MARCIA SILVA QUEIROZ
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- Insulin Glargine U100 Improved Glycemic Control and Reduced Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease Stages 3 and 4(2019) BETONICO, Carolina C.; TITAN, Silvia Maria O.; LIRA, Aecio; PELAES, Tatiana S.; CORREA-GIANNELLA, Maria Lucia C.; NERY, Marcia; QUEIROZ, MarciaPurpose: Glycemic control in patients with chronic kidney disease (CKD) is particularly hard to achieve because of a slower insulin degradation by the kidney. It might modify the long-acting insulin analogue pharmacokinetics, increasing its time-action and the risk of hypoglycemia. However, because this insulin has no peak action, it might be a more tolerable approach to patients with CKD. This hypothesis remains to be tested, because no study has thus far examined the efficacy and safety profile of long-acting basal analogues in patients with significant loss of renal function. The purpose of this study was to compare the glycemic response to treatment with glargine U100 or neutral protamine Hagedorn (NPH) insulin in patients with type 2 diabetes mellitus (T2DM) and CKD stages 3 and 4. Methods: Thirty-four patients were randomly assigned to glargine U100 or NPH insulin after a 2-way crossover open-label design. The primary end point was the difference in glycosylated hemoglobin (HbA(1c)) and in the number of hypoglycemic events between weeks 1 and 24, whereas secondary end points included changes in glycemic patterns, weight and body mass index, and total daily dose of insulin. HbA(1)(c) was determined by ion-exchange HPLC, and hypoglycemia was defined as glucose concentration of 54 mg/dL (3.0 mmol/L) detected by self-monitoring of plasma glucose or continuous glucose monitoring. Findings: After 24 weeks, mean HbA(1c )decreased on glargine U100 treatment (-0.91%; P < 0.001), but this benefit was not observed for NPH (0.23%; P = 0.93). Moreover, incidence of nocturnal hypoglycemia was 3 times lower with glargine than with NPH insulin (P = 0.047). (C) 2019 Published by Elsevier Inc.
- Short-term effects of intravitreal bevacizumab in contrast sensitivity of patients with diabetic macular edema and optimizing glycemic control(2019) MOTTA, Augusto A. L.; BONANOMI, Maria Teresa B. C.; FERRAZ, Daniel A.; PRETI, Rony C.; SOPHIE, Raafay; ABALEM, Maria F.; QUEIROZ, Marcia S.; PIMENTEL, Sergio L. G.; TAKAHASHI, Walter Y.; DAMICO, Francisco M.Aims: To analyze contrast sensitivity of intravitreal bevacizumab injections with optimizing glycemic control versus optimizing glycemic control (in combination with sham injections) in eyes with Diabetic Macular Edema (DME). Design: Prospective, interventional, masked, randomized controlled trial. Methods: Forty-one eyes of 34 patients with type 2 diabetes mellitus and DME with glycated hemoglobin (HbA1c) < 11% received either intravitreal bevacizumab injection (Group 1) or sham injection (Group 2) at 0 and 6 weeks along with optimizing glycemic control. Mean change in best-corrected visual acuity (BCVA), contrast sensitivity (CS), optical coherence tomography (OCT)-measured by central macular thickness (CMT) were compared and correlated at baseline, 2, 6 and 12 weeks. Results: The study showed a mean CS improved in group 1 from 1.14 +/- 0.36 logCS to 1.32 +/- 0.24 logCS and also in group 2 from 1.11 +/- 0.29 logCS to 1.18 +/- 0.29 logCS at 12 weeks (P = 0.12). CS and CMT promptly decreased in group 1 compared to group 2 at 2 weeks (Delta CS = 0.15 +/- 0.25 vs. 0.03 +/- 0.15 logCS; P = 0.04; Delta CMT = 116 +/- 115 vs. 17 +/- 71 mu m; P = 0.01). There was a mean reduction of approximately 0.5% in HbA1c levels in both groups at 12 weeks (P = 0.002). Conclusion: The use of bevacizumab in combination with optimizing glycemic control results in earlier improvement of contrast sensitivity in type 2 diabetes patients with DME. However, the optimizing glycemic control itself has shown also to be effective at 12 weeks.
bookPart Doença renal diabética(2022) LIRA, Aécio Lopes de Araújo; BATTAINI, Ligia Costa; QUEIROZ, Márcia Silva; ZATZ, Roberto- Serum RBP4 and CKD: Association with insulin resistance and lipids(2017) DOMINGOS, Maria Alice M.; QUEIROZ, Marcia; LOTUFO, Paulo Andrade; BENSENOR, Isabela Judith; TITAN, Silvia Maria de OliveiraObjective: Serum RBP4 is new adipokine and it has been related to insulin resistance and diabetes risk in animal and clinical studies. However, there is controversy on this relationship among CKD patients. In this study, we evaluated the association of serum RBP4 with insulin resistance and cardiovascular risk factors in CKD. Methods: Baseline data from the PROGREDIR Study (Sao Paulo, Brazil) comprising 454 participants (mainly stages 3 and 4) was analyzed. Results: In univariable analysis, RBP4 was inversely related to renal function, age and HDL, and positively related to other lipids, insulinemia, HOMA, glycemia, albumin, phosphorus and right hepatic lobe diameter. After adjustment for sex, age and eGFR, HOMA and lipids remained associated to RBP4. In multivariable analysis, eGFR and triglyceride remained significantly associated with RBP4, while HOMA showed no longer a significant positive association. An interaction term between RBP4 and eGFR was significantly related to HOMA. Conclusions: Renal function is inversely related to serum RBP4. As GFR decreases, the relationship between RBP4 and HOMA is attenuated. On the other hand, triglycerides remained strongly related to RBP4 and this was not affected by eGFR, suggesting that in the CKD population triglycerides may be a better marker of RBP4-associated metabolic effects.
bookPart Insulinoterapia Ambulatorial(2016) QUEIROZ, Márcia Silva; GIANNELLA, Maria Lúcia C. C.; NERY, Marcia- 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.
conferenceObject Increased serum expression of miR-518d-3p and miR-618 in individuals with type 1 diabetes with microvascular chronic complications(2018) SANTOS-BEZERRA, D. P.; SANTOS, A. S.; GUIMARAES, G. C.; ADMONI, S. N.; PEREZ, R. V.; PELAES, T. S.; MACHADO, C. G.; PASSARELLI, M.; MACHADO, U. F.; QUEIROZ, M. S.; SILVA, M. E. R.; CORREA-GIANNELLA, M. L. C.- Improvement in medication adherence and self-management of diabetes with a clinical pharmacy program: a randomized controlled trial in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital(2015) CANI, Catarina Gomes; LOPES, Laura da Silva Girao; QUEIROZ, Marcia; NERY, MarciaOBJECTIVE: To evaluate the impact of a clinical pharmacy program on health outcomes in patients with type 2 diabetes undergoing insulin therapy at a teaching hospital in Brazil. METHOD: A randomized controlled trial with a 6-month follow-up period was performed in 70 adults, aged 45 years or older, with type 2 diabetes who were taking insulin and who had an HbA1c level >= 8%. Patients in the control group (CG) (n = 36) received standard care, patients in the intervention group (IG) (n = 34) received an individualized pharmacotherapeutic care plan and diabetes education. The primary outcome measure was change in HbA1c. Secondary outcomes included diabetes and medication knowledge, adherence to medication, insulin injection and home blood glucose monitoring techniques and diabetes-related quality of life. Outcomes were evaluated at baseline and 6 months using questionnaires. RESULTS: Diabetes knowledge, medication knowledge, adherence to medication and correct insulin injection and home blood glucose monitoring techniques significantly improved in the intervention group but remained unchanged in the control group. At the end of the study, mean HbA1c values in the control group remained unchanged but were significantly reduced in the intervention group. Diabetes-related quality of life significantly improved in the intervention group but worsened significantly in the control group. CONCLUSION: The program improved health outcomes and resulted in better glycemic control in patients with type 2 diabetes undergoing insulin therapy.
- 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.