Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes.

BACKGROUND AND AIMS: Since hyperglycemia promotes inflammation by different pathways and inflammation participates in the development of chronic diabetes complications, we investigated the association between the leukotriene (LT) pathway and microvascular diabetes complications. METHODS AND RESULTS: Quantitative polymerase chain reaction was employed to quantify the expression of ALOX5 (encodes 5-lipoxygenase), LTB4R (encodes one of the LTB4 receptors), and MYD88 in peripheral blood mononuclear cells from 164 type 1 diabetes (T1D) individuals presenting or not diabetes kidney disease, retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy (CAN); 26 nondiabetic subjects were included as controls. LTB4 plasmatic concentrations were also evaluated. The expression of LTB4R was significantly higher in T1D individuals than in controls. T1D individuals with microvascular complications presented lower MYD88 mRNA expression when compared to those without microvascular complications. Higher LTB4 concentrations were found in individuals with CAN versus without CAN. The observation of two distinct subgroups of T1D individuals in the correlation analyses motivated us to evaluate the characteristics of each one of these groups separately. The group presenting higher expression of ALOX5 and of LTB4R also presented higher values of HbA1C, of fructosamine, and of plasmatic LTB4. CONCLUSION: In the diabetes setting, the LT pathway is not only activated by hyperglycemia but is also modulated by the status of the autonomic nervous system.

Micro-RNAs 518d-3p and 618 Are Upregulated in Individuals With Type 1 Diabetes With Multiple Microvascular Complications.

Objective: To compare the serum micro-RNAs (miRNAs) profile of individuals with type 1 diabetes without microvascular complications vs. those with multiple severe microvascular complications, in order to identify epigenetically modulated pathways in these two groups of individuals. Research Design and Methods: A total of 10 subjects were selected among individuals followed in the Diabetes Outpatient Clinic and sorted according to the absence or presence of all microvascular complications. Samples from these participants were used for evaluation of serum miRNA expression profile employing a qRT-PCR assay with hydrolysis probes based on the Taqman Low Density Arrays (TLDA) system. The top six most differentially expressed miRNAs between the aforementioned groups were validated by qRT-PCR in additional 47 type 1 diabetes individuals sorted according to the absence or presence of all microvascular complications and matched for age, sex, degree of metabolic control, diabetes duration, and age at diagnosis. Results: Twenty one out of three hundred and seventy seven miRNAs were upregulated in the group of individuals with all microvascular complications vs. the group without complications. The following miRs were validated: 518-3p, 34a-5p, 126-5p, 425-5p, 618, and 139-5p and logistic regression analyses showed that miRNA-518-3p and miRNA-618 were positively associated with multiple microvascular complications after adjustment for age, sex, diabetes duration, HbA1c and use of statin, angiotensin-converting enzyme inhibitors and amlodipine. Conclusions: In this cohort of type 1 diabetes individuals, serum miR-518d-3p and miR-618 were upregulated in those with diabetes kidney disease, diabetes retinopathy, peripheral neuropathy, and cardiovascular autonomic neuropathy in comparison to individuals with no microvascular complications.

Dietary advanced glycated end-products and medicines influence the expression of SIRT1 and DDOST in peripheral mononuclear cells from long-term type 1 diabetes patients.

Quantitative polymerase chain reaction was employed to quantify expression of two genes coding for advanced glycation end-product receptors [RAGE ( AGER) and AGER1 ( DDOST)] and of the gene coding the deacetylase SIRT1 ( SIRT1) in peripheral blood mononuclear cells from type 1 diabetes patients without [Group A, n = 35; 28.5 (24-39) years old; median (interquartile interval)] or with at least one microvascular complication [Group B, n = 117; 34.5 (30-42) years old]; 31 healthy controls were also included. In a subgroup of 48 patients, daily advanced glycation end-products intake before blood collection was assessed. Lower expression of DDOST was found in patients than in controls after adjustment for sex, age, use of statins, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Higher expressions of AGER, DDOST and SIRT1 were observed in Group A. Stratifying by complications, AGER and DDOST expressions were higher in those without retinopathy and without diabetic kidney disease, respectively, compared to patients with these complications. Patients using statins or angiotensin receptor blockers presented higher expression of DDOST. Expression of SIRT1 was higher in patients consuming ≥12,872 KU daily of advanced glycation end-products. Although AGER, DDOST and SIRT1 are differently expressed in peripheral blood mononuclear cells from type 1 diabetes patients with and without microvascular complications, they are also influenced by dietary advanced glycation end-products and by statins and angiotensin receptor blockers.

[Diabetes immersion training as teaching method to medical practitioners]. / Curso de imersão em diabetes como técnica educativa para profissionais médicos.

This study evaluated the effectiveness of theoretical and practical teaching method in diabetes and doctors' position about feasibility of intensive blood glucose control. Forty-eight internal medicine or endocrinology residents participated in a two-day diabetes immersion course. The participants received training on self-blood glucose monitoring, techniques of insulin administration and carbohydrate counting. They were also instructed to behave as patients with diabetes and to follow individual medical prescription. They were assessed through questionnaires. In knowledge assessment, a significant increase of 12% was observed between the beginning and the end of the course (61.2% and 73.2%, respectively, with p < 0.0001). Before the course, 70.8% and 89.6% of the participants believed there were complications in performing carbohydrate counting and blood glucose monitoring, respectively. After the experience, 82.9% of them had difficulties in carbohydrate counting and 80.8% in self-monitoring; 40.4% took all medications prescribed and 36.1% monitored blood glucose correctly. These results show that the methodology of this course is an effective way to disseminate knowledge and that it contributes to doctors becoming more sensitive to daily problems faced by patients with diabetes melito concerning the acceptance of medical recommendations.

Curso de imersão em diabetes como técnica educativa para profissionais médicos / Diabetes immersion training as teaching method to medical practitioners

Este estudo avaliou a eficácia do método de ensino teórico e prático sobre diabetes e a atitude de profissionais médicos quanto à realização de controle glicêmico intensivo. Participaram de um curso de imersão em diabetes, com dois dias de duração, 48 médicos-residentes de clínica médica ou endocrinologia. Os participantes receberam treinamento de monitorização de glicemia capilar, técnicas de aplicação de insulina e contagem de carboidratos, sendo orientados a se portarem como diabéticos e a seguir prescrição médica individual. Foram avaliados através de questionários. No questionário de conhecimentos, observou-se um aumento significante de 12 por cento no índice de acertos entre o início e o final do curso (61,2 por cento e 73,2 por cento, respectivamente, com p < 0,0001). Antes do curso, 70,8 por cento dos participantes diziam ter dificuldades na contagem de carboidratos e 89,6 por cento, na automonitorização glicêmica. Após a experiência prática, 82,9 por cento dos participantes encontraram dificuldades na realização de contagem de carboidratos e 80,8 por cento, na automonitorização; 40,4 por cento fizeram uso de todas as medicações prescritas e 36,1 por cento monitorizaram todas as glicemias. Os resultados deste estudo mostram que esse tipo de curso é eficaz para a aquisição de conhecimentos e contribui com a sensibilização do profissional médico quanto às dificuldades cotidianas enfrentadas pelo portador de diabetes melito na aderência às recomendações.

This study evaluated the effectiveness of theoretical and practical teaching method in diabetes and doctors' position about feasibility of intensive blood glucose control. Forty-eight internal medicine or endocrinology residents participated in a two-day diabetes immersion course. The participants received training on self-blood glucose monitoring, techniques of insulin administration and carbohydrate counting. They were also instructed to behave as patients with diabetes and to follow individual medical prescription. They were assessed through questionnaires. In knowledge assessment, a significant increase of 12 percent was observed between the beginning and the end of the course (61.2 percent and 73.2 percent, respectively, with p < 0.0001). Before the course, 70.8 percent and 89.6 percent of the participants believed there were complications in performing carbohydrate counting and blood glucose monitoring, respectively. After the experience, 82.9 percent of them had difficulties in carbohydrate counting and 80.8 percent in self-monitoring; 40.4 percent took all medications prescribed and 36.1 percent monitored blood glucose correctly. These results show that the methodology of this course is an effective way to disseminate knowledge and that it contributes to doctors becoming more sensitive to daily problems faced by patients with diabetes melito concerning the acceptance of medical recommendations.