The study by Balkau et al. (1) finds that people who are thinner and have more poorly controlled diabetes gain the most weight when started on insulin. While weight gain is a legitimate concern for patients and clinicians, we should take care not to immediately equate weight gain in this setting with harm, as it is changes in body composition that are more important. Hyperglycemia increases the osmotic pressure of the extracellular fluid, leading to a net movement of water from the cellular compartment into the extracellular fluid causing intracellular dehydration; at the same time, glycosuria may also cause decreased tubular reabsorption of fluid and concomitant extracellular fluid dehydration by osmotic diuresis (2). Insulin therapy, which decreases plasma glucose and glycosuria, may increase the hydration of fat-free mass (FFM) or could even reverse sarcopenia that can coexist with type 2 diabetes (3). Using the reference four-component model that compartmentalizes the body into fat, mineral (from bone mineral content), total body protein, and total body water (TBW), we have shown that insulin treatment increased fat and FFM similarly in patients with poorly controlled type 2 diabetes, with the FFM gain due entirely to TBW (4)—i.e., rehydration. It is perhaps therefore not surprising that Balkau et al. found that the patients who showed the most weight gain were least obese by BMI and had the most poorly controlled diabetes by A1C. What really matters more than body weight change per se is the balance between any benefits from improved glycemic control with insulin therapy on symptoms and metabolic risk factors against potential metabolic penalties from any weight gain. This area remains under-researched with contradictory data in the literature (5), perhaps as a result of the poor relationship between changes in weight or BMI to body composition changes.
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Duality of Interest. No potential conflicts of interest relevant to this article were reported.
