Insulin Requirements and Carbohydrate to Insulin Ratio in Normal Weight, Overweight, and Obese Women With Type 1 Diabetes Under Pump Treatment During Pregnancy: A Lesson From Old Technologies.

Aim: The primary aim of this study was to assess insulin requirements and carbohydrate to insulin ratio (CHO/IR) in normal weight, overweight, and obese pregnant women with type 1 diabetes across early, middle, and late pregnancy. Methods: In this multicenter, retrospective, observational study we evaluated 86 of 101 pregnant Caucasian women with type 1 diabetes under pump treatment. The women were trained to calculate CHO/IR daily by dividing CHO grams of every single meal by insulin units injected. Since the purpose of the study was to identify the CHO/IR able to reach the glycemic target, we only selected the CHO/IR obtained when glycemic values were at target. Statistics: SPSS 20. Results: We studied 45 normal weight, 31 overweight, and 10 obese women. Insulin requirements increased throughout pregnancy (p < 0.0001 and <0.001 respectively) in the normal and overweight women, while it remained unchanged in the obese women. Insulin requirements were different between groups when expressed as an absolute value, but not when adjusted for body weight. Breakfast CHO/IR decreased progressively throughout pregnancy in the normal weight women, from 13.3 (9.8-6.7) at the first stage of pregnancy to 6.2 (3.8-8.6) (p = 0.01) at the end stage, and in the overweight women from 8.5 (7.1-12.6) to 5.2 (4.0-8.1) (p = 0.001), while in the obese women it remained stable, moving from 6.0 (5.0-7.9) to 5.1 (4.1-7.4) (p = 0.7). Likewise, lunch and dinner CHO/IR decreased in the normal weight and overweight women (p < 0.03) and not in the obese women. The obese women gained less weight than the others, especially in early pregnancy when they even lost a median of 1.25 (-1 -1.1) kg (p = 0.005). In early pregnancy, we found a correlation between pregestational BMI and insulin requirements (IU/day) or CHO/IR at each meal (p < 0.001 and p = 0.001, respectively). In late pregnancy, a relationship between pre-gestational BMI and CHO/IR change was found (P = 0.004), as well as between weight gain and CHO/IR change (p=0.02). The significance was lost when both variables were included in the multiple regression analysis. There was no difference in pregnancy outcomes except for a higher pre-term delivery rate in the obese women. Conclusion: Pre-gestational BMI and weight gain may play a role in determining CHO/IR during pregnancy in women with type 1 diabetes under pump treatment.

A Study of the Carbohydrate-to-Insulin Ratio in Pregnant Women with Type 1 Diabetes on Pump Treatment.

AIM: The aim of this study was to assess carbohydrate (CHO)-to-insulin ratio (CHO/IR) values in pregnant women with type 1 diabetes and to describe differences in CHO/IR across each week of pregnancy. MATERIALS AND METHODS: This was a multicenter, retrospective, observational study (2006-2012) of 101 white pregnant women with a mean age of 32 (range, 18-43) years who had type 1 diabetes and were under continuous subcutaneous insulin infusion (CSII) therapy. These patients had the following characteristics: type 1 diabetes duration was 1 year (range, 1-31 years), the pregestational glycosylated hemoglobin level was 6.9% (range, 6.8-12.1%), the median weight gain during pregnancy was 14 kg (-3; 25 kg), with delivery at 37 weeks (range, 30-40 weeks), and the child had a birth weight of 3.530 kg (range, 1.480-5.250 kg). The CHO/IR was measured by dividing the CHO (in g) of each meal by insulin unit injected to acquire and maintain the following glycemic targets: fasting <90 mg/dL and 1-h postprandial <130 mg/dL. Simultaneously, CHO/IR indices were calculated through 500/total daily doses of insulin and 300/total daily doses of insulin. Education and management before and during pregnancy were in agreement with Italian Association of Dietitians, Association of Medical Diabetologists, and Italian Society of Diabetology recommendations. Data were analyzed using SPSS software (version 20.0; SPSS, Inc., Chicago, IL). RESULTS: The CHO/IR decreased on average from 9.6 (5-18) to 5.4 (2.3-8) at breakfast, from 10 (3.5-16) to 8.4 (3.0-17.8) at lunch, and from 12.5 (8-20) to 6.1 (4.2-12) at dinner. The CHO/IR calculated using the "500 rule" decreased from 14.3 (10-20.3) to 8.6 (4.1-15.9). Using the "300 rule," the ratios decreased from 8.5 (6-12.1) to 5.2 (2.4-9.5). The bivariate correlation between the values calculated more appropriate values using the "300 rule" for breakfast and the "500 rule" for lunch and dinner across all weeks of pregnancy. CONCLUSIONS: CHO/IR reduction in pregnancy is likely due to an increase in insulin resistance.

Sexual dimorphism in growth and insulin-like growth factor-I in children with type 1 diabetes mellitus.

OBJECTIVE: Impaired linear growth and reduced IGF-I levels in children with type 1 diabetes (T1DM) have been related to poor metabolic control. The aim of this study was to identify additional factors which may negatively affect growth and IGF system in patients with T1DM. DESIGN: Ninety-one T1DM children (54 males, age=: 11.73±3years, disease duration=5.6±2.1years) were studied. All children were on intensive insulin therapy: 62 children were on multiple injection therapy (MI) and 29 children on continuous subcutaneous insulin infusion (CSII). RESULTS: Height velocity (HV) SDS and IGF-I levels were higher in females and in pubertal children [HV SDS: females=0.6±2.4 vs males=-0.45±2.3 (p=0.04); IGF-I SDS: females=-1.09±0.58 vs males=-1.4±0.6 (p=0.02); IGF-I/IGFBP-3 molar ratio: females=0.25±0.1 vs males=0.21±0.08 (p=0.04); IGF-I SDS: pre-pubertal=-1.58±0.46 vs pubertal=-1.15±0.65 (p<0.001); IGF-I/IGFBP-3 molar ratio: pre-pubertal=0.16±0.08 vs pubertal=0.26±0.09 (p<0.001)]. No differences between children on CSII or MI therapy were found. IGF-I SDS was positively related to C peptide level (p<0.001), puberty (p<0.001) and female gender (p=0.02) and negatively related to HbA1c (p=0.04). IGF-I/IGFBP-3 molar ratio was positively affected by C peptide level (p<0.001), puberty (p<0.001) and daily insulin dose (p<0.001). CONCLUSIONS: Our results indicate that despite intensive insulin therapy, T1DM still negatively affects IGF-I secretion and linear growth. Growth impairment is more severe in males and primarily related to poor glycemic control and loss of the residual beta cell mass.

Anti thyroperoxidase and anti thyroglobulin antibodies in diabetic pregnancies.

INTRODUCTION: Thyroid autoimmunity is very frequent in women of reproductive age and is associated with many adverse pregnancy outcomes; also, diabetes mellitus in pregnancy, of any type, is associated to many complications. In type 1 diabetes, the prevalence of thyroid autoimmunity is higher than in healthy population. Instead, the association of thyroid autoimmunity with other types of diabetes is less clear; however, there are some studies claiming that the prevalence is higher in gestational diabetes too. Poor data about type 2 diabetes in pregnancy are available. It is also unclear how diabetes and thyroid function influence each other and if levothyroxine therapy is necessary in pregnancy with positive autoimmunity but normal thyroid function. MATERIALS AND METHODS: The aim of this article was to find in the literature studies on thyroid autoimmunity in different types of diabetes in pregnancy, in order to detect any difference in prevalence. Data were found through pubmed database from 1990 to 2013. CONCLUSIONS: Several studies found a higher prevalence of thyroid autoimmunity in GDM compared to healthy controls; therefore it would be appropriate to extend screening for thyroid diseases to women with GDM. More studies are needed on the possible requirement of therapy for thyroid autoimmunity when the function is normal.

Residual ß-cell mass influences growth of prepubertal children with type 1 diabetes.

BACKGROUND: The growth deceleration observed in children with type 1 diabetes (T1D) has been related to poor glycemic control. It is unclear whether growth impairment persists despite the optimization of therapy. We analyzed the effects of intensive insulin treatment on prepubertal growth. METHODS: One hundred and four T1D children were evaluated from T1D diagnosis up to puberty onset. Height, weight, insulin requirement and glycated hemoglobin (HbA1c) were recorded at 3- to 6-month intervals. Residual ß-cell mass was estimated by fasting C-peptide at T1D onset. RESULTS: Age at T1D onset was 5.91 ± 1.9 years. Follow-up duration was 4.84 ± 1.58 years. Height velocity standard deviation score (SDS) was -0.14 ± 1.84. Height SDS changed from 0.52 ± 1.04 at T1D onset, to 0.36 ± 1.10 at the end of follow-up (p = 0.04). BMI SDS increased from -0.04 ± 1.48 to 0.32 ± 1.03 (p = 0.01). Multivariate analysis showed that height velocity was directly affected by C-peptide (p = 0.03) and insulin requirement (p = 0.004) and inversely related to HbA1c (p = 0.006). BMI gain was negatively influenced by HbA1c (p = 0.01) and positively related to T1D duration (p = 0.01). CONCLUSION: Despite insulin intensive therapy, T1D still negatively affects growth. Residual ß-cell mass has a direct positive impact on growth, independently from the quality of glycemic control.

Comparison of Insulin Lispro Protamine Suspension with NPH Insulin in Pregnant Women with Type 2 and Gestational Diabetes Mellitus: Maternal and Perinatal Outcomes.

Insulin therapy is still the gold standard in diabetic pregnancy. Insulin lispro protamine suspension is an available basal insulin analogue. Aim. To study pregnancy outcomes of women with type 2 and gestational diabetes mellitus when insulin lispro protamine suspension or human NPH insulin was added to medical nutrition therapy and/or short-acting insulin. Methods. In this retrospective study, for maternal outcome we recorded time and mode of delivery, hypertension, glycaemic control (fasting blood glucose and HbA1c), hypoglycemias, weight increase, and insulin need. For neonatal outcome birth weight and weight class, congenital malformations was recorded and main neonatal complications. Two-tail Student's t-test and chi-square test were performed when applicable; significant P < 0.05. Results. Eighty-nine pregnant women (25 with type 2 diabetes and 64 with gestational diabetes mellitus; 53 under insulin lispro protamine suspension and 36 under human NPH insulin) were recruited. Maternal and neonatal outcomes were quite similar between the two therapeutic approaches; however, insulin need was higher in NPH. At the end of pregnancy, eight women with gestational diabetes continued to use only basal insulin analogue. Conclusions. Pregnancy outcome in type 2 and gestational diabetes mellitus with insulin lispro protamine suspension was similar to that with NPH insulin, except for a lower insulin requirement.

Experiences of continuous subcutaneous insulin infusion in pregnant women with type 1 diabetes during delivery from four Italian centers: a retrospective observational study.

OBJECTIVES: An optimized metabolic control during delivery is mandatory to prevent maternal-neonatal complications. The primary aim of this study was to evaluate the efficacy and safety of continuous subcutaneous insulin infusion (CSII) during delivery in pregnant women with type 1 diabetes. The secondary aim was to assess the impact of real-time continuous glucose monitoring (RT-CGM) added to CSII versus CSII alone. RESEARCH DESIGN AND METHODS: This was a multicenter observational retrospective study. A standardized protocol, to use CSII throughout pregnancy and delivery, foresaw three different insulin basal rates according to blood glucose level: profile A, the last basal rate in use; profile B, preventive 50% reduction of the last basal rate in use; and profile C, 0.1-0.2 U/h for blood glucose level <70 mg/dL, activated just before anesthesia or at the beginning of active labor. An alternative intravenous protocol (IVP) was given in case of complications and relevant metabolic deterioration. Blood glucose in the target range (70-140 mg/dL) throughout delivery and percentage of activation of the IVP were primary outcomes. RESULTS: Sixty-five pregnant women with diabetes included in the study (56-86% cesarean section; 9-14% spontaneous/stimulated vaginal delivery). Mean blood glucose level was 102 ± 31 mg/dL at 0 min, 109 ± 42 mg/dL at 30 min, 120 ± 48 mg/dL at 60 min, and 99 ± 34 mg/dL at 24 h. Mean basal rate during delivery was 0.6 ± 0.4 U/h (profile B). Mean capillary blood glucose (CBG) level was lower in the RT-CGM group relative to the CSII-alone group: 80 ± 14 mg/dL versus 111 ± 32 mg/dL at 0 min (P<0.01), 79 ± 11 mg/dL versus 109 ± 42 mg/dL at 30 min (P<0.02), and 98 ± 20 mg/dL versus 125 ± 51 mg/dL at 60 min (difference not significant). Eleven newborns experienced transient neonatal hypoglycemia. None of the women switched to IVP. No major differences were observed according to delivery procedure. CONCLUSIONS: CSII is possible and safe in different types of delivery in selected and educated women. RT-CGM helps to obtain better outcomes in terms of maternal peripartum CBG level.

Continuous glucose monitoring during breastfeeding in women with recent gestational diabetes mellitus.

AIMS: This study monitored blood glucose profiles in normotolerant breastfeeding women, with and without previous gestational diabetes, in real life in order to identify normal blood glucose fluctuations during breastfeeding. SUBJECTS AND METHODS: Two groups were studied: (1) 18 women with recent gestational diabetes mellitus but normotolerant postpartum (pGDM-N group) and (2) 15 women normotolerant both during pregnancy and postpartum (pN-N group). All participants underwent continuous glucose monitoring during which they recorded their main daily activities and three standardized events: "suckling," "meal," and "meal and suckling." Other than these three events, these women were essentially on an "ad lib" diet. Data were expressed as median and SD values. Student's t test and Fisher's test were used to compare mean, variances, and percentages. Differences were significant with P<0.05. Clustering analysis was used to determine the normal range of glucose values. RESULTS: The two groups were matched for age, follow-up duration, and monitoring measurements but not for body mass index. Blood glucose levels and variances were higher in the pGDM-N group, particularly during daytime and the three standardized events, and were not related to body mass index. Suckling had no direct effect on glucose profile during both the non-fed and the fed state. Blood glucose levels that best represent the normal breastfeeding population were between 50 and 126 mg/dL (from 2.8 to 7.0 mmol/L). CONCLUSIONS: Three months after delivery, normotolerant women with recent gestational diabetes had higher daily blood glucose levels than women who were always normotolerant, with no direct effect of suckling. The blood glucose profiles of healthy subjects could be representative of the normal range of the population during breastfeeding.