Cetoacidosis diabética normoglicémica en el embarazo: caso clínico / Normoglycemic diabetic ketoacidosis in pregnancy: report of one case

Normoglycemic diabetic ketoacidosis should be suspected in pregnant women presenting nausea, vomiting, abdominal pain and anorexia. We report a 39 years old woman with a 32 weeks pregnancy who sought emergency care due to hyperemesis. She was hospitalized with the following diagnoses: pregnancy hypertension syndrome, gestational diabetes, morbid obesity and poor prenatal control. The evaluation of the feto-placental unit showed perception of fetal movements, non-reactive non-stress baseline record and a biophysical profile of 6/8. Fetal maturation was initiated. Laboratory tests showed a metabolic acidosis, a low pH, an increased Gap anion, elevated ketonemia and a blood glucose of 172 mg/dl. A diagnosis of normoglycemic diabetic ketoacidosis was formulated and treatment with hydration and regular insulin according to capillary blood glucose levels was started. An emergency caesarean section was performed. The newborn weighed 2.650 kg, had a length of 46 cm, was large for gestational age, had an Apgar score of 2.7, had perinatal asphyxia, convulsive syndrome and a possible congenital cardiopathy. Once the ketoacidosis was resolved during the immediate puerperium, slow acting insulin was initiated.

Associação entre perfil glicêmico materno e o índice de líquido amniótico em gestações complicadas pelo Diabetes mellituspré-gestacional / Association between maternal glycemic profile and amniotic fluid index in pregnancies complicated by pregestational Diabetes Mellitus

OBJETIVOS: Estudar a relação entre o volume de líquido amniótico e o perfil glicêmico em gestantes com Diabetes mellitus tipo 1 e tipo 2 acompanhadas em ambulatório especializado e multidisciplinar. MÉTODOS: Este estudo observacional foi realizado entre janeiro de 2001 e dezembro de 2004. Os critérios de inclusão adotados foram: gestação única, diagnóstico de Diabetes mellitus pré-gestacional, início do pré-natal antes da 26ª semana, ausência de anomalias fetais. Foram excluídos os casos em que o recém-nascido apresentou-se pequeno para a idade gestacional. O índice de líquido amniótico (ILA) foi avaliado semanalmente a partir da 27ª semana de gestação até o parto e comparado com o perfil glicêmico da semana precedente ao exame ultrassonográfico. O perfil glicêmico foi analisado pela média glicêmica. A correlação entre o perfil glicêmico e ILA foi analisada pelo índice de Spearman. RESULTADOS: Foram estudadas 60 gestantes, perfazendo um total de 659 correlações entre o ILA e o perfil glicêmico. Em nenhuma idade gestacional estudada houve correlação entre o ILA e o perfil glicêmico. No grupo com ILA <18 cm a média glicêmica foi de 103,7 mg/dl (13,69) e no grupo com ILA > 18 cm a média glicêmica foi de 103,67 mg/dl (DP=11,46), não apresentando diferença significativa. CONCLUSÃO: Em gestantes diabéticas tipo 1 e 2, com tratamento padronizado e controle rigoroso metabólico, não houve relação entre o ILA e o perfil glicêmico materno no terceiro trimestre de gestação.

BACKGROUND: to study the relation between amniotic fluid volume and glycemic control in pregnancies complicated by diabetes mellitus type 1 and 2, followed in a specialized multidisciplinary prenatal care service. METHODS: This descriptive study was performed between January 2001 and December 2004. Inclusion criteria were: simple pregnancy, diagnosis of pregestational diabetes, beginning of prenatal care before the 26th week and absence of fetal anomaly. Cases with newborns small for gestational age were excluded. The amniotic fluid index (AFI) was measured weekly, beginning at the 27th week of gestation and continued until delivery and the maternal glycemic profile was obtained a week before ultrasound assessment. This profile consisted of the glycemic level averages and percentages of the abnormal high values. Correlation between the glycemic profile and the AFI was shown by the Spearman correlation test. RESULTS: Sixty pregnant women were assessed and 659 correlations between the AFI and glycemic profile were obtained. No correlation was observed in any of the gestational weeks studied. The mean glycemic value was 103.69 mg/dl (SD=13.69) in the group with AFI £18 cm, and the 103.67 mg/dl (SD=11.46) in the group with AFI < 18 cm and no significant difference was detected. CONCLUSION: This study showed no correlation between AFI and maternal glycemic profile during the third trimester in type 1 and 2 diabetic pregnant women, undergoing standardized treatment and rigorous metabolic control.

Relato de caso: diabetes Flatbush - da cetoacidose ao tratamento não-farmacológico / Case report: diabetes Flatbush - from ketoacidosis to non pharmacological treatment

Um subgrupo de pacientes, em sua maioria negros ou hispânicos e obesos, tem a cetoacidose diabética (CAD) como forma de apresentação de diabetes mellitus (DM), mas, devido à sua evolução clínica, posteriormente é classificado como DM tipo 2. Estes indivíduos têm pesquisa de auto-anticorpos anti-GAD, anti-IA2 e anti-insulina negativa, mas freqüentemente em associação com HLA classe II de risco para DM tipo 1 (DRB1*03 e/ou DRB1*04). Este subtipo peculiar de DM é denominado diabetes flatbush. Neste artigo, relatamos o caso de uma paciente de origem caucasiana com tais características, na qual foi possível retirada da insulinoterapia. Os possíveis fatores associados a esta evolução favorável serão discutidos.

A subgroup of patients presents diabetic ketoacidosis at the onset of diabetes mellitus (DM) but later is classified as type 2 DM based on the clinical follow-up. These individuals, most commonly obese of African or Hispanic origin, have negative auto-antibodies associated with type 1 DM, but frequently HLA class II DRB1*03 and/or DRB1*04 are detected. This peculiar subtype of DM is commonly referred to as diabetes flatbush. Here we report the case of a Caucasian patient that exhibited the described evolution and in whom it was possible to withdraw insulin therapy. The possible factors associated with this favorable development are also discussed.

Foetomaternal complications in pregnancies with diabetes mellitus: association with the amount of insulin requirement, mean terminal blood glucose and HbA1C levels.

Pregnancy hyperglycaemia can lead to foetomaternal complications. Normoglycaemia with exercise, diet and/or insulin can alter outcomes. The insulin requirement itself may alter outcomes independently. Two hundred and forty patients of pregnancy with diabetes mellitus were selected of which 176 belonged to gestational diabetes mellitus and 64 pregestational diabetes mellitus groups. Insulin requirement of pregestational diabetes mellitus group was 1.8 times higher than the gestational diabetes mellitus group. There were no insulin related increased complications in either group. The foetal complications were higher in pregestational diabetes mellitus group (62.5%) than in the gestational diabetes mellitus group (27.3 and 40% in < 15 units or > or = 15 units insulin requirement respectively). The terminal glycaemic parameters (fasting plasma glucose, 2 hours postprandial plasma glucose, HbA1C%) were not different in case of gestational diabetes mellitus between those with and without foetal complications, except for fasting plasma glucose where 'with complications' fasting plasma glucose was lower than without (79.4 +/- 13.14 versus 75.28 +/- 3.68 mg/dl). For pregestational diabetes mellitus patients those without complications had a significantly lower level of all the parameters (fasting plasma glucose 69.75 +/- 0.5 versus 122 +/- 14.14 mg/dl, postprandial plasma glucose 95 +/- 7.4 versus 131.5 +/- 12.02 mg/dl; HbA1C 6.8 +/- 0.28 versus 7.3 +/- 3.6%) compared with those having complications. Maternal complications could not be segregated as all the subgroups had a very incidence of caesarean section (60%-100%). However, when lower segment caesarean section was excluded and maternal complications segregated, for gestational diabetes mellitus patients, only fasting plasma glucose was significantly lower in cases without complications while in pregestational diabetes mellitus patients the fasting plasma glucose as well as HbA1C were significantly lower in cases without complications.

Are there structural alterations in the enamel organ of offspring of rats with alloxan-induced diabetes mellitus?

A hipoplasia de esmalte é a mais comum dentre as alterações de desenvolvimento do dente humano, e ocorre com freqüência em dentes decíduos de filhos de mães diabéticas. O presente estudo experimental analisou, por meio de microscopia óptica e morfometria, o órgão do esmalte de incisivos inferiores de filhotes de ratas com diabetes aloxânico, induzido previamente à gestação. Os resultados mostraram que não foram observadas pela microscopia óptica alterações significantes nos germes dentais dos animais descendentes de ratas diabéticas, com exceção de um caso. A análise morfométrica dos órgãos do esmalte de ratos nascidos de mães diabéticas tratadas e não tratadas evidenciou as seguintes diferenças estatisticamente significantes: menor espessura da matriz de esmalte, menor altura dos ameloblastos e área de seus núcleos. Nos animais nascidos de ratas diabéticas tratadas, observou-se núcleos dos ameloblastos mais elípticos e aumento da área correspondente ao interstício do retículo estrelado. Estes resultados indicam que há alterações estruturais no órgão do esmalte de descendentes de ratas com diabetes aloxânico as quais poderiam induzir a hipoplasia do esmalte dental visto por microscopia eletrônica de varredura, possivelmente refletindo as alterações metabólicas observadas nesta condição. Estudos futuros devem ser realizados a fim de determinar se estas alterações são transitórias ou permanentes.

Enamel hypoplasia in a litter of rats with alloxan-induced diabetes mellitus

Enamel hypoplasia is an important clinical problem commonly seen in children born to diabetic women. We aimed to characterize the enamel hypoplasia in Wistar rats born to alloxan-induced diabetes mellitus rats. Groups consisted of pregnant rats supplemented (ISDR) or not (NISDR) with insulin and controls, in which sterile saline solution was administered instead of alloxan or insulin. The mandibular incisors of one-month-old rats born to these mothers were analyzed. Whitish defective enamel was found macroscopically in both experimental groups (ISDR = 37.5 percent, NISDR = 33.3 percent) but not in the control group. Mild to severe enamel hypoplasia was observed by scanning electron microscopy (ISDR = 93.8 percent; NISDR = 100 percent, control = 4.2 percent). The severity of hypoplasia correlated positively with the maternal level of blood glucose. In conclusion, the intensity of enamel hypoplasia in the teeth of the litter born to alloxan-induced diabetic rats was variable and was dependent on the glycemic level of the pregnant rat

Polymerization of fetal fibrin and alterations in fibrin network characteristics during diabetic pregnancy.

The present study compares plasma fibrin network characteristics of fetal blood and that of normal and diabetic pregnant women. Plasma fibrinogen concentration, clotting curves, mass-length ratio of the fibrin fibers, gross permeability and tensile strength of the networks, have been measured. Plasma glucose and glycated hemoglobin are used as glycemic index in diabetic gestational women. The fetal plasma has a lower concentration of fibrin and exhibits delayed clotting, the networks are made up of thinner fibers, are more cross-linked, have lower permeability, and increased tensile strength than in normal adults. The tensile strength of the networks prepared from the plasma of diabetic gestational women are more highly crosslinked than those made from plasma of normal women of corresponding length of pregnancy. The fibrin fiber-thickness is increased during the first and second trimester but is significantly reduced during the third trimester in the diabetic gestational women. The gross permeability of the networks is significantly reduced during the second and third trimester in the diabetic gestational women. The SDS-PAGE shows characteristic pattern of alpha, beta, and gamma-polypeptides in both normal and diabetic gestational women.

Serum lipid and lipoprotein composition in infants of diabetic mothers.

Diabetes mellitus (DM) alters carbohydrate and lipid metabolism to a great extent. This study was planned to determine whether infants of insulin dependent and gestational diabetic mothers have abnormal lipid metabolism. Three groups of newborns were included in the study; group I consisted of 7 infants of diabetic mothers (IDM) with insulin dependent DM (Type 1 DM), group II of 18 infants of gestational diabetic mothers and group III of 20 control neonates whose mothers had no history of DM. Total cholesterol (TC), triglyceride (TG) and high density lipoprotein-cholesterol (HDL-C) values in groups I and II were no different compared to those in group III (p > 0.05). However, low density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio were similar between groups I and II (p > 0.05) but significantly higher in both infants of type 1 diabetic mothers and gestational diabetic mothers compared to control infants (p < 0.05). Apolipoprotein A-I (Apo A-1) and apolipoprotein B (Apo B) levels, Apo A-I/Apo B and HDL-C/Apo A-I ratios were similar in between groups. However, Apo B/LDL-C ratio was significantly lower in groups I and II compared to control group (p < 0.05). In conclusion, diabetes in pregnant women causes a tendency to LDL hypercholesterolemia in the offspring. These infants should be longitudinally followed up to assess whether this observation imposes an increased risk for atherosclerosis for advanced ages.

Diabetes and experimental pregnancy in rats: course of maternal blood glucose levels and its repercussions on the blood glucose levels and pancreas of newborn pups

The objective of the present investigation was to determine the course of maternal blood glucose levels in pregnant rats and its repercussions on the glucose levels an pancreas of their newborn pups. Diabetes was induced by alloxan (42mg/Kg body weight) and steptozotocin (40mg/Kg). Sixty-two pregnant Wistar rats weighing 180 to 250 g were divided into a control group and two groups with moderate (120 to 200 mg/dl glucose) and severe diabetes (greater than 200 mg/dl glucose), respectively. Blood glucose levels were measured in the dams on the 1st, 14th, and 21st days of pregnancy and in the pups at birth. The results were pooled for each litter. The fetal pancrases were removed after cesarian section performed on the 21st day of pregnancy, pooled for each litter and processed for histopathologic examination by light microscopy. Maternal blood glucose levels were significantly increased compared with the first day of pregnancy in both normal and diabetic ratsd starting on the 14 th day of pregnancy. Fetal blood glucose levels correlated with maternal levels. The histopathologic changes characterized by vacuolization and basophilia of the cytoplasm of endocrine pancreas of newborn pups from dams with moderate or severe diabetes suggested pancreatic hyperactivity

An evaluation of glycosylated hemoglobin measurement by a colorimetric method as a screening test for gestational diabetes mellitus.

To assess the potential value of glycosylated hemoglobin measurement (HbA1) in screening for gestational diabetes mellitus (GDM), HbA1 by a colorimetric method, plasma glucose level 1 hr after 50 g oral glucose loading, and 3-hr 100 g oral glucose tolerance test (3-hr OGTT) were performed in 334 pregnant women at Ramathibodi Hospital. These subjects carried high risk factors of GDM. Gestational ages varied from 24 to 38 wks. Twenty-four cases were diabetic (7.2%) by O'Sullivan and Mahan's criteria (1964). As a screening test to select subjects for 3-hr OGTT, plasma glucose level 1 hr after 50 g oral glucose load (plasma glucose level 7.8 mmol/L and above) has sensitivity: 87.50 per cent, specificity: 64.19 per cent. HbA1 level of 5.60 per cent (upper 95% confidence limit of the mean) and above yield sensitivity: 66.67 per cent, specificity: 61.29 per cent. Thus, glycosylated hemoglobin measurement as a screening test for GDM is not as effective as the conventional 50 g oral glucose loading test.

Serum bilirubin level in newborn of diabetic and hypertensive mothers

A total number of 140 newborn infants were studied for bilirubin levels. They were divided to forty infants of diabetic mothers [20 oxytocin induced labour and 20 oxytocin augmented], 40 infants of hypertensive mothers [20 oxytocin induced and 20 augmented labours] and 60 controls [20 induced, 20 augmented and 20 with no oxytocin given]. It was found that total and unconjugated bilirubin levels were higher in infants delivered after induction of labour, whether they were diabetic, hypertensive or not, than in infants of non induced labours. Bilirubin levels were also mildly high in infants of augmented diabetics after delivery which was nullified after 24 hours. These results suggest that the increased bilirubin levels are related to induced labours rather than to the medical problem of the mothers, provided that the newborns are of average weight

Perinatal outcome in relation to maternal glycaemic control in diabetic mothers.

The relationship between glycaemic control and perinatal outcome was assessed in 60 pregnant diabetic women, divided into three groups on the basis of the mean plasma glucose level. Group I, had mean plasma glucose less than 120 mg/dl (32 patients); group II, mean plasma glucose 121-140 mg/dl (13 patients); and group III, mean plasma glucose exceeding 140 mg/dl (15 patients). The degree of maternal glycaemic control appeared to affect the perinatal outcome. Neonatal morbidity was minimum in group I (31.25%) followed by group II infants (46.15%) and maximum in group III infants (66.6%). Maintenance of maternal plasma glucose level at or below 120 mg/dl was thus associated with minimum neonatal morbidity.

The oral glucose tolerance test is a poor predictor of hyperglycemia during pregnancy

1. In the order to assess the efficacy of the use of the diurnal plasma glucose profile rather than that of the glucose tolerance tes (GTT) to predict hyperglycemia during pregnancy, we compared the results of the two tests. A total of 192 pregnant women seen at the Prenatal Clinic of the Faculty of Medicine of Botucatu were submitted to the glucose tolerance test (GTT) and determination of diurnal plasma glucose profile. 2. On the basis of two blood tests (GTT) and diurnal plasma glucose profile). the subjects were divided into four groups: Group I-A, normal GTT and profile (79 patients, 41.2%); Group I-B, normal GTT and altered profile (63 patients, 32.8%); Group II-A, altered GTT and normal profile (18 patients, 9.4%) Group II-B, altered Gtt and profile (32 patients, 16,7%). 3. Large babies were delivered by 25.6% of Group I-A, 53.8% of GroupI-B28.6% of Group II-A and 51.9% of Group II-B patients. Group I-A patients are normoglycemic, Group I-B patients have intolerance to carbohydrates, protein and lipides, Group II-A patients have intolerance to high carbohydrate amounts, especially in the form of glucose, and Group II-B patients are diabetic. 4. We propose that Group I-A patients should receive no treatment, Group II-A patients should be adivised to avoid excess carbohydrate intake and Groups I-B and II-B patients should be places on a low-calorie diet and treated with insulin if necessary to obtain normal blood glucose levels. 5. Routine determination of blod glucose levels under fasting conditions represents a screening method for diabetes and values of > ou = 90 mg/dl identify a population at risk that should be submitted to GTT and determination of plasma glucose profile

A random plasma glucose method for screening for gestational diabetes.

Low renal threshold for glucose during pregnancy renders glycosuria less specific for the diagnosis of gestational diabetes. Screening for gestational diabetes was done by utilising random plasma glucose (RPG). RPG was done at the first antenatal visit. In 12,623 patients who registered for antenatal care at the N.W.M. Hospital, 1371 patients had a RPG more than 100 mg%. An oral glucose tolerance test was advised in these patients. The pick-up rate of gestational diabetes correlated with RPG level. Thirty-six cases of gestational diabetes were picked up. The pick up rate is significantly higher as compared to that which would have been detected utilising conventional screening criteria.