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Supporting people with type 2 diabetes in effective use of their medicine through mobile health technology integrated with clinical care (SuMMiT-D pilot): results of a feasibility randomised trial.
, , Farmer, AJ, Allen, J, Bartlett, YK, Bower, P, Chi, Y, French, DP, Gudgin, B, Holmes, E, Horne, R, et al
Pilot and feasibility studies. 2024;(1):15
Abstract
BACKGROUND The purpose of this 6-month intervention pilot feasibility randomised trial was to test sending brief messages using mobile phones to promote self-management through taking medication as prescribed to people with type 2 diabetes. This was to inform the design and conduct of a future large-scale United Kingdom-based clinical trial and establish the feasibility of recruitment, the technology used, follow-up, and data collection. METHODS A multicentre individually randomised, controlled parallel group trial in primary care, recruiting adults (≥ 35 years) with type 2 diabetes in England. Consenting participants were randomly allocated to receive short message system text messages up to four times a week, or usual care, for a period of 6 months; messages contained behavioural change techniques targeting medication use. The primary outcome was the rate of recruitment to randomisation of participants to the trial with a planned rate of 22 participants randomised per month. The study also aimed to establish the feasibility of follow-up at 6 months, with an aim of retaining more than 80% of participants. Data, including patient-reported measures, were collected at baseline and the end of the 6-month follow-up period, and a notes review was completed at 24 months. RESULTS The trial took place between 26 November 2018 and 30 September 2019. In total 209 participants were randomly allocated to intervention (n = 103) or usual care (n = 106). The maximum rate of monthly recruitment to the trial was 60-80 participants per month. In total, 12,734 messages were sent to participants. Of these messages, 47 were identified as having failed to be sent by the service provider. Participants sent 2,864 messages to the automated messaging system. Baseline data from medical records were available for > 90% of participants with the exception of cholesterol (78.9%). At 6 months, a further HbA1c measurement was reported for 67% of participants. In total medical record data were available at 6 months for 207 (99.0%) of participants and completed self-report data were available for 177 (84.7%) of participants. CONCLUSION The feasibility of a large-scale randomised evaluation of brief message intervention for people with type 2 diabetes appears to be high using this efficient design. Failure rate of sending messages is low, rapid recruitment was achieved among people with type 2 diabetes, clinical data is available on participants from routine medical records and self-report of economic measures was acceptable. TRIAL REGISTRATION ISCTRN ISRCTN13404264. Registered on 10 October 2018.
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Associations of microvascular complications with all-cause death in patients with diabetes and COVID-19: The CORONADO, ABCD COVID-19 UK national audit and AMERICADO study groups.
Hadjadj, S, Saulnier, PJ, Ruan, Y, Zhu, X, Pekmezaris, R, Marre, M, Halimi, JM, Wargny, M, Rea, R, Gourdy, P, et al
Diabetes, obesity & metabolism. 2023;(1):78-88
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AIM: To provide a detailled analysis of the microvascular burden in patients with diabetes hopitalized for COVD-19. MATERIALS AND METHODS We analysed data from the French CORONADO initiative and the UK Association of British Clinical Diabetologists (ABCD) COVID-19 audit, two nationwide multicentre studies, and the AMERICADO, a multicentre study conducted in New York area. We assessed the association between risk of all-cause death during hospital stay and the following microvascular complications in patients with diabetes hospitalized for COVID-19: diabetic retinopathy and/or diabetic kidney disease and/or history of diabetic foot ulcer. RESULTS Among 2951 CORONADO, 3387 ABCD COVID-19 audit and 9327 AMERICADO participants, microvascular diabetic complications status was ascertained for 1314 (44.5%), 1809 (53.4%) and 7367 (79.0%) patients, respectively: 1010, 1059 and 1800, respectively, had ≥1 severe microvascular complication(s) and 304, 750 and 5567, respectively, were free of any complications. The patients with isolated diabetic kidney disease had an increased risk of all-cause death during hospital stay: odds ratio [OR] 2.53 (95% confidence interval [CI] 1.66-3.83), OR 1.24 (95% CI 1.00-1.56) and OR 1.66 (95% CI 1.40-1.95) in the CORONADO, the ABCD COVID-19 national audit and the AMERICADO studies, respectively. After adjustment for age, sex, hypertension and cardiovascular disease (CVD), compared to those without microvascular complications, patients with microvascular complications had an increased risk of all-cause death during hospital stay in the CORONADO, the ABCD COVID-19 diabetes national audit and the AMERICADO studies: adjusted OR (adj OR) 2.57 (95% CI 1.69-3.92), adj OR 1.22 (95% CI 1.00-1.52) and adj OR 1.33 (95% CI 1.15-1.53), respectively. In meta-analysis of the three studies, compared to patients free of complications, those with microvascular complications had an unadjusted OR for all-cause death during hospital stay of 2.05 (95% CI 1.42-2.97), which decreased to 1.62 (95% CI 1.19-2.119) after adjustment for age and sex, and to 1.50 (1.12-2.02) after hypertension and CVD were further added to the model. CONCLUSION Microvascular burden is associated with an increased risk of death in patients hospitalized for COVID-19.
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A UK nationwide study of adults admitted to hospital with diabetic ketoacidosis or hyperosmolar hyperglycaemic state and COVID-19.
Field, BCT, Ruan, Y, Várnai, KA, Davies, J, Ryder, REJ, Gandhi, R, Harris, S, Nagi, D, Patel, D, Kempegowda, P, et al
Diabetes, obesity & metabolism. 2023;(7):2012-2022
Abstract
AIMS: To investigate characteristics of people hospitalized with coronavirus-disease-2019 (COVID-19) and diabetic ketoacidosis (DKA) or hyperosmolar hyperglycaemic state (HHS), and to identify risk factors for mortality and intensive care admission. MATERIALS AND METHODS Retrospective cohort study with anonymized data from the Association of British Clinical Diabetologists nationwide audit of hospital admissions with COVID-19 and diabetes, from start of pandemic to November 2021. The primary outcome was inpatient mortality. DKA and HHS were adjudicated against national criteria. Age-adjusted odds ratios were calculated using logistic regression. RESULTS In total, 85 confirmed DKA cases, and 20 HHS, occurred among 4073 people (211 type 1 diabetes, 3748 type 2 diabetes, 114 unknown type) hospitalized with COVID-19. Mean (SD) age was 60 (18.2) years in DKA and 74 (11.8) years in HHS (p < .001). A higher proportion of patients with HHS than with DKA were of non-White ethnicity (71.4% vs 39.0% p = .038). Mortality in DKA was 36.8% (n = 57) and 3.8% (n = 26) in type 2 and type 1 diabetes respectively. Among people with type 2 diabetes and DKA, mortality was lower in insulin users compared with non-users [21.4% vs. 52.2%; age-adjusted odds ratio 0.13 (95% CI 0.03-0.60)]. Crude mortality was lower in DKA than HHS (25.9% vs. 65.0%, p = .001) and in statin users versus non-users (36.4% vs. 100%; p = .035) but these were not statistically significant after age adjustment. CONCLUSIONS Hospitalization with COVID-19 and adjudicated DKA is four times more common than HHS but both associate with substantial mortality. There is a strong association of previous insulin therapy with survival in type 2 diabetes-associated DKA.
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Association Between SGLT2 Inhibitor Treatment and Diabetic Ketoacidosis and Mortality in People With Type 2 Diabetes Admitted to Hospital With COVID-19.
Khunti, K, Ruan, Y, Davies, J, Field, BCT, Harris, S, Kosiborod, M, Nagi, D, Narendran, P, Patel, D, Ryder, REJ, et al
Diabetes care. 2022
Abstract
OBJECTIVE To determine the association between prescription of SGLT2 inhibitors (SGLT2is) and diabetic ketoacidosis (DKA) incidence or mortality in people with type 2 diabetes (T2D) hospitalized with COVID-19. RESEARCH DESIGN AND METHODS This was a retrospective cohort study based on secondary analysis of data from a large nationwide audit from a network of 40 centers in the U.K. with data collection up to December 2020. The study was originally designed to describe risk factors associated with adverse outcomes among people with diabetes who were admitted to hospital with COVID-19. The primary outcome for this analysis was DKA on or during hospital admission. The secondary outcome was mortality. Crude, age-sex adjusted, and multivariable logistic regression models were used to generate odds ratios (ORs) and 95% CIs for people prescribed SGLT2i compared with those not prescribed SGLT2i. RESULTS The original national audit included 3,067 people with T2D who were admitted to hospital with COVID-19, of whom 230 (7.5%) were prescribed SGLT2is prior to hospital admission. The mean age of the overall cohort was 72 years, 62.3% were men, and 34.9% were prescribed insulin. Overall, 2.8% of the total population had DKA and 35.6% of people in the study died. The adjusted odds of DKA were not significantly different between those prescribed SGLT2is and those not (OR 0.56; 95% CI 0.16-1.97). The adjusted odds of mortality associated with SGLT2is were similar in the total study population (OR 1.13; 95% CI 0.78-1.63), in the subgroup prescribed insulin (OR 1.02; 95% CI 0.59-1.77), and in the subgroup that developed DKA (OR 0.21; 95% CI 0.01-8.76). CONCLUSIONS We demonstrate a low risk of DKA and high mortality rate in people with T2D admitted to hospital with COVID-19 and limited power, but no evidence, of increased risk of DKA or in-hospital mortality associated with prescription of SGLT2is.
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Association of statin and/or renin-angiotensin-aldosterone system modulating therapy with mortality in adults with diabetes admitted to hospital with COVID-19: A retrospective multicentre European study.
Harris, S, Ruan, Y, Wild, SH, Wargny, M, Hadjadj, S, Delasalle, B, Saignes, M, Ryder, RE, Field, BCT, Narendran, P, et al
Diabetes & metabolic syndrome. 2022;(5):102484
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BACKGROUND & AIMS To assess the impact of pre-admission renin-angiotensin-aldosterone system inhibitor (RAASi) and statin use on mortality following COVID-19 hospitalization in adults with pre-existing diabetes. METHODS Retrospective cohort study of adults with diabetes admitted to ninety-nine participating hospitals in the United Kingdom, France and Spain during the first wave of the COVID-19 pandemic. Logistic regression models adjusted for demographic factors and comorbidity were used to describe associations with mortality in hospital or within 28 days of admission and individual or combined RAASi and statin therapy prescription followed by a country level meta-analysis. RESULTS Complete data were available for 3474 (42.6%) individuals. Prescribing patterns varied by country: 25-50% neither RAASi nor statin therapy, 14-36% both RAASi and statin therapy, 9-24% RAASi therapy alone, 12-36% statin alone. Overall, 20-37% of patients died within 28 days. Meta-analysis found no evidence of an association between mortality and prescription of RAASi therapy (OR 1.09, CI 0.78-1.52 (I2 22.2%)), statin (OR 0.97, CI 0.59-1.61 (I2 72.9%)) or both (OR 1.14, CI 0.67-1.92 (I2 78.3%)) compared to those prescribed neither drug class. CONCLUSIONS This large multicentre, multinational study found no evidence of an association between mortality from COVID-19 infection in people with diabetes and use of either RAASi, statin or combination therapy. This provides reassurance that clinicians should not change their RAASi and statin therapy prescribing practice in people with diabetes during the COVID-19 pandemic.
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The association between macrovascular complications and intensive care admission, invasive mechanical ventilation, and mortality in people with diabetes hospitalized for coronavirus disease-2019 (COVID-19).
Llauradó, G, Vlacho, B, Wargny, M, Ruan, Y, Franch-Nadal, J, Domingo, P, Gourdy, P, Saulnier, PJ, Hadjadj, S, Wild, SH, et al
Cardiovascular diabetology. 2022;(1):216
Abstract
BACKGROUND It is not clear whether pre-existing macrovascular complications (ischemic heart disease, stroke or peripheral artery disease) are associated with health outcomes in people with diabetes mellitus hospitalized for COVID-19. METHODS We conducted cohort studies of adults with pre-existing diabetes hospitalized for COVID-19 infection in the UK, France, and Spain during the early phase of the pandemic (between March 2020-October 2020). Logistic regression models adjusted for demographic factors and other comorbidities were used to determine associations between previous macrovascular disease and relevant clinical outcomes: mortality, intensive care unit (ICU) admission and use of invasive mechanical ventilation (IMV) during the hospitalization. Output from individual logistic regression models for each cohort was combined in a meta-analysis. RESULTS Complete data were available for 4,106 (60.4%) individuals. Of these, 1,652 (40.2%) had any prior macrovascular disease of whom 28.5% of patients died. Mortality was higher for people with compared to those without previous macrovascular disease (37.7% vs 22.4%). The combined crude odds ratio (OR) for previous macrovascular disease and mortality for all four cohorts was 2.12 (95% CI 1.83-2.45 with an I2 of 60%, reduced after adjustments for age, sex, type of diabetes, hypertension, microvascular disease, ethnicity, and BMI to adjusted OR 1.53 [95% CI 1.29-1.81]) for the three cohorts. Further analysis revealed that ischemic heart disease and cerebrovascular disease were the main contributors of adverse outcomes. However, proportions of people admitted to ICU (adjOR 0.48 [95% CI 0.31-0.75], I2 60%) and the use of IMV during hospitalization (adjOR 0.52 [95% CI 0.40-0.68], I2 37%) were significantly lower for people with previous macrovascular disease. CONCLUSIONS This large multinational study of people with diabetes mellitus hospitalized for COVID-19 demonstrates that previous macrovascular disease is associated with higher mortality and lower proportions admitted to ICU and treated with IMV during hospitalization suggesting selective admission criteria. Our findings highlight the importance correctly assess the prognosis and intensive monitoring in this high-risk group of patients and emphasize the need to design specific public health programs aimed to prevent SARS-CoV-2 infection in this subgroup.
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Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i.
Blonde, L, Fainberg, U, Kaltoft, MS, Mosenzon, O, Ramesh, C, Rea, R
Diabetes, obesity & metabolism. 2021;(10):2234-2241
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AIMS: The LIRA-ADD2SGLT2i trial demonstrated that liraglutide + sodium-glucose cotransporter-2 inhibitors (SGLT2is) ± metformin significantly improved glycaemic control (not body weight) versus placebo in adults with type 2 diabetes (T2D). This post-hoc analysis assessed whether baseline characteristics influenced these findings. MATERIALS AND METHODS LIRA-ADD2SGLT2i (NCT02964247) was a placebo-controlled, double-blind, multinational trial, wherein participants received liraglutide (≤1.8 mg/day) or placebo (randomized 2:1). Changes from baseline to week 26 in haemoglobin A1c (HbA1c), body weight and waist circumference stratified by HbA1c, body mass index (BMI), diabetes duration, duration of pre-trial SGLT2i use and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were analysed. These five baseline characteristics were divided into tertiles, and the treatment effect was evaluated using the trial product estimand. RESULTS Data from all 303 participants were analysed. There was a significant interaction between baseline HbA1c tertiles (7.0%-<7.6%; 7.6%-8.1%; ≥8.2%-9.5%) and glycaemic control at week 26 (p[interaction] = .011), with the lowest HbA1c estimated treatment difference (95% confidence interval) observed in patients with lowest baseline HbA1c [-0.20% (-0.59, 0.19); -0.68% (-1.03, -0.33); -0.98% (-1.33, -0.64), respectively]. There were no significant interactions in glycaemic control across baseline BMI, diabetes duration, insulin resistance determined by HOMA-IR or SGLT2i use duration (p[interaction] > .05, all). Across the five characteristics assessed, no significant interactions were found for body weight or waist circumference changes from baseline (p[interaction] > .05, all). CONCLUSION For individuals with T2D and inadequate glycaemic control despite therapy with SGLT2is ± metformin, liraglutide 1.8 mg would provide an effective treatment intensification option, irrespective of HbA1c, BMI, diabetes duration, insulin resistance determined by HOMA-IR and SGLT2i use duration.
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A UK nationwide study of people with type 1 diabetes admitted to hospital with COVID-19 infection.
Ruan, Y, Ryder, REJ, De, P, Field, BCT, Narendran, P, Iqbal, A, Gandhi, R, Harris, S, Nagi, D, Aziz, U, et al
Diabetologia. 2021;(8):1717-1724
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AIMS/HYPOTHESIS The aim of this work was to describe the clinical characteristics of adults with type 1 diabetes admitted to hospital and the risk factors associated with severe coronavirus disease-2019 (COVID-19) in the UK. METHODS A retrospective cohort study was performed using data collected through a nationwide audit of people admitted to hospital with diabetes and COVID-19, conducted by the Association of British Clinical Diabetologists from March to October 2020. Prespecified demographic, clinical, medication and laboratory data were collected from the electronic and paper medical record systems of the participating hospitals by local clinicians. The primary outcome of the study, severe COVID-19, was defined as death in hospital and/or admission to the adult intensive care unit (AICU). Logistic regression models were used to generate age-adjusted ORs. RESULTS Forty UK centres submitted data. The final dataset included 196 adults who were admitted to hospital and had both type 1 diabetes and COVID-19 on admission (male sex 55%, white 70%, with mean [SD] age 62 [19] years, BMI 28.3 [7.3] kg/m2 and last recorded HbA1c 76 [31] mmol/mol [9.1 (5.0)%]). The prevalence of pre-existing microvascular disease and macrovascular disease was 56% and 39%, respectively. The prevalence of diabetic ketoacidosis on admission was 29%. A total of 68 patients (35%) died or were admitted to AICU. The proportions of people that died were 7%, 38% and 38% of those aged <55, 55-74 and ≥75 years, respectively. BMI, serum creatinine levels and having one or more microvascular complications were positively associated with the primary outcome after adjusting for age. CONCLUSIONS/INTERPRETATION In people with type 1 diabetes and COVID-19 who were admitted to hospital in the UK, higher BMI, poorer renal function and presence of microvascular complications were associated with greater risk of death and/or admission to AICU. Risk of severe COVID-19 is reassuringly very low in people with type 1 diabetes who are under 55 years of age without microvascular or macrovascular disease. IN PEOPLE WITH TYPE 1 DIABETES AND COVID-19 ADMITTED TO HOSPITAL IN THE UK, BMI AND ONE OR MORE MICROVASCULAR COMPLICATIONS HAD A POSITIVE ASSOCIATION AND LOW SERUM CREATINE LEVELS HAD A NEGATIVE ASSOCIATION WITH DEATH/ADMISSION TO INTENSIVE CARE UNIT AFTER ADJUSTING FOR AGE.
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Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial.
Blonde, L, Belousova, L, Fainberg, U, Garcia-Hernandez, PA, Jain, SM, Kaltoft, MS, Mosenzon, O, Nafach, J, Palle, MS, Rea, R
Diabetes, obesity & metabolism. 2020;(6):929-937
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AIM: To compare the effect of liraglutide or placebo added on to sodium-glucose co-transporter-2 inhibitor (SGLT2i) ± metformin on glycaemic control in patients with type 2 diabetes. MATERIALS AND METHODS Patients with type 2 diabetes on a stable SGLT2i dose ± metformin (with HbA1c 7.0%-9.5% and body mass index [BMI] ≥ 20 kg/m2 ) were randomized 2:1 to add-on liraglutide 1.8 mg/day or placebo in this parallel, double-blind, multinational trial. Primary and confirmatory secondary endpoints were changes in HbA1c and body weight from baseline to week 26, respectively. The proportions of patients achieving HbA1c (<7.0%) targets and safety events after week 26 were also assessed. RESULTS Of 303 patients randomized (one in error), 280 completed treatment. Mean changes in HbA1c from baseline to week 26 with liraglutide (n = 202) and placebo (n = 100) were - 0.98% and - 0.30%, respectively (estimated treatment difference [ETD]: -0.68% [95% CI: -0.89, -0.48]; P < 0.001). Mean body weight changes from baseline were - 2.81 versus -1.99 kg, respectively (ETD: -0.82 kg [95% CI: -1.73, 0.09]; P = 0.077); 51.8% of liraglutide-treated patients achieved HbA1c < 7.0% versus 23.2% receiving placebo (odds ratio: 5.1 [95% CI: 2.67, 9.87]; P < 0.001). More patients treated with liraglutide reported ≥1 treatment-emergent adverse events (66.3%) versus placebo (47.0%). CONCLUSIONS Liraglutide significantly improved glycaemic control compared with placebo in patients with type 2 diabetes, insufficiently controlled with SGLT2is with/without metformin, with no unexpected safety findings.
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The Effect of the Association between Donepezil and Choline Alphoscerate on Behavioral Disturbances in Alzheimer's Disease: Interim Results of the ASCOMALVA Trial.
Carotenuto, A, Rea, R, Traini, E, Fasanaro, AM, Ricci, G, Manzo, V, Amenta, F
Journal of Alzheimer's disease : JAD. 2017;(2):805-815
Abstract
BACKGROUND Behavioral and psychological symptoms of dementia (BPSD) are a group of psychological reactions, psychiatric symptoms, and behaviors commonly found in Alzheimer's disease (AD). Four clusters of BPSD have been described: mood disorders (depression, anxiety, and apathy), psychotic symptoms (delusions and hallucinations), aberrant motor behaviors (pacing, wandering, and other purposeless behaviors), and inappropriate behaviors (agitation, disinhibition, and euphoria). Most of them are attributed to acetylcholine deficiency. OBJECTIVE To evaluate if a higher amount of acetylcholine obtained by associating donepezil and choline alphoscerate might have a favorable effect on BPSD. METHODS BPSD were measured at baseline and after 24 months in 113 mild/moderate AD patients, included in the double-blind randomized trial ASCOMALVA, by the Neuropsychiatric Inventory (NPI). Two matched groups were compared: group A treated with donepezil (10 mg/day) plus choline alphoscerate (1200 mg/day), and group B treated with donepezil (10 mg/day) plus placebo. RESULTS Data of NPI revealed a significant decrease of BPSD severity and distress of the caregiver in patients of group A compared with group B. Mood disorders (depression, anxiety and apathy) were significantly decreased in subjects treated with donepezil and choline alphoscerate, while their severity and frequency was increased in the other group. CONCLUSIONS Patients treated with donepezil plus choline alphoscerate showed a lower level of behavioral disturbances than subjects treated with donepezil only, suggesting that the association can have beneficial effects.