Abstract
Objective
The objective is to formulate clinical practice guidelines for the treatment of diabetes in older adults.
Conclusions
Diabetes, particularly type 2, is becoming more prevalent in ...the general population, especially in individuals over the age of 65 years. The underlying pathophysiology of the disease in these patients is exacerbated by the direct effects of aging on metabolic regulation. Similarly, aging effects interact with diabetes to accelerate the progression of many common diabetes complications. Each section in this guideline covers all aspects of the etiology and available evidence, primarily from controlled trials, on therapeutic options and outcomes in this population. The goal is to give guidance to practicing health care providers that will benefit patients with diabetes (both type 1 and type 2), paying particular attention to avoiding unnecessary and/or harmful adverse effects.
Screening, treatment, and management of diabetes mellitus and complications in older patients.
Either endogenous or exogenous hyperinsulinemia in the setting of insulin resistance promotes phosphorylation and activation of farnesyltransferase, a ubiquitous enzyme that farnesylates Ras protein. ...Increased availability of farnesylated Ras at the plasma membrane enhances mitogenic responsiveness of cells to various growth factors, thus contributing to progression of cancer and atherosclerosis. This effect is specific to insulin, but is not related to the type of insulin used. Stimulatory effect of hyperinsulinemia on farnesyltransferase in the presence of insulin resistance represents one potential mechanism responsible for mitogenicity and atherogenicity of insulin.
Current nutritional approaches to metabolic syndrome and type 2 diabetes generally rely on reductions in dietary fat. The success of such approaches has been limited and therapy more generally relies ...on pharmacology. The argument is made that a re-evaluation of the role of carbohydrate restriction, the historical and intuitive approach to the problem, may provide an alternative and possibly superior dietary strategy. The rationale is that carbohydrate restriction improves glycemic control and reduces insulin fluctuations which are primary targets. Experiments are summarized showing that carbohydrate-restricted diets are at least as effective for weight loss as low-fat diets and that substitution of fat for carbohydrate is generally beneficial for risk of cardiovascular disease. These beneficial effects of carbohydrate restriction do not require weight loss. Finally, the point is reiterated that carbohydrate restriction improves all of the features of metabolic syndrome.
As any other aspect of contemporary life, an old and established field of CME undergoes a transformation into a "digital age." Virtual patient simulation (VPS) has shown to be an interactive and ...efficient way of engaging healthcare professionals (HCP) in continuing medical education. VPS can identify gaps in knowledge and improve competence, using engaging, online tools. The Edocate VPS Platform has been developed by a group of physicians, education experts, and computer specialists. In this communication, we report the experience of several hundreds of HCP using the Edocate VPS application in the fields of type 2 diabetes (T2DM) and hyperlipidemia. The Edocate VPS application, displaying both simple and complex clinical situations, was presented to an international group of HCPs who had the task to perform physical exams, order lab and imaging tests, update the medical record with the right diagnoses, prescribe medications, and perform long-term follow-up through multiple visits. The HCPs received personalized, guideline-based, feedback on their actions. The analytical capabilities of the Edocate VPS platform run very deep and allow in-depth analysis of learners' competence in achieving the best outcomes, while teaching to apply a personalized approach, avoiding side effects of medications, and providing instantaneous access to the most current references in the field. The data collected from the program has shown significant gaps in knowledge and adherence to guidelines in the areas of management of T2DM and hyperlipidemia. Only about 50% of all participants achieved guideline-compatible glycemic control - namely HbA1c below 7%. Furthermore, only 41% of practicing physicians and 23% of family medicine residents achieved levels of LDL below 70 mg/dl in their virtual patients. In conclusion, the data presented in this communication strongly suggests that this novel simulation platform can enable medical organizations to create immersive VPS cases for their primary educational and CME efforts.
Insulin resistance is concomitant with type 2 diabetes, obesity, hypertension, and other features of the metabolic syndrome. Because insulin resistance is associated with cardiovascular disease, both ...scientists and physicians have taken great interest in this disorder. Insulin resistance is associated with compensatory hyperinsulinemia, but individual contributions of either of these two conditions remain incompletely understood and a subject of intense investigation. One possibility is that in an attempt to overcome the inhibition within the metabolic insulin-signaling pathway, hyperinsulinemia may continue to stimulate the mitogenic insulin-signaling pathway, thus exerting its detrimental influence. Here we discuss some of the effects of insulin resistance and mechanisms of potentially detrimental influence of hyperinsulinemia in the presence of metabolic insulin resistance.
The goals of Type 2 diabetes (T2DM) management include achievement of glycemic, blood pressure (BP), and lipid control. All three variables must be addressed adequately in order to prevent diabetic ...complications. Aim: Using a proprietary smartphone-based application (APP) developed by Edocate Ltd, that simulates virtual visits, we assessed how well healthcare providers (HCPs) manage T2DM.
Materials & Methods: A total of 461 HCPs (247 MD, MD/PhD, or DO and 214 NPs) downloaded and used the APP to treat their virtual patients over multiple visits. All patients presented with poorly controlled T2DM, hypertension (HTN) and hyperlipidemia. HCPs chose the first, second and third lines of medications, made diagnostic adjustments, initiated appropriate referrals to specialists, and ordered laboratory tests of their choice. Based on their selections, the APP simulated the course of diabetes and its complications, requiring diverse management decisions on the subsequent virtual visits.
Results: In the Edocate virtual clinic, only 53% of HCPs achieved good glycemic control (A1c < 7%), 41% achieved BP control (<130/80 mmHg), and 66% prescribed high-intensity statins. NPs performed slightly but not significantly better than the physician cohort. Only 48% of HCPs checked microalbuminuria, 54% ordered creatinine and 55% ordered LDL. Interestingly, 79% of HCPs either kept or started Metformin as the first line medication. The most commonly ordered second line of medications for glycemic control was either GLP-1 receptor agonists (39%) or SGLT2 inhibitors (36%), while 23% of HCPs kept their patients on or added sulfonylurea or basal insulin (11%).
Conclusions: Despite a worldwide effort in diabetes education, the knowledge of T2DM management remains suboptimal (as assessed by the simulation APP) and underscores the need for better professional education. Innovative patient simulation-based learning applications can dramatically improve the level of competency in HCPs.
Disclosure
B. Draznin: None. I. Iancu: None.
Objective:
A writing committee of the Planning Research in Inpatient Diabetes (PRIDE) group has written this consensus article on behalf of the group in response to a specific request for input from ...the Centers for Medicare and Medicaid Services (CMS). The purpose of this article is to respond to the March 13, 2015 statement from that agency regarding plans to enforce prohibition of the off-label use of point of care (POC) capillary blood glucose monitor (BGM) testing in most critically ill patients. The article discusses: 1) how POC BGM testing is currently regulated; 2) how POC BGM testing is currently used in the United States; and 3) how POC BGM testing can be safely and effectively regulated in the future through cooperation between the clinician, laboratory, regulatory, industry, and patient communities.
Participants:
Nine members of PRIDE volunteered to write the statement on behalf of the entire group.
Evidence:
Descriptions of current medical practice for critically ill patients were derived from the experience of the authors. Descriptions of the performance of various methods for measuring glucose levels for intensive insulin therapy came from a literature review.
Consensus Process:
Eleven questions were developed by the PRIDE writing group. After extensive electronic and telephone discussion, the article was written and reviewed by all nine authors and then reviewed by two outside experts in the care of critically ill patients. All suggestions by the authors and the outside experts were incorporated.
Conclusions:
Although the CMS is attempting to protect patients with abnormal glycemic control from harm due to inaccurate POC fingerstick capillary BGM testing, their plan will result in more harm than good. A moratorium on enforcement of the prohibition of off-label use of POC capillary BGM testing is needed.
Insulin maintains vascular smooth muscle cell (VSMC) quiescence yet can also promote VSMC migration. The mechanisms by which insulin exerts these contrasting effects were examined using alpha-smooth ...muscle actin (alpha-SMA) as a marker of VSMC phenotype because alpha-SMA is highly expressed in quiescent but not migratory VSMC. Insulin alone maintained VSMC quiescence and modestly stimulated VSMC migration. Wortmannin, a phosphatidylinositol 3-kinase (PI3K) inhibitor, decreased insulin-stimulated expression of alpha-SMA mRNA by 26% and protein by 48% but had no effect on VSMC migration. PD98059, a mitogen-activated protein kinase (MAPK) kinase inhibitor, decreased insulin-induced VSMC migration by 52% but did not affect alpha-SMA levels. Platelet-derived growth factor (PDGF) promoted dedifferentiation of VSMC, and insulin counteracted this effect. Furthermore, insulin increased alpha-SMA mRNA and protein levels to 111 and 118%, respectively, after PDGF-induced dedifferentiation, an effect inhibited by wortmannin. In conclusion, insulin's ability to maintain VSMC quiescence and reverse the dedifferentiating influence of PDGF is mediated via the PI3K pathway, whereas insulin promotes VSMC migration via the MAPK pathway. Thus, with impaired PI 3-kinase signaling and intact MAPK signaling, as seen in insulin resistance, insulin may lose its ability to maintain VSMC quiescence and instead promote VSMC migration.
The insulin resistance of normal pregnancy is necessary to divert fuels to the fetus to meet fetal growth demands and is mediated by placental hormones. We recently demonstrated that human placental ...GH (hPGH) can trigger severe insulin resistance in transgenic (TG) mice. In this study we sought to elucidate the cellular mechanisms by which hPGH interferes with insulin signaling in muscle in TG mice. Insulin-stimulated GLUT-4 translocation to the plasma membrane (PM) was reduced in the TG compared with wild-type (WT) mice (P = 0.05). Insulin receptor (IR) levels were modestly reduced by 19% (P < 0.01) in TG mice, but there were no changes in phosphorylation of IR or IR substrate-1 (IRS-1) between WT and TG mice. A singular finding was a highly significant increase in the p85α regulatory subunit of phosphatidylinositol 3-kinase (PI 3-kinase; P < 0.001), yet a reduced ability of insulin to stimulate IRS-1-associated PI 3-kinase activity (P < 0.05). Although the levels of the p110 catalytic subunit protein of PI 3-kinase and IRS-1 were unchanged in the TG mice, insulin’s ability to stimulate p110 association with IRS-1 was markedly reduced (P < 0.0001). We demonstrate a unique mechanism of insulin resistance and suggest that hPGH may contribute to the insulin resistance of normal pregnancy by increasing the expression of the p85α monomer, which competes in a dominant negative fashion with the p85-p110 heterodimer for binding to IRS-1 protein.
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