1) Diabetes is identified as a risk factor for worse outcomes from COVID-19 based on studies from China. Mortality was 10% in COVID-19 patients with diabetes versus 2.5% for non-diabetic patients. 2) People with diabetes have an increased risk of severe COVID-19 infection due to defects in innate immunity from hyperglycemia and an increased inflammatory response. 3) The interaction between the SARS-CoV-2 virus and the renin-angiotensin-aldosterone system, which regulates blood pressure and fluid balance, may help explain the link between diabetes, hypertension, and increased COVID-19 severity. The virus relies on binding to ACE2 receptors to infect

1. COVID-19 and &
Diabetes Mellitus
Dr Shahjada Selim
Associate Professor
Department of Endocrinology
Bangabandhu Sheikh Mujib Medical University, Dhaka
Email: selimshahjada@gmail.com, info@shahjadaselim.com

2. The novel coronavirus
MERS, Middle East Respiratory Syndrome
Andersen KG et al. Nat Med 2020. https://doi.org/10.1038/s41591-020-0820-9
COVID-19 coronavirus particles, coloured transmission electron micrograph (tEM)
● First identified in Wuhan, China, in Dec 2019
● It is an enveloped RNA (ribonucleic acid) virus
● Also called severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2)
● SARS-CoV-2 is the seventh coronavirus known
to infect humans
● SARS-CoV, MERS-CoV and SARS-CoV-2 can
cause severe disease, whereas HKU1, NL63,
OC43 and 229E are associated with mild
symptoms
● SARS-CoV-2 causes the disease COVID-
19 CoronaVIrus Disease – 2019 (COVID-
19)

3. Presenting symptoms of COVID-19
Xie et al. Int J Infect Dis. https://doi.org/10.1016/j.ijid.2020.03.071
Studies Huang et al. Chen et al. Wang et al. Guan et al.
Symptoms
Fever (%) 98 83 98.6 87.9
Cough (%) 76 82 59.4 67.7
Myalgia (%) 44 11 34.8 14.8
Fatigue (%) NA 69.6 38.1
Shortness of breath (%) 55 31 31.2 31-55
Headache(%) 8 8 6.5 13.6
Diarrhea (%) 3 2 10.1 3.7
Loss of smell and taste are more recently identified symptoms
Presenting symptoms of COVID-19

4. Key time-to-event distributions
Li et al. N Engl J Med 2020;382:1199-207.
0.25
0.20
0.15
0.10
0.05
0.00
0 14 217
RelativeFrequency
Days from Infection to Symptom Onset
0.20
0.15
0.10
0.05
0.00
0 14 217
RelativeFrequency
Serial Interval (days)
0.25
0.20
0.15
0.10
0.05
0.00
0 6 123
RelativeFrequency
Days from Illness Onset to First Medical Visit
9
Onset before January 1
Onset during January 1-11
A B
C D
0.15
0.10
0.05
0.00
0 2010
RelativeFrequency
Days from Illness Onset to Hospitalization
30
Onset before January 1
Onset during January 1-11
Key time-to-event distributions

5. Epidemiology characteristics of COVID-19 compared to SARS and
MERS
*the data were accepted for publication on 15 April 2020
Xie et al. Int J Infect Dis. https://doi.org/10.1016/j.ijid.2020.03.071
COVID-19 SARS MERS
Original location Wuhan, China Guangdong, China Jeddah, Saudi Arabia
Total cases (global)
1,980,003+*
8096 2229
Total death (global) 126,557+* 774 791
Healthcare worker cases (%) 3.8 21 18.6
Reproductive number 3.28 3.0 <1.0
Incubation period (days) 4.75-6.4 4.0 4.5-5.2
Serial interval (days) 2.6-7.5 8.4 12.6
Case-fatality rate (%) 3.0 9.6 35.5
CFR with comorbidities (%) 73.3 46.0 60.0
Epidemiology characteristics of COVID-19 compared to SARS and
MERS

6. Source: https://coronavirus.jhu.edu/map.html

7. Bangladesh is also declared the
COVID 19 infection reported from
Directorate General of Health
Service on daily basis with 1,012
confirmed cases and 46
deaths having community
transmission (dated till April 14,
2020) for total tests 13,128.
Bangladesh Scenario
Source: IEDCR
Mortality among
Physicians: 02 (15.042020)

8. Estimates of case fatality ratio shows strong age gradient in risk of
death
Verity et al. Lancet Infect Dis 2020. https://doi.org/10.1016/S1473-3099(20)30243-7
Rest of China Wuhan
≥80
70−79
60−69
50−59
40−49
30−39
20−29
10−19
0−9
0.3 0.2 0.1 0 0.1 0.2 0.3
Age,years
Proportion of cases
0.20
0.15
0.10
0.05
0.00
0−9 10−19 20−29 30−39 40−49 50−59 60−69 70−79 ≥80
Age (years)Casefatalityratio
Estimates of case fatality ratio shows strong age gradient in risk of
death

9. Bangladesh Data (Updated -11.04.2020)
Source: IEDCR

10. Prevalence of comorbidities in COVID 19 infection
Yang J et al. Int J Infect Dis. S1201-9712(20)30136-3. doi: 10.1016/j.ijid.2020.03.017. [Epub ahead of print]
Meta analysis of 8 studies with 46,248 COVID-19 patients showed the most
prevalent comorbidity:
Hypertension
17±7
(95% CI 14-22%)
Diabetes
8±6
(95% CI 6-11%)
Cardiovascular
diseases
5±4
(95% CI 4-7%)
Respiratory
system diseases
2±0
(95% CI 1-3%)
Prevalence of comorbidities in COVID 19 infection

11. Underlying diseases in COVID-19 inpatients
Xie et al. Int J Infect Dis. https://doi.org/10.1016/j.ijid.2020.03.071
Studies Huang et al. Chen et al. Wang et al. Guan et al.
Mean Age (yrs) 49 55.5 56 47
Sex ratio (male: female) 73:27 68:32 54.3:45.7 58.1:41.9
Exposure history (%) 66 49 8.7 71.8
Underlying diseases (%) 32 50 NA 23.2
Diabetes (%) 20 13 10.1 7.4
Hypertension (%) 15 NA 31.2 14.9
Cardio-cerebrovascular diseases (%) 15 40 19.6 3.9
Malignancy (%) NA 1 7.2 0.9
Underlying diseases in COVID-19 inpatients

12. Comparison of the time-dependent risk of reaching to the composite endpoints. a) The time-
dependent risk of reaching to the composite endpoints between patients with (orange curve) or
without any comorbidity (dark blue curve). b) The time-dependent risk of ...
Wei-jie Guan et al. Eur Respir J doi:10.1183/13993003.00547-2020
©2020 by European Respiratory Society

13. Disease severity, treatment, and prognosis of
COVID-19 patients
DM, diabetes mellitus; ECMO, extracorporeal membrane oxygenation.
Zhang Y et al. https://www.medrxiv.org/content/10.1101/2020.03.24.20042358v1
Total DM Non-DM p
Variable (N=258) (n=63) (n=195)
Severity, n (%)
Mild to moderate 87 (33.7) 18 (28.6) 69 (35.4) 0.028
Severe 116 (45.0) 24 (38.1) 92 (47.2)
Critical 55 (21.3) 21 (33.3) 34 (17.4)
Complications, n (%)
Acute respiratory distress 62 (24.0) 24 (38.1) 38 (19.5) 0.001
Acute cardiac injury 19 (7.4) 9 (14.5) 10 (5.1) 0.016
Acute kidney injury 7 (2.7) 3 (4.8) 4 (2.1) 0.250
Total DM Non-DM p
Variable (N=258) (n=63) (n=195)
Oxygen support, n (%)
Nasal cannula 148 (57.4) 30 (47.6) 118 (60.5) 0.037
High-flow oxygen 24 (12.4) 8 (12.7) 24 (12.3)
Non-invasive ventilation 26 (10.1) 10 (15.9) 16 (8.2)
Invasive mechanical ventilation 16 (6.2) 7 (11.1) 9 (4.6)
ECMO 1 (0.4) 1 (1.6) 0 (0)
Prognosis, n (%)
Discharged 87 (33.7) 16 (35.7) 71 (36.4) 0.039
Not discharged yet 156 (60.5) 40 (63.5) 116 (59.5)
Death 15 (5.8) 7 (11.1) 8 (4.1)
Disease severity, treatment, and prognosis of
COVID-19 patients

14. Associations of diabetes and FBG with fatality of COVID-19
FBG, fasting blood glucose
Zhang Y et al. https://www.medrxiv.org/content/10.1101/2020.03.24.20042358v1
Model Ia Model IIb Model IIIc
Variable AHR
(95% CI)
P AHR
(95% CI)
P AHR
(95% CI)
P
DM 2.80
(1.01,7.80)
0.048 2.840
(1.01, 8.01)
0.048 3.64
(1.09, 12.21)
0.036
FBG
(mmol/L)
1.14
(1.06,1.22)
<0.001 1.142
(1.07, 1.23)
<0.001 1.19
(1.08, 1.31)
<0.001
AHR, adjusted hazard ratio; CI: confidence interval. DM: diabetes mellitus; FBG: fasting blood glucose.
a Adjusted for age.
b Additionally adjusted for preexisting cardiovascular disease and chronic kidney disease.
c Additionally adjusted for inflammatory biomarkers (leucocytes, neutrophils, lymphocyte, eosinophil, NLR, neutrophil-to-lymphocyte ratio; C-reactive protein,
procalcitonin).
Associations of diabetes and FBG with fatality of COVID-19

15. Diabetes is a risk factor for mortality of COVID-19
1. Zhang BC, et al. medRxiv preprint , 2020 online
2. Guan WJ，et al. medRxiv preprint , 2020 online
3.China CDC Weekly，2020, 2(8): 113-122
4.《Report of the WHO-China Joint Mission on Coronavirus Disease 2019 (COVID-19)，2020
 A large national sample study in China showed that the mortality of patients with diabetes was significantly
higher than that of non-diabetic patients（10% vs 2.5% P<0.0012) (Figure 1）
 Chinese CDC declared that patients who reported no comorbid conditions had a case fatality rate（CFR**)
of 0.9%, while patients with comorbid conditions had much higher rates--7.3% for diabetes.3（Figure 2）
3.1%
10.0%
2.5%
0%
4%
8%
12%
All patients Diabetic Non- diabetic
P<0.001
Figure 1：The mortality of 1590
COVID-19 patients
N=1590 N=130 N=1460
Casefatalityrate（%）
2.3%
7.3%
0.9%
0%
2%
4%
6%
8%
All patients Diabetic No comorbid
conditions*
Figure 2：The mortality of COVID-19
patients reported by China CDC
N=20,982 N=1,102 N=15,536
Casefatalityrate（%）
* The comorbid condition variable, only includes a total of 20,812 patients and 504 deaths and these values were used to calculate percentages in the confirmed cases and
deaths columns.
**The Joint Mission acknowledges the known challenges and biases of reporting crude CFR early in an epidemic.

16. People with DM have an increased risk of infection because of
innate immunity defects
• Linked to hyperglycaemia
• Both acute and chronic effects
Increased risk of severe infection because of increased cytokines
Why the association?
Ma and Holt Diabet Med 2020. DOI: 10.1111/dme.14300
Why the association?

17. • Glucose and Glutamide are preferred by SARS-CoV-2
• COVID-19 infection will heighten the state of insulin
resistance in DM
• IL-6 produced as the result of COVID-19 infection
increases the chances fatal consequences the infection
in DM
Why the association?
Ma and Holt Diabet Med 2020. DOI: 10.1111/dme.14300
Why the association?

18. Why the association?
ACE, angiotensin-converting enzyme, ARB angiotensin-receptor blocker
Vaduganathan et al. N Eng J Med. DOI: 10.1056/NEJMsr2005760
Interaction between
SARS-CoV-2 and the
Renin–Angiotensin–Aldosterone
System
ACE2 links diabetes mellitus,
hypertension and cardiovascular
disease to COVID-19
SARS-CoV-2
Spike protein
Binding to ACE2
ACE2
Angiotensin
(1-9)
Angiotensin
(1-7)
Angiotensin
I
Angiotensin
II
ACE
inhibitors
ARBs
Local or systemic
infection or sepsis
ACE
Angiotensin II
Type 1 receptor
Viral entry, replication,
and ACE2
down-regulation
Acute lung injury
Adverse myocardial
remodeling
Vasoconstriction
Vascular permeability
ACE2
Why the association?

19. There may be interruption or non-
standard treatment with OAD in
isolation wards, resulting in
glucose fluctuationIrregular diet, reduced
exercise, gastrointestinal
symptoms, etc., affect diet,
resulting in glucose
fluctuation
Stress conditions like
infection increase
glucocorticoids secretion
The use of glucocorticoids
in treatment can lead to a
sharp rise in glucose
COVID-19 can cause human body
to produce a large number of
inflammatory cytokines and lead
to extreme stress in some severe
and critical patients
Fear, anxiety and tension
may increase glucose level
and induce glucose
fluctuation
Reasons for glucose fluctuation in patients with diabetes and COVID-19
Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219

20. Different challenges for diabetes management during
the COVID-19 pandemic
Panic
Home
quarantine
Shortage of
medical resources

21. Clinical scenarios of diabetes management during the COVID-19 pandemic
Stressful,
anxious,
depressed
Increased consumption
of alcohol
Insomnia/hypersomnia
/change in diurnal
rhythms
Change in regimen
(withdraw or change
medications )
No exercise/
over-exercise
Change in
compliance to
medications (dosing
time and frequency)
Miss routine
visit
Eat too much/
miss meals
Delayed visit
to emergency
care
Change in diet
composition

22. Recommendations on diabetes management during the COVID-19 pandemic
by International Diabetes Federation — diabetes combined with COVID-19
https://www.idf.org/our-network/regions-members/europe/europe-news/196:information-on-corona-virus-disease-2019-covid-19-outbreak-and-guidance-for-people-with-diabetes.html
There hasn’t been enough evidence of evidence-
based medicine on COVID-19 management in
diabetes. Referring to Standards of Care of Type 2
diabetes, IDF refers to follow the recommendations
for the SICK DAY RULES for the patients with
diabetes and COVID-19, for better medical care and
improved prognosis.

23. Target stratification of glucose management
Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
Target stratification of glucose management：
 For mild and moderate non-elderly COVID-19 patients, stick to strict/ tight control target
 For mild and moderate elderly patients, or patients who have been using glucocorticoid, set up a low or
medium control target
 For severe and critical patients, elderly patients, hypoglycemia intolerable patients, or patients who have organ
dysfunction or serious cardiovascular and cerebrovascular diseases, set up a low control target
Target stratification of glucose management in hospitalized patients
Hypoglycemia occurrence should be minimized during glucose management in diabetes
patients with COVID-19. Medical care should be performed in time if hypoglycemia
occurs.
High Medium Low
FPG/PPG (mmol/L) 4.4-6.1 6.1-7.8 7.8-10.0
2h PPG/GLU (mmol/L) 6.1-7.8 7.8-10.0 7.8-13.9

24. Therapeutic principle of glucose management
Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
Insulin treatment is the first choice if diabetes is combined with severe infection：
 For non-critical patients, insulin s.c. injection is recommended, and basic dosage can refer to the out-of-
hospital dosage
 For critical patients, CSII is recommended
 IV insulin treatment should be started in combination with aggressive fluid infusion if serious glucose
metabolism disorder with water and electrolyte and acid-base disorders is seen
If clinical condition is stable and eating pattern is regular, patients can continue OAD
treatment as before admission
Using NPH and long-acting insulin during glucocorticoid treatment to control glucose
Measure 7 point glucose (if necessary, plus nocturnal glucose) during insulin treatment
Metformin Not recommended in severe/critical patients; with gastrointestinal symptoms or lack of oxygen
Secretagogue
Mild/moderate patients using glucocorticoid: for early stage chose short-acting agents; for advanced stage chose
middle/long-acting agents if FPG and/or PPG is increased
α-glucosidase inhibitor Can be used to control PPG. Not recommended in severe/critical patients; with gastrointestinal symptoms
TZD
Can be used during the process of glucocorticoid treatment; regimen should be adjusted according to treatment
effect
DPP-4i Not recommended/ Recommended
SGLT-2i Not recommended for COVID-19 patients have stress reaction at different levels

25. Glucose management strategies for different types of
diabetes patients with COVID-19
Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
 Insulin pump or basal +
bolus insulin treatment is
the optimal regime
 Recommend insulin
analogues as first choice
 Insulin treatment should
be individualized
T1DM
 For mild COVID-19 patients
with low-moderate glucose
increase, non-insulin diabetes
drugs can be used
 For patients with fever or
treated by glucocorticoids,
insulin treatment is the first
choice
 For critical patients, IV insulin
is recommended
T2DM
 It is important to monitor
blood glucose after lunch
and before dinner as
glucocorticoid-induced
increased glucose often
occurs between after lunch
and before sleep.
 Insulin is the first choice
Glucocorticoid-
associated diabetes

26. Glucose management strategies for different clinical
classification
Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
 Both OAD and insulin treatment can be maintained and it is not necessary to
adjust original regimen
 Progress of COVID-19 can be rapid and worsen with hyperglycemia. It is
recommended in diabetes patients with COVID-19, even mild, to increase glucose
measurement frequency, and consult with physicians to adjust regimen in time if
glucose target cannot be achieved
Mild
 Maintain original regimen if patient’s mental condition, appetite and glucose
control are within normal range
 Switch OAD to insulin for patients with obvious COVID-19 symptoms who can’t
eat regularly
 Suggest switching premix insulin regime to basal-bolus regime or insulin pump to
flexibly manage glucose
Moderate
 IV Insulin should be the first-line treatment.
 For patients who are in process of continuous renal replacement therapy (CRRT),
the proportion of glucose and insulin in the replacement solution should be
increased or decreased according to glucose monitoring result to avoid
hypoglycemia and severe glucose fluctuation.
Severe and
critical

27. BES Position Statement for COVID-19 Pandemic
What endocrinologists can do:
o We should guide our patients to better control their diabetes and
complications through direct consultation, email, message, videocall or social
media.
o If our clinical Judgement (for patients having fever, cough and shortness of
breath) points toward suspected case, refer them to nearby designated
hospitals.
o We should remind our patients about sick day management rules (keep
hydrated, maintain nutrition including CHO and salty food, monitor blood
glucose and monitor temperature)
o If DM is well controlled, we can minimize the disaster.

28. BES Position Statement for COVID-19 Pandemic
What patients should do:
• Continue to take your prescribed medications.
• Monitor your blood glucose regularly and adjust dose of medication.
• Keep reserve of medications and glucose testing kit and strips
supplies for 1-3 months.
• Perform home-based exercise like treadmill, stationary cycling bike,
free hand exercise or aerobics, walking in room if it is big, roof and in
parking area or stair up-down.
• Maintain healthy diet. Take plenty of vegetables and citrous foods. If
needed take multivitamins and multiminerals (Fe, Cu, Zn, Selenium, Vit
A).

29. BES Position Statement for COVID-19 Pandemic
What patients should do:
• Wash fruits and vegetables before eating.
• Take more water or sugar-free drinks in hot weather.
• When you do go out in public, avoid crowds & limit close
contact (<2M).
• Avoid non-essential travel.
• Stay home if ill.

30. BES Position Statement for COVID-19 Pandemic
What patients should do:
• Wash your hands with soap and water regularly, for at least
20 seconds, especially before eating or drinking and after
using bathroom and blowing your nose, coughing or sneezing
and after being in public.
• If soap and water are not readily available, use an alcohol-
based sanitizer with at least 60% alcohol.
• Cover your nose and mouth when coughing or sneezing with
a tissue or a flexed elbow, then throw the tissue in the bin.

31. Together, we unite for diabetes and
to win the war!