XI. STRATEGIES FOR IMPROVING DIABETES CARE D iabetes is a chronic illness that requires continuing medical care and patient self-management education to prevent acute complications and to reduce the risk of long-term complications. Diabetes care is complex and requires that many issues, beyond glycemic control, be addressed. A large body of evidence exists that supports a range of interventions to improve diabetes outcomes. These standards of care are intended to provide clinicians, patients, researchers, payors, and other interested individuals with the components of diabetes care, treatment goals, and tools to evaluate the quality of care. While individual preferences, comorbidities, and other patient factors may require modification of goals, targets that are desirable for most patients with diabetes are provided. These standards are not intended to preclude more extensive evaluation and management of the patient by other specialists as needed. For more detailed information, refer to Bode (Ed.): Medical Management of Type 1 Diabetes (1), Burant (Ed): Medical Management of Type 2 Diabetes (2), and Klingensmith (Ed): Intensive Diabetes Management (3). The recommendations included are diagnostic and therapeutic actions that are known or believed to favorably affect health outcomes of patients with diabetes. A grading system (Table 1), developed by the American Diabetes Association (ADA) and modeled after existing methods, was utilized to clarify and codify the evidence that forms the basis for the recommendations. The level of evidence that supports each recommendation is listed after each recommendation using the letters A, B, C, or E.

Standards of Medical Care in Diabetes

The metabolic syndrome

The aim of this updated guideline is to provide comprehensive and timely evidence-based recommendations on the prevention of future stroke among survivors of ischemic stroke or transient ischemic attack. The guideline is addressed to all clinicians who manage secondary prevention for these patients. Evidence-based recommendations are provided for control of risk factors, intervention for vascular obstruction, antithrombotic therapy for cardioembolism, and antiplatelet therapy for noncardioembolic stroke. Recommendations are also provided for the prevention of recurrent stroke in a variety of specific circumstances, including aortic arch atherosclerosis, arterial dissection, patent foramen ovale, hyperhomocysteinemia, hypercoagulable states, antiphospholipid antibody syndrome, sickle cell disease, cerebral venous sinus thrombosis, and pregnancy. Special sections address use of antithrombotic and anticoagulation therapy after an intracranial hemorrhage and implementation of guidelines.

/pdf/guidelines-for-the-prevention-of-stroke-in-patients-with-4s66xf1dte.pdf

Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(05)67528-9.pdf

Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial.

The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.

/pdf/glutamate-receptor-ion-channels-structure-regulation-and-148yts0p6h.pdf

Glutamate Receptor Ion Channels: Structure, Regulation, and Function

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(14)60976-4.pdf

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial

Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control : Results from the pioneer study

OBJECTIVE When oral therapy for type 2 diabetes is ineffective, adding basal insulin improves glycemic control. However, when glycated hemoglobin (HbA 1c ) remains elevated because of postprandial hyperglycemia, the next therapeutic step is controversial. We examined the efficacy and safety of lixisenatide in patients with HbA 1c still elevated after initiation of insulin glargine. RESEARCH DESIGN AND METHODS This double-blind, parallel-group trial enrolled patients with HbA 1c 7–10% despite oral therapy. Insulin glargine was added and systematically titrated during a 12-week run-in, after which candidates with fasting glucose ≤7.8 mmol/L and HbA 1c 7–9% were randomized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued. The primary end point was HbA 1c change after randomization. RESULTS The randomized population ( n = 446) had mean diabetes duration of 9.2 years, BMI 31.8 kg/m 2 , and daily glargine dosage of 44 units. HbA 1c had decreased during run-in from 8.6 to 7.6%; adding lixisenatide further reduced HbA 1c by 0.71 vs. 0.40% with placebo (least squares mean difference, –0.32%; 95% CI, –0.46 to –0.17; P 1c P P P = 0.0012). Nausea, vomiting, and symptomatic hypoglycemia CONCLUSION Adding lixisenatide to insulin glargine improved overall and postprandial hyperglycemia and deserves consideration as an alternative to prandial insulin for patients not reaching HbA 1c goals with recently initiated basal insulin.

https://care.diabetesjournals.org/content/diacare/36/9/2497.full.pdf

Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine: A 24-Week, Randomized, Placebo-Controlled Study (GETGOAL-DUO-1)

Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine

C-reactive protein (CRP) is a liver-derived pattern recognition molecule that is increased in inflammatory states. It rapidly increases within hours after tissue injury, and it is suggested that it is part of the innate immune system and contributes to host defense. Since cardiovascular disease is at least in part an inflammatory process, CRP has been investigated in the context of arteriosclerosis and subsequent vascular disorders. Based on multiple epidemiological and intervention studies, minor CRP elevation [high-sensitivity CRP (hsCRP)] has been shown to be associated with future major cardiovascular risk (hsCRP: 10 mg/L=unspecific elevation). It is recommended by the American Heart Association that patients at intermediate or high risk of coronary heart disease may benefit from measurement of hsCRP with regard to their individual risk prediction. Elevation of hsCRP is associated with increased risk of type 2 diabetes development in patients with all levels of metabolic syndrome. In type 1 and type 2 diabetes mellitus, hemoglobin A1c significantly correlates with hsCRP levels and future cardiovascular risk. Also, hsCRP levels increase with the stage of beta-cell dysfunction and insulin resistance. Non-diabetes drugs that have been shown to reduce hsCRP concentrations include aspirin, statins, cyclooxygenase-2 inhibitors, and fibrates. Recent intervention studies have also demonstrated the distinct efficacy of different anti-diabetes treatments on a variety of cardiovascular risk markers. Intensive insulin therapy may reduce inflammation, but this effect may be influenced by the degree of weight gain. Treatment with peroxisome proliferator-activated receptor gamma has lead to substantial reduction of hsCRP and other cardiovascular risk markers in several comparator studies. Since this effect was shown to be independent of the degree of glycemic improvement, it can be regarded as a classspecific effect. Whether these findings translate into a reduction of overall cardiovascular mortality will soon be shown by the currently running thiazolidinedione outcome studies. Positive results in these trials will further strengthen the value and acceptance of hsCRP, which is recommended as a predictive laboratory marker for cardiovascular disease risk also in patients with diabetes mellitus.

Thomas Forst

Papers

Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (AWARD-6): a randomised, open-label, phase 3, non-inferiority trial

Improvement of cardiovascular risk markers by pioglitazone is independent from glycemic control : Results from the pioneer study

Adding Once-Daily Lixisenatide for Type 2 Diabetes Inadequately Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine: A 24-Week, Randomized, Placebo-Controlled Study (GETGOAL-DUO-1)

Controlled With Newly Initiated and Continuously Titrated Basal Insulin Glargine

High-sensitivity C-reactive protein as cardiovascular risk marker in patients with diabetes mellitus.