LIFE WITH DIABETES IN THE COVID-19 ERA

. The outbreak of the COVID-19 pandemic has changed the lives of billions of people, especially those with chronic diseases such as diabetes. The aim of this study was to evaluate the impact of the pandemic on the physical and mental health of diabetics living in the Balkans. The study was conducted as an online survey in April 2023. 129 people participated in the survey. 76 of them were diagnosed with type 1 and 53 with type 2 diabetes. 6.97% of all respondents had a close family member who died from the consequences of SARS-CoV-2 infection, and as many as 77.78% of these decedents suffered from diabetes and/or cardiovascular disease. The majority of the respondents were also infected with SARS-CoV-2. Most of them were diagnosed with diabetes before infection, and SARS-CoV-2-induced diabetes was mainly type 2. Although they regularly took prescribed pharmacotherapy and nutritional supplements, blood glucose was elevated in half of them, while D-dimer levels were elevated mainly in type 2 diabetics. Also, hospitalization during the acute phase was more frequent in type 2 diabetic patients. Most diabetics suffered from sleep disorders ( p < 0.01), and type 2 diabetics also suffered from nightmares (p < 0.05). Consequently, the use of anxiolytics and antidepressants was more frequent in type 2 diabetic patients. Recovery was significantly faster in type 1 diabetics, due to less comorbidities such as hypertension, cardiovascular and liver diseases, which were more common in type 2 patients.


Introduction
With almost 770 million confirmed cases and nearly 7 million directly caused deaths (WHO, 2023), the outbreak of the COVID-19 pandemic has changed the lives of billions of people globally, especially those ones with chronic diseases such as diabetes mellitus, mainly because of the bidirectional relationship between SARS-CoV-2 infection and diabetes (Lima-Martínez et al., 2021).
Namely, like many other viruses, such as cytomegalovirus, Epstein-Barr virus, varicellazoster, enterovirus, rubeola, Coxsackie B, etc. (Jaeckel et al., 2002), COVID-19 can act as a diabetogenic agent.To wit, through binding to the ACE2 receptors of the pancreatic islet cells it can cause the dysfunction of the β cells, acute hyperglycemia and, finally, diabetes (Liu et al., 2020).
On the other hand, people who previously had diabetes, due to the already decreased immunity, elevated levels of oxidative stress and inflammation (Iacobellis, 2020), as well as risks of ketoacidosis (Vorgučin et al., 2022) had a much higher chance for hospital admission, severe pneumonia, and death than non-diabetics (Yang et al., 2020).
Additionally, media pressure, anxiety, depression, and less physical activity caused by lockdowns (Vujčić et al., 2021), together with comorbidities such as cardiovascular diseases and hypertension (Zhou et al. 2020;Vosko et al., 2023) contributed to the elevated level of severe outcomes of the SARS-CoV-2 infection.
The aim of this study was to evaluate the impact of the COVID-19 pandemic on the physical and mental health of diabetics living in the Balkans.

Material and methods
This was a cross-sectional survey conducted online with the help of Diabetes Association of Serbia, Diabetes Association of Belgrade, Serbia, Diabetes Association of Niš, Serbia, and Diabetics without borders, Balkans, during April 2023.The research was performed by surveying a total of 129 respondents.The questionnaire was a combination of open and closed question response formats.Questions were divided into four domains related to demographic data (such as gender, age group, place of residence), dietary habits (adherence to the diet prescribed by a physician), dietary supplements usage (a type of supplements and phytotherapy remedies used), pharmacotherapy usage, and medical history (type of diabetes diagnosed, presence of comorbidities, previous infection with SARS-CoV-2).The research was performed by surveying a total of 129 respondents.The data were statistically analyzed and processed using chi-square test of independence in GraphPad Prism 5 (GraphPad Software, La Jolla California USA).Statistical significance was accepted if p was less than 0.05.

Results
The research included 129 people, 104 females and 25 males, of which 70.54% were living in Serbia, 16.28% in Bosnia and Herzegovina, 7.75% in Croatia, 0.78% in Montenegro, while 4.65% of them were people born in the Balkans and leaving abroad.55.91% of respondents were diagnosed with type 1 and 44.09% with type 2 diabetes.The mean age of participants with type 1 diabetes was 37.72±9.94,and with type 2 diabetes 53.09±11.13years.
The primary therapy for treating type 1 diabetics was insulin (100%), while only 2.63% of them were treated with metformin and dapagliflozin as well.Type 2 diabetics were mostly treated with metformin (77.35%), insulin (35.84%), dapagliflozin (22.64%), and sulfonylureas (3.77%) (Graph. 1 (a)).Vitamins and minerals were more commonly used by type 1 than by type 2 diabetics as supplementary therapies (50 and 19.73% of DM1 and 37.73 and 9.43% of DM2 respondents, respectively), while the use of herbal remedies was only slightly more frequent within type 2 diabetics (28.3% of DM2 and 23.68% of DM1 respondents, respectively) (Graph. 1 (b)).Although the majority of both type 1 and type to diabetics had the dietary plan recommended by their physician (75% and 69.81% of DM1 and DM2 patients, respectively) (Graph. 2 (a)), adherence to the dietary plan was more common within type 1 diabetics, while even 43.24% of type 2 diabetics did not follow dietary recommendations (Graph. 2 (b)).

Graph. 3. Comorbidities of respondents Grafik 3. Pridružene bolesti ispitanika
The majority of both type 1 (68.42%) and type 2 diabetics (73.58%) had sleep disturbances (Graph 4 (a)) and of all of these people, even 55.26% of type 1 and 62.26% of type 2 diabetics had nightmares as well (Graph 4 (b)).Although the occasional usage of anxiolytics and antidepressants was more frequent in type 2 diabetics (47.17 and 28.95% of DM2 and DM1, respectively) (Graph 4 (c)), of all the people who use those pharmaceuticals, even 54.54% of type 1 and 64% of type 2 diabetics used them on the everyday basis (Graph 4 (d)) Most of the respondents, i.e., 71.05% of type 1 and 67.92% of type 2 diabetics had been infected with SARS-CoV-2 (p < 0.01) (Graph 5 (a)).However, only 6.58% of type 1 and 11.32% of type 2 diabetics developed diabetes mellitus as a result of COVID-19 (Graph 5(D)).22.86% of type 1 and even 38.09% of type 2 diabetes patients had elevated levels of D-dimer (Graph 4. (b)).The blood glucose levels were elevated in 44.44% of respondents with type 1, and 58.33% of those with type 2 diabetes (Graph 5 (e)).Hospitalization due to COVID-19 infection for more frequent in type 2 diabetic patients (13.89% of DM2 and 1.85% of DM1 who were infected) (Graph 5 (c)).Similarly, the recovery was significantly faster in type 1 diabetics (p < 0.01).Namely, 68.52% of DM1 fully recovered in less than a month, 12.96% in less than 2 months, while only 38.89% of DM2 patients recovered within 30 days, and 33.33% of them in less than 60 days.However, there were no statistically significant differences in patients who needed more than 3 months to recover (18.52% of DM1 and 27.78% of DM2 respondents) (Graph.5 (f)).Interestingly, even 6.97% of all respondents had a close family member who died from the consequences of SARS-CoV-2 infection, and as many as 77.78% of these decedents suffered from diabetes and/or cardiovascular disease.

Discussion
This study determined the influence of COVID-19 pandemic on the psychological and physical health of diabetics living in the Balkans.
Although the majority of our respondents developed diabetes before the COVID-19, we have noticed that diabetes resulted from this infection was mainly type 2 (Graph.5 (d)).Interestingly, only 3.77% of the survey respondents with type 2 diabetes are treated with sulfonylureas and 35.84% of them are using insulin injections (Graph. 1 (a)).Having in mind that together with metformin, sulfonylureas are the standard drug for type 2 diabetes in a period where there are still at least some functional pancreatic β cells (Panten et al., 1996), we might conclude that are respondents developed the late-stage type 2 diabetes, or even latent autoimmune diabetes of adults (LADA).These results are similar to the study of Joshi and Pozzilli (2022) who proposed that COVID-19 induced diabetes might be considered as a new form of diabetes where type 2 diabetes is sometimes not even characterized by insulin receptor insensibility, but rather unavailability of insulin caused by β cell damages.f) The faster recovery from the infection in type 1 than in type 2 diabetics can be explained by more precautions in terms of dietary habits, more physical activity, younger age, and the presence of fewer comorbidities (Zhou et al. 2020;Vujčić et al., 2021;Vosko et al., 2023).
The sleep deprivation and presence of nightmares that our respondents suffered from (Graph 4 (a, b) can be explained by the blood glucose fluctuations frequent in diabetics, SARS-CoV-2 infection, and most importantly, by elevated anxiety, stress and depression caused by fear of unknown and especially by lockdowns (Huang et al., 2019;Vujčić et al., 2021;Dai at al., 2021).Moreover, having in mind that even 6.97% of all the respondents had a close family member who died from the consequences of SARS-CoV-2 infection, and as many as 77.78% of these decedents suffered from diabetes and/or cardiovascular disease, the high prevalence of people using anxiolytics and antidepressants observed in this study (Graph 4 (c,d)) is not surprising.
However, the fact that 25% of the surveyed people that are diagnosed with type 1, and even 31% of them diagnosed with type 2 diabetes do not have any dietary plan recommended by a physician or dietitian, is surprising.Having in mind that diabetes cannot be treated only with pharmacotherapy but have to be supplemented with proper diet and life-style changes (IDF, 2021), and the fact that the most of our respondents were diagnosed with diabetes before the outbreak of COVID-19, we can notice that the healthcare system has been fractured even before the pandemic.