Glucose-lowering in type 2 diabetes may be mediated by improved proinsulin processing without better β-cell compensation.
Ravi Retnakaran, Junwei Shen, Mihir Parikh et al.
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In 30 seconds
This randomized controlled trial evaluated the role of proinsulin processing in glucose-lowering among 90 adults with type 2 diabetes (mean A1c 6.5%). Participants received different insulin treatments over 8 weeks. Results showed that A1c levels decreased significantly with improved proinsulin processing, while beta-cell compensation remained unchanged. The fasting proinsulin-to-C-peptide ratio was identified as a key mediator of A1c treatment effects.
Key findings
- A1c levels decreased from 6.5% to 6.2%, 5.9%, and 5.8% across treatment groups (P = 0.007).
- Fasting proinsulin-to-C-peptide ratio decreased from 0.013 to 0.009 and 0.008 (P = 0.01).
- No differences in insulin sensitivity or beta-cell compensation were observed among treatment groups.
- Fasting proinsulin-to-C-peptide ratio was the sole mediator of A1c treatment effects for Glar/Lispro and Glar/Exe.
Why it matters
Understanding the mechanisms behind glucose-lowering in type 2 diabetes is crucial for developing effective treatments. This study highlights the potential of targeting proinsulin processing as a therapeutic strategy, which may lead to improved management of glycemic control.