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Kidney Week

Abstract: SA-PO145

Intensive Insulin Therapy Reduces Urinary Angiotensinogen in Type 1 Diabetes: A Possible Mechanism of Renoprotection via Renin Angiotensin System (RAS) Downregulation

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Ba aqeel, Sheeba Habeeb, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Sanchez, Alejandro, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Ye, Minghao, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Wysocki, Jan, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Molitch, Mark E., Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
  • Batlle, Daniel, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States
Background

Optimal glycemic control is well known to protect people with diabetes from developing kidney disease but the mechanism is unknown. Kidney angiotensinogen (AOG) gene expression has been shown to be regulated by glucose that stimulates AOG mRNA and also by insulin that inhibits glucose induced stimulation of AOG transcription in proximal tubule cells via an insulin responsive element that binds two transcription factors, hnRNP F & hnRNP K. We examined if in patients with type1 diabetes and microalbuminuria, urinary angiotensinogen (uAOG) is reduced by intensive insulin therapy. For this, we evaluated uAOG in biosamples from the Diabetes Control and Complications Trial (DCCT) participants with type1 diabetes and microalbuminuria allocated to either intensive or standard insulin therapy

Methods

Urine samples from DCCT participants provided by the NIDDK repository consisted of participants who had been allocated to intensive (n=58) or standard insulin (n=41) and had microalbuminuria at study entry. uAOG was measured after a median of 5years of therapy (range 3-6) in both groups. Patients were not taking any medications such as RAS blockers that could have influenced uAOG results. Mann-Whitney test was used to measure the differences in levels of uAOG between the two groups

Results

At the study entry, there were no significant differences in age, gender, disease duration, blood pressure, GFR, albumin excretion rate and HbA1C between the two groups. At the study visit there were again no significant differences in age, gender, disease duration, blood pressure or GFR. Albumin excretion rate was also not significantly different. HbA1c was higher in the group on standard when compared to intensive therapy (median 8.9, range 5.7-9.2 vs 7.0, 6.8-12% P<0.001). uAOG was significantly decreased in participants on intensive compared to standard therapy (median 3.98, range 0.4-96 vs 7.4, range 1.3-295ng/mg, P=0.005)

Conclusion

In type1 diabetes with microalbuminuria, intensive insulin decreases uAOG when compared to standard insulin. This suggests that optimization of glycemic control with intensive insulin, by suppressing uAOG downregulates kidney RAS overactivity and unravels an important mechanism for the well-known renoprotective effect of insulin in humans.

Funding

  • NIDDK Support