Background: Pharmacological post-MI treatment is routinely initiated at intensive/cardiac care units. However, solid evidence for an early start of these therapies is only available for dual platelet therapy and statins, whereas data on beta blockers and RAAS inhibitors are heterogenous and mainly limited to STEMI and heart failure patients. Recently, the EMMY trial provided the first evidence on the beneficial effects of SGLT2 inhibitors (SGLT2i) when initiated early after PCI. In patients with type 2 diabetes mellitus, SGLT2i are considered “sick days drugs” and it, therefore, remains unclear if very early SGLT2i initiation following MI is as safe and effective as delayed initiation. Methods and results: The EMMY trial evaluated the effect of empagliflozin on NT-proBNP and functional and structural measurements. Within the Empagliflozin group, 22 (9.5%) received early treatment (< 24 h after PCI), 98 (42.2%) within a 24 to < 48 h window (intermediate), and 111 (48.1%) between 48 and 72 h (late). NT-proBNP levels declined by 63.5% (95%CI: − 69.1; − 48.1) in the early group compared to 61.0% (− 76.0; − 41.4) in the intermediate and 61.9% (− 70.8; − 45.7) in the late group (n.s.) within the Empagliflozin group with no significant treatment groups—initiation time interaction (p_int = 0.96). Secondary endpoints of left ventricular function (LV-EF, e/e`) as well as structure (LVESD and LVEDD) were also comparable between the groups. No significant difference in severe adverse event rate between the initiation time groups was detected. Conclusion: Very early administration of SGLT2i after acute myocardial infarction does not show disadvantageous signals with respect to safety and appears to be as effective in reducing NT-proBNP as well as improving structural and functional LV markers as initiation after 2–3 days.

The aim of the study was to assess the amount of orally administered carbohydrates needed to maintain euglycemia during moderate-intensity exercise in individuals with type 1 diabetes. Nine participants with type 1 diabetes (four women, age 32.1 ± 9.0 years, BMI 25.5 ± 3.9 kg/m², HbA_1c 55 ± 7 mmol/mol (7.2 ± 0.6%)) on insulin Degludec were randomized to cycle for 55 min at moderate intensity (63 ± 7% VO_2peak) for five consecutive days on either 75% or 100% of their regular basal insulin dose. The impact of pre-exercise blood glucose concentration on the carbohydrate requirement was analyzed by one-way ANOVA stratified for pre-exercise blood glucose quartiles. The effect of the basal insulin dose on the amount of orally administered carbohydrates was evaluated by Wilcoxon matched-pairs signed-rank test. The amount of orally administered carbohydrates during the continuous exercise sessions was similar for both trial arms (75% or 100% basal insulin) with median [IQR] of 36 g (9–62 g) and 36 g (9–66 g) (p = 0.78). The amount of orally administered carbohydrates was determined by pre-exercise blood glucose concentration for both trial arms (p = 0.03). Our study elucidated the importance of pre-exercise glucose concentration related orally administered carbohydrates to maintain euglycemia during exercise in individuals with type 1 diabetes.

Background: In patients with type 2 diabetes mellitus (T2DM) an association between severe hypoglycaemic episodes and the risk of cardiovascular (CV) morbidity and mortality has been previously established. Methods: We aimed to investigate the influence of hypoglycaemia on several diabetes-related and platelet-related miRNAs selected based on bioinformatic analysis and literature search, including hsa-miR-16, hsa-miR-34a, hsa-miR-129-2, hsa-miR-15a, hsa-miR-15b, hsa-miR-106a, miR-223, miR-126. Selected miRNAs were validated by qRT-PCR in 14 patients with T2DM on metformin monotherapy, without established CV disease and antiplatelet therapy during a stepwise hypoglycaemic clamp experiment and a follow-up 7 days after the clamp event. In order to identify which pathways and phenotypes are associated with validated miRNAs we performed target prediction on genes expressed with high confidence in platelets. Results: Circulating levels of miR-106a-5p, miR-15b, miR-15a, miR-16-5p, miR-223 and miR-126 were increased after euglycaemic clamp followed by hypoglycaemic clamp, each with its distinctive time trend. On the contrary, miR-129-2-3p, miR-92a-3p and miR-34a-3p remained unchanged. MiR-16-5p was negatively correlated with interleukin (IL)-6, intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) (p = 0.002, p < 0.001, p = 0.016, respectively), whereas miR-126 was positively correlated with VCAM (p < 0.001). There were negative correlations between miR-16-5p, miR-126 and coagulation factors, including factor VIII and von Willebrand factor (vWF). Among all studied miRNAs, miR-126, miR-129-2-3p and miR-15b showed correlation with platelet function. Bioinformatic analysis of platelet-related targets of analyzed miRNAs showed strong enrichment of IL-2 signaling. We also observed significant enrichment of pathways and diseases related to cancer, CV diseases, hyperglycemia, and neurological diseases. Conclusions: Hypoglycaemia can significantly influence the expression of platelet-enriched miRNAs, with a time trend paralleling the time course of platelet activation. This suggests miRNAs could be exploited as biomarkers for platelet activation in response to hypoglycaemia, as they are probably released by platelets upon activation by hypoglycaemic episodes. Should they hold their promise in clinical endpoint studies, platelet-derived miRNAs might become helpful markers of CV risk in subjects with diabetes. Trial registration The study was registered at clinical trials.gov; Impact of Hypoglycaemia in Patients With DIAbetes Mellitus Type 2 on PLATElet Activation (Diaplate), trial number: NCT03460899

Metabolic regulation of glucose can be altered by fasting periods. We examined glucose metabolism and metabolomics profiles after 12 h and 36 h fasting in non-obese and obese participants and people with type 2 diabetes using oral glucose tolerance (OGTT) and intravenous glucose tolerance testing (IVGTT). Insulin sensitivity was estimated by established indices and mass spectrometric metabolomics was performed on fasting serum samples. Participants had a mean age of 43 ± 16 years (62% women). Fasting levels of glucose, insulin and C-peptide were significantly lower in all cohorts after 36 h compared to 12 h fasting (p < 0.05). In non-obese participants, glucose levels were significantly higher after 36 h compared to 12 h fasting at 120 min of OGTT (109 ± 31 mg/dL vs. 79 ± 18 mg/dL; p = 0.001) but insulin levels were lower after 36 h of fasting at 30 min of OGTT (41.2 ± 34.1 mU/L after 36 h vs. 56.1 ± 29.7 mU/L; p < 0.05). In contrast, no significant differences were observed in obese participants or people with diabetes. Insulin sensitivity improved in all cohorts after 36 h fasting. In line, metabolomics revealed subtle baseline differences and an attenuated metabolic response to fasting in obese participants and people with diabetes. Our data demonstrate an improved insulin sensitivity after 36 h of fasting with higher glucose variations and reduced early insulin response in non-obese people only.

The EndoBarrier™ medical device is a duodenal-jejunal bypass liner designed to mimic the effects of gastric bypass surgery to induce weight loss and glycaemic improvement. In this study, 10 participants with type 2 diabetes mellitus (T2DM), a mean body mass index (BMI) of 43.3 ± 5.0 (kg/m²) and a mean glycated haemoglobin A1c (HbA1c) of 60.6 ± 8.6 mmol/mol were examined at baseline (before implantation of EndoBarrier™), 4 weeks after implantation, at 36 weeks (right before explantation) and 24 weeks after the removal of the device to explore the short and long-term effects on glucose metabolism. Besides a significant reduction in body weight and fat mass, EndoBarrier™ treatment significantly improved insulin sensitivity during Botnia clamp investigations after four weeks of implantation. The beneficial effects decreased over time but remained significant 24 weeks after removal of the device.

To assess intermittently scanned continuous glucose monitoring (isCGM) performance for different rates of change in plasma glucose (RCPG) during glycemic challenges in type 1 diabetes (T1D). Nineteen people with T1D (7 females; age 35 ± 11 years; HbA_1c 7.3 ± 0.6% (56 ± 7 mmol/mol)) performing two glycemic challenges (OGTT) were included. During OGTTs, plasma glucose was compared against sensor glucose for timepoints 0 min (pre-OGTT), +15 min, +30 min, +60 min, +120 min, +180 min, and +240 min by means of median absolute (relative) difference (MARD and MAD) and Clarke Error Grid (CEG), then was stratified for RCPG and glycemic ranges. Overall, MARD was 8.3% (4.0–14.8) during hypoglycemia level 1 18.8% (15.8–22.0), euglycemia 9.5% (4.3–15.1), hyperglycemia level 1 9.4% (4.0–17.2), and hyperglycemia level 2 7.1% (3.3–11.9). The MARD was associated with the RCPG (p < 0.0001), detailing significant differences in comparison of low, moderate, high, and very high RCPG (p = 0.014). Overall, CEG resulted in 88% (212 values) of comparison points in zone A, 12% (29 values) in zone B, and 0.4% (1 value) in zone D. The isCGM system was accurate during OGTTs. Its performance was dependent on the RCPG and showed an overestimation of the actual reference glucose during hypoglycemia.