DIABETES MANAGEMENT OF PATIENTS WITH COVID-19 INFECTION - RSUD Dr. Soetomo
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DIABETES MANAGEMENT OF
PATIENTS WITH COVID-19
INFECTION
Prof DR Dr Agung Pranoto, Mkes, SpPD, K-EMD, FINASIM
Dr Deasy Ardiany, SpPD, K-EMD, FINASIM
Diabetes & Nutrition Center
Division of Endocrinology Metabolism
Department of Internal Medicine
RSUD Dr.Soetomo General Hospital-Medical Faculty of Airlangga University
PowerPoint Presentation Date 2
OUTLINE
About Link between Prevention Summary
COVID-19 COVID-19 and
and Diabetes Treatment
WORLDWIDE COVID-19 OUTBREAK
SITUATION
102,628,183 2,216,279 74,327,556 221
Countries,
Confirmed Confirmed Recovered/ areas or
cases Deaths Discharged territories with
cases
Ref: World Health Organization (update on 30th January, 2021), worldometers.info/coronavirus/coronavirus-cases/
INDONESIA COVID-19 OUTBREAK
SITUATION
1,051,795 29,518 852,260 9,124,005
Confirmed Recovered/ Total COVID-
Confirmed 19 tests
cases deaths Discharged conducted
Ref: World Health Organization (update on 30th January, 2021), worldometers.info/coronavirus/coronavirus-cases/
PREVALENCE OF COMORBIDITIES IN COVID 19
INFECTION
Meta analysis of 8 studies with 46,248 COVID-19 patients showed the most prevalent
comorbidity:
Cardiovascular Respiratory
Hypertension Diabetes diseases system disease
17±7 8±6 5±4 2±0
(95% CI 14-22%) (95% CI 6-11%) (95% CI 4-7%) (95% CI 1-3%)
Yang J et al. Int J Infect Dis. S1201-9712(20)30136-3. doi: 10.1016/j.ijid.2020.03.017.
PowerPoint Presentation Date 6
OUTLINE
About Link between Prevention Summary
COVID-19 COVID-19 and
and Diabetes Treatment
DIABETES AND COVID-19
• People with diabetes are NOT MORE likely to get COVID-19 than the general population
• Diabetes is one of the high risk groups for developing severe illness from COVID-19
• The risk of having worse outcomes is similar for people with T1D and T2D
T1D, type 1 diabetes; T2D, type 2 diabetes
ADA: https://www.diabetes.org/coronavirus-covid-19; CDC: https://www.cdc.gov/coronavirus/2019-ncov/specific-groups/people-at-higher-risk.html
SURVIVAL RATE IN COVID-19 PATIENT WITH DIABETES
• Survival rate of COVID-19 patient with Diabetes
is worse than patient without diabetes
Shi Q,. Diabetes Care. 2020 May 14.
DIABETES MAY ACCENTUATE COVID-19: POTENTIAL MECHANISM
Overactivation of TLR4 signaling in diabetes
may lead to severe disease and death
• High levels of IL-6, TNF-α and other
SARS-CoV
inflammatory cytokines in people with Activate
diabetes1
• Coronavirus likely to activate TLR3 and
Promotes
TLR4, leading to IL-6-dominated cytokine Diabetes
storms2,3
• IL-6 associated with death of COVID-19
patients4
1. Reza F, et al. Cytokine ,2019, 125 (2020) 154832 3. Allison L. T, et al. mBio, 2015 , 3:e00638-15
2. Travis B. ，et al. mBio, 2017 8:e00818-17. 4. Zhou F , et al. The Lancet 2020 March 9 online
Factors leading to high morbidity and mortality of COVID-19
in patients with type 2 diabetes
CVD Dyslipidemia AGE
BP Type 2 Diabetes IR
Obesity Inflammation Glycemia
Hyper immune
response ACE2
SARS
Severity of COVID-19 CoV2
Rajpal A,. Journal of diabetes. 2020 Jul 16.VICIOUS CYCLE BETWEEN DIABETES AND
COVID-19
Viral infections could
Patients with T2DM have induce diabetes, and lead
an increased grade of to fluctuations in blood
severity to SARS-CoV-2 glucose in diabetic patients,
due to immune dysfunction. which adversely influence
prognosis.
Viral infection can cause high blood glucose.
High level of inflammatory cytokines such In a study of SARS, it was found that mild
as IL-6 and TNF-a in diabetic patients and patients who were not treated with
animal models suggested that diabetes glucocorticoids still had high fasting blood
significantly promoted the production of glucose level.
TLR4-induced IL-6. Another study has found that ACE2 protein
IL-6-dominated cytokine storms have been shows a strong immunostaining in islets, but
identified as one of the leading causes of weak in exocrine tissues. It is suggested
death from pneumonia caused by SARS- that SARS-CoV-2 contribute to the
CoV-2. development of diabetes by severely
damaging pancreatic islet.
1. Timely blood glucose management for the outbreak of 2019 novel coronavirus disease (COVID-19) is urgently needed, Wang A, Diabetes Research & Clinical Practice :162(2020)108118
2. COVID-19: consider cytokine storm syndromes and immunosuppression, Mehta P et al. The Lancet, CORRESPONDENCE| VOLUME 395, ISSUE 10229, P1033-1034, MARCH 28, 2020
3. Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219
4. https://www.touchendocrinology.com/insight/covid-19-infection-in-people-with-diabetes/ as accessed on 9th April, 2020COVID-19 MAY ACCENTUATE DIABETES: POTENTIAL MECHANISM
• ACE2 is the functional receptor of SARS-CoV (SARS
SARS mortality was higher in
epidemic) patients with hyperglycemia1
• ACE2 expression in the pancreatic tissue
suggests SARS-CoV may damage pancreatic
islets1
• SARS-CoV-2 (COVID-19 pandemic) is able to
efficiently use human ACE2 as a receptor for cellular
entry2
1. YangJ-K, et al Acta Diabetol. 2010;47(3):193-199
2. WuF, et al. Nature. February 2020.
ACE2 - Angiotensin converting enzyme 2WHY THE ASSOCIATION?
Interaction between Local or systemic infection
or sepsis
SARS-CoV-2 and the SARS-CoV-2
Spike protein
Angiotensin
Binding to ACE2
Renin–Angiotensin–Aldosterone (1-9)
Angiotensin
I
ACE
inhibitors
System
Angiotensin ACE
(1-7)
Angiotensin
II ARBs
ACE2 links diabetes mellitus,
ACE2
hypertension and cardiovascular disease
ACE2
to COVID-19 Angiotensin II
Type 1 receptor
ACE, angiotensin-converting enzyme, ARB angiotensin-receptor blocker
Vaduganathan et al. N Eng J Med. DOI: 10.1056/NEJMsr2005760
Acute lung injury
Adverse myocardial remodeling
Viral entry, replication, Vasoconstriction
and ACE2 Vascular permeability
down-regulationPotential pathogenic mechanisms in patients with T2DM and Covid-19 S. Lim, J.H. Bae. Nat. Rev. Endocrinol. 17 (2021) 11–30,
Potential
accentuated
clinical processes
after SARS-CoV-2
infection in people
with diabetes
mellitus
S. Lim, J.H. Bae. Nat. Rev. Endocrinol. 17 (2021) 11–30,PowerPoint Presentation Date 16 Umpierrez & Pasquel, 2017
Clinical characteristics and outcomes in patients with diabetes mellitus and COVID-19
Well Controlled
Glycemic Good
Prognostic
HbA1c > 7.5% Bad
Prognostic
S. Lim, J.H. Bae. Nat. Rev. Endocrinol. 17 (2021) 11–30,CLINICAL SCENARIOS OF DIABETES MANAGEMENT DURING THE
COVID-19 PANDEMIC
Stressful, anxious, Insomnia/hypersomnia/c No exercise/ Eat too much/ Change in diet
depressed hange in diurnal over-exercise miss meals composition
rhythms
Increased consumption Change in regimen Change in Miss routine Delayed visit to
of alcohol (withdraw or change compliance to visit emergency
medications ) medications (dosing care
time and frequency)
Recommendations for COVID-19 Prevention in Diabetes Patients Endorsed by Chinese Diabetes Society (CDS).
CDS website: www.diab.net.cn CDS WeChat: CDS-TNBDIABETES PROMOTES SEVERE PROGRESSION IN COVID-19
PATIENTS
• The presence of coexisting diabetes was more common among COVID-19 patients with severe disease than among those
with non-severe disease (16.2% vs.5.7%).*1
• Another nationwide analysis of comorbidity and its impact on 1,590 patients with COVID-19 in China also revealed that，
（22.9% vs 6.8%)2
The risk of reaching to the composite endpoints*
COVID-19 patients with comorbidities1 and disease severity among patients with COVID-192
PDIABETES IS A RISK FACTOR FOR MORTALITY OF COVID-19
• A large national sample study showed that the mortality of patients with diabetes was significantly higher than that of non-diabetic
patients（10% vs 2.5% PASSOCIATIONS OF DIABETES AND FBG WITH FATALITY
OF COVID-19
Model Ia Model IIb Model IIIc
Variable AHR P AHR P AHR P
(95% CI) (95% CI) (95% CI)
DM 2.80 (1.01,7.80) 0.048 2.840 0.048 3.64 0.036
(1.01, 8.01) (1.09, 12.21)
FBG (mmol/L) 1.14 (1.06,1.22)PowerPoint Presentation Date 22 Zhu, L., She, Z.G., Cheng, X., Qin, J.J., Zhang, X.J., Cai, J., Lei, F., Wang, H., Xie, J., Wang, W. and Li, H., 2020. Association of blood glucose control and outcomes in patients with COVID-19 and pre-existing type 2 diabetes. Cell metabolism.
PowerPoint Presentation Date 23
OUTLINE
About Link between Prevention Summary
COVID-19 COVID-19 and
and Diabetes TreatmentGUIDANCE FOR PEOPLE WITH DIABETES TO PREPARE FOR COVID-
19
People with diabetes should have ready
Contact information Adequate stock of Enough stock of Glucagon and ketone
of health care medications and simple carbohydrates strips, in case of poor
provider supplies for like regular soda, glycaemic control
monitoring blood honey, jam, etc. to
glucose manage low blood
glucose
ADA, https://www.diabetes.org/coronavirus-covid-19; IDF, 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; Diabetes UK,
https://www.diabetes.org.uk/about_us/news/coronavirus; Public Health UK, https://www.gov.uk/government/publications/covid-19-guidance-on-social-
distancing-and-for-vulnerable-people/guidance-on-social-distancing-for-everyone-in-the-uk-and-protecting-older-people-and-vulnerable-adultsPowerPoint Presentation Date 25 PERKENI RECOMMENDATION https://pbperkeni.or.id/pernyataan-resmi-dan-rekomendasi-penanganan-diabetes-mellitus-di-era-pandemi-covid-19/
PowerPoint Presentation Date 26 PERKENI RECOMMENDATION https://pbperkeni.or.id/pernyataan-resmi-dan-rekomendasi-penanganan-diabetes-mellitus-di-era-pandemi-covid-19/
MANAGEMENT OF PEOPLE WITH DIABETES INFECTED WITH COVID-19
RECOMMENDATIONS
Anti-diabetic Maintain
Monitoring
medication glycaemic control
• Patients should follow the • Blood glucose levels should be frequently • Management of COVID-
advice of the physician checked (generally, every 2-3 hours) 19 infection by patient
(diabetes care team) on and HCPs should follow
adjustments to their anti- sick day rules appropriate
diabetic medication(s) to any other infection
• Patients should be aware
of signs and symptoms of
hyperglycaemia
General:
1) Patients are advised to drink lots of fluids to stay hydrated. To avoid dehydration, patients should have small sips every 15 minutes or so
throughout the day if they are having trouble keeping water down.
2) Hands should be washed, and injection/infusion and finger-stick sites should be cleaned with soap and water or rubbing alcohol.
3) Recommendations of local authority should be followed if suspected of COVID-19 symptoms.
ADA, https://www.diabetes.org/coronavirus-covid-19; Diabetes UK, https://www.diabetes.org.uk/about_us/news/coronavirus; IDF,
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; ISPAD, https://www.ispad.org/news/494473/COVID-19-and-Children-with-Diabetes.htmPowerPoint Presentation Date 28
TIMELY BLOOD GLUCOSE MANAGEMENT FOR THE OUTBREAK OF 2019 NOVEL
CORONAVIRUS DISEASE (COVID-19) IS URGENTLY NEEDED
Blood glucose should For critical cases, early • During the 4-week follow-up
period after discharge, blood
be controlled for all identification and timely glucose homeostasis should be
patients during reduction adverse drug maintained continuously and
hospitalization to reaction (for instance, patients need to avoid infectious
glucocorticoid-induced diseases due to a lower immune
monitor the progress response. Long-term follow-up is
hyperglycemia) could
of illness and avoid prevent worse still essential for diabetic patients
aggravation. to reduce diabetes-related
symptoms. complications and mortality
Critical After
Hospitalized
Case discharge
For the COVID-19 patients with diabetes, tailored therapeutic strategy and optimal goal of glucose control
should be formulated based on clinical classification, coexisting comorbidities, age and other risk factors.
https://www.diabetesresearchclinicalpractice.com/article/S0168-8227(20)30368-5/pdfTarget stratification of glucose management：
ü For mild and moderate non-elderly COVID-19 patients, stick to strict high control
target
ü For mild and moderate elderly patients, or patients who have been using
glucocorticoid, set up a low or medium control target
ü 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
High (mmol/L) Medium (mmol/L) Low (mmol/L) (mg/dL)
(mg/dL) (mg/dL)
FPG/PPG 4.4-6.1 (79.2-109.8) 6.1-7.8 (109.8-140.4) 7.8-10.0 (140.4-180)
2h PPG/GLU 6.1-7.8 (109.8-140.4) 7.8-10.0 (140.4-180) 7.8-13.9 (140.4-250.2)
Hypoglycemia occurrence should be minimized during glucose management in diabetes patients
with COVID-19. Medical care should be performed in time if hypoglycemia occurs.
• Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med. 2020 Mar;37(3):215-219CATEGORIZED GUIDANCE TO MANAGE DIABETES IN CRITICAL
INFECTIONS
General guidelines to manage Diabetes during COVID-191
• Take diabetes medication as usual. Insulin treatment should
never be stopped
• Test blood glucose every four hours, and keep track of the
results
• Drink extra (calorie-free) fluid*, and try to eat as normal
• Weigh yourself every day. Losing weight while eating normally
is a sign of high blood glucose
• Check temperature every morning and evening. A fever may be
a sign of infection
Individualized target based treatment strategies2
Patient BG Targets Management
1. International Diabetes Federation, sick day rules Accessed 8 Category FPG 2h PG
March 2020.
2. Sichuan Da Xue Xue Bao Yi Xue Ban. 2020 Mar;51(2):146- Mildly ill 4.4-6.1 mmol/L 6.1-7.8 mmol/L Maintain Strict Glycemic
150.
© 2020 Eli Lilly and Company. Patients 79.2-109.8 mg/dL 109.8-140.4 mg/dL Control
Moderately ill 6.1-7.8 mmol/L 7.8-10.0 mmol/L Subcutaneous Insulin
109.8-140.4 mg/dL 140.4-180 mg/dL Delivery system
Critically Ill 7.8-10.0 mmol/L 7.8-13.9 mmol/L IV Insulin Infusion
patients 140.4-180 mg/dL 140.4-250.2 mg/dL04/02/2021
CORTICOSTEROID-INDUCED
HYPERGLYCEMIA
• Steroids are the main cause of drug-induced hyperglycemia.
• Patients with known diabetes à exacerbate hyperglycemia
• Patients without documented hyperglycemia before the initiation of
glucocorticoids (GC) therapy à cause DM , with an incidence that can reach up
to 46% of patients, and increases in glucose levels up to 68% compared to
baseline.
• Precipitate acute complications à nonketotic hyperosmolar state, and diabetic
ketoacidosis.
• Patophysiology: Increase in insulin resistance with increased glucose production
and inhibition of the production and secretion of insulin by pancreatic β-cells
Tamez-Pérez HE et al . Steroid hyperglycemia: A narrative review. World J Diabetes 2015 July 25; 6(8): 1073-1081PowerPoint Presentation Date
CONSENSUS RECOMMENDATIONS FOR COVID-19 AND
METABOLIC DISEASE
Hypoglycemia (< 70 mg/dl)
• Less than 4%
• < 1% in frail and older people
Bornstein, S.R., Rubino, F., Khunti, K., Mingrone, G., Hopkins, D., Birkenfeld, A.L., Boehm, B., Amiel, S., Holt, R.I., Skyler, J.S. and DeVries, J.H., 2020.
Practical recommendations for the management of diabetes in patients with COVID-19. The lancet Diabetes & endocrinology.Use of antidiabetic medications in patients with T2DM and COVID-19
S. Lim, J.H. Bae. Nat. Rev. Endocrinol. 17 (2021) 11–30,How do we handle anti-diabetic medications in patients with COVID-19?
Diabetes & Primary Care Vol 20 No 1 2018 15STRATEGI PENGELOLAAN KADAR GLUKOSA
BERDASARKAN TIPE DIABETES
MELITUS PADA PASIEN COVID-19
Pedoman Tatalaksana Covid-19, Desember 2020STRATEGI
PENGELOLA
AN KADAR
GLUKOSA
BERDASAR
KAN TIPE
DIABETES
MELITUS
PADA PASIEN
COVID-19
Pedoman Tatalaksana Covid-19, Desember 2020STRATEGI
PENGELOLAAN
KADAR GLUKOSA
BERDASARKAN
KLASIFIKASI
KONDISI KLINIS
Pedoman Tatalaksana Covid-19, Desember 2020STRATEGI
PENGELOLAAN
KADAR GLUKOSA
BERDASARKAN
KLASIFIKASI
KONDISI KLINIS
Pedoman Tatalaksana Covid-19, Desember 2020STRATEGI
PENGELOLAAN
KADAR GLUKOSA
BERDASARKAN
KLASIFIKASI
KONDISI KLINIS
Pedoman Tatalaksana Covid-19, Desember 2020PRINSIP
PENGELOLAAN
KADAR
GLUKOSA
Pedoman Tatalaksana Covid-19, Desember 202004/02/2021
41
JBDS-IP, 2014PowerPoint Presentation Date 42
TREATMENT OF HYPERGLYCEMIA IN CRITICALLY
ILL PATIENTS
• Continuous IV insulin infusion à the most effective method for achieving
specific glycemic targets. Because of the very short half-life of circulating insulin,
IV delivery allows rapid dosing adjustments to address alterations in the status of
patients.
• IV insulin therapy à the glucose level should be maintained between 140 and
180 mg/dl (7.8 and 10.0 mmol/l).
• Transition to subcutaneously administered insulin à begin eating regular meals
or are transferred to lower-intensity care.
• A percentage (usually 75– 80%) of the total daily IV infusion dose is proportionately
divided into basal and prandial components & must be given 1– 4 h before
discontinuation of IV insulin therapy in order to prevent hyperglycemia
AACE/ADA consensus on inpatient glycemic control. Diabetes Care 2009 Jun; 32(6): 1119-1131.04/02/2021
MANAGEMENT OF CORTICOSTEROID-
INDUCED HYPERGLYCEMIA
• In hospitalized patients, monitoring should start with capillary glucose determination from the
start of steroid treatment.
• Since almost 94% of cases of hyperglycemia develop within 1-2 d of initiation of steroid
therapy in the hospital setting, in nondiabetic patients who maintain glucose levels < 140
mg/dL without insulin requirements for 24-48 h, glycemic monitoring can be discontinued.
• in patients with glucose levels > 140 mg/dL with persistent insulin requirements, a basal/ bolus
subcutaneous insulin scheme must be established.
• in patients with severe and/or persistent hyperglycemia despite the subcutaneous scheme,
insulin by infusion pump should be started.
Tamez-Pérez HE et al . Steroid hyperglycemia: A narrative review. World J Diabetes 2015 July 25; 6(8): 1073-1081CLINICAL SITUATIONS THAT INCREASE THE RISK FOR
HYPOGLYCEMIA AND HYPERGLYCEMIA IN THE HOSPITAL INCLUDE
THE FOLLOWING:
1. Changes in caloric or carbohydrate intake (“nothing by mouth” status, enteral nutrition, or
parenteral nutrition)
2. Change in clinical status or medications (for example, corticosteroids or vasopressors)
3. Failure of the clinician to make adjustments to glycemic therapy based on daily BG patterns
4. Prolonged use of SSI (Sliding Scale Insulin) as monotherapy
5. Poor coordination of BG testing and administration of insulin with meals
6. Poor communication during times of patient transfer to different care teams
7. Use of long-acting sulfonylureas in elderly patients and those with kidney or liver insufficiency
8. Errors in order writing and transcription
AACE/ADA consensus on inpatient glycemic control. Diabetes Care 2009 Jun; 32(6): 1119-1131.BG MONITORING
• Bedside BG monitoring with use of pointof-care (POC) glucose meters is performed before
meals and at bedtime in most inpatients who are eating usual meals.
• In patients who are receiving continuous enteral or parenteral nutrition, glucose monitoring is
optimally performed every 4 – 6 h.
• In patients who are receiving cycled enteral nutrition or parenteral nutrition, the schedule for
glucose monitoring can be individualized but should be frequent enough to detect
hyperglycemia during feedings and the risk of hypoglycemia when feedings are interrupted
• More frequent BG testing, ranging from every 30 min to every 2 h, is required for patients
receiving IV insulin infusions.
AACE/ADA consensus on inpatient glycemic control. Diabetes Care 2009 Jun; 32(6): 1119-1131.PowerPoint Presentation Date 47
OUTLINE
About Link between Prevention Summary
COVID-19 COVID-19 and
and Diabetes TreatmentCONCLUSIONS üUnderlying diabetes mellitus risk factors for increased coronavirus disease 2019 (COVID-19) disease severity and worse outcomes, including higher mortality. üPotential pathogenetic links between COVID-19 and diabetes mellitus include effects on glucose homeostasis, inflammation, altered immune status and activation of the renin–angiotensin–aldosterone system (RAAS). üDuring the COVID-19 pandemic, tight control of glucose levels and prevention of diabetes complications might be crucial in patients with diabetes mellitus to keep susceptibility low and to prevent severe courses of COVID-19. üTarget stratification of glucose management depends the disease severity & improvement
04/02/2021 49 LESSON LEARNED • DM is the bad prognostic outcome • Diabetes is one of the high risk groups for developing severe illness from COVID-19 • Intensive Insulin glucose regulation • Strictly glucose monitoring (CGM/FGM) • Needs continuously of management improvement
PowerPoint Presentation Date
50
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