Managing Diabetes in a COVID World

Disclosure of Relevant Financial Relationships

I have no relationships to disclose

Objectives

• Describe factors that may increase the risk of COVID-19 in diabetic patients

• Review management strategies for patients with diabetes

• Discuss information and key points to provide patients with diabetes during counseling

Diabetes in America 2020

• One of the most common medical conditions globally

• Expected to increase even if the prevalence of obesity remains stable

• 13% (34 mil) of adults have diabetes• 26.8% among those aged 65

years and older

• 35% (88 mil) of adults have prediabetes

CDC. National Diabetes Statistics Report, 2020. https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.htmlWild S, Roglic G, Green A, et al. Global prevalence of diabetes: Estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27:1047-53.

Diabetes Health Outcomes

Kazemian P,e t al. Evaluation of the Cascade of Diabetes Care in the United States, 2005-2016. JAMA Intern Med. 2016; 179(10):1376-85.

A 10-Year Perspective

Diabetes and Infectious Disease

Secrest AM, et al Mortality in Type 1 Diabetes. In: Diabetes in America, 3rd edition. Aug 2018

Prior to 1940’s

• Approximately 20% of diabetics died of infections

1940’s

After the 1960s

• Less 6% of diabetics died due to infections

1960’s

Insulin and Antibiotics

Vaccinations

Casqueiro J, at al. Infections in patients with diabetes mellitus: A review of pathogenesis. Indian J Endocrinol Metab. 2012;16(Suppl 1): s27-36.

Which Infections?

• Skin and subcutaneous tissues

• Cellulitis

• Superficial mycoses and onychomycosis

• Skin lesions

• Soft tissues, bones, joints

• Necrotizing fasciitis

• Diabetic foot

• Osteomyelitis

• Urinary Tract infections

• Head and neck

• Periodontal disease

• Malignant otitis externa

Toniolo A, et al. The diabetes pandemic and associated infections: suggestions for clinical microbiology. Reviews in Medical Microbiology. 2019;30:1-17.

Respiratory Infections

Organism Incidence Outcomes

TB Greater Worse

Other fungal/aypical histo,blasto, coccidiomycosis

Presumed Presumed

Gram negative and Staph pneumonias

Greater Worse

Pneumococcal pneumonia

Not different Worse

Influenza Not different Worse

SARS 2003 ?? Increased mortality

SARS-CoV-2/COVID-19

Peleg AY. Common infections in diabetes: pathogenesis, management and relationship to glycaemic control. Diabetes Metab Res Rev. 2007;23(1):3-13.Yang JK, et al. Plasma glucose levels and diabetes are independent predictors for mortality and morbidity in patients with SARS. Diabet Med. 2006;23(6):623-8.

COVID-19 in Critically Ill Patients -Seattle Region

• 24 patients from 9 Seattle area hospitals

• ICU admissions

• Positive for SARS-CoV-2

• Mean age 64 years

• 63% male

• 50% fever

• 58% diabetes

Pagan K, et al. Covid-19 in critically ill patients in the Seattle region - case series. N Engl J Med. 2020;382:2012-22.

ACTT-1 Study

• 1063 patients enrolled

• Hypertension: 50%

• Obesity 45%

• Type 2 diabetes: 30%

• More than half of patients had two or more chronic conditions

Beigel JH, et al. Remdemsivir for the treatment of COVID-19 - final report. N Engl J Med. 2020:383:1813-26.

COVID-19 Patients Hospitalized in NYC

• 5700 patients

• Median age: 63 years

• 60% male

• Hypertension: 56.6%

• Obesity: 41.7%

• Diabetes: 33.8%

Richardson et al. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020;323(20):2052-59.

Are patients with diabetes more likely to get infected

with COVID-19?

Does having diabetes increase chances of contracting COVID-19 infection?

• Diabetes does not appear to increase susceptibility of COVID-19, although it may be more frequent in patients with severe infection

Gangopadhyay KK. Dose having diabetes increase chances of contracting COVID-19 infection? Diabetes Metab Syndr. 2020;14(5):765-66.

COVID-19: Outcomes According to Pre-existing Diabetes

Apicella M, et al. COVID-19 in people with diabetes: understanding the reasons or worse outcomes. Lancet Diabetes Endocrinol. 2020:8;782-92.

Type 1 vs. Type 2: Is There a Difference in Outcomes?

• Hospitalization

• Belgium study of 2336 patients with Type 1 diabetes showed no evidence of increased hospitalization

• 5 (0.21%) patients were admitted for COVID-19 treatment

• This rate is comparable to the general population

Vangoitsenhoven R, et al. No Evidence of Increased Hospitalization Rate for COVID-19 in Community-Dwelling Patients With Type 1 Diabetes. Diabetes Care. 2020;43(10):e118-9.

Type 1 vs. Type 2: Is There a Difference in Outcomes?

Morbidity and Mortality

Barron E, et al. Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet

Diabetes Endocrinol. 2020;8:813-22.

Gregory JM, et al. COVID-19 severity is tripled in the diabetes community: A Prospective analysis of the pandemic’s impact in type 1 and type 2 diabetes. Diabetes Care. Dec 2020: online ahead of print

Why is Diabetes a Risk for Adverse Outcomes?

Pugliese G, et al. Is diabetes mellitus a risk factor for COronaVIrus Disease 19 (COVID-19)? Acta Diabetologica. 2020:57;1275-85.

Lim S, et al. COVID-19 and diabetes mellitus: from pathophysiology to clinical management. Nat Rev Endocrinol. 2021;17(1):11-30.

COVID-19 and Obesity

SAnchis-Gomar F et al. Obesity and outcomes in COVID-19: When an epidemic and pandemic collide. Mayo Clin Proc.

2020;95(7):1445-53.

The CORONADO Study

Cariou B et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO study. Diabetologia. 2020:63(8):1500-15.

CDC. National Diabetes Statistics Report, 2020. https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html

Other Risk Factors

Holman N et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort. Lancet Diabetes Endocrinol. 2020;8(10);823-33.

COVID-19 and Glucose Control

• Outcomes separated by blood glucose levels• >180 mg/dL - Poorly controlled

• <180 mg/dL – Well controlled

Singh AK, et al. Does poor glucose control increase the severity and mortality in patients with diabetes and COVID-19? Diabetes Metab Syndr. 14(5):725-7.

COVID-19 and Glucose Control

• 453 patients admitted to Union Hospital in Wuhan, classified as:

• Normal glucose

• Hyperglycemia (fasting 5.6-6.9 mmol/L, HbA1c 5.7-6.4%)

• Newly diagnosed diabetes (fasting >7.0 mmol/L, HbA1c >6.5%)

• Known diabetes

Li h, et al. Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19. Diabetes Obes Metab. 2020;22(10):1897-1906.

COVID-19 and Hyperglycemia

Caballero AE et al. COVID-19 in people living with diabetes: An international consensus. J Diabetes Complications. 2020;34(9):107671

Glucose on Admission

• 271 patients hospitalized patients with COVID-19

• Hyperglycemia was a strong independent predictor of mortality

Coppelli A, et al. Hyperglyceia at hospital admission is associated with severity of the prognosis in patients hopsitalized for COVID-19: the Pisa COVID-19 study. Diabetes Care. 2020;43:2345-48.

Admission Glucose Predicts COVID Severity

• Overall All-Cause Mortality• 41.1% with admission blood

glucose >180 mg/dL

• 33% with admission blood glucose 140-180 mg/dL

• 15.7% with admission blood glucose <140 mg/dL

Carrasco-Sanchez FJ, et al. Admission hyperglycaemia as a predictor of mortality in patients hospitalized with COVID-19

regardless of diabetes status: data from the Spanish SEMI-COVID-19 Registry. Ann Med. 2021;53(1):103-16.

Glycemic Targets

Glycemic Recommendations for nonpregnant adults with diabetes

ADA

A1C <7%

Preprandial plasma glucose 80-130 mg/dL

Peak postprandial plasma glucose <180 mg/dL

Individualization is KEY!!

Diabetes Care. 2021;44 (Suppl 1):S73-84.

How Are We Doing?

Kazemian P,e t al. Evaluation of the Cascade of Diabetes Care in the United States, 2005-2016. JAMA Intern Med. 2016; 179(10):1376-85.

Type 2 Pharmacologic Treatment

Diabetes Care. 2021;44 (Suppl 1):S111-24.

Biguanide

Generic/trade name Site of action Common side effects

A1c loweringeffects

FBG lowering effect

Considerations

Metformin (Glucophage,Glucophage XR, Fortamet, Riomet, Glumetza)

Liver, skeletal muscle, adipose tissue

Diarrhea, nausea, abdominal pain, metallic tasteWeight neutral

1% - 2% 60 – 80 mg/dL

If GFR < 30, do not use

If GFR <45, don’t start

If GFR falls to 30-45, evaluate risk vs. benefit, consider decreasing dose

Metformin and COVID-19

• Retrospective study of 6256 patients hospitalized with COVID

• Compared patients with type 2 diabetes or obesity who had been on metformin at home to those who had not

• Metformin was associated with decreased mortality in women with obesity or type 2 diabetes who were admitted to the hospital with COVID

Bramante CT, et al. Metformin and risk of mortality in patients hospitalised with COVID-19: a retrospective cohort analysis. Lancet Healthy Longev. 2021;2:e34-41.

Dipeptidyl Peptidase-4 Inhibitors

• Incretin Enhancers• Inhibits DPP-4 increasing the amount of endogenous GLP-1

• Therapeutic effects• Enhancing glucose dependent insulin secretion

• Reduce hepatic glucagon production

• Lowering effect primarily on postprandial levels

Dipeptidyl Peptidase-4 Inhibitors

Generic/trade name Site of action

Common side effects

A1c loweringeffects

Considerations

Sitagliptin (Januvia)

GI Tract Well tolerated, headache

0.6% - 0.8%

Report signs of pancreatitis

Saxagliptin and alogliptincan increase risk of heart failure.

Saxagliptin (Onglyza)

Linagliptin (Tradjenta)

Alogliptin (Nesina)

DPP-4 Inhibitors and COVID-19

• ACE2 is the entry receptor for SARS-CoV-2

• DPP4 is the entry receptor for MERS-CoV

• DPP4 is associated with maintaining lymphocyte composition and function

• May modulate cytokines, chemokines, and peptide hormones

Chen CF, et al. Role of dipeptidyl peptidase-4 inhibitors in patients with diabetes infected with coronavirus-19. J Chin Med Assoc. 2020;83(8):710-1.

Sitagliptin Treatment May Improve Outcomes

• 338 patients with type 2 diabetes and COVID-19 admitted in Northern Italy hospitals

• 169 started on sitagliptin + standard of care

• 169 were on standard of care only

• Treatment with sitagliptin at the time of hospitalization was associated with reduced mortality (18% vs. 37%) with an improvement in clinical outcomes (60% vs. 38%) and with a greater number of hospital discharges (120 vs. 89) compared with patients receiving standard of care, respectively.

Solerte SB, et al. Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study. Diabetes Care:2020;2999-3006.

Sodium Glucose Cotransporter 2 Inhibitors

Vhao EC. SGLT-2 Inhibitors: a new mechanism for glycemic control. Clin Diabetes 2014;32:4-11

Sodium Glucose Cotransporter 2 Inhibitors: Benefits

• Lower A1C b 0.6% to 1.5%

• Reduce weight by ~3 to 4 kg

• Reduce systolic BP by ~ 5 to 6 mmHg

• Low risk of hypoglycemia

• May be renal protective

Peene et al. sodium glucose transporter protein 2 inhibitors: focusing on the kidney to treat type 2 diabetes. Ther Adv Endocrinol Metab. 2014;5:124-36.

SGLT-2 Inhibitors

Generic/trade name Site of action

Common side effects

A1c loweringeffects

Considerations

Canaglifozin (Invokana)

kidneys Hypotension, UTIs, increased urination, genital infections, ketoacidosis

0.6% - 1.5%

Monitor GFR: • Canagliflozin: do not use if GFR <30• Dapagliflozin and Empagliflozin: do not

use if GFR <45• Ertugliflozin: do not use if GFR <60.

*Empagliflozin, Dapagliflozin, & Canagliflozin: - Reduce risk of CV death, heart failure

and preserve long-term kidney function.

Dapagliflozin (Farxiga)

Empagliflozin (Jardiance)

Ertugliflozin (Steglatro)

SGLT-2 Inhibitors and COVID-19

• COVID-19 may increase insulin demand and present with gastrointestinal symptoms

• SGLT-2 inhibitors predisposes a patient to volume depletion

• Rare complication: diabetic ketoacidosis/euglycemic DKA

• These agents should be discontinued in any patient suspected of having COVID-19 due to the increased risk of DKA

Fang J, et al. COVID-19 precipitating euglycaemic diabetic ketoacidosis with SGLT2 inhibitor use. Eur J Case Rep Intern Med. 2020;7(11):001943

Glucagon-like Peptide 1 Receptor Agonists

Generic/trade name Common side effects

A1c loweringeffects

Considerations

Exenatide (Byetta)Exenatide XR (Bydureon) Nausea, diarrhea,

weight loss injection site pain, headache

Report signs of acute pancreatitis

0.5% - 1.6%

Black box warning: Thyroid C-cell tumor warning for exenatide XR, liraglutide, dulaglutide, and semaglutide (avoid if family history of medullary thyroid tumor).

*Significantly reduces risk of CV death, heart attack, and stroke.

Liraglutide (Victoza)*

Dulaglutide (Trulicity)*

Lixisenatide (Adlyxin)

Semaglutide(Ozempic*, Rybelsus)

GLP-1 RAs and COVID-19

• May be protective against CVD and kidney disease

• Has the potential to help patients lose weight

• Recommended to continue treatment during the pandemic

Antidiabetic Treatment During COVID19

Apicella M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020:8;782-92.

Recommendations for Diabetes Care

Bornstein SR, et al. Practical recommendations for the management of diabetes in patients withCOVID-19. Lancet Diabetes Endocrinol. 2020;8:546-50.

Key Guidance for Persons with Diabetes

• Prevention

• Reudce exposure to the virus

• Follow current CDC guidelines and local recommendations

• Reduce risk of severe illness

• Improve baseline health status

• Manage blood glucose levels

• Prepare in advance of illness

• Sick day diabetes management plan

• Ensure adequate insulin, medications, diabetes supplies

Sick Day Management

• Stay hydrated

• 8oz sugar-free and caffeine-free liquids every hour

• If unable, frequent sips of liquid

• Sugar free popsicles, sugar free gelatin

• Try to follow regular meal plan

• If unable to eat, substitute regular carbohydrate intake with liquids

• Regular soda, gelatin, popsicles, Gatorade or Pedialyte, sherbet, soup

• Monitoring

• Blood glucose at least every 4 hours or continuous monitoring

• Ketones (urine or blood) every 4 hours

Ketone Monitoring

• If blood glucose is greater than 300 mg/dL if using insulin injections or 240 mg/dL if on an insulin pump

• When ill or vomiting

• Symptoms

• Frequent urination

• Excess thirst

• Nausea/vomiting

• Stomach pain

• Flushed skin

• Weakness

• Rapid heartrate

• Shortness of breath

• Deep or troubled breathing

• Confusion

CDC Advice for People with Diabetes

• Having type 2 diabetes increases your risk of severe illness from COVID-19. Based on what we know at this time, having type 1 or gestational diabetes might increase your risk of severe illness from COVID-19.

• Actions to take

• Continue taking your diabetes pills and insulin as usual.

• Test your blood sugar and keep track of the results, as directed by your healthcare provider.

• Make sure that you have at least a 30-day supply of your diabetes medicines, including insulin.

• Follow your healthcare provider’s instructions if you are feeling ill as well as the sick day tips for people with diabetes.

• Call your healthcare provider if you have concerns about your condition or feel sick.

• If you don’t have a healthcare provider, contact your nearest community health centerexternal icon or health department.

• Minimize physical interactions with others

• Maintain strict personal hygiene

• Avoid touching face with unwashed hands

• Routinely disinfect high-touch surfaces in home

• Avoid any non-essential travel

• Convert healthcare visits to telemedicine where possible

• Extra precautions when out in public:• Cloth mask or face covering

• Maintain 6 feet distance

Summary

• The risk of developing COVID-19 is not greater for those with diabetes

• In-hospital mortality and disease severity may be worse

• Important to stress glucose control

• Do not prophylactically discontinue medication

• Stress the importance of continuing preventative measures to prevent COVID infection

Apicella M, et al. COVID-19 in people with diabetes: understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol. 2020:8;782-92.

Resources

https://professional.diabetes.org/content-page/covid-19

Thank You!