Summary of clinical investigation plan for The DIATEC trial: in-hospital diabetes management by a diabetes team and continuous glucose monitoring or point of care glucose testing - a randomised controlled trial.

BACKGROUND: Worldwide, up to 20 % of hospitalised patients have diabetes mellitus. In-hospital dysglycaemia increases patient mortality, morbidity, and length of hospital stay. Improved in-hospital diabetes management strategies are needed. The DIATEC trial investigates the effects of an in-hospital diabetes team and operational insulin titration algorithms based on either continuous glucose monitoring (CGM) data or standard point-of-care (POC) glucose testing. METHODS: This is a two-armed, two-site, prospective randomised open-label blinded endpoint (PROBE) trial. We recruit non-critically ill hospitalised general medical and orthopaedic patients with type 2 diabetes treated with basal, prandial, and correctional insulin (N = 166). In both arms, patients are monitored by POC glucose testing and diabetes management is done by ward nurses guided by in-hospital diabetes teams. In one of the arms, patients are monitored in addition to POC glucose testing by telemetric CGM viewed by the in-hospital diabetes teams only. The in-hospital diabetes teams have operational algorithms to titrate insulin in both arms. Outcomes are in-hospital glycaemic and clinical outcomes. DISCUSSION: The DIATEC trial will show the glycaemic and clinical effects of in-hospital CGM handled by in-hospital diabetes teams with access to operational insulin titration algorithms in non-critically ill patients with type 2 diabetes. The DIATEC trial seeks to identify which hospitalised patients will benefit from CGM and in-hospital diabetes teams compared to POC glucose testing. This is essential information to optimise the use of healthcare resources before broadly implementing in-hospital CGM and diabetes teams. TRIAL REGISTRATION: Prospectively registered at ClinicalTrials.gov with identification number NCT05803473 on March 27th 2023.

Statistical Packages and Algorithms for the Analysis of Continuous Glucose Monitoring Data: A Systematic Review.

BACKGROUND: Continuous glucose monitoring (CGM) measures glucose levels every 1 to 15 minutes and is widely used in clinical and research contexts. Statistical packages and algorithms reduce the time-consuming and error-prone process of manually calculating CGM metrics and contribute to standardizing CGM metrics defined by international consensus. The aim of this systematic review is to summarize existing data on (1) statistical packages for retrospective CGM data analysis and (2) statistical algorithms for retrospective CGM analysis not available in these statistical packages. METHODS: A systematic literature search in PubMed and EMBASE was conducted on September 19, 2023. We also searched Google Scholar and Google Search until October 12, 2023 as sources of gray literature and performed reference checks of the included literature. Articles in English and Danish were included. This systematic review is registered with PROSPERO (CRD42022378163). RESULTS: A total of 8731 references were screened and 46 references were included. We identified 23 statistical packages for the analysis of CGM data. The statistical packages could calculate many metrics of the 2022 CGM consensus and non-consensus CGM metrics, and 22/23 (96%) statistical packages were freely available. Also, 23 statistical algorithms were identified. The statistical algorithms could be divided into three groups based on content: (1) CGM data reduction (eg, clustering of CGM data), (2) composite CGM outcomes, and (3) other CGM metrics. CONCLUSION: This systematic review provides detailed tabular and textual up-to-date descriptions of the contents of statistical packages and statistical algorithms for retrospective analysis of CGM data.

Management of diabetes and hyperglycaemia in non-intensive care units.

Diabetes and hyperglycaemia are frequent diagnoses in the hospital, and in-hospital hyperglycaemia is associated with adverse clinical outcomes. Insulin is the preferred treatment for in-hospital hyperglycaemia. This review summarises the management of hyperglycaemia in Danish hospitals. In Denmark, sliding-scale insulin is often applied with the addition of basal insulin after 1-2 days with hyperglycaemia which differs from international guidelines recommending a basal-bolus regimen. The optimal non-intensive care unit glucose targets, the safety and efficacy level of non-insulin antidiabetic agents, and continuous glucose monitoring are subjects of further research.

[Christmas article: The search for the (glycaemic) optimal christmas dinner].

INTRODUCTION: The Danish Christmas meal is not the healthiest and might increase blood glucose fluctuations, which can affect health negatively. Studies have shown that these large blood sugar fluctuations can be reduced by eating a meal in a particular order rather than eating it all at once. We investigated if sequential eating of a Danish Christmas meal affected post-prandial glucose fluctuations. METHODS: In a prospective randomised trial, 11 healthy subjects ate a standardised Danish Christmas meal. The subjects ate the meal three times with a wash-out day in between. On the first day, the subjects consumed the meal as they preferred. The following meals were divided into a starter (fresh red cabbage or pork roast) and the rest of the meal, and the opposite starter on the last intervention day. The glucose levels of the participants were monitored by continuous glucose monitoring (Freestyle Libre 2). We used a linear mixed model to compare the effects of the different orders of meal intake on glucose fluctuations. RESULTS: Nine of 11 participants were women with a mean age of 41.2 (range 25.0-64.0) years and mean glucose levels of 5.2 mmol/L. No differences in the postprandial glucose levels between the meals were found (all p > 0,05). CONCLUSION: We found no differences in the postprandial glucose levels in relation to the order of intake of fibers (salad) or protein (roast pork) before carbohydrates. We conclude that it is safe in terms of glycaemic control for healthy people without diabetes to eat a traditional Danish Christmas meal in any order. FUNDING: none. TRIAL REGISTRATION: not relevant.

Glycemic variability assessed by continuous glucose monitoring in hospitalized patients with community-acquired pneumonia.

BACKGROUND: Glycemic variability (GV) has only been sparsely studied in patients with community-acquired pneumonia (CAP). This study aimed to quantify in-hospital GV in CAP patients, including determining the impact of type 2 diabetes mellitus (T2DM) and glucocorticoid (GC) treatment on GV. METHODS: This is a prospective cohort study of CAP patients (N = 40) with or without T2DM and treated or not with GCs. The primary endpoint was GV measured as glucose standard deviation (SD), coefficient of variation (CV), and postprandial glucose excursions (PPGE) based on continuous glucose monitoring (CGM). Analysis of glucose data was split into daytime and nighttime when possible. RESULTS: Patients included had a mean age of 74 (range 55 to 91) years. SD (95%CI) increased by a factor of 1.93 (1.40 to 2.66) and 2.29 (1.38 to 3.81) in patients with T2DM and not treated with GCs during the daytime and the nighttime, respectively (both P < 0.01), and by a factor of 1.42 (1.04 to 1.97) in patients treated with GCs but without T2DM during the daytime (P = 0.031) compared to patients without T2DM and not treated with GCs. CV (95%CI) increased by 5.1 (0.0 to 10.1) and 8.1 (1.0 to 15.2) percentage points during the daytime and the nighttime, respectively, in patients with T2DM and not treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.046 and P = 0.026, respectively). PPGE (95% CI) increased during lunch by 2.5 (0.7 to 4.3) mmol/L (45 (13 to 77) mg/dL) in patients with T2DM and treated with GCs compared to patients without T2DM and not treated with GCs (P = 0.018). CONCLUSIONS: CAP patients receiving GCs, especially those with T2DM, are at great risk of developing high GV and therefore require clinical attention to mitigate GV. This applies particularly during the daytime. Results support the 1 to 2-h post-lunch screening procedure for glucocorticoid-induced hyperglycemia in patients without diabetes. SD was positively correlated with hospital length of stay.

Telemetric Continuous Glucose Monitoring During the COVID-19 Pandemic in Isolated Hospitalized Patients in Denmark: A Randomized Controlled Exploratory Trial.

Objective: To investigate whether telemetric continuous glucose monitoring (CGM) in hospitalized and isolated patients with diabetes mellitus and coronavirus disease 2019 (COVID-19) is associated with better glycemic outcomes and fewer patient health care worker contacts compared to blood glucose monitoring by traditional point-of-care (POC) glucose testing and to investigate the user aspect of implementing a CGM-system in-hospital. Materials and Methods: A randomized controlled exploratory trial was performed on hospitalized and isolated patients with diabetes and COVID-19 from May 2020 until February 2021 at Nordsjællands Hospital, Denmark. Participants were randomized to nonblinded telemetric CGM (as the only glucose monitoring method) or traditional POC glucose testing + blinded CGM. The primary endpoint was time in range (TIR) based on CGM data in both groups. A questionnaire about the user aspect of the CGM system was answered by health care personnel (HCP). Results: We included 64 participants in the analysis, 31 in the CGM group and 33 in the POC glucose group. TIR median was 46% for the CGM group and 68% for the POC glucose group (P = 0.368). The mean glucose value for the CGM group was 11.1 and 10.8 mmol/L in the POC glucose group (P = 0.372). CGM was associated with fewer POC glucose measurements (P < 0.001). Out of 30 HCPs, 28 preferred telemetric CGM over POC glucose testing. Conclusion: Remote glucose monitoring by CGM did not improve glycemic outcomes compared to traditional POC glucose testing, but was associated with fewer patient-personnel contacts, saving time for HCPs performing diabetes-related tasks. Most HCPs preferred CGM. The study is registered at http://www.clinicaltrials.gov (#NCT04430608).

In-hospital management of type 2 diabetes in Denmark is inconsistent with international guidelines.

INTRODUCTION: Insulin is the preferred treatment for hyperglycaemia in hospitalised patients with type 2 diabetes mellitus (T2DM). However, which insulin regimen to prefer is debated. We described Danish regional guidelines on the management of non-critically ill hospitalised patients with T2DM and compared them with international guidelines. METHODS: The Danish regional guidelines have been obtained via Danish regional web portals and by request to the regions. The guidelines were reviewed independently by the authors of this article to ensure uniformity in the interpretation of their contents. RESULTS: The recommended treatment of in-hospital hyperglycaemia is sliding scale insulin (SSI) in all five Danish regions. Insulin dosing by SSI is adjusted to bodyweight in two of the five regions. The recommended number of daily glucose point-of-care tests ranges from 4-8 to reach glucose levels of 5-10 mmol/l (90-180 mg/dl). In all regions, continuation of out-hospital insulin and non-insulin antidiabetic drugs is recommended; however, the latter is paused on wide indications. CONCLUSIONS: In-hospital hyperglycaemia for non-critically ill hospitalised patients with T2DM is treated by SSI, based on short-acting insulin, in all five Danish regions. International guidelines recommend a basal-bolus or basal-plus regimen based on both short- and long-acting insulin for most hospitalised non-critically ill patients with diabetes and discourage SSI. Danish regions should consider replacing SSI with a basal-bolus or basal-plus regimen. FUNDING: none. TRIAL REGISTRATION: not relevant.

[Christmas article: Influence of christmassy spices on blood glucose levels after intake of rice pudding meal].

Introduction The glucose-lowering effect of cinnamon is well known and has been used for this purpose since ancient times. Other christmassy spices, like ginger and cloves, have also been shown to affect blood glucose levels but are not as extensively examined. We aimed to explore the potential glucose-lowering effects of cinnamon, ginger and cloves by postprandial glucose excursions (PPGE) and maximum glucose level during rice pudding intake in healthy participants with use of continuous glucose monitoring during ingestion of the traditional Danish Christmas dish, rice pudding. Methods Participants wore an intermittently scanned continuous glucose monitor for five days in total. Day 0 was a 24h run-in stabilization period. Day 1 was used for baseline with ingestion of a standardized rice pudding meal without any spices. On days 2-4, participants had the same standardized rice pudding with one of the three Christmas spices on top. The participants ate rice pudding for breakfast (low-dose spice) and lunch (high-dose spice). A questionnaire was also developed to investigate the satisfaction level with the rice pudding and spice combinations. Results Data from 12 people were analyzed with mean age (range) of ~ 42 (25-63) years. Mean fasting glucose level (95% CI) was 4.7 (4.0-5.5) mmol/l. PPGE levels were higher for 6 g of ginger, compared to 3 g of ginger with mean difference of 1.02 mmol/l (0.12-1.92) (p = 0.030). No other differences between the different doses of spices or between spices and baseline were found regarding PPGE or the maximum glucose-level during intake of rice pudding. Most people preferred cinnamon on top of the rice pudding, however, eight out of 12 would rather risk complications from a higher blood glucose than eating Christmas spices on top of their rice pudding. Conclusion Putting christmassy spices on top of rice pudding did not have a glucose-lowering effect in this study. This was probably for the best, since we learned from the questionnaire, that the use of Christmas spices on top of rice pudding was rated worse than the risk of complications from having high blood glucose levels. Thus, implementation of Christmas spices as a preventative strategy is not recommended. Funding none. Trial registration none.