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1.
Pharmacol Rev ; 76(2): 267-299, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351071

RESUMO

Type 2 diabetes (T2D) mellitus has emerged as a major global health concern that has accelerated in recent years due to poor diet and lifestyle. Afflicted individuals have high blood glucose levels that stem from the inability of the pancreas to make enough insulin to meet demand. Although medication can help to maintain normal blood glucose levels in individuals with chronic disease, many of these medicines are outdated, have severe side effects, and often become less efficacious over time, necessitating the need for insulin therapy. G protein-coupled receptors (GPCRs) regulate many physiologic processes, including blood glucose levels. In pancreatic ß cells, GPCRs regulate ß-cell growth, apoptosis, and insulin secretion, which are all critical in maintaining sufficient ß-cell mass and insulin output to ensure euglycemia. In recent years, new insights into the signaling of incretin receptors and other GPCRs have underscored the potential of these receptors as desirable targets in the treatment of diabetes. The signaling of these receptors is modulated by GPCR kinases (GRKs) that phosphorylate agonist-activated GPCRs, marking the receptor for arrestin binding and internalization. Interestingly, genome-wide association studies using diabetic patient cohorts link the GRKs and arrestins with T2D. Moreover, recent reports show that GRKs and arrestins expressed in the ß cell serve a critical role in the regulation of ß-cell function, including ß-cell growth and insulin secretion in both GPCR-dependent and -independent pathways. In this review, we describe recent insights into GPCR signaling and the importance of GRK function in modulating ß-cell physiology. SIGNIFICANCE STATEMENT: Pancreatic ß cells contain a diverse array of G protein-coupled receptors (GPCRs) that have been shown to improve ß-cell function and survival, yet only a handful have been successfully targeted in the treatment of diabetes. This review discusses recent advances in our understanding of ß-cell GPCR pharmacology and regulation by GPCR kinases while also highlighting the necessity of investigating islet-enriched GPCRs that have largely been unexplored to unveil novel treatment strategies.


Assuntos
Diabetes Mellitus Tipo 2 , Células Secretoras de Insulina , Insulinas , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glicemia/metabolismo , Estudo de Associação Genômica Ampla , Células Secretoras de Insulina/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Quinases de Receptores Acoplados a Proteína G/metabolismo , Arrestinas/metabolismo , Insulinas/metabolismo , Fosforilação
2.
J Vis Exp ; (203)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38345259

RESUMO

Diabetes mellitus (DM) is caused by insufficient insulin release from the pancreatic ß-cells (Type1 DM) and insulin sensitivity in muscles, liver, and adipose tissues (Type2 DM). Insulin injection treats DM patients but leads to hypoglycemia as a side effect. Cortisol and catecholamines are released to activate glucose production from the liver to recover hypoglycemia, called counter-regulatory responses (CRR). In DM research using rodent models, glucose tolerance tests and 2-deoxy-glucose injection are used to measure insulin release and CRR, respectively. However, blood glucose concentrations change persistently during experiments, causing difficulties in assessing net insulin release and CRR. This article describes a method in which blood glucose is kept at 250 mg/dL or 50 mg/dL in conscious mice to compare the release of insulin and CRR hormones, respectively. Polyethylene tubing is implanted in the mice's carotid artery and jugular vein, and the mice are allowed to recover from the surgery. The jugular vein tubing is connected to a Hamilton syringe with a syringe pump to enable insulin or glucose infusion at a constant and variable rate. The carotid artery tubing is for blood collection. For the hyperglycemic clamp, 30% glucose is infused into the vein, and blood glucose levels are measured from the arterial blood every 5 min or 10 min. The infusion rate of 30% glucose is increased until the blood glucose level becomes 250 mg/dL. Blood is collected to measure insulin concentrations. For hypoglycemic clamp, 10 mU/kg/min insulin is infused together with 30% glucose, whose infusion rate is variable to maintain 50 mg/dL of blood glucose level. Blood is collected to measure counter-regulatory hormones when both glucose infusion and blood glucose reach a steady state. Both hyperglycemic and hypoglycemic clamps have the same surgical procedure and experimental setups. Thus, this method is useful for researchers of systemic glucose metabolism.


Assuntos
Diabetes Mellitus , Hipoglicemia , Humanos , Camundongos , Animais , Glicemia/metabolismo , Hipoglicemiantes/farmacologia , Técnica Clamp de Glucose , Hipoglicemia/metabolismo , Insulina/metabolismo , Glucose/metabolismo
3.
BMC Infect Dis ; 24(1): 242, 2024 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-38389045

RESUMO

BACKGROUND: Diabetes mellitus (DM) has a direct impact on the clinical manifestation and prognosis of active tuberculosis disease (TB) and is known to increase the chance of developing the condition. We sought to determine the prevalence of DM in adult Ugandan patients with recently diagnosed TB and the associated sociodemographic, anthropometric, and metabolic characteristics of TB-DM comorbidity. METHODS: In this cross-sectional study conducted at the adult TB treatment centres of three tertiary healthcare facilities in Uganda, we screened adult participants with recently diagnosed TB (diagnosed in < 2 months) for DM. All participants were screened with five tests; initially with a random blood glucose (RBG) test, and then later with fasting blood glucose (FBG), laboratory-based glycated hemoglobin (HbA1c), point-of-care (POC) HbA1c, and oral glucose tolerance test (OGTT) if the RBG was ≥ 6.1 mmol/l. The WHO guidelines for diagnosing and managing DM were used to support the DM diagnosis. To identify the factors associated with DM-TB comorbidity, logistic regression was used. RESULTS: A total of 232 participants with recently diagnosed TB were screened for DM. Of these, 160 (69%) were female. The median (IQR) age, body mass index, and RBG of all study participants was 35 (27-42) years, 19.2 (17.6-21.3) kg/m2, and 6.1 (5.5-7.2) mmol/l, respectively. About half of the participants (n = 117, 50.4%) had RBG level ≥ 6.1 mmol/l. Of these, 75 (64.1%) participants returned for re-testing. Diabetes mellitus was diagnosed in 32 participants, corresponding to a prevalence of 13.8% (95% CI 9.9-18.9). A new diagnosis of DM was noted in 29 (90.6%) participants. On logistic regression, age ≥ 40 years was associated with increased odds of TB and DM comorbidity (AOR 3.12, 95% CI 1.35-7.23, p = 0.008) while HIV coinfection was protective (AOR 0.27, 95% CI 0.10-0.74, p = 0.01). CONCLUSION: TB and DM comorbidity was relatively common in this study population. Routine screening for DM in adult Ugandan patients with recently diagnosed TB especially among those aged ≥ 40 years and HIV-negative patients should be encouraged in clinical practice.


Assuntos
Diabetes Mellitus , Tuberculose , Adulto , Humanos , Feminino , Masculino , Uganda/epidemiologia , Hemoglobinas Glicadas , Glicemia/metabolismo , Estudos Transversais , Tuberculose/complicações , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Comorbidade , Prevalência
4.
Nutrients ; 16(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38337650

RESUMO

In a study addressing the high risk of chronic diseases in people with diabetes and obesity linked to metabolic syndrome, the impact of a Golden Berry diet was investigated using a diabetic animal model. Obese rats with diabetic characteristics were fed a diet containing five percent Golden Berry for 16 days. This study focused on various parameters including organ weights, expression of metabolic genes, and urinary biomarkers. Post-Golden Berry intake, there was a notable decrease in the body, liver, pancreas, visceral, and subcutaneous adipose tissue weights in these obese, hyperglycemic rats. In contrast, an increase in brown adipose tissue (BAT) cell mass was observed. This diet also resulted in reduced blood glucose levels and normalized plasma biochemical profiles, including cholesterol, triglycerides, LDL, and HDL levels. Additionally, it modulated specific urinary biomarkers, particularly pipe-colic acid, a primary marker for type 2 diabetes. Bioinformatics analysis linked these dietary effects to improved insulin signaling and adipogenesis. Regular consumption of Golden Berry effectively prevented insulin resistance and obesity in rats, underscoring its significant health benefits and the protective role of an antioxidant-rich diet against metabolic syndrome. These findings offer promising insights for future therapeutic strategies to manage and prevent obesity and related chronic diseases.


Assuntos
Diabetes Mellitus Tipo 2 , Frutas , Resistência à Insulina , Síndrome Metabólica , Physalis , Animais , Humanos , Ratos , Biomarcadores , Glicemia/metabolismo , Doença Crônica , Dieta Hiperlipídica , Frutas/metabolismo , Insulina , Obesidade/metabolismo
5.
Mol Nutr Food Res ; 68(4): e2300086, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38332571

RESUMO

SCOPE: Secretion of the gut hormones glucagon-like peptide (GLP-1) and peptide YY (PYY) are induced by nutrients reaching the lower small intestine which regulate insulin and glucagon release, inhibit appetite, and may improve ß-cell regeneration. The aim is to test the effect of a slowly digested isomaltulose (ISO) compared to the rapidly digested saccharose (SAC) as a snack given 1 h before a standardized mixed meal test (MMT) on GLP-1, PYY, glucose-dependent insulinotropic peptide (GIP), and metabolic responses in participants with or without type 2 diabetes (T2DM). METHODS AND RESULTS: Fifteen healthy volunteers and 15 patients with T2DM consumed either 50 g ISO or SAC 1 h preload of MMT on nonconsecutive days. Clinical parameters and incretin hormones are measured throughout the whole course of MMT. Administration of 50 g ISO as compared to SAC induced a significant increase in GLP-1, GIP, and PYY responses over 2 h after intake of a typical lunch in healthy controls. Patients with T2DM showed reduced overall responses of GLP-1 and delayed insulin release compared to controls while ISO significantly enhanced the GIP and almost tripled the PYY response compared to SAC. CONCLUSION: A snack containing ISO markedly enhances the release of the metabolically advantageous gut hormones PYY and GLP-1 and enhances GIP release in response to a subsequent complex meal.


Assuntos
Diabetes Mellitus Tipo 2 , Hormônios Gastrointestinais , Isomaltose/análogos & derivados , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Peptídeo 1 Semelhante ao Glucagon , Insulina/metabolismo , Polipeptídeo Inibidor Gástrico , Peptídeo YY , Glicemia/metabolismo
6.
Diabetologia ; 67(4): 703-713, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38372780

RESUMO

AIMS/HYPOTHESIS: Gestational diabetes mellitus (GDM) is the most common disorder in pregnancy; however, its underlying causes remain obscure. This study aimed to investigate the genetic and molecular risk factors contributing to GDM and glycaemic traits. METHODS: We collected non-invasive prenatal test (NIPT) sequencing data along with four glycaemic and 55 biochemical measurements from 30,699 pregnant women during a 2 year period at Shenzhen Baoan Women's and Children's Hospital in China. Genome-wide association studies (GWAS) were conducted between genotypes derived from NIPTs and GDM diagnosis, baseline glycaemic levels and glycaemic levels after glucose challenges. In total, 3317 women were diagnosed with GDM, while 19,565 served as control participants. The results were replicated using two independent cohorts. Additionally, we performed one-sample Mendelian randomisation to explore potential causal associations between the 55 biochemical measurements and risk of GDM and glycaemic levels. RESULTS: We identified four genetic loci significantly associated with GDM susceptibility. Among these, MTNR1B exhibited the highest significance (rs10830963-G, OR [95% CI] 1.57 [1.45, 1.70], p=4.42×10-29), although its effect on type 2 diabetes was modest. Furthermore, we found 31 genetic loci, including 14 novel loci, that were significantly associated with the four glycaemic traits. The replication rates of these associations with GDM, fasting plasma glucose levels and 0 h, 1 h and 2 h OGTT glucose levels were 4 out of 4, 6 out of 9, 10 out of 11, 5 out of 7 and 4 out of 4, respectively. Mendelian randomisation analysis suggested that a genetically regulated higher lymphocytes percentage and lower white blood cell count, neutrophil percentage and absolute neutrophil count were associated with elevated glucose levels and an increased risk of GDM. CONCLUSIONS/INTERPRETATION: Our findings provide new insights into the genetic basis of GDM and glycaemic traits during pregnancy in an East Asian population and highlight the potential role of inflammatory pathways in the aetiology of GDM and variations in glycaemic levels. DATA AVAILABILITY: Summary statistics for GDM; fasting plasma glucose; 0 h, 1 h and 2h OGTT; and the 55 biomarkers are available in the GWAS Atlas (study accession no.: GVP000001, https://ngdc.cncb.ac.cn/gwas/browse/GVP000001) .


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Criança , Gravidez , Feminino , Humanos , Estudo de Associação Genômica Ampla , Gestantes , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/genética , Fatores de Risco
7.
Nutr J ; 23(1): 24, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413933

RESUMO

BACKGROUND AND AIMS: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global metabolic problem which can lead to irreversible liver fibrosis. It has been shown that vitamin D and its receptors contribute to fibrogenic pathways in the liver. However, the effect of vitamin D supplementation on liver fibrosis related factors have not been examined. This double blinded placebo controlled clinical trial was designed to investigate the effects on vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients. METHODS: Forty six MASLD patients after block matching for sex and BMI were randomly assigned to receive 4000 IU/d vitamin D or placebo for 12 weeks. Weight, height and waist circumference were measured. Serum fibrogenic microRNAs, laminin, collagen type IV, hyaluronic acid, vitamin D, VDR, PTH, blood fasting glucose, serum fasting insulin, lipid profile, ALT and AST were determined at the baseline and at the end of the trial. Insulin resistance and insulin sensitivity were calculated using the HOMA-IR and QUICKI equation. RESULTS: Supplementation with vitamin D for 12 weeks led to the significant increases in serum 25(OH) vitamin D, VDR and HDL-C compared to placebo (P < 0.001, P = 0.008 and P < 0.001). There were significant decreases in ALT, AST, FBS and LDL-C levels in the vitamin D group as compared to the placebo (P < 0.05). Laminin and hyaluronic acid concentrations were significantly decreased in the vitamin D group as compared to the placebo group, by -10.6 and - 28.7 ng/mL, respectively. Supplementation with vitamin D for 12 weeks resulted in a significant lower MiR-21 and MiR-122 gene expressions compared to the placebo group (P = 0.01 and P < 0.001, respectively). DISCUSSION: As the first randomized controlled trial on the effect of vitamin D supplementation on serum levels of VDR, fibrogenic factors and fibrogenic MicroRNAs in MASLD patients, we found a significant reduction in some liver fibrogenic factors, in liver transaminases and corresponding changes in some fibrosis-related MiRs and some metabolic factors. Further clinical trials with larger sample sizes and direct measures of liver fibrosis are needed to confirm these findings. TRIAL REGISTRATION NUMBER: (available at: http://www.irct.ir , identifier: IRCT201405251485N13), Registration date: 14-03-2017.


Assuntos
Resistência à Insulina , MicroRNAs , Humanos , Receptores de Calcitriol/genética , MicroRNAs/genética , Ácido Hialurônico , Suplementos Nutricionais , Vitamina D , Vitaminas , Cirrose Hepática/tratamento farmacológico , Laminina , Glicemia/metabolismo , Método Duplo-Cego
8.
J Nutr Sci Vitaminol (Tokyo) ; 70(1): 76-81, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38417855

RESUMO

The major characteristic of type 2 diabetes is insulin resistance, which is associated with plasma level of 12-hydroxylated bile acids (BAs) in humans. In this study, we investigated whether the rise of enterohepatic 12-hydroxylated BAs associates with glucose tolerance and/or insulin secretion using rats fed a diet supplemented with cholic acid (CA) at a level of 0.5 g/kg diet. Almost no increase was observed in plasma insulin in response to the intraperitoneal glucose administration in the CA-fed rats despite the significant increase of plasma insulin in control with the same treatment. In contrast, the changes in insulin secretion were observed in both groups and no difference was detected between the groups in the oral glucose tolerance test. Increases were observed in pancreatic expressions of Ins1 and Ins2 although the insulin protein content decreased in the pancreas without any sign in ectopic fat accumulation and histological damage in the CA-fed rats. Our results suggest that enterohepatic 12-hydroxylated BAs modulate insulin secretion in response to intraperitoneal glucose administration. The decrease in insulin store might be responsible for the reduction in the insulin secretion in the CA-fed rats.


Assuntos
Diabetes Mellitus Tipo 2 , Glucose , Humanos , Ratos , Animais , Glucose/metabolismo , Ácido Cólico , Secreção de Insulina , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Ácidos e Sais Biliares , Insulina , Suplementos Nutricionais
9.
Zhonghua Xin Xue Guan Bing Za Zhi ; 52(2): 158-164, 2024 Feb 24.
Artigo em Chinês | MEDLINE | ID: mdl-38326067

RESUMO

Objective: To investigate the relationship between cardio-metabolic abnormalities in the first trimester and adverse pregnancy outcomes (APO). Methods: This cohort study recruited singleton pregnancies in the first trimester (6-13+6 weeks of gestation) from Shenzhen Maternal and Child Health Care Hospital between January 1, 2021, and October 31, 2022. Cardiometabolic markers, including body mass index (BMI), blood pressure, fasting plasma glucose (FPG), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG), were recorded during the first trimester. Incidence of APO, including gestational hypertension, preeclampsia, gestational diabetes mellitus, preterm birth, fetal growth restriction, small for gestational age infant, and placental abruption, was documented. Cardiovascular metabolic abnormalities in the first trimester were defined as meeting one or more of the following criteria: elevated BMI (BMI≥24 kg/m²), elevated TG (TG≥1.7 mmol/L), decreased HDL-C (HDL-C<1.0 mmol/L), elevated blood pressure (systolic pressure≥130 mmHg (1 mmHg=0.133 kPa) and/or diastolic pressure≥85 mmHg), elevated FPG (FPG≥5.6 mmol/L). Enrolled women were categorized into abnormal cardio-metabolic and normal cardio-metabolic groups. Poisson regression was employed to analyze the association between cardio-metabolic abnormalities in the first trimester and APO. Results: The study included 14 197 pregnant women with an age of (32.0±4.1) years. There were 8 139 women in the normal cardio-metabolic group and 6 058 women in the abnormal cardio-metabolic group. Women with cardio-metabolic disorders in the first trimester had a younger gestational age and higher incidence rates of preterm birth, gestational hypertension, preeclampsia, and gestational diabetes mellitus (all P<0.05). In multivariable Poisson regression, elevated BMI (RR=1.22, 95%CI 1.15-1.29), elevated FPG (RR=1.59, 95%CI 1.38-1.82), elevated TG (RR=1.22, 95%CI 1.13-1.31), and elevated blood pressure (RR=1.50, 95%CI 1.39-1.63) were independent risk factors for APO, while decreased HDL-C (RR=0.93, 95%CI 0.70-1.23) was not. Elevated blood pressure (RR=5.57, 95%CI 4.58-6.78), elevated BMI (RR=1.71, 95%CI 1.40-2.09), and elevated TG (RR=1.38, 95%CI 1.10-1.74) had the greatest impact on the risk of developing preeclampsia. Elevated FPG (RR=1.70, 95%CI 1.45-1.99) had the greatest impact on the risk of gestational diabetes. Conclusions: Elevated blood pressure, BMI, TG and FPG in the first trimester are closely related to APO.


Assuntos
Diabetes Gestacional , Hipertensão Induzida pela Gravidez , Pré-Eclâmpsia , Nascimento Prematuro , Humanos , Recém-Nascido , Criança , Feminino , Gravidez , Adulto , Resultado da Gravidez , Diabetes Gestacional/epidemiologia , Primeiro Trimestre da Gravidez , Estudos de Coortes , Pré-Eclâmpsia/epidemiologia , Glicemia/metabolismo , Placenta/metabolismo , Triglicerídeos , HDL-Colesterol
10.
BMJ Paediatr Open ; 8(1)2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341196

RESUMO

OBJECTIVE: To explore the glucose-related hormone profile of very low birthweight (VLBW) infants and assess the association between neonatal hyperglycaemia and insulin resistance during the admission period. DESIGN: A prospective observational study-the Very Low Birth Weight Infants, Glucose and Hormonal Profiles over Time study. SETTING: A tertiary neonatal intensive care unit and four neonatal units in county hospitals in Sweden. PATIENTS: 48 infants born <1500 g (VLBW) during 2016-2019. OUTCOME MEASURES: Plasma concentrations of glucose-related hormones and proteins (C-peptide, insulin, ghrelin, glucagon-like peptide 1 (GLP-1), glucagon, leptin, resistin and proinsulin), insulin:C-peptide and proinsulin:insulin ratios, Homoeostatic Model Assessment 2 (HOMA2) and Quantitative Insulin Sensitivity Check (QUICKI) indices, measured on day of life (DOL) 7 and at postmenstrual age 36 weeks. RESULTS: Lower gestational age was significantly associated with higher glucose, C-peptide, insulin, proinsulin, leptin, ghrelin, resistin and GLP-1 concentrations, increased HOMA2 index, and decreased QUICKI index and proinsulin:insulin ratio. Hyperglycaemic infants had significantly higher glucose, C-peptide, insulin, leptin and proinsulin concentrations, and lower QUICKI index, than normoglycaemic infants. Higher glucose and proinsulin concentrations and insulin:C-peptide ratio, and lower QUICKI index on DOL 7 were significantly associated with longer duration of hyperglycaemia during the admission period. CONCLUSIONS: VLBW infants seem to have a hormone profile consistent with insulin resistance. Lower gestational age and hyperglycaemia are associated with higher concentrations of insulin resistance markers.


Assuntos
Hiperglicemia , Resistência à Insulina , Recém-Nascido , Humanos , Lactente , Proinsulina , Leptina , Grelina , Resistina , Estudos Prospectivos , Peptídeo C , Glicemia/metabolismo , Insulina/metabolismo , Recém-Nascido de muito Baixo Peso , Peptídeo 1 Semelhante ao Glucagon , Hiperglicemia/epidemiologia , Insulina Regular Humana
11.
Physiol Rep ; 12(3): e15948, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38346816

RESUMO

Obstructive sleep apnea (OSA) is associated with increased risk for diabetes, and standard treatment with positive airway pressure (PAP) device shows inconsistent effects on glucose metabolism. Metformin is known to treat and prevent diabetes, but its effects on skeletal muscle mitochondrial function are not completely understood. Here, we evaluate the effects of metformin on glucose metabolism and skeletal muscle mitochondrial function in patients with OSA. Sixteen adults with obesity (50.9 ± 6.7 years, BMI: 36.5 ± 2.9 kg/m2 ) and moderate-to-severe OSA were provided with PAP treatment and randomized to 3 months of placebo (n = 8) or metformin (n = 8) treatment in a double-blind parallel-group design. Whole body glucose metabolism was determined by oral glucose tolerance test. A skeletal muscle biopsy was obtained to evaluate mitochondrial respiratory capacity and expression of proteins related to mitochondrial dynamics and energy metabolism. Whole body insulin-sensitivity (Matsuda index) did not change in metformin or placebo treated groups. However, metformin treatment prevented increases in insulin release relative to placebo during follow-up. Insulin area under the curve (AUC) and insulin to glucose AUC ratio increased in placebo but remained unchanged with metformin. Furthermore, metformin treatment improved skeletal muscle mitochondrial respiratory capacity and dynamics relative to placebo. Metformin treatment prevented the decline in whole body glucose homeostasis and skeletal muscle mitochondrial function in patients with moderate to severe OSA. Patients with OSA may benefit from the addition of metformin to prevent diabetes.


Assuntos
Diabetes Mellitus , Metformina , Apneia Obstrutiva do Sono , Adulto , Humanos , Metformina/farmacologia , Metformina/uso terapêutico , Projetos Piloto , Glicemia/metabolismo , Apneia Obstrutiva do Sono/complicações , Insulina , Glucose
12.
Cardiovasc Diabetol ; 23(1): 55, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331900

RESUMO

BACKGROUND: Hypoglycaemia has been shown to induce a systemic pro-inflammatory response, which may be driven, in part, by the adrenaline response. Prior exposure to hypoglycaemia attenuates counterregulatory hormone responses to subsequent hypoglycaemia, but whether this effect can be extrapolated to the pro-inflammatory response is unclear. Therefore, we investigated the effect of antecedent hypoglycaemia on inflammatory responses to subsequent hypoglycaemia in humans. METHODS: Healthy participants (n = 32) were recruited and randomised to two 2-h episodes of either hypoglycaemia or normoglycaemia on day 1, followed by a hyperinsulinaemic hypoglycaemic (2.8 ± 0.1 mmol/L) glucose clamp on day 2. During normoglycaemia and hypoglycaemia, and after 24 h, 72 h and 1 week, blood was drawn to determine circulating immune cell composition, phenotype and function, and 93 circulating inflammatory proteins including hs-CRP. RESULTS: In the group undergoing antecedent hypoglycaemia, the adrenaline response to next-day hypoglycaemia was lower compared to the control group (1.45 ± 1.24 vs 2.68 ± 1.41 nmol/l). In both groups, day 2 hypoglycaemia increased absolute numbers of circulating immune cells, of which lymphocytes and monocytes remained elevated for the whole week. Also, the proportion of pro-inflammatory CD16+-monocytes increased during hypoglycaemia. After ex vivo stimulation, monocytes released more TNF-α and IL-1ß, and less IL-10 in response to hypoglycaemia, whereas levels of 19 circulating inflammatory proteins, including hs-CRP, increased for up to 1 week after the hypoglycaemic event. Most of the inflammatory responses were similar in the two groups, except the persistent pro-inflammatory protein changes were partly blunted in the group exposed to antecedent hypoglycaemia. We did not find a correlation between the adrenaline response and the inflammatory responses during hypoglycaemia. CONCLUSION: Hypoglycaemia induces an acute and persistent pro-inflammatory response at multiple levels that occurs largely, but not completely, independent of prior exposure to hypoglycaemia. Clinical Trial information Clinicaltrials.gov no. NCT03976271 (registered 5 June 2019).


Assuntos
Diabetes Mellitus Tipo 1 , Hipoglicemia , Humanos , Glicemia/metabolismo , Proteína C-Reativa , Hipoglicemia/induzido quimicamente , Hipoglicemia/diagnóstico , Epinefrina , Insulina , Hipoglicemiantes/efeitos adversos
13.
Nutrients ; 16(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337679

RESUMO

This study aimed to compare newly developed diabetes-specific complete smoothie formulas with a standard diabetes-specific nutritional formula (DSNF) regarding their effects on glucose homeostasis, insulin levels, and lipid metabolism in obese type 2 diabetes (T2DM) patients. We conducted a randomized, double-blind, crossover study with 41 obese T2DM participants to compare two developed diabetes-specific complete smoothie formulas, a soy-based regular smoothie (SM) and a smoothie with modified carbohydrate content (SMMC), with the standard DSNF, Glucerna. Glycemic and insulin responses were assessed after the participants randomly consumed 300 kilocalories of each formulation on three separate days with a 7-day gap between. Postprandial effects on glycemic control, insulin levels, and lipid metabolism were measured. SMMC resulted in a significantly lower glucose area under the curve (AUC0-240) compared to Glucerna and SM (p < 0.05 for both). Insulin AUC0-240 after SMMC was significantly lower than that after SM and Glucerna (p < 0.05). During the diets, the suppression of NEFA was more augmented on SM, resulting in a less total AUC0-240 of NEFA compared to the SMMC diet (p < 0.05). C-peptide AUC0-240 after SMMC was significantly lower than that after Glucerna (p < 0.001). Conversely, glucagon AUC0-240 after SMMC was significantly higher than that after SM and Glucerna (p < 0.05). These results highlight SMMC as the better insulin-sensitive formula, potentially achieved through increased insulin secretion or a direct reduction in glucose absorption. The unique composition of carbohydrates, amino acids, and fats from natural ingredients in the smoothies may contribute to these positive effects, making them promising functional foods for managing diabetes and obesity.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Estudos Cross-Over , Ácidos Graxos não Esterificados , Insulina/metabolismo , Obesidade/complicações , Glucose , Período Pós-Prandial/fisiologia , Glicemia/metabolismo
14.
Nutrients ; 16(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38337683

RESUMO

Gestational diabetes mellitus (GDM) is a common metabolic disorder that often develops during pregnancy, characterized by glucose intolerance and insulin resistance (IR). To ensure the well-being of both the mother and the fetus, the body undergoes multiple metabolic and immunological changes that result in peripheral IR and, under certain hereditary or acquired abnormalities, GDM in predisposed women. The adverse short- and long-term effects of GDM impact both the mother and the fetus. Nutrition seems to play an important role to prevent GDM or improve its evolution. An emphasis has been given to the proportion of carbohydrates (CHO) relative to protein and lipids, as well as dietary patterns, in GDM. The effects of CHO on postprandial glucose concentrations are reflected in the glycemic index (GI) and glycemic load (GL). Diets rich in GI and GL may induce or exacerbate IR, whereas diets low in GI and GL appear to enhance insulin sensitivity and improve glycemic control. These positive outcomes may be attributed to direct interactions with insulin and glucose homeostasis or indirect effects through improved body composition and weight management. This comprehensive narrative review aims to explore the significance of nutrition, with a focus on the critical evaluation of GI and GL in the dietary management of women with GDM.


Assuntos
Diabetes Gestacional , Carga Glicêmica , Resistência à Insulina , Gravidez , Feminino , Humanos , Diabetes Gestacional/prevenção & controle , Índice Glicêmico , Dieta , Insulina , Glucose , Glicemia/metabolismo , Carboidratos da Dieta
15.
Nutrients ; 16(3)2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38337705

RESUMO

Lentils have potential to improve metabolic health but there are limited randomized clinical trials evaluating their comprehensive impact on metabolism. The aim of this study was to assess the impact of lentil-based vs. meat-based meals on fasting and postprandial measures of glucose and lipid metabolism and inflammation. Thirty-eight adults with an increased waist circumference (male ≥ 40 inches and female ≥ 35 inches) participated in a 12-week dietary intervention that included seven prepared midday meals totaling either 980 g (LEN) or 0 g (CON) of cooked green lentils per week. Linear models were used to assess changes in fasting and postprandial markers from pre- to post-intervention by meal group. Gastrointestinal (GI) symptoms were assessed through a survey randomly delivered once per week during the intervention. We found that regular consumption of lentils lowered fasting LDL (F = 5.53, p = 0.02) and total cholesterol levels (F = 8.64, p < 0.01) as well as postprandial glucose (ß = -0.99, p = 0.01), IL-17 (ß = -0.68, p = 0.04), and IL-1ß (ß = -0.70, p = 0.03) responses. GI symptoms were not different by meal group and all symptoms were reported as "none" or "mild" for the duration of the intervention. Our results suggest that daily lentil consumption may be helpful in lowering cholesterol and postprandial glycemic and inflammatory responses without causing GI stress. This information further informs the development of pulse-based dietary strategies to lower disease risk and to slow or reverse metabolic disease progression in at-risk populations.


Assuntos
Lens (Planta) , Lens (Planta)/metabolismo , Glucose , Glicemia/metabolismo , Jejum , Colesterol , Refeições , Período Pós-Prandial/fisiologia , Insulina/metabolismo , Estudos Cross-Over
16.
Sensors (Basel) ; 24(3)2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38339464

RESUMO

The use of continuous glucose monitors (CGMs) in individuals living without diabetes is increasing. The purpose of this study was to profile various CGM metrics around nutritional intake, sleep and exercise in a large cohort of physically active men and women living without any known metabolic disease diagnosis to better understand the normative glycemic response to these common stimuli. A total of 12,504 physically active adults (age 40 ± 11 years, BMI 23.8 ± 3.6 kg/m2; 23% self-identified as women) wore a real-time CGM (Abbott Libre Sense Sport Glucose Biosensor, Abbott, USA) and used a smartphone application (Supersapiens Inc., Atlanta, GA, USA) to log meals, sleep and exercise activities. A total of >1 M exercise events and 274,344 meal events were analyzed. A majority of participants (85%) presented an overall (24 h) average glucose profile between 90 and 110 mg/dL, with the highest glucose levels associated with meals and exercise and the lowest glucose levels associated with sleep. Men had higher mean 24 h glucose levels than women (24 h-men: 100 ± 11 mg/dL, women: 96 ± 10 mg/dL). During exercise, the % time above >140 mg/dL was 10.3 ± 16.7%, while the % time <70 mg/dL was 11.9 ± 11.6%, with the remaining % within the so-called glycemic tight target range (70-140 mg/dL). Average glycemia was also lower for females during exercise and sleep events (p < 0.001). Overall, we see small differences in glucose trends during activity and sleep in females as compared to males and higher levels of both TAR and TBR when these active individuals are undertaking or competing in endurance exercise training and/or competitive events.


Assuntos
Hiperglicemia , Hipoglicemia , Masculino , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Glucose , Hipoglicemia/diagnóstico , Hiperglicemia/diagnóstico , Automonitorização da Glicemia , Glicemia/metabolismo
17.
J Theor Biol ; 581: 111756, 2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38307451

RESUMO

The dominant paradigm for modeling the obesity-induced T2DM (type 2 diabetes mellitus) today focuses on glucose and insulin regulatory systems, diabetes pathways, and diagnostic test evaluations. The problem with this approach is that it is not possible to explicitly account for the glucose transport mechanism from the blood to the liver, where the glucose is stored, and from the liver to the blood. This makes it inaccurate, if not incorrect, to properly model the concentration of glucose in the blood in comparison to actual glycated hemoglobin (A1C) test results. In this paper, we develop a mathematical model of glucose dynamics by a system of ODEs. The model includes the mechanism of glucose transport from the blood to the liver, and from the liver to the blood, and explains how obesity is likely to lead to T2DM. We use the model to evaluate the efficacy of an anti-T2DM drug that also reduces weight.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glicemia/metabolismo , Glucose , Insulina/metabolismo , Obesidade/complicações , Obesidade/tratamento farmacológico , Modelos Teóricos
18.
Sci Rep ; 14(1): 3823, 2024 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-38360784

RESUMO

Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.


Assuntos
Diabetes Mellitus , Hiperglicemia , Animais , Feminino , Masculino , Hipoglicemiantes/farmacologia , Limoneno , Peixe-Zebra/metabolismo , Glicemia/metabolismo , Espectroscopia de Prótons por Ressonância Magnética , Obesidade/metabolismo , Dieta Hiperlipídica , Hiperglicemia/complicações
19.
Cardiovasc Diabetol ; 23(1): 56, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331780

RESUMO

BACKGROUND: SGLT2 inhibitors and DPP4 inhibitors have been suggested to affect lipid metabolism. However, there are few randomized controlled trials comparing the effects on the lipid metabolism between the two types of antidiabetic drugs. The SUCRE study (UMIN ID: 000018084) was designed to compare the effects of ipragliflozin and sitagliptin on serum lipid and apolipoprotein profiles and other clinical parameters. METHODS: This is a multicenter, open-label, randomized, controlled trial. Patients with type 2 diabetes (20-74 years old) with HbA1c levels of 7.0-10.5% and serum triglyceride levels of 120-399 mg/dL (1.35-4.50 mmol/L) on diet and/or oral hypoglycemic agents were enrolled. Subjects were randomized to treatment with ipragliflozin (50 mg/day, n = 77) or sitagliptin (50 mg/day, n = 83). Laboratory measurements were performed at 0, 1, 3, and 6 months of treatment. RESULTS: Ipragliflozin and sitagliptin reduced fasting plasma glucose, glycoalbumin, and HbA1c almost equally. Ipragliflozin increased HDL-C and decreased apo E. Sitagliptin decreased TG, apo B48, CII, and CIII, but increased LDL-C. The between-treatment differences were significant for HDL-C (P = 0.02) and apo B48 (P = 0.006), and nearly significant for apo A1 (P = 0.06). In addition, ipragliflozin reduced body weight, blood pressure, serum liver enzymes, uric acid, and leptin, and increased serum ketones compared with sitagliptin. CONCLUSIONS: While ipragliflozin and sitagliptin showed similar effects on glycemic parameters, the effects on serum lipid and apolipoprotein profiles were different. Ipragliflozin may have an anti-atherogenic effect through modulation of HDL-C and apo E compared to sitagliptin through TG and apo B48, CII, and CIII in patients with type 2 diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Glucosídeos , Fosfato de Sitagliptina , Tiofenos , Adulto , Idoso , Humanos , Pessoa de Meia-Idade , Adulto Jovem , Apolipoproteínas , Apolipoproteínas E , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Hipoglicemiantes/farmacologia , Fosfato de Sitagliptina/farmacologia
20.
Physiol Rep ; 12(3): e15949, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38346802

RESUMO

Toll-like receptor-7 (TLR7) activation promotes autoimmunity, and metabolic syndrome (MetS) is a common comorbidity in patients with autoimmune disease. We previously demonstrated hyperinsulinemia in TLR7 agonist imiquimod (IMQ)-treated, high-fat diet (HFD)-fed female C57BL/6 mice. Since mouse strains differ in susceptibility to MetS and target organ damage, this study investigated whether 12 weeks of exposure to HFD and IMQ promoted MetS, autoimmunity, and target organ damage in female FVB/N mice. Supporting early-stage autoimmunity, spleen-to-tibia ratio, and anti-nuclear antibodies (ANA) were significantly increased by IMQ. No significant effect of IMQ on urinary albumin excretion or left ventricular hypertrophy was observed. HFD increased liver-to-tibia ratio, which was further exacerbated by IMQ. HFD increased fasting blood glucose levels at the end of 12 weeks, but there was no significant effect of IMQ treatment on fasting blood glucose levels at 6 or 12 weeks of treatment. However, oral glucose tolerance testing at 12 weeks revealed impaired glucose tolerance in HFD-fed mice compared to control diet mice together with IMQ treatment exacerbating the impairment. Accordingly, these data suggest TLR7 activation also exacerbates HFD-induced dysregulation of glucose handling FVB/N mice, supporting the possibility that endogenous TLR7 activation may contribute to dysglycemia in patients with autoimmune disease.


Assuntos
Doenças Autoimunes , Síndrome Metabólica , Humanos , Feminino , Camundongos , Animais , Imiquimode/farmacologia , Dieta Hiperlipídica/efeitos adversos , Glicemia/metabolismo , Receptor 7 Toll-Like/metabolismo , Controle Glicêmico , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos
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