Abstract
The effects of long-term administration of phenethyl-biguanide hydrochloride (PBG) on glucose tolerance (oral and IV) and lactate dynamics were studied in obese nondiabetic and chemical diabetic subjects. In the obese nondiabetic subjects, parameters of glucose tolerance—glucose curve areas and glucose disappearance rates (K g)—were not significantly altered by PBG. However, significant elevations of immunoreactive insulin (IRI) in the oral glucose tolerance test (OGTT) and intravenous glucose tolerance test (IVGTT) were observed while being treated with PBG, suggesting some degree of “insulin resistance”. Means of blood lactate levels during the OGTT were similar before and while on PBG treatment. Lactate dynamics revealed an increased lactate pool distributed in a larger volume, without significant changes in fasting blood lactate. In the obese chemical diabetic patients, glucose curve areas during the OGTT were corrected in the PBG period, despite the presence of decreased insulin responses to glucose. In the IVGTT, similar glucose curve areas and K g values were shown in the presence of reduced insulin responses. These changes suggest some degree of PBG-induced facilitation of glucose entry into the cell in obese chemical diabetics. Blood lactate levels in the OGTT were higher at all times during PBG treatment, including fasting values. Lactate dynamics revealed that PBG increased the endogenous production rate of lactate, with expansion of the total lactate pool and no variation in the space of distribution. Plasma lactate concentrations increased significantly. These results show different effects of PBG in obese nondiabetics and obese chemical diabetics, in relation to glucose and lactate dynamics. Furthermore it seems that its effects on lactate dynamics are only exerted in the basal metabolic state of the patients.
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