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Magdalena Kozela,1 Agnieszka Matras,1 Karolina Koziara,1 Maciej T Małecki,2 Andrzej Pająk1 1Department of Epidemiology and Population Studies, Institute of Public Health Jagiellonian University Medical College, Krakow, Poland; 2Department of Metabolic Diseases, Jagiellonian University Medical College, Krakow, PolandCorrespondence: Karolina Koziara, Department of Epidemiology and Population Studies, Institute of Public Health, Skawińska St. 8, Kraków, 31-066, Poland, Tel +48 12 43 32 836, Email karolina.koziara@uj.edu.plPurpose: The study assessed the relationship between prior diagnosis of diabetes and its control with depression score, differences in socioeconomic, lifestyle, health characteristics and diabetes control by adherence to treatment in population-based sample of older individuals.Patients and Methods: The analysis of the sub-sample of Polish cohort of the HAPIEE (Health, Alcohol, and Psychosocial Factors in Eastern Europe) study was conducted; 464 participants were interviewed and random first 360 (78%) underwent physical examination and blood sample tests. Depressive symptoms were assessed using the Center for Epidemiological Studies Depression Scale. The robust regression method was applied to assess the association between depression score and diabetes diagnosis as well as diabetes control.Results: There were 97 participants (21.0%) at mean age of 73.6 years (SD=6.31 years) with prior diagnosis of diabetes. Mean HbA1c concentration was 6.65% (SD=1.0) The majority of patients (55.7%) used oral medication with diet. Nearly 20% declared the use of oral treatment alone, and 10.3% used combined treatment of oral medications, insulin, and diet. In this study, 86.6% of the participants with diabetes confirmed self-monitoring of blood glucose levels and 58.8% were on high-quality diet. No differences in socioeconomic, lifestyle, health characteristics or control of diabetes by adherence to diabetes treatment were found. After adjustment for age and gender, diagnosis of diabetes was associated with greater depressive score by about 2 points (β=2.02, 95% CI=0.16;3.88). However, no significant association between depression score and any indicator of diabetes control was found.Conclusion: In older individuals with diabetes, depression score was higher compared to those without diabetes, but it was not related to poorer diabetes control. No differences in socioeconomic, lifestyle, health characteristics and control of diabetes by adherence to diabetes treatment may suggest that in this age group some other, less known factors are substantial for achievement of treatment targets.Keywords: diabetes, depression, older adults, control

Introduction and Objectives: Type 1 diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. Education is the cornerstone of effective diabetes care. In this implementation project, we aimed to improve compliance with best practices regarding type 1 diabetes educational interventions for adult hospitalized patients., Methods: This project was guided by the JBI Evidence Implementation Framework. A baseline audit was conducted involving 20 nurses and 20 type 1 diabetes patients who received regular educational measures. Areas of non-compliance were identified and an improvement strategy was implemented. A follow-up audit was then conducted to evaluate the effectiveness of the improvement strategy. The project was conducted in Poland in 2021 in a tertiary referral unit that specializes in the diagnosis and treatment of diabetes., Results: Substantial improvements were noted for all audit criteria after the implementation of strategies to address areas of non-compliance. Use of the education program improved from 0% to 100%. Compliance regarding patients receiving handouts and personalization of the program increased to 100%. We observed a significant improvement from 0% to 80% in the structuring of the program content., Conclusions: This project successfully improved the quality of education provided for type 1 diabetes patients in all relevant areas. We devised an education program, covering important aspects of diabetes education, with the patients reporting increased satisfaction with the personalized educational measures during their hospital stay., Spanish Abstract: http://links.lww.com/IJEBH/A215., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 JBI. Unauthorized reproduction of this article is prohibited.)

Objective: To identify predictors of body weight (BW) reduction of ≥15% with tirzepatide treatment and to describe associated clinical parameters of participants with type 2 diabetes (T2D) who achieved different categorical measures of BW reduction (<5%, ≥5 to <10%, ≥10 to <15%, and ≥15%) across four studies from the phase 3 SURPASS clinical trial program for T2D., Research Design and Methods: The multivariate model for predictor of a BW reduction of ≥15% included age, sex, race, BW, HbA1c, tirzepatide dose and baseline metformin use, fasting serum glucose, and non-HDL cholesterol. Baseline characteristics and change from baseline to week 40/42 for efficacy parameters were described and analyzed in treatment-adherent participants (≥75% doses administered and on treatment at week 40/42) receiving once weekly tirzepatide (5 mg, 10 mg, or 15 mg) (N = 3,188)., Results: Factors significantly associated with achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, and lower HbA1c, fasting serum glucose, and non-HDL cholesterol at baseline. With higher categorical BW reduction, there were greater reductions in HbA1c, triglycerides, ALT, waist circumference, and blood pressure., Conclusions: Baseline factors associated with a higher likelihood of achieving a BW reduction of ≥15% with tirzepatide were higher tirzepatide doses, female sex, White or Asian race, younger age, metformin background therapy, better glycemic status, and lower non-HDL cholesterol. With greater BW reduction, participants with T2D achieved larger improvements in glycemia and cardiometabolic risk parameters. These findings help inform which people with T2D are most likely to achieve greater BW reduction with improved cardiometabolic risk factors with tirzepatide., (© 2023 by the American Diabetes Association.)

Aim: Several studies have assessed the association between personality traits and metabolic outcomes in children and adolescents with type 1 diabetes (T1DM). The aim of this observational single-visit study was to investigate whether specific personality traits were related to the degree of metabolic control/diabetes duration in adult T1DM patients., Method: Data were collected from 56 adults (40 men) with T1DM treated in a tertiary care center. "Big Five" personality traits were assessed using the NEO-Five Factor Inventory questionnaire. Several variables were obtained from the insulin pumps, glucometers and blinded continuous glucose monitoring system., Results: All personality traits but neuroticism (low level of the trait) showed average intensity. Agreeableness was associated with most variables from CGMS data. Higher conscientiousness was associated with longer diabetes duration. Higher neuroticism was correlated with greater glycemic variability (GV), while high Extraversion was associated with lower GV. Lower Openness was associated with prolonged time in clinically significant hypoglycaemia., Conclusions: Our study suggest that personality traits manifest in individual approach to diabetes management and emotion regulation, translating also into the attitude to treatment. On the other hand, T1DM patients' overall trait scores were consistent with healthy nonpsychiatric norms, which debunks myths and stereotypes suggesting that chronic disease is usually associated with psychopathology.

Objective: Lipohypertrophy (LH) is a common complication of insulin therapy in type 1 diabetes mellitus (T1DM). We examined whether an intervention consisting of LH assessment and retraining on insulin infusion set use improves glycemic control on subcutaneous insulin infusion (CSII) in patients with T1DM., Methods: The intervention was conducted in 79 consecutive patients with T1DM. Data on glucose levels, glycated hemoglobin (HbA1c), and insulin doses were collected at baseline and after a median of 22 weeks (20-31.75 weeks)., Results: A total of 46 patients with T1DM (23 [50%] women) participating in the follow-up were characterized by a median age of 29 years (25-33.8 years), body mass index of 24.6 ± 3.3 kg/m 2 , T1DM duration of 16.5 years (8.3-20 years), and subcutaneous insulin infusion duration of 7 years (4-10.8 years). Patients' median HbA1c fell from 7.4% (6.7%-8.2%) to 7.05% (6.4%-7.6%) (P < .001), daily insulin dose/kg decreased (0.7 ± 0.20 vs 0.68 ± 0.15 IU/kg; P = .017) together with the total daily insulin dose (50.3 [40.5-62.7] vs 47.6 [39.8-62.1] IU; P = .019]. Furthermore, the percentage of basal insulin dose increased (43.0% [36-50] vs 44.0% [39.0-50.0]; P = .010], whereas the percentage of bolus dose decreased (57% [50-64] vs 56% [50-61], P = .010)., Conclusions: The structured LH-related intervention in patients with T1DM on insulin pumps resulted in better glycemic control and a decrease in total daily insulin dose., Competing Interests: Disclosure The authors have no multiplicity of interest to disclose., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

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/m 2 ] 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)., (© 2022 John Wiley & Sons Ltd.)

Introduction: Proper use of insulin infusion sets (IIS) plays an important role in pump therapy of patients with type 1 diabetes mellitus (T1DM). We assessed the habits associated with the use of IIS in patients with T1DM treated with insulin pump., Materials and Methods: This study included 79 T1DM patients who were examined for the presence of lipohypertrophy (LH) and retrained for proper IIS use. They completed a standard questionnaire regarding IIS at the time of study entry and at the follow-up. R e s u l t s: At baseline, most of the patients declared to have been using a plastic cannula (n = 68; 86.1%), changing the infusion set regularly (n = 65; 82.3%), and placing the infusion sets on the abdomen wall (n = 68; 86.1%). The most common rotation habit was the "curve pattern" on both sides of the umbilicus (n = 16; 20.3%). After a median of 23 weeks (IQR 20-34), 58 patients were available for the follow-up. A rise in the proportion of patients who declared to change IIS regularly (n = 48; 82.8% vs. n = 57; 98.3%, p = 0.016), change IIS every 2 to 3 days (n = 27; 46.6% vs. n = 35; 60.3%, p = 0.043), use "crisscross" rotation (n = 5; 8.8% vs. n = 12; 21.4%, p = 0.027) was observed. There were less patients reporting not having repeatable rotation manner (n = 15; 26.3% vs. n = 2; 5.4%, p = 0.009). C o n c l u s i o n s: A substantial proportion of T1DM patients on pump therapy declare that they do not follow the recommended principles of IIS use. The intervention consisting of LH assessment and retrain- ing of proper use of IIS might be effective in improving patient compliance.

Background: Cardiovascular diseases including arterial hypertension are common comorbidities among patients hospitalized due to COVID-19. We assessed the influence of preexisting hypertension and its pharmacological treatment on in-hospital mortality in patients hospitalized with COVID-19., Methods: We studied all consecutive patients who were admitted to the University Hospital in Krakow, Poland, due to COVID-19 between March 2020 and May 2021. Data of 5191 patients (mean age 61.9±16.7 years, 45.2% female) were analyzed., Results: The median hospitalization time was 14 days, and the mortality rate was 18.4%. About a quarter of patients had an established cardiovascular disease including coronary artery disease (16.6%) or stroke (7.6%). Patients with hypertension (58.3%) were older and had more comorbidities than patients without hypertension. In multivariable logistic regression analysis, age above median (64 years), male gender, history of heart failure or chronic kidney disease, and higher C-reactive protein level, but not preexisting hypertension, were independent risk factors for in-hospital death in the whole study group. Patients with hypertension already treated (n=1723) with any first-line antihypertensive drug (angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, calcium channel blockers, or thiazide/thiazide-like diuretics) had a significantly lower risk of in-hospital death (odds ratio, 0.25 [95% CI, 0.2-0.3]; P <0.001) compared to nontreated hypertensives (n=1305)., Conclusions: Although the diagnosis of preexisting hypertension per se had no significant impact on in-hospital mortality among patients with COVID-19, treatment with any first-line blood pressure-lowering drug had a profound beneficial effect on survival in patients with hypertension. These data support the need for antihypertensive pharmacological treatment during the COVID-19 pandemic.

Background: HNF1A-MODY is a monogenic form of diabetes caused by variants in the HNF1A gene. Different HNF1A variants are associated with differences in age of disease onset, but other factors are postulated to influence this trait. Here, we searched for genetic variants influencing age of HNF1A-MODY onset., Methods: Blood samples from 843 HNF1A-MODY patients from Czech Republic, France, Poland, Slovakia, the UK and the US were collected. A validation set consisted of 121 patients from the US. We conducted a genome-wide association study in 843 HNF1A-MODY patients. Samples were genotyped using Illumina Human Core arrays. The core analysis was performed using the GENESIS package in R statistical software. Kinship coefficients were estimated with the KING and PC-Relate algorithms. In the linear mixed model, we accounted for year of birth, sex, and location of the HNF1A causative variant., Results: A suggestive association with age of disease onset was observed for rs2305198 (p = 2.09E-07) and rs7079157 (p = 3.96E-06) in the HK1 gene, rs2637248 in the LRMDA gene (p = 2.44E-05), and intergenic variant rs2825115 (p = 2.04E-05). Variant rs2637248 reached nominal significance (p = 0.019), while rs7079157 (p = 0.058) and rs2825115 (p = 0.068) showed suggestive association with age at diabetes onset in the validation set., Conclusions: rs2637248 in the LRMDA gene is associated with age at diabetes onset in HNF1A-MODY patients., (© 2022. The Author(s).)

Introduction: Some patients with type 1 diabetes (T1DM) are free from advanced complications despite long‑standing disease. These patients may be carriers of gene mutations responsible for maturity‑onset diabetes of the young and may have been misdiagnosed with T1DM., Objectives: We aimed to determine the clinical characteristics of patients with long‑term T1DM, without advanced microvascular complications, and with well‑preserved kidney function. A search for mutations in monogenic diabetes genes was performed., Patients and Methods: Patients were recruited at 2 Polish university centers based on the following criteria: T1DM duration of 40 years or longer and absence of advanced complications defined as chronic kidney disease (estimated glomerular filtration rate [eGFR] <60 ml/min/1.73 m2 ), overt proteinuria, blindness, and diabetic foot syndrome. Mutations in the 7 most frequent monogenic diabetes genes were identified using next‑generation sequencing., Results: We enrolled 45 patients with T1DM (mean [SD] age at examination, 59.2 [8.0] years; mean [SD] age at T1DM diagnosis, 14.6 [6.7] years). Mean (SD) hemoglobin A1c levels were 7.6% (1.4%); daily insulin dose, 0.48 (0.17) U/kg; high‑density lipoprotein (HDL) cholesterol levels, 1.9 (0.6) mmol/l; body mass index (BMI), 26.4 (5.0) kg/m2 ; and eGFR, 82.2 (12.1) ml/min/1.73 m2 . Albuminuria and retinopathy were reported in 7 and 39 patients, respectively. We were not able to assign a causative role to any of 10 genetic variants identified by next‑generation sequencing in this cohort., Conclusions: Patients with long‑term T1DM and preserved kidney function have good glycemic control, elevated HDL cholesterol levels, low insulin requirements, near ‑normal BMI, and a rare occurrence of mutations in monogenic diabetes genes.

Introduction: Patients with hepatocyte nuclear factor-1 beta (HNF1B) mutations present a variable phenotype with two main symptoms: maturity onset diabetes of the young (MODY) and polycystic kidney disease (PKD)., Objectives: Identification of serum metabolites specific for HNF1Bmut and evaluation of their role in disease pathogenesis., Methods: We recruited patients with HNF1Bmut (N = 10), HNF1Amut (N = 10), PKD: non-dialyzed and dialyzed (N = 8 and N = 13); and healthy controls (N = 12). Serum fingerprinting was performed by LC-QTOF-MS. Selected metabolite was validated by ELISA (enzyme-linked immunosorbent assay) measurements and then biologically connected with HNF1B by in silico analysis. HepG2 were stimulated with lysophosphatidic acid (LPA) and HNF1B gene was knocked down (kd) by small interfering RNA. Transcriptomic analysis with microarrays and western blot measurements were performed., Results: Serum levels of six metabolites including: arachidonic acid, hydroxyeicosatetraenoic acid, linoleamide and three LPA (18:1, 18:2 and 20:4), had AUC (the area under the curve) > 0.9 (HNF1Bmut vs comparative groups). The increased level of LPA was confirmed by ELISA measurements. In HepG2 HNF1Bkd cells LPA stimulation lead to downregulation of many pathways associated with cell cycle, lipid metabolism, and upregulation of steroid hormone metabolism and Wnt signaling. Also, increased intracellular protein level of autotaxin was detected in the cells. GSK-3alpha/beta protein level and its phosphorylated ratio were differentially affected by LPA stimulation in HNF1Bkd and control cells., Conclusions: LPA is elevated in sera of patients with HNF1Bmut. LPA contributes to the pathogenesis of HNF1B-MODY by affecting Wnt/GSK-3 signaling., (© 2022. The Author(s).)

In this study, we verified the hypothesis that Raman signature of urinary extracellular vesicles (UEVs) can be used to stratify patients with diabetes at various stages of chronic kidney disease (CKD). Patients with type 2 diabetes diagnosed with different stages of CKD and healthy subjects were enrolled in the study. UEVs were isolated using low-vacuum filtration followed by ultracentrifugation. Correlation analysis, multiple linear regression and principal component analysis were used to find differences between spectral fingerprints of UEVs derived from both groups of patients. Electron microscopy and nanoparticle tracking analysis were applied to characterize the size and morphology of UEVs. We observed significant correlations between selected Raman bands measured for UEVs and clinical parameters. We found significant differences in the area under the specific bands originating mainly from proteins and lipids between the study groups. Based on the tryptophan and amide III bands, we were able to predict the estimated glomerular filtration rate (eGFR). Principal component analysis, partial least squares regression (PLSR) and correlation analysis of the UEV Raman spectra supported the results obtained from the direct analysis of Raman spectra. Our analysis revealed that PLSR and a regression model including tryptophan and amide III bands allows to estimate the value of eGFR., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The relationship between the gut and skeleton is increasingly recognized as a component of the regulation of carbohydrate metabolism. The aim of our study was to assess the relationship between bone mineral density (BMD), incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), intestinotrophic peptide glucagon-like peptide-2 (GLP-2) and osteocalcin isoforms in patients with long-term type 1 diabetes (T1D) when compared to healthy controls., Methods: Eighty two patients with long term T1D, treated in the Department of Metabolic Diseases and 53 healthy controls were recruited to the study. Long term disease duration was defined as lasting for more than 10 years. The control group was selected among age- and sex-matched healthy people. Fasting blood samples were collected to measure levels of incretin hormones (GLP-1, GLP-2, GIP), two forms of osteocalcin (uncarboxylated (ucOC), and carboxylated (cOC)), and additional biochemical parameters associated with glucose and bone metabolism (HbA1c, calcium, phosphorus, 25(OH)D3, PTH)., Results: Patients with T1D had higher BMI than in controls (p = 0.02). There was no difference in BMD at the lumbar spine and the femoral neck between patients with long-term T1D and healthy ones. Z-score values in both groups were within normal ranges. The level of GIP was significantly higher in T1D patients (p = 0.0002) in comparison to the healthy ones. The levels of GLP-1 and GLP-2 did not differ between T1D patients and controls. In the T1D group, strong, positive associations were found between serum levels of GLP-1 and cOC (r = 0.546, p < 0.001) and between GLP-1 and total OC (r = 0.51, p < 0.001), also after adjusting for BMI (p < 0.001 and p < 0.001, respectively). Significant positive associations were also found between serum levels of GLP-2 and cOC (r = 0.27, p = 0.013) and between GLP-2 and total OC (r = 0.25, p = 0.018), also in a multivariate regression (p = 0.009, p = 0,175, respectively). Moreover, in T1D patients, GLP-1 correlated positively with the femoral neck BMD (g/cm 2 ) (r = 0.265, p = 0.016) and this association was statistically significant after adjusting for BMI (p = 0.011). These correlations were not present in the control group. The only significant correlation observed in the control group was between OC and BMD of the neck (p = 0.049 for neck BMD g/cm 2 , and p = 0.041 for neck Z-score)., Conclusions: Our data suggests an effect of gut hormones on bone in long-term T1D, which could be associated with OC activity, however we did not find a direct connection with glucose metabolism. GLP-1 could have a possible, protective role on bone mineral density in patients with T1D. The data from our study suggests that gut hormones could be considered as a new link in the skeleton - pancreatic endocrine loop in patients with T1D., (Copyright © 2021. Published by Elsevier Inc.)

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., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Magdalena Wilk et al.)

Background: The COVID-19 pandemic has challenged the worldviews of most people. Social isolation after the COVID-19 lockdown has not only led to economic difficulties but also resulted in adverse psychological reactions. As in most countries, including Poland, this situation has been very challenging for patients with type 1 diabetes mellitus (T1DM). In Poland, a crisis intervention team for patients with T1DM was established. The goal of the team was to provide psychological support for these patients, if needed, and to present information concerning how these patients may obtain medical consultations and prescriptions., Objective: We aimed to analyze the psychological parameters and main emotional reactions of patients with T1DM during the COVID-19 lockdown., Methods: An email with information concerning the possibility of having a web-based consultation with psychologists and psychiatrists and an attached set of psychological tests was sent to all patients with T1DM who were under the care of an outpatient diabetes clinic. The consultations were performed by licensed clinical psychologists and psychologists. This study was approved by the Bioethics Committee of the Jagiellonian University in Krakow, Poland., Results: The patients who decided to use psychological support had statistically higher levels of anxiety (state P=.043; trait P=.022), stress (P=.001) than those of patients from the group who did not seek support., Conclusions: The presented intervention team may be perceived as an example of important and successful cooperation and communication between specialists of different fields of medicine (diabetology, psychiatry, and psychology) in a crisis situation., (©Katarzyna Cyranka, Dominika Dudek, Maciej Tadeusz Małecki, Bartłomiej Matejko, Tomasz Klupa. Originally published in JMIR Mental Health (https://mental.jmir.org), 30.06.2021.)

The studies on microbiome in the human digestive tract indicate that fungi could also be one of the external factors affecting development of diabetes. The aim of this study was to evaluate the quantitative and qualitative mycobiome composition in the colon of the adults with type 1 (T1D), n = 26 and type 2 (T2D) diabetes, n = 24 compared to the control group, n = 26. The gut mycobiome was characterized in the stool samples using the analysis of the whole internal transcribed spacer (ITS) region of the fungal rDNA gene cluster by next-generation sequencing (NGS) with increased sensitivity. At the L2 (phylum) level, Basidiomycota fungi were predominant in all 3 study groups. Group T1D presented significantly lower number of Ascomycota compared to the T2D group, and at the L6 (genus) level, the T1D group presented significantly lower number of Saccharomyces genus compared to control and T2D groups. In the T1D group, a significant positive correlation between total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and fungi of the genus Saccharomyces, and in the T2D group, a negative correlation between the total cholesterol level and Malassezia genus was found. The obtained results seem to be a good foundation to extend the analysis of the relationship between individual genera and species of fungi and the parameters determining the metabolism of carbohydrates and lipids in the human body.

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.

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 (β = - 0.69, p = 0.056). This BMI association was confirmed on 1889 patients from FHS cohort (β = - 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&#95;pval = 0.0241), while interaction of rs3021088 in MT-ND2 and rs41542013 in POLRMT led to BMI increase (inter&#95;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.

Elevated levels of plasma pentraxin 3 (PTX3), a marker of inflammation, are associated with the risk of developing cardiovascular diseases in the general population, as well as in patients with type 2 diabetes (DM2). In this study, we aimed to determine factors associated with PTX3 serum concentrations in men and women with DM2. The study included 116 consecutive patients (67 men and 49 women) with DM2 from an outpatient diabetic clinic. Men were characterised by lower age and higher uric acid, creatinine and bilirubin concentrations and waist/hip ratio than women. In women, low-density lipoprotein cholesterol (LDL-C) levels were higher than in men. In men, median (interquartile range) values of PTX3 concentration were 4.02 (1.99), and in women they were 4.53 (3.31) ng/ml (NS). In men, PTX3 concentrations correlated with total cholesterol (TC), triglycerides, apolipoprotein (Apo) C3, Apo B48, Glc and creatinine levels. In women, PTX3 correlated significantly with TC and LDL-C and Apo B100. Partial regression analysis revealed that after adjusting for age, PTX3 concentrations in men were significantly associated with TC, LDL-C, triglycerides, creatinine, Apo C3 and Apo B48, while in women they were associated with TC, LDL-C and Apo B100. The results could be of importance in sex-specific prevention of vascular complications in DM2 patients.

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.

Introduction: Nonalcoholic fatty liver disease (NAFLD) is common in patients with type 2 diabetes (T2D). Pentraxin 3 (PTX3), a marker of inflammation, is a cardiovascular risk factor., Objectives: We examined clinical and biochemical factors associated with serum PTX3 concentrations in patients with T2D with and without NAFLD., Patients and Methods: Serum material was obtained from 116 patients with T2D (mean age, 59.1 years), including 79 patients with NAFLD., Results: Median (interquartile range) PTX3 level was 4.264 (2.293) ng/ml in patients with and 3.773 (3.223) ng/ml in patients without NAFLD (P = 0.93). In the whole group, PTX3 level was associated with total cholesterol, low‑density lipoprotein cholesterol (LDL‑C), apolipoprotein (apo) B100, apo C3, triglyceride (TG) concentrations, and waist circumference after adjustment for age and gender. As indicated by partial regression coefficient b, increase of independent variable LDL‑C by 1 mmol/l was associated with the rise of PTX3 by 1.2017 ng/ml, increase of apo B100 by 1 mg/dl with the rise of PTX3 by 1.0051 ng/ml, and increase of apo C3 by 1 μg/dl with the rise of PTX3 by 1.0012 ng/ml. In patients with T2D with NAFLD, total cholesterol, LDL‑C, TG, apo C3, and apo B100 were associated with PTX3. Associations of PTX3 with apolipoproteins were observed only in the NAFLD group., Conclusions: Reported associations of PTX3 level add new insight into possible mechanisms of its atherogenic actions.

Aim: The impact of maturity onset diabetes of the young (MODY) on quality of life (QoL) has never been examined. We assessed disease impact on QoL among patients with HNF1A-MODY and GCK mutation carrier status., Methods: The study included 80 patients with HNF1A-MODY and 89 GCK gene mutation carriers. We also examined 128 type 1 diabetes (T1DM) patients for comparison. Diabetes-specific QoL was assessed using the Audit of Diabetes Dependent Quality of Life questionnaire., Results: HNF1A-MODY and GCK-MODY groups had similar mean age (41.7 vs. 38.0 years, respectively) and BMI (24.1 vs. 24.3 kg/m 2 ), whereas T1DM patients were on average younger (34.2 years) with similar BMI (25.0 kg/m 2 ). Less than a third of GCK mutation carriers were on pharmacotherapy (n = 20, 31%), while the majority of HNF1A mutation carriers used oral drugs or insulin (n = 66, 82.5%). While current QoL was similar across the three groups (p = 0.66), two other major indices-the impact of diabetes on QoL and the average weighted impact (AWI)-differed among them (p < 0.001 for both comparisons). The impact of diabetes on patient QoL and AWI observed in both MODY groups was smaller than in T1DM. Etiological diagnosis of diabetes and a diagnosis of retinopathy were the only independent factors influencing the impact of diabetes on QoL and AWI in regression analysis. In HNF1A-MODY, all three major indices of QoL were more heavily influenced for patients on insulin in comparison to other treatment sub-groups., Conclusion: MODY has a smaller negative impact on QoL compared to T1DM. Mode of treatment further stratifies QoL decline for HNF1A-MODY subjects.

Raman spectroscopy was applied to the measurement of urinary and in vitro endothelium-derived extracellular vesicles (EVs) isolated by hydrostatic filtration dialysis (HFD) method. Raman spectra obtained for urinary EVs (UEVs) showed distinct differences in the fingerprint region. In contrast, average Raman spectra of endothelium-derived EVs samples were almost identical. Cluster Analysis of UEVs significantly discriminated diabetic samples from control, moreover endothelium-derived EVs revealed stronger similarity between long hyperglycemia and normoglycemia samples compared to short hyperglycemia. Results obtained from Partial Least Squares analysis corresponded well with integral intensities of selected bands. Our proof-of-concept approach demonstrates the potential for Raman spectroscopy to be used both for identification of EVs molecular signatures in urine samples from patients with type 2 diabetes mellitus and good glycemic control and unsatisfactory glycemic control as well as for in vitro hyperglycemic model. This noninvasive technique may be useful in identifying new biomarkers of diabetes and renal complications., (Copyright © 2019 Elsevier Inc. All rights reserved.)

INTRODUCTION It is widely believed that patients with diabetes are at increased risk of severe and premature coronary artery disease (CAD) when compared with nondiabetic individuals. OBJECTIVES The aim of the study was to evaluate the prevalence, 7‑year incidence, predictors, and outcomes of obstructive and nonobstructive CAD in patients with long‑lasting type 1 diabetes. PATIENTS AND METHODS We enrolled 2330 patients at a median age of 50 years and a median diabetes duration of 32 years. All participants underwent diagnostic workup for CAD with an exercise treadmill test (ETT), single‑photon emission computed tomography (SPECT), or both. Coronary angiography was performed in patients with abnormal ETT/SPECT results and repeated during the study if clinically indicated. RESULTS The prevalence of obstructive and nonobstructive CAD was 6.9% and 42%, respectively, while the 7‑year incidence, 1.9% and 7.4%, respectively. Of the 160 revascularized patients, 38% underwent complete revascularization. Acute coronary syndromes were reported in 3.6% of patients (54% with nonobstructive CAD). Cardiac deaths were reported in 1.07% of the population, and only in patients with obstructive CAD. Age, diabetes duration, hypertension, and renal failure were predictors of obstructive CAD, while type 1 diabetes duration, glycated hemoglobin A1c levels, frequent severe hypoglycemia, hypertension, triglyceride levels, renal failure, and cardiac autonomic neuropathy predicted nonobstructive CAD. CONCLUSIONS Nonobstructive CAD was the most frequent coronary complication in patients with type 1 diabetes. Both obstructive and nonobstructive CAD showed a similar incidence of nonfatal outcomes and selected predictors. Positive ETT/SPECT results were related to glycemic control only in patients with nonobstructive CAD.

Introduction Scientific data indicate a possible influence of gut microbiota on the development of type 1 and type 2 diabetes mellitus (T1DM and T2DM, respectively). Sequence analysis of 16S ribosomal RNA identified several hundred bacterial species of the intestinal ecosystem, most of which cannot be cultured. Objectives We aimed to evaluate gut microbiota composition in adult patients with T1DM and T2DM and establish a link between microbiological test results and patients' clinical data. Patients and methods We examined DNA isolated from fecal samples in 3 groups: healthy volunteers (n = 23), patients with T1DM (n = 22), and patients with T2DM (n = 23). Next‑generation sequencing was performed on the MiSeq platform. Results At the phylum level, the Firmicutes bacteria prevailed (>77%) in all groups. At the taxonomic levels L2 (phylum) and L6 (genus), significant differences were demonstrated in bacterial profiles, particularly in the T2DM group. A negative correlation was observed between several genera of bacteria and the percentage of glycated hemoglobin A1c in the T2DM group, while a positive correlation was revealed between bacteria belonging to the genus Bifidobacterium and high‑density lipoprotein cholesterol levels in both T1DM and T2DM groups. Conclusions Our results provide grounds for conducting research in the field of gut microbiota in order to develop individualized therapy for patients with diabetes based on modifying the microbiota composition, as a new method for controlling glycemia. Next‑generation sequencing allows a rapid identification of the DNA of all bacteria present in the sample and their taxonomic classification.

Ectosomes ( Ects ) are a subpopulation of extracellular vesicles formed by the process of plasma membrane shedding. In the present study, we profiled ectosome-specific microRNAs (miRNAs) in patients with type 2 diabetes mellitus (T2DM) and analyzed their pro- and anti-angiogenic potential. Methods: We used different approaches for detecting and enumerating Ects , including atomic force microscopy, cryogenic transmission electron microscopy, and nanoparticle tracking analysis. Furthermore, we used bioinformatics tools to analyze functional data obtained from specific miRNA enrichment signatures during angiogenesis and vasculature development. Results: Levels of miR-193b-3p, miR-199a-3p, miR-20a-3p, miR-26b-5p, miR-30b-5p, miR-30c-5p, miR-374a-5p, miR-409-3p, and miR-95-3p were significantly different between Ects obtained from patients with T2DM and those obtained from healthy controls. Conclusion : Our results showed differences in the abundance of pro- and anti-angiogenic miRNAs in Ects of patients with T2DM, and are suggestive of mechanisms underlying the development of vascular complications due to impaired angiogenesis in such patients., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

Background: Estimated monogenic diabetes (MD) prevalence increases as screening programs proceeds., Objective: To estimate prevalence of MD among Polish children., Subjects: Patients and their family members suspected of suffering from MD (defined as causative mutation in one of the Maturity Onset Diabetes of the Young or permanent neonatal diabetes mellitus genes) were recruited between January 2005 and December 2015., Methods: Nationwide prevalence was estimated based on data from 6 administrative provinces (out of 16 in Poland) with high referral rates of patients (>10 per 100 000 children)., Results: During the analysis, probands from 322 of 788 screened families tested positive yielding a total of 409 children and 299 family members with MD. An average of 70 probands/year were referred. Screening success rate reached 40% over the study period. We estimated the prevalence of MD in 2015 to 7.52/100 000 children (1 in 13 000). The most frequent MODY in this group was GCK- MODY (6.88/100 000). The prevalence estimates increased nearly 2-fold since our report in 2011 (4.4/100 000). However, the figure reached a plateau because of screening saturation in 2014 what was also proven by lowering of the median age of diagnosis lowered in time (R = -0.73, P = .0172) along with shortening of the delay between clinical and genetic diagnosis (R = -0.65, P = .0417)., Conclusions: The screening for childhood MD in Poland reached a plateau phase after 10 years showing a stable prevalence estimate. The true frequency of MD in the overall population may be higher given later onset of reportedly more frequent types of MD than GCK -MODY., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Hypoglycemic syndromes associated with immune reactions against insulin are rare phenomena described predominantly in Asians. Steroid therapy, immunosuppression or plasmapheresis is often required., Case Report: A 73-year-old White woman with a 20-year history of type 2 diabetes was admitted to hospital due to recurrent incidents of hypoglycemia that started several months after insulin initiation (lispro 75/25) and increased in severity over the next 5 years. They were accompanied by postprandial hyperglycemia up to 25 mmol/l. The patient’s glycated hemoglobin (HbA1c) was 70 mmol/ mol (8.6%). During hypoglycemic episodes recorded serum C-peptide was 0.57-0.73 nmol/l (1.7-2.2 ng/ml), while insulin concentration exceeded 7000 pmol/l (1000 mIU/l). Surreptitious insulin administration was ruled out as was, based on diagnostic imaging, the presence of an insulin secreting tumor. Anti-insulin antibody (AIA) level measured by 125I-insulin binding method was 92.5% (normal < 8.2%). Hypoglycemic episodes occurred for four days after discontinuation of insulin therapy and then resolved completely. Good glycemic control was maintained with metformin, acarbose and dapagliflozin. Three months later dapagliflozin was replaced with vildagliptine due to poor tolerance of a SGLT-2 inhibitor. Patient’s HbA1c was 54 mmol/mol (7.1%), total fasting insulin level 2577 pmol/l and AIA binding 85.9%. Over the next year the patient has not experienced hypoglycemia and maintained good glycemic control, as HbA1c level was 53 mmol/l (7.0%) and AIA binding 39.5%., Conclusions: In this rare case of a patient with diabetes and hypoglycemic syndrome related to AIA, we achieved a rapid and stable remission of hypoglycemia without immunosuppression. Good glycemic control, despite 20-year history of diabetes was achieved with oral hypoglycemic agents.

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 follow‑up period was divided into 3 5‑year periods. RESULTS    Differences in the age of patients between the 3 follow‑up 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 rapid‑acting 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 follow‑up.

Patients with familial hypercholesterolemia (FH) are at increased risk of premature cardiovascular disease. We compared factors associated with the presence of carotid plaques and carotid intima-media thickness (cIMT), markers of subclinical atherosclerosis, in 241 patients with FH (98, 40.7% men; mean age 41 ± 18.4 years). Patients with FH having carotid plaques (36.5%) had mean age, apolipoprotein (apo) B, glucose, apoA1, systolic blood pressure (SBP) and diastolic BP, waist/hip ratio (WHR), and body mass index higher than patients without plaques. Logistic regression revealed that apoB (odds ratio [OR] per 1 unit change 1.03,P= .005), high-density lipoprotein cholesterol (HDL-C; OR per 1 standard deviation [SD] change 0.59,P= .015), and non-HDL-C (OR per 1SD change 1.53,P= .04) were significantly associated with the presence of plaques. The cIMT correlated with obesity parameters, BP, apoB, glucose, high-sensitivity C-reactive protein, creatinine, γ-glutamyl transpeptidase, and alanine transaminase (P< .001). Regression analysis revealed that cIMT was significantly associated with apoB, SBP, and WHR. These results confirm the role of apoB-containing lipoproteins and low HDL-C with the presence of carotid plaques and apoB, BP, and WHR with cIMT., (© The Author(s) 2015.)

There is no doubt that behavioral intervention is crucial for type 2 diabetes mellitus (T2DM) prevention and management. We aimed to estimate dietary habits and diet-oriented knowledge as well as the level of physical activity in 2500 insulin-treated Polish type 2 diabetes mellitus (T2DM) patients (55.4% women). The mean age of the study participants was 64.9 ± 9.3 years, mean BMI was 31.4 kg/m 2 ± 4.5, mean diabetes duration was 12.4 ± 6.9 years, and mean baseline HbA1c was 8.5%  ± 1.2. At the study onset, all the patients completed a questionnaire concerning health-oriented behavior. Results showed a significant lack of diet-related knowledge. For example, only 37.5% recognized that buckwheat contains carbohydrates; the percentage of correct answers in questions about fruit drinks and pasta was 56.4% and 61.2%, respectively. As for the physical activity, only 57.4% of examined T2DM patients declared any form of deliberate physical activity. To conclude, the cohort of poorly controlled insulin-treated T2DM patients studied by us is characterized by insufficient diet-related knowledge and by a very low level of physical activity. Further studies on other populations of insulin-treated T2DM patients are required to confirm these findings.

Aims: Diabetes is considered a state of increased oxidative stress. This study evaluates blood concentrations of selected markers of antioxidant defense in patients with type 2 diabetes., Methods: The study included 80 type 2 diabetes patients and 79 apparently healthy controls. Measured markers included ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamyltransferase (GGT) and uric acid serum, and plasma and/or hemolysate levels., Results: FRAP, uric acid, CRP, and GGT levels were significantly higher in patients with diabetes. Plasma and hemolysate GR was significantly higher whereas GPx activity was significantly lower in patients with diabetes. There were no significant differences in antioxidant defense markers between patients with and without chronic diabetes complications. Fasting serum glucose correlated with plasma GPx, plasma and hemolysate GR, FRAP, and serum GGT, and HbA1c correlated with serum GGT. Only FRAP and serum uric acid were significantly higher in obese (BMI > 30 kg/m(2)) patients with diabetes than in nonobese patients., Conclusions: Some components of antioxidant defense such as GR, uric acid, and GGT are increased in patients with type 2 diabetes. However, the whole system cannot compensate for an enhanced production of ROS as reflected by the trend toward decreased erythrocytes GSH.

Introduction: Molecular diagnosis of monogenic diabetes mellitus is important for individualized patient care. Next-generation sequencing (NGS) enables a simultaneous analysis of multiple genes in a single test., Objectives: We aimed to assess the feasibility of using NGS for detecting mutations in a set of known monogenic diabetes gene mutations in a cohort of Polish patients with maturity-onset diabetes of the young (MODY) with earlier negative Sanger sequencing results for HNF1A-MODY or GCK-MODY., Patients and Methods: We selected a panel of 28 chromosomal genes in which mutations have been reported to cause monogenic diabetes. The MiSeq platform was used for NGS. An exon-capture assay was designed to include coding regions and splice sites. A total of 54 patients with existing negative Sanger sequencing screening results for HNF1A or GCK gene mutations were selected for the study., Results: NGS results were generated for all 54 patients and 9 positive controls with previously identified HNF1A or GCK gene mutation. All selected positive controls were confirmed by NGS. Among 28 genes, mutations were detected in 16. The type of the analyzed genetic changes was described in the NGS study as high (n = 3) or moderate (n = 76). Among the detected mutations, there were 4 known GCK gene mutations that had been previously missed in Sanger sequencing. So far, Sanger sequencing allowed us to confirm 21 gene mutations detected by NGS, and segregation with diabetes in 14 pedigrees., Conclusions: Our pilot study using NGS for monogenic diabetes screening in the MODY cohort confirmed that it improves the detection of diabetes-related sequence differences. The screening with NGS should also include diabetic patients for whom Sanger-based screening for particular subtypes of MODY provided negative results.

Introduction: Prandial insulin is a key component in insulin treatment of type 1 diabetes mellitus (T1DM) and in many patients with type 2 diabetes mellitus (T2DM). The evidence-based data supporting the choice of an insulin preparation are still limited., Objectives: We performed a systematic review to summarize and update the evidence on relative efficacy and safety of insulin aspart (IAsp) and regular human insulin (RHI) in both types of diabetes., Methods: Randomized controlled trials comparing IAsp with RHI in patients with either T1DM or T2DM and conducted until May 2013 were retrieved from a systematic search of MEDLINE, EMBASE, and Cochrane Library., Results: Of 16 relevant trials, 11 involved patients with T1DM and 5--with T2DM. In the T1DM population, IAsp, when compared with RHI, provided a greater reduction in hemoglobin A₁c (HbA₁c) levels (weighted mean difference [WMD], -0.11%; 95% confidence interval [CI], -0.16 to -0.05; WMD, -1.2 mmol/mol; 95% CI, -1.7 to -0.5), and improved postprandial glucose levels following breakfast (WMD, -1.40 mmol/l; 95% CI, -1.72 to -1.07), lunch (WMD, -1.01 mmol/l; 95% CI, -1.61 to -0.41), and dinner (WMD, -0.89 mmol/l; 95% CI, -1.19 to -0.59). The risk of nocturnal hypoglycemia was lower in T1DM patients receiving IAsp (relative risk, 0.76; 95% CI, 0.64-0.91), while no difference was observed for severe hypoglycemia. In T2DM patients, IAsp led to a greater reduction in HbA₁c levels (WMD, -0.22%; 95% CI, -0.39 to -0.05; -2.4 mmol/mol, -4.3 to -0.5) and postprandial blood glucose. The risk of overall hypoglycemia and severe adverse effects was comparable between the groups., Conclusions: IAsp provides better glycemic control when compared with RHI in patients with T1DM and T2DM. Fewer T1DM patients treated with IAsp experienced nocturnal hypoglycemia, while both interventions showed a comparable risk of severe hypoglycemic events in both types of diabetes.

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.

Aims/introduction: Type 2 diabetes is often complicated by diabetic foot syndrome (DFS). We analyzed the circulating stem cells, growth factor and anti-oxidant gene expression profiles in type 2 diabetes patients without or with different forms of DFS., Materials and Methods: Healthy volunteers (n = 13) and type 2 diabetes patients: (i) without DFS (n = 10); or with (ii) Charcot osteoneuropathy (n = 10); (iii) non-infected (n = 17); (iv) infected (n = 11); and (v) healed ulceration were examined (n = 12). Peripheral blood endothelial progenitor cells (EPC), mesenchymal stem cells (MSC), hematopoietic stem cells (HSC) and very small embryonic-like (VSEL) cells were phenotyped using flow cytometry. Plasma cytokine concentrations and gene expressions in blood cells were measured by Luminex and quantitative real-time polymerase chain reaction assays, respectively., Results: Patients with non-complicated type 2 diabetes showed reduced HMOX1 expression, accompanied by HMOX2 upregulation, and had less circulating EPC, MSC or HSC than healthy subjects. In contrast, VSEL cells were elevated in the type 2 diabetes group. However, subjects with DFS, even with healed ulceration, had fewer VSEL cells, more CD45-CD29(+)CD90(+)MSC, and upregulated HMOX1 when compared with the type 2 diabetes group. Patients with Charcot osteopathy had lowered plasma fibroblast growth factor-2. Elevated plasma tumor necrosis factor-α and decreased catalase expression was found in all diabetic patients., Conclusions: Patients with type 2 diabetes and different forms of DFS have an altered number of circulating stem cells. Type 2 diabetes might also be associated with a changed plasma growth factor and anti-oxidant gene expression profile. Altogether, these factors could contribute to the pathogenesis of different forms of DFS.

Background: There is evidence that nonalcoholic fatty liver disease (NAFLD) is associated with increased cardiovascular risk. In this study we examined factors associated with the presence of NAFLD and the prevalence of macroangiopathy in patients with type 2 diabetes., Material and Methods: Subjects were 101 consecutive patients with type 2 diabetes: 72 with NAFLD and 29 free of NAFLD. NAFLD was diagnosed by ultrasonography. Serum lipids were measured enzymatically and glycated hemoglobin HbA1c was measured by HPLC., Results: The mean age of patients was 53.1 ± 10.4 in the NAFLD group and 44.9 ± 10.9 years in patients without NAFLD (p<0.001). The mean duration of diabetes was 10 ± 6.3 years in patients with NAFLD and 15.1 ± 7.8 years in those without NAFLD (p<0.001). Mean values of glycated hemoglobin A1c were similar in both groups. Patients with NAFLD were characterized by a significantly higher prevalence of coronary angioplasty (20.8% vs. 0%, p=0.008). Overweight and obesity were observed in a higher percentage of patients with NAFLD (p<0.001). Patients with NAFLD were characterized by significantly higher values of alanine transaminase (p=0.033), and lower serum concentrations of HDL-cholesterol (p<0.001) and creatinine (p=0.034). Logistic regression analysis (p<0.001) revealed that NAFLD was positively associated with waist circumference above normal (women >80 cm, men >94 cm) (p=0.0083) and alanine transaminase activity (p=0.0164), and negatively with creatinine concentration (p=0.0226). In a second logistic regression model (p<0.001), waist circumference (p<0.007) and total cholesterol (p<0.008) were positive predictors, while HDL-C (p<0.003) was a negative predictor of NAFLD., Conclusions: The results of the study suggest that NAFLD is associated with visceral obesity and low HDL-cholesterol in patients with type 2 diabetes.

The prevalence of all types of diabetes mellitus is increasing worldwide. Diabetes is a common metabolic complication of pregnancy. For many years, pregnancy complicated by type 1 diabetes was associated with a particularly poor prognosis, and while this has changed dramatically over the last 2 decades, a lot has yet to be done. The continuous relationship between the maternal glucose level and the prevalence of pregnancy complications is well‑documented. The list of outcomes includes congenital malformations, stillbirths, neonatal mortality, macrosomia, hypoglycemia, and many others. Several new therapeutic and monitoring tools have become available over the recent years, for example, short- and long‑acting insulin analogs, personal pumps, and continuous glucose monitoring systems. Interestingly, pregnancy planning and preconception education proved to be particularly effective in improving glycemic control in type 1 diabetic women and achieving therapeutic goals recommended by clinical guidelines. This resulted in the reduction of some maternal and neonatal pregnancy outcomes reported from various populations, but despite this remarkable progress the prevalence of the most common complication, neonatal macrosomia, is still substantially higher than in the newborns of mothers without diabetes. The likely causes of this phenomenon are short episodes of hyperglycemia, particularly postprandial ones, liberal diet, maternal obesity, and substantial weight gain during pregnancy - these potential reasons should be addressed in clinical practice. In the future, new therapeutic devices, such as close‑loop insulin pumps, may help further improve the prognosis in pregnant women with type 1 diabetes.

Introduction and Objective: The ability to perceive the symptoms of hypoglycemia during the early decrease in plasma glucose concentration may be critical for the safety of T1DM patients treated with intensive insulin therapy, including those treated with continuous subcutaneous insulin infusion (CSII). In the presented observational study an attempt was made to asses clinical factors that might affect subjective awareness of hypoglycemia in CSII-treated T1DM patients, with special attention to factors specific for this mode of treatment., Materials and Methods: For the purpose of the study, data of 110 CSII-treated T1DM patients were collected (78 females and 32 males). The records were analyzed from glucose meters (200-300 measurements/download, depending on meter type) and insulin pumps (total insulin dose, basal/bolus ratio, number of boluses/day, bolus calculator and dual wave/square bolus usage, continuous glucose monitoring data) from the last 3 years., Results: It was found that the level of subjective hypoglycemia perception inversely correlated with the number of hypoglycemic episodes per 100 measurements, age, duration of diabetes, time on insulin pump, and positively correlated with mean glycemia (n = 98; r = 0.22; p = 0.0286). With respect to CSII-related factors, hypoglycemia perception inversely correlated with the percentage of basal insulin (n = 106; r = -0.20; p = 0.0354). In stepwise regression analysis, independent predictors for impaired hypoglycemia perception were: age β = -0.29 (p = 0.023), duration of diabetes β = -0.24 (p = 0.029) and number of the hypoglycemia episodes for 100 measurements β = -0.33 (p = 0.0005)., Conclusions: Risk factors for impaired hypoglycemia perception in CSII-treated patients include those identified previously for the general population of T1DM individuals. In addition, the presented results suggest that a higher basal/bolus ratio may lead to impairment of the ability to perceive early symptoms of hypoglycemia.

Aims: Recently, an association between two polymorphisms (1181G>C and 245T>G) of the osteoprotegerin (OPG) gene and diabetic Charcot neuroarthropathy was suggested on the basis of studies of a limited number of samples derived from subjects from one geographical region (Italy). The aim of this study was to assess the presence of various osteoprotegerin gene polymorphisms in patients with diabetes and Charcot neuroarthropathy compared with subjects with diabetic neuropathy but no Charcot foot and healthy controls from another geographical region (Poland)., Methods: DNA was isolated from 54 patients with Charcot neuroarthropathy, 35 subjects with diabetic neuropathy but no Charcot foot, and 95 healthy controls to evaluate OPG gene polymorphisms and their possible contribution to the development of Charcot neuroarthropathy., Results: Statistically significant differences between the group of subjects with neuropathy but no Charcot neuroarthropathy and the control group were found for 1217C>T, 950T>C and 245T>G polymorphisms, between the group of patients with Charcot neuroarthropathy and the control group for 1181G>C and 950T>C polymorphisms, and between the group of subjects with neuropathy but no Charcot neuroarthropathy and the group of patients with Charcot neuroarthropathy for 1217C>T and 245T>G polymorphisms., Conclusion: We suggest that genetic factors, particularly OPG gene polymorphisms, may play a role in the development of diabetic Charcot neuroarthropathy., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

The purpose of this investigation was to characterize a new mutation in the LDL-receptor (LDLR) gene in three families with clinically diagnosed familial hypercholesterolemia (FH) from the South-Eastern part of Poland. Mutational screening with exon by exon sequencing analysis was performed in all probands. The novel mutation c986G>T (Cys308Phe) in the exon 7 of LDLR gene was found in three apparently unrelated probands with FH. Analysis of the receptor activity of peripheral blood lymphocytes by binding and uptake of DiL-LDL showed a significant reduction (by 24% versus healthy control) of the fluorescent label in the lymphocytes of patients heterozygous for this mutation. Concentrations of serum LDL-C in probands before treatment were between 9.5 and 10.5 mmol/l. All patients had corneal arcus and tendon xanthoma. Clinically, families were characterized by premature coronary artery disease. This mutation occurred relatively frequently in our group of patients with FH, but this could be explained by a founder effect since we demonstrated their common ancestors.

Introduction and Objective: Continuous subcutaneous insulin infusion (CSII) via personal insulin pump is a valuable therapeutic tool in T1DM patients. However, adherence to recommended CSII-related behaviours may be of concern to young adults with intensive, variable daily activities (students, young professionals). The aim of this observational study was to estimate treatment outcomes in young adult patients with T1DM, and compare them with older individuals., Materials and Methods: Overall, 140 adults with T1DM on CSII were examined, divided into 2 subgroups: 77 patients younger than 26 years of age (mean 20.6 years) and 63 older subjects (mean 39.0). We compared the glycaemic control in both groups of T1DM subjects and analyzed treatment attitudes to identify potentially modifiable behaviours influencing the efficacy of the treatment., Results: The younger individuals were characterized by significantly worse treatment outcomes, compared to the older ones: the mean HbA1c levels were 7.6 ± 1.3% and 6.9±1.3% (p=0.00001), while the mean glucose levels based on glucometer downloads were 161±33.6 mg/dL and 136±21.8 mg/dL (p=0.00001), respectively. The frequency of self-monitoring of blood glucose (SMBG) was lower in younger individuals (5.3±2.1 vs. 7.0±2.8 daily, p=0.0005, respectively); they were also less frequently used advanced pump functions, e.g. the bolus calculator (48% vs. 67% users, p=0.0014, respectively)., Conclusions: The efficacy of CSII treatment observed in young T1DM adults was worse than in older patients. The reason for this phenomenon remains unclear, it may be due simply to age-dependend behaviours, to social environment, or both.