38 results found
Bhattarai S, Godsland IF, Misra S, et al., 2019, Metabolic health and vascular complications in type 1 diabetes, Journal of Diabetes and its Complications, ISSN: 1056-8727
AIMS: Optimal glycaemic control benefits risk of microvascular and macrovascular complications in type 1 diabetes (T1DM) but the importance of other components of metabolic health is less certain, particularly in the context of routine clinical practice. METHODS: Data for this cross-sectional analysis derived from a database covering inner North West London adult diabetes clinics. People with T1DM and with complete information for height, weight, blood pressure and serum high and low-density lipoprotein cholesterol (HDL-c and LDL-c) and triglyceride concentration measurements were included. RESULTS: Among the 920 participants, those with complications were older and had longer duration of diabetes but had similar HbA1c to people without complications. Systolic hypertension and low HDL-c were independently associated with complications. From having 0 risk factors, the prevalence of micro and macrovascular disease increased with increasing number of risk factors. Relative to those with ≥1 risk factor, those with 0 risk factors (n = 179) were at lower risk of retinopathy (OR 0.6 (0.4-0.9), p = 0.01) and nephropathy [OR 0.1 (0.04-0.3), p = 0.002], independent of individual characteristics. CONCLUSIONS: In routine clinical management of T1DM, associations between lipid and blood pressure risk factors and prevalent micro and macrovascular disease remain, implying that more intensive risk factor management may be beneficial.
Huddy JR, Ni M, Misra S, et al., 2019, Development of the Point-of-Care Key Evidence Tool (POCKET): a checklist for multi-dimensional evidence generation in point-of-care tests, Clinical Chemistry and Laboratory Medicine, Vol: 57, Pages: 845-855, ISSN: 1434-6621
BackgroundThis study aimed to develop the Point-of-Care Key Evidence Tool (POCKET); a multi-dimensional checklist to guide the evaluation of point-of-care tests (POCTs) incorporating validity, utility, usability, cost-effectiveness and patient experience. The motivation for this was to improve the efficiency of evidence generation in POCTs and reduce the lead-time for the adoption of novel POCTs.MethodsA mixed qualitative and quantitative approach was applied. Following a literature search, a three round Delphi process was undertaken incorporating a semi-structured interview study and two questionnaire rounds. Participants included clinicians, laboratory personnel, commissioners, regulators (including members of National Institute for Health and Care Excellence [NICE] committees), patients, industry representatives and methodologists. Qualitative data were analysed based on grounded theory. The final tool was revised at an expert stakeholder workshop.ResultsForty-three participants were interviewed within the semi-structured interview study, 32 participated in the questionnaire rounds and nine stakeholders attended the expert workshop. The final version of the POCKET checklist contains 65 different evidence requirements grouped into seven themes. Face validity, content validity and usability has been demonstrated. There exists a shortfall in the evidence that industry and research methodologists believe should be generated regarding POCTs and what is actually required by policy and decision makers to promote implementation into current healthcare pathways.ConclusionsThis study has led to the development of POCKET, a checklist for evidence generation and synthesis in POCTs. This aims to guide industry and researchers to the evidence that is required by decision makers to facilitate POCT adoption so that the benefits they can bring to patients can be effectively realised.
Misra S, Mathieu C, 2018, Are newer insulin analogues better for people with type 1 diabetes?, Diabetic Medicine, ISSN: 0742-3071
Achieving optimal blood glucose control in Type 1 diabetes is a delicate balance between ensuring tight glycaemic control and achieving this without the expense of hypoglycaemia and weight gain, two major factors impacting quality of life. This is a real challenge for people with Type 1 diabetes and underpins many of the struggles they face in self‐managing on a day‐to‐day basis. The main goals of insulin delivery are to try to simulate the physiology of β‐cell insulin secretion as closely as possible and to overcome the challenges of peripheral insulin administration by achieving rapidity of onset with mealtime insulins and stability of the glucose‐lowering effects of long‐acting insulins. Since the early days of human insulin use, there have been many developments in insulin formulations that aim to achieve these goals as much as possible, thus contributing to better glycaemic control whilst minimizing hypoglycaemia. In the present review we discuss the currently available insulin analogues and the challenges of achieving glucose control using current analogues in those on multiple daily injections, and appraise the evidence base for newer‐generation insulin analogues, such as insulin degludec, glargine U300, faster‐acting insulin aspart and BioChaperone lispro. We also highlight new insulins in development and unmet needs in people with Type 1 diabetes.
Misra S, Owen K, 2018, Genetics of monogenic diabetes: present clinical challenges, Current Diabetes Reports, Vol: 18, ISSN: 1534-4827
Purpose of ReviewMonogenic forms of diabetes have specific treatments that differ from the standard care provided for type 1 and type 2 diabetes, making the appropriate diagnosis essential. In this review, we discuss current clinical challenges that remain, including improving case-finding strategies, particularly those that have transethnic applicability, and understanding the interpretation of genetic variants as pathogenic, with clinically meaningful impacts.Recent FindingsBiomarker approaches to the stratification for genetic testing now appear to be most effective in identifying cases of monogenic diabetes, and use of genetic risk scores may also prove useful. However, applicability in all ethnic groups is lacking. Challenges remain in the classification of genes as diabetes-causing and the interpretation of genetic variants at the clinical interface.SummarySince the discovery that genetic defects can cause neonatal or young-onset diabetes, multiple causal genes have been identified and there have been many advances in strategies to detect genetic forms of diabetes and their treatments. Approaches learnt from monogenic diabetes are now being translated to polygenic diabetes.
Misra S, vedovato N, cliff E, et al., 2018, Permanent neonatal diabetes: combining sulphonylureas with insulin may be an effective treatment, Diabetic Medicine, Vol: 35, Pages: 1291-1296, ISSN: 0742-3071
BackgroundPermanent neonatal diabetes caused by mutations in the KCNJ11 gene may be managed with high‐dose sulfonylureas. Complete transfer to sulfonylureas is not successful in all cases and can result in insulin monotherapy. In such cases, the outcomes of combining sulfonylureas with insulin have not been fully explored. We present the case of a woman with diabetes due to a KCNJ11 mutation, in whom combination therapy led to clinically meaningful improvements.CaseA 22‐year‐old woman was found to have a KCNJ11 mutation (G334V) following diagnosis with diabetes at 3 weeks. She was treated with insulin‐pump therapy, had hypoglycaemia unawareness and suboptimal glycaemic control. We assessed the in vitro response of the mutant channel to tolbutamide in Xenopus oocytes and undertook sulfonylurea dose‐titration with C‐peptide assessment and continuous glucose monitoring. In vitro studies predicted the G334V mutation would be sensitive to sulfonylurea therapy [91 ± 2% block (n = 6) with 0.5 mM tolbutamide]. C‐peptide increased following a glibenclamide test dose (from 5 to 410 pmol/l). Glibenclamide dose‐titration was undertaken: a lower glibenclamide dose did not reduce blood glucose levels, but at 1.2 mg/kg/day insulin delivery was reduced to 0.1 units/h. However, when insulin was stopped, hyperglycaemia ensued. Glibenclamide was further increased (2 mg/kg/day), but once‐daily long‐acting insulin was still required to maintain glycaemia. This resulted in improved HbA1c of 52 mmol/mol (6.9%), restoration of hypoglycaemia awareness and reduced glycaemic variability.ConclusionIn people with KCNJ11 mutations causing permanent neonatal diabetes, and where complete transfer is not possible, consideration should be given to dual insulin and sulfonylurea therapy.
Hill NE, Deighton K, Matu J, et al., 2018, Continuous glucose monitoring at high altitude effects on glucose homeostasis, Medicine and Science in Sports and Exercise, Vol: 50, Pages: 1679-1686, ISSN: 0195-9131
PURPOSE: Exposure to high altitude has been shown to enhance both glucose and lipid utilization depending on experimental protocol. In addition, high and low blood glucose levels have been reported at high altitude. We hypothesized that gradual ascent to high altitude results in changes in glucose levels in healthy young adults. METHODS: 25 adult volunteers, split into two teams, took part in the British Services Dhaulagiri Medical Research Expedition completing 14 days of trekking around the Dhaulagiri circuit in Nepal reaching a peak altitude of 5300m on Day 11 of the trek. Participants wore blinded continuous glucose monitors (CGM) throughout. Blood samples for c-peptide, pro-insulin and triacylglycerides were taken at sea level (UK) and in acclimatisation camps at 3600m, 4650m and 5120m. Energy intake was determined from food diaries. RESULTS: There was no difference in time spent in hypoglycemia stratified by altitude. Nocturnal CGM readings (22.00-06.00 hrs) were chosen to reduce the short-term impact of physical activity and food intake and showed a significant (p<0.0001) increase at 3600m (5.53±0.22mmol/L), 4650m (4.77±0.30mmol/L) and 5120m (4.78±0.24mmol/L) compared to baseline altitude 1100m (vs 4.61±0.25mmol/L). Energy intake did not differ by altitude. Insulin resistance and B-cell function, calculated by homeostatic model assessment, was reduced at 3600m compared to sea level. CONCLUSIONS: We observed a significant increase in nocturnal CGM glucose at 3600m and above despite gradual ascent from 1100m. Taken with the changes in insulin resistance and B-cell function, it is possible that the stress response to high altitude dominates exercise enhanced insulin sensitivity, resulting in relative hyperglycemia.
Walkey HC, Bravis V, Akaal K, et al., 2018, The relationship between islet autoantibody status and the clinical characteristics of children and adults with incident type 1 diabetes in a UK cohort, BMJ Open, Vol: 8, ISSN: 2044-6055
Srivanichakorn W, Godsland IF, Thomson H, et al., 2017, Fasting plasma glucose and variation in cardiometabolic risk factors in people with high-risk HbA1c-defined prediabetes: a cross-sectional multiethnic study., Diabetes Research and Clinical Practice, Vol: 134, Pages: 183-190, ISSN: 0168-8227
AIMS: Variation in cardiometabolic risk in prediabetes and any impacts of ethnicity on such variation have been little studied. In an ethnically diverse dataset, selected according to a high-risk HbA1c-based definition of prediabetes, we have investigated relationships between glycaemia and cardiometabolic risk factors and the influence of ethnicity on these relationships. METHODS: We undertook a cross-sectional analysis of baseline data from a diabetes prevention study in the UK and a chronic care clinic in Thailand, selected for people without diabetes (fasting plasma glucose <7.0 mmol/l) with HbA1c 6.0% - 6.4% (42-47 mmol/mol). Thai (n=158) and UK White (n=600), South Asian (n=112), Black (n=70) and other/mixed (n=103) groups were distinguished and measurements included fasting plasma glucose (FPG), blood pressure (BP), lipids and insulin resistance-related risk factors (IRFs). RESULTS: Independently of individual characteristics including ethnicity, only systolic BP was weakly associated with FPG (beta coefficient 1.76 (95%CI 0.10 to 3.42), p=0.03), and only LDL-c with IFG (FPG 5.6-<7) (adjusted -0.14 (-0.27, -0.003) p 0.04). There were no significant independent associations with cardiometabolic risk factors when categories of impaired fasting glucose (FPG ≥ 6.1 to <7.0 mmol/L) were considered. Relative to White, South Asian ethnicity was independently associated with lower systolic and diastolic BP, Black with lower triglycerides, cholesterol/HDL-c ratio and having 2 or more IRFs, and Thai with lower cholesterol/HDL-c ratio and all three non-white ethnicities with lower total and LDL cholesterol. CONCLUSION: In high-risk HbA1c-defined prediabetes additional measurement of FPG will add little to evaluation of cardiometabolic risk. Additionally, UK Whites tend to have the most adverse cardiometabolic profile of any ethnic group.
Misra S, 2017, Pancreatic autoantibodies: who to test and how to interpret the results, PRACTICAL DIABETES, Vol: 34, ISSN: 2047-2897
Walkey HC, Kaur A, Bravis V, et al., 2017, Rationale and protocol for the After Diabetes Diagnosis REsearch Support System (ADDRESS): an incident and high risk type 1 diabetes UK cohort study., BMJ Open, Vol: 7, ISSN: 2044-6055
INTRODUCTION: Type 1 diabetes is heterogeneous in its presentation and progression. Variations in clinical presentation between children and adults, and with ethnic group warrant further study in the UK to improve understanding of this heterogeneity. Early interventions to limit beta cell damage in type 1 diabetes are undergoing evaluation, but recruitment is challenging. The protocol presented describes recruitment of people with clinician-assigned, new-onset type 1 diabetes to understand the variation in their manner of clinical presentation, to facilitate recruitment into intervention studies and to create an open-access resource of data and biological samples for future type 1 diabetes research. METHODS AND ANALYSIS: Using the National Institute for Health Research Clinical Research Network, patients >5 years of age diagnosed clinically with type 1 diabetes (and their siblings) are recruited within 6 months of diagnosis. Participants agree to have their clinical, laboratory and demographic data stored on a secure database, for their clinical progress to be monitored using information held by NHS Digital, and to be contacted about additional research, in particular immunotherapy and other interventions. An optional blood sample is taken for islet autoantibody measurement and storage of blood and DNA for future analyses. Data will be analysed statistically to describe the presentation of incident type 1 diabetes in a contemporary UK population. ETHICS AND DISSEMINATION: Ethical approval was obtained from the independent NHS Research Ethics Service. Results will be presented at national and international meetings and submitted for publication to peer-reviewed journals.
Aakre KM, Oosterhuis WP, Misra S, et al., 2017, Could accreditation bodies facilitate the implementation of medical guidelines in laboratories?, CLINICAL CHEMISTRY AND LABORATORY MEDICINE, Vol: 55, Pages: 806-808, ISSN: 1434-6621
Kaur A, Walkey H, Godsland IF, et al., 2017, Characteristics Associated with Diabetic Ketoacidosis in Children and Adults Newly Diagnosed with Type 1 Diabetes: Data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) Cohort, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A467-A467, ISSN: 0012-1797
Misra S, Kaur A, Walkey H, et al., 2017, The Extent of Diabetes Misclassification One Year after a Diagnosis of Type 1 Diabetes: Data from the After Diabetes Diagnosis Research Support System (ADDRESS-2) Cohort, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A411-A412, ISSN: 0012-1797
Walkey HC, Kaur A, Godsland IF, et al., 2017, Clinical Presentation and Islet Autoantibody Status in a UK Multi-ethnic Cohort of Children and Adults with New-Onset Type 1 Diabetes-The After Diabetes Diagnosis Research Support System-2 (ADDRESS-2), 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A467-A468, ISSN: 0012-1797
Misra S, Godsland I, Lupak L, et al., 2017, Predictors of C-Peptide in a Young-Onset Diabetes UK Multiethnic Cohort: Results from the MY DIABETES Study, 77th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A421-A421, ISSN: 0012-1797
Misra S, Colclough K, Halleron K, et al., 2017, Type 1 diabetes phenotype in white and South Asian people with young onset diabetes in the UK: results from the MY DIABETES study, Spring Meeting on Clinician Scientists in Training, Publisher: ELSEVIER SCIENCE INC, Pages: 69-69, ISSN: 0140-6736
Misra S, Huddy J, Hanna G, et al., 2016, Validation and regulation of point of care devices for medical applications, Medical Biosensors for Point of Care (POC) Applications, Pages: 27-44, ISBN: 9780081000724
© 2017 Elsevier Ltd All rights reserved. Point of care test (POCT) devices for medical applications require validation and regulation before they can be implemented into clinical practice. Undertaking method validation of devices ensures that their performance meets pre-specified analytical criteria and is a requirement assessed by accreditation bodies. Verifying these criteria also assesses real-world performance of analysers by end users and uncovers potential bias or variability in performance. Clinical validation of POCT devices defines the clinical need and assesses the effect of introducing the device into clinical pathways as well as demonstrating performance in a specific clinical context. Taken together these two stages of evaluation ensure that devices perform to an acceptable quality standard and, if undertaken appropriately, further provide evidence of clinical effectiveness. In this chapter, we review the features of method validation, which involves an analytical and clinical component and the regulation of POCT devices whilst also discussing the key considerations when implementing these devices for medical applications.
Misra S, Shields B, Colclough K, et al., 2016, South Asian individuals with diabetes who are referred for MODY testing in the UK have a lower mutation pick-up rate than white European people, Diabetologia, Vol: 59, Pages: 2262-2265, ISSN: 0012-186X
Misra S, Hassanali N, Smith C, et al., 2016, A Homozygous Loss of Function HNF1A Variant Resulting in Sulfonylurea-Responsive Early-Onset Diabetes, 76th Scientific Sessions of the American-Diabetes-Association, Publisher: AMER DIABETES ASSOC, Pages: A418-A418, ISSN: 0012-1797
Barth JH, Misra S, Aakre KM, et al., 2015, Why are clinical practice guidelines not followed?, Clinical Chemistry and Laboratory Medicine, Vol: 54, Pages: 1133-1139, ISSN: 1437-4331
Clinical practice guidelines (CPG) are written with the aim of collating the most up to date information into a single document that will aid clinicians in providing the best practice for their patients. There is evidence to suggest that those clinicians who adhere to CPG deliver better outcomes for their patients. Why, therefore, are clinicians so poor at adhering to CPG? The main barriers include awareness, familiarity and agreement with the contents. Secondly, clinicians must feel that they have the skills and are therefore able to deliver on the CPG. Clinicians also need to be able to overcome the inertia of “normal practice” and understand the need for change. Thirdly, the goals of clinicians and patients are not always the same as each other (or the guidelines). Finally, there are a multitude of external barriers including equipment, space, educational materials, time, staff, and financial resource. In view of the considerable energy that has been placed on guidelines, there has been extensive research into their uptake. Laboratory medicine specialists are not immune from these barriers. Most CPG that include laboratory tests do not have sufficient detail for laboratories to provide any added value. However, where appropriate recommendations are made, then it appears that laboratory specialist express the same difficulties in compliance as front-line clinicians
Misra S, Oliver N, 2015, Response to Rosival: Pathophysiology of diabetic ketoacidosis, DIABETIC MEDICINE, Vol: 32, Pages: 1527-1528, ISSN: 0742-3071
Misra S, Oliver NS, 2015, Diabetic ketoacidosis in adults, BMJ-BRITISH MEDICAL JOURNAL, Vol: 351, ISSN: 1756-1833
Misra S, Moberg-Aakre K, Langlois M, et al., 2015, How Useful are Laboratory Practice Guidelines?, EJIFCC, Vol: 26, Pages: 190-196, ISSN: 1650-3414
Clinical practice guidelines (CPGs) relating to laboratory diagnostic testing are increasingly produced with the aim of standardizing practice and improving patient care based on the best available evidence. However, the production of a CPG is merely the first step in the process of getting evidence into practice, to be undertaken by laboratories and other stakeholders. This process should evaluate the information provided in the guidelines on laboratory tests, devise a strategy for implementing the CPG or the laboratory aspects of the CPG and finally, once implemented, assess the impact of the CPG on clinical practice, patient outcomes and costs of care. The purpose of CPG evaluation by the laboratory is to determine whether sufficient information is provided on the particular test recommended. CPGs may not always be written with the involvement of a laboratory specialist and this underlies the paucity of relevant information in some national guidelines. When laboratory specialists are involved, CPGs can provide practical information which supports local laboratories as well as clinicians in the implementation and appropriate use of recommendations. Implementation of CPGs is an often neglected area that needs attention and thought. There are many barriers to successful implementation, which may vary at local level. These need to be identified early if CPGs are to be successfully adhered to. The effectiveness of CPGs also needs to be audited using process and health outcome indicators. Clinical audit is an effective tool for assessing adherence to recommendations and for measuring the impact and success of the CPG.
Brouwers MCGJ, Ham JC, Wisse E, et al., 2015, Elevated Lactate Levels in Patients With Poorly Regulated Type 1 Diabetes and Glycogenic Hepatopathy: A New Feature of Mauriac Syndrome, DIABETES CARE, Vol: 38, Pages: E11-E12, ISSN: 0149-5992
El-Laboudi A, Misra S, Martineau M, et al., 2015, INTENTIONAL LARGE INSULIN OVERDOSE CAPTURED ON A CONTINUOUS GLUCOSE MONITOR: A NOVEL CASE REPORT, DIABETES TECHNOLOGY & THERAPEUTICS, Vol: 17, Pages: A75-A76, ISSN: 1520-9156
Misra S, Oliver NS, 2015, Utility of ketone measurement in the prevention, diagnosis and management of diabetic ketoacidosis, DIABETIC MEDICINE, Vol: 32, Pages: 14-23, ISSN: 0742-3071
Tan TM, Salem V, Troke RC, et al., 2014, Combination of Peptide YY3-36 with GLP-1(7-36) amide Causes an Increase in First-Phase Insulin Secretion after IV Glucose, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 99, Pages: E2317-E2324, ISSN: 0021-972X
Aakre KM, Langlois MR, Barth JH, et al., 2014, The quality of laboratory aspects of troponin testing in clinical practice guidelines and consensus documents needs to be improved, CLINICA CHIMICA ACTA, Vol: 437, Pages: 58-61, ISSN: 0009-8981
Misra S, Barth JH, 2014, How good is the evidence base for test selection in clinical guidelines?, CLINICA CHIMICA ACTA, Vol: 432, Pages: 27-32, ISSN: 0009-8981
Jayasena CN, Comninos AN, Veldhuis JD, et al., 2013, A single injection of kisspeptin-54 temporarily increases luteinizing hormone pulsatility in healthy women, CLINICAL ENDOCRINOLOGY, Vol: 79, Pages: 558-563, ISSN: 0300-0664
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