Effectiveness and Safety of SGLT2 Inhibitors in Clinical Routine Treatment of Patients with Diabetes Mellitus Type 2

The aim of this study was to investigate the effectiveness of SGLT2 inhibitors with regard to metabolic parameters and patient safety under routine ambulatory conditions. Retrospective longitudinal study of 95 patients with type 2 diabetes (diabetes duration 13.3 y; HbA1c 8.9%; eGFR 80.1 mL/min) receiving SGLT-2-inhibitors. Metabolic control and adverse event profile were evaluated. The mean follow-up time was 1.2 ± 0.8 years. The following changes were observed: HbA1c −1.0% ± 1.9 (p p p = 0.118), bodyweight −3.0 kg ± 5.8 (p p = 0.01), diastolic blood pressure −2 mmHg ± 14 (p = 0.243). 53 participants continuously applied the therapy. Twenty-eight participants discontinued SGLT-2-inhibitors due to various reasons: 20 participants because of genital- or urinary tract infections. One for dysuria, seven due to reduced eGFR below 45 mL/min. This study showed a considerable reduction of HbA1c and a modest reduction of eGFR, bodyweight and systolic blood pressure under clinical routine conditions. Genital infections occurred markedly more often than in randomized controlled trials. To apply SGLT-2-inhibitors more safely in clinical routine individual risks for genital and urinary tract infections should be considered and re-evaluated during therapy

Salvation Expectations of Patients of Medicine, Complementary and Alternative Medicine and Religion

Health and holistic quality of life, physical and emotional needs, somatic and spiritual aspects contain a comprehensive promise of healing. The aim of the current study is to measure the expectations of patients of medicine, alternative medicine and religion related to health and illness. The survey was carried out among 103 patients of a rural general practitioner from May to June 2013 and among 103 patients of the outpatient department for endocrinology and metabolic disease of the Jena University Hospital in 2013. All patients were asked by one interviewer (HM) on fears in relation to health/illness and expectations of help for its own life, medicine, alternative medicine and religion. The biggest fear of patients is 'being in need of help of others.' There is no significant difference between religious and non-religious patients. Overall, the expectations of medicine were significantly higher in all sectors than in alternative medicine or religion. Comparing alternative medicine and religion, the expectations of alternative medicine were significantly higher excluding consolation and inner peace. The expectations for medicine in general and for the physician are very high and comprehensive and go beyond diagnosis and realization of therapies. Patients expect hope, guidance, support, comfort, inner peace and advice most from medicine. This results in considerable challenges for the physician, especially in a healthcare system with limited resources and without suitable offers. There is an urgent need to integrate these requirements into daily routine

Successful treatment with bedtime basal insulin added to metformin without weight gain or hypoglycaemia over three years

The aim of this observational study was to follow-up patients with bedtime basal insulin (NPH insulin) added to metformin. In 285 patients with type 2 diabetes, a therapy with bedtime basal insulin added to metformin was started due to failure to achieve a glycaemic goal. Up until July 2019, 272 patients (95.4%) were followed-up (59.5 y, 92.6 kg, diabetes duration 6.6 y, HbA1c 8.4%/68.6 mmol/mol). HbA1c decreased by −1.2% and bodyweight by −1.7 kg after a duration of 31.7 ± 29.1 (range 2–133) months. Severe hypoglycaemia did not occur. In 144/272 patients (52.9%), the therapeutic goal for HbA1c was achieved over 32.7 months. In 69/272 patients (25.4%), the HbA1c target was achieved over 25.0 months (afterwards, therapy with basal insulin was discontinued because HbA1c was under target). In 36/272 patients (13.2%), the HbA1c goal was achieved until the submission of this manuscript (mean duration of treatment 57.4 ± 28.2 (range 13–121) months). Over 90% of patients with type 2 diabetes and failure of metformin reached their HbA1c goal with additional basal insulin at bedtime over several years in association with a reduction of bodyweight and without any event of severe hypoglycaemia

The Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Empagliflozin Reverses Hyperglycemia-Induced Monocyte and Endothelial Dysfunction Primarily through Glucose Transport-Independent but Redox-Dependent Mechanisms

Purpose: Hyperglycaemia-induced oxidative stress and inflammation contribute to vascular cell dysfunction and subsequent cardiovascular events in T2DM. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin significantly improves cardiovascular mortality in T2DM patients (EMPA-REG trial). Since SGLT-2 is known to be expressed on cells other than the kidney cells, we investigated the potential ability of empagliflozin to regulate glucose transport and alleviate hyperglycaemia-induced dysfunction of these cells. Methods: Primary human monocytes were isolated from the peripheral blood of T2DM patients and healthy individuals. Primary human umbilical vein endothelial cells (HUVECs) and primary human coronary artery endothelial cells (HCAECs), and fetoplacental endothelial cells (HPECs) were used as the EC model cells. Cells were exposed to hyperglycaemic conditions in vitro in 40 ng/mL or 100 ng/mL empagliflozin. The expression levels of the relevant molecules were analysed by RT-qPCR and confirmed by FACS. Glucose uptake assays were carried out with a fluorescent derivative of glucose, 2-NBDG. Reactive oxygen species (ROS) accumulation was measured using the H2DFFDA method. Monocyte and endothelial cell chemotaxis were measured using modified Boyden chamber assays. Results: Both primary human monocytes and endothelial cells express SGLT-2. Hyperglycaemic conditions did not significantly alter the SGLT-2 levels in monocytes and ECs in vitro or in T2DM conditions. Glucose uptake assays carried out in the presence of GLUT inhibitors revealed that SGLT-2 inhibition very mildly, but not significantly, suppressed glucose uptake by monocytes and endothelial cells. However, we detected the significant suppression of hyperglycaemia-induced ROS accumulation in monocytes and ECs when empagliflozin was used to inhibit SGLT-2 function. Hyperglycaemic monocytes and endothelial cells readily exhibited impaired chemotaxis behaviour. The co-treatment with empagliflozin reversed the PlGF-1 resistance phenotype of hyperglycaemic monocytes. Similarly, the blunted VEGF-A responses of hyperglycaemic ECs were also restored by empagliflozin, which could be attributed to the restoration of the VEGFR-2 receptor levels on the EC surface. The induction of oxidative stress completely recapitulated most of the aberrant phenotypes exhibited by hyperglycaemic monocytes and endothelial cells, and a general antioxidant N-acetyl-L-cysteine (NAC) was able to mimic the effects of empagliflozin. Conclusions: This study provides data indicating the beneficial role of empagliflozin in reversing hyperglycaemia-induced vascular cell dysfunction. Even though both monocytes and endothelial cells express functional SGLT-2, SGLT-2 is not the primary glucose transporter in these cells. Therefore, it seems likely that empagliflozin does not directly prevent hyperglycaemia-mediated enhanced glucotoxicity in these cells by inhibiting glucose uptake. We identified the reduction of oxidative stress by empagliflozin as a primary reason for the improved function of monocytes and endothelial cells in hyperglycaemic conditions. In conclusion, empagliflozin reverses vascular cell dysfunction independent of glucose transport but could partially contribute to its beneficial cardiovascular effects

The Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitor Empagliflozin Reverses Hyperglycemia-Induced Monocyte and Endothelial Dysfunction Primarily through Glucose Transport-Independent but Redox-Dependent Mechanisms

Purpose: Hyperglycaemia-induced oxidative stress and inflammation contribute to vascular cell dysfunction and subsequent cardiovascular events in T2DM. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin significantly improves cardiovascular mortality in T2DM patients (EMPA-REG trial). Since SGLT-2 is known to be expressed on cells other than the kidney cells, we investigated the potential ability of empagliflozin to regulate glucose transport and alleviate hyperglycaemia-induced dysfunction of these cells. Methods: Primary human monocytes were isolated from the peripheral blood of T2DM patients and healthy individuals. Primary human umbilical vein endothelial cells (HUVECs) and primary human coronary artery endothelial cells (HCAECs), and fetoplacental endothelial cells (HPECs) were used as the EC model cells. Cells were exposed to hyperglycaemic conditions in vitro in 40 ng/mL or 100 ng/mL empagliflozin. The expression levels of the relevant molecules were analysed by RT-qPCR and confirmed by FACS. Glucose uptake assays were carried out with a fluorescent derivative of glucose, 2-NBDG. Reactive oxygen species (ROS) accumulation was measured using the H2DFFDA method. Monocyte and endothelial cell chemotaxis were measured using modified Boyden chamber assays. Results: Both primary human monocytes and endothelial cells express SGLT-2. Hyperglycaemic conditions did not significantly alter the SGLT-2 levels in monocytes and ECs in vitro or in T2DM conditions. Glucose uptake assays carried out in the presence of GLUT inhibitors revealed that SGLT-2 inhibition very mildly, but not significantly, suppressed glucose uptake by monocytes and endothelial cells. However, we detected the significant suppression of hyperglycaemia-induced ROS accumulation in monocytes and ECs when empagliflozin was used to inhibit SGLT-2 function. Hyperglycaemic monocytes and endothelial cells readily exhibited impaired chemotaxis behaviour. The co-treatment with empagliflozin reversed the PlGF-1 resistance phenotype of hyperglycaemic monocytes. Similarly, the blunted VEGF-A responses of hyperglycaemic ECs were also restored by empagliflozin, which could be attributed to the restoration of the VEGFR-2 receptor levels on the EC surface. The induction of oxidative stress completely recapitulated most of the aberrant phenotypes exhibited by hyperglycaemic monocytes and endothelial cells, and a general antioxidant N-acetyl-L-cysteine (NAC) was able to mimic the effects of empagliflozin. Conclusions: This study provides data indicating the beneficial role of empagliflozin in reversing hyperglycaemia-induced vascular cell dysfunction. Even though both monocytes and endothelial cells express functional SGLT-2, SGLT-2 is not the primary glucose transporter in these cells. Therefore, it seems likely that empagliflozin does not directly prevent hyperglycaemia-mediated enhanced glucotoxicity in these cells by inhibiting glucose uptake. We identified the reduction of oxidative stress by empagliflozin as a primary reason for the improved function of monocytes and endothelial cells in hyperglycaemic conditions. In conclusion, empagliflozin reverses vascular cell dysfunction independent of glucose transport but could partially contribute to its beneficial cardiovascular effects

Effects of metabolic control, patient education and initiation of insulin therapy on the quality of life of patients with type 2 diabetes mellitus

OBJECTIVE:The objective of this study was to evaluate the impact of initiation of insulin therapy, metabolic control and structured patient education on the diabetes-related quality of life (QoL) in insulin-treated patients with type 2 diabetes mellitus. METHODS: This prospective study was conducted with 71 consecutively recruited patients with insulin-treated diabetes at the University hospital. All patients participated an inpatient diabetes treatment and teaching program (DTTP) for conventional insulin therapy (mean age 68.9 years, HbA1c 10.1+/-1.4%, diabetes duration 11.2 years (range: 0-25.5 years), body-mass-index 28.7+/-5.7 kg/m(2). Diabetes-related quality of life was assessed before and 6 months after participation in the DTTP using the standardized questionnaire of Lohr analysing the subscales: social relations, physical complaints, worries about the future, dietary restrictions, fear of hypoglycaemia, and daily struggles. RESULTS: Only patients switched on insulin therapy showed significant improvement in diabetes-related quality of life 6 months after participation in the DTTP (p=0.03), fewer physical complaints (p=0.03), fewer worries about the future (p=0.02), fewer daily struggles (p=0.01) and less fear of hypoglycaemia (p<0.001), while patients, who were already on insulin therapy showed no improvements in diabetes-related quality of life. Though, residual analysis reveals that effects on patients&#039; QoL are mainly caused by improvements in metabolic control. CONCLUSIONS: Improvements in metabolic control have a significant effect on different diabetes-related quality of life domains in patients with diabetes mellitus. PRACTICE IMPLICATIONS: Appropriate interventions resulting in better metabolic control, such as starting on insulin therapy within a structured patient education program seem to be an effective approach to improve patients&#039; diabetes-related quality of life