Clinical trial NCT03661684: Effect of Short Course of Glucocorticoid in Patients With Diabetes Mellitus(DM) Type 2
Official title: Glucocorticoid Effects in Patients With DM Type 2
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Diabetes
Hyperglycemia Steroid-induced
Keywords: Diabetes
Glucocorticoids
Hyperglycemia
Lead sponsor: Cook County Health
Sponsor class: OTHER_GOV
First posted: 2018-09-07
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: Two groups. Condition group and Control group, both receiving the investigated medication using the same protocol
Primary purpose: BASIC_SCIENCE

Brief summary: Participants will receive prednisone 40 mg for 3 days. 75 g oral glucose tolerance test (OGTT), insulin and C-peptide will be measured on day 1 (before prednisone) and day 3 (after prednisone). Also capillary glucose values will be obtained during and after the period of prednisone intake.

Detailed description: On their scheduled day, participants will be instructed to come to the clinic after an overnight fast of a minimum of 8 hours (subjects can drink water). The participants will be asked to refrain from drinking alcohol for a period of 24 hours before the study days and to not perform strenuous exercise for a period of 48 hours before the study days. The participants will be directed to avoid alcohol and strenuous exercise for the duration of the study.

On days 1 and 3 of the study period, participants will be checked into the clinic. A physical examination, including height, weight and waist circumference, and finger-stick glucose will be performed. A 75-g OGTT will be performed with venous samples for measurement of glucose, insulin and C-peptide levels obtained at 0, 30 and 60 minutes starting immediately after the ingestion of the 75 g glucose solution. After samples are collected on day 1, participants will be administered their first dose of steroid, prednisone 40 mg, and be given a packet of two additional doses for the rest of the study period. The investigators may only give 1 additional dose to them and have the participants take the last dose in clinic on day 3 two hours before the OGTT. Subjects will take prednisone 40 mg once daily for three days to be consumed around 8:00am on days 2 and 3. This dose was chosen as a typical high-dose glucocorticoid regimen. On the third day, the participants will again visit the clinic after an overnight fast of a minimum 8 hours and undergo a physical examination and OGTT just as on day 1.

Participants will be instructed to check pre-prandial (before breakfast, lunch and dinner), and bed time (around 10:00 pm) blood glucose (BG) levels and to record all values for a total of five days (three days while on prednisone and for two days after the second study visit). A member of the study staff will call each participant daily around 7:00 pm to obtain BG values. Compliance with the study protocol will be assessed at this time as well. Any subject not compliant with study medications will be excluded from the study.

Eligibility criteria: Experimental Group

Inclusion Criteria:

1. Males or non-pregnant females between the ages of 18-50 years being followed in the Diabetes Center.
2. Type 2 Diabetes for ≤ 1 year and only on metformin
3. BMI 24.0-35.0 kg/ m2
4. HBA1c ≤ 9.0%

Exclusion Criteria:

1. Patients on any other antidiabetes medication.
2. Patients with impaired renal function (estimated Glomerular Filtration Rate (GFR) less than 60 ml/min based on results from Cerner).
3. Patient who have received glucocorticoid therapy within six months of study.
4. Patients who do shift work.
5. Blood glucose level ≥ 250 mg/dl on finger-stick at clinic visit.
6. Signs or symptoms of infection.

Control Group

Inclusion Criteria:

1. Males or non-pregnant females between the ages of 18-50 years in good physical health as determined by medical history, physical examination, and screening blood tests
2. Normoglycemia defined by fasting plasma glucose \< 5.6 mmol/L (or 100 mg/dL) and 2h glucose \<7.8 mmol/L (or 140 mg/dL) after a 75 g OGTT
3. BMI: 22.0 - 28.0 kg/m2

Exclusion Criteria:

1. Presence of any disease or use of any medication
2. Patients with a first-degree relative with Type 2 Diabetes
3. Patients who smoke
4. Patients with history of steroid use in previous 6 months.
5. Patients who do shift work
6. Signs or symptoms of infection.
7. Patients with recent changes in weight or physical activity

Primary outcomes:
measure: AUC for glucose during OGTT
timeFrame: Throughout the course of 3 days
Secondary outcomes:
measure: HOMA index
timeFrame: At day 1 and at day 3
measure: AUC for Insulin during OGTT
timeFrame: Throughout the course of 3 days
Other outcomes:
Locations:
Study officials:
References:
citation: Donihi AC, Raval D, Saul M, Korytkowski MT, DeVita MA. Prevalence and predictors of corticosteroid-related hyperglycemia in hospitalized patients. Endocr Pract. 2006 Jul-Aug;12(4):358-62. doi: 10.4158/EP.12.4.358.
citation: Hwang JL, Weiss RE. Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment. Diabetes Metab Res Rev. 2014 Feb;30(2):96-102. doi: 10.1002/dmrr.2486.
citation: van Raalte DH, Brands M, van der Zijl NJ, Muskiet MH, Pouwels PJ, Ackermans MT, Sauerwein HP, Serlie MJ, Diamant M. Low-dose glucocorticoid treatment affects multiple aspects of intermediary metabolism in healthy humans: a randomised controlled trial. Diabetologia. 2011 Aug;54(8):2103-12. doi: 10.1007/s00125-011-2174-9. Epub 2011 May 12.
citation: Shah M, Adel MM, Tahsin B, Guerra Y, Fogelfeld L. Effect of short-term prednisone on beta-cell function in subjects with type 2 diabetes mellitus and healthy subjects. PLoS One. 2020 May 5;15(5):e0231190. doi: 10.1371/journal.pone.0231190. eCollection 2020.