Histone deacetylase inhibitors target diabetes via chromatin remodeling or as chemical chaperones?

Globally, obesity and diabetes (particularly type 2 diabetes) represents a major challenge to world health. Despite decades of intense research efforts, the genetic basis involved in diabetes pathogenesis & conditions associated with obesity are still poorly understood. Recent advances have led to exciting new developments implicating epigenetics as an important mechanism underpinning diabetes and obesity related disease. One epigenetic mechanism known as the "histone code" describes the idea that specific patterns of post-translational modifications to histones act like a molecular "code" recognised and used by non-histone proteins to regulate specific chromatin functions. One modification which has received significant attention is that of histone acetylation. The enzymes which regulate this modification are described as lysine acetyltransferases or KATs and histone deacetylases or HDACs. Due to their conserved catalytic domain HDACs have been actively targeted as a therapeutic target. Some of the known inhibitors of HDACs (HDACi) have also been shown to act as "chemical chaperones" to alleviate diabetic symptoms. In this review, we discuss the available evidence concerning the roles of HDACs in regulating chaperone function and how this may have implications in the management of diabetes. © 2009 Bentham Science Publishers Ltd.

Nurse-led behavioral management of diabetes and hypertension in community practices: a randomized trial.

BACKGROUND: Several trials have demonstrated the efficacy of nurse telephone case management for diabetes (DM) and hypertension (HTN) in academic or vertically integrated systems. Little is known about the real-world potency of these interventions. OBJECTIVE: To assess the effectiveness of nurse behavioral management of DM and HTN in community practices among patients with both diseases. DESIGN: The study was designed as a patient-level randomized controlled trial. PARTICIPANTS: Participants included adult patients with both type 2 DM and HTN who were receiving care at one of nine community fee-for-service practices. Subjects were required to have inadequately controlled DM (hemoglobin A1c [A1c] ≥ 7.5%) but could have well-controlled HTN. INTERVENTIONS: All patients received a call from a nurse experienced in DM and HTN management once every two months over a period of two years, for a total of 12 calls. Intervention patients received tailored DM- and HTN- focused behavioral content; control patients received non-tailored, non-interactive information regarding health issues unrelated to DM and HTN (e.g., skin cancer prevention). MAIN OUTCOMES AND MEASURES: Systolic blood pressure (SBP) and A1c were co-primary outcomes, measured at 6, 12, and 24 months; 24 months was the primary time point. RESULTS: Three hundred seventy-seven subjects were enrolled; 193 were randomized to intervention, 184 to control. Subjects were 55% female and 50% white; the mean baseline A1c was 9.1% (SD = 1%) and mean SBP was 142 mmHg (SD = 20). Eighty-two percent of scheduled interviews were conducted; 69% of intervention patients and 70% of control patients reached the 24-month time point. Expressing model estimated differences as (intervention--control), at 24 months, intervention patients had similar A1c [diff = 0.1 %, 95 % CI (-0.3, 0.5), p = 0.51] and SBP [diff = -0.9 mmHg, 95% CI (-5.4, 3.5), p = 0.68] values compared to control patients. Likewise, DBP (diff = 0.4 mmHg, p = 0.76), weight (diff = 0.3 kg, p = 0.80), and physical activity levels (diff = 153 MET-min/week, p = 0.41) were similar between control and intervention patients. Results were also similar at the 6- and 12-month time points. CONCLUSIONS: In nine community fee-for-service practices, telephonic nurse case management did not lead to improvement in A1c or SBP. Gains seen in telephonic behavioral self-management interventions in optimal settings may not translate to the wider range of primary care settings.

3-Deoxyfructose concentrations are increased in human plasma and urine in diabetes

3-Deoxyglucosone (3-DG) is a reactive dicarbonyl sugar thought to be a key intermediate in the nonenzymatic polymerization and browning of proteins by glucose. 3-DG may be formed in vivo from fructose, fructose 3-phosphate, or Amadori adducts to protein, such as N epsilon-fructoselysine (FL), all of which are known to be elevated in body fluids or tissues in diabetes. Modification of proteins by 3-DG formed in vivo is thought to be limited by enzymatic reduction of 3-DG to less reactive species, such as 3-deoxyfructose (3-DF). In this study, we have measured 3-DF, as a metabolic fingerprint of 3-DG, in plasma and urine from a group of diabetic patients and control subjects. Plasma and urinary 3-DF concentrations were significantly increased in the diabetic compared with the control population (0.853 +/- 0.189 vs. 0.494 +/- 0.072 microM, P <0.001, and 69.9 +/- 44.2 vs. 38.7 +/- 16.1 nmol/mg creatinine, P <0.001, respectively). Plasma and urinary 3-DF concentrations correlated strongly with one another, with HbA1c (P <0.005 in all cases), and with urinary FL (P <0.02 and P = 0.005, respectively). The overall increase in 3-DF concentrations in plasma and urine in diabetes and their correlation with other indexes of glycemic control suggest that increased amounts of 3-DG are formed in the body during hyperglycemia in diabetes and then metabolized to 3-DF. These observations are consistent with a role for increased formation of the dicarbonyl sugar 3-DG in the accelerated browning of tissue proteins in diabetes.

HDLs, diabetes, and metabolic syndrome.

The prevalence of type 2 diabetes mellitus and of the metabolic syndrome is rising worldwide and reaching epidemic proportions. These pathologies are associated with significant morbidity and mortality, in particular with an excess of cardiovascular deaths. Type 2 diabetes mellitus and the cluster of pathologies including insulin resistance, central obesity, high blood pressure, and hypertriglyceridemia that constitute the metabolic syndrome are associated with low levels of HDL cholesterol and the presence of dysfunctional HDLs. We here review the epidemiological evidence and the potential underlying mechanisms of this association. We first discuss the well-established association of type 2 diabetes mellitus and insulin resistance with alterations of lipid metabolism and how these alterations may lead to low levels of HDL cholesterol and the occurrence of dysfunctional HDLs. We then present and discuss the evidence showing that HDL modulates insulin sensitivity, insulin-independent glucose uptake, insulin secretion, and beta cell survival. A dysfunction in these actions could play a direct role in the pathogenesis of type 2 diabetes mellitus.

Barns upplevelser av att leva med diabetes mellitus typ 1 : samt sjuksköterskans betydelse i deras omvårdnad

Syftet med denna studie har varit att beskriva hur barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom samt vilken betydelse sjuksköterskan kunde ha i omvårdnaden av dessa barn. Studien har utförts som en systematisk litteraturstudie och tillvägagångssättet har varit att systematiskt söka, kritiskt granska och sammanställa resultat inom det valda ämnesområdet från olika studier. Sökningen har skett i databaserna Elin@Dalarna, Cinahl och Blackwell Synergy. Sökorden som har använts var: diabetes mellitus type 1, diabetes mellitus, children, adolescents, experiences, perspective, nurs* och care i olika kombinationer. Sammanställningen från resultatet visade att barn med diagnosen diabetes mellitus typ 1 upplever sin sjukdom olika utifrån sina egna förutsättningar, kön eller ålder. Det framkom även att sjuksköterskan hade en viktig roll när det gällde att fånga upp barnens upplevelser kring den förändrade livssituationen som uppstått och utifrån detta kartlägga barnens resurser att hantera denna situation. Att då kunna bemöta barnen och deras familjer utifrån egna förutsättningar och att motivera dessa till att sköta den livslånga behandlingen, kan vara avgörande för att få en bra kontroll över diabetes och på så sätt en ökad livskvalité och ett gott välbefinnande.

Efeito da retirada da carne vermelha da dieta sobre a função renal e perfil lipídico sérico de pacientes com diabetes melito tipo 2 e nefropatia diabética

Resumo não disponível.

Syzygium cumini (L.) Skells no tratamento do diabetes melito tipo 2 : resultado de um ensaio clínico randomizado, controlado, duplo-cego e double-dummy

Resumo não disponível.

Raça, etnia e as complicações crônicas do diabetes melito tipo 2

Fatores genéticos e ambientais são apontados como fatores causais para explicar as diferenças no desenvolvimento de problemas de saúde entre grupos étnicos. O conceito de raça/etnia é definido, assim como as indicações de seu uso. Diabetes melito (DM) como um estado de doença com uma marcada variabilidade étnico-racial é utilizado como exemplo de análise. Através de estudo transversal avaliou-se a prevalência das complicações vasculares em uma amostra de pacientes com DM tipo 2. Um total de 864 pacientes, incluindo 656 brancos, 104 mulatos e 104 pretos, classificados por auto-definição, foram avaliados através de protocolo padrão para doença arterial coronariana (DAC), doença vascular periférica (DVP), acidente vascular cerebral (AVC), retinopatia diabética (RD), nefropatia diabética (ND) e neuropatia diabética sensório-motora distal (NSMD). Pacientes brancos e mulatos eram mais velhos que os pacientes pretos (61,0 ± 9,3 vs. 60,1 ± 10,3 vs. 56,0 ± 10,3 anos; P <0,001), embora o tempo de duração do DM fosse semelhante entre os grupos (14,8 ± 8,2 vs. 14,2 ± 6,7 vs. 13,3 ± 7,0 anos; P = 0,169). Parâmetros antropométricos (índice de massa corporal e medida da cintura), prevalência de síndrome metabólica, hipertensão arterial sistêmica, níveis de hemoglobina glicada, também foram similares entre os grupos. Em relação às complicações crônicas do DM, brancos, mulatos e pretos apresentaram-se com uma prevalência similar de DVP, AVC e NSMD. Mulatos e pretos, quando comparados com brancos, apresentaram uma maior prevalência de DAC (45,4% vs. 60,4% vs. 39,2% ; P=0,004). As prevalências de microalbuminúria (22,4%, 21,2 e 22,1%; P= 0,906) e macroalbuminuria (16,2%, 19,2% and 13,5%; P= 0,915) foram similares entre os grupos. Doença renal avançada (diálise) (9% vs. 8,7% vs. 18,3%; P=0,012) e RDP (21,5% vs. 15,4% vs. 34,6%; P=0,005) foram mais freqüentes em pretos. Estas diferenças se mantiveram após ajustes para possíveis fatores de confusão. Concluindo, em pacientes com DM tipo 2 com o mesmo tipo de assistência médica, controle pressórico e metabólico, foi observada uma prevalência maior de DAC, RDP e doença renal avançada em pacientes pretos. Os mecanismos pelos quais estas diferenças ocorrem não são claros e componentes genéticos e/ou ambientais devem ser melhor explorados. Entretanto, até que este melhor entendimento seja disponível, uma abordagem mais agressiva na avaliação e manejo dos fatores de risco para as complicações do DM nos indivíduos pretos deve ser pensada.

Estudo dos genes do complexo do antígeno leucocitário humano (hla) associados à susceptibilidade ao diabetes mellitus tipo 1

Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region, mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1 constituting haplotypes, and further, a combination of more than one haplotype, providing multilocus genotypes are associated with susceptibility, protection and neutrality to DM1. Thus, the aim of present study was to verified the association of polymorphisms of HLA genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied. Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the extraction kit Illustra Triple Prep®, GE Healthcare. For HLA typing was used DNA LABType system by One Lambda kit applying Luminex® technology to the method of PCRSSO typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g, *05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03, *15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8 haplotypes, were significantly associated with T1D protection Despite the major racial Brazilian, even at the regional level, these results are similar to the majority of alleles, genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D, extensively described in the literature for Caucasian population. Children with age at diagnosis less than 5 years of age had significantly higher frequency of the heterozygous genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old. These results also demonstrate strong association of the genetic profile of the class II HLA for this age group, possibly associated with the severity and rapid progression to the onset of T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the prediction of T1D

A experiência de adolescentes portadores de diabetes Mellitus Tipo 1: seus significados e sentido

Worldwide, the diabetes mellitus is considered a serious problem of public health; it also involves high costs for its treatment and its complications. Even though the onset of diabetes mellitus type 1 is on 5% to 10% of the diabetic population, it is the most aggressive type of anifestation; furthermore, it is the commonest chronic disease in childhood and adolescence. Such data show the importance of understanding the development of this disease from the moment the individual perceives it, according to their experience, observing the complexity of the phenomenon thoroughly. This study aimed to comprehend the experience of the adolescent with onset of diabetes mellitus type 1 in order to learn how these young individuals perceive and reason their place in the world when they experience this illness. The methodological strategy was based on qualitative research of phenomenological inspiration. We applied the main ideas of heideggerian ontology and some concepts of existential phenomenological psychology to guide our reflexive path. The participants were 10 young individuals (06 female and 04 male), ages between 15 and 18, under treatment in the city of Recife, Pernambuco. The methodological resource was the narrative, which allowed us access to the adolescents experience. The comprehension of the reports was based on the heideggerian hermeneutics, whose priority is the interpretation of the meaning expressed by the participants speech. The results showed that factors such as social, family, economic and cultural context greatly influence the perception and the way the individuals deal with, perceive and reason their experience. We noticed that the diabetes type 1 may often represent a limitation, but it does not make it impossible to be part of the world with others. The data show a significant affective ambivalence regarding the content more directly related to the disease. This demonstrates the unique way which each one gives meaning and reasons their condition of existence. This research points out the need to understand the complexity of this phenomenon in a more complete manner, considering the adolescent in their timely and historical context. We believe we can encourage thinking that may become actions which are more fit to the reality researched regarding all the parties involved with the subject, such as health professionals, adolescents, family, support programs and public health policies

MODY 2: Mutation identification and molecular ancestry in a Brazilian family

Maturity Onset Diabetes of the Young (MODY) is a heterogeneous group of genetic diseases characterized by a primary defect in insulin secretion and hyperglycemia, non-ketotic disease, monogenic autosomal dominant mode of inheritance, age at onset less than 25. years, and lack of auto-antibodies. It accounts for 2-5% of all cases of non-type 1 diabetes. MODY subtype 2 is caused by mutations in the glucokinase (GCK) gene. In this study, we sequenced the GCK gene of two volunteers with clinical diagnosis for MODY2 and we were able to identify four mutations including one for a premature stop codon (c.76C>T). Based on these results, we have developed a specific PCR-RFLP assay to detect this mutation and tested 122 related volunteers from the same family. This mutation in the GCK gene was detected in 21 additional subjects who also had the clinical features of this genetic disease. In conclusion, we identified new GCK gene mutations in a Brazilian family of Italian descendance, with one due to a premature stop codon located in the second exon of the gene. We also developed a specific assay that is fast, cheap and reliable to detect this mutation. Finally, we built a molecular ancestry model based on our results for the migration of individuals carrying this genetic mutation from Northern Italy to Brazil. © 2012 Elsevier B.V.

Avaliação da relação entre diabetes mellitus e doença periodontal: um estudo em pacientes pertencentes à Casa do Diabético no município de Belém-PA

O diabetes mellitus é uma doença caracterizada por anormalidades endócrinas e matabólicas, que resulta em alterações em muitos setores do organismo. Ao passo que a doença periodontal é uma lesão infecto-inflamatória que envolve os tecidos de sustentação dos dentes. Convém, esclarecer a relação entre o diabetes mellitus e a doença periodontal por uma associação biológica, na qual diabéticos apresentam deficiência na resposta orgânica e aumento da suscetibilidade para muitos tipos de infecção, incluindo a infecção perioodntal. Este trabalho tem como objetivo comparar indivíduos com adequado controle metabólico do diabetes mellitus e indivíduos com pobre controle glicêmico da doença, em diferentes tempos de duração do diabetes. Foram avaliados periodontalmente 31 indivíduos com controle glicêmico adequado e 29 sujeitos com pobre controle metabólico. Os resultados revelaram que a condições de higiene bucal e de inflamação gengival são similares entre os indivíduos com diferentes anos de diabetes, independente da qualidade do controle metabólico do diabetes mellitus. A profundidade de sondagem revelou maior severidade em indivíduos com mais de cinco anos de doença, principalmente no grupo com pobre controle glicêmico. Em conclusão, indivíduos diabéticos com mais de cinco anos de duração da doença e com pobre controle metabólico do nível de glicemia apresentam maiores perdas de estrutura periodontal.

Necessidades especiais de escolares com diabetes mellitus tipo 1 identificadas por familiares

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)