¹Dr. Omer Yassin,  ¹Dr.Abad, ¹Dr. Omhaggan

¹Global Care Hospital

Background: Trial to use icatibant/lanadelumab in cases of “IDDM type 1” associated with systemic angioedema and urticaria due to intrinsic insulin allergy.

Method(s): 3 sisters and their niece – all female – at middle different age, with the same history of IDDM type 1 caused by intrinsic insulin allergy, probable genetically linked.  The clinical picture presents as high-grade insulin resistance and idiopathic urticaria resulting in the initial diagnosis of Type 1 – insulin dependent diabetes mellitus. In fact, when started on icatibant the patients recovered their own insulin production – proven by normalised c-peptide levels. Ketones rise when fasting or eating carbs, tests showed normal insulin levels, which is caused by either resistance against insulin versus intrinsic allergy against insulin – deactivating insulin action. The effect of giving insulin resulted in generalised urticaria all over their bodies, itching and lung oedema associated with SOB

Result(s): Started management: We started firazyr (icatibant) with the 1st  patient in May 2022 and she felt much better with the first injection, observing reduced oedema and improved control of her CBG readings between 200-233mg/dl and while it was up 400mgdl+ with complication of DKA and admission to the ICU. The first follow up lab test showed a reduction of the HBA1c from >13% to 7.4% after three months. And more importantly the patient did not observe any generalised edema nor urticaria. However, when intermittent delay of provision of icatibant delayed her doses (initially twice weekly injections – currently daily injections) this 1st patient started to develop symptoms again like swelling of her face, leg oedema, acute vertigo, neck pain and headache with HbA1c rising to 9.2% again.

In November 2022 this 1st patient was started on lanadelumab as add on but could not be sustained for insurance reasons. Goal would have been to reduce daily injections to twice monthly injection. In November 2022 the 2nd patient was started on Firazyr – within 6 months – her C-peptide level, initially at zero (0) rose to normal level. By now she cannot be considered DM type 1 anymore.

In March 2023 and April 2023 patients 3 and 4 were started on Firazyr twice weekly injections with equal improved reduction of HbA1c through improved CBG control via use of their own insulin.

Conclusion(s): Icatibant, sold under the brand name Firazyr was developed for patients with HAE – who have an absence or dysfunction of C1-esterase-inhibitor which leads to the production of bradykinin. The presence of bradykinin may cause symptoms of localized and generalised swelling, inflammation, pain and angioedema. Icatibant inhibits bradykinin from binding at the B2 receptor, thereby treating the symptoms associated with acute attack.

Lanadelumab / Takhzyro comes as a further solution as it reduces the dosing to twice monthly.

Currently all 4 patients are either without external insulin doses, or much reduced need for insulin as their own pancreas restarted insulin production.

We will need to observe the course and report again next year.