The dangers of early-onset type 2 diabetes

Type 2 diabetes is increasingly being diagnosed among people under the age of 40. Early-onset diabetes is associated with an increased risk of complications and requires more intensive intervention, according to Professor Melanie Davies, speaking at the recent Primary Care Diabetes Europe Conference in Barcelona. Dr Susan Aldridge reports.

Professor Davies, Consultant Diabetologist at University Hospitals, Leicester, noted that early-onset type 2 diabetes is being described in different ways. In Leicester, their youngest type 2 diabetes patient is only eight years old, but early-onset may also refer to type 2 diabetes in those aged 18 to 25, or diagnosed in someone under the age of 40. “However early-onset type 2 diabetes is described, we know that it represents a different phenotype from later-onset type 2 diabetes,” she said. “If diagnosed under the age of 40, type 2 diabetes has worse outcomes.” 

She referred to a ‘fairly typical’ case study, who has obesity, hypertension, polycystic ovary syndrome (PCOS) and acanthosis nigricans. “This is the scary reality for people living with early-onset type 2 diabetes,” she said. “Obesity is almost always a comorbidity. Around half present with hypertension, one in four have PCOS and half have acanthosis nigricans.” 

Early-onset type 2 diabetes is now on the increase in most regions of the world, bringing a worrying burden of complications and premature mortality. A recent paper based on data from the Swedish Diabetes Registry shows that younger age at diagnosis of type 2 diabetes worsens outcomes for cardiovascular disease, including acute myocardial infarction and heart failure, and for chronic kidney disease. “So age at diagnosis is prognostically important for survival and cardiovascular risk,” said Professor Davies. “This has implications for the timing and intensity of interventions. We need to approach this group differently and more proactively.” 

The TODAY study

In 2004, The National Institute of Diabetes and Digestive and Kidney Diseases in the US set up a study to find the best way of treating early-onset type 2 diabetes, with an initial 699 participants aged between 10 and 17 years. The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study compared metformin, metformin plus rosiglitazone and metformin plus intensive lifestyle intervention. This showed that metformin therapy is inadequate, beta cell decline is rapid and response to intensive lifestyle interventions is minimal in this group. “Although there is some fantastic data here, it is also really very sad when you look at the incidence of complications in this study,” said Professor Davies. 

TODAY showed that some young people already have complications at baseline and these were set to get worse over time. The second phase of the TODAY study was published in 2021 and involved 500 participants diagnosed with early-onset type 2 diabetes at a mean age of 13 and followed up for 13 years, by which time two-thirds had hypertension, over half had dyslipidaemia and over half had diabetic kidney disease. Meanwhile, 32% had neuropathy and 51% had retinopathy, which had increased from 13% in 2011. In summary, by the age of 26, 50% of this population had one complication and 28.4% had at least two.   

The study also showed that young women with type 2 diabetes had 260 pregnancies. Only 13.5% were using contraception and 65% experienced pregnancy complications. One-quarter of the pregnancies was lost pre-term, and there was a very high incidence of small or large offspring. So the TODAY findings so far show that this cohort with early-onset type 2 diabetes has a very high risk for poor outcomes overall.  

A different approach

Professor Davies and colleagues have been doing their own research on early-onset type 2 diabetes in Leicester. For example, they have just published some data on depression in this population. “Those diagnosed around age 20 have a high level of depression and diabetes distress, and less self-compassion,” said Professor Davies. “Self-compassion is a good predictor of outcomes, so we need to get better at boosting self-compassion.” 

Their research showed that heart function was already impaired in people with early-onset type 2 diabetes, independent of obesity. The team has also carried out a study among people in their early 40s, offering either routine care, a DiRECT-type low-calorie diet or supervised exercise training. The exercise arm, but not the diet arm, showed an improvement in diastolic dysfunction. “So we are now doing an ongoing study,” said Professor Davies. “These people are asymptomatic, but may already have markers of early diastolic dysfunction. We need to be thinking about early interventions to address that.”

However, when it comes to choosing interventions, there is an issue with the evidence base. People in the younger age groups account for less than 5% of participants in diabetes clinical trials. In cardiorenal trials, the proportion drops to 0.97% and is not much higher in trials of lifestyle interventions and self-management. “This means that much of the evidence we base our practice on is not from people in these younger age groups,” noted Professor Davies.  

She recalled speaking about early-onset type 2 diabetes back in 2013 and observing that this group is ‘under-screened, under-supported and under-treated’. “I am not sure that things have really moved on since 2013,” she said. In the UK, recent audit data showed that take-up of care processes and the evidence base around early-onset type 2 is still poor. “The traditional outpatient clinic approach is not appropriate,” she continued. “We need to engage more around activity, psychological support and community. We also need to look at the way we build cities and work in schools.” 

To this end, Professor Davies’ team has a programme grant now in its second year, which involves the design of a new approach in Leicester, with multi-site interventional development to address multimorbidity in early-onset type 2 diabetes. “I think we really need to grasp this challenge of early-onset type 2 diabetes,” she concluded. “It is continuing to increase and those affected have a higher burden of complications and worse outcomes.” 

Any opinions expressed in this article are the responsibility of the EASD e-Learning Programme Director, Dr Eleanor D Kennedy.