Location: Children's Nutrition Research CenterTitle: 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
|KIM, JOON - University Of Pittsburgh Medical Center|
|BACHA, FIDA - Children'S Nutrition Research Center (CNRC)|
|TFAYLI, HALA - American University Of Beirut|
|MICHALISZYN, SARA - Youngstown State University|
|YOUSUF, SHAHWAR - University Of Pittsburgh Medical Center|
|ARSLANIAN, SILVA - University Of Pittsburgh Medical Center|
Submitted to: Diabetes Care
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/25/2018
Publication Date: 2/1/2019
Citation: Kim, J.Y., Bacha, F., Tfayli, H., Michaliszyn, S.F., Yousuf, S., Arslanian, S. 2019. 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. 42(2):265-272. https://doi.org/10.2337/dc18-1178.
Interpretive Summary: Insulin resistance reflects a decreased effectiveness of insulin action in body tissues and is found in the early stages of diabetes. In this study, we evaluated insulin resistance in the fat (or adipose) tissue in 205 adolescents with different levels of glucose control form normal to diabetes. We wanted to understand what drives this insulin resistance in the fat tissue. To do that, we used an index of adipose tissue insulin resistance derived from fasting blood levels of fatty acids and insulin. We found that fat tissue insulin resistance was higher (worse) in youth with obesity compared to normal weight youth. It was also higher in youth with prediabetes and type 2 diabetes compared to obese youth with normal glucose tolerance. It was related to total body fat and to abdominal fat and was higher in females compared to males with abnormal glucose metabolism. The insulin resistance at the level of the fat tissue was a good predictor for abnormality in glucose levels. Therefore, this index of adipose tissue insulin resistance derived from fasting blood measures of fatty acids and insulin can be used in future studies to increase detection of youth at risk for diabetes.
Technical Abstract: Adipose tissue insulin resistance is one of the pathophysiological components of type 2 diabetes. Herein we investigated: 1) adipose insulin resistance index (Adipose-IR) (calculated as fasting insulin x free fatty acids [FFAs]) in youth across the spectrum of adiposity from normal weight to obese and the spectrum from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) to type 2 diabetes, 2) the relationship of Adipose-IR with physical and metabolic characteristics, and 3) the predictive power of Adipose-IR for determining dysglycemia in youth. A total of 205 youth had fasting glucose, insulin, FFA, Adipose-IR, body composition, visceral adipose tissue (VAT), leptin, and adiponectin evaluated. 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). Females with dysglycemia (IGT and type 2 diabetes) had higher Adipose-IR than their male counterparts (P < 0.001). Adipose-IR correlated positively with total body and visceral adiposity, fasting glucose, HOMA-IR, and leptin and negatively with adiponectin. Receiver operating characteristic curve analysis yielded an optimal cutoff for Adipose-IR of 9.3 uU/mL x mmol/L for determining dysglycemia with 80% predictive power. Adipose-IR is a simple surrogate estimate that reflects pathophysiological alterations in adipose tissue insulin sensitivity in youth, with progressive deterioration from normal weight to obese and from NGT to IGT to type 2 diabetes. Adipose-IR can be applied in large-scale epidemiological/observational studies of the natural history of youth-onset type 2 diabetes and its progression or reversal with intervention strategies.