MedicalResearch.com Interview with:
Jolanta U Weaver, FRCP MRCS PhD CTLHE
Senior Lecturer in Diabetes Medicine
Honorary Consultant Diabetologist
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Vascular stem cells, which are associated with an improvement of heart disease, are improved in type 1 diabetes by repurposing metformin, known to reduce heart disease in type 2 diabetes.
We treated patients with type 1 diabetes with metformin for 8 weeks. The metformin dose varied between 500 mg a day to 2000 mg a day, depending on what patients were happy to take. Subjects were requested to keep diabetic control unchanged to study the direct effect of metformin on heart disease. Circulating endothelial progenitor cells (vascular stem cells) count, Hill’s colonies and pro angiogenic cells function (in test tube) improved in comparison to patients, who did not take metformin but remained on standard therapy.
Endothelial cells associated with vascular damage, on the other hand, were reduced following metformin therapy confirming improved vascular health. The glycaemic control remained unchanged (as planned at the onset of the study) to allow us to examine the effect of metformin ALONE on vascular health. Patients did not suffer any serious side effects.
MedicalResearch.com: How does metformin work to lower blood sugar levels and protect the heart?
Response: Metformin reduces glucose release from the liver. However this study was not about lowering glucose level but about improving heart disease in type 1 diabetes beyond the effect of metformin on glucose levels. We aimed to keep blood glucose levels unchanged to study the effect of metformin ALONE on stem cells, important in heart disease. Patients were requested to adjust dose of insulin to keep glucose levels safe and unchanged. In fact most of patients on metformin reduced the dose of insulin in comparison to patients in standard therapy group (insulin injections and insulin pumps)
How metformin works to protect the heart is currently unknown but actively studied by our group. Previous work was done in test tube and animals but at high doses of metformin, patients would not be able to tolerate.
Recently we have published in February 2016, in Cardiovascular Diabetology, that physiological concentrations of metformin improved new blood vessels formation in test tube by increasing expression of VEGFA ( pro-angiogenic factor) in CD34+ cells (stem cells from the cord blood used for treatment of acute heart attack) and inhibition of angiogenic inhibitors: chemokine (C-X-C Motif) ligand 10 (CXCL10) and tissue inhibitor of metalloproteinase 1 (TIMP1).
MedicalResearch.com: Is Metformin well tolerated?
Response: Metformin needs to be commenced slowly from 500 mg a day and gradually increased after 2 weeks to 1000 mg a day etc. to avoid gastrointestinal side effects. Some patients may be able to tolerate only a very small dose of metformin. The improvement in cEPCs and other indicators of vascular health was seen even at the low doses of metformin used by our patients. Patients with eGFR< 45 should not be commenced on metformin as when patients eGFR is reduced further ( usually during inter-current illness, infections, dehydration etc) there is a risk of lactic acidosis.
MedicalResearch.com: What’s the most important thing people with type 1 diabetes need to know from your study?
Response: Addition of metformin to insulin therapy has NOT been shown in our study to be associated with any serious side effects. However careful adjustment of insulin doses is required to avoid hypoglycemia. Starting metformin therapy needs to be slow to avoid side effects.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We are following up our patients but large randomized trials are required to examine the outcome of CVD in type 1 diabetes following metformin therapy.
MedicalResearch.com: Is there anything else you’d like to add?
Response: We have shown both in test tube and in patients the mechanism behind the cardioprotective effects of metformin. This is likely to lead to development of new drugs for heart disease in diabetes.
Cardiovasc Diabetol. 2016 Aug 26;15(1):116. doi: 10.1186/s12933-016-0413-6.
Metformin improves circulating endothelial cells and endothelial progenitor cells in type 1 diabetes: MERIT study.
Ahmed FW1,2, Rider R1, Glanville M2, Narayanan K1, Razvi S1,3, Weaver JU4,5.
Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.
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