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Newly diagnosed diabetes in patients with mild to moderate COVID-19

Background and aims We aimed to study newly diagnosed diabetes in patients with mild to moderate COVID-19. Methods This was a retrospective cohort study of COVID-19 patients who were admitted to a tertiary care hospital in India from May to October 2020. Results Of 102 patients, 21 (20.6%) had newly diagnosed diabetes on admission. Of which, four (19.0%) had marked hyperglycemia with no ketosis or ketoacidosis. Conclusion In this study of patients with mild to moderate COVID-19, newly diagnosed diabetes and marked hyperglycemia in those with newly diagnosed diabetes were common.


Introduction
Coronavirus disease 2019 (COVID-19) infection in people with pre-existing diabetes can worsen glycemia, cause acute metabolic complications such as ketosis and ketoacidosis, and lead to worse outcomes [1,2]. Intriguingly, emerging evidence shows that newly diagnosed diabetes is frequently observed in COVID-19 patients and is a risk factor for poor prognosis, particularly in those with severe to critical COVID-19 [3e5]. However, there is a dearth of evidence regarding newly diagnosed diabetes in patients with mild to moderate COVID-19 who constitute about 80% of COVID-19 infections [6]. We aimed to study the proportion of newly diagnosed diabetes in COVID-19 patients with mild to moderate illness. We also aimed to examine the glycemic characteristics and clinical outcomes of patients with newly diagnosed diabetes.

Study design and participants
This was a retrospective cohort study of 102 patients who were admitted with mild to moderate COVID-19 to the designated wards at a tertiary care hospital in Chennai, India. These patients were hospitalized between May and October 2020. COVID-19 was diagnosed based on a positive reverse transcription polymerase chain reaction (RT-PCR) test.

Data collection
Patients' data on demographics, clinical signs and symptoms, laboratory investigations, treatment measures, and clinical outcomes were retrieved from the case report forms. Blood samples were taken within 24 h of admission and before the administration of steroids. Plasma glucose and HbA1c were measured using standard assays and protocols [7].

Definitions
Newly diagnosed diabetes was defined as fasting plasma glucose 126 mg/dl or 2-hr post prandial blood glucose 200 mg/dl or HbA1c 6.5% in those without a prior history of diabetes [7]. Marked hyperglycemia was defined as random blood glucose (RBG) > 140 mg/dl [7].

Results
Of 102 patients, 21 (20.6%) had newly diagnosed diabetes on admission. Among these 21 patients, the HbA1c of 19 (90.4%) was 6.5% (range: 6.5%e8.5%), while the remaining two did not have an HbA1c value. The mean age of those with newly diagnosed diabetes was 50.2 (SD: 13.1) years, and the majority (76.2%) were male. The most common symptoms of these patients were fever, cough, and myalgia or fatigue. Sp02 was more than 90% at all times during hospitalization.
Of 21 patients with newly diagnosed diabetes, 4 (19.1%) had marked hyperglycemia with RBG values ranging from 148 to 321 mg/dl ( Table 1). All these four patients were tested negative for urinary ketones. None of them showed signs and symptoms of ketoacidosis during hospitalization, and all were discharged alive. Patients were treated with dexamethasone, low molecular weight heparin, and non-invasive supplemental oxygen. No anti-virals, oral anti-hyperglycemic medications, or insulin therapy were given. At the time of discharge, patients were given lifestyle change advice and were asked to follow-up with their routine healthcare providers for a repeat blood glucose test and further management.

Discussion
In this study of 102 mild to moderate cases of COVID-19, 20.6% were newly diagnosed with diabetes on admission. Nearly all of those with newly diagnosed diabetes had an HbA1c value of 6.5%. This suggests that they likely had previously undiagnosed diabetes. About 19.1% of those with newly diagnosed diabetes had presented with marked hyperglycemia with no acute metabolic complications.
Studies have reported a widely varying proportion of newly diagnosed diabetes (from 0.6% to 46.2%) in COVID-19 patients, the majority of whom had severe or critical illness [5]. COVID-19 infection in people with diabetes (including newly diagnosed diabetes) can cause marked hyperglycemia through several complex but inter-related factors. These include, but are not limited to, the inflammatory response triggered by the virus and subsequent release of counterregulatory hormones, activation of the reninangiotensinogen system, and destruction of pancreatic b cells by the virus itself or by the cytokines triggered by the virus [8,9].
In the literature, there are a few case reports and case series of marked hyperglycemia in patients with mild to moderate COVID-19 who were newly diagnosed with diabetes ( Table 1). The RBG values of these cases ranged between 353 and 940 mg/dl, which were much higher than those of our patients with newly diagnosed diabetes. Further, they had developed ketosis or ketoacidosis, whereas none of our patients had any of these complications. Of note, the HbA1c of these cases was very high (12.0%e15.1%). This indicates that they had poor glycemic control before admission and their underlying chronic inflammatory state was severe, such that even a mild COVID-19 infection was enough to precipitate acute metabolic complications.
Studies have shown that newly diagnosed diabetes is a risk factor for poor prognosis in COVID-19 patients, mainly in those with severe to critical illness [4,10]. However, none of our patients with newly diagnosed diabetes progressed to severe illness or died, probably because of the mild infection. Nevertheless, COVID-19 patients with newly diagnosed diabetes, particularly those with marked hyperglycemia, should be followed-up for the emergence of full-blown diabetes and other cardiometabolic disorders [5,11].
In conclusion, in this study of patients with mild to moderate COVID-19, newly diagnosed diabetes and marked hyperglycemia in those with newly diagnosed diabetes were common.

Ethics approval
The study was approved by the ethics committee of Sree Balaji Medical College and Hospital, Chennai, Tamil Nadu, India. The requirement for written informed consent from the patients was waived by the ethics committee, given the retrospective nature of the study.

Declaration of competing interest
Nothing to declare.