Update on Protocol insulin therapy in

Hyperglycemia Diabetes Patient with Covid-19 &

What we learn from Clinical Practice

MAT-ID-2000804 (11/2020)
 Diabetes and COVID-19 Infections

• Patients with diabetes represent 25% to 34% of the patient population receiving care in ICU
and non-ICU settings for COVID-19

• COVID-19 in turn leads to worsening of glucose control in people with diabetes mellitus.

• Drugs being used to treat COVID-19 can also adversely affect glucose control.

• Appropriate glycemic management contributes to a reduction in adverse clinical outcomes in

acute illness but also requires intensive patient interactions for bedside glucose monitoring,
intravenous and subcutaneous insulin administration, as well as rapid intervention for
hypoglycemia events

Mary Korytkowski, et al. The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 9, September 2020 : 3076–3087
Rimesh Pal, Sanjay K, Bhadada. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. Volume 14, Issue 4, July–August 2020, Pages 513-517
 Diabetes Management in COVID‐19

Most patients with mild infection and with normal oral intake can continue the usual
antihyperglycemic medications.
• Discontinue SGLT-2 inhibitors and metformin
• Doses of other antihyperglycemic drugs like sulfonylureas and insulin may have to be
altered depending upon the blood glucose level

Most hospitalized patient with COVID--‐19, especially those with respiratory distress, would
require insulin.
• Intravenous insulin infusion with frequent monitoring of blood glucose (every hour or every
two hours) • insulin infusion (CSII)
• Subcutaneous short acting insulin analogues
• Single dose of basal insulin
• Insulin pump or continuous subcutaneous

Singh AK, Gupta R, Ghosh A, Misra A. Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations. Diabetes Metab Syndr. 2020;14(4):303-310.
doi:10.1016/j.dsx.2020.04.004
Characteristics of and Lessons Learned From China

• Case-fatality rate (CFR)

• 2.3% (1023 of 44 672 confirmed cases)
• 14.8% in patients aged >80 years (208 of 1408)
• 8.0% in patients aged 70-79 years (312 of 3918)
• 49.0% in critical cases (1023 of 2087)
• CFR was elevated among those with pre-existing 3 times fold higher
comorbid conditions mortality rate in Diabetes
• 10.5% for cardiovascular disease
• 7.3% for diabetes
• 6.3% for chronic respiratory disease People with Diabetes do face a higher chance of
experiencing serious complications from COVID-19*
• 6.0% for hypertension
• 5.6% for cancer Summary of a Report of 72 314 Cases From
Wu Z and McGoogan JM. JAMA Published online February 24, 2020. https://jamanetwork.com/ on 02/24/2020 the Chinese Center for Disease Control and
*Gupta R et.al. Diabetes & Metabolic Syndrome: Clinical Research & Reviews 14 (2020) 211e212
Prevention
 Reasons for Glucose Fluctuation in Patients with
Diabetes and COVID-19
Irregular diet, reduced exercise, There may be interruption or non-
gastrointestinal symptoms, etc., standard treatment with OAD in
affect diet, resulting in glucose isolation wards, resulting in glucose
fluctuation fluctuation

Stress conditions like Fear, anxiety and tension may

infection increase increase glucose level and
glucocorticoids secretion induce glucose fluctuation

COVID 19 can cause human body to

The use of glucocorticoids in produce large number of inflammatory
treatment can lead to a sharp cytokines and lead to extreme stress in
rise in glucose some severe and critical patients

Expert Recommendation on Glucose Management Strategies of Diabetes Combine with COVID-19. J Clin Intern Med 2020 Mar; 37 (3): 215-219
 Hospitalized Diabetes and COVID-19 patients

Insulin
Recommended

SC Insulin
IV Insulin Basal or basal plus bolus correction insulin
Critically ill patients in the ICU Non-critically ill patients

Papadokostaki et.al. COVID-19 and diabetes: What does the clinician need to know? Primary Care Diabetes 14 (2020) 558–563
 Kebutuhan Insulin Pada Pasien Rawat Inap

PASIEN RAWAT INAP

KRITIS TIDAK KRITIS

KEGAWAT DARURATAN KEGAWAT DARURATAN JUMLAH ASUPAN NUTRISI GLUKOSA DARAH

DIABETES NON-DIABETES SUKAR/TIDAK
Sepsis TERKENDALI :
Ketoasisosis Metabolik
Infark miokard akut Pemakaian steroid
Hipeosmolar Non Ketotik
Stroke Operasi dengan kendali GD
TERATUR TIDAK TERATUR buruk / harus puasa lebih
Ketidakstabilan hemodinamik dari 2x makan
Perencanaan operasi segera Stroke yang membutuhkan
dengan glukosa darah tinggi nutrisi parenteral total

Sub Kutan
Sub Kutan
dosis terbagi
dosis terbagi
Infus IV kontinyu/ tetap + dosis Infus IV kontinyu/
Infus IV kontinyu tetap
Sub Kutan koreksional Sub Kutan

Konsensus Insulin Perkeni 2019

 Inpatient Glycemic Targets

Individualized glycemic goal; depends on patient’s clinical condition

Critically ill Non-critically ill

Preferred route Intravenous Subcutaneous

Glucose target (mg/dl) 140-180 mg/dl Premeal <140 mg/dl
(ADA 2015) (Selected patients* 110 -140 mg/dl) Random <180 mg/dl

Glucose target (mg/dl) Premeal 110-140 mg/dl

(ESC 2012) Random 140-180 mg/dl

Not recommended Acceptable Recommended Not recommended

<110 110-140 140-180 >180
*centers with extensive experience and appropriate nursing support, cardiac surgical patients,
and patients with stable glycemic control without hypoglycemia

American Diabetes Association. Standards of Medical Care in Diabetes—2015. Diabetes Care. 2015 ; 38(1): S1-S93
Umpierrez GE, et al. an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012. 97:16–38.
 Protokol Insulin IV Kontinyu

Dosis awal 0,5-1 U/jam

Sasaran glukosa darah

< 100 mg/dL atau

klinis didapatkan 100-<140 mg/dL 140-180mg/dL 140-180mg/dL
hipoglikemia

Stop insulin Dosis diturunkan

sampai 50% dari Penurunan Penurunan
IV kontinyu
dosis terakhir glukosa darah glukosa darah <
> 60 mg/dL 60 mg/dL

Penurunan glukosa Penurunan glukosa Turunkan dosis Naikan dosis

darah > 60 mg/dL darah < 60 mg/dL 25% dari dosis 25% dari
terakhir dosis terakhir
Dosis diturunkan
Lanjutkan dosis
sampai 25% dari
sebelumnya
dosis terakhir

PERKENI. Terapi Insulin pada Pasien Rawat Inap dengan Hiperglikemia. 2019
The Use of Subcutaneous Insulin
in Critically ill Patients

Management hyperglycemia in COVID-19–infected patients based on a personalized risk

stratification that includes different levels of hyperglycemia and insulin resistance, prior
diabetes control, presence of obesity, needs and type of nutritional support, renal
dysfunction, vasopressor support, and disease activity
Initial Subcutaneous insulin dosing guideline for critically ill
COVID-19 patients admitted with high glucose

Gianchandani, Roma, et al. Diabetes 2020;69:2048–2053

Gianchandani, Roma, et al. Diabetes 2020;69:2048–2053
Gianchandani, Roma, et al. Diabetes 2020;69:2048–2053
 Blood
Glucose in
Cytokine
Storm

Patients admitted with COVID-19–related pneumonia, acute respiratory distress syndrome, & important surges. Patient A: well
Gianchandani, Roma, et al. Diabetes controlled prior to admission on oral antiglycemic agents. Patient B, requiring prior insulin.
2020;69:2048–2053
 Covid-19 & Diabetes: high insulin requirement during peak
inflammatory response

Insulin requirements and inflammatory markers depicted for the eight patients throughout the course of admission. Total daily dose (units) is depicted in blue, and CRP
(mg/L) is depicted in red. Patients 2, 3 and 6 were newly diagnosed with diabetes
Wu, Linda, et al. Clinical Endocrinology. 2020;93:390–393.
 Study of Continuous Insulin Infusion Protocols in the
Medical Intensive Care Unit by using Glulisine

300

250
Standard
200
Glucommander

Glucose (mg/dL)
150

100
• Both treatment algorithms
resulted in significant
50
improvement in glycemic
control in critically ill patients in
0 the medical ICU.
0 1 2 3 4 5 6 7 8 9 10

Standard (n) 77 77 55 35 24 14 13 10 7 7 3
Glucommander (n) 76 76 50 37 31 32 18 17 15 11 8

Time on Infusion (Days)

Newton CA, et al. Journal of Hospital Medicine. 2010;5(8):432–7.

 Study of Glucose Control using Glulisine in the
Coronary Care Unit

Glucose levels over the course of

the trial were significantly lower in the insulin arm.

P-values standard therapy

1 NS
Insulin arm
2 <0.05
DESIGN AND METHODS

Glucose (mmol/L)
3 <0.005
4 <0.0005
Total 287 participants with an acute
STEMI and a capillary glucose ≥ 8.0
mmol/L were randomized to insulin
arm (insulin glulisine infusion in the
CCU, and insulin glargine once-
daily in ward) versus standard
therapy arm (physicians free to add
insulin therapy to treat high glucose
level) for 30 days

Time
Nerenbergh et al., Diabetes Care 35:19–24, 2012
 Transition From IV Insulin to SC Insulin

• Stable BG levels <180mg/dl for at least 4 -6 hrs

• Resolution of acidosis in DKA.
• Hemodynamically stable without use of vasopressors.
• Stable nutrition plan
• Stable IV drip rates(low variability).
• Because of short half-life of IV insulin, SC basal insulin should be administered at least
1-2 hours prior to discontinuing the drip

Umpierrez G, et al. J Clin Endocrinol Metab. 2012;97:16-38

Kreider KE,Lien LF.CurrDiab Rep; 2015; 15: 23.
 Converting iv to sc insulin
Example: Patient has received an average of 2 U/h IV during previous 6 h. Recommended doses are as
follows: SC TDD is 80% of 24-h insulin requirement:

2 Unit/h x 24 h = 80% x 48 Units =

48 Units 38 Units

Basal dose is 50% of SC TDD:

◦ 50% of 38 Units = 19 Units of long-acting insulin

Bolus total dose is 50% of SC TDD:

◦ 50% of 38 Units = 19 Units. Give as ~6 Units with each meal

Correction dose is actual BG minus target BG divided by the CF, and CF is equal to 1700 divided by TDD:
CF = 1700 ÷ 38 = ~40 mg/dL
Correction dose = (BG - 100) ÷ 40

BG, blood glucose; CF, correction factor; IV, intravenous; SC, subcutaneous; TDD, total daily dose.
Bode BW, et al. Endocr Pract. 2004;10(suppl 2):71-80.
 Rabbit 2 Trial: Changes In Glucose Levels With Basal-bolus Vs.
Sliding Scale Insulin
Prospective, multicenter, randomized, open-label trial, 130 nonsurgical insulin-naïve patients age 18-80 with known type 2
diabetes admitted to noncritical care unit

Treatment with
basal-bolus
(Glargine-Glulisine)

Therapy results
in significant
improvement of

Glycemic control
compared with
sliding scale insulin
(Regular insulin)
aP<.01. bP<.05.

Target glycaemia achieved (BG<140 mg/dL), Basal-bolus : 2/3rd of patients, SSI : 1/3rd of patients

Umpierrez GE, et al. Diabètes Care. 2007;30(9):2181-2186.

 Blood Glucose Monitoring in Hospitalized
Patients with COVID-19

To reduce interactions between patients and healthcare providers,

limit exposure to COVID-19, and reduce the waste of personal
protective equipment (PPE):
• use of home-use blood glucose meters as an option to provide
relief and support to healthcare professionals in the hospital
• use of continuous glucose monitoring (CGM) devices
• Another option is to place the drips requiring frequent titration to
a location outside the patient room

Pole for maintaining IV medications

outside a patient’s room.
Zhou, Keren,et al. Cleveland Clinic Journal of Medicine July 2020, DOI: https://doi.org/10.3949/ccjm.87a.ccc012
 Blood Glucose Monitoring in
Hospitalized Patients with COVID-19
To reduce interactions between patients and
healthcare providers, limit exposure to COVID-19, and
reduce the waste of personal protective equipment
(PPE):
• use of home-use blood glucose meters as an option
to provide relief and support to healthcare
professionals in the hospital
• use of continuous glucose monitoring (CGM) devices
• Another option is to place the drips requiring
frequent titration to a location outside the patient
room

Pole for maintaining IV medications

outside a patient’s room.
Zhou, Keren,et al. Cleveland Clinic Journal of Medicine July 2020, DOI: https://doi.org/10.3949/ccjm.87a.ccc012
 Take Home Message
• Insulin therapy is the preferred treatment regimen for hospitalized diabetes patients with Covid-
19
• Critical care: IV insulin, Non-critical: SC Basal bolus/plus
• Target glucose range 140 – 180 mg/dl
• Consider alternative protocols for management hyperglycemia with less frequent monitoring and
medication administration.
• Insulin glulisine can be used for IV infusion
• Treatment with basal-bolus (Glargline-Glusine) Therapy results in significant improvement of
Glycemic control compared with sliding scale insulin regular insulin
• For monitoring blood glucose in hospitalized diabetes with Covid-19 consider use of use of home-
use blood glucose meters & continuous glucose monitoring systems, as appropriate.