Maria Cândida Ribeiro Parisi

Comparison of three systems of classification in predicting the outcome of diabetic foot ulcers in a Brazilian population

OBJECTIVE The aim was to compare three ulcer classification systems as predictors of the outcome of diabetic foot ulcers: the Wagner, the University of Texas (UT) and the size (area, depth), sepsis, arteriopathy, denervation system (S(AD)SAD) systems in a specialist clinic in Brazil. METHODS Ulcer area, depth, appearance, infection and associated ischaemia and neuropathy were recorded in a consecutive series of 94 subjects. A novel score, the S(AD)SAD score, was derived from the sum of individual items of the S(AD)SAD system, and was evaluated. Follow-up was for at least 6 months. The primary outcome measure was the incidence of healing. RESULTS Mean age was 57.6 years; 57 (60.6%) were male. Forty-eight ulcers (51.1%) healed without surgery; 11 (12.2%) subjects underwent minor amputation. Significant differences in terms of healing were observed for depth (P=0.002), infection (P=0.006) and denervation (P=0.002) using the S(AD)SAD system, for UT grade (P=0.002) and stage (P=0.032) and for Wagner grades (P=0.002). Ulcers with an S(AD)SAD score of <or=9 (total possible 15) were 7.6 times more likely to heal than scores >or=10 (P<0.001). CONCLUSIONS All three systems predicted ulcer outcome. The S(AD)SAD score of ulcer severity could represent a useful addition to routine clinical practice. The association between outcome and ulcer depth confirms earlier reports. The association with infection was stronger than that reported from the centres in Europe or North America. The very strong association with neuropathy has only previously been observed in Tanzania. Studies designed to compare the outcome in different countries should adopt systems of classification, which are valid for the populations studied.

Delayed Small Intestinal Transit in Patients with Long-Standing Type 1 Diabetes Mellitus: Investigation of the Relationships with Clinical Features, Gastric Emptying, Psychological Distress, and Nutritional Parameters

BACKGROUND Studies on small intestinal transit in type 1 diabetes mellitus have reported contradictory results. This study assessed the orocecal transit time (OCTT) in a group of patients with type 1 diabetes mellitus and its relationships with gastrointestinal symptoms, glycemic control, chronic complications of diabetes, anthropometric indices, gastric emptying, small intestinal bacterial overgrowth (SIBO), and psychological distress. SUBJECTS AND METHODS Twenty-eight patients with long-standing (>10 years) type 1 diabetes mellitus (22 women, six men; mean age, 39 ± 9 years) participated in the study. The lactulose hydrogen breath test was used to determine OCTT and the occurrence of SIBO. The presence of anxiety and depression was assessed by the Hospital Anxiety and Depression scale. Gastric emptying was measured by scintigraphy. Anthropometric indices included body mass index, percentage body fat, midarm circumference, and arm muscle area. RESULTS There was a statistically significant increase in OCTT values in diabetes patients (79 ± 41 min) in comparison with controls (54 ± 17 min) (P=0.01). Individual analysis showed that OCTT was above the upper limit (mean+2 SD) in 30.8% of patients. All anthropometric parameters were significantly decreased (P<0.05) in patients with prolonged OCTT in comparison with those with normal OCTT. In contrast, there was no statistically significant association between prolonged OCTT and gastrointestinal symptoms, peripheral neuropathy, diabetic retinopathy, glycated hemoglobin, delayed gastric emptying, SIBO, anxiety, or depression. CONCLUSIONS Small bowel transit may be delayed in about one-third of patients with long-standing type 1 diabetes mellitus. This abnormality seems to have a negative effect on nutritional status in these patients.

Association of genetic variants in the promoter region of genes encoding p22phox (CYBA) and glutamate cysteine ligase catalytic subunit (GCLC) and renal disease in patients with type 1 diabetes mellitus

BackgroundOxidative stress is recognized as a major pathogenic factor of cellular damage caused by hyperglycemia. NOX/NADPH oxidases generate reactive oxygen species and NOX1, NOX2 and NOX4 isoforms are expressed in kidney and require association with subunit p22phox (encoded by the CYBA gene). Increased expression of p22phox was described in animal models of diabetic nephropathy. In the opposite direction, glutathione is one of the main endogenous antioxidants whose plasmatic concentrations were reported to be reduced in diabetes patients. The aim of the present investigation was to test whether functional single nucleotide polymorphisms (SNPs) in genes involved in the generation of NADPH-dependent O2•- (-675 T → A in CYBA, unregistered) and in glutathione metabolism (-129 C → T in GCLC [rs17883901] and -65 T → C in GPX3 [rs8177412]) confer susceptibility to renal disease in type 1 diabetes patients.Methods401 patients were sorted into two groups according to the presence (n = 104) or absence (n = 196) of overt diabetic nephropathy or according to glomerular filtration rate (GFR) estimated by Modification of Diet in Renal Disease (MDRD) equation: ≥ 60 mL (n = 265) or < 60 mL/min/1.73 m2 (n = 136) and were genotyped.ResultsNo differences were found in the frequency of genotypes between diabetic and non-diabetic subjects. The frequency of GFR < 60 mL/min was significantly lower in the group of patients carrying CYBA genotypes T/A+A/A (18.7%) than in the group carrying the T/T genotype (35.3%) (P = 0.0143) and the frequency of GFR < 60 mL/min was significantly higher in the group of patients carrying GCLC genotypes C/T+T/T (47.1%) than in the group carrying the C/C genotype (31.1%) (p = 0.0082). Logistic regression analysis identified the presence of at least one A allele of the CYBA SNP as an independent protection factor against decreased GFR (OR = 0.38, CI95% 0.14-0.88, p = 0.0354) and the presence of at least one T allele of the GCLC rs17883901 SNP as an independent risk factor for decreased GFR (OR = 2.40, CI95% 1.27-4.56, p = 0.0068).ConclusionsThe functional SNPs CYBA -675 T → A and GCLC rs17883901, probably associated with cellular redox imbalances, modulate the risk for renal disease in the studied population of type 1 diabetes patients and require validation in additional cohorts.

Linkage disequilibrium with HLA-DRB1-DQB1 haplotypes explains the association of TNF-308G>A variant with type 1 diabetes in a Brazilian cohort

BACKGROUND A functional variant in the promoter region of the gene encoding tumor necrosis factor (TNF; rs1800629, -308G>A) showed to confer susceptibility to T1D. However, TNF rs1800629 was found, in several populations, to be in linkage disequilibrium with HLA susceptibility haplotypes to T1D. We evaluated the association of TNF rs1800629 with T1D in a cohort of Brazilian subjects, and assessed the impact of HLA susceptibility haplotypes in this association. METHODS 659 subjects with T1D and 539 control subjects were genotyped for TNF-308G>A variant. HLA-DRB1 and HLA-DQB1 genes were genotyped in a subset of 313 subjects with T1D and 139 control subjects. RESULTS Associations with T1D were observed for the A-allele of rs1800629 (OR 1.69, 95% CI 1.33-2.15, p<0.0001, in a codominant model) and for 3 HLA haplotypes: DRB1*03:01-DQB1*02:01 (OR 5.37, 95% CI 3.23-8.59, p<0.0001), DRB1*04:01-DQB1*03:02 (OR 2.95, 95% CI 1.21-7.21, p=0.01) and DRB1*04:02-DQB1*03:02 (OR 2.14, 95% CI 1.02-4.50, p=0.04). Linkage disequilibrium was observed between TNF rs1800629 and HLA-DRB1 and HLA-DQB1 alleles. In a stepwise regression analysis HLA haplotypes, but not TNF rs1800629, remained independently associated with T1D. CONCLUSION Our results do not support an independent effect of allelic variations of TNF in the genetic susceptibility to T1D.

Association of single nucleotide polymorphisms in the gene encoding GLUT1 and diabetic nephropathy in Brazilian patients with type 1 diabetes mellitus

Mesangial cells subject to high extracellular glucose concentrations, as occur in hyperglycaemic states, are unable to down regulate glucose influx, resulting in intracellular activation of deleterious biochemical pathways. A high expression of GLUT1 participates in the development of diabetic glomerulopathy. Variants in the gene encoding GLUT1 (SLC2A1) have been associated to this diabetic complication. The aim of this study was to test whether polymorphisms in SLC2A1 confer susceptibility to diabetic nephropathy (DN) in Brazilian type 1 diabetes patients. Four polymorphisms (rs3820589, rs1385129, rs841847 and rs841848) were genotyped in a Brazilian cohort comprised of 452 patients. A prospective analysis was performed in 155 patients. Mean duration of follow-up was 5.6 ± 2.4 years and the incidence of renal events was 18.0%. The rs3820589 presented an inverse association with the prevalence of incipient DN (OR: 0.36, 95% CI: 0.16 - 0.80, p=0.01) and with progression to renal events (HR: 0.20; 95% CI: 0.03 - 0.70; p=0.009). AGGT and AGAC haplotypes were associated with the prevalence of incipient DN and the AGAC haplotype was also associated with the prevalence of established/advanced DN. In conclusion, rs3820589 in the SLC2A1 gene modulates the risk to DN in Brazilian patients with inadequate type 1 diabetes control.

Cintilografia de perfusão miocárdica na detecção da isquemia silenciosa em pacientes diabéticos assintomáticos

type of therapy, systemic arterial hypertension, dyslipidemia, nephropathy, retinopathy, peripheral neuropathy, smoking, and familial history of CAD. Results: MPS was abnormal in 15 patients (25.4%): 12 (20.3%) with perfusion abnormalities, and 3 with isolated left ventricular dysfunction. The strongest predictors for abnormal myocardial perfusion were: age 60 years and above (p = 0.017; odds ratio [OR] = 6.0), peripheral neuropathy (p = 0.028; OR = 6.1), nephropathy (p = 0.031; OR = 5.6), and stress ECG positive for ischemia (p = 0.049; OR = 4.08). Conclusion: Silent myocardial ischemia occurs in more than one in five asymptomatic diabetic patients. The strongest predictors of ischemia in this

Dyspeptic symptoms in patients with type 1 diabetes: endoscopic findings, Helicobacter pylori infection, and associations with metabolic control, mood disorders and nutritional factors

OBJECTIVES To evaluate, in a group of patients with long-standing type 1 diabetes (DM1), an association of dyspepsia symptoms with: changes in the gastroduodenal mucosa, infection by Helicobacter pylori, glycemic control, and psychological and nutritional factors. SUBJECTS AND METHODS A total of 32 patient with DM1 were studied (age: 38 ± 9 years; females: 25; diabetes duration: 22 ± 5 years). All patients answered a standardized questionnaire for the evaluation of gastrointestinal symptoms and underwent upper gastrointestinal endoscopy, with gastric biopsies for the evaluation of Helicobacter pylori infection. The presence of anxiety and depression was evaluated by the HAD scale. Nutritional parameters were BMI, arm and waist circumference, skinfold measurement, and body fat percentage. RESULTS Upper endoscopy detected lesions in the gastric mucosa in 34.4% of the patients, with similar frequency in those with (n = 21) and without dyspepsia (n = 11). The patients with dyspepsia complaints showed greater frequency of depression (60% vs. 0%; p = 0.001), higher values for HbA1c (9.6 ± 1.7 vs. 8.2 ± 1.3%; p = 0.01) and lower values for BMI (24.3 ± 4.1 vs. 27.2 ± 2.6 kg/m2; p = 0.02), body fat percentage (26.6 ± 6.2 vs. 30.8 ± 7.7%; p = 0.04), and waist circumference (78.7 ± 8 vs. 85.8 ± 8.1 cm; p = 0.02). No association was found between the symptoms and the presence of Helicobacter pylori. CONCLUSIONS Dyspepsia symptoms in patients with long-standing DM1 were associated with glycemic control and depression, and they seem to negatively influence the nutritional status of these patients.

Gain-of-function variants in NLRP1 protect against the development of diabetic kidney disease: NLRP1 inflammasome role in metabolic stress sensing?

Although inflammasome plays a well-known role in animal models of renal injury, limited studies in humans are available, and its participation in diabetic kidney disease (DKD) remains unknown. Aim of this study was to elucidate the contribution of inflammasome genetics in the development of DKD in type-1 diabetes (T1D). The association of functional variants in inflammasome genes with DKD was assessed by multivariate analysis in a retrospective and in a prospective cohort. NLRP1 rs2670660 and rs11651270 polymorphisms were significantly associated with a decrease risk to develop DKD (padj<0.01), and rs11651270 also with a lower risk of new renal events during follow-up (padj=0.01). Supporting these findings, diabetes metabolites (glycated albumin and high glucose) were able to modulate NLRP1 expression. This study is the first to suggest a protective role of NLRP1 in DKD, highlighting an emerging role of NLRP1 as a homeostatic factor against metabolic stress.

DIFICULDADES ASSOCIADAS À AUTOAPLICAÇÃO DE INSULINA EM PACIENTES PORTADORES DE DIABETES MELLITUS TIPO 2 EM SERVIÇO DE ATENÇÃO TERCIÁRIA

No tratamento do Diabetes Mellitus (DM), a insulinoterapia está presente em mais de 50% das prescrições. No entanto, ainda encontramos muitos entraves ao tratamento, tais como o não domínio da técnica, falta de instrumental adequado, limitações físicas dos pacientes e profissionais com falta de conhecimentos necessários para o ensino da técnica de autoaplicação, o que contribui para a perpetuação de erros de aplicação que podem refletir no mau controle metabólico e baixa qualidade do cuidado. Diante do exposto, o presente estudo objetiva investigar as dificuldades associadas à autoaplicação de insulina em um grupo de pacientes portadores de Diabetes Mellitus tipo 2, elencando os causadores da aplicação errônea do medicamento.

Clinical predictors of cardiac autonomic neuropathy in patients with type 1 diabetes

Results CAN was diagnosed in 39 (38.2%) patients. No statistically significant differences were found in age (34.87±9.71 vs. 33.90±11.74 yrs.; p=0.467), age at diagnosis (15.10±9.16 vs. 17.38±11.29 yrs.; p=0.495) and HbA1c (9.26%±2.04 vs. 8.84%±2.07; p=0.144) between groups. Hypertension and dyslipidemia were seen more frequently in patients with CAN (61.5 vs. 19%; p≤0.001 and 51.3 vs. 22.2%; p=0.002, respectively). Patients with CAN had higher total cholesterol (p=0.009) and triglycerides (p=0.004). Patients with CAN complained more often of post-prandial sweating