Fernanda H.S. Corrêa

Acompanhamento ambulatorial de gestantes com diabetes mellitus no Hospital Universitário Pedro Ernesto - UERJ

UNLABELLED In this study we assessed neonatal complications of diabetic in 50 pregnant women at a University Hospital during 2001-2002: 13 (26%) with type 1 diabetes (DM1), 16 with DM2, and 21 (42%) with gestational DM (GDM). The mean outpatient follow-up was at 16.3+/-8 wk for patients with DM1, 22.9+/-7.5 wk for DM2, and 26.0+/-8.9 wk for GDM. Mean HbA1c, fasting and 2-h post-prandial glycemia on first attendance were respectively: 6.1+/-1,1% (RV: 2.6-6.2%), 132+/-39 mg/dL and 190+/-54 mg/dL. 22 patients were on insulin and 15 were on oral antidiabetic agents (OA) at first evaluation. OA were taken on conception and during the first pregnancy trimester and no malformations were seen in the children. Their metabolic profile was similar to other pregnant women. Caesarean section was needed in 54.5% of deliveries. COMPLICATIONS 56.1% were macrosomic babies, with a mean fetal weight of 3.48+/-0.73 Kg, with no differences according to treatment (insulin vs. OA). We conclude that diabetic pregnant women begin their prenatal care at a later period, often taking OA that are not officially advised to be used during pregnancy and are not in a regular metabolic control. As a result, they have macrosomic infants. Even though we have found no complications related to the OA use during pregnancy, we should not encourage their use until more safety studies are available.

Influência da gordura corporal no controle clínico e metabólico de pacientes com diabetes mellitus tipo 2

We evaluate the relationship between body adiposity (BA) by bioelectrical impedance, body mass index (BMI) and waist circumference (WC) in some clinical and laboratorial parameters in 43 patients with type 2 diabetes (DM2), 26F/17M, matched for age, with a DM duration of 13.6±9.1 years. Women had greater BMI: 30.3±5.4 vs. 26.9±3.0kg/m2 (p= 0.04), BA: 35.4±6.2 vs. 19.6±6.2% (p= 0,000), cholesterol: 235± 41 vs. 204±39mg/dL (p= 0,017), triglycerides (TG): 146±61 vs. 116± 57mg/dL (p= 0.06) and HbA1c (HPLC): 7.1±1.7 vs. 6.9±1.4% (p= 0,02) than men, but HDL and LDL cholesterol were not different. When correlated to BA, the following variables were statistically significant: TG, HbA1c, diastolic blood pressure (DBP) and WC. In the stepwise multiple regression analysis using BA, WC and BMI as independent variables and TG (r= 0.34; r2= 0.11; p= 0.02) and DBP (r= 0.39; r2= 0.15; p= 0.008) as the dependent ones, BA was found to be statistically significant. By using the same model having HbA1c as the dependent variable, BA (r= 0.31; r2= 0.10; p= 0.037) and BMI (r= 0.43; r2= 0.19; p= 0.01) became significant. In conclusion, elevated BA in patients with DM2 is an important risk factor to worse metabolic control and blood pressure levels. Women, by virtue of their greater BA and worst plasma lipid profile must need more aggressive intervention to reduce body fat.

Avaliação da secreção e resistência insulínica em indivíduos com diferentes graus de tolerância à glicose - do metabolismo normal ao diabetes mellitus

AIM AND METHODS Our main aim was to determine the association between clinical, demographical parameters and different insulin resistance and secretion indices in apparently healthy subjects, without previous knowledge of their own level of glucose tolerance. For that purpose, we evaluated 105 individuals from February to August 2003 by means of OGTT, aged 33.4+/-1.4 years old, 57.1% female. We allocated them in four groups: group 0 (normal): individuals with BMI < 25 Kg/m(2) and normal glucose metabolism, group 1 (obese): BMI >or= 25 Kg/m(2) and normal glucose metabolism, group 2 (IFG): impaired fasting glucose and group 3 (IGT): impaired glucose tolerance. RESULTS We have found statistical difference on all variables during OGTT between all groups: fasting glucose (p < 0.05), 2-hour glucose (p < 0.05), glucose peak value (p < 0.05), glucose delta (p = 0.02), glucose incremental percentage (p = 0.047), area under curve (p < 0.05), and glucose peak time (p = 0.022). We have not found difference on any variable in insulin curves or on glucose incremental velocity. Regarding insulin secretion indices there were no statistical significance in insulinogenic or delta indices, but they became significant after being corrected by insulin resistance (p = 0.008). When we evaluated insulin resistance alone, by using HOMA and QUICKI indices and the fasting glucose to insulin index, we have found statistical significance (p = 0.005; p = 0.005; p = 0.053). CONCLUSION Although studying a small sample, we could suggest that individuals with impaired fasting glucose and impaired glucose tolerance are in different stages of diabetes natural history disease. We found out that the best indices of insulin resistance are both HOMA and QUICKI. We also suggest that pancreatic secretion indices should be corrected by the insulin resistance, which could best reflect type 2 diabetes natural history.

Sensibilidade, especificidade e valor preditivo dos níveis basais da 17-hidroxiprogesterona no diagnóstico da forma não-clássica da hiperplasia adrenal congênita por deficiência da 21-hidroxilase

Screening for non-classic congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD) is performed with baseline 17-hydroxyprogesterone (17OHPb) and confirmed with the ACTH test. Because the cutoff level of 17OHPb that prompts an ACTH testing is still a matter of discussion, we evaluated the levels of 17OHPb in diagnosing CAH caused by 21OHD. An ACTH (0.25 mg IV) test was performed in 87 hyperandrogenic women, 24.8±0.8 years old. 17OHP levels greater than 1,500 ng/dL, 60min after administration of ACTH were considered diagnostic. 21OHD was confirmed in 11 patients (12.6%); in the remainder 76 the test was negative. Sensitivity, specificity, positive and negative predictive values for 17OHPb >200 ng/dL were 0.91, 0.62, 0.26 and 0.98, respectively. For 17OHPb >350 ng/dL these values were 0.91, 0.91, 0.59 and 0.99 and for 17OHPb >500 ng/dL, 0.82, 0.99, 0.9 and 0.97. Clinical findings (hirsutism, menstrual irregularities and obesity) and levels of androstenedione and total testosterone were similar between both groups. We conclude that clinical findings and androgen levels cannot differentiate patients with and without 21OHD, and suggest the ACTH test to be performed whenever 17OHPb is >350 ng/dL, a highly sensitive cutoff with good negative predictive value.

Insulin signaling pathways in a patient with insulin resistance of difficult management - a case report.

Insulin signalling pathways were investigated in a 33 year-old woman with immunologic insulin resistance. Her past medical history was remarkable for intermittent use of insulin and allergic reactions to several drugs, and measure of plasma anti-insulin antibodies level corroborated the clinical suspicion of immune mediated insulin resistance (8074 nU/ml - RIA - Ref value: <60). Treatment with several immunosuppressive regimens was tried, however the results were disappointing. Possible subcellular mechanisms of insulin resistance were investigated by performing analysis of insulin receptor and post receptor signaling in skeletal muscle biopsy. The expression of insulin receptor (IR), insulin receptor substrate 1 (IRS-1) and glucose transporter 4 (GLUT-4) was evaluated in total extract from muscle tissue by Western blotting. Basal IR, IRS-1 and GLUT-4 expression was detected, however receptor autophosphorylation was not observed. A study of translocation of GLUT-4 to plasma membrane showed that tissue presented low levels of membrane-associated GLUT-4. When in vitro stimulation was undertaken, tissue was capable to be responsive to insulin. Our results suggest that even though IR expression was normally occurring, IR β-subunit tyrosine kinase activity in muscle was down-regulated leading to alterations in insulin post receptor signaling. Consistent with normal insulin receptor and post receptor signaling, our results were compatible with decreased insulin binding to IR probably due to neutralization by anti-insulin antibodies. In conclusion, this patient has immunologic insulin resistance and treatment should be based on immunosuppressive drugs as tolerated.

Avaliação da microalbuminúria em indivíduos não diabéticos

AIM To evaluate the presence of microalbuminuria in non-diabetic subjects, associating it to the presence of cardiovascular risk factors like hypertension, smoking, dislipidemia and obesity. The urinary albumin excretion rate (UAE) was also evaluated regarding to insulin secretion and resistance indices. DESIGN AND METHODS 105 subjects aged 33.4 +/- 1.4 years (57.1% women), received 75 g dextrose for an OGTT, and the following variables were evaluated for glucose and insulin curves: basal and 2 hours values, peak values (PV) and area under the curves (AUC). To evaluate insulin secretion and resistance, we used the insulinogenic, delta, HOMA, QUICKI, glucose to insulin ratio and the relation between insulinogenic and HOMA indices. A urine sample was collected overnight for albuminuria. Individuals were allocated in two groups: 1) normal, and 2) altered glucose metabolism. RESULTS The two groups differed in age, BMI, BP, abdominal circumference (AC), WHR, cholesterol, triglycerides (TG), glycemias (basal and 2h), AUCg, HOMA and QUICKI indices and the relation between insulinogenic and HOMA. Mean UAE was 4.28 +/- 2.73 microg/mL, correlating to DBP, glycemias, AUCg, GPV, HOMA, 2h insulin, IPV e AUCi. By stepwise multiple-regression analysis, only AUCg was predictive of UAE. By comparing interquartile intervals of UAE, we found statistical significance between the 1st and 4th quartile for: BMI, SBP, DBP, AC, waist, 2h glucose, TG, LDL, AUCg, AUCi, GPV and HOMA and QUICKI indices. CONCLUSION Although in the absence of microalbuminuric individuals, we found differences among UAE in individuals across a range of glucose tolerance and differences between clinical and laboratorial variables in the interquartile analysis. Our findings suggest that in non-diabetic individuals, UAE is associated to some characteristics of the metabolic syndrome, probably predisposing to greater atherogenic susceptibility.

Resistência insulínica imunológica: apresentação de caso

Resistencia insulinica imunologica e uma entidade reconhecida na pratica clinica ha muitos anos. Sua patogenese esta relacionada ao aparecimento de anticorpos anti-insulina, e o tratamento baseia-se em imunossupressao. Apresentamos aqui o caso de uma paciente de 33 anos, com diagnostico de diabetes desde a infância, que referia uso de hipoglicemiantes orais durante a adolescencia. Durante o acompanhamento em nosso servico, a dose de insulina foi progressivamente reduzida ate ser substituida por hipoglicemiantes orais. Permaneceu 11 meses com esquema de glibenclamida, metformina e acarbose ate ser internada em coma hiperosmolar nao-cetotico. Apos internacao prolongada, recebeu alta usando insulina NPH, sendo necessario o aumento da dose nos meses subsequentes. Quando atingiu a dose de 2,7U/Kg/dia, foi investigada e excluida a possibilidade de diabetes secundario, sendo diagnosticada resistencia insulinica imunologica. Foram tentados diversos esquemas imunossupressores sem sucesso. A paciente esta atualmente em uso de bomba de infusao subcutânea de insulina Lispro, micofenolato mofetil e prednisona com melhora do controle glicemico.