No Effect of Deferoxamine Therapy on Glucose Homeostasis and Insulin Secretion in Individuals With NIDDM and Elevated Serum Ferritin J. BRUCE REDMON, KATHRYN L. PYZDROWSKI, AND R. PAUL ROBERTSON Deferoxamine has been proposed as a potentially important therapy for individuals with NIDDM and mild elevations in serum ferritin. Previously, iron chelation therapy with intravenous deferoxamine over a 5-13-wk period has been reported to normalize serum ferritin and markedly improve glycemic control. To confirm these results and to study potential beneficial effects of deferoxamine on insulin secretion, 9 individuals with NIDDM and elevated serum ferritin levels were treated twice weekly with deferoxamine infusion, following a previously described protocol. Although 8 of 9 subjects achieved normal or near-normal serum ferritin values after deferoxamine therapy, we found little evidence that it produced beneficial effects on glycemic control. Fasting glucose levels pre- and post-deferoxamine therapy were unchanged (11.6 ± 1.2 and 11.3 ± 1.5 mM, respectively, P= 0.80). GHb levels declined slightly after deferoxamine therapy (9.3 ± 0.7 vs. 8.8 ± 0.7%, P < 0.05); however, this effect was small and was not associated with elimination of or even substantial reduction in insulin or oral hypoglycemic therapy. Deferoxamine therapy did not significantly alter fasting insulin or C-peptide levels, nor stimulated insulin or C-peptide responses to intravenous arginine or glucose. During follow-up studies 1.5-8 mo after deferoxamine therapy, serum ferritin levels again were elevated in 5 of 8 subjects who showed an initial response. Thus, although deferoxamine therapy reduced serum ferritin levels in our subjects, we were unable to confirm a previous report that this effect was associated with any meaningful improvement in glycemic control or insulin secretion. Diabetes 42:544-49,1993 From the Diabetes Center and Division of Endocrinology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota. Address correspondence and reprint requests to R. Paul Robertson, MD, Diabetes Center and the Division of Endocrinology, Box 101 UMHC, Univer- sity of Minnesota, Minneapolis, MN 55455. Received for publication 20 July 1992 and accepted in revised form 19 November 1992. NIDDM, non-insulin-dependent diabetes mellitus; RIA, radioimmunoassay; HPLC, high-pressure liquid chromatography; BMI, body mass index. D iabetes mellitus is a common and early mani- festation of severe iron overload in individuals with primary, familial hemochromatosis (1-4). Reduction of body iron stores by repeated venesection results in improvement or normalization of carbohydrate metabolism in up to 40% of individuals with hemochromatosis, suggesting that diabetes in these individuals is a secondary and reversible manifestation of iron overload (4-6). Cutler reported a trial of iron chela- tion therapy in a group of 9 patients with elevated serum ferritin levels and NIDDM (7). Treatment of those pa- tients with intravenous administration of the iron chelator deferoxamine normalized their serum ferritin levels, and 8 of 9 showed a dramatic clinical response character- ized by cessation of insulin or oral hypoglycemic ther- apy, normalization of GHb values, and normalization or near-normalization of fasting glucose levels. Cutler pos- tulated that disordered iron metabolism may be com- mon in diabetic individuals and may represent a here- tofore unrecognized and reversible form of secondary diabetes mellitus. However, he did not assess the pos- sible mechanisms through which deferoxamine im- proved glucose control. In particular, no measurements of basal or glucose-stimulated insulin secretion were reported. To confirm the results reported by Cutler and to exam- ine the potential beneficial effects of deferoxamine on p-cell function, we conducted a trial of deferoxamine therapy in patients with NIDDM and elevated serum ferritin, following the same protocol described by Cutler (7). RESEARCH DESIGN AND METHODS Individuals with a clinical diagnosis of NIDDM were recruited from our clinic population and through ad- vertisement in the local media. After giving informed 544 DIABETES, VOL. 42, APRIL 1993 Downloaded from http://diabetesjournals.org/diabetes/article-pdf/42/4/544/359881/42-4-544.pdf by guest on 18 February 2024