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2.
BMC Public Health ; 24(1): 493, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365654

RESUMO

BACKGROUND: Early COVID-19 pandemic research found changes in health care and diabetes management, as well as increased diabetes distress. This study aims to determine the association between COVID-19 pandemic-related healthcare interruptions and diabetes distress among adults with Type 1 and Type 2 diabetes in the US in 2021. METHODS: Multinomial logistic regression was used to analyze moderate and high levels of diabetes distress (reference = no diabetes distress) in 228 individuals with Type 1 diabetes and 2534 individuals with Type 2 diabetes interviewed in the National Health Interview Survey in 2021. RESULTS: Among adults with Type 1 diabetes, 41.2% experienced moderate diabetes distress and 19.1% experienced high diabetes distress, and among adults with Type 2 diabetes, 40.8% experienced moderate diabetes distress and 10.0% experienced high diabetes distress. In adults with Type 1 diabetes, experiencing delayed medical care was associated with an adjusted odds ratio (aOR) of 4.31 (95% CI: 1.91-9.72) for moderate diabetes distress and 3.69 (95% CI: 1.20-11.30) for high diabetes distress. In adults with Type 2 diabetes, experiencing delayed medical care was associated with an aOR of 1.61 (95% CI: 1.25-2.07) for moderate diabetes distress and 2.27 (95% CI: 1.48-3.49) for high diabetes distress. Similar associations were observed between not receiving medical care due to the pandemic and diabetes distress. CONCLUSION: Among people with diabetes, experiencing delayed medical care and not receiving care due to the pandemic were associated with higher reports of diabetes distress.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/terapia , Pandemias , COVID-19/epidemiologia , Atenção à Saúde
3.
Trials ; 25(1): 129, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365744

RESUMO

BACKGROUND: The guidelines of the American Diabetes Association and European Association for the Study of Diabetes suggest that patients with obesity type 2 diabetics and chronic kidney disease need either glucagon-like peptide 1 receptor analogues or sodium-glucose cotransporter-2 inhibitors. If neither achieve metabolic control, then the recommendation is to combine both drugs. The evidence base for combining glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors is not well researched, and hence, the impact of the guidelines is limited. The aim of this randomized controlled trial is to test the impact of the combination of glucagon-like peptide 1 receptor analogues/sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage, in patients with type 1 diabetes and chronic kidney disease. In addition, we will explore the associated changes in the metabolic pathways with each of the treatments used in this randomized controlled trial. METHODS: In this 6-month randomized control trial, 60 participants aged between 21 and 65 years, with a body mass index above 25 kg/m2, and type 1 diabetics with chronic kidney disease will be randomized to receive 1 of 5 possible treatments: (1) standard care (control), (2) glucagon-like peptide 1 receptor analogues alone, (3) sodium-glucose cotransporter-2 inhibitors alone, (4) combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors and (5) combination of glucagonlike peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors with intensive lifestyle advice. The primary objective will be the percentage change in total body weight from baseline at 6 months. The secondary objectives are to compare the change in glycaemia; blood pressure; dyslipidaemia; albuminuria; proportion of participants reaching weight loss of ≥ 5%, ≥ 10% and ≥ 15%; and change in BMI (kg/m2) from baseline and change in waist circumference (cm). All the experiments will be conducted at the Dasman Diabetes Institute after approval from the local research and ethics committee. DISCUSSION: The present randomized controlled trial aims to investigate the impact of the combination of glucagon-like peptide 1 receptor analogues and sodium-glucose cotransporter-2 inhibitors on body weight and kidney damage in patients with type 1 diabetes mellitus and chronic kidney disease, as well as exploring the associated changes in the metabolic pathways with each of the treatments used. This study addresses the current gap in the evidence base regarding the combination of these two drugs, which is particularly relevant given the American Diabetes Association and European Association for the Study of Diabetes guidelines recommending their combined use for patients with obesity, type 2 diabetes, and chronic kidney disease who do not achieve metabolic control with either drug alone. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05390307 Trial registration date - 25th May 2022.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/efeitos adversos , Peptídeo 1 Semelhante ao Glucagon , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/tratamento farmacológico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/complicações , Glucose , Sódio , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Clinics (Sao Paulo) ; 79: 100325, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38330787

RESUMO

INTRODUCTION: Pregnancy and diabetes mellitus promote several musculoskeletal changes predisposing this population to complaints of Lower Back (LB) and Pelvic Pain (PP). OBJECTIVE: To assess the frequency of LB and PP and associated factors in type 1 Diabetic (DM1) pregnant women. METHOD: An observational analytical cross-sectional study. Thirty-six pregnant women with DM1 were evaluated through a postural assessment with a focus on pelvic positioning and what patients reported. The associated factors were assessed using the State-Trait Anxiety Inventory (STAI), the International Consultation on Incontinence Questionnaire Short Form (ICIQ-SF), and the Female Sexual Function Index (FSFI). RESULTS: The frequency of LB and PP was 55.6 % and 30.6 %, respectively. The presence of anxiety was not associated with a higher prevalence of pain. The incidence of sexual dysfunctions was higher in the GD. DM1 duration had a mean of 14.9 years (± 8.2 SD) in the GD and 9.0 years (± 6.9 SD) in the GSD, which was statistically significant (p ≤ 0.050). In the multiple binary regression analysis for the occurrence of pain, the independent factor was DM1 duration ≥ 17 years (OR = 11.2; 95 % CI = 1.02‒124.75). The association between DM1 duration ≥ 17 years and being overweight showed a probability of 95 % for the studied population in the analysis of the probabilities of occurrence of the pain event. CONCLUSION: There was a high frequency of LB and PP related to pregnancy in DM1 pregnant women in the second trimester of pregnancy. The incidence of sexual dysfunction and DM1 duration ≥ 17 years increases the chance that DM1 pregnant women will experience pain. There was no association between anxiety. urinary incontinence and pain in DM1 pregnant women.


Assuntos
Diabetes Mellitus Tipo 1 , Dor Lombar , Disfunções Sexuais Fisiológicas , Feminino , Gravidez , Humanos , Gestantes , Dor Lombar/epidemiologia , Dor Lombar/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Estudos Transversais , Dor Pélvica/epidemiologia , Dor Pélvica/etiologia , Inquéritos e Questionários
5.
PLoS One ; 19(2): e0291594, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38354168

RESUMO

Accurate prediction of blood glucose levels is essential for type 1 diabetes optimizing insulin therapy and minimizing complications in patients with type 1 diabetes. Using ensemble learning algorithms is a promising approach. In this regard, this study proposes an improved stacking ensemble learning algorithm for predicting blood glucose level, in which three improved long short-term memory network models are used as the base model, and an improved nearest neighbor propagation clustering algorithm is adaptively weighted to this ensemble model. The OhioT1DM dataset is used to train and evaluate the performance of the proposed model. This study evaluated the performance of the proposed model using the Root Mean Square Error (RMSE), Mean Absolute Error (MAE), and Matthews Correlation Coefficient (MCC) as the evaluation metrics. The experimental results demonstrate that the proposed model achieves an RMSE of 1.425 mg/dL, MAE of 0.721 mg/dL, and MCC of 0.982 mg/dL for a 30-minute prediction horizon(PH), RMSE of 3.212 mg/dL, MAE of 1.605 mg/dL, and MCC of 0.950 mg/dL for a 45-minute PH; and RMSE of 6.346 mg/dL, MAE of 3.232 mg/dL, and MCC of 0.930 mg/dL for a 60-minute PH. Compared with the best non-ensemble model StackLSTM, the RMSE and MAE were improved by up to 27.92% and 65.32%, respectively. Clarke Error Grid Analysis and critical difference diagram revealed that the model errors were within 10%. The model proposed in this study exhibits state-of-the-art predictive performance, making it suitable for clinical decision-making and of significant importance for the effective treatment of diabetes in patients.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicemia/análise , Algoritmos , Insulina , Aprendizado de Máquina
6.
Genome Med ; 16(1): 31, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38355597

RESUMO

BACKGROUND: Population screening for risk of type 1 diabetes (T1D) has been proposed to identify those with islet autoimmunity (presence of islet autoantibodies). As islet autoantibodies can be transient, screening with a genetic risk score has been proposed as an entry into autoantibody testing. METHODS: Children were recruited from eight general pediatric and specialty clinics across Virginia with diverse community settings. Recruiters in each clinic obtained informed consent/assent, a medical history, and a saliva sample for DNA extraction in children with and without a history of T1D. A custom genotyping panel was used to define T1D genetic risk based upon associated SNPs in European- and African-genetic ancestry. Subjects at "high genetic risk" were offered a separate blood collection for screening four islet autoantibodies. A follow-up contact (email, mail, and telephone) in one half of the participants determined interest and occurrence of subsequent T1D. RESULTS: A total of 3818 children aged 2-16 years were recruited, with 14.2% (n = 542) having a "high genetic risk." Of children with "high genetic risk" and without pre-existing T1D (n = 494), 7.0% (34/494) consented for autoantibody screening; 82.4% (28/34) who consented also completed the blood collection, and 7.1% (2/28) of them tested positive for multiple autoantibodies. Among children with pre-existing T1D (n = 91), 52% (n = 48) had a "high genetic risk." In the sample of children with existing T1D, there was no relationship between genetic risk and age at T1D onset. A major factor in obtaining islet autoantibody testing was concern over SARS-CoV-2 exposure. CONCLUSIONS: Minimally invasive saliva sampling implemented using a genetic risk score can identify children at genetic risk of T1D. Consent for autoantibody screening, however, was limited largely due to the SARS-CoV-2 pandemic and need for blood collection.


Assuntos
Diabetes Mellitus Tipo 1 , Criança , Humanos , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/genética , Virginia , Fatores de Risco , Autoanticorpos/genética , Autoimunidade/genética
7.
Nat Commun ; 15(1): 1337, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351043

RESUMO

Tyrosine kinase 2 (TYK2), a member of the JAK family, has attracted attention as a potential therapeutic target for autoimmune diseases. However, the role of TYK2 in CD8+ T cells and autoimmune type 1 diabetes (T1D) is poorly understood. In this study, we generate Tyk2 gene knockout non-obese diabetes (NOD) mice and demonstrate that the loss of Tyk2 inhibits the development of autoreactive CD8+ T-BET+ cytotoxic T lymphocytes (CTLs) by impairing IL-12 signaling in CD8+ T cells and the CD8+ resident dendritic cell-driven cross-priming of CTLs in the pancreatic lymph node (PLN). Tyk2-deficient CTLs display reduced cytotoxicity. Increased inflammatory responses in ß-cells with aging are dampened by Tyk2 deficiency. Furthermore, treatment with BMS-986165, a selective TYK2 inhibitor, inhibits the expansion of T-BET+ CTLs, inflammation in ß-cells and the onset of autoimmune T1D in NOD mice. Thus, our study reveals the diverse roles of TYK2 in driving the pathogenesis of T1D.


Assuntos
Antineoplásicos , Diabetes Mellitus Tipo 1 , Camundongos , Animais , Linfócitos T CD8-Positivos , Linfócitos T Citotóxicos , Diabetes Mellitus Tipo 1/genética , TYK2 Quinase/genética , Camundongos Knockout , Camundongos Endogâmicos NOD
8.
Sci Rep ; 14(1): 3611, 2024 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-38351110

RESUMO

Diabetic nephropathy is a critical complication of patients with type 1 diabetes, while epidemiological studies were scarce among Asian countries. We conducted a cross-sectional study to identify factors associated with diabetic nephropathy by questionnaires, using student's t-test, chi-square test, and multivariable logistic regression. Among 898 participants, 16.7% had diabetic nephropathy. Compared with non-diabetic nephropathy patients, the patients with diabetic nephropathy had significantly higher percentage with onset age of type 1 diabetes between puberty and under 30 years old (female ≥ 12 or male ≥ 13 years old to 29 years old), longer diabetes duration, having family history of diabetes and diabetic nephropathy, accompanied with hypertension, hyperlipidemia, or coronary artery disease (CAD). Compared with patients with onset age before puberty, the odds of diabetic nephropathy occurrence increased to 1.61 times in patients with onset age between puberty and under 30 years old (p = 0.012) after adjusting diabetes duration. Age of diabetes onset between puberty and under 30 years old, diabetes duration, HbA1c, hospital admission within 3 years, diabetic retinopathy, hypertension, systolic blood pressure (SBP), triglyceride levels, and use of angiotensin converting enzyme inhibitor (ACEI) and/or angiotensin receptor blockers (ARB) were independent factors associated with diabetic nephropathy Screening for proteinuria is important in daily clinical practice and should be part of diabetes self-management education for patients with type 1 diabetes.


Assuntos
Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Hipertensão , Humanos , Masculino , Feminino , Adulto , Lactente , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Idade de Início , Inibidores da Enzima Conversora de Angiotensina , Antagonistas de Receptores de Angiotensina , Estudos Transversais , Hipertensão/complicações , Hipertensão/epidemiologia , Puberdade
9.
BMJ Open Diabetes Res Care ; 12(1)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38302432

RESUMO

INTRODUCTION: Impaired awareness of hypoglycemia (IAH) refers to a diminished capacity to detect hypoglycemia. IAH can result in severe and even life-threatening outcomes for individuals with diabetes, especially those in advanced stages of the disease. This study aimed to assess the prevalence of IAH in people with diabetes on hemodialysis. RESEARCH DESIGN AND METHODS: We conducted a single-center audit to assess the prevalence of IAH using the Clarke questionnaire. Simultaneously, we measured fear of hypoglycemia with an adapted version of the Hypoglycemia Survey and recorded the incidence of severe hypoglycemia. Data were presented as mean±SD or counts/percentages. Logistic regression was then employed to analyze the association between IAH and various sociodemographic and clinical factors. RESULTS: We included 56 participants with diabetes on hemodialysis, with a mean age of 67.2 years (±12.9), of whom 51.8% were male. The ethnic distribution was 23.2% white, 23.2% black, 19.6% Asian, and 33.9% unspecified. The mean HbA1c was 52 mmol/mol (±18.6). The majority (91.1%) had a diagnosis of type 2 diabetes, and 55.4% of those were treated with insulin. The use of diabetes technology was low, with 2.8% of the participants using a continuous glucose monitor. IAH prevalence was 23.2%, and among the 57 participants, 23.6% had a history of severe hypoglycemia, and 60.6% reported fear of hypoglycemia. There were no significant differences in sociodemographic and clinical characteristics between those with IAH and normal hypoglycemia awareness. CONCLUSIONS: We observed that 23.2% of individuals with diabetes undergoing hemodialysis had IAH. IAH was more prevalent in people who reported a fear of hypoglycemia and had a history of severe hypoglycemia episode. The study highlights the unmet needs and disparities in access to diabetes technology within this population.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Hipoglicemia , Humanos , Masculino , Idoso , Feminino , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Hipoglicemia/diagnóstico , Glicemia , Insulina/efeitos adversos
10.
BMJ Open ; 14(2): e076882, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341215

RESUMO

INTRODUCTION: Sphingolipids regulate proinsulin folding, insulin secretion and control beta cells apoptosis. Recent evidence has demonstrated that, among other factors, reduced amounts of sulfatide may be relevant in the development of type 1 diabetes (T1D). Thus, fenofibrate, which activates sulfatide biosynthesis, may prolong remission in subjects with T1D. The aim of the study is to evaluate clinical efficacy of fenofibrate on the maintenance of residual beta-cell function in children with newly diagnosed T1D. METHODS AND ANALYSIS: A total of 102 children aged 10-17 years with newly diagnosed T1D will be enrolled in a double-blind, two-centre randomised, non-commercial, placebo-controlled trial. Subjects who will meet all inclusion criteria will be randomly assigned to receive fenofibrate at a dose of 160 mg or an identically appearing placebo, orally, once daily, for 12 months. The primary endpoint will be the area under the curve of the C-peptide level during 2-hour responses to a mixed-meal tolerance test (MMTT). Secondary endpoints include fasting and maximum C-peptide concentration in the MMTT, parameters of diabetes control and glucose fluctuations, daily insulin requirement, inflammation markers, genetic analysis, safety and tolerance of the fenofibrate ETHICS AND DISSEMINATION: The study protocol was approved by the Bioethics Committee. The results of this study will be submitted to a peer-reviewed diabetic journal. Abstracts will be submitted to international and national conferences. TRIAL REGISTRATION NUMBER: EnduraCT 2020-003916-28.


Assuntos
Diabetes Mellitus Tipo 1 , Fenofibrato , Criança , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Fenofibrato/uso terapêutico , Peptídeo C , Sulfoglicoesfingolipídeos/uso terapêutico , Insulina/uso terapêutico , Método Duplo-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Sci Rep ; 14(1): 3520, 2024 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347052

RESUMO

To assess full-field electroretinogram findings in long-term type 1 diabetes patients without diabetic retinopathy. Prospective study including 46 eyes of 23 patients with type 1 diabetes and 46 age-matched healthy eyes evaluated by the RETI-port/scan21 and the portable system RETeval following ISCEV guidelines. The average duration of diabetes was 28.88 ± 8.04 years. In scotopic conditions, using the RETI-port/scan21, diabetic patients showed an increase in b-wave implicit time (IT) (p = 0.017) with the lowest stimuli; a diminished b-wave amplitude (p = 0.005) in the mixed response, an increased IT (p = 0.004) with the high-intensity stimuli and an OP2 increased IT (p = 0.008) and decreased amplitude (p = 0.002). Under photopic conditions, b-wave amplitude was lower (p < 0.001) and 30-Hz flicker response was diminished (p = 0.021). Using the RETeval, in scotopic conditions, diabetic patients showed a reduction in the rod b-wave amplitude (p = 0.009), an increase in a-wave IT with the 280 Td.s stimulus (p = 0.005). OP2 had an increased IT and diminished amplitude (p = 0.003 and p = 0.002 respectively). 16 Td.s flicker showed an increased IT (p = 0.008) and diminished amplitude (p = 0.048). Despite variations in values between both systems, nearly all results displayed positive correlations. Long-term type 1 diabetes patients without diabetic retinopathy exhibit alterations in scotopic conditions, as evidenced by both conventional and portable electroretinogram devices. These findings suggest a modified retinal function, particularly in rod-driven pathways, even in the absence of vascular signs.


Assuntos
Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Humanos , Retinopatia Diabética/diagnóstico , Estudos Prospectivos , Retina , Eletrorretinografia , Estimulação Luminosa , Regulador Transcricional ERG
12.
Cardiovasc Diabetol ; 23(1): 65, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38347569

RESUMO

Heart failure (HF) is increasing at an alarming rate, primary due to the rising in aging, obesity and diabetes. Notably, individuals with type 1 diabetes (T1D) face a significantly elevated risk of HF, leading to more hospitalizations and increased case fatality rates. Several risk factors contribute to HF in T1D, including poor glycemic control, female gender, smoking, hypertension, elevated BMI, and albuminuria. However, early and intensive glycemic control can mitigate the long-term risk of HF in individuals with T1D. The pathophysiology of diabetes-associated HF is complex and multifactorial, and the underlying mechanisms in T1D remain incompletely elucidated. In terms of treatment, much of the evidence comes from type 2 diabetes (T2D) populations, so applying it to T1D requires caution. Sodium-glucose cotransporter 2 inhibitors have shown benefits in HF outcomes, even in non-diabetic populations. However, most of the information about HF and the evidence from cardiovascular safety trials related to glucose lowering medications refer to T2D. Glycemic control is key, but the link between hypoglycemia and HF hospitalization risk requires further study. Glycemic variability, common in T1D, is an independent HF risk factor. Technological advances offer the potential to improve glycemic control, including glycemic variability, and may play a role in preventing HF. In summary, HF in T1D is a complex challenge with unique dimensions. This review focuses on HF in individuals with T1D, exploring its epidemiology, risk factors, pathophysiology, diagnosis and treatment, which is crucial for developing tailored prevention and management strategies for this population.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Humanos , Feminino , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/tratamento farmacológico , Glucose
13.
Int J Mol Sci ; 25(3)2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38338666

RESUMO

Diabetic kidney disease (DKD) is characterized by histological changes including fibrosis and inflammation. Evidence supports that DKD is mediated by the innate immune system and more specifically by the complement system. Using Ins2Akita T1D diabetic mice, we studied the connection between the complement cascade, inflammation, and fibrosis in early DKD. Data were extracted from a previously published quantitative-mass-spectrometry-based proteomics analysis of kidney glomeruli of 2 (early DKD) and 4 months (moderately advanced DKD)-old Ins2Akita mice and their controls A Spearman rho correlation analysis of complement- versus inflammation- and fibrosis-related protein expression was performed. A cross-omics validation of the correlation analyses' results was performed using public-domain transcriptomics datasets (Nephroseq). Tissue sections from 43 patients with DKD were analyzed using immunofluorescence. Among the differentially expressed proteins, the complement cascade proteins C3, C4B, and IGHM were significantly increased in both early and later stages of DKD. Inflammation-related proteins were mainly upregulated in early DKD, and fibrotic proteins were induced in moderately advanced stages of DKD. The abundance of complement proteins with fibrosis- and inflammation-related proteins was mostly positively correlated in early stages of DKD. This was confirmed in seven additional human and mouse transcriptomics DKD datasets. Moreover, C3 and IGHM mRNA levels were found to be negatively correlated with the estimated glomerular filtration rate (range for C3 rs = -0.58 to -0.842 and range for IGHM rs = -0.6 to -0.74) in these datasets. Immunohistology of human kidney biopsies revealed that C3, C1q, and IGM proteins were induced in patients with DKD and were correlated with fibrosis and inflammation. Our study shows for the first time the potential activation of the complement cascade associated with inflammation-mediated kidney fibrosis in the Ins2Akita T1D mouse model. Our findings could provide new perspectives for the treatment of early DKD as well as support the use of Ins2Akita T1D in pre-clinical studies.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Nefropatias Diabéticas , Humanos , Camundongos , Animais , Nefropatias Diabéticas/genética , Nefropatias Diabéticas/metabolismo , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Experimental/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Proteínas do Sistema Complemento/genética , Proteínas do Sistema Complemento/metabolismo , Fibrose , Rim/metabolismo
14.
Int J Mol Sci ; 25(3)2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38338843

RESUMO

Type 1 diabetes (T1D) is a progressive disorder leading to the development of microangiopathies and macroangiopathies. Numerous cytokines and chemokines are involved in the pathogenesis of T1D complications. The study aimed to assess the presence of complications in patients with long-standing T1D and its relationship with serum biomarker concentrations. We examined 52 T1D subjects, with a disease duration ≥4 years and 39 healthy controls. The group of T1D patients was further divided into subgroups based on the duration of the disease (<7 years and ≥7 years) and the metabolic control assessed by the HbAlc level (<8% and ≥8%). We used Luminex Technology to assess a wide range of biomarker concentrations. A 24 h urine test was done to evaluate the rate of albuminuria. Optical coherence tomography (OCT) was conducted to detect early retinopathic changes. Subclinical atherosclerosis was assessed by measuring the carotid intima-media thickness (IMT). T1D patients showed remarkably higher concentrations of EGF, eotaxin/CCL11, MDC/CCL22, sCD40L, TGF-α, and TNF-α. Moreover, we reported statistically significant correlations between cytokines and IMT. Biomarker concentrations depend on numerous factors such as disease duration, metabolic control, and the presence of complications. Although the majority of pediatric T1D patients do not present signs of overt complications, it is indispensable to conduct the screening for angiopathies already in childhood, as its early recognition may attenuate the further progression of complications.


Assuntos
Aterosclerose , Diabetes Mellitus Tipo 1 , Humanos , Criança , Diabetes Mellitus Tipo 1/patologia , Citocinas , Espessura Intima-Media Carotídea , Aterosclerose/complicações , Biomarcadores
15.
Int J Mol Sci ; 25(3)2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38339075

RESUMO

Recent research suggests that T-cell receptor (TCR) sequences expanded during human immunodeficiency virus and SARS-CoV-2 infections unexpectedly mimic these viruses. The hypothesis tested here is that TCR sequences expanded in patients with type 1 diabetes mellitus (T1DM) and autoimmune myocarditis (AM) mimic the infectious triggers of these diseases. Indeed, TCR sequences mimicking coxsackieviruses, which are implicated as triggers of both diseases, are statistically significantly increased in both T1DM and AM patients. However, TCRs mimicking Clostridia antigens are significantly expanded in T1DM, whereas TCRs mimicking Streptococcal antigens are expanded in AM. Notably, Clostridia antigens mimic T1DM autoantigens, such as insulin and glutamic acid decarboxylase, whereas Streptococcal antigens mimic cardiac autoantigens, such as myosin and laminins. Thus, T1DM may be triggered by combined infections of coxsackieviruses with Clostridia bacteria, while AM may be triggered by coxsackieviruses with Streptococci. These TCR results are consistent with both epidemiological and clinical data and recent experimental studies of cross-reactivities of coxsackievirus, Clostridial, and Streptococcal antibodies with T1DM and AM antigens. These data provide the basis for developing novel animal models of AM and T1DM and may provide a generalizable method for revealing the etiologies of other autoimmune diseases. Theories to explain these results are explored.


Assuntos
Doenças Autoimunes , Infecções por Coxsackievirus , Diabetes Mellitus Tipo 1 , Enterovirus , Miocardite , Infecções Estreptocócicas , Animais , Humanos , Doenças Autoimunes/complicações , Infecções por Coxsackievirus/complicações , Autoantígenos , Streptococcus , Infecções Estreptocócicas/complicações , Antígenos de Bactérias , Receptores de Antígenos de Linfócitos T
16.
Diabetes Metab Res Rev ; 40(2): e3774, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38340050

RESUMO

AIMS: Recently, exosomal miRNAs have been shown to play important roles in multiple diseases, including type 1 diabetes (T1D). To assess the biomarker potential of exosomal miRNAs for T1D, we measured the expression profiles of plasma-derived exosomal miRNAs in T1D and explored their potential functions by bioinformatic analysis. MATERIALS AND METHODS: In the discovery phase, exosome samples were isolated from plasma by size exclusion chromatography from 10 T1D patients and 10 sex- (p = 0.36), age- (p = 0.97), and body mass index-matched (p = 0.47) healthy control subjects. Exosomal miRNA expression profiles were measured using the Illumina NovaSeq 6000 platform. With verification by quantitative real-time PCR (qRT-PCR), we used multiple bioinformatics approaches to explore the potential biological functions of the identified differentially expressed miRNAs. The diagnostic signature of exosomal miRNAs was evaluated by least absolute shrinkage and selection operator (LASSO) regression and evaluated based on the area under the receiver operating characteristic curve (AUC). RESULTS: In total, 43 differentially expressed miRNAs, among which 34 were upregulated and 9 were downregulated, were identified in T1D. After correcting for multiple testing using false discovery rate, 11 identified exosomal miRNAs still showed statistical significance. Among the 5 selected miRNAs, 3 miRNAs (miR-103a-3p, miR-144-5p and miR-454-3p) were successfully validated by qRT-PCR. The biological analysis-enriched terms included protein autophosphorylation and the Hedgehog signalling pathway. The highest AUC of exosomal miRNA was 0.889 under the LASSO model. The expression levels of 5 selected exosomal miRNAs were correlated with multiple clinical characteristics such as fasting C-peptide and postprandial C-peptide. CONCLUSIONS: Our results indicated that plasma-derived exosomal miRNAs could serve as promising diagnostic biomarkers of T1D.


Assuntos
Diabetes Mellitus Tipo 1 , MicroRNAs , Humanos , Diabetes Mellitus Tipo 1/genética , Peptídeo C , Perfilação da Expressão Gênica/métodos , Proteínas Hedgehog/genética , MicroRNAs/genética
17.
Cardiovasc Diabetol ; 23(1): 62, 2024 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-38341550

RESUMO

Currently, the differentiation between type 1 diabetes (T1D) and type 2 diabetes (T2D) is not straightforward, and the features of both types of diabetes coexist in one subject. This situation triggered the need to discriminate so-called double diabetes (DD), hybrid diabetes or type 1.5 diabetes, which is generally described as the presence of the insulin resistance characteristic of metabolic syndrome in individuals diagnosed with T1D. DD not only raises the question of proper classification of diabetes but is also associated with a significantly greater risk of developing micro- and macroangiopathic complications, which was independent of glycaemic control. When considering the global obesity pandemic and increasing incidence of T1D, the prevalence of DD may also presumably increase. Therefore, it is of the highest priority to discover the mechanisms underlying the development of DD and to identify appropriate methods to prevent or treat DD. In this article, we describe how the definition of double diabetes has changed over the years and how it is currently defined. We discuss the accuracy of including metabolic syndrome in the DD definition. We also present possible hypotheses connecting insulin resistance with T1D and propose possible methods to identify individuals with double diabetes based on indirect insulin resistance markers, which are easily assessed in everyday clinical practice. Moreover, we discuss adjuvant therapy which may be considered in double diabetic patients.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Resistência à Insulina , Síndrome Metabólica , Humanos , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Diabetes Mellitus Tipo 1/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/complicações , Obesidade/complicações
18.
Front Endocrinol (Lausanne) ; 15: 1335435, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344660

RESUMO

Type 1 diabetes (T1D) is a complex metabolic autoimmune disorder that affects millions of individuals worldwide and often leads to significant comorbidities. However, the precise trigger of autoimmunity and disease onset remain incompletely elucidated. This integrative perspective article synthesizes the cumulative role of gene-environment interaction in the pathophysiology of T1D. Genetics plays a significant role in T1D susceptibility, particularly at the major histocompatibility complex (MHC) locus and cathepsin H (CTSH) locus. In addition to genetics, environmental factors such as viral infections, pesticide exposure, and changes in the gut microbiome have been associated with the development of T1D. Alterations in the gut microbiome impact mucosal integrity and immune tolerance, increasing gut permeability through molecular mimicry and modulation of the gut immune system, thereby increasing the risk of T1D potentially through the induction of autoimmunity. HLA class II haplotypes with known effects on T1D incidence may directly correlate to changes in the gut microbiome, but precisely how the genes influence changes in the gut microbiome, and how these changes provoke T1D, requires further investigations. These gene-environment interactions are hypothesized to increase susceptibility to T1D through epigenetic changes such as DNA methylation and histone modification, which in turn modify gene expression. There is a need to determine the efficacy of new interventions that target these epigenetic modifications such as "epidrugs", which will provide novel avenues for the effective management of T1D leading to improved quality of life of affected individuals and their families/caregivers.


Assuntos
Diabetes Mellitus Tipo 1 , Interação Gene-Ambiente , Humanos , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/epidemiologia , Qualidade de Vida , Suscetibilidade a Doenças , Epigênese Genética
19.
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
20.
MMW Fortschr Med ; 166(2): 28-29, 2024 02.
Artigo em Alemão | MEDLINE | ID: mdl-38332276
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