Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review

For individuals affected by Type 1 diabetes (T1D), a chronic disease in which the pancreas does not produce any insulin, maintaining the blood glucose (BG) concentration as much as possible within the safety range (70-180\ua0mg/dl) allows avoiding short- and long-term complications. The tuning of exogenous insulin infusion can be difficult, especially because of the inter- and intra-day variability of physiological and behavioral factors. Continuous glucose monitoring (CGM) sensors, which monitor glucose concentration in the subcutaneous tissue almost continuously, allowed improving the detection of critical hypo- and hyper-glycemic episodes. Moreover, their integration with insulin pumps for continuous subcutaneous insulin infusion allowed developing algorithms that automatically tune insulin dosing based on CGM measurements in order to mitigate the incidence of critical episodes. In this work, we aim at reviewing the literature on methods for CGM-based automatic attenuation or suspension of basal insulin with a focus on algorithms, their implementation in commercial devices and clinical evidence of their effectiveness and safety

Optimisation of the Investigation of Antibody-Mediated Dysglycaemia

Two rare and severe disorders of insulin action, namely insulin autoimmune syndrome (IAS) and type B insulin resistance (TB-IR), are caused by pathogenic antibodies against insulin or the insulin receptor, respectively. These may arise in isolation or may complicate management of pre-existing diabetes mellitus, and milder forms of the conditions are often suspected in patients with insulin-treated diabetes and labile glycaemic control. Antibody depletion can effectively treat either condition in many cases. This research aimed to target major limitations of existing diagnostics, specifically, that anti-insulin antibody (IA) testing alone does not establish whether antibodies alter insulin action to a clinically-significant degree, and that no clinically-accredited diagnostic test for TB-IR currently exists. An initial collaborative study examined the ability of a panel of commercial insulin assays to quantify ten different insulin preparations. Significant variability in performance of assays against animal-derived and insulin analogues was seen, with certain insulin analogues not detected at all, with important implications for the use of insulin immunoassays in insulin-treated patients. A suite of techniques for investigation of the clinical significance of IAs were then developed and assessed. In a study of five widely-used insulin immunoassays, dilution of IAS plasma led to increased insulin recovery, and polyethylene glycol (PEG) precipitation of IAS plasma decreased insulin recovery in the majority of assays. Gel filtration chromatography (GFC) discriminated high molecular weight and monomeric insulin, while ex vivo addition of exogenous insulin to plasma increased sensitivity of insulin immunocomplex detection. An observational study was performed of 7 patients, all ultimately diagnosed with IAS. IAs were measured using radioligand-binding assay and enzyme-linked immunosorbent assay (ELISA). Method comparison showed results to differ in rank order and relative magnitude. For one patient whose screening IA result was not grossly elevated using either IA assay method, immunosubtraction studies were consistent with the presence of an IgA, a class of antibody under-/not detected in the IA assays studied. Competitive radioligand-binding studies demonstrated IAs to have a range of affinities. 4 patients treated with individualised regimens of immunosuppressive therapy varied in clinical response, and 3 were managed conservatively. Plasma insulin and C-peptide measurements made using mass spectrometry demonstrated under-estimation of insulin and over-estimation of C-peptide concentration using immunoassay in IAS. An observational laboratory and clinical study was also undertaken of 30 insulin-treated patients with diabetes and unexplained labile glycaemia. IA, and plasma insulin before and after PEG precipitation, were determined. Three groups were identified: the first were ‘negative’ for actionable IA; the second had demonstrable IAs of potential significance that warrant further study; and the third included 3 patients for whom immunomodulation therapy was indicated, with 1 other patient showing marked improvement of glycaemic control with close supervision and manipulation of insulin. Finally, anti-insulin receptor antibodies were detected using a newly developed ELISA utilising Chinese hamster ovary-expressed myc-tagged wild-type human insulin receptor. ‘Proof of principle’ was demonstrated for the new assay, with clear scope established for future diagnostic development. The ability to robustly prove, or conversely to rule out, the presence, of insulin–antibody complexes and/or anti-insulin receptor antibodies is invaluable in the investigation of patients with insulin resistance and/or unexplained labile glycaemia, and may decisively alter care pathways. Knowledge gained by this research has advanced understanding of the limitations of current laboratory diagnostics, and has thereby aided clinical-decision making for affected patients.PhD was funded by a Diabetes Research and Wellness Fellowship Sutherland–Earl Clinical Fellowship (RG68554). Funding was also received from the Medical Research Council (MRC_MC_UU_ 12012/5) and the United Kingdom National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre

Diagnosis and Management of Pediatric Diseases

A screenshot of some the most rapidly evolving fields in Neonatology and Pediatrics with articles reviewing some metabolic dysregulations as well as non-oncologic diseases that may occur in infancy, childhood, youth. The illustrative material with original photographs and drawings highlighting some pathogenetic concepts are keystones of this book

Hypoglycemia

Glucose is an essential metabolic substrate of all mammalian cells being the major carbohydrate presented to the cell for energy production and also many other anabolic requirements. Hypoglycemia is a disorder where the glucose serum concentration is usually low. The organism usually keeps the glucose serum concentration in a range of 70 to 110 mL/dL of blood. In hypoglycemia the glucose concentration normally remains lower than 50 mL/dL of blood. This book provides an abundance of information for all who need them in order to help many people worldwide

Vitamin D in pediatric age: consensus of the Italian Pediatric Society and the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Federation of Pediatricians.

Vitamin D plays a pivotal role in the regulation of calcium-phosphorus metabolism, particularly during pediatric age when nutritional rickets and impaired bone mass acquisition may occur.Besides its historical skeletal functions, in the last years it has been demonstrated that vitamin D directly or indirectly regulates up to 1250 genes, playing so-called extraskeletal actions. Indeed, recent data suggest a possible role of vitamin D in the pathogenesis of several pathological conditions, including infectious, allergic and autoimmune diseases. Thus, vitamin D deficiency may affect not only musculoskeletal health but also a potentially wide range of acute and chronic conditions. At present, the prevalence of vitamin D deficiency is high in Italian children and adolescents, and national recommendations on vitamin D supplementation during pediatric age are lacking. An expert panel of the Italian Society of Preventive and Social Pediatrics reviewed available literature focusing on randomized controlled trials of vitamin D supplementation to provide a practical approach to vitamin D supplementation for infants, children and adolescents

Sphingolipids

Although sphingolipids are ubiquitous components of cellular membranes, their abundance in cells is generally lower than glycerolipids or cholesterol, representing less than 20% of total lipid mass. Following their discovery in the brain—which contains the largest amounts of sphingolipids in the body—and first description in 1884 by J.L.W. Thudichum, sphingolipids have been overlooked for almost a century, perhaps due to their complexity and enigmatic nature. When sphingolipidoses were discovered, a series of inherited diseases caused by enzyme mutations involved in sphingolipid degradation returned to the limelight. The essential breakthrough came decades later, in the 1990s, with the discovery that sphingolipids were not just structural elements of cellular membranes but intra- and extracellular signaling molecules. It turned out that their lipid backbones, including ceramide and sphingosine-1-phosphate, had selective physiological functions. Thus, sphingolipids emerged as essential players in several pathologies including cancer, diabetes, neurodegenerative disorders, and autoimmune diseases. The present volume reflects upon the unexpectedly eclectic functions of sphingolipids in health, disease, and therapy. This fascinating lipid class will continue to be the subject of up-and-coming future discoveries, especially with regard to new therapeutic strategies

Inventor Business Card: Prof. Naila Rabbani

The launch of "Qatar University Research Magazine" marks the university's numerous achievements in the field of scientific research. It will also serve as a platform to highlight all our research related initiatives and activities carried out by the various research centers and colleges within the university

Hypoglycaemia in children and adults with type 1 diabetes: clinical implications

The proposed thesis will examine three areas of research: (1) the effects of hypoglycaemia on cognitive function in adults with and without T1DM, (2) the symptoms and awareness of hypoglycaemia in children and adolescents with T1DM and (3) hypoglycaemia and driving in people with insulin-treated diabetes: self-treatment and adherence to recommendations for avoidance. (1) Executive cognitive function governs organisation of thoughts, prioritisation of tasks, and time management. This study examined the effect of acute hypoglycaemia on executive function in adults with and without diabetes. Thirty-two adults with and without type 1 diabetes were studied. Two hyperinsulinaemic glucose clamps were performed at least 2 weeks apart in a single-blind, counterbalanced order. Executive functions were assessed with a validated test suite (Delis-Kaplan Executive Function). A general linear model (repeated-measures ANOVA) was used. Compared with euglycaemia, executive functions (with one exception) were significantly impaired during hypoglycaemia; lower test scores were recorded with more time required for completion. Large Cohen d values (>0.8) suggest that hypoglycaemia induces decrements in aspects of executive function with large effect sizes. In some tests, the performance of participants with diabetes was more impaired than those without diabetes. Executive cognitive function, which is necessary to carry out many everyday activities, is impaired during hypoglycaemia in adults with and without type 1 diabetes. (2) In children with type 1 diabetes mellitus (T1DM) the prevalence of impaired awareness of hypoglycaemia (IAH) is uncertain. Questionnaires were completed by 98 children with T1DM (mean age 10.6 years) and their parent(s); hospital admission data for the previous year were collected. Awareness of hypoglycaemia was assessed using two questionnaire-based methods that have been validated in adults. For 4 weeks, participants performed routine blood glucose measurements and completed questionnaires after each episode of hypoglycaemia. The ‘Gold’ questionnaire classified a greater proportion of the participants as having IAH than the ‘Clarke’ questionnaire (68.4 vs. 22.4%). Using the ‘Clarke’ method, but not the ‘Gold’ method, children with IAH were younger and more likely to require external assistance or hospital admission. In contrast to adults, behavioural symptoms were the best predictors of awareness status. IAH affects a substantial minority of children and impending hypoglycaemia may be heralded by behavioural symptoms. The ‘Clarke’ method was more effective at identifying those at increased risk. (3) A clinical survey of an outpatient clinic population to ascertain current knowledge and practice among drivers with insulin-treated diabetes. A representative sample of 202 current drivers with insulin-treated diabetes completed a structured questionnaire. A minimum blood glucose level of 4.0 mmol/L or higher was considered necessary for driving by 74.8%, and 87.1% reported always keeping carbohydrate in their vehicle. However, 38.1% reported never carrying a glucose meter when driving, and 59.9% that they never test blood glucose before driving, or test only if symptomatic of hypoglycaemia. Most participants 89% would stop driving to treat hypoglycaemia although only 13.9% would wait longer than 30 min. Compliance with statutory requirements to inform the licensing authority and motor insurer is good