Tight versus less tight 1-hour postprandial glycemic target in women with gestational diabetes mellitus - a single-center cohort study.

OBJECTIVES: We aimed to assess the impact of the change of 1-hour postprandial glycemic target from < 6.7 mmol/L (120 mg/dL) to < 7.8 mmol/L (140 mg/dL) on gestational diabetes mellitus (GDM) treatment and pregnancy outcomes. MATERIAL AND METHODS: In a retrospective analysis of 1021 GDM patients from the Department of Metabolic Diseases, University Hospital in Cracow, Poland, we compared insulin therapy regimens and pregnancy outcomes between women admitted in 2014-2016 (before the change) and in 2018-2019 (after it). RESULTS: A total of 377 patients were admitted between 2014 and 2016 (TIGHT group) and 644 between 2018 and 2019 (LESS TIGHT group). Women from the LESS TIGHT group were older (32 vs 30 years, p < 0.001) and gained less weight during pregnancy (7.0 vs 9.0 kg, p < 0.001). There was no change in the frequency of any insulin therapy (51.6% vs 56.1%, p = 0.168). In the LESS TIGHT group, the basal insulin-only model was used more frequently (32.5% vs 10.2%, p < 0.001), while the prandial insulin and basal-bolus model less frequently (23.6% vs 42.6% and 21.4% vs 36.7%, p < 0.001, respectively) than in the TIGHT group. There were no differences in the frequency of cesarean sections, preterm births, Hbd of delivery, mean birth weight or prevalence of perinatal complications. CONCLUSIONS: Less tight glycemic targets in women with GDM, compared to tighter targets, were associated with less frequent use of prandial insulin, with insulin therapy often limited to basal administration. The change in glycemic targets did not affect the prevalence of adverse pregnancy outcomes, providing evidence supporting new recommendations.

Comparison of the clinical characteristics, glycemic control, and pregnancy outcomes between women with gestational diabetes mellitus in waves I and III of the COVID-19 pandemic: a reference center report.

OBJECTIVES: The medical care of patients with gestational diabetes mellitus (GDM) during the COVID-19 pandemic was influenced by changing epidemiological conditions and government regulations. Aim - To compare the clinical pregnancy data of GDM women between waves I and III of the pandemic. MATERIAL AND METHODS: We performed a retrospective analysis of medical records from the GDM clinic and compared the periods of March-May 2020 (wave I) and March-May 2021 (wave III). RESULTS: Women with GDM during wave I (n = 119) compared to wave III (n = 116) were older (33.0 ± 4.7 vs 32.1 ± 4.8 years; p = 0.07), booked later (21.8 ± 8.4 vs 20.3 ± 8.5 weeks; p = 0.17), and had their last appointment earlier (35.5 ± 2.0 vs 35.7 ± 3.2 weeks; p < 0.01). Telemedicine consultations were used more frequently during wave I (46.8% vs 24.1%; p < 0.01), while insulin therapy was used less often (64.7% vs 80.2%; p < 0.01). Mean fasting self-measured glucose did not differ (4.8 ± 0.3 vs 4.8 ± 0.3 mmol/L; p = 0.49), but higher postprandial glucose was reported during wave I (6.6 ± 0.9 vs 6.3 ± 0.6 mmol/l; p < 0.01). Pregnancy outcome data were available for 77 wave I pregnancies and 75 wave III pregnancies. The groups were similar in terms of gestational week of delivery (38.3 ± 1.4 vs 38.1 ± 1.6 weeks), cesarean sections (58.4% vs 61.3%), APGAR scores (9.7 ± 1.0 vs 9.7 ± 1.0 pts), and birth weights (3306.6 ± 457.6 g vs 3243.9 ± 496.8 g) (p = NS for all). The mean wave I neonate length was slightly higher (54.3 ± 2.6 cm vs 53.3 ± 2.6 cm; p = 0.04). CONCLUSIONS: We identified differences between wave I and wave III pregnancies for several clinical characteristics. However, nearly all pregnancy outcomes were found to be similar.

Insulin pump therapy with and without continuous glucose monitoring in pregnant women with type 1 diabetes: a prospective observational Orchestra Foundation study in Poland.

AIMS: The effects of continuous subcutaneous insulin infusion (CSII) therapy with or without continuous glucose monitoring (CGM) on neonatal outcomes and glycemic outcomes of pregnant women with type 1 diabetes (T1D), living in Poland, were assessed. METHODS: This prospective observational study enrolled women with T1D (N = 481, aged 18-45 years) who were pregnant or planned pregnancy. All used CSII therapy and a subset used CGM with CSII (CSII + CGM). Neonatal outcomes (e.g., rate of large for gestational age [LGA] delivery [birth weight > 90th percentile]) and maternal glycemia (e.g., HbA1c and percentage of time at sensor glucose ranges) were evaluated. RESULTS: Overall HbA1c at trimesters 1, 2, and 3 was 6.8 ± 1.1% (50.9 ± 12.3 mmol/mol, N = 354), 5.8 ± 0.7% (40.1 ± 8.0 mmol/mol, N = 318), and 5.9 ± 0.7% (41.4 ± 8.0 mmol/mol, N = 255), respectively. A HbA1c target of < 6.0% (42 mmol/mol) at each trimester was achieved by 20.9% (74/354), 65.1% (207/318), and 58.0% (148/255), respectively. For women using CSII + CGM versus CSII only, HbA1c levels at trimesters 1, 2, and 3 were 6.5 ± 0.9% versus 7.1 ± 1.3% (47.8 ± 9.7 mmol/mol versus 54.3 ± 14.0 mmol/mol, p < 0.0001), 5.7 ± 0.6% versus 6.0 ± 0.9% (38.9 ± 6.5 mmol/mol versus 41.6 ± 9.3 mmol/mol, p = 0.0122), and 5.8 ± 0.6% versus 6.1 ± 0.8% (40.3 ± 6.9 mmol/mol versus 42.9 ± 9.1 mmol/mol, p = 0.0117), respectively. For the overall, CSII only, and CSII + CGM groups, rates of LGA delivery were 22.7% (74/326), 24.6% (34/138), and 21.3% (40/188), respectively. CONCLUSIONS: Observational assessment of women with T1D using CSII therapy demonstrated low HbA1c throughout pregnancy and low rates of LGA. The addition of CGM to CSII therapy compared to CSII therapy alone was associated with some improved maternal glycemic and neonatal outcomes. GOV IDENTIFIER: NCT01779141 (January 2013).

Assessment of the spectrum of depression and bipolarity in patients with type 1 diabetes.

AIMS: The aim of the study was to check the prevalence of unipolarity (depression), bipolarity, as well as the quality of sleep and temperament traits in patients with type 1 diabetes (T1DM) who are provided with optimal conditions of diabetes care and to identify possible risk factors connected with affective traits. MATERIALS AND METHODS: Out of the 107 T1DM patients, 78 (54 females, 24 males) were included for the analysis (HbA1c [%] 7.11 ± 1.0, BMI [kg/m2 ] 25.3 ± 5.6; Years of disease duration [N] 13.7 ± 8.3). The patients filled in a set of questionnaires during their regular visit to the outpatient clinic. Three patients from the whole group were on intensive insulin therapy with Multiple Daily Injections (MDI) and Self-Monitoring of Blood Glucose (SMBG), all the rest were on various types of personal insulin pumps (years on insulin pump [N] 9.1 ± 4.5). All the patients were on regular diabetologist care, with regular visits in a Centre for Advanced Technologies in Diabetes (at least every 6 months). RESULTS: In QIDS-S (full explanation and abbreviation 26 patients (33.8%) were screened positive for depression, in PHQ (full explanation and ab 57.7% of the patients (45 patients) had symptoms of depression (age was negatively correlated with PHQ score [r = -0.26; p = 0.023]). In CES-D 16 (20%) of the patients assessed their present affect as depressed. None of the analysed clinical variables correlated with depression scores. In the Mood Disorder Questionnaire (MDQ), 16 patients reported having symptoms of bipolarity (20.5% vs. 79.5%). Hypomania Checklist (HCL) analysis indicated 10 patients with bipolar traits (>14) (14.9% vs. 85.1%). None of the analysed clinical variables correlated with HCL results. 11.5% of patients were indicated to be of morning type. Morningness was more often seen in younger patients (r = 0.39; p = 0.001). As many as 46.6% declared that they had poor sleep quality. The temperament traits analysis correlated with clinical parameters: Cyclothymic temperament trait was negatively correlated with age (r = -0.30; p = 0.007) and positively with HbA1c level (r = 0.30; p = 0.025). Hyperthymic temperament was positively correlated with (BMI r = 0.28; p = 0.016). Quality of sleep was highly correlated with depressive symptoms CESD (r = 0.61, p = 0.001), PHQ Score (r = 0.62; p = 0.001), QISD (r = 0.68; p = 0.001) and bipolarity MDQ (p = 0.50, p = 0.001) and HCL (r = 0.42, p = 0.001). In addition, QIDS was shown to be correlated with the following features of temperament: depressive factor (r = 0.41; p = 0.001), irritable factor (r = 0.53; p = 0.001), cyclothymic factor (r = 0.59; p = 0.001), anxious factor (r = 0.58, p = 0.001). CONCLUSIONS: The prevalence of affective disorders and poor sleep quality in the examined T1DM patients was much higher than in the general population. Even if the patients have in general good glycaemic control, their mental health condition should not be neglected. Well organised cooperation between patients, diabetologists, psychiatrists and psychotherapists is needed (Clinical Trials Identifier: NCT04616391).

Higher scanning frequency is correlated with less fear of hypoglycemia in type 1 diabetes patients using isCGM.

Background: Frequent scanning of intermittently scanned continuous glucose monitoring (isCGM) devices is associated with improvements in glycemic indices. Limited data is available for its correlation with fear of hypoglycemia (FOH), an established factor affecting quality of life and glycemic control in type 1 diabetes (T1DM). Aim: The aim of the study was to analyze the association of sensor scanning frequency with FOH and glycemic indices in T1DM patients using isCGM. Subjects and methods: T1DM patients using isCGM were eligible. Clinical data and Ambulatory Glucose Profile (AGP) reports were obtained from medical records. At outpatient visits, AGP of last 14 days prior to visit were analyzed and FOH was assessed using Hypoglycemia Fear Survey II (HFS II). Results: We included 77 consecutive T1DM patients (58 females, 19 males). Mean age was 34.1 ± 10.2 years and mean T1DM duration was 14.7 ± 12.0 years. Baseline mean glycemic indices were as follows: mean glucose - 155.8 ± 29.8 mg/dL; GMI - 53.3 ± 7.5 mmol/mol; TIR - 66.4 ± 17.8%; TBR70 - 4.5 ± 4.1%; TBR54 - 0.6 ± 1.2%; TAR180 - 29.2 ± 17.9%; TAR250 - 9.6 ± 10.4%; %CV - 36.7 ± 8.3. Average scanning frequency was 13.8 ± 7.8 scans/day. Mean HFS II scores were 16.1 ± 7.2 and 18.7 ± 12.2 in behavior and worry subscale, respectively. Correlation was confirmed between scanning frequency and mean glucose, GMI, TIR, TBR70, TAR180, TAR250, %CV and HFS II total, and HFS II - B (p<0.05 for all statistics). Conclusions: For the first time, we report that higher scanning frequency is associated not only with better glycemic indices but also with less FOH in T1DM adult patients using isCGM.

Low prevalence of diabetic retinopathy in patients with long-term type 1 diabetes and current good glycemic control - one-center retrospective assessment.

PURPOSE: Despite progress in type 1 diabetes (T1DM) therapy, diabetic retinopathy (DR) is still a common complication. We analysed predictors and prevalence of DR in patients with T1DM lasting 10 years or more. All of the patients were considered to be currently in excellent glycemic control and treated using modern therapies. METHODS: Study included 384 (80.7% women) T1DM patients participating in the Program of Comprehensive Outpatient Specialist Care at the University Hospital in Krakow between the years 2014 and 2020. A retrospective analysis of medical records was conducted. RESULTS: The patients were on average 34 ± 9.2 years old, had a BMI 25.0 ± 3.9 and a T1DM duration of 20.5 ± 7.9 years. The mean level of HbA1c throughout the follow-up (mean duration 4.9 ± 1.4 years) was 6.9 ± 1%. The group included 238 (62.0%) patients treated with insulin pumps and 99 (25.8%) on multiple daily injections, 47 (12.2%) used both methods; almost all patients were on insulin analogues. DR was confirmed in 150 (39.1%) patients, from which 109 (28.4%) were diagnosed de novo. Severe DR was occurred in just 31 cases (8.1%). In the multivariate logistic regression, independent risk factors for the presence of DR were T1DM duration (OR 1.13; 95% CI, 1.09-1.19), HbA1c level (OR 1.41; 95% CI, 1.08-1.84), LDL level (OR 1.79; 95% CI, 1.16-2.87), and the combined presence of non-DR micro- and macrovascular chronic complications (OR 1.86; 95% CI, 1.16-3.03). CONCLUSIONS: In this highly-selected group of T1DM patients, mostly female, the prevalence of both DR at any stage and severe DR was lower than earlier reported results from other cohorts. Independent risk factors for the DR cohort did not differ from previously reported studies.

Type 1 Diabetes and COVID-19: the level of anxiety, stress and the general mental health in comparison to healthy control. / Cukrzyca typu 1 i COVID-19: poziom leku, stresu i ogólnego stanu zdrowia psychicznego u pacjentów w porównaniu z grupa kontrolna.

OBJECTIVES: Assessment of mental state of patients with T1DM - the level of anxiety, stress and general mental health in the stressful conditions of an epidemic. Moreover, it was checked whether the stress response to the epidemic in the T1DM group differed from that in the control group. This is the first study to address these questions in the type 1 diabetes population in Poland. METHODS: An e-mail was sent to all T1DM patients under the care of a diabetes clinic with information about the possibility of online consultation with a psychologist / psychiatrist, with a set of psychological tests attached. The study included 49 patients with T1DM who responded within the first month and agreed to participate in the study. 38 people from the control group were randomly recruited. Each person completed a set of psychological tools. RESULTS: In both groups, the level of stress was higher than typical for the general population in the situation without stressor. T1DM patients who have been ill for over 10 years more often cope with stress through a task-oriented approach. Patients who have been ill for less than 10 years use avoidance strategies. In the first phase of the epidemic,women with T1DM used avoidance strategies. Patients with diabetes and mental disorders react more anxiously and thus require special care in coping with diabetes. CONCLUSIONS: In a situation of stress such as a epidemic, patients suffering from T1DM require optimization of treatment and cooperation of specialists in the field of diabetes and psychology / psychiatry.

Diabetes Management Delivery and Pregnancy Outcomes in Women with Gestational Diabetes Mellitus during the First Wave of the 2020 COVID-19 Pandemic: A Single-Reference Center Report.

OBJECTIVES: The COVID-19 pandemic has forced a rapid adaptation of healthcare services to secure care for many patient groups. This includes women with gestational diabetes mellitus (GDM). We evaluated the impacts of the first COVID-19 wave on parameters such as the GDM treatment, glycemic control, and pregnancy outcomes. METHODS: In this retrospective study from a reference diabetes center (Krakow, Poland), we compared patient data from two different time periods: the first wave of the COVID-19 pandemic (March 2020-June 2020) and the preceding five months (October 2019-February 2020). Data was collected from the medical records and telephone surveys. RESULTS: We included 155 consecutive women (group N1 = 73 and group N2 = 82 from the COVID-19 pandemic period and non-COVID-19 period, respectively). During the COVID-19 pandemic, almost half of all GDM women (N1 = 36, 49.3%) used telemedicine as a method of contacting their diabetic specialists while this tool was not utilized in the earlier period. Moreover, these patients reported difficulties in performing blood glucose self-control more often (N1 = 20, 27.4%, vs N2 = 7, 8.5%; p ≤ 0.01) and spent less time on diabetes education than the control group on average (N1 = 39, 53.4%, vs N2 = 9, 9.8% below 2 hours of training; p ≤ 0.01). Most analyzed glycemic parameters and pregnancy outcomes were similar. Differences were found with respect to the incidence of prolonged labor (N1 = 12, 16.4%, vs N2 = 3, 3.7%; p ≤ 0.01) and preeclampsia (N1 = 0 vs N2 = 7, 8.5%; p = 0.01). CONCLUSION: In this single-center observational study, the first wave of the COVID-19 pandemic did not seem to have a negative impact on pregnancy outcomes in GDM women, despite the difficulties in diabetes management delivery.

Continuous glucose monitoring and insulin pump therapy in pregnant women with type 1 diabetes mellitus.

OBJECTIVES: We examined the impact of continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring systems (CGM) during pregnancy in women with pre-gestational type 1 diabetes (T1DM) on glycemic control and subsequent adverse outcomes. MATERIAL AND METHODS: In this observational, one-center study we analyzed records of consecutive 109 T1DM pregnancies (2016-2017). The final analyzed group consisted of 81 singleton pregnancies who met inclusion and exclusion criteria. We searched for the association between the use of CSII with or without CGM and pregnancy planning with glycated hemoglobin A1c (HbA1c) through pregnancy and after delivery as well as maternal and infant outcomes. RESULTS: Patients using CSII and CGM vs CSII without CGM and MDI (multiple daily injections) users had the lowest HbA1c levels during and after pregnancy (5.3%, 5.3%, 5.2% and 5,5% in the 1st, 2nd, 3rd trimester and postpartum visit, p = 0.003, p = 0.030, p = 0.039 and p = 0.002, respectively). Patients treated with insulin pumps with CGM and additional functions of automatic insulin delivery suspension on low glucose level (SLG) or predictive low glucose suspend (PLGS) during the third trimester and after pregnancy achieved a significantly lower HbA1c than the other CSII patients. We did not find any differences between the study groups in gestational age at delivery, preterm births, birth weight or macrosomia risk. Despite very good glycemic control, the risk of macrosomia remained high (19.7%). CONCLUSIONS: The use of pumps equipped with CGM, especially with automatic insulin delivery suspension, may improve glycemic control in pregnant T1DM women. The proportion of macrosomia remained high.

The transcriptome-wide association search for genes and genetic variants which associate with BMI and gestational weight gain in women with type 1 diabetes.

BACKGROUND: Clinical data suggest that BMI and gestational weight gain (GWG) are strongly interconnected phenotypes; however, the genetic basis of the latter is rather unclear. Here we aim to find genes and genetic variants which influence BMI and/or GWG. METHODS: We have genotyped 316 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays. The GIANT, ARIC and T2D-GENES summary statistics were used for TWAS (performed with PrediXcan) in adipose tissue. Next, the analysis of association of imputed expression with BMI in the general and diabetic cohorts (Analysis 1 and 2) or GWG (Analysis 3 and 4) was performed, followed by variant association analysis (1 Mb around identified loci) with the mentioned phenotypes. RESULTS: In Analysis 1 we have found 175 BMI associated genes and 19 variants (p < 10-4) which influenced GWG, with the strongest association for rs11465293 in CCL24 (p = 3.18E-06). Analysis 2, with diabetes included in the model, led to discovery of 1812 BMI associated loci and 207 variants (p < 10-4) influencing GWG, with the strongest association for rs9690213 in PODXL (p = 9.86E-07). In Analysis 3, among 648 GWG associated loci, 2091 variants were associated with BMI (FDR < 0.05). In Analysis 4, 7 variants in GWG associated loci influenced BMI in the ARIC cohort. CONCLUSIONS: Here, we have shown that loci influencing BMI might have an impact on GWG and GWG associated loci might influence BMI, both in the general and T1DM cohorts. The results suggest that both phenotypes are related to insulin signaling, glucose homeostasis, mitochondrial metabolism, ubiquitinoylation and inflammatory responses.

Mitochondrial GWAS and association of nuclear - mitochondrial epistasis with BMI in T1DM patients.

BACKGROUND: BMI is a strong indicator of complications from type I diabetes, especially under intensive treatment. METHODS: We have genotyped 435 type 1 diabetics using Illumina Infinium Omni Express Exome-8 v1.4 arrays and performed mitoGWAS on BMI. We identified additive interactions between mitochondrial and nuclear variants in genes associated with mitochondrial functioning MitoCarta2.0 and confirmed and refined the results on external cohorts: the Framingham Heart Study (FHS) and GTEx data. Linear mixed model analysis was performed using the GENESIS package in R/Bioconductor. RESULTS: We find a borderline significant association between the mitochondrial variant rs28357980, localized to MT-ND2, and BMI (ß = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (ß = - 0.312, p = 0.047). Next, we searched for additive interactions between mitochondrial and nuclear variants. MT-ND2 variants interacted with variants in the genes SIRT3, ATP5B, CYCS, TFB2M and POLRMT. TFB2M is a mitochondrial transcription factor and together with TFAM creates a transcription promoter complex for the mitochondrial polymerase POLRMT. We have found an interaction between rs3021088 in MT-ND2 and rs6701836 in TFB2M leading to BMI decrease (inter_pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter_pval = 0.0004). The influence of these interactions on BMI was confirmed in external cohorts. CONCLUSIONS: Here, we have shown that variants in the mitochondrial genome as well as additive interactions between mitochondrial and nuclear SNPs influence BMI in T1DM and general cohorts.

Changes in the clinical characteristics of women with gestational diabetes mellitus - a retrospective decade-long single center analysis.

AIMS: Gestational diabetes mellitus (GDM) is an emerging worldwide problem. Changes in clinical characteristics of women affected by GDM in a long-term perspective are still not properly investigated. We aimed to examine such changes over a decade in a retrospective single-center analysis. METHODS: The medical documentation from Department of Metabolic Diseases, Krakow, Poland was analyzed. We included 633 women consecutively diagnosed with GDM in one of three time intervals: 2007-2008 (N = 157), 2012-2013 (N = 272), 2016-2017 (N = 234). Statistical analyses were performed. RESULTS: Comparison of the three groups identified differences in the mean age of women at the GDM diagnosis (30.7 ± 5.0 years vs. 31.2 ± 4.7 vs. 32.5 ± 4.7, respectively, starting from the earliest 2007-2008 group), pregnancy week at GDM diagnosis (28.0 ± 5.3 wks. vs. 25.9 ± 4.9 vs. 23.4 ± 6.8), the proportion of women diagnosed before the 24th week of pregnancy (12.8% vs. 16.5% vs. 31.3%), and gestational weight gain (12.4 ± 5.0 kg vs. 10.4 ± 5.2 vs. 10.0 ± 5.7); (p = 0.001 or less for all comparisons). We also found differences for glucose values on fasting and at 2 hours with the highest (0 min) and lowest level (120 min) in the 2016-2017, respectively. Finally, a borderline difference for the weight, but not for BMI, was found (64.1 ± 14.1 kg vs. 66.2 ± 13.1 vs. 67.8 ± 15.6; p = 0.04). Differences were also identified in the post hoc analysis between cohorts. CONCLUSION: This retrospective analysis illustrates changes in characteristics of women with GDM occurring over the period of decade in Poland. They likely result from both epidemiological trends and modifications of the WHO criteria for the GDM diagnosis.

Genetic Parameters and QTLs for Total Phenolic Content and Yield of Wheat Mapping Population of CSDH Lines under Drought Stress.

A doubled haploid population of 94 lines from the Chinese Spring × SQ1 wheat cross (CSDH) was used to evaluate additive and epistatic gene action effects on total phenolic content, grain yield of the main stem, grain number per plant, thousand grain weight, and dry weight per plant at harvest based on phenotypic and genotypic observations of CSDH lines. These traits were evaluated under moderate and severe drought stress and compared with well-watered plants. Plants were grown in pots in an open-sided greenhouse. Genetic parameters, such as additive and epistatic effects, affecting total phenolic content, were estimated for eight year-by-drought combinations. Twenty-one markers showed a significant additive effect on total phenolic content in all eight year-by-drought combinations. These markers were located on chromosomes: 1A, 1B, 2A, 2B, 2D, 3A, 3B, 3D, 4A, and 4D. A region on 4AL with a stable QTL controlling the phenolic content, confirmed by various statistical methods is particularly noteworthy. In all years and treatments, three markers significantly linked to QTLs have been identified for both phenols and yield. Thirteen markers were coincident with candidate genes. Our results indicated the importance of both additive and epistatic gene effects on total phenolic content in eight year-by-drought combinations.

Continuous subcutaneous insulin infusion vs multiple daily injections in pregnant women with type 1 diabetes mellitus: a systematic review and meta-analysis of randomised controlled trials and observational studies.

BACKGROUND: Randomised controlled trials (RCTs) have shown an advantage of continuous subcutaneous insulin infusion (CSII) over multiple daily injections (MDI) in the general type 1 diabetes mellitus (T1DM) population. RCT data on T1DM management in pregnancy remain limited. OBJECTIVE: We performed a systematic review of both RCTs and non-RCTs evaluating CSII vs MDI in T1DM-complicated pregnancy. STUDY DESIGN: Electronic databases were searched for studies comparing CSII with MDI in T1DM-complicated pregnancy. METHODS: A meta-analysis provided point estimates with 95% confidence intervals (CI). Continuous outcomes were reported as weighted mean differences (WMD) or standardised mean differences (SMD), and dichotomous data as relative risk (RR). RESULTS: The search identified 47 studies, including 43 non-RCTs, reporting on 7824 pregnancies. The meta-analysis showed a lower HbA1c level with CSII vs MDI in the first trimester (WMD: -0.45%; 95%CI: -0.62, -0.27). This difference decreased in subsequent trimesters. Compared to MDI, therapy with CSII resulted in higher gestational weight gain (GWG) (WMD: 1.02 kg; 95%CI: 0.41, 1.62), and lower daily insulin dose requirements in the first (SMD: -0.46; 95%CI: -0.68, -0.24) and subsequent trimesters. Moreover, infants from the CSII group were more likely to be large for gestational age (LGA) (RR: 1.16; 95%CI: 1.07, 1.24) and less likely to be small for gestational age (SGA) (RR: 0.66; 95%CI: 0.45; 0.97). CONCLUSIONS: In T1DM-complicated pregnancy, CSII compared to MDI therapy resulted in better first trimester glycaemic control; this difference decreased in subsequent trimesters. CSII therapy was associated with lower insulin requirements, higher GWG and altered risk for infants being LGA and SGA.

Risk of macrosomia remains glucose-dependent in a cohort of women with pregestational type 1 diabetes and good glycemic control.

Macrosomia risk remains high in type 1 diabetes (T1DM) complicated pregnancies. A linear relationship between macrosomia risk and glycated hemoglobin A1c (HbA1c) was described; however, low range of HbA1c has not been studied. We aimed to identify risk factors and examine the impact of HbA1c on the occurrence of macrosomia in newborns of T1DM women from a cohort with good glycemic control. In this observational retrospective one-center study we analyzed records of 510 consecutive T1DM pregnancies (1998-2012). The analyzed group consisted of 375 term singleton pregnancies. We used multiple regression models to examine the impact of HbA1c and self-monitored glucose in each trimester on the risk of macrosomia and birth weight. The median age of T1DM women was 28 years, median T1DM duration-11 years, median pregestational BMI-23.3 kg/m2. Median birth weight reached 3520 g (1st and 3rd quartiles 3150 and 3960, respectively) at median 39 weeks of gestation. There were 85 (22.7 %) macrosomic (>4000 g) newborns. Median HbA1c levels in the 1st, 2nd, and 3rd trimester were 6.4, 5.7, and 5.6 %. Third trimester HbA1c, mean fasting self-monitored glucose and maternal age were independent predictors of birth weight and macrosomia. There was a linear relationship between 3rd trimester HbA1c and macrosomia risk in HbA1c range from 4.5 to 7.0 %. Macrosomia in children of T1DM mothers was common despite excellent metabolic control. Glycemia during the 3rd trimester was predominantly responsible for this condition.

Changes in preconception treatment and glycemic control in women with type 1 diabetes mellitus: a 15­year single­center follow­up.

INTRODUCTION    Pregnancy in women with type 1 diabetes mellitus (T1DM) is associated with higher risk of complications. Strict glycemic control before conception reduces the risk of unfavorable outcomes. OBJECTIVES    The aim of the study was to assess changes in clinical characteristics, preconception treatment, and glycemic control of women with T1DM at the first antinatal visit. PATIENTS AND METHODS    We analyzed the records from the first antenatal visit of 524 women with T1DM in the years 1998-2012. The follow­up period was divided into 3 5­year periods. RESULTS    Differences in the age of patients between the 3 follow­up periods were observed (28.2 ±5.7 years for 1998-2002; 27.3 ±4.5 years for 2003-2007; and 29.4 ±4.8 years for 2008-2012; P <0.0001). The number of women planning pregnancy did not change and reached 32.1% in the first, 44.4% in the second, and 40.4% in the third period (P = 0.2). The use of rapid­acting insulin analogues increased from 2.6% to 46.5% and then to 95.6% (P <0.001). The rate of therapy with personal insulin pumps before pregnancy increased from 4.6% in the first, through 23.5% in the second, to 33.3% in the third period (P <0.001). Over the subsequent periods, we observed a decrease in hemoglobin A1c (HbA1c) levels at the first antenatal visit (from 7.4% ±1.6%, through 6.9% ±1.4%, to 7.0% ±1.4%; P = 0.06), as well as a decrease in HbA1c levels between the subgroups of women planning pregnancy (6.8% ±1.4%, 6.6% ±1.2%, and 6.1% ±0.8%, P = 0.015). CONCLUSIONS    In the years 1998-2012, an increase in the use of insulin analogues and personal insulin pumps by women with T1DM before conception was observed, and these changes were accompanied by a slight improvement in glycemic control, particularly among women planning pregnancy. The percentage of women planning pregnancy did not change during the follow­up.

Factors associated with glycemic control in adult type 1 diabetes patients treated with insulin pump therapy.

Continuous subcutaneous insulin infusion (CSII) by insulin pump seems to improve glycemia and quality of life as compared to conventional insulin therapy in type 1 diabetes (T1DM). However, while many T1DM subjects achieve excellent glycemic control, some others cannot reach recommended goals. In a retrospective analysis, we searched for factors associated with glycemic control in T1DM patients treated with insulin pump therapy. Data from 192 patients (133 women and 59 men) treated with personal insulin pumps at the Department of Metabolic Diseases, University Hospital, Krakow, Poland were analyzed. Sources of information included medical records, memory read-outs from insulin pumps and data from glucose meters. Univariate, multivariate linear and logistic regression analysis for the association with hemoglobin A1c (HbA1c) level were performed. The mean age of the subjects was 28.9 (±11.2) years, the mean duration of T1DM-14.6 (±7.6) years, mean body mass index-23.5 (±3.1) kg/m2. The mean HbA1c level in the entire study group was 7.4% (57 mmol/mol). In the multivariate linear regression analysis, HbA1c correlated with the mean number of daily blood glucose measurements, number of hypoglycemic episodes per 100 blood glucose measurements, age at the examination, and continuous glucose monitoring system use. Multivariate logistic regression analysis for reaching the therapeutic target of HbA1c<7.0% (53 mmol/mol) showed that the independent predictors of achieving this goal included the same four variables. In a large clinical observation, we identified that patient-related and technological factors associated with glycemic control in adult pump-treated T1DM subjects.

Diabetic pregnancy: an overview of current guidelines and clinical practice.

PURPOSE OF REVIEW: We review the recent changes in diagnostic criteria of gestational diabetes mellitus (GDM), describe problems with maintaining and monitoring adequate blood glucose, especially in type 1 diabetes, and provide a brief overview of the currently approved glucose-lowering therapies in pregnancy. RECENT FINDINGS: After the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study, the definition of GDM was revised under the auspices of the International Association of Diabetes and Pregnancy Study Groups. The guidelines, with minor modifications, were endorsed by WHO in 2013. Intensive debate continues, focused on the expected large increase in prevalence of GDM and shortage of experimental evidence of clinical benefits from the new diagnostic criteria. Despite a very good glycaemic control, the prevalence of macrosomia remains high. This indicates a serious deficiency in current monitoring tools and the available therapies. So far, the only glucose-lowering medications approved for use during pregnancy are insulins. SUMMARY: The HAPO study provides a very suggestive evidence for a strong, continuous association of maternal glucose levels with an increased risk of excessive foetal weight gain. The new definition of GDM results in higher healthcare expenditure, but remains cost-effective. The current therapeutic goals require careful revision to further reduce the risk of adverse outcomes. New glucose-monitoring strategies and markers, and approval of new pharmacotherapies are needed.

Alleviation of osmotic stress effects by exogenous application of salicylic or abscisic acid on wheat seedlings.

The aim of the study was to assess the role of salicylic acid (SA) and abscisic acid (ABA) in osmotic stress tolerance of wheat seedlings. This was accomplished by determining the impact of the acids applied exogenously on seedlings grown under osmotic stress in hydroponics. The investigation was unique in its comprehensiveness, examining changes under osmotic stress and other conditions, and testing a number of parameters simultaneously. In both drought susceptible (SQ1) and drought resistant (CS) wheat cultivars, significant physiological and biochemical changes were observed upon the addition of SA (0.05 mM) or ABA (0.1 µM) to solutions containing half-strength Hoagland medium and PEG 6000 (-0.75 MPa). The most noticeable result of supplementing SA or ABA to the medium (PEG + SA and PEG + ABA) was a decrease in the length of leaves and roots in both cultivars. While PEG treatment reduced gas exchange parameters, chlorophyll content in CS, and osmotic potential, and conversely, increased lipid peroxidation, soluble carbohydrates in SQ1, proline content in both cultivars and total antioxidants activity in SQ1, PEG + SA or PEG + ABA did not change the values of these parameters. Furthermore, PEG caused a two-fold increase of endogenous ABA content in SQ1 and a four-fold increase in CS. PEG + ABA increased endogenous ABA only in SQ1, whereas PEG + SA caused a greater increase of ABA content in both cultivars compared to PEG. In PEG-treated plants growing until the harvest, a greater decrease of yield components was observed in SQ1 than in CS. PEG + SA, and particularly PEG + ABA, caused a greater increase of these yield parameters in CS compared to SQ1. In conclusion, SA and ABA ameliorate, particularly in the tolerant wheat cultivar, the harmful effects and after effects of osmotic stress induced by PEG in hydroponics through better osmotic adjustment achieved by an increase in proline and carbohydrate content as well as by an increase in antioxidant activity.