A European, multicentre, retrospective, non-interventional study (EU-TREAT) of the effectiveness of insulin degludec after switching basal insulin in a population with type 1 or type 2 diabetes.

AIMS: To evaluate the clinical effectiveness of switching to insulin degludec (IDeg) in insulin-treated patients with either type 1 diabetes (T1DM) or type 2 diabetes (T2DM) under conditions of routine clinical care. MATERIALS AND METHODS: This was a multicentre, retrospective, chart review study. In all patients, basal insulin was switched to IDeg at least 6 months before the start of data collection. Baseline was defined as the most recent recording during the 3-month period before first prescription of IDeg. Values are presented as mean [95%CI]. RESULTS: T1DM (n = 1717): HbA1c decreased by -2.2 [-2.6; -2.0] mmol/mol (-0.20 [-0.24; -0.17]%) at 6 months vs baseline (P < .001). Rate ratio of overall (0.79 [0.69; 0.89]), non-severe nocturnal (0.54 [0.42; 0.69]) and severe (0.15 [0.09; 0.24]) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period (P < .001 for all). Total daily insulin dose decreased by -4.88 [-5.52; -4.24] U (-11%) at 6 months vs baseline (P < .001). T2DM (n = 833): HbA1c decreased by -5.6 [-6.3; -4.7] mmol/mol (-0.51 [-0.58; -0.43] %) at 6 months vs baseline (P < .001). Rate ratio of overall (0.39 [0.27; 0.58], P < .001), non-severe nocturnal (0.10 [0.06; 0.16], P < .001) and severe (0.075 [0.01; 0.43], P = .004) hypoglycaemia was significantly lower in the 6-month post-switch period vs the pre-switch period. Total daily insulin dose decreased by -2.48 [-4.24; -0.71] U (-3%) at 6 months vs baseline (P = .006). Clinical outcomes for T1DM and T2DM at 12 months were consistent with results at 6 months. CONCLUSIONS: This study demonstrates that switching patients to IDeg from other basal insulins improves glycaemic control and significantly reduces the risk of hypoglycaemia in routine clinical practice.

Effects of analogue insulin in multiple daily injection therapy of type 2 diabetes on postprandial glucose control and cardiac function compared to human insulin: a randomized controlled long-term study.

BACKGROUND: The prevention of cardiovascular disease, including diastolic cardiac dysfunction with its high prevalence and ominous prognosis, is a therapeutic challenge for patients with type 2 diabetes. Both short and long-acting insulin analogues (AI) have been shown to reduce glucose variability and provide potential benefit for cardiovascular disease although the effects on cardiac function have not yet been evaluated. This long-term, prospective, randomized controlled trial in patients with type 2 diabetes (T2D) tested the hypothesis that a multiple daily injection regimen (MDI) with AI improves postmeal glucose excursions in comparison to human insulin (HI) and that the effects of AI improve diastolic cardiac function. METHODS: For 36 months, MDI treatment in 109 T2D patients was adapted every 3 months (targets: fasting glucose ≤ 110 mg/dl, postmeal glucose ≤ 150 mg/dl) in both groups: AI (insulin detemir and insulin aspart, n = 61) and HI (NPH-insulin and regular HI, n = 48). Diastolic cardiac function (myocardial velocity E' using tissue Doppler imaging and the mitral inflow ratio E/A) and vascular function were assessed before and 2 h after a standardized breakfast (48 g carbohydrates). At baseline, both groups were comparable with regards to demographic, cardiac and metabolic data. Analysis of data included traditional statistics as well as the use of a multiple imputation technique shown in brackets [ ]. RESULTS: At 36 months, the primary endpoint, postmeal glucose, decreased by 20 ± 62 mg/dl, p = 0.038 [p = 0.021] with AI and increased insignificantly with HI (inter-group p = 0.032 [p = 0.047]) to postmeal glucose levels of 161 ± 39 with AI vs. 195 ± 54 mg/dl with HI (inter-group p = 0.002 [p = 0.010]) whereas the levels of fasting glucose and HbA1c were comparable. With AI, postmeal E' improved by 0.6 ± 1.4 cm/s, p = 0.009 [p = 0.002] and fasting E' by 0.4 ± 1.4 cm/s, p = 0.069 [p = 0.013], however, E' remained unchanged with HI. These changes were consistent with those of the traditional parameter E/A. CONCLUSIONS: MDI with AI results in better postmeal glucose control compared to HI. The treatment with AI is associated with improved diastolic cardiac function. ClinicalTrials.gov (NTC00747409).

Continuous Glucose Monitoring and Physical Activity.

Continuous glucose monitoring (CGM) use has several potential positive effects on diabetes management. These benefits are, e.g., increased time in range (TIR), optimized therapy, and developed documentation. Physical activity is a recommended intervention tool in diabetes management, especially for people with type 2 diabetes (T2D). The benefits of physical activity for people with diabetes can be seen as an improvement of glycemic control, glycemic variability, and the reduction of insulin resistance. In relation to the physical activity of people with T2D, the benefits of CGM use can even be increased, and CGM can be a helpful tool to prevent adverse events due to physical activity of people with diabetes, such as hypoglycemic events and nocturnal hypoglycemia after sports. This narrative review aims to provide solid recommendations for the use of CGM in everyday life physical activities based on the noted benefits and to give a general overview of the guidelines on physical activity and CGM use for people with diabetes.

Impact of Immunotherapies on SARS-CoV-2-Infections and Other Respiratory Tract Infections during the COVID-19 Winter Season in IBD Patients.

Background: COVID-19 represents one of the most significant medical problems of our time. Aims: This study is focused on the question whether patients with inflammatory bowel disease (IBD) who receive immunotherapies are more vulnerable to respiratory tract infections and SARS-CoV-2 infections in comparison to medical staff, as a cohort with an increased infection risk, and to the general population in a COVID-19 hotspot. Methods: We analysed data regarding respiratory tract infections that were collected in our IBD registry and compared them with corresponding data from medical employees in our associated Isarklinikum hospital and from the healthy general population in Munich, Germany, over the same time frame in April and June 2020. Patients were tested for SARS-CoV-2 immunoglobulins (Ig). Results: Symptoms of respiratory tract infections occurred equally frequent in IBD patients with immunotherapies as compared to those without. Older age (>49 years), TNF-inhibitor, and ustekinumab treatment showed a significantly protective role in preventing respiratory tract symptomatic COVID-19 infections that occurred in 0.45% of all our 1.091 IBD patients. Of those, 1.8% were positive for SARS-CoV-2 Ig, identically to the general population of Munich with also 1.8% positivity. Whilst more than 3% of all COVID-19 subjects of the general population died during the first wave, none of our IBD patients died or needed referral to the ICU or oxygen treatment. Conclusions: In our study, IBD patients are as susceptible to respiratory tract infections or SARS-CoV-2 as the normal population. There is no evidence of an association between IBD therapies and increased risk of COVID-19. Interestingly, a reduced rate of COVID-19 deaths in IBD patients, the majority on immunomodulator therapy, was observed, compared to the general population. Therefore, no evidence was found to suggest that IBD medication should be withheld, and adherence should be encouraged to prevent flares. In addition to older age (>49 years), TNF inhibitors and ustekinumab show a protective role in preventing respiratory tract infections. In addition, these results add to the growing evidence that supports further investigation of TNF inhibitors as a possible treatment in the early course of severe COVID-19.

Effectiveness and Safety of Insulin Glulisine When Initiating Supplementary Prandial Insulin Treatment (SIT) in Insulin-Naïve Patients with Type 2 Diabetes: The Observational IGLU-SIT Study.

INTRODUCTION: The IGLU-SIT study documented the effectiveness of initiating supplementary prandial insulin treatment (SIT) with insulin glulisine after failure of oral antidiabetic drugs alone in patients with type 2 diabetes (T2DM) in a real-world setting in Germany. METHODS: The IGLU-SIT study was an open-label, prospective, multicentre, non-interventional study with an observation period of 12 ± 1 months. The primary objective was to determine the proportion of patients reaching their pre-defined glycosylated haemoglobin (HbA1c) goal at 3, 6, 9 and 12 months. Selected secondary objectives were absolute change in HbA1c, a 7-point blood glucose profile, and rate of hypoglycaemia. Data were evaluated overall and by age group (< 65, 65-74 and ≥ 75 years). RESULTS: Overall, 215 patients with T2DM were observed in 64 centres. Baseline HbA1c was 8.3%, and mean HbA1c target was 6.8% (baseline 8.1% and target 6.9% in patients ≥ 75 years). Individual HbA1c target attainment in patients peaked at 38.9% (95% confidence interval [CI] 32.1-46.1%) after 12 months; this was 45.9% in patients aged ≥ 75 years. The mean HbA1c reduction was 1.12 ± 1.05% (p < 0.0001) with only minor differences by age group. A 7-point blood glucose profile revealed significant reductions (p < 0.0001) at all time-points. The rate of confirmed symptomatic hypoglycaemia was 2.2% (95% CI 0.7-5.1) during the 12-month follow-up; rates were increased in patients aged ≥ 75 years (7.0%; 95% CI 1.5-19.1) as were the rates of adverse events (17.8 vs. 6.1%). CONCLUSION: Initiating SIT with insulin glulisine is an appropriate treatment option in patients whose T2DM is insufficiently controlled. Particular attention should be paid to elderly patients in whom higher attainment rates of treatment target were associated with adverse events. TRIAL REGISTRATION: https://awbdb.bfarm.de ; Identifier: 6819; Date of registration: 23.06.2016.

Effectiveness and Safety of Switching Rapid-Acting Insulins to Insulin Glulisine in Patients with Diabetes: The Observational IGLU-S Study.

INTRODUCTION: The IGLU-S study assessed the effectiveness of insulin glulisine after switching from human insulin/other rapid-acting insulin analogues in patients with type 1 diabetes (T1DM) and type 2 diabetes (T2DM) in a real-world setting in Germany. METHODS: Open-label, prospective, multicentre, non-interventional study in Germany. The primary outcome was proportion of patients reaching pre-defined glycosylated haemoglobin A1c (HbA1c) goal at 3, 6, 9 and 12 months. Secondary outcomes included absolute changes in HbA1c, rate of hypoglycaemia and 7-point blood glucose profiles. RESULTS: Overall, 432 (55 T1DM, 377 T2DM) patients were enrolled. Baseline HbA1c was 8.2% (T1DM) and 8.3% (T2DM); individual HbA1c targets were 6.8% and 6.9%, respectively. After insulin glulisine introduction, the proportion of patients achieving their individual HbA1c increased to 43.6% (T1DM) and 39.6% (T2DM) of patients at 12 months. At 12 months, mean HbA1c was reduced by 0.86 ± 1.03% (p < 0.0001) in T1DM and 1.01 ± 1.02 (p < 0.0001) in T2DM. The 7-point blood glucose profile showed a significant reduction in patients with T2DM (p< 0.0001) and a non-significant reduction in T1DM patients. Confirmed symptomatic hypoglycaemia was 5.7% (T1DM) and 1.6% (T2DM). There were no cases of severe hypoglycaemia. CONCLUSION: Switching prandial insulin to insulin glulisine resulted in improved effectiveness with 43.6% of T1DM and 39.6% of T2DM patients reaching their individual pre-defined HbA1c target within 1 year. Switching was safe and was associated with a low rate of hypoglycaemia and adverse events. TRIAL REGISTRATION: https://awbdb.bfarm.de ; Identifier: 6818; Date of registration: 23.06.2016.

A Difference Between Bedtime and Pre-Breakfast Plasma Glucose Levels Indicates the Need for Prandial Insulin in Basal Insulin-Treated Type 2 Diabetic Patients with Normal Fasting Glucose.

AIM: In the present analysis, we characterised the efficacy and safety of adding a single daily injection of insulin glulisine to optimised basal-supported oral therapy (BOT) in patients with a high BeAM value, defined as a more than 50 mg/dl difference between bedtime and pre-breakfast blood glucose. METHODS: The BeAM value was retrospectively calculated for patients pooled from two clinical trials that supplemented BOT with glulisine. Data regarding changes in HbA1c, fasting plasma glucose (FPG), and postprandial glucose (PPG) levels from observation periods of 3 to 6 months were assessed. RESULTS: Out of 358 patients that received BOT/glulisine, 182 had a high BeAM value. Patients with a high BeAM value were older and had a longer diabetes duration than patients with a medium BeAM value. Significant reductions in HbA1c (7.5% to 7.2% [59 to 55 mmol/mol], p<0.0001) and PPG (202 to 143 mg/dl, p<0.0001) levels were documented. The proportion of patients with a high BeAM value achieving an HbA1c <7% [53 mmol/mol], alone or in combination with no hypoglycaemia, was lower than that of patients with a medium BeAM value. CONCLUSION: The analysis indicates that the supplementation of BOT with a single daily injection of prandial insulin is safe and effective for reducing HbA1c and PPG levels in patients with a high BeAM value (more than 50 mg/dl). However, patients with a medium BeAM value also responded well, which suggests that they should also be considered candidates for this change in therapy.

AGP and Nutrition - Analysing postprandial glucose courses with CGM.

Nutritional therapies are one of the fundamentals of effective management of diabetes type 1 and type 2. Lifestyle interventions, including nutritional recommendations, are also part of the basic therapy for people with prediabetes or obesity. It is recommended that the diet should be individually adapted to personal circumstances, preferences and metabolic goals. In the age of digitalisation, mHealth interventions, like continuous glucose monitoring systems (CGM), are increasingly finding their way into nutrition therapy. The ambulatory glucose profile (AGP), a structured and graphical compilation of the obtained CGM data, can also be used as a support for dietary adjustment. After assessment of the glycaemic situation (hypoglycaemia, variability and stability of glucose levels). This publication aims to provide a general overview of nutritional recommendations, especially in Germany, and to describe the benefits of CGM measurements with regard to nutrition.

Two clinical cases of adjunctive use of a SGLT-2 inhibitor in type 1 diabetes.

Type 1 diabetes mellitus (T1DM) prevalence is increasing and despite all available modern treatment options, an overall small but noticeable increase of mean HbA1c was recently observed in various registries. Authorized adjunctive pharmacological treatment options to insulin therapy are still scarce for T1DM. In February 2019, the European Medicines Agency (EMA) approved dapagliflozin as first in class sodium/glucose co-transporter 2 inhibitor (SGLT-2i) adjunctive therapy to insulin in patients with T1DM, which is currently still not approved by the FDA in the United States. SGLT-2is have shown significant improvement in HbA1c, reducing body weight and increasing time-in-range by reducing glycaemic variability, as well as reductions in total daily insulin dose in the trials in persons with T1DM. The cases presented here translate some of the observations gained from clinical trials into a real-world environment. They demonstrate that even highly practised and educated patients can benefit from the addition of a SGLT-2i as adjunctive treatment to insulin in T1DM. In summary, these cases demonstrate that a variety of patients with T1DM in a real-world setting may benefit from SGLT-2i treatment, as they have the potential to improve HbA1c, excess of body weight and increasing TiR among other things.

Rationale for Timely Insulin Therapy in Type 2 Diabetes Within the Framework of Individualised Treatment: 2020 Update.

Type 2 diabetes is characterised by chronic hyperglycaemia and variable degrees of insulin deficiency and resistance. Hyperglycaemia and elevated fatty acids exert harmful effects on ß-cell function, regeneration and apoptosis (gluco-lipotoxicity). Furthermore, chronic hyperglycaemia triggers a vicious cycle of insulin resistance, low-grade inflammation and a cascade of pro-atherogenic processes. Thus, timely near to normal glucose control is of utmost importance in the management of type 2 diabetes and prevention of micro- and macroangiopathy. The majority of patients are multimorbid and obese, with critical comorbidities such as cardiovascular disease, heart failure and chronic kidney disease. Recently published guidelines therefore recommend patient-centred risk/benefit-balanced use of oral glucose-lowering drugs or a glucagon-like peptide 1 (GLP-1) receptor agonist, or switching to insulin with glycated haemoglobin (HbA1c) out of target. This article covers the indications of early insulin treatment to prevent diabetes-related complications, particularly in subgroups with severe insulin deficit, and to achieve recovery of residual ß-cell function. Furthermore, the individualised, risk/benefit-balanced, timely initiation of insulin as second and third option is analysed. Timely insulin initiation may prevent diabetes progression, reduce diabetes-related complications and has less serious adverse effects. Basal insulin is the preferred option in most clinical situations with consequences of undertreatment of chronic hyperglycaemia.

Clinical Recommendations for the Use of the Ambulatory Glucose Profile in Diabetes Care.

BACKGROUND: The ambulatory glucose profile (AGP) uses the wealth of data that are generated by continuous glucose monitoring, including flash glucose monitoring technologies, to provide a visual representation of glucose levels over a typical standard day of usually the most recent two weeks for a person with diabetes and helps to identify patterns and trends in glucose control. The AGP allows certain patterns of glucose levels to be identified and analyzed, such that treatment adjustments can be made, and new individual treatment goals can be defined. This helps to ensure increased treatment satisfaction and adherence, quality of life, and an improvement in metabolic management for people with diabetes. OBJECTIVE: To date, a range of approaches exists for interpreting the information contained in an AGP, with different priorities given to identifying and targeting patterns of hypoglycemia and the degree of variability and stability underlying the glucose levels. The objective of the present recommendation is to describe the steps for assessing an AGP in detail and to illustrate these steps using visual examples. CONCLUSION: This paper describes the consensus recommendations from a group of German expert diabetologists on the necessary steps for assessing an AGP in a structured and detailed way and to explain these steps using practical clinical examples.

Comparative Dose Accuracy of Durable and Patch Insulin Pumps Under Laboratory Conditions.

Background: Recent studies demonstrate variable results of the accuracy with which patch pumps infuse insulin. Aim of this evaluation was to measure dose accuracies of the patch pump mylife™ OmniPod® (OP) in comparison with the durable insulin pump MiniMed® 640G (MM) simulating real-life clinical situations under laboratory conditions. Methods: Thirty-two OP and 15 MM were tested using insulin aspart at five different boluses (0.5, 1, 5, 10, and 15 international units [IU]) and three basal rates (0.2, 0.6, and 1.8 IU/h) at different time points during a 70 h investigation period. Owing to malfunctions only 22 OP and 11 MM could be analyzed. Dose accuracy was measured by an experimental setting based on IEC 60601-2-24:2012 with determination of weight differences of insulin collection tubes before and after experiments using a precision scale. A maximal tolerance of ±5% for boluses and basal rates was considered adequate according to IEC 60601-2-24:2012. Results: For the five boluses, the percentages of measurement results within the ±5% accuracy threshold were as follows: OP (18.6%, 26.5%, 89.0%, 96.0%, and 96.0%); MM (21.7%, 44.1%, 88.1%, 98.3%, and 100.0%). Both pumps were more accurate at higher bolus volumes (5, 10, and 15 IU), later bolus periods, and if the accuracy threshold was lowered to <10%, <15%, or >15%. For the three basal rates, the percentages within the ±5% accuracy threshold were as follows: OP (66.7%, 22.7%, and 16.7%); MM (14.3%, 0.0%, and 0.0%). Conclusion: This study demonstrates low accuracy for basal rates and single bolus deliveries at low insulin doses for both pump models. Clinicians should be aware of this variability when initiating insulin pump therapy especially in insulin-sensitive patients with low insulin dose requirements.

Therapy Adjustments Based on Trend Arrows Using Continuous Glucose Monitoring Systems.

Continuous glucose monitoring (CGM) systems use trend arrows to accurately display the anticipated glucose curve for the user. These are used for both "real-time" glucose monitoring and for intermittent scanning glucose monitoring. Trend arrow data are used by people with diabetes to make corrections to their glucose control. It is essential that they are correctly interpreted when adjusting insulin doses and to ensure that appropriate treatment decisions are made. The aim of this article is to provide general treatment guidance for diabetes teams and for people with diabetes using CGM in the context of trend arrows. This is based on previous recommendations for interpreting trend arrows without losing sight of the need for individual therapy adjustment.

Rosiglitazone, but not glimepiride, improves myocardial diastolic function in association with reduction in oxidative stress in type 2 diabetic patients without overt heart disease.

The effects of thiazolidinediones on cardiac function are controversial in humans with type 2 diabetes (T2DM) and in animals. Given the high prevalence and prognostic relevance of diastolic myocardial dysfunction in T2DM, we tested the hypothesis that by reducing oxidative stress rosiglitazone, but not glimepiride, may improve diastolic function. This randomised cross-over study investigated 12 metformin-treated T2DM patients without cardiovascular disease before and after 16 weeks of additional therapy with rosiglitazone (8 mg daily) or glimepiride (3 mg daily). Systolic and diastolic myocardial velocity (E') were assessed with tissue Doppler. In spite of similar non-significant lowering of glycosylated haemoglobin (HbA1C), rosiglitazone, but not glimepiride, significantly improved E' (p=0.04), reduced malondialdehyde (p=0.028), lowered high-sensitivity C-reactive protein (hsCRP) (p=0.019), and increased adiponectin (p=0.002). For rosiglitazone, multivariate regression analysis revealed malondialdehyde reduction as an independent determinant of treatment-induced improvement in E'. The rosiglitazone-induced improvements of diastolic function and oxidative stress may be of prognostic relevance in choosing therapy for T2DM patients without overt heart disease.

A higher blood glucose level pre-breakfast in comparison to bedtime is a contraindication for intensification of prandial insulin therapy in patients with type 2 diabetes - The impact of a negative BeAM value.

AIMS: The BeAM value refers to the difference between a patient's blood glucose level at bedtime (Be) and the following morning before breakfast (AM). The clinical impact of a negative BeAM value (AM blood glucose reading compared to that taken at bedtime) is unknown. METHODS: T2DM patients of the OPAL and POC trials were pooled and their BeAM values calculated. RESULTS: From a total of 358 patients, 31 were calculated as having a negative BeAM value at baseline, while 182 had a high value. Patients in the negative BeAM group were younger, had shorter diabetes duration, and lower HbA1c levels. Fasting blood glucose levels were higher in the negative BeAM group, and these increased to a greater extent during the trial periods. No significant differences in hypoglycaemia occurrence were observed. Multivariate adjusted analysis indicated no association between a negative BeAM value and achievement of HbA1c < 7%, or composite endpoints that additionally included no hypoglycaemia and no weight gain. CONCLUSIONS: Supplementation of BOT with prandial insulin is not beneficial for patients who have a higher blood glucose reading before breakfast in comparison to before bedtime. Further investigation into the cause of the high morning reading in these patients is indicated.