Glucose on Admission: Unfavourable Effects on Hospitalisation and Outcomes in Type 2 Diabetes Mellitus Patients with COVID-19 Pneumonia

Dear Editor,

Coronavirus Disease 2019 (COVID-19) pneumonia may be aggravated by comorbidities, notably hypertension, diabetes and heart disease [1]. In our earlier study, diabetes mellitus and hypertension emerged as the major risk factors of mortality in COVID-19 pneumonia [1].

Medical records of 133 type 2 diabetes mellitus (T2DM) patients hospitalised with COVID-19 pneumonia, confirmed with real-time polymerase chain reaction (RT-PCR) of nasopharyngeal specimens, were retrospectively analysed. We recorded glucose upon admission, treatment with metformin and dipeptidyl-peptidase-4 inhibitor (DDP-4is) (yes vs. no), age, gender, days of hospitalisation, respiratory failure, and clinical outcome (intubation, death). The study was approved by the institutional ethics committee and patients gave their informed consent.

The majority of patients were men (51.1%). The mean age was 69.18±10.10 years. Respiratory failure was present in 80.5%, intubation was needed in 17.3% and 18% died. Mean blood glucose upon admission was 209.61±77.78 mg/dl. In 53.4% of patients, glucose>180 mg/dl was observed. Overall, 81 patients (60.9%) were on metformin and 52 patients (39.1%) on DDP4-is.

Hospitalisation was significantly (p=0.004) prolonged in patients with glucose>180 mg/dl than those with lower levels (13 vs. 11 days, respectively. It was a significant risk factor (p<0.001) for severe clinical outcomes (intubation, death). Mean blood glucose was 196.39±72.73 mg/dl for moderate-severe COVID-19 pneumonia vs. 272.83±70.98 mg/dl for intubated patients (p<0.001). Metformin or DDP-4is had no effect on hospitalisation and clinical outcomes ([Table 1]).

Table 1 Duration of hospitalisation and clinical outcomes in association with glucose upon admission and treatment with metformin or dipeptidyl-peptidase-4 inhibitor (DDP-4is).

	GLUCOSE			Age- and gender-adjusted OR (95% CI)
	≤180 mg/dl	>180 mg/dl	P value
Number of patients	62	71
Hospitalisation (days)	11 (8–13)	13 (11–16)	0.004	–
Intubation (n, %)	3 (4.8)	20 (28.2)	<0.001	8.90 (2.43–32.61)
Death (n, 5%)	3 (4.8)	21 (29.6)	<0.001	9.11 (2.51–33.03)
	TREATMENT WITH METFORMIN
	No	Yes
Number of patients	52	81
Hospitalisation (days)	11.5 (9–17)	12 (9–14)	0.561	–
Intubation (n, %)	7 (13.5)	16 (19.8)	0.349	1.61 (0.61–4.26)
Death (n, %)	7 (13.5)	17 (21.0)	0.271	1.78 (0.68–4.70)
	TREATMENT WITH DDP4-is
	No	Yes
Number of patients	81	52
Hospitalisation (days)	12 (9–14)	11.5 (9–17)	0.561	–
Intubation (n, %)	16 (19.8)	7 (13.5)	0.349	0.62 (0.24–1.65)
Death (n, %)	17 (21.0)	7 (13.5)	0.271	0.56 (0.21–1.48)

Hospitalisation was expressed as median value and interquartile range and compared using the Mann-Whitney U test. Categorical variables were expressed as numbers and percentages (%) and compared using the chi-square test. Αdjusted odds ratios (OR) with their 95% confidence intervals (95% CI) were obtained using logistic regression models adjusted for age and gender.

In our series, glucose on admission was associated with longer hospitalisation and severe clinical outcomes. In one cohort study of more than 7000 COVID-19 patients, excess blood glucose levels were correlated with worse prognosis and higher mortality rates [2]. Several studies have found the association between elevated blood glucose and elevated inflammatory parameters including IL-6, IL-8 and CRP and increased risk of an uncontrolled inflammatory response [2] [3]. Increased glucose levels have been suggested to directly promote viral replication and cytokine expression [2].

There is evidence of reduced mortality due to COVID-19 pneumonia among subjects receiving metformin [4]. This may be attributable to anti-inflammatory and immunomodulatory beneficial effects [4] [5]. Such beneficial role of DDP-4 is has also been discussed [6]. By contrast, we found no favourable effect of these agents. Certainly, more research is needed.

In conclusion, blood glucose>180 mg/dl upon admission was associated with longer hospitalisation and worse clinical outcomes among T2DM patients with COVID-19 pneumonia. Metformin or DPP-4is had no beneficial effect. These results underline the importance of hyperglycaemia in T2DM on outcomes of COVID-19 pneumonia prolonging hospitalisation and increasing the risk of intubation and death.

Publication History

Received: 19 August 2021
Received: 10 October 2021

Accepted: 26 October 2021

Article published online:
29 November 2021

• References

• 1 Petrakis V, Panagopoulos P, Papazoglou D. et al. Diabetes mellitus and hypertension as major risk factors of mortality from covid-19 pneumonia. Exp Clin Endocrinol Diabetes. 2020 [Online ahead of print]
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• 3 Huang Y, Guo H, Zhou Y. et al. The associations between fasting plasma glucose levels and mortality of COVID-19 in patients without diabetes. Diabetes Res Clin Pract 2020; 169: 108448
• 4 Kow CS, Hasan SS. Mortality risk with preadmission metformin use in patients with COVID-19 and diabetes: A meta-analysis. J Med Virol 2021; 93: 695-697
• 5 Cameron AR, Morrison VL, Levin D. et al. Anti-inflammatory effects of metformin irrespective of diabetes status. Circ Res 2016; 119: 652-665
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