Experimental Hyperglycemia for Type 1 Diabetes

Overseen By Anjali Kumar, PA-C

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Minnesota

Must be taking: Insulin

Must not be taking: Glucocorticoids, Niacin

Disqualifiers: Pregnancy, Hypertension, Neuropathy, Retinopathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

50 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will explore the cerebral mechanisms of impaired awareness of hypoglycemia (IAH) in type 1 diabetics following exposure to experimental recurrent hypoglycemia (HG). To induce IAH, patients with T1D identified to have normal awareness of hypoglycemia (NAH) will undergo three 2-hour long hypoglycemic clamps. Neurochemical profiles will be measured by high field MRS before and after induction of IAH. Subject glycemic variability and activity/sleep for 1 week before each study will be monitored as all factors have been shown to alter responses to HG.

Will I have to stop taking my current medications?

The trial requires that you stop taking drugs that can alter glucose metabolism, like glucocorticoids and niacin, but you can continue using insulin and other glucose-lowering drugs for diabetes.

Is there any safety data available for experimental hyperglycemia treatment in type 1 diabetes?

The safety of SGLT2 inhibitors, which are sometimes used in type 1 diabetes, has been systematically evaluated, but they are controversial due to potential risks. Long-term safety data for basal insulins in type 1 diabetes is limited, though some studies have been conducted. ^{1 2 3 4 5}

How does the treatment for experimental hyperglycemia in type 1 diabetes differ from other treatments?

This treatment is unique because it involves inducing hyperglycemia (high blood sugar) experimentally to study its effects, unlike standard treatments that aim to control or reduce blood sugar levels. It may help understand how hyperglycemia affects insulin resistance and beta-cell function in type 1 diabetes. ^{6 7 8 9 10}

Research Team

Elizabeth R Seaquist, MD

Principal Investigator

University of Minnesota

Eligibility Criteria

This trial is for people with Type 1 diabetes who've had it for 2-30 years and have a Hemoglobin A1C below 8.5%. It's not for those pregnant, with uncontrolled high blood pressure, substance abuse issues, unable to undergo MRI scans due to various reasons like claustrophobia or having certain implants, over 300 lbs., or with a history of serious heart conditions, depression requiring hospitalization, arrhythmias in the last five years.

Inclusion Criteria

Your average blood sugar level (Hemoglobin A1C) is less than 8.5%.

I have had diabetes for 2 to 30 years.

I have been diagnosed with Type 1 diabetes.

Exclusion Criteria

Unable to complete all study visits or procedures, as determined by the investigator

I am not taking medication that affects my blood sugar, except for diabetes treatment.

I have symptoms like dizziness when standing up or slow stomach emptying.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-study Monitoring

Participants' glycemic variability and activity/sleep are monitored for 1 week before each study

1 week

Induction of Hypoglycemia

Participants undergo three 2-hour long hypoglycemic clamps to induce impaired awareness of hypoglycemia

6 hours

Neurochemical Measurement

Neurochemical profiles are measured by high field MRS before and after induction of impaired awareness of hypoglycemia

1 session

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Experimental hyperglycemia

Trial Overview The study tests how repeated low blood sugar episodes affect the brain's ability to detect hypoglycemia in Type 1 diabetics. Participants will experience controlled low blood sugar events while their brain responses are monitored using advanced imaging techniques.

Participant Groups

Group I: 300 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 300 mg/dL

Group II: 225 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 225 mg/dL

Group III: 150 mg/dL Experimental Treatment 1 Intervention

Hyperglycemia target of 150 mg/dL

Who Is Running the Clinical Trial?

University of Minnesota

Lead Sponsor

Trials

1,459

Recruited

1,623,000+

Findings from Research

SGLT2 inhibitors significantly lower key diabetes markers in type 1 diabetes patients, including glycated hemoglobin (HbA1c) and fasting plasma glucose, while also reducing body weight and total insulin dosage, based on a meta-analysis of 16 randomized controlled trials involving 7192 patients.

Importantly, the use of SGLT2 inhibitors does not increase the risk of hypoglycemia, urinary tract infections, or diarrhea, suggesting they can be safely integrated into treatment regimens for type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials. Nan, J., Wang, D., Zhong, R., et al.[2023]

A study analyzing FDA Adverse Event Reporting System data from January 2013 to March 2022 found that different DPP-4 inhibitors have varying risks for serious side effects, such as acute kidney injury and pemphigoid, which can guide treatment choices for diabetes patients.

Specifically, alogliptin showed a significantly lower risk of acute kidney injury compared to sitagliptin, but a higher risk of pemphigoid, highlighting the importance of selecting the appropriate DPP-4 inhibitor based on a patient's specific health concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System. Ogura, T., Shiraishi, C.[2023]

Incretin-based therapies, including DPP-4 inhibitors and GLP-1 receptor agonists, provide effective glycemic control in type 2 diabetes with lower rates of hypoglycemia compared to other diabetes medications, based on a review of 112 clinical trials lasting at least 26 weeks.

The most common side effects were infections for DPP-4 inhibitors and gastrointestinal issues for GLP-1 receptor agonists, but serious concerns like pancreatitis and thyroid tumors were rare, indicating a favorable safety profile, though long-term safety monitoring is still necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of incretin-based therapies in type 2 diabetes. Evans, M., Bain, SC., Vora, J.[2019]

In a study of patients with type 1 diabetes, those using insulin glargine 300 U/mL (IG300) and insulin degludec (ID) showed similar long-term safety and efficacy compared to those continuing with insulin glargine 100 U/mL (IG100), with low rates of severe hypoglycemia and stable HbA1c levels over an average follow-up of 1.1 to 1.6 years.

Patients on IG100 experienced higher rates of severe adverse events and mortality (1.95%) compared to those on IG300 (0.7%) and ID (0.8%), suggesting that IG300 and ID may offer better safety profiles for long-term management of type 1 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatment with New Basal Insulin Analogues in Type 1 Diabetes: Nation-Wide Survey. Svensson, AM., Ekelund, J., Miftaraj, M., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Sodium glucose cotransporter2 inhibitors for type 1 diabetes mellitus: A meta-analysis of randomized controlled trials. [2023]

2. New Zealand pubmed.ncbi.nlm.nih.gov

Comparison of Adverse Events Occurred During Administration of Dipeptidyl Peptidase-4 Inhibitor in Patients with Diabetes Using FDA Adverse Event Reporting System. [2023]

3. England pubmed.ncbi.nlm.nih.gov

A systematic review of the safety of incretin-based therapies in type 2 diabetes. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatment with New Basal Insulin Analogues in Type 1 Diabetes: Nation-Wide Survey. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Predictors of Hypoglycemia in the ASPIRE In-Home Study and Effects of Automatic Suspension of Insulin Delivery. [2018]

6. China pubmed.ncbi.nlm.nih.gov

[Evaluation of insulin resistance in type 1 diabetes with euglycemic-hyperinsulinemic clamp]. [2014]

7. United States pubmed.ncbi.nlm.nih.gov

Control of insulin secretion during fasting hyperglycemia in adult diabetics and in nondiabetic subjects during infusion of glucose. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Iatrogenic Hyperinsulinemia, Not Hyperglycemia, Drives Insulin Resistance in Type 1 Diabetes as Revealed by Comparison With GCK-MODY (MODY2). [2020]

9. United States pubmed.ncbi.nlm.nih.gov

In praise of the hyperglycemic clamp. A method for assessment of beta-cell sensitivity and insulin resistance. [2019]

10. Scotland pubmed.ncbi.nlm.nih.gov

Diazoxide-induced long-term hyperglycemia. I. Preservation of B-cell insulin-releasing capacity. [2018]