Fast-acting insulin aspart: a review of its pharmacokinetic and pharmacodynamic properties and the clinical consequences

Fast-acting insulin aspart (faster aspart) is insulin aspart (IAsp) with two added excipients, L-arginine and niacinamide, to ensure formulation stability with accelerated initial absorption after subcutaneous administration compared with previously developed rapid-acting insulins. The pharmacokinetic/pharmacodynamic properties of faster aspart have been characterised in clinical pharmacology trials with comparable overall methodology. In subjects with type 1 (T1D) or type 2 (T2D) diabetes, the serum IAsp concentration-time and glucose-lowering effect profiles are left-shifted for faster aspart compared with IAsp. In addition, faster aspart provides earlier onset, doubling of initial exposure, and an up to 2.5-fold increase in initial glucose-lowering effect within 30 min of subcutaneous injection, as well as earlier offset of exposure and effect. Similar results have been shown using continuous subcutaneous insulin infusion (CSII). The improved pharmacological properties of faster aspart versus IAsp are consistent across populations, i.e. in the elderly, children, adolescents and the Japanese. Thus, the faster aspart pharmacological characteristics more closely resemble the mealtime insulin secretion in healthy individuals, giving faster aspart the potential to further improve postprandial glucose control in subjects with diabetes. Indeed, change from baseline in 1-h postprandial glucose increment is in favour of faster aspart versus IAsp when used as basal-bolus or CSII treatment in phase III trials in subjects with T1D or T2D. This review summarises the currently published results from clinical pharmacology trials with faster aspart and discusses the potential clinical benefits of faster aspart compared with previous rapid-acting insulin products

Walking a tightrope - as a next-of-kin to an adolescent or young adult with cancer facing eating difficulties

Purpose: Eating difficulties cause reduced food intake and poor quality of life among adolescents and young adults (AYAs) with cancer. Therefore, next-of-kin eating support is crucial. The purpose of this study was to explore the lived experiences of being close to AYAs with cancer in the context of eating when they are at home between high-emetogenic chemotherapy (HEC) sessions. Method: In-depth interviews were conducted with 12 next-of-kin to AYAs (15–29 years old) with oncological or haematological diseases, treated with HEC. Van Manen’s hermeneuticphenomenological approach guided the design. Results: The essential meaning of the next-of-kin experiences is reflected in the overarching theme “Utilizing meals as an action-opportunity” consisting of two subthemes: ’Being on constant alert’ and “Walking a tightrope to maintain usual everyday life.” Conclusions: Findings revealed that utilizing meals as an action-opportunity towards AYAs’ food intake involved existential feelings including fear of losing their loved ones. Next-of-kin experienced that providing support through and with food was their only avenue of action. However, this sparked feelings of frustration and powerlessness.publishedVersio

Pårørendes oplevelser i en demensklinik

Dette studie undersøger, hvordan pårørende til patienter med nydiagnosticeret alzheimers demens oplever et forløb i en demensklinik. Studiet er en kvalitativ undersøgelse og bygger på fire semi-strukturerede interviews med pårørende. Med inspiration fra Kvale og Brinkmanns analysestrategi viste analysen fire fund: 1. Jeg ville ønske, jeg var blevet bedre forberedt, 2. Det giver tryghed at have kontakt til demensklinikken, 3. Forløbet har været givende og betryggende og 4. Hvad skal der nu ske? Det konkluderes, at pårørende har en fælles oplevelse af, at forløbet i demensklinikken har været betryggende og givende. Dog ses samtidig mangeartede oplevelser af forløbet. Nogle pårørende oplever sig informerede og på forkant med fremtiden efter forløbet i demensklinikken, mens andre pårørende oplever sig “(...)forladt til sig” selv når forløbet afsluttes. Ud fra disse forskellige oplevelser kan det antages, at pårørendes oplevelser kan have relation til pårørendes individuelle behov og ressourcer. Studiets mangeartede fund peger i retning af, at det er vanskeligt at placere pårørende i et standardiseret forløb. Dermed kan studiet anvendes til at belyse diskrepans mellem standardiserede patientforløb og individuelle ressourcer. Dette kan skabe refleksion blandt læger og sygeplejersker i demensklinikken og således øge opmærksomheden på patienters og pårørendes individuelle behov indenfor standardiserede, organisatoriske rammer

Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes

IntroductionThis study investigated the degree and direction (kHR) of the heart rate to performance curve (HRPC) during cardio-pulmonary exercise (CPX) testing and explored the relationship with diabetes markers, anthropometry and exercise physiological markers in type 1 diabetes (T1DM).Material and methodsSixty-four people with T1DM (13 females; age: 34 ± 8 years; HbA1c: 7.8 ± 1% (62 ± 13 mmol.mol-1) performed a CPX test until maximum exhaustion. kHR was calculated by a second-degree polynomial representation between post-warm up and maximum power output. Adjusted stepwise linear regression analysis was performed to investigate kHR and its associations. Receiver operating characteristic (ROC) curve was performed based on kHR for groups kHR 0.20 in relation to HbA1c.ResultsWe found significant relationships between kHR and HbA1c (β = -0.70, P < 0.0001), age (β = -0.23, P = 0.03) and duration of diabetes (β = 0.20, P = 0.04). Stepwise linear regression resulted in an overall adjusted R2 of 0.57 (R = 0.79, P < 0.0001). Our data revealed also significant associations between kHR and percentage of heart rate at heart rate turn point from maximum heart rate (β = 0.43, P < 0.0001) and maximum power output relativized to bodyweight (β = 0.44, P = 0.001) (overall adjusted R2 of 0.44 (R = 0.53, P < 0.0001)). ROC curve analysis based on kHR resulted in a HbA1c threshold of 7.9% (62 mmol.mol-1).ConclusionOur data demonstrate atypical HRPC during CPX testing that were mainly related to glycemic control in people with T1DM

Insulin detemir is associated with more predictable glycemic control and reduced risk of hypoglycemia than NPH insulin in patients with type 1 diabetes on a basal-bolus regimen with premeal insulin aspart

WSTĘP. Insulina detemir jest rozpuszczalnym, długodziałającym analogiem insuliny. Cechuje się wyjątkowym, wydłużonym profilem działania, pozwalającym na zmniejszenie zmienności glikemii, związanej ze stosowaniem konwencjonalnych insulin długodziałających. W badaniu porównano insulinę detemir i insulinę NPH pod względem uzyskanej kontroli glikemii, ryzyka hipoglikemii oraz wpływu na masę ciała u chorych na cukrzycę typu 1, otrzymujących przedposiłkowe wstrzyknięcia insuliny krótkodziałającej aspart. MATERIAŁ I METODY. Do badania zakwalifikowano metodą randomizacji 448 chorych na cukrzycę typu 1, którym podawano insulinę detemir lub NPH w stosunku 2:1. Badanie typu otwartego, w którym porównywano równolegle obie grupy pacjentów, trwało 6 miesięcy i było prowadzone w 46 ośrodkach, w 5 krajach. WYNIKI. Po 6 miesiącach badania wartości hemoglobiny glikowanej (HbA1c) w obu grupach były porównywalne. Glikemia na czczo była nieco niższa u chorych leczonych insuliną detemir, jednak różnica ta nie była istotna statystycznie (&#8211;0,76 mmol/l; p = 0,097). Zmienność glikemii na czczo określana na podstawie samokontroli u poszczególnych pacjentów była mniejsza przy stosowaniu insuliny detemir niż insuliny NPH (SD 3,37 vs. 3,78 mmol/l; p < 0,001). Ryzyko niedocukrzenia było o 22% niższe w grupie leczonej insuliną detemir niż w grupie przyjmującej insulinę NPH (p < 0,05); a ryzyko nocnych niedocukrzeń (23.00-06.00) &#8212; o 34% niższe (p < 0,005). Profil glikemii w porze nocnej był bardziej stabilny i stały podczas stosowania insuliny detemir (p = 0,05). Na końcu badania u pacjentów leczonych insuliną detemir zaobserwowano istotnie niższą masę ciała (p < 0,001). WNIOSKI. Leczenie insuliną detemir wiąże się z bardziej przewidywalną kontrolą glikemii, z mniejszymi wahaniami glikemii w ciągu doby oraz istotnym zmniejszeniem ryzyka niedocukrzeń w porównaniu ze stosowaniem insuliny NPH. Zmniejszenie masy ciała podczas terapii insuliną detemir jest dodatkowym, potencjalnie korzystnym efektem. Schematy leczenia oparte na insulinie detemir mogą umożliwić lepszą kontrolę glikemii niż schematy oparte na insulinie NPH.INTRODUCTION. Insulin detemir is a soluble basal insulin analog with a unique mechanism of protracted action designed to reduce the variability associated with conventional basal insulins. This trial compared the glycemic control, risk of hypoglycemia, and effect on body weight of insulin detemir and NPH insulin in patients with type 1 diabetes treated with rapid-acting insulin aspart at meals. MATERIAL AND METHODS. This study was a 6-month multinational open parallel-group comparison conducted at 46 centers in five countries and included 448 patients with type 1 diabetes randomized 2:1 to insulin detemir or NPH insulin, respectively. RESULTS. After 6 months, comparable HbA1c levels were found between the two treatment groups. Fasting plasma glucose tended to be lower in patients treated with insulin detemir, but this difference was not statistically significant (&#8211;0.76 mmol/l, P = 0.097). Within-subject variation in self-measured fasting blood glucose was lower with insulin detemir than with NPH insulin (SD 3.37 vs. 3.78 mmol/l, P < 0.001). Risk of hypoglycemia was 22% lower with insulin detemir than with NPH insulin (P < 0.05) and 34% lower for nocturnal (2300&#8211;0600) hypoglycemia (P < 0.005). Nightly plasma glucose profiles were smoother and more stable with insulin detemir (P < 0.05). Body weight was significantly lower with insulin detemir at the end of the trial (P < 0.001). CONCLUSIONS. Treatment with insulin detemir resulted in more predictable glycemic control, with smoother plasma glucose profiles than NPH insulin and a significant reduction in the risk of hypoglycemia. The reduction in body weight with insulin detemir is a potential additional advantage. Regimens optimized for insulin detemir may be able to improve glycemic control beyond that possible with NPH insulin

Psychological Flexibility as a Buffer against Caregiver Distress in Families with Psychosis

Background: Research has shown that caregivers of persons with psychosis play an invaluable role in recovery, but unfortunately, often report high levels of distress. While cognitive models of caregiver distress have been well-supported, there is still limited knowledge of the psychological factors involved. Recent advances in cognitive behavioral therapy seem to converge on the importance of acceptance- and mindfulness based processes.Aim: To examine the impact of psychological flexibility on caregiver distress in the early phases of psychosis, while controlling for known predictors of caregiver distress.Method: Within a cross-sectional design, 101 caregivers of 38 persons with first-episode psychosis in a clinical epidemiological sample completed a series of self-report measures.Results: A linear mixed model analysis found that, after controlling for caregiver socio-demographic factors, service user symptoms, drug use and global functioning, psychological flexibility was a significant predictor of caregiver distress.Conclusion: Greater level of psychological flexibility in caregivers, seems to be related to lower levels of caregiver distress. This finding corresponds to studies within a broad range of emotional disorders. There may be important clinical implications in terms of facilitating the process of acceptance through interventions from the ‘third-wave’ or contextual cognitive behavioral therapies

Differences in Physiological Responses to Cardiopulmonary Exercise Testing in Adults With and Without Type 1 Diabetes: A Pooled Analysis

OBJECTIVE To investigate physiological responses to cardiopulmonary exercise (CPX) testing in adults with type 1 diabetes compared with age-, sex-, and BMI-matched control participants without type 1 diabetes.RESEARCH DESIGN AND METHODS We compared results from CPX tests on a cycle ergometer in individuals with type 1 diabetes and control participants without type 1 diabetes. Parameters were peak and threshold variables of VO2, heart rate, and power output. Differences between groups were investigated through restricted maximum likelihood modeling and post hoc tests. Differences between groups were explained by stepwise linear regressions (P < 0.05).RESULTS Among 303 individuals with type 1 diabetes (age 33 [interquartile range 22; 43] years, 93 females, BMI 23.6 [22; 26] kg/m2, HbA1c 6.9% [6.2; 7.7%] [52 (44; 61) mmol/mol]), VO2peak (32.55 [26.49; 38.72] vs. 42.67 ± 10.44 mL/kg/min), peak heart rate (179 [170; 187] vs. 184 [175; 191] beats/min), and peak power (216 [171; 253] vs. 245 [200; 300] W) were lower compared with 308 control participants without type 1 diabetes (all P < 0.001). Individuals with type 1 diabetes displayed an impaired degree and direction of the heart rate-to-performance curve compared with control participants without type 1 diabetes (0.07 [−0.75; 1.09] vs. 0.66 [−0.28; 1.45]; P < 0.001). None of the exercise physiological responses were associated with HbA1c in individuals with type 1 diabetes.CONCLUSIONS Individuals with type 1 diabetes show altered responses to CPX testing, which cannot be explained by HbA1c. Intriguingly, the participants in our cohort were people with recent-onset type 1 diabetes; heart rate dynamics were altered during CPX testing

Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes

BackgroundTo explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes.MethodsSixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder.ResultsHbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01).ConclusionsPoor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity