Carbs vs. fat vs. protein: Which one triggers more insulin release?

• Carbohydrate intake has long been known to affect blood sugar levels, resulting in insulin release by pancreatic cells more than other nutrients.
• Novel laboratory research now suggests that individuals might actually exhibit unique insulin responses to different nutrients, with some showing larger reactions to proteins or fats.
• It’s unclear if the findings translate to living humans, but experts are optimistic that further clinical research will enhance personalized nutrition strategies for managing blood sugar.

A groundbreaking study published in Cell Metabolism has shed new light on how different macronutrients — carbohydrates , proteins, and fats—might affect insulin secretion.

The study examined insulin responses in pancreatic islets from deceased human donors with and without type 2 diabetes , as well as stem cell-derived pancreatic islets.

Pancreatic islets are small clusters of pancreatic cells, including beta cells , crucial in regulating blood sugar levels by producing hormones like insulin and glucagon in response to nutrient intake.

It has long been understood that carbohydrates significantly contribute to blood sugar levels, prompting insulin release, while proteins have a moderate effect, and fats have minimal immediate impact.

However, this study suggests that insulin secretion in response to nutrients may actually be more complex and individualized than previously believed.

For the first time, researchers identified subsets of human pancreatic islets exhibiting larger insulin responses to proteins or fats than carbohydrates.

Although lab studies on pancreatic islets might not directly translate to living humans, the findings could greatly influence future personalized nutrition strategies for better blood sugar management , ultimately improving overall health outcomes.

The effects of each macronutrient on insulin responses

Researchers at the University of British Columbia studied how human pancreatic islets secrete insulin in response to different nutrients.

Between 2016 and 2022, the researchers examined pancreatic islets from 140 deceased donors of various ages, including those with and without type 2 diabetes.

They exposed the islets to glucose (carbohydrates), amino acids (proteins), and fatty acids (fats) while monitoring insulin secretion.

The researchers also analyzed gene expression changes in pancreas cells from donors with and without type 2 diabetes to understand their impact on insulin production.

Using ribonucleic acid (RNA) sequencing and proteomics analysis, they measured over 20,000 messenger RNAs (mRNAs) and around 8,000 proteins. This helped them to evaluate the link between insulin production and changes in gene expression in the pancreatic islet samples.

Macronutrients produce unique insulin responses in pancreatic cells

Aligned with current understanding, most donors’ islets showed the strongest insulin response to glucose, a moderate response to amino acids, and little response to fatty acids.

As expected, compared to islets from donors without diabetes, islets from donors with type 2 diabetes had fewer insulin-producing beta cells, a delay in their peak insulin time in response to high glucose, and a lower insulin response to glucose overall.

While much of the findings were anticipated, there were some surprising results.

About 9% of donors’ pancreatic islets responded more strongly to proteins than carbohydrates, and 8% responded more strongly to fats.

Islets that reacted more to proteins often came from donors with type 2 diabetes but had similar long-term blood sugar levels (measured by HbA1c ) as others. However, this heightened protein response was linked to longer lab culture times.

On the other hand, islets that reacted more to fats were usually from donors with worse HbA1c levels but were otherwise similar to other donors. The researchers suggest this reaction to fat might be due to beta cell immaturity, as observed in immature stem cell-derived islet cells.

In exploring the source of the variations, they compared donor characteristics and found no differences based on body mass index (BMI) or age. However, they did observe sex differences in insulin responses.

Specifically, compared to males, female donor islets secreted less insulin in response to moderate glucose exposure, meaning their cells were not as efficient in producing insulin.

This might be due to known sex differences in diabetes , but the underlying reasons have yet to be determined.

Overall, the results suggest that insulin responses to different nutrients may vary among individuals. However, the authors note that it’s unclear if this variability is actually due to natural differences in pancreatic islet cell responses or if adaptations to lab conditions were behind the differences.

Notably, they did not observe the same level of varied responses to different macronutrients in male and female mouse pancreatic islets of various ages. This potentially lends support to the idea that lab conditions may have influenced the responses of human islets.

How might the findings apply to living humans?

Medical News Today spoke with Jason Fung, MD , a physician and New York Times bestselling author of The Obesity Code and The Diabetes Code, who was not involved in the study.

Discussing the potential relevance to living humans, Fung remarked, “Deceased donors are presumed to be reflective of the general population. It’s a reasonable assumption, but not necessarily true.”

Thomas M. Holland, MD, MS , a physician-scientist and assistant professor at the RUSH Institute for Healthy Aging, RUSH University, College of Health Sciences, who was also not involved in the study, provided further details.

“[T]he study’s findings from pancreatic islets of deceased donors offer sincerely valuable insights into insulin production in response to different macronutrients [but] there are limitations when translating these findings directly to living humans,” he told MNT.

The environment in living bodies, including factors like blood flow, hormone levels for signaling, and nervous system interactions, can affect insulin response and might differ from the “isolated” beta-islet cell environment. While the study highlights the variability among individuals, living humans experience additional influences such as lifestyle factors like diet, stress, and physical activity that can further modulate our insulin responses.
— Thomas M. Holland, MD, MS

“Additionally, deceased donors may not perfectly represent the healthy population, especially if they had underlying health conditions that might have influenced pancreatic function,” he pointed out.

The study authors, too, acknowledged limitations in applying their findings, such as the lack of confirmed type 2 diabetes diagnoses in organ donors and the absence of any human clinical trials to support their findings.

They hope their research will inspire clinical studies involving larger and more diverse groups, enhancing the applicability of their results to real-world settings.

What are the implications for practitioners and the public?

“The findings from this research open the door for the possibility of a more customized dietary care plan for diabetes treatment,” said Sheri Gaw, RDN, CDCES , a registered dietitian, certified diabetes care and education specialist, and owner of The Plant Strong Dietitian, who was not involved in the study.

Fung also emphasized that this study’s findings could hold significant importance for dietary choices.

“Insulin can cause weight gain, and for most people, cutting refined carbs is a very good method of reducing insulin and provoking weight loss. But for some people, a low fat diet may be more effective,” he explained.

The study authors, on the other hand, proposed that protein-rich diets could benefit individuals with type 2 diabetes based on their findings. However, they emphasized the need for further research.

Ultimately, “traditional diabetes diets focus on controlling carbs, based on the well-established link between glucose and insulin secretion, specifically refined grains and sugar,” but this study suggests the need for personalized approaches based on individual insulin responses to different macronutrients, said Holland.

“The difference is largely genetically determined, as pointed out by the study,” Fung agreed.

To this point, Gaw said, “In the future, there may be genetic tests that a practitioner can use to determine a macronutrient ratio that is best for an individual’s insulin response.”

In the meantime, Holland advises individuals to follow current dietary guidelines with a willingness to make adjustments. Work closely with your primary care physician or registered dietitian to identify the dietary patterns and lifestyle changes that best support your unique needs for maintaining healthy blood sugar levels and optimal health.