title: Improved glucose tolerance after effective lipid-lowering therapy with bezafibrate in a patient with lipoatrophic diabetes mellitus: a putative role for Randle's cycle in its pathogenesis?
abstract: This report describes a patient with lipoatrophic diabetes mellitus (LDM), which is a rare clinical syndrome characterized by lipoatrophy and severe insulin resistance. Although a genetic abnormality is suspected in the development of LDM, no functional mutations in key domains of the insulin receptor gene were detected. Therapy was directed primarily at decreasing the availability of non-esterified fatty acids (NEFA), and thereby improving glucose tolerance (Randle's cycle), by the administration of a lipid-lowering drug, bezafibrate. Serial changes in fasting levels of the hormones of glucose homeostasis and lipids were measured, as well as glucose and insulin responses to a 75-g oral glucose challenge at onset and following 3 and 6 months of fibrate therapy. Progressive reductions in the patient's levels of triglycerides and NEFA were paralleled by an improvement in beta-cell function, a decrease in insulin resistance, and the attainment of normal glucose homeostasis. We conclude that the pathogenesis of LDM may be related primarily to abnormal regulation of lipid, rather than glucose, metabolism.
authors.affiliation: Carbohydrate and Lipid Metabolism Research Group, University of the Witwatersrand Medical School, Johannesburg, South Africa.
authors.forename: V R
authors.initials: VR
authors.lastname: Panz
authors.forename: J R
authors.initials: JR
authors.lastname: Wing
authors.forename: F J
authors.initials: FJ
authors.lastname: Raal
authors.forename: M A
authors.initials: MA
authors.lastname: Kedda
authors.forename: B I
authors.initials: BI
authors.lastname: Joffe
mesh_terms: D000293:Adolescent; D001629:Bezafibrate / Q000627:therapeutic use*; D001786:Blood Glucose / Q000378:metabolism; D003923:Diabetes Mellitus, Lipoatrophic / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050356:Lipid Metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D007328:Insulin; D014280:Triglycerides; D001629:Bezafibrate