Abstract Introduction Type 1A diabetes (T1D) is an autoimmune disease resulting from the selective destruction of pancreatic beta cells by T cells most likely due to interaction of environmental and ...genetic factors. The CD4(+) T cells, largely implicated in this disease, comprise different subsets; based on the cytokines they produce. These subsets include Th1, Th2, regulatory T cells and another population of recently described T cells called Th17 cells. Increased expression of interleukin 17 (IL-17) has been detected in sera and in target tissues of patients with various autoimmune diseases. The differentiation of Th17 cells from naïve T cells appears to involve signals from TGF-beta, IL-6, IL-21, IL-1beta and IL-23. IL-23, a member of the IL-12 family, which activate the effector function of Th17 cells to promote inflammatory responses. In animal models, IL-23 is involved in the development of autoimmune diabetes. In humans, it seems to cause multi-organ inflammation, contributing to rheumatoid arthritis, inflammatory bowel disease and celiac disease manifestations. Conclusions The discovery that certain autoimmune disorders might be largely mediated by an unregulated IL-23/IL-17 response has important implications for the development of novel therapies for these diseases.
•IL-17RA expression in peripheral CD3/CD4 T cells is decreased in recent-onset T1D.•IL-17RA expression in CD8T cells and IL17A serum levels were similar between groups.•IL17A pathway seems down ...regulated at peripheral tissues in -onset T1D patients.•IL-17A allelic variants were not related with T1D susceptibility.
Evaluate the participation of IL-17 pathway in T1D pathogenesis. T helper 17 cells are potent, highly inflammatory cells that produce interleukin 17A (IL-17A), considered a mediator of various immune disorders. However, their role in Type 1 diabetes (T1D) pathogenesis in humans is not totally elucidated.
The expression of IL-17 Receptor A (IL-17RA) in peripheral T lymphocytes and IL-17A serum levels in recent-onset patients with T1D were compared with healthy controls. IL-17A gene variants were evaluated in a greater cohort.
Patients with recent-onset T1D (less than 6 months of diagnosis) exhibited lower expression of IL-17RA in CD3+ T (% of cells = 31.3% × 43.6%; p = .041) and CD4+ T cells (11.1% × 25.2%; p = .0019) and lower number of IL-17RA in CD4+ T cells (MFI = 1.16 × 4.56; p = .03) than controls. IL-17RA expression in CD8+ T cells and IL-17A serum levels were similar in both groups. The coding regions and boundary intron sequences of IL17A were sequenced. Seventeen allelic variants, including three novel variants in exon 3 (3′UTR n) were identified, but no one was associated with T1D susceptibility, as well as the resulting haplotypes and diplotypes. The expression of IL-17RA was not correlated with metabolic variables (glucose and HbA1c levels) or pancreatic autoantibodies titers.
The lower expression of IL-17RA in CD3+ and CD4+ T cells suggests a reduced effect of IL-17A in immune response of recent-onset T1D patients, at least at peripheral tissues. IL-17A allelic variants were not related with T1D susceptibility.
IntroductionCOVID-19 may lead to persistent and potentially incapacitating clinical manifestations (post-acute sequelae of SARS-CoV-2 infection (PASC)). Using easy-to-apply questionnaires and scales ...(often by telephone interviewing), several studies evaluated samples of COVID-19 inpatients from 4 weeks to several months after discharge. However, studies conducting systematic multidisciplinary assessments of PASC manifestations are scarce, with thorough in-person objective evaluations restricted to modestly sized subsamples presenting greatest disease severity.Methods and analysesWe will conduct a prospective observational study of surviving individuals (above 18 years of age) from a cohort of over 3000 subjects with laboratory-confirmed COVID-19 who were treated as inpatients at the largest academic health centre in Sao Paulo, Brazil (Hospital das Clínicas, Faculdade de Medicina, Universidade de São Paulo). All eligible subjects will be consecutively invited to undergo a 1–2-day series of multidisciplinary assessments at 2 time-points, respectively, at 6–9 months and 12–15 months after discharge. Assessment schedules will include detailed multidomain questionnaires applied by medical research staff, self-report scales, objective evaluations of cardiopulmonary functioning, physical functionality and olfactory status, standardised neurological, psychiatric and cognitive examinations, as well as diagnostic laboratory, muscle ultrasound and chest imaging exams. Remaining material from blood tests will be incorporated by a local biobank for use in future investigations on inflammatory markers, genomics, transcriptomics, peptidomics and metabolomics.Ethics and disseminationAll components of this programme have been approved by local research ethics committees. We aim to provide insights into the frequency and severity of chronic/post-COVID multiorgan symptoms, as well as their interrelationships and associations with acute disease features, sociodemographic variables and environmental exposures. Findings will be disseminated in peer-reviewed journals and at scientific meetings. Additionally, we aim to provide a data repository to allow future pathophysiological investigations relating clinical PASC features to biomarker data extracted from blood samples.Trial registration numberRBR-8z7v5wc; Pre-results.
Blood glucose control is fundamental albeit not enough to prevent diabetic macrovascular complications. Dipeptidyl peptidase-4 (DPP-4) inhibitors are effective in improving metabolic parameters in ...patients with type 2 diabetes mellitus (T2DM) but little is known about its cardiovascular effects. We compared the DPP-4 inhibitor sitagliptin with bedtime NPH insulin (NPH) as add-on therapy in patients with T2DM, aiming to ascertain which drug would have additional cardioprotective effects.
Thirty-five T2DM patients inadequately controlled with metformin plus glyburide were randomized to receive sitagliptin (n = 18) or NPH (n = 17) for 24 weeks. Fasting plasma glucose, HbA1c, lipid profile, C-reactive protein, active glucagon-like peptide (aGLP-1) levels, 24-hour ambulatory blood pressure measurement and comprehensive 2-dimensional echocardiogram were determined before and after treatments.
Both sitagliptin and NPH therapies decreased HbA1c levels after 24 weeks. Fasting plasma glucose and triglyceride levels decreased in the NPH group whereas only sitagliptin increased aGLP-1 levels. Left ventricular diastolic dysfunction (LVDD) was detected in 58.6% of twenty-nine patients evaluated. Beneficial effects in LVDD were observed in 75% and 11% of patients treated with sitagliptin and NPH, respectively (p = 0.015). Neither therapy changed C-reactive protein or blood pressure.
Sitagliptin and bedtime NPH were similarly effective on glucose control. Improvement in LVDD in T2DM patients treated with sitagliptin was suggested, probably related to the increase of aGLP-1 levels. Therefore, DPP-4 inhibitor seems to have cardioprotective effects independent of glucose control and may have a role in the prevention of diabetic cardiomyopathy.
Type 2 diabetes mellitus (T2D) is a complex disease associated with several chronic complications, including bone fragility and high fracture risk due to mechanisms not yet fully understood. The ...influence of the gastrointestinal tract and its hormones on bone remodeling has been demonstrated in healthy individuals. Glucagon-like peptide 2 (GLP-2), an enteric hormone secreted in response to nutrient intake, has been implicated as a mediator of nutrient effects on bone remodeling. This study aimed to analyze the dynamics of bone resorption marker C-terminal telopeptide of type I collagen (CTX), bone formation marker osteocalcin, and GLP-2 in response to a mixed meal in diabetic postmenopausal women.
Forty-three postmenopausal women with osteopenia or osteoporosis (20 controls - group CO - and 23 diabetic - group T2D) were subjected to a standard mixed meal tolerance test, with determination of serum CTX, plasma osteocalcin and serum GLP-2 concentrations at baseline and 30, 60, 120 and 180 minutes after the meal.
T2D women had higher body mass index as well as higher femoral neck and total hip bone mineral density. At baseline, luteinizing hormone, follicle-stimulating hormone, osteocalcin and CTX levels were lower in group T2D. In response to the mixed meal, CTX and osteocalcin levels decreased and GLP-2 levels increased in both groups. The expected CTX suppression in response to the mixed meal was lower in group T2D.
Bone turnover markers were significantly reduced in T2D women at baseline. Confirming the role of nutrient intake as a stimulating factor, GLP-2 increased in response to the mixed meal in both groups. Importantly, CTX variation in response to the mixed meal was reduced in T2D women, suggesting abnormal response of bone remodeling to nutrient intake in T2D.
The effects of isolated estrogen therapy on the hemostatic system and arterial distensibility were determined in postmenopausal females with type 2 diabetes mellitus. This was a prospective ...nonrandomized study of 19 subjects (age, 56.2 ± 4.7 years; body mass index, 27.8 ± 2.4 kg/m
2 mean ± SD). Inclusion was done after 2 months of glycemic and blood pressure control. The study consisted of 4 months of placebo treatment immediately followed by an equal period of oral conjugated equine estrogens (CEE) 0.625 mg/d. Measures included anthropometrics, a metabolic profile (oral glucose tolerance test and fasting glycated hemoglobin, total cholesterol and fractions, and triglyceride levels), and coagulation and fibrinolytic factors at the end of the placebo period and after 4 months of oral CEE. Conjugated equine estrogen therapy decreased plasminogen activator inhibitor 1 (placebo × CEE: 16.33 ± 9.11 × 13.08 ± 8.87 UI/mL,
P < .03) and increased factor VIII activity (134.11% ± 46.18% × 145.33% ± 42.04%,
P < .04). An increase in high-density lipoprotein cholesterol levels (placebo × CEE: 42.47 ± 6.80 × 53.32 ± 11.89 mg/dL,
P < .01), and a decrease in glycated hemoglobin (8.45% ± 1.30% vs 7.58% ± 1.06%,
P < .02) and in fasting glucose levels (121.51 ± 21.05 x111.21 ± 20.74 mg/dL,
P = .02) followed CEE therapy. Pulse wave velocity and augmentation index were performed by applanation tonometry and were obtained at the end of the placebo period (placebo), again after an intravenous load of 1.25 mg of CEE (short-term), and after 4 months of oral CEE (long-term). A significant decrease in central (carotid-femoral) pulse wave velocity was seen both after short- and long-term CEE (placebo vs short-term vs long-term: 9.36 ± 2.58 vs 8.26 ± 2.20 vs 7.98 ± 1.90 m/s, respectively analysis of variance,
P < .03; placebo vs short-term,
P < .05; placebo vs long-term,
P < .01), whereas augmentation index decreased only after long-term CEE (placebo vs short-term vs long-term: 39.14% ± 6.94% vs 37.48% ± 8.67% vs 34.3.3% ± 8.11% analysis of variance,
P < .05, respectively; placebo vs long-term,
P < .05). Long-term administration of CEE leads to an improvement in fibrinolysis and arterial distensibility, associated with an increase of the intrinsic coagulation pathway in postmenopausal women with type 2 diabetes mellitus.
Introduction Diabetes mellitus (DM) is associated with severe forms of COVID-19 but little is known about the diabetes--related phenotype considering pre-admission, on-admission and data covering the ...entire hospitalization period. Methods We analyzed COVID-19 inpatients (n = 3327) aged 61.2(48.2-71.4) years attended from March to September 2020 in a public hospital. Results DM group (n = 1218) differed from Non-DM group (n = 2109) by higher age, body mass index (BMI), systolic blood pressure and lower O2 saturation on admission. Gender, ethnicity and COVID-19-related symptoms were similar. Glucose and several markers of inflammation, tissue injury and organ dysfunction were higher among patients with diabetes: troponin, lactate dehydrogenase, creatine phosphokinase (CPK), C-reactive protein (CRP), lactate, brain natriuretic peptide, urea, creatinine, sodium, potassium but lower albumin levels. Hospital (12 x 11 days) and intensive care unit permanence (10 x 9 days) were similar but DM group needed more vasoactive, anticoagulant and anti-platelet drugs, oxygen therapy, endotracheal intubation and dialysis. Lethality was higher in patients with diabetes (39.3% x 30.7%) and increased with glucose levels and age, in male sex and with BMI < 30 kg/m2 in both groups (obesity paradox). It was lower with previous treatment with ACEi/BRA in both groups. Ethnicity and education level did not result in different outcomes between groups. Higher frequency of comorbidities (hypertension, cardiovascular/renal disease, stroke), of inflammatory (higher leucocyte number, RCP, LDH, troponin) and renal markers (urea, creatinine, potassium levels and lower sodium, magnesium) differentiated lethality risk between patients with and without diabetes. Conclusions Comorbidities, inflammatory markers and renal disfunction but not Covid-19-related symptoms, obesity, ethnicity and education level differentiated lethality risk between patients with and without diabetes. Keywords: Diabetes, COVID-19, Clinical data, Laboratory data, Outcome
The objective of this study was to use a questionnaire to evaluate knowledge concerning diabetic retinopathy among the physicians present at the 12th Latin American Congress on Diabetes held in São ...Paulo, Brazil, September 2004.
A questionnaire about their experience and management of patients with diabetes mellitus and the ophthalmologic examination was administered to 168 endocrinologists attending the meeting.
Among the 168 physicians, only 36.9% correctly referred patients with diabetes type 1 to an ophthalmologist, whereas 86.9% referred patients with the type 2 disorder as recommended by the American Academy of Ophthalmology. Regarding the correct indication for screening for diabetic retinopathy, more physicians who had received their degree less than 5 years previously implemented this practice (54.8%), as opposed to those who had received their MD 20 years or more ago (22.6%). Regarding their experience in funduscopy during their specialty training, 52.4% claimed to have experience, but only 21.4% of those interviewed performed this examination on their patients. According to 84.5% of the interviewees, the fundus examination influenced their clinical treatment program.
Our study demonstrates that medical knowledge among medical practitioners and endocrinologists on preventive measures and periodicity of diabetic retinopathy examinations appears to be far from ideal for diabetes type 1, but satisfactory for diabetes type 2. Therefore, refresher courses emphasizing the correct management of diabetic patients are necessary, because the social and economic impact of retinopathy is significant.
Preti RC, Saraiva F, Trein Junior JA, Takahashi W Y, Rossi da Silva. M E. Quanta informação os Médicos Gerais e Endócrinologistas tem sobre Retinopatia Diabética? Clinics. 2007;62(3):273-8.
O objetivo deste estudo foi avaliar através de questionário o conhecimento dos médicos presentes no 12° Congresso Latino Americano de Diabetes Realizado em São Paulo – Brasil, Setembro de 2004.
Através de um questionário aplicado a 168 especialistas em endocrinologia presentes no 12° Congresso Latino Americano de Diabetes realizado São Paulo - Brasil em Setembro de 2004, os autores interrogaram sobre a experiência e conduta em relação à Retinopatia Diabética e ao exame oftalmológico.
Dos 168 médicos, apenas 36,9% encaminhavam corretamente ao oftalmologista os pacientes com diabetes do tipo 1, enquanto 86,9% o faziam de acordo com a Academia Americana de Oftalmologia para os diabéticos do tipo 2. Quanto ao correto encaminhamento dos pacientes para exame de fundo de olho: os médicos com tempo de formação inferior a cinco anos foram os que mais realizam esta prática (54,8%), comparados àqueles com 20 ou mais anos (22,1%). Quanto à experiência em fundoscopia durante a especialização, embora 52,40% afirmassem possuir experiência, apenas 21,4% dos entrevistados realizavam fundo de olho em seus pacientes. Para 84,5% dos entrevistados, o exame de fundo de olho influenciava o tratamento clínico sistemico.
O estudo demonstra que o conhecimento médico das medidas preventivas e de periodicidade do exame da Retinopatia Diabética apresenta-se distante do ideal, para diabéticos tipo 1 e satisfatória para diabéticos tipo 2. Médicos graduados ate 5 anos apresentaram maior porcentagem de correto encaminhamento. A presença de retinopatia diabética no exame de fundo de olho influencia o tratamento clinico sistêmico da maioria dos médicos entrevistados.
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