Urological Complications of Obesity and Diabetes in Males and Females of Three Mouse Models: Temporal Manifestations.

Diabetic bladder dysfunction is a frequent complication of diabetes. While many mouse models of diabetes now exist, there has been little systematic effort to characterize them for timing of onset and severity of bladder dysfunction. We monitored metabolic status and tested bladder function by void spot assay and limited anesthetized cystometry in both males and females of three models of obesity and diabetes: a type 1 diabetes model (Akita mouse) and two type 2 diabetes models (Diet Induced Obesity (DIO) model, and ob/ob mouse). Akita mice had insulin pellets implanted subcutaneously every 3 months to mimic poorly controlled type 1 diabetes in humans. Mice were hyperglycemic by 48 days following implants. Female mice exhibited no bladder dysfunction at any age up to 20 months and gained weight normally. In contrast, by seven months, male Akita developed a profound polyuria and failed to show normal weight gain. There were no observable signs of bladder dysfunction in either gender. DIO mice on high/low fat diets for 16 months, exhibited mild hyperglycemia in the females (not in males), mild weight gain and no evidence of bladder dysfunction. Ob/ob mice were followed for eight months and became extremely obese. Males and females were glucose intolerant, insulin intolerant and hyperinsulinemic at four months. By eight months, their metabolic status had improved but was still abnormal. Urine volume increased in males, but not in females. Bladder dysfunction was observed in the spotting patterns of females at four and six months of age, resolving by eight months. We conclude there are dramatic gender-related differences in lower urinary tract function in these models. Akita males may be a good model for polyuria-related bladder remodeling, while ob/ob females may better mimic storage problems related to loss of outlet control in a setting of type 2 diabetes complicated by obesity.