RESUMO
AIM: Oral semaglutide, an innovative orally administered GLP-1 receptor agonist for type 2 diabetes (T2D) management was herein evaluated for its effectiveness in a multi-center retrospective real-world study. METHODS: We included new-users of oral semaglutide from 18 specialist care centres and collected retrospective data on baseline clinical characteristics. Updated values of HbA1c and body weight were analyzed using the mixed model for repeated measures. RESULTS: The study included 166 individuals with T2D, predominantly men (64.5%), with a mean age of 64.4 years and a mean diabetes duration of 10.1 years. In the majority of patients (68.3%) oral semaglutide was used as a second-line drug, mostly with metformin. At baseline, mean BMI was 28.9 kg/m2 and HbA1c was 7.5%. During the 18-month observation period, oral semaglutide demonstrated significant reductions in HbA1c, with a maximum change of - 0.9%, and 42.1% of patients achieved HbA1c values below 7.0%. Additionally, there was a substantial reduction in body weight, with an estimated change of - 3.4 kg at 18 months, and 30.3% of patients experienced a 5% or greater reduction in baseline body weight. Only 24.2% of patients reached the 14 mg dose. Subgroup analysis revealed that baseline HbA1c > 7%, persistence on drug, not being on a prior therapy with DPP-4 inhibitors, and loosing 5% or more the initial body weight were associated with greater HbA1c reductions. CONCLUSION: This study supports oral semaglutide as an effective option for T2D treatment, offering improved glucose control and weight management in a real-world setting.
Assuntos
Glicemia , Peso Corporal , Diabetes Mellitus Tipo 2 , Peptídeos Semelhantes ao Glucagon , Hipoglicemiantes , Humanos , Peptídeos Semelhantes ao Glucagon/administração & dosagem , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/sangue , Peso Corporal/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/análise , Glicemia/metabolismo , Administração Oral , Idoso , Hemoglobinas Glicadas/análise , Controle Glicêmico/métodos , Resultado do Tratamento , SeguimentosRESUMO
PURPOSE: In mice, adipose tissue-derived stem cells (ASCs) reach the systemic circulation and establish ectopic adipose depots fostering insulin resistance, but whether this occurs in humans is unknown. We examined circulating ASCs in individuals with various combination of metabolic syndrome traits. METHODS: We enrolled patients attending a routine metabolic evaluation or scheduled for bariatric surgery. We quantified ASCs as CD34+CD45-CD31-(CD36+) cells in the stromal vascular fraction of subcutaneous and visceral adipose tissue samples and examined the presence and frequency of putative ASCs in peripheral blood. RESULTS: We included 111 patients (mean age 59 years, 55% males), 40 of whom were scheduled for bariatric surgery. The population of CD34+CD45-CD31- ASCs was significantly more frequent in visceral than subcutaneous adipose depots (10.4 vs 4.1% of the stromal vascular fraction; p < 0.001), but not correlated with BMI or metabolic syndrome traits. The same phenotype of ASCs was detectable in peripheral blood of 58.6% of patients. Those with detectable circulating ASCs had significantly higher BMI (37.8 vs 33.3 kg/m2; p = 0.003) and waist (111.2 vs 105.4 cm; p = 0.001), but no difference in other metabolic syndrome traits (p = 0.84). After bariatric surgery, patients with detectable circulating ASCs had greater BMI reductions at 6 months (- 10.4 vs - 7.8 kg/m2; p = 0.014). CONCLUSION: Presence of putative circulating ASCs, antigenically similar to those observed in the adipose tissue, is associated with greater adiposity and larger BMI reduction after surgery, but not with clinical signs of metabolic impairment. The role of circulating ASCs in adipose tissue biology and systemic metabolism deserves further investigation.
Assuntos
Cirurgia Bariátrica , Síndrome Metabólica , Masculino , Humanos , Camundongos , Animais , Pessoa de Meia-Idade , Feminino , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Tecido Adiposo/metabolismo , Células-Tronco/metabolismoRESUMO
AIM: To compare effectiveness of dapagliflozin versus DPP-4 inhibitors on individualized HbA1c targets and extra-glycaemic endpoints among elderly patients with type 2 diabetes (T2D). METHODS: This was a multicentre retrospective study on patients aged 70-80 years with HbA1c above individualized target and starting dapagliflozin or DPP-4 inhibitors in 2015-2017. The primary outcome was the proportion reaching individualized HbA1c targets. Confounding by indication was addressed by inverse probability of treatment weighting (IPTW), multivariable adjustment (MVA), or propensity score matching (PSM). RESULTS: Patients initiating dapagliflozin (n = 445) differed from those initiating DPP-4i (n = 977) and balance between groups was achieved with IPTW or PSM. The median follow-up was 7.5 months and baseline HbA1c was 8.3%. A smaller proportion of patients initiating dapagliflozin attained individualized HbA1c target as compared to those initiating DPP-4 inhibitors (RR 0.73, p < 0.0001). IPTW, MVA, and PSM yielded similar results. Between-group difference in the primary outcome was observed among patients with lower eGFR or longer disease duration. Dapagliflozin allowed greater reductions in body weight and blood pressure than DPP-4 inhibitors. CONCLUSIONS: Elderly patients with T2D initiating dapagliflozin had a lower probability of achieving individualized HbA1c targets than those initiating DPP-4 inhibitors but displayed better improvements in extra-glycaemic endpoints.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Idoso , Humanos , Estudos Retrospectivos , Hemoglobinas Glicadas , Compostos Benzidrílicos , Hipoglicemiantes , Resultado do Tratamento , GlicemiaRESUMO
AIMS: Post-prandial hyperglycemia remains an unmet need in the management of type 1 diabetes (T1D). In randomized trials, faster insulin aspart (FIA) showed modest but significant reductions of glycemic spikes after meals. Whether such benefit is evident in routine clinical practice is unclear. METHODS: We analyzed data of patients with T1D at the time they switched from a prior bolus insulin to FIA and at the first available follow-up. The primary endpoint was the change in the time spent in hyperglycemia > 250 mg/dl during daytime from flash glucose monitoring (FGM). Secondary outcomes included the change in HbA1c, body weight, insulin dose and other FGM metrics. RESULTS: We included 117 patients with T1D on multiple daily injections who switched to FIA, 57 of whom had data from FGM. Patients were 41-year-old, 51.3% men, with 19.3 years diabetes duration and a baseline HbA1c of 7.7% (60 mmol/mol). Mean observation time was 4.3 months. After switching to FIA, HbA1c declined by 0.1% (1 mmol/mol) only in patients with baseline HbA1c > 7.0% (53 mmol/mol). Time spent in hyperglycemia > 250 mg/dl during daytime was significantly reduced from 14.8 to 11.9% (p = 0.006). Time in range improved from 48.3 to 51.0% (p = 0.028). Results were consistent across various patient characteristics. CONCLUSIONS: Under routine care, patients with T1D who switched to FIA experienced a reduction in the time spent in hyperglycemia > 250 mg/dl during daytime and an increase in time in range. These improvements may be due to better control of post-prandial hyperglycemia, as observed in trials.
Assuntos
Diabetes Mellitus Tipo 1 , Hiperglicemia , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Feminino , Hemoglobinas Glicadas/análise , Controle Glicêmico , Humanos , Hiperglicemia/induzido quimicamente , Hiperglicemia/tratamento farmacológico , Hiperglicemia/prevenção & controle , Hipoglicemiantes , Insulina , Insulina Aspart/uso terapêutico , MasculinoRESUMO
BACKGROUND: Transferring results obtained in cardiovascular outcome trials (CVOTs) to the real-world setting is challenging. We herein transposed CVOT results to the population of patients with type 2 diabetes (T2D) seen in routine clinical practice and who may receive the medications tested in CVOTs. METHODS: We implemented the post-stratification approach based on aggregate data of CVOTs and individual data of a target population of diabetic outpatients. We used stratum-specific estimates available from CVOTs to calculate expected effect size for the target population by weighting the average of the stratum-specific treatment effects according to proportions of a given characteristic in the target population. Data are presented as hazard ratio (HR) and 95% confidence intervals. RESULTS: Compared to the target population (n = 139,708), the CVOT population (n = 95,816) was younger and had a two to threefold greater prevalence of cardiovascular disease. EMPA-REG was the CVOT with the largest variety of details on stratum-specific effects, followed by TECOS, whereas DECLARE and PIONEER-6 had more limited stratum-specific information. The post-stratification HR estimate for 3 point major adverse cardiovascular event (MACE) based on EMPA-REG was 0.88 (0.74-1.03) in the target population, compared to 0.86 (0.74-0.99) in the trial. The HR estimate based on LEADER was 0.88 (0.77-0.99) in the target population compared to 0.87 (0.78-0.97) in the trial. Consistent results were obtained for SUSTAIN-6, EXSCEL, PIONEER-6 and DECLARE. The effect of DPP-4 inhibitors observed in CVOTs remained neutral in the target population. CONCLUSIONS: Based on CVOT stratum-specific effects, cardiovascular protective actions of glucose lowering medications tested in CVOTs are transferrable to a much different real-world population of patients with T2D.
Assuntos
Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Fatores Etários , Idoso , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Bases de Dados Factuais , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Humanos , Hipoglicemiantes/efeitos adversos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Projetos de Pesquisa , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: The infection by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly spread all over the world, becoming pandemic. Several studies have shown that diabetes mellitus (DM) is an independent risk factor that increases mortality and other adverse outcomes of coronavirus disease-19 (COVID-19). Studies have suggested that SARS-CoV-2 may bind dipeptidyl peptidase-4 (DPP4) for entering cells of the respiratory tract. Besides, DPP4 takes part in immune system regulation. Thus, DPP-4 inhibitors (DPP4i) may play a role against COVID-19. METHODS: We focused on the impact of DPP4i treatment on COVID-19-related outcomes in people with DM. For this purpose, we conducted a systematic review and meta-analysis to summarize the existing evidence on this topic. RESULTS: Retrospective observational studies provide inconsistent results on the association between use of DPP4i and outcomes of COVID-19. While two studies reported significantly lower mortality rates among patients with DM who received DPP4i versus those who did not, a series of other studies showed no effect of DPP4i or even worse outcomes. A meta-analysis of 7 studies yielded a neutral estimate of the risk ratio of COVID-19-related mortality among users of DPP4i (0.81; 95% CI 0.57-1.15). CONCLUSION: In the absence of randomized controlled trials, observational research available so far provides inconclusive results and insufficient evidence to recommend use of DPP4i against COVID-19.
Assuntos
Tratamento Farmacológico da COVID-19 , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Dipeptidil Peptidase 4/metabolismo , Humanos , SARS-CoV-2/metabolismo , Resultado do TratamentoAssuntos
Instituições de Assistência Ambulatorial , COVID-19 , Defesa Civil , Controle de Doenças Transmissíveis , Complicações do Diabetes , Diabetes Mellitus Tipo 2 , Pacientes não Comparecentes , Telemedicina , Fatores Etários , Instituições de Assistência Ambulatorial/organização & administração , Instituições de Assistência Ambulatorial/estatística & dados numéricos , COVID-19/epidemiologia , COVID-19/prevenção & controle , COVID-19/psicologia , Cardiotônicos/uso terapêutico , Defesa Civil/organização & administração , Defesa Civil/normas , Controle de Doenças Transmissíveis/métodos , Controle de Doenças Transmissíveis/organização & administração , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/etiologia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Acessibilidade aos Serviços de Saúde/organização & administração , Humanos , Uso da Internet/estatística & dados numéricos , Itália/epidemiologia , Pacientes não Comparecentes/psicologia , Pacientes não Comparecentes/estatística & dados numéricos , Inovação Organizacional , Distanciamento Físico , SARS-CoV-2 , Telemedicina/métodos , Telemedicina/normasRESUMO
AIM: Type 2 diabetes (T2D) is a risk factor for metabolic dysfunction-associated fatty liver disease (MAFLD), which is becoming the commonest cause of chronic liver disease worldwide. We estimated MAFLD prevalence among patients with T2D using the hepatic steatosis index (HSI) and validated it against liver ultrasound. We also examined whether glucose-lowering medications (GLM) beneficially affected HSI. METHODS: We collected data from 46 diabetes clinics (n = 281,381 T2D patients), extracted data to calculate HSI and validated it against ultrasound-detected hepatic steatosis. We then examined changes in HSI among patients with a follow-up visit within 1 year after initiating newer GLMs. RESULTS: MAFLD (defined by HSI > 36, i.e., a high probability of steatosis) was present in 76.3% of the 78,895 included patients, while only 2.7% had HSI < 30 (low probability of steatosis). After age- and sex-adjusting, higher HSI was associated with higher prevalence of chronic kidney disease (odds ratio 1.35; 95%CI 1.22-1.51) and macroangiopathy (odds ratio 1.18; 95%CI 1.07-1.30). Among 2,179 subjects in the validation cohort, the prevalence of MAFLD was 67.8% and was greater in those with high HSI. Performance of HSI for ultrasound-detected MAFLD was moderate (AUROC 0.70), yet steatosis prevalence was > threefold higher among subjects with HSI > 36 than among those with HSI < 30. Notably, HSI declined significantly ~ 6 months after initiation of dapagliflozin or incretin-based therapies, but not gliclazide. CONCLUSION: About three quarters of patients with T2D have HSI values suggestive of MAFLD, a condition associated with macroangiopathy and nephropathy. Treatment with dapagliflozin or incretin therapies might improve MAFLD in T2D.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Fígado Gorduroso/complicações , Fígado Gorduroso/epidemiologia , Hipoglicemiantes/uso terapêutico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Fígado Gorduroso/terapia , Feminino , Seguimentos , Gliclazida/uso terapêutico , Humanos , Incretinas/uso terapêutico , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Ultrassonografia , Adulto JovemRESUMO
BACKGROUND: Heart failure (HF) is considered an important contributor to cardiovascular morbidity and mortality in diabetes mellitus. However, a precise identification of hyperglycemia as contributor for HF is missing. OBJECTIVES: We performed a review and a meta-regression of the available observational studies on the incidence of HF in type 1 diabetes (T1D). DATA SOURCE AND ANALYSIS: We conducted a systematic search of the literature on the incidence of HF in patients with T1D identifying suitable studies published between January 1970 and June 2018 using the following search string: "type 1 diabetes" AND, "heart failure" OR "cardiac failure" OR "congestive heart failure" AND "incidence" NOT "type 2 diabetes" OR "diabetes type 2". Six observational studies were included. A random effect meta-regression model has been estimated to evaluate the incidence rate ratio (IRR) of HF in T1D compared to healthy controls. RESULTS: The mean ± SD age of patients with T1D was 42 ± 11 years, the mean HbA1c was 8.4 ± 0.3%, and average follow-up was 11 ± 3 years. The age-adjusted model shows an incidence rate ratio (IRR) effect of 3.18 (p < 0.001), in correspondence of the mean age at enrollment of studies involved in the analysis. A negative correlation was observed between IRR and average age. CONCLUSIONS: This review shows that the incidence rate of HF is three times higher in patients with T1D than in controls. A careful surveillance of the risk factors for this condition should be included, since the onset of T1D may be important to reduce HF risk in these patients.
Assuntos
Diabetes Mellitus Tipo 1 , Insuficiência Cardíaca , Adulto , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Hiperglicemia/diagnóstico , Hiperglicemia/etiologia , Incidência , Estudos Observacionais como Assunto , Medição de RiscoRESUMO
BACKGROUND AND PURPOSE: Diabetes reduces the levels of hematopoietic stem/progenitor cells (HSPCs), which can contribute to organ and tissue homeostasis. Among patients with diabetes, lower HSPC levels predict the development or worsening of micro- and macro-angiopathy. High glucose variability is also associated with diabetic complications and we have previously shown that acute hypoglycaemia can stimulate stem/progenitor cells. Thus, we evaluated the relationship between glucose variability or time in hypoglycaemia and HSPCs in patients with type 1 diabetes (T1D). METHODS: Patients with T1D were compared to healthy subjects. HSPCs (CD34+, CD133+, CD34+CD133+, CD34 + CD45dim) were quantified by flow cytometry. Using flash glucose monitoring system for 90 days, we calculated several measures of glucose variability and time in hypoglycaemia. RESULTS: Forty-four patients with T1D and 44 healthy subjects were enrolled. Compared to healthy controls, T1D patients had significantly lower levels of HSPCs and duration of diabetes was inversely correlated with HSPC levels. Significant direct correlations were found between HSPC levels and the coefficient of variation of glucose levels or time in hypoglycaemia, which were stronger in patients with short-term than in those with long-standing diabetes. CONCLUSION: This study confirms the pauperization of HSPCs in T1D patients and demonstrates a potential HSPC-stimulatory effect of hypoglycaemia, which mitigates with long-lasting diabetes. These data are consistent with a model whereby disease chronicity progressively blunts the release of HSPCs in response to adrenergic triggers, like hypoglycaemic events.
Assuntos
Células da Medula Óssea/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Glucose/metabolismo , Células-Tronco Hematopoéticas/patologia , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Feminino , Seguimentos , Glucose/administração & dosagem , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
BACKGROUND AND AIMS: The rising tide of diabetes mellitus (DM) and prediabetes (PDM) is urgently calling for strategies easily applicable to anticipate diagnosis. We assessed the effectiveness of random capillary blood glucose (RCBG), administration of a validated DM risk questionnaire, or the combination of both. MATERIALS AND METHODS: RCBG measurement and/or questionnaire administration were offered to all individuals presenting at gazebos organized during the World Diabetes Day or similar public initiatives on diabetes awareness. Subjects with suspicious DM or PDM were invited to the Diabetes Center (DC) for laboratory confirmation (fasting plasma glucose and HbA1c). RESULTS: Among 8563 individuals without known diabetes undergoing RCBG measurement, 341 (4%) had suspicious values. Diagnosis of DM was confirmed in 36 (41.9%) of the 86 subjects who came to the DC and PDM was found in 40 (46.5%). Among 3351 subjects to whom the questionnaire was administered, 480 (14.3%) had suspicious scores. Diagnosis of DM was confirmed in 40 (10.1%) of the 397 who came to the DC and PDM was found in 214 (53.9%). These 3351 subjects also had RCBG measurement and 30 out of them had both tests positive. Among them, 27 subjects came to DC and DM was diagnosed in 17 (63.0%) and PDM was found in 9 (33.3%). CONCLUSIONS: These data suggest that RCBG definitely outperforms the questionnaire to identify unknown DM and PDM. RCBG measurement, with questionnaire as an adjunctive tool, appears to be a simple, fast, and feasible opportunistic strategy in detecting undiagnosed DM and PDM.
Assuntos
Biomarcadores/sangue , Glicemia/análise , Diabetes Mellitus Tipo 2/diagnóstico , Estado Pré-Diabético/diagnóstico , Idoso , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Seguimentos , Teste de Tolerância a Glucose , Hemoglobinas Glicadas/análise , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Estado Pré-Diabético/epidemiologia , Prognóstico , Fatores de Risco , Inquéritos e QuestionáriosAssuntos
Infecções por Coronavirus/epidemiologia , Diabetes Mellitus/epidemiologia , Pneumonia Viral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Betacoronavirus/isolamento & purificação , COVID-19 , China/epidemiologia , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Diabetes Mellitus/fisiopatologia , Diabetes Mellitus/virologia , Feminino , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Prevalência , SARS-CoV-2RESUMO
BACKGROUND AND AIMS: In routine clinical practice, early discontinuation of newly initiated glucose-lowering medications (GLM) is relatively common. We herein evaluated if the clinical characteristics associated with early discontinuation of dapagliflozin were different from those associated with early discontinuation of other GLM. METHODS: The DARWIN-T2D was a multicenter retrospective study conducted at diabetes specialist outpatient clinics in Italy. We included 2484 patients who were initiated on dapagliflozin in 2015-2016 and 14,801 patients who were initiated on other GLM (DPP-4 inhibitors, GLP-1 receptor agonists, or gliclazide) in the same period. After excluding patients who had not (yet) returned to follow-up, we compared the characteristics of patients who persisted on drug versus those who were no longer on drug at the first available follow-up after at least 3 months. RESULTS: As compared to those who persisted on drug, patients who discontinued dapagliflozin (51.7%) were more often female, had higher baseline fasting plasma glucose (FPG), HbA1c, and eGFR, and less common use of metformin. Upon multiple regression, higher HbA1c, higher eGFR, and lower metformin use remained independently associated with early discontinuation. Among patients who had been initiated on other GLM, 41.7% discontinued. Variables independently associated with discontinuation were older age, longer diabetes duration, higher HbA1c, eGFR, and albumin excretion, more common use of insulin and less metformin. CONCLUSION: In routine clinical practice, all variables associated with dapagliflozin discontinuation were also associated with discontinuation of other GLM. Thus, despite a distinctive mechanism of action and a peculiar tolerability profile, no specific predictor of dapagliflozin discontinuation was detected.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Idoso , Glicemia , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Suspensão de TratamentoRESUMO
AIMS: Patients with type 2 diabetes (T2D) have an increased risk of cardiovascular disease. Recent cardiovascular outcome trials (CVOTs) with liraglutide, semaglutide, and albiglutide have shown significant reduction in major adverse cardiovascular events. Conversely, the CVOT with exenatide long-acting release (ELAR) confirmed cardiovascular safety of the drug, but did not reached superiority versus placebo. Herein, we systematically evaluated the effect of ELAR versus placebo or active comparators on cardiovascular events and mortality in patients with T2D. METHODS: We screened the literature for randomized controlled trials reporting cardiovascular events and deaths in patients receiving ELAR versus those receiving placebo or any other glucose-lowering medications. Event rates were pooled and compared using the random-effects model. RESULT: We retrieved 16 trials comparing the occurrence of cardiovascular events and mortality in patients treated with ELAR versus placebo or active comparators. The pooled rate ratio for cardiovascular events was similar in the two groups (0.99; 95% CI 0.92-1.06). The rate ratio for all-cause mortality was significantly lower in exenatide group than in comparators (0.87; 95% CI 0.77-0.97). When results of the EXSCEL trial were omitted, the pooled rate ratio for cardiovascular events and mortality was 0.80 (95% CI 0.40-1.63) and 0.75 (95% CI 0.30-1.84), respectively. CONCLUSIONS: Treatment with ELAR does not increase the risk of cardiovascular events and may reduce all-cause mortality.
Assuntos
Preparações de Ação Retardada/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Angiopatias Diabéticas/epidemiologia , Exenatida/farmacologia , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Sistema Cardiovascular/efeitos dos fármacos , Causas de Morte , Preparações de Ação Retardada/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/mortalidade , Angiopatias Diabéticas/tratamento farmacológico , Angiopatias Diabéticas/mortalidade , Exenatida/administração & dosagem , Feminino , Peptídeos Semelhantes ao Glucagon/uso terapêutico , Humanos , Incidência , Liraglutida/uso terapêutico , Masculino , Pessoa de Meia-Idade , MortalidadeRESUMO
PURPOSE: In patients with type 1 diabetes (T1D), the prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 10 to 53% and contrasting evidence suggests that vitamin D deficiency may favor liver fat accumulation. Here, we investigated the association between vitamin D status and NAFLD in adults with T1D. METHODS: 220 consecutive adult T1D patients on multiple daily injections or continuous subcutaneous insulin infusion and not taking calcium or vitamin D supplements were included. Patient characteristics, 25(OH)D serum levels, and metabolic parameters were analyzed. Vitamin D status was defined as sufficiency ( ≥ 75 nmol/L; 30 ng/ml), insufficiency (50-75 nmol/L; 20-30 ng/ml), or deficiency ( < 50 nmol/L; 20 ng/ml). NAFLD was diagnosed at ultrasound examination and graded 0-3. RESULTS: NAFLD was present in 57 patients (29.5%): 51 grade 1, 5 grade 2, and 1 grade 3. Median 25(OH)D levels were 53 nmol/L (IQR 38-70) in patients with NAFLD and 50 nmol/L (34-69) in patients without (p = 0.46). At multivariable analysis, NAFLD was not associated with 25(OH)D levels (p = 0.42) or vitamin D deficiency (p = 0.55), while BMI (OR 1.16, 95% CI 1.07-1.27) and serum triglycerides (OR 1.02, 95% CI 1.01-1.03) were independently associated with NAFLD. CONCLUSIONS: Vitamin D status appears to have no link with low-grade NAFLD in patients with type 1 diabetes.
Assuntos
Biomarcadores/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/sangue , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Deficiência de Vitamina D/complicações , Vitamina D/sangue , Vitaminas/sangue , Adolescente , Adulto , Estudos Transversais , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/etiologia , Prevalência , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Good glycaemic control during pregnancy is key to reduce maternal and foetal complications. Insulin degludec, an ultralong acting analogue with a "peakless" and stable pharmacokinetic profile, has the potential advantage of reducing hypoglycaemia and glucose variability compared to other basal insulins. Therefore, degludec could be a reasonable therapeutic option for pregnant women with type 1 diabetes (T1D). However, degludec is not licensed for use during pregnancy owing to the lack of safety data. METHODS AND RESULTS: We herein report details on pregnancy and foetal outcomes in three women with uncontrolled T1D treated with insulin degludec during the first trimester or the whole pregnancy. In addition, we report an updated review of similar cases reported in literature. Overall, no congenital neonatal malformation was observed in the six cases described. Three babies required neonatal intensive care unit admission for respiratory distress, apnoeas, bilirubin increase or hypoglycaemia. However, the observed neonatal complications were deemed unlikely to be related to degludec treatment. CONCLUSIONS: In summary, while awaiting for the results of an ongoing randomized controlled trial, data on six cases of degludec exposure during pregnancy reassuringly suggest no embryo-foetal toxicity. More information is needed before degludec can be safely recommended during pregnancy.
Assuntos
Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Gestacional/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Gravidez em Diabéticas/tratamento farmacológico , Adulto , Biomarcadores/análise , Glicemia/análise , Diabetes Mellitus Tipo 1/complicações , Feminino , Hemoglobinas Glicadas/análise , Humanos , Recém-Nascido , Insulina de Ação Prolongada , Masculino , Gravidez , Resultado da Gravidez , Adulto JovemRESUMO
AIMS: Type 2 diabetes (T2D) accelerates the decline in glomerular function; however, some individuals do not develop chronic kidney disease despite advanced age and long-lasting T2D. We aimed to phenotype patients with T2D aged 80 years or older who presented with a fully preserved kidney function. METHODS: From an Italian population of 281,217 T2D outpatients, we collected data on demographics, anthropometrics, diabetes duration, HbA1c, fasting plasma glucose, lipids, liver enzymes, estimated glomerular filtration rate (eGFR), albumin excretion rate (AER), chronic complications, and medication use. We primarily compared patients with a fully preserved kidney function (eGFR > 90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G1A1) with those with mild kidney impairment (eGFR 60-90 ml/min/1.73 m2 and AER < 30 mg/24 h, or G2A1). RESULTS: N = 113,860 had available data for eGFR and AER, 21,648 of whom were aged ≥ 80. G1A1 (n = 278) and G2A1 (n = 6647) patients represented 1.3 and 30.7% of aged T2D patients, respectively, with an average diabetes duration of 16 years. Differences between the G1A1 and G2A1 groups were entered in a multiple logistic regression analysis with and without imputation of missing data. After adjustment and in both imputed and non-imputed datasets, younger age, lower BMI and lower triglycerides were associated with fully preserved versus mildly impaired kidney function. The comparison between G1A1 and G1A2/3 yielded different results. CONCLUSIONS: In a rare population of patients with a fully preserved kidney function despite old age and long-lasting diabetes, lower BMI and triglycerides suggest that protection from lipotoxicity may preserve kidney function over time.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/epidemiologia , Rim/fisiologia , Fenótipo , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Feminino , Taxa de Filtração Glomerular , Humanos , MasculinoRESUMO
Diabetes is a chronic metabolic disease characterized by hyperglycemia and several associated biochemical abnormalities. Diabetes leads to multiorgan complications that collectively reduce life expectancy. Hematopoietic stem cells (HSCs) are nested within bone marrow (BM) niches whence they can be mobilized to the peripheral circulation. Clinically, this is done for HSC collection and autologous or allogenic transplantation. A great amount of data from basic and clinical studies support that diabetic patients are poor HSC mobilizers owing to BM remodeling. Dysfunction of the BM shares pathophysiological features and pathways with typical chronic diabetic complications that affect other issues (e.g. the retina and the kidney). From a clinical perspective, impaired HSC mobilization translates into the failure to collect a minimum number of CD34+ cells to achieve a safe engraftment after transplantation. Furthermore, blunted mobilization is associated with reduced steady-state levels of circulating HSCs, which have been consistently described in diabetic patients and associated with increased risk of adverse outcomes, including cardiovascular events and death. In this review, we discuss the most clinically relevant pharmacological options to overcome impaired HSC mobilization in diabetes. These therapeutic strategies may result in an improved outcome of diabetic patients undergoing HSC transplantation and restore circulating HSC levels, thereby protecting from adverse cardiovascular outcomes.
Assuntos
Diabetes Mellitus/tratamento farmacológico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Hipoglicemiantes/uso terapêutico , Animais , Anti-Inflamatórios não Esteroides/uso terapêutico , Glicemia/efeitos dos fármacos , Diabetes Mellitus/sangue , Diabetes Mellitus/fisiopatologia , Dipeptidil Peptidase 4/fisiologia , Humanos , Hipoglicemiantes/farmacologia , Receptores CXCR4/antagonistas & inibidoresRESUMO
BACKGROUND: Randomized controlled trials (RCTs) in the field of diabetes have limitations inherent to the fact that design, setting, and patient characteristics may be poorly transferrable to clinical practice. Thus, evidence from studies using routinely accumulated clinical data are increasingly valued. AIMS: We herein describe rationale and design of the DARWIN-T2D (DApagliflozin Real World evIdeNce in Type 2 Diabetes), a multicenter retrospective nationwide study conducted at 50 specialist outpatient clinics in Italy and promoted by the Italian Diabetes Society. DATA SYNTHESIS: The primary objective of the study is to describe the baseline clinical characteristics (particularly HbA1c) of patients initiated on dapagliflozin from marketing authorization approval to the end of 2016. Secondary and exploratory objectives will evaluate the changes in glycaemic and extraglycaemic efficacy parameters after initiation of dapagliflozin or after initiation of comparator glucose lowering medications (DPP-4 inhibitors, gliclazide extended release, and long-acting GLP-1 receptor agonists). An automated software will extract relevant data from the same electronic chart system at all centres, thereby minimizing data treatment and human intervention. CONCLUSION: The study is expected to collect an enormous dataset of information on dapagliflozin- and comparator-using patients. After study completion, the Italian Diabetes Society will launch an open crowdsourcing call on the DARWIN-T2D database, challenging diabetes researchers to apply their ideas and approaches to address new unmet needs and knowledge gaps in diabetes. We believe this will move DARWIN-T2D to the next generation of real world studies.
Assuntos
Compostos Benzidrílicos/uso terapêutico , Crowdsourcing , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicina Baseada em Evidências , Glucosídeos/uso terapêutico , Hipoglicemiantes/uso terapêutico , Compostos Benzidrílicos/efeitos adversos , Biomarcadores/sangue , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Mineração de Dados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Glucosídeos/efeitos adversos , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/efeitos adversos , Itália , Projetos de Pesquisa , Estudos Retrospectivos , Transportador 2 de Glucose-Sódio/metabolismo , Inibidores do Transportador 2 de Sódio-Glicose , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND AND AIMS: Degludec is an ultralong-acting insulin analogue with a flat and reproducible pharmacodynamic profile. As some patients with type 1 diabetes (T1D) fail to achieve 24-h coverage with glargine or detemir despite twice-daily injections, we studied the effect of switching T1D patients from twice-daily glargine or detemir to degludec. METHODS AND RESULTS: In this prospective observational study, T1D patients on twice-daily glargine or detemir were enrolled. At baseline and 12 weeks after switching to degludec, we recorded HbA1c, insulin dose, 30-day blood glucose self monitoring (SMBG) or 14-day continuous glucose monitoring (CGM), treatment satisfaction (DTSQ), fear of hypoglycemia (FHS). We included 29 patients (mean age 34 ± 11 years; diabetes duration 18 ± 10 years). After switching to degludec, HbA1c decreased from 7.9 ± 0.6% (63 ± 6 mmol/mol) to 7.7 ± 0.6% (61 ± 6 mmol/mol; p = 0.028). SMBG showed significant reductions in the percent and number of blood glucose values <70 mg/dl and in the low blood glucose index (LBGI) during nighttime. CGM showed a significant reduction of time spent in hypoglycemia, an increase in daytime spent in target 70-180 mg/dl, and a reduction in glucose variability. Total insulin dose declined by 17% (p < 0.001), with 24% reduction in basal and 10% reduction in prandial insulin. DTSQ and FHS significantly improved. CONCLUSION: Switching from twice-daily glargine or detemir to once daily degludec improved HbA1c, glucose profile, hypoglycemia risk and treatment satisfaction, while insulin doses decreased. ClinicalTrials.govNCT02360254.