Aktürk, Halis Kaan

Background: Given the faster onset and shorter duration of action of ultra-rapid insulin lispro-aabc (URLi, Lyumjev™ insulin), compared with insulin lispro (a rapid-acting insulin [RAI]), the present study investigated the safety and glycemic outcomes of MiniMed™ 780G advanced hybrid closed-loop (AHCL) use with URLi in youths and adults with T1D. Methods: This 19-site, single-arm, clinical trial enrolled children and adolescents (aged 7–17 years) and adults (aged 18–80 years) with T1D who underwent a run-in period (∼2 weeks) using open loop or automated basal only with an RAI (aspart or lispro), followed by a 3-month study period using URLi with AHCL (AHCL + URLi). End-of-study glycemic metrics and A1c were compared to predefined thresholds and to data from baseline/run-in. Use of recommended optimal settings (ROS, 100 mg/dL glucose target with an active insulin time [AIT] of 2 h) was also assessed. Results: In an intention-to-treat population ( N = 101 pediatric and N = 110 adult participants), percentage of time in range (%TIR) during the last ∼6 weeks of the study period was significantly greater than the predefined thresholds for both the pediatric and adult participants. A1c was unchanged in the pediatric cohort but significantly reduced in the adult cohort (from 7.4 ± 0.9% to 6.9 ± 0.6% [ P < 0.001]). Compared with run-in, study period %TIR and percentage of time in tight target range (%TITR) were significantly increased (pediatric mean %TIRΔ [17.4%] and %TITRΔ [16.0%], respectively, and adult mean %TIRΔ [10.6%] and %TITRΔ [11.6%], respectively; P < 0.001 for all). Additionally, % time above range for both groups was significantly reduced. Use of ROS allowed more participants to achieve recommended glycemic targets. There were no severe hypoglycemia or diabetic ketoacidosis events. Most caregivers agreed that mealtime versus premeal URLi delivery simplified pediatric meal management. Conclusions: Similar to previous studies investigating automated URLi delivery, URLi use in the MiniMed™ 780G system was safe, and glycemic outcomes were favorable for pediatric and adult participants.

OBJECTIVE To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring. RESEARCH DESIGN AND METHODS At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks. RESULTS Prestudy, AID was used by 48% and MDI by 45%. Mean ± SD HbA1c was 7.57% ± 0.97% at baseline and 7.62% ± 1.06% at 17 weeks in the TI group and 7.59% ± 0.80% and 7.54% ± 0.77%, respectively, in the UC group (adjusted difference 0.11%, 95% CI −0.10 to 0.33, P value for noninferiority = 0.01). HbA1c improved from baseline to 17 weeks by &gt;0.5% (5.5 mmol/mol) in 12 (21%) in the TI group and in 3 (5%) in the UC group and worsened by &gt;0.5% (5.5 mmol/mol) in 15 (26%) in the TI group and in 2 (3%) in the UC group. The most common TI side effect was a brief cough; eight participants discontinued TI due to side effects. CONCLUSIONS In adults with type 1 diabetes, HbA1c after 17 weeks with a regimen of TI and degludec was noninferior to UC, which consisted predominately of either AID or MDI. TI should be considered an option for people with type 1 diabetes, particularly those who are motivated to further reduce postprandial hyperglycemia.

OBJECTIVE To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS The primary outcome, the treatment group difference in area under the curve for glucose &gt;180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose &lt;70 mg/dL occurred in one participant in each group. CONCLUSIONS Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.

ABSTRACT Background: Cannabis is widely used among patients with type 1 diabetes (T1D) in Colorado. Despite increasing use of cannabis among patients with T1D, the frequency and characteristics of unhealthy cannabis use are unknown. We investigated the differences in unhealthy cannabis use in recreational and medical cannabis users with T1D. Methods: Adult cannabis users with T1D completed an in-person questionnaire regarding their cannabis use patterns. They further divided into 2 categories; recreational and medical users. Cannabis Use Disorder Identification Test-Revised (CUDIT-R) was used to identify unhealthy cannabis use (CUDIT-R ≥ 8). Characteristics of cannabis users and unhealthy cannabis use between recreational and medical cannabis users were compared using unpaired t test. Results: Out of 117 patients, 85 patients reported recreational and 32 patients reported medical cannabis use. Based on CUDIT-R scores, 37.6% of adults with T1D had unhealthy cannabis use. Frequency of cannabis use ≥4 times a week was higher among medical users compared to recreational users (59.4% vs 28.2%, P < 0.01). There was no difference between the groups in duration of cannabis use. There was no difference in mean overall CUDIT-R score (7.14 vs 7.5, P = 0.76) between recreational and medical cannabis users. There were also no significant differences in mean CUDIT-R score between recreational and medical users within the nonhazardous use category (3.70 vs 4.4, P = 0.15) and unhealthy cannabis use category (12.84 vs 12.67, P = 0.92). Conclusions: Our study showed no difference in unhealthy cannabis use among recreational and medical cannabis users with T1D. Unhealthy cannabis use should be considered among users with T1D regardless of the reason for its use. Contexte: Le cannabis est largement utilisé chez les patients atteints de diabète de type 1 (DT1) au Colorado. Malgré l’augmentation de la consommation de cannabis chez les patients atteints de DT1, la fréquence et les caractéristiques d’une consommation de cannabis malsaine sont inconnues. Nous avons étudié les différences entre la consommation de cannabis malsaine chez les consommateurs de cannabis récréatifs et médicaux atteints de DT1. Méthodes: Les consommateurs de cannabis adultes atteints de DT1 ont rempli un questionnaire personnel sur leurs habitudes de consommation de cannabis. Ils ont été ensuite divisés en deux catégories; utilisateurs récréatifs et médicaux. Le Test d’identification des troubles liés à l’utilisation du cannabis révisé (CUDIT-R) a été utilisé pour identifier une utilisation malsaine du cannabis (CUDIT-R ≥8). Les caractéristiques des consommateurs de cannabis, ainsi que ceux d’une consommation de cannabis malsaine, entre les consommateurs de cannabis récréatifs et médicaux ont été comparées en utilisant un test t non apparié. Résultats: Sur 117 patients, 85 patients ont signalé des activités récréatives et 32 patients ont déclaré avoir utilisé du cannabis à des fins médicales. D’après les scores CUDIT-R, 37,6% des adultes atteints de DT1 avaient une consommation de cannabis malsaine. La fréquence de consommation de cannabis ≥ 4 fois par semaine était plus élevée chez les utilisateurs de médicaments que chez les utilisateurs récréatifs (59,4% contre 28,2%, p < 0,01). Il n’y avait pas de différence entre les groupes quant à la durée de consommation de cannabis. Il n’y avait pas de différence dans le score CUDIT-R global moyen (7,14 vs 7,5, p = 0,76) entre les utilisateurs de cannabis à des fins récréatives et médicales. Il n’existait pas non plus de différence significative entre le score CUDIT-R moyen entre les utilisateurs récréatifs et les utilisateurs à des fins médicales dans la catégorie d’usages non dangereux (3,70 contre 4,4, p = 0,15) et dans la catégorie d’abus de cannabis (12,84 contre 12,67, p = 0,92). Conclusions: Notre étude n’a montré aucune différence dans la consommation de cannabis malsaine chez les consommateurs de cannabis récréatifs et médicaux atteints de DT1. Une consommation de cannabis malsaine doit être envisagée chez les utilisateurs atteints de DT1, quelle que soit la raison de sa consommation.

Aim To conduct a systematic review and meta‐analysis to understand the timing and factors associated with anti‐programmed cell death protein‐1 ( PD ‐1)/anti‐programmed cell death protein‐1 ligand ( PD ‐L1) inhibitor‐induced Type 1 diabetes. Methods We searched MEDLINE , EMBASE , SCOPUS and Cochrane databases (August 2000–2018) for studies of any design on immune checkpoint inhibitors. A total of 71 cases were reviewed from 56 publications. Comparisons were made using Fisher's exact and Student's t ‐tests. Results The mean ± sd age at Type 1 diabetes presentation was 61.7±12.2 years, 55% of cases were in men, and melanoma (53.5%) was the most frequent cancer. The median time to Type 1 diabetes onset was 49 (5–448) days with ketoacidosis in 76% of cases. The average ± sd HbA 1c concentration was 62 ± 0.3 mmol/mol (7.84±1.0%) at presentation. All cases had insulin deficiency and required permanent exogenous insulin treatment. Half of the cases had Type 1 diabetes‐associated antibodies at presentation, and those with antibodies had a more rapid onset ( P =0.005) and higher incidence of diabetic ketoacidosis ( P =0.02) compared to people without antibodies. Conclusions Many people developed Type 1 diabetes within 3 months of initial PD ‐1/ PD ‐L1 inhibitor exposure. People presenting with Type 1 diabetes‐associated antibodies had a more rapid onset and higher incidence of ketoacidosis than those without antibodies. Healthcare providers caring for people receiving these state‐of‐the‐art therapies need to be aware of this potential severe adverse event.

Summary Objective Surgery is a stressor that can be categorized by duration and severity and induces a systemic stress response that includes increased adrenal cortisol production. However, the precise impact of surgical stress on the cortisol response remains to be defined. Design We performed a systematic review and meta‐analysis to assess the cortisol stress response induced by surgery and to stratify this response according to different parameters. Methods We conducted a comprehensive search in several databases from 1990 to 2016. Pairs of reviewers independently selected studies, extracted data and evaluated the risk of bias. Cortisol concentrations were standardized, pooled in meta‐analysis and plotted over time. Results We included 71 studies reporting peri‐operative serum cortisol measurements in 2953 patients. The cortisol response differed substantially between moderately/highly invasive and minimally invasive surgical procedures. Minimally invasive procedures did not show a peri‐operative cortisol peak, whereas more invasive surgeries caused a cortisol surge that was more pronounced in older subjects, women and patients undergoing open surgery and general anaesthesia. The duration of the procedure and the use of etomidate for induction of anaesthesia did not affect the cortisol response. Conclusions The peri‐operative cortisol stress response is dynamic and influenced by patient‐specific, surgical and anaesthetic features. However, the available evidence is derived from highly heterogeneous studies, with only two of 71 studies measuring cortisol by mass spectrometry, which currently prevents a precise and reproducible definition of this response.