Lactate generation following glucose ingestion: relation to obesity, carbohydrate tolerance and insulin sensitivity

To examine early metabolic abnormalities in obesity prior to the development of carbohydrate intolerance, we studied 14 lean and 37 obese subjects with normal glucose tolerance. All subjects underwent a standard 75 g oral glucose tolerance test (OGTT) with the addition of lactate measurement. As expected, there was a positive relationship between basal insulin and body mass index (BMI kg/m2;r=0.64, P less than 0.0001). In addition, even though the subjects had normal glucose tolerance, both basal glucose and sum of glucose during OGTT showed significant positive associations with obesity. Basal lactate correlated significantly and positively with obesity (r = 0.29, P = 0.04). When incremental areas during OGTT were examined, glucose area during OGTT was positively associated with BMI and insulin area was positively associated with both BMI and sum of glucose. Conversely, the incremental area of lactate decreased as BMI increased (r = -0.41, P = 0.003), despite the increasing glucose area. The results indicate that even prior to frank carbohydrate intolerance, progressive changes in basal levels of glucose, insulin, and lactate, as well as sum of glucose, accompany the expansion of adipose mass in obesity. Two different aspects of lactate metabolism have been examined in obesity. First, the association of increased basal lactate levels with increased obesity may reflect increased lactate production from enlarged adipocytes and an increased fat mass. Secondly, the inverse association between acute lactate generation following glucose ingestion and obesity, despite the increased sum of glucose in obese subjects, may reflect a decreased ability of adipose and/or extra-adipose tissues to convert glucose to lactate due to insulin resistance.