[Diabetes and pregnancy: physio-pathogenetic and epidemiologic aspects]. / Diabete e gravidanza: aspetti fisio-patogenetici ed epidemiologici.

Diabetes mellitus is one of the most common maternal illnesses resulting in congenital malformations. All complications of pregnancy, either with diabetes pregestational or gestational, are directly or indirectly related to the degree of metabolic control. If it is not treated properly, diabetes in pregnancy causes major problems for both mother and fetus. The only way to reduce complications to the minimum and locate them near to those of the normal population, is to achieve a good metabolic control. Multi-disciplinary approach in which obstetricians, physicians, paediatricians are involved, combined with intensive monitoring and therapy throughout pregnancy, could achieve successful results in women with complicated diabetes. This objective is subordinate to early diagnosis for gestational diabetes and planning of pregnancy for diabetic women.

Congenital malformations in infants of 517 pregestational diabetic mothers.

To determine whether the maternal metabolic control and/or the use of hypoglycemic drugs during early gestation is associated with a risk of congenital malformations, beginning on January 1989 to December 1994, clinical data from 16 Italian centers were collected retrospectively and entered in a computerized data base: 517 pregnant women with pregestational diabetes mellitus, 362 with insulin-dependent diabetes mellitus (IDDM) (mean age 28.13 +/- 4.8 years), 130 with non insulin-dependent diabetes mellitus (NIDDM) (mean age 33.01 +/- 5.32 years) and 25 with impaired glucose tolerance (IGT) (mean age 32.48 +/- 6.2 years). The percentage of congenital malformations in NIDDM that took oral hypoglycemic drugs was 11.6% respect to 1.4% of NIDDM that did not take hypoglycemic drugs (p < 0.01) and 3.7% of IDDM. Fasting blood glucose, glycosylated hemoglobin and urine keton bodies were more elevated in IDDM respect to NIDDM (p < 0.005). The percentage of malformations in offspring of NIDDM mothers is higher with respect to that of IDDM women, in spite of a better metabolic control.

Predictive factors for insulin treatment in women with diagnosis of gestational diabetes.

To evaluate if at diagnosis some factors are predictive of the insulin treatment, 75 pregnant women with gestational diabetes mellitus (GDM) and 75 with normal glucose tolerance were examined. The GDM group underwent a diet containing 25 kcal/kg/24 h and insulin was started when fasting and 2 h after meals glucose levels were respectively > 95 and > 125 mg/dl. 52 patients were treated with diet (GDd) and 23 with diet and insulin (GDi). Diagnosis week, prepregnancy body mass index (BMI), weight gain, glucose levels during oral glucose tolerance test (OGTT) (0', 60', 120' and 180'), area under curve (AUC), triglyceride levels and infant weight at delivery were evaluated. Triglyceride levels were higher in GDi respect to NGT group (232.2 +/- 110.7 mg/dl vs 147.4 +/- 70 mg/dl; p < 0.001). Diagnosis was earlier and 180' glucose levels, AUC and BMI were higher in GDi than GDd group. In conclusion, triglyceride and 180' glucose levels, AUC, pregestational BMI and diagnosis week are predictive factors for insulin treatment in gestational diabetes.

Analysis of T-lymphocyte subsets after phytohemagglutinin stimulation in normal and type 1 diabetic mothers and their infants.

PROBLEM: Our aim was to investigate the immunological status of diabetic pregnancy, which is an overlap of diabetic immunity abnormalities and the immunological modifications normally occurring during pregnancy. METHOD: We studied lymphocyte subpopulations and lymphokine production, after 96 h of phytohemagglutinin (PHA) stimulation, from normal and Type I diabetic pregnant women at delivery time and from the respective cord blood. RESULTS: Peripheral blood mononuclear cells (PBMC) from both normal and Type I diabetic mothers showed an increase in CD8+ and a decrease in CD4+ cells compared to the respective cord blood mononuclear cells (CBMC). Moreover, Type I PBMC showed a lower number of "activated" CD3+ DR+ cells and a higher number of CD8+ CD25+ cells with respect to normal women, which may reflect the dysregulatory pattern due to the autoimmune condition. Type I CBMC showed a big increase in the number of CD4+ Leu8+ cells, a cell subpopulation characterized by inhibitory activity. Finally, as regards lymphokine release in culture supernatants, type I diabetes seemed to be associated with an over-production of IL1 and IL6, although the latter increase is less evident in CBMC cultures. CONCLUSIONS: The present study shows that diabetic pregnancy is associated with major alterations of cell-mediated immunity leading to a state of immunodepression. Moreover, our study suggests that the maternal immunological status influences fetal immunity, as demonstrated by the increase in the number of regulatory cells and by the altered pattern of lymphokine production (IL1 and IL6) by lymphocytes derived from diabetic CBMC. The latter phenomenon perfectly mirrors maternal PBMC characteristics.

[Fetal macrosomia in children of diabetic mothers: relationship with excess weight in early years of life]. / Macrosomia fetale nei figli di madre diabetica: relazione con l'eccedenza ponderale nei primi anni di vita.

One hundred children (4.1 +/- 1.9 years) were examined: 31 of type I diabetic mothers, 25 of type II diabetic mothers and 44 of gestational diabetic mothers. The fetal body weight index at delivery was determined according to Babson. The weight/height index was determined according to Tunner's Centiles, when the children were examined. At delivery 41% of babies examined was greater than 90 degrees C for gestational age; when the babies were reexamined 23% was greater than 90 degrees C. On the contrary, during the early years of life we found that the 51% of children is greater than 90 degrees C and of this, the 27% became obese. The diabetic mother's children develop obesity more frequently than those of non diabetic mother's ones. The body weight at birth influences but is not the cause of obesity in the early years of life.

Evaluation of B-cell secretion and peripheral insulin resistance during pregnancy and after delivery in gestational diabetes mellitus with obesity.

Nine pregnant women with gestational diabetes mellitus (GDM) were studied. Six normal pregnant women and six normal nonpregnant women were evaluated as control groups. All the women underwent oral glucose tolerance test and glucose clamp during the third trimester of pregnancy and two months after delivery. During OGTT, glucose, C-peptide and insulin plasma levels were determined. C-peptide and insulin values in the late phase of OGTT were higher during pregnancy than after delivery in both groups. In gestational diabetic women, the M-value in the second steady-state during glucose clamp was lower than in controls, both during pregnancy and after delivery. Nevertheless, in both groups the M-value during pregnancy was lower than after delivery. Moreover, in gestational diabetic women there was an inverse correlation between M-value in the second steady-state and ponderal excess index after delivery. In conclusion, the impaired peripheral glucose utilization and the pancreatic pattern of gestational diabetic women compared to normal suggested altered B-cell secretion response, increased peripheral resistance and overweight to be the main changes in GDM.

[Comparison of intensified traditional insulin therapy and micropump therapy in pregnant women with type 1 diabetes mellitus]. / Confronto fra terapia insulinica tradizionale ottimizzata e con microinfusore in gravide affette da diabete mellito di tipo I.

Ten pregnant women, affected by type I diabetes mellitus, observed for the first time during the II-III month of pregnancy, were examined. These patients were divided in two groups at random: group A underwent continuous subcutaneous insulin infusion with micropump CPI 9100 Lilly; group B underwent intensified insulin therapy with three daily doses of MC rapid insulin, two of which associated with MC intermediate insulin. All the patients were able to monitor their own blood glucose levels at home by means of reactive strips and reflectometer. In both the groups the mean glycemic values during fast and two hours after meals, and the eventual presence of urinary keton bodies and hypoglycemic crisis were evaluated during the course of pregnancy: these parameters turned out to be identical in the two groups. The increased need of insulin, the maternal body weight gain, the week and mode of delivery, the neonatal weight and the maternal and fetal complications also turned out to be identical in the two groups. To conclude, a good maternal metabolic control can be obtained either with the intensified conventional insulin therapy of with micropumps, if the patients, being properly instructed, are responsible for the monitoring of their own blood glucose levels at home.

Treatment of non insulin-dependent diabetic women during pregnancy.

From 1981 to 1984 90 cases of diabetic pregnancy were seen at the Palermo Center. Twenty-nine patients (32%) had prepregnancy type 2 diabetes, 20 (69%) of these were obese and were studied further. The patients were divided into 2 groups of 13 and 7 patients. The first group was given a diet of 30 kcal/kg ideal prepregnancy weight. The second group was prescribed a low energy diet of on average 1200 kcal/day. In the diet-restricted group, weight gain was less pronounced (7.9 +/- 1.2 SD vs. 12.7 +/- 8.6 kg), insulin requirement was lower (0.56 +/- 0.22 vs. 1.00 +/- 0.34 U/kg body weight) and the metabolic control was better than observed in the group given 30 kcal/kg body weight. The weight gain during pregnancy was proportional to the fetal weight index at birth (r = 0.72, P less than 0.0005). It is concluded that obese type 2 diabetic women are best treated by a low caloric diet and, when necessary, small doses of insulin. To establish the optimal caloric intake for obese pregnant type 2 diabetic women, the following formula is proposed: (30 kcal/kg prepregnancy ideal body weight/24 h) - X, where X is the % of prepregnancy obesity exceeding 120.

Triglyceride and cholesterol levels during pregnancy in type I, type II and gestational diabetic women.

Longitudinal observation of fasting triglyceride and total cholesterol levels throughout gestation in 16 type I, 13 type II, 11 GDM and 14 normal pregnant women was made. There were no significant differences between the groups examined, except the higher levels of triglycerides in GDM group during the second trimester (p less than 0.05). Probably these results are due to "good" metabolic compensation, achieved in diabetic pregnant women.

Placental lactogen, progesterone, total estriol and prolactin plasma levels in pregnant women with insulin-dependent diabetes mellitus.

Fifteen insulin-dependent diabetic (White's class B-C) and 10 healthy pregnant women were examined from the 12th to the 36th wk. Every 4 wk, a blood sample was drawn to determine total estriol, progesterone, placental lactogen and prolactin. Throughout the pregnancy, total estriol and progesterone in diabetic and non-diabetic women are very similar. On the contrary, the PRL levels are constantly lower in diabetic pregnant women, even though the difference is statistically significant only for the 24th wk determination. The hPL level is instead significantly lower in diabetic pregnant women at the 12th, 20th, 24th, 32nd and 36th wk. A negative correlation exists between the hPL value and the mean blood glucose level, performed the same day as the hormonal test. This correlation is statistically significant at the 12th, 16th, 20th, 28th and 36th wk. No significant difference is found between the two groups examined for the delivery week, the placental weight, the birth weight and the fetal body weight index. To conclude, while estriol and progesterone are not affected by the higher variability of glucose levels during pregnancy in diabetics, compared to normals, hPL and perhaps also PRL may be influenced by the mild hyperglycemia consequent to diabetes.

[Effects of acute ingestion of ethanol on several metabolic parameters (blood sugar, triglycerides, non-esterified fatty acids, lactic acid and uric acid) in subjects with type I diabetes mellitus]. / Effetti dell'ingestione acuta di etanolo su alcuni parametri metabolici (glicemia, trigliceridemia, NEFAemia, lattacidemia, uricemia) in soggetti con diabete mellito di tipo I.

7 diabetic type I patients and 17 normal subjects underwent to acute ethanol oral load (0,8 g/Kg), in order to investigate the modifications produced on glucose, triglycerides, FFA, lactate and uric acid plasma values. Our results show basal differences between diabetics and controls in all these parameters; furthermore, acute ethanol ingestion produces no significant variations of blood glucose in both groups, a significant decrease in FFA levels, an increase of triglyceridemic levels, more evident in diabetics and an increase of lactate, earlier in normals. On the other hand, there is no significant modification in uric acid plasma levels in controls, whereas in diabetics there is an increase, probably due to more elevated lactacidemic values in the late phase of the test.

[Plasma levels of triglycerides, cholesterol, non-esterified fatty acids and uric acid, during oral glucose load, in subjects with type II diabetes and diminished glucose tolerance]. / Livelli plasmatici di trigliceridi, colesterolo, NEFA ed acido urico, in corso si carico orale di glucosio, in soggetti con diabete di tipo II e con diminuita tolleranza glicidica.

In order to study triglycerides, cholesterol, FFA and uric acid plasma levels after OGTT, 10 type II diabetics, 8 IGT subjects, 10 controls were studied. A progressive decrease of FFA plasma values in all groups is shown; there is also an increase in triglycerides vs. basal values in all groups, at 240'. In diabetics and IGT groups there are higher cholesterol levels than controls; IGT subjects have the highest uric acid levels, which in all groups decrease at 180' and 240'. We conclude triglycerides, FAA, uric acid are modified, cholesterol levels are unaffected by glucose oral load in all groups.

Study on maternal, fetal and amniotic prolactin in gestational diabetic women, at term.

In order to determine whether prolactin secretion was affected in diabetic pregnancy, maternal, fetal and amniotic fluid prolactin (PRL) concentrations were measured in gestational non treated diabetic women at parturition. Amniotic fluid PRL levels, though higher than those in maternal and fetal serum, were significantly lower than those of the controls (p less than 0.005); no case of respiratory distress syndrome or congenital malformation was found at birth.

[Variations in blood prolactin in man during enflurane or Alfatésine anesthesias]. / Variations de la prolactinémie chez l'homme pendant l'anesthésie par enflurane ou Alfatésine.

Blood prolactin levels (PRL) rise significantly in man following stress or the administration of many drugs. This finding led the authors to study variations in PRL during anaesthesia with Enflurane or Alfatesine. Repeated estimations of PRL were made in 38 subjects: in 8 cases (3 female and 5 male) under anaesthesia with Enflurane only, in 10 cases (6 female and 4 male) with Alfatesine only, in 10 cases (5 female and 5 male) with Enflurane and surgery and in 10 other cases (5 female and 5 male) with Alfatesine with surgery. No significant increase in PRL was seen during the administration of anaesthesia without surgery. By contrast, significant changes were seen when surgery was performed. No significant difference was seen in the results between the two sexes in each group. Taking into account the results of earlier experiments, the authors conclude that Enflurane or Alfatesine alone do not influence the hypothalamo-pituitary axis, but do not protect it during surgical and/or pharmacological stress.

[Effects of prolonged fasting and vagotomy on the ultrastructure of contractile myocardium in pigeons]. / Effetti del digiuno prolungato e della vagotomia sull'ultra struttura del miocardio contrattile degli uccelli.

Ultrastructural changes in pigeon heart following long fasting and vagotomy are reported. In the fasting pigeons several fat droplets surrounding the adjacent nearest mitochondria represent the most important finding. Conversely, in the fasting and vagotomized pigeons the mean finding is a large decrease of fat droplets. Ultrastructural findings appear related with biochemical changes by different experimental conditions.