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Background: Real-world studies of people with type 2 diabetes (T2D) have shown insufficient dose adjustment during basal insulin titration in clinical practice leading to suboptimal treatment. Thus, 60% of people with T2D treated with insulin do not reach glycemic targets. This emphasizes a need for methods supporting efficient and individualized basal insulin titration of people with T2D. However, no systematic review of basal insulin dose guidance for people with T2D has been found., Objective: To provide an overview of basal insulin dose guidance methods that support titration of people with T2D and categorize these methods by characteristics, effect, and user experience., Methods: The review was conducted according to the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies about basal insulin dose guidance, including adults with T2D on basal insulin analogs published before September 7, 2022, were included. Joanna Briggs Institute critical appraisal checklists were applied to assess risk of bias., Results: In total, 35 studies were included, and three categories of dose guidance were identified: paper-based titration algorithms, telehealth solutions, and mathematical models. Heterogeneous reporting of glycemic outcomes challenged comparison of effect between the three categories. Few studies assessed user experience., Conclusions: Studies mainly used titration algorithms to titrate basal insulin as telehealth or in paper format, except for studies using mathematical models. A numerically larger proportion of participants seemed to reach target using telehealth solutions compared to paper-based titration algorithms. Exploring capabilities of machine learning may provide insights that could pioneer future research while focusing on holistic development., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Author P.V. is head of research at the Steno Diabetes Center North Denmark, funded by the Novo Nordisk Foundation. Author M.H.J is a former Novo Nordisk employee and holds Novo Nordisk shares.

Background and Aims: Hypoglycemia may lead to anxiety, poor adherence, and hypoglycemia unawareness and is especially a threat during the night in patients with insulin-treated type 2 diabetes (T2D). It would therefore be beneficial to warn patients at risk of hypoglycemia at bedtime so they can react accordingly and avoid the episode. Hence, the aim of the present study was to develop a model for predicting nocturnal hypoglycemia., Methods: Continuous glucose monitoring (CGM), mealtime, and insulin data were collected from 67 insulin-treated patients with T2D (NCT01819129). Data were structured into 24-hour periods and labeled as nocturnal hypoglycemia or not depending on whether 15 consecutive minutes were spent below 3.0 mmol/L (54 mg/dL) during the following night. Each period was divided into "last night," "morning," "day," and "evening" for feature extraction purposes, and 72 potential features were extracted for every period. A five-fold cross-validation was used to select features by forward selection and for training and validating a model based on logistic regression., Results: The prediction model was based on 30 patients with 60/496 periods resulting in nocturnal hypoglycemia. Forward selection revealed that the best features were based on CGM and involved the last value and mean value during the evening, as well as the relative difference in maximum value during the day between the present period and previous periods. The model obtained a mean area under the receiver operating characteristics curve (AUC) of 0.82 with an accuracy of 0.79., Conclusions: The model was able to predict nocturnal hypoglycemia with an acceptable accuracy and could therefore prevent such cases., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The effect of telemedicine solutions in diabetes remains inconclusive. However, telemedicine studies have shown a positive trend in regards to glycemic control. The telemedicine interventions that facilitate adjustment of medication seems to improve glycemic control more effectively. Hence, it is recommended that future telemedicine studies for patients with diabetes include patient-specific suggestions for changes in medicine. Hence, the aim of the trial is to explore the effect of telemonitoring in patients with type 2 diabetes (T2D) on insulin therapy., Methods: The trial is an open-label randomized controlled trial with a trial period of 3 months conducted in two sites in Denmark. Patients with T2D on insulin therapy will be randomized (1:1) to a telemonitoring group (intervention) or a usual care group (control). The telemonitoring group will use a continuous glucose monitor (CGM), an insulin pen, an activity tracker, and smartphone applications throughout the trial. Hospital staff will monitor the telemonitoring group and contact the subjects by telephone repeatedly throughout the trial period. The usual care group will use a blinded CGM the first and last 20 days of the trial and will use a blinded insulin pen for the entire period. The primary endpoint will be changed from baseline in CGM time in range (3.9-10.0 mmol/L) 3 months after randomization. Secondary endpoints include change from baseline in glycated hemoglobin (HbA1c), total daily dose, time above range, and time below range 3 months after randomization. Exploratory endpoints include health-related quality of life, diabetes-related quality of life, etc. DISCUSSION: The DiaMonT trial will test a telemonitoring setup including various devices. Such a setup may be criticized, because it is impossible to determine which element(s) add to the potential effect. However, it is not possible and counterproductive to test the elements individually, since it is the full telemedicine setup that is being evaluated. The DiaMonT trial is the first Danish trial to explore the effect of telemonitoring on patients on insulin therapy. Thus, the DiaMonT trial has the potential to form the basis for the implementation of telemedicine for patients with T2D in Denmark., Trial Registration: ClinicalTrials.gov NCT04981808. Registered on 8 June 2021., (© 2022. The Author(s).)

Background: Continuous glucose monitoring (CGM) is a powerful tool to be considered both in clinical practice and clinical trials. However, CGM has been criticized for being inaccurate for many reasons including a physiological delay. This study sought to investigate the current delay issue and propose a simple post-processing procedure., Method: More than a million hours of the Dexcom G4 CGM from 472 subjects investigated in a state-of-the-art clinical trial were analyzed by time shifting the CGM measurements and comparing them to plasma glucose (PG) measurements. The resultant CGM measurements were then assessed in relation to real-world clinical research endpoints., Results: A CGM time shift of -9 minutes was optimal and reduced mean absolute relative difference (MARD) statistically significantly with 1.0% point. The MARD reduction resulted in better clinical research endpoints of hypoglycemia and postprandial glucose increments., Conclusions: The delay in CGM is still an issue. The delay in this study was identified to be 9 minutes compared to PG. With a simple post-processing approach of time shifting the CGM measurements with -9 minutes, it was possible to obtain a statistically significantly lower MARD and subsequently obtain clinical research endpoints of improved validity.

Background: Lowering glucose levels is a complex task for patients with type 1 diabetes, and they often lack contact with health care professionals. Intermittently scanned continuous glucose monitoring (isCGM) has the potential to aid them with blood glucose management at home. The aim of this study was to investigate the long-term effect of isCGM on HbA1c in type 1 diabetes patients with poor glycaemic control in a region-wide real-world setting. Methods: All patients with type 1 diabetes receiving an isCGM due to poor glycaemic control (≥70 mmol/mol [≥8.6%]) in the period of 2020–21 in Region North Denmark ("T1D-CGM") were compared with all type 1 diabetes patients without isCGM ("T1D-NOCGM") in the same period. A multiple linear regression model adjusted for age, sex, diabetes duration and use of continuous subcutaneous insulin infusion was constructed to estimate the difference in change from baseline HbA1c between the two groups and within subgroups of T1D-CGM. Results: A total of 2,527 patients (T1D-CGM: 897; T1D-NOCGM: 1,630) were included in the study. The estimated adjusted difference in change from baseline HbA1c between T1D-CGM vs T1D-NOCGM was -5.68 mmol/mol (95% CI: (-6.69 to -4.67 mmol/mol; p<0.0001)). Older patients using isCGM dropped less in HbA1c. Conclusions: Our results indicate that patients with type 1 diabetes in poor glycaemic control from Region North Denmark in general benefit from using isCGM with a sustained 24-month improvement in HbA1c, but the effect on HbA1c may be less pronounced for older patients. [ABSTRACT FROM AUTHOR]

Aims: To evaluate the risk of severe hypoglycaemia for patients with Type 1 diabetes (T1D) when exposed to insulin regimens including human insulin only or insulin analogues. Methods: A total of 19 896 patients with T1D were extracted from the Danish National Patient Register. Of these, 6379 T1D patients experiencing 1 of more severe hypoglycaemic episodes (total of 17 242 episodes) were matched 1:1 with T1D patients without severe hypoglycaemia. A logistic regression model with last insulin regimen used as exposure was constructed to analyse the effect on severe hypoglycaemia. Results: People on a basal–bolus regimen with insulin analogues had a reduced risk of severe hypoglycaemia of 39% (odds ratio: 0.61, 95% confidence interval: 0.54–0.68) compared to patients on a basal–bolus human insulin only regimen. Furthermore, patients on a premixed regimen containing an insulin analogue had a 58% (odds ratio: 0.42, 95% confidence interval: 0.36–0.49) reduced risk of severe hypoglycaemia compared to patients on premixed human insulin only. Conclusion: This study indicates that use of a basal–bolus insulin regimen with an insulin analogue is safer with respect to severe hypoglycaemia in patients with T1D than the use of a basal–bolus human insulin only regimen. [ABSTRACT FROM AUTHOR]

This systematic review aims to identify current methods used for the assessment of insulin adherence in adults with insulin-treated type 2 diabetes. The primary goal is to offer recommendations for clinical practice to improve quantification of adherence. The review was conducted in accordance with PRISMA 2020 and registered at PROSPERO (CRD42022334134). PubMed, Embase, CINAHL, and PsycINFO were searched on 15 November 2022 and included three blocks: Type 2 diabetes, insulin, and adherence. We considered primary full-text studies describing an assessment method and a threshold for assessment of insulin adherence in adults with insulin-treated type 2 diabetes. A final sample of 50 studies were included. Identified methods fell into four categories: self-report, pharmacy claims, inulin count, and data from an insulin pen device. Commonly reported methods included: The Morisky Medication Adherence Scale, the (adjusted) Medication Possession Ratio, and the Proportions of Days Covered. A threshold of <80% was used to define non-adherence in nearly half of the studies. Yet, several thresholds were reported. Most available methods for assessing insulin adherence in adults with insulin-treated type 2 diabetes are severely limited in providing in-depth insights into timing, dosing size, injection patterns, and adherence behavior. However, recognizing diverse types of non-adherence is crucial, as they denote unique behavioral entities requiring targeted intervention. Employing insulin injection data (e.g., from a smart insulin pen cap) to underlie an assessment method is a potential new approach to objectively assess insulin timing and dosing adherence in adults with insulin-treated type 2 diabetes. • Various diverse methods are used to assess insulin adherence in adults. • The usefulness of a method depends on the assessment aim and resources available. • Most methods used do not account for the complexity of insulin therapy. • Insulin pen data is a novel method to assess insulin adherence in adults. [ABSTRACT FROM AUTHOR]

Aims: Real-world evidence of the safety of insulin degludec compared with insulin glargine U100 is sparse. This study sought to investigate the risk of major cardiovascular events, severe hypoglycaemia, and all-cause mortality after initiation of degludec or glargine U100 in the population of Denmark.Materials and Methods: All Danish people with diabetes initiating treatment on degludec (n=5159) or glargine (n=4041) in 2016 to 2017 were included in the study. The effect of insulin treatment on the endpoints of major cardiovascular events, severe hypoglycaemia, and all-cause mortality was analysed with Cox proportional hazard models. The models were adjusted for age, sex, diabetes duration, diabetes type, highest completed education, and annual income. The model of severe hypoglycaemia was also adjusted for severe hypoglycaemia prior to baseline. The model of mortality was also adjusted for history of alcohol abuse, use of antidepressants, use of opioids, and use of anxiolytics. Lastly, the models of major cardiovascular events and mortality were also adjusted for Charlson comorbidity index.Results: Use of degludec resulted in an almost twofold decrease in risk of death (hazard rate [HR]: 0.54, 95% CI: 0.44-0.65) compared with use of glargine. No statistically significant risk changes were found for major cardiovascular events (HR: 0.86, 95% CI: 0.62-1.19) and severe hypoglycaemia (HR: 1.13, 95% CI: 0.66-1.93). The proportion of cause of death due to malignant neoplasm of pancreas was almost doubled for glargine compared with degludec.Conclusions: These results indicate that insulin degludec has a safer profile with respect to all-cause mortality as compared with insulin glargine U100. [ABSTRACT FROM AUTHOR]