Largest study to date reveals high blood sugar accelerates heart damage in healthy youth

In the present study, 1,595 adolescents drawn from the University of Bristol's Children of the 90s cohort were followed up from age 17 until 24 years. To assess the prevalence of prediabetes, which refers to high fasting blood glucose levels, two alternative cutpoints were used, a stricter cutpoint of ≥5.6 mmol/L recommended by the American Diabetes Association, and ≥6.1 mmol/L , which is the present recommendation in many countries.

Altogether, 6.2% 17-year old adolescents had fasting blood sugar of ≥5.6 mmol/L, which increased nearly fivefold to 26.9% by age 24 years. Only 1.1% adolescents had a level of ≥6.1 mmol/L, but the prevalence increased fivefold to 5.6% by age 24 years.

The prevalence of excessive heart enlargement (left ventricular hypertrophy) increased threefold from 2.4% at age 17 years to 7.1% at age 24 years, while the prevalence of heart dysfunction increased from 9.2% in adolescence to 15.8% in young adulthood.

Persistent fasting blood sugar of ≥5.6 mmol/L from age 17 to 24 years was associated with a 46% increased risk of left ventricular hypertrophy. The risk was threefold if fasting blood sugar was persistently ≥6.1 mmol/L. High blood glucose also decreased heart muscle relaxation, altered normal heart function, and excessively increased the pressure of blood flow returning to the heart. Persistent insulin resistance was associated with a 10% increased risk of premature and worsening heart damage. During the 7-year growth period, increased glucose levels contributed 0.57 g/m^2.7 to cardiac mass increase in females compared to a 0.11 g/m^2.7 increase in males.

Previous studies among adults have shown that high blood glucose and insulin resistance in youth strongly predict the risk of type 2 diabetes mellitus in people in their mid-fifties. Also, it is known that the younger one is diagnosed with type 2 diabetes, the more severe and rapid the complications may be, if untreated. However, no study in the world has previously examined the earliest manifestation of the consequence of high blood glucose and insulin resistance on the heart. This is due to the scarcity of repeated echocardiography assessments of the heart in a large population of healthy youth.

The current study is the largest and the longest follow-up of glucose concentration and repeated echocardiography study in a relatively healthy young population in the world. The participants' fasting blood glucose and insulin were measured at ages 17 and 24 years, and they had echocardiography measurements of the heart structure and function at ages 17 and 24 years. Insulin resistance was computed from fasting glucose and insulin. Other fasting blood samples were also repeatedly measured for low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and high-sensitivity C-reactive protein. Blood pressure, heart rate, socio-economic status, family history of cardiovascular disease, smoking status, accelerometer measure of sedentary behaviour and physical activity as well as dual-energy X-ray absorptiometry measured fat mass and lean mass were accounted for in the analyses.

"Earlier results from the same cohort indicate that late adolescence is a critical period in the evolution of cardiometabolic diseases. The current findings further confirm that even healthy-looking adolescents and young adults who are mostly normal weight may be on a path towards cardiovascular diseases, if they have high blood glucose and insulin resistance. Surprisingly, we observed that high blood sugar may aggressively damage females' hearts five times faster than males'; therefore, special attention should be paid to girls in terms of prevention," says Andrew Agbaje, physician and associate professor (docent) of Clinical Epidemiology and Child Health at the University of Eastern Finland.

Worsening insulin resistance and increased fat mass have a bidirectional reinforcing vicious cycle. In the new study, we observed that two-thirds of the effect of insulin resistance on excessive heart enlargement was explained by increased total body fat. The five-fold increase in the prevalence of prediabetes within 7 years of growth from adolescence to young adulthood underscores the critical importance of lifestyle behaviour and dietary habits, especially after adolescents have become independent from their family."

Andrew Agbaje, Physician and Associate Professor (Docent), Clinical Epidemiology and Child Health, University of Eastern Finland

Agbaje's research group (urFIT-child) is supported by research grants from Jenny and Antti Wihuri Foundation, the Finnish Cultural Foundation Central Fund, the Finnish Cultural Foundation North Savo Regional Fund, the Orion Research Foundation, the Aarne Koskelo Foundation, the Antti and Tyyne Soininen Foundation, the Paulo Foundation, the Yrjö Jahnsson Foundation, the Paavo Nurmi Foundation, the Finnish Foundation for Cardiovascular Research, Ida Montin Foundation, Eino Räsänen Fund, Matti and Vappu Maukonen Fund, Foundation for Pediatric Research, Alfred Kordelin Foundation and Novo Nordisk Foundation.