In the largest study of its kind, researchers from the University of Eastern Finland found that even healthy-looking adolescents and young adults – of mostly normal weight – who have high blood sugar, may be at risk of major heart damage, with females’ risk five times higher than males.
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. To assess the prevalence of prediabetes, or 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% of 17-year-old adolescents had fasting blood sugar of ≥5.6 mmol/L, which increased nearly fivefold to 26.9% by 24 years. Only 1.1% adolescents had a level of ≥6.1 mmol/L, but the prevalence increased fivefold to 5.6% by 24.
The prevalence of excessive heart enlargement (left ventricular hypertrophy) increased threefold from 2.4% at 17 to 7.1% at 24, 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 17 to 24 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 seven-year growth period, increased glucose levels contributed 0.57 g/m to cardiac mass increase in females compared with a 0.11 g/m 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-50s. 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, and they had echocardiography measurements of the heart structure and function at the same age.
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,” said Andrew Agbaje, physician and associate professor (docent) of Clinical Epidemiology and Child Health at the University of Eastern Finland.
“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, so special attention should be paid to girls in terms of prevention.”
He said 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 seven 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,” he added.
Study details
Persistent hyperglycaemia and insulin resistance with the risk of worsening cardiac damage in adolescents: A 7-year longitudinal study of the ALSPAC birth cohort
Andrew Agbaje, Justin Zachariah, Alan Barker et al.
Published in Diabetes Care on 29 April 2025
Objective
Insulin resistance (IR) and dysglycaemia can induce cardiac remodelling in adulthood, but little evidence exists with respect to cardiac remodelling in youth with and without evidence of new-onset glucose metabolic alterations. This study investigated whether changes in metabolic status from adolescence to young adulthood are associated with the risk of progressive cardiac remodelling and examined potential mechanistic pathways.
Research design and methods
From the Avon Longitudinal Study of Parents and Children (ALSPAC), U.K. cohort, 1,595 adolescents, mean (SD) age 17.7 (0.4) years, who had data on fasting plasma glucose and insulin levels, and echocardiography left ventricular (LV) mass indexed for height raised to the power of 2.7 (LVMI2.7) and in whom these factors repeatedly were measured at a clinic visit when they were aged 24 years were included. HOMA-IR was computed, hyperglycaemia was defined as glucose concentration of ≥5.6 mmol/L and ≥6.1 mmol/L, and LV hypertrophy was defined as LVMI2.7 ≥51g/m2.7.
Results
The prevalence of LV hypertrophy increased from 2.4% at baseline to 7.1% at follow-up. Each unit increase of glucose (β = 0.37 g/m2.7 [95% CI 0.23–0.52]; P < 0.001) and HOMA-IR (1.10 g/m2.7 [0.63–1.57]; P < 0.001) was independently associated with increased LVMI2.7 over 7 years. Persistent hyperglycaemia of 5.6 mmol/L and 6.1 mmol/L was associated with higher odds (odds ratio [OR] 1.46 [95% CI 1.35–1.47], P < 0.001; and 3.10 [95% CI 1.19–8.08], P = 0.021, respectively) of worsening LV hypertrophy over 7 years. Increased fat mass (62% mediation) significantly mediated the association of increased HOMA-IR with increased LVMI2.7.
Conclusions
Persistent adolescent hyperglycaemia and worsening IR were associated with the risk of worsening structural and functional cardiac damage, and these were largely explained by increased fat mass.
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