SHARON NINA ADMONI
Projetos de Pesquisa
Unidades Organizacionais
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
LIM/18 - Laboratório de Carboidratos e Radioimunoensaios, Hospital das Clínicas, Faculdade de Medicina
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- Leukotriene Pathway Activation Associates with Poor Glycemic Control and with Cardiovascular Autonomic Neuropathy in Type 1 Diabetes(2020) SANTOS-BEZERRA, Daniele P.; FILGUEIRAS, Luciano R.; MONTEIRO, Maria Beatriz; ADMONI, Sharon N.; V, Ricardo Perez; CAVALEIRO, Ana M.; MACHADO, Cleide G.; MACHADO, Ubiratan F.; PASSARELLI, Marisa; JANCAR, Sonia; CORREA-GIANNELLA, Maria LuciaBackground 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 HbA(1)C, 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.
- Distal Symmetric and Cardiovascular Autonomic Neuropathies in Brazilian Individuals with Type 2 Diabetes Followed in a Primary Health Care Unit: A Cross-Sectional Study(2020) MATOS, Mozania Reis de; SANTOS-BEZERRA, Daniele Pereira; CAVALCANTE, Cristiane das Gracas Dias; CARVALHO, Jacira Xavier de; LEITE, Juliana; NEVES, Jose Antonio Januario; ADMONI, Sharon Nina; PASSARELLI, Marisa; PARISI, Maria Candida; CORREA-GIANNELLA, Maria LuciaThe paucity of epidemiological data regarding diabetes complications in Brazil motivated us to evaluate the prevalence rates of distal symmetric polyneuropathy (DSP) and of cardiovascular autonomic neuropathy (CAN) in individuals with type 2 diabetes (T2D) followed in a primary care unit. A total of 551 individuals (59.3% women, 65 years old; diabetes duration of 10 years; HbA1c of 7.2%, medians) were included in this cross-sectional study. DSP was diagnosed by sum of the Neuropathy Symptoms Score (NSS) and Modified Neuropathy Disability Score (NDS) and by the Semmes-Weinstein monofilament. CAN was diagnosed by cardiovascular autonomic reflex tests combined with spectral analysis of heart rate variability. The prevalence rates of DSP were 6.3% and 14.3%, as evaluated by the sum of NSS and NDS and by the Semmes-Weinstein monofilament, respectively. Those with DSP diagnosed by monofilament presented longer diabetes duration, worse glycemic control and a higher stature. The prevalence rates of incipient and definitive CAN were 12.5% and 10%, respectively. Individuals with definitive CAN presented a higher frequency of hypercholesterolemia and of arterial hypertension. The higher prevalence rate of DSP with the use of the monofilament suggests that it may be a more appropriate tool to diagnose DSP in the primary care setting in Brazil.
- Genetic variants in DNMT1 and the risk of cardiac autonomic neuropathy in women with type 1 diabetes(2019) SANTOS-BEZERRA, Daniele Pereira; ADMONI, Sharon Nina; MORI, Rosana Cristina; PELAES, Tatiana Souza; PEREZ, Ricardo Vesoni; MACHADO, Cleide Guimaraes; MONTEIRO, Maria Beatriz; PARISI, Maria Candida; PAVIN, Elizabeth Joao; QUEIROZ, Marcia Silva; PASSARELLI, Marisa; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaAims/Introduction Epigenetics participate in the pathogenesis of metabolic memory, a situation in which hyperglycemia exerts prolonged deleterious effects even after its normalization. We tested the hypothesis that genetic variants in an epigenetic gene could predispose to diabetes complications. Material and Methods We assessed the frequency of five single-nucleotide polymorphisms in the gene encoding deoxyribonucleic acid methytransferase 1 (DNMT1; rs8112895, rs7254567, rs11085721, rs17291414 and rs10854076), and their associations with diabetic kidney disease, retinopathy, distal polyneuropathy and autonomic cardiovascular neuropathy in 359 individuals with long-term type 1 diabetes. Results None of the single-nucleotide polymorphisms studied was significantly associated with the presence of chronic complications in the overall population. However, after sex stratification, the minor allele C of rs11085721 conferred risk for cardiovascular neuropathy in women after adjustment for confounding variables (odds ratio 2.32; 95% confidence interval 1.26-4.33; P = 0.006). Conclusions The fact that heterozygous mutations in DNMT1 are associated with hereditary sensory autonomic neuropathy provides plausibility to the present finding. If confirmed in independent samples, it suggests that genetic variants in epigenetic genes might predispose to more or fewer epigenetic changes in the face of similar metabolic derangements triggered by hyperglycemia, constituting the ""genetics of epigenetics"" for microvascular diabetes complications.
- Micro-RNAs 518d-3p and 618 Are Upregulated in Individuals With Type 1 Diabetes With Multiple Microvascular Complications(2019) SANTOS-BEZERRA, Daniele P.; SANTOS, Aritania S.; GUIMARAES, Gabriel C.; ADMONI, Sharon N.; V, Ricardo Perez; MACHADO, Cleide G.; PELAES, Tatiana S.; PASSARELLI, Marisa; MACHADO, Ubiratan F.; QUEIROZ, Marcia S.; SILVA, Maria Elizabeth R. da; CORREA-GIANNELLA, Maria LuciaObjective: 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, HbA(1)c 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.
- New digital tool to facilitate subcutaneous insulin therapy orders: an inpatient insulin dose calculator(2015) TOYOSHIMA, Marcos Tadashi Kakitani; SOUZA, Alexandre Barbosa Camara de; ADMONI, Sharon Nina; CUKIER, Priscilla; LOTTENBERG, Simao Augusto; LATRONICO, Ana Claudia; NERY, MarciaBackground: Inpatient hyperglycemia is associated with adverse outcomes in hospitalized patients, with or without known diabetes. The adherence to American College of Endocrinology and American Diabetes Association guidelines recommendations for inpatient glycemic control is still poor, probably because of their complexity and fear of hypoglycemia. Objective: To create software system that can assist health care providers and hospitalists to manage the insulin therapy orders and turn them into a less complicated issue. Methods: A software system was idealized and developed, according to recommendations of major consensus and medical literature. Results: HTML software was developed to be readily accessed from a workstation, tablet or smartphone. Standard initial daily total dose of insulin was 0.4 units/kg and could be modified by distinct factors, such as chronological age, renal and liver function, and high dose corticosteroids use. Insulin therapy consisted of basal, prandial and correction insulin according to nutritional support, glycemic control and outpatient treatment for diabetes. Human insulin or insulin analogues could be options for insulin therapy. Sensitivity factor was based on 1800 Rule for rapid-acting insulin and the 1500 Rule for short-acting insulin. Insulin-naive patients with initial BG level less than 250 mg/dL were considered to have an initial step-wise approach with prandial and correction insulin. The calculator system has allowed insulin dose readjustments periodically, according to daily average blood glucose measurements. Conclusion: We developed software that can be a useful tool for all public hospitals, where generally human insulin is the only available.