Clinical features resembling subcutaneous insulin resistance observed in a patient with type 2 diabetes and severe COVID-19-associated pneumonia: a case report

Abstract

We report the case of a 52-year-old hyperglycemic woman with type 2 diabetes and severe coronavirus disease 2019 (COVID-19)-associated pneumonia, possibly involving the subcutaneous insulin resistance (SIR) syndrome. After admission for pneumonia, her average daily blood glucose (BG) levels remained at 300–400 mg/dL, although the required dosage of subcutaneous insulin markedly increased (~ 150 units/day; ~ 2.63 units/kg/day). Furthermore, the patient had generalized edema along with hypoalbuminemia, developed extensive abdominal purpuras, and had increased plasma D-dimer levels during treatment, suggestive of coagulation abnormalities. Therefore, intravenous infusion of regular insulin was initiated. The BG level subsequently decreased to < 200 mg/dL 2 days after administering 18 units/day of insulin infusion and 118 units/day of subcutaneous insulin, suggesting that subcutaneous insulin alone might have been ineffective in reducing hyperglycemia, which is clinically consistent with the characteristics of an SIR syndrome. Impaired skin microcirculation arising from coagulation abnormalities, subcutaneous edema associated with inflammation-related hypoalbuminemia or vascular hyperpermeability, and/or reduction in subcutaneous blood flow due to COVID-19-induced downregulation of angiotensin-converting enzyme 2 might be associated with the development of pathological conditions that resemble SIR syndrome, leading to impaired subcutaneous insulin absorption. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-021-00500-x.

Insulin Requirements During Severe COVID-19 Were Relatively Low in Japanese Patients With Type 2 Diabetes: Two Case Reports

“…Considering these findings and the fact that our patients' maximal insulin requirements were lower than those of previous cases, despite the absence of apparent differences in BMI, this patient's insulin sensitivity may have been higher before the onset of COVID-19. The only case reported by Satomura et al was from East Asia, like our cases, but required high insulin doses, probably because of an unusual condition resembling insulin subcutaneous resistance syndrome [16]. Second, the administration of tocilizumab, an IL-6 receptor monoclonal antibody, might have affected insulin requirements.…”

Case of type 2 diabetes mellitus with edema resulting in subcutaneous insulin resistance syndrome

“…Paulsen et al 4 advised that clinical symptoms of SIR syndrome should be accompanied by no increase in the plasma-free insulin level and increased insulin degradation activity in subcutaneous tissues after subcutaneous injection. However, most reported cases of SIR syndrome were clinically diagnosed, and plasma-free insulin levels after administering a subcutaneous insulin injection 5 and insulin degradation at the tissue levels could not be determined in the cases 2 . Therefore, the diagnosis of SIR syndrome might not necessarily require changes in plasma-free insulin levels.…”

“…Intravenous insulin and hypodermic insulin normally have similar effects 1 . It is rarely reported that a patient with hypodermic injection of insulin has no response, but intravenous injection has a good response, which is called subcutaneous insulin resistance (SIR) syndrome 2 .…”

HbA1c level may be a risk factor for oxygen therapy requirement in patients with coronavirus disease 2019

“…Considering that increased HbA1c levels might be associated with dysregulated immune cell function 32,33 , fasting plasma glucose and HbA1c levels already increased on admission may reflect the aggravated inflammation of COVID-19 and the vulnerability to the inflammation, possibly leading to an increased risk of severity and mortality in patients with COVID-19. On the other hand, tight glycemic control using intravenous insulin infusion was shown to reduce disease severity and mortality in patients with COVID-19 and hyperglycemia 34,35 . These findings suggest that poor glycemic control on admission might lead to the severity of COVID-19-related pneumonia, and that early recognition and treatment of hyperglycemia may greatly benefit these patients.…”