Smoking affects the oral glucose tolerance test profile and the relationship between glucose and HbA1c in gestational diabetes mellitus.

AIMS: Current smokers in the general population have a lower 2 h plasma glucose after an oral glucose tolerance test (OGTT) and a higher HbA1c than non-smokers, but the relationships between OGTT/HbA1c and smoking status have not been addressed in pregnancy. We analysed glycaemic measurements in women with gestational diabetes mellitus in relation to smoking status. METHODS: We performed a review of the prospectively collected database of the diabetes and pregnancy clinic. We included women with gestational diabetes mellitus and a singleton pregnancy who delivered between 1986 and 2006. Bivariate and multivariate analyses were used to evaluate patient characteristics in relation to smoking status. RESULTS: A total of 2361 women met the inclusion criteria: 556 (23.5%) were active smokers, 266 (11.3%) quit during pregnancy and 1539 (65.2%) were non-smokers. Most baseline characteristics were similar across groups. Diagnostic OGTT was performed at a gestational age of [median (25th, 75(th) centiles)] 29 weeks (26, 33). Women who smoked at the beginning of pregnancy had a higher 1-h plasma glucose than non-smokers [11.8 (11, 12.7), 11.6 (11, 12.6) and 11.5 (10.8, 12.5) mmol/l, for active smokers, those who quit during pregnancy and non-smokers, respectively, P < 0.001] and a lower 3-h plasma glucose [7.3 (5.9, 8.4), 7.6 (6.4, 8.7) and 8.0 (6.8, 9.0) mmol/l, respectively, P < 0.001]. HbA1c was higher in women who smoked at the beginning of pregnancy. Multiple regression analysis confirmed the independent association of smoking status with HbA1c and OGTT plasma glucose. CONCLUSIONS: In women with gestational diabetes mellitus who smoke at the beginning of pregnancy, the shape of the OGTT is consistent with accelerated glucose absorption, and HbA1c is higher than expected for glycaemic values.

Poorer perinatal outcome in male newborns of women with pregestational diabetes mellitus.

AIMS: To assess perinatal outcome in women with pregestational diabetes mellitus according to the sex of the fetus. METHODS: A retrospective review of all singleton pregnancies of women with pregestational diabetes progressing to a gestational age of 22 weeks or more who attended the diabetes and pregnancy clinic from 1981 to 2006 (n=455). We compared maternal characteristics and perinatal outcomes (perinatal mortality, major congenital malformations, small and large for gestational age newborns, preterm birth and a composite of the former) according to the sex of the fetus. A logistic regression analysis was performed using the composite perinatal outcome as the dependent variable and all maternal variables and sex of fetus as potential predictors. RESULTS: Maternal characteristics did not differ in mothers of male and female newborns. In the whole cohort, the composite perinatal outcome was significantly higher in male fetuses; adjusted OR 1.61 (95% CI 1.04-2.50). CONCLUSIONS: In women with pregestational diabetes, perinatal outcome was poorer in male newborns despite similar maternal characteristics.

Insulin requirements throughout pregnancy in women with type 1 diabetes mellitus: three changes of direction.

AIMS/HYPOTHESIS: The aim of the study was to analyse the insulin requirements of women with type 1 diabetes mellitus throughout pregnancy. METHODS: We have examined the weekly mean blood glucose (mmol/l), insulin requirements (U kg(-1) day(-1)) and total insulin requirements (U/day) in 65 women with type 1 diabetes mellitus and tight metabolic control since before pregnancy (HbA(1c) < or =6.0%). RESULTS: Both insulin requirement and total insulin requirement displayed a peak in week 9, a nadir in week 16 and a second peak in week 37. For the change in insulin requirement (4.08% per week) and in total insulin requirement (5.19% per week), the sharpest slope was observed from week 16 to week 37. However, two changes of direction took place in the first 11 weeks and eight out of nine episodes of severe hypoglycaemia requiring treatment with glucagon or i.v. glucose took place in the first 16 weeks. CONCLUSIONS/INTERPRETATION: Pregnant women with type 1 diabetes mellitus and tight metabolic control since before pregnancy displayed changes in insulin requirement and total insulin requirement with successive changes of direction. The sharpest slope was observed between 16 and 37 weeks, but insulin requirements were more unstable in the first 16 weeks. This information could help patients and physicians to react to changes in glycaemic pattern in a prompt and adequate way.

In women with gestational diabetes mellitus factors influencing growth have a larger effect on placental weight than on birth weight.

BACKGROUND AND AIMS: Excessive fetal and placental growth are very common in diabetic pregnancy. We aimed to analyze in women with gestational diabetes mellitus (GDM) the association with birth weight (BW), placental weight (PW) and placental-to-birth weight (PWBW) ratio of acknowledged BW predictors. MATERIAL AND METHODS: We performed a retrospective analysis of a prospective cohort database from a tertiary hospital. Inclusion criteria were singleton pregnancy, diagnosis of GDM, delivery between 1982 and 2011 and gestational age at birth ≥23 weeks. Multiple regression analysis was performed using as dependent variables BW, PW and PWBW ratio and as independent ones maternal characteristics at baseline, metabolic characteristics (GDM diagnosis, treatment, control), pregnancy-induced hypertension, gestational age at delivery and fetal sex. Two sensitivity analyses were performed. RESULTS: We evaluated 2547 women, PW being available in 85.3%. BW was 3260g (2976, 3575), PW 620g (540, 720) and PWBW ratio 19.27 (17.20, 21.47). Among the 24 analyzed variables, there was an important overlap among those associated with BW, PW and PWBW ratio. For most characteristics associated with both BW and PW, the magnitude of the association was greater for the latter, both when promoting growth (i.e. prepregnancy body mass index, 3h plasma glucose at diagnosis) and when restricting it (insulin treatment). CONCLUSION: We conclude that in women with GDM and singleton pregnancies, variables associated with BW, PW and PWBW ratio overlap. The latter is the result of disproportionate associations with BW and PW, usually larger with PW.

Gestational diabetes mellitus in women with multiple pregnancies: is the metabolic abnormality milder?

OBJECTIVE: We aimed to compare maternal characteristics and dysglycemia after delivery in women with gestational diabetes mellitus (GDM) according to pregnancy being multiple (MP) or singleton (SP). The hypothesis was that women with GDM and MP would have a milder glycemic abnormality before and after pregnancy than those with SP. METHODS: We performed a cohort study of 2908 women giving birth between 1986 and 2009. Logistic regression was performed to discriminate between MP and SP after anamnestic pre-pregnancy characteristics. Kaplan-Meier and Cox regression analyses were performed to assess if MP was independently associated with both impaired fasting glucose (IFG)/impaired glucose tolerance (IGT) and diabetes after delivery. RESULTS: Family history of diabetes was the only independent anamnestic pre-pregnancy characteristic discriminating MP versus SP, OR 2.04 (95% CI 1.12, 3.70, p 0.019). The median time to progress to IFG/IGT was 7.52 years in SP (95% CI 6.92, 8.13) and 7.41 in MP (95% CI 3.84, 10.98), ns and the progression to DM did not differ. In addition, MP was not associated to IFG/IGT or to DM in the Cox regression analysis. CONCLUSIONS: In this cohort of women with GDM, those with MP did not demonstrate a lesser degree of dysglycemia after controlling for other pregnancy characteristics and pregnancy-independent factors.

Insulin antibody response to a short course of human insulin therapy in women with gestational diabetes.

OBJECTIVE: To assess the insulin antibody (IA) response to human insulin (HI) therapy in women with gestational diabetes. RESEARCH DESIGN AND METHODS: IAs were measured by a competitive radiobinding assay in 50 women with gestational diabetes before and during treatment with HI and after delivery. At delivery, 15 maternal-cord blood sample pairs were analyzed for IA. As a reference, we searched for IA in 25 new-onset type I diabetic patients, before and at 3, 6, and 12 months after insulin therapy. RESULTS: Insulin autoantibodies (IAAs) were detected in 1 of 50 women with gestational diabetes and 4 of 16 type I diabetic patients (P < 0.05). At the end of pregnancy after 9.3 +/- 6.8 weeks on insulin therapy, 22 of 50 (44%) women with gestational diabetes became IA+ and 4 additional women were found to be positive 2 months postpartum. After 3 months on insulin, type I diabetic patients showed a higher rate of IA positivity (92%, P < 0.001). IA titers at the end of pregnancy were associated with the cumulative insulin dose (r = 0.29, P < 0.05). Postpartum, IA disappeared slowly in most IA+ women, but two women still showed IA 2 years after delivery Titers in cord blood were strongly related to those in maternal blood (r = 0.74, P < 0.01). The rate of adverse fetal outcome did not differ in IA and IA- mothers (27 vs. 40%, NS). CONCLUSIONS: HI is immunogenic, and a short course of HI therapy induces IA in approximately 50% of women with gestational diabetes and 92% of type I diabetic patients. In women with gestational diabetes, insulin dose is slightly associated with IA titers. These IAs apparently cross the placenta. Fetal outcome does not differ according to the maternal IA status, and IAs disappear gradually after delivery but may remain positive for 2 years after delivery.

Postpartum thyroiditis in women with hypothyroidism antedating pregnancy?

In women with hypothyroidism, levothyroxine (LT) requirements after delivery are assumed to return to prepregnancy values. The occasional observation of discordances prompted this study. Forty-one women (31 receiving LT replacement therapy and 10 receiving suppressive therapy for thyroid carcinoma) were followed during the first year after delivery. A control group of 31 nonpregnant women with hypothyroidism (n = 21) or thyroid carcinoma (n = 10) were also followed during a similar period. Twenty-three patients of 41 (56.1%) had discordant requirements at follow-up after delivery vs. 3 of 31 in the control group (9.7%; P < 0.001). The patterns of discordance in the postdelivery group were hyperthyroidism in 12, increase in LT dose in 5, hyper- and hypothyroidism in 5, and recurrence of Graves' disease in 1 women. Those in the control group were increase in LT dose, hyperthyroidism, and hypo- and hyperthyroidism. The rate of patients with discordant prepregnancy-postpartum LT doses was higher in the noncarcinoma subgroup (67.7% vs. 20.0%; P < 0.01), whereas in the control group, both subgroups displayed a similar rate of discordance (9.5% vs. 10%; P = NS). In conclusion, this study documents that women with hypothyroidism antedating pregnancy display changes in LT requirements in the first year after delivery that suggest postpartum thyroiditis.

Melatonin concentration before and during testosterone replacement in primary hypogonadic men.

OBJECTIVE: To study circadian levels of melatonin in primary hypogonadic adult men before and after testosterone treatment. DESIGN AND METHODS: Circadian serum melatonin profiles were studied in six men with primary hypogonadism before and during testosterone substitution and compared with an age-matched control group (n = 6). RESULTS: Hypogonadal patients had higher plasma melatonin concentrations than the control group during day time (34.2 +/- 8.8 compared with 5.4 +/- 0.5 ng/l, means +/- SD; P < 0.005) and night-time (74.8 +/- 34.5 compared with 30.8 +/- 3.2 ng/l). A 3 months course of testosterone replacement treatment in the hypogonadal group was followed by a diminution of the amplified melatonin circadian rhythm, with lower mean values both during the day (34.2.8 +/- 8 compared with 12.7 +/- 2.45 ng/l, P < 0.001) and at night (74.8 +/- 34.5 compared with 41.5 +/- 13.5 ng/l, P < 0.01), and a decrease in the total area under the curve (958 +/- 318 compared with 475.5 +/- 222.9, P = 0.046). There was a significant negative correlation between melatonin (r = -0.69) and testosterone concentrations. CONCLUSIONS: These data indicate that diminished testosterone in male primary hypogonadism is associated with enhanced plasma levels of melatonin, and that testosterone substitution treatment induces a deamplification of the circadian rhythm of melatonin values in humans.

Is selective screening for gestational diabetes mellitus worthwhile everywhere?

We assessed if selective screening for gestational diabetes mellitus (GDM) as recommended by the Fourth Workshop on GDM is worthwhile in our centre. Detection is performed using universal screening in three pregnancy periods using the tests recommended by the first three Workshops. We have analysed the prevalence of low-risk characteristics for GDM in the 917 women delivering in the centre in 1992 and in the whole cohort of 1635 women with GDM delivering between 1986 and 1998. The rate of women with all low risk characteristics was 7.0% among the general pregnant population and 1.3% in the cohort of women with GDM (p<0.001). We conclude that in our population, selective screening of GDM is reliable in identifying women at low risk of GDM, but since only a negligible subset of the pregnant population would not need to be screened, adherence to these guidelines would make the screening policy unnecessarily complicated.

Does preconceptional counselling in diabetic women influence perinatal outcome?

We aimed to assess the impact of a preconceptional clinic (PC) on the perinatal outcome (PO) of diabetic pregnancies attended in our centre. We studied 185 pregnancies attended in the 1986-1996 period (152 in women with insulin dependent diabetes mellitus (IDDM) and 33 with non insulin-dependent diabetes mellitus (NIDDM)) and we analysed the perinatal outcome for both mother and fetus. Sixty-six women (36.1%) had enrolled in the PC, 41.4% for IDDM and 9.1% for NIDDM pregnancies, p < 0.01. First pregnancy HbA1c (in SD around the mean) was 3.98 +/- 3.00 in non-attenders (NA) vs 2.57 +/- 2.41 in attenders (A), p < 0.01. The final HbA1c was in the normal range in both groups. D-R class according to White classification was 33.0% for NA vs 54.5% for A, p < 0.01. There were no differences in the rates of abortion and major malformations (8.8% NA vs 3.6% A, ns). Both groups differed in the rate of cesarean sections (54.9% NA vs 71.0% A, p < 0.05) and in the rate of small for gestational age infants (SGA) (8.7% NA vs 1.8% A, p < 0.05). There were no differences between groups in maternal or neonatal outcomes. In this group of diabetic women with a moderate although less than optimal metabolic control at the beginning of pregnancy, the impact of PC on PO is less evident than described.