Katarzyna Cyganek

Glycemic Control and Selected Pregnancy Outcomes in Type 1 Diabetes Women on Continuous Subcutaneous Insulin Infusion and Multiple Daily Injections: The Significance of Pregnancy Planning

BACKGROUND Two regimens are used to achieve excellent glycemic control during pregnancy in type 1 diabetes mellitus (T1DM): continuous subcutaneous insulin infusion (CSII) and multiple daily injections (MDI). We assessed their efficacy and safety and the effect of pregnancy planning. METHODS We examined 269 pregnant T1DM women: 157 treated with MDI (MDI group), 42 with CSII (CSII group), and 70 who switched from MDI to CSII in the first trimester (MDI/CSII group). There were 116 women who planned pregnancy: 58 in the MDI group, 38 in the CSII group, and 20 in the MDI/CSII group. The estimated differences in glycemic control and maternal and fetal outcomes were adjusted for baseline characteristics. RESULTS Mean glycated A1c (HbA1c) in the first trimester in the whole group was 6.9%, and the women differed depending on whether they planned pregnancy or not (P < 0.0001). A multiple regression model showed an average difference of about 0.9% in favor of pregnancy planning, with no interaction between the planning and treatments. In the second trimester, HbA1c decreased to a mean value of 5.8%, with improvement of HbA1c across all treatments: by 1.5% in not-planning and 0.9% in planning women. Despite greater improvement, not-planning women still had a higher HbA1c (by 0.3%, P = 0.05). In the third trimester, there was no further significant changes; nevertheless, women who planned pregnancy still had a lower HbA1c (by 0.5%, P = 0.02). There were 14 malformations, stillbirths, and perinatal infant deaths in the not-planning versus five in the planning group (P = 0.07). Patients in the CSII group had a 2 kg greater weight gain compared to the MDI group (15.0 kg vs. 13.0 kg; P = 0.005). CONCLUSIONS In pregnancy with T1DM, both MDI and CSII can provide excellent glycemic control. Pregnancy planning has a beneficial effect on glycemic control, independent from the therapy model. CSII seems to predispose to a larger weight gain in mothers.

Clinical risk factors and the role of VDR gene polymorphisms in diabetic retinopathy in Polish type 2 diabetes patients.

Evidence exists that some clinical, metabolic and genetic risk factors are associated with the development of diabetic retinopathy (DR). The aim of the study was: (1) to define the prevalence of DR in the examined group of 267 patients with type 2 diabetes mellitus (T2DM) from a Polish population; (2) to identify in crosssectional analysis, the clinical features associated with DR in the study group; and (3) to search for the association of 4 markers of vitamin D receptor (VDR), a candidate gene for vascular complications in diabetes, with DR. The examined group consisted of 146 female and 121 male T2DM patients (mean age at examination: 61.3±9.4 years; age at T2DM diagnosis: 50.0±9.2; T2DM duration: 11.3±7.8 years; body mass index (BMI): 30.5±5.5 kg/m2; HbA1c: 7.8±1.5%). In all patients, the clinical and metabolic profile was determined. Diagnosis of DR was determined by a trained ophthalmologist by ophthalmoscopy after pupillary dilatation. Colour photographic documentation was made. The examined T2DM patients were genotyped for FokI, ApaI, BsmI and TaqI frequent VDR polymorphisms based on the restriction fragment length polymorphism method. The statistical analysis was performed using univariate and multivariate logistic regression (SAS) and haplotype analysis (Haplostat). DR was detected in 85 (31.8%) patients with T2DM. The multivariate analysis revealed that significant predictors of this complication were: never-smoking status (odds ratio 2.2, 95% confidence interval 1.2–4), urea serum level (1.3, 1.1–1.5), HbA1c level (1.4, 1.1–1.8) and insulin treatment (2.7, 1.4–5.1). Other features such as age of T2DM diagnosis, T2DM duration prior to ophthalmic exam, obesity (BMI>30), serum creatinine level, albumin/creatinine ratio and arterial hypertension were univariate predictors of DR, however they lost significance as independent predictors in multivariate analysis. Similarly, the alleles, genotypes, haplotype and haplotype combination of VDR were not associated with the examined complication. However, there was a suggestion of a possible slight association between the fbaT haplotype and DR (p=0.11). In conclusion, our study showed that DR in T2DM patients remains a frequent complication in Polish T2DM patients. We were able to confirm the role of some clinical risk factors, surprisingly including not-smoking status, as was previously shown in the UK Prospective Diabetes Study (UKPDS). VDR gene polymorphisms did not constitute a risk factor for this size of study group.

Vitamin D binding protein gene and genetic susceptibility to type 2 diabetes mellitus in a Polish population.

Polymorphisms of the genes involved in the metabolism of vitamin D may predispose to type 2 diabetes mellitus (T2DM). For example, there is evidence suggesting that vitamin D binding protein (DBP) amino acid variants at codons 416 (aspartic acid-->glutamic acid) and 420 (threonine-->lysine) may affect genetic susceptibility to T2DM. The aims of this study are: (1) to determine the allele, genotype, haplotype and haplotype combination frequencies of those DBP amino acid variants in a Polish population and (2) to examine their role in the genetic susceptibility to T2DM in a Polish population. Overall 393 individuals were included in this study: 231 T2DM patients and 162 controls. The sequence of DBP exon 11, which contains both examined variants, was amplified by polymerase chain reaction (PCR). Alleles and genotypes were determined based on electrophoresis of the DNA digestion products by specific restriction enzymes HaeIII and StyI. Since variants of DBP were in very strong linkage disequilibrium, haplotypes could be assigned to phase-unknown individuals. Differences in distributions between the groups were examined by chi(2) test. At codon 416 the frequency of Asp/Glu alleles was 44.6/55.4% in T2DM patients and 40.7/59.3% in controls (chi(2)=2.1, d.f.=1, P=0.28). At codon 420 the frequency of Thr/Lys alleles were 69.4/30.6% and 71.6/28.4%, (chi(2)=0.41, d.f.=1, P=0.52), respectively. Distribution of genotypes, haplotypes and haplotype combinations were similar in both groups. In conclusion, the frequency of amino acid variants at codons 416 and 420 of vitamin D binding protein gene in a Polish population is similar to other Caucasian populations, but differs significantly from other races. No evidence was found for an association between DBP frequent polymorphisms and T2DM in this population.

The Ala45Thr polymorphism of BETA2/NeuroD1 gene and susceptibility to type 2 diabetes mellitus in a Polish population.

Abstract. The BETA2/NeuroD1 gene product is a transcription factor, a member of a helix-loop-helix (HLH) family that is specifically expressed in the endocrine pancreas. HLH and homeobox proteins are involved in the development and function of pancreatic islets cells. Mice homozygous for a targeted disruption of BETA2/NeuroD1 showed abnormal pancreatic islet morphogenesis and developed overt diabetes. Mutations in the NeuroD/BETA2 gene were linked to the development of type 2 diabetes (T2DM). The aims of the study were to determine the allele and genotype frequency of Ala45Thr polymorphism of BETA2/NeuroD1 in a Polish population and to examine the role of this amino acid variant in the genetic susceptibility to T2DM. We included 394 individuals into this study: 223 T2DM patients with the age at diagnosis above 35 years and 171 controls without a family history of T2DM. The fragment of the gene, corresponding to the Ala45Thr amino acid variant, was amplified by polymerase chain reaction. Alleles and genotypes were determined based on electrophoresis of the specific restriction enzyme EcoI57 DNA digestion products. Differences in distribution between the groups were examined by χ2 test. The frequencies of the Ala and Thr alleles in T2DM patients (62% and 37.9%) were similar to those in the controls (65.5% and 34.5%; p=0.32). Similarly, there was no difference between the groups when we analyzed the genotype distribution (p=0.24). The stratification analysis based on family history of T2DM, obesity, and age of diagnosis did not show any difference between the groups. In conclusion, the frequency of Ala45Thr polymorphism in this studied Polish population is similar to its frequency in other Caucasians. We did not find evidence that the Ala45Thr polymorphism of BETA2/NeuroD1 played a role in the risk of T2DM in the examined Polish population.

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.

Insulin Pump Therapy is Equally Effective and Safe in Elderly and Young Type 1 Diabetes Patients

OBJECTIVES It is generally accepted that in adult type 1 diabetes patients (T1D) continuous subcutaneous insulin infusion (CSII) via a personal pump is more effective than the multiple daily injections (MDI) model. However, it is not clear whether all age groups of adult T1D patients may equally benefit from CSII therapy. We aimed to compare the glycemic control and use of selected pump tools in T1D subjects using CSII over the age of 50 (50+ T1D) with patients younger than 50 years of age. METHODS The last available insulin pump/blood glucose meter downloads and last available HbA1c levels of 124 adult T1D subjects using CSII were reviewed. We divided our cohort into two subgroups: 50+ T1D patients (n = 13) and younger patients (n = 111). RESULTS There were no differences in glycemic control achieved with CSII treatment in 50+ T1D patients vs. younger subjects. HbA1c levels were 7.01 ± 0.67% and 7.34 ± 1.24% (p = 0.46), and the mean glycemia based on glucometer downloads was 141.8 ± 17.7 mg/dl and 150.8 ± 35.7 mg/dl (p = 0.69), respectively. Also, there were no differences with respect to the use of important personal pump options and tools. CONCLUSION In conclusion, insulin pump therapy appears to be effective and safe in T1D patients regardless of age.

Postpregnancy Glycemic Control and Weight Changes in Type 1 Diabetic Women

OBJECTIVE Pregnancy in type 1 diabetes requires excellent glycemic control. Most pregnant type 1 diabetic women achieve normoglycemia; however, there is scarce data on their postdelivery characteristics. We aimed to examine postpregnancy glycemic control and weight changes in type 1 diabetes. RESEARCH DESIGN AND METHODS We identified and followed (median 20 months) 254 women with singleton pregnancies receiving postdelivery medical care at a single institution. RESULTS Study subjects were 28.3 ± 4.7 years of age (mean ± SD), with a diabetes duration of 12.0 ± 7.7 years. Mean A1C before conception was 6.9 ± 1.4%, and preconception weight and BMI were 64.4 ± 10.0 kg and 23.9 ± 3.3 kg/m2, respectively. Mean A1C decreased during pregnancy, reaching 5.7 ± 0.8% in the third trimester. We observed a mean weight gain of 14.4 ± 6.5 kg during pregnancy. Within 6 months after delivery, A1C increased by 0.8% (P < 0.0001) compared with the last trimester, and body weight and BMI were 4.4 kg and 2.5 kg/m2 higher (P < 0.0001) compared with the preconception baseline. A1C further deteriorated by 0.8% until the end of follow-up. For women in the “pregnancy planning” program (n = 117), A1C >12 months after delivery was worse compared with before conception (7.1 vs. 6.5%, P = 0.0018), whereas in women with unplanned pregnancies, it was similar to the pregestational levels (7.3 vs.7.4%, P = 0.59). Weight and BMI in the entire study group did not return to prepregnancy levels and were 2.5 kg (P = 0.0079) and 0.9 kg/m2 higher (P = 0.0058). CONCLUSIONS In this clinical observation, type 1 diabetic women showed postpregnancy deterioration in glycemic control and were unable to return to prepregnancy weight. Type 1 diabetic women seem to require special attention after delivery to meet therapeutic targets.

Altered fibrin-clot properties are associated with retinopathy in type 2 diabetes mellitus.

AIM The development and progression of diabetic retinopathy (DR) in type 2 diabetes mellitus (T2DM) have been associated with poor glycaemic control, long disease duration and other clinical features. However, the pathogenesis of the complication is still poorly understood. As the formation of dense fibrin clots resistant to lysis has been described in diabetes patients, this study tested the hypothesis that altered clot structure and function are associated with DR in T2DM patients. METHODS The study included 101 T2DM subjects without DR (NDR) and 60 with DR. Plasma fibrin-clot permeation was assessed using a pressure-driven system, and expressed as the permeation coefficient (K(s)), indicating pore size, and as the time required for a 50% decrease in clot turbidity (t(50%)) as a marker of susceptibility to fibrinolysis. All patients underwent ophthalmological examination. Clinical and biochemical co-variables were also measured. Determinants of DR were identified using stepwise, multivariable, logistic-regression analyses. RESULTS Patients with DR had lower clot permeability (K(s): 6.15 ± 1.18 vs. 7.53 ± 1.24 10(-9) cm(2); P < 0.0001) and slower fibrin-clot lysis (t(50%): 10.12 ± 1.24 vs. 9.12 ± 1.4 min; P < 0.0001) than NDR subjects. Logistic analysis revealed associations between DR and K(s), t(50%), fasting glucose and diabetes duration, as well as insulin treatment and statin non-use (P < 0.05). After adjusting for these variables as well as for age and gender, associations between K(s) and t(50%) with DR proved to be significant. CONCLUSION Formation of compact fibrin clots and impaired clot lysis are both associated with DR in T2DM patients. However, it is unclear whether these abnormalities lead to the development of DR or merely constitute a marker of its presence.

Use of sensor-augmented insulin pump in patient with diabetes and cystic fibrosis: evidence for improvement in metabolic control.

Cystic fibrosis-related diabetes (CFRD) is a frequent complication of cystic fibrosis. We report the significant improvement of diabetes control and quality of life in a CFRD patient using the sensor-augmented insulin pump. The system gives the patient the highest degree of flexibility, which is required in CFRD since food intake and activity levels vary widely from day to day, depending on the rapid changes of health status.

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.