Link between IGF-1 levels and T2D risk mediated by birth weight

20 Apr 2021 bởiRoshini Claire Anthony
Link between IGF-1 levels and T2D risk mediated by birth weight

Insulin-like growth factor-1 (IGF-1) levels are inversely associated with the risk of type 2 diabetes (T2D). However, this association appears to be limited to individuals with a birth weight of ≥2.5 kg, according to a recent study.

“Birth weight significantly modifies the relation between adulthood levels of circulating IGF-1 and the risk of T2D,” said the investigators.

“Our findings highlight the importance of early-life risk factors in the development of lifecourse prevention strategies targeting IGF-1 and T2D,” they said.

For this study, the researchers used data of 181,090 adults aged 39–70 years enrolled in the prospective UK Biobank Study without cardiovascular disease or T2D at baseline. The participants self-reported their demographics, diet, lifestyle factors, early life exposures (including birth weight), and medical information, while biological samples and physical measurements were taken at recruitment.

Genetic Risk Score (GRS) was used to identify genetically determined birth weight, with scores ranging from 0.7–14.0, and higher scores indicating a higher genetic predisposition to low birth weight. Participants who were related, had excessive heterozygosity and high levels of missingness and mismatched sex, and non-Europeans were excluded. Chemiluminescent immunoassay was used to identify serum IGF-1 levels.

Over a mean 9.9 years of follow-up, 3,299 incident cases of T2D were recorded. After adjusting for demographics, lifestyle risk factors, and clinical biomarkers, increasing levels of IGF-1 were associated with a lower risk of T2D. Compared with the lowest IGF-1 quintile, the hazard ratios (HRs) for T2D for the second, third, fourth, and fifth quintiles were 0.85 (95 percent confidence interval [CI], 0.76–0.95), 0.84 (95 percent CI, 0.74–0.94), 0.72 (95 percent CI, 0.63–0.82), and 0.80 (95 percent CI, 0.70–0.92), respectively (ptrend<0.001). Every standard deviation (SD) increase in IGF-1 levels was associated with a 7 percent reduced risk of T2D (HR, 0.93). [BMJ Open Diabetes Res Care 2021;9:e001885]

Adjusting for birth weight affected the IGF-1–T2D association (pinteraction=0.02). Among individuals with a birth weight of ≥2.5 kg, there was an inverse association between IFG-1 levels and T2D risk (ptrend<0.001), where compared with the lowest IGF-1 quintile, the HRs for T2D for the second, third, fourth, and fifth quintiles were 0.86 (95 percent CI, 0.76–0.97), 0.82 (95 percent CI, 0.72–0.93), 0.71 (95 percent CI, 0.61–0.81), and 0.74 (95 percent CI, 0.64–0.85), respectively. The risk of T2D was reduced by 9 percent with each 1-SD increase in IGF-1 levels.

In contrast, there was no apparent IGF-1–T2D association among individuals with a birth weight <2.5 kg (pinteraction=0.001).

The effect of birth weight on the IGF-1–T2D association was evident in men but not women (pinteraction=0.01 and 0.11, respectively). In men, the inverse association between IGF-1 and T2D risk was significant with birth weight ≥2.5 kg and not with <2.5 kg (ptrend<0.001 and 0.61, respectively).

There was no significant interaction between IGF-1 levels and the GRS of birth weight with T2D risk (pinteraction=0.47), suggesting that “the association between IGF-1 and T2D was not modified by genetic predisposition to birth weight,” said the investigators.

According to the investigators, several biological mechanisms may explain the role of birth weight in the IGF-1 and T2D association.

“Experimental studies indicate that intrauterine growth restriction can result in persistent reduction of serum IGF-1 through modifying epigenetic characteristics, [and] low birth weight is a widely accepted indicator for prenatal malnutrition and intrauterine growth restriction,” they said.

Prenatal malnutrition may also have long-lasting impact on glucose–insulin metabolism, they added.

The prospective observational study design limited determination of causality. The investigators also called for similar studies in other populations, based on prior evidence suggesting variance in IGF-1 levels by ethnicity.