The comments of Greenfield et al. (1) in this issue of Diabetes Care regarding the recent editorial entitled “Coronary Disease in Type 1 Diabetes: Causal Contiguity and Clinical Implications” (2) are most appreciated. What was stated in the editorial regarding insulin resistance in type 1 diabetes is found in the following paragraph: “On purely statistical grounds, one would anticipate insulin resistance in many people with type 1 diabetes. In addition, however, intensive treatment of type 1 diabetes appears to increase central obesity. In fact, it has been noted that ‘insulin treatment of type 1 diabetic patients creates the insulin resistance syndrome in a significant number’ (3).” The study by Greenfield et al. (4) is certainly interesting as a case-control study demonstrating insulin resistance in the relatively small sample of individual subjects with type 1 diabetes compared with control subjects. However, the fact that no difference was observed in central abdominal adiposity in those with or without type 1 diabetes and that the apparent insulin resistance in those with type 1 diabetes appeared to be unrelated to abdominal obesity are certainly not conclusive in view of the small sample size.
From a heuristic perspective, it is important to note that “femoral fat is the feature of gynecoid obesity, which is not associated with insulin resistance… whereas increased abdominal visceral and subcutaneous fat characterize insulin resistance” (5). In Greenfield et al.’s study (4), the results in women are consistent with this sex-dependent difference in fat distribution and apparent relationships to insulin resistance. Thus, the actual sample size relevant to the issue of the relationship between insulin resistance and visceral fat is even smaller.
Greenfield et al. may be guilty of ignoratio elenchi (answering a question or responding to a point that was not the central point made). The main point of my editorial was to underscore the original observations of Orchard et al. (6), who studied a large cohort of patients with type 1 diabetes. All of the patients were initially free from clinically overt coronary artery disease. The development of coronary artery disease after their enrollment in the Orchard study was associated with insulin resistance rather than the metabolic derangements of type 1 diabetes per se in the absence of concomitant insulin resistance.
The extent to which visceral fat participates in the linkage between insulin resistance and coronary artery disease has not been fully elucidated. Visceral fat, through elaboration of tumor necrosis factor-α and other cytokines, may potentiate the development of insulin resistance. Both insulin resistance and accumulation of visceral fat may share common biological and biochemical ancestors. Despite the elegant metabolic studies performed by Greenfield et al., the fat is still in the fire with respect to deleterious consequences, including predisposing one to premature coronary artery disease.
