Activation of the lectin pathway of the complement system, as demonstrated by elevated levels of mannan-binding lectin proteins (MBL), contributes to vascular pathology in type 1 diabetes (T1D). Vascular complications are greatest in T1D individuals with concomitant insulin resistance (IR), however, whether IR amplifies activiation of the lectin pathway in T1D is unknown. We pooled pretreatment data from two RCTs and performed a cross-sectional analysis on 46 T1D individuals. We employed estimated glucose disposal rate (eGDR), a validated IR surrogate with cut-points of: <5.1, 5.1-8.7, and > 8.7 mg/kg/min to determine IR status, with lower eGDR values conferring higher degrees of IR. Plasma levels of MBL-associated proteases (MASP-1, MASP-2, and MASP-3) and their regulatory protein MAp44 were compared among eGDR classifications. In a subset of 14 individuals, we assessed change in MASPs and MAp44 following improvement in IR. We found that MASP-1, MASP-2, MASP-3, and MAp44 levels increased in a stepwise fashion across eGDR thresholds with elevated MASPs and MAp44 levels conferring greater degrees of IR. In a subset of 14 patients, improvement in IR was associated with significant reductions in MASPs, but not MAp44, levels. In conclusion, IR in T1D amplifies levels of MASP-1/2/3 and their regulator MAp44, and improvement of IR normalizes MASP-1/2/3 levels. Given that elevated levels of these proteins contribute to vascular pathology, amplification of the lectin pathway of the complement system may offer mechanistic insight into the relationship between IR and vascular complications in T1D.

• Klíčová slova
• complement, insulin resistance, mannan-binding lectin-associated serine proteases, type 1 diabetes,
• MeSH
• diabetes mellitus 1. typu * MeSH
• inzulinová rezistence * MeSH
• komplement MeSH
• lektin vázající mannosu * MeSH
• lektiny metabolismus   MeSH
• lidé MeSH
• průřezové studie MeSH
• serinové proteasy asociované s proteinem vázajícím mannosu metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• komplement MeSH
• lektin vázající mannosu * MeSH
• lektiny MeSH
• serinové proteasy asociované s proteinem vázajícím mannosu MeSH

• Klíčová slova
• community health center, intervention, public health, randomized controlled trial, type 2 diabetes mellitus,
• MeSH
• diabetes mellitus * terapie   MeSH
• lidé MeSH
• telemedicína * MeSH
• zdraví rodiny * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• práce podpořená grantem MeSH

OBJECTIVE: Our aim in this study was to assess attitudes toward exercise and quality of life (QoL) in adults with type 1 diabetes (T1D) with and without insulin resistance (IR). METHODS: We pooled baseline pretreatment data from a subset of individuals with T1D from 2 randomized controlled trials. Estimated glucose disposal rate (eGDR), a validated surrogate marker of IR, was calculated using an established formula to classify individuals according to IR status with a cutpoint of <6 mg/kg/min for the determination of IR. Self-reported barriers to exercise were obtained using a validated questionnaire, the Barriers to Physical Activity in T1D (BAPAD-1). In addition, QoL was determined using the 36-item Short Form (SF-36) questionnaire. Differences between dichotomized variables were assessed using the independent t test, Mann-Whitney U test, or Fisher exact test. Linear regression was employed to explore the association of eGDR with BAPAD-1 and QoL scores, with sequential adjustment for potential confounders. RESULTS: Of the 85 individuals included in our study, 39 were classified as having IR. The mean BAPAD-1 total score was higher for individuals with IR (IR: 3.87±0.61; non-IR: 2.83±0.55; p<0.001). The highest exercise barrier scores for individuals with IR were risk of hypoglycemia (5.67±1.26) and risk of hyperglycemia (5.23±1.20), whereas the highest scoring exercise barrier scores for non-IR individuals were not diabetes-related, with low level of fitness (3.91±1.26) and physical health status, excluding diabetes (3.67±1.48), ranked highest. QoL scores were comparable between groups (p>0.05). CONCLUSIONS: Risk of hypoglycemia was the greatest barrier to exercise in individuals with T1D with IR, whereas non-diabetes-related barriers to exercise were more salient in individuals with T1D without IR.

• Klíčová slova
• activité physique, attitudes envers l’exercice, attitudes toward exercise, diabète de type 1, insulin resistance, physical activity, quality of life, qualité de vie, résistance à l’insuline, type 1 diabetes,
• MeSH
• cvičení MeSH
• diabetes mellitus 1. typu * MeSH
• dospělí MeSH
• glukosa MeSH
• hypoglykemie * epidemiologie   prevence a kontrola   MeSH
• inzulinová rezistence * MeSH
• kvalita života MeSH
• lidé MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa MeSH

• MeSH
• draslík MeSH
• hyperkalemie * epidemiologie   terapie   MeSH
• lidé MeSH
• urgentní služby nemocnice MeSH
• výsledek terapie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH
• Názvy látek
• draslík MeSH

OBJECTIVES: Circulating insulin concentrations mediate vascular-inflammatory and prothrombotic factors. However, it is unknown whether interindividual differences in circulating insulin levels are associated with different inflammatory and prothrombotic profiles in type 1 diabetes (T1D). We applied an unsupervised machine-learning approach to determine whether interindividual differences in rapid-acting insulin levels associate with parameters of vascular health in patients with T1D. METHODS: We re-analyzed baseline pretreatment meal-tolerance test data from 2 randomized controlled trials in which 32 patients consumed a mixed-macronutrient meal and self-administered a single dose of rapid-acting insulin individualized by carbohydrate counting. Postprandial serum insulin, tumour necrosis factor (TNF)-alpha, plasma fibrinogen, human tissue factor (HTF) activity and plasminogen activator inhibitor-1 (PAI-1) were measured. Two-step clustering categorized individuals based on shared clinical characteristics. For analyses, insulin pharmacokinetic summary statistics were normalized, allowing standardized intraindividual comparisons. RESULTS: Despite standardization of insulin dose, individuals exhibited marked interpersonal variability in peak insulin concentrations (48.63%), time to peak (64.95%) and insulin incremental area under the curve (60.34%). Two clusters were computed: cluster 1 (n=14), representing increased serum insulin concentrations; and cluster 2 (n=18), representing reduced serum insulin concentrations (cluster 1: 389.50±177.10 pmol/L/IU h-1; cluster 2: 164.29±41.91 pmol/L/IU h-1; p<0.001). Cluster 2 was characterized by increased levels of fibrinogen, PAI-1, TNF-alpha and HTF activity; higher glycated hemoglobin; increased body mass index; lower estimated glucose disposal rate (increased insulin resistance); older age; and longer diabetes duration (p<0.05 for all analyses). CONCLUSIONS: Reduced serum insulin concentrations are associated with insulin resistance and a prothrombotic milieu in individuals with T1D, and therefore may be a marker of adverse vascular outcome.

• Klíčová slova
• apprentissage automatique, diabète de type 1, insulin pharmacokinetics, interpersonal variability, machine learning, pharmacocinétique de l’insuline, type 1 diabetes, variabilité interpersonnelle,
• MeSH
• diabetes mellitus 1. typu * komplikace   MeSH
• fibrinogen terapeutické užití   MeSH
• hypoglykemika farmakologie   terapeutické užití   MeSH
• inhibitor aktivátoru plazminogenu 1 terapeutické užití   MeSH
• injekce subkutánní MeSH
• inzulin terapeutické užití   MeSH
• inzulinová rezistence * MeSH
• krátkodobě působící inzuliny terapeutické užití   MeSH
• krevní glukóza analýza   MeSH
• lidé MeSH
• postprandiální období MeSH
• strojové učení MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• fibrinogen MeSH
• hypoglykemika MeSH
• inhibitor aktivátoru plazminogenu 1 MeSH
• inzulin MeSH
• krátkodobě působící inzuliny MeSH
• krevní glukóza MeSH

The glycemic response to ingested glucose for the treatment of hypoglycemia following exercise in type 1 diabetes patients has never been studied. Therefore, we aimed to characterize glucose dynamics during a standardized bout of hypoglycemia-inducing exercise and the subsequent hypoglycemia treatment with the oral ingestion of glucose. Ten male patients with type 1 diabetes performed a standardized bout of cycling exercise using an electrically braked ergometer at a target heart rate (THR) of 50% of the individual heart rate reserve, determined using the Karvonen equation. Exercise was terminated when hypoglycemia was reached, followed by immediate hypoglycemia treatment with the oral ingestion of 20 g of glucose. Arterialized blood glucose (ABG) levels were monitored at 5 min intervals during exercise and for 60 min during recovery. During exercise, ABG decreased at a mean rate of 0.11 ± 0.03 mmol/L·min-1 (minimum: 0.07, maximum: 0.17 mmol/L·min-1). During recovery, ABG increased at a mean rate of 0.13 ± 0.05 mmol/L·min-1 (minimum: 0.06, maximum: 0.19 mmol/L·min-1). Moreover, 20 g of glucose maintained recovery from hypoglycemia throughout the 60 min postexercise observation window.

• Klíčová slova
• exercise, glycemic excursion, hypoglycemia, hypoglycemia treatment, insulin therapy, type 1 diabetes,
• MeSH
• aplikace orální MeSH
• cvičení * MeSH
• cyklistika MeSH
• diabetes mellitus 1. typu krev   farmakoterapie   MeSH
• dospělí MeSH
• glukosa aplikace a dávkování   MeSH
• hypoglykemie farmakoterapie   MeSH
• inzulin krev   MeSH
• krevní glukóza analýza   MeSH
• lidé MeSH
• pilotní projekty MeSH
• srdeční frekvence MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mužské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukosa MeSH
• inzulin MeSH
• krevní glukóza MeSH