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Dr. Lukasz Szczerbinski
Clinical Research Centre; Medical University of Bialystok

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0 Bariatric Surgery
0 Diabetes
0 Diet
0 Endocrinology
0 Genetics

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Diabetes
Bariatric Surgery
Obesity
Genetics
Insulin Resistance
physical activity

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Journal article
Published: 07 August 2021 in Vaccines
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Since the declaration of the SARS-CoV-2 pandemic confirmed by World Health Organization, work on the development of vaccines has been stimulated. When vaccines are commonly available, a major problem is persistent vaccine hesitancy in many European countries. The main goal of our study was to understand the multidimensional factors inducing this phenomenon in Poland. Our study was carried out at the third wave’s peak of the pandemic, with record rates of daily cases and deaths associated with COVID-19. The results indicate that vaccine hesitancy/acceptability should always be considered in an interdisciplinary manner and according to identified factors where most negative attitudes could be altered. Our analyses included the assessment of a representative quota sample of adult Poles (N = 1000). The vaccine hesitancy in the studied group reached 49.2%. We performed stepwise logistic regression modeling to analyze variables set into six trajectories (groups) predicting the willingness to vaccinate. Apart from typical, socio-demographic and economic determinants, we identified the fear of vaccines’ side effects, beliefs in conspiracy theories and physical fitness. We were also able to establish the order of importance of factors used in a full model of all impact trajectories.

ACS Style

Paweł Sowa; Łukasz Kiszkiel; Piotr Laskowski; Maciej Alimowski; Łukasz Szczerbiński; Marlena Paniczko; Anna Moniuszko-Malinowska; Karol Kamiński. COVID-19 Vaccine Hesitancy in Poland—Multifactorial Impact Trajectories. Vaccines 2021, 9, 876 .

AMA Style

Paweł Sowa, Łukasz Kiszkiel, Piotr Laskowski, Maciej Alimowski, Łukasz Szczerbiński, Marlena Paniczko, Anna Moniuszko-Malinowska, Karol Kamiński. COVID-19 Vaccine Hesitancy in Poland—Multifactorial Impact Trajectories. Vaccines. 2021; 9 (8):876.

Chicago/Turabian Style

Paweł Sowa; Łukasz Kiszkiel; Piotr Laskowski; Maciej Alimowski; Łukasz Szczerbiński; Marlena Paniczko; Anna Moniuszko-Malinowska; Karol Kamiński. 2021. "COVID-19 Vaccine Hesitancy in Poland—Multifactorial Impact Trajectories." Vaccines 9, no. 8: 876.

Preprint content
Published: 16 July 2021
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Skeletal muscle fiber composition and capillary density influence physical performance and whole-body metabolic properties. ~45% of the variance in fiber type is heritable, which motivated us to perform a genome-wide association study of skeletal muscle histology from 656 Swedish men. Four independent variants were associated (p < 5x10− 8) with proportion of type IIx fibers or capillary-to-fiber ratio (C:F). The strongest signal localized to the rs115660502 variant, where the G-allele corresponded with increased C:F and reduced skeletal muscle expression of the proximal gene, RAB3 GTPase Activating Non-Catalytic Protein Subunit 2 (RAB3GAP2). The G-allele was less frequent in elite short-track sprinters and more frequent in endurance athletes than in matched non-athlete (population) controls; RAB3GAP2 expression was reduced by high-intensity intermittent training. RAB3GAP2 protein was not uniformly expressed in muscle tissue but localized to the endothelium and capillaries. Experimental reduction of RAB3GAP2 in human endothelial cells led to increased tube formation in vitro, to regulation of secreted factors promoting angiogenesis and T-cell activation, to reduced intracellular levels of von Willebrand factor (VWF) and, post-implantation, to increased endothelial cell density in vivo in mice. The amount of RAB3GAP2 in skeletal muscle was positively associated with exercise-induced release of VWF in vivo in humans. By regulating the release of protein factors (VWF, CD70, TNC, TNXB, MCP1, IGFBP3, COL1A1, TFPI2 and tPA), RAB3GAP2 influences fitness adaptation after exercise by improving muscle healing and promotion of capillary formation.

ACS Style

Kristoffer Ström; Nikolay Oskolkov; Tugce Karaderi; Sebastian Kalamajski; Ola Ekström; Eri Miyamoto-Mikami; Claes Ladenvall; Ellen Kakulidis; Steven Reid; Anna-Maria Dutius Andersson; Dmytro Kryvokhyzha; Enming Zhang; João Fadista; Motoyuki Iemitsu; Anubha Mahajan; Emma Ahlqvist; Rashmi Prasad; Kay Pruefer; Maria Sabater-Lleal; Nicholas Smith; Abbas Abbas Dehghan; Lars Lind; Kerry McGawley; Andrew Morris; Mikko Lehtovirta; Łukasz Szczerbiński; Adam Kretowski; Guan Wang; Yannis Pitsiladis; Alejandro Santos-Lozano; Alejandro Lucia; Noriyuku Fuku; Hans-Christer Holmberg; Leif Groop; Maria Gomez; Karl-Fredrik Eriksson; Kristian Pietras; Cecilia Lindgren; Paul Franks; Ola Hansson. Genetic variation at RAB3GAP2 and its role in exercise-related adaptation and recovery. 2021, 1 .

AMA Style

Kristoffer Ström, Nikolay Oskolkov, Tugce Karaderi, Sebastian Kalamajski, Ola Ekström, Eri Miyamoto-Mikami, Claes Ladenvall, Ellen Kakulidis, Steven Reid, Anna-Maria Dutius Andersson, Dmytro Kryvokhyzha, Enming Zhang, João Fadista, Motoyuki Iemitsu, Anubha Mahajan, Emma Ahlqvist, Rashmi Prasad, Kay Pruefer, Maria Sabater-Lleal, Nicholas Smith, Abbas Abbas Dehghan, Lars Lind, Kerry McGawley, Andrew Morris, Mikko Lehtovirta, Łukasz Szczerbiński, Adam Kretowski, Guan Wang, Yannis Pitsiladis, Alejandro Santos-Lozano, Alejandro Lucia, Noriyuku Fuku, Hans-Christer Holmberg, Leif Groop, Maria Gomez, Karl-Fredrik Eriksson, Kristian Pietras, Cecilia Lindgren, Paul Franks, Ola Hansson. Genetic variation at RAB3GAP2 and its role in exercise-related adaptation and recovery. . 2021; ():1.

Chicago/Turabian Style

Kristoffer Ström; Nikolay Oskolkov; Tugce Karaderi; Sebastian Kalamajski; Ola Ekström; Eri Miyamoto-Mikami; Claes Ladenvall; Ellen Kakulidis; Steven Reid; Anna-Maria Dutius Andersson; Dmytro Kryvokhyzha; Enming Zhang; João Fadista; Motoyuki Iemitsu; Anubha Mahajan; Emma Ahlqvist; Rashmi Prasad; Kay Pruefer; Maria Sabater-Lleal; Nicholas Smith; Abbas Abbas Dehghan; Lars Lind; Kerry McGawley; Andrew Morris; Mikko Lehtovirta; Łukasz Szczerbiński; Adam Kretowski; Guan Wang; Yannis Pitsiladis; Alejandro Santos-Lozano; Alejandro Lucia; Noriyuku Fuku; Hans-Christer Holmberg; Leif Groop; Maria Gomez; Karl-Fredrik Eriksson; Kristian Pietras; Cecilia Lindgren; Paul Franks; Ola Hansson. 2021. "Genetic variation at RAB3GAP2 and its role in exercise-related adaptation and recovery." , no. : 1.

Journal article
Published: 26 October 2020 in Diabetes
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There is a limited understanding of how genetic loci associated with glycemic traits and type 2 diabetes (T2D) influence the response to antidiabetic medications. Polygenic scores provide increasing power to detect patterns of disease predisposition that might benefit from a targeted pharmacologic intervention. In the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH), we constructed weighted polygenic scores using known genome-wide significant associations for T2D, fasting glucose, and fasting insulin, comprising 65, 43, and 13 single nucleotide polymorphisms, respectively. Multiple linear regression tested for associations between scores and glycemic traits as well as pharmacodynamic end points, adjusting for age, sex, race, and BMI. A higher T2D score was nominally associated with a shorter time to insulin peak, greater glucose area over the curve, shorter time to glucose trough, and steeper slope to glucose trough after glipizide. In replication, a higher T2D score was associated with a greater 1-year hemoglobin A1c reduction to sulfonylureas in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) study (P = 0.02). Our findings suggest that individuals with a higher genetic burden for T2D experience a greater acute and sustained response to sulfonylureas.

ACS Style

Josephine H. Li; Lukasz Szczerbinski; Adem Y. Dawed; Varinderpal Kaur; Jennifer N. Todd; Ewan R. Pearson; Jose C. Florez. A Polygenic Score for Type 2 Diabetes Risk Is Associated With Both the Acute and Sustained Response to Sulfonylureas. Diabetes 2020, 70, 293 -300.

AMA Style

Josephine H. Li, Lukasz Szczerbinski, Adem Y. Dawed, Varinderpal Kaur, Jennifer N. Todd, Ewan R. Pearson, Jose C. Florez. A Polygenic Score for Type 2 Diabetes Risk Is Associated With Both the Acute and Sustained Response to Sulfonylureas. Diabetes. 2020; 70 (1):293-300.

Chicago/Turabian Style

Josephine H. Li; Lukasz Szczerbinski; Adem Y. Dawed; Varinderpal Kaur; Jennifer N. Todd; Ewan R. Pearson; Jose C. Florez. 2020. "A Polygenic Score for Type 2 Diabetes Risk Is Associated With Both the Acute and Sustained Response to Sulfonylureas." Diabetes 70, no. 1: 293-300.

Journal article
Published: 10 July 2020 in Journal of Clinical Medicine
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Due to a global increase in the prevalence of type 2 diabetes mellitus (T2DM), there is an urgent need for early identification of prediabetes, as these people have the highest risk of developing diabetes. Circulating miRNAs have shown potential as progression biomarkers in other diseases. This study aimed to conduct a baseline comparison of serum-circulating miRNAs in prediabetic individuals, with the distinction between those who later progressed to T2DM and those who did not. The expression levels of 798 miRNAs using NanoString technology were examined. Spearman correlation, receiver operating characteristic (ROC) curve analysis, and logistic regression modeling were performed. Gene ontology (GO) and canonical pathway analysis were used to explore the biological functions of the miRNA target genes. The study revealed that three miRNAs were upregulated in the serum samples of patients who later progressed to T2DM. Pathway analysis showed that the miRNA target genes were mainly significantly enriched in neuronal NO synthase (nNOS) signaling in neurons, amyloid processing, and hepatic cholestasis. ROC analysis demonstrated that miR-491-5p, miR-1307-3p, and miR-298 can be introduced as a diagnostic tool for the prediction of T2DM (area under the curve (AUC) = 94.0%, 88.0%, and 84.0%, respectively). Validation by real-time quantitative polymerase chain reaction (qRT-PCR) confirmed our findings. The results suggest that circulating miRNAs can potentially be used as predictive biomarkers of T2DM in prediabetic patients.

ACS Style

Iwona Sidorkiewicz; Magdalena Niemira; Katarzyna Maliszewska; Anna Erol; Agnieszka Bielska; Anna Szalkowska; Edyta Adamska-Patruno; Lukasz Szczerbinski; Maria Gorska; Adam Kretowski. Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study. Journal of Clinical Medicine 2020, 9, 2184 .

AMA Style

Iwona Sidorkiewicz, Magdalena Niemira, Katarzyna Maliszewska, Anna Erol, Agnieszka Bielska, Anna Szalkowska, Edyta Adamska-Patruno, Lukasz Szczerbinski, Maria Gorska, Adam Kretowski. Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study. Journal of Clinical Medicine. 2020; 9 (7):2184.

Chicago/Turabian Style

Iwona Sidorkiewicz; Magdalena Niemira; Katarzyna Maliszewska; Anna Erol; Agnieszka Bielska; Anna Szalkowska; Edyta Adamska-Patruno; Lukasz Szczerbinski; Maria Gorska; Adam Kretowski. 2020. "Circulating miRNAs as a Predictive Biomarker of the Progression from Prediabetes to Diabetes: Outcomes of a 5-Year Prospective Observational Study." Journal of Clinical Medicine 9, no. 7: 2184.

Journal article
Published: 20 February 2020 in International Journal of Molecular Sciences
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Multiple mechanisms have been suggested to confer to the pathophysiology of metabolic syndrome (MetS), however despite great interest from the scientific community, the exact contribution of each of MetS risk factors still remains unclear. The present study aimed to investigate molecular signatures in peripheral blood of individuals affected by MetS and different degrees of obesity. Metabolic health of 1204 individuals from 1000PLUS cohort was assessed, and 32 subjects were recruited to four study groups: MetS lean, MetS obese, “healthy obese”, and healthy lean. Whole-blood transcriptome next generation sequencing with functional data analysis were carried out. MetS obese and MetS lean study participants showed the upregulation of genes involved in inflammation and coagulation processes: granulocyte adhesion and diapedesis (p < 0.0001, p = 0.0063), prothrombin activation pathway (p = 0.0032, p = 0.0091), coagulation system (p = 0.0010, p = 0.0155). The results for “healthy obese” indicate enrichment in molecules associated with protein synthesis (p < 0.0001), mitochondrial dysfunction (p < 0.0001), and oxidative phosphorylation (p < 0.0001). Our results suggest that MetS is related to the state of inflammation and vascular system changes independent of excess body weight. Furthermore, “healthy obese”, despite not fulfilling the criteria for MetS diagnosis, seems to display an intermediate state with a lower degree of metabolic abnormalities, before they proceed to a full blown MetS.

ACS Style

Magdalena Paczkowska-Abdulsalam; Magdalena Niemira; Agnieszka Bielska; Anna Szałkowska; Beata Anna Raczkowska; Sini Junttila; Attila Gyenesei; Edyta Adamska-Patruno; Katarzyna Maliszewska; Anna Citko; Łukasz Szczerbiński; Adam Krętowski. Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects. International Journal of Molecular Sciences 2020, 21, 1455 .

AMA Style

Magdalena Paczkowska-Abdulsalam, Magdalena Niemira, Agnieszka Bielska, Anna Szałkowska, Beata Anna Raczkowska, Sini Junttila, Attila Gyenesei, Edyta Adamska-Patruno, Katarzyna Maliszewska, Anna Citko, Łukasz Szczerbiński, Adam Krętowski. Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects. International Journal of Molecular Sciences. 2020; 21 (4):1455.

Chicago/Turabian Style

Magdalena Paczkowska-Abdulsalam; Magdalena Niemira; Agnieszka Bielska; Anna Szałkowska; Beata Anna Raczkowska; Sini Junttila; Attila Gyenesei; Edyta Adamska-Patruno; Katarzyna Maliszewska; Anna Citko; Łukasz Szczerbiński; Adam Krętowski. 2020. "Evaluation of Transcriptomic Regulations behind Metabolic Syndrome in Obese and Lean Subjects." International Journal of Molecular Sciences 21, no. 4: 1455.

Journal article
Published: 12 December 2019 in Journal of Clinical Medicine
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The liver plays a central role in the glucose and lipid metabolism. Studies performed on animal models have shown an important role of lipid accumulation in the induction of insulin resistance. We sought to explain whether in obese humans, the insulin resistance is associated with hepatic ceramide accumulation. The experiments were conducted on obese men and women. Each gender was divided into three groups: Normal glucose tolerance group (NGT), Impaired glucose tolerance group (IGT), and Type 2 diabetic subjects (T2D). Ceramide (Cer) content was analyzed with the use of LC/MS/MS. An oral glucose tolerance test (OGTT), glycosylated hemoglobin (HbA1c), percentage body fat (FAT%), and body mass index (BMI) was also measured. Total hepatic ceramide was significantly higher in T2D females as compared to NGT females (p < 0.05), whereas in males, total ceramide was significantly higher in IGT and T2D as compared to NGT (p < 0.05). In both, men and women, the highest increase in T2D subjects, was observed in C16:0-Cer, C18:0:-Cer, C22:0-Cer, and C24:0-Cer (p < 0.05) as compared to NGT group. Interestingly, glucose (at 0′ and at 120′ in OGTT) and HbA1c positively correlated with the ceramide species that most increased in T2D patients (C16:0-Cer, C18:0-Cer, C22:0-Cer, and C24:0-Cer). In men glucose and HbA1c significantly correlated with only C22:0-Cer. This is one of the few studies comparing hepatic ceramide content in severely obese patients. We found that, ceramide content increased in diabetic patients, both in men and women, and the content of ceramide correlated with glycemic parameters. These data indicate ceramide contribution to the induction of hepatic insulin resistance.

ACS Style

Hady Razak Hady; Agnieszka U. Błachnio-Zabielska; Łukasz Szczerbiński; Piotr Zabielski; Monika Imierska; Jacek Dadan; Adam J. Krętowski. Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients. Journal of Clinical Medicine 2019, 8, 2197 .

AMA Style

Hady Razak Hady, Agnieszka U. Błachnio-Zabielska, Łukasz Szczerbiński, Piotr Zabielski, Monika Imierska, Jacek Dadan, Adam J. Krętowski. Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients. Journal of Clinical Medicine. 2019; 8 (12):2197.

Chicago/Turabian Style

Hady Razak Hady; Agnieszka U. Błachnio-Zabielska; Łukasz Szczerbiński; Piotr Zabielski; Monika Imierska; Jacek Dadan; Adam J. Krętowski. 2019. "Ceramide Content in Liver Increases Along with Insulin Resistance in Obese Patients." Journal of Clinical Medicine 8, no. 12: 2197.

Comparative study
Published: 09 October 2019 in Nutrients
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Bariatric surgery rapidly and effectively treats obesity and its comorbidities like dysregulated glucose homeostasis. Despite the sex-balanced incidence of obesity in most human populations, women have sought this intervention more frequently than men. However, as the number of bariatric surgeries rapidly rises, it is increasingly urgent to understand how sex-specific differences may emerge in metabolic and anthropometric parameters. Hundred fifty-four obese patients (47% men and 53% women) from the Bialystok Bariatric Surgery Study underwent sleeve gastrectomy and were measured for 25 parameters at baseline (immediately prior to surgery) and at four follow-up visits over one year. We used generalized linear mixed models to detect sex-specific differences in the time series of responses parameters. Unlike most previous studies with older cross-sections of men than women, our cohort was age-matched, and men were less healthy at baseline. Of parameters that showed a significant cohort-wide (across-sex) response, 14 (56%) also showed sex-specific responses with men improving more than women. In particular, men remitted in diabetes symptoms more strongly, rapidly, and durably than women. Taken together, our results indicate that men may benefit more from sleeve gastrectomy and that this difference in improvement may be related to more progressed morbidity prior to surgery independent of age.

ACS Style

Mark A. Taylor; Lukasz Szczerbinski; Anna Citko; Magdalena Niemira; Maria Gorska; Hady Razak Hady; Adam Kretowski. Sex-Specific Glucose Homeostasis and Anthropometric Responses to Sleeve Gastrectomy in Obese Patients. Nutrients 2019, 11, 2408 .

AMA Style

Mark A. Taylor, Lukasz Szczerbinski, Anna Citko, Magdalena Niemira, Maria Gorska, Hady Razak Hady, Adam Kretowski. Sex-Specific Glucose Homeostasis and Anthropometric Responses to Sleeve Gastrectomy in Obese Patients. Nutrients. 2019; 11 (10):2408.

Chicago/Turabian Style

Mark A. Taylor; Lukasz Szczerbinski; Anna Citko; Magdalena Niemira; Maria Gorska; Hady Razak Hady; Adam Kretowski. 2019. "Sex-Specific Glucose Homeostasis and Anthropometric Responses to Sleeve Gastrectomy in Obese Patients." Nutrients 11, no. 10: 2408.

Review
Published: 15 August 2019 in Journal of Clinical Medicine
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Bariatric surgery is an efficient treatment for weight loss in obese patients and for resolving obesity comorbidities. However, the mechanisms behind these outcomes are unclear. Recent studies have indicated significant alterations in the transcriptome after surgery, specifically in the differential expression of microRNAs. In order to summarize the recent findings, we conducted a systematic summary of studies comparing microRNA expression levels before and after surgery. We identified 17 animal model and human studies from four databases (Ovid, Scopus, Web of Science, and PubMed) to be enrolled in this meta-analysis. From these studies, we identified 14 miRNAs which had the same direction of modulation of their expression after surgery in at least two studies (downregulated: hsa-miR-93-5p, hsa-miR-106b-5p, hsa-let-7b-5p, hsa-let-7i-5p, hsa-miR-16-5p, hsa-miR-19b-3p, hsa-miR-92a-3p, hsa-miR-222-3p, hsa-miR-142-3p, hsa-miR-140-5p, hsa-miR-155-5p, rno-miR-320-3p; upregulated: hsa-miR-7-5p, hsa-miR-320c). Pathway analysis for these miRNAs was done using database resources (DIANA-TarBase and KEGG pathway database) and their predicted target genes were discussed in relation with obesity and its comorbidities. Discrepancies in study design, such as miRNA source, bariatric surgery type, time of observation after surgery, and miRNA profiling methods, were also discussed.

ACS Style

Gladys Langi; Lukasz Szczerbinski; Adam Kretowski. Meta-Analysis of Differential miRNA Expression after Bariatric Surgery. Journal of Clinical Medicine 2019, 8, 1220 .

AMA Style

Gladys Langi, Lukasz Szczerbinski, Adam Kretowski. Meta-Analysis of Differential miRNA Expression after Bariatric Surgery. Journal of Clinical Medicine. 2019; 8 (8):1220.

Chicago/Turabian Style

Gladys Langi; Lukasz Szczerbinski; Adam Kretowski. 2019. "Meta-Analysis of Differential miRNA Expression after Bariatric Surgery." Journal of Clinical Medicine 8, no. 8: 1220.

Journal article
Published: 24 July 2019 in Journal of Clinical Medicine
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Glycemic responses to bariatric surgery are highly heterogeneous among patients and defining response types remains challenging. Recently developed data-driven clustering methods have uncovered subtle pathophysiologically informative patterns among patients without diabetes. This study aimed to explain responses among patients with and without diabetes to bariatric surgery with clusters of glucose concentration during oral glucose tolerance tests (OGTTs). We assessed 30 parameters at baseline and at four subsequent follow-up visits over one year on 154 participants in the Bialystok Bariatric Surgery Study. We applied latent trajectory classification to OGTTs and multinomial regression and generalized linear mixed models to explain differential responses among clusters. OGTT trajectories created four clusters representing increasing dysglycemias that were discordant from standard diabetes diagnosis criteria. The baseline OGTT cluster increased the predictive power of regression models by over 31% and aided in correctly predicting more than 83% of diabetes remissions. Principal component analysis showed that the glucose homeostasis response primarily occurred as improved insulin sensitivity concomitant with improved the OGTT cluster. In sum, OGTT clustering explained multiple, correlated responses to metabolic surgery. The OGTT is an intuitive and easy-to-implement index of improvement that stratifies patients into response types, a vital first step in personalizing diabetic care in obese subjects.

ACS Style

Lukasz Szczerbinski; Mark A. Taylor; Anna Citko; Maria Gorska; Steen Larsen; Hady Razak Hady; Adam Kretowski. Clusters of Glycemic Response to Oral Glucose Tolerance Tests Explain Multivariate Metabolic and Anthropometric Outcomes of Bariatric Surgery in Obese Patients. Journal of Clinical Medicine 2019, 8, 1091 .

AMA Style

Lukasz Szczerbinski, Mark A. Taylor, Anna Citko, Maria Gorska, Steen Larsen, Hady Razak Hady, Adam Kretowski. Clusters of Glycemic Response to Oral Glucose Tolerance Tests Explain Multivariate Metabolic and Anthropometric Outcomes of Bariatric Surgery in Obese Patients. Journal of Clinical Medicine. 2019; 8 (8):1091.

Chicago/Turabian Style

Lukasz Szczerbinski; Mark A. Taylor; Anna Citko; Maria Gorska; Steen Larsen; Hady Razak Hady; Adam Kretowski. 2019. "Clusters of Glycemic Response to Oral Glucose Tolerance Tests Explain Multivariate Metabolic and Anthropometric Outcomes of Bariatric Surgery in Obese Patients." Journal of Clinical Medicine 8, no. 8: 1091.

Journal article
Published: 06 June 2019 in Polish Archives of Internal Medicine
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Environmental and genetic factors play an important role in the development of type 2 diabetes (T2D). One of the most important lifestyle factors is a low level of physical activity (PA), but no studies have explicitly compared the amount of variation in diabetes prevalence explained by variation in PA compared with the amount explained by genetic variation. We examined associations between PA and patients stratified by the levels of genetic susceptibility to T2D and the prevalence of the disease. We assessed the level of PA and family history (FH) of T2D in first‑degree relatives as well as calculated the genetic risk score (GRS). We examined associations of PA, GRS, and FH with the prevalence of T2D among 1195 individuals enrolled in the 1000 Polish Longitudinal University Study (1000‑PLUS) by stratifying the sample according to GRS, FH, and PA. We found that FH, in contrast to GRS, was positively associated with a higher prevalence of T2D (23.4% in patients with positive FH [FH+], 11.6% in those with negative [FH-]; P <0.001), with the association being stronger in men than in women. The prevalence of T2D was slightly lower among physically active individuals in the FH- group (10.6% in high PA vs 14.7% in low PA) as well as in the FH+ group (19.2% in high PA vs 34.0% in low PA), but the differences were not significant. Similar results were found for high and low GRSs. We confirmed that PA is significantly associated with glucose homeostasis parameters and T2D prevalence, and that this association may be stronger in individuals who are more genetically predisposed to diabetes.

ACS Style

Lukasz Szczerbinski; Joanna Goscik; Witold Bauer; Natalia Wawrusiewicz-Kurylonek; Magdalena Paczkowska-Abdulsalam; Magdalena Niemira; Anna Citko; Edyta Adamska-Patruno; Maria Gorska; Adam Kretowski. Efficacy of family history, genetic risk score, and physical activity in assessing the prevalence of type 2 diabetes. Polish Archives of Internal Medicine 2019, 129, 442 -450.

AMA Style

Lukasz Szczerbinski, Joanna Goscik, Witold Bauer, Natalia Wawrusiewicz-Kurylonek, Magdalena Paczkowska-Abdulsalam, Magdalena Niemira, Anna Citko, Edyta Adamska-Patruno, Maria Gorska, Adam Kretowski. Efficacy of family history, genetic risk score, and physical activity in assessing the prevalence of type 2 diabetes. Polish Archives of Internal Medicine. 2019; 129 ():442-450.

Chicago/Turabian Style

Lukasz Szczerbinski; Joanna Goscik; Witold Bauer; Natalia Wawrusiewicz-Kurylonek; Magdalena Paczkowska-Abdulsalam; Magdalena Niemira; Anna Citko; Edyta Adamska-Patruno; Maria Gorska; Adam Kretowski. 2019. "Efficacy of family history, genetic risk score, and physical activity in assessing the prevalence of type 2 diabetes." Polish Archives of Internal Medicine 129, no. : 442-450.

Journal article
Published: 04 June 2019 in Diabetes
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Whether genetics can help predict response to type 2 diabetes (T2D) drugs is unknown. We set out to examine whether genetic risk scores (GRSs) composed of single nucleotide polymorphisms (SNPs) known to be associated with glycemic traits and T2D are associated with glycemic traits and the acute response to metformin and glipizide in SUGAR-MGH. We measured plasma glucose, insulin, glucagon, proinsulin, c-peptide, GLP-1, and GIP levels in 1,000 participants naïve to antidiabetes medications at 0, 30, 60, 90, 120, 180, and 240 minutes following administration of 5 mg glipizide (Visit 1, day 1), and during a 75-g oral glucose tolerance test following a short metformin course (Visit 2, day 8). We constructed a T2D, fasting glucose (FG), and fasting insulin (FI) GRS (with 65, 43 and 13 SNPs respectively) by summing the number of risk alleles carried by each person based on known genome-wide significant associations. Linear regression tested for associations between GRSs and glycemic traits as well as pharmacodynamic endpoints, adjusting for age, sex, race, and BMI. The FG GRS predicted FG in our cohort (β=0.46 increase in FG in mg/dL*allele, P<0.001). The FI GRS predicted fasting insulin (β=0.02 increase in ln FI in µU/mL*allele, P=0.04). A higher T2D GRS was associated with a shorter time to insulin peak, greater glucose area over the curve, shorter time to glucose trough, and steeper slope to glucose trough (P<0.05) after glipizide administration, indicating a stronger response. When we set a more stringent P-value of 0.008 to correct for multiple comparisons, the FG GRS remained associated with FG and the T2D GRS remained associated with the insulin-based endpoint. We conclude that established genetic determinants of glycemic traits predict FG and FI in our cohort of individuals free of overt diabetes; moreover, T2D risk alleles may predispose individuals to a greater insulin response to glipizide treatment. Disclosure J.H. Li: None. L. Szczerbinski: None. V. Kaur: None. J. Todd: None. J.C. Florez: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (R01DK-088214, R03DK-077675, P30-DK-036836); Joslin Clinical Research Center; Harvard Catalyst; National Center for Research Resources/National Center for Advancing Translational Sciences (M01-RR-01066, 1UL1-RR-025758-04, 88UL1-TR-000170-05; Harvard University

ACS Style

Josephine H. Li; Lukasz Szczerbinski; Varinderpal Kaur; Jennifer Todd; Jose C. Florez. 1723-P: Genetic Risk Scores Predict Glycemic Traits and Response to Glipizide Treatment in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH). Diabetes 2019, 68, 1723 .

AMA Style

Josephine H. Li, Lukasz Szczerbinski, Varinderpal Kaur, Jennifer Todd, Jose C. Florez. 1723-P: Genetic Risk Scores Predict Glycemic Traits and Response to Glipizide Treatment in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH). Diabetes. 2019; 68 (Supplement):1723.

Chicago/Turabian Style

Josephine H. Li; Lukasz Szczerbinski; Varinderpal Kaur; Jennifer Todd; Jose C. Florez. 2019. "1723-P: Genetic Risk Scores Predict Glycemic Traits and Response to Glipizide Treatment in the Study to Understand the Genetics of the Acute Response to Metformin and Glipizide in Humans (SUGAR-MGH)." Diabetes 68, no. Supplement: 1723.

Journal article
Published: 04 June 2019 in Diabetes
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Skeletal muscle is a major contributor to overall glucose homeostasis in the body and together with the liver is chiefly responsible for the whole-body insulin sensitivity. However, few studies have investigated the transcriptional signature of insulin resistance in skeletal muscles, at different stages of T2D development. Thus, the aim of this study was to identify the transcriptional signature of dysregulated glucose metabolism in skeletal muscle in humans by profiling the transcriptome with next-generation sequencing (NGS). We selected 40 sedentary males, aged 40-65 years, with BMI 26-33 kg/m2, diagnosed into three groups: 18 normoglycemics, 14 prediabetics and 8 subjects with type 2 diabetes. mRNA was extracted from biopsied Vastus lateralis muscles and sequenced with Illumina HiSeq 4000.Comparing normoglycemic and diabetic subjects revealed 4404 significantly differentially expressed (DE) genes, which represents around 30% of all mapped genes in studied samples. For the comparison between type 2 diabetics and prediabetics, the number of DE genes was 4055 genes. Interestingly we found no significantly DE genes between normoglycemics and prediabetics. KEGG enrichment analysis revealed that DE pathways between diabetics vs. nondiabetics were enriched for pathways related to oxidative phosphorylation, thermogenesis, nonalcoholic fatty liver disease and neurological diseases, which share the same underlying mechanism: mitochondrial dysfunction.These results indicate that skeletal muscle contributes most to overt T2D, with a possible indication that the liver contributes most to early stages the disease development. Differences observed between type 2 diabetics and the two remaining groups, occurring primarily in oxidative phosphorylation and electron transport chain pathways suggests that mitochondrial dysfunction plays the predominant role in the pathogenesis of T2D. Disclosure L. Szczerbinski: None. M. Niemira: None. K. Szczerbinski: None. U. Puchta: None. E. Siewiec: None. A. Citko: None. J. Zapolska: None. M. Taylor: None. S. Larsen: None. M. Gorska: None. A. Kretowski: None.

ACS Style

Lukasz Szczerbinski; Magdalena Niemira; Karol Szczerbinski; Urszula Puchta; Elwira Siewiec; Anna Citko; Joanna Zapolska; Mark Taylor; Steen Larsen; Maria Gorska; Adam Kretowski. 294-LB: Transcriptome-Wide Signals Converge Upon Mitochondrial Function in Developmental Stages of Type 2 Diabetes in Human Skeletal Muscle. Diabetes 2019, 68, 294 .

AMA Style

Lukasz Szczerbinski, Magdalena Niemira, Karol Szczerbinski, Urszula Puchta, Elwira Siewiec, Anna Citko, Joanna Zapolska, Mark Taylor, Steen Larsen, Maria Gorska, Adam Kretowski. 294-LB: Transcriptome-Wide Signals Converge Upon Mitochondrial Function in Developmental Stages of Type 2 Diabetes in Human Skeletal Muscle. Diabetes. 2019; 68 (Supplement):294.

Chicago/Turabian Style

Lukasz Szczerbinski; Magdalena Niemira; Karol Szczerbinski; Urszula Puchta; Elwira Siewiec; Anna Citko; Joanna Zapolska; Mark Taylor; Steen Larsen; Maria Gorska; Adam Kretowski. 2019. "294-LB: Transcriptome-Wide Signals Converge Upon Mitochondrial Function in Developmental Stages of Type 2 Diabetes in Human Skeletal Muscle." Diabetes 68, no. Supplement: 294.

Journal article
Published: 23 February 2019 in Microvascular Research
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Flow Mediated Skin Fluorescence (FMSF) is a novel technique for non-invasive evaluation of the microcirculation and metabolic regulation. This study describes the diagnostic potential of FMSF for type 1 diabetes (DM1). All study participants, in both the control (n = 31) and DM1 (n = 40) groups, were between the ages of 30–49 y. The patients in the DM1 group had all been suffering from diabetes for at least 10 y. The parameters HRindex, HRmax and MR inversely correlate with age and BMI. An unidentified compensatory effect was observed among the younger members of the DM1 group. The majority of DM1 patients with HRindex < 8% showed signs of dysfunctional metabolic regulation. FMSF appears to be an extremely useful technique for monitoring diabetic patients over time, enabling early diagnosis of potentially dysfunctional microcirculation and metabolic regulation.

ACS Style

Joanna Katarzynska; Anna Borkowska; Przemyslaw Czajkowski; Agnieszka Los; Lukasz Szczerbinski; Agnieszka Milewska-Kranc; Andrzej Marcinek; Adam Kretowski; Katarzyna Cypryk; Jerzy Gebicki. Flow Mediated Skin Fluorescence technique reveals remarkable effect of age on microcirculation and metabolic regulation in type 1 diabetes. Microvascular Research 2019, 124, 19 -24.

AMA Style

Joanna Katarzynska, Anna Borkowska, Przemyslaw Czajkowski, Agnieszka Los, Lukasz Szczerbinski, Agnieszka Milewska-Kranc, Andrzej Marcinek, Adam Kretowski, Katarzyna Cypryk, Jerzy Gebicki. Flow Mediated Skin Fluorescence technique reveals remarkable effect of age on microcirculation and metabolic regulation in type 1 diabetes. Microvascular Research. 2019; 124 ():19-24.

Chicago/Turabian Style

Joanna Katarzynska; Anna Borkowska; Przemyslaw Czajkowski; Agnieszka Los; Lukasz Szczerbinski; Agnieszka Milewska-Kranc; Andrzej Marcinek; Adam Kretowski; Katarzyna Cypryk; Jerzy Gebicki. 2019. "Flow Mediated Skin Fluorescence technique reveals remarkable effect of age on microcirculation and metabolic regulation in type 1 diabetes." Microvascular Research 124, no. : 19-24.

Journal article
Published: 05 December 2017 in Pediatric Diabetes
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Neonatal diabetes mellitus (NDM) caused by mutations in KCNJ11 can be successfully treated with high dose oral sulfonylureas; however, little data is available on the risk of hypoglycemia. To determine the frequency, severity, and clinical significance of hypoglycemia in KCNJ11-related NDM. Utilizing the University of Chicago Monogenic Diabetes Registry, parents completed an online questionnaire addressing hypoglycemia. Continuous glucose monitoring (CGM) data was available for 7 subjects. Thirty subjects with KCNJ11-related permanent NDM (166 patient-years on sulfonylurea) had median sulfonylurea dose of 0.39 mg/kg/day (0.24-0.88 IQR, interquartile range) with median HbA1c 5.7% (39 mmol/mol) (5.5-6.1 IQR, 37-43 mmol/mol). Hypoglycemia (<70 mg/dL) was reported monthly once or less frequently in 89.3% of individuals, but 3 (10.7%) reported once weekly or more. Of all hypoglycemic episodes reported, none involved seizures or unconsciousness and thus did not meet the current ISPAD definition of severe hypoglycemia. Seven individuals wore a CGM for a total of 912 hours with blood sugars falling below 70 mg/dL for 5.8% of the time recorded, similar to ranges reported for people without diabetes. In our cohort of KCNJ11-related permanent NDM, hypoglycemia is infrequent and mild despite the high doses of sulfonylurea used and near-normal level of glycemic control. Long-term follow-up on larger numbers will be required to clarify the incidence and determinants of hypoglycemia in this unique population.

ACS Style

Monica S Lanning; David Carmody; Łukasz Szczerbiński; Lisa R Letourneau; Rochelle N Naylor; Siri Atma W Greeley. Hypoglycemia in sulfonylurea-treated KCNJ11 -neonatal diabetes: Mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures. Pediatric Diabetes 2017, 19, 393 -397.

AMA Style

Monica S Lanning, David Carmody, Łukasz Szczerbiński, Lisa R Letourneau, Rochelle N Naylor, Siri Atma W Greeley. Hypoglycemia in sulfonylurea-treated KCNJ11 -neonatal diabetes: Mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures. Pediatric Diabetes. 2017; 19 (3):393-397.

Chicago/Turabian Style

Monica S Lanning; David Carmody; Łukasz Szczerbiński; Lisa R Letourneau; Rochelle N Naylor; Siri Atma W Greeley. 2017. "Hypoglycemia in sulfonylurea-treated KCNJ11 -neonatal diabetes: Mild-moderate symptomatic episodes occur infrequently but none involving unconsciousness or seizures." Pediatric Diabetes 19, no. 3: 393-397.

Correspondence
Published: 31 May 2017 in Diabetes & Metabolism
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ACS Style

E. Adamska; Adam Kretowski; J. Goscik; A. Citko; Witold Bauer; M. Waszczeniuk; K. Maliszewska; M. Paczkowska-Abdulsalam; Magdalena Niemira; Lukasz Szczerbinski; Michal Ciborowski; M. Gorska. The type 2 diabetes susceptibility TCF7L2 gene variants affect postprandial glucose and fat utilization in non-diabetic subjects. Diabetes & Metabolism 2017, 44, 379 -382.

AMA Style

E. Adamska, Adam Kretowski, J. Goscik, A. Citko, Witold Bauer, M. Waszczeniuk, K. Maliszewska, M. Paczkowska-Abdulsalam, Magdalena Niemira, Lukasz Szczerbinski, Michal Ciborowski, M. Gorska. The type 2 diabetes susceptibility TCF7L2 gene variants affect postprandial glucose and fat utilization in non-diabetic subjects. Diabetes & Metabolism. 2017; 44 (4):379-382.

Chicago/Turabian Style

E. Adamska; Adam Kretowski; J. Goscik; A. Citko; Witold Bauer; M. Waszczeniuk; K. Maliszewska; M. Paczkowska-Abdulsalam; Magdalena Niemira; Lukasz Szczerbinski; Michal Ciborowski; M. Gorska. 2017. "The type 2 diabetes susceptibility TCF7L2 gene variants affect postprandial glucose and fat utilization in non-diabetic subjects." Diabetes & Metabolism 44, no. 4: 379-382.

Journal article
Published: 01 May 2015 in Endocrine Abstracts
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ACS Style

Lukasz Szczerbinski; Witold Bauer; Joanna Gościk; Natalia Wawrusiewicz-Kurylonek; Magdalena Paczkowska; Magdalena Niemira; Anna Citko; Michal Ciborowski; Katarzyna Maliszewska; Edyta Adamska; Adam Kretowski; Maria Gorska. Can physical activity modify the impact of the genes on the incidence of type 2 diabetes mellitus? Endocrine Abstracts 2015, 1 .

AMA Style

Lukasz Szczerbinski, Witold Bauer, Joanna Gościk, Natalia Wawrusiewicz-Kurylonek, Magdalena Paczkowska, Magdalena Niemira, Anna Citko, Michal Ciborowski, Katarzyna Maliszewska, Edyta Adamska, Adam Kretowski, Maria Gorska. Can physical activity modify the impact of the genes on the incidence of type 2 diabetes mellitus? Endocrine Abstracts. 2015; ():1.

Chicago/Turabian Style

Lukasz Szczerbinski; Witold Bauer; Joanna Gościk; Natalia Wawrusiewicz-Kurylonek; Magdalena Paczkowska; Magdalena Niemira; Anna Citko; Michal Ciborowski; Katarzyna Maliszewska; Edyta Adamska; Adam Kretowski; Maria Gorska. 2015. "Can physical activity modify the impact of the genes on the incidence of type 2 diabetes mellitus?" Endocrine Abstracts , no. : 1.

Research brief
Published: 01 December 2014 in Indian Pediatrics
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To examine the association between hematological indices and serum uric acid in adolescents with hyperuricemia.

ACS Style

Marian J. Stelmach; Lukasz Szczerbinski; Natalia Wasilewska; Piotr Protas; Anna Wasilewska. Hematological parameters in adolescents with hyperuricemia. Indian Pediatrics 2014, 51, 1003 -1005.

AMA Style

Marian J. Stelmach, Lukasz Szczerbinski, Natalia Wasilewska, Piotr Protas, Anna Wasilewska. Hematological parameters in adolescents with hyperuricemia. Indian Pediatrics. 2014; 51 (12):1003-1005.

Chicago/Turabian Style

Marian J. Stelmach; Lukasz Szczerbinski; Natalia Wasilewska; Piotr Protas; Anna Wasilewska. 2014. "Hematological parameters in adolescents with hyperuricemia." Indian Pediatrics 51, no. 12: 1003-1005.