Intact GLP-1 Levels as a Predictor of Type 2 Diabetes Risk in an Indonesian Population

Introduction

Understanding the physiological determinants of type 2 diabetes mellitus (T2DM) is vital for developing preventive and therapeutic strategies. Among these, glucagon-like peptide-1 (GLP-1), an incretin hormone that enhances insulin secretion and inhibits glucagon release, has emerged as a key player in glucose homeostasis. The study by Lastya and colleagues (2014) investigated the association between fasting and post-prandial levels of intact GLP-1 and the risk of T2DM among Indonesians BioMed CentralPubMed.

Study Design & Methods

• Type: Case–control study conducted at Sanglah Hospital in Denpasar, Bali, between February and April 2014.

• Participants: 40 native Indonesian adults (aged 18–70 years), comprising 20 individuals with diagnosed T2DM and 20 controls with normal glucose tolerance (NGT) BioMed Central.

• GLP-1 Measurements:

  • Fasting intact GLP-1 (FGLP-1)

  • One hour post 75 g glucose load (1hGLP-1)

  • Change in GLP-1 (ΔGLP-1) was computed as the difference between post-load and fasting levels.

• Thresholds: Low GLP-1 levels were defined as FGLP-1 <2.21 pg/L, 1hGLP-1 <2.57 pg/L, and ΔGLP-1 <0.029 pg/L (cut-offs based on mean minus one standard deviation of NGT group) BioMed Central+2BioMed Central+2.

• Statistical Analysis: Mann–Whitney test, chi-square test, odds ratios (ORs), with significance threshold at p < 0.05 BioMed Central.

Key Findings

1. GLP-1 Levels: T2DM vs. NGT

• Fasting GLP-1: Significantly lower in T2DM (2.06 ± 0.43 pg/L) compared to NGT (2.87 ± 0.67 pg/L), p < 0.01.

• 1-hour GLP-1: Also lower in T2DM (2.49 ± 0.60 pg/L) vs. NGT (3.42 ± 0.85 pg/L), p = 0.002 BioMed Central.

2. Risk of T2DM with Low GLP-1

• Fasting GLP-1: Low FGLP-1 was observed in 60% of T2DM subjects vs. 10% of NGT; OR = 13.5 (95% CI: 2.434–74.867), p = 0.001.

• 1-Hour GLP-1: Low 1hGLP-1 occurred in 50% of T2DM vs. 15% of NGT; OR = 5.667 (95% CI: 1.254–25.606), p = 0.018 BioMed Central.

• ΔGLP-1: No significant risk association was found (OR = 1.0, p = 1.0), though T2DM subjects exhibited a slightly lower ΔGLP-1 (0.43 pg/L) compared to controls (0.55 pg/L) BioMed Central+1.

Interpretation & Context

These findings highlight that lower levels of intact GLP-1—both fasting and post-glucose stimulation—are strongly linked to elevated T2DM risk in Indonesians. This aligns with literature across diverse populations showing diminished GLP-1 responses in T2DM and pre-diabetes, likely reflecting impaired incretin secretion or increased degradation BioMed CentralPMC. Though GLP-1 response magnitude (ΔGLP-1) did not reach significance, the trend suggests potential impairments in dynamic incretin response that may warrant further investigation.

Relevance for Peptide and Incretin Research

For Coastal Peptides, the study underscores the significance of preserving active, intact GLP-1 levels for metabolic regulation:

• Diagnostic insights: Monitoring GLP-1 could help identify individuals with impaired incretin function.

• Peptide therapeutics: Strategies that enhance GLP-1 stability or mimic its activity—such as peptide analogues or DPP-4-resistant modifications—may hold promise for early intervention.

• Population-specific data: Given genetic and metabolic diversity, findings in Indonesian subjects emphasize the need for region-specific peptide research and tailored therapeutic design.

Summary Table: GLP-1 Metrics & T2DM Association

Disclaimer & References

Disclaimer: This blog post provides a research-focused summary of findings from a peer-reviewed publication and should not be construed as medical or diagnostic advice.

References:

• Lastya A, Saraswati MR, Suastika K. The low level of glucagon-like peptide-1 (GLP-1) is a risk factor of type 2 diabetes mellitus. BMC Res Notes. 2014;7:849. BioMed Central+2BioMed Central+2