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Campus de Presidente Prudente
MARIANA DE CARVALHO PINTO
PARÂMETROS NEUROPÁTICOS NO DIABETES MELLITUS
Presidente Prudente
2014
Faculdade de Ciências e TecnologiaSeção de Pós-GraduaçãoRua Roberto Simonsen, 305 CEP 19060 -900 Presidente Prudente SPTel 18 3229-5352 fax 18 3223-4519 posgrad@fct.unesp.br
1
Campus de Presidente Prudente
MARIANA DE CARVALHO PINTO
PARÂMETROS NEUROPÁTICOS NO DIABETES MELLITUS
Dissertação apresentada à Faculdade de Ciências e Tecnologia -FCT/UNESP, campus de Presidente Prudente, para obtenção dotítulo de Mestre no Programa de Pós -Graduação em Fisioterapia
Orientadora: Profa. Dra. Cristina Elena Prado Teles Fregonesi
Presidente Prudente
2014
Faculdade de Ciências e TecnologiaSeção de Pós-GraduaçãoRua Roberto Simonsen, 305 CEP 19060 -900 Presidente Prudente SPTel 18 3229-5352 fax 18 3223-4519 posgrad@fct.unesp.br
1
Campus de Presidente Prudente
MARIANA DE CARVALHO PINTO
PARÂMETROS NEUROPÁTICOS NO DIABETES MELLITUS
Dissertação apresentada à Faculdade de Ciências e Tecnologia -FCT/UNESP, campus de Presidente Prudente, para obtenção dotítulo de Mestre no Programa de Pós -Graduação em Fisioterapia
Orientadora: Profa. Dra. Cristina Elena Prado Teles Fregonesi
Presidente Prudente
2014
Faculdade de Ciências e TecnologiaSeção de Pós-GraduaçãoRua Roberto Simonsen, 305 CEP 19060 -900 Presidente Prudente SPTel 18 3229-5352 fax 18 3223-4519 posgrad@fct.unesp.br
1
Campus de Presidente Prudente
MARIANA DE CARVALHO PINTO
PARÂMETROS NEUROPÁTICOS NO DIABETES MELLITUS
Dissertação apresentada à Faculdade de Ciências e Tecnologia -FCT/UNESP, campus de Presidente Prudente, para obtenção dotítulo de Mestre no Programa de Pós -Graduação em Fisioterapia
Orientadora: Profa. Dra. Cristina Elena Prado Teles Fregonesi
Presidente Prudente
2014
Faculdade de Ciências e TecnologiaSeção de Pós-GraduaçãoRua Roberto Simonsen, 305 CEP 19060 -900 Presidente Prudente SPTel 18 3229-5352 fax 18 3223-4519 posgrad@fct.unesp.br
2
FICHA CATALOGRÁFICA
Pinto, Mariana de Carvalho.P729p Parâmetros Neuropáticos no Diabetes Mellitus / Mariana de Carvalho
Pinto. - Presidente Prudente : [s.n], 201475 f.
Orientador: Cristina Elena Prado Teles FregonesiDissertação (mestrado) - Universidade Estadual Paulista, Faculdade de
Ciências e TecnologiaInclui bibliografia
1. Fisioterapia. 2. Diabetes Mellitus. 3. Neuropatia Periférica. 4.Vasculopatia Periférica. 5. Variabilidade da Frequência Cardíaca. 6. Risco deQueda. I. Fregonesi, Cristina Elena Prado Teles. II. Universidade EstadualPaulista. Faculdade de Ciências e Tecnologia. III. Título.
3
4
-Dedicatória-
5
Dedico este trabalho especialmente a minha mãe.
À minha orientadora Cristina Elena Prado Teles Fregonesi.
Deus obrigada por toda luz enviada em meu auxílio.
6
-Agradecimentos-
7
Primeiramente agradeço a Deus por me amparar e trazer luz quando não mais havia
esperança.
Agradeço imensamente à Cristina Elena Prado Teles Fregonesi, por ter muita
paciência em me orientar, mas mais do que isso pela cumplicidade e orientação em questões
da vida. Não há palavras para descrever minha gratidão.
Alessandra, sem você nada do que es ta aqui seria possível. Espero que um dia possa
retribuir...
Regina obrigada por me ajudar. Sei que mesmo a distância você está perto...
Rose obrigada por me incentivar a seguir em frente e não desistir de um sonho.
As minhas amigas Naty, Taís, Pri e Mi qu e mesmo a distância sempre me estimularam
a seguir em frente.
A Denise e Lúcia, que primeiramente eram minhas pacientes, mas tornaram -se amigas
e tiveram muita paciência e sabedoria para me confortar em momentos difíceis.
Enfim, a todos que direta ou indiretamente contribuíram para este momento tão
especial na minha vida, o meu mais sincero...
...Muito Obrigada!
8
-Epígrafe-
9
“A pureza de coração é inseparável da simplicidade e da humildade; ela excluitodo pensamento de egoísmo e de orgulho; é por isso que Jesus toma a criança
como símbolo dessa pureza, como a tomou por símbolo de humildade. ”
Allan Kardec
10
-Sumário-
11
SUMÁRIO
Apresentação.................................................................................................. ........................ 12
Resumo Geral .................................................................................................................... .... 14
Abstract................................................................................................................................... 16
Introdução Geral.................................................................................................................... 18
Referências Bibliográficas da Introdução ........................................................................... 21
Artigo I: Mariana de Carvalho Pinto, Cristina Elena Prado Teles Fregonesi. Neuropatia
Autonômica no Diabetes Mellitus. A ser submetido no periódico: Cardiovascular
Diabetology (ISSN 1475-2840)......................................................................... ...................... 22
Artigo II: Mariana de Carvalho Pinto, Cristina Elena Prado Teles Fregonesi. Risco de
Quedas no Diabetes Mellitus. A ser submetido no periódico: Diabetes Research and
Clinical Practice (ISSN 0168-8227)........................................................................................ 34
Conclusão Geral..................................................................................................................... 46
Anexo 1:
Normas da Revista Cardiovascular Diabetology (ISSN 1475-2840)...................................... 48
Anexo 2:
Normas da Revista Diabetes Research and Clinical Practice (ISSN 0168-8227)................... 65
12
-Apresentação-
13
APRESENTAÇÃO
Esta dissertação é composta de resumo, introdução, dois artigos científicos e
conclusão provenientes da pesquisa “Parâmetros Neuropáticos no Diabetes Mellitus”,
desenvolvida no Laboratório de Estudos Clínicos em Fisioterapia (LECFisio) do
Departamento de Fisioterapia da Faculdade de Ciências e Tecnologia - Universidade Estadual
Paulista Julio de Mesquita Filho – Campus Presidente Prudente.
Em consonância com as normas do Programa de Pós-graduação em Fisioterapia desta
instituição, o artigo foi redigido de acordo com as normas dos periódicos: Cardiovascular
Diabetology (ISSN 1475-2840) e Diabetes Research and Clinical Practice (ISSN 0168-8227),
respectivamente, correspondentes aos artigos I e II.
Artigo I: Mariana de Carvalho Pinto , Cristina Elena Prado Teles Fregonesi. Neuropatia
Autonômica no Diabetes Mellitus. A ser submetido no periódico: Cardiovascular
Diabetology (ISSN 1475-2840).
Artigo II: Mariana de Carvalho Pinto, Cristina Elena Prado Teles Fregonesi. Risco de
Quedas no Diabetes Mellitus. A ser submetido no periódico: Diabetes Research and
Clinical Practice (ISSN 0168-8227).
14
-Resumo Geral-
15
A neuropatia diabética é caracterizada por uma síndrome clínica ou sub -clínica que afeta o
sistema nervoso central e periférico, incluindo o autonômico. Frente ao crescente número de
novos casos de diabetes mellitus e a elevada incidência de manifestações crônico -
degenerativas, como a neuropatia periférica e a neuropatia autonômica cardiovascular, este
estudo objetivou: a) fazer uma comparação da variabilidade cardíaca (VC), em indivíduos
com diabetes mellitus tipo 2 com confirmação de neuropatia diabética periférica, e indivíduo s
saudáveis.; b) identificar o risco de queda através de um teste de mobilidade funcional em não
diabéticos, diabéticos neuropatas e diabéticos neuropata -vasculopatas. Para tanto, no primeiro
estudo participaram 108 indivíduos divididos em grupo controle (GC) (n=34) e grupo
diabético neuropata (GDN) (n=74). Inicialmente, foram reali zados testes para confirmação da
neuropatia. Em seguida, a avaliação da atividade do sistema nervoso autônomo (SNA) foi
realizada por meio da VC com o auxílio do software Nerve-Express® (Heart Rhythm
Instruments, Metuchen, NJ, EUA). Já o segundo estudo, foi composto por 61 sujeitos de
ambos os gêneros divididos em GC (n=32), GDN (n=18) e grupo diabético neuropata
vasculopata (GDNV) (12). Os indivíduos passaram por avaliação inicial, por testes de
sensibilidade somatossensitiva, Escala para Diagnóstico da Polineuropatia Distal Diabética e
índice tornozelo/braço. A seguir, realizou -se “Time Up and Go Test” (TUGT) para avaliar oequilíbrio dinâmico. Foi observado, no primeiro e studo, na análise no domínio do tempo,
diminuição da VC na população diabética com neuropatia quando comparado ao GC,
representada pelo menor desvio padrão dos intervalos RR. A relação entre SNA simpático e
parassimpático apresentou valores superiores ao G C, indicado pelo índice LF/HF,
representando menor equilíbrio simpato vagal. No domínio da frequência, constatou -se
predomínio do SNA simpático em diabéticos, indicado pelo índice LF, que apresentou valores
superiores ao GC, não significante, porém limítro fe. No segundo estudo, os três grupos que
contem a amostra apresentaram homogeneidade entre si. Os valores referentes aos índices
glicêmicos de jejum apresentaram -se superiores nos grupos diabéticos. Já o aumento no índice
glicêmico pós prandial foi signif icativo no GDNV, quando comparado ao GC. O índice
glicêmico pós prandial do GDN foi superior ao do GC, porém não significante. Foi observado
um aumento progressivo e significante no tempo decorrido para a realização do teste de
mobilidade TUGT entre os trê s grupos, com valores maiores para o GDNV em relação ao
GDN e GC e para o GDN em relação ao GC. Por fim, conclui-se que a neuropatia diabética
representa danos à integridade do sistema nervoso autônomo bem como na função do sistema
músculo esquelético.
Palavras-chave: Diabetes Mellitus; Neuropatia Periférica; Vasculopatia Periférica;Variabilidade da Freqüência Cardíaca.
16
-Abstract-
17
Diabetic neuropathy is characterized by clinical or sub -clinical syndrome that affects the
central and peripheral nervous system including the autonomic. Tackle the growing number of
new cases of diabetes mellitus and the high incidence of chronic degenera tive disorders, such
as peripheral neuropathy and cardiovascular autonomic neuropathy, this study aimed to: a)
make a comparison of heart rate variability (CV), in individuals with diabetes mellitus type 2
with confirmation of diabetic peripheral neuropath y, and healthy individuals .; b) identify the
risk of falling through a functional mobility test in non -diabetic, diabetic neuropathy and
diabetic neuropathy-vasculopathies. Therefore, in the first study participated 108 individuals
divided into a control group (CG) (n = 34) and diabetic neuropathy group (GDN) (n = 74).
Initially, to confirm the neuropathy tests were performed. Then, the evaluation of the activity
of the autonomic nervous system (ANS) was performed by the VC with the help of Nerve -
Express® software (Heart Rhythm Instruments, Metuchen, NJ, USA). The second study
consisted of 61 subjects of both genders divided into GC (n = 32), GDN (n = 18) and diabetic
neuropathy vasculopata group (GDNV) (12). Individuals underwent initial evaluation by
somatosensory sensitivity tests, diagnosis of polyneuropathy for Scale Distal Diabetic and
ankle / brachial index. The following took place "Time Up and Go Test" (TUGT) to assess the
dynamic balance. Was observed in the first study, the analysis in the time do main, decreased
VC in the diabetic population with neuropathy when compared to the CG, represented by the
lower standard deviation of RR intervals. The relationship between sympathetic and
parasympathetic SNA was higher for the CG, indicated by the LF / HF ratio, representing less
sympathetic vagal balance. In the frequency domain, there was predominance of the
sympathetic ANS in diabetics, indicated by LF ratio, which values above the GC, not
significant, but borderline. In the second study, the three grou ps containing the sample
showed homogeneity among themselves. The values for the fasting glycemic indices were
higher in diabetic groups. The increase in post prandial glycemic index was significant in
GDNV when compared to GC. The postprandial glycemic in dex GDN was superior to the
CG, but not significant. A progressive and significant increase in the time taken to perform
the TUGT mobility test was observed between the three groups, with higher values for the
GDNV regarding the GDN and GC and the GDN comp ared to the CG. Finally, it is concluded
that the diabetic neuropathy is damage to the autonomic nervous system integrity and function
of the musculoskeletal system.
Keywords: Diabetes Mellitus; Peripheral Neuropathy ; Peripheral vascular disease; Heart Rate
Variability.
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-Introdução Geral-
19
A população mundial de indivíduos com diabetes mellitus tem-se apresentado
crescente. Por meio de um estudo com 91 países, estimou-se que entre 2010 e 2030 haveria
um aumento de 69% no número de adultos com diabetes , nos países em desenvolvimento, e
um aumento de 20%, nos países desenvolvidos. No Brasil esta população chegaria a
12.708.000 em 20301, entretanto no Censo realizado em 2010 essa população já che gou a
valores aproximados, com 12.054.827 diabéticos2.
Uma das complicações mais comuns do diabetes é a neuropatia. A Neuropatia
Diabética Periférica é caracterizada por uma síndrome clínica ou sub -clínica que afeta
diferentes tipos de nervos, tendo evolução que varia desde manifestações silenciosas até a
ocorrência de sinais e sintomas 2, como perda de sensibilidade somatossensitiva,
propriocepção e aumento da instabilidade postural ou oscilação corporal 3. Além disso, há
dificuldade de locomoção e diminuição da força muscular em pacientes diabéticos, devido a
anormalidades intrínsecas ao músculo acarretadas pelo diabetes, bem como recrutamento
capilar diminuído, doença arterial periférica e polineuropatia di abética4
A Mononeuropatia diabética aguda é comum em pacientes diabéticos e envolve o
nervo oculomotor seguido pelo troclear e nervo fa cial nesta ordem de freqüência 2. A
Mononeuropatia diabética múltipla e radiculopatia é uma síndrome dolorosa múltipla
unilateral ou assimétrica tende a ocorrer em pacientes mais velhos. Vários nervos são afetados
em uma distribuição aleatória, como na mononeuropatia o início é abrupto e o
comprometimento nervoso ocorre sequencialmente e de forma irregular 5.
A Neuropatia Autonômica Diabética, a qual acarreta um distúrbio no sistema nervoso
autônomo ou distúrbios metabólicos, pode afetar o sistema gastrintestinal, urogenital , a
função sudomotora e o sistema cardiovascular6. Na Neuropatia Gastrointestinal Autonômica
as funções motara, sensorial e secretora são moduladas pela interação do sistema nervoso
autônomo (simpático e parassimpático) e pelo sistema nervoso entérico , cuja ritmicidade é
20
proporcionada pelas células intersticia is localizadas no músculo liso . A Disfunção Eréctil dos
homens diabéticos ocorre como resultado de uma disfunção endotelial somada a neuropatia
autonômica. A Disfunção da Bexiga Diabética afeta predominantemente fibras sensoriais e
nervosas autonômicas. A Disfunção Diabética Sudomotora inicialmente resulta numa perda
da termorregulação a qual pode acarretar em anidrose global geralmente acompanhada de
uma neuropatia autonômica grave 5.
A Neuropatia autonômica cardiovascular é definida como o comprometimento do
controle autonômico do sistema cardiovascular5, que geralmente se manifesta como
taquicardia em repouso, intolerância ao exercício, hipotensão ortostática e alteração na
variabilidade cardíaca, influenciando a taxa de mortalidade de indivíduos diabéticos 7.
Pacientes com diabetes mellitus são considerados de risco para quedas e seus agravos,
principalmente por apresentarem desenvolvimento de neuropatia periférica, visão reduzida,
uso de polifarmácia, tonturas, distúrbio auditivo, hipoglicemia decorrente do mau uso de
medicação8 ou estratégias que o corpo adota a fim de compensar a falta de informação
somatossensorial nestes indivíduos 9.
Diante da elevada taxa de morbi mortalidade do diabetes, podendo ser consequente a
presença de neuropatia periférica associada ou não a neuropatia autonômica cardiovascular,
culminando em possíveis alterações na variabilidade cardíaca e aumento no risco a queda,
este estudo objetivou: a) fazer uma comparação da variabilidade cardíaca em indivíduos com
diabetes mellitus tipo 2, com confirmação de neuropatia diabética periférica, e indivíduos
saudáveis.; b) identificar o risco de queda através de um teste de mobilidade funcional em não
diabéticos, diabéticos neuropatas e diabéticos neuropata -vasculopatas.
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REFERÊNCIAS BIBLIOGRÁFICAS DA INTRODUÇÃO
1. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010and 2030. Diabetes research and clinical practice 2010; 87:4 -14..
2. IBGE/Censo 2010. Disponível em: < http://censo2010.ibge.gov.br/>. Acesso em: 13 jun.2014.
3. Kyoungjin Lee, Seungwon Lee and Changho Song. Whole -Body Vibration TrainingImproves Balance, Muscle Strength and Glycosylated Hemoglobin in Elderly Patients withDiabetic Neuropathy. Tohoku J. Exp. Med., 2013, 231, 305-314.
4. IJzerman, T. H.; Schaper, N. C.; Melai, T.; Meijer, K.; Willems, P. J.B.; Savelberg, H.H.C.M. Lower extremity muscle strength is reduced in people with type 2 diabetes, with andwithout polyneuropathy, and is associated with impaired mobility and reduced quality of life.Diabetes Research and Clinical Practice 95 (2012) 345 -351.
5. Deli G, et al. Diabetic Neuropathies: Diagnosis and Management. Neuroendocrinology2013;98:267–280.
6. Tesfaye et al. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria,Estimation of Severity, and Treatments DIABETES CARE, VOLUME 33, NUMBER 10,OCTOBER 2010.
7. Vinik et al. Diabetic cardiac autonomic neuropathy, inflammation and cardiovasculardisease. Journal of Diabetes Investigation Volume 4 Issue 1 January 2013.
8. OLIVEIRA, P.P.; FACHIN, S. M.; TOZATTI, J.; FERREIRA, M. C.; MARINHEIRO, L.P. F. Análise comparativa do risco de quedas entre pacientes com e sem diabetes mellitus tipo2. Rev Assoc Med Bras 2012; 58(2):234-239.
9. Tabassom Ghanavati , Mohammad Jafar Shaterzadeh Yazdi , Shahin Goharpey ,Ali -AsgharArastoo. Functional balance in elderly with diabetic neuropathy.Diabetes Research andClinical Practice 96(2012)24-28.
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-Artigo I-
23
NEUROPATIA AUTONÔMICA NO DIABETES MELLITUS
Autonomic neuropathy in diabetes mellitus
Mariana de Carvalho Pinto1, Cristina Elena Prado Teles Fregonesi 2.
1- Discente do Programa de Pós -Graduação Stricto Sensu (nível mestrado) em
Fisioterapia da Faculdade de Ciências e Tecnologia, Universidade Estadual Paulista,
Presidente Prudente – SP.
2- Professor Doutor do Departamento de Fisioterapia e do Programa de Pós -Graduação
em Fisioterapia da Faculdade de Ciências e Tecnologia, Universidade Estadual
Paulista, Presidente Prudente – SP.
Autor responsável: Mariana de Carvalho PintoEndereço: Rua Santos, 72. Vila Lessa. Presidente Prudente -SPCEP: 19020-450. Presidente Prudente – São Paulo – Brasil.Telefone: (18) 98125-2292. Fax: (18) 3229-5555e-mail: marianacarvalhofisiopp@yahoo.com.br
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RESUMO
IntroduçãoA avaliação do reflexo cardiovascular é o padrão ouro nos testes autonômicos clínicos. Aanálise da variabilidade cardíaca (VC) mede a atividade parassimpática e simpática,fornecendo informações sobre o balanço autonômico do sistema cardiovascular. Sendo assim,o presente estudo optou por fazer uma comparação da VC, em indivíduos com diabetesmellitus tipo 2 com confirmação de neuropatia diabética periférica, e indivíduos saudáveis.MetodologiaNeste estudo participaram 108 indivíduos divididos em grupo co ntrole (GC) (n=34) e grupodiabético neuropata (GDN) (n=74). Inicialmente, foram realizados testes para confirmação daneuropatia. Em seguida, a avaliação da atividade do sistema nervoso autônomo (SNA) foirealizada por meio da VC com o auxílio do software Nerve-Express® (Heart RhythmInstruments, Metuchen, NJ, EUA).ResultadosNa análise no domínio do tempo foi observada diminuição da VC na população diabética comneuropatia quando comparado ao GC, representada pelo menor desvio padrão dos intervalosRR. A relação entre SNA simpático e parassimpático apresentou valores superiores ao GC,indicado pelo índice LF/HF, representando menor equilíbrio simpato vagal. No domínio dafrequência, constatou-se predomínio do SNA simpático em diabéticos, indicado pelo índ iceLF, que apresentou valores superiores ao GC, não significante, porém limítrofe.DiscussãoOs dados obtidos da VC no presente estudo sugerem que a modulação autonômica do coraçãoé afetada pelo diabetes, uma vez que há alteração significativa dos índice s LH/HF e SDNN.Desta maneira, o estudo da neuropatia autonômica como uma forma de identificar alteraçõessistêmicas, independente dos sintomas clínicos, possibilita que o tratamento adequado sejainiciado o quanto antes.
Trial registration: RBR-9FWV27
Palavras-chave: Diabetes Mellitus, Neuropatia Diabética Periférica, Variabilidade da
Freqüência Cardíaca.
25
ABSTRACT
IntroductionThe assessment of the cardiovascular reflex is the gold standard in clinical autonomic tests.The analysis of heart rate variability (HRV) measures the parasympathetic and sympatheticactivity, providing information on the autonomic balance of the cardiovascular system. Thus,this study made a comparison of the HRV in individuals with type 2 diabetes mellitus withdiabetic peripheral neuropathy’s evidence, and healthy individuals.MethodologyIn this study 108 people attented to it, which were divided into a control group (CG) (n = 34)and diabetic neuropathy group (GDN) (n = 74). Initially, tests were performed to confirm th eneuropathy. Then, the evaluation of the activity of the autonomic nervous system (ANS) wasperformed by the HRV with the help of Nerve -Express® software (Heart RhythmInstruments, Metuchen, NJ, USA).ResultsAt the domain of the time analysis was observe d a decrease in HRV at the diabetic populationwith neuropathy when compared to the CG, represented by the lower standard deviation ofRR intervals. The relationship between sympathetic and parasympathetic ANS was higher forthe CG, indicated by the LF/HF ratio, representing lower sympathetic vagal balance. In thefrequency domain, there was predominance of the sympathetic ANS in diabetics, indicated byLF ratio, which values were above the CG, not significant, but borderline.DiscussionThe data obtained from the HRV in this study suggests that the autonomic modulation of theheart is affected by diabetes since there is significant change in the levels of LH / HF andSDNN. Therefore, the study of autonomic neuropathy as a way to identify systemic changes,independent of clinical symptoms, enables proper treatment to an early start.
Trial registration: RBR-9FWV27
Keywords: Diabetes Mellitus, Diabetic Peripheral Neuropathy, Heart Rate Variability.
26
INTRODUÇÃOA população mundial de indivíduos com diabetes tem -se apresentado crescente. No
Brasil, estimativas anteriores previam que em 2030 essa população chegaria a 12.708.000 1,
entretanto no Censo realizado em 2010 essa população já chegou a valores aproximados , com
12.054.827 diabéticos2.
A neuropatia é uma das complicações mais comuns do diabetes. A prevalência desta é
estimada em cerca de 8% para pacientes com diagnóstico recente e maior que 50% para
pacientes com período prolongado da doença 3,4.
Diversas são as formas de manifestação da neuropatia diabética, dentre elas a
Neuropatia sensoriomotora, Mononeuropatia diabé tica aguda, Mononeuropatia diabé tica
múltipla e radiculopatia3,4 e a Neuropatia Autonômica 5. Esta última pode afetar o sistema
cardiovascular, gastrintestinal, urogenital e a função sudomotora5.
A neuropatia autonômica cardiovascular (NAC) possui prevalência entre 2,5 e 50%,
dependendo do teste diagnóstico utilizado e do uso de valores normativos relacionados à
idade e a população estudada. Pode chegar a 65% com o aumento da idade e duração do
diabetes4,5.
A etiologia da NAC não é bem compreendida e seus preditores e correlatos clínicos
adicionais incluem alteração da glicemia, pressão arterial e níveis de colesterol e triglicérides;
presença de neuropatia diabética periféric a (NDP), nefropatia, retinopatia, obesidade e
tabagismo4,5,6.
Além dos correlatos clínicos, sinais e sintomas que caracterizam a disfunção
autonômica cardíaca podem ser observados, como taquicardia, hipotensão ortostática e baixa
tolerância a exercícios simples, aumento da incidência de isquemia assintomática, infarto do
miocárdio e diminuição da taxa de sobrevivência após infarto do miocárdio 4,5,6.
A avaliação do reflexo cardiovascular é o padrão ouro nos testes autonômicos clínicos.
A análise da variabilidade cardíaca (VC) mede a atividade parassimpática e simpática,
27
fornecendo informações sobre o balanço autonômico do sistema cardiovascular. Este teste
tem boa sensibilidade, especificidade e reprodutibilidade, não é invasivo e é facilmente
realizado5,7.
Resultados de investigações recentes da “Action to Control Cardiovascular Risk in
Diabetes (ACCORD)” confirmam que os indivíduos com NAC têm 1,55 a 2,14 vezes mais
probabilidades de morrer do que indivíduos sem NAC. Além disso, a NAC na presença de
neuropatia periférica foi o maior preditor de mortalidade por doenças cardiovasculares 4,7.
Sendo assim, o presente estudo optou por fazer uma comparação da VC, em indivíduos com
diabetes mellitus tipo 2 (DM2) com confirmação de neuropatia diabética periférica, e
indivíduos saudáveis.
METODOLOGIA
Caracterização do estudo
Trata-se de um estudo transversal observacional controlado, desenvolvido no
Laboratório de Estudos Clínicos em Fisioterapia (LECFisio) da Faculdade de Ciências e
Tecnologia (FCT) - Universidade Estadual Paulista (UNESP), campus de Presidente
Prudente.
Todos os participantes, em concordância com os meios e fins da pesquisa, assinaram
um “Termo de Consentimento Livre e Esclarecido”, cujos procedimentos adotados obedecem
aos princípios éticos para pesquisa clínica envolvendo seres humanos, sendo aprovado pelo
Comitê de Ética em Pesquisa da FCT/UN ESP (protocolo número: 10/2011) e pelo Registro de
Ensaios Clínicos Brasileiro (RBR-9FWV27).
Amostra
O presente estudo contou com dois grupos: Grupo Diabético Neuropata (GDN) e
Grupo Controle (GC). Os quais foram submetidos a uma avaliação inicial para obtenção de
dados pessoais e antropométricos (massa corpórea, estatura e índice de massa corporal).
28
Para inclusão no GDN, foi necess ária confirmação médica de diabetes, NDP
confirmada por insensibilidade ao monofilamento Semmes-Weinstein (Sorri-Bauru,Brasil) de
10g8 e pela Escala para Diagnóstico da Polineuropatia Distal Diabética 9. Para a exclusão de
indivíduos neuropatas no GC foi n ecessária a sensibilidade ao monofilamento de 2g ,
confirmando a normalidade da sensibilidade somatossensorial dos pés 8. Em ambos os grupos
era obrigatória a ausência de outra doença neurológica ou neuropática , ausência de doença
cardiovascular, com exceção dos fatores de risco, e capacidade de compreensão dos testes.
Protocolo de avaliação autonômica
A avaliação da atividade do SNA (simpático e parassimpático) foi realizada por meio
da VC com o auxílio do software Nerve-Express® (Heart Rhythm Instruments, Metuchen, NJ,
EUA). A captação dos dados se deu por um cinto transmissor (Polar ® T31 coded™
transmitter, Electro Oi, Finlândia) colocado no tórax do participante na altura do processo
xifoide e um receptor de frequência cardíaca preso à cintura, acoplado a um computador para
transformação e armazenamento dos dados captados 10.
O sujeito iniciava o teste em decúbito dorsal sobre um divã e após 192 batimentos
cardíacos o mesmo era orientado a passar para a posição ortostática e, por fim, permanecer
nela até a ocorrência de 448 batimentos cardíacos, conforme configurações do próprio
equipamento11, dessa forma, foi possível avaliar o sistema nervoso autônomo (SNA) por meio
da reação cronotrópica do indivíduo.
Análise Estatística
Foi realizada a análise descritiva, média e desvio padrão, para as variáveis idade e
IMC. A análise estatística foi realizada, inicialmente, por meio da aplicação do teste de
Komolgorov-Smirnov para verificação da distribuição quanto à normalidade de todas as
variáveis do estudo. Para dados normais foi aplicado o teste t de Student e para não normais o
Mann Whitney. Foi adotado o nível de significância de 5% e utilizado o software Graph Pad
Prisma® versão 5.0.
29
RESULTADOS
A amostra contou com 108 indivíduos: GC (n=34), sendo 7,15% do gênero masculino
e 92,15% do gênero feminino, GDN (n=74), composto por 35,14% do gênero masculino e
64,86% do feminino.
A caracterização da amostra segue descrita na Tabela 1 e os resultados obtidos na
captação da variabilidade cardíaca na Tabela 2 e Tabela 3.
Tabela 1. Caracterização da amostra por meio de média±desvio -padrão do grupo controle(GC), grupo diabético neuropata (GDN) para as variáveis idade, Índice de Massa Corporal(IMC). (n=108)
GDN (n=74) GC (n=34)Idade (anos) 62,60±8,17 59,25±7,94IMC (kg/m2) 28,12±5,57 29,05±4,88
Tabela 2: Índices da variabilidade cardíaca captados no grupo controle (GC) e grupodiabético neuropata (GDN) no domínio do tempo . (n=108)Variável GDN (n=74) GC (n=34) p-valorMean RR (ms) 759,85±135,60 827,13±153,04 0,1061SDNN (ms) 26,36±29,11 41,55±47,33 0,0229*pNN50 (ms) 1,85±3,21 4,99±7,97 0,0771Nota: *diferença significante (p<0,05). Mean RR: Média entre intervalos RR; SDNN: Desvio padrão dosintervalos RR; pNN50: Porcentagem dos intervalos RR com diferença de duração maior que 50ms.
Tabela 3: Índices da variabilidade cardíaca captados no grupo controle (GC) e grupodiabético neuropata (GDN) no domínio da frequência .Variável GDN (n=74) GC (n=34) p-valorLF (nu) 60,89±24,38 53,96±22,15 0,0589HF (nu) 38,86±24,12 44,39±23,01 0,0790LF/HF 2,56±1,78 1,77±1,49 0,0406*Nota: *diferença significante (p<0,05). LF: Componente de baixa frequência; HF: Componente de altafrequência; FL/HF: Relação entre baixa e alta frequência.
DISCUSSÃO
O presente estudo comparou a VC de indivíduos diabéticos com neuropatia e
indivíduos saudáveis. Os índices obtidos para analise da VC, tanto no domínio do tempo
como no domínio da freqüência, mostram a evolução do sistema nervoso autônomo e
30
confirmam a atuação vagal do nó sinusal 12. Quanto maior a VFC melhor será a adaptação
cardiovascular frente a um estímulo. Reações mais rápidas aos estímulos 13.
Na análise no domínio do tempo, observou -se diminuição da VC na população
diabética com neuropatia quando comparado ao GC (p-valor=0,0229), representada pelo
menor desvio padrão dos intervalos RR, indicado pelo índice SDNN. Fakhrzadeh et al.
(2012), já encontraram índices inferiores do SDNN em indivíduos diabéticos sem
neuropatia14.
No domínio da frequência, constatou-se predomínio do SNA simpático em diabéticos,
indicado pelo índice LF, que apresentou valores superiores ao GC, não significante, porém
limítrofe (p-valor=0,0589), concordando com Sucharita et al. (2011). Porém, outro estudo
observou diminuição do tônus simpático Fakhrzadeh et al. (2012). A relação entre SNA
simpático e parassimpático apresentou valores superiores ao GC ( p-valor=0,0406), indicado
pelo índice LF/HF, representando menor equilíbrio simpato vagal.
No estudo de Bagherzadeh et al. (2013), os índices HF, LF e LF/HF, apresentaram a
diferença semelhante ao grupo diabético em relação ao controle daqueles observados no
presente estudo. Os autores relatam que tais alterações tem relação com o enrijecimento
arterial, hiperinsulinemia e a neuropatia autonômica em DM2 , as quais colaboram para o
desenvolvimento de doenças cardiovasculares em diabéticos 15. O presente estudo não
objetivou avaliar as alterações cardiovasculares, porém, no relato dos pacientes, observou -se
uma incidência de 50% de hipertensão arterial no GDN, destoando dos 11% encontrado no
GC.
O aumento do tônus simpático pode ser associado à hiperinsulinemia, que por sua vez
pode estar associada a diminuição da VC. Contudo ao associar o SNA e a Doença Arterial
Periférica, o ramo parassimpático parece ser o que mais influencia, sendo que sua relação –
entre sistema autônomo e doença arterial periférica - pode ser explicada pela resistência a
insulina, uma característica comum em pacientes com DM2 12.
31
No presente estudo não foi demonstrado alteração no índice HF ( p-valor=0,0790),
representativa da modulação autonômica parassimpática. Diferindo de alguns autores que
observaram esta alteração, mesmo no inicio do DM2. O estudo de Fakhrzadeh et al. (2012)
mostrou que a disfunção autonômica, principalmente do ramo parassimpático, es ta presente
desde o inicio do DM2 e que a aterosclerose é uma evidencia subclínica encontrada nessa
população14. E o estudo de Sucharita et al. (2011) demonstrou que há envolvimento dos dois
componentes autonômicos, com o predomínio do parassimpático 16.
Sugere-se que os danos graves às fibras nervosas mielinizadas em grande quantidade
somados a uma degeneração neurológica generalizada normalmente é capaz de afetar as
pequenas fibras nervosas do sistema nervoso autônomo no DM2 14. Em adição, a presença de
neuropatia periférica associada a neuropatia autonômica cardiovascular, influencia na
mortalidade por doenças cardiovasculares 4,7. Além disso, a redução da VC esta diretamente
ligada com o aumento das causas da mortalidade em decorrência de u m evento cardíaco14.
Os dados obtidos da VC no presente estudo sugerem que a modulação autonômica do
coração é afetada pelo diabetes, uma vez que há alteração significativa dos índices LH/HF e
SDNN. Contudo a maneira como interpretar tal alteração ainda nã o esta clara, mas evidencia
que há sim diferença entre diabéticos e não diabéticos. Assim pode -se inferir que a alteração
de tais índices pode estar relacionada com aumento dos riscos de mortalidade. Desta maneira,
o estudo da neuropatia autonômica como uma forma de identificar alterações sistêmicas,
independente dos sintomas clínicos, possibilita que o tratamento adequado seja iniciado o
quanto antes16.
O estudo tem como limitação a não existência de um escore de normalidade para os
índices da VC. As pesquisas se baseiam em comparações do grupo experimental com grupos
controle formados por indivíduos saudáveis/sem doenças associadas. Porém acredita -se que
fatores diversos, como, por exemplo, doenças emocionais não diagnosticadas, podem
32
influenciar tais resultados. Assim, sugere-se que sejam realizados trabalhos futuros com
avaliação mais específica dessas variáveis.
Lista de abreviaçãoes
NAC: neuropatia autonômica cardiovascular; NDP: neuropatia diabética periférica; VC:
variabilidade cardíaca; DM2: Diabet es mellitus tipo 2; GDN: Grupo Diabético Neuropata;
GC: Grupo Controle; SNA: Sistema nervoso autônomo; Mean RR: Média entre intervalos
RR; SDNN: Desvio padrão dos intervalos RR; pNN50: Porcentagem dos intervalos RR com
diferença de duração maior que 50ms; LF: Componente de baixa frequência; HF:
Componente de alta frequência; FL/HF: Relação entre baixa e alta frequência.
Conflito de interesse
Não há conflito de interesse.
Contribuição dos autores
Todos os autores contribuíram para o desenvolvimento do trabalho, e leram e aprovaram o
manuscrito final.
Informações dos Autores
1Pinto, M. C. Discente do Programa de Pós-Graduação Stricto Sensu (nível mestrado) em
Fisioterapia da Faculdade de Ciências e Tecnologia, Universidade Esta dual Paulista,
Presidente Prudente – SP. 2Fregonesi, C. E. P. T. Professor Doutor do Departamento de
Fisioterapia e do Programa de Pós -Graduação em Fisioterapia da Faculdade de Ciências e
Tecnologia, Universidade Estadual Paulista, Presidente Prudente – SP.
REFERÊNCIAS
1. Shaw, J.E.; Sicree, R.A.; Zimmet, P.Z. Global estimates of the prevalence of diabetes for2010 and 2030. Diabetes research and clinical practice , v. 87, p. 4-14, nov. 2010.
2. IBGE/Censo 2010. Disponível em: < http://censo2010.ibge.gov.br/>. Acesso em: 13 jun.2014.
33
3. Deli, G. et al. Diabetic Neuropathies: Diagnosis and Management. Neuroendocrinology , v.98, p. 267–280, jan. 2013.
4. Vinik, A.I. et al. Diabetic Neuropathy. Endocrinol Metab Clin N Am , v. 42, p.747–787.2013
5. Tesfaye, S. et al. Diabetic Neuropathies: Update on Definitions, Diagnostic Criteria,Estimation of Severity, and Treatments. Diabetes Care.; v. 33, n. 10, p. 2285–2293, oct.2010.
6. Spallone, V. et al. Cardiovascular autonomic neuropathy in diabetes: clinical impact,assessment, diagnosis, and management. Diabetes Metab Res Rev , v. 27, p. 639–653. 2011.
7. Vinik, A.I. et al. Autonomic imbalance: prophet of doom or scop e for hope? Diabet Med,v. 28, p. 643–651. 2011.
8. Yamane, N.K.K. et al. Effectiveness of Semmes –Weinstein monofilament examination fordiabetic peripheral neuropathy screening. Journal of Diabetes and Its Complications , v. 19,p. 47– 53. 2005.
9. Moreira, R.O. et al. Tradução para o português e avaliacao da confiabilidade de uma escalapara diagnostico da polineuropatia. Arq bras endocrinol metab , v.49, n. 6, p. 944-950. 2005.
10. Kerppers, I.I. et al. Heart rate variability in individuals with cerebra l palsy. Arch MedSci, v. 5, n. 1, p. 45-50. 2009.
11. Negri, A.P. et al. A influência da equoterapia na modulação autonômica da frequênciacardíaca de crianças com paralisia cerebral. Ter man, v. 7, n. 33, p. 376-381, set-out. 2009
12. Canani, L.H. et al. Cardiovascular autonomic neuropathy in type 2 diabetes mellituspatients with peripheral artery disease. Diabetology & Metabolic Syndrome , v. 5, n. 54.2013.
13. VANDERLEI, L.C.M. et al. Noções básicas de variabilidade da frequência cardíaca e suaaplicabilidade clínica. Rev Bras Cir Cardiovasc .v. 24, n. 2, p. 205-217. 2009.
14. Fakhrzadeh, H. et al. Cardiac Autonomic Neuropathy Measured by Heart Rate Variabilityand Markers of Subclinical Atherosclerosis in Early Type 2 Diabetes. ISRN Endocrinology,2012.
15. Bagherzadeh, A. et al. Association of cardiac autonomic neuropathy with arterial stiffnessin type 2 diabetes mellitus patients. Journal of Diabetes & Metabolic Disorders , v. 12, n.55, 2013.
16. Sucharita, S. et al. Autonomic nervous system function in type 2 diabetes usingconventional clinical autonomic tests, heart rate and blood pressure variability measures.Indian Journal of Endocrinology and Metabolism , v. 15, n. 3, jul-sep. 2011.
34
-Artigo II-
35
RISCO DE QUEDAS NO DIABETES MELLITUS
RISK OF FALLS IN DIABETES MELLITUS
Mariana de Carvalho Pinto1; Cristina Elena Prado Teles Fregonesi 2.
Programa de Pós-Graduação em Fisioterapia – Faculdade de Ciência e
Tecnologia/Universidade Estadual Paulista, Presidente Prudente, São Paulo, Brasil.
1Discente do Programa de Pós -Graduação Stricto Sensu em Fisioterapia – Faculdade de
Ciência e Tecnologia/Universidade Estadual Paulista, Presidente Prudente, São Paulo, Brasil2Docente do Programa de Pós -Graduação Stricto Sensu em Fisioterapia – Faculdade de
Ciência e Tecnologia/Universidade Estadual Paulista, Presidente Prudente, São Paulo, Brasil
Conflito de interesse
Declaramos não haver nenhum tipo de conflito de interesse envolvendo o presente estudo .
Endereço para correspondência:
Autor correspondente: Mariana de Carvalho Pinto.
Endereço: Rua Santos, 72. Vila Lessa. Presidente Prudente -SP
CEP: 19020-450. Presidente Prudente – São Paulo – Brasil.
Telefone: (18) 98125-2292. Fax: (18) 3229-5555
e-mail: marianacarvalhofisiopp@yahoo.com.br
36
RESUMO
Objetivos
Identificar o risco de queda através de um teste de mobilidade funcional em não diabéticos,
diabéticos neuropatas e diabéticos neuropata -vasculopatas.
Metodologia
Foi composto por 61 sujeitos de ambos os gêneros divididos em GC (n=32), GDN (n=18) e
grupo diabético neuropata vasculopata (GDNV) (12). Os indivíduos passaram por avaliação
inicial, por testes de sensibilidade somatossensitiva, Escala para Diagnóstico da
Polineuropatia Distal Diabética e índice tornozelo/braço. A seguir, realizou -se “Time Up and
Go Test” (TUGT) para avaliar o equilíbrio dinâmico .
Resultados
Os três grupos que contem a amostra apresentaram homogeneidade entre si. Os valores
referentes aos índices glicêmicos de jejum apresentaram-se superiores nos grupos diabéticos.
Já o aumento no índice glicêmico pós prandial foi significativo no GDNV, quando comparado
ao GC. O índice glicêmico pós prandial do GDN foi superior ao do GC, porém não
significante. Foi observado um aumento progressivo e significante no tempo decorrido para a
realização do teste de mobilidade TUGT entre os três grupos, com valores maiores para o
GDNV em relação ao GDN e GC e para o GDN em relação ao GC.
Conclusão
A confirmação ou não da predisposi ção ao risco de queda pode contribuir para maior enfoque
na intervenção precoce, com atividades direta ou indiretamente relacionadas ao equilíbrio
corporal, podendo contribuir para a prevenção de queda nesta população.
Palavras-chave: Diabetes Mellitus, Neuropatia Diabética Periférica, Risco de queda
37
ABSTRACT
Aims
Identify the risk of falling through a functional mobility test in non -diabetic, diabetic
neuropathy and diabetic neuropathy -vasculopathies.
Methodology
It was composed of 61 subjects of both genders divided into GC (n = 32), GDN (n = 18) and
diabetic neuropathy vasculopata group (GDNV) (12). Individuals underwent initial evaluation
by somatosensory sensitivity tests, diagnosis of polyneuropathy for Scale Distal Diabetic and
ankle / brachial index. The following took place "Time Up and Go Test" (TUGT) to assess the
dynamic balance.
Results
The three groups containing the sample showed homogeneity among themselves. The values
for the fasting glycemic indices were higher in diabetic groups. The increase in post prandial
glycemic index was significant in GDNV when compared to GC. The postprandial glycemic
index GDN was superior to the CG, but not significant. A progressive and significant increase
in the time taken to perform the TUGT mobility test was observed between the three groups,
with higher values for the GDNV regarding the GDN and GC and the GDN compared to the
CG.
Conclusion
Confirmation or no predisposing risk of falling can contribute to greater focus on early
intervention, with activities directly or indirectly related to body balance, contributing to the
fall prevention in this population.
Keywords: Diabetes Mellitus, Diabetic Neuropathy Peripheral, Risk of Falls.
38
INTRODUÇÃO
O diabetes mellitus (DM) tipo 2 é uma das enfermidades crônicas mais diagnosticadas,
chegando a atingir mais de 300 milhões de indivíduos no mundo e independe do grau de
desenvolvimento do país. Aproximadamente 20% dos adultos entre 65 e 76 anos possuem o
diagnóstico de DM21.
O aumento da expectativa de vida da população , em combinação com uma mudança
de comportamento no estilo de vida, decorrente da urbanização, resultou num aumento da
prevalência de doenças crônico degenerativas2. Em contrapartida, doenças crônicas como DM
acelera o processo de envelhecimento. Ess e complexo processo, inerente a todas as estruturas
e funções do organismo, é contínuo, desencadeando alterações que podem culminar no
declínio da agilidade e do equilíbrio dinâmico corporal3.
Assim, as complicações crônicas decorrentes do diabetes são mais acentuadas com o
envelhecimento. A neuropatia diabética periférica (NDP), complicação mais frequente, está
presente em até metade das pessoas com diabetes, a qual acarreta em um comprometimento
sensório motor e autonômico, podendo predispor ao risco de queda 4.
Ademais, quando a NDP está associada a vasculopatia periférica, alterações sensório
motoras, como a diminuição da mobilidade, diminuição da massa e força muscular, mais
pronunciadas nos membros inferiores, podem ser mais acentuadas , resultando em maior
predisposição de desequilíbrios corporais 6.
Por sua vez, o risco de queda em decorrência da diminuição do tempo de reação a
estímulos externos, como em situações de mudança de decúbito ou alteração n o sentido da
marcha5, pode estar associado a alteração na atuação da insulina a qual acarreta constantes
mudanças na concentração da glicose sanguínea, afetando a função cerebral 3.
Diante do exposto e das implicações que podem existir em situações de queda em
indivíduos com diabetes, principalmente quando associado ao envelhecimento, uma vez que a
maioria das complicações diabéticas surge em fases mais tardias do desenvolvimento da
39
doença, este estudo tem o objetivo de identificar o risco de queda através de um teste de
mobilidade funcional em não diabéticos, diabéticos neuropatas e diabéticos neuropata -
vasculopatas.
METODOLOGIA
Trata-se de um estudo transversal observacional controlado, desenvolvid o no
Laboratório de Estudos Clínicos em Fisioterapia (LECFisio) da Faculdade de Ciências e
Tecnologia (FCT) - Universidade Estadual Paulista (UNESP), campus de Presidente
Prudente.
O presente estudo está de acordo com as orientações do Comitê de Ética em P esquisa
da FCT/UNESP (protocolo número: 10/2011) e Registro de Ensaios Clínicos Brasileiro RBR-
9FWV27. Todos os participantes do estudo assinaram o “Termo de Consentimento Livre e
Esclarecido”, cujos procedimentos adotados obedecem aos princípios éticos pa ra pesquisa
clínica com seres humanos.
População e critérios de seleção
A amostra foi composta de indivíduos distribuídos em três grupos: Grupo Diabético
Neuropata (GDN), Grupo Neuropata e Vasculopata (GDNV) e Grupo Controle (GC). Os
quais foram submetidos a uma avaliação inicial para obtenção de dados pessoais e
antropométricos (massa corpórea, estatura e índice de massa corporal).
Para inclusão no GDN e GDNV, foi necessária confirmação médica de diabetes, NDP
confirmada por insensibilidade ao monofilamento Semmes-Weinstein (Sorri-Bauru,Brasil) de
10g7 e pela Escala para Diagnóstico da Polineuropatia Distal Diabética 8. Para o GDNV foi
necessária também a confirmação da alteração na circulação e perfusão sang uínea periférica,
detectada, respectivamente, pelo índice tornozelo/braço e por oximetria 9. Para a exclusão de
indivíduos neuropatas no GC foi necessária a sensibilidade ao monofilamento de 2g ,
confirmando a normalidade da sensibilidade somatossensorial do s pés7. Em ambos os grupos
40
era obrigatória a ausência de outra doença neurológica ou neuropática e boa capacidade de
compreensão dos testes.
Procedimentos
Avaliação inicial
Os indivíduos foram submetidos a uma avaliação inicial para obtenção de dados
pessoais, antropométricos e glicemia capilar pós-prandial. A glicemia de jejum foi coletada
por meio de relato do paciente, referente a última mensuração. Realizou-se a inspeção dos
pés, para verificação das condições d a pele ou presença de ulceração e/ou amputação, e o teste
de sensibilidade somatossensitiva para confirmação ou não da NDP7.
A confirmação da vasculopatia foi possível por meio da avaliação da circulação
periférica pelo índice tornozelo/braço (ITB) entre os membros superiores e inferiores . O ITB
foi obtido pelo quociente entre a pressão sistólica de maior valor braquial e a pressão sistólica
do tornozelo. Quando inferior a 0,90 considerou -se indicativo de doença arterial obstrutiva
periférica9,10,11. A avaliação da perfusão sanguínea foi obti da por um oxímetro de dedo
(Nonim Onix®, EUA). A saturação foi coletada no hálux, de ambos os pés, e os resultados
foram comparados com os valores médios obtidos nos dedos indicadores de ambas as mãos.
A oximetria do hálux foi considerada alterada quando a saturação de oxigênio foi inferior a do
dedo indicador em mais de dois pontos percentuais9.
Avaliação do equilíbrio dinâmico
Realizou-se “Time Up and Go Test” (TUGT)12 para avaliar o equilíbrio dinâmico. Foi
solicitado ao indivíduo se posicionar sentado em uma cadeira e, ao sinal do examinador, foi
requerido que ele se levantasse, andasse três metros, voltasse e sentasse novamente, o mais
rápido possível sem correr. Foi registrado o tempo decorrido, em segundos, para realização da
tarefa.
41
Análise estatística
Foi realizado testes de Kolmogorov-Smirnov e Shapiro-wilk que confirmaram a
normalidade dos dados. As variáveis foram comparadas entre grupos por meio do teste
ANOVA oneway com auxílio do pós -teste de Tukey. Para investigar a relação entre as demais
variáveis com o TUGT foi utilizado o teste de Correlação Parcial ajustado pelo grau de
comprometimento. Por fim, as relações significativas foram avançadas para o teste de
Regressão Linear. Os testes foram realizados por meio do software SPSS versão 13.0.
RESULTADOS
A amostra contou com 61 indivíduos. O GC (n=32) foi composto por 18,75% do
gênero masculino e 81,25% do gênero feminino, o GDN (n=18), por 22,22% do gênero
masculino e 77,78% do feminino e GDNV (12), por 72,73% do gênero masculino e 27,27%
do feminino. A caracterização da amostra segue descrita na Tabela 1 e os resultados obtidos
no TUGT e a mensuração da glicose na Tabela 2.
Tabela 1. Dados antropométricos dos indivíduos do Grupo controle (GC), Grupo DiabéticoNeuropata (GDN) e Grupo Diabético Neuropata Vasculopata (GDNV). n=61
GC (n=32) GDN (n=18) GDNV (n=12) f p-valorIdade (anos) 64,77±6,86 64,33±6,45 60,64±7,84 1,503 0,231Massa (kg) 69,47±14,22 76,71±16,37 77,03±16,09 1,782 0,177Estatura (m) 1,58±0,11 1,61±0,08 1,65±0,09 1,762 0,181IMC (kg/m2) 27,53±4,01a 31,52±6,92b 28,52±6,15ab 3,171 0,049*IMC: Índice de Massa Corporal .Nota: letras diferentes nas linhas indicam diferença significativa entre os grupos (p<0,05).
Tabela 2. Valores do índice glicêmico em jejum e pós prandial , em mg/dl, e tempo derealização do teste de mobilidade , em segundos, dos indivíduos do Grupo controle (GC),Grupo Diabético Neuropata (GDN) e Grupo Diabético Neuropata Vasculo pata (GDNV).n=61
GC (n=32) GDN (n=18) GDNV (n=12) F p-valorGli_PPrandial 134,91±33,91a 164,55±43,34ab 181,73±104,79b 3,581 0,034*Gli_Jejum 93,64±18,97a 154,82±48,46b 165,55±96,48b 7,464 0,002*TUGT (s) 10,58±1,81a 13,88±2,79b 16,44±5,19c 18,532 <0,0001*Gli_PPrandial: índice glicêmico pós prandial; Gli_Jejum: índice glicêmico de jejum; TUGT: “Time Up and GoTest”. Nota: letras diferentes nas linhas indicam diferença signifi cativa entre os grupos (p<0,05).
42
No teste de correlação nota-se que o TUGT teve relação com a glicemia pós -prandial
(r=0,325, p=0,038) e a glicemia em jejum (r=0,420, p=0,006), sendo esta última mais
significativa. Essas relações foram ajustadas pelo grau de comprometimento detectável nos
grupos, podendo indicar que a relação per siste independente do grau de complicação. A
seguir, essa relação progrediu para um teste de regressão linear e os dados seguem na Tabela
3.
Tabela 3. Regressão linear entre índices glicêmicos e Time Up and Go Test (TUGT) dosindivíduos do Grupo Controle, Diabético Neuropata e Diabético Neuropata Vasculopata .n=61
TUGT (ajustado pelo grau de comprometimento)Variáveis β IC (95%) p-valorGlicemia_PPrandial 0,263 0,001; 0,035 0,043Glicemia_Jejum 0,520 0,016; 0,047 ≤0,001Gli_PPrandial: índice glicêmico pós prandial; Gli_Jejum: índice glicêmico em jejum .
Na inspeção dos pés do GC e GDN não foi observado nenhum tipo de ulceração e/ou
amputação. Contudo para o GDNV foi observado indivíduos com ulcerações e amputações de
um ou mais artelhos. Um com ulceração, três com amputação, quatro com ulceração e
amputação e quatro sem alterações.
DISCUSSÃO
O presente estudo se propôs a verificar o risco de queda, por meio de um teste de
equilíbrio dinâmico, em indivíduos diabéticos com neuropatia e se este risco é agravado
quando a vasculopatia está associada. A NDP é caracterizada por uma síndrome clínica ou
sub-clínica que afeta diferentes tipos de nervos, tendo evolução que varia desde manifestações
silenciosas até a ocorrência de sinais e sintomas, como diminuição da sensibilidade
somatossensitiva, propriocepção e aumento da instabilidade postural ou oscilação corporal 5.
Quando associada a vasculopatia periférica, essas manifestaç ões podem ser mais evidentes13.
43
Os três grupos que contem a amostra apresentaram homogeneidade entre si. Os
valores referentes aos índices glicêmicos de jejum apresentaram -se superiores nos grupos
diabéticos. Já o aumento no índice glicêmico pós prandial foi significativo no GDNV, quando
comparado ao GC. O índice glicêmico pós prandial do GDN foi superior ao do GC, porém
não significante. Essa não significância poderia estar relacionada a grande oscilação glicêmica
normalmente observada na população diabética, gerando um elevado desvio padrão .
Corroborando com o presente estudo, alguns autores relacionam a hiperglicemia pós prandial
com aumento de disfunção vascular no DM tipo 2 14.
Foi observado um aumento progressivo e significante no tempo decorrido para a
realização do teste de mobilidade TUGT entre os três grupos, com valores maiores para o
GDNV em relação ao GDN e GC e para o GDN em relação ao GC. Pode-se inferir que,
quanto maior o comprometimento periférico, maior o tempo de realização do teste e , portanto,
maior o risco de queda. Ghanavati et al. (2012) observou uma correlação direta entre
progressão da gravidade da neuropatia com a progressão da instabilidade postural. Quanto
mais grave se torna a neuropatia pior é a execução das tarefas de vida diária com
funcionalidade15.
Acredita-se que a condição diabética em si já predispõe ao risco a queda, independente
da condição neuropática16. Entretanto, a neuropatia associada ao diabetes contribui ainda mais
para o aumento do risco a quedas 15. Ademais, o desenvolvimento concomitante de
vasculopatia, principalmente nos membros inferiores, piora este risco13,15.
Logo, como a interação entre o sistema vestibular e cerebelo fica comprometida, o
equilíbrio corporal também se altera, aumentando ainda mais o risco de queda. Dados
apontam que a taxa de risco de queda é de 1,5 vezes maior em pacientes com neuropatia
diabética do que em pessoas normais 5.
Observou-se correlação positiva entre o TUGT e os índices glicêmicos, tanto de jejum
quanto pós prandial. O TUGT, ajustado pelo grau de comprometimento, evidencia maior
44
associação com a glicemia de jejum do que pela pós prandial. Assim, quanto maior o índice
glicêmico, maior o tempo de deambulação no TUGT. A marcha fica mais lenta
provavelmente para compensar o déficit de equilíbrio e o risco de queda.
Como valores maiores do índice glicêmico estão diretamente relacionados com maior
predisposição ao comprometimento vascular 13, o maior risco a queda do GDNV pode estar
relacionado a elevação deste índice, associada a condição ne uropática e vasculopática em si.
Entretanto, não pode ser descartada a possibilidade que a presença de ulcerações e
amputações nos pés de parte dos indivíduos do GDNV po ssa ser uma variável confundidora,
podendo estar relacionada com o maior tempo de deambulação no TUGT deste grupo.
O presente estudo analisou o comprometimento neurovascular periférico com o risco
de queda, em indivíduos diabéticos neuropatas e neuropata -vasculopata, por acreditar que a
confirmação ou não da predisposição ao risco de queda pode contribuir para maior enfoque na
intervenção precoce, com atividades direta ou indiretamente relacionadas ao equilíbrio
corporal, podendo contribuir para a prevenção de queda nesta população.
REFERÊNCIAS
1. OLIVEIRA P P, FACHIN S M, TOZATTI J , FERREIRA, M C, MARINHEIRO, L P F.Análise comparativa do risco de quedas entre pacientes com e sem diabetes mellitus tipo 2.Rev Assoc Med Bras 2012; 58(2):234-239.
2. VAZ M M et al. Postural Control and Functional Strength in Patients With Type 2 DiabetesMellitus With and Without Perip heral Neuropathy. Arch of Phy Medi and Rehabi2013;94:2465-70.
3. ALVARENGA P P, PEREIRA D S, ANJOS D M C. Mobilidade funcional e funçãoexecutiva em idosos diabéticos e não diabéticos. Rev Bras Fisioter, São Carlos 2010;14(6):491-6.
4. KARMAKAR et al. Investigating the role of neuropathic pain relief in decreasing gaitvariability in diabetes mellitus patients with neuropathic pain: a randomized, double -blindcrossover trial. J of NeuroEngin and Rehabi 2014, 11:125.
45
5. KYOUNGJIN L, SEUNGWON L and CHANGHO S. Whole-Body Vibration TrainingImproves Balance, Muscle Strength and Glycosylated Hemoglobin in Elderly Patients withDiabetic Neuropathy. Tohoku J. Exp. Med., 2013, 231:305-314.
6. IJZERMAN TH, SCHAPER NC, MELAI T, MEIJER K, WILLEMS PJB, SAVELBERGHHCM. Lower extremity muscle strength is reduced in people with type 2 diabetes, with andwithout polyneuropathy, and is associated with impaired mobility and reduced quality of life.Diab Res and Clin Prac., 2012, 95:345-351.
7. Yamane, N.K.K. et al. Effectiveness of Semmes–Weinstein monofilament examination fordiabetic peripheral neuropathy screening. J of Dia and Its Complic., 2005, 19:47– 53.
8. MOREIRA RO et al. Tradução para o português e avalia ção da confiabilidade de umaescala para diagnostico da polineuropatia. Arq bras endocrinol metab., 2005, 49(6):944-950.
9. PARAMESWARAN GI, BRAND K, DOLAN J. Pulse oximetry as a potential screeningtool for lower extremity arterial disease in asymptomatic patients with diabetes mellitus. Archof Inter Medi., 2005, 165:442-446.
10. ADA. American Diabetes Association. Diagnosis and Classification of Diabetes Mellitus.Diabetes Care., 2010, 33: 62-69.
11. KALLIO M, FORSBLOM C, GROOP P, GROOP L, LEPÄNTALO M. Development ofNew Peripheral Arterial Occlusive Disease in Patients With Type 2 Diabetes During a MeanFollow-Up of 11 Years. Diab Care. , 2003; 26: 1241-1245.
12. MATHIAS S, NAYAK US, ISAACS B . Balance in elderly patients: the “get -up and go”test. Arch Phys Med Rehabil., 1986, 67:387-9.
13. X.-m. Jiao, X.-g. Zhang, X.u-p. Xu, C. Yi, C. Bin, Q.-p. Cheng, Q.-q. Gong, X.-f. Lv.Blood glucose fluctuation aggravates lower extremity vascular disease in type 2 diabetes EuroRev for Medi and Pharmac Sci. , 2014; 18: 2025-2030.
14. TORIMOTO et al. Relationship between fluctuations in glucose levels measured bycontinuous glucose monitoring and vascular endothelial dysfunction in type 2 diabetesmellitus. Cardio Diabet., 2013, 12:1.
15. TABASSOM G, MOHAMMAD J S Y, SHAHIN G, ALI-ASGHAR A. Functionalbalance in elderly with diabetic neuropathy. Diab Res and Clin Prac., 2012, 96:24-28.
16. LIM et al. Comparison of Balance Ability Between Patients With Type 2 Diabetes andWith and Without Peripheral Neuropathy. PM R 2014, 6:209-214.
46
-Conclusão Geral-
47
Os dados obtidos da variabilidade cardíaca no presente estudo sugerem que a
modulação autonômica do coração é afetada pelo diabetes, p ortanto, o estudo da neuropatia
autonômica como uma forma de identificar alterações sistêmicas possibilita que o tratamento
adequado seja iniciado o quanto antes.
Com relação a análise do equilíbrio corporal constatou -se que a interação entre o
sistema vestibular e cerebelo fica comprometida alterando o equilíbrio corporal e,
consequentemente aumenta o risco de queda.
O estudo tem como limitação a não existência de um escore de normalidade para os
índices da VC, logo, sugere -se que sejam realizados trabalhos futuros com avaliação mais
específica dessas variáveis. E ao analisar o comprometimento neurovascular periférico com o
risco de queda, em indivíduos diabéticos neuropatas e neuropata -vasculopata, sugere-se que
um enfoque na intervenção precoce, com atividades direta ou indiretamente relacionadas ao
equilíbrio corporal, podem contribuir para a prevenção de queda nesta população.
48
-Anexo I-
49
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Published abstract
Zvaifler NJ, Burger JA, Marinova -Mutafchieva L, Taylor P, Maini RN: Mesenchymal cells,
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Schnepf E: From prey via endosymbiont to plastids: comparative studies in dinoflagellates. In
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Book with institutional author
Advisory Committee on Genetic Modification: Annual Report. London; 1999.
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Stanford University, Computer Science Department; 1995.
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Dataset with persistent identifier
Zheng, L-Y; Guo, X-S; He, B; Sun, L-J; Peng, Y; Dong, S-S; Liu, T-F; Jiang, S;
Ramachandran, S; Liu, C-M; Jing, H-C (2011): Genome data from sweet and grain sorghum
(Sorghum bicolor). GigaScience Database. http://dx.doi.org/10.5524/100012.
Clinical trial registration record with persistent identifier
Mendelow, AD (2006): Surgical Trial in Lobar Intracerebral Haemorrhage. Current
Controlled Trials. http://dx.doi.org/10.1186/ISRCTN22153967
Preparing illustrations and figures
Illustrations should be provided as separate files, not embedded in the text file. Each
figure should include a single illustration and should fit on a single page in portrait format. If
a figure consists of separate parts, it is important that a single composite illustration file be
submitted which contains all parts of the figure. There is no charge for the use of color
figures.
Please read our figure preparation guidelines for detailed instructions on maximising
the quality of your figures.
Formats
The following file formats can be accepted:
PDF (preferred format for diagrams)
DOCX/DOC (single page only)
PPTX/PPT (single slide only)
EPS
PNG (preferred format for photos or images)
TIFF
JPEG
BMP
60
Figure legends
The legends should be included in the main manuscript text file at the end of the
document, rather than being a part of the figure file. For each figure, the following
information should be provided: Figure number (in sequence, using Arabic numerals - i.e.
Figure 1, 2, 3 etc); short title of figure (maximum 15 words); detailed legend, up to 300
words.
Please note that it is the responsibility of the author(s) to obtain permission from the
copyright holder to reproduce figures or tables that have previously been published elsewhere.
Preparing a personal cover page
If you wish to do so, you may submit an image which, in the event of publication, will
be used to create a cover page for the PDF version of your article. The cover page will also
display the journal logo, article title and citation details. The image may either be a figure
from your manuscript or another relevant image. You must have permission from the
copyright to reproduce the image. Images that do not meet our requirements will not be used.
Images must be 300dpi and 155mm square (1831 x 1831 pixels for a raster image).
Allowable formats - EPS, PDF (for line drawings), PNG, TIFF (for photographs and
screen dumps), JPEG, BMP, DOC, PPT, CDX, TGF (ISIS/Draw).
Preparing tables
Each table should be numbered and cited in sequence using Arabic numerals (i.e.
Table 1, 2, 3 etc.). Tables should also have a title (above the table) that summarizes the whole
table; it should be no longer than 15 words. Detailed legends may then follow, but they should
be concise. Tables should always be cited in text in consecutive numerical order.
Smaller tables considered to be integral to the manuscript can be pasted into the end of
the document text file, in A4 portrait or landscape format. These will be typeset and displ ayed
in the final published form of the article. Such tables should be formatted using the 'Table
object' in a word processing program to ensure that columns of data are kept aligned when the
file is sent electronically for review; this will not always be the case if columns are generated
by simply using tabs to separate text. Columns and rows of data should be made visibly
distinct by ensuring that the borders of each cell display as black lines. Commas should not be
used to indicate numerical values. Colo r and shading may not be used; parts of the table can
be highlighted using symbols or bold text, the meaning of which should be explained in a
table legend. Tables should not be embedded as figures or spreadsheet files.
61
Larger datasets or tables too wide f or a landscape page can be uploaded separately as
additional files. Additional files will not be displayed in the final, laid -out PDF of the article,
but a link will be provided to the files as supplied by the author.
Tabular data provided as additional fi les can be uploaded as an Excel spreadsheet
(.xls) or comma separated values (.csv). As with all files, please use the standard file
extensions.
Preparing additional files
Although Cardiovascular Diabetology does not restrict the length and quantity of da ta
included in an article, we encourage authors to provide datasets, tables, movies, or other
information as additional files.
Please note: All Additional files will be published along with the article. Do not
include files such as patient consent forms, c ertificates of language editing, or revised
versions of the main manuscript document with tracked changes. Such files should be sent by
email to CardiovascDiabetol.Office@sheba.health.gov.il, quoting the Manuscript ID number.
Results that would otherwise be indicated as "data not shown" can and should be
included as additional files. Since many weblinks and URLs rapidly become broken,
Cardiovascular Diabetology requires that supporting data are included as additional files, or
deposited in a recognized repository. Please do not link to data on a personal/departmental
website. The maximum file size for additional files is 20 MB each, and files will be virus -
scanned on submission.
Additional files can be in any format, and will be downloadable from the final
published article as supplied by the author. We recommend CSV rather than PDF for tabular
data.
Certain supported files formats are recognized and can be displayed to the user in the
browser. These include most movie formats (for users with the Quicktime plugin), mini -
websites prepared according to our guidelines, chemical structure files (MOL, PDB),
geographic data files (KML).
If additional material is provided, please list the following information in a separate
section of the manuscript text:
File name (e.g. Additional file 1)
File format including the correct file extension for example .pdf, .xl s, .txt, .pptx
(including name and a URL of an appropriate viewer if format is unusual)
62
Title of data
Description of data
Additional files should be named "Additional file 1" and so on and should be referenced
explicitly by file name within the body of the article, e.g. 'An additional movie file shows this
in more detail [see Additional file 1]'.
Additional file formats
Ideally, file formats for additional files should not be platform -specific, and should be
viewable using free or widely available tools. T he following are examples of suitable formats.
Additional documentation
PDF (Adode Acrobat)
Animations
SWF (Shockwave Flash)
Movies
MP4 (MPEG 4)
MOV (Quicktime)
Tabular data
XLS, XLSX (Excel Spreadsheet)
CSV (Comma separated values)
As with figure files, files should be given the standard file extensions.
Mini-websites
Small self-contained websites can be submitted as additional files, in such a way that
they will be browsable from within the full text HTML version of the article. In order to do
this, please follow these instructions:
Create a folder containing a starting file called index.html (or index.htm) in the root.
Put all files necessary for viewing the mini -website within the folder, or sub-folders.
Ensure that all links are relative (ie "images/p icture.jpg" rather than "/images/picture.jpg" or
"http://yourdomain.net/images/picture.jpg" or "C: \Documents and Settings\username\My
Documents\mini-website\images\picture.jpg") and no link is longer than 255 characters.
Access the index.html file and brow se around the mini-website, to ensure that the most
commonly used browsers (Internet Explorer and Firefox) are able to view all parts of the
mini-website without problems, it is ideal to check this on a different machine .
63
Compress the folder into a ZIP, ch eck the file size is under 20 MB, ensure that index.html is
in the root of the ZIP, and that the file has .zip extension, then submit as an additional file
with your article.
Style and language
General
Currently, Cardiovascular Diabetology can only accept manuscripts written in English.
Spelling should be US English or British English, but not a mixture.
There is no explicit limit on the length of articles submitted, but authors are
encouraged to be concise.
Cardiovascular Diabetology will not edit submitted manuscripts for style or language;
reviewers may advise rejection of a manuscript if it is compromised by grammatical errors.
Authors are advised to write clearly and simply, and to have their article checked by
colleagues before submission. In-house copyediting will be minimal. Non -native speakers of
English may choose to make use of a copyediting service.
Help and advice on scientific writing
The abstract is one of the most important parts of a manuscript. For guidance, please
visit our page on Writing titles and abstracts for scientific articles.
Tim Albert has produced for BioMed Central a list of tips for writing a scientific
manuscript. American Scientist also provides a list of resources for science writing. For more
detailed guidance on preparing a manuscript and writing in English, please visit the BioMed
Central author academy.
Abbreviations
Abbreviations should be used as sparingly as possible. They should be defined when
first used and a list of abbreviations can be provided following the main manuscript text.
Typography
Please use double line spacing.
Type the text unjustified, without hyphenating words at line breaks.
Use hard returns only to end headings and paragraphs, not to rearrange lines.
64
Capitalize only the first word, and proper nouns, in the title.
All pages should be numbered.
Use the Cardiovascular Diabetology reference format.
Footnotes are not allowed, but endnotes are permitted.
Please do not format the text in multiple columns.
Greek and other special characters may be included. If you are unable to reproduce a
particular special character, please type out the name of the symbol in full. Please
ensure that all special characters used are embedded in the text, otherwise they will be
lost during conversion to PDF.
Units
SI units should be used throughout (liter and molar are permitted, however).
65
-Anexo II-
66
Normas da Revista DIABETES RESEARCH AND CLINICAL PRACTICE
(ISSN 0168-8227)
Manuscript Submission
Manuscripts should be submitted online at http://ees.elsevier.com/diab and the instructions
on the site should be followed closely. Authors may submit manuscripts and track their
progress to final decision. Reviewers can download manuscripts and submit their reports to
the Editors.
The full contact details for the Editorial Office are shown below:
Diabetes Research and Clinical Practice Editorial Office, Elsevier Ltd., The Boulevard,
Langford Lane, Kidlington, Oxford, OX 5 1GB, UK; Phone: +44 (0) 1865 843753 Fax: +44
(0) 1865 843977 Email: Diab@elsevier.com
Journal Principles
All manuscripts submitted to Diabetes Research and Clinical Practice should report original
research not previously published or being considered fo r publication elsewhere, make
explicit any conflict of interest, identify sources of funding and generally be of a high ethical
standard.
Submission of a manuscript to this journal gives the publisher the right to publish that paper if
it is accepted. Manuscripts may be edited to improve clarity and expression. Submission of a
paper to Diabetes Research and Clinical Practice is understood to imply that it has not
previously been published and that it is not being considered for publication elsewhere.
Authorship
The Corresponding Author must submit a completed Author Consent Form to DRCP with
their manuscript. All authors must sign theAuthor Consent Form.
All authors should have made substantial contributions to all of the following: (1) the
conception and design of the study, or acquisition of data, or analysis and interpretation of
66
Normas da Revista DIABETES RESEARCH AND CLINICAL PRACTICE
(ISSN 0168-8227)
Manuscript Submission
Manuscripts should be submitted online at http://ees.elsevier.com/diab and the instructions
on the site should be followed closely. Authors may submit manuscripts and track their
progress to final decision. Reviewers can download manuscripts and submit their reports to
the Editors.
The full contact details for the Editorial Office are shown below:
Diabetes Research and Clinical Practice Editorial Office, Elsevier Ltd., The Boulevard,
Langford Lane, Kidlington, Oxford, OX 5 1GB, UK; Phone: +44 (0) 1865 843753 Fax: +44
(0) 1865 843977 Email: Diab@elsevier.com
Journal Principles
All manuscripts submitted to Diabetes Research and Clinical Practice should report original
research not previously published or being considered fo r publication elsewhere, make
explicit any conflict of interest, identify sources of funding and generally be of a high ethical
standard.
Submission of a manuscript to this journal gives the publisher the right to publish that paper if
it is accepted. Manuscripts may be edited to improve clarity and expression. Submission of a
paper to Diabetes Research and Clinical Practice is understood to imply that it has not
previously been published and that it is not being considered for publication elsewhere.
Authorship
The Corresponding Author must submit a completed Author Consent Form to DRCP with
their manuscript. All authors must sign theAuthor Consent Form.
All authors should have made substantial contributions to all of the following: (1) the
conception and design of the study, or acquisition of data, or analysis and interpretation of
66
Normas da Revista DIABETES RESEARCH AND CLINICAL PRACTICE
(ISSN 0168-8227)
Manuscript Submission
Manuscripts should be submitted online at http://ees.elsevier.com/diab and the instructions
on the site should be followed closely. Authors may submit manuscripts and track their
progress to final decision. Reviewers can download manuscripts and submit their reports to
the Editors.
The full contact details for the Editorial Office are shown below:
Diabetes Research and Clinical Practice Editorial Office, Elsevier Ltd., The Boulevard,
Langford Lane, Kidlington, Oxford, OX 5 1GB, UK; Phone: +44 (0) 1865 843753 Fax: +44
(0) 1865 843977 Email: Diab@elsevier.com
Journal Principles
All manuscripts submitted to Diabetes Research and Clinical Practice should report original
research not previously published or being considered fo r publication elsewhere, make
explicit any conflict of interest, identify sources of funding and generally be of a high ethical
standard.
Submission of a manuscript to this journal gives the publisher the right to publish that paper if
it is accepted. Manuscripts may be edited to improve clarity and expression. Submission of a
paper to Diabetes Research and Clinical Practice is understood to imply that it has not
previously been published and that it is not being considered for publication elsewhere.
Authorship
The Corresponding Author must submit a completed Author Consent Form to DRCP with
their manuscript. All authors must sign theAuthor Consent Form.
All authors should have made substantial contributions to all of the following: (1) the
conception and design of the study, or acquisition of data, or analysis and interpretation of
67
data, (2) drafting the article or revising it critically for important intellectual content, (3) final
approval of the version to be submitted.
Acknowledgements
All contributors who do not meet the criteria for authorship as defined above should be listed
in an acknowledgements section. Examples of those who might be acknowledged include a
person who provided purely technical help, writing assistance, or a department chair who
provided only general support. Authors should disclose whether they had any writing
assistance and identify the entity that paid for this assistance.
Ethics
Work on human beings that is submitted to the journal should comply with the principles laid
down in the Declaration of Helsinki "Recommendations guiding physicians in biomedical
research involving human subjects", adopted by the 18th World Medical Assembly, Helsinki,
Finland, June 1964 (and its successive amendments). The manuscript should contain a
statement that the work has been approved by the appropriate ethical committees related to
the institution(s) in which it was performed. Studies involving experiments with animal s must
state that their care was in accordance with institution guidelines.
Patients and Study Participants
Studies on patients or volunteers require ethics committee approval and informed consent
which should be documented in your paper.
Patients have a right to privacy. Therefore identifying information, including patient's
photographs, pedigree, images, names, initials, or hospital numbers, should not be included in
the submissions unless the information is essential for scientific purposes and written
informed consent has been obtained for publication in print and electronic form from the
patient (or parent, guardian or next of kin ). If such consent is made subject to any conditions,
Elsevier must be made aware of all such conditions. Written consents must be provided to the
journal on request.
68
Even where consent has been given, identifying details should be omitted if they are not
essential. Complete anonymity is difficult to achieve. For example, masking the eye region in
photographs of patients is inadequate protection of anonymity. If identifying characteristics
are altered to protect anonymity, such as in genetic pedigrees, authors should provide
assurance that alterations do not distort scientific meaning and editors should so note.
Clinical Trials
* All randomised controlled trials submitted to Diabetes Research and Clinical Practice whose
primary purpose is to affect clinical practice (phase 3 trials) must be registered in accordance
with the principles outlined by the International Committee of Medical Journal Ed itors
(ICMJE; http://www.icmje.org/). ICMJE-approved registries currently include the
following: http://www.anzctr.org.au, http://www.clinicaltrials.gov,
http://www.ISRCTN.org, http://www.umin.ac.jp/ctr/index/htm,
http://www.trialregister.nl , and https://eudract.ema.europa.eu/ . Please include the unique
trial number and registry name on manuscript submission.
Conflict of Interest Statement
All authors must disclose any financial and personal relationships with other people or
organisations that could inappropriately influence (bias) their work, all within 3 years of
beginning the work submitted. If there are no conflicts of interest, authors should state that
there are none. This statement will be included in the published article.
Article Types
N.B. For reasons of available space, manuscripts that exceed the required word limits (below)
will be declined automatically. All articles other than Editorials and Letters to the Editor are
subject to full peer review.
1. Editorials are either written or commissioned by the Editors and should not exceed 1000
words (not including a maximum of 20 references; one small figure can be i ncluded).
2. Commentaries (1000 words not including a maximum of 20 references and one small
68
Even where consent has been given, identifying details should be omitted if they are not
essential. Complete anonymity is difficult to achieve. For example, masking the eye region in
photographs of patients is inadequate protection of anonymity. If identifying characteristics
are altered to protect anonymity, such as in genetic pedigrees, authors should provide
assurance that alterations do not distort scientific meaning and editors should so note.
Clinical Trials
* All randomised controlled trials submitted to Diabetes Research and Clinical Practice whose
primary purpose is to affect clinical practice (phase 3 trials) must be registered in accordance
with the principles outlined by the International Committee of Medical Journal Ed itors
(ICMJE; http://www.icmje.org/). ICMJE-approved registries currently include the
following: http://www.anzctr.org.au, http://www.clinicaltrials.gov,
http://www.ISRCTN.org, http://www.umin.ac.jp/ctr/index/htm ,
http://www.trialregister.nl , and https://eudract.ema.europa.eu/ . Please include the unique
trial number and registry name on manuscript submission.
Conflict of Interest Statement
All authors must disclose any financial and personal relationships with other people or
organisations that could inappropriately influence (bias) their work, all within 3 years of
beginning the work submitted. If there are no conflicts of interest, authors should state that
there are none. This statement will be included in the published article.
Article Types
N.B. For reasons of available space, manuscripts that exceed the required word limits (below)
will be declined automatically. All articles other than Editorials and Letters to the Editor are
subject to full peer review.
1. Editorials are either written or commissioned by the Editors and should not exceed 1000
words (not including a maximum of 20 references; one small figure can be i ncluded).
2. Commentaries (1000 words not including a maximum of 20 references and one small
68
Even where consent has been given, identifying details should be omitted if they are not
essential. Complete anonymity is difficult to achieve. For example, masking the eye region in
photographs of patients is inadequate protection of anonymity. If identifying characteristics
are altered to protect anonymity, such as in genetic pedigrees, authors should provide
assurance that alterations do not distort scientific meaning and editors should so note.
Clinical Trials
* All randomised controlled trials submitted to Diabetes Research and Clinical Practice whose
primary purpose is to affect clinical practice (phase 3 trials) must be registered in accordance
with the principles outlined by the International Committee of Medical Journal Ed itors
(ICMJE; http://www.icmje.org/). ICMJE-approved registries currently include the
following: http://www.anzctr.org.au, http://www.clinicaltrials.gov,
http://www.ISRCTN.org, http://www.umin.ac.jp/ctr/index/htm,
http://www.trialregister.nl , and https://eudract.ema.europa.eu/ . Please include the unique
trial number and registry name on manuscript submission.
Conflict of Interest Statement
All authors must disclose any financial and personal relationships with other people or
organisations that could inappropriately influence (bias) their work, all within 3 years of
beginning the work submitted. If there are no conflicts of interest, authors should state that
there are none. This statement will be included in the published article.
Article Types
N.B. For reasons of available space, manuscripts that exceed the required word limits (below)
will be declined automatically. All articles other than Editorials and Letters to the Editor are
subject to full peer review.
1. Editorials are either written or commissioned by the Editors and should not exceed 1000
words (not including a maximum of 20 references; one small figure can be i ncluded).
2. Commentaries (1000 words not including a maximum of 20 references and one small
69
figure) offer a stimulating, journalistic and accessible insight into issues of common interest.
They are usually commissioned by the Editors but unsolicited arti cles will be considered.
Debates comprise two commentaries of opposing or contrasting opinion written by two
different groups of authors. Controversial opinions are welcomed as long as they are set in the
context of the generally accepted view.
3. Original Research Articles should be designated either (a) Basic Research (b) Clinical
Research or (c) Epidemiology and should be a maximum of 5000 words. The word limit
includes a combined total of five figures or tables with legends, but does not include up to 50
references and an abstract of up to 200 words structured according to Aims, Methods, Results,
Conclusions and Keywords. Divide the manuscript into the following sections: Title Page;
Structured Abstract; Introduction; Subjects, Materials and Methods; Re sults; Discussion;
Acknowledgements; References; figures and tables with legends.
4. Brief Reports should not exceed 1000 words, including a summary of no more than 50
words (but not including up to 20 references) and may be a preliminary report of work
completed, a final report or an observation not requiring a lengthy write -up.
5. Review articles should be a maximum of 5000 words, including a summary of no more
than 200 words (not including up to 75 references) with subheadings in the text to highlight
the content of different sections. The word limit includes a combined total of five figures or
tables with legends. Reviews are generally commissioned by the Editors but unsolicited
articles will be considered.
6. Letters to the Editor should be no more than 400 words.
Brief Reports and Letters to the Editor will only be published electronically but will be listed
in the print Table of Contents. These articles can be cited by Digital Object Identifier (DOI)
rather than page number.
70
Manuscript Style and Format
Abbreviations should be avoided in most cases or at least fully defined on first use. Clinical
research values and units should be in Systme International (SI) form. Kilocalories should be
used rather than kilojoules.
The term 'diabetic' should be avoided. Preferred terminology is, for example, 'person with
diabetes' or 'in the group without diabetes'. The terms 'Type 1' and 'Type 2 diabetes mellitus'
should be used.
HbA1c Values
Authors should report glycated haemoglob in (HbA1c) measurement in derived NGSP units
(%; to one decimal point) in addition to IFCC (International Federation of Clinical Chemistry)
units (mmol/mol; no decimal point). NGSP units should be listed first followed by IFCC units
in parentheses.
Style. Headlines and subheadlines should be employed liberally in the Methods, Results, and
Discussion sections. Use short paragraphs whenever possible. Clarity of expression, good
syntax and the avoidance of jargon is appreciated by the editors and readers. Abb reviations
should be explained in the text.
The Title Page should include authors' names, highest earned degrees, academic addresses,
address for correspondence, and grant support. Authorship should be assumed only by those
workers who have contributed mat erially to the work and its report. Colleagues who have
otherwise assisted or collaborated should be recognized in the Acknowledgment section, as
should sources of funding. The title should be informative and concise. Avoid use of
extraneous words such as "study," "investigation," etc. If data from the manuscript have been
presented at a meeting, list the full name, date and location of the meeting and reference any
previously published abstracts in the bibliography.
Structured Abstract: Original Research Articles
71
An abstract of no more than 250 words should be structured as per following:
• Aims: Reflects the purpose of the study (the hypothesis that is being tested);
• Methods: The setting for the study, the subjects (number and type), the treatment or
intervention, and the type(s) of statistical analysis used;
• Results: The outcome(s) of the study and, if appropriate, its/their statistical significance;
• Conclusions: The significance of the results.
Abstracts for other articles (Commentaries and Revie ws) should be written as a single
paragraph not to exceed 200 words. Key Wordsshould also be provided in the manuscript;
normally 3-5 items should be included.
The Introduction should be brief and set out the purposes for which the study has been
performed.
The Materials and Methods should be sufficiently detailed so that readers and reviewers can
understand precisely what has been done without studying the references directly. The
description may be abbreviated when well -accepted techniques are used.
The Results should be presented precisely and concisely. Keep discussion of their importance
to a minimum in this section of the manuscript.
The Discussion should relate directly to the study being reported with clear conclusions plus a
perspective on possible future research. Do not include a general review of the topic.
References. The author(s) is/are responsible for the accuracy and completeness of the
references, which should be identified in the text by Arabic numerals within square brackets
in the order of first citation (i.e. [1,2]) and listed in numerical order at the end of the text.
References must include author(s) last name(s), followed by initials (listing all authors if six
or fewer, or the first six authors followed by et al. if seven or more), title of article, title of
journal abbreviated according to the Index Medicus, year of publication in parentheses,
volume (and supplement if appropriate) and first and last page numbers. References to books
must include author(s) last name(s) followed b y initials, title of chapter, editor(s) last name(s)
72
and initials, title of book, publisher, place of publication, year of publication, and first and last
page numbers. 'Articles in press' can be included in the reference list but submitted work
under consideration at a publisher must be cited in the main text as 'Author X, unpublished
data'. Draft analyses can be referred to in the main text as 'Author X, personal
communication'.
Journal Reference Example
Lu P, Liu F, Yan L, Peng T, Liu T, Yao Z et al. Stem cell therapy for type 1 diabetes.
Diabetes Res. Clin. Pract., 2007;78:1-7.
Book Reference Example
1. Drury P, Gatling W. Diabetes: Your Questions Answered. Churchill Livingstone,
Edinburgh, 2005.
Figures must be suitable for high-quality reproduction. Lettering should be complete, of
professional quality, and of a size appropriate to that of the illustration or drawing, with the
necessary reduction in size taken into account. If, together with your accepted article, you
submit usable colour figures, El sevier will ensure that these figures appear free -of-charge in
colour in the electronic version of your accepted article, regardless of whether or not these
illustrations are reproduced in colour in the printed version. Colour illustrations can only be
included in print if the additional cost of reproduction is contributed by the author: you will
receive information regarding the costs from Elsevier after receipt of your accepted article.
Please go to http://ees.elsevier.com/diab and click on the Artwork Guidelines.
Supplementary files offer the author additional possibilities to publish supporting
applications, movies, animation sequences, high -resolution images, background datasets,
sound clips and more. Supplementary files supplied will be published online alongside the
electronic version of your article in Elsevier web products, including ScienceDirect:
http://www.sciencedirect.com. In order to ensure that your submitted material is directly
usable, please ensure that data is provided in one of our recommended file formats. Authors
72
and initials, title of book, publisher, place of publication, year of publication, and first and last
page numbers. 'Articles in press' can be included in the reference list but submitted work
under consideration at a publisher must be cited in the main text as 'Author X, unpublished
data'. Draft analyses can be referred to in the main text as 'Author X, personal
communication'.
Journal Reference Example
Lu P, Liu F, Yan L, Peng T, Liu T, Yao Z et al. Stem cell therapy for type 1 diabetes.
Diabetes Res. Clin. Pract., 2007;78:1-7.
Book Reference Example
1. Drury P, Gatling W. Diabetes: Your Questions Answered. Churchill Livingstone,
Edinburgh, 2005.
Figures must be suitable for high-quality reproduction. Lettering should be complete, of
professional quality, and of a size appropriate to that of the illustration or drawing, with the
necessary reduction in size taken into account. If, together with your accepted article, you
submit usable colour figures, El sevier will ensure that these figures appear free -of-charge in
colour in the electronic version of your accepted article, regardless of whether or not these
illustrations are reproduced in colour in the printed version. Colour illustrations can only be
included in print if the additional cost of reproduction is contributed by the author: you will
receive information regarding the costs from Elsevier after receipt of your accepted article.
Please go to http://ees.elsevier.com/diab and click on the Artwork Guidelines.
Supplementary files offer the author additional possibilities to publish supporting
applications, movies, animation sequences, high -resolution images, background datasets,
sound clips and more. Supplementary files supplied will be published online alongside the
electronic version of your article in Elsevier web products, including ScienceDirect:
http://www.sciencedirect.com. In order to ensure that your submitted material is directly
usable, please ensure that data is provided in one of our recommended file formats. Authors
72
and initials, title of book, publisher, place of publication, year of publication, and first and last
page numbers. 'Articles in press' can be included in the reference list but submitted work
under consideration at a publisher must be cited in the main text as 'Author X, unpublished
data'. Draft analyses can be referred to in the main text as 'Author X, personal
communication'.
Journal Reference Example
Lu P, Liu F, Yan L, Peng T, Liu T, Yao Z et al. Stem cell therapy for type 1 diabetes.
Diabetes Res. Clin. Pract., 2007;78:1-7.
Book Reference Example
1. Drury P, Gatling W. Diabetes: Your Questions Answered. Churchill Livingstone,
Edinburgh, 2005.
Figures must be suitable for high-quality reproduction. Lettering should be complete, of
professional quality, and of a size appropriate to that of the illustration or drawing, with the
necessary reduction in size taken into account. If, together with your accepted article, you
submit usable colour figures, El sevier will ensure that these figures appear free -of-charge in
colour in the electronic version of your accepted article, regardless of whether or not these
illustrations are reproduced in colour in the printed version. Colour illustrations can only be
included in print if the additional cost of reproduction is contributed by the author: you will
receive information regarding the costs from Elsevier after receipt of your accepted article.
Please go to http://ees.elsevier.com/diab and click on the Artwork Guidelines.
Supplementary files offer the author additional possibilities to publish supporting
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been established for authors whose articles have been accepted for publication in an Elsevier
journal and whose underlying research is supported by one of the following funding bodies:
• National Institutes of Health : Elsevier will send a version of the author's accepted
manuscript that includes author revisions following peer -review for public access posting 12
months after final publication. Because the NIH 'Public Access' policy is voluntary, authors
may elect not to deposit such articles in PMC. If you wish to 'opt out' and not deposit to PMC,
you may indicate this by sending an e -mail to NIHauthorrequest@elsevier.com. More
information regarding the agreement between Elsevier and the National Institutes of Health
can be found at http://www.elsevier.com/wps/find/authorshome.authors/nihauthorrequest
• The Wellcome Trust: Elsevier will send to PMC the version of the author's manuscript that
reflects all author-agreed changes including those made post peer review, for public access
posting immediately after final publication. Authors are required to initially subsidize their
manuscript with fees reimbursed by the Wellcome Trust. Wellcome Trust authors, whose
manuscripts are subsidized, will have the corresponding articles made free to non -subscribers
on ScienceDirect www.sciencedirect.com and Elsevier's electronic publishing platforms.
More information regarding the agreement between Elsevier and The Wellcome Trust can be
found at http://www.elsevier.com/wps/find/authorshome.authors/wellcometrustauthors .
Diabetes Research and Clinical Practice is the official journal of the International
Diabetes Federation.
74
Special Subject Repositories
Certain repositories such as PubMed Central ('PMC') are authorized under special
arrangement with Elsevier to process and post certain articles. The following agreements have
been established for authors whose articles have been accepted for publication in an Elsevier
journal and whose underlying research is supported by one of the following funding bodies:
• National Institutes of Health : Elsevier will send a version of the author's accepted
manuscript that includes author revisions following peer -review for public access posting 12
months after final publication. Because the NIH 'Public Access' policy is voluntary, authors
may elect not to deposit such articles in PMC. If you wish to 'opt out' and not deposit to PMC,
you may indicate this by sending an e -mail to NIHauthorrequest@elsevier.com. More
information regarding the agreement between Elsevier and the National Institutes of Health
can be found at http://www.elsevier.com/wps/find/authorshome.authors/nihauthorrequest
• The Wellcome Trust: Elsevier will send to PMC the version of the author's manuscript that
reflects all author-agreed changes including those made post peer review, for public access
posting immediately after final publication. Authors are required to initially subsidize their
manuscript with fees reimbursed by the Wellcome Trust. Wellcome Trust authors, whose
manuscripts are subsidized, will have the corresponding articles made free to non -subscribers
on ScienceDirect www.sciencedirect.com and Elsevier's electronic publishing platforms.
More information regarding the agreement between Elsevier and The Wellcome Trust can be
found at http://www.elsevier.com/wps/find/authorshome.authors/wellcometrustauthors .
Diabetes Research and Clinical Practice is the official journal of the International
Diabetes Federation.
74
Special Subject Repositories
Certain repositories such as PubMed Central ('PMC') are authorized under special
arrangement with Elsevier to process and post certain articles. The following agreements have
been established for authors whose articles have been accepted for publication in an Elsevier
journal and whose underlying research is supported by one of the following funding bodies:
• National Institutes of Health : Elsevier will send a version of the author's accepted
manuscript that includes author revisions following peer -review for public access posting 12
months after final publication. Because the NIH 'Public Access' policy is voluntary, authors
may elect not to deposit such articles in PMC. If you wish to 'opt out' and not deposit to PMC,
you may indicate this by sending an e -mail to NIHauthorrequest@elsevier.com. More
information regarding the agreement between Elsevier and the National Institutes of Health
can be found at http://www.elsevier.com/wps/find/authorshome.authors/nihauthorrequest
• The Wellcome Trust: Elsevier will send to PMC the version of the author's manuscript that
reflects all author-agreed changes including those made post peer review, for public access
posting immediately after final publication. Authors are required to initially subsidize their
manuscript with fees reimbursed by the Wellcome Trust. Wellcome Trust authors, whose
manuscripts are subsidized, will have the corresponding articles made free to non -subscribers
on ScienceDirect www.sciencedirect.com and Elsevier's electronic publishing platforms.
More information regarding the agreement between Elsevier and The Wellcome Trust can be
found at http://www.elsevier.com/wps/find/authorshome.authors/wellcometrustauthors .
Diabetes Research and Clinical Practice is the official journal of the International
Diabetes Federation.
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