By Dr Shivani Misra, Honorary Clinical Research Fellow, Faculty of Medicine, Department of Medicine
This Diabetes Week, it’s important to remember that there are more than just two types of diabetes and how global insights into ethnic-specific types can benefit local people with diabetes.
Most people have heard of the two main types of diabetes. Type 1 diabetes is caused by destruction of the beta-cells that make insulin in the pancreas. Without insulin injections, people with type 1 diabetes are at risk of a life-threatening complication called diabetic ketoacidosis, where the blood gradually becomes acidic due to the accumulation of ketones. Type 2 diabetes is different and is primarily related to insulin resistance; the beta-cells make insulin, but the body tissues don’t respond to it appropriately. Type 2 diabetes can initially be managed with tablets.
In the past you could be pretty sure that if a person presented to hospital with diabetic ketoacidosis, this meant they had type 1 diabetes and needed lifelong insulin. We had all learnt this from textbooks at medical school – that the dangerous complication of ketoacidosis only occurred when there was no insulin in the body and therefore should not be seen in people with type 2 diabetes, who continue to make insulin. But what if we were wrong? What if there was another type of diabetes – not quite type 1, not quite type 2, somewhere between the two?
Findings that challenged conventional wisdom
The textbook teaching was thrown out the window when reports first emerged in 1987(1) and later in 1994, from Flatbush, New York (2). Authors of this key publication described a strange type of diabetes, in which young people of African-American heritage presented with diabetic ketoacidosis and needed insulin injections, just like you’d expect in type 1 diabetes. However, unlike type 1 diabetes, over the ensuing months, they were gradually able to stop insulin and in some cases the diabetes went away completely.
This fascinating report shook the diabetes world to its core! OK, well maybe not to the core, but there were ripples.… the truth was that many diabetologists all over the world had seen this type of presentation, but weren’t necessarily sure how to classify it. It couldn’t be type 2 diabetes (they had ketoacidosis!) and it definitely didn’t fit with type 1 diabetes (they didn’t need long-term insulin!).
Understanding diabetes around the world
Doctors in Sub-Saharan Africa had reported a similar type of diabetes – insulin-requiring at first, but gradually not needing insulin and in many cases managing off all treatment for years to come.
The definitive study came from Paris, where doctors at one of the main hospitals had observed the same type of diabetes in Sub-Saharan African migrants and followed them up for 10 years (3). They found that in 76% of people insulin could be stopped, however after 10 years, 90% of the people studied had relapsed – either with ketoacidosis or by progressively becoming diabetic again. They called it ketosis-prone type 2 diabetes, recognising the overlapping features of type 1 and type 2 diabetes.
The diagnosis is tricky and needs specialist input
We now know much more about ketosis-prone type 2 diabetes (KPDM). We see it often within our diabetes service at Imperial College Healthcare NHS Trust, in people of African-Caribbean heritage, but it has also been described in all other ethnic groups.
Critically, the diagnosis can only really be made in retrospect, so everyone newly presenting to hospital with diabetic ketoacidosis should always be treated as a person with type 1 diabetes UNTIL PROVEN OTHERWISE.
In our London diabetes service, we frequently review people with suspected KPDM from a variety of ethnic groups and undertake specialist tests, whilst monitoring closely. Decisions around the best treatment are always made by a diabetes specialist team – this is really important as if the wrong decision is made, insulin could be stopped inappropriately, with life-threatening consequences.
The Imperial experience
There is much to learn about why people with KPDM seesaw in and out of diabetes and are at risk of developing ketoacidosis, even though they still make insulin. Many research groups are working to address these questions around the world, including at Imperial. We’ve reached out to other clinical teams around London to try to harmonise how we look after people with suspected KPDM. Our team also reviewed KPDM in this paper, if you want more information(4).
We’re also working hard to describe in detail all the different types of diabetes that can be encountered in those with young-onset diabetes from African-Caribbean and south Asian heritage, via the MY DIABETES study, which recruits at over 35 sites around the country. We’re using this information to better classify diabetes types in different ethnic groups and preliminary results should be published soon.
So, what have we learnt?
Every day we advance our understanding of different types of diabetes and how they present. Sometimes we have to look globally to gain a greater understanding of what we see locally. There are many different types of diabetes (more than I’ve discussed here!) and classifying them appropriately ensures that affected individuals get the right treatment, which is of course, the goal.
For me (someone researching different diabetes types), the concept of KPDM has been a game-changer as it has unravelled and exposed our knowledge gaps in how diabetes progresses and presents. The more people with diabetes we see, the more we learn and there is much, still, to learn!
Winter WE, Maclaren NK, Riley WJ, Clarke DW, Kappy MS, Spillar RP. Maturity-onset diabetes of youth in black Americans. N Engl J Med. 1987;316(6):285–91.
Banerji MA, Chaiken RL, Huey H, Tuomi T, Norin AJ, Mackay IR, et al. GAD Antibody Negative NIDDM in Adult Black Subjects with Diabetic Ketoacidosis and Increased Frequency of Human Leukocyte Antigen DR3 and DR4: Flatbush Diabetes. Diabetes. 1994 Jun 1;43(6):741 LP-745.
Mauvais-Jarvis F, Sobngwi E, Porcher R, Riveline J-P, Kevorkian J-P, Vaisse C, et al. Ketosis-Prone Type 2 Diabetes in Patients of Sub-Saharan African Origin. Diabetes. 2004 Mar 1;53(3):645 LP-653.
Misra S, Oliver N, Dornhorst A. Diabetic ketoacidosis: not always due to type 1 diabetes. BMJ. 2013;346.