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BACKGROUND AND AIMS: The role of overweight and obesity in the development of atrial fibrillation (AF) is well established; however, the differential effect on the occurrence and recurrence of AF remains uncertain. The aim of this review is to compare the effect of underweight and varying degrees of obesity on onset of AF and in recurrent post-ablation AF, and, when possible, in relation to sex. METHODS: A systematic literature search was conducted in PubMed, Embase, and Cochrane Library from inception to January 31, 2023. Studies reporting frequency of newly-diagnosed AF and of recurrent post-ablation AF in different BMI categories, were included. 3400 records were screened and 50 met the inclusion criteria. Standardized data search and abstraction were performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. Data were extracted from the manuscripts and were analyzed using a random effect model. The outcome was the occurrence of AF in population studies and in patients undergoing ablation. RESULTS: Data from 50 studies were collected, of which 27 for newly-diagnosed AF and 23 for recurrent post-ablation AF, for a total of 15,134,939 patients, of which 15,115,181 in studies on newly-diagnosed AF and 19,758 in studies on recurrent post-ablation AF. Compared to normal weight, the increase in AF was significant (p < 0.01) for overweight, obese, and morbidly obese patients for newly-diagnosed AF, and for obese and morbidly obese patients for recurrent post-ablation AF. Newly-diagnosed AF was more frequent in obese female than obese male patients. CONCLUSION: The effect of increased BMI was greater on the onset of AF, and obese women were more affected than men.
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Aim of this review is to compare visceral and subcutaneous fat loss with all available strategies (diet and exercise, weight-loss promoting agents and bariatric surgery). Eighty-nine studies, all full papers, were analyzed to evaluate visceral and subcutaneous fat changes, measured through ultrasound, computerized tomography, magnetic resonance imaging and expressed as thickness, weight, area and volume. Studies were included in a meta-analysis (random-effects model). Intervention effect (absolute and percent changes of visceral and subcutaneous fat) was expressed as standardized mean differences, with 95% confidence intervals. Publication bias was formally assessed. The result was that subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; decrease of subcutaneous fat was greater than visceral fat when measured as area, volume and weight, not as thickness; percent decrease of visceral fat was always greater than percent decrease of subcutaneous fat, with no differences between different strategies. No intervention preferentially targets visceral fat. Basal visceral fat depots are smaller than basal subcutaneous fat depots. Visceral fat loss is linked to subcutaneous fat loss. With all strategies, percent decrease of visceral fat prevails on subcutaneous fat loss.
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Fármacos Antiobesidade/farmacologia , Cirurgia Bariátrica , Dieta , Exercício Físico/fisiologia , Gordura Intra-Abdominal/patologia , Obesidade/prevenção & controle , Gordura Subcutânea Abdominal/patologia , Redução de Peso/fisiologia , Fármacos Antiobesidade/uso terapêutico , Índice de Massa Corporal , Humanos , Obesidade/patologia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND: Uncontrolled studies have indicated appearance or progression of diabetic retinopathy in obese diabetic patients after bariatric surgery. The aim of this systematic review and meta-analysis was to compare the rate of appearance, as well as progression or regression of diabetic retinopathy in studies comparing medical and surgical treatment of obese type 2 diabetes. METHODS AND FINDINGS: Intervention effect (new cases of retinopathy, and cases with any change of diabetic retinopathy score) was expressed as odds ratio (OR), with 95% confidence intervals (CIs); change of diabetic retinopathy score was expressed as standardized mean difference (SMD), with 95% CIs. Meta-analyses were performed by a random-effects model according to DerSimonian and Laird. Heterogeneity was assessed through Q and I2 statistics for each comparison, and potential sources of heterogeneity were discussed where appropriate. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seven studies were analyzed, and incident cases of retinopathy were fewer with bariatric surgery than with medical treatment; change of retinopathy score (three studies) was not different, while only two studies were available on numbers of patients showing progression or regression of retinopathy. Heterogeneity was not significant, and publication bias was not present. CONCLUSIONS: Bariatric surgery seems to prevent new cases of diabetic retinopathy, but available studies are not sufficient to support progression or regression of retinopathy. Further studies are needed to draw firm conclusions on the effect of bariatric surgery on diabetic retinopathy.
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Cirurgia Bariátrica , Retinopatia Diabética/epidemiologia , Progressão da Doença , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/terapia , Humanos , Obesidade/cirurgia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Type 2 diabetes mellitus (T2DM) is associated with increased risk of severe comorbidities and mortality; its prevalence is increasing worldwide, linked with the increasing prevalence of obesity. Weight loss prevents the development of T2DM in obese subjects, and can reverse T2DM in morbid obesity. This paper reviews bariatric surgery as a means for prevention and treatment of T2DM and its complications, in comparison with medical treatment, and analyzes the possible mechanisms involved. In morbidly obese patients bariatric surgery results in stable weight loss and long-term reduction in incidence and prevalence of obesity-related comorbidities, especially T2DM. The efficacy of bariatric surgery in improving and normalizing glucose levels has been confirmed by a large number of studies, comparing surgery with medical therapy. When compared to each other, malabsorptive and mixed malabsorptive/restrictive surgery techniques have shown better outcomes than restrictive techniques in terms of T2DM remission. However it is demonstrated that T2DM can reappear in the following years, especially in patients with advanced age, female sex, longer duration of T2DM, poorer glycemic control, use of insulin before surgery and weight regain. Bariatric surgery is superior to conventional medical therapy in inducing significant weight loss and control of T2DM. Weight loss has pleiotropic effects: T2DM can disappear and then re-appear as a result of persistent beta-cells impairment, while other effects last much longer, as reduction of blood pressure and improvement of lipids and of kidney function. This is probably the reason for long-term prevention of cardiovascular events and of mortality in obese and in obese-diabetic patients. The effect of bariatric surgery on diabetic retinopathy is still controversial.
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Cirurgia Bariátrica/métodos , Diabetes Mellitus Tipo 2/terapia , Hipoglicemiantes/uso terapêutico , Complicações do Diabetes/cirurgia , Complicações do Diabetes/terapia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/cirurgia , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgiaRESUMO
AIMS: Obesity is associated with increased cardiovascular (CV) morbidity and mortality. Weight loss improves several risk factors for CV diseases, but anti-obesity medications and lifestyle interventions have failed to modify primary CV endpoints. This paper reviews bariatric surgery in prevention of CV diseases and CV mortality, and analyzes the possible mechanisms involved. DATA SYNTHESIS: In morbidly obese patients bariatric surgery results in stable weight loss and in long-term reduction in the prevalence and incidence of obesity-related comorbidities; controlled trials have shown superiority of bariatric surgery over medical therapy in inducing significant weight loss and improvement of CV risk factors. Bariatric surgery induces several metabolic improvements (resolution of type 2 diabetes mellitus, improvement of lipid metabolism and of insulin resistance, reduction of visceral fat, of subclinical endothelial dysfunction and inflammation), and functional improvements (reduction of hypertension, of sympathetic overactivity, of left and right ventricular hypertrophy), which can explain the protective effect towards CV disease. CONCLUSIONS: Reduction of CV diseases is mediated by the pleiotropic effects of weight loss through surgery. Available data do not allow conclusions on the comparative efficacy of different surgical techniques; the choice of the surgical technique for a single patient remains an open question, and it is likely that the degree of prevention of CV diseases depends, among other factors, on the baseline conditions of patients. Large prospective studies are needed to address this issue in morbidly obese patients.
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Cirurgia Bariátrica , Doenças Cardiovasculares/prevenção & controle , Medicina Baseada em Evidências , Obesidade Mórbida/cirurgia , Medicina de Precisão , Cirurgia Bariátrica/efeitos adversos , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/mortalidade , Comorbidade , Gastrectomia/efeitos adversos , Derivação Gástrica/efeitos adversos , Gastroplastia/efeitos adversos , Humanos , Obesidade Mórbida/epidemiologia , Redução de PesoRESUMO
AIM: Different intervention strategies can prevent type 2 diabetes (T2DM). Aim of the present systematic review and meta-analysis was to evaluate the effectiveness of different strategies. METHODS: Studies were grouped into 15 different strategies: 1: diet plus physical activity; 2: physical activity; 3-6: anti-diabetic drugs [glitazones, metformin, beta-cell stimulating drugs (sulphanylureas, glinides), alfa-glucosidase inhibitors]; 7-8: cardiovascular drugs (ACE inhibitors, ARB, calcium antagonists); 9-14 [diets, lipid-affecting drugs (orlistat, bezafibrate), vitamins, micronutrients, estrogens, alcohol, coffee]; 15: bariatric surgery. Only controlled studies were included in the analysis, whether randomized, non-randomized, observational studies, whether primarily designed to assess incident cases of diabetes, or performed with other purposes, such as control of hypertension, of ischemic heart disease or prevention of cardiovascular events. Appropriate methodology [preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement] was used. Seventy-one studies (490 813 subjects), published as full papers, were analysed to identify predictors of new cases of T2DM, and were included in a meta-analysis (random-effects model) to study the effect of different strategies. Intervention effect (new cases of diabetes) was expressed as odds ratio (OR), with 95% confidence intervals (C.I.s). Publication bias was formally assessed. RESULTS: Body mass index was in the overweight range for 13 groups, obese or morbidly obese in lipid-affecting drugs and in bariatric surgery. Non-surgical strategies, except for beta-cell stimulating drugs, estrogens and vitamins, were able to prevent T2DM, with different effectiveness, from 0.37 (C.I. 0.26-0.52) to 0.85 (C.I. 0.77-0.93); the most effective strategy was bariatric surgery in morbidly obese subjects [0.16 (C.I. 0.11,0.24)]. At meta-regression analysis, age of subjects and amount of weight lost were associated with effectiveness of intervention. CONCLUSIONS: These data indicate that several strategies prevent T2DM, making it possible to make a choice for the individual subject.
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Diabetes Mellitus Tipo 2/prevenção & controle , Medicina Baseada em Evidências , Obesidade Mórbida/terapia , Obesidade/terapia , Sobrepeso/terapia , Fármacos Antiobesidade/uso terapêutico , Cirurgia Bariátrica , Fármacos Cardiovasculares/uso terapêutico , Terapia Combinada , Ensaios Clínicos Controlados como Assunto , Diabetes Mellitus Tipo 2/etiologia , Dieta Redutora , Humanos , Hipoglicemiantes/uso terapêutico , Estilo de Vida , Atividade Motora , Obesidade/dietoterapia , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia , Obesidade Mórbida/fisiopatologia , Obesidade Mórbida/cirurgia , Sobrepeso/dietoterapia , Sobrepeso/tratamento farmacológico , Sobrepeso/fisiopatologia , Redução de Peso/efeitos dos fármacosRESUMO
Lifestyle changes to healthy diet (HD) and habitual physical activity (HPA) are recommended in type 2 diabetes mellitus (T2DM). Yet, for most people with diabetes, it may be difficult to start changing. We investigated the stage of change toward healthier lifestyles according to Prochaska's model, and the associated psychological factors in T2DM patients, as a prerequisite to improve strategies to implement behavior changes in the population. A total of 1,353 consecutive outpatients with T2DM attending 14 tertiary centers for diabetes treatment completed the validated EMME-3 questionnaire, consisting of two parallel sets of instruments to define the stage of change for HD and HPA, respectively. Logistic regression was used to determine the factors associated with stages that may hinder behavioral changes. A stage of change favoring progress to healthier behaviors was more common in the area of HD than in HPA, with higher scores in action and maintenance. Differences were observed in relation to gender, age and duration of disease. After adjustment for confounders, resistance to change toward HD was associated with higher body mass index (BMI) (odds ratio (OR) 1.05; 95 % confidence interval (CI) 1.02-1.08). Resistance to improve HPA also increased with BMI (OR 1.06; 95 % CI 1.03-1.10) and decreased with education level (OR 0.74; 95 % CI 0.64-0.92). Changing lifestyle, particularly in the area of HPA, is not perceived as an essential part of treatment by many subjects with T2DM. This evidence must be considered when planning behavioral programs, and specific interventions are needed to promote adherence to HPA.
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Diabetes Mellitus Tipo 2/dietoterapia , Estilo de Vida , Motivação , Atividade Motora , Adulto , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/psicologia , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e QuestionáriosRESUMO
Bariatric surgery developed in the late 1970 to treat severe hyperlipidemias in overweight individuals, not necessarily obese. Several techniques have been developed, and the concept has come first of a surgery for morbid obesity, then of a cure for diabetes in morbid obesity. There are other aspects of bariatric surgery that deserve attention, beyond BMI and diabetes, such as hypertension, poor life expectancy, increased prevalence of cancer, congestive heart failure, social inadequacy. The aim of this presentation is to review some recent development in clinical research, in the fields of liver steatosis, ferritin metabolism, and cholesterol metabolism. Liver steatosis, also called fatty liver encompasses a graduation of diseases with different clinical relevance and prognosis. NAFLD correlates with atherosclerosis, insulin resistance and diabetes mellitus. There is now evidence that weight loss, obtained through diet or restrictive surgery, reduces the prevalence (and the severity) of NAFLD. An other issue is represented by serum ferritin concentrations, that are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients, especially in the presence of obesity. Body iron contributes to excess oxidative stress already at non iron overload concentrations. Moreover, serum ferritin is an important and independent predictor of the development of diabetes. Weight loss is accompanied by reduction of ferritin, more after restrictive than malabsorptive surgery. Metabolic changes are greater after malabsorptive or mixed surgery than after purely restrictive surgery, and this has been ascribed to a greater weight loss. Studies comparing the two kinds of surgery indicate that, for the same amount of weight loss, decrease of cholesterol is greater with the former than with the latter techniques, and this difference is mainly due to a greater reduction of intestinal absorption of cholesterol. In the choice of surgery for the single patient, among other aspects, malabsorptive surgery seems to be more indicated in subjects with hyperlipidemia, especially with high cholesterol levels.
La cirugía bariátrica se desarrolló a finales de la década de los 70 para tratar la hiperlipidemia severa en personas con sobrepeso, no necesariamente obesos. A lo largo de los años se han desarrollado varias técnicas quirúrgicas que han sido utilizadas en primer lugar en la obesidad mórbida y posteriormente en el tratamiento de la diabetes. Hay otros aspectos de la cirugía bariátrica que merecen atención más allá del IMC y la diabetes, como la hipertensión, la pobre esperanza de vida, una mayor prevalencia de cáncer, insuficiencia cardíaca e inadaptación social. El objetivo de este artículo es revisar los recientes avances clínicos en campos de investigación relacionados con la esteatosis hepática, el metabolismo de ferritina y el metabolismo del colesterol. La esteatosis hepática, también llamada hígado graso abarca una serie de las enfermedades con diferente pronóstico y relevancia clínica. El Hígado Graso No Alcohólico (NAFLD siglas en ingles) se correlaciona con la aterosclerosis, resistencia a la insulina y diabetes mellitus. Hoy en día existen evidencias de que la pérdida de peso que se obtiene a través de la dieta o cirugía restrictiva, reduce la prevalencia (y la gravedad) de la NAFLD. Otro tema de estudio incluye las concentraciones de ferritina sérica, que están fuertemente asociadas con la fibrosis e inflamación lobular y portal en pacientes con NAFLD, especialmente en presencia de obesidad. El exceso de hierro corporal en obesos contribuye a un aumento del estrés oxidativo debido a una sobrecarga en su concentración. Por otra parte, la ferritina sérica es un indicador importante e independiente del desarrollo de la diabetes. La pérdida de peso se acompaña de una disminución de la ferritina. Esta disminución es más evidente tras una cirugía restrictiva que tras una malabsortiva. Los cambios metabólicos son mayores después de una cirugía malabsortiva o mixta que tras una cirugía puramente restrictiva, y esto se ha atribuido a una mayor pérdida de peso. Estudios que comparan los dos tipos de cirugía indican que, para la mismo índice de pérdida de peso, la disminución de colesterol es mayor con las primeras técnicas que con las últimas, y esta diferencia se debe principalmente a una mayor reducción de la absorción intestinal del colesterol. En la elección de la cirugía para un paciente concreto, entre otros aspectos, la cirugía de malabsorción parece estar más indicada en sujetos con hiperlipemia, especialmente con altos niveles de colesterol.
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Cirurgia Bariátrica , Colesterol/metabolismo , Fígado Gorduroso/cirurgia , Ferritinas/metabolismo , Humanos , Hepatopatia Gordurosa não AlcoólicaAssuntos
Diabetes Mellitus/tratamento farmacológico , Balão Gástrico/efeitos adversos , Nefropatias/patologia , Metformina/efeitos adversos , Obesidade Mórbida/complicações , Adulto , Feminino , Humanos , Nefropatias/etiologia , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/fisiopatologia , Fatores de RiscoRESUMO
AIM: Aim of this study was to analyse clinical correlates of HbA1c, and of overall, nocturnal, and severe hypoglycaemia, through direct-weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta-analysis. METHODS: Appropriate methodology (PRISMA statement) was used. Sixty-seven randomized studies, published as full papers were analysed to identify predictors of both HbA1c and hypoglycaemia; studies were included in a meta-analysis to study the effect of different insulin regimens or insulin analogues on HbA1c and hypoglycaemia during the first year of insulin treatment in type 2 diabetes patients. RESULTS: Final HbA1c, change of HbA1c, hypoglycaemia, nocturnal hypoglycaemia and severe hypoglycaemia were associated with intensity of treatment. Final HbA1c was higher with basal than with twice-a-day or prandial, and with twice-a-day than with prandial regimen, with opposite figures for hypoglycaemia. Within basal regimens, detemir and glargine were similar to NPH insulin on HbA1c, with less hypoglycaemia and nocturnal hypoglycaemia; within prandial regimens, new analogues were more effective than regular insulin on HbA1c, and induced less hypoglycaemia. The effect of glargine on HbA1c and on hypoglycaemia vanished with increasing number of insulin injections. CONCLUSION: Metabolic control and hypoglycaemia are associated with intensity of treatment. Basal regimens have a reduced effect on metabolic control, but are associated with lower frequency of hypoglycaemia. Newer analogues, short- and long-acting, yield better control and less hypoglycaemia than older analogues.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hemoglobinas Glicadas/metabolismo , Hipoglicemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina/uso terapêutico , Peso Corporal/efeitos dos fármacos , Diabetes Mellitus Tipo 2/sangue , Feminino , Humanos , Hipoglicemia/sangue , Hipoglicemiantes/farmacologia , Insulina/análogos & derivados , Insulina/farmacologia , Insulina de Ação Prolongada/farmacologia , Insulina de Ação Prolongada/uso terapêutico , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do TratamentoRESUMO
AIMS: To compare the efficacy and safety of insulin lispro protamine suspension (ILPS) versus insulin glargine once daily in a basal-bolus regimen in type 2 diabetes mellitus (T2DM) patients. METHODS: Three hundred eighty-three insulin-treated patients were randomized to either ILPS plus lispro or glargine plus lispro in this open-label 24-week European study. Insulin doses were titrated to predefined blood glucose (BG) targets. Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of the 95% confidence interval (CI) for the change of HbA1c from baseline to week 24 (adjusted for country and baseline HbA1c) with the non-inferiority margin of 0.4%. Secondary endpoints included HbA1c categories, BG profiles, insulin doses, hypoglycaemic episodes, adverse events and vital signs. RESULTS: Non-inferiority of ILPS versus glargine in the change of HbA1c from baseline was shown: least-square mean between-treatment difference (95% CI) was 0.1% (-0.11; 0.31). Mean changes at week 24 were -1.05% (ILPS) and -1.20% (glargine). HbA1c <7.0% was achieved by 21.7 versus 29.4% of patients. Mean basal/mealtime insulin doses at week 24 were 29.6/36.2 IU/day (ILPS) versus 32.8/42.2 IU/day (glargine); the difference was not statistically significant for total dose (p = 0.7). In both groups, 56.1/25.7% versus 63.6/19.3% of patients experienced any/nocturnal hypoglycaemia (p = 0.2 for both). No relevant differences were noted in any other variables. CONCLUSIONS: A basal-bolus regimen with ILPS once daily resulted in non-inferior glycaemic control compared to a similar regimen with glargine, without statistically significant or clinically relevant differences in hypoglycaemia. ILPS-based regimens can be considered an alternative to basal-bolus regimens with glargine for T2DM patients.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Insulina Lispro/uso terapêutico , Insulina de Ação Prolongada/uso terapêutico , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemiantes/administração & dosagem , Insulina Glargina , Insulina Lispro/administração & dosagem , Insulina de Ação Prolongada/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
AIM: This systematic review and meta-analysis was to evaluate the body weight increase and its clinical correlates, through direct weighted regressions, as well as the effect of different insulin regimens and insulin analogues, through meta-analysis. METHODS: Appropriate methodology according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was adhered to. Forty-six randomized studies, published as full papers, reporting the effect of insulin treatment on change in body weight were identified, and used to identify predictors of weight change; studies were included in a meta-analysis to study the effect of different insulin regimens or insulin analogues on weight change. RESULTS: Intensity of treatment [aim of study (fasting blood glucose, mg/dl), dose of insulin, final HbA1c, change of HbA1c and frequency of hypoglycaemia] was significantly associated with body weight increase, with small differences between basal versus twice-a-day and prandial regimen. At meta-analysis, body weight increase was lower with basal regimen than with twice-a-day regimen and than with a prandial regimen. Within all regimens, body weight increase was lower with detemir than with NPH, with no difference between glargine and NPH; only two studies directly compared detemir and glargine, indicating lower weight gain with the former insulin. Within twice-a-day regimens and within prandial regimens, comparison was between newer analogues and older drugs, with no significant difference in body weight increase. CONCLUSION: Body weight increase during the first year of insulin treatment is associated with the intensity of treatment; body weight increase also depends on the insulin regimen applied.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/efeitos adversos , Insulina/administração & dosagem , Insulina/efeitos adversos , Aumento de Peso/efeitos dos fármacos , Biomarcadores/sangue , Peso Corporal/efeitos dos fármacos , Esquema de Medicação , Feminino , Hemoglobinas Glicadas/efeitos dos fármacos , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/análogos & derivados , Masculino , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
AIMS/HYPOTHESIS: We determined the contribution to insulin resistance of the PH domain leucine-rich repeat protein phosphatase (PHLPP), which dephosphorylates Akt at Ser473, inhibiting its activity. We measured the abundance of PHLPP in fat and skeletal muscle from obese participants. To study the effect of PHLPP on insulin signalling, PHLPP (also known as PHLPP1) was overexpressed in HepG2 and L6 cells. METHODS: Subcutaneous fat samples were obtained from 82 morbidly obese and ten non-obese participants. Skeletal muscle samples were obtained from 12 obese and eight non-obese participants. Quantification of PHLPP-1 in human tissues was performed by immunoblotting. The functional consequences of recombinant PHLPP1 overexpression in hepatoma HepG2 cells and L6 myoblasts were investigated. RESULTS: Of the 82 obese participants, 31 had normal fasting glucose, 33 impaired fasting glucose and 18 type 2 diabetes. PHLPP-1 abundance was twofold higher in the three obese groups than in non-obese participants (p = 0.004). No differences were observed between obese participants with normal fasting glucose, impaired fasting glucose or type 2 diabetes. PHLPP-1 abundance was correlated with basal Akt Ser473 phosphorylation (r = -0.48; p = 0.001), BMI (r = 0.44; p < 0.0001), insulin (r = 0.35; p < 0.0001) and HOMA (r = 0.38; p < 0.0001). PHLPP-1 abundance was twofold higher in the skeletal muscle of 12 obese participants than in that of eight non-obese participants (p < 0.0001). Insulin treatment of HepG2 cells resulted in a dose- and time-dependent upregulation of PHLPP-1. Overexpression of PHLPP1 in HepG2 cells and L6 myoblasts resulted in impaired insulin signalling involving Akt/glycogen synthase kinase 3, glycogen synthesis and glucose transport. CONCLUSIONS/INTERPRETATION: Increased abundance of PHLPP-1, production of which is regulated by insulin, may represent a new molecular defect in insulin-resistant states such as obesity.
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Resistência à Insulina/fisiologia , Proteínas Nucleares/metabolismo , Obesidade/metabolismo , Obesidade/fisiopatologia , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Adolescente , Adulto , Idoso , Animais , Western Blotting , Linhagem Celular , Feminino , Células Hep G2 , Humanos , Técnicas In Vitro , Resistência à Insulina/genética , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/genética , Obesidade/genética , Fosfoproteínas Fosfatases/genética , Ratos , Adulto JovemRESUMO
AIM: The aim of this study was to estimate the prevalence of depressive symptoms in patients affected by subclinical hypothyroidism by means of Hamilton Rating Scale for Depression (HAM-D) and Montgomery-Asberg Depression Rating Scale (MADRS); to assess which depressive symptoms are prevalent in our population, with references to the factorialization of HAM-D by Cleary and Guy (1977); to verify whether levothyroxine replacement therapy alone can induce total remission of depressive symptoms. METHODS: The study enrolled 63 patients affected by subclinical hypothyroidism undergoing follow-up at the endocrinology service of San Paolo Hospital in Milan. All patients underwent an evaluation by means of HAM-D and MADRS scales and serum TSH, free T4, free T3, TPO-Ab and Tg-Ab levels were measured. RESULTS: We estimated a prevalence of depressive symptoms in our population of 63.5%. Concerning the qualitative assessment of psychiatric disturbances in the population we considered, our results showed that the most frequent symptoms were part of four factors, according to the Cleary and Guy factorialization of HAM-D: these factors are representative of anxiety and somatisation (factor I), cognitive impairment disturbances (factor III), psychomotor retardation (factor V) and sleep disorders (factor VI). Levothyroxine replacement therapy alone wasn't effective in inducing total remission of depressive symptoms. CONCLUSION: This study suggests the importance of a psychiatric evaluation in patients affected by subclinical hypothyroidism.
Assuntos
Depressão/epidemiologia , Hipotireoidismo/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Assintomáticas , Autoanticorpos/sangue , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Depressão/diagnóstico , Feminino , Terapia de Reposição Hormonal , Humanos , Hipotireoidismo/diagnóstico , Hipotireoidismo/tratamento farmacológico , Hipotireoidismo/psicologia , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Escalas de Graduação Psiquiátrica , Tireotropina/sangue , Tiroxina/sangue , Tiroxina/uso terapêutico , Resultado do Tratamento , Tri-Iodotironina/sangue , Adulto JovemRESUMO
BACKGROUND AND AIMS: Several mechanisms are probably involved in obesity-related hypertension. This study was aimed to investigate the effect of significant weight loss on blood pressure and plasma renin activity (PRA) and aldosterone levels, other then on metabolic profile, in normotensive and hypertensive obese subjects. METHODS AND RESULTS: Forty hypertensive and 55 normotensive obese subjects were studied under basal conditions and again 1 year after significant weight loss obtained through laparoscopic adjustable gastric banding (LAGB). Weight, waist circumference, blood glucose, insulin, electrolytes (Na and K), lipids and supine and upright PRA and aldosterone were evaluated. All parameters evaluated improved, except for total cholesterol, and electrolytes that did not change. Blood pressure decreased in hypertensive subjects, with a concordant decrease in PRA and supine aldosterone levels, not observed in normotensive patients. CONCLUSION: Weight loss is associated with reduction of blood pressure and of PRA and aldosterone levels in obese hypertensive subjects.
Assuntos
Aldosterona/sangue , Cirurgia Bariátrica/métodos , Pressão Sanguínea , Hipertensão/etiologia , Laparoscopia , Obesidade Mórbida/cirurgia , Renina/sangue , Redução de Peso , Adulto , Glicemia/metabolismo , Regulação para Baixo , Feminino , Humanos , Hipertensão/sangue , Hipertensão/fisiopatologia , Insulina/sangue , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade Mórbida/sangue , Obesidade Mórbida/complicações , Obesidade Mórbida/fisiopatologia , Potássio/sangue , Sistema Renina-Angiotensina , Sódio/sangue , Fatores de Tempo , Resultado do Tratamento , Circunferência da CinturaRESUMO
BACKGROUND AND AIM: Bariatric surgery induces significant weight loss and improves glucose metabolism in obese patients (BMI>35 kg/m(2)). Our aim was to compare restrictive (LAGB, laparoscopic gastric banding) and malabsorptive approaches (BIBP, biliary-intestinal bypass) on the loss of fat-free mass (FFM), fat mass (FM), and on changes of glucose and lipid metabolism. METHODS AND RESULTS: Body composition (bio-impedance analysis, BIA), blood glucose (BG), insulin, triglycerides, total- and HDL-cholesterol, liver enzymes (AST and ALT) were measured at baseline and 1 year after surgery in patients undergoing LAGB, BIBP, and in diet-treated control patients. In the main study, with patients matched for initial BMI (43-55 kg/m(2), LAGB=24, BIBP=12, controls=6), decreases of BMI, FM, BG and cholesterol were greater in patients with BIBP than with LAGB (p<0.01), while decreases of FFM, insulin, HOMA-IR and triglycerides were similar. No effects on BMI, FM, FFM, BG, insulin, HOMA-IR or cholesterol were observed in the control patients. Decreases of BG, insulin, HOMA-IR, cholesterol and triglycerides correlated with FM but not with FFM decrease. Similar results were obtained in an additional study in patients with a different initial BMI (LAGB=25, BIBP=6, controls=24) and when considering all subjects together. A decrease of liver enzymes (ALT) was greater with LAGB than with BIBP, and HDL-cholesterol increased with LAGB and decreased with BIBP. CONCLUSION: BMI, FM, BG and cholesterol decrease more with malabsorptive than with restrictive surgery, while FFM, insulin, HOMA-IR and triglycerides decrease in a similar way. FFM loss is of low entity. Changes of glucose and lipid metabolism are proportional to a decrease of fat mass but not of fat-free mass.
Assuntos
Tecido Adiposo/patologia , Cirurgia Bariátrica/métodos , Glicemia/metabolismo , Índice de Massa Corporal , Absorção Intestinal , Derivação Jejunoileal , Metabolismo dos Lipídeos , Obesidade/sangue , Obesidade/cirurgia , Adulto , Biomarcadores/sangue , Composição Corporal , Colesterol/sangue , Gastroplastia/métodos , Humanos , Insulina/sangue , Laparoscopia , Pessoa de Meia-Idade , Obesidade/patologia , Período Pós-Operatório , Triglicerídeos/sangueRESUMO
BACKGROUND: Glycogen storage diseases are inherited defects which cause accumulation of glycogen in the tissues. Hepatic steatosis is defined as accumulation of fat within hepatocytes. On sonography, liver shows increased echogenicity both in glycogen storage diseases and steatosis. Liver hyperechogenicity in glycogen storage diseases may depend on accumulation of glycogen and/or fat. Chemical-shift magnetic resonance imaging can discriminate tissues only containing water from those containing both fat and water. AIM: The primary aim of the present study was to evaluate the usefulness of liver chemical-shift magnetic resonance imaging for detecting liver steatosis in patients with metabolic impairment due to glycogen storage diseases. SUBJECTS: Twelve patients with type I (n=8) or type III (n=4) glycogen storage diseases were studied and compared to 12 obese-overweight subjects with known liver steatosis. As control group 12 lean normal voluntary subjects were recruited. METHODS: Liver was evaluated by sonography and chemical-shift magnetic resonance imaging to calculate hepatic fat fraction. RESULTS: A significant difference in echogenicity between patients with glycogen storage diseases and normal subjects was observed (p<0.05), while this difference was not present between overweight-obese and glycogen storage diseases patients. On the contrary, fat fraction was similar between glycogen storage diseases patients and normal subjects and different between glycogen storage diseases patients and overweight-obese (p<0.05). CONCLUSION: The present data suggest that chemical-shift magnetic resonance imaging may exclude fat deposition as a cause of liver hyperechogenicity in subjects with glycogen storage diseases.
Assuntos
Fígado Gorduroso/complicações , Fígado Gorduroso/diagnóstico , Doença de Depósito de Glicogênio/complicações , Imageamento por Ressonância Magnética , Adolescente , Adulto , Criança , Fígado Gorduroso/diagnóstico por imagem , Feminino , Doença de Depósito de Glicogênio/metabolismo , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , UltrassonografiaRESUMO
Diagnosis of erectile dysfunction (ED) requires anamnestic investigation, being rarely spontaneously declared by patients. ED occurs frequently in diabetes mellitus, and anecdotal evidence suggests that ED occurs in obesity and in hypothyroidism. The aim of this study was to evaluate the prevalence of ED in patients affected by thyroid disorders (hypothyroidism and hyperthyroidism), in comparison with control subjects and with patients at risk for ED, such as patients with obesity and with type II diabetes mellitus, and the role of age. Spontaneous deposition and International Index of Erectile Dysfunction (IIEF)-5 questionnaire were considered for control subjects and for all patients. Spontaneous deposition of ED occurred for three diabetic patients, never for obese patients, thyroid patients and controls, confirming the value of IIEF-5 in detecting ED. ED was more frequent in obese subjects (42%), and in patients affected by thyroid diseases (59%), than in controls (30%), although less frequent than in type II diabetes mellitus (81%). Both below and above the age of 50 years, ED score was worse in thyroid patients than in control subjects, while ED was more frequent in obese patients than in control subjects only below the age of 50 years.