Early signs of adult type 2 diabetes visible in children as young as 8 years old, study reveals
Early signs of being more susceptible to type 2 diabetes as an adult can be seen in children as young as 8 years old, decades before it is likely to be diagnosed, according to researchers from the University of Bristol, UK, and University of Oxford, UK. The study was conducted among young people who were generally free of type 2 diabetes and other chronic diseases to see how early in life the effects of being more susceptible to adult diabetes become visible. Researchers tracked 4,761 participants in the Children of the 90s -- a health study established at the University of Bristol in the early 1990s. Also known as the Avon Longitudinal Study of Parents and Children (ALSPAC), it is a long-term health research project that enrolled more than 14,000 pregnant women in 1991 and 1992.
The team examined the effects of a genetic risk score for developing type 2 diabetes as an adult on metabolism measured from blood samples taken from the participants in the study when they were aged 8 (early childhood), 16 (adolescence), 18 (young adulthood), and 25 years (adulthood). They combined genetic information with an approach called ‘metabolomics,’ which involves measuring many small molecules in a blood sample, to try and identify patterns that are specific to early stages of type 2 diabetes development. The analysis shows that in particular, certain types of high-density lipoprotein (HDL) cholesterol -- also referred to as good cholesterol -- were reduced at age 8 before other types of cholesterol, including low-density lipoprotein (LDL, also known as bad cholesterol) were raised. Inflammation and amino acids were also elevated by 16 and 18 years old. These differences widened over time, found researchers.
The body needs cholesterol to build healthy cells, but too much can lead to a build-up in the blood vessels. Cholesterol comes in different types. High-density lipoprotein (HDL) ‘good’ cholesterol, which should be 1 mmol/L or above, is thought to have a protective effect against heart attack and stroke, by mopping up excess ‘bad' cholesterol. Non-HDL 'bad’ cholesterol, which should be as low as possible, around 2 mmol/L, can block blood supply and lead to heart attacks and strokes. “At age 8 years, associations were most evident for type 2 diabetes liability with lower lipids in HDL subtypes. At 16 years, associations were stronger with pre-glycemic traits, including citrate and with glycoprotein acetyls, and at 18 years, associations were stronger with branched-chain amino acids. At 25 years, associations had strengthened with VLDL lipids (very low density lipoprotein) and remained consistent with previously altered traits, including HDL lipids,” say the authors in their analysis published in Diabetes Care. They add, “Our results support perturbed HDL lipid metabolism as one of the earliest features of type 2 diabetes liability, alongside higher branched-chain amino acid and inflammatory levels. Several features are apparent in childhood as early as age 8 years, decades before the clinical onset of disease.”
Type 2 diabetes develops for many years before diagnosis. According to the study, type 2 diabetes is a metabolic disease affecting over 400 million people globally. Its incidence is driven largely by increased adiposity -- a condition of being severely overweight, or obese -- which is considered a strong causal risk factor. But the difficulty of achieving and maintaining weight loss makes disease management a lifelong and expensive task, explain researchers. This is particularly problematic considering that potentially half of those living with type 2 diabetes are undiagnosed and that the future burden is expected to be greatest in lower-income countries, they add. Accordingly, the research team conducted the study to reveal early metabolic features characterizing liability to type 2 diabetes.
“We knew that diabetes doesn't develop overnight. What we didn't know is how early in life the first signs of disease activity become visible and what these early signs look like. We addressed these by looking at the effects of being more genetically prone to type 2 diabetes in adulthood on measures of metabolism taken across early life. This would not have been possible without the Children of the 90s study,” says Dr Joshua Bell, one of the leading investigators from the University of Bristol, in the analysis.
“Diabetes is most common in older age, but we see signs of disease susceptibility very early on, about 50 years before it's usually diagnosed. Knowing what these early signs look like widens our window of opportunity to intervene much earlier and stop diabetes before it becomes harmful,” says Dr Bell. He explained that the study is talking about the effects of susceptibility rather than of clinical disease itself. This does not mean that young people already have adult diabetes, but these are subtle differences in the metabolism of young people who are more prone to developing it later in life, says the team.
“These findings help reveal the biology of how diabetes unfolds and what features may be targetable much earlier on to prevent the onset of disease and its complications. This is important because we know that the harmful effects of blood glucose, such as on heart disease, are not exclusive to people with diagnosed diabetes but extend to a smaller degree to much of the population,” says Dr Bell.