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AIMS/HYPOTHESIS: Our aim was to investigate structural changes of cutaneous Schwann cells (SCs), including nociceptive Schwann cells (nSCs) and axons, in individuals with diabetic polyneuropathy. We also aimed to investigate the relationship between these changes and peripheral neuropathic symptoms in type 1 diabetes. METHODS: Skin biopsies (3 mm) taken from carefully phenotyped participants with type 1 diabetes without polyneuropathy (T1D, n=25), type 1 diabetes with painless diabetic polyneuropathy (T1DPN, n=30) and type 1 diabetes with painful diabetic polyneuropathy (P-T1DPN, n=27), and from healthy control individuals (n=25) were immunostained with relevant antibodies to visualise SCs and nerve fibres. Stereological methods were used to quantify the expression of cutaneous SCs and nerve fibres. RESULTS: There was a difference in the number density of nSCs not abutting to nerve fibres between the groups (p=0.004) but not in the number density of nSCs abutting to nerve fibres, nor in solitary or total subepidermal SC soma number density. The overall dermal SC expression (measured by dermal SC area fraction and subepidermal SC process density) and peripheral nerve fibre expression (measured by intraepidermal nerve fibre density, dermal nerve fibre area fraction and subepidermal nerve fibre density) differed between the groups (all p<0.05): significant differences were seen in participants with T1DPN and P-T1DPN compared with those without diabetic polyneuropathy (healthy control and T1D groups) (all p<0.05). No difference was found between participants in the T1DPN and P-T1DPN group, nor between participants in the T1D and healthy control group (all p>0.05). Correlational analysis showed that cutaneous SC processes and nerve fibres were highly associated, and they were weakly negatively correlated with different neuropathy measures. CONCLUSIONS/INTERPRETATION: Cutaneous SC processes and nerves, but not SC soma, are degenerated and interdependent in individuals with diabetic polyneuropathy. However, an increase in structurally damaged nSCs was seen in individuals with diabetic polyneuropathy. Furthermore, dermal SC processes and nerve fibres correlate weakly with clinical measures of neuropathy and may play a partial role in the pathophysiology of diabetic polyneuropathy in type 1 diabetes.
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Diabetes Mellitus Tipo 1 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 1/complicações , Fibras Nervosas/patologia , Nervos Periféricos/patologia , Células de Schwann/patologiaRESUMO
INTRODUCTION: Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage-SFN, LFN, and MFN-in T1DM-associated DPN, both with and without pain. RESEARCH DESIGN AND METHODS: In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests). RESULTS: MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern. CONCLUSIONS: DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.
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Diabetes Mellitus Tipo 1 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/epidemiologia , Neuropatias Diabéticas/epidemiologia , Neuropatias Diabéticas/patologia , Neuropatias Diabéticas/diagnóstico , Neuropatias Diabéticas/etiologia , Masculino , Estudos Transversais , Feminino , Adulto , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Prevalência , Estudos de Casos e Controles , Seguimentos , Condução Nervosa/fisiologia , Prognóstico , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity. METHODS: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial. DISCUSSION: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future. ADMINISTRATIVE INFORMATION: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023.
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BACKGROUND AND OBJECTIVES: Diabetic polyneuropathy (DPN) is a complication of diabetes characterized by pain or lack of peripheral sensation, but the underlying mechanisms are not yet fully understood. Recent evidence showed increased cutaneous macrophage infiltration in patients with type 2 diabetes and painful DPN, and this study aimed to understand whether the same applies to type 1 diabetes. METHODS: The study included 104 participants: 26 healthy controls and 78 participants with type 1 diabetes (participants without DPN [n = 24], participants with painless DPN [n = 29], and participants with painful DPN [n = 25]). Two immune cells, dermal IBA1+ macrophages and epidermal Langerhans cells (LCs, CD207+), were visualized and quantified using immunohistological labeling and stereological counting methods on skin biopsies from the participants. The IBA1+ macrophage infiltration, LC number density, LC soma cross-sectional area, and LC processes were measured in this study. RESULTS: Significant difference in IBA1+ macrophage expression was seen between the groups (p = 0.003), with lower expression of IBA1 in participants with DPN. No differences in LC morphologies (LC number density, soma cross-sectional area, and process level) were found between the groups (all p > 0.05). In addition, IBA1+ macrophages, but not LCs, correlated with intraepidermal nerve fiber density, Michigan neuropathy symptom inventory, (questionnaire and total score), severity of neuropathy as assessed by the Toronto clinical neuropathy score, and vibration detection threshold in the whole study cohort. DISCUSSION: This study showed expressional differences of cutaneous IBA1+ macrophages but not LC in participants with type 1 diabetes-induced DPN compared with those in controls. The study suggests that a reduction in macrophages may play a role in the development and progression of autoimmune-induced diabetic neuropathy.
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Diabetes Mellitus Tipo 1 , Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Humanos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/patologia , Neuropatias Diabéticas/complicações , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/patologia , Pele/patologia , DorRESUMO
Introduction: Multidisciplinary Team Conferences (MDTs) are complex interventions in the modern healthcare system and they promote a model of coordinated patient care and management. However, MDTs within chronic diseases are poorly defined. Therefore, the aim of this scoping review was to summarise the current literature on physician-led in-hospital MDTs in chronic non-malignant diseases. Method: Following the PRISMA-ScR guideline for scoping reviews, a search on MDT interventions in adult patients, with three or more medical specialties represented, was performed. Results: We identified 2790 studies, from which 8 studies were included. The majority of studies were non-randomised and focused on a single disease entity such as infective endocarditis, atrial fibrillation, IgG4-related disease, or arterial and venous thrombosis. The main reason for referral was confirmation or establishment of a diagnosis, and the MDT members were primarily from medical specialties gathered especially for the MDT. Outcomes of the included studies were grouped into process indicators and outcome indicators. Process indicators included changes in diagnostic confirmation as well as therapeutic strategy and management. All studies reporting process indicators demonstrated significant changes before and after the MDT. Conclusion: MDTs within chronic diseases appeared highly heterogeneous with respect to structure, reasons for referral, and choice of outcomes. While process indicators, such as change in diagnosis, and treatment management/plan seem improved, such have not been demonstrated through outcome indicators.
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Background The aim of this study was to prospectively evaluate the effects of renal artery stenting in consecutive patients with severe atherosclerotic renal artery stenosis and high-risk clinical presentations as defined in a national protocol developed in 2015. Methods and Results Since the protocol was initiated, 102 patients have been referred for revascularization according to the following high-risk criteria: severe renal artery stenosis (≥70%) with true resistant hypertension, rapidly declining kidney function, or recurrent heart failure/sudden pulmonary edema. At baseline, the mean 24-hour ambulatory systolic blood pressure was 166.2 mm Hg (95% CI, 162.0-170.4), the defined daily dose of antihypertensive medication was 6.5 (95% CI, 5.8-7.3), and the estimated glomerular filtration rate was 41.1 mL/min per 1.73m2 (95% CI, 36.6-45.6). In 96 patients with available 3-month follow-up data, mean 24-hour ambulatory systolic blood pressure decreased by 19.6 mm Hg (95% CI, 15.4-23.8; P<0.001), the defined daily dose of antihypertensive medication was reduced by 52% (95% CI, 41%-62%; P<0.001), and estimated glomerular filtration rate increased by 7.8 mL/min per 1.73m2 (95% CI, 4.5-11.1; P<0.001). All changes persisted after 24 month follow-up. Among 17 patients with a history of hospitalization for acute decompensated heart failure, 14 patients had no new episodes after successful revascularization. Conclusions In this prospective cohort study, we observed a reduction in blood pressure and antihypertensive medication, an increase in estimated glomerular filtration rate, and a decrease in new hospital admissions attributable to heart failure/sudden pulmonary edema after renal artery stenting. Registration URL: https://clinicaltrials.gov. Identifier: NCT02770066.
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Angioplastia com Balão , Obstrução da Artéria Renal , Angioplastia com Balão/efeitos adversos , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea , Estudos de Coortes , Taxa de Filtração Glomerular , Humanos , Estudos Prospectivos , Artéria Renal , Obstrução da Artéria Renal/complicações , Obstrução da Artéria Renal/terapia , Stents , Resultado do TratamentoRESUMO
INTRODUCTION: Kidney transplantation is the optimal treatment for many patients with end-stage renal disease (ESRD). Due to shortage of donor kidneys in Denmark, there is a need to expand the possibilities for donation. At the Odense University Hospital (OUH), we have introduced ABO-incompatible kidney transplantation. We used antigenspecific immunoadsorptions to remove blood group antibodies and anti-CD20 antibody (rituximab) to inhibit the antibody production. The aim of introducing the ABO-incompatible kidney transplantation at the OUH was to increase the rate of living donor kidney transplantation without increasing rejection or mortality rates. MATERIAL AND METHODS: Retrospective evaluation. Eleven patients received ABO-incompatible kidney transplantation. The patients were followed for 3-26 months. RESULTS: One patient had an antibody-mediated rejection, one patient suffered T-cell-mediated rejection, and one patient died of myocardial infarction with a functioning graft on the third post-operative day. Both rejections were treated effectively. Among the patients, the average serum creatinine level was 128 micromol/l. CONCLUSION: The rejection and mortality rates for ABO-incompatible kidney transplantation at the OUH are similar to the results from ABO-compatible kidney transplantations performed at the OUH and at other hospitals.
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Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos/imunologia , Falência Renal Crônica/cirurgia , Transplante de Rim/métodos , Adulto , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos/uso terapêutico , Antígenos CD20/imunologia , Incompatibilidade de Grupos Sanguíneos/sangue , Creatinina/sangue , Dinamarca , Feminino , Rejeição de Enxerto , Humanos , Fatores Imunológicos/uso terapêutico , Imunossupressores/uso terapêutico , Falência Renal Crônica/sangue , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/análogos & derivados , Ácido Micofenólico/uso terapêutico , Estudos Retrospectivos , Rituximab , Tacrolimo/uso terapêuticoRESUMO
OBJECTIVE: Twin studies are used extensively to decompose the variance of a trait, mainly to estimate the heritability of the trait. A second purpose of such studies is to estimate to what extent the non-genetic variance is shared or specific to individuals. To a lesser extent the twin studies have been used in bivariate or multivariate analysis to elucidate common genetic factors to two or more traits. METHODS AND RESULTS: In the present study the variances of traits related to lipid metabolism is decomposed in a relatively large Danish twin population, including bivariate analysis to detect possible common genetic factors of the traits. CONCLUSIONS: The heritabilities of apolipoprotein B and E, cholesterol, LDL, and high density lipoprotein (HDL) were significant in the general population, although gender-specific levels and significance were detected. Heritabilities of apolipoprotein A1, triglycerides, and very low density protein (VLDL) were only significant when the population was stratified according to gender.
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Apolipoproteínas/sangue , Colesterol/sangue , Característica Quantitativa Herdável , Triglicerídeos/sangue , Adulto , Idoso , Apolipoproteínas/genética , Colesterol/genética , Dinamarca , Feminino , Humanos , Lipoproteínas/sangue , Lipoproteínas/genética , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores Sexuais , Triglicerídeos/genéticaRESUMO
OBJECTIVE: To perform an audit on the examination of hirsute patients and to establish a rational routine examination program in an outpatient endocrine clinic. DESIGN: Systematic, retrospective audit. SETTING: Academic tertiary-care medical center. PATIENT(S): Three hundred forty women with hirsutism as the referral diagnosis. INTERVENTION(S): Hormone analyses and ACTH tests during cycle days 2-8, 2 hours of oral glucose tolerance test (OGTT), and vaginal ultrasound. MAIN OUTCOME MEASURE(S): End diagnosis, fasting, 30-, 60-, and 120-minute oral glucose-stimulated levels of insulin and capillary blood glucose. RESULT(S): Two hundred one patients were diagnosed as having idiopathic hirsutism (IH) and 134 as having polycystic ovary syndrome (PCOS). End diagnosis: prolactinoma: n = 1, Cushing's syndrome: n = 1, androgen-producing ovarian tumor: n = 1, late-onset 21-hydroxylase defects: n = 2. During OGTT, 4.9% (13 of 263) had previously undiagnosed diabetes; no significant difference in diabetes prevalence was found between idiopathic hirsutism and PCOS. For 50.8%, fasting insulin values were in the upper quartile for a reference population. CONCLUSION(S): Initial evaluation of hirsute patients with irregular menses should include serum (s)-17alpha-hydroxyprogesterone, s-prolactin, s-Testosterone (T), and s-sex hormone-binding globulin. Further evaluation is needed in patients with markedly elevated s-T or with clinical Cushing's syndrome. Hirsute patients have a high risk of diabetes, although this could be due to the high number of overweight patients among this population.
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Doenças do Sistema Endócrino/complicações , Doenças do Sistema Endócrino/epidemiologia , Intolerância à Glucose/complicações , Intolerância à Glucose/epidemiologia , Hirsutismo/complicações , Pré-Menopausa , População Branca , Hiperplasia Suprarrenal Congênita/classificação , Hiperplasia Suprarrenal Congênita/epidemiologia , Adulto , Androgênios/biossíntese , Síndrome de Cushing/complicações , Síndrome de Cushing/epidemiologia , Diabetes Mellitus/epidemiologia , Jejum/sangue , Feminino , Teste de Tolerância a Glucose , Humanos , Insulina/sangue , Resistência à Insulina , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/metabolismo , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/epidemiologia , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/epidemiologia , Prevalência , Prolactinoma/complicações , Prolactinoma/epidemiologia , Encaminhamento e ConsultaRESUMO
In conditions with albuminuria, plasminogen is aberrantly filtered across the glomerular barrier and activated along the tubular system to plasmin. In the collecting duct, plasmin activates epithelial sodium channels (ENaC) proteolytically. Hyperactivity of ENaC could link microalbuminuria/proteinuria to resistant hypertension. Amiloride, an ENaC inhibitor, inhibits urokinase-type plasminogen activator. We hypothesized that amiloride (1) reduces blood pressure (BP); (2) attenuates plasminogen-to-plasmin activation; and (3) inhibits urine urokinase-type plasminogen activator in patients with resistant hypertension and type 2 diabetes mellitus (T2DM).In an open-label, non-randomized, 8-week intervention study, a cohort (n = 80) of patients with resistant hypertension and T2DM were included. Amiloride (5 mg/d) was added to previous triple antihypertensive treatment (including a diuretic and an inhibitor of the renin-angiotensin-aldosterone system) and increased to 10 mg if BP control was not achieved at 4 weeks. Complete dataset for urine analysis was available in 60 patients. Systolic and diastolic BP measured by ambulatory BP monitoring and office monitoring were significantly reduced. Average daytime BP was reduced by 6.3/3.0 mm Hg. Seven of 80 cases (9%) discontinued amiloride due to hyperkalemia >5.5 mol/L, the most frequent adverse event. Urinary plasmin(ogen) and albumin excretions were significantly reduced after amiloride treatment (P < .0001). Urokinase activity was detectable in macroalbuminuric urine, with a tendency toward reduction in activity after amiloride treatment. Amiloride lowers BP, urine plasminogen excretion and activation, and albumin/creatinine ratio, and is a relevant add-on medication for the treatment of resistant hypertension in patients with T2DM and microalbuminuria.
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Amilorida/uso terapêutico , Diabetes Mellitus Tipo 2/urina , Bloqueadores do Canal de Sódio Epitelial/uso terapêutico , Hipertensão/tratamento farmacológico , Plasminogênio/urina , Adulto , Idoso , Albuminúria/tratamento farmacológico , Anti-Hipertensivos/uso terapêutico , Western Blotting , Creatinina/urina , Diuréticos/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Humanos , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Espironolactona/uso terapêutico , Resultado do TratamentoRESUMO
BACKGROUND: The increased risk of cardiovascular morbidity and mortality associated with arterial hypertension is particularly pronounced in patients with type 2 diabetes mellitus. Blood pressure control is, therefore, decisively important but often not sufficiently achieved. OBJECTIVE: The primary objective of this study was to evaluate the antihypertensive effect of low dose spironolactone added to triple therapy for resistant hypertension in patients with type 2 diabetes measured by ambulatory monitoring. Secondary objectives were to evaluate the effects on glycaemic control and urinary albumin excretion as well as adverse effects. METHODS: In a multicentre, double-blind, randomized, placebo-controlled study 119 patients with blood pressure at or above 130/80 mmHg despite triple antihypertensive therapy were included. One tablet of 25 mg spironolactone or placebo was added to previous treatment and increased to two if blood pressure below 130/80 mmHg was not achieved after 4 weeks. Blood pressure was measured by ambulatory monitoring at baseline and after 16 weeks. RESULTS: The study was completed by 112 patients, 57 randomized to spironolactone and 55 to placebo. Average daytime placebo-corrected blood pressure was reduced by 8.9 (4.7-13.2)/3.7 (1.5-5.8) mmHg. Also office blood pressure, night-time, 24-h and pulse pressures were reduced significantly. Urinary albumin/creatinine ratio was significantly reduced in the spironolactone group. Glycaemic control remained unchanged. Hyperkalemia was the most frequent adverse event leading to dose reduction in three cases and discontinuation in one, whereas gynaecomastia was not reported. CONCLUSION: Low dose spironolactone exerts significant BP and urinary albumin creatinine ratio lowering effects in high-risk patients with resistant hypertension and type 2 diabetes mellitus.
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Pressão Sanguínea/efeitos dos fármacos , Complicações do Diabetes/tratamento farmacológico , Hipertensão/tratamento farmacológico , Espironolactona/administração & dosagem , Espironolactona/uso terapêutico , Adulto , Idoso , Albuminas/química , Aldosterona/metabolismo , Anti-Hipertensivos/uso terapêutico , Monitorização Ambulatorial da Pressão Arterial , Diabetes Mellitus Tipo 2 , Método Duplo-Cego , Feminino , Humanos , Hipertensão/diagnóstico , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Continuous subcutaneous insulin infusion (CSII) was introduced in the outpatient diabetes clinic in Fredericia, Denmark, in 2005. The aim of this study was to evaluate the quality of metabolic control and patient satisfaction in type 1 diabetic patients treated with CSII. MATERIAL AND METHODS: In 2009-2010, a database with registration of metabolic variables and patient satisfaction was established. The collected material is a combination of retrospective and prospective data. Patient satisfaction was measured by use of the Diabetes Treatment Satisfaction Questionnaire Status (DTSQs) and change (DTSQc) versions. RESULTS: By 31 December 2010, the database contained data from 68 active patients. Compared with before the initiation of CSII, glycohaemoglobin (HbA1c) had decreased significantly from 8.0% (5.8-13.7%) to 7.6% (6.1-9.5%). The improved glycaemic control was maintained each year until ≤ 4 years after initiation of CSII (p < 0.01).The fraction of patients with an HbA1c ≤ 7% had increased from 13% to 24%, the fraction of patients with an HbA1c > 9% had decreased from 18% to 3%, and the number of serious attacks of hypoglycaemia had decreased (p < 0.05). Only three episodes of ketoacidosis were observed. The DTSQs and DTSQc showed a higher patient satisfaction during CSII treatment (p < 0.01) than before its introduction. Compared with before the introduction of CSII, the patient satisfaction score had increased from 19 (12-33) to 34.5 (27-36) (p < 0.01). CONCLUSION: Type 1 diabetes patients who were changed from treatment with multi-injection therapy to CSII showed improved glycaemic control, a reduced number of hypoglycaemic attacks and improved and very high levels of patient satisfaction.
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Diabetes Mellitus Tipo 1/tratamento farmacológico , Infusões Subcutâneas , Insulina/administração & dosagem , Satisfação do Paciente , Adulto , Idoso , Assistência Ambulatorial , Glicemia/metabolismo , Dinamarca , Diabetes Mellitus Tipo 1/sangue , Cetoacidose Diabética/etiologia , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Hipoglicemia/induzido quimicamente , Infusões Subcutâneas/efeitos adversos , Insulina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Monitorização Ambulatorial , Inquéritos e Questionários , Adulto JovemRESUMO
BACKGROUND: The development of obesity is still a poorly understood process that is dependent on both genetic and environmental factors. OBJECTIVE: The objective was to examine how physical activity and the proportion of energy as protein in the diet modify the genetic variation of body mass index (BMI), waist circumference, and percentage body fat. DESIGN: Twins from Denmark (756 complete pairs) and Finland (278 complete pairs) aged 18-67 and 21-24 y, respectively, participated. The proportion of energy as protein in the diet was estimated by using food-frequency questionnaires. The participants reported the frequency and intensity of their leisure time physical activity. Waist circumference and BMI were measured. Percentage body fat was assessed in Denmark by using a bioelectrical impedance method. The data were analyzed by using gene-environment interaction models for twin data with the Mx statistical package (Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA). RESULTS: High physical activity was associated with lower mean values, and a high proportion of protein in the diet was associated with higher mean BMI, waist circumference, and percentage body fat and a reduction in genetic and environmental variances. Genetic modification by physical activity was statistically significant for BMI (-0.18; 95% CI: -0.31, -0.05) and waist circumference (-0.14; 95% CI: -0.22, -0.05) in the merged data. A high proportion of protein in the diet reduced genetic and environmental variances in BMI and waist circumference in Danish men but not in women or in Finnish men. CONCLUSIONS: Our results suggest that, in physically active individuals, the genetic variation in weight is reduced, which possibly suggests that physical activity is able to modify the action of the genes responsible for predisposition to obesity, whereas the protein content of the diet has no appreciable effect.
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Composição Corporal/genética , Tamanho Corporal/genética , Proteínas Alimentares/farmacologia , Doenças em Gêmeos/genética , Exercício Físico , Predisposição Genética para Doença , Obesidade/genética , Tecido Adiposo , Adolescente , Adulto , Idoso , Composição Corporal/efeitos dos fármacos , Índice de Massa Corporal , Tamanho Corporal/efeitos dos fármacos , Dinamarca , Proteínas Alimentares/administração & dosagem , Feminino , Finlândia , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Característica Quantitativa Herdável , Fatores Sexuais , Circunferência da Cintura , Adulto JovemRESUMO
Questionnaire-based zygosity assessment in twins has generally been found to be valid. In this report we evaluate sex- and age-differences in the validity of such questionnaire-based classification when using the four questions that have been the basis of zygosity assessment in The Danish Twin Registry for half a century. Three hundred and forty-two male and 531 female twin pairs were zygosity diagnosed using genetic markers and the results compared with the original questionnaire based classification. We found significant differences in the accuracy of questionnaire based zygosity diagnosis when stratifying the data for sex as well as age: males and monozygotic having the highest misclassification. However, even in the group with the highest misclassification rate the frequency was less than 8%. The overall misclassification rate was only 4%, with a clear tendency towards a higher proportion of misclassified monozygotic than dizygotic twins. The results demonstrate that questionnaire based zygosity diagnosis can still be regarded as a valid and valuable classification method for most purposes.
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Inquéritos e Questionários , Gêmeos Dizigóticos , Gêmeos Monozigóticos , Fatores Etários , Distribuição de Qui-Quadrado , Estudos de Coortes , Feminino , Humanos , Masculino , Sistema de Registros , Reprodutibilidade dos Testes , Fatores Sexuais , Inquéritos e Questionários/normasRESUMO
A well-known transformation from the bell-shaped Gaussian (normal) curve to a straight line in the rankit plot is investigated, and a tool for evaluation of the distribution of reference groups is presented. It is based on the confidence intervals for percentiles of the calculated Gaussian distribution and the percentage of cumulative points exceeding these limits. The process is to rank the reference values and plot the cumulative frequency points in a rankit plot with a logarithmic (In=log(e)) transformed abscissa. If the distribution is close to In-Gaussian the cumulative frequency points will fit to the straight line describing the calculated In-Gaussian distribution. The quality of the fit is evaluated by adding confidence intervals (CI) to each point on the line and calculating the percentage of points outside the hyperbola-like CI-curves. The assumption was that the 95% confidence curves for percentiles would show 5% of points outside these limits. However, computer simulations disclosed that approximate 10% of the series would have 5% or more points outside the limits. This is a conservative validation, which is more demanding than the Kolmogorov-Smirnov test. The graphical presentation, however, makes it easy to disclose deviations from In-Gaussianity, and to make other interpretations of the distributions, e.g., comparison to non-Gaussian distributions in the same plot, where the cumulative frequency percentage can be read from the ordinate. A long list of examples of In-Gaussian distributions of subgroups of reference values from healthy individuals is presented. In addition, distributions of values from well-defined diseased individuals may show up as In-Gaussian. It is evident from the examples that the rankit transformation and simple graphical evaluation for non-Gaussianity is a useful tool for the description of sub-groups.
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Valores de Referência , Distribuições Estatísticas , Análise Química do Sangue/normas , Intervalos de Confiança , Interpretação Estatística de Dados , Humanos , Estado Pré-Diabético/diagnósticoRESUMO
Body mass index (BMI), a simple anthropometric measure, is the most frequently used measure of adiposity and has been instrumental in documenting the worldwide increase in the prevalence of obesity witnessed during the last decades. Although this increase in overweight and obesity is thought to be mainly due to environmental changes, i.e., sedentary lifestyles and high caloric diets, consistent evidence from twin studies demonstrates high heritability and the importance of genetic differences for normal variation in BMI. We analysed self-reported data on BMI from approximately 37,000 complete twin pairs (including opposite sex pairs) aged 20-29 and 30-39 from eight different twin registries participating in the GenomEUtwin project. Quantitative genetic analyses were conducted and sex differences were explored. Variation in BMI was greater for women than for men, and in both sexes was primarily explained by additive genetic variance in all countries. Sex differences in the variance components were consistently significant. Results from analyses of opposite sex pairs also showed evidence of sex-specific genetic effects suggesting there may be some differences between men and women in the genetic factors that influence variation in BMI. These results encourage the continued search for genes of importance to the body composition and the development of obesity. Furthermore, they suggest that strategies to identify predisposing genes may benefit from taking into account potential sex specific effects.