Diabetes Care Volume 37, May 2014 e87

Mohammed S.B. Huda,1 Tyrosine Kinase Inhibitor Sunitinib Stephanie A. Amiel,1 Paul Ross,2 and Allows Insulin Independence Simon J.B. Aylwin3 in Long-standing Type 1 Diabetes Diabetes Care 2014;37:e87–e88 | DOI: 10.2337/dc13-2132

Sunitinib, a tyrosine kinase inhibitor worsened, and insulin was reduced b-cell mass (4). Dasatinib given for 2 (TKI), along with other TKIs, is reported from 7 units TDD to 1 unit TDD over 2 weeks in a patient with type 2 diabetes to lower blood glucose in type 2 diabe- months, stopping completely after 3 and chronic myelogenous leukemia re- tes and in recent-onset type 1 diabetes months. Thyroid, renal, adrenal func- sulted in doubling of fasted C-peptide (T1D) (1,2). We report a case of sunitinib tion, and IGF-1 were within normal limits. levels (5). apparently inducing remission in long- For the next 3 months, she was ambu- Remission of T1D in this patient standing T1D. lant, eating regular small meals, and might have arisen due to promoting in- A 48-year-old woman, with T1D diag- insulin independent, without hypergly- sulin release or through an insulin-like nosed at age 9 and requiring lifelong cemia or ketosis, and preprandial capil- effect on target tissues through activa- insulin therapy, presented in 2004 lary blood glucose readings were tion of downstream signaling pathways. with a pancreatic neuroendocrine tu- between 90–144 mg/dL (5–8 mmol/L). After 5 months of sunitinib, our patient mor secreting gastrin. She proceeded HbA1c was 7.9% (62.8 mmol/mol) on had detectable C-peptide production. to pancreaticoduodenectomy with ad- starting sunitinib and decreased to However, using an accepted cutoff for juvant 5-fluorouracil chemotherapy. 6.7% (49 mmol/mol) after 5 months of fasted C-peptide of .0.3 nmol/L, she She had retinopathy, peripheral neu- treatment. During that time period, her remained in the range associated with ropathy, and impaired hypoglycemia body weight also steadily increased insulin-deficient T1D. Somatostatin awareness. Diabetes treatment in- from 62.5 kg to 76.8 kg with no edema, analogs may suppress ketogenesis and cluded insulin aspart and glargine, total duetoimprovedappetiteandwell- counterregulatory responses, leading to daily dose (TDD) of 25–35 units. Her being. Fasted serum C-peptide after 5 insulin reduction but not remission. pancreatic neuroendocrine tumor re- months of sunitinib treatment was Taken together, this case and the extant mained in clinical and radiological re- 69.5 ng/mL (0.21 nmol/L), with corre- literature suggest that further research mission until 2007 when multiple liver sponding glucose 129.6 mg/dL (7.2 into the effect of TKIs on the insulin sig- and pancreatic metastases were found mmol/L). In December 2011, 3 months naling pathway and the effect on pa- eLETTERS on surveillance imaging. Octreotide after stopping insulin, she died of pneu- tients with T1D would be of value. was introduced, and due to subse- monia and severe sepsis. fi quent hypoglycemia, her insulin TDD To our knowledge, this is the rst – wasprogressivelyreducedto6–7units. report of a TKI allowing a patient with a OBSERVATIONS Duality of Interest. No potential conflicts – – HbA1c remained between 7 7.5% (53 40-year duration of T1D to discontinue of interest relevant to this article were 58 mmol/mol). insulin for several months. Studies in a reported. Her metastatic disease progressed, rodent autoimmune diabetes model Author Contributions. M.S.B.H. wrote the and sunitinib 50 mg per day was com- have shown that imatinib and sunitinib initial main text of the manuscript. S.A.A., P.R., and S.J.B.A. contributed to editing and pre- menced in June 2011, with later dose can both induce long-term remission (3). paring the manuscript for submission. M.S.B.H. reduction to 25 mg per day after gastro- Imatinib induces diabetes remission in is the guarantor of this work and, as such, had intestinal side effects. Hypoglycemia the db/db mouse, possibly by increasing full access to all the data in the study and takes

1King’s Diabetes Research Group, King’s College, London, U.K. 2Department of Oncology, King’s College Hospital, London, U.K. 3Department of Endocrinology, King’s College Hospital, London, U.K. Corresponding author: Mohammed S.B. Huda, [email protected]. © 2014 by the American Diabetes Association. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. e88 Sunitinib and Type 1 Diabetes Diabetes Care Volume 37, May 2014

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