Endocrine Abstracts (2016) 45 OC8.7 | DOI: 10.1530/endoabs.45.OC8.7

Clarifying the natural history of human insulin receptoropathy

David Johnston, David Bulger, Julie Harris & Robert Semple


Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK.


Background: Insulin resistance is the reduced responsiveness of the body to the glucose-lowering activity of insulin. It is usually associated with obesity, but in a minority of patients, this is not the case. Single gene mutations can often be found in such patients, some of which affect the insulin receptor (INSR). There is a spectrum of genetic insulin receptoropathies. These can be considered as two groups. One group comprises rare, severe, autosomal recessive disorders: Donohue syndrome (DS) and Rabson-Mendenhall syndrome (RMS). The other group consists of Type A Insulin Resistance (TA), which is typically autosomal dominant.

Aims: To investigate the effect of different degrees of INSR function on birth weight, and on the biochemical profile, including HDL-Cholesterol, Triglyceride, and Adiponectin. Previous research has shown that patients with DS and RMS have reduced birth weight, and that patients with human insulin receptoropathy typically have preserved or elevated adiponectin levels, and do not have metabolic dyslipidemia (hypertriglyceridemia and low HDL-Cholesterol levels).

Methods: Patient notes were reviewed to add to an incomplete database of 185 patients with INSR mutations collected between 1992 and 2015. The mean values of birth weight, HDL-Cholesterol, Triglyceride, and Adiponectin were compared for patients with DS, RMS, and TA, using Student’s t-tests.

Results: The mean birth weight for DS patients was significantly lower than for RM or TA patients (P<0.0005). The mean HDL-Cholesterol for DS patients was significantly lower than for TA patients (P<0.005). The mean Triglyceride in TA was significantly lower than in DS (P<0.05), and significantly higher than in RM (P<0.005). The mean Adiponectin did not vary significantly between DS, RM, and TA patients.

Conclusion: Patients with different degrees of INSR function have significantly different birth weights and measurable biochemical results. These findings of differences between degrees of INSR function add to previous research which found characteristic biochemical results for insulin receptoropathies as a group. These differences in biochemical results could be further studied, to help direct genetic sequencing in patients for specific INSR mutations.

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