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1.
Endocr Pract ; 29(3): 174-178, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36581082

RESUMO

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/m2, 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.


Assuntos
Diabetes Mellitus Tipo 1 , Humanos , Feminino , Adulto , Masculino , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hemoglobinas Glicadas , Hipoglicemiantes/uso terapêutico , Glicemia , Controle Glicêmico , Insulina , Insulina Regular Humana/uso terapêutico , Sistemas de Infusão de Insulina
2.
Mol Med ; 28(1): 113, 2022 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104811

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/genética , Fator 1-alfa Nuclear de Hepatócito/genética , Humanos , Fenótipo
3.
J Cardiovasc Electrophysiol ; 33(9): 2064-2071, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35771566

RESUMO

INTRODUCTION: The effect of epicardial left atrial appendage (LAA) occlusion therapy on lipid and glucose metabolism in atrial fibrillation (AF) patients over the long-term follow-up are unclear. METHODS: In a single-center prospective observational study, 60 patients with longstanding persistent AF with cardiovascular risk factors had undergone an epicardial exclusion procedure. Anthropometric parameters and glucose, glycated hemoglobin (HbA1c), insulin, leptin, adiponectin, free fatty acids, beta-hydroxybutyrate, and total cholesterol levels were evaluated on fasting at baseline before the procedure and compared with levels at 24 h, 7 days, 1, 3, 6, and 24 months follow the procedure. RESULTS: The mean age of the patients was 67.5 ± 8.1. Insulin levels significantly increased at 7 days, 1, 3, 6, 12, and 24 months follow-up. The leptin levels showed a significant increase in 6, 12, and 24 months when compared to baseline. Whereas the adiponectin levels showed a significant decrease at 3, 6, 12, and 24 months when compared to baseline levels. In patients with the epicardial procedure, when compared to baseline, glucose, glycated hemoglobin, total cholesterol, and beta-hydroxybutyrate levels did not show any significant changes at baseline and 24 months follow-up. CONCLUSION: The epicardial exclusion ligation in AF patients was associated with significant changes in insulin, leptin, and adiponectin over long follow-up.


Assuntos
Apêndice Atrial , Fibrilação Atrial , Insulinas , Ácido 3-Hidroxibutírico , Adiponectina , Apêndice Atrial/cirurgia , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Colesterol , Glucose , Hemoglobinas Glicadas , Humanos , Leptina , Resultado do Tratamento
4.
Metabolomics ; 18(3): 15, 2022 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-35179657

RESUMO

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 HepG2HNF1Bkd 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.


Assuntos
Quinase 3 da Glicogênio Sintase , Doenças Renais Císticas , Quinase 3 da Glicogênio Sintase/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Lisofosfolipídeos , Metabolômica , Mutação/genética
5.
Nanomedicine ; 39: 102468, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619362

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Insuficiência Renal Crônica , Biomarcadores/metabolismo , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Vesículas Extracelulares/metabolismo , Humanos , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/metabolismo , Análise Espectral Raman , Ultracentrifugação
6.
Folia Med Cracov ; 62(4): 5-23, 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36854083

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 1 , Insulinas , Humanos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Hábitos
7.
Mol Med ; 27(1): 6, 2021 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472578

RESUMO

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.


Assuntos
Quimiocina CCL24/genética , Diabetes Mellitus Tipo 1/genética , Perfilação da Expressão Gênica/métodos , Ganho de Peso na Gestação/genética , Polimorfismo de Nucleotídeo Único , Sialoglicoproteínas/genética , Adulto , Índice de Massa Corporal , Feminino , Estudos de Associação Genética , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Gravidez , Sequenciamento do Exoma
8.
Folia Med Cracov ; 60(4): 19-29, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33821848

RESUMO

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.


Assuntos
Diabetes Gestacional , Adulto , Glicemia , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Jejum , Feminino , Humanos , Polônia/epidemiologia , Gravidez , Estudos Retrospectivos
9.
Cardiovasc Diabetol ; 18(1): 49, 2019 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-30992036

RESUMO

BACKGROUND: Type 2 diabetes mellitus (T2DM) is associated with a hypercoagulable state and increased neutrophil extracellular traps formation (NETosis). We investigated predictors of NETosis and cell death markers in circulating blood and their association with a prothrombotic state in T2DM. METHODS: In a cross-sectional study involving 113 T2DM patients aged 63.7 ± 8.2 years, we investigated citrullinated histone H3 (H3Cit), cell-free deoxyribonucleic acid (cfDNA), myeloperoxidase, neutrophil elastase, and inflammation markers, along with thrombin generation (TG), plasma clot lysis time (CLT), clot permeability (Ks) and fibrinolysis inhibitors. RESULTS: On multivariate logistic regression analysis adjusted for age and gender, predictors of high H3Cit (≥ 7.36 ng/mL, upper quartile) were: glycated hemoglobin (HbA1c) ≥ 7.0% and interleukin-6. Interleukin-6 was also found to be a predictor of high cfDNA (≥ 2.84 µg/mL, upper quartile) along with glucose. Citrullinated histone H3 and cfDNA correlated positively with CLT and inversely with Ks, while TG associated solely with cfDNA. These associations were not seen with myeloperoxidase and neutrophil elastase. Patients with previous myocardial infarction (n = 21, 18.6%) had higher H3Cit (+108%, p < 0.001) and cfDNA (+45%, p = 0.022). On multivariable analysis adjusted for potential confounders, H3Cit and cfDNA, along with plasminogen activator inhibitor-1 and concomitant cardiovascular disease, were predictors of CLT. Citrullinated histone H3 alone was a predictor of Ks and only cfDNA was a predictor of peak thrombin generated. CONCLUSIONS: In T2DM, NETosis detectable in circulating blood is associated with inflammatory state and a prothrombotic state, especially hypofibrinolysis.


Assuntos
Diabetes Mellitus Tipo 2/sangue , Armadilhas Extracelulares/metabolismo , Fibrinólise , Trombose/sangue , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Ácidos Nucleicos Livres/sangue , Citrulinação , Estudos Transversais , DNA/sangue , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Hemoglobinas Glicadas/metabolismo , Histonas/sangue , Humanos , Mediadores da Inflamação/sangue , Elastase de Leucócito/sangue , Masculino , Pessoa de Meia-Idade , Peroxidase/sangue , Fatores de Risco , Trombina/metabolismo , Trombose/diagnóstico , Trombose/etiologia
10.
Eur J Clin Invest ; 49(4): e13067, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30600541

RESUMO

BACKGROUND: Diabetes and its complications constitute a rising medical challenge. Special attention should be given to diabetic foot syndrome (DFS) due to its high rate of associated amputation and mortality. Negative pressure wound therapy (NPWT) is a frequently used supportive modality in a diabetic foot with ulcerations (DFUs). DESIGN: Here, we reviewed the current knowledge concerning the tissue and molecular mechanisms of NPWT action with an emphasis on diabetes research followed by a summary of clinical DFU studies and practice guidelines. RESULTS: Negative pressure wound therapy action results in two types of tissue deformations-macrodeformation, such as wound contraction, and microdeformation occurring at microscopic level. Both of them stimulate a wound healing cascade including tissue granulation promotion, vessel proliferation, neoangiogenesis, epithelialization and excess extracellular fluid removal. On the molecular level, NPWT results in an alteration towards more pro-angiogenic and anti-inflammatory conditions. It increases expression of several key growth factors, including vascular endothelial growth factor and fibroblast growth factor 2, while expression of inflammatory cytokinesis reduced. The NPWT application also alters the presence and function of matrix metalloproteinases. Clinical studies in DFU patients showed a superiority of NPWT over standard therapy in terms of efficacy outcomes, primarily wound healing and amputation rate, without a rise in adverse events. International guidelines point to NPWT as an important adjuvant therapy in DFU whose use is expected to increase. CONCLUSIONS: This current knowledge improves our understanding of NPWT action and its tailoring for application in diabetic patients. It may inform the development of new treatments for DFU.


Assuntos
Pé Diabético/terapia , Tratamento de Ferimentos com Pressão Negativa , Animais , Citocinas/metabolismo , Pé Diabético/fisiopatologia , Modelos Animais de Doenças , Humanos , Metaloproteinases da Matriz/metabolismo , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Cicatrização/fisiologia
11.
Int J Clin Pract ; 73(11): e13411, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31456268

RESUMO

AIMS: Fear of hypoglycaemia seems to be one of the strongest barrier to physical activity for individuals with type 1 diabetes mellitus (T1DM).The aim of the study was to describe clinical characteristics of participants with T1DM in the intense sporting event of runs and bike rides"SPORTGIVECHANCE-Diabetic runners and cyclists for more sport for all in Europe", and investigate factors associated with self-reported hypoglycaemia episodes during the competition, in particular the use of continuous and flash glucose monitoring systems (CGM/FGM). METHODS: The sporting event took place in Spoleto, Italy from 30 August 2018 to 2 September 2018. An online survey was distributed among 150 participants with diabetes. Only T1DM patients were invited to complete the survey that included questions on baseline clinical characteristics as well as glucose control and meal related issues during the competition. Logistic regression was used to determine factors associated with reported hypoglycaemia. RESULTS: There were 35 T1DM individuals who completed the questionnaire: eight subjects were continuous glucose monitoring system (CGM) users, 10 used flash glucose monitoring systems (FGM), while the others performed self-measured blood glucose measurements (SMBG) on glucose meters. Mild hypoglycaemia episodes during the competition were reported by four CGM/FGM users and six non-users (OR: 0.73, CI: 0.34-1.53). No severe hypoglycaemic episode was reported. Body mass index (BMI) (OR: 1.47, CI: 1.01-2.13) and subjectively very hard or maximal intensity of the competition (OR: 4.90, CI: 1.51-15.89) were associated with a higher risk of hypoglycaemia. CONCLUSIONS: Data obtained from the self-selected sample of T1DM patients suggests that T1DM individuals can participate in intense sport competitions with moderate risk of mild hypoglycaemia regardless of CGM/FGM or SMBG use.


Assuntos
Diabetes Mellitus Tipo 1/terapia , Exercício Físico/fisiologia , Hipoglicemia/sangue , Esportes , Adulto , Glicemia , Automonitorização da Glicemia , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/complicações , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Fatores de Risco
12.
Nanomedicine ; 17: 137-149, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30703535

RESUMO

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.


Assuntos
Diabetes Mellitus Tipo 2/diagnóstico , Células Endoteliais/patologia , Vesículas Extracelulares/patologia , Hiperglicemia/diagnóstico , Diabetes Mellitus Tipo 2/urina , Células Endoteliais/química , Vesículas Extracelulares/química , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Hiperglicemia/urina , Masculino , Análise Espectral Raman/métodos , Urinálise/métodos , Urina/química
13.
Pediatr Diabetes ; 19(1): 53-58, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28436179

RESUMO

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.


Assuntos
Diabetes Mellitus/genética , Criança , Diabetes Mellitus/epidemiologia , Testes Genéticos , Humanos , Polônia/epidemiologia , Prevalência
14.
Przegl Lek ; 74(1): 41-3, 2017.
Artigo em Polonês | MEDLINE | ID: mdl-29694001

RESUMO

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.


Assuntos
Acarbose/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemia/tratamento farmacológico , Metformina/uso terapêutico , Acarbose/administração & dosagem , Administração Oral , Idoso , Anticorpos/sangue , Compostos Benzidrílicos/administração & dosagem , Compostos Benzidrílicos/uso terapêutico , Quimioterapia Combinada , Feminino , Glucosídeos/administração & dosagem , Glucosídeos/uso terapêutico , Humanos , Hipoglicemiantes/uso terapêutico , Insulina Lispro/imunologia , Insulina Lispro/uso terapêutico , Metformina/administração & dosagem
15.
Diabetologia ; 59(7): 1463-1473, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27059371

RESUMO

AIMS/HYPOTHESIS: We aimed to identify microRNAs (miRNAs) under transcriptional control of the HNF1ß transcription factor, and investigate whether its effect manifests in serum. METHODS: The Polish cohort (N = 60) consisted of 11 patients with HNF1B-MODY, 17 with HNF1A-MODY, 13 with GCK-MODY, an HbA1c-matched type 1 diabetic group (n = 9) and ten healthy controls. Replication was performed in 61 clinically-matched British patients mirroring the groups in the Polish cohort. The Polish cohort underwent miRNA serum level profiling with quantitative real-time PCR (qPCR) arrays to identify differentially expressed miRNAs. Validation was performed using qPCR. To determine whether serum content reflects alterations at a cellular level, we quantified miRNA levels in a human hepatocyte cell line (HepG2) with small interfering RNA knockdowns of HNF1α or HNF1ß. RESULTS: Significant differences (adjusted p < 0.05) were noted for 11 miRNAs. Five of them differed between HNF1A-MODY and HNF1B-MODY, and, amongst those, four (miR-24, miR-27b, miR-223 and miR-199a) showed HNF1B-MODY-specific expression levels in the replication group. In all four cases the miRNA expression level was lower in HNF1B-MODY than in all other tested groups. Areas under the receiver operating characteristic curves ranged from 0.79 to 0.86, with sensitivity and specificity reaching 91.7% (miR-24) and 82.1% (miR-199a), respectively. The cellular expression pattern of miRNA was consistent with serum levels, as all were significantly higher in HNF1α- than in HNF1ß-deficient HepG2 cells. CONCLUSIONS/INTERPRETATION: We have shown that expression of specific miRNAs depends on HNF1ß function. The impact of HNF1ß deficiency was evidenced at serum level, making HNF1ß-dependent miRNAs potentially applicable in the diagnosis of HNF1B-MODY.


Assuntos
Fator 1-alfa Nuclear de Hepatócito/metabolismo , Fator 1-beta Nuclear de Hepatócito/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , Regulação da Expressão Gênica/genética , Regulação da Expressão Gênica/fisiologia , Hemoglobinas Glicadas/genética , Hemoglobinas Glicadas/metabolismo , Células Hep G2 , Fator 1-alfa Nuclear de Hepatócito/genética , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , RNA Interferente Pequeno/genética , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real
17.
Curr Opin Obstet Gynecol ; 26(6): 431-7, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25268167

RESUMO

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.


Assuntos
Diabetes Gestacional/terapia , Medicina Baseada em Evidências , Saúde Global , Guias de Prática Clínica como Assunto , Gravidez em Diabéticas/terapia , Terapia Combinada , Consenso , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/epidemiologia , Diabetes Gestacional/fisiopatologia , Dieta para Diabéticos , Feminino , Macrossomia Fetal/epidemiologia , Macrossomia Fetal/etiologia , Macrossomia Fetal/prevenção & controle , Transição Epidemiológica , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/uso terapêutico , Insulina Regular Humana/análogos & derivados , Insulina Regular Humana/genética , Insulina Regular Humana/uso terapêutico , Fenômenos Fisiológicos da Nutrição Materna , Gravidez , Gravidez em Diabéticas/diagnóstico , Gravidez em Diabéticas/epidemiologia , Gravidez em Diabéticas/fisiopatologia , Diagnóstico Pré-Natal/tendências , Proteínas Recombinantes/química , Proteínas Recombinantes/uso terapêutico , Risco
18.
Ginekol Pol ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38717224

RESUMO

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

19.
Endocrine ; 2024 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-38448676

RESUMO

INTRODUCTION: Diabetes distress (DD) and diabetes burnout (DB) are recognized psychological phenomena in patients with T1DM (type 1 diabetes mellitus). Still, there is an urgent need to create professional psychological intervention procedures to provide patients with adequate care. AIM: The aim of the study was to assess the level of DD and DB in T1DM patients at baseline and after 5 of sessions psychological intervention in the group of participants who applied for help. METHODS: 34 T1DM patients who requested psychological support (22 females, 12 males) and 30 patients in a control group (14 females, 16 males) participated in the study. At baseline clinical test results between groups were compared. Next, in the studied group measurements were repeated after a set of five psychological face-to-face individual interventions which lasted 30-60 min each. They were support sessions with elements of cognitive-behavioral interventions done by clinical psychologists. Session 1: introduction, interview and collection of test results; session 2-4: work on the indicated by the patient and test results most problematic aspect of diabetes, session 5: a summary and plan for further treatment if needed. The control group results were obtained only at baseline. Research tools: DDS; PAID, Diabetes Burnout test by Polonsky. RESULTS: At the baseline, significant differences were observed between the studied group and control group: in DB/DD levels: DB (3.9 ± 1.7 vs 2.4 ± 1.6; p < 0.001); DDS (3.2 ± 1.0 vs 2.7 ± 1.0; p = 0.064); PAID (62.3 ± 14.1vs 34.4 ± 21.0; p < 0.001). There were also group differences in HbA1c levels (8.7 ± 2.4 vs 7.3 ± 1.5; p = 0.028). After psychological interventions, there was a significant improvement in DB (3.9 ± 1.7vs 2.9 ± 1.2; p < 0.001; DDS (3.2 ± 1 vs 3.0 ± 0.7; p = 0.03); PAID (62.3 ± 14.1 vs 51.8 ± 12.5; p < 0.001). CONCLUSIONS: DD and DB constitute a significant problem in the group of T1DM patients, but providing appropriate specialist care may help them accept diabetes and improve life satisfaction, as well as regain control over their diabetes management.

20.
JBI Evid Implement ; 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38899903

RESUMO

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.

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