MARCIA SILVA QUEIROZ
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- Beta-2-microglobulin (B2M) expression in the urinary sediment correlates with clinical markers of kidney disease in patients with type 1 diabetes(2016) MONTEIRO, Maria Beatriz; THIEME, Karina; SANTOS-BEZERRA, Daniele Pereira; QUEIROZ, Marcia Silva; WORONIK, Viktoria; PASSARELLI, Marisa; MACHADO, Ubiratan Fabres; GIANNELLA-NETO, Daniel; OLIVEIRA-SOUZA, Maria; CORREA-GIANNELLA, Maria LuciaPurpose. After observing variation in the expression of the housekeeping gene B2M in cells of the urinary sediment during a study of candidate genes potentially involved in diabetic kidney disease (DKD), we hypothesized that B2M mRNA expression in the urinary sediment could reflect the presence of DKD. Methods. qPCR was used to quantify B2M mRNA expression in cells of the urinary sediment of 51 type 1 diabetes (T1D) patients (61% women, 33.5 [27.0-39.7] years old, with diabetes duration of 21.0 [15.0-28.0] years and HbA1c of 8.2% [7.3-8.9]; median [interquartile interval]) sorted according to the diabetic nephropathy (DN) stages; 8 focal segmental glomerulosclerosis (FSGS) patients and 10 healthy controls. B2M mRNA expression was also evaluated in human embryonic kidney epithelium-like (HEK-293) cells exposed to 25 mM glucose and to albumin in order to mimic, respectively, a diabetic and a proteinuric milieu. Results. No differences were found in B2M mRNA expression among healthy controls, FSGS and T1D patients. Nonetheless B2M mRNA expression was higher in the group composed by T1D patients with incipient or overt DN combined with FSGS patients versus T1D patients without DN combined with healthy controls (P = 0.0007). B2M mRNA expression was higher in T1D patients with incipient or overt DN versus without DN (P = 0.03). B2M mRNA expression positively correlated with albuminuria in the overall T1D population (r = 0.43; P = 0.01) and negatively correlated with estimated glomerular filtration rate in male T1D patients (r = - 0.57; P = 0.01). Increased B2M expression was observed in HEK-293 cells exposed to 25 mM glucose and to albumin. Conclusions. B2M mRNA expression in cells of the urinary sediment is higher in T1D patients with DKD and in patients with FSGS in comparison to healthy subjects, maybe reflecting a tubulointerstitial injury promoted by albumin. Given the proinflammatory nature of B2M, we suggest that this protein contributes to diabetic (and possibly, to non-diabetic) tubulopathy.
- Glutathione peroxidase 4 functional variant rs713041 modulates the risk for cardiovascular autonomic neuropathy in individuals with type 1 diabetes(2019) ADMONI, Sharon Nina; SANTOS-BEZERRA, Daniele Pereira; PEREZ, Ricardo Vesoni; PATENTE, Thiago Andrade; MONTEIRO, Maria Beatriz; CAVALEIRO, Ana Mercedes; PARISI, Maria Candida; NETO, Arnaldo Moura; PAVIN, Elizabeth Joao; QUEIROZ, Marcia Silva; NERY, Marcia; CORREA-GIANNELLA, Maria LuciaCardiac autonomic neuropathy is a neglected diabetic chronic complication for which genetic predictors are rarely reported. Oxidative stress is implicated in the pathogenesis of microvascular complications, and glutathione peroxidase 4 is involved in the detoxification of peroxides and of reactive oxygen species. Thus, the association of a functional variant in the gene encoding glutathione peroxidase 4 (rs713041) with this diabetic complication was investigated in 341 individuals with type 1 diabetes evaluated for cardiac autonomic neuropathy status (61.7% women, 34 [27-42] years old; diabetes duration: 21 [15-27] years; HbA1c: 8.3% [7.4-9.4]; as median [interquartile interval]). Cardiac autonomic neuropathy was present in 29% of the participants. There was an inverse association of the minor T allele of rs713041 with cardiac autonomic neuropathy (odds ratio = 0.39; 95% confidence interval = 0.17-0.90; p = 0.0271) after adjustment for potential confounders. The functional glutathione peroxidase 4 variant rs713041 modulated the risk for cardiac autonomic neuropathy in the studied population with type 1 diabetes.
- Allelic variations in genes belonging to glutathione system increase proliferative retinopathy risk in type 1 diabetes individuals(2019) PEREZ, Ricardo Vessoni; MACHADO, Cleide Guimaraes; SANTOS-BEZERRA, Daniele Pereira; ADMONI, Sharon Nina; PATENTE, Thiago Andrade; MONTEIRO, Maria Beatriz; CAVALEIRO, Ana Mercedes; QUEIROZ, Marcia Silva; NERY, Marcia; CORREA-GIANNELLA, Maria LuciaAims: Given the participation of oxidative stress in the pathogenesis of diabetic complications, we evaluated, in type 1 diabetes (T1D) individuals, the association between diabetic retinopathy (DR) and functional single nucleotide polymorphisms (SNPs) in regulatory regions of two genes belonging to the antioxidant glutathione (GSH) system: rs17883901 in GCLC and rs713041 in GPX4. Methods: A cross-sectional case-control study included 288 individuals (61% women, 34[+/- 11] years old, diabetes duration of 22[+/- 9] years, mean [+/- SD]) sorted according to DR stages: absence of DR (ADR), non proliferative DR (NPDR) and proliferative DR (PDR). SNPs were genotyped by real-time PCR using fluorescent labelled probes. Logistic regression models with adjustment for confounding covariates were employed. Results: The presence of at least one T-allele of rs17883901 in GCLC was an independent risk factor for PDR (OR 4.13, 95% CI 1.38-13.66, p = 0.014) in a polytomous regression model (PDR versus ADR). The presence of at least one T-allele of rs713041 in GPX4 conferred protection against PDR (OR 0.30, 95% CI 0.11-0.80, p = 0.017) in female T1D individuals. Conclusion: The functional SNPs rs17883901 and rs713041 modulate the risk for PDR in the studied population of T1D individuals, widening the spectrum of candidate genes for this complication.
- Serum albumin modified by carbamoylation impairs macrophage cholesterol efflux in diabetic kidney disease(2021) LIRA, Aecio Lopes de Araujo; SANTANA, Monique de Fatima Mello; PINTO, Raphael de Souza; MINANNI, Carlos Andre; IBORRA, Rodrigo Tallada; LIMA, Adriana Machado Saldiba de; CORREA-GIANNELLA, Maria Lucia; PASSARELLI, Marisa; QUEIROZ, Marcia SilvaBackground and aims: Abnormalities in lipid metabolism, accumulation of uremic toxins and advanced glycation end products may contribute to worsening atherosclerosis. This study characterized the glycation and carbamoylation profile of serum albumin isolated from individuals with diabetic kidney disease and its influence on cholesterol efflux. Material and methods: 49 patients with type 2 diabetes (T2DM) and different eGFR evaluated glycation and carbamoylation profile by measurement of carboxymethyl lysine (CML) and carbamoylated proteins (CBL) in plasma by ELISA, homocitrulline (HCit) in plasma by colorimetry. In the isolated albumins, we quantified CBL (ELISA) and total AGE and pentosidine by fluorescence. Macrophages were treated with albumin isolated, and 14C-Cholesterol efflux mediated by HDL2 or HDL3 was measured. Kruskal-Wallis test, Jonckheere-Terpstra test and Brunner's posttest were used for comparisons among groups. Results: Determination of CML, HCit, CBL in plasma, as total AGE and pentosidine in albumins, did not differ between groups; however, CBL in the isolated albumins was higher in the more advanced stages of CKD (p = 0.0414). There was reduction in the 14C-cholesterol efflux after treatment for 18 h with albumin isolated from patients with eGFR<60 mL/min/1.73m2 compared with control group mediated by HDL2 (p = 0.0288) and HDL3 (p < 0.0001), as well as when compared with eGFR >= 60 mL/min/1.73m2 per HDL2 (p = 0.0001) and HDL3 (p < 0.0001). Treatment for 48 h showed that eGFR<15 mL/min/1.73m2 had a lower percentage of 14Ccholesterol efflux mediated by HDL2 compared to control and other CKD groups (p = 0.0274). Conclusions: Albumins isolated from individuals with T2DM and eGFR<60 mL/min/1.73m2 suffer greater carbamoylation, and they impair the cholesterol efflux mediated by HDL2 and HDL3. In turn, this could promote lipids accumulation in macrophages and disorders in reverse cholesterol transport.
- Celiac crisis in an adult type 1 diabetes mellitus patient: a rare manifestation of celiac disease(2013) TOYOSHIMA, Marcos Tadashi Kakitani; QUEIROZ, Marcia Silva; SILVA, Maria Elizabeth Rossi; CORREA-GIANNELLA, Maria Lucia C.; NERY, MarciaCeliac crisis, an acute severe onset of celiac disease, is a rare and life-threatening manifestation. We report a 30-year-old woman with type 1 diabetes mellitus who arrived at our service with one-month history of severe acute watery diarrhea associated with nausea, vomiting, abdominal pain, and weight loss of 9 kg. The diagnostic hypothesis of celiac crisis was reached based on profuse diarrhea leading to dehydration, severe metabolic and electrolyte abnormalities, and subsequent improvement after introduction of a gluten-free diet.
- 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.
- Variants inHSD11B1gene modulate susceptibility to diabetes kidney disease and to insulin resistance in type 1 diabetes(2021) MORI, Rosana Cristina; SANTOS-BEZERRA, Daniele Pereira; PELAES, Tatiana Souza; ADMONI, Sharon Nina; PEREZ, Ricardo Vessoni; MONTEIRO, Maria Beatriz; MACHADO, Cleide Guimaraes; QUEIROZ, Marcia Silva; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaBackground and aim 11 beta-Hydroxysteroid dehydrogenase 1 has been implicated in insulin resistance (IR) in the setting of metabolic disorders, and single nucleotide polymorphisms (SNPs) in its encoding gene (HSD11B1) have been associated with type 2 diabetes and metabolic syndrome. In type 1 diabetes (T1D), IR has been related to the development of chronic complications. We investigated the association ofHSD11B1SNPs with microvascular complications and with IR in a Brazilian cohort of T1D individuals. Materials and methods Five SNPs were genotyped in 466 T1D individuals (57% women; median of 37 years old, diabetes duration of 25 years and HbA1c of 8.4%). Results The minor allele T of rs11799643 was nominally associated with diabetic retinopathy (OR = 0.52; confidence interval [CI] 95% = 0.28-0.96;P= .036). The minor allele C of rs17389016 was nominally associated with overt diabetic kidney disease (DKD) (OR = 1.90; CI 95% = 1.07-3.37;P= .028). A follow-up study revealed that 29% of the individuals lost >= 5 mL min(-1)x 1.73 m(2)per year of the estimated glomerular filtration rate (eGFR). In these individuals (eGFR decliners), C allele of rs17389016 was more frequent than in non-decliners (OR = 2.10; CI 95% = 1.14-3.89;P= .018). Finally, minor allele T of rs846906 associated with higher prevalence of arterial hypertension, higher body mass index and waist circumference, thus conferring risk to a lower estimated glucose disposal rate, a surrogate marker of insulin sensitivity (OR = 1.23; CI 95% = 1.06-1.42;P= .004). Conclusion SNPs in theHSD11B1gene may confer susceptibility to DKD and to IR in T1D individuals.
conferenceObject Comparison of Insulin Glargine vs. NPH Insulin in Basal-Bolus Therapies in T2DM Patients and CKD: Preliminary Results of a Prospective, Randomized, Open-Label Trial(2016) BETONICO, Carolina Castro Rocha; TITAN, Silvia Maria De Oliveira; CORREA-GIANNELLA, Maria Lucia; NERY, Marcia; QUEIROZ, Marcia Silva- Thioredoxin interacting protein expression in the urinary sediment associates with renal function decline in type 1 diabetes(2016) MONTEIRO, Maria Beatriz; SANTOS-BEZERRA, Daniele Pereira; THIEME, Karina; ADMONI, Sharon Nina; PEREZ, Ricardo Vessoni; MACHADO, Cleide Guimaraes; QUEIROZ, Marcia Silva; NERY, Marcia; OLIVEIRA-SOUZA, Maria; WORONIK, Viktoria; PASSARELLI, Marisa; GIANNELLA-NETO, Daniel; MACHADO, Ubiratan Fabres; CORREA-GIANNELLA, Maria LuciaAims: Thioredoxin interacting protein (TXNIP), an inhibitor of antioxidant thioredoxin (Trx), is upregulated by hyperglycemia and implicated in pathogenesis of diabetes complications. We evaluated mRNA expressions of genes encoding TXNIP and Trx (TXN) in urinary sediment and peripheral blood mononuclear cells (PBMC) of type 1 diabetes (T1D) patients with different degrees of chronic complications. Methods: qPCR was employed to quantify target genes in urinary sediment (n=55) and PBMC (n=161) from patients sorted by presence or absence of diabetic nephropathy (DN), retinopathy, peripheral and cardiovascular neuropathy; 26 healthy controls and 13 patients presenting non-diabetic nephropathy (focal and segmental glomerulosclerosis, FSGS) were also included. Results: Regarding the urinary sediment, TXNIP (but not TXN) expression was higher in T1D (p=0.0023) and FSGS (p=0.0027) patients versus controls. Expressions of TXNIP and TXN were higher, respectively, in T1D patients with versus without DN (p=0.032) and in those with estimated glomerular filtration rate (eGFR) <60 versus >= 60 mL/min/1.73 m(2) (p=0.008). eGFR negatively correlated with TXNIP (p=0.04, r=-0.28) and TXN (p=0.04, r=-0.30) expressions. T1D patients who lost >= 5 mL/min/1.73 m(2) yearly of eGFR presented higher basal TXNIP expression than those who lost<5 mL/min/1.73 m(2) yearly after median follow-up of 24 months. TXNIP (p<0.0001) and TXN (p=0.002) expressions in PBMC of T1D patients were significantly higher than in controls but no differences were observed between patients with or without chronic complications. Conclusions: TXNIP and TXN are upregulated in urinary sediment of T1D patients with diabetic kidney disease (DKD), but only TXNIP expression is associated with magnitude of eGFR decline.
- Association between health literacy and glycemic control in elderly patients with type 2 diabetes and modifying effect of social support(2020) SOUZA, Jonas Gordilho; FARFEL, Jose Marcelo; JALUUL, Omar; QUEIROZ, Marcia Silva; NERY, MarciaObjective: To investigate the association between inadequate functional health literacy, considering the Short Assessment of Health Literacy for Portuguese-speaking Adults, and glycemic control in elderly patients with type 2 diabetes, and to examine this association in low social support settings, according to Medical Outcomes Study. Methods: Cross-sectional study conducted at the diabetes referral center of a university hospital. Participants were recruited among type 2 diabetes patients aged 60 years or older, between May 2013 and November 2014. The primary outcome was the most recent glycated hemoglobin value measured within the last 6 months. Results: A total of 398 elderly patients with type 2 diabetes were evaluated. Of these, 232 were not eligible to participate. The final sample comprised 166 participants. Hierarchical multiple linear regression was performed. The following variables were entered in three blocks: sociodemographic characteristics, clinical variables and health literacy scores. Regression analysis of the interaction between health literacy and social support as a determinant of glycemic control was also performed. Mean age of subjects was 68.0 years (standard deviation of 5.9). Mean glycated hemoglobin value was 8.5% (standard deviation of 1.4). Short assessment of health literacy for Portuguese speaking adults score was independently associated with glycated hemoglobin (B=-0.059; p=0.043). The interaction between social support and health literacy score (p=0.003) was a determinant of glycemic control. Conclusion: Health literacy is associated with glycemic control. Social support may modify the relation between health literacy and glycemic control.