Fat over-spills from the liver into the pancreas trigger Type 2 diabetes

For the first time, scientists have been able to observe people developing type 2 diabetes - and confirmed that fat over-spills from the liver into the pancreas, triggering the chronic condition.
The research, led by Professor Roy Taylor at Newcastle University, UK, is published in the academic journal, Cell Metabolism.

The study involved a group of people from Tyneside who previously had Type 2 diabetes but had lost weight and successfully reversed the condition as part of the DiRECT trial, which was funded by Diabetes UK and led by Professors Roy Taylor and Mike Lean (Glasgow University).

The majority remained non-diabetic for the rest of the two year study, however, a small group went on to re-gain the weight and re-developed Type 2 diabetes.

Professor Roy Taylor, from the Newcastle University Institute of Translational and Clinical Research, explained what the advanced scanning techniques and blood monitoring revealed.

He said:We saw that when a person accumulates too much fat, which should be stored under the skin, then it has to go elsewhere in the body. The amount that can be stored under the skin varies from person to person, indicating a 'personal fat threshold' above which fat can cause mischief.

When fat cannot be safely stored under the skin, it is then stored inside the liver, and over-spills to the rest of the body including the pancreas. This 'clogs up' the pancreas, switching off the genes which direct how insulin should effectively be produced, and this causes Type 2 diabetes."

This research by Professor Taylor confirms his Twin Cycle Hypothesis - that Type 2 diabetes is caused by excess fat actually within both the liver and pancreas, and especially that this process is reversible.

Body of research

This latest paper builds on previous Newcastle studies supported by Diabetes UK showing exactly why Type 2 diabetes can be reversed back to normal glucose control. Those studies led to the large DiRECT trial which showed that Primary Care staff can achieve remission of Type 2 diabetes by using a low calorie diet with support to maintain the weight loss.

A quarter of participants achieved a staggering 15 kg or more weight loss, and of these, almost nine out of 10 people put their Type 2 diabetes into remission. After two years, more than one third of the group had been free of diabetes and off all diabetes medication for at least two years.

In 2020, this approach to management of short duration Type 2 diabetes is to be piloted in the NHS in up to 5,000 people across England, and a similar program is being rolled out in Scotland.

Professor Taylor adds:This means we can now see Type 2 diabetes as a simple condition where the individual has accumulated more fat than they can cope with. 

Importantly this means that through diet and persistence, patients are able to lose the fat and potentially reverse their diabetes. The sooner this is done after diagnosis, the more likely it is that remission can be achieved."

The team are continuing work to establish what may affect an individual's personal threshold and are supporting the roll out of the NHS Initiatives in both England and Scotland. 'Life Without Diabetes - The definitive guide to understanding and reversing your Type 2 diabetes' by Professor Roy Taylor will be published by Short Books on 26th December 2019.

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Now, reversible antiplatelet therapy to fight clotting, cancer metastasis

Now, a new study published on Wednesday says that a reversible, drug-free antiplatelet therapy could reduce the risk of blood clots and potentially prevent cancer metastasis.

The therapeutic approach involves modifying human platelets to create "decoys" that are still capable of binding to some cells but will not aggregate or carry out the other normal platelet functions, including chemical signalling associated with the clotting process.

Speaking about it, lead author  said, “The reversibility and immediate onset of action are major advantages of our platelet decoys, and we envision them to be useful in hospital-based situations."

She added, "The therapy could prevent clotting in high-risk patients just before they undergo surgery, or be given to cancer patients alongside chemotherapy to prevent existing tumors from spreading."

While platelets play a vital role in halting bleeding and help protecting against minor and life-threatening bleeding, hyperactive platelets can also contribute to various disorders, including severe blood clots, heart disease and cancer.

While several anti-platelet drugs fight clots, their effects are not easily reversible, leaving patients vulnerable if they develop unexpected severe bleeding or are in need of an emergency surgical procedure.

Platelets also play an important part in cancer metastasis by binding to tumour cells and protecting them both from the body's immune system and shear stress as they circulate in the bloodstream. They may also help the cancer cells exit through blood vessels and seed distant tissues during the process of metastasis.

In their journey towards creating decoy platelets, the research team used a detergent treatment and centrifugation to strip natural human platelets of their inner structures and remove their basic activation and aggregation abilities.

These decoy platelets became about one-third the size of a regular platelet while retaining a majority of adhesion receptors on their surface. This allows them to bind to other cells in the bloodstream, such as cancer cells, but not become active during the blood clotting process.

The researchers, first examined how the decoys might impede the formation of blood clots. The team injected the decoys into a microfluidic blood-vessel-mimicking device and observed how the decoys reacted to various platelet-stimulating chemicals.

They found the decoys did not show typical clotting behaviours, and when added to human blood within the device, the normal platelets showed a reduced ability to aggregate and create a clot by binding to the vessel's walls. Furthermore, the researchers quickly reversed the effects of the decoys on normal platelets by introducing fresh platelets into the blood.

Dr. said, “Our ability to reverse the platelet inhibiting effects with a simple reintroduction of normal platelets is very encouraging as currently available anti-platelet agents are often difficult to reverse in emergency settings such as severe bleeding.”

Based on the key role platelets play in supporting cancer metastasis in the bloodstream, the team sought to target circulating tumour cells with their cellular approach. The decoy platelets were able to compete with normal platelets when binding to cancer cells and were effective in preventing cancer cell extrusion out of a vasculature-emulating microfluidic chip model.

Furthermore, in a model of metastasis, there was a significant reduction in the burden of established metastatic tumours when cancer cells were introduced simultaneously with platelets and decoys. 

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Red meat may increase levels of chemical linked with heart disease

New research has found that eating a diet high in red meat could increase levels of trimethylamine N-oxide (TMAO), a chemical generated in the gut and linked to a higher risk of heart disease.

Carried out by researchers at Cleveland Clinic and the National Heart, Lung, and Blood Institute (NHLBI), the small-scale study looked at 113 healthy men and women to see whether different sources of dietary protein -- red meat, white meat, or non-meat sources -- had different effects on TMAO production. 

Participants followed each of the three diets for one month, with the red meat diet including roughly the equivalent of about 8 ounces of steak daily, or two quarter-pound beef patties, daily. The findings, showed that participants who ate a diet rich in red meat had triple the TMAO levels of those who eat a diet rich in either white meat or mostly plant-based proteins.

However, the good news is that the effect was reversible, with the researchers finding that removing red meat from the diet and switching to either a white meat or non-meat diet for another month significantly lowered the TMAO levels.

TMAO is formed by gut bacteria during digestion and comes partly from nutrients that which are found in red meat.

Although the high level of saturated fat in red meat is known to contribute to heart disease, which is the leading cause of death in the United States, a number of new studies now suggest that TMAO may also increase the risk of the condition. 
 
"This study shows for the first time what a dramatic effect changing your diet has on levels of TMAO, which is increasingly linked to heart disease," said senior author. "It suggests that you can lower your heart disease risk by lowering TMAO."
 
"These findings reinforce current dietary recommendations that encourage all ages to follow a heart-healthy eating plan that limits red meat," added study author. "This means eating a variety of foods, including more vegetables, fruits, whole grains, low-fat dairy foods, and plant-based protein sources such as beans and peas."

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