ORCID Profile
0000-0002-3957-1981
Current Organisation
University of Dundee
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Publisher: American Diabetes Association
Date: 25-07-2022
DOI: 10.2337/DC21-2502
Abstract: Hypoglycemia poses an immediate threat for cognitive function. Due to its association with acute cognitive impairment, the International Hypoglycemia Study Group (IHSG) defines a blood glucose level & .0 mmol/L as “level 2 hypoglycemia.” In the current study we investigated whether having diabetes, type of diabetes, or hypoglycemia awareness moderates this association. Adults with type 1 diabetes with normal (n = 26) or impaired (n = 21) hypoglycemic awareness or with insulin-treated type 2 diabetes (n = 15) and age-matched control subjects without diabetes (n = 32) underwent a hyperinsulinemic-euglycemic-hypoglycemic glucose cl (2.80 ± 0.13 mmol/L [50.2 ± 2.3 mg/dL]). At baseline and during hypoglycemia, calculation ability, attention, working memory and cognitive flexibility were measured with the Paced Auditory Serial Addition Test (PASAT) and the Test of Attentional Performance (TAP). For the whole group, hypoglycemia decreased the mean ± SD proportion of correct answers on the PASAT by 8.4 ± 12.8%, increased reaction time on the TAP Alertness task by 32.1 ± 66.6 ms, and increased the sum of errors and omissions on the TAP Working Memory task by 2.0 ± 5.5 (all P & 0.001). Hypoglycemia-induced cognitive declines were largely irrespective of the presence or type of diabetes, level of symptomatic awareness, diabetes duration, or HbA1c. IHSG level 2 hypoglycemia impairs cognitive function in people with and without diabetes, irrespective of type of diabetes or hypoglycemia awareness status. These findings support the cutoff value of hypoglycemia & .0 mmol/L (& mg/dL) as being clinically relevant for most people with diabetes.
Publisher: JMIR Publications Inc.
Date: 29-09-2023
DOI: 10.2196/42100
Publisher: Wiley
Date: 22-06-2022
DOI: 10.1111/DME.14892
Abstract: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor‐detected hypoglycaemia (SDH) is unclear. Hypo‐METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. We will recruit 600 participants: 350 with insulin‐treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self‐detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient‐reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer‐reviewed journal publications and conference presentations.
Publisher: Springer Science and Business Media LLC
Date: 15-01-2020
DOI: 10.1007/S00125-019-05076-5
Abstract: Approximately 25% of people with type 1 diabetes have suppressed counterregulatory hormonal and symptomatic responses to insulin-induced hypoglycaemia, which renders them at increased risk of severe, disabling hypoglycaemia. This is called impaired awareness of hypoglycaemia (IAH), the cause of which is unknown. We recently proposed that IAH develops through habituation, a form of adaptive memory to preceding hypoglycaemia. Consistent with this hypothesis, we demonstrated restoration of defective counterregulatory hormonal responses to hypoglycaemia (referred to as dishabituation) in a rodent model of IAH following introduction of a novel stress stimulus (high intensity training [HIT]). In this proof-of-concept study we sought to further test this hypothesis by examining whether a single episode of HIT would lify counterregulatory responses to subsequent hypoglycaemia in people with type 1 diabetes who had IAH (assessed by Gold score ≥4, modified Clarke score ≥4 or Dose Adjustment For Normal Eating (DAFNE) hypoglycaemia awareness rating 2 or 3). The primary outcome was the difference in adrenaline response to hypoglycaemia following both a single episode of HIT and rest. In this randomised, crossover study 12 participants aged between 18 and 55 years with type 1 diabetes for ≥5 years and an HbA 1c mmol/mol (9%) were recruited. In iduals were randomised using computer generated block randomisation to start with one episode of HIT (4 × 30 s cycle sprints [2 min recovery] at 150% of maximum wattage achieved during $$ \\dot{V}{\\mathrm{O}}_{2\\mathrm{peak}} $$ V ̇ O 2 peak assessment) or rest (control). The following day they underwent a 90 min hyperinsulinaemic–hypoglycaemic cl study at 2.5 mmol/l with measurement of hormonal counterregulatory response, symptom scores and cognitive testing (four-choice reaction time and digit symbol substitution test). Each intervention and subsequent cl study was separated by at least 2 weeks. The participants and investigators were not blinded to the intervention or measurements during the study. The investigators were blinded to the primary outcome and blood analysis results. All participants (six male and six female, age 19–54 years, median [IQR] duration of type 1 diabetes 24.5 [17.3–29.0] years, mean [SEM] HbA 1c 56 [3.67] mmol/mol 7.3% [0.34%]) completed the study (both interventions and two cl s). In comparison with the rest study, a single episode of HIT led to a 29% increase in the adrenaline (epinephrine) response (mean [SEM]) (2286.5 [343.1] vs 2953.8 [384.9] pmol/l) a significant increase in total symptom scores (Edinburgh Hypoglycaemia Symptom Scale: 24.25 [2.960 vs 27.5 [3.9] p .05), and a significant prolongation of four-choice reaction time (591.8 [22.5] vs 659.9 [39.86] ms p .01] during equivalent hypoglycaemia induced the following day. These findings are consistent with the hypothesis that IAH develops in people with type 1 diabetes as a habituated response and that introduction of a novel stressor can restore, at least partially, the adapted counterregulatory hormonal, symptomatic and cognitive responses to hypoglycaemia. ISRCTN15236211.
Publisher: Public Library of Science (PLoS)
Date: 17-03-2023
DOI: 10.1371/JOURNAL.PONE.0283148
Abstract: The aim of this study was to determine the acceptability and psychometric properties of the Hypo-METRICS (Hypoglycemia MEasurement, ThResholds and ImpaCtS) application (app): a novel tool designed to assess the direct impact of symptomatic and asymptomatic hypoglycemia on daily functioning in people with insulin-treated diabetes. 100 adults with type 1 diabetes mellitus (T1DM, n = 64) or insulin-treated type 2 diabetes mellitus (T2DM, n = 36) completed three daily ‘check-ins’ (morning, afternoon and evening) via the Hypo-METRICs app across 10 weeks, to respond to 29 unique questions about their subjective daily functioning. Questions addressed sleep quality, energy level, mood, affect, cognitive functioning, fear of hypoglycemia and hyperglycemia, social functioning, and work roductivity. Completion rates, structural validity, internal consistency, and test-retest reliability were explored. App responses were correlated with validated person-reported outcome measures to investigate convergent (r s ±0.3) and ergent (r s ±0.3) validity. Participants’ mean±SD age was 54±16 years, diabetes duration was 23±13 years, and most recent HbA1c was 56.6±9.8 mmol/mol. Participants submitted mean±SD 191±16 out of 210 possible ‘check-ins’ (91%). Structural validity was confirmed with multi-level confirmatory factor analysis showing good model fit on the adjusted model (Comparative Fit Index .95, Root-Mean-Square Error of Approximation .06, Standardized Root-Mean-square Residual .08). Scales had satisfactory internal consistency (all ω≥0.5), and high test-retest reliability (r s ≥0.7). Convergent and ergent validity were demonstrated for most scales. High completion rates and satisfactory psychometric properties demonstrated that the Hypo-METRICS app is acceptable to adults with T1DM and T2DM, and a reliable and valid tool to explore the daily impact of hypoglycemia.
Publisher: Wiley
Date: 05-02-2020
DOI: 10.1111/DME.14240
Abstract: Hypoglycaemia is the most frequent complication of treatment with insulin or insulin secretagogues in people with diabetes. Severe hypoglycaemia, i.e. an event requiring external help because of cognitive dysfunction, is associated with a higher risk of adverse cardiovascular outcomes and all‐cause mortality, but underlying mechanism(s) are poorly understood. There is also a gap in the understanding of the clinical, psychological and health economic impact of ‘non‐severe’ hypoglycaemia and the glucose level below which hypoglycaemia causes harm. To increase understanding of hypoglycaemia by addressing the above issues over a 4‐year period. Hypo‐RESOLVE is structured across eight work packages, each with a distinct focus. We will construct a large, sustainable database including hypoglycaemia data from clinical trials to examine predictors of hypoglycaemia and establish glucose threshold(s) below which hypoglycaemia constitutes a risk for adverse biomedical and psychological outcomes, and increases healthcare costs. We will also investigate the mechanism(s) underlying the antecedents and consequences of hypoglycaemia, the significance of glucose sensor‐detected hypoglycaemia, the impact of hypoglycaemia in families, and the costs of hypoglycaemia for healthcare systems. The outcomes of Hypo‐RESOLVE will inform evidence‐based definitions regarding the classification of hypoglycaemia in diabetes for use in daily clinical practice, future clinical trials and as a benchmark for comparing glucose‐lowering interventions and strategies across trials. Stakeholders will be engaged to achieve broadly adopted agreement. Hypo‐RESOLVE will advance our understanding and refine the classification of hypoglycaemia, with the ultimate aim being to alleviate the burden and consequences of hypoglycaemia in people with diabetes.
Publisher: Springer Science and Business Media LLC
Date: 23-03-2022
Publisher: Elsevier BV
Date: 06-2023
Publisher: Springer Science and Business Media LLC
Date: 02-02-2021
DOI: 10.1007/S00125-021-05382-X
Abstract: It is generally accepted that hypoglycaemia can negatively impact the quality of life (QoL) of people living with diabetes. However, the suitability of patient-reported outcome measures (PROMs) used to assess this impact is unclear. The aim of this systematic review was to identify PROMs used to assess the impact of hypoglycaemia on QoL and examine their quality and psychometric properties. Systematic searches (MEDLINE, EMBASE, PsycINFO, CINAHL and The Cochrane Library databases) were undertaken to identify published articles reporting on the development or validation of hypoglycaemia-specific PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL) in adults with diabetes. A protocol was developed and registered with PROSPERO (registration no. CRD42019125153). Studies were assessed for inclusion at title/abstract stage by one reviewer. Full-text articles were scrutinised where considered relevant or potentially relevant or where doubt existed. Twenty per cent of articles were assessed by a second reviewer. PROMS were evaluated, according to COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) guidelines, and data were extracted independently by two reviewers against COSMIN criteria. Assessment of each PROM’s content validity included reviewer ratings ( N = 16) of relevance, comprehensiveness and comprehensibility: by researchers ( n = 6) clinicians ( n = 6) and adults with diabetes ( n = 4). Of the 214 PROMs used to assess the impact of hypoglycaemia on QoL (or domains of QoL), eight hypoglycaemia-specific PROMS were identified and subjected to full evaluation: the Fear of Hypoglycemia 15-item scale the Hypoglycemia Fear Survey the Hypoglycemia Fear Survey version II the Hypoglycemia Fear Survey-II short-form the Hypoglycemic Attitudes and Behavior Scale the Hypoglycemic Confidence Scale the QoLHYPO questionnaire and the Treatment-Related Impact Measure-Non-severe Hypoglycemic Events (TRIM-HYPO) questionnaire. Content validity was rated as ‘inconsistent’, with most as ‘(very) low’ quality, while structural validity was deemed ‘unsatisfactory’ or 'indeterminate'. Other measurement properties (e.g. reliability) varied, and evidence gaps were apparent across all PROMs. None of the identified studies addressed cross-cultural validity or measurement error. Criterion validity and responsiveness were not assessed due to the lack of a ‘gold standard’ measure of the impact of hypoglycaemia on QoL against which to compare the PROMS. None of the hypoglycaemia-specific PROMs identified had sufficient evidence to demonstrate satisfactory validity, reliability and responsiveness. All were limited in terms of content and structural validity, which restricts their utility for assessing the impact of hypoglycaemia on QoL in the clinic or research setting. Further research is needed to address the content validity of existing PROMs, or the development of new PROM(s), for the purpose of assessing the impact of hypoglycaemia on QoL. CRD42019125153
Publisher: Springer Science and Business Media LLC
Date: 05-2022
DOI: 10.1038/S41591-022-01790-7
Abstract: Type 2 diabetes (T2D) is a complex chronic disease characterized by considerable phenotypic heterogeneity. In this study, we applied a reverse graph embedding method to routinely collected data from 23,137 Scottish patients with newly diagnosed diabetes to visualize this heterogeneity and used partitioned diabetes polygenic risk scores to gain insight into the underlying biological processes. Overlaying risk of progression to outcomes of insulin requirement, chronic kidney disease, referable diabetic retinopathy and major adverse cardiovascular events, we show how these risks differ by patient phenotype. For ex le, patients at risk of retinopathy are phenotypically different from those at risk of cardiovascular events. We replicated our findings in the UK Biobank and the ADOPT clinical trial, also showing that the pattern of diabetes drug monotherapy response differs for different drugs. Overall, our analysis highlights how, in a European population, underlying phenotypic variation drives T2D onset and affects subsequent diabetes outcomes and drug response, demonstrating the need to incorporate these factors into personalized treatment approaches for the management of T2D.
Publisher: Wiley
Date: 29-11-2022
DOI: 10.1111/DME.15007
Abstract: Assessment of patient‐reported outcome measures (PROMs), including quality of life (QoL), is essential in diabetes research and care. However, a recent review concluded that current hypoglycaemia‐specific PROMs have limited evidence of validity, reliability and responsiveness for assessing the impact of hypoglycaemia on QoL in people living with diabetes. None of the PROMs identified could be used directly to inform the cost‐effectiveness of treatments and interventions. There is a need for a new hypoglycaemia‐specific QoL PROM, which can be used directly to inform economic evaluations. This project has three aims: (a) To develop draft PROM content for measuring the impact of hypoglycaemia on QoL in adults with diabetes. (b) To refine the draft content using cognitive debriefing interviews and psychometrics. This will result in a condition‐specific PROM that can be used to quantify the impact of hypoglycaemia upon QoL. (c) To generate a preference‐based measure (PBM) that will enable utility values to be calculated for economic evaluation. A mixed‐methods, three‐stage design is used: (a) Qualitative interviews will inform the draft PROM content. (b) Cognitive debriefing interview data will be used to refine the draft PROM content. The PROM will be administered in a large‐scale survey to enable psychometric validation. Final item selection for the PROM will be informed by psychometric performance, translatability assessment and input from stakeholder groups. (c) A classification system will be generated, comprising a reduced number of items from the PROM. A valuation survey will be conducted to derive a value set for the PBM.
Publisher: Elsevier BV
Date: 05-2019
Publisher: BMJ
Date: 08-2022
DOI: 10.1136/BMJDRC-2022-002890
Abstract: The aim of this study was to determine the psychometric properties of the 12-Item Hypoglycemia Impact Profile (HIP12), a brief measure of the impact of hypoglycemia on quality of life (QoL) among adults with type 1 (T1D) or type 2 diabetes (T2D). Adults with T1D (n=1071) or T2D (n=194) participating in the multicountry, online study, ‘Your SAY: Hypoglycemia’, completed the HIP12. Psychometric analyses were undertaken to determine acceptability, structural validity, internal consistency, convergent/ ergent validity, and known-groups validity. Most (98%) participants completed all items on the HIP12. The expected one-factor solution was supported for T1D, T2D, native English speaker, and non-native English speaker groups. Internal consistency was high across all groups (ω=0.91–0.93). Convergent and ergent validity were satisfactory. Known-groups validity was demonstrated for both diabetes types, by frequency of severe hypoglycemia (0 vs ≥1 episode in the past 12 months) and self-treated episodes ( vs 2–4 vs ≥5 per week). The measure also discriminated by awareness of hypoglycemia in those with T1D. The HIP12 is an acceptable, internally consistent, and valid tool for assessing the impact of hypoglycemia on QoL among adults with T1D. The findings in the relatively small s le with T2D are encouraging and warrant replication in a larger s le.
Publisher: Elsevier BV
Date: 07-2019
Publisher: BMJ
Date: 02-2022
DOI: 10.1136/BMJOPEN-2021-051651
Abstract: Hypoglycaemia is a frequent adverse event and major barrier for achieving optimal blood glucose levels in people with type 1 or type 2 diabetes using insulin. The Hypo-RESOLVE (Hypoglycaemia—Redefining SOLutions for better liVEs) consortium aims to further our understanding of the day-to-day impact of hypoglycaemia. The Hypo-METRICS (Hypoglycaemia—MEasurement, ThResholds and ImpaCtS) application (app) is a novel app for smartphones. This app is developed as part of the Hypo-RESOLVE project, using ecological momentary assessment methods that will minimise recall bias and allow for robust investigation of the day-to-day impact of hypoglycaemia. In this paper, the development and planned psychometric analyses of the app are described. The three phases of development of the Hypo-METRICS app are: (1) establish a working group—comprising diabetologists, psychologists and people with diabetes—to define the problem and identify relevant areas of daily functioning (2) develop app items, with user-testing, and implement into the app platform and (3) plan a large-scale, multicountry study including interviews with users and psychometric validation. The app includes 7 modules (29 unique items) assessing: self-report of hypoglycaemic episodes (during the day and night, respectively), sleep quality, well-being/cognitive function, social interactions, fear of hypoglycaemia/hyperglycaemia and work roductivity. The app is designed for use within three fixed time intervals per day (morning, afternoon and evening). The first version was released mid-2020 for use (in conjunction with continuous glucose monitoring and activity tracking) in the Hypo-METRICS study an international observational longitudinal study. As part of this study, semistructured user-experience interviews and psychometric analyses will be conducted. Use of the novel Hypo-METRICS app in a multicountry clinical study has received ethical approval in each of the five countries involved (Oxford B Research Ethics Committee, CMO Region Arnhem-Nijmegen, Ethikkommission der Medizinischen Universität Graz, Videnskabsetisk Komite for Region Hovedstaden and the Comite Die Protection Des Personnes SUD Mediterranne IV). The results from the study will be published in peer review journals and presented at national and international conferences. NCT04304963 .
Publisher: Springer Science and Business Media LLC
Date: 21-11-2016
Publisher: Springer Science and Business Media LLC
Date: 04-07-2012
Publisher: Elsevier BV
Date: 12-2016
Publisher: Elsevier BV
Date: 05-2017
Publisher: JMIR Publications Inc.
Date: 23-08-2022
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Rory McCrimmon.