Optimizing Therapeutic Outcomes With Oral Semaglutide: A Patient-Centered Approach.

In September 2019, the U.S. Food and Drug Administration approved oral semaglutide as the first orally administered glucagon-like peptide 1 (GLP-1) receptor agonist for treating people with type 2 diabetes. Although injectable GLP-1 receptor agonists are well-established treatment options for people with type 2 diabetes, clinical experience with an oral formulation in this class is limited. This article provides practical guidance for diabetes care and education specialists on how to effectively counsel patients initiating therapy with oral semaglutide on appropriate administration of the treatment and its possible effects on glycemic control, body weight, and quality of life. Strategies for mitigating potential side effects typical of the GLP-1 receptor agonist class, namely nausea, vomiting, and diarrhea, are also provided. Involving patients in treatment decisions and educating them about available and prescribed medications are key strategies for encouraging treatment adherence and ensuring optimal therapeutic outcomes.

Improvement of Insulin Injection Technique: Examination of Current Issues and Recommendations.

PURPOSE: Correct insulin injection technique is a crucial aspect of diabetes management. The purpose of this article is (1) to outline the medical literature, including patient-based studies and surveys, surrounding the type of issues and problems that patients encounter with injectable insulin therapy and the degree to which correct insulin technique is being applied and (2) to review the latest recommendations for insulin injection technique and discuss the key aspects that diabetes educators and other health care professionals should be communicating to their patients to ensure that injection technique is optimized. CONCLUSIONS: Examination of the literature and multiple patient surveys demonstrates that patients continue to have many issues with insulin injection technique, highlighting the pressing need for effective patient education. In addition, many patients are not using insulin pen devices correctly. Widespread lack of injection site rotation and reuse of needles have resulted in high rates of lipohypertrophy. Lipohypertrophy has in turn been associated with significantly increased levels of unexplained hypoglycemia and glycemic variability and significantly increased insulin costs. By providing clear, evidence-based consensus recommendations, initiatives such as the Forum for Injection Technique are helping to address these issues but will be successful only if concerted efforts in patient education and reeducation are made to ensure that these recommendations are implemented consistently. This should involve all stakeholders in insulin therapy-particularly diabetes educators, who are at the forefront of patient education.

Inducing mitophagy in diabetic platelets protects against severe oxidative stress.

Diabetes mellitus (DM) is a growing international concern. Considerable mortality and morbidity associated with diabetes mellitus arise predominantly from thrombotic cardiovascular events. Oxidative stress-mediated mitochondrial damage contributes significantly to enhanced thrombosis in DM A basal autophagy process has recently been described as playing an important role in normal platelet activation. We now report a substantial mitophagy induction (above basal autophagy levels) in diabetic platelets, suggesting alternative roles for autophagy in platelet pathology. Using a combination of molecular, biochemical, and imaging studies on human DM platelets, we report that platelet mitophagy induction serves as a platelet protective mechanism that responds to oxidative stress through JNK activation. By removing damaged mitochondria (mitophagy), phosphorylated p53 is reduced, preventing progression to apoptosis, and preserving platelet function. The absence of mitophagy in DM platelets results in failure to protect against oxidative stress, leading to increased thrombosis. Surprisingly, this removal of damaged mitochondria does not require contributions from transcription, as platelets lack a nucleus. The considerable energy and resources expended in "prepackaging" the complex mitophagy machinery in a short-lived normal platelet support a critical role, in anticipation of exposure to oxidative stress.

Hyperglycemia repression of miR-24 coordinately upregulates endothelial cell expression and secretion of von Willebrand factor.

An elevated level of von Willebrand factor (VWF) in diabetic patients is associated with increased risk of thrombotic cardiovascular events. The underlying mechanism of how VWF expression is upregulated in diabetes mellitus is poorly understood. We now report that hyperglycemia-induced repression of microRNA-24 (miR-24) increases VWF expression and secretion in diabetes mellitus. In diabetic patients and diabetic mouse models (streptozotocin/high-fat diet-induced and db/db mice), miR-24 is reduced in both tissues and plasma. Knockdown of miR-24 in mice leads to increased VWF mRNA and protein levels and enhanced platelet tethering (spontaneous thrombosis). miR-24 tightly controls VWF levels through pleiotropic effects, including direct binding to the 3' untranslated region of VWF and targeting FURIN and the histamine H1 receptor, known regulators of VWF processing and secretion in endothelial cells. We present a novel mechanism for miR-24 downregulation through hyperglycemia-induced activation of aldose reductase, reactive oxygen species, and c-Myc. These findings support a critical role for hyperglycemic repression of miR-24 in VWF-induced pathology. miR-24 represents a novel therapeutic target to prevent adverse thrombotic events in patients with diabetes mellitus.

Aldose reductase-mediated phosphorylation of p53 leads to mitochondrial dysfunction and damage in diabetic platelets.

BACKGROUND: Platelet abnormalities are well-recognized complications of diabetes mellitus. Mitochondria play a central role in platelet metabolism and activation. Mitochondrial dysfunction is evident in diabetes mellitus. The molecular pathway for hyperglycemia-induced mitochondrial dysfunction in platelets in diabetes mellitus is unknown. METHODS AND RESULTS: Using both human and humanized mouse models, we report that hyperglycemia-induced aldose reductase activation and subsequent reactive oxygen species production lead to increased p53 phosphorylation (Ser15), which promotes mitochondrial dysfunction, damage, and rupture by sequestration of the antiapoptotic protein Bcl-xL. In a glucose dose-dependent manner, severe mitochondrial damage leads to loss of mitochondrial membrane potential and platelet apoptosis (cytochrome c release, caspase 3 activation, and phosphatidylserine exposure). Although platelet hyperactivation, mitochondrial dysfunction, aldose reductase activation, reactive oxygen species production, and p53 phosphorylation are all induced by hyperglycemia, we demonstrate that platelet apoptosis and hyperactivation are 2 distinct states that depend on the severity of the hyperglycemia and mitochondrial damage. Combined, both lead to increased thrombus formation in a mouse blood stasis model. CONCLUSIONS: Aldose reductase contributes to diabetes-mediated mitochondrial dysfunction and damage through the activation of p53. The degree of mitochondrial dysfunction and damage determines whether hyperactivity (mild damage) or apoptosis (severe damage) will ensue. These signaling components provide novel therapeutic targets for thrombotic complications in diabetes mellitus.

Insulin initiation in type 2 diabetes: what are the treatment regimen options and how can we best help patients feel empowered?

PURPOSE: This article summarizes treatment regimens and issues involved in initiating insulin therapy in type 2 diabetes (T2D). Progressive deterioration of beta-cell mass and function characterizes the course of T2D. Following diet and exercise, oral antidiabetic drugs (OADs), and incretin therapies, many patients require insulin, but initiation is often delayed until complications develop. DATA SOURCES: Published guidelines for the management of T2D, primary and review articles, and Food and Drug Administration (FDA) prescribing information. CONCLUSIONS: The diabetes nurse practitioner should encourage patients to initiate insulin when appropriate; patients need to know that this represents a natural step in treatment, not a personal failing. Initiation often occurs when OADs no longer confer adequate glycemic control. Treatment regimens available include once-daily basal insulin, sometimes with addition of prandial insulin, or premix/biphasic insulin. Insulin analogs confer less risk of hypoglycemia and weight gain, and greater dosing flexibility compared with conventional insulins. Insulin efficacy may be enhanced by continuing metformin and/or incretin therapies, while discontinuing other drugs as appropriate. IMPLICATIONS FOR PRACTICE: The well-versed diabetes nurse practitioner assists the patient in selecting the most appropriate option for his/her specific needs. It is essential to help patients overcome barriers, including fears of injection pain, public embarrassment, and hypoglycemia risk.

Effects on post-prandial glucose and AGE precursors from two initial insulin strategies in patients with type 2 diabetes uncontrolled by oral agents.

OBJECTIVE: Progressive ß-cell dysfunction in Type 2 diabetes results in the need for insulin therapy in many patients. Yet the best regimen to prescribe to patients transitioning from oral anti-hyperglycemic drugs (OADs) is not clear. We sought to compare the effects of two standard initial insulin strategies (basal insulin alone versus premixed insulin) on post-prandial glucose metabolism and precursors of advanced glycation end-products in patients with type 2 diabetes suboptimally controlled on OADs. RESEARCH DESIGN AND METHODS: This was a 6-month, open-label, single-center study using a cross-over design. 14 subjects were randomized to one of two protocols: once daily insulin glargine or twice-daily 75%/25% neutral protamine lispro/lispro mix. At 12 weeks, the subjects were crossed-over to the opposite protocol. During each period, insulin doses were titrated to target fasting blood glucose of 90-110 mg/dL. At baseline and after the two 12-week treatment periods, subjects were studied in the Clinical Research Center; they consumed three liquid mixed isocaloric meals at 4-h intervals, and glucose, free fatty acids (FFA), lipids, and α-dicarbonyls (3-deoxyglucosone [3-DG] and methylglyoxal [MG]) were measured before and after each meal. Patient data were analyzed in the context of their assigned insulin strategy groups. RESULT: Both insulin regimens led to a significant improvement in glycemic profiles, including fasting glucose and HbA1c, compared to baseline. However, mean post-prandial glucose was lower with lispro mix than with glargine (153 ± 36 vs. 199 ± 49 mg/dL, respectively; P=0.001). Likewise, there was a reduction in both fasting (48 ± 13 vs. 57 ± 19, P=0.047) and post-prandial (53 ± 19 vs. 63 ± 23; P=0.007) 3DG levels with lispro mix as compared to glargine. No differences were noted in MG concentrations. CONCLUSION: In type 2 diabetes patients failing OAD therapy, an initial insulin regimen of twice daily premixed insulin results in significantly improved post-prandial glucose levels as well as a reduction in a precursor of AGEs. The effect of these two initial insulin regimens on long-term diabetic complications requires further study.

Understanding GLP-1 analogs and enhancing patients success.

Recent research into the mechanisms of type 2 diabetes reveals intricate interactions among many hormonal processes. Ultimately, these pathways lead to hyperglycemia, pancreatic beta-cell failure, and the emergence of type 2 diabetes. The incretin hormones, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are now known to play major roles in endogenous glucose control, including regulation of insulin, glucagon, and hepatic glucose metabolism. Investigation of the incretin system has led to development of drugs that mimic or enhance the endogenous hormones, including GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors. This supplement describes the role of incretin hormones in the pathophysiology of type 2 diabetes and their potential as therapeutic targets for disease management. In addition, safety and efficacy profiles of the GLP-1 receptor agonists are reviewed, and the advantages and limitations of these medications are discussed from the perspective of promoting their successful implementation in individualized treatment regimens. As understanding of the underlying pathophysiology and pathogenesis of type 2 diabetes advances, the number of new therapeutic approaches expands. GLP-1 receptor agonists address several aspects of the pathophysiology of type 2 diabetes. A large body of data reveals the efficacy, safety, and tolerability of these drugs. A clear understanding of the evidence base for these drugs will translate into improved education of patients regarding their options to improve glycemic control and, ultimately, to better patient care.

Insulin devices: addressing barriers to insulin therapy with the ideal pen.

PURPOSE: The purpose of this article was to identify and address barriers to initiating insulin therapy in patients with type 2 diabetes. RESULTS: Insulin pen devices address many of the mechanical barriers associated with a syringe and vial. In addition, pen devices are increasingly being improved, offering long-term pen users benefits over earlier pen users. These devices can be tailored to address the specific needs of different patient populations, such as elderly patients or those with visual or manual dexterity disabilities. Although insulin devices offer benefits over the syringe and vial, features desirable in the ideal pen have not been established. CONCLUSIONS: Data suggest that currently available insulin pens possess various features that make them suitable for particular patients. Individual needs of each patient should be considered before an insulin pen device is prescribed.

Dose accuracy and injection force dynamics of a novel disposable insulin pen.

SoloStar (sanofi-aventis) is a new, disposable insulin pen for the administration of insulin glargine (Lantus, sanofi-aventis) or insulin glulisine (Apidra, sanofi-aventis). SoloStar was developed to address a wide range of patient needs and demonstrates advancement over previous devices, owing to its appropriate combination of ergonomically-tested and mechanically improved features. The authors report the results of key investigations carried out by sanofi-aventis as part of the SoloStar development plan, including dose accuracy and injection force testing. Comparisons between SoloStar and two commonly used pens, FlexPen (Novo Nordisk) and the Humulin/Humalog pen (Eli Lilly) establish SoloStar as a state of the art pen that is suitable for most patients with diabetes.

Diabetic neuropathies: diagnosis and treatment.

Diabetic neuropathy can affect every organ system of the body. Diagnosis of diabetic neuropathy is usually one of exclusion. Clinical guidelines and the introduction of new medications for pain relief in peripheral neuropathy are improving medical and nursing management. Simpler diagnostic tests for cardiac autonomic neuropathy, which can be performed in an office setting, may mean earlier recognition and treatment with less mortality. Oral medications for the treatment of erectile dysfunction make it easier for the patient to seek treatment for a condition that impact quality of life.

Promoting continuing education in diabetes management.

Diabetes knowledge among hospital nurses is suboptimal. Studies that measured basic diabetes knowledge among nurses in a variety of clinical settings have consistently reported poor understanding of hemoglobin A1C, medication usage and side effects, and self-care diabetes management. Although diabetes is a common diagnosis among hospitalized patients, many nurses report they have never attended an update on diabetes management. To promote advances in glycemic control within the hospital setting, the nursing staff must be better educated in the theoretical framework and clinical practice guidelines for diabetes management. The methods used to promote continuing education in diabetes among staff nurses need to be cost-effective as well as flexible to accommodate work shifts and learning needs. Because many hospitals are facing staff shortages and increased patient acuity, staff development needs may not be a high priority. To be successful, updating diabetes knowledge must be a collaborative effort involving clinical care, research, and education. Mentoring and peer support also are useful methods for improving glycemia in the hospital setting.

A culturally competent intervention of education and care for black women with type 2 diabetes.

This article reports on the development and pilot feasibility testing of a culturally competent intervention of education and care for black women with type 2 diabetes mellitus (T2DM). Using a one group, pretest posttest quasi-experimental design, the intervention was tested with a convenience sample of 25 community black women with T2DM. The conceptual basis, process, and content of the intervention as well as the feasibility and acceptability of study materials and methods are described. Significant improvements from baseline to 3 months were observed in measures of glycemic control, weight, body mass index, and diabetes-related emotional distress. The findings suggest that a culturally sensitive intervention of nurse practitioner diabetes care and education is beneficial for black women with T2DM, resulting in program attendance, kept appointments, improved glycemic control and weight, and decreased diabetes-related emotional distress.