One in Six Billion (Andrew Hattersley and Maggie Shepherd)

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In this episode Andrew and Maggie are joined by Emma Matthews. Emma talks about her son Jack who was diagnosed with diabetes when 2 weeks old. Jack’s life was transformed when a genetic cause was found for his diabetes.

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In this episode Maggie and Andrew talk to Anna Gloyn, the  scientist who discovered the gene that was altered when very young babies were diagnosed with neonatal diabetes.  

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In this episode we hear about how sulphonylurea tablets were discovered to be an unexpected. and remarkably effective, new treatment for neonatal diabetes. 

Maggie and Andrew talk to Professor Ewan Pearson, the  doctor scientist, who worked with doctors around the world to prove how good this treatment was and how it worked.

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In this special episode Maggie Shepherd talks with co-presenter Andrew Hattersley exploring what led to him ending up as a research scientist and diabetes consultant in Exeter in 1995.  They go back into how he became a doctor and what took him into research including surprising revelations about a transformative time in Africa as an 18-year-old!  

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In this episode we hear from Agnes Graja and Helen John, two of the national team of Genetic Diabetes Nurses that spread the news about neonatal diabetes across the UK. They identified and improved treatment in insulin-treated adults who had been diagnosed with diabetes in the first 6 months of life.

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In this episode, we hear from Laurie and Mike Jaffe from Chicago, USA.  They spread the word about neonatal diabetes to over 100M people around the world by an inspirational media campaign focused on their daughter, Lilly and how the diagnosis and resulting treatment change transformed her life. 

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In this episode Maggie and Andrew talk to Dame Frances Ashcroft the remarkable Oxford scientist who has dedicated her life to understanding the key role of potassium channel in insulin secretion by the pancreatic beta-cell.  Her work was crucial both before and after the Exeter genetic discovery in neonatal diabetes

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In this episode, Maggie and Andrew talk to Dr Pam Bowman, the doctor scientist, whose research has greatly advanced our understanding of neonatal diabetes. Pam showed treatment with sulphonylurea tablets control the glucose excellently in the long term and she transformed our understanding of how thinking, and development are altered by the change in the potassium channel gene.

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In this episode, Maggie and Andrew start by talking to Carsyn Underwood and her mums Karla and Donna about Carsyn’s diagnosis of neonatal diabetes and how she got the right treatment very early and had an the excellent outcome as a result,.  

They go on to talk to Professor Tim McDonald, a top NHS laboratory scientist, who has been researching into how we can make sure everyone is diagnosed early by developing universal screening for neonatal diabetes in the first week of life.

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In this episode, Maggie and Andrew talk to Dr Elisa De Franco, the Exeter based genetic scientist whose research has discovered more genetic causes of diabetes than anyone else in the world.

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In this special episode Andrew Hattersley talks with co-presenter Maggie Shepherd to identify what led to her joining the Exeter team in 1995 and ending up becoming the leading nurse for monogenic diabetes with a role combining clinical care, research and education 

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In this episode, Maggie and Andrew talk to Imran Bashir about the difficult journey he and his family have been on since his daughter was born without a pancreas.  They also hear from star scientist Dr Elisa De Franco about the long and challenging scientific journey to solve the genetic mystery of why her pancreas did not develop.

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In this special episode, we hear from Professor Sian Ellard who, like Andrew and Maggie, started in Exeter in 1995.  Sian set up the Exeter molecular genetics laboratory from scratch.  Through Sian’s leadership, this laboratory became world leading for both research and NHS diagnostic testing.

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In this special episode, we hear from Professor Tim Frayling who was Andrew and Sian’s first PhD student in 1995. He rapidly became the head of the analysis for the genetic susceptibility for Type 2 diabetes.  His leadership has made Exeter an international leader in polygenic trait genetics.

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We talk to Tim Frayling and Rachel Freathy about how they discovered the “Fat gene”.  Working with Oxford, the Exeter team showed a genetic change near FTO predisposed to obesity. This was the first and largest common genetic change altering weight.

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Moira Murphy and Mark McCarthy talk about how a unified UK team of scientists came to be world leaders in decoding the genetic susceptibility to Type 2 diabetes.

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Jean Dudderidge and Jill Epton talk about what it has been like to live with Type 1 diabetes for over 50 years. They discuss the massive advances in the measurement of blood sugar over the decades and how they now benefit greatly from continuous glucose monitoring.

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Professor Partha Kar has made sure the technical advances in measuring blood sugar are available to everyone living with Type 1 diabetes in the UK.  Partha had to overcame massive hurdles to make sure the technology was not just available to a privileged few. He discusses with Maggie and Andrew his inspirational leadership style and philosophy that have helped him to move mountains in the NHS.

Vote for One in Six Billion in the British Podcast Awards: https://www.britishpodcastawards.com/voting

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Professor Richard Oram had the innovative idea of turning complex analysis of the genetic changes  into a single number that estimate the likelihood of developing Type 1 diabetes. He explains to Andrew and Maggie how this has helped diagnosis of Type 1 diabetes and is being used around the world in studies aiming to prevent or delay diabetes in children.

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We hear from Mendy Korer about the enormous challenges of living with a child who was diagnosed with Type 1 diabetes aged 11 months. Matt Johnson, a research fellow in Exeter talks about his exciting work understanding what makes the immune system destroy the insulin making beta-cells in very young children. 

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Dr Jean Claude Katte explains how in Sub Saharan Africa diagnosis, treatment and monitoring of Type 1 diabetes in children and young adults is so much harder than in Europe.  He discusses with Maggie and Andrew his own exciting research that has shown that around 60% of African children with diabetes do not have the typical autoimmune Type 1 diabetes seen in over 90% of children with diabetes in Europe. Jean Claude aims to do more research to discover what causes this new cause of severe young-onset diabetes in Sub Saharan Africa.

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Simon Goode was diagnosed with Type 2 diabetes aged 28.  He explains how it took 6 months of feeling unwell before it was realised he had Type 1 diabetes instead. Exeter Professor, Angus Jones, has done research showing that mistakes in the diagnosis Type of 1 diabetes are common in the older adult and offers solutions to help doctors get the diagnosis right. 

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Dr Nick Thomas talks about Type 1 diabetes in the older adult. In an iconoclastic study he showed most cases of Type 1 diabetes occur in adults rather than children. In older adults it is very hard to recognise as 98-99% of people with diabetes have Type 2 diabetes. Older adults with Type 1 diabetes have just as rapid a decline in their own insulin and need all the expert care offered to children. 

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Mary Humphries tells how her son Dan was diagnosed with diabetes aged 16 and it was assumed he had type 1 diabetes and treated with insulin.  On insulin he had terrible problems with low blood sugars frequently losing consciousness and not managing to concentrate at school or at home.  Mary was very worried that he was getting worse on the insulin and asked about genetic tests because she had recently been diagnosed with Type 2 diabetes and there was diabetes in all generations of her family.  She was not listened to; the insulin was continued, and Dan got worse.  Searching the internet for answers she found the Exeter diabetesgenes.org website which led her to talking to Andrew and Maggie. 

They were able to rapidly diagnose that this was Maturity-onset Diabetes of the Young (MODY), subtype HNF1A . with a genetic test.   Maggie  helped Dan to stop his insulin and get excellent control on a quarter of the sulphonylurea tablet called gliclazide.  Dan rapidly improved off the insulin and passed his A levels with flying colours going to Bristol where he achieved his life’s ambition to become a large animal vet.  

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Kevin Colclough describes how the genetic testing in diabetes has improved over the 2 decades he has worked in the Exeter NHS diagnostic lab.  His work means now over 60 types of single gene diabetes are looked for in one sequencing test. Bev Shields talks about how she developed the amazing MODY calculator that uses common clinical characteristics to work out how likely a person with diabetes is to have maturity onset diabetes of the young (MODY).

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Mary Lee was thought to have Type 1 diabetes for over 3 decades; she was finally diagnosed with HNF1A MODY and was able to stop her insulin injections and get excellent blood sugar control with a sulphonylurea tablet.  We hear from Ewan Pearson how sulphonylurea tablets were found to be excellent glucose lowering treatment when Andrew’s clinical observations of his HNF1A MODY patients were followed up by Ewan with a clinical trial.

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In this episode we talk to Janette and her daughter Alice who were both correctly diagnosed with HNF4A MODY having been initially told they had Type 1 diabetes. The diagnosis not only allowed them to stop insulin but also explained the mystery of two of Jeanette’s children that were born as large babies and collapsed soon after birth with low blood sugar. Andrew explains how it was discovered that babies that inherited the HNF4A genetic change were on average over 800g heavier and were at high risk of low blood glucose around birth

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In this episode we talk to Andrew Lotery about how he was found to have a raised fasting glucose on an insurance medical. He was treated as Type 2 diabetes but he questioned this as he was young. slim and physically fit. A chance reading of a research funder’s newsletter led him to the Exeter team and a diagnosis of glucokinase MODY.  

Amanda Stride worked as a research registrar in Exeter.  She showed that in glucokinase MODY the fasting glucose was raised from birth and remained stable and regulated throughout life with treatment not changing the blood glucose. 

Anna Steele showed in her PhD that patients with glucokinase MODY did not get complications affecting the eye or kidney even after 50 years of raised glucose.  So in glucokinase MODY treatment with insulin or tablets is not needed and does not work; patients should be discharged and not followed up.

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It was a great surprise for Gill Preston, who was active and slim, when she was diagnosed with gestational diabetes in her first pregnancy. Her raised fasting glucose did not come down with tablets or insulin. Luckily she met Andrew Hattersley in the diabetes pregnancy clinic, who recognised she had glucokinase MODY. Gill Spyer, working for her PhD as a research doctor showed that in glucokinase pregnancy the size of the baby depended on whether they inherited the genetic change from the mother and was not altered by insulin treatment. When the baby had the mutation it would grow normally and no treatment of the mother was needed. Ali Chakera continued research into glucokinase pregnancy; his research showed that slim women ( BMI <25) with a raised fasting glucose of above 5.5mmol/l had a 1 in 3 chance of having GCK MODY and should be tested. He also looked into genetic testing the fetus directly rather than trying to infer from fetal growth on ultrasound.

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Natalie Raphael was diagnosed as having glucokinase MODY at the end of her first pregnancy. In her second pregnancy she had a recently introduced blood test that showed her fetus had not inherited her change in the glucokinase gene so was at risk of growing large. As a result of this she was given long-acting insulin to lower her glucose.  Alice Hughes is the researcher who did the key study that proved the new blood test was both practical and accurate in glucokinase pregnancy.

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Grant King talks about his diagnostic journey where his low birth weight, childhood kidney disease, diabetes, liver dysfunction and infertility were at 32 years finally recognised as all being due to a change in the HNF1Beta gene. Dr Coralie Bingham explains how her research during her PhD in Exeter led to HNF1Beta being established as the commonest cause of inherited kidney disease and all the key parts of the HNF1Beta syndrome being recognised.

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Ru Kovvuri explains about her battle to get a diagnosis and support for her daughter who had multiple medical problems and learning difficulties as a result of a deletion of the HNF1B gene. Rhian Clissold discusses her research to improve the diagnosis of the HNF1B syndrome and recognise the associated learning difficulties seen with loss (deletion)  but not the spelling mistakes (mutations) in the HNF1B gene.

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Julie Reynolds describes how she gradually lost her hearing in her 30’s and developed diabetes in her 40’s these 2 conditions also developed in in her mother, her children and other maternal relative. This led to a diagnosis of maternally inherited diabetes and deafness that results from a change in the mitochondrial DNA.  Kash Patel explains the science between diabetes, deafness and a maternal inheritance and why there is a lot of variation in the presence and severity of clinical features

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We talk to John Dennis, a data science researcher working in the University of Exeter. He used data from 1 million people with Type 2 diabetes to discover how the clinical characteristics of a patient alter the glucose lowering with different treatments. John’s 5 drug model, published in the Lancet in late February 2025, uses simple clinical information to identify, for the first time, the best glucose lowering treatment for a patient.  The model selected best treatment lowers the glucose most, doubles  the time before another medication is needed and reduces long term complications of diabetes. See www.1in6b.com for more details. 

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Rebecca Goodman talks to Andrew and Maggie about what it is like to grow up with Bardet-Biedl syndrome. Features of Bardet-Biedl syndrome include extra fingers and toes, progressive blindness, kidney problems, obesity due to an uncontrolled appetite, insulin resistance and diabetes. Despite this long list of medical issues Rebecca lives independently and enjoys a full and fun life.