BACKGROUND: Diabetes mellitus (DM) is a chronic disease with prevalence increasing worldwide. The aim of this study was to investigate satisfaction with the current method of insulin delivery (INS) amongst patient with type 1 diabetes mellitus (T1DM) using multiple daily injection (MDI) or continuous subcutaneous insulin infusion (CSII). Furthermore, a sub-aim was to test the effect of selected variables on patient satisfaction with MDI or CSII using regression analysis. METHODS: A cross-sectional study carried out in the territory of Moravia in the Czech Republic. A quantitative approach using the Insulin Delivery System Rating Questionnaire (IDSRQ) among 197 respondents with T1DM with INS delivery with MDI or CSII for at least 1 year. Statistical methods used were descriptive statistics, Student's t-tests and regression analysis. RESULTS: Highly significant differences were found between CSII and MDI patients in satisfaction with the current method of INS delivery (p < 0.001), in how the current method of delivery helps patients maintain stable blood glucose values, prevent high blood glucose (p < 0.001), and in overall satisfaction with the current method of INS delivery (p < 0.001). The average overall satisfaction score was 56.19 points for MDI and 62.08 points for CSII. Regression analysis revealed predictors of overall satisfaction on the mean score on how the current method of INS delivery helps MDI patients (p < 0.01). The effect of other selected variables was not confirmed. CONCLUSION: The results of the study showed higher overall satisfaction with the method of INS delivery in CSII patients. The current method of INS delivery does not interfere with daily life and activities in most patients.

• Klíčová slova
• Continuous subcutaneous insulin infusion, Insulin delivery system rating questionnaire, Multiple daily injection, Regression analysis, Type 1 diabetes mellitus,
• MeSH
• diabetes mellitus 1. typu * farmakoterapie   krev   psychologie   MeSH
• dospělí MeSH
• hypoglykemika * aplikace a dávkování   terapeutické užití   MeSH
• injekce subkutánní MeSH
• inzulin * aplikace a dávkování   terapeutické užití   MeSH
• inzulinové infuzní systémy * MeSH
• krevní glukóza MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• průřezové studie MeSH
• průzkumy a dotazníky MeSH
• spokojenost pacientů * MeSH
• subkutánní infuze MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• hypoglykemika * MeSH
• inzulin * MeSH
• krevní glukóza MeSH

The quantitative characterization of residue contributions to protein-protein binding across extensive flexible interfaces poses a significant challenge for biophysical computations. It is attributable to the inherent imperfections in the experimental structures themselves, as well as to the lack of reliable computational tools for the evaluation of all types of noncovalent interactions. This study leverages recent advancements in semiempirical quantum-mechanical and implicit solvent approaches embodied in the PM6-D3H4S/COSMO2 method for the development of a hierarchical computational protocols encompassing molecular dynamics, fragmentation, and virtual glycine scan techniques for the investigation of flexible protein-protein interactions. As a model, the binding of insulin to its receptor is selected, a complex and dynamic process that has been extensively studied experimentally. The interaction energies calculated at the PM6-D3H4S/COSMO2 level in ten molecular dynamics snapshots did not correlate with molecular mechanics/generalized Born interaction energies because only the former method is able to describe nonadditive effects. This became evident by the examination of the energetics in small-model dimers featuring all the present types of noncovalent interactions with respect to DFT-D3 calculations. The virtual glycine scan has identified 15 hotspot residues on insulin and 15 on the insulin receptor, and their contributions have been quantified using PM6-D3H4S/COSMO2. The accuracy and credibility of the approach are further supported by the fact that all the insulin hotspots have previously been detected by biochemical and structural methods. The modular nature of the protocol has enabled the formulation of several variants, each tailored to specific accuracy and efficiency requirements. The developed computational strategy is firmly rooted in general biophysical chemistry and is thus offered as a general tool for the quantification of interactions across relevant flexible protein-protein interfaces.

• MeSH
• inzulin metabolismus   chemie   MeSH
• konformace proteinů MeSH
• lidé MeSH
• receptor inzulinu * chemie   metabolismus   MeSH
• simulace molekulární dynamiky * MeSH
• termodynamika MeSH
• vazba proteinů MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• inzulin MeSH
• receptor inzulinu * MeSH

AIMS: To assess the efficacy and safety of switching from premixed insulin to a once-daily, fixed-ratio combination of insulin glargine 100 U/mL + lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D). METHODS: In this phase 4, 24-week, single-arm study, participants switched from once-daily or twice-daily premixed insulin to iGlarLixi (EudraCT number 2021-003711-25). Key inclusion criteria: ≥18 years; premixed insulin therapy for ≥3 months and < 10 years; ± 1-2 oral antidiabetic drugs (OADs); HbA1c ≥7.5% to ≤10.0%. The primary endpoint was the change in HbA1c from baseline to Week 24. Secondary endpoints included: participants achieving HbA1c <7% and change in body weight at Week 24, and safety. RESULTS: Overall, 162 participants switched to iGlarLixi (89.5% from twice-daily premixed insulin); mean duration of diabetes was 15.7 (standard deviation [SD]: 8.3) years. Mean baseline HbA1c (8.5%) reduced by least squares (LS) mean of 1.2% (95% confidence interval [CI]: -1.4, -1.1) at Week 24, and 37.6% of participants had achieved an HbA1c target of <7% (95% CI: 30.0, 45.7). LS mean body weight change from baseline to Week 24 was -1.0 kg (95% CI: -1.6, -0.5). Fasting and post-prandial plasma glucose decreased from baseline to Week 24 by 45.6 mg/dL (SD ± 52.4) and 67.6 mg/dL (SD ± 65.1), respectively. Confirmed symptomatic hypoglycaemia occurred in 38.3% of participants (ADA level 1: 35.8%; level 2: 15.4%; level 3: 0.0%). CONCLUSIONS: iGlarLixi initiation was associated with improved glycaemic control, without body weight gain or increased hypoglycaemia over 24 weeks.

• Klíčová slova
• clinical trial, iGlarLixi, insulin glargine, lixisenatide, phase IV study, type 2 diabetes,
• MeSH
• diabetes mellitus 2. typu * farmakoterapie   krev   MeSH
• dospělí MeSH
• fixní kombinace léků MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemie chemicky indukované   MeSH
• hypoglykemika * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• inzulin glargin * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• krevní glukóza účinky léků   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhrada léků * MeSH
• peptidy * aplikace a dávkování   škodlivé účinky   terapeutické užití   MeSH
• receptor pro glukagonu podobný peptid 2 MeSH
• rozvrh dávkování léků MeSH
• senioři MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky, fáze IV MeSH
• multicentrická studie MeSH
• Názvy látek
• fixní kombinace léků MeSH
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hypoglykemika * MeSH
• inzulin glargin * MeSH
• krevní glukóza MeSH
• lixisenatide MeSH Prohlížeč
• peptidy * MeSH
• receptor pro glukagonu podobný peptid 2 MeSH

Diabetes requires precise insulin management to maintain glycemic control and prevent severe complications. Glucose-responsive delivery systems envision an autonomous approach to improve insulin therapy. Here, a glucose-sensitive insulin delivery system comprising hyaluronic acid conjugated with a diboronate glucose binder as a carrier for diol-modified insulin is shown. This approach seeks improved precision in insulin delivery, leveraging bidentate glucose binding to achieve enhanced glucose affinity and specificity. Modification of insulin with a diol motif preserves its native conformation and function. These insulin formulations correct blood glucose in diabetic mice, including glucose-responsive function when subjected to a glucose challenge. However, the absence of secondary interactions, such as electrostatic complexation, ultimately limits the duration of function relative to that of previous platforms. Integrating complementary interactions alongside dynamic-covalent glucose binders therefore enhances the functional duration and therapeutic efficacy in the design of glucose-responsive polymeric carriers, offering design insights into the development of new carriers for glucose-responsive insulin delivery.

• MeSH
• experimentální diabetes mellitus * farmakoterapie   MeSH
• glukosa * metabolismus   MeSH
• hypoglykemika * aplikace a dávkování   chemie   MeSH
• inzulin * aplikace a dávkování   chemie   farmakologie   MeSH
• krevní glukóza účinky léků   MeSH
• kyselina hyaluronová * chemie   MeSH
• kyseliny boronové * chemie   MeSH
• lékové transportní systémy * MeSH
• myši MeSH
• nosiče léků * chemie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa * MeSH
• hypoglykemika * MeSH
• inzulin * MeSH
• krevní glukóza MeSH
• kyselina hyaluronová * MeSH
• kyseliny boronové * MeSH
• nosiče léků * MeSH

OBJECTIVE: This study examined the association between diabetic ketoacidosis (DKA) at type 1 diabetes diagnosis and long-term glycemic outcomes, insulin requirements, BMI SD score (SDS), and diabetes technology uptake in youth. RESEARCH DESIGN AND METHODS: Data were from nine countries (Austria, Czechia, Germany, Italy, Luxembourg, New Zealand, Slovenia, Switzerland, and U.S. [Colorado]), including youth (0.5-15.9 years) diagnosed with type 1 diabetes in 2019-2020 and followed for 2 years thereafter. Participants were divided into three groups: no DKA, nonsevere, and severe DKA at diagnosis. HbA1c, insulin requirements, BMI SDS, and use of technology, including automated insulin delivery (AID), were assessed. RESULTS: The analysis included 9,269 individuals (54.8% males, mean age 9.0 years). DKA at diagnosis was observed in 34.2% of participants and severe DKA in 12.8%. After 1 year, adjusted mean HbA1c was higher in the severe DKA group (7.41%) compared with nonsevere DKA (7.23%, P = 0.001) and no DKA groups (7.14, P < 0.001), and this difference persisted after 2 years (7.58% vs. 7.38% [P < 0.001] and vs. 7.32% [P < 0.001]). Higher BMI SDS was observed in both DKA groups compared with no DKA. The use of AID was associated with lower HbA1c levels compared with other treatment modalities and moderated differences between DKA groups after 2 years of follow-up (P = 0.072). CONCLUSIONS: Severe and nonsevere DKA at type 1 diabetes diagnosis were both associated with persistently higher HbA1c and higher BMI SDS. AID use diminishes the association of DKA at diagnosis and higher HbA1c over time.

• MeSH
• diabetes mellitus 1. typu * komplikace   farmakoterapie   epidemiologie   krev   MeSH
• diabetická ketoacidóza * epidemiologie   etiologie   MeSH
• dítě MeSH
• glykovaný hemoglobin metabolismus   MeSH
• inzulin terapeutické užití   aplikace a dávkování   MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• následné studie MeSH
• předškolní dítě MeSH
• registrace MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Nový Zéland epidemiologie   MeSH
• Názvy látek
• glykovaný hemoglobin MeSH
• inzulin MeSH

Significance: Type 2 diabetes as a world-wide epidemic is characterized by the insulin resistance concomitant to a gradual impairment of β-cell mass and function (prominently declining insulin secretion) with dysregulated fatty acids (FAs) and lipids, all involved in multiple pathological development. Recent Advances: Recently, redox signaling was recognized to be essential for insulin secretion stimulated with glucose (GSIS), branched-chain keto-acids, and FAs. FA-stimulated insulin secretion (FASIS) is a normal physiological event upon postprandial incoming chylomicrons. This contrasts with the frequent lipotoxicity observed in rodents. Critical Issues: Overfeeding causes FASIS to overlap with GSIS providing repeating hyperinsulinemia, initiates prediabetic states by lipotoxic effects and low-grade inflammation. In contrast the protective effects of lipid droplets in human β-cells counteract excessive lipids. Insulin by FASIS allows FATP1 recruitment into adipocyte plasma membranes when postprandial chylomicrons come late at already low glycemia. Future Directions: Impaired states of pancreatic β-cells and peripheral organs at prediabetes and type 2 diabetes should be revealed, including the inter-organ crosstalk by extracellular vesicles. Details of FA/lipid molecular physiology are yet to be uncovered, such as complex phenomena of FA uptake into cells, postabsorptive inactivity of G-protein-coupled receptor 40, carnitine carrier substrate specificity, the role of carnitine-O-acetyltransferase in β-cells, and lipid droplet interactions with mitochondria. Antioxid. Redox Signal. 42, 566-622.

• Klíčová slova
• fatty acid-stimulated insulin secretion, insulin resistance, lipotoxicity, pancreatic beta cells, type-2 diabetes,
• MeSH
• beta-buňky metabolismus   MeSH
• diabetes mellitus 2. typu metabolismus   MeSH
• glukosa metabolismus   MeSH
• inzulin * metabolismus   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• mastné kyseliny * metabolismus   MeSH
• metabolismus lipidů MeSH
• oxidace-redukce MeSH
• sekrece inzulinu MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• glukosa MeSH
• inzulin * MeSH
• mastné kyseliny * MeSH

The study focused on the changes in C-peptide, glycemia, insulin concentration, and insulin resistance according to LDL-cholesterol concentration ranges. The metabolic profile of individuals in the Czech Republic (n = 1840) was classified by quartiles of LDL-cholesterol into four groups with the following ranges: 0.46-2.45 (n = 445), 2.46-3.00 (n = 474), 3.01-3.59 (n = 459), and 3.60-7.18 mmol/l (n = 462). The level of glucose, C-peptide, insulin, and area of parameters during OGTT and HOMA IR were compared with a relevant LDL-cholesterol range. The evaluation involved correlations between LDL-cholesterol and the above parameters, F-test and t-test. Generally, mean values of glucose homeostasis-related parameters were higher with increasing LDL-cholesterol levels, except for mean HOMA IR values which rapidly increased (2.7-3.4) between LDL-cholesterol ranges of 3.00-3.59 and 3.60-7.18 mmol/l. Glucose, C-peptide, insulin concentrations, and the area of parameters reached greater changes especially after glucose load during OGTT (p ≤ 0.001). Considerable changes were already observed for the above parameters between groups with LDL-cholesterol ranges of 2.46-3.00 and 3.01-3.59 mmol/l. HOMA IR increased with higher LDL-cholesterol concentrations, but the differences in mean values were not statistically significant. Most important differences appeared in glucose metabolism at LDL-cholesterol concentrations of 3.60-7.18 mmol/l in comparison to LDL-cholesterol lower ranges. In particular, the areas of C-peptide, glucose, and insulin ranges showed statistically significant differences between all groups with growing LDL-cholesterol ranges. The variances of HOMA IR statistically differed between groups created according to LDL-cholesterol concentrations ranges.

• Klíčová slova
• C-peptide, Glucose, HOMA IR, Insulin, LDL-cholesterol,
• MeSH
• C-peptid krev   MeSH
• dospělí MeSH
• glukózový toleranční test MeSH
• inzulin krev   MeSH
• inzulinová rezistence MeSH
• krevní glukóza * metabolismus   analýza   MeSH
• LDL-cholesterol * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• C-peptid MeSH
• inzulin MeSH
• krevní glukóza * MeSH
• LDL-cholesterol * MeSH

AIM: To determine whether people with type 1 diabetes (T1D) initiating glucose sensor monitoring experience greater improvements in HbA1c when provided with education on carbohydrate counting and flexible insulin dosing than those who do not receive nutrition education. MATERIALS AND METHODS: Our retrospective observational study included 329 people with T1D initiating glucose sensor monitoring between 2015 and 2021. The participants were divided into two groups: one group attended at least one structured educational session with a registered dietitian (n = 126), while the other group did not receive structured education (n = 203). After 12 months of glucose sensor initiation, we compared glycaemic outcomes and CGM metrics between the two groups. RESULTS: At glucose sensor initiation, both groups with and without education had similar HbA1c levels (7.64% [60.0 mmol/mol] vs. 7.66% [60.2 mmol/mol]). After twelve months, the education group demonstrated greater improvement in glycemic outcomes (HbA1c 7.17% [54.9mmol/mol] vs. 7.37% [57.1 mmol/mol], p < 0.05) and spent significantly more time in the target range than did the group without structured education (68.8% vs. 64.1%, p < 0.05). We observed an inverse correlation between the number of completed educational sessions and HbA1c after 12 months, as well as between the number of educational sessions and the change in HbA1c. CONCLUSIONS: People with T1D who initiated glucose sensor monitoring alongside nutrition education showed greater improvements in HbA1c and increased time spent in the target glucose range compared to individuals who did not receive structured education. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT06264271.

• Klíčová slova
• glucose sensors, glycemic outcomes, nutrition education, type 1 diabetes,
• MeSH
• diabetes mellitus 1. typu * krev   farmakoterapie   dietoterapie   MeSH
• dospělí MeSH
• glykovaný hemoglobin analýza   MeSH
• hypoglykemika aplikace a dávkování   terapeutické užití   MeSH
• inzulin aplikace a dávkování   MeSH
• krevní glukóza * analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• regulace glykemie * metody   MeSH
• retrospektivní studie MeSH
• selfmonitoring glykemie * metody   MeSH
• vzdělávání pacientů jako téma * metody   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• glykovaný hemoglobin MeSH
• hemoglobin A1c protein, human MeSH Prohlížeč
• hypoglykemika MeSH
• inzulin MeSH
• krevní glukóza * MeSH

BACKGROUND: Hyperkalaemia is a life-threatening electrolyte disturbance and also a potential cause of cardiac arrest. The objective was to assess the effects of acute pharmacological interventions for the treatment of hyperkalaemia in patients with and without cardiac arrest. METHODS: The review was reported according to PRISMA guidelines and registered on PROSPERO (CRD42023440553). We searched OVID Medline, EMBASE, and CENTRAL on September 9, 2024 for randomized trials, non-randomized trials, observational studies, and experimental animal studies. Two investigators performed abstract screening, full-text review, data extraction, and bias assessment. Outcomes included potassium levels, ECG findings, and clinical outcomes. Certainty of evidence was evaluated using GRADE. RESULTS: A total of 101 studies were included, with two studies including patients with cardiac arrest. In meta-analyses including adult patients without cardiac arrest, treated with insulin in combination with glucose, inhaled salbutamol, intravenous salbutamol dissolved in glucose, or a combination, the average reduction in potassium was between 0.7 and 1.2 mmol/l (very low to low certainty of evidence). The use of bicarbonate had no effect on potassium levels (very low certainty of evidence). In neonatal and paediatric populations, inhaled salbutamol and intravenous salbutamol reduced the average potassium between 0.9 and 1.0 mmol/l (very low to low certainty of evidence). There was no evidence to support a clinical beneficial effect of calcium for treatment of hyperkalemia. CONCLUSIONS: Evidence supports treatment with insulin in combination with glucose, inhaled or intravenous sal-butamol, or the combination. No evidence supporting a clinical effect of calcium or bicarbonate for hyperkalaemia was identified.

• Klíčová slova
• Beta2-agonists, Bicarbonate, Calcium, Hyperkalaemia, Insulin, Pharmacological interventions, Systematic review,
• MeSH
• albuterol aplikace a dávkování   terapeutické užití   MeSH
• draslík krev   MeSH
• hyperkalemie * farmakoterapie   komplikace   MeSH
• inzulin aplikace a dávkování   terapeutické užití   MeSH
• lidé MeSH
• srdeční zástava * etiologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• metaanalýza MeSH
• systematický přehled MeSH
• Názvy látek
• albuterol MeSH
• draslík MeSH
• inzulin MeSH

This report presents a fatal case of a young female Type I diabetic patient who developed convulsions and loss of consciousness after taking methamphetamine and spending some time in a dance club. During the convulsions, she was given sugar and when no response occurred, her boyfriend who was not experienced in the use of insulin administered a dose of insulin to her. The woman lost consciousness and died despite the efforts of the emergency service. A biochemical analysis revealed a high level of insulin (196.67 mU/L) and low levels of glucose (2.96 mmol/L) and C-peptide (26 pmol/L). Toxicological analysis revealed a methamphetamine concentration of 389 ng/mL and an amphetamine concentration of 19 ng/mL. The forensic perspective of the difficult determination of the contribution of each of the factors to the death, i.e., the pre-existing medical condition (Type I diabetes), the use of methamphetamine, the physical exertion at the dance club, and, finally, the non-indicated administration of insulin, is discussed. The ruling of the court is also reported.

• Klíčová slova
• Hypoglycemia, Insulin overdose, Legal consequences, Methamphetamine, Type I diabetes,
• MeSH
• bezvědomí etiologie   chemicky indukované   MeSH
• C-peptid krev   MeSH
• diabetes mellitus 1. typu * komplikace   krev   farmakoterapie   MeSH
• fatální výsledek MeSH
• hypoglykemika * krev   škodlivé účinky   MeSH
• inzulin * krev   aplikace a dávkování   MeSH
• krevní glukóza analýza   MeSH
• lidé MeSH
• methamfetamin * krev   škodlivé účinky   otrava   MeSH
• poruchy spojené s užíváním amfetaminu * komplikace   MeSH
• stimulanty centrálního nervového systému * krev   škodlivé účinky   MeSH
• tanec MeSH
• tělesná námaha MeSH
• záchvaty chemicky indukované   etiologie   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• kazuistiky MeSH
• Názvy látek
• C-peptid MeSH
• hypoglykemika * MeSH
• inzulin * MeSH
• krevní glukóza MeSH
• methamfetamin * MeSH
• stimulanty centrálního nervového systému * MeSH