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1.
Diabetes Obes Metab ; 26(5): 1670-1677, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38297915

RESUMO

AIM: To compare the efficacy and safety of saxagliptin/dapagliflozin and insulin glargine in people with latent autoimmune diabetes in adults (LADA). METHODS: In this phase 2b multicentre, open-label, comparator-controlled, parallel-group, non-inferiority study, we randomly assigned 33 people with LADA who had a fasting C-peptide concentration ≥0.2 nmol/L (0.6 ng/mL) to receive 1-year daily treatment with either the combination of saxagliptin (5 mg) plus dapagliflozin (10 mg) or insulin glargine (starting dose: 10 IU), both on top of metformin. The primary outcome was the 2-h mixed meal-stimulated C-peptide area under the curve (AUC), measured 12 months after randomization. Secondary outcomes were glycated haemoglobin (HbA1c) levels, change in body mass index (BMI), and hypoglycaemic events. RESULTS: In the modified intention-to-treat analysis, the primary outcome was similar in participants assigned to saxagliptin/dapagliflozin or to insulin glargine (median C-peptide AUC: 152.0 ng*min/mL [95% confidence interval {CI} 68.2; 357.4] vs. 122.2 ng*min/mL [95% CI 84.3; 255.8]; p for noninferiority = 0.0087). Participants randomized to saxagliptin/dapagliflozin lost more weight than those randomized to insulin glargine (median BMI change at the end of the study: -0.4 kg/m2 [95% CI -1.6; -0.3] vs. +0.4 kg/m2 [95% CI -0.3; +1.1]; p = 0.0076). No differences in HbA1c or in the number of participants experiencing hypoglycaemic events were found. CONCLUSIONS: Saxagliptin/dapagliflozin was non-inferior to glargine in terms of ß-cell function in this 12-month, small, phase 2b study, enrolling people with LADA with still viable endogenous insulin production. Weight loss was greater with saxagliptin/dapagliflozin, with no differences in glycaemic control or hypoglycaemic risk.


Assuntos
Adamantano/análogos & derivados , Compostos Benzidrílicos , Diabetes Mellitus Tipo 2 , Dipeptídeos , Glucosídeos , Diabetes Autoimune Latente em Adultos , Metformina , Adulto , Humanos , Insulina Glargina/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas , Peptídeo C , Projetos Piloto , Glicemia , Resultado do Tratamento , Hipoglicemiantes/efeitos adversos , Metformina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada
2.
Cardiovasc Diabetol ; 22(1): 204, 2023 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-37563618

RESUMO

BACKGROUND: We assessed whether hepatic steatosis with or without significant fibrosis (determined by validated non-invasive biomarkers) is associated with an increased 10-year estimated risk for cardiovascular disease (CVD) in people with type 1 diabetes mellitus (T1DM). METHODS: We conducted a retrospective, multicenter, cross-sectional study involving 1,254 adults with established T1DM without pre-existing CVD. We used the hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting hepatic steatosis (defined as HSI > 36), with or without coexisting significant fibrosis (defined as FIB-4 index ≥ 1.3 or < 1.3). We calculated the Steno type 1 risk engine and the atherosclerotic CVD (ASCVD) risk score to estimate the 10-year risk of developing a first fatal or nonfatal CVD event. RESULTS: Using the Steno type 1 risk engine, a significantly greater proportion of patients with hepatic steatosis and significant fibrosis (n = 91) had a high 10-year estimated CVD risk compared to those with hepatic steatosis alone (n = 509) or without steatosis (n = 654) (75.8% vs. 23.2% vs. 24.9%, p < 0.001). After adjustment for sex, BMI, diabetes duration, hemoglobin A1c, chronic kidney disease, and lipid-lowering medication use, patients with hepatic steatosis and significant fibrosis had an increased 10-year estimated risk of developing a first fatal or nonfatal CVD event (adjusted-odds ratio 11.4, 95% confidence interval 3.54-36.9) than those without steatosis. We observed almost identical results using the ASCVD risk calculator. CONCLUSIONS: The 10-year estimated CVD risk is remarkably greater in T1DM adults with hepatic steatosis and significant fibrosis than in their counterparts with hepatic steatosis alone or without steatosis.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Estudos Retrospectivos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/complicações , Estudos Transversais , Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia
3.
Diabetes Metab Res Rev ; 39(3): e3601, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36533777

RESUMO

INTRODUCTION: Diabetes mellitus worsens the prognosis of SARS-CoV-2 infection, and vaccination has been the major tool for reducing the risk of hospitalisation, and mortality. The primary aim of this study was to evaluate the response to the SARS-CoV-2 vaccine in subjects with diabetes and controls. Differences between type 1 (T1D) and type 2 (T2D) diabetes and clinical determinants of vaccination response were also evaluated. METHODS: 128 subjects with diabetes (60 with T1D and 62 with T2D) and 202 subjects acting as controls who completed a full vaccination cycle with two doses of mRNA vaccine were enroled. People with previous SARS-CoV-2 infection were excluded. Antibodies (Ab) directed against the spike protein of the SARS-CoV-2 were evaluated at one and 6 months after vaccination. RESULTS: In the whole cohort, the Ab level was higher among women than in men (p = 0.011) and negatively correlated with age (rho = -0.155, p = 0.005). Subjects with diabetes showed decreased levels of Ab after one month compared to controls (1217[747-1887]BAU/mL vs. 1477[942-2556]BAU/mL, p = 0.002), even after correction for age and gender (p = 0.002). No difference was found between subjects with T1D and T2D. After 6 months, antibody levels significantly decreased in people with and without diabetes, with no differences between groups, although some subjects were lost at follow-up. In subjects with diabetes, only a significant correlation was found between Ab level and renal function (rho 0.190, p = 0.042). CONCLUSIONS: Both T1D and T2D are associated with a reduced early response to vaccination. The serum concentration of Ab significantly reduced over time in both groups, highlighting the relevance of vaccination boosters independently of the presence of diabetes.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Masculino , Feminino , Humanos , Diabetes Mellitus Tipo 2/complicações , Seguimentos , RNA Viral , Vacinas contra COVID-19 , COVID-19/prevenção & controle , SARS-CoV-2 , Vacinação , Anticorpos
4.
Int J Mol Sci ; 24(21)2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37958794

RESUMO

Chitotriosidase (CHIT), a mammalian chitinase secreted by neutrophils and activated macrophages, is increased in both cardiovascular disease (CVD) and type 2 diabetes (T2D). Arterial stiffness rises early in T2D and increases the risk of CVD. The aim of this study is to evaluate CHIT activity as an early biomarker of arterial stiffness in people with T2D free from overt vascular complications. In this cross-sectional study, arterial stiffness as measured using standard pulse wave velocity (PWV) was evaluated in 174 people with T2D without overt vascular disease. Then, we measured CHIT serum activity with an electrochemiluminescence assay in two subgroups of participants: 35 with the highest (high-PWV) and 40 with the lowest (low-PWV) PWV values. CHIT activity was no different between the low-PVW and high-PWV groups (12.7 [9.6-17.9] vs. 11.4 [8.8-15.0] nmol/mL/h, respectively). Compared with the low-PWV group, the high-PWV participants were older (p < 0.001); had a longer duration of diabetes (p = 0.03); higher ankle-brachial index ABI (p = 0.04), systolic blood pressure (p = 0.002), diastolic blood pressure (p = 0.005), fasting blood glucose (p = 0.008), and HbA1c (p = 0.005); and lower eGFR (p = 0.03) and body mass index (BMI) (p = 0.01). No association was present with sex, duration of diabetes, age, BMI, peripheral blood pressure, laboratory parameters, and glucose-lowering medications or ongoing antihypertensive therapy. Although no association was found, this study provides novel data about the association of CHIT activity with CVD, focusing on a specific outcome (arterial stiffness) in a well-defined population of subjects with T2D without established CVD.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Rigidez Vascular , Humanos , Rigidez Vascular/fisiologia , Análise de Onda de Pulso/efeitos adversos , Estudos Transversais , Fatores de Risco
5.
Diabetes Metab Res Rev ; 38(5): e3526, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35262260

RESUMO

OBJECTIVE: To build a clinical risk score to aid risk stratification among hospitalised COVID-19 patients. METHODS: The score was built using data of 417 consecutive COVID-19 in patients from Kuwait. Risk factors for COVID-19 mortality were identified by multivariate logistic regressions and assigned weighted points proportional to their beta coefficient values. A final score was obtained for each patient and tested against death to calculate an Receiver-operating characteristic curve. Youden's index was used to determine the cut-off value for death prediction risk. The score was internally validated using another COVID-19 Kuwaiti-patient cohort of 923 patients. External validation was carried out using 178 patients from the Italian CoViDiab cohort. RESULTS: Deceased COVID-19 patients more likely showed glucose levels of 7.0-11.1 mmol/L (34.4%, p < 0.0001) or >11.1 mmol/L (44.3%, p < 0.0001), and comorbidities such as diabetes and hypertension compared to those who survived (39.3% vs. 20.4% [p = 0.0027] and 45.9% vs. 26.6% [p = 0.0036], respectively). The risk factors for in-hospital mortality in the final model were gender, nationality, asthma, and glucose categories (<5.0, 5.5-6.9, 7.0-11.1, or 11.1 > mmol/L). A score of ≥5.5 points predicted death with 75% sensitivity and 86.3% specificity (area under the curve (AUC) 0.901). Internal validation resulted in an AUC of 0.826, and external validation showed an AUC of 0.687. CONCLUSION: This clinical risk score was built with easy-to-collect data and had good probability of predicting in-hospital death among COVID-19 patients.


Assuntos
COVID-19 , Glucose , Mortalidade Hospitalar , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco
6.
Diabetes Obes Metab ; 23(7): 1624-1630, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33764666

RESUMO

AIM: To assess the effect of the coronavirus disease 2019 (COVID-19) lockdown on glycaemic control in subjects with type 2 diabetes (T2D). MATERIALS AND METHODS: In this observational, multicentre, retrospective study conducted in the Lazio region, Italy, we compared the differences in the HbA1c levels of 141 subjects with T2D exposed to lockdown with 123 matched controls with T2D who attended the study centres 1 year before. Basal data were collected from 9 December to 9 March and follow-up data from 3 June to 10 July in 2020 for the lockdown group, and during the same timeframes in 2019 for the control groups. Changes in HbA1c (ΔHbA1c) and body mass index (ΔBMI) during lockdown were compared among patients with different psychological well-being, as evaluated by tertiles of the Psychological General Well-Being Index (PGWBS). RESULTS: No difference in ΔHbA1c was found between the lockdown and control groups (lockdown group -0.1% [-0.5%-0.3%] vs. control group -0.1% [-0.4%-0.2%]; p = .482). Also, no difference was found in ΔBMI (p = .316) or ΔGlucose (p = .538). In the lockdown group, subjects with worse PGWBS showed a worsening of HbA1c (p = .041 for the trend among PGWBS tertiles) and BMI (p = .022). CONCLUSIONS: The COVID-19 lockdown did not significantly impact glycaemic control in people with T2D. People with poor psychological well-being may experience a worsening a glycaemic control because of restrictions resulting from lockdown. These findings may aid healthcare providers in diabetes management once the second wave of COVID-19 has ended.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 2 , Glicemia , Controle de Doenças Transmissíveis , Diabetes Mellitus Tipo 2/epidemiologia , Controle Glicêmico , Humanos , Itália/epidemiologia , Estudos Retrospectivos , SARS-CoV-2
7.
Cardiovasc Diabetol ; 19(1): 164, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004045

RESUMO

BACKGROUND: Cardiometabolic disorders may worsen Covid-19 outcomes. We investigated features and Covid-19 outcomes for patients with or without diabetes, and with or without cardiometabolic multimorbidity. METHODS: We collected and compared data retrospectively from patients hospitalized for Covid-19 with and without diabetes, and with and without cardiometabolic multimorbidity (defined as ≥ two of three risk factors of diabetes, hypertension or dyslipidaemia). Multivariate logistic regression was used to assess the risk of the primary composite outcome (any of mechanical ventilation, admission to an intensive care unit [ICU] or death) in patients with diabetes and in those with cardiometabolic multimorbidity, adjusting for confounders. RESULTS: Of 354 patients enrolled, those with diabetes (n = 81), compared with those without diabetes (n = 273), had characteristics associated with the primary composite outcome that included older age, higher prevalence of hypertension and chronic obstructive pulmonary disease (COPD), higher levels of inflammatory markers and a lower PaO2/FIO2 ratio. The risk of the primary composite outcome in the 277 patients who completed the study as of May 15th, 2020, was higher in those with diabetes (Adjusted Odds Ratio (adjOR) 2.04, 95%CI 1.12-3.73, p = 0.020), hypertension (adjOR 2.31, 95%CI: 1.37-3.92, p = 0.002) and COPD (adjOR 2.67, 95%CI 1.23-5.80, p = 0.013). Patients with cardiometabolic multimorbidity were at higher risk compared to patients with no cardiometabolic conditions (adjOR 3.19 95%CI 1.61-6.34, p = 0.001). The risk for patients with a single cardiometabolic risk factor did not differ with that for patients with no cardiometabolic risk factors (adjOR 1.66, 0.90-3.06, adjp = 0.10). CONCLUSIONS: Patients with diabetes hospitalized for Covid-19 present with high-risk features. They are at increased risk of adverse outcomes, likely because diabetes clusters with other cardiometabolic conditions.


Assuntos
Betacoronavirus , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Pneumonia Viral/diagnóstico , Pneumonia Viral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , COVID-19 , Doenças Cardiovasculares/metabolismo , Infecções por Coronavirus/metabolismo , Diabetes Mellitus/metabolismo , Feminino , Seguimentos , Humanos , Masculino , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Doenças Metabólicas/metabolismo , Pessoa de Meia-Idade , Multimorbidade/tendências , Pandemias , Pneumonia Viral/metabolismo , Prognóstico , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2
8.
Clin Ther ; 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38964935

RESUMO

PURPOSE: Diabetic nephropathy represents the leading cause of end-stage kidney disease in developed countries. Cardiovascular outcome trials have found that in participants who received a glucagon-like peptide-1 receptor agonist (GLP1RA) and a sodium-glucose cotransporter 2 inhibitor (SGLT2i), the risk of incidence and progression of diabetic nephropathy in type 2 diabetes mellitus was reduced. The aim of this study was to compare the decline in estimated glomerular filtration rate (eGFR) among people taking a GLP1RA with that among people taking an SGLT2i in a real-world setting. METHODS: Data for 478 patients with type 2 diabetes mellitus who initiated therapy with a GLP1RA (n = 254) or an SGLT2i (n = 224) between January 1, 2018 and December 31, 2021 were extracted. The primary outcome was any reduction ≥30% in eGFR after the start of therapy. Weight loss and drug discontinuation were also assessed. FINDINGS: Over a median follow-up of 24 months, an eGFR reduction ≥30% occurred in 34 of 254 patients (13.4%) starting a GLP1RA and in 26 of 223 patients (11.6%) starting an SGLT2i (hazard ratio = 0.89; 95% CI, 0.54-1.49; P = 0.67). Median eGFR change over the whole follow-up was similar between groups (SGLT2i: median, -2 mL/min/1.73 m2; 25th, 75th percentile, -13, 8 mL/min/1.73 m2; GLP1RA: median, 0 mL/min/1.73 m2; 25th, 75th percentile, -10, 7 mL/min/1.73 m2; P = 0.54). No worsening of kidney function was observed, even when considering the ratio eGFR mean. The value of eGFR at baseline indicated a statistically significant indirect correlation with the observed absolute value of eGFR change over the follow-up (ρ = -0.36; P < 0.001). The difference in eGFR changes over time observed by eGFR categories was statistically significant (P = 0.0001) in both treatment groups. No significant differences in weight loss and drug discontinuations were observed between groups. IMPLICATIONS: Although acting on different molecular mechanisms, both GLP1RA and SGLT2i might have similar effects on eGFR decline in diabetes, as suggested by the results of the present study conducted in a real-world setting. (Clin Ther. 2024;46:XXX-XXX) © 2024 Elsevier HS Journals, Inc.

9.
Diabetes Metab ; 50(1): 101497, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37992857

RESUMO

AIM: We examined whether metabolic dysfunction-associated steatotic liver disease (MASLD) with or without significant fibrosis (assessed by validated non-invasive biomarkers) was associated with an increased risk of prevalent chronic kidney disease (CKD) or diabetic retinopathy in people with type 1 diabetes mellitus (T1DM). METHODS: We performed a retrospective multicenter cross-sectional study involving 1,409 adult outpatients with T1DM, in whom hepatic steatosis index (HSI) and fibrosis (FIB)-4 index were calculated for non-invasively detecting hepatic steatosis (defined by HSI > 36), with or without coexisting significant fibrosis (FIB-4 index ≥ 1.3 or < 1.3). CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urine albumin/creatinine ratio ≥ 3.0 mg/mmol. The presence of diabetic retinopathy was also recorded in all participants. RESULTS: Patients with MASLD and significant fibrosis (n = 93) had a remarkably higher prevalence of CKD and diabetic retinopathy than their counterparts with MASLD without fibrosis (n = 578) and those without steatosis (n = 738). After adjustment for sex, diabetes duration, hemoglobin A1c, hypertension, and use of antihypertensive or lipid-lowering medications, patients with SLD and significant fibrosis had a higher risk of prevalent CKD (adjusted-odds ratio 1.76, 95 % confidence interval 1.05-2.96) than those without steatosis. Patients with MASLD without fibrosis had a higher risk of prevalent retinopathy (adjusted-odds ratio 1.49, 95 % CI 1.13-1.46) than those without steatosis. CONCLUSION: This is the largest cross-sectional study showing that MASLD with and without coexisting significant fibrosis was associated, independently of potential confounders, with an increased risk of prevalent CKD and retinopathy in adults with T1DM.


Assuntos
Diabetes Mellitus Tipo 1 , Retinopatia Diabética , Fígado Gorduroso , Insuficiência Renal Crônica , Doenças Retinianas , Adulto , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Retinopatia Diabética/epidemiologia , Prevalência , Estudos Transversais , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Fígado Gorduroso/complicações , Doenças Retinianas/complicações , Fibrose , Cirrose Hepática/complicações , Cirrose Hepática/epidemiologia
10.
J Clin Endocrinol Metab ; 108(9): e789-e798, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-36881927

RESUMO

CONTEXT: Patients with type 1 diabetes (T1D) have higher cardiovascular disease (CVD) risk than the general population. OBJECTIVE: This observational study aims to evaluate sex-related differences in CVD prevalence and CVD risk estimates in a large cohort of T1D adults. METHODS: We conducted a multicenter, cross-sectional study involving 2041 patients with T1D (mean age 46 years; 44.9% women). In patients without pre-existing CVD (primary prevention), we used the Steno type 1 risk engine to estimate the 10-year risk of developing CVD events. RESULTS: CVD prevalence (n = 116) was higher in men than in women aged ≥55 years (19.2 vs 12.8%, P = .036), but comparable between the 2 sexes in those aged <55 years (P = .91). In patients without pre-existing CVD (n = 1925), mean 10-year estimated CVD risk was 15.4 ± 0.4% without any significant sex difference. However, stratifying this patient group by age, the 10-year estimated CVD risk was significantly higher in men than in women until age 55 years (P < .001), but this risk equalized after this age. Carotid artery plaque burden was significantly associated with age ≥55 years and with a medium and high 10-year estimated CVD risk, without any significant sex difference. Diabetic retinopathy and sensory-motor neuropathy were also associated with higher 10-year CVD risk and female sex. CONCLUSION: Both men and women with T1D are at high CVD risk. The 10-year estimated CVD risk was higher in men aged <55 years than in women of similar age, but these sex differences disappeared at age ≥55 years, suggesting that female sex was no longer protective.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 1 , Adulto , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Criança , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/complicações , Fatores de Risco , Caracteres Sexuais , Estudos Transversais , Fatores de Risco de Doenças Cardíacas
11.
Diabetes Metab ; 49(6): 101477, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37708990

RESUMO

AIM: We examined whether different insulin administration modalities, i.e., multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII by insulin pumps), are differently associated with the risk of having metabolic dysfunction-associated fatty liver disease (MAFLD), with or without coexisting significant liver fibrosis (assessed by validated non-invasive biomarkers), in adults with type 1 diabetes mellitus (T1DM). METHODS: We conducted a retrospective, multicenter, cross-sectional study involving 1,417 adult individuals with established T1DM treated with MDI or CSII. We calculated hepatic steatosis index (HSI) and fibrosis (FIB)-4 index for non-invasively detecting MAFLD (defined by HSI >36), with or without coexisting significant fibrosis (defined by FIB-4 index ≥ 1.3 or <1.3, respectively). RESULTS: Compared to the MDI group (n = 1,161), insulin-pump users (n = 256; 18.1%) were more likely to be younger (mean age: 40 vs. 48 years, P < 0.001), had better glycemic control (mean hemoglobin A1c: 7.7%  vs. 7.9%, P = 0.025) and a markedly lower prevalence of MAFLD with coexisting significant fibrosis (2.7%  vs. 8.1%, P = 0.010), but a comparable prevalence of MAFLD without fibrosis. In multinomial logistic regression analysis, CSII therapy was associated with a ∼70%-lower risk of MAFLD with significant fibrosis (unadjusted odds ratio 0.32, 95% confidence interval 0.14-0.70; P = 0.004), but this association was no longer significant after adjustment for age, hemoglobin A1c and other potential confounders. CONCLUSION: The lower prevalence of MAFLD with coexisting significant fibrosis we observed in adults with T1DM using CSII therapy, compared to those using MDI therapy, is primarily mediated by inter-group differences in age.


Assuntos
Diabetes Mellitus Tipo 1 , Hepatopatia Gordurosa não Alcoólica , Adulto , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/epidemiologia , Hemoglobinas Glicadas , Estudos Retrospectivos , Estudos Transversais , Insulina/efeitos adversos , Sistemas de Infusão de Insulina , Fibrose
12.
J Clin Endocrinol Metab ; 107(9): e3857-e3865, 2022 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-35595474

RESUMO

AIM: To evaluate early, before the onset of cardiovascular events and of chronic renal insufficiency, the association between chronic kidney disease (CKD)-mineral bone disorder (MBD) biomarkers and vascular stiffness [Cardio Ankle Vascular Index (CAVI)] in the course of type 2 diabetes (T2DM). METHOD: We evaluated 174 T2DM patients [median age 56 years; male/female (M/F) 100/74] with diabetes duration < 10 years and without decreased estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m2) or macrovascular complications. Thirty-four age-matched healthy subjects [M/F 13/21; age 53.5 (50.0-57.7) years; eGFR 107.5 (97.0-119.7) mL/ min1.73 m2] served as local reference control for CAVI (pathological: ≥8) and the novel CKD-MBD biomarkers. RESULTS: Albumin-to-creatinine ratio (ACR) averaged 8.5 mg/g (5.6-17.2) with 12.6% of the patients showing pathologic values, indicative of incipient diabetic nephropathy. Serum parathyroid hormone, fibroblast growth factor 23, and sclerostin were higher while 1,25-dihydroxyvitamin D and Klotho were lower than a control group. CAVI was normal (<8) in only 54% and correlated positively with age (P < 0.001), hemoglobin 1A1c (P = 0.036), and systolic (P = 0.021) and diastolic blood pressure (DBP) (P = 0.001) and negatively correlated with 25-hydroxyvitamin D (P = 0.046). In multivariate analysis, age, DBP, ACR, and serum Klotho were independent positive predictors of CAVI. CONCLUSION: In the absence of overt cardiovascular disease and of chronic renal insufficiency, CAVI is frequently pathologic in T2DM. DBP and ACR are modifiable risk factors of vascular stiffness in T2DM, thus warranting optimal assessment.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Rigidez Vascular , Biomarcadores , Pressão Sanguínea/fisiologia , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Fatores de Risco , Rigidez Vascular/fisiologia
13.
Expert Opin Investig Drugs ; 30(12): 1209-1219, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34936848

RESUMO

INTRODUCTION: Immunotherapies for type 1 diabetes mellitus (T1D) have been the focus of intense research over the past few decades. Nevertheless, the results of clinical trials have not matched expectations. However, thanks to the recent and promising results on T1D prevention, among all the different immune-intervention strategies, clinical evidence on anti-CD3 monoclonal antibodies (mAb) deserves particular attention and in-depth evaluation.In this narrative review, we introduce the role of T-cells and their co-receptor CD3 in the pathogenesis of T1D and examine the potential of anti-CD3 mAbs as a treatment for preventing or curing T1D. We discuss pre-clinical studies and phase II/III clinical trials testing the anti-CD3 mAb teplizumab in subjects at T1D high risk, and testing teplizumab and otelixizumab in T1D recent onset patients. In this work, we discuss the current evidence gathered on anti-CD3 therapy to offer insights on the treatment strengths, limitations, and unmet needs.Recent phase II clinical trials with teplizumab in individuals at high-risk of developing T1D seem encouraging, but benefits associated with the use of anti-CD3 mAb in recent-onset T1D are still controversial. A better patient selection, based on immunological profiles and specific biomarkers, is crucial to improve clinical outcomes in T1D immunotherapies.


Assuntos
Anticorpos Monoclonais , Complexo CD3/antagonistas & inibidores , Diabetes Mellitus Tipo 1 , Anticorpos Monoclonais/farmacologia , Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/prevenção & controle , Humanos , Imunoterapia , Linfócitos T , Terapias em Estudo
14.
Intern Emerg Med ; 16(7): 1975-1985, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34273056

RESUMO

Contrasting data have been published about the impact of cardiovascular disease on Covid-19. A comprehensive synthesis and pooled analysis of the available evidence is needed to guide prioritization of prevention strategies. To clarify the association of cardiovascular disease with Covid-19 outcomes, we searched PubMed up to 26 October 2020, for studies reporting the prevalence of cardiovascular disease among inpatients with Covid-19 in relation to their outcomes. Pooled odds-ratios (OR) for death, for mechanical ventilation or admission in an intensive care unit (ICU) and for composite outcomes were calculated using random effect models overall and in the subgroup of people with comorbid diabetes. Thirty-three studies enrolling 52,857 inpatients were included. Cardiovascular disease was associated with a higher risk of death both overall (OR 2.58, 95% confidence intervals, CI 2.12-3.14, p < 0.001, number of studies 24) and in the subgroup of people with diabetes (OR 2.91, 95% CI 2.13-3.97, p < 0.001, number of studies 4), but not with higher risk of ICU admission or mechanical ventilation (OR 1.35, 95% CI 0.73-2.50, p = 0.34, number of studies 4). Four out of five studies reporting OR adjusted for confounders failed to show independent association of cardiovascular disease with Covid-19 deaths. Accordingly, the adjusted-OR for Covid-19 death in people with cardiovascular disease dropped to 1.31 (95% CI 1.01-1.70, p = 0.041). Among patients hospitalized for Covid-19, cardiovascular disease confers higher risk of death, which was highly mitigated when adjusting the association for confounders.


Assuntos
COVID-19/mortalidade , Doenças Cardiovasculares/mortalidade , Cuidados Críticos/estatística & dados numéricos , COVID-19/complicações , Doenças Cardiovasculares/complicações , Comorbidade , Humanos , Unidades de Terapia Intensiva , Respiração Artificial/mortalidade
15.
Diabetes Res Clin Pract ; 179: 109022, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34450248

RESUMO

In patients with autoimmune diabetes no significant differences were observed in glucose control, expressed as time in range evaluated by continuous glucose monitoring comparing the 3 days after Sars-Cov2 vaccine with the 14 days preceding the vaccine.


Assuntos
COVID-19 , Diabetes Mellitus Tipo 1 , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glucose , Humanos , RNA Viral , SARS-CoV-2 , Vacinação
16.
Diabetes Res Clin Pract ; 173: 108681, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33516784

RESUMO

AIMS: The aim of this real-world study is to evaluate the effect of glucagon-like peptide1 receptor-agonist (GLP1 RA) and sodium-glucose co-transporter2 inhibitor (SGLT2i) on coronary heart disease (CHD) risk, in patients with type 2 diabetes (T2D) in primary cardiovascular prevention. METHODS: Data from 312 patients with T2D, without CHD history, starting treatment with GLP1 RA (n = 174) or SGLT2i (n = 138), were retrospectively collected. UKPDS-RE score was used to estimate 10-years risk for CHD before and 6, 12 and 24 months after prescription. RESULTS: The 10-year CHD risk significantly decreased over 24 months in both GLP1 RA and SGLT2i groups (p = 0.037 and p < 0.001, respectively), with 3% and 7% CHD risk reduction already obtained after the first 6 months of GLP1 RA and SGLT2i therapy respectively (p < 0.001 in both groups. Analyses by categories of baseline CHD risk showed significant reductions of CHD risk in the severe risk categories of both groups (p < 0.001). CHD risk reduction obtained with SGLT2i was higher than with GLP1 RA at 6 and 12 months but not at 24 months. CONCLUSION: This real-world study shows that both GLP1 RA and SGLT2i reduce the 10-year risk for cardiovascular disease in patients with T2D in primary cardiovascular prevention.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Feminino , Seguimentos , Fatores de Risco de Doenças Cardíacas , Humanos , Hipoglicemiantes/farmacologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia , Fatores de Tempo
17.
Maturitas ; 137: 37-44, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32498935

RESUMO

An increasing number of new cases of autoimmune diabetes occur during adulthood. Most are cases of latent autoimmune diabetes in adults (LADA), a form of autoimmune diabetes with older mean age at onset, slower rate of beta-cell loss and longer period of insulin independence after onset when compared with type 1 diabetes. Unfortunately, patients with LADA are often misdiagnosed as having type 2 diabetes, the most frequent form of adult-onset diabetes, and show a sustained poor glycemic control over time. Recent evidence shows that this translates into a significantly increased risk of complications. Therefore, an enhanced awareness of LADA is essential. In this narrative review we aim to provide an update on knowledge about LADA pathophysiology and clinical implications by critically reporting the most recent evidence.


Assuntos
Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/imunologia , Adulto , Idade de Início , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/terapia , Humanos
18.
Diabetes Res Clin Pract ; 169: 108454, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32971157

RESUMO

AIMS: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. METHODS: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. RESULTS: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases. CONCLUSIONS: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes.


Assuntos
COVID-19/complicações , Diabetes Mellitus Tipo 2/patologia , Doença Pulmonar Obstrutiva Crônica/patologia , Insuficiência Renal Crônica/patologia , SARS-CoV-2/isolamento & purificação , Idoso , Idoso de 80 Anos ou mais , COVID-19/transmissão , COVID-19/virologia , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/virologia , Feminino , Hospitalização , Humanos , Incidência , Itália/epidemiologia , Masculino , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/virologia , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/virologia
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