Insulin-dependent diabetes mellitus (
IDDM) can lead to
ventilatory depression and decreased sensitivity to
hypercapnia. We examined relationships between ventilation, plasma
insulin,
leptin,
ketones, and
blood glucose levels in two mouse models of
IDDM: (1)
streptozotocin-induced diabetes in C57BL/6J mice on a regular diet or with induced
obesity from a high fat diet; and (2) spontaneous
diabetes mellitus in NOD-Ltj mice. In both mouse models,
IDDM resulted in depression of the hypercapnic ventilatory response (HCVR). This
ventilatory depression was not associated with decreases in plasma
insulin or
leptin levels. There was, however, a strong association between the duration of
hyperglycemia, the decline in HCVR, and increased glycosylation of the diaphragm.
Hyperventilation was observed in only six of 14 C57BL/6J obese wild-type mice, despite a significant degree of
diabetic ketoacidosis (DKA) in all 14 animals. In mice with DKA, there was a significant correlation between the increase in baseline minute ventilation (V E) and hyperleptinemia (r = 0.77, p < 0.01). In
leptin-deficient C57BL/6J-Lep(ob) mice, low levels of both V E and
ketones were observed. These results suggest that: (1) depression of the HCVR in
IDDM is associated with
hyperglycemia and glycosylation of the diaphragm; and (2) the
hyperventilation of DKA is
leptin dependent.