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AIM: To evaluate the impact of aldosterone excess on renal function in individuals with primary aldosteronism and to compare its evolution after surgery or mineralocorticoid receptor antagonist (MRA) treatment. METHODS: A multicentre, retrospective cohort study of primary aldosteronism patients in follow-up in 36 Spanish tertiary hospitals, who underwent specific treatment for primary aldosteronism (MRA or adrenalectomy). RESULTS: A total of 789 patients with primary aldosteronism were included, with a median age of 57.5âyears and 41.8% being women. At primary aldosteronism diagnosis, the prevalence of chronic kidney disease (CKD) was 10.7% (nâ=â84), with 75% of cases classified as state 3a (nâ=â63). Primary aldosteronism patients with CKD had a longer duration of hypertension, a higher prevalence of type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. Unilateral adrenalectomy was performed in 41.8% of cases (nâ=â330), and 459 patients were treated with MRA. After a median follow-up of 30.7âmonths (range 13.3-68.4), there was a significant decline in the estimated glomerular filtration rate (eGFR) in operated patients and those receiving MRA. During follow-up, 24.4% of patients with CKD at the time of primary aldosteronism diagnosis had normalized renal function, and 39% of those with albuminuria had albuminuria remission. There were no differences in renal function or albuminuria regression between the two therapy groups. However, development of albuminuria was less common in operated than in medically treated patients (0 vs. 6.0%, Pâ=â0.009). CONCLUSION: CKD affects around 10% of the patients with primary aldosteronism, with a higher risk in individuals with long-term hypertension, type 2 diabetes, dyslipidaemia, cardiovascular events, hypokalaemia, and albuminuria. At short-term, both MRA and surgical treatment lead to a reduction of renal function, but adrenalectomy led to higher renal protection.
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The introduction of closed-loop systems in the pediatric population has been a revolution in the management and evolution of diabetes. However, there are not many published studies in situations in which the feeding, schedules, and activities of the children deviate from the routine for which the systems were programmed, as in the case of a summer camp for children and adolescents with diabetes, where the specific programming of this device is not well known. It was a single-center prospective preliminary study. A total of twenty-seven patients (mean age 11.9 ± 1.9 years, 40% male, duration of diabetes 6.44 ± 2.83 years) were included (twenty with Medtronic MiniMed 780G system and seven with Tandem Control-IQ). Glucometric variables and pump functionality were monitored during the 7-day camp and in the following 3 weeks. There was no decrease from the objective TIR 70% at any moment. The worst results in Time Below Range were at 72 h from starting the camp, and the worst results in Time Above Range were in the first 24 h, with a progressive improvement after that. No episodes of level 3 hypoglycemia or ketoacidosis occurred. The use of specific programming in two integrated systems, with complex blood glucose regulation algorithms and not-prepared-for situations with increased levels of physical activity or abrupt changes in feeding routines, did not result in an increased risk of level 3 hypoglycemia and ketoacidosis for our pediatric type 1 diabetes (T1D) patients, regardless of the closed-loop device.
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Glicemia , Diabetes Mellitus Tipo 1 , Sistemas de Infusão de Insulina , Insulina , Humanos , Criança , Masculino , Adolescente , Feminino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/sangue , Estudos Prospectivos , Insulina/administração & dosagem , Automonitorização da Glicemia/instrumentação , Hipoglicemiantes/administração & dosagem , Acampamento , Controle Glicêmico/métodos , Algoritmos , Hipoglicemia/prevenção & controleRESUMO
Type 1 diabetes (T1D) is a complex chronic disease associated with major health and economic consequences, also involving important issues in the psychosocial sphere. In this regard, T1D-related distress, defined as the emotional burden of living with T1D, has emerged as a specific entity related to the disease. Diabetes distress (DD) is an overlooked but prevalent condition in people living with T1D, and has significant implications in both glycemic control and mental health in this population. Although overlapping symptoms may be found between DD and mental health disorders, specific approaches should be performed for the diagnosis of this problem. In recent years, different DD-targeted interventions have been postulated, including behavioral and psychosocial strategies. Moreover, new technologies in this field may be helpful to address DD in people living with T1D. In this article, we summarize the current knowledge on T1D-related distress, and we also discuss the current approaches and future perspectives in its management.
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Diabetes Mellitus Tipo 1 , Humanos , Diabetes Mellitus Tipo 1/psicologia , Diabetes Mellitus Tipo 1/terapia , Diabetes Mellitus Tipo 1/complicações , Estresse Psicológico , Angústia Psicológica , Qualidade de VidaRESUMO
Purpose: To compare the clinical and hormonal characteristics of patients with familial hyperaldosteronism (FH) and sporadic primary aldosteronism (PA). Methods: A systematic review of the literature was performed for the identification of FH patients. The SPAIN-ALDO registry cohort of patients with no suspicion of FH was chosen as the comparator group (sporadic group). Results: A total of 360 FH (246 FH type I, 73 type II, 29 type III, and 12 type IV) cases and 830 sporadic PA patients were included. Patients with FH-I were younger than sporadic cases, and women were more commonly affected (P = 0.003). In addition, the plasma aldosterone concentration (PAC) was lower, plasma renin activity (PRA) higher, and hypokalemia (P < 0.001) less frequent than in sporadic cases. Except for a younger age (P < 0.001) and higher diastolic blood pressure (P = 0.006), the clinical and hormonal profiles of FH-II and sporadic cases were similar. FH-III had a distinct phenotype, with higher PAC and higher frequency of hypokalemia (P < 0.001), and presented 45 years before sporadic cases. Nevertheless, the clinical and hormonal phenotypes of FH-IV and sporadic cases were similar, with the former being younger and having lower serum potassium levels. Conclusion: In addition to being younger and having a family history of PA, FH-I and III share other typical characteristics. In this regard, FH-I is characterized by a low prevalence of hypokalemia and FH-III by a severe aldosterone excess causing hypokalemia in more than 85% of patients. The clinical and hormonal phenotype of type II and IV is similar to the sporadic cases.
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Hiperaldosteronismo , Hipopotassemia , Feminino , Humanos , Aldosterona , Hiperaldosteronismo/complicações , Hiperaldosteronismo/genética , Hiperaldosteronismo/epidemiologia , Hipopotassemia/etiologia , PotássioRESUMO
INTRODUCTION: Primary aldosteronism (PA) is associated with several cardiometabolic comorbidities. Specific treatment by mineralocorticoid receptor antagonists (MRA) or adrenalectomy has been reported to reduce the cardiometabolic risk. However, the cardiovascular benefit could depend on plasma renin levels in patients on MRA. AIM: To compare the development of cardiovascular, renal and metabolic complications between medically treated patients with PA and those who underwent adrenalectomy, taking the renin status during MRA treatment into account. METHODS: A multicenter retrospective study (SPAIN-ALDO Register) of patients with PA treated at 35 Spanish tertiary hospitals. Patients on MRA were divided into two groups based on renin suppression (n = 90) or non-suppression (n = 70). Both groups were also compared to unilateral PA patients (n = 275) who achieved biochemical cure with adrenalectomy. RESULTS: Adrenalectomized patients were younger, had higher plasma aldosterone concentration, and lower potassium levels than MRA group. Patients on MRA had similar baseline characteristics when stratified into treatment groups with suppressed and unsuppressed renin. 97 (55.1%) of 176 patients without comorbidities at diagnosis, developed at least one comorbidity during follow-up (median 12 months vs. 12.5 months' follow-up after starting MRA and surgery, respectively). Surgery group had a lower risk of developing new cardiovascular events (HR 0.40 [95% CI 0.18-0.90]) than MRA group. Surgical treatment improved glycemic and blood pressure control, increased serum potassium levels, and required fewer antihypertensive drugs than medical treatment. However, there were no differences in the cardiometabolic profile or the incidence of new comorbidities between the groups with suppressed and unsuppressed renin levels (HR 0.95 [95% CI 0.52-1.73]). CONCLUSION: Cardiovascular, renal, and metabolic events were comparable in MRA patients with unsuppressed and suppressed renin. Effective surgical treatment of PA was associated with a decreased incidence of new cardiovascular events when compared to MRA therapy.
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Doenças Cardiovasculares , Hiperaldosteronismo , Hipertensão , Humanos , Adrenalectomia , Aldosterona , Biomarcadores , Doenças Cardiovasculares/tratamento farmacológico , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/tratamento farmacológico , Hiperaldosteronismo/epidemiologia , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Hipertensão/epidemiologia , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Potássio/metabolismo , Sistema de Registros , Renina/metabolismo , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
OBJECTIVE: Advanced hybrid closed-loop systems (AHCL) have been shown to improve glycemic control and patient-reported outcomes in type 1 diabetes. The aim was to analyze the outcomes of two commercially available AHCL in real life. RESEARCH DESIGN AND METHODS: A prospective study was performed, including adolescents and adults with type 1 diabetes, AHCL naïve, from 14 centers, who initiated the use of MM780G with SmartGuard or Tandem t:slimX2 with Control-IQ. Baseline and 3-month evaluations were performed, assessing HbA1c, time in different glycemic ranges, and patient-reported outcomes. The primary outcome was the between-group time in range 70-180 mg/dL difference from beginning to end of follow-up. RESULTS: One hundred fifty participants were included, with 75 initiating each system (age: 39.9 ± 11.4 years [16-72]; 64% female; diabetes duration: 21.6 ± 11.9 years). Time in range increased from 61.53 ± 14.01% to 76.17 ± 9.48% (P < 0.001), with no between-group differences (P = 0.591). HbA1c decreased by 0.56% (95% CI 0.44%, 0.68%) (6 mmol/mol, 95% CI 5, 7) (P < 0.001), from 7.43 ± 1.07% to 6.88 ± 0.60% (58 ± 12 to 52 ± 7 mmol/mol) in the MM780G group, and from 7.14 ± 0.70% to 6.56 ± 0.53% (55 ± 8 to 48 ± 6 mmol/mol) in the Control-IQ group (both P < 0.001 to baseline, P = 0.819 between groups). No superiority of one AHCL over the other regarding fear of hypoglycemia or quality of life was found. Improvement in diabetes-related distress was higher in Control-IQ users (P = 0.012). Sleep quality was improved (PSQI: from 6.94 ± 4.06 to 6.06 ± 4.05, P = 0.004), without differences between systems. Experience with AHCL, evaluated by the INSPIRE measures, exceeded the expectations. CONCLUSIONS: The two AHCL provide significant improvement in glucose control and satisfaction, with no superiority of one AHCL over the other.
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Diabetes Mellitus Tipo 1 , Adolescente , Adulto , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Glicemia , Hemoglobinas Glicadas , Estudos Prospectivos , Qualidade de Vida , Medidas de Resultados Relatados pelo Paciente , Insulina , Hipoglicemiantes/uso terapêutico , Sistemas de Infusão de Insulina , Automonitorização da GlicemiaRESUMO
Both oxidative stress and intestinal permeability are increased in hyperglycemic situations and have been shown to be reduced by metformin in type 2 diabetes mellitus (T2DM) patients. The aim of this study was to elucidate the effect of metformin on oxidative stress and intestinal permeability in women with gestational diabetes mellitus (GDM) treated with metformin compared to those treated with insulin and healthy controls. A total of 120 women were included from August 2016 to February 2022: 41 received metformin (MET group), 38 received insulin (INS group), and 41 were healthy controls. Baseline and antenatal visits were carried out at 25.4 ± 4.8 and 36.1 ± 0.8 weeks of pregnancy, respectively. Advanced oxidation protein products (AOPPs), total antioxidant capacity (TAC), and zonulin levels were measured at every visit. Zonulin levels from baseline to prepartum visit increased significantly in both healthy controls (0.6 ± 0.9 to 1.2 ± 1.7 ng/mL, p = 0.004) and the INS group (0.4 ± 0.3 to 0.6 ± 0.5 ng/mL, p = 0.034) but did not significantly change in the MET group (0.4 ± 0.4 to 0.5 ± 0.4 ng/mL, p = 0.202). However, TAC and AOPP levels significantly increased in women with GDM, both in the INS and MET groups but not in the healthy controls. In conclusion, in our population, metformin has been shown to avoid an increase in intestinal permeability but failed to avoid an increase in oxidative stress related to hyperglycemia.
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PURPOSE: To evaluate whether the clinical, biochemical and radiological features of patients with primary aldosteronism (PA) can predict both main subtypes of PA. METHODS: A retrospective multicenter study of PA patients followed in 27 Spanish tertiary hospitals (SPAIN-ALDO Register). Only patients with confirmed unilateral or bilateral PA based on adrenal venous sampling (AVS) and/or postsurgical biochemical cure after adrenalectomy were included. Supervised regression techniques were used for model development. RESULTS: 328 patients [270 unilateral PA (UPA), 58 bilateral PA (BPA)] were included. The area under the curve (AUC) for aldosterone/potassium ratio and aldosterone responses following saline infusion test were 0.602 [95%CI 0.520 to 0.684] and 0.574 [95% CI 0.446-0.701], respectively, to differentiate UPA from BPA. The AUC was 0.825 [95% 0.764-0.886] when the prediction model with seven parameters - comorbidities (dyslipidemia, cerebrovascular disease, sleep apnea syndrome [SAS]), systolic blood pressure (SBP), plasma aldosterone levels (PAC), hypokalemia and unilateral adrenal nodule >1 cm and normal contralateral adrenal gland on CT/MRI - was used. In patients without comorbidities, hypokalemia, SBP > 160 mmHg, PAC > 40 ng/dL, and unilateral adrenal lesions were associated with a likelihood of having a UPA of 98.5%. The chance of BPA was higher in individuals with comorbidities, SBP < 140 mmHg, normokalemia, low PAC levels, and no adrenal tumors on the CT/MRI (91.5%). CONCLUSION: A combination of high PAC, SBP > 160 mmHg, low serum potassium, a unilateral adrenal nodule>1 cm and no comorbidities could predict a UPA with a 98.5% accuracy.
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CONTEXT: Patients with obesity have an overactivated renin-angiotensin-aldosterone system (RAAS) that is associated with essential hypertension. However, the influence of obesity in primary aldosteronism (PA) is unknown. OBJECTIVE: We analyzed the effect of obesity on the characteristics of PA, and the association between obesity and RAAS components. METHODS: A retrospective study was conducted of the Spanish PA Registry (SPAIN-ALDO Registry), which included patients with PA seen at 20 tertiary centers between 2018 and 2022. Differences between patients with and without obesity were analyzed. RESULTS: A total of 415 patients were included; 189 (45.5%) with obesity. Median age was 55 years (range, 47.3-65.2 years) and 240 (58.4%) were male. Compared to those without obesity, patients with obesity had higher rates of diabetes mellitus, chronic kidney disease, obstructive apnea syndrome, left ventricular hypertrophy, prior cardiovascular events, higher means of systolic blood pressure, and required more antihypertensive drugs. Patients with PA and obesity also had higher values of serum glucose, glycated hemoglobin A1c, creatinine, uric acid, and triglycerides, and lower levels of high-density lipoprotein cholesterol. Levels of blood aldosterone (PAC) and renin were similar between patients with and without obesity. Body mass index was not correlated with PAC nor renin. The rates of adrenal lesions on imaging studies, as well as the rates of unilateral disease assessed by adrenal vein sampling or I-6ß-iodomethyl-19-norcholesterol scintigraphy, were similar between groups. CONCLUSION: Obesity in PA patients involves a worse cardiometabolic profile, and need for more antihypertensive drugs but similar PAC and renin levels, and rates of adrenal lesions and lateral disease than patients without obesity. However, obesity implicates a lower rate of hypertension cure after adrenalectomy.
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Hiperaldosteronismo , Hipertensão , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Hiperaldosteronismo/complicações , Hiperaldosteronismo/diagnóstico , Hiperaldosteronismo/epidemiologia , Anti-Hipertensivos/uso terapêutico , Aldosterona , Renina , Estudos Retrospectivos , Hipertensão/tratamento farmacológico , Adrenalectomia , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/tratamento farmacológicoRESUMO
Purpose: The aim of this study was to evaluate the prevalence of autonomous cortisol secretion (ACS) in patients with primary aldosteronism (PA) and its implications on cardiometabolic and surgical outcomes. Methods: This is a retrospective multicenter study of PA patients who underwent 1 mg dexamethasone-suppression test (DST) during diagnostic workup in 21 Spanish tertiary hospitals. ACS was defined as a cortisol post-DST >1.8 µg/dL (confirmed ACS if >5 µg/dL and possible ACS if 1.8-5 µg/dL) in the absence of specific clinical features of hypercortisolism. The cardiometabolic profile was compared with a control group with ACS without PA (ACS group) matched for age and DST levels. Results: The prevalence of ACS in the global cohort of patients with PA (n = 176) was 29% (ACS-PA; n = 51). Ten patients had confirmed ACS and 41 possible ACS. The cardiometabolic profile of ACS-PA and PA-only patients was similar, except for older age and larger tumor size of the adrenal lesion in the ACS-PA group. When comparing the ACS-PA group (n = 51) and the ACS group (n = 78), the prevalence of hypertension (OR 7.7 (2.64-22.32)) and cardiovascular events (OR 5.0 (2.29-11.07)) was higher in ACS-PA patients than in ACS patients. The coexistence of ACS in patients with PA did not affect the surgical outcomes, the proportion of biochemical cure and clinical cure being similar between ACS-PA and PA-only groups. Conclusion: Co-secretion of cortisol and aldosterone affects almost one-third of patients with PA. Its occurrence is more frequent in patients with larger tumors and advanced age. However, the cardiometabolic and surgical outcomes of patients with ACS-PA and PA-only are similar.
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An adverse intrauterine or periconceptional environment, such as hyperglycemia during pregnancy, can affect the DNA methylation pattern both in mothers and their offspring. In this study, we explored the epigenetic profile in maternal peripheral blood samples through pregnancy to find potential epigenetic biomarkers for gestational diabetes mellitus (GDM), as well as candidate genes involved in GDM development. We performed an epigenome-wide association study in maternal peripheral blood samples in 32 pregnant women (16 with GDM and 16 non-GDM) at pregnancy week 24-28 and 36-38. Biochemical, anthropometric, and obstetrical variables were collected from all the participants. The main results were validated in an independent cohort with different ethnic origin (European = 307; South Asians = 165). Two hundred and seventy-two CpGs sites remained significantly different between GDM and non-GDM pregnant women across two time points during pregnancy. The significant CpG sites were related to pathways associated with type I diabetes mellitus, insulin resistance and secretion. Cg01459453 (SELP gene) was the most differentiated in the GDM group versus non-GDM (73.6 vs. 60.9, p = 1.06E-11; FDR = 7.87E-06). Three CpG sites (cg01459453, cg15329406, and cg04095097) were able to discriminate between GDM cases and controls (AUC = 1; p = 1.26E-09). Three differentially methylated positions (DMPs) were replicated in an independent cohort. To conclude, epigenetic marks during pregnancy differed between GDM cases and controls suggesting a role for these genes in GDM development. Three CpGs were able to discriminate GDM and non-GDM groups with high specificity and sensitivity, which may be biomarker candidates for diagnosis or prediction of GDM.
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Diabetes Gestacional , Hiperglicemia , Gravidez , Humanos , Feminino , Diabetes Gestacional/genética , Metilação de DNA , Epigenoma , Hiperglicemia/genética , Biomarcadores , Epigênese GenéticaRESUMO
Diabetes is a metabolic disorder of glucose homeostasis in which ß cell destruction occurs silently and is detected mainly when symptoms appear. In the last few years, it has emerged a great interest in developing markers capable of detecting pancreatic ß cell death focused on improving early diagnosis and getting a better treatment response, mainly in type 1 diabetes. But other types of diabetes would also benefit from early detection of ß cell death. Differentially methylated circulating DNA is being studied as minimally invasive biomarker of cell death. We aimed to explore whether the unmethylated/methylated ratio of the insulin and amylin genes might be a good biomarker of ß cell death in different types of diabetes. A lower index ∆Ct indicates a higher rate of ß-cell death. Plasma samples from subjects without diabetes, pregnant women, pregnant with gestational diabetes (GDM), type 1 diabetes and type 2 diabetes were analyzed. A qPCR reaction with specific primers for both methylated and unmethylated fragments of insulin and amylin genes were carried out. Pregnant women, GDM and non- GDM, showed a higher ß-cell death for both markers (∆INS = 3.8 ± 2.1 and ∆Amylin = 8.5 ± 3.6), whereas T1D presented lower rate (∆INS = 6.2 ± 2.1 and ∆Amylin = 10.7 ± 2.9) comparable to healthy subjects. The insulin methylation index was associated with the newborn birth weight (r = 0.46; p = 0.033) and with insulin resistance (r = -0.533; p = 0.027) in the GDM group. The higher rate of ß-cell death was observed in pregnant women independently of their metabolic status. These indexes could be a good indicator of ß cell death in processes caused by defects on insulin secretion, insulin action, or both.
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Gestational diabetes mellitus (GDM) increases the risk of developing metabolic disorders in both pregnant women and their offspring. Factors such as nutrition or the intrauterine environment may play an important role, through epigenetic mechanisms, in the development of GDM. The aim of this work is to identify epigenetic marks involved in the mechanisms or pathways related to gestational diabetes. A total of 32 pregnant women were selected, 16 of them with GDM and 16 non-GDM. DNA methylation pattern was obtained from Illumina Methylation Epic BeadChip, from peripheral blood samples at the diagnostic visit (26-28 weeks). Differential methylated positions (DMPs) were extracted using ChAMP and limma package in R 2.9.10, with a threshold of FDR <0.05, deltabeta >|5|% and B >0. A total of 1.141 DMPs were found, and 714 were annotated in genes. A functional analysis was performed, and we found 23 genes significantly related to carbohydrate metabolism. Finally, a total of 27 DMPs were correlated with biochemical variables such as glucose levels at different points of oral glucose tolerance test, fasting glucose, cholesterol, HOMAIR and HbA1c, at different visits during pregnancy and postpartum. Our results show that there is a differentiated methylation pattern between GDM and non-GDM. Furthermore, the genes annotated to the DMPs could be implicated in the development of GDM as well as in alterations in related metabolic variables.