Reduction of podocytes number in late diabetic alloxan nephropathy: prevention by glycemic control

OBJETIVO: Avaliar o número de podócitos e espessamento da membrana basal glomerular (MBG) em ratos diabéticos com e sem controle glicêmico com 6 e 12 meses da indução. MÉTODOS: 100 ratos Wistar com 200-300g compuseram 6 grupos: Normal (N6, N12 - 25 animais) Diabético (D6,D12 - 25 animais) e diabético tratado com insulina 1,8 a 3,0 U/Kg e acarbose misturada a ração (50g para cada 100g de ração) (DT6 e DT12 - 25 animais). Aloxana foi ministrada via endovenosa na dose de 42mg/Kg. Peso, ingestão hídrica e diurese de 24 horas e glicemia e glicosúria foram determinados antes da inoculação, 7 e 14 dias após e mensalmente. No 14ª dia foi iniciado o tratamento. Três grupos de animais (N6, D6 e DT6) foram sacrificados no 6° mês e três grupos (N12, D12 e DT12), no 12ª mês sendo o tecido renal processado para estudo à microscopia eletrônica. RESULTADOS: A glicemia dos animais DT6 e DT12 diferiram significativamente, dos ratos D6 e D12, e não diferiram dos grupos N6 e N12. O número de podócitos do grupo DT6 não diferiu de N6 e D6 (mediana=11); o número de podócitos de DT12 (mediana=11) diferiu de D12 (mediana=8) e não diferiu de N12 (mediana=11). O espessamento da MBG de D6 (0,18 micrômetros) foi menor que D12 (0,29 micrômetros); de DT6 (0,16 micrômetros) foi menor que D6 (0,18 micrômetros) e de DT12 (0,26 micrômetros) foi menor que D12 (0,29 micrômetros). CONCLUSÃO: O controle da hiperglicemia preveniu o espessamento da MBG na nefropatia diabética aloxânica precoce (6 meses) e tardia (12 meses), e a diminuição do número de podócitos.

Influence of glycemic control on fetal lung maturity in gestations affected by diabetes or mild hyperglycemia

Objective. To evaluate the influence of glycemic control on fetal lung maturity in pregnancies affected by diabetes or mild hyperglycemia. Design. Cross-sectional study. Setting. Level III maternity center. Population. A total of 187 pregnant women were submitted to routine amniocentesis for the assessment of fetal lung maturity up to 72 hours before delivery. Methods. Fetal lung maturity thresholds were: Clements-positive at a dilution of 0.5; OD(650) nm >= 0.15; and lamellar body count (LBC) >= 32,000/mu l. The relation of test results with adequate (<= 6.7 mmol/l) or poor (> 6.7 mmol/l) glycemic mean (GM) at term and at preterm was evaluated. Main outcome measure. Delay in fetal lung maturity when glycemic control was poor. Results. Glycemic control was adequate in 146 (78.1%) women. Clements maturity rates were higher at term (91.9%) than at preterm (64.7%) when GM <= 6.7 mmol/l (p < 0.001), but not when control was inadequate. LBC median was higher at term (99.0; 62.0-154.0) than at preterm (66.5; 40.5-108.25) (p = 0.009) when GM <= 6.7 mmol/l, while GM > 6.7 mmol/l did not lead to any difference between these rates at term or preterm. When glycemic control was adequate, OD(650) nm medians at term and at preterm were similar. However, when GM > 6.7 mmol/l, OD(650) nm median at term (0.29; 0.22-0.40) was higher than that observed at preterm (0.15; 0.12-0.18) (p < 0.001). Conclusions. Our results suggest that in term pregnancies routine amniocentesis for the assessment of fetal lung maturity should be abandoned. In preterm pregnancies, or when glycemic control is inadequate it is recommended.

Determinants of blood pressure in type 2 diabetic subjects with high occurrence of inadequate glycemic control

Study design: Association study Objective: To analyze the association between different biological/behavioral risk factors and blood pressure in a sample of type 2 diabetes mellitus patients with poor glycemic control. Methods: A sample of 121 type 2 diabetic patients was selected in the Public Healthcare System in a middle size Brazilian city. Blood pressure was measured using an aneroid device, previously calibrated. Six determinants of blood pressure were taken into count: age, hypoglycemic agents, general obesity, abdominal obesity, eating behaviors and physical activity level. Results: The type 2 diabetic patients presented mean age of 60.1±8.9 years-old and, at least, one risk factor. Eating behaviors (OR adj= 0.31 [0.12-0.75]) and sports practice (OR adj= 0.12 [0.02-0.75]) constituted protective factors associated with lower systolic blood pressure. On the other hand, age was positively associated with high systolic blood pressure (OR adj= 3.81 [1.39-10.38]). Patients with 5-6 risk factors, presented higher values of systolic and (F= 3.857; p= 0.011 [post hoc with p= 0.039]), diastolic blood pressure (F= 4.158; p= 0.008 [post hoc with p= 0.036]) and increased occurrence of hypertension (p= 0.010). Conclusion: Our findings indicate that, behavioral variables were important determinants of blood pressure in type 2 diabetic patients with poor glycemic control and clustering of behavioral and biological risk factors increase the hypertension occurrence.

Insulinoterapia, controle glicêmico materno e prognóstico perinatal - Diferença entre o diabetes gestacional e o clínico

PURPOSE: to evaluate the insulin therapy protocol and its maternal and perinatal outcome in patients with clinical or gestational diabetes in a high risk reference service. METHODS: descriptive and prospective study including 103 pregnant women with gestational or clinical diabetes treated with insulin and attended by the reference service from October 2003 to December 2005. Gemellarity, miscarriages, unfinished prenatal care and deliveries not attended by the service were excluded. The gestational age at the beginning of the treatment, dosage, doses/day, increment of insulin (UI/kg), glycemic index (GI) and perinatal outcomes were compared. ANOVA, Fisher's exact test and Goodman's test considering p<0.05 were used. RESULTS: multiparity (92 versus 67.9%), pre-gestational body mass index (BMI) >25 kg/m 2 (88 versus 58.5%), weight gain (WG) <8 kg (36 versus 17%) and a high increment of insulin characterized the gestational diabetes. For the patients with clinical diabetes, despite the highest GI (120 mg/dL (39.2 versus 24%)) at the end of the gestational period, insulin therapy started earlier (47.2 versus 4%), lasted longer (56.6 versus 6%) and higher doses of insulin (92 versus 43 UI/day) were administered up to three times a day (54.7 versus 16%). Macrosomia was higher among newborns from the cohort of patients with gestational diabetes (16 versus 3.8%), being the only significant neonatal outcome. There were no neonatal deaths, except for one fetal death in the cohort of patients with clinical diabetes. There were no differences in the other neonatal complications in both cohorts, and most of the newborns were discharged from hospital up to seven days after delivery (46% versus 55.8%). CONCLUSIONS: the analysis of these two cohorts has shown differences in the insulin therapy protocol in quantity (UI/day), dosage (UI/kg weight) and number of doses/day, higher for the clinical diabetes cohort, and in the increment of insulin, higher for the gestational diabetes cohort. Indirectly, the quality of maternal glycemic control and the satisfactory perinatal outcome have proven that the treatment protocol was adequate and did not depend on the type of diabetes.

DNA Damage and Its Cellular Response in Mother and Fetus Exposed to Hyperglycemic Environment

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of Bauhinia forficata extract in diabetic pregnant rats: maternal repercussions

Bauhinia forficata, commonly known as paw-of-cow, is widely used in Brazil folk medicine for the treatment of Diabetes mellitus. The purposes of present study were to determine the repercussions of diabetes on the defense system against oxidative stress in pregnant female rats and to characterize the influence of the treatment with Bauhinia forficata extract on the antioxidant system, glycemic control, hepatic glycogen, cholesterol, triglycerides, total proteins and lipids. Virgin female Wistar rats were injected with 40 mg/kg streptozotocin (STZ) before mating. Oral administration of an aqueous extract of Bauhinia forficata leaves was given to non-diabetic and diabetic pregnant rats in 3 doses: 500 mg/kg from 0 to 4(th) day of pregnancy, 600 mg/kg from 5(th) to 14(th) day and 1000 mg/kg from 15(th) to 20(th) day. All the females were killed on the day 21 of pregnancy. A maternal blood sample was collected by venous puncture and the maternal liver was removed for biochemical measurement. The diabetic pregnant rats presented hyperglycemia, hyperlipemia, bypertriglyceridemia, hypercholesterolemia, hyperuricemia, decreased determinations of reduced glutathione (GSH) and superoxide dismutase (SOD). Treatment with B. forficata extract did not interfere in the albumin, total protein and lipid, triglyceride, cholesterol and SOD determinations. Increased hepatic glycogen, decreased uric acid concentration and increased GSH activity was observed. This last fact suggests that the plant may have some action on antioxidant defense system. However, the demonstration of the active component present in B. forficata responsible for its antioxidant effect and the increase in hepatic glycogen deserve further investigation.

Association of diabetes and cigarette smoke exposure on the glycemia and liver glycogen of pregnant Wistar rats

Purpose: To evaluate cigarette smoke exposure and/or diabetes association effects on the glycemia and liver glycogen levels of pregnant Wistar rats. Methods: 60 adult rats were randomly distributed into (n= 10/group): non-diabetic exposed to filtered air (G1); non-diabetic exposed to cigarette smoke only before pregnancy (G2); non-diabetic exposed to cigarette smoke before and during pregnancy (G3); diabetic exposed to filtered air (G4); diabetic exposed to cigarette smoke only before pregnancy (G5), and diabetic exposed to cigarette smoke before and during pregnancy (G6). Glycemia was determined at days 0 and 21 of pregnancy. Liver samples were collected for liver glycogen determinations. Results: At day 21 of pregnancy, glycemia was higher in G5 and G6 compared to G4 group. G2 (2.43 +/- 0.43), G3 (3.20 +/- 0.49), G4 (2.62 +/- 0.34), G5 (2.65 +/- 0.27) and G6 groups (1.94 +/- 0.35) presented decreased liver glycogen concentrations compared to G1 (4.20 +/- 0.18 mg/100mg liver tissue) (p<0.05). G5 and G6 groups presented decreased maternal weight gain and litter weight. Conclusions: Severe diabetes and cigarette smoke exposure, alone or associated, caused impairment in liver glycogen storage at term pregnancy. Due to the fact that liver glycogen storages were considered determinant for glucose tolerance, it is relevant to point out a rigid clinical glycemic control and to stop smoking so earlier in pregnancy programming.

Morphometric study of placental villi and vessels in women with mild hyperglycemia or gestational or overt diabetes

In this study, morphometric measures of placental terminal villi and villous vessels were compared in overt, as well as gestational diabetes mellitus, and mild hyperglycemia diagnosed by oral 100 g glucose tolerance test (100 g-OGTT) and glucose profile (GP). At delivery (gestational age >= 34 weeks) a total of 207 placentas were assigned to a control group (n = 56) or to one of three groups complicated by mild hyperglycemia (n = 5 1), gestational diabetes (n = 59) and overt diabetes (n = 4 1). Placenta samples were randomly selected for blind morphometric assessment with an image analyser. Morphometric measures obtained included area and number of terminal villi and their respective villous vessels. Statistical analyses were performed using the chi-square test, ANOVA and stepwise regression (p <= 0.05). Glycemic means were 86.2 mg/dL in controls, 98.9 mg/dL in mild hyperglycemia, 114.1 mg/dL in gestational diabetes and 122.1 mg/dL in overt diabetes. Our results show that abnormal maternal glycemic levels may change the placental morphometric characteristics related to materno-fetal exchanges. (C) 2007 Elsevier B.V.. All rights reserved.

Evaluation of Cell Proliferation and Apoptosis in Placentas of Rats with Severe Diabetes

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Cardiotocografia Anteparto e Prognóstico Perinatal em Gestações Complicadas pelo Diabete: Influência do Controle Metabólico Materno

Objetivo: relacionar a qualidade do controle metabólico com os resultados da cardiotocografia (CTG) anteparto e avaliar sua capacidade preditiva no prognóstico perinatal de gestações associadas ao diabete. Pacientes e Métodos: estudo retrospectivo de 125 gestantes, portadoras de diabete gestacional ou clínico, no qual se relacionou a última CTG anteparto (intervalo máximo de 48 horas) à qualidade do controle metabólico materno e aos resultados perinatais. A qualidade do controle metabólico foi definida pela média glicêmica do dia do exame (MGd) e da gestação (MG) e pelo comportamento da requisição de insulina (R/insulina). Para os resultados perinatais foram analisados os índices de Apgar de 1º e 5º minuto, a classificação peso/idade gestacional, o tempo de internação, a necessidade de cuidados de UTI e a ocorrência de óbito neonatal (ONN) precoce. A capacidade diagnóstica da CTG anteparto foi avaliada pelos índices de sensibilidade, especificidade e valor preditivo positivo e negativo. Resultados: a MGd adequada (<120 mg/dL) associou-se a 2,9% dos resultados de CTG anteparto alterados e a inadequada ( > ou = 120 mg/dL), a 26,1% (p<0,005). A MG mantida inadequada se relacionou a 13,7% de CTG anteparto alterada e a adequada, a apenas 2,7% (p<0,005). O comportamento da requisição de insulina não interferiu nos resultados da CTG anteparto. Os índices de Apgar de 1º e 5º minuto, a necessidade de cuidados de UTI e a ocorrência de ONN precoce não dependeram do último traçado da CTG anteparto. O exame diferenciou o tempo de internação dos recém-nascidos: quando normal, 46,4% tiveram alta hospitalar até o 3º dia de vida e, quando alterado, 62,5% deles ficaram internados por mais de sete dias. Conclusões: os resultados alterados da última CTG anteparto relacionaram-se com níveis inadequados de MG, diária e da gestação, e não dependeram da R/insulina. O resultado normal da CTG anteparto foi adequado para garantir a saúde neonatal. Ao contrário, os resultados alterados indicaram risco de complicações nos filhos de mães diabéticas.

Hypertensive disorders in pregnant women with diabetes mellitus

The present study was performed to assess the rate of hypertensive complications in diabetic pregnant patients and the influence of White's classification and the quality of the diabetic control. This study included 169 diabetic pregnant women who had delivered at the University Hospital of Botucatu Brazil from 1980 to 1981. The hypertensive disorders occurred in 29.8% of the cases. The incidence of the hypertensive process was the same in all classes of diabetic patients, and it was independent of the glycemic control. In patients with gestational diabetes (classes A and AB), chronic hypertension was the commnest type found; in patients with short-term diabetes (classes B and C) pregnancy-induced hypertension (PIH) and chronic hypertension with superimposed PIH was the most frequent type, and diabetic patients with vasculopathies (classes D-R) had preeclampsia and chronic hypertension with superimposed preeclampsia as the commonest type found.

Influência do controle metabólico materno nos resultados da cardiotocografia anteparto e sua relação com o prognóstico perinatal, nas gestações complicadas pelo diabete

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB

Maturidade pulmonar fetal em gestações complicadas por diabete ou hiperglicemia leve

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Estudo das alterações estruturais e da função diastólica cardíaca em mulheres portadoras de diabetes melito gestacional

Pós-graduação em Ginecologia, Obstetrícia e Mastologia - FMB