Is the Fat Still in the Fire?: Response to Greenfield et al.

doi:10.2337/diacare.26.9.2703-a

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Letters: Comments and Responses
Letter

Is the Fat Still in the Fire?

Response to Greenfield et al.

Burton E. Sobel, MD

From the Department of Medicine, University of Vermont College of Medicine, Burlington, Vermont

Address correspondence to Burton E. Sobel, MD, Department of Medicine, University of Vermont, Colchester Research Facility, 208 South Park Dr., Colchester, VT 05446. E-mail: burt.sobel{at}vtmednet.org

The comments of Greenfield et al. (1) in this issue of DiabetesCare regarding the recent editorial entitled "Coronary Diseasein Type 1 Diabetes: Causal Contiguity and Clinical Implications"(2) are most appreciated. What was stated in the editorial regardinginsulin resistance in type 1 diabetes is found in the followingparagraph: "On purely statistical grounds, one would anticipateinsulin resistance in many people with type 1 diabetes. In addition,however, intensive treatment of type 1 diabetes appears to increasecentral obesity. In fact, it has been noted that ‘insulintreatment of type 1 diabetic patients creates the insulin resistancesyndrome in a significant number’ (3)." The study by Greenfieldet al. (4) is certainly interesting as a case-control studydemonstrating insulin resistance in the relatively small sampleof individual subjects with type 1 diabetes compared with controlsubjects. However, the fact that no difference was observedin central abdominal adiposity in those with or without type1 diabetes and that the apparent insulin resistance in thosewith type 1 diabetes appeared to be unrelated to abdominal obesityare certainly not conclusive in view of the small sample size.

From a heuristic perspective, it is important to note that "femoralfat is the feature of gynecoid obesity, which is not associatedwith insulin resistance... whereas increased abdominal visceraland subcutaneous fat characterize insulin resistance" (5). InGreenfield et al.’s study (4), the results in women areconsistent with this sex-dependent difference in fat distributionand apparent relationships to insulin resistance. Thus, theactual sample size relevant to the issue of the relationshipbetween insulin resistance and visceral fat is even smaller.

Greenfield et al. may be guilty of ignoratio elenchi (answeringa question or responding to a point that was not the centralpoint made). The main point of my editorial was to underscorethe original observations of Orchard et al. (6), who studieda large cohort of patients with type 1 diabetes. All of thepatients were initially free from clinically overt coronaryartery disease. The development of coronary artery disease aftertheir enrollment in the Orchard study was associated with insulinresistance rather than the metabolic derangements of type 1diabetes per se in the absence of concomitant insulin resistance.

The extent to which visceral fat participates in the linkagebetween insulin resistance and coronary artery disease has notbeen fully elucidated. Visceral fat, through elaboration oftumor necrosis factor- ${alpha}$ and other cytokines, may potentiate thedevelopment of insulin resistance. Both insulin resistance andaccumulation of visceral fat may share common biological andbiochemical ancestors. Despite the elegant metabolic studiesperformed by Greenfield et al., the fat is still in the firewith respect to deleterious consequences, including predisposingone to premature coronary artery disease.

References

Greenfield JR, Samaras K, Campbell LV, Chisholm DJ: Type 1 diabetes is not associated with increased central abdominal obesity (Letter). Diabetes Care 26:2703, 2003.[Free Full Text]
Sobel BE: Coronary disease in type 1 diabetes: causal contiguity and clinical implications (Editorial). Diabetes Care 26:1629–1630, 2003[Free Full Text]
Lebovitz HE: Types of diabetes and their implications regarding heart and vascular disease. In Medical Management of Diabetes and Heart Disease. New York, Marcel Dekker, 2002, p. 9–33
Greenfield JR, Samaras K, Chisholm DJ: Insulin resistance, intra-abdominal fat, cardiovascular risk factors, and androgens in healthy young women with type 1 diabetes mellitus. J Clin Endocrinol Metab 87:1036–1040, 2002[Abstract/Free Full Text]
Mavri A, Alessi MC, Bastelica D, Geel-Georgelin O, Fina F, Sentocnik JT, Stegnar M, Juhan-Vague I: Subcutaneous abdominal, but not femoral fat expression of plasminogen activator inhibitor-1 (PAI-1) is related to plasma PAI-1 levels and insulin resistance and decreases after weight loss. Diabetologia 44:2025–2031, 2001[Medline]
Orchard TJ, Olson JC, Erbey JR, Williams K, Forrest KY-Z, Smithline Kinder L, Ellis D, Becker DJ: Insulin resistance–related factors, but not glycemia, predict coronary artery disease in type 1 diabetes: 10-year follow-up data from the Pittsburgh Epidemiology of Diabetes Complications study. Diabetes Care 26:1374–1379, 2003.[Abstract/Free Full Text]