RESUMO
BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) prevent microalbuminuria in normoalbuminuric type 2 diabetic patients. We assessed whether combined therapy with the 2 medications may prevent microalbuminuria better than ACE inhibitor or ARB monotherapy. METHODS AND FINDINGS: VARIETY was a prospective, randomized, open-label, blinded endpoint (PROBE) trial evaluating whether, at similar blood pressure (BP) control, combined therapy with benazepril (10 mg/day) and valsartan (160 mg/day) would prevent microalbuminuria more effectively than benazepril (20 mg/day) or valsartan (320 mg/day) monotherapy in 612 type 2 diabetic patients with high-normal albuminuria included between July 2007 and April 2013 by the Istituto di Ricerche Farmacologiche Mario Negri IRCCS and 8 diabetology or nephrology units in Italy. Time to progression to microalbuminuria was the primary outcome. Analyses were intention to treat. Baseline characteristics were similar among groups. During a median [interquartile range, IQR] follow-up of 66 [42 to 83] months, 53 patients (27.0%) on combination therapy, 57 (28.1%) on benazepril, and 64 (31.8%) on valsartan reached microalbuminuria. Using an accelerated failure time model, the estimated acceleration factors were 1.410 (95% CI: 0.806 to 2.467, P = 0.229) for benazepril compared to combination therapy, 0.799 (95% CI: 0.422 to 1.514, P = 0.492) for benazepril compared to valsartan, and 1.665 (95% CI: 1.007 to 2.746, P = 0.047) for valsartan compared to combination therapy. Between-group differences in estimated acceleration factors were nonsignificant after adjustment for predefined confounders. BP control was similar across groups. All treatments were safe and tolerated well, with a slight excess of hyperkalemia and hypotension in the combination therapy group. The main study limitation was the lower than expected albuminuria at inclusion. CONCLUSIONS: Risk/benefit profile of study treatments was similar. Dual renin-angiotensin system (RAS) blockade is not recommended as compared to benazepril or valsartan monotherapy for prevention of microalbuminuria in normoalbuminuric type 2 diabetic patients. TRIAL REGISTRATION: EudraCT 2006-005954-62; ClinicalTrials.gov NCT00503152.
Assuntos
Albuminúria/etiologia , Albuminúria/prevenção & controle , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Benzazepinas/uso terapêutico , Diabetes Mellitus Tipo 2/complicações , Valsartana/uso terapêutico , Idoso , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Hypertension is usually associated with increased cardiovascular mortality. Uncertainty exists about the possible role of hypertension as a poor prognostic factor for cancer-specific mortality (CSM). To assess the association between pre-existing hypertension and the risk of mortality and relapse after a diagnosis of cancer, we performed a systematic review and meta-analysis of published studies. METHODS: PubMed, Scopus, Web of Science, the Cochrane Library and EMBASE were searched from inception until May 2020, without language restrictions, for observational studies reporting the prognosis of patients with hypertension and cancer. The primary outcome of the study refers to CSM in hypertensive vs nonhypertensive patients, and secondary endpoints were overall mortality (OM) and progression- or relapse-free survival. The effect size was reported as hazard ratios (HRs) with 95% CIs. RESULTS: Mortality and relapse associated with hypertension in patients with various cancers were evaluated among 1 603 437 participants (n = 66 studies). Overall, diagnosis of cancer and hypertension was associated with an increased independent risk of OM (HR = 1.2 [95% CI, 1.13-1.27], P < .01) and CSM (HR = 1.12 [95% CI, 1.04-1.21], P < .01) but not of relapse (HR = 1.08 [95% CI, 0.98-1.19], P = .14). CONCLUSIONS: Among cancer patients, those with pre-existing hypertension have a poorer outcome, probably due to multifactorial reasons. Adequate control of lifestyle, more intensive follow-ups, monitoring for hypertension- and anticancer-related cardiovascular complications, and establishing multidisciplinary cardio-oncology units can be useful measures for reducing mortality and improving care in this setting.
Assuntos
Hipertensão/epidemiologia , Neoplasias/mortalidade , Causas de Morte , Comorbidade , Intervalo Livre de Doença , Humanos , Recidiva Local de Neoplasia/epidemiologia , Modelos de Riscos Proporcionais , Taxa de SobrevidaRESUMO
AIMS: To evaluate whether angiotensin-converting enzyme (ACE) inhibitor and angiotensin II receptor blocker (ARB) combination therapy is more nephroprotective than ACE inhibitor or ARB monotherapy in people with type 2 diabetes and overt nephropathy. MATERIALS AND METHODS: In this prospective, randomized, open, blind-endpoint phase III trial sponsored by the Italian Drug Agency, 103 consenting patients with type 2 diabetes, aged >40 years, with serum creatinine levels 159 to 309 µmol/L, spot morning urinary albumin-creatinine ratio > 1000 mg/g (or > 500 mg/g in those on ACE inhibitor or ARB therapy at inclusion) were stratified by centre and randomized to 4.5-year treatment with valsartan 320 mg/d (n = 36), benazepril 20 mg/d (n = 34) or halved doses of both medications (n = 33). The primary endpoint was end-stage renal disease (ESRD). Modified intention-to-treat analyses were performed. RESULTS: Recruitment took place between June 2007 and February 2013 at 10 centres in Italy and one in Slovenia. A total of 77 participants completed the study and 26 were prematurely withdrawn. During a median (interquartile range) of 41 (18-54) months, 12 participants on benazepril (35.3%) and nine on combination therapy (27.3%) progressed to ESRD, versus five on valsartan (13.9%). Differences between benazepril (hazard ratio [HR] 3.59, 95% confidence interval [CI] 1.25-10.30; P = 0.018) or combination therapy (HR 3.28, 95% CI 1.07-10.0; P = 0.038) and valsartan were significant, even after adjustment for age, gender and baseline serum creatinine, systolic blood pressure and 24-hour proteinuria (HR 5.16, 95% CI 1.50-17.75, P = 0.009 and HR 4.75, 95% CI 1.01-22.39, P = 0.049, respectively). Adverse events were distributed similarly among the groups. CONCLUSIONS: In people with type 2 diabetes with nephropathy, valsartan (320 mg/d) safely postponed ESRD more effectively than benazepril (20 mg/d) or than halved doses of both medications.
Assuntos
Benzazepinas/administração & dosagem , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Valsartana/administração & dosagem , Adulto , Idoso , Benzazepinas/efeitos adversos , Biomarcadores/análise , Pressão Sanguínea/efeitos dos fármacos , Quimioterapia Combinada , Feminino , Humanos , Itália , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Eslovênia , Resultado do Tratamento , Valsartana/efeitos adversosRESUMO
PURPOSE: To overview the recent literature regarding the relationship between COVID-19 vaccines and glycemic control. METHODS: Data were extracted from text and tables of all available articles published up to September 2023 in PubMed Database describing glucose homeostasis data in subjects exposed to COVID-19 vaccines, focusing on patients with diabetes mellitus (DM). RESULTS: It is debated if the immune system impairment observed in diabetic patients makes them susceptible to lower efficacy of vaccines, but evidence suggests a possible improvement in immune response in those with good glycemic control. Despite their proven protective role lowering infection rates and disease severity, COVID-19 vaccines can result in diabetic ketoacidosis, new-onset diabetes, or episodes of hyper- or hypoglycemia. CONCLUSIONS: Evidence with COVID-19 vaccines highlights the strong relationship existing between DM and immune system function. Clinicians should strive to achieve optimal glucose control before vaccination and promptly manage possible glucose homeostasis derangement following vaccine exposure.
Assuntos
Glicemia , Vacinas contra COVID-19 , COVID-19 , Diabetes Mellitus , Humanos , Vacinas contra COVID-19/imunologia , Glicemia/metabolismo , COVID-19/prevenção & controle , COVID-19/imunologia , Diabetes Mellitus/imunologia , Controle Glicêmico/métodos , SARS-CoV-2/imunologia , Hipoglicemia/prevenção & controle , Hipoglicemia/imunologiaRESUMO
BACKGROUND: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. METHODS: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months. RESULTS: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040], chemotherapy-induced menopause (OR 6.48, P < .001), preexisting VFs (OR 25.36, P < .001), baseline T-score less than or equal to -2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P < .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001). CONCLUSIONS: Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab.
Assuntos
Conservadores da Densidade Óssea , Densidade Óssea , Neoplasias da Mama , Difosfonatos , Pré-Menopausa , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Estudos Retrospectivos , Densidade Óssea/efeitos dos fármacos , Adulto , Pessoa de Meia-Idade , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/uso terapêutico , Fraturas da Coluna Vertebral/prevenção & controle , Fraturas da Coluna Vertebral/etiologia , Fraturas da Coluna Vertebral/epidemiologia , Denosumab/uso terapêutico , Denosumab/efeitos adversos , Osteoporose/tratamento farmacológico , Osteoporose/induzido quimicamenteRESUMO
There are no adequate studies that have formally tested the performance of different estimating formulas in patients with type 2 diabetes both with and without overt nephropathy. Here we evaluated the agreement between baseline GFRs, GFR changes at month 6, and long-term GFR decline measured by iohexol plasma clearance or estimated by 15 creatinine-based formulas in 600 type 2 diabetics followed for a median of 4.0 years. Ninety patients were hyperfiltering. The number of those identified by estimation formulas ranged from 0 to 24:58 were not identified by any formula. Baseline GFR was significantly underestimated and a 6-month GFR reduction was missed in hyperfiltering patients. Long-term GFR decline was also underestimated by all formulas in the whole study group and in hyper-, normo-, and hypofiltering patients considered separately. Five formulas generated positive slopes in hyperfiltering patients. Baseline concordance correlation coefficients and total deviation indexes ranged from 32.1% to 92.6% and from 0.21 to 0.53, respectively. Concordance correlation coefficients between estimated and measured long-term GFR decline ranged from -0.21 to 0.35. The agreement between estimated and measured values was also poor within each subgroup considered separately. Thus, our study questions the use of any estimation formula to identify hyperfiltering patients and monitor renal disease progression and response to treatment in type 2 diabetics without overt nephropathy.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Taxa de Filtração Glomerular , Rim/fisiopatologia , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatinina/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/sangue , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/fisiopatologia , Progressão da Doença , Humanos , Iohexol , Itália , Pessoa de Meia-Idade , Modelos Biológicos , Valor Preditivo dos Testes , Ensaios Clínicos Controlados Aleatórios como Assunto , Eslovênia , Fatores de TempoRESUMO
Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 µg/min was significantly associated with increased risk compared with albuminuria <1 µg/min (HR, 1.04; 95% CI, 1.02-1.07). This relationship was similar in the subgroup originally randomly assigned to non-ACEI therapy. Among those originally receiving ACEI therapy, however, the event rate was uniformly low and was not significantly associated with albuminuria. Taken together, among normoalbuminuric patients with type 2 diabetes, any degree of measurable albuminuria bears significant cardiovascular risk. The association with risk is continuous but is lost with early ACEI therapy.
Assuntos
Albuminúria/complicações , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/complicações , Idoso , Albuminúria/urina , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Biomarcadores/urina , Cardiotônicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Indóis/uso terapêutico , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Verapamil/uso terapêuticoRESUMO
PURPOSE: Telephone coaching and health apps are effective means to support subjects with diabetes. Patient support programs (PSP) on type 2 diabetes are scanty, and none has been conducted in Italy. In a pilot phase, conducted during the COVID-19 pandemic, we aimed to examine the feasibility and acceptance of such program. METHODS: The "BE THere for diabetes CARE" (BETHCARE) project is a real-world PSP conducted through telephone and digital coaching system to provide educational and emotional support to Italian adults with diabetes receiving long-acting basal insulin degludec. This pilot phase was conducted in 11 centres that enrolled a total of 63 patients (89% with type-2 diabetes). Counselors contacted patients to define a set of emotional, physical and nutritional targets, and monitoring calls were performed on a monthly basis. Data were collected on socio-demographic and anthropometric characteristics, selected clinical information, quality of life, achievement of targets and patient satisfaction. RESULTS: Fifty-eight subjects (92%) chose to participate by telephone and 5 (8%) by mobile app. Most participants (ie, ≥80%) evaluated counselors' calls "useful/very useful", duration of calls "adequate/adequately long", were satisfied with the educational pathway and declared to be more confident in diabetes management after the program. About half of participants were confident to maintain their targets after the PSP. Achievement of nutritional targets improved during counseling, from a mean score of 1.56 at week 1 to 1.88 at week 16 (p-value = 0.03). No significant variations in the achievement of emotional and physical targets emerged. Mean patients weight decreased from 84.9 kg (week 1) to 84.3 kg (week 4) and then levelled off (84.2 kg, week 16). CONCLUSION: This project demonstrated the feasibility and patient appreciation of a PSP in diabetes care, which is particularly important for a chronic disease of the elderly and during a pandemic period when face-to-face counseling is problematic.
RESUMO
AIMS: Investigating whether and to what extent changes in glomerular hemodynamic parameters, beyond glomerular hyperfiltration, could predict glomerular filtration rate (GFR) decline in hypertensive, non-proteinuric type 2 diabetic patients. MATERIALS AND METHODS: We estimated baseline afferent (Ra) and efferent (Re) arteriolar resistances and glomerular hydrostatic pressure in 60 consecutive patients from DEMAND study, using the Gomez' equations. Baseline renal plasma flow was measured by para-aminohippurate plasma clearance, and GFR was measured by iohexol plasma clearance at baseline and every 6 months for a median of 4.0 years [IQR 3.5-4.0 years]. Patients with a GFR decline > or ≤ 3 mL/min/1.73 m2/year were categorized as "Progressors" and "Non-progressors," respectively. Predictors of GFR decline were studied by univariable and multivariable logistic regression analysis. RESULTS: â¢The GFR declined by a median [IQR] of 4.06 [5.46-2.00] mL/min/1.73 m2/year in the study group as a whole and by 5.35 [6.60-4.48] mL/min/1.73 m2/year and 1.71 [2.14-1.33] mL/min/1.73 m2/year in Progressors and Non-progressors, considered separately. Progressors had a higher baseline Ra (3487.3 ± 1349.3 dyneâ¢secâ¢cm-5 vs. 2877.0 ± 668.9 dyneâ¢secâ¢cm-5, p < 0.05) and higher Ra/Re ratio (1.4 ± 0.5 vs. 1.1 ± 0.3, p < 0.01) than Non-progressors. At multivariable logistic regression analysis, Ra/Re ratio and arterial hypertension duration were independently associated with GFR decline (odds ratio [95% CI] 8.50 [1.56-46.28] and 1.14 [1.01-1.28]), respectively. CONCLUSIONS: Increased Ra/Re ratio and arterial hypertension duration predict early GFR decline in hypertensive non-proteinuric type 2 diabetic patients. These findings could be explained by glomerular hypoperfusion and chronic ischemic injury related to pre-glomerular arteriolar narrowing. CLINICAL TRIAL REGISTRATION: DEMAND, NCT00157586, September 12, 2005.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/diagnóstico , Taxa de Filtração Glomerular , Hemodinâmica , Humanos , Glomérulos RenaisRESUMO
AIMS: In type 2 diabetic patients with obesity, hyperfiltration is a risk factor for accelerated glomerular filtration rate (GFR) decline and is ameliorated by calorie restriction (CR). We assessed whether CR-induced amelioration of hyperfiltration could translate into slower long-term GFR decline in this population. METHODS: In this academic, single-center, parallel-group, prospective, randomized, open-label, blinded endpoint trial, consenting >40-year-old patients with type 2 diabetes, BMI ≥27 kg/m2, creatinine <1.2 mg/dL and albuminuria ≤300 mg/24 h were randomized (1:1) to two-year 25% CR (n = 53) or standard diet (SD, n = 50). Primary outcome was 6-month measured GFR. Analyses were by modified intention-to-treat. RESULTS: At 6 months GFR decreased by 5.16 ± 10.03 mL/min (P = 0.001) with CR, and by 0.98 ± 9.71 mL/min (P = 0.497) with SD. Between-group difference was significant (P = 0.044). GFR decline from 6 to 24 months was significant with SD (P < 0.01), but not with CR (P = 0.075). Between-group difference, however, was not significant (P = 0.414). Body weight, BMI, waist circumference, systolic blood pressure, HbA1c, blood glucose, serum triglycerides decreased and ApoA-I concentration increased with CR. No changes were observed with SD. Between-group differences were significant. CR was tolerated well. CONCLUSIONS: In obese type 2 diabetic patients, CR ameliorated glomerular hyperfiltration and several cardiovascular risk factors, and blunted long-term GFR decline. TRIAL REGISTRATION: NCT01930136.
Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Adulto , Albuminúria/complicações , Restrição Calórica , Diabetes Mellitus Tipo 2/complicações , Nefropatias Diabéticas/etiologia , Feminino , Taxa de Filtração Glomerular/fisiologia , Humanos , Rim , Masculino , Obesidade/complicações , Sobrepeso/complicações , Estudos ProspectivosRESUMO
OBJECTIVES: Diabetes mellitus (DM) is associated with an elevated risk of various cancers, including colorectal cancer (CRC). Similarly, pre-existing DM may also influence prognosis among patients with CRC. We performed a systematic review and meta-analysis to assess the association between DM and risk of death and relapse after a diagnosis of CRC. METHODS: PubMed, Scopus, Web of Science, The Cochrane Library and Embase were searched from inception until July 2019 for studies reporting prognosis of patients with DM and CRC. The primary outcome of the study refers to overall mortality in patients with vs without diabetes. Secondary endpoints were cancer-specific mortality and progression or relapse-free survival. The risk of death and relapse are reported as hazard ratio (HR) with 95% confidence interval (CI), and an HR >1 was associated with worst outcome in patients with diabetes compared to those without diabetes. RESULTS: Mortality and relapse associated with DM in patients with CRC were evaluated among 5,267,980 participants (total of 82 studies). Overall, concomitant diagnosis of CRC and DM were associated with an independent increased risk of overall mortality (HR, 1.21; 95% CI, 1.17 to 1.25; p<0.01) and CSM (HR, 1.11; 95% CI, 1.05 to 1.17; p<0.01). Patients were also at increased risk of relapse (HR, 1.09; 95% CI, 1.02 to 1.16; p<0.01). CONCLUSIONS: In CRC patients with DM, diabetes decreased survival and increased the risk of relapse. Adequate control of lifestyle choices, more intensive follow ups, use of some oral antidiabetics, dietary restrictions, physical activity and monitoring of diabetes-associated complications are measures for reducing mortality in this setting.
Assuntos
Neoplasias Colorretais/mortalidade , Complicações do Diabetes/mortalidade , Diabetes Mellitus Tipo 2/mortalidade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Complicações do Diabetes/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Progressão da Doença , Humanos , Hipoglicemiantes/uso terapêutico , Mortalidade , Recidiva , Análise de SobrevidaRESUMO
Importance: Obesity, defined as a body mass index (BMI) greater than 30, is associated with a significant increase in the risk of many cancers and in overall mortality. However, various studies have suggested that patients with cancer and no obesity (ie, BMI 20-25) have worse outcomes than patients with obesity. Objective: To assess the association between obesity and outcomes after a diagnosis of cancer. Data Sources: PubMed, the Cochrane Library, and EMBASE were searched from inception to January 2020. Study Selection: Studies reporting prognosis of patients with obesity using standard BMI categories and cancer were included. Studies that used nonstandard BMI categories, that were limited to children, or that were limited to patients with hematological malignant neoplasms were excluded. Screening was performed independently by multiple reviewers. Among 1892 retrieved studies, 203 (17%) met inclusion criteria for initial evaluation. Data Extraction and Synthesis: The Meta-analysis of Observational Studies in Epidemiology (MOOSE) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines were reporting guideline was followed. Data were extracted by multiple independent reviewers. Risk of death, cancer-specific mortality, and recurrence were pooled to provide an adjusted hazard ratio (HR) with a 95% CI . A random-effects model was used for the retrospective nature of studies. Main Outcomes and Measures: The primary outcome of the study was overall survival (OS) in patients with cancer, with and without obesity. Secondary end points were cancer-specific survival (CSS) and progression-free survival (PFS) or disease-free survival (DFS). The risk of events was reported as HRs with 95% CIs, with an HR greater than 1 associated with a worse outcome among patients with obesity vs those without. Results: A total of 203 studies with 6â¯320â¯365 participants evaluated the association of OS, CSS, and/or PFS or DFS with obesity in patients with cancer. Overall, obesity was associated with a reduced OS (HR, 1.14; 95% CI, 1.09-1.19; P < .001) and CSS (HR, 1.17; 95% CI, 1.12-1.23; P < .001). Patients were also at increased risk of recurrence (HR, 1.13; 95% CI, 1.07-1.19; P < .001). Conversely, patients with obesity and lung cancer, renal cell carcinoma, or melanoma had better survival outcomes compared with patients without obesity and the same cancer (lung: HR, 0.86; 95% CI, 0.76-0.98; P = .02; renal cell: HR, 0.74; 95% CI, 0.53-0.89; P = .02; melanoma: HR, 0.74; 95% CI, 0.57-0.96; P < .001). Conclusions and Relevance: In this study, obesity was associated with greater mortality overall in patients with cancer. However, patients with obesity and lung cancer, renal cell carcinoma, and melanoma had a lower risk of death than patients with the same cancers without obesity. Weight-reducing strategies may represent effective measures for reducing mortality in these patients.
Assuntos
Neoplasias/mortalidade , Obesidade/epidemiologia , Saúde Global , Humanos , Incidência , Neoplasias/etiologia , Obesidade/complicações , Taxa de Sobrevida/tendênciasRESUMO
BACKGROUND: There is no data available on the best insulin treatment to counteract the effects of glucose excursions due to a moderate alcohol intake associated with portions of slight fat and protein-containing food, as often the case during social happenings or "happy hours". INTRODUCTION: This study analyzes the glycemic control and quality of life in 8 adult type 1 diabetic (T1D) patients on insulin-pump therapy which were invited to consume a traditional Italian aperitif ("Spritz" and chips). METHODS: Patients consumed Spritz aperitif twice: using their habitual bolus, based on carbohydrates (CHO) counting (V1), or with a personalized, advanced bolus (V2) calculated from insulin/Kcal derived from Fats and Proteins (FPU). Post-prandial glucose was continuously monitored; glucose incremental areas (iAUC), glucose peak and time to peak, and estimated change from V1 to V2 from repeated- measures models were computed. Each patient fulfilled validated questionnaires on quality of life, knowledge about diabetes and CHO counting. RESULTS: After the educational program, a reduced iAUC (0-80 min: -306, p=ns; 40-80 min: -400, p=0.07) due to greater (p=0.03) and prolonged double-wave insulin boluses was observed. Blood glucose peak and time to peak were also reduced. Moreover, improvements in the psycho-affective dimension, as well as in the alimentary knowledge were detected. CONCLUSION: Therefore, a personalized educational program on CHO + FPU counting together with insulin bolus management can improve glycemic control during social consumption of alcohol, with positive reflections on the psycho-affective dimension. Further studies are mandatory to confirm such preliminary results.
Assuntos
Consumo de Bebidas Alcoólicas/metabolismo , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Educação de Pacientes como Assunto , Adulto , Consumo de Bebidas Alcoólicas/efeitos adversos , Consumo de Bebidas Alcoólicas/psicologia , Glicemia/análise , Estudos Cross-Over , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 1/psicologia , Carboidratos da Dieta/análise , Gorduras na Dieta/análise , Proteínas Alimentares/análise , Feminino , Humanos , Sistemas de Infusão de Insulina , Masculino , Pessoa de Meia-Idade , Período Pós-Prandial , Qualidade de Vida , Adulto JovemRESUMO
INTRODUCTION: Dulaglutide, a long-acting glucagon-like peptide-1 receptor agonist (GLP-1RA), became available in Italy in April 2016. The aim of ANDREW (Active Notes on Dulaglutide in the REal World), a multicenter, prospective, observational study, was to evaluate glycemic control and weight (co-primary outcomes) for up to 24 months in the real-life setting in consecutive outpatients with type 2 diabetes (T2D) who initiated dulaglutide. Co-secondary outcomes were durability of treatment effects on both glycated hemoglobin (HbA1c) and body weight. METHODS: Overall, 1584 subjects (696 women, 888 men) with T2D (mean age [± standard deviation] 61.7 ± 10.2 years; mean T2D duration 9.9 ± 6.9 years) were treated with dulaglutide (0.75 or 1.5 mg once weekly) between April 2016 and December 2019. RESULTS: A total of 1130 patients completed 12 months of follow-up, while 170 patients interrupted treatment before the 12-month endpoint. At 12 months, average HbA1c and average fasting plasma glucose (FPG) were significantly lower compared to baseline levels (- 10 mmol/mol and - 24.9 mg/dL, respectively), as were body weight (- 3.4 kg) and waist circumference (- 3.3 cm) values (all p < 0.0001). Among subjects that completed 24 months of follow-up (n = 270), the rapid decline in HbA1c and FPG values in the first 12 months was followed by stabilization in the following 12 months (p value for 12-24 months trend: 0.4 and 0.6, respectively). CONCLUSIONS: Dulaglutide is an effective drug for the treatment of T2D that is administered once weekly using a simple auto-injector device. Real-life data confirm the observations in randomized controlled trials that persistent treatment with dulaglutide may help patients with T2D achieve an improvement in some metabolic features and in body weight. It is important that the benefits of therapy with dulaglutide, i.e., the effects of the "glycemic" and the so-called "extra-glycemic" actions of GLP-1RAs, are supported by diabetes care teams emphasizing the need for patients to maintain a healthy lifestyle.
RESUMO
Clinical guidelines, while representing an objective reference to perform correct therapeutic choices, contain grey zones, where recommendations are not supported by solid evidence. In a conference held in Bergamo in October 2018, an attempt was made to highlight some of the main grey zones in Cardiology and, through a comparison between experts, to draw shared conclusions that can illuminate our clinical practice. This manuscript contains the statements of the symposium concerning the controversies in diabetes mellitus and cardiovascular disease. The first topic concerns the appropriateness of second level cardiovascular screening of the entire population of diabetic patients. The second gap in evidence concerns the validity of a target of glycated hemoglobin considering the last trials. The work has also been implemented with the evidences deriving from important randomized studies published after the date of the Conference.
Assuntos
Cardiologia , Doenças Cardiovasculares , Diabetes Mellitus , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Diabetes Mellitus/epidemiologia , Prova Pericial , HumanosRESUMO
INTRODUCTION: Recent guidelines for the treatment of type 2 diabetes mellitus (T2DM) provide evidence supporting limited use of sulphonylureas (SUs), especially in specific risk patient categories, yet data from national registries still suggest their widespread use. The aim of this study was to investigate characteristics of patients with diabetes treated with SUs and quantify the proportion of patients that met the recommendations for use of SUs by recent guidelines and of those presenting characteristics representing an inappropriate prescription risk (IPR). METHODS: A multicenter, retrospective, cross-sectional, observational study in patients with T2DM receiving treatment with SUs (as monotherapy or in combination with another diabetes therapy) was conducted between 2017 and 2018 in 22 outpatient diabetes clinics across Italy. Exclusion criteria were type 1 diabetes, diabetes mellitus secondary to other conditions, and presence of severe/life-threatening diseases. RESULTS: A total of 510 patients with T2DM (306 men, 204 women; mean age ± standard deviation 69.8 ± 9.3 years) who were receiving treatment with a SU (as monotherapy or in combination therapy) were assessed in the study. Overall, 70.6% [n = 360; 95% confidence interval (CI) 66.4%, 74.5%] were assessed to have an IPR. Of these, approximately half presented one factor for risk of inappropriate prescription, and 27 and 10.6% presented two and three factors, respectively. In terms of factors contributing to the total burden of risk of inappropriate treatment with SUs, 37.5% (95% CI 33.2%, 41.8%) of all patients were obese; 33.3% (95% CI 29.3%, 37.6%)] were aged ≥ 75 years; 18.6% (95% CI 15.3%, 22.3%) had a history of cardiovascular disease; 14.1% (95% CI 11.2%, 17.4%) had chronic renal insufficiency; 1.8% (95% CI 0.8%, 3.3%) had a history of severe hypoglycemia; 1.8% (95% CI 0.8%; 3.3%) had cognitive impairment; and 2.4% (95% CI 1.2%, 4.1%) had a risky occupation. CONCLUSIONS: The results of this study provide evidence of a high rate of inappropriate SU prescription risk among patients with T2DM, especially among those with overweight/obesity, older age, history of cardiovascular disease, and hypoglycemia.
RESUMO
INTRODUCTION: Sitagliptin is a dipeptidyl peptidase 4 inhibitor for the treatment of type 2 diabetes (T2D). Limited real-world data on its effectiveness and safety are available from an Italian population. RESEARCH DESIGN AND METHODS: We evaluated long-term clinical data from the single-arm PERsistent Sitagliptin Treatment & Outcomes (PERS&O) study, which collected information on 440 patients with TD2 (275 men, 165 women; mean age 64.1 years; disease median duration: 12 years) treated with sitagliptin 'add-on'. For each patient, we estimated the 10-year cardiovascular (CV) risk using the UK Prospective Diabetes Study (UKPDS) Risk Engine (RE). Drug survival was evaluated using Kaplan-Meier survival curves; repeated measures mixed effects models were used to evaluate the evolution of glycated hemoglobin (HbA1c) and CV risk during sitagliptin treatment. RESULTS: At baseline, most patients were overweight or obese (median body mass index (BMI) (kg/m2) 30.2); median HbA1c was 8.4%; median fasting plasma glucose: 172 mg/dL; median UKPDS RE score: 24.8%, being higher in men (median 30.2%) than in women (median 17.0%) as expected. Median follow-up from starting sitagliptin treatment was 5.6 years. From Kaplan-Meier curves, the estimated median drug survival was 32.8 months when considering discontinuation for any cause and 58.4 months when considering discontinuation for loss of efficacy. A significant improvement in HbA1c was evident during treatment with sitagliptin (p<0.01): the reduction was rapid (median HbA1c after 4-6 months: 7.5%) and continued at longer follow-up. When comparing patients treated with sitagliptin versus those stopping sitagliptin and switching to another antihyperglycemic drug, we detected a significant difference in the evolution of HbA1c in favor of patients who continued sitagliptin treatment. The UKPDS RE score at 10 years and the BMI significantly improved during treatment with sitagliptin (p<0.001). Adverse events were relatively uncommon. CONCLUSION: Patients with T2D treated with sitagliptin achieved an improvement in metabolic control and a reduction in CV risk and did not experience relevant adverse events.
Assuntos
Diabetes Mellitus Tipo 2 , Inibidores da Dipeptidil Peptidase IV , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Dipeptidil Peptidase 4 , Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fosfato de Sitagliptina/uso terapêuticoRESUMO
Background Evidence accumulated that some glucose-lowering medications protect against cardiovascular events ( CVEs ) in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease. The present study evaluated if and how glucose-lowering medication prescription pattern changes in T2DM after a CVE. Methods and Results DATAFILE (Diabetes Therapy After a Cardiovascular Event) was a retrospective multicenter study conducted at 12 diabetes mellitus specialist outpatient clinics in Italy. We identified T2DM patients with an incident CVE for whom a follow-up visit was available after the event. We selected control T2DM patients without an incident CVE , who were matched with cases for age, sex, known diabetes mellitus duration, baseline hemoglobin A1c, kidney function, and follow-up time. We extracted clinical variables and compared prescribed therapies at baseline and follow-up. We included 563 patients with and 497 matched patients without an incident CVE . As expected, patients with a subsequent CVE had a higher baseline prevalence of ischemic heart disease. After a median of 9.5 months, in patients with versus those without a CVE , there was a significant increase in the prescription of beta-blockers, loop diuretics, dual antiplatelet therapy, and, among glucose-lowering medications, a significant decrease in metformin. Hemoglobin A1c marginally declined only in the control group, whereas low-density lipoprotein cholesterol decreased only in patients with CVE . Conclusions This study highlights that occurrence of a CVE in T2DM patients did not prime the prescription of glucose-lowering medications provided with cardiovascular protective effects, even though glucose control remained poor. These data emphasize the need to optimize the therapeutic regimen of T2DM patients with established cardiovascular disease, according to updated guidelines.
Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Hipoglicemiantes/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Antagonistas Adrenérgicos beta/uso terapêutico , Idoso , Antagonistas de Receptores de Angiotensina/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Doenças Cardiovasculares/complicações , LDL-Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Terapia Antiplaquetária Dupla , Feminino , Hemoglobinas Glicadas/metabolismo , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Itália , Masculino , Metformina/uso terapêutico , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Infarto do Miocárdio/tratamento farmacológico , Isquemia Miocárdica/complicações , Isquemia Miocárdica/tratamento farmacológico , Revascularização Miocárdica , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêuticoRESUMO
Complement activation has been increasingly implicated in the pathogenesis of type 2 diabetes and its chronic complications. It is unknown whether complement factor H (CFH) genetic variants, which have been previously associated with complement-mediated organ damage likely due to inefficient complement modulation, influence the risk of renal and cardiovascular events and response to therapy with angiotensin-converting enzyme inhibitors (ACEi) in type 2 diabetic patients. Here, we have analyzed the c.2808G>T, (p.Glu936Asp) CFH polymorphism, which tags the H3 CFH haplotype associated to low plasma factor H levels and predisposing to atypical hemolytic uremic syndrome, in 1,158 type 2 diabetics prospectively followed in the Bergamo nephrologic complications of type 2 diabetes randomized, controlled clinical trial (BENEDICT) that evaluated the effect of the ACEi trandolapril on new onset microalbuminuria. At multivariable Cox analysis, the p.Glu936Asp polymorphism (Asp/Asp homozygotes, recessive model) was associated with increased risk of microalbuminuria [adjusted hazard ratio (HR) 3.25 (95% CI 1.46-7.24), P = 0.0038] and cardiovascular events [adjusted HR 2.68 (95% CI 1.23-5.87), P = 0.013]. The p.Glu936Asp genotype significantly interacted with ACEi therapy in predicting microalbuminuria. ACEi therapy was not nephroprotective in Asp/Asp homozygotes [adjusted HR 1.54 (0.18-13.07), P = 0.691 vs. non-ACEi-treated Asp/Asp patients], whereas it significantly reduced microalbuminuria events in Glu/Asp or Glu/Glu patients [adjusted HR 0.38 (0.24-0.60), P < 0.0001 vs. non-ACEi-treated Glu/Asp or Glu/Glu patients]. Among ACEi-treated patients, the risk of developing cardiovascular events was higher in Asp/Asp homozygotes than in Glu/Asp or Glu/Glu patients [adjusted HR 3.26 (1.29-8.28), P = 0.013]. Our results indicate that type 2 diabetic patients Asp/Asp homozygotes in the p.Glu936Asp CFH polymorphism are at increased risk of microalbuminuria and cardiovascular complications and may be less likely to benefit from ACEi therapy. Further studies are required to confirm our findings.
RESUMO
BACKGROUND: Pasta is a refined carbohydrate with a low glycemic index. Whether pasta shares the metabolic advantages of other low glycemic index foods has not really been investigated. The aim of this study is to document, in people with type-2 diabetes, the consumption of pasta, the connected dietary habits, and the association with glucose control, measures of adiposity, and major cardiovascular risk factors. METHODS: We studied 2562 participants. The dietary habits were assessed with the European Prospective Investigation into Cancer and Nutrition (EPIC) questionnaire. Sex-specific quartiles of pasta consumption were created in order to explore the study aims. RESULTS: A higher pasta consumption was associated with a lower intake of proteins, total and saturated fat, cholesterol, added sugar, and fiber. Glucose control, body mass index, prevalence of obesity, and visceral obesity were not significantly different across the quartiles of pasta intake. No relation was found with LDL cholesterol and triglycerides, but there was an inverse relation with HDL-cholesterol. Systolic blood pressure increased with pasta consumption; but this relation was not confirmed after correction for confounders. CONCLUSIONS: In people with type-2 diabetes, the consumption of pasta, within the limits recommended for total carbohydrates intake, is not associated with worsening of glucose control, measures of adiposity, and major cardiovascular risk factors.