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      Flying under the radar: treatment of refractory hyperglycemia

      research-article
      1 , 2 , , 1 , 2 ,
      Endocrinology, Diabetes & Metabolism Case Reports
      Bioscientifica Ltd

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          Summary

          Clinicians are often presented with the scenario of what to do when one medication in a drug class has failed a therapeutic trial on a patient. We encountered a patient who developed profound resistance to glargine, aspart and regular insulin, but had a rapid and sustained response to detemir. The mechanism of the increased sensitivity to detemir is unclear, but may be related to an additional carbon chain on detemir shielding it from an antibody response. This case highlights the profound impact that subtle differences in molecular structure can have on biological activity and thus patient outcomes.

          Learning points

          • Subtle differences in molecular structure can have a profound impact on biological activity, and thus patient outcomes.

          • Poor outcomes with one medication in a drug class should not be used to rule out the efficacy of all related medications.

          • Detemir has been shown to be less immunogenic than other insulins, and should be considered in patients with insulin resistance.

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          Most cited references2

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          2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid, an amino acid for the synthesis of mimics of O-linked glycopeptides.

          Amino acids with N-alkylaminooxy side chains have proven effective for the rapid synthesis of neoglycopeptides. Chemoselective reaction of reducing sugars with peptides containing these amino acids provides glycoconjugates that are structurally similar to their natural counterparts. 2-(N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid (Fmoc: 9-fluorenylmethoxycarbonyl; Boc: t-butyloxycarbonyl) was synthesized from Boc-Ser-OH in >40% overall yield and incorporated into peptides by standard Fmoc chemistry based solid phase peptide synthesis. The resulting peptides are efficiently glycosylated and serve as mimics of O-linked glycopeptides. The synthesis of this derivative greatly expands the availability of the N-alkylaminooxy strategy for neoglycopeptides.
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            Resistance to insulin due to neutralizing antibodies.

              Author and article information

              Journal
              Endocrinol Diabetes Metab Case Rep
              Endocrinol Diabetes Metab Case Rep
              edm
              EDM Case Reports
              Endocrinology, Diabetes & Metabolism Case Reports
              Bioscientifica Ltd (Bristol )
              2052-0573
              6 July 2016
              2016
              : 2016
              : 160052
              Affiliations
              [1 ]Yale Waterbury Internal Medicine Residency Program , Yale University School of Medicine, New Haven, Connecticut, USA
              [2 ]Department of Medicine , Waterbury Hospital, Waterbury, Connecticut, USA
              Author notes
              Correspondence should be addressed to S M Kandel; or J A Cosgriff; Email: sean.kandel@ 123456yale.edu or jcosgriff@ 123456wtbyhosp.org
              Article
              EDM160052
              10.1530/EDM-16-0052
              4949489
              27441092
              ba9f2366-c39e-49d0-b7c8-27cf21ec8d5e
              © 2016 The authors

              This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License.

              History
              : 18 May 2016
              : 8 June 2016
              Categories
              Insight into Disease Pathogenesis or Mechanism of Therapy

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