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BACKGROUND: Primary aldosteronism (PA) is a frequent cause of hypertension. Aldosterone excess together with high dietary salt intake aggravates cardiovascular damage, despite guideline-recommended mineralocorticoid receptor antagonist (MRA) treatment. OBJECTIVES: To investigate the antihypertensive impact of a moderate dietary salt restriction and associated physiological changes, including mental well-being. METHODS: A total of 41 patients with PA on a stable antihypertensive regimen-including MRA-followed a dietary salt restriction for 12 weeks with structured nutritional training and consolidation by a mobile health app. Salt intake and adherence were monitored every 4 weeks using 24-h urinary sodium excretion and nutrition protocols. Body composition was assessed by bioimpedance analysis and mental well-being by validated questionnaires. RESULTS: Dietary salt intake significantly decreased from 9.1 to 5.2 g/d at the end of the study. In parallel, systolic (130 vs. 121 mm Hg) and diastolic blood pressure (BP) (84 vs. 81 mm Hg) improved significantly. Patients' aptitude of estimating dietary salt content was refined significantly (underestimation by 2.4 vs. 1.4 g/d). Salt restriction entailed a significant weight loss of 1.4 kg, improvement in pulse pressure (46 vs. 40 mm Hg) and normalization of depressive symptoms (PHQD scale, p < 0.05). Salt restriction, cortisol after dexamethasone suppression test and dosage of renin-angiotensin-aldosterone-system (RAAS) blockers were independently associated with BP reduction. CONCLUSION: A moderate restriction of dietary salt intake in patients with PA substantially reduces BP and depressive symptoms. Moreover, the findings underline that a sufficient RAAS blockade seems to augment the effects of salt restriction on BP and cardiovascular risk.
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Hiperaldosteronismo , Hipertensão , Humanos , Aldosterona , Anti-Hipertensivos/farmacologia , Pressão Sanguínea , Hiperaldosteronismo/tratamento farmacológico , Cloreto de Sódio na DietaRESUMO
Background/objective Type 2 diabetes related to metabolic syndrome is often partially reversible after weight loss. We conducted a pilot trial on whether complete remission to the point of a normalized real-life glucose profile, measured by continuous subcutaneous monitoring, can be achieved. Methods We conducted a mono-center, single-arm intervention trial between January 20, 2020, and January 12, 2021, in Munich, Germany. Ten participants had type 2 diabetes related to metabolic syndrome for a maximum of six years. They received a six-month lifestyle intervention including up to three months of a very-low-calorie formula diet, followed by stepwise food reintroduction and regular behavioral lifestyle counseling. The primary outcome was the status of glucose control at the end of the intervention. Complete remission was defined as normalization of the real-life glucose profile without glucose-lowering medication over at least five days. We measured anthropometric and biochemical parameters, body fat distribution by MRI, and insulin secretory reserve by an arginine stimulation test. Results Seven participants completed the trial, one reached complete remission, three achieved partial remission, and three displayed improved glucose control still in the diabetic range. A reduction of median glycosylated hemoglobin by -10 mmol/mol (-22.0 to -5.0; p = 0.016) co-occurred with weight loss of -6.4 kg (-14.2 to -3.5; p = 0.031). The insulin secretory reserve remained unchanged. Conclusions Complete remission of type 2 diabetes related to metabolic syndrome to the point of a normalized real-life glucose profile is possible through lifestyle intervention. Full intervention success remains challenging even with intensive counseling and support.
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AIMS: Women after gestational diabetes mellitus (GDM) are a risk group for cardiometabolic diseases but are hard to reach by conventional lifestyle programs. Therefore, we tested whether a novel, smartphone-delivered intervention, TRIANGLE, is accepted by women after GDM and alters cardiometabolic risk behaviors and outcomes. TRIANGLE targets gradual habit change of mind and emotion, physical activity, nutrition, and sleep. METHODS: We conducted a 6-month multicenter, randomized-controlled trial of TRIANGLE versus standard care with 66 women 3-18 months after GDM in Germany. The primary outcome was the proportion of women achieving ≥3 out of 5 Diabetes Prevention Program goals, i.e. physical activity ≥150 min/week (moderate to high intensity), fiber intake ≥15 g/1,000 kcal, fat intake <30% of total energy intake, saturated fat intake <10% of total energy intake, and weight reduction ≥5% if BMI ≥23 kg/m2 or weight maintenance if BMI <23 kg/m2. Intervention participants also rated the TRIANGLE app in the Mobile Application Rating Scale (uMARS). RESULTS: In the predefined, modified intention-to-treat analysis including 64 women, 6 out of 27 women in the intervention group [22%(10-40)] and 3 out of 27 women in the control group [11%(3-27)] reached the primary outcome (p = 0.47). In the predefined per-protocol intervention subgroup, the proportion was 4 out of 14 women [29%(11-55); p = 0.20 vs. control]. TRIANGLE app users were active on 42% of days and rated the app's quality and perceived impact with 4.3±0.8 out of 5 uMARS points. CONCLUSIONS: This first trial did not show the efficacy of the TRIANGLE intervention. However, the app was well accepted and considered helpful by most users. Therefore, this trial supports further development and testing of TRIANGLE and other app interventions for women after GDM. Additionally, it identifies necessary adaptations in trial design to better accommodate non-intensive lifestyle interventions for this target group. TRIAL REGISTRATION: Trial registration at drks.de (DRKS00012996).
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Doenças Cardiovasculares , Diabetes Gestacional , Aplicativos Móveis , Diabetes Gestacional/prevenção & controle , Feminino , Humanos , Estilo de Vida , Masculino , Gravidez , Assunção de RiscosRESUMO
BACKGROUND: The myokine myostatin regulates muscle mass and has been linked to insulin resistance and metabolic syndrome. However, data on its role in humans is still limited. We, therefore, investigated the associations of serum myostatin with muscle mass, physical fitness, and components of the metabolic syndrome in a cohort of premenopausal women. METHODS: We undertook a cross-sectional analysis of 233 women from the monocenter study PPSDiab, conducted in Munich, Germany. Participants had recently completed a pregnancy with or without gestational diabetes. Our analysis included medical history, anthropometrics, oral glucose tolerance testing, laboratory chemistry, cardiopulmonary exercise testing, and magnetic resonance imaging (n=142) of visceral fat volume, left quadriceps muscle mass, and muscle fat content. Serum myostatin was quantified by a competitive enzyme-linked immunosorbent assay. RESULTS: We observed positive correlations of serum myostatin with body mass index (ρ=0.235; p=0.0003), body fat percentage (ρ=0.166; p=0.011), waist circumference (ρ=0.206; p=0.002), intraabdominal fat volume (ρ=0.182; p=0.030) and high-sensitivity C-reactive protein (ρ=0.175; p=0.008). These correlations were reproduced in linear regression analyses with adjustment for age and time after delivery. We saw no correlations with muscle mass, physical fitness, insulin sensitivity, triglycerides, HDL cholesterol, and blood pressure. CONCLUSIONS: Our observation of elevated serum myostatin in women with a higher body fat percentage, visceral obesity, and elevated c-reactive protein suggests that this myokine contributes to the altered muscle-adipose tissue crosstalk in metabolic syndrome. Elevated myostatin may advance this pathophysiologic process and could also impair the efficacy of exercise interventions. Further mechanistic studies, therefore, seem warranted.
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Resistência à Insulina , Síndrome Metabólica , Índice de Massa Corporal , Peso Corporal , Proteína C-Reativa/metabolismo , Estudos Transversais , Feminino , Humanos , Insulina , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/metabolismo , Músculos/metabolismo , Miostatina , Aptidão Física/fisiologia , GravidezRESUMO
INTRODUCTION: Ten years ago, Germany started offering screening for gestational diabetes mellitus (GDM) to all pregnant women. This approach revealed more but also, on average, less severe cases of GDM than the risk-based screening practiced previously. We now examined the incidence of pre-diabetes and diabetes following a GDM diagnosis in the era of universal screening in Germany and compared our results with studies in the previous period. Additionally, we examined the year-to-year fluctuations of glucose tolerance after a pregnancy complicated by GDM. RESEARCH DESIGN AND METHODS: We report 5-year follow-up data from 202 women in the prospective, monocenter, postpartum study PPSDiab. Consecutive recruitment took place in Munich, Germany between 2011 and 2016. In the study, we conducted yearly examinations that included anthropometrics, laboratory chemistry and oral glucose tolerance testing. RESULTS: During the first 5 years post partum, 111 (55%) and 12 (6%) of the women developed pre-diabetes and type 2 diabetes, respectively, while 2 (1%) developed type 1 diabetes. Impaired fasting glucose (IFG) was the most common first manifestation of disturbed glucose tolerance, followed by impaired glucose tolerance (IGT), the combination of IFG and IGT, and diabetes. Glucose tolerance did not deteriorate steadily in most women but fluctuated from year to year. CONCLUSIONS: In our analysis, the incidence of diabetes, both type 1 and type 2, after GDM diagnosed in universal screening was substantially lower than in studies from the previous period of risk-based screening. Nevertheless, the high incidence of pre-diabetes we observed after GDM still confirms the importance of this diagnosis as a risk marker. Additionally, we documented frequent fluctuations of glucose tolerance from 1 year to the next. Therefore, a single postpartum glucose tolerance test, as currently practiced in routine care, may be insufficient for reliable risk stratification after GDM.
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Diabetes Mellitus Tipo 2 , Diabetes Gestacional , Estado Pré-Diabético , Glicemia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Feminino , Seguimentos , Humanos , Estado Pré-Diabético/epidemiologia , Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: Women with gestational diabetes mellitus (GDM) often develop type 2 diabetes later in life. It remains unclear whether this results solely from a common underlying predisposition or, whether a pregnancy itself persistently impairs glucose metabolism in predisposed women. We therefore examined how an additional pregnancy affected different aspects of glucose metabolism in women with previous GDM. RESEARCH DESIGN AND METHODS: Nested case-control study within the prospective cohort study PPSDiab, recruited in Munich, Germany from 2011-16. Cases (n = 41): women with previous GDM who completed an additional pregnancy; controls: no additional pregnancy, pairwise matching. ENDPOINTS: change of the area under the glucose curve (AUGC) of an oral glucose tolerance, of plasma glucose at 60' of the test (PG 60'), of the insulin sensitivity index (ISI) and of the disposition index (DI), all between before and after the additional pregnancy in cases/the corresponding observation period in controls. RESULTS: We observed no significant difference between cases and controls in the primary [ratio AUGC 1.05(0.92-1.15) vs. 0.97(0.85-1.14); p = 0.21] and in the secondary endpoints [difference PG 60', ratio ISI and ratio DI. CONCLUSION: We did not find a deleterious effect of an additional pregnancy on glucose metabolism in women with previous GDM.
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Glicemia/metabolismo , Diabetes Gestacional/sangue , Resultado da Gravidez/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Gravidez , Estudos Prospectivos , Fatores de RiscoRESUMO
OBJECTIVE: Clinically, type 2 diabetes mellitus (T2DM) is heterogeneous, but the prevailing pathophysiologic hypothesis nevertheless contends that components of metabolic syndrome are central to all cases of T2DM. Here, we re-evaluated this hypothesis. RESEARCH DESIGN AND METHODS: We conducted a cross-sectional analysis of 138 women from the monocenter, post gestational diabetes study PPSDiab, 73 of which had incident prediabetes or T2DM. Additionally, we examined all the 412 incident cases of T2DM in phases 3 to 9 of the Whitehall II study in comparison to healthy controls. Our analysis included a medical history, anthropometrics, oral glucose tolerance testing, and laboratory chemistry in both studies. Additional analyses from the PPSDiab Study consisted of cardiopulmonary exercise testing, magnetic resonance imaging, auto-antibody testing, and the exclusion of glucokinase maturity-onset diabetes of the young. RESULTS: We found that 33 (45%) of the women with prediabetes or T2DM in the PPSDiab study displayed no components of metabolic syndrome. They reached no point for metabolic syndrome in the National Cholesterol Education Program Adult Treatment Panel III score other than hyperglycemia and, moreover, had levels of liver fat content, plasma triglycerides, high-density lipoprotein cholesterol, c-reactive protein, and blood pressure that were comparable to healthy controls. In the Whitehall II study, 62 (15%) of the incident T2DM cases fulfilled the same criteria. In both studies, these cases without metabolic syndrome revealed insulin resistance and inadequately low insulin secretion. CONCLUSIONS: Our results contradict the hypothesis that components of metabolic syndrome are central to all cases of T2DM. Instead, they suggest the common occurrence of a second, unrelated pathophysiology.
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Diabetes Mellitus Tipo 2/etiologia , Diabetes Gestacional/epidemiologia , Síndrome Metabólica/epidemiologia , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Gestacional/patologia , Feminino , Alemanha/epidemiologia , Teste de Tolerância a Glucose , Humanos , Incidência , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/patologia , Gravidez , Fatores de RiscoRESUMO
BACKGROUND: An adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. METHODS: We compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45â¯min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. RESULTS: We found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15-20â¯min. CONCLUSION: We conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.
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Terapia por Exercício , Exercício Físico , Hormônios/sangue , Obesidade/metabolismo , Obesidade/terapia , Sobrepeso/metabolismo , Sobrepeso/terapia , Hormônio Adrenocorticotrópico/sangue , Adulto , Glicemia/análise , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/terapia , Teste de Esforço , Ácidos Graxos não Esterificados/sangue , Feminino , Hormônio do Crescimento Humano/sangue , Humanos , Insulina/metabolismo , Pré-MenopausaRESUMO
OBJECTIVE: The occurrence of pneumonia separates severe cases of COVID-19 from the majority of cases with mild disease. However, the factors determining whether or not pneumonia develops remain to be fully uncovered. We therefore explored the associations of several lifestyle factors with signs of pneumonia in COVID-19. METHODS: Between May and July 2020, we conducted an online survey of 201 adults in Germany who had recently gone through COVID-19, predominantly as outpatients. Of these, 165 had a PCR-based diagnosis and 36 had a retrospective diagnosis by antibody testing. The survey covered demographic information, eight lifestyle factors, comorbidities and medication use. We defined the main outcome as the presence vs. the absence of signs of pneumonia, represented by dyspnea, the requirement for oxygen therapy or intubation. RESULTS: Signs of pneumonia occurred in 39 of the 165 individuals with a PCR-based diagnosis of COVID-19 (23.6%). Among the lifestyle factors examined, only overweight/obesity was associated with signs of pneumonia (odds ratio 2.68 (1.29-5.59) p = 0.008). The observed association remained significant after multivariate adjustment, with BMI as a metric variable, and also after including the antibody-positive individuals into the analysis. CONCLUSIONS: This exploratory study finds an association of overweight/obesity with signs of pneumonia in COVID-19. This finding suggests that a signal proportional to body fat mass, such as the hormone leptin, impairs the body's ability to clear SARS-CoV-2 before pneumonia develops. This hypothesis concurs with previous work and should be investigated further to possibly reduce the proportion of severe cases of COVID-19.