Glycemic Control in Neurological Intensive Care Unit Patients

Critically ill patients often develop hyperglycemia because of the metabolic response to trauma and stress. In response to any form of damage to the organism, it reacts by increasing its own glucose production which subsequently causes hyperglycemia. This adaptive reaction of the organism is directed to aid in the rapid restoration after the damage. Therefore, glucose is an indispensable substrate in the critically ill which aids the reparation process. Severe and persistent hyperglycemia is associated with unfavorable outcomes and is considered to be an independent predictor of in-hospital mortality. The discussion remains on whether hyperglycemia is just a marker of increased stress which makes it a surrogate indicator of disease severity or if it is the reason for the unfavorable outcome. A few years ago, several published articles suggested that a tight glycemic control within the normal range improves treatment outcome. Over time, researchers have changed their point of view and currently there is a discussion on this matter in the scientific literatures. At the same time, the question of what glycemic level should be maintained for patients in the Neurological Intensive Care Unit is a matter of discussion. In this review, the authors analyzed the latest guidelines on treatment of critical patients with neurosurgical and neurological pathologies, specifically the glycemic control in this category of patients.

Potential overtreatment of type 2 diabetes therapy in real clinical practice: Omsk Oblast register data

Backgraund: The total number of patients with type 2 diabetes mellitus (T2DM) in the Russian Federation as of 01.01.2019 is 4.24 million. The majority of patients with T2DM are elderly people and older, forming groups with high comorbidity and the risk of severe hypoglycemia, including those associated with excess hypoglycemic therapy. Foreign studies indicate that a significant proportion of older adults with diabetes are potentially exposed to excessive sugar-lowering therapy.Aims: to study the frequency of excessive decrease in HbA1c in a group of patients with T2DM according to a sample from the regional diabetes register.Materials and methods: A content analysis of the regional register of diabetes mellitus was carried out as of ­December 31, 2019. Based on the register data, an individual target level of HbA1c was calculated and the compliance of the achieved HbA1c level with the target level was assessed.Results: The analysis included data from 1202 patients with T2DM, which amounted to 2.35% of the total number of patients with T2DM in the region (n = 51,163). The age of the included individuals was 66 years (LQ 60.0; UQ 72), 360 men (29.95%). The duration of T2DM 8.0 years. The HbA1c level in the general group was 7.1%. Persons over 60 years of age accounted for 75.21% (n = 904). When analyzing HbA1c in the age groups, there were no statistically significant differences (p> 0.05). HbA1c was above the target level in 43.34% of cases (n = 521). The level of HbA1c <6.5% was noted in a quarter of cases (24.62%), including HbA1c <6.0% was recorded in 97 cases, which accounted for a third of all cases of tight glycemic control. At the same time, the majority of observations of HbA1c <6.5% were in patients 60 years and older (79.73%). Among young and middle-aged patients with HbA1c <6.5%, 8.33% of cases had risk factors for severe hypoglycemia in the presence of SU and / or insulin therapy. In the older age group (in comparison with young and middle-aged patients), HbA1c <7% (p <0.05) was significantly more often detected, there was a tendency for a higher frequency of HbA1c <6.5% (p = 0.067). Among elderly and senile patients with HbA1c <6.5%, in 41.53% of cases there were risk factors for severe hypoglycemia, in a quarter of cases in T2DM therapy SU and / or insulin were used (24.58%), almost every fifth patient (19.07%), risk factors for severe hypoglycemia, received SU and / or insulin.Conclusion: According to our data, at least a quarter of patients in the older age group (24.58%) had overtreatment and need de-intensification of therapy. Perhaps that in this group of patients, the risks associated with treatment may outweigh the benefits of tight glycemic control, and these patients require planned de-intensification of glucose-lowering therapy. Taking into account the position of some expert communities on determining the target range of HbA1c in the older age group, the need for de-intensification of antihyperglycaemic therapy may be even higher. Further research is required in order to develop a full-fledged domestic concept of de-intensification of hypoglycemic therapy.

Mild Cognitive Impairment Screening in Older Adults With Type 2 DM

Introduction: Older adults (O-A), more than 65 years old, are a heterogeneous group of patients in terms of functionality, social support and health status that implies a wide range of co-morbidities including mild cognitive impairment (MCI) and unidentified dementia. De-intensification of treatment is recommended for O-A with T2DM, tight glycemic control and high risk of hypoglycemia. Assessment of all geriatric domains (medical, functional, social and psychological including screening for MCI) is encouraged to support a complete clinical picture that leads to appropriate targets and adequate therapeutic approach. The literature suggests that de-intensification of treatment in this population is uncommon, which calls for the development of new strategies to prevent potential harm, however we also question if previously established tools are being used. Methods: We performed a retrospective chart review of a community-dwelling Veterans with at least two office visits in the Geriatric Clinic between January 1st 2018 to December 31st 2019. 210 patients with 65 years of age or older with T2DM and A1C &lt; 7.5 were found. 64 (30%) of the patients where on hypoglycemic medication including sulfonylureas or insulin. From this subgroup, only 9 (14%) patients where recommended to de-intensify therapy. 189 (90%) of all the patients were screened for memory disorders. Interestingly 20 patients (31%) of those using sulfonylureas or insulin as part of their diabetes treatment were not screened, which was a higher percentage compared to 48 (25%) patients not on hypoglycemic medications also not screened for memory disorders. Conclusion: similar to previous studies de-intensification is uncommon not only among endocrinologist but in other sub-specialties involved in the care of the Geriatric population. This data emphasizes the importance of using previously developed treatment tools specially in those with at higher risk of overtreatment side effects such as older adults with tight glycemic control and hypoglycemic medication

Lessons from Human Islet Transplantation Inform Stem Cell-Based Approaches in the Treatment of Diabetes

Diabetes mellitus is characterized by the body’s inability to control blood glucose levels within a physiological range due to loss and/or dysfunction of insulin producing beta cells. Progressive beta cell loss leads to hyperglycemia and if untreated can lead to severe complications and/or death. Treatments at this time are limited to pharmacologic therapies, including exogenous insulin or oral/injectable agents that improve insulin sensitivity or augment endogenous insulin secretion. Cell transplantation can restore physiologic endogenous insulin production and minimize hyper- and hypoglycemic excursions. Islet isolation procedures and management of transplant recipients have advanced over the last several decades; both tight glycemic control and insulin independence are achievable. Research has been conducted in isolating islets, monitoring islet function, and mitigating the immune response. However, this procedure is still only performed in a small minority of patients. One major barrier is the scarcity of human pancreatic islet donors, variation in donor pancreas quality, and variability in islet isolation success. Advances have been made in generation of glucose responsive human stem cell derived beta cells (sBCs) and islets from human pluripotent stem cells using directed differentiation. This is an emerging promising treatment for patients with diabetes because they could potentially serve as an unlimited source of functional, glucose-responsive beta cells. Challenges exist in their generation including long term survival of grafts, safety of transplantation, and protection from the immune response. This review focuses on the progress made in islet allo- and auto transplantation and how these advances may be extrapolated to the sBC context.

Monitoring the Impact of Aggressive Glycemic Intervention during Critical Care after Cardiac Surgery with a Glycemic Expert System for Nurse-Implemented Euglycemia: The MAGIC GENIE Project

A novel, multi-dimensional protocol named GENIE has been in use for intensive insulin therapy (IIT, target glucose <140 mg/dL) in the surgical intensive care unit (SICU) after open heart surgery (OHS) at VA Pittsburgh since 2005. Despite concerns over increased mortality from IIT after the publication of the NICE-SUGAR Trial, it remains in use, with ongoing monitoring under the MAGIC GENIE Project showing that GENIE performance over 12 years (2005-2016) aligns with the current consensus that IIT with target blood glucose (BG) <140 mg/dL is advisable only if it does not provoke severe hypoglycemia (SH). Two studies have been conducted to monitor glucometrics and outcomes during GENIE use in the SICU. One compares GENIE ( n = 382) with a traditional IIT protocol (FORMULA, n = 289) during four years of contemporaneous use (2005-2008). The other compares GENIE’s impact overall ( n = 1404) with a cohort of patients who maintained euglycemia after OHS (euglycemic no-insulin [ENo-I], n = 111) extending across 12 years (2005-2016). GENIE performed significantly better than FORMULA during contemporaneous use, maintaining lower time-averaged glucose, provoking less frequent, severe, prolonged, or repetitive hypoglycemia, and achieving 50% lower one-year mortality, with no deaths from mediastinitis (0 of 8 cases vs 4 of 9 on FORMULA). Those benefits were sustained over the subsequent eight years of exclusive use in OHS patients, with an overall one-year mortality rate (4.2%) equivalent to the ENo-I cohort (4.5%). The results of the MAGIC GENIE Project show that GENIE can maintain tight glycemic control without provoking SH in patients undergoing OHS, and may be associated with a durable survival benefit. The results, however, await confirmation in a randomized control trial.

PERI-OPERATIVE MANAGEMENT IN DIABETES MELLITUS

In diabetic patients, managing the glycemic levels in the perioperative period is challenging. Surgical stress and anesthesia have great impact on blood glucose levels, thus the healthcare professionals should be more cautious to maintain the optimal glycemic level. Almost 50% of diabetes patient undergoing surgery, has great chance of post-operative mortality when compared with normal glucose tolerant patient. In addition to this, there is 5 times greater risk of developing end organ damage and infections in uncontrolled diabetic patients. Hence, there is a need to optimize and improve the blood glycemic control before surgery. Tight glycemic control with intensive insulin therapy (IIT) has shown to reduce morbidity and mortality and improve the survival after the surgery. However, evidence suggest that severe hypoglycaemia and adverse outcomes with tight glycemic control brings its safety and efficacy into query. Hence, avoidance of hyperglycemia is clearly beneficial in the perioperative patients, although IIT continues to be standard of care, current consensus guidelines recommend less stringent glycemic goals, typically between 80-150mg|dl.

Differential Effects of Empagliflozin on Microvascular Complications in Murine Models of Type 1 and Type 2 Diabetes

Microvascular complications account for the significant morbidity associated with diabetes. Despite tight glycemic control, disease risk remains especially in type 2 diabetes (T2D) patients and no therapy fully prevents nerve, retinal, or renal damage in type 1 diabetes (T1D) or T2D. Therefore, new antidiabetic drug classes are being evaluated for the treatment of microvascular complications. We investigated the effect of empagliflozin (EMPA), an inhibitor of the sodium/glucose cotransporter 2 (SGLT2), on diabetic neuropathy (DPN), retinopathy (DR), and kidney disease (DKD) in streptozotocin-induced T1D and db/db T2D mouse models. EMPA lowered blood glycemia in T1D and T2D models. However, it did not ameliorate any microvascular complications in the T2D model, which was unexpected, given the protective effect of SGLT2 inhibitors on DKD progression in T2D subjects. Although EMPA did not improve DKD in the T1D model, it had a potential modest effect on DR measures and favorably impacted DPN as well as systemic oxidative stress. These results support the concept that glucose-centric treatments are more effective for DPN in T1D versus T2D. This is the first study that provides an evaluation of EMPA treatment on all microvascular complications in a side-by-side comparison in T1D and T2D models.