Impact of Physical Inactivity on Subcutaneous Adipose Tissue Metabolism in Healthy Young Male Offspring of Patients With Type 2 Diabetes

OBJECTIVE

Physical inactivity is a risk factor for type 2 diabetes and may be more detrimental in first-degree relative (FDR) subjects, unmasking underlying defects of metabolism. Using a positive family history of type 2 diabetes as a marker of increased genetic risk, the aim of this study was to investigate the impact of physical inactivity on adipose tissue (AT) metabolism in FDR subjects.

RESEARCH DESIGN AND METHODS

A total of 13 FDR and 20 control (CON) subjects participated in the study. All were studied before and after 10 days of bed rest using the glucose clamp technique combined with measurements of glucose uptake, lipolysis, and lactate release from subcutaneous abdominal (SCAAT) and femoral (SCFAT) adipose tissue by the microdialysis technique. Additionally, mRNA expression of lipases was determined in biopsies from SCAAT.

RESULTS

Before bed rest, the FDR subjects revealed significantly increased glucose uptake in SCAAT. Furthermore, mRNA expression of lipases was significantly decreased in the SCAAT of FDR subjects. Bed rest significantly decreased lipolysis and tended to increase glucose uptake in the SCFAT of both CON and FDR subjects. In response to bed rest, SCAAT glucose uptake significantly increased in CON subjects but not in FDR subjects.

CONCLUSIONS

FDR subjects exhibit an abnormal AT metabolism including increased glucose uptake prior to bed rest. However, the differences between FDR and CON subjects in AT metabolism were attenuated during bed rest due to relatively more adverse changes in CON subjects compared with FDR subjects. Physical inactivity per se is not more deleterious in FDR subjects as compared with CON subjects with respect to derangements in AT metabolism.Type 2 diabetes is the product of a complex interplay between genetic susceptibility and environmental factors. The best known environmental modifiable risk factors for type 2 diabetes are obesity and a low level of habitual physical activity (1).Even though there is substantial evidence that a change toward a healthy lifestyle halts the progression of type 2 diabetes (2), certain groups, including first-degree relatives (FDRs) of patients with type 2 diabetes, are at increased risk of developing the disease (3). Type 2 diabetes has a major hereditary component (4), and FDR subjects show multiple abnormalities in intermediary metabolism and pancreatic islet cell function, displaying insulin resistance despite normal glucose tolerance (5). The metabolic defects include insufficient insulin secretion (6), decreased peripheral glucose uptake (7), and the impaired antilipolytic effect of insulin in subcutaneous adipose tissue (AT) (8).AT is an active compartment in the lipid and glucose metabolism of humans, but the role of AT metabolism in the development of type 2 diabetes is not clarified. AT, along with skeletal muscle, is a site of peripheral insulin resistance in type 2 diabetes (9). The role of AT in the pathophysiology of insulin resistance can partly be attributed to lipolytic activity resulting in the mobilization of free fatty acids (FFAs), which are deleterious for glucose utilization and insulin action (10). However, AT may play a more direct role since it is a site of deranged glucose metabolism. Although AT is of minor quantitative importance for whole-body glucose disposal, the tissue produces lactate (11), which functions as a gluconeogenic precursor in the liver (12). Previous studies have demonstrated increased plasma lactate (13) and lactate release from adipocytes (14) in FDR subjects.In this study, we investigated in vivo AT glucose uptake, lipolysis, and lactate release, as well as subcutaneous abdominal adipose tissue (SCAAT) mRNA expression of lipases and GLUT-4 in FDR and control (CON) subjects prior to and after 10 days of bed rest. We hypothesized that FDR subjects would show abnormalities in baseline AT metabolism and be more sensitive to the unhealthy effects of physical inactivity.