Disclosures: The authors report no relevant financial disclosures.
January 20, 2022
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Arterial stiffness in adolescence may drive insulin resistance in adulthood

Disclosures: The authors report no relevant financial disclosures.
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Arterial stiffness in adolescence may be a causal risk factor for hyperinsulinemia and insulin resistance in young adulthood, driving risk for incident type 2 diabetes, according to research published in Hypertension.

Emerging evidence among healthy adults followed for a median of 3.72 years suggests higher arterial stiffness may precede higher fasting blood glucose and could be a novel risk factor in the causal pathway of incident type 2 diabetes, Andrew O. Agbaje, MD, MPH, a clinical epidemiologist with the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland, and colleagues wrote in the study background. More research is needed on whether altered arterial function and structure in adolescents and young adults, independent of known risk factors, precede the risk for dysglycemia, hyperinsulinemia and insulin resistance that are precursors of young-onset type 2 diabetes, they wrote.

Graphical depiction of source quote presented in the article
Andrew O. Agbaje, MD, MPH, a clinical epidemiologist with the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland.

“The largest temporal causal longitudinal study among adolescents conducted to date revealed that arterial stiffness may be an emerging causative risk factor for several early-onset metabolic disease processes such as hyperinsulinemia, insulin resistance and possibly dyslipidemia,” Agbaje, also a principal investigator for the urFIT-child research group at the University of Eastern Finland, told Healio. “We have shown previously that higher arterial stiffness in adolescence may cause elevated blood pressure/hypertension and overweight/obesity in young adulthood. These studies may potentially alter our thinking on disease development, so that rather than treating arterial stiffness as a consequence of metabolic dysfunction, stiffened arteries may be a ‘silent’ cause of several pathologies beginning in adolescence.”

Measuring arterial structure

Agbaje and colleagues analyzed data from 3,862 participants in the Avon Longitudinal Study of Parents and Children who were followed for 7 years. Researchers measured carotid-femoral pulse wave velocity and carotid intima-media thickness at age 17.7 years and again at age 24.5 years. Participants also provided fasting blood samples during both visits to calculate homeostatic model assessment (HOMA) of insulin resistance and the percentage of pancreatic beta-cell function.

At age 24.5 years, 9.2%, 41.6%, 24.5%, 7.5% and 10.3% of participants were at risk for high glucose, insulin, LDL, triglycerides and low HDL, respectively. Fewer than eight participants had youth-onset type 2 diabetes at age 17.7 and 24.5 years.

Researchers found that a higher carotid-femoral pulse wave velocity measured at age 17.7 years was associated with higher insulin at age 24.5 years (OR = 1.25; 95% CI. 1.08-1.44; P = .003); however, the association did not persist after adjustment for cardiometabolic and lifestyle factors. Higher carotid intima-media thickness measured at age 17.7 years was associated with lower insulin (OR = 0.06; 95% CI, 0.01-0.95; P = .046) at age 24.5 years, with results persisting after adjustment for other factors.

In mixed-effect models, the 7-year progression of carotid-femoral pulse wave velocity was directly associated with a 7-year increase in HDL (effect estimate, 0.58 mmol/L; 95% CI, 0.29-0.88; P < .0001) and triglyceride levels (effect estimate, 0.15 mmol/L; 95% CI, 0.01-0.28; P = .036), whereas carotid-femoral pulse wave velocity progression was associated with increased beta-cell function only among participants with overweight or obesity (effect estimate, 0.53; 95% CI, 0.06-1.01; P = .027).

A 7-year progression in carotid intima-media thickness was directly associated with a 7-year increase in LDL, HDL, triglyceride level and glucose but negatively associated with HOMA-percentage of pancreatic beta-cell function (–0.06; 95% CI, –0.09 to –0.04; P < .0001).

Target risk factors early

“Among our participants, arterial stiffness preceded higher insulin and insulin resistance but did not precede higher glucose,” the researchers wrote. “This is in contrast to the adult study where increased brachial-ankle pulse wave velocity temporally preceded fasting blood glucose. This adult study lacked information on fasting insulin and insulin resistance, and the disparity in findings may also be associated with the modality of arterial stiffness measured and participants’ age.”

Agbaje said the study findings suggest a novel therapeutic approach targeting arterial stiffness concurrently with diabetes therapy could lead to better health outcomes.

“Since these emerging studies showed the potential deleterious effect of arterial stiffness, it is critical to identify modifiable risk factors that precipitate arterial stiffness in adolescents, of whom the majority are normal weight and healthy,” Agbaje said.

For more information:

Andrew O. Agbaje, MD, MPH, can be reached at andrew.agbaje@uef.fi.