 93.6%, respectively) (log-rank test: P < .001), and a 2.43-fold higher risk for death (HR: 2.43, 95% CI: 1.82-3.27). CONCLUSIONS: In Taiwan, DM patients with CP have a higher incidence of DKA, HHS, hypoglycemia, and mortality. More attention is needed for preventing hyperglycemia crisis and hypoglycemia prevention in this population.


Assuntos
Diabetes Mellitus Tipo 1/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Cetoacidose Diabética/mortalidade , Hiperglicemia/mortalidade , Hipoglicemia/mortalidade , Pancreatite Crônica/fisiopatologia , Adolescente , Adulto , Idoso , Biomarcadores/análise , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/patologia , Cetoacidose Diabética/etiologia , Cetoacidose Diabética/patologia , Feminino , Seguimentos , Humanos , Hiperglicemia/etiologia , Hiperglicemia/patologia , Hipoglicemia/etiologia , Hipoglicemia/patologia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Taiwan , Adulto Jovem
17.
Br J Nutr ; 123(3): 308-318, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31915077

RESUMO

The rate of hyperglycaemia in people around the world is increasing at an alarming rate at present, and innovative methods of alleviating hyperglycaemia are needed. The effects of Jerusalem artichoke inulin on hyperglycaemia, liver-related genes and the intestinal microbiota in mice fed a high-fat diet (HFD) and treated with streptozotocin (STZ) to induce hyperglycaemia were investigated. Inulin-treated hyperglycaemic mice had decreased average daily food consumption, body weight, average daily water consumption and relative liver weight and blood concentrations of TAG, total cholesterol, HDL-cholesterol and fasting blood glucose. Liver-related gene expressions in hyperglycaemic (HFD-fed and STZ-treated) compared with control mice showed eighty-four differentially expressed genes (forty-nine up-regulated and thirty-five down-regulated). In contrast, hyperglycaemic mice treated with inulin had twenty-two differentially expressed genes compared with control ones. Using Illumina high-throughput sequencing technology, the rarefaction and the rank abundance curves as well as the α diversity indices showed the treatment-induced differences in bacterial diversity in intestine. The linear discriminant analysis of effect size showed that the inulin treatment improved intestinal microbiota; in particular, it significantly increased the number of Bacteroides in the intestine of mice. In conclusion, inulin is potentially an effective functional food for the prevention and/or treatment of hyperglycaemia.


Assuntos
Diabetes Mellitus Experimental/terapia , Microbioma Gastrointestinal/efeitos dos fármacos , Helianthus/química , Hiperglicemia/terapia , Inulina/farmacologia , Tubérculos/química , Animais , Diabetes Mellitus Experimental/etiologia , Dieta Hiperlipídica/efeitos adversos , Hiperglicemia/etiologia , Camundongos , Camundongos Obesos
18.
Circ Res ; 126(4): 456-470, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-31896304

RESUMO

RATIONALE: Lipid overload-induced heart dysfunction is characterized by cardiomyocyte death, myocardial remodeling, and compromised contractility, but the impact of excessive lipid supply on cardiac function remains poorly understood. OBJECTIVE: To investigate the regulation and function of the mitochondrial fission protein Drp1 (dynamin-related protein 1) in lipid overload-induced cardiomyocyte death and heart dysfunction. METHODS AND RESULTS: Mice fed a high-fat diet (HFD) developed signs of obesity and type II diabetes mellitus, including hyperlipidemia, hyperglycemia, hyperinsulinemia, and hypertension. HFD for 18 weeks also induced heart hypertrophy, fibrosis, myocardial insulin resistance, and cardiomyocyte death. HFD stimulated mitochondrial fission in mouse hearts. Furthermore, HFD increased the protein level, phosphorylation (at the activating serine 616 sites), oligomerization, mitochondrial translocation, and GTPase activity of Drp1 in mouse hearts, indicating that Drp1 was activated. Monkeys fed a diet high in fat and cholesterol for 2.5 years also exhibited myocardial damage and Drp1 activation in the heart. Interestingly, HFD decreased nicotinamide adenine dinucleotide (oxidized) levels and increased Drp1 acetylation in the heart. In adult cardiomyocytes, palmitate increased Drp1 acetylation, phosphorylation, and protein levels, and these increases were abolished by restoration of the decreased nicotinamide adenine dinucleotide (oxidized) level. Proteomics analysis and in vitro screening revealed that Drp1 acetylation at lysine 642 (K642) was increased by HFD in mouse hearts and by palmitate incubation in cardiomyocytes. The nonacetylated Drp1 mutation (K642R) attenuated palmitate-induced Drp1 activation, its interaction with voltage-dependent anion channel 1, mitochondrial fission, contractile dysfunction, and cardiomyocyte death. CONCLUSIONS: These findings uncover a novel mechanism that contributes to lipid overload-induced heart hypertrophy and dysfunction. Excessive lipid supply created an intracellular environment that facilitated Drp1 acetylation, which, in turn, increased its activity and mitochondrial translocation, resulting in cardiomyocyte dysfunction and death. Thus, Drp1 may be a critical mediator of lipid overload-induced heart dysfunction as well as a potential target for therapy.


Assuntos
Dinaminas/metabolismo , Lipídeos/análise , Miócitos Cardíacos/metabolismo , Acetilação , Animais , Cardiomegalia/genética , Cardiomegalia/fisiopatologia , Morte Celular/genética , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dinaminas/genética , Feminino , Hiperglicemia/etiologia , Hiperglicemia/metabolismo , Hiperinsulinismo/etiologia , Hiperinsulinismo/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hipertensão/etiologia , Hipertensão/metabolismo , Macaca mulatta , Masculino , Camundongos Endogâmicos C57BL , Mutação , Miócitos Cardíacos/patologia , Obesidade/etiologia , Obesidade/metabolismo , Ratos Sprague-Dawley
19.
Acta Diabetol ; 57(3): 253-262, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31304560

RESUMO

Positron emission tomography/computed tomography (PET/CT) is a standard procedure for imaging cancer commonly used in the clinical practice for several diseases, in particular for cancer staging, restaging, treatment monitoring and radiation therapy planning. Despite the availability of many radiotracers, 18F-fluoro-2-deoxy-2-D-glucose ([18F]FDG) is the most used. International PET/CT guidelines propose protocols for patients' correct preparation before [18F]FDG injection, in particular with the regard of diabetic patients and therapy management. Hyperglycemic conditions and oral or insulin medication showed advantages and disadvantages on PET/CT scan accuracy: A correct knowledge of effects of these conditions on glucose metabolism assumes a fundamental role on patients management before [18F]FDG PET/CT scan.


Assuntos
Fluordesoxiglucose F18/efeitos adversos , Hiperglicemia/etiologia , Neoplasias/diagnóstico por imagem , Animais , Fluordesoxiglucose F18/administração & dosagem , Humanos , Hiperglicemia/metabolismo , Estadiamento de Neoplasias , Neoplasias/patologia , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons/efeitos adversos
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