Outcomes Related to Obesity, Ketosis, and Diabetes Management in the COVID-19 Era

April 22, 2020

COVID-19 infection may cause ketosis and ketoacidosis

This study examined a cohort of patients who died or were discharged from January 1, 2020–March 3, 2020.

‍Obvious omissions:

The hospital(s) from which these data came are not listed in the paper.
658 patients were included in the study. Ketosis was defined as having +urine or serum ketones. No serum or urine ketone data were presented.

Overall mortality in this cohort was 9.7%. The median age was 57.5, 45.1% were male and 6.4% of patients presented with ketosis. The patients presenting with ketosis were younger (47 years), and had higher rates of pre-existing diabetes (diabetes (35.7% vs 18.5%, P=0.007). Fifteen of the 42 total patients who had ketosis also had diabetes.

Question: Were any of these patients with diabetes taking a SGLT-2 inhibitor?
Of those 15 patients with diabetes and ketosis, three developed DKA. Error: the number of males in the ketosis group in paper and in the table do not match.
Death rate was higher in the group that developed ketosis 21.4% versus 8.9% and all patients in the ketosis group who died had a history of cardiovascular disease or cerebrovascular disease. Increased mortality with viral infections such as SARS has been previously reported in people with diabetes, often as much as 3-fold.

The discussion of this paper states that COVID-19 caused ketosis and ketoacidosis in patients with diabetes. The following 4 points raise serious questions about this assertion of causality and the overall validity of the authors conclusions:

This is a difficult to understand conclusion when no data regarding SGLT-2 inhibitor use was presented for any of the patients. SGLT-2 medications are well known to induce a mild ketosis, and this is promptly and prominently reflected in urinary ketone excretion.
An early sign of COVID-19 infection is loss of taste and small, frequently followed by GI symptoms. These are likely to cause decreased caloric intake, which can induce starvation ketosis. The more symptomatic the COVID-19 presentation, the more likely the starvation metabolic response, and the more likely a negative clinical outcome that is not causally related to the presence of ketones. Sadly, it is a classic error to conflate association with causality.
The conclusions include a recommendation that people with ketosis who do not have a history of diabetes need to watch their diet and exercise as they are at higher risk of developing diabetes. This is an assertion based neither on evidence nor common sense.

Overall, this paper has several errors, missing data and misconceptions regarding ketosis

Obesity and SARS-CoV-2: a population to safeguard

Peer reviewed and published in Diabetes Metabolism Research and Reviews. Commentary and Hypothesis as to why obesity may lead to poor outcomes after COVID-19 infection.

Summary of COVID/Obesity publications at time of paper.

A study from China found that non-survivors 88.24% were overweight while only 18.95% of the survivors were overweight
A NHS study out of the UK found that 38% of patients who were admitted to the ICU with COVID were obese (higher than the population overall which has a 30% obesity rate). Additionally, 57.6% of patients with obesity died in the ICU compared to only 45% of non-obese ICU admissions.
A French study found that 76% of ICU admissions were obese.
A United States study found that, among patients with pulmonary complications from COVID-19 infection and aged <60 years, those with a BMI between 30 and 35 and those with one over 35 were 1.8 and 3.6 times more likely to be admitted to critical care, respectively, compared to individuals with a BMI <30

Possible links with obesity and worsening COVID

Low-grade systemic inflammation is associated with obesity
Obesity is known to cause complement system overactivation.
Visceral adipose tissue is capable of secreting Interleukin 6 (IL-6), whose levels were found to be retrospectively increased in SARS-CoV-2 non-survivors.
ACE2 which has been proposed as part of the mechanism for viral entry, is found on adipocytes.
Obesity is associated with many comorbidities including diabetes.

Obesity is associated with severe forms of COVID-19

Letter to the Editor of Obesity.

This letter was written in response to a previously published study in Obesity which found a very high rate of obesity in COVID patients who required mechanical ventilation. The authors raise the question of generalizability of the study as 1. There is no standard as to when mechanical ventilation should be applied in worsening COVID, and 2. The rate of obesity in the surrounding community may be a significant factor. They report on outcomes from Lyon University Hospital, France, from 291 consecutive patients admitted to ICU for SARS-CoV-2 between February 27th and April 8th 2020. In the Lyon community the rate of obesity was much lower (11.3 %) compared to the community of the previous study (28.2%) and the requirement for mechanical ventilation was lower 58.4% versus 68.6%. They hypothesize the difference may be due to differing obesity rates or an increased use of high-flow oxygen delivery by opti-flow. **the rate of non-mechanical ventilation interventions for either site were not reported. Despite differing numbers, both studies did find that obesity was a risk for mechanical ventilation use.

Diabetes self-management amid COVID-19 pandemic

Peer reviewed and published in Diabetes & Metabolic Syndrome: Clinical Research & Reviews. Narrative review.

Concern is raised that chronic diabetes care is imperative during the current pandemic as diabetes is a significant risk factor for poor outcomes with COVID-19 and that improved glycemic control would help boost the innate immune system.

A study from China found worsening glycemic control in elderly patients with diabetes during the pandemic. This was postulated to occur due to change in nutrition due to access, decreased physical activity due to lockdowns and social distancing, decreased access to medication and testing supplies, increased stress and decreased access to diabetes care providers.

Recommendations for improved glycemic control are given. These recommendations are made for the population in India. Barriers to the implementation of recommendations are also made.