This study was undertaken to determine the mechanism of ketosis resistance, which is often observed among patients with growth-onset diabetes in the tropics. Lipolysis was tested in vivo in the ketosis-resistant patients with growth-onset diabetes by determining: (1) Plasma immunoreactive insulin (IRI), blood glucose, and serum free fatty acid (FFA) concentrations during tests with epinephrine, phentolamine and epinephrine, and propranolol and epinephrine in twenty-five patients; and (2) blood ketone bodies during epinephrine and propranolol and epinephrine tests in fifteen patients. The findings were compared with results obtained in a similar number of ketosis-prone subjects with growth-onset diabetes and twenty-two normal controls.
The mean fasting plasma IRI levels were significantly lower in the ketosis-resistant diabetics than in the normal subjects, although the fasting blood glucose levels were three and one-half times greater in these diabetics than in the controls. There was no significant change in the glucose and IRI levels during the three tests. Fasting serum FFA levels were significantly lower in the ketosis-resistant than those in the ketosis-prone diabetics. No detectable serum FFA response was observed in the ketosisresistant patients during any of the three tests. Blood ketone levels were comparable with the values obtained in the normal controls, but were significantly lower than those in the ketosisprone patients. Blood ketones also did not change significantly during epinephrine and propranolol with epinephrine tests in the ketosis-resistant patients.
These results are interpreted to indicate that the mobilization of FFA from the adipose tissue is inadequate in the growth-onset diabetics who are ketosis resistant. The tailure is attributed to insensitivity of the adrenergic receptor sites and/or unresponsiveness of the adenyl cyclase-cyclic AMP-lipase system in the adipose tissue of these young diabetics. The absence of ketonemia in these diabetics is attributable to an insufficient delivery of the substrate (FFA) from the adipose tissue to the liver.