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 carbohydrateto insulin ratio (CHO/IR) in normal weight, overweight, and obese pregnant women withtype 1 diabetes across early, middle, and late pregnancy.Methods:In this multicenter, retrospective, observational study we evaluated 86 of 101pregnant Caucasian women with type 1 diabetes under pump treatment. The womenwere trained to calculate CHO/IR daily by dividing CHO grams of every single meal byinsulin units injected. Since the purpose of the study was to identify the CHO/IR able toreach the glycemic target, we only selected the CHO/IR obtained when glycemic valueswere at target. Statistics: SPSS 20.Results:We studied 45 normal weight, 31 overweight, and 10 obese women. Insulinrequirements increased throughout pregnancy (p < 0.0001 and <0.001 respectively) inthe 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 progressivelythroughout pregnancy in the normal weight women, from 13.3 (9.8–6.7) at thefirst stageof pregnancy to 6.2 (3.8–8.6) (p = 0.01) at the end stage, and in the overweight womenFrontiers in Endocrinology | www.frontiersin.orgFebruary 2021 | Volume 12 | Article 6108771Edited by:Elena Succurro,University of Magna Graecia, ItalyReviewed by:Cristina Bianchi,Azienda Ospedaliero-UniversitariaPisana, ItalyMaria Grazia Dalfra’,University of Padua, Italy*Correspondence:Camilla [email protected] section:This article was submitted toObesity,a section of the journalFrontiers in EndocrinologyReceived:27 September 2020Accepted:14 January 2021Published:25 February 2021Citation:Festa C,Fresa R,Visalli N,Bitterman O,Giuliani C,Suraci C,Bongiovanni M andNapoli A (2021)Insulin Requirements andCarbohydrate to Insulin Ratio inNormal Weight, Overweight, andObese Women With Type 1Diabetes Under Pump TreatmentDuring Pregnancy: A LessonFrom Old Technologies.Front. Endocrinol. 12:610877.doi: 10.3389/fendo.2021.610877ORIGINAL RESEARCHpublished: 25 February 2021doi: 10.3389/fendo.2021.610877 from 8.5 (7.1–12.6) to 5.2 (4.0–8.1) (p = 0.001), while in the obese women it remainedstable, moving from 6.0 (5.0–7.9) to 5.1 (4.1–7.4) (p = 0.7). Likewise, lunch and dinnerCHO/IR decreased in the normal weight and overweight women (p < 0.03) and not in theobese women. The obese women gained less weight than the others, especially in earlypregnancy when they even lost a median of 1.25 (−1−1.1) kg (p = 0.005). In earlypregnancy, 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 latepregnancy, 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). Thesignificance was lost when both variables were included in the multiple regressionanalysis. There was no difference in pregnancy outcomes except for a higher pre-termdelivery rate in the obese women.Conclusion:Pre-gestational BMI and weight gain may play a role in determining CHO/IRduring pregnancy in women with type 1 diabetes under pump treatment

Association between type 1 diabetes and female sexual dysfunction

Background: This study aims to evaluate: 1) the prevalence of Female Sexual Dysfunction (FSD) in women affected by type 1 Diabetes Mellitus (DM) and the control group; 2) the correlation between duration of DM, HbA1C levels and sexual life quality; 3) the relationship between different methods of insulin administration and sexual life quality; 4) the correlation between FSD and diabetes complications. Methods: We selected 33 women with type 1 DM and 39 healthy women as controls. Each participant underwent a detailed medical history and physical examination and completed the 6-item Female Sexual Function Index questionnaire (FSFI-6). In patients affected by type 1 DM, the different methods of insulin administration (Multi Drug Injection - MDI or Continuous Subcutaneous Insulin Infusion - CSII) and the presence of DM complications were also investigated. Results: The prevalence of FSD (total score≤19) was significantly higher in the type 1 DM group than in the control group (12/33, 36.4% and 2/39, 5.2%, respectively; p =0.010). No statistically significant differences were found regarding FSD according to the presence of complications, method of insulin administration or previous pregnancies. Conclusions: This study underlined that FSD is higher in women affected by type 1 DM than in healthy controls. This could be due to the diabetic neuropathy/angiopathy and the type of insulin administration. Therefore, it is important to investigate FSD in diabetic women, as well as erectile dysfunction in diabetic men

Gestational Diabetes Mellitus pregnancy by pregnancy. early, late and nonrecurrent GDM

Aims: To assess the GDM recurrence rate in a cohort of pregnant women with prior GDM, to compare two consecutive pregnancies complicated by GDM, to compare women with nonrecurrent and recurrent GDM and to stratify the latter in women with early and late recurrent GDM.Methods: Retrospective study including 113 women with GDM in an index pregnancy (G1), at least a postindex pregnancy (G2) and normal glucose tolerance in between. The GDM recurrence rate was assessed, and maternal and neonatal outcomes and pancreatic beta cell function of the index pregnancy were compared with those of the postindex pregnancy (G1 vs. G2). Women with nonrecurrent GDM were compared with those with recurrent GDM.Results: The GDM recurrence rate was 83.2% and the minimum prevalence of early recurrent GDM was 43,4%. The pregravid BMI of women with recurrent GDM increased between the two pregnancies (27.3 +/- 5.98 vs. 28.1 +/- 6.19 kg/m(2), p < 0.05). Women with recurrent GDM had a higher prepregnancy BMI than those with nonrecurrent GDM either at the index (27.3 +/- 5.98 vs. 23.1 +/- 4.78 kg/m(2), p < 0.05) or the postindex pregnancy (27 +/- 6vs.24 +/- 4,4 kg/m2, p < 0.05).Conclusions: GDM shows a high recurrence rate in our cohort of slightly overweight women, with an early GDM minimum prevalence of 43.4%

Glucokinase deficit prevalence in women with diabetes in pregnancy. a matter of screening selection

Introduction: The prevalence among pregnant women with diabetes of monogenic diabetes due to glucokinase deficit (GCK-MODY) varies from 0 to 80% in different studies, based on the chosen selection criteria for genetic test. New pregnancy-specific Screening Criteria (NSC), validated on an Anglo-Celtic pregnant cohort, have been proposed and include pre-pregnancy BMI <25 kg/m2 and fasting glycemia >99 mg/dl. Our aim was to estimate the prevalence of GCK-MODY and to evaluate the diagnostic performance of NSC in our population of women with diabetes in pregnancy. Patients and Methods: We retrospectively selected from our database of 468 diabetic pregnant patients in Sant'Andrea Hospital, in Rome, from 2010 to 2018, all the women who received a genetic test for GCK deficit because of specific clinical features. We estimated the prevalence of GCK-MODY among tested women and the minimum prevalence in our entire population with non-autoimmune diabetes. We evaluated diagnostic performance of NSC on the tested cohort and estimated the eligibility to genetic test based on NSC in the entire population. Results: A total of 409 patients had diabetes in pregnancy, excluding those with autoimmune diabetes; 21 patients have been tested for GCK-MODY, 8 have been positive and 13 have been negative (2 of them had HNF1-alfa mutations and 1 had HNF4-alfa mutation). We found no significant differences in clinical features between positive and negative groups except for fasting glycemia, which was higher in the positive group. The minimum prevalence of monogenic diabetes in our population was 2.4%. The minimum prevalence of GCK-MODY was 1.95%. In the tested cohort, the prevalence of GCK-MODY was 38%. In this group, NSC sensitivity is 87% and specificity is 30%, positive predictive value is 43%, and negative predictive value is 80%. Applying NSC on the entire population of women with non-autoimmune diabetes in pregnancy, 41 patients (10%) would be eligible for genetic test; considering a fasting glycemia >92 mg/dl, 85 patients (20.7%) would be eligible. Discussion: In our population, NSC have good sensitivity but low specificity, probably because there are many GDM with GCK-MODY like features. It is mandatory to define selective criteria with a good diagnostic performance on Italian population, to avoid unnecessary genetic tests

Glucokinase deficit and birthweight: does maternal hyperglycemia always meet fetal needs?

Aims: Many authors do not recommend hypoglycemic treatment during pregnancy in women affected by monogenic diabetes due to heterozygous glucokinase (GCK) mutations (MODY 2) in case of affected fetus, because maternal hyperglycemia would be necessary to achieve a normal birthweight. We aimed to evaluate differences in birthweight between MODY 2 affected children according to the parent who carried the mutation. Methods: We retrospectively studied 48 MODY 2 affected children, whose mothers did not receive hypoglycemic treatment during pregnancy, divided into two groups according to the presence of the mutation in the mother (group A) or in the father (group B). Data were extracted from the database of the Regional Centre of Pediatric Diabetology of the University of Campania, Naples, collected from 1996 to 2016. We analyzed birthweight and centile birthweight. Results: Percentage of small for gestational age was significantly higher in group B than in group A. We found three large for gestational age in the group that inherited the deficit from the mother, all with the same novel GCK mutation (p.Lys458-Cys461del). Conclusions: We hypothesize that not all MODY 2 affected fetuses need the same levels of hyperglycemia to have an appropriate growth, maybe because different kinds of GCK mutations may result in different phenotypes. Consequently, a “tailored therapy” of maternal hyperglycemia, based on fetal growth frequently monitored through ultrasounds, is essential in MODY 2 pregnancies

VEP and Psycomotor outcome in children of type1 diabetic mothers, 3 years after delivery.

Background: The exposure to diabetic environment during pregnancy may have negative effects on brain functions of the offspring. Evoked potentials are sensitive indexes of central nervous system function. Aim: to analyze maturation of Visual Evoked Potentials (VEPs) and psychomotor development during the first 3 years of life in Infants of type-1 Diabetic Mothers (IDMs). Materials and methods: VEPs and psychomotor development were assessed serially between 2 months and 3 years of age in 16 IDMs (11 females, 5 males). Latency and amplitude of VEPs were compared with data obtained from a matched control group of 23 healthy children of non-diabetic mothers.VEP recording: 1.Binocular stimulation (white light, intensity 0,3 Joule, repetition rate 2 Hz) 2.Responses were recorded according to the American Electroencephalografic Society guidelines with a bandpass of 1-100 Hz. At least two trials of 100 artefact-free responses were recorded within 512 ms after stimulus. 3.Peak latencies and peak-to-peak amplitudes of all components were measured but only the most stable components (III, IV, V) were used for statistical comparisons

Flash on gut microbiome in gestational diabetes: a pilot study

Pregnancy induces a deep modification of women's gut microbiota composition. These changes may influence hormonal and metabolic factors, increasing insulin resistance and leading to hyperglycaemia in susceptible women. Data on 29 women in pregnancy showed insignificant reductions in the Bacteroidetes/Firmicutes ratio in women with (n.14) and without (n.15) gestational diabetes (GDM). Gut microbiota compositions at the genera and species level were further analysed in ten pregnant women with and ten without GDM (9 samples were excluded due to low DNA quality/quantity), showing differences in functionally specific patterns affecting host energy dietary polysaccharide metabolism pathways. According to our results, gut microbiome alteration may play a role in GDM pathogenesis through an increase of gut permeability and higher intestinal energetic balance

Long Lasting Effects of Breastfeeding on Metabolism in Women with Prior Gestational Diabetes

Background & Aims: Breastfeeding improves glucose tolerance in the early postpartum period of women with prior gestational diabetes GDM, but it is unclear whether future risk of metabolic alterations, like type 2 diabetes, is reduced. The aim of this study was to investigate the effect of lactation, three years after pregnancy, on glucose and lipid metabolism in women with prior gestational diabetes. Materials & Methods: A population of women with prior gestational diabetes (Carpenter and Coustan Criteria) was evaluated with comparison of results for “lactating” [BF] versus “nonlactating women” [non BF]. Breast feeding was defined [BF] if lasting? 4 weeks. In each woman a 75-g oral glucose tolerance test (OGTT) was performed to analyze the glucose tolerance, insulin sensitivity/resistance and b-cell function. Fasting serum was used to study their lipid profile (total cholesterol, high-density lipoprotein [HDL] cholesterol, low-density lipoprotein [LDL] cholesterol, and triglycerides), apolipoprotein B, apolipoprotein A1, homocysteine, fibrinogen, hs- CRP, uric acid, microalbuminuria. Statistics: Paired and Un-paired t-test, Mann-Whitney and χ2 tests were used, as appropriate. Results: A total of 81 women were evaluated (62 [BF] and 19 [non BF]). Maternal age (37.1 ± 4.6 vs 37.4 ± 4.9 years), body mass index (26.3 ± 5.6 vs 26.4 ± 5.3 kg/m2), parity (1.9 ± 0.8 vs 1.7 ± 0.8) and length of follow-up (32.2 ± 20.2 vs 32.1 ± 20,0) were not different between the two groups. No effect was visible on glucose tolerance, HOMA-IR and other b-cell function indexes as well as hs-CRP (not significantly lower in non BF), uric acid, total cholesterol, HDL and LDL cholesterol. Levels of significance were only reached for “HOMA-IS” [BF] 1.0 ± 0.7 vs [non BF] 0.6 ± 0.4, p = 0.04) and triglycerides [BF] 83.8 ± 46.7 vs [non BF] 123.2 ± 94.0 mg/dl, p = 0.02). Conclusions: Breastfeeding does not improve the glucose tolerance of our women with prior GDM three years after delivery, even though lower levels of triglycerides and improved insulin sensitivity are still visible