During the COVID-19 pandemic, it has been observed that individuals with diabetes have a significantly increased risk of developing a severe form of the illness and a higher mortality rate following infection with SARS-CoV-2 [1]. This is consistent with the long-established connection between diabetes and increased susceptibility and severity of infections, which is attributed to hyperglycaemia. Hyperglycaemia leads to cytokine dysregulation and immune response alteration, resulting in a pro-inflammatory and procoagulant state that promotes immune dysfunction through various pathways ^[2][3][2,3]. Individuals with diabetes also exhibit increased rates of hospitalization and mortality resulting from infections. The risk of infections escalates with worsening glycaemic control, with type 1 diabetes patients being at greater risk ^[4][5][6][4,5,6]. Individuals diagnosed with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) frequently present with comorbid medical conditions, such as hypertension, obesity, and cardiovascular disease, which have been linked to an increased risk of contracting COVID-19 as well as an increased risk of infection-related mortality [7]. As the COVID-19 pandemic is constantly evolving, it has become more apparent that individuals with COVID-19 may experience hyperglycaemia, regardless of whether they have diabetes. This observation could imply a mutually influential relationship between COVID-19 and diabetes. Recent research suggests that a combination of insulin resistance and possible issues with insulin secretion may be responsible for the development of hyperglycaemia in COVID-19 patients who did not previously have diabetes ^[8][9][8,9].

The SARS-CoV-2 virus has the ability to attach itself to receptors called angiotensin-converting enzyme 2 (ACE2), which are present in various crucial metabolic organs and tissues, such as pancreatic 𝛽-cells, adipose tissue, kidneys, and the small intestine. This suggests that SARS-CoV-2 may potentially interfere with the glucometabolic pathways, leading to complications and even contributing to the development of new disease mechanisms [1]. Various mechanisms have been suggested to explain the occurrence of diabetes in conjunction with COVID-19 infection, including direct invasion of 𝛽-cells by the virus, leading to their impaired function, induction of insulin resistance through systemic inflammation, or endocrine alterations inciting this response [10]. It is presently uncertain if the emergence of SARS-CoV-2-induced diabetes is due to established mechanisms of type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2D) or if it constitutes an atypical diabetes form. It is unknown whether COVID-19 patients are still vulnerable to developing new-onset diabetes or diabetes-related complications even after virus clearance and recovery ^[2][3][2,3]. Furthermore, glucocorticoids, which are frequently prescribed for moderate to severe COVID-19 cases, have been known to cause hyperglycaemia and insulin resistance, which could contribute to the incidence of new-onset diabetes [11]. Some studies have found that COVID-19 patients who develop new-onset diabetes tend to have worse outcomes than those with no diabetes or with previous diabetes ^{[11][12][13][14]}[11,12,13,14].

The association between diabetes and COVID-19 is probably bidirectional. Diabetes is known as a serious disease and comorbidity associated with a more severe clinical presentation and worse prognosis in many infectious and other diseases ^{[15][16][17][18][19][20][21][21]}[67,68,69,70,71,72,73,73]. New-onset hyperglycaemia has been increasingly observed in adults with no history of diabetes in association with COVID-19, accompanied with significant morbidity and mortality. Although infection-induced inflammation and cytokine activation leading to insulin resistance may cause stress hyperglycaemia, it is unknown to what extent the direct destruction of islet cells by the virus, resulting in decreased insulin production and release, contributes [9]. Interestingly, COVID-19 infection has been linked to the development of diabetes, evident through sudden onset hyperglycaemia in non-diabetic individuals, diabetic ketoacidosis in pre-existing diabetic patients with COVID-19, and the emergence of diabetes in patients with COVID-19 ^{[13][22][23][24]}[13,74,75,76], shown in Table 1.

Like other viruses, SARS-CoV-2 infections can trigger a stress response that may decrease insulin secretion, activate the release of cortisol and adrenaline, and stimulate excessive gluconeogenesis, leading to temporary hyperglycaemia. These mechanisms do not inevitably result in diabetes ^[32][80]. COVID-19 infection has been associated with a distinctive range of newly developed diabetes variations, including some that appear to be unique to the disease. While most large-scale studies have categorized new-onset diabetes as either type 1 or type 2, recent case reports have suggested that COVID-induced diabetes can take on different forms. Omotosho et al. presented a case study of a woman who developed latent autoimmune diabetes of adulthood (LADA) following a COVID-19 infection ^[33][81]. Positive tests for islet cell and glutamic acid decarboxylase (GAD) antibodies confirmed the patient’s type 1 diabetes diagnosis. Marchand et al. also reported a case of LADA in a patient infected with COVID-19 ^[34][82].

A random effects meta-analysis determined that the overall incidence of new-onset diabetes among COVID-19 patients was 14.4% ^[25][62]. Additionally, a systematic review and meta-analysis of eight cohort studies, which included over forty-seven million individuals, demonstrated that COVID-19 was associated with a 66% increase in the risk of diabetes compared to those who did not contract COVID-19. The risk was not influenced by variables such as age, gender, or study quality ^[35][83]. Patients with newly diagnosed diabetes as a result of COVID-19 have a greater risk of hospitalization and death compared to those who are normoglycaemic or have only temporary hyperglycaemia. These patients with pre-existing or new-onset diabetes associated with COVID-19 also have more severe complications, such as acute respiratory distress syndrome, acute renal failure, shock, and low albumin levels, compared to those with normal or temporarily elevated blood sugar levels [11]. Furthermore, patients with COVID-19 are also more prone to ketoacidosis ^[36][37][38][84,85,86], which could indicate the diabetogenic potential of SARS-CoV-2. The mechanisms mentioned were proposed by Sathish et al. ^[39][87] and some other authors ^[40][41][88,89]. Some studies showed that diabetes is related to prolonged hospitalization of patients with COVID-19 ^[42][90] and with worse disease outcomes ^{[31][43][44][45][46][47][48][49][50]}[27,28,79,91,92,93,94,95,96]. It is also concluded that patients with diabetes mellitus are more prone to developing severe symptoms of COVID-19 ^{[44][47][48][50]}[28,93,94,96]. Moreover, newly diagnosed diabetes during SARS-CoV-2 infection has been linked to an even worse prognosis than pre-existing, probably due to insufficient diabetes regulation ^{[25][46][47][51]}[62,92,93,97].

A previous study that involved more than 180,000 veterans showed that individuals who had recovered from COVID-19 were 40% more likely to develop diabetes than those who had not previously been diagnosed with COVID-19. As mentioned, another study revealed that as much as 14% of individuals who were hospitalized for COVID-19 were subsequently diagnosed with diabetes ^[35][83]. Another meta-analysis that included 4,270,747 SARS-CoV-2 positive patients surviving the disease and 43,203,759 control patients demonstrated a higher risk of diagnosing diabetes in recovered COVID-19 patients than in the control group ^[35][83]. Those data could be in favour of the diabetogenic potential of SARS-CoV-2 or could have a connection with corticosteroid treatment, which can worsen hyperglycaemia, resulting in a negative impact on patients’ physiological processes ^[44][52][28,98]. However, the SARS-CoV-2 pandemic influenced diabetic patients in other ways, such as health availability and support, which were mostly insufficient, at least at the beginning of the pandemic ^{[53][54][55][56]}[99,100,101,102].

Although type 1 diabetes is autoimmune in nature, its onset usually necessitates an environmental trigger, such as an infection ^[57][103]. In the case of SARS-CoV-2, it is suggested that direct infection, coupled with the inflammatory response and interactions with the renin–angiotensin system, can lead to damage to pancreatic cells and the development of new-onset diabetes. Case reports of individuals with recent SARS-CoV-2 infection presenting with new-onset T1DM and DKA suggest that SARS-CoV-2 infection may expedite the development of T1DM or elevate the susceptibility to its metabolic complications ^{[28][29][30][58]}[66,77,78,104]. There is much speculation surrounding the suggestion that exposure to SARS-CoV-2 could have triggered the onset of T1DM, which may have contributed to the rise in DKA. However, there is insufficient evidence to confirm whether this new-onset diabetes represents classic T1DM or a distinct form of diabetes. It remains unclear whether the severe COVID-19-induced hyperglycaemia observed in some individuals would resolve over time, as was observed with SARS-CoV-1-induced diabetes [1]. The precise mechanisms by which SARS-CoV-2 increases the risk of T1DM are still being investigated. However, it is known that the destruction of 𝛽-cells can initiate the spread of epitopes, leading to the activation of CD-8 T cells and the production of a broader spectrum of autoantibodies that target various islet cells, such as insulin, glutamic acid decarboxylase, and protein tyrosine phosphatase. This autoimmune response depletes functional 𝛽-cells, resulting in hyperglycemia and the clinical manifestation of type 1 diabetes ^[59][105].

Studies have indicated that acute COVID-19 more often may exacerbate pre-existing prediabetes or T2DM ^[60][106]. Individuals who are hospitalized for acute COVID-19 infections may have undetected diabetes mellitus. The pandemic-related changes in lifestyle, such as decreased physical activity due to measures like lockdowns, may have played a role in the increased weight gain and glyco-metabolic syndrome observed in people with prediabetes. Such changes may also raise the risk of developing new-onset diabetes in the post-infectious stage ^[31][79]. COVID-19 can elevate stress hormones, such as adrenaline and cortisol, which may trigger the production of glucose, resulting in hyperglycaemia ^[61][107]. Also, direct cytotoxic injury to pancreatic cells caused by SARS-CoV-2 infection may result in reduced insulin production ^[62][108]. COVID-19 may exacerbate pre-existing T2DM or prediabetes. Certain studies suggest that these conditions are transient and may resolve with time, but this hypothesis requires ongoing investigation in the future ^[60][106].

There are speculations about the impact of COVID-19 vaccines on diabetes mellitus development. For now, there are mostly case reports for such events; patients are usually presenting with ketoacidosis ^[63][64][65][109,110,111], hyperglycaemia ^[66][67][68][112,113,114], or hyperosmolar state ^[67][113]. There were some observations that vaccines could precipitate hyperglycaemia and other complications in patients that already have diabetes ^[69][115], but a study conducted on 350,936 cases did not find such a link ^[70][116], as well as a study completed in paediatric patients ^[71][117]. Furthermore, there are reports about more frequent adverse reactions to the vaccines with diabetic patients ^[72][73][118,119], but other researchers did not find such a relation ^[74][58]. There were concerns that, since diabetes mellitus is a procoagulatory state, vaccines could precipitate thromboembolic incidents, but a study investigating coagulation pathways in T1DM and T2DM patients after vaccination did not find significant differences compared to healthy individuals ^[75][59]. Vaccines not only reduce the chance of severe clinical presentation and hospital admission in diabetic patients ^[76][120] but could also have a protective effect and reduce the possibility of developing diabetes mellitus after COVID-19 in healthy individuals ^[62][77][108,121]. Nevertheless, patients with diabetes mellitus have decreased antibody and memory 𝛽-cell response to the vaccine ^[74][78][79][58,122,123], and there are reports that vaccines could be less effective in those individuals ^[80][81][124,125].