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

AMP-activated protein kinase (AMPK) is a crucial cellular energy sensor. Once activated by falling energy status, it promotes ATP production by increasing the activity or expression of proteins involved in catabolism while conserving ATP by switching off biosynthetic pathways. AMPK also regulates metabolic energy balance at the whole-body level. For example, it mediates the effects of agents acting on the hypothalamus that promote feeding and entrains circadian rhythms of metabolism and feeding behaviour. Finally, recent studies reveal that AMPK conserves ATP levels through the regulation of processes other than metabolism, such as the cell cycle and neuronal membrane excitability.

/pdf/ampk-a-nutrient-and-energy-sensor-that-maintains-energy-19efb6eva0.pdf

AMPK: a nutrient and energy sensor that maintains energy homeostasis

I read this book the same weekend that the Packers took on the Rams, and the experience of the latter event, obviously, colored my judgment. Although I abhor anything that smacks of being a handbook (like, \"How to Earn a Merit Badge in Neurosurgery\") because too many volumes in biomedical science already evince a boyscout-like approach, I must confess that parts of this volume are fast, scholarly, and significant, with certain reservations. I like parts of this well-illustrated book because Dr. Sj6strand, without so stating, develops certain subjects on technique in relation to the acquisition of judgment and sophistication. And this is important! So, given that the author (like all of us) is somewhat deficient in some areas, and biased in others, the book is still valuable if the uninitiated reader swallows it in a general fashion, realizing full well that what will be required from the reader is a modulation to fit his vision, propreception, adaptation and response, and the kind of problem he is undertaking. A major deficiency of this book is revealed by comparison of its use of physics and of chemistry to provide understanding and background for the application of high resolution electron microscopy to problems in biology. Since the volume is keyed to high resolution electron microscopy, which is a sophisticated form of structural analysis, but really morphology in a modern guise, the physical and mechanical background of The instrument and its ancillary tools are simply and well presented. The potential use of chemical or cytochemical information as it relates to biological fine structure , however, is quite deficient. I wonder when even sophisticated morphol-ogists will consider fixation a reaction and not a technique; only then will the fundamentals become self-evident and predictable and this sine qua flon will become less mystical. Staining reactions (the most inadequate chapter) ought to be something more than a technique to selectively enhance contrast of morphological elements; it ought to give the structural addresses of some of the chemical residents of cell components. Is it pertinent that auto-radiography gets singled out for more complete coverage than other significant aspects of cytochemistry by a high resolution microscopist, when it has a built-in minimal error of 1,000 A in standard practice? I don't mean to blind-side (in strict football terminology) Dr. Sj6strand's efforts for what is \"routinely used in our laboratory\"; what is done is usually well done. It's just that …

Methods in Enzymology.

The TRIPOD (Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis) Statement includes a 22-item checklist, which aims to improve the reporting of studies developing, validating, or updating a prediction model, whether for diagnostic or prognostic purposes. The TRIPOD Statement aims to improve the transparency of the reporting of a prediction model study regardless of the study methods used. This explanation and elaboration document describes the rationale; clarifies the meaning of each item; and discusses why transparent reporting is important, with a view to assessing risk of bias and clinical usefulness of the prediction model. Each checklist item of the TRIPOD Statement is explained in detail and accompanied by published examples of good reporting. The document also provides a valuable reference of issues to consider when designing, conducting, and analyzing prediction model studies. To aid the editorial process and help peer reviewers and, ultimately, readers and systematic reviewers of prediction model studies, it is recommended that authors include a completed checklist in their submission. The TRIPOD checklist can also be downloaded from www.tripod-statement.org.

/pdf/transparent-reporting-of-a-multivariable-prediction-model-3n8wy14hp9.pdf

Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis (TRIPOD): explanation and elaboration.

Non-thrombotic PE does not represent a distinct clinical syndrome. It may be due to a variety of embolic materials and result in a wide spectrum of clinical presentations, making the diagnosis difficult. With the exception of severe air and fat embolism, the haemodynamic consequences of non-thrombotic emboli are usually mild. Treatment is mostly supportive but may differ according to the type of embolic material and clinical severity.

/pdf/guidelines-on-the-diagnosis-and-management-of-acute-1usqw9xdub.pdf

Guidelines on the Diagnosis and Management of Acute Pulmonary Embolism: The Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC)

Three patients present with chest pain to their general practitioner. In all three cases, the patient is suspected of acute coronary syndrome (ACS). In the first case, a coronary artery disease causing the complaints is ruled out since troponin levels remain within the normal range. In the second case, troponin is elevated due to non STelevated myocardial infarction. In the third case, troponin is elevated due to cardiac cell damage in severe pneumonia (i.e. cardiac damage is not caused by a coronary artery occlusion). In cardiology, diagnostic tools for ruling ACS in or out are becoming increasingly sensitive. In general practice, diagnostic means to discriminate between ACS and less severe causes of chest complaints remain poor. Both situations challenge physicians working in their respective fields. Cardiologists must deal with a decrease in testing specificity due to the increasing analytical sensitivity of high-sensitivity troponin, and face the dilemma of whether or not to perform invasive coronary angiography in cases of doubt instead of while general practitioners are still lacking adequate diagnostic tools. These difficulties are illustrated in three cases where patients’ present chest complaints in primary care and are eventually referred to a cardiologist. Notwithstanding the presence of the aforementioned dilemmas, combining clinical reasoning with current definitions of ACS and myocardial infarction leads to an unambiguous diagnosis in all three cases.

https://www.longdom.org/open-access/diagnosing-acute-coronary-syndrome-2165-7548.1000242.pdf

Diagnosing Acute Coronary Syndrome: A Challenge for General Practitioners and Cardiologists

Preface J.F.C. Glatz. 1. Cellular lipid binding proteins as facilitators and regulators of lipid metabolism J.F.C. Glatz, et al. 2. Critical steps in cellular fatty acid uptake and utilization G.J. van der Vusse, et al. 3. Mechanism of cellular uptake of long-chain fatty acids: do we need cellular proteins? J.A. Hamilton, F. Kamp. 4. Human and rodent fatty acid-binding proteins from liver, intestine, adipose tissue and heart muscle display similar mechanisms of fatty acid transfer to membranes J. Storch, et al. 5. Cytosolic fatty acid binding proteins catalyze two distinct steps in intracellular transport of their ligands R.A. Weisiger. 6. Insights into binding of fatty acids by fatty binding proteins T. Hanhoff, et al. 7. The effect of charge reversal mutations in the -helical region of liver fatty acid binding protein on the binding of fatty acul-CoAs, lysophospholipids and bile acids R.M. Hagan, et al. 8. Solution structure of fatty acid-binding protein from human brain M. Rademacher, et al. 9. Evolution of the family of intracellular lipid binding in vertebrates F.G. Schaap, et al. 10. Intracellular lipid binding proteins of the small intestine L.B. Agellon, et al. 11. Analysis on the phenotype of E-FABP-gene knock-out mice Y. Owada, et al. 12. Sterol carrier protein-2: not just for cholesterol anymore E.J. Murphy. 13. Fatty acid binding protein gene expression in different human adipose tissue depots in relation to rates of lipolysis and insulin concentration in obese individuals R.M. Fischer, et al. 14. Protein acylation in the cardiac muscle like cell line, H9c2 D.M. Hasselbaink, et al. 15. Alternative lipid mobilization: the insect shuttle system D.J. Van der Horst, et al. 16. Giant membrane vesicles as a model to study cellular substrate uptake dissected from metabolism D.P.Y. Koonen, et al. 17. Peroxisome proliferator-activated receptors: lipid binding proteins controlling gene expression M. van Bilsen, et al. 18. New insights into the fatty acid binding protein (FABP) family in the small intestine P. Besnard, et al. 19. Regulation of the ileal bile acid-binding protein gene: an approach to determine its physiological function(s) J.-F. Landrier, et al. 20. Role of adipocyte lipid-binding protein (ALBP) and acyl-CoA binding protein (ACBP) in PPAR-mediated transactivation T. Helledie, et al. 21. Analysis of tissue-specific and PPARa-dependent induction of FABP gene expression in the mouse liver by an in vivo DNA electroporation method K. Fujishiro, et al. 22. Characterization of a new fatty acid response element that controls the expression of the locust muscle FABP gene Q. Wu, et al. 23. Regulation of cellular fatty acid transport and membrane transporters in health and disease A. Bonen, et al. 24. The impact of overexpression and deficiency of fatty acid translocase (FAT/CD36) M. Febbraio, et al. 25. Intestinal lipid absorption is not affected in CD36 deficient mice J.R. Goudriaan, et al. 26. Surface expression of fatty acid translocase (FAT/CD36) on platelets in myeloproliferative disorders and non-insulin dependent diabetes mellitus: Effect on ara

Cellular lipid binding proteins

Biomarkers of Myocardial Cell Damage: Heart-Type Fatty Acid Binding Protein (H-FABP) for the Early Evaluation of Suspected Acute Coronary Syndrome

The heart is metabolically flexible. Under physiological conditions, it mainly uses lipids and glucose as energy substrates. In uncontrolled diabetes, the heart switches towards predominant lipid utilization, which over time is detrimental to cardiac function. Additionally, diabetes is accompanied by high plasma ketone levels and increased utilization of energy provision. The administration of exogenous ketones is currently being investigated for the treatment of cardiovascular disease. Yet, it remains unclear whether increased cardiac ketone utilization is beneficial or detrimental to cardiac functioning. The mechanism of lipid-induced cardiac dysfunction includes disassembly of the endosomal proton pump (named vacuolar-type H+-ATPase; v-ATPase) as the main early onset event, followed by endosomal de-acidification/dysfunction. The de-acidified endosomes can no longer serve as a storage compartment for lipid transporter CD36, which then translocates to the sarcolemma to induce lipid accumulation, insulin resistance, and contractile dysfunction. Lipid-induced v-ATPase disassembly is counteracted by the supply of specific amino acids. Here, we tested the effect of ketone bodies on v-ATPase assembly status and regulation of lipid uptake in rodent/human cardiomyocytes. 3-β-hydroxybutyrate (3HB) exposure induced v-ATPase disassembly and the entire cascade of events leading to contractile dysfunction and insulin resistance, similar to conditions of lipid oversupply. Acetoacetate addition did not induce v-ATPase dysfunction. The negative effects of 3HB could be prevented by addition of specific amino acids. Hence, in sedentary/prediabetic subjects ketone bodies should be used with caution because of possible aggravation of cardiac insulin resistance and further loss of cardiac function. When these latter maladaptive conditions would occur, specific amino acids could potentially be a treatment option.

https://www.mdpi.com/1422-0067/23/21/12909/pdf?version=1667801912

Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type H+-ATPase Disassembly—Rescue by Specific Amino Acid Supplementation

Heart-type fatty acid-binding protein (H-FABP) is a small cytosolic protein abundant in heart muscle cells. It offers great potential as a sensitive biomarker for early diagnosis of acute myocardial infarction (AMI). Ninety-one patients presented to the Emergency Department suspected of AMI with a median symptom onset of 6 h (IQR 3–20 h), of which 75 (82.4%) had AMI. The diagnostic performance of a point-of-care immunotest for H-FABP was compared with those of cardiac troponin T (cTnT), creatinine kinase MB (CK-MB), and myoglobin. The H-FABP immunotest was found to have a significant better sensitivity than the other markers and a better specificity than myoglobin and CK-MB. The H-FABP Immunotest gave the greatest area under the receiver operating characteristic (ROC) curve (0.864) for those admitted within 6 h after the onset of symptoms; whereas, cTnT gave the greatest area under the ROC curve (0.936) for those admitted 6–24 h. The H-FABP was also found to be the most efficient marker to diagnose patien...

http://repository.ust.hk/ir/bitstream/1783.1-6769/1/OriginalArticle_RennebergR_AnalLett2010.pdf

Jan F. C. Glatz

Papers

Diagnosing Acute Coronary Syndrome: A Challenge for General Practitioners and Cardiologists

Cellular lipid binding proteins

Biomarkers of Myocardial Cell Damage: Heart-Type Fatty Acid Binding Protein (H-FABP) for the Early Evaluation of Suspected Acute Coronary Syndrome

Ketone Body Exposure of Cardiomyocytes Impairs Insulin Sensitivity and Contractile Function through Vacuolar-Type H+-ATPase Disassembly—Rescue by Specific Amino Acid Supplementation

A point-of-care immunotest for bedside determination of heart-type fatty acid-binding protein