Reduced GLP-1 Precedes Type 2 Diabetes Development

Only Diabetes Duration Tied to Microvascular Events
Only Diabetes Duration Tied to Microvascular Events
Reduction in glucagon-like peptide-1 (GLP-1) is not necessarily a consequence of type 2 diabetes but occurs earlier in disease development.

Reduction in the glucose-regulating hormone glucagon-like peptide-1 (GLP-1) appears to occur before the development of type 2 diabetes and obesity, according to research published in Diabetes.

“We have found that GLP-1 is reduced by up to 25% among people with prediabetes and up to 20% among obese people compared to normal-weight people. This indicates that the reduction in GLP-1 is not a consequence of type 2 diabetes, but appears much earlier in the disease development and may predispose people to type 2 diabetes,” study investigator Kristine Færch, PhD, senior research fellow at the Steno Diabetes Center in Gentofte, Denmark, said in a press release.

Dr. Færch and colleagues evaluated GLP-1 response to oral glucose in a large study population of lean and obese men and women with normal and impaired glucose regulation. Using an oral glucose tolerance test (OGTT), circulating concentrations of glucose, insulin and GLP-1 were assessed in participants with normal glucose tolerance (n=774), prediabetes (n=523) or screen-detected type 2 diabetes (n=163) from the Danish ADDITION-PRO study (n=1,462).

Results showed that GLP-1 response to an OGTT was 25% lower in women with prediabetes or type 2 diabetes vs. those with normal glucose tolerance. Similarly, 120-minute GLP-1 concentrations were 16% to 21% lower for both men and women with prediabetes or type 2 diabetes, regardless of age or obesity.

In obese and overweight participants, GLP-1 response to an OGTT was 20% lower, as compared with normal-weight participants.

Data also linked higher GLP-1 responses to better insulin sensitivity and beta cell function, older age and lower degree of obesity.

“It is a novel finding,” another study investigator, Sørensen Torekov, MSc, PhD, of the University of Copenhagen, said in the release. “And what is surprising is that we have also found pronounced differences in GLP-1 secretion between men and women. We have observed a higher GLP-1 response among women than men, but when glucose tolerance worsens, the decline in GLP-1 secretion is more pronounced in women than in men.”

These results could have potential clinical implications as well, according to the researchers. For instance, principal investigator Marit Eika Jørgensen, MD, PhD, also of the Steno Diabetes Center, noted that GLP-1 analogs may help delay onset of type 2 diabetes.

“We should use the findings in prevention strategies for type 2 diabetes, and I hope to see results from longitudinal studies in the future, where we can follow the development in GLP-1 secretion over time in people who develop diabetes,” Dr. Jørgensen said in the release.


  1. Færch K et al. Diabetes. 2015;doi:10.2337/db14-1751.