Insulinoma in Patients with Diabetes- A Systematic Review of Previously Reported Cases

Paradoxical co-existence of insulinoma and diabetes is extremely rare. Although a few case reports addressed this association, a comprehensive study elucidating this relationship has been lacking. We performed a systematic review of published cases of insulinoma in diabetes.

We conducted a literature search using PubMed and Google Scholar, employing various combinations of the following terms: 'insulinoma', 'diabetes', 'nesidioblastosis', 'endogenous hyperinsulinism', 'hypoglycaemia', and 'hyperglycaemia' (from January 1900 to January 30, 2024). Exclusion criteria included non-English publications, duplicate articles, reports lacking sufficient data, cases of endogenous hyperinsulinemic hypoglycaemia other than insulinoma, and inaccessible articles. Statistical analysis was performed using appropriate methods.

Sixty patients were considered for the final analysis. Mean age was 61 ± 15 years (range: 17-96 years) with a slight female preponderance; 88.3% had type-2 diabetes with a median duration of 8 years. The median delay in diagnosis of insulinoma was 6 months. Median blood glucose varied from 30.5 mg/dL to 235 mg/dL, with a mean HbA1c of 5.6 ± 1.3% (range: 2.9%-8.2%). Critical sampling data were available in 75% of cases. The median size of the insulinoma was 2 cm. Furthermore, 5.2% of insulinomas were extra-pancreatic. Among pancreatic insulinomas, 14.5% were multi-focal. One-third of cases were malignant. Surgical resection was done in 70.9% of cases, while 40% received drug therapy and 12.7% received both, with 20.7% overall mortality. Malignant insulinoma (P = 0.007), micro-angiopathic (P = 0.018) and macro-angiopathic complications (P = 0.039), and other co-morbidities (P = 0.009) were associated with unfavourable prognosis, while being overweight and obese (P = 0.020) at presentation was associated with favourable prognosis.

This first systematic review provides insights into the uniqueness of insulinoma in diabetes.