̽��ֱ�� of Cambridge - diabetes

Map of brain’s appetite centre could enable new treatments for obesity and diabetes

Anonymous — Wed, 05 Feb 2025 16:00:15 +0000

Published today in Nature, this comprehensive resource, called HYPOMAP, provides an unparalleled view of the brain’s appetite centre and promises to accelerate the development of treatments for obesity and type 2 diabetes.

̽��ֱ��hypothalamus is often described as the brain’s ‘control centre’, orchestrating many of the body’s most vital processes. While much of our knowledge of the hypothalamus comes from animal studies, especially in mice, translating these findings to humans has long been a challenge. HYPOMAP bridges this gap by providing an atlas of the individual cells within the human hypothalamus. This resource not only charts over 450 unique cell types but also highlights key differences between the human and mouse hypothalamus — differences that have major implications for drug development.

“This is a game-changer for understanding the human hypothalamus,” said Professor Giles Yeo, senior author of the study from the Institute of Metabolic Science-Metabolic Research Laboratories (IMS-MRL) and MRC Metabolic Diseases Unit, ̽��ֱ�� of Cambridge.

“HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity. It gives us a roadmap to develop more effective, human-specific therapies.”

Together with researchers at the Max Planck Institute for Metabolism Research in Cologne, Professor Yeo and colleagues used cutting-edge technologies to analyse over 400,000 cells from 18 human donors. HYPOMAP allows researchers to pinpoint specific cell types, understand their genetic profiles, and explore how they interact with neighbouring cells. This detailed cellular resolution offers invaluable insights into the circuits that regulate appetite and energy balance, as well as other functions such as sleep and stress responses.

Comparison with a mouse hypothalamus atlas revealed both similarities and critical differences. Notably, some neurons in the mouse hypothalamus have receptors for GLP-1 — targets of popular weight-loss drugs like semaglutide — that are absent in humans.

"While drugs like semaglutide have shown success in treating obesity, newer therapies target multiple receptors such as GLP-1R and GIPR. Understanding how these receptors function specifically in the human hypothalamus is now crucial for designing safer and more effective treatments," said Dr Georgina Dowsett from the Max Planck Institute for Metabolism Research and formerly at the IMS-MRL.

“Our map of the human hypothalamus is an essential tool for basic and translational research,” added Professor Jens C. Brüning, Director at the Max Planck Institute. “It allows us to pinpoint which mouse nerve cells are most comparable to human cells, enabling more targeted preclinical studies.”

HYPOMAP’s open-access nature ensures that it will be an invaluable resource for scientists worldwide. By offering insights into the hypothalamus’s role in conditions ranging from obesity to cachexia (a wasting condition associated with several illness, which involves extreme loss of muscle and fat), it provides a foundation for tackling some of the most pressing health challenges of our time.

Dr John Tadross, Consultant Pathologist at Addenbrooke’s Hospital and lead author from IMS-MRL, said: “This is just the beginning. ̽��ֱ��atlas itself is a milestone, but what could really make a difference for patients is understanding how the hypothalamus changes in people who are overweight or underweight. This could fundamentally shift our approach to metabolic health and enable more personalised therapies.”

With HYPOMAP, researchers have a new tool to unlock the secrets of the human brain’s metabolic control centre. By better understanding the human hypothalamus, science takes a significant step toward combating obesity, type 2 diabetes, and related conditions.

Reference
Tadross, JA, Steuernagel, L & Dowsett, GKC et al. A comprehensive spatio-cellular map of the human hypothalamus. Nature; 5 Feb 2025; DOI: 10.1038/s41586-024-08504-8

Adapted from a story by the Institute of Metabolic Science-Metabolic Research Laboratories and the Max Planck Institute for Metabolism Research

Scientists have created the most detailed map to date of the human hypothalamus, a crucial brain region that regulates body weight, appetite, sleep, and stress.

HYPOMAP confirms the critical role of the hypothalamus in body-weight regulation and has already allowed us to identify new genes linked to obesity

Giles Yeo

Sander Dalhuisen

Person holding burger bun with vegetables and meat

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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Red and processed meat consumption associated with higher type 2 diabetes risk

Anonymous — Tue, 20 Aug 2024 22:30:56 +0000

̽��ֱ��findings are published today in ̽��ֱ��Lancet Diabetes and Endocrinology.

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, a team led by researchers at the ̽��ֱ�� 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.

̽��ֱ��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. ̽��ֱ��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 ̽��ֱ�� 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.”

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

Reference
Li, C et al. Meat consumption and incident type 2 diabetes: a federated meta-analysis of 1·97 million adults with 100,000 incident cases from 31 cohorts in 20 countries. Lancet Diabetes Endocrinol.; 20 August 2024

Adapted form a press release from the MRC Epidemiology Unit

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 almost two million participants has found.

Our research supports recommendations to limit the consumption of processed meat and unprocessed red meat to reduce type 2 diabetes cases in the population

Nita Forouhi

Lauri Patterson

Preparing a Monte Cristo Sandwich, with Black Forest Ham

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‘Diabetes distress’ increases risk of mental health problems among young people living with type 1 diabetes

cjb250 — Wed, 17 Jul 2024 09:00:45 +0000

̽��ֱ��findings highlight the urgent need for monitoring and support for the mental health of young people diagnosed with type 1 diabetes.

According to the charity JDRF, there are 8.7 million people living with type 1 diabetes around the world, including over 400,000 people in the UK. It is a chronic, life-threatening condition, usually diagnosed in childhood, that has a life-long impact.

Currently, people with type 1 diabetes rely on a routine of finger-prick blood tests and insulin injections or infusions, because their pancreas no longer produces insulin itself, although recent developments in artificial pancreas technology are helping transform this care.

Previous studies have shown potential links between childhood-onset type 1 diabetes and a number of mental health disorders in adulthood. However, it is not clear whether these links can be best explained by the impacts of living with the condition and its treatment, or whether underlying common biological mechanisms may be implicated, for example the impact of unstable blood sugar levels on the developing adolescent brain.

To help answer this question, a team of researchers turned to data from over 4,500 children with type 1 diabetes on a national register in the Czech Republic and from large-scale European DNA studies.Their findings are published today in Nature Mental Health.

From the national register data, the researchers found that children diagnosed with type 1 diabetes – compared to children without the condition – were over twice as likely to develop a mood disorder and more than 50% more likely to develop an anxiety disorder. They were also more than four times more likely to develop behavioural syndromes including eating and sleep disorders

Conversely, children with type 1 diabetes were at a much lower risk of developing psychotic disorders, such as schizophrenia – almost half the risk compared to their peers.

̽��ֱ��findings are consistent with the results from two other national register studies in Sweden and in Denmark, suggesting that the results would likely apply to other countries, too, including the UK.

̽��ֱ��team used a statistical technique known as Mendelian Randomisation to probe causal links between type 1 diabetes and these various psychiatric disorders, but found little evidence in support of a common underlying biological mechanism.

Tomáš Formánek, a PhD student at the ̽��ֱ�� of Cambridge and the National Institute of Mental Health, Klecany, Czech Republic, said: “Although we found a concerning increase in the risk of mental health problems among people living with type 1 diabetes, our study – and others before it – suggests this is unlikely to be the result of common biological mechanisms. This emphasises the importance of prevention and sustained attention to the mental health needs of children and young people with type 1 diabetes.”

̽��ֱ��researchers say that mental health problems in later life may be a result of children with type 1 diabetes being forced to make significant changes to their lives, with a constant focus on monitoring their food intake and a need to check blood sugar levels and administer insulin injections. This often leaves these children feeling excluded from social events and singled-out by peers, teachers and even family members.

Dr Benjamin Perry from the Department of Psychiatry, ̽��ֱ�� of Cambridge, said: “We know that people diagnosed with type 1 diabetes can experience ‘diabetes distress’. This can include extreme frustration with blood sugars and feelings of isolation and can lead to burnout, hopelessness, and a feeling of lack of control. It’s little wonder, then, that they are at risk of compounding mental health problems, spanning into their adult lives.”

Professor Peter Jones, also from the Department of Psychiatry, ̽��ֱ�� of Cambridge, added: “Our findings emphasise the urgent need to support children diagnosed with type 1 diabetes, look out for signs of mental health problems and offer timely, expert help. That way, it may be possible to help these children early, before these problems fully take root.”

̽��ֱ��research was supported by the National Institute for Health and Care Research Applied Research Collaboration East of England at Cambridgeshire and Peterborough NHS Foundation Trust and the Ministry of Health, Czech Republic, with additional funding from Wellcome and the UKRI Medical Research Council.

Reference
Formánek, T et al. Childhood-Onset Type 1 Diabetes and Subsequent Adult Psychiatric Disorders: A Nationwide Cohort and Genome-wide Mendelian Randomization Study. Nature Mental Health; 17 July 2024; DOI: 10.1038/s44220-024-00280-8

Children diagnosed with type 1 diabetes are at significantly higher risk of a number of mental health issues, including mood and anxiety disorders, a study from a team in the UK and the Czech Republic has found.

We know that people diagnosed with type 1 diabetes can experience ‘diabetes distress’. It’s little wonder, then, that they are at risk of compounding mental health problems, spanning into their adult lives

Benjamin Perry

kyotokushige

Teenager With Type 1 Diabetes Takes at Home Test

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US Food and Drug Administration approves Cambridge-developed artificial pancreas

cjb250 — Fri, 24 May 2024 12:39:44 +0000

This means that even more people living with the disease will be able to use this life-changing app. For the first time, the FDA authorised the use of the artificial pancreas system in pregnancy.

CamAPS FX, produced by Cambridge spinout company CamDiab (www.camdiab.com), is an Android app that can be used to help manage glucose levels in people with type 1 diabetes, including during pregnancy.

̽��ֱ��app allows a compatible insulin pump and a compatible continuous glucose monitor to ‘talk to each other’, creating an artificial pancreas.

̽��ֱ��CamAPS FX closed loop algorithm was given FDA authorisation on Thursday 23 May. It had already been CE-marked for use in the UK and the EU.

CamAPS FX creator Roman Hovorka is Professor of Metabolic Technology at the Institute of Metabolic Science and Department of Paediatrics at the ̽��ֱ�� of Cambridge, where the technology was developed.

He said: "We set out to help people with type 1 diabetes and their families live better lives and we’re delighted that the FDA has reviewed the safety and effectiveness of CamAPS FX and has given the technology its approval."

"It has been extensively tested and we’re proud that it is considered by many to be the best algorithm out there."

CamAPS FX is already used by more than 27,000 people in 15 countries across Europe and Australia. Artificial pancreas systems such as CamAPS FX have been granted approval for wide use by the NHS in November 2023 by the National Institute for Health and Care Excellence (NICE).

Scientists identify how fasting may protect against inflammation

cjb250 — Tue, 30 Jan 2024 09:55:30 +0000

In research published in Cell Reports, the team describes how fasting raises levels of a chemical in the blood known as arachidonic acid, which inhibits inflammation. ̽��ֱ��researchers say it may also help explain some of the beneficial effects of drugs such as aspirin.

Scientists have known for some time that our diet – particular a high-calorie Western diet – can increase our risk of diseases including obesity, type 2 diabetes and heart disease, which are linked to chronic inflammation in the body.

Inflammation is our body’s natural response to injury or infection, but this process can be triggered by other mechanisms, including by the so-called ‘inflammasome’, which acts like an alarm within our body’s cells, triggering inflammation to help protect our body when it senses damage. But the inflammasome can trigger inflammation in unintentional ways – one of its functions is to destroy unwanted cells, which can result in the release of the cell’s contents into the body, where they trigger inflammation.

Professor Clare Bryant from the Department of Medicine at the ̽��ֱ�� of Cambridge said: “We’re very interested in trying to understand the causes of chronic inflammation in the context of many human diseases, and in particular the role of the inflammasome.

“What's become apparent over recent years is that one inflammasome in particular – the NLRP3 inflammasome – is very important in a number of major diseases such as obesity and atherosclerosis, but also in diseases like Alzheimer's and Parkinson's disease, many of the diseases of older age people, particularly in the Western world.”

Fasting can help reduce inflammation, but the reason why has not been clear. To help answer this question, a team led by Professor Bryant and colleagues at the ̽��ֱ�� of Cambridge and National Institute for Health in the USA studied blood samples from a group of 21 volunteers, who ate a 500kcal meal then fasted for 24 hours before consuming a second 500kcal meal.

̽��ֱ��team found that restricting calorie intake increased levels of a lipid known as arachidonic acid. Lipids are molecules that play important roles in our bodies, such as storing energy and transmitting information between cells. As soon as individuals ate a meal again, levels of arachidonic acid dropped.

When the researchers studied arachidonic acid’s effect in immune cells cultured in the lab, they found that it turns down the activity of the NLRP3 inflammasome. This surprised the team as arachidonic acid was previously thought to be linked with increased levels of inflammation, not decreased.

Professor Bryant, a Fellow of Queens’ College, Cambridge, added: “This provides a potential explanation for how changing our diet – in particular by fasting – protects us from inflammation, especially the damaging form that underpins many diseases related to a Western high calorie diet.

“It’s too early to say whether fasting protects against diseases like Alzheimer's and Parkinson's disease as the effects of arachidonic acid are only short-lived, but our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction. It suggests that regular fasting over a long period could help reduce the chronic inflammation we associate with these conditions. It's certainly an attractive idea.”

̽��ֱ��findings also hint at one mechanism whereby a high calorie diet might increase the risk of these diseases. Studies have shown that some patients that have a high fat diet have increased levels of inflammasome activity.

“There could be a yin and yang effect going on here, whereby too much of the wrong thing is increasing your inflammasome activity and too little is decreasing it,” said Professor Bryant. “Arachidonic acid could be one way in which this is happening.”

̽��ֱ��researchers say the discovery may also offer clues to an unexpected way in which so-called non-steroidal anti-inflammatory drugs such as aspirin work. Normally, arachidonic acid is rapidly broken down in the body, but aspirin stops this process, which can lead to an increase in levels of arachidonic acid, which in turn reduce inflammasome activity and hence inflammation.

Professor Bryant said: “It’s important to stress that aspirin should not be taken to reduce risk of long terms diseases without medical guidance as it can have side-effects such as stomach bleeds if taken over a long period.”

̽��ֱ��research was funded by Wellcome, the Medical Research Council and the US National Heart, Lung, and Blood Institute Division of Intramural Research.

Reference
Pereira, M & Liang, J et al. Arachidonic acid inhibition of the NLRP3 inflammasome is a mechanism to explain the anti-inflammatory effects of fasting. Cell Reports; 23 Jan 2024; DOI: 10.1016/j.celrep.2024.113700

Cambridge scientists may have discovered a new way in which fasting helps reduce inflammation – a potentially damaging side-effect of the body’s immune system that underlies a number of chronic diseases.

Our work adds to a growing amount of scientific literature that points to the health benefits of calorie restriction

Clare Bryant

Carol Yepes (Getty Images)

Intermittent fasting conceptual image

Yes

“Incredible” diabetes management app now recommended by NICE

cg605 — Tue, 07 Nov 2023 16:22:48 +0000

̽��ֱ��National Institute for Health and Care Excellence (NICE) has today (7 November 2023) recommended hybrid closed loop systems including the CamAPS FX app for use in managing type 1 diabetes, meaning that even more people living with the disease will be able to use this life-changing app.

Type 2 diabetes diagnosis at age 30 can reduce life expectancy by up to 14 years

cjb250 — Tue, 03 Oct 2023 09:00:51 +0000

Even people who do not develop the condition until later in life – with a diagnosis at age 50 years – could see their life expectancy fall by up to six years, an analysis of data from 19 high-income countries found.

̽��ֱ��researchers say the findings, published in ̽��ֱ��Lancet Diabetes & Endocrinology, highlight the urgent need to develop and implement interventions that prevent or delay onset of diabetes, especially as the prevalence of diabetes among younger adults is rising globally.

Increasing levels of obesity, poor diet and increased sedentary behaviour are driving a rapid rise in the number of cases of type 2 diabetes worldwide. In 2021, 537 million adults were estimated to have diabetes worldwide, with an increasing number diagnosed at younger ages.

Type 2 diabetes increases an individual’s risk of a range of complications including heart attack and stroke, kidney problems, and cancer. Previous estimates have suggested that adults with type 2 diabetes die, on average, six years earlier than adults without diabetes. There is uncertainty, however, about how this average reduction in life expectancy varies according to age at diagnosis.

To answer this question, a team led by scientists at the ̽��ֱ�� of Cambridge and ̽��ֱ�� of Glasgow examined data from two major international studies – the Emerging Risk Factors Collaboration and UK Biobank – comprising a total of 1.5 million individuals.

̽��ֱ��earlier an individual was diagnosed with type 2 diabetes, the greater the reduction in their life expectancy. Overall, every decade of earlier diagnosis of diabetes was associated with about four years of reduced life expectancy.

Using data from US population it was estimated that, individuals with type 2 diabetes diagnosed at ages 30, 40, and 50 years died on average about 14, 10, and 6 years earlier, respectively, than individuals without the condition. These estimates were slightly higher in women (16, 11, and 7 years, respectively) than they were in men (14, 9, and 5 years, respectively).

̽��ֱ��findings were broadly similar in analyses using EU data, with corresponding estimates being about 13, 9, or 5 years earlier death on average.

Professor Emanuele Di Angelantonio from the Victor Phillip Dahdaleh Heart and Lung Research Institute (VPD-HLRI), ̽��ֱ�� of Cambridge, said: “Type 2 diabetes used to be seen as a disease that affected older adults, but we’re increasingly seeing people diagnosed earlier in life. As we’ve shown, this means they are at risk of a much shorter life expectancy than they would otherwise have.”

Dr Stephen Kaptoge, also from the VPD-HLRI, said: “Type 2 diabetes can be prevented if those at greatest risk can be identified and offered support – whether that’s to make changes to their behaviour or to provide medication to lower their risk. But there are also structural changes that we as a society should be pursuing, including relating to food manufacturing, changes to the built environment to encourage more physical activity, and so on.

“Given the impact type 2 diabetes will have on people’s lives, preventing – or at least delaying the onset – of the condition should be an urgent priority.”

̽��ֱ��researchers found that the majority of the reduction in life expectancy associated with diabetes was due to ‘vascular deaths’ – deaths related to conditions such as heart attack, stroke and aneurysms. Other complications such as cancer also contributed to lowering life expectancy.

Professor Naveed Sattar from the Institute of Cardiovascular & Medical Sciences, ̽��ֱ�� of Glasgow, added: “Our findings support the idea that the younger an individual is when they develop type 2 diabetes, the more damage their body accumulates from its impaired metabolism. But the findings also suggest that early detection of diabetes by screening followed by intensive glucose management could help prevent long-term complications from the condition.”

̽��ֱ��Cambridge team was supported by the Medical Research Council, British Heart Foundation, Health Data Research UK and NIHR Cambridge Biomedical Research Centre.

Reference
Emerging Risk Factors Collaboration. Life expectancy associated with different ages at diagnosis of diabetes: 23 million person-years of observation. Lancet Diabetes & Endocrinology; 11 Sept 2023; DOI: 10.1016/S2213-8587(23)00223-1

An individual diagnosed with type 2 diabetes at age 30 years could see their life expectancy fall by as much as 14 years, an international team of researchers has warned.

Given the impact type 2 diabetes will have on people’s lives, preventing – or at least delaying the onset – of the condition should be an urgent priority

Stephen Kaptoge

Elva Etienne (Getty Images)

Man using blood sugar measurement device to monitor diabetes - stock photo

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

Yes

DNA discovery highlights how we maintain healthy blood sugar levels after meals

cjb250 — Thu, 08 Jun 2023 15:00:48 +0000

̽��ֱ��findings, published today in Nature Genetics, could help inform future treatments of type 2 diabetes, which affects around 4 million people in the UK and over 460 million people worldwide.

Several factors contribute to an increased risk of type 2 diabetes, such as older age, being overweight or having obesity, physical inactivity, and genetic predisposition. If untreated, type 2 diabetes can lead to complications, including eye and foot problems, nerve damage, and increased risk of heart attack and stroke.

A key player in the development of the condition is insulin, a hormone that regulates blood sugar – glucose – levels. People who have type 2 diabetes are unable to correctly regulate their glucose levels, either because they don’t secrete enough insulin when glucose levels increase, for example after eating a meal, or because their cells are less sensitive to insulin, a phenomenon known as ‘insulin resistance’.

Most studies to date of insulin resistance have focused on the fasting state – that is, several hours after a meal – when insulin is largely acting on the liver. But we spend most of our time in the fed state, when insulin acts on our muscle and fat tissues.

It’s thought that the molecular mechanisms underlying insulin resistance after a so-called ‘glucose challenge’ – a sugary drink, or a meal, for example – play a key role in the development of type 2 diabetes. Yet these mechanisms are poorly-understood.

Professor Sir Stephen O’Rahilly, Co-Director of the Wellcome-MRC Institute of Metabolic Science at the ̽��ֱ�� of Cambridge, said: “We know there are some people with specific rare genetic disorders in whom insulin works completely normally in the fasting state, where it’s acting mostly on the liver, but very poorly after a meal, when it’s acting mostly on muscle and fat. What has not been clear is whether this sort of problem occurs more commonly in the wider population, and whether it’s relevant to the risk of getting type 2 diabetes.”

To examine these mechanisms, an international team of scientists used genetic data from 28 studies, encompassing more than 55,000 participants (none of whom had type 2 diabetes), to look for key genetic variants that influenced insulin levels measured two hours after a sugary drink.

̽��ֱ��team identified new 10 loci – regions of the genome – associated with insulin resistance after the sugary drink. Eight of these regions were also shared with a higher risk of type 2 diabetes, highlighting their importance.

One of these newly-identified loci was located within the gene that codes for GLUT4, the critical protein responsible for taking up glucose from the blood into cells after eating. This locus was associated with a reduced amount of GLUT4 in muscle tissue.

To look for additional genes that may play a role in glucose regulation, the researchers turned to cell lines taken from mice to study specific genes in and around these loci. This led to the discovery of 14 genes that played a significant role in GLUT 4 trafficking and glucose uptake – with nine of these never previously linked to insulin regulation.

Further experiments showed that these genes influenced how much GLUT4 was found on the surface of the cells, likely by altering the ability of the protein to move from inside the cell to its surface. ̽��ֱ��less GLUT4 that makes its way to the surface of the cell, the poorer the cell’s ability to remove glucose from the blood.

Dr Alice Williamson, who carried out the work while a PhD student at the Wellcome-MRC Institute of Metabolic Science, said: “What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work – and in particular how, when these mechanisms go wrong, they can lead to common diseases such as type 2 diabetes.”

Given that problems regulating blood glucose after a meal can be an early sign of increased type 2 diabetes risk, the researchers are hopeful that the discovery of the mechanisms involved could lead to new treatments in future.

Professor Claudia Langenberg, Director of the Precision Healthcare ̽��ֱ�� Research Institute (PHURI) at Queen Mary ̽��ֱ�� of London and Professor of Computational Medicine at the Berlin Institute of Health, Germany, said: “Our findings open up a potential new avenue for the development of treatments to stop the development of type 2 diabetes. It also shows how genetic studies of dynamic challenge tests can provide important insights that would otherwise remain hidden.”

̽��ֱ��research was supported by Wellcome, the Medical Research Council and the National Institute for Health and Care Research.

Reference
Williamson, A et al. Genome-wide association study and functional characterisation identifies candidate genes for insulin-stimulated glucose uptake. Nat Gen; 8 June 2023; DOI: 10.1038/s41588-023-01408-9

A study of the DNA of more than 55,000 people worldwide has shed light on how we maintain healthy blood sugar levels after we have eaten, with implications for our understanding of how the process goes wrong in type 2 diabetes.

What’s exciting about this is that it shows how we can go from large scale genetic studies to understanding fundamental mechanisms of how our bodies work

Alice Williamson

eak_kkk (Pixabay)

Cola

̽��ֱ��text in this work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. Images, including our videos, are Copyright © ̽��ֱ�� of Cambridge and licensors/contributors as identified. All rights reserved. We make our image and video content available in a number of ways – as here, on our main website under its Terms and conditions, and on a range of channels including social media that permit your use and sharing of our content under their respective Terms.

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