Red and processed meat consumption associated with higher type 2 diabetes risk, study of two million people finds

 Meat consumption, particularly consumption of processed meat and unprocessed red meat, is associated with a higher type 2 diabetes risk, an analysis of data from 1.97 million participants, published today in The Lancet Diabetes and Endocrinology, has found.

Global meat production has increased rapidly in recent decades and meat consumption exceeds dietary guidelines in many countries. Earlier research indicated that higher intakes of processed meat and unprocessed red meat are associated with an elevated risk of type 2 diabetes, but the results have been variable and not conclusive.

Poultry such as chicken, turkey, or duck is often considered to be an alternative to processed meat or unprocessed red meat, but fewer studies have examined the association between poultry consumption and type 2 diabetes.

To determine the association between consumption of processed meat, unprocessed red meat and poultry and type 2 diabetes, the team led by researchers at the University of Cambridge used the global InterConnect project to analyse data from 31 study cohorts in 20 countries. Their extensive analysis took into account factors such as age, gender, health-related behaviours, energy intake and body mass index.

The researchers found that the habitual consumption of 50 grams of processed meat a day -- equivalent to 2 slices of ham -- is associated with a 15% higher risk of developing type 2 diabetes in the next 10 years. The consumption of 100 grams of unprocessed red meat a day -- equivalent to a small steak -- was associated with a 10% higher risk of type 2 diabetes.

Habitual consumption of 100 grams of poultry a day was associated with an 8% higher risk, but when further analyses were conducted to test the findings under different scenarios the association for poultry consumption became weaker, whereas the associations with type 2 diabetes for each of processed meat and unprocessed meat persisted.

Professor Nita Forouhi of the Medical Research Council (MRC) Epidemiology Unit at the University of Cambridge, and a senior author on the paper, said:

"Our research provides the most comprehensive evidence to date of an association between eating processed meat and unprocessed red meat and a higher future risk of type 2 diabetes. It supports recommendations to limit the consumption of processed meat and unprocessed red meat to reduce type 2 diabetes cases in the population.

While our findings provide more comprehensive evidence on the association between poultry consumption and type 2 diabetes than was previously available, the link remains uncertain and needs to be investigated further."

InterConnect uses an approach that allows researchers to analyse individual participant data from diverse studies, rather than being limited to published results. This enabled the authors to include as many as 31 studies in this analysis, 18 of which had not previously published findings on the link between meat consumption and type 2 diabetes. By including this previously unpublished study data the authors considerably expanded the evidence base and reduced the potential for bias from the exclusion of existing research.

Lead author Dr Chunxiao Li, also of the MRC Epidemiology Unit, said:

"Previous meta-analysis involved pooling together of already published results from studies on the link between meat consumption and type 2 diabetes, but our analysis examined data from individual participants in each study. This meant that we could harmonise the key data collected across studies, such as the meat intake information and the development of type 2 diabetes.

Using harmonised data also meant we could more easily account for different factors, such as lifestyle or health behaviours, that may affect the association between meat consumption and diabetes. "

Professor Nick Wareham, Director of the MRC Epidemiology Unit, and a senior author on the paper said:

"InterConnect enables us to study the risk factors for obesity and type 2 diabetes across populations in many different countries and continents around the world, helping to include populations that are under-represented in traditional meta-analyses.

Most research studies on meat and type 2 diabetes have been conducted in USA and Europe, with some in East Asia. This research included additional studies from the Middle East, Latin America and South Asia, and highlighted the need for investment in research in these regions and in Africa.

Using harmonised data and unified analytic methods across nearly 2 million participants allowed us to provide more concrete evidence of the link between consumption of different types of meat and type 2 diabetes than was previously possible."

InterConnect was initially funded by the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no 602068.

Story Source:

Materials provided by University of Cambridge. The original text of this story is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Note: Content may be edited for style and length.

Journal Reference:

1. Chunxiao Li et al. Meat consumption and incident type 2 diabetes: an individual-participant federated meta-analysis of 1·97 million adults with 100 000 incident cases from 31 cohorts in 20 countries. The Lancet Diabetes & Endocrinology, 2024 DOI: 10.1016/S2213-8587(24)00179-7

Courtesy:

University of Cambridge. "Red and processed meat consumption associated with higher type 2 diabetes risk, study of two million people finds." ScienceDaily. ScienceDaily, 20 August 2024. <www.sciencedaily.com/releases/2024/08/240820221808.htm>.

A switch for immune memory and anti-tumor immunity

 A Ludwig Cancer Research study has identified a metabolic switch in the immune system's T cells that is essential to the generation of memory T cells -- which confer lasting immunity to previously encountered pathogens -- and a T cell subtype found in tumors that drives anti-tumor responses during immunotherapy.

Led by Ludwig Lausanne's Ping-Chih Ho and Alessio Bevilacqua and published in the current issue of Science Immunology, the study identifies PPARβ/δ, a master regulator of gene expression, as that essential molecular switch. Ho, Bevilacqua and their colleagues also show that the switch's dysfunction compromises T cell "memory" of previously encountered viruses as well as the induction of anticancer immune responses in mice.

"Our findings suggest that we might be able to engage this switch pharmacologically to improve the efficacy of cancer immunotherapies," said Ho.

When killer (or CD8+) T cells, which kill sick and cancerous cells, are activated by their target antigen, they switch on metabolic pathways that most other healthy cells only use when starved of oxygen. This type of metabolism -- involving a metabolic process known as aerobic glycolysis -- supports multiple processes essential to the killer T cell's ability to proliferate and destroy its target cells.

Most killer T cells die off after they've cleared an infection. A few, however, transform into central memory CD8+ T cells (Tcms) that linger in the circulation to establish what we call immunity: the ability to mount a swift and lethal response to the same pathogen if it is ever encountered again. To achieve this transformation, T cells switch off aerobic glycolysis and otherwise adapt their metabolism to persist over the long term in tissues or in the circulation. How precisely they do this was until now unknown.

Aware that PPARβ/δ activates many of the metabolic processes characteristic of Tcms, Ho, Bevilacqua and their colleagues hypothesized it might play a key role in Tcm formation. They examined immunologic gene expression data collected from yellow fever vaccine recipients long after vaccination and, as expected, saw that the PPARβ/δ was produced abundantly in their Tcms.

Their studies in mice revealed that PPARβ/δ is activated in T cells not in the peak phase of the immune response to viral infection but as that response winds down. Further, CD8+ T cells were unable to make the metabolic switch required to become circulating Tcms if they failed to express PPARβ/δ. Disrupting its expression impaired survival of such Tcms and resident memory T cells in the intestines following infection.

The researchers show that T cell exposure to interleukin-15 -- an immune factor important for Tcm formation -- and their expression of a protein named TCF1 engages the PPARβ/δ pathway. TCF1 is already known to be critical to the rapid expansion of Tcms when they encounter their target pathogen. The researchers show in this study that it is also important to the maintenance of TCMs.

As it happens, TCF1 expression is a hallmark of a subset of CD8+ T cells -- progenitor-exhausted T cells -- that are found in tumors. These progenitor-exhausted T cells follow one of two paths: they either become completely lethargic, "terminally exhausted" T cells; or, given the appropriate stimulus, proliferate to produce "effector" CD8+ T cells that kill cancer cells. Checkpoint blockade immunotherapies, like anti-PD-1 antibodies, can provide such stimulus.

The observation that TCF1 modulates the PPARβ/δ pathway in T cells raised the possibility that it might also be essential to the formation and maintenance of progenitor-exhausted T cells. The researchers showed that this is indeed the case. Deleting the PPARβ/δ gene from T cells led to the loss of progenitor-exhausted T cells in a mouse model of melanoma. They also demonstrate that the PPARβ/δ pathway curtails the tendency of progenitor-exhausted T cells to stagger toward terminal exhaustion.

To assess the therapeutic potential of their findings, Ho, Bevilacqua and their colleagues exposed T cells to a molecule that stimulates PPARβ/δ activity and used the treated cells against a mouse model of melanoma. These cells delayed the growth of melanoma tumors in mice more efficiently than their untreated counterparts and bore biochemical hallmarks of progenitor exhausted T cells primed to generate cancer-killing descendants.

"Based on these findings," said Bevilacqua, "we suggest that targeting PPARβ/δ signaling may be a promising approach to improve T cell-mediated anti-tumor immunity.

How exactly this might be achieved in people is a subject for further study that will doubtless be pursued by the Ho laboratory.

This study was supported by Ludwig Cancer Research, the Swiss National Science Foundation, the European Research Council, the Swiss Cancer Foundation, the Cancer Research Institute, Helmut Horten Stiftung, the Melanoma Research Alliance, the Taiwan Ministry of Science and Technology, the NYU Abu Dhabi Research Institute Award and Academia Sinica.

Ping-Chih Ho is a member of the Lausanne Branch of the Ludwig Institute for Cancer Research and a full professor at the University of Lausanne.

Story Source:

Materials provided by Ludwig Institute for Cancer Research. Note: Content may be edited for style and length.

Journal Reference:

1. Alessio Bevilacqua, Fabien Franco, Ya-Ting Lu, Nabil Rahiman, Kung-Chi Kao, Yu-Ming Chuang, Yanan Zhu, Werner Held, Xin Xie, Kristin C. Gunsalus, Zhengtao Xiao, Shih-Yu Chen, Ping-Chih Ho. PPARβ/δ-orchestrated metabolic reprogramming supports the formation and maintenance of memory CD8 + T cells. Science Immunology, 2024; 9 (98) DOI: 10.1126/sciimmunol.adn2717

Courtesy:

Ludwig Institute for Cancer Research. "A switch for immune memory and anti-tumor immunity." ScienceDaily. ScienceDaily, 23 August 2024. <www.sciencedaily.com/releases/2024/08/240823185109.htm>.