Is there a difference in glucose tolerance based on body weight and adipose tissue in type 2 diabetes?
In a healthy individual, adipose tissue is sensitive to insulin as it metabolizes glucose and lipids via fatty acids and adipokines after the individual ingests a meal. Insulin promotes an increase of adipose tissue mass and regulates free fatty acid secretion into the blood. But what happens when a young individual has type 2 diabetes and increased body weight? There has been conflicting results in previous studies.
For type 2 diabetes, it is already known that adipose tissue is resistant to insulin. So in this study, adipose insulin resistance was analyzed as an adipose insulin resistance index (Adipose-IR): fasting insulin x free fatty acids [FFAs]. This was evaluated in youth of different weights (normal weight to obesity), as well as different tolerances of glucose (including normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes). The correlation between adipose insulin resistance with physical and metabolic characteristics was also investigated. And lastly, the adipose insulin resistance was used to predict the youths’ dysglycemia (which is IGT and type 2 diabetes).
There were 205 youth who participated in the study “(age 10 to 20 years, Tanner stages IV and V, 99 African American and 106 American and white, and 70 male and 135 female) from our National Institutes of Health.” For the youth with normal glucose tolerance, 49 participants were of normal weight, and 89 youth had excess weight or obesity. For those with impaired glucose tolerance, 38 had obesity. And of the youth with type 2 diabetes, 29 had obesity. Those excluded involved “participants with isolated impaired fasting glucose (IFG)… because IGT and combined IFG and IGT groups are characterized as having insulin resistance, whereas those with isolated IFG are not, while both have impaired b-cell function.”
Eight components were analyzed: insulin, fasting glucose, free fatty acids, body composition, Adipose-IR, visceral adipose tissue (VAT), adiponectin, and leptin. It was found that body weight of the youth had a negative association with glucose tolerance. “Adipose-IR was 2.2-fold higher in obese NGT, 4.3-fold higher in IGT, and 4.6-fold higher in type 2 diabetes compared with that in normal-weight peers (all P < 0.05).” This demonstrates that an increase in the youths’ body weight results in a decrease in glucose tolerance, where type 2 diabetes had the least tolerance. The youths’ sex also played a role in dysglycemia because the sex would affect the adipose insulin resistance: “Females with dysglycemia (IGT and type 2 diabetes) had higher Adipose-IR than their male counterparts (P < 0.001).” It would help to conduct further research on whether higher Adipose-IR in females can be affected by sex-related therapeutic response.
In addition to a negative correlation with glucose tolerance and higher adipose insulin resistance in females, adipose insulin resistance was associated positively with “total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin and negatively with adiponectin.” A curve analysis demonstrated a cutoff for adipose insulin resistance of 9.3 mU/mL x mmol/L for predicting dysglycemia at 80% predictive power.
Adipose-IR was an accurate and simple way to measure changes in youths’ adipose tissue insulin sensitivity. On a spectrum going from normal weight to obesity, and from NGT to IGT to type 2 diabetes, adipose insulin resistance progresses (insulin sensitivity becomes worse). Since this was a cross-sectional study, no causal relationships can be demonstrated between Adipose-IR and other type 2 diabetes pathogenic factors.
- Three main factors in this study for youth with type 2 diabetes include: 1) adipose insulin resistance index (fasting insulin x free fatty acids [FFAs]), 2) the relationship between adipose insulin resistance with physical and metabolic characteristics, and 3) how adipose insulin resistance could determine dysglycemia in these youth
- Insulin, fasting glucose, free fatty acids, body composition, Adipose-IR, visceral adipose tissue (VAT), adiponectin, and leptin were evaluated in 205 youth participants.
- There was more adipose insulin resistance in females than that of males, and total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin were positively associated with adipose insulin resistance, while adiponectin was negatively correlated with Adipose-IR.
Arslanian, Silva; Bacha, Fida; Kim, Joon Young; Michaliszyn, Sara F.; Tfayli, Hala; and Yousuf, Shahwar. “Adipose Tissue Insulin Resistance in Youth on the Spectrum From Normal Weight to Obese and From Normal Glucose Tolerance to Impaired Glucose Tolerance to Type 2 Diabetes.” Diabetes Care. November 2018. http://care.diabetesjournals.org/content/early/2018/11/08/dc18-1178. 4 February 2019.
Annahita Forghan, Pharm.D. Candidate 2019, LECOM College of Pharmacy