Glycaemic Control Among People with Type 1 Diabetes During Lockdown for the SARS-CoV-2 Outbreak in Italy

Achieving glycaemic control is a complex task for people with type 1 diabetes (T1D) as it involves multiple domains of daily functioning [1, 2]. To maintain glucose levels that are as much as possible within range, patients need to pay attention to meals, insulin doses, exercise regimens, working activities, social relations and psychological stress, as well as exercise self-control [3]. This continuous challenge results in people with T1D occasionally deprioritizing glycaemic control in favour of other activities [4]. Glucose control may improve during holidays, but this improvement is highly variable [5‐7].

In December 2019, a new coronavirus (CoV) strain that causes severe acute respiratory syndrome emerged in Wuhan (China), ultimately referred to as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and rapidly spread throughout the world [8]. In February and March 2020, Italy was the second most affected country worldwide [9]. To reduce the spread of infection, in late February 2020, the Italian Government issued a series of restrictions that, in March 2020, culminated in an almost complete lockdown of the country [10]. This lockdown intially involved all sport and educational activities but was then extended to commercial activities and most non-essential services. During lockdown, all citizens were requested to “stay at home” [11]. Outpatient clinics were closed while hospitals were coping with thousands of patients infected with SARS-CoV-2. The SARS-CoV-2 pandemic not only caused morbidity and mortality among people with CoV disease but also imposed a heavy burden on societal and population health [12]. It is expected that individuals with chronic disease, such as diabetes, will suffer the most from the prolonged lockdown due to limitations in access to outpatient clinics and services.

Remote glycaemic monitoring through cloud platforms has enabled diabetes specialists to interact with individuals with T1D during the SARS-CoV-2 pandemic lockdown. The widespread use of the flash glucose monitoring system (FGM) among patients with T1D [13] has allowed healthcare professionals (HCPs) to monitor these patients through a web-based interface that records real-time sensor readings. Of note, telemedicine has been shown to improve psychosocial outcomes in young adults with diabetes [14]. According to a recent meta-analysis, FGM has the potential to improve overall glucose control [15] and to reduce hypoglycaemia in individuals with T1D [16, 17].

In this study, we examined glycaemic control during the first week of lockdown against the spread of SARS-CoV-2 in people with T1D using FGM in Italy in comparison to the pre-lockdown period.

The study was approved by the Ethical Committee of the University Hospital of Padova. All procedures were performed in accordance with the Helsinki Declaration of 1964, and its later amendments, and was in agreement with national regulations. The study was conceived as a retrospective data collection, and all patients provided written informed consent to the reuse of clinical data for research purposes.

A total of 33 patients with T1D were enrolled in the study, then categorized into one of two groups based on whether they stopped working (n = 20) or continued working (n = 13) during the lockdown. Clinical characteristics of the two groups are reported in Table 1. None of the patients were known to be (have been) infected with SARS-CoV-2 nor to be (have been) quarantined for close contact with infected people.

The 20 patients who stopped working due to the lockdown had an average age of 36.9 years, 60% were male and average diabetes duration was 15 years. The mean latest available HbA1c value was 7.6%, and the prevalence of complications was low. When data collected during the week before the SARS-CoV-2 outbreak in Italy were compared to those of the first week of lockdown (period 2), average glucose had decreased from 177.7 ± 45.6 mg/dl (9.9 ± 2.5 mmol/l) to 161.0 ± 40.3 mg/dl (8.9 ± 2.2 mmol/l; p = 0.005; Fig. 1b), which is equal to a reduction of 16.7 ± 24.5 mg/dl (0.9 ± 1.4 mmol/l). The standard deviation of sensor readings decreased from 58.9 ± 19.6 mg/dl (3.3 ± 1.1 mmol/l) to 53.2 ± 19.9 mg/dl (3.0 ± 1.1 mmol/l; p = 0.004). As a result of the simultaneous improvement in average glucose and the standard deviation, patients moved from a high-unstable profile towards a low-stable profile (Fig. 1c). The number of patients in the low-stable profile area increased from three to eight (p = 0.02). However, the CV%, which is a better measure of glycaemic stability according to international consensus and recommendations [20, 21], did not change substantially across the periods considered.

Time in hypoglycaemia was not significantly changed, whereas time in range increased (from 54.4 ± 4.2 to 65.2 ± 4.2%; p = 0.010) and time in hyperglycaemia decreased (from 42.3 ± 4.8 to 31.6 ± 4.4%; p = 0.016; Fig. 1d). The number of scans per day did not change significantly (from 12.6 ± 2.4 to 13.4 ± 2.9; p = 0.479). Reduction of average glucose was directly correlated with baseline average glucose (r = 0.47; p = 0.016), but not with the number of scans per day.

When data collected during period 2 were compared to those collected during the 3 months before SARS-CoV-2 spread, the same significant improvements were noted (Table 2). Data collected during period 1 were not significantly different from those collected 1 week or 3 months before SARS-CoV-2 outbreak.

Patients who continued working during the lockdown (n = 13) had an average age of 45 years, 53.8% were male and average diabetes duration was 24.6 years (and thus longer than that of the group not working). Eight patients were on insulin pump therapy. None of the patients who continued to work showed improvement in any of the measures of glucose control during the lockdown period (period 2) compared to the 3 months or the week before the SARS-CoV-2 outbreak: average glucose, standard deviation, CV%, time in hypoglycaemia, time in range and time in hyperglycaemia remained unchanged (Table 2), as did the number of scans per day. No difference was observed regarding any change in glucose control metrics among those who were on the insulin pump and those who were on a regimen of multiple daily insulin injections.

Our data show that, during the first week of lockdown due to the SARS-CoV-2 outbreak in North-East Italy, patients with T1D who stayed at home achieved a significant improvement in glucose control. Among patients with T1D followed at the same clinic who continued working in the same period, many of whom were on insulin pump therapy, no deterioration of glucose control was observed.

The SARS-CoV-2 pandemic represents a huge challenge to public health worldwide [22], and healthcare services have faced severe challenges during outbreaks of the coronavirus disease (COVID-19), resulting in major cut backs in the care provided to people with chronic diseases, including diabetes [23, 24]. Many outpatient clinics have had to change their routine interactions with patient and use telemedicine to monitor patients at home [25]. In Italy, the widespread use of FGM among people with T1D allowed these patients to be remotely connected to the clinic through the cloud. Diabetes professionals were concerned that glucose control could worsen during lockdown because of the limited possibility to exercise and the severe psychologic stress imposed by social distancing in a cultural environment heavily reliant on direct inter-personal relationships. During the outbreak, most non-essential activities were shut down, and most citizens stopped their usual working routine or turned to working at home. However, some people, such as those involved in healthcare or the food supply chain, continued to work during the lockdown. Our observation that glucose control improved during the first week of lockdown in people with T1D who stayed at home is reassuring and suggests that a slowing down of routine activities can have favourable effects on glucose control in the short term. Remarkably, the reduction in average glucose and the increase in time in range were not paralleled by an increased time in hypoglycaemia, which remained stable. We speculate that such an improvement occurred because patients had more time to concentrate on diabetes control and had a more regular lifestyle, including the timing and composition of meals, while not being exposed to workplace stress [26]. In addition, the knowledge that diabetes worsens the outcomes of COVID-19 [27, 28] may have improved patients’ awareness and compliance to diabetes management.

To evaluate whether glucose control changed in all patients with T1D during lockdown, irrespectively of whether they stayed at home or not, we included a group of patients who continued working. The observation that glucose control did not improve in this subgroup of T1D patients supports our interpretation. However, the groups of patients who stopped working and those who continued their usual working activities were not comparable because the latter had a better baseline glucose control than those who stayed at home, and > 60% were on insulin pump therapy. Users of pump therapy represent approximately 30% of patients with T1D at our clinic, and 13% of T1D patients nationwide [29]. The frequent use of insulin pump therapy among this group of patients is probably related to the fact that most were healthcare workers and/or shift workers who often need pump therapy to cope with their lifestyle and working schedules. Patients who continued working had a higher time in range at baseline, such that further improvements were more difficult to obtain. Yet, it is reasonable to assume that these individuals were subjected to stronger challenges during lockdown, including exercise limitations, social distancing, workplace stress, and fear of infection. Therefore, that these patients maintained good glycaemic control is reassuring in terms of their effective self-management of diabetes. We speculate that the use of FGM combined with insulin pump therapy contributed to this effect [30]; for example by limiting diabetes-related distress [31].

We acknowledge that detailed information to interpret the drivers of glucose control during lockdown, such as changes in insulin doses, consumption of snacks and exercise, were not available and should be investigated in future studies. In addition, we included patients with T1D having relatively good glycaemic control and showing frequent sensor use. Therefore, it remains unclear whether the same results would apply to patients with worse glucose glycaemic control or less frequent sensor scans. Finally, we did not analyse glycaemic control in the subsequent weeks of lockdown because most patients were remotely contacted by the physicians from the clinic with advice on how to manage diabetes, thereby introducing bias. Hence, the medium- and long-term impact of lockdown on glucose control remains unknown.

In summary, we report that glucose control improved in people with T1D who stayed at home during the first week of lockdown due to COVID-19. This observation suggests that slowing down routine activities can have beneficial effects on T1D control in the short term. However, the long-term effects of lockdown and the factors that affect glucose control in this particular situation deserve future investigation.