The impact of the COVID-19 pandemic on diabetes services: planning for a global recovery.

The COVID-19 pandemic has disproportionately affected certain groups, such as older people (ie, >65 years), minority ethnic populations, and people with specific chronic conditions including diabetes, cardiovascular disease, kidney disease, and some respiratory diseases. There is now evidence of not only direct but also indirect adverse effects of COVID-19 in people with diabetes. Recurrent lockdowns and public health measures throughout the pandemic have restricted access to routine diabetes care, limiting new diagnoses, and affecting self-management, routine follow-ups, and access to medications, as well as affecting lifestyle behaviours and emotional wellbeing globally. Pre-pandemic studies have shown that short-term delays in delivery of routine care, even by 12 months, are associated with adverse effects on risk factor control and worse microvascular, macrovascular, and mortality outcomes in people with diabetes. Disruptions within the short-to-medium term due to natural disasters also result in worse diabetes outcomes. However, the true magnitude of the indirect effects of the COVID-19 pandemic on long-term outcomes and mortality in people with diabetes is still unclear. Disasters tend to exacerbate existing health disparities; as we recover ambulatory diabetes services in the aftermath of the pandemic, there is an opportunity to prioritise those with the greatest need, and to target resources and interventions aimed at improving outcomes and reducing inequality.

The Place and Value of Sodium-Glucose Cotransporter 2 Inhibitors in the Evolving Treatment Paradigm for Type 2 Diabetes Mellitus: A Narrative Review.

Over recent years, the expanding evidence base for sodium-glucose cotransporter-2 inhibitor (SGLT2i) therapies has revealed benefits beyond their glucose-lowering efficacy in the treatment of Type 2 diabetes mellitus (T2DM), resulting in their recognition as cardiorenal medicines. While SGLT2is continue to be recommended among the second-line therapies for the treatment of hyperglycaemia, their true value now extends to the prevention of debilitating and costly cardiovascular and renal events for high-risk individuals, with particular benefit shown in reducing major adverse cardiac events and heart failure (HF) and slowing the progression of chronic kidney disease. However, SGLT2i usage is still suboptimal among groups considered to be at greatest risk of cardiorenal complications. The ongoing coronavirus disease 2019 (COVID-19) pandemic has intensified financial pressures on healthcare systems, which may hamper further investment in newer effective medicines. Emerging evidence indicates that glycaemic control should be prioritised for people with T2DM in the era of COVID-19 and practical advice on the use of T2DM medications during periods of acute illness remains important, particularly for healthcare professionals working in primary care who face multiple competing priorities. This article provides the latest update from the Improving Diabetes Steering Committee, including perspectives on the value of SGLT2is as cost-effective therapies within the T2DM treatment paradigm, with particular focus on the latest published evidence relating to the prevention or slowing of cardiorenal complications. The implications for ongoing and future approaches to diabetes care are considered in the light of the continuing coronavirus pandemic, and relevant aspects of international treatment guidelines are highlighted with practical advice on the appropriate use of SGLT2is in commonly occurring T2DM clinical scenarios. The 'SGLT2i Prescribing Tool for T2DM Management', previously published by the Steering Committee, has been updated to reflect the latest evidence and is provided in the Supplementary Materials to help support clinicians delivering T2DM care.

Tirzepatide versus insulin glargine in type 2 diabetes and increased cardiovascular risk (SURPASS-4): a randomised, open-label, parallel-group, multicentre, phase 3 trial.

BACKGROUND: We aimed to assess efficacy and safety, with a special focus on cardiovascular safety, of the novel dual GIP and GLP-1 receptor agonist tirzepatide versus insulin glargine in adults with type 2 diabetes and high cardiovascular risk inadequately controlled on oral glucose-lowering medications. METHODS: This open-label, parallel-group, phase 3 study was done in 187 sites in 14 countries on five continents. Eligible participants, aged 18 years or older, had type 2 diabetes treated with any combination of metformin, sulfonylurea, or sodium-glucose co-transporter-2 inhibitor, a baseline glycated haemoglobin (HbA1c) of 7·5-10·5% (58-91 mmol/mol), body-mass index of 25 kg/m2 or greater, and established cardiovascular disease or a high risk of cardiovascular events. Participants were randomly assigned (1:1:1:3) via an interactive web-response system to subcutaneous injection of either once-per-week tirzepatide (5 mg, 10 mg, or 15 mg) or glargine (100 U/mL), titrated to reach fasting blood glucose of less than 100 mg/dL. The primary endpoint was non-inferiority (0·3% non-inferiority boundary) of tirzepatide 10 mg or 15 mg, or both, versus glargine in HbA1c change from baseline to 52 weeks. All participants were treated for at least 52 weeks, with treatment continued for a maximum of 104 weeks or until study completion to collect and adjudicate major adverse cardiovascular events (MACE). Safety measures were assessed over the full study period. This study was registered with ClinicalTrials.gov, NCT03730662. FINDINGS: Patients were recruited between Nov 20, 2018, and Dec 30, 2019. 3045 participants were screened, with 2002 participants randomly assigned to tirzepatide or glargine. 1995 received at least one dose of tirzepatide 5 mg (n=329, 17%), 10 mg (n=328, 16%), or 15 mg (n=338, 17%), or glargine (n=1000, 50%), and were included in the modified intention-to-treat population. At 52 weeks, mean HbA1c changes with tirzepatide were -2·43% (SD 0·05) with 10 mg and -2·58% (0·05) with 15 mg, versus -1·44% (0·03) with glargine. The estimated treatment difference versus glargine was -0·99% (multiplicity adjusted 97·5% CI -1·13 to -0·86) for tirzepatide 10 mg and -1·14% (-1·28 to -1·00) for 15 mg, and the non-inferiority margin of 0·3% was met for both doses. Nausea (12-23%), diarrhoea (13-22%), decreased appetite (9-11%), and vomiting (5-9%) were more frequent with tirzepatide than glargine (nausea 2%, diarrhoea 4%, decreased appetite <1%, and vomiting 2%, respectively); most cases were mild to moderate and occurred during the dose-escalation phase. The percentage of participants with hypoglycaemia (glucose <54 mg/dL or severe) was lower with tirzepatide (6-9%) versus glargine (19%), particularly in participants not on sulfonylureas (tirzepatide 1-3% vs glargine 16%). Adjudicated MACE-4 events (cardiovascular death, myocardial infarction, stroke, hospitalisation for unstable angina) occurred in 109 participants and were not increased on tirzepatide compared with glargine (hazard ratio 0·74, 95% CI 0·51-1·08). 60 deaths (n=25 [3%] tirzepatide; n=35 [4%] glargine) occurred during the study. INTERPRETATION: In people with type 2 diabetes and elevated cardiovascular risk, tirzepatide, compared with glargine, demonstrated greater and clinically meaningful HbA1c reduction with a lower incidence of hypoglycaemia at week 52. Tirzepatide treatment was not associated with excess cardiovascular risk. FUNDING: Eli Lilly and Company.

COVID-19, Hyperglycemia, and New-Onset Diabetes.

Certain chronic comorbidities, including diabetes, are highly prevalent in people with coronavirus disease 2019 (COVID-19) and are associated with an increased risk of severe COVID-19 and mortality. Mild glucose elevations are also common in COVID-19 patients and associated with worse outcomes even in people without diabetes. Several studies have recently reported new-onset diabetes associated with COVID-19. The phenomenon of new-onset diabetes following admission to the hospital has been observed previously with other viral infections and acute illnesses. The precise mechanisms for new-onset diabetes in people with COVID-19 are not known, but it is likely that a number of complex interrelated processes are involved, including previously undiagnosed diabetes, stress hyperglycemia, steroid-induced hyperglycemia, and direct or indirect effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the ß-cell. There is an urgent need for research to help guide management pathways for these patients. In view of increased mortality in people with new-onset diabetes, hospital protocols should include efforts to recognize and manage acute hyperglycemia, including diabetic ketoacidosis, in people admitted to the hospital. Whether new-onset diabetes is likely to remain permanent is not known, as the long-term follow-up of these patients is limited. Prospective studies of metabolism in the setting of postacute COVID-19 will be required to understand the etiology, prognosis, and treatment opportunities.

Glycaemic control during the lockdown for COVID-19 in adults with type 1 diabetes: A meta-analysis of observational studies.

AIMS: To assess the effects of lockdown due to COVID-19 pandemic on glucose metrics, measured by glucose monitoring systems, in adult individuals with type 1 diabetes. METHODS: We conducted a systematic literature search for English language articles from MEDLINE, Scopus and Web of Science up to February 28, 2021, using "diabetes", "lockdown", and "glucose" as key search terms. Time in range (TIR) was the main outcome; other metrics were time above range (TAR), time below range (TBR), mean blood glucose (MBG) and its variability (%CV), estimated HbA1c (eA1c) or glucose management indicator (GMI). RESULTS: Seventeen studies for a total of 3,441 individuals with type 1 diabetes were included in the analysis. In the lockdown period, TIR 70-180 mg/dl increased by 3.05% (95% CI 1.67-4.43%; p < 0.0001) while TAR (>180 mg/dL and > 250 mg/dL) declined by 3.39% (-5.14 to -1.63%) and 1.96% (-2.51 to -1.42%), respectively (p < 0.0001 for both). Both TBR < 70 and <54 mg/dL remained unchanged. MBG slightly decreased by 5.40 mg/dL (-7.29 to -3.51 mg/dL; p < 0.0001) along with a reduction in %CV. Pooled eA1c and GMI decreased by 0.18% (-0.24 to -0.11%; p < 0.0001) and a similar reduction was observed when GMI alone was considered (0.15%, -0.23 to -0.07%; p < 0.0001). Sensor use was only slightly but not significantly reduced during lockdown. CONCLUSIONS: This meta-analysis shows that well-controlled people with type 1 diabetes on both MDI and CSII with continuous or flash glucose monitoring did not experience a deterioration in glucose control throughout the COVID-19 lockdown, showing a modest, though statistically significant improvement in many glucose control parameters.

Telemonitoring, Telemedicine and Time in Range During the Pandemic: Paradigm Change for Diabetes Risk Management in the Post-COVID Future.

People with diabetes are at greater risk for negative outcomes from COVID-19. Though this risk is multifactorial, poor glycaemic control before and during admission to hospital for COVID-19 is likely to contribute to the increased risk. The COVID-19 pandemic and restrictions on mobility and interaction can also be expected to impact on daily glucose management of people with diabetes. Telemonitoring of glucose metrics has been widely used during the pandemic in people with diabetes, including adults and children with T1D, allowing an exploration of the impact of COVID-19 inside and outside the hospital setting on glycaemic control. To date, 27 studies including 69,294 individuals with T1D have reported the effect of glycaemic control during the COVID-19 pandemic. Despite restricted access to diabetes clinics, glycaemic control has not deteriorated for 25/27 cohorts and improved in 23/27 study groups. Significantly, time in range (TIR) 70-180 mg/dL (3.9-10 mmol/L) increased across 19/27 cohorts with a median 3.3% (- 6.0% to 11.2%) change. Thirty per cent of the cohorts with TIR data reported an average clinically significant TIR improvement of 5% or more, possibly as a consequence of more accurate glucose monitoring and improved connectivity through telemedicine. Periodic consultations using telemedicine enables care of people with diabetes while limiting the need for in-person attendance at diabetes clinics. Reports that sustained hyperglycaemia and early-stage diabetic ketoacidosis may go untreated because of the lockdown and concerns about potential exposure to the risk of infection argue for wider access to glucose telemonitoring. Therefore, in this paper we have critically reviewed reports concerning use of telemonitoring in the acute hospitalized setting as well as during daily diabetes management. Furthermore, we discuss the indications and implications of adopting telemonitoring and telemedicine in the present challenging time, as well as their potential for the future.

Impact of COVID-19 lockdown on glucose control of elderly people with type 2 diabetes in Italy.

AIMS: to evaluate the effect of home confinement related to COVID-19 lockdown on metabolic control in subjects with T2DM in Italy. METHODS: we evaluated the metabolic profile of 304 individuals with T2DM (65% males; age 69 ± 9 years; diabetes duration 16 ± 10 years) attending our Diabetes Unit early at the end of lockdown period (June 8 to July 7, 2020) and compared it with the latest one recorded before lockdown. RESULTS: There was no significant difference in fasting plasma glucose (8.6 ± 2.1 vs 8.8 ± 2.5 mmol/L; P = 0.353) and HbA1c (7.1 ± 0.9 vs 7.1 ± 0.9%; P = 0.600) before and after lockdown. Worsening of glycaemic control (i.e., ΔHbA1c ≥ 0.5%) occurred more frequently in older patients (32.2% in > 80 years vs 21.3% in 61-80 years vs 9.3% in < 60 years; P = 0.05) and in insulin users (28.8 vs 16.5%; P = 0.012). On multivariable analysis, age > 80 years (OR 4.62; 95%CI: 1.22-16.07) and insulin therapy (OR 1.96; 95%CI: 1.10-3.50) remained independently associated to worsening in glycaemic control. CONCLUSIONS: Home confinement related to COVID-19 lockdown did not exert a negative effect on glycaemic control in patients with T2DM. However, age and insulin therapy can identify patients at greatest risk of deterioration of glycaemic control.

Guida pratica alla prevenzione e gestione dell’infezione da COVID-19 nelle persone con diabete

SommarioLa pandemia di COVID-19 rappresenta un’enorme sfida per il sistema sanitario nazionale. Sulla base dei dati ad oggi disponibili è emerso che le persone con diabete mellito presentano un maggior rischio di complicanze e morte per COVID-19. Pertanto, adottare misure preventive di igiene e di distanziamento sociale è cruciale, a maggior ragione in questa categoria di soggetti. A sostegno dei pazienti con diabete sono state intraprese molteplici iniziative al fine di garantire la continuità assistenziale, tra cui la proroga della validità dei piani terapeutici per i farmaci ipoglicemizzanti, le procedure per il rinnovo della patente di guida e l’attivazione di servizi di telemedicina. In caso di infezione da COVID-19 e sintomi lievi è possibile una gestione domiciliare della persona con diabete, raccomandando un attento monitoraggio glicemico. Il paziente diabetico che necessita di ospedalizzazione richiede una gestione multidisciplinare che includa il diabetologo, con l’obiettivo di mantenere un adeguato controllo glicemico in assenza di ipoglicemie. Le persone con diabete rappresentano un gruppo vulnerabile per il quale devono essere poste in atto strategie specifiche sia in termini di prevenzione che di trattamento.

Type 1 diabetes and COVID-19: The "lockdown effect".

AIMS: The aim of this study was to evaluate the effect the lockdown imposed during COVID-19 outbreak on the glycemic control of people with Type 1 diabetes (T1D) using Continuous (CGM) or Flash Glucose Monitoring (FGM). MATERIALS AND METHODS: We retrospectively analyzed glucose reading obtained by FGM or CGM in T1D subjects. Sensor data from 2 weeks before the lockdown (Period 0, P0), 2 weeks immediately after the lockdown (period 1, P1), in mid-lockdown (Period 2, P2) and immediately after end of lockdown (Period 3, P3) were analyzed. RESULTS: The study included 63 T1D patients, (FGM: 52, 82%; CGM:11, 18%). Sensor use (91%) were slightly reduced. Despite this reduction, Time in Range increased in P1 (62%), P2 (61%) and P3 (62%) as compared to P0 (58%, all p < 0.05 or less) with concomitant reduction in the Time Above Range (P0: 38%; P1: 34%, P2: 34%, P3: 32%, all p < 0.05 or less vs. P0). Average glucose and GMI improved achieving statistical difference in P3 (165 vs. 158 mg/dl, p = 0.040 and 7.2% (55 mmol/mol) vs. 7.0% (53 mmol/mol), p = 0.016) compared to P0. Time Below Range (TBR) and overall glucose variability remained unchanged. Bi-hourly analysis of glucose profile showed an improvement particularly in the early morning hours. CONCLUSIONS: In T1D subjects with good glycemic control on CGM or FGM, the lockdown had no negative impact. Rather a modest but significant improvement in glycemic control has been recorded, most likely reflecting more regular daily life activities and reduces work-related distress.

Hyperglycemia at Hospital Admission Is Associated With Severity of the Prognosis in Patients Hospitalized for COVID-19: The Pisa COVID-19 Study.

OBJECTIVE: To explore whether at-admission hyperglycemia is associated with worse outcomes in patients hospitalized for coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: Hospitalized COVID-19 patients (N = 271) were subdivided based on at-admission glycemic status: 1) glucose levels <7.78 mmol/L (NG) (N = 149 [55.0%]; median glucose 5.99 mmol/L [range 5.38-6.72]), 2) known diabetes mellitus (DM) (N = 56 [20.7%]; 9.18 mmol/L [7.67-12.71]), and 3) no diabetes and glucose levels ≥7.78 mmol/L (HG) (N = 66 [24.3%]; 8.57 mmol/L [8.18-10.47]). RESULTS: Neutrophils were higher and lymphocytes and PaO2/FiO2 lower in HG than in DM and NG patients. DM and HG patients had higher D-dimer and worse inflammatory profile. Mortality was greater in HG (39.4% vs. 16.8%; unadjusted hazard ratio [HR] 2.20, 95% CI 1.27-3.81, P = 0.005) than in NG (16.8%) and marginally so in DM (28.6%; 1.73, 0.92-3.25, P = 0.086) patients. Upon multiple adjustments, only HG remained an independent predictor (HR 1.80, 95% CI 1.03-3.15, P = 0.04). After stratification by quintile of glucose levels, mortality was higher in quintile 4 (Q4) (3.57, 1.46-8.76, P = 0.005) and marginally in Q5 (29.6%) (2.32, 0.91-5.96, P = 0.079) vs. Q1. CONCLUSIONS: Hyperglycemia is an independent factor associated with severe prognosis in people hospitalized for COVID-19.

COVID-19 in people with diabetes: understanding the reasons for worse outcomes.

Since the initial COVID-19 outbreak in China, much attention has focused on people with diabetes because of poor prognosis in those with the infection. Initial reports were mainly on people with type 2 diabetes, although recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. The reason for worse prognosis in people with diabetes is likely to be multifactorial, thus reflecting the syndromic nature of diabetes. Age, sex, ethnicity, comorbidities such as hypertension and cardiovascular disease, obesity, and a pro-inflammatory and pro-coagulative state all probably contribute to the risk of worse outcomes. Glucose-lowering agents and anti-viral treatments can modulate the risk, but limitations to their use and potential interactions with COVID-19 treatments should be carefully assessed. Finally, severe acute respiratory syndrome coronavirus 2 infection itself might represent a worsening factor for people with diabetes, as it can precipitate acute metabolic complications through direct negative effects on ß-cell function. These effects on ß-cell function might also cause diabetic ketoacidosis in individuals with diabetes, hyperglycaemia at hospital admission in individuals with unknown history of diabetes, and potentially new-onset diabetes.

Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters.

Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.

Bariatric and metabolic surgery during and after the COVID-19 pandemic: DSS recommendations for management of surgical candidates and postoperative patients and prioritisation of access to surgery.

The coronavirus disease 2019 pandemic is wreaking havoc on society, especially health-care systems, including disrupting bariatric and metabolic surgery. The current limitations on accessibility to non-urgent care undermine postoperative monitoring of patients who have undergone such operations. Furthermore, like most elective surgery, new bariatric and metabolic procedures are being postponed worldwide during the pandemic. When the outbreak abates, a backlog of people seeking these operations will exist. Hence, surgical candidates face prolonged delays of beneficial treatment. Because of the progressive nature of obesity and diabetes, delaying surgery increases risks for morbidity and mortality, thus requiring strategies to mitigate harm. The risk of harm, however, varies among patients, depending on the type and severity of their comorbidities. A triaging strategy is therefore needed. The traditional weight-centric patient-selection criteria do not favour cases based on actual clinical needs. In this Personal View, experts from the Diabetes Surgery Summit consensus conference series provide guidance for the management of patients while surgery is delayed and for postoperative surveillance. We also offer a strategy to prioritise bariatric and metabolic surgery candidates on the basis of the diseases that are most likely to be ameliorated postoperatively. Although our system will be particularly germane in the immediate future, it also provides a framework for long-term clinically meaningful prioritisation.