We have recently suggested (1) that patients with multiple symmetric lipomatosis (MSL) may represent a paradigm for metabolically innocent fat accumulation. Harsch and colleagues (2,3) raise some justified words of caution with respect to the generalization of this statement. It is probably true that we cannot make general metabolic inferences on the syndrome of MSL as such based on our rather limited sample size. But this was not our intention, and we welcome the opportunity to clarify our line of argument.

The original idea was to present a situation where a substantial increase in body fat mass was not accompanied by decreased insulin sensitivity, which is in much contrast to common belief. And in fact, fat accumulation, if confined to the subcutaneous compartment, was not associated with much insulin resistance. By selecting these two specific patients for argument’s sake, we may have introduced a bias. But this is beside the point because even if everything we said held true for only these two subjects and no other patient with MSL, our findings would be no less interesting. And this is the reason why we specifically put “paradigm” in the title rather than the syndrome alone. Nevertheless, Harsch et al. (2) appropriately pointed out that fat accumulation in MSL need not necessarily be confined to the subcutaneous compartment and that, without doubt, if it included the visceral compartment, insulin resistance would be present.

Since our observation was accepted for publication, we were able to recruit two more patients with the clinical appearance of MSL and very little visceral fat. The whole-body fat volume of the two subjects was ∼14 and 20 l, respectively. The subcutaneous-to-visceral abdominal fat ratio as measured by magnetic resonance imaging was 3.3 and 5.9, respectively, compared with BMI-, age-, and sex-matched control groups (1.6 and 1.4, respectively). Consistent with the small visceral fat mass, liver fat was much lower in both patients. Intramyocellular lipids in soleus and tibialis anterior muscles were also lower than those in the control groups. And again, both MSL patients were substantially more insulin sensitive than their respective control groups. For the sake of completeness we also came across a subject with clinical MSL and type 2 diabetes. But there are a number of reasons, which have little to do with our line of argument, for such a patient to acquire secondary types of diabetes, for example, via alcohol-induced pancreatitis.

Finally, the comment of Harsch et al. regarding a higher prevalence of obstructive sleep apnea syndrome (OSAS) among patients with MSL is interesting and valuable. OSAS seems to be an independent risk factor for insulin resistance (4). Upon reexamination of our small cohort, we indeed identified a man with documented OSAS (not among the ones reported). This patient appeared to be insulin sensitive and otherwise healthy, but due to his extreme obesity (BMI 64 kg/m2) would not fit into the magnetom, and we were unable to assess his visceral fat mass. This aspect is not necessarily in conflict with our original hypothesis but just another mechanism to render someone insulin resistant. Probably, among two equally obese subjects with OSAS, the one with only subcutaneous fat accumulation is more insulin sensitive.

In conclusion, at some point the reasoning becomes circular and our way of presenting these selected patients with MSL may be just another way of demonstrating that subcutaneous fat is metabolically more innocent than visceral fat (5).

Haap M, Siewecke C, Thamer C, Machann J, Schick F, Haring HU, Szeimies RM, Stumvoll M: Multiple symmetric lipomatosis: a paradigm of metabolically innocent obesity? (Brief Report).
Diabetes Care
Harsch IA, Michaeli P, Hahn EG, Ficker JH, Konturek PC: Launois-Bensaude syndrome in a female with type 2 diabetes.
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Harsch IA, Schahin SP, Wiedman R: Multiple symmetric lipomatosis: a paradigm of metabolically innocent obesity? (Letter).
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Harsch IA, Schahin SP, Radespiel-Troger M, Weintz O, Jahreiss H, Fuchs FS, Wiest GH, Hahn EG, Lohmann T, Konturek PC, Ficker JH: Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome.
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