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Open access

S M Kandel and J A Cosgriff

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.

Open access

Dominic Cavlan, Shanti Vijayaraghavan, Susan Gelding and William Drake

Summary

A state of insulin resistance is common to the clinical conditions of both chronic growth hormone (GH) deficiency and GH excess (acromegaly). GH has a physiological role in glucose metabolism in the acute settings of fast and exercise and is the only anabolic hormone secreted in the fasting state. We report the case of a patient in whom knowledge of this aspect of GH physiology was vital to her care. A woman with well-controlled type 1 diabetes mellitus who developed hypopituitarism following the birth of her first child required GH replacement therapy. Hours after the first dose, she developed a rapid metabolic deterioration and awoke with hyperglycaemia and ketonuria. She adjusted her insulin dose accordingly, but the pattern was repeated with each subsequent increase in her dose. Acute GH-induced lipolysis results in an abundance of free fatty acids (FFA); these directly inhibit glucose uptake into muscle, and this can lead to hyperglycaemia. This glucose–fatty acid cycle was first described by Randle et al. in 1963; it is a nutrient-mediated fine control that allows oxidative muscle to switch between glucose and fatty acids as fuel, depending on their availability. We describe the mechanism in detail.

Learning points

  • There is a complex interplay between GH and insulin resistance: chronically, both GH excess and deficiency lead to insulin resistance, but there is also an acute mechanism that is less well appreciated by clinicians.

  • GH activates hormone-sensitive lipase to release FFA into the circulation; these may inhibit the uptake of glucose leading to hyperglycaemia and ketosis in the type 1 diabetic patient.

  • The Randle cycle, or glucose–fatty acid cycle, outlines the mechanism for this acute relationship.

  • Monitoring the adequacy of GH replacement in patients with type 1 diabetes is difficult, with IGF1 an unreliable marker.