Abstract
IMPORTANCE: Primary hyperparathyroidism (PHPT) is linked to insulin resistance, glucose intolerance, and diabetes. Whether parathyroidectomy is associated with lower risk of diabetes has not been evaluated in a large cohort. OBJECTIVE: To examine the independent association between parathyroidectomy and the risk of incident diabetes in patients with PHPT. DESIGN, SETTING, AND PARTICIPANTS: Patients diagnosed with PHPT between January 2006 and December 2023 were identified from a territorywide electronic health database in Hong Kong and classified into surgical and nonsurgical groups based on presence of subsequent parathyroidectomy. They were followed up with from the index date (first diagnosis of PHPT), until the outcome of interest (incident diabetes), death, or end of the study period (December 2023), whichever came first. EXPOSURE: Parathyroidectomy vs nonsurgical management. MAIN OUTCOMES AND MEASURES: The primary outcome of this study was incident diabetes. Inverse probability of treatment weighting was used to balance all baseline characteristics. Cox proportional hazards regression was used to evaluate the hazard of incident diabetes associated with parathyroidectomy. RESULTS: A total of 3135 patients with PHPT were included (596 [19.0%] surgical and 2539 [81.0%] nonsurgical). The mean (SD) age was 67.5 (14.2) years, and 2211 (70.5%) individuals were female. A total of 518 patients in the nonsurgical group developed incident diabetes during a median (IQR) follow-up of 2.2 (0.9-4.3) years, compared to 156 patients in the surgical group during a median (IQR) follow-up of 5.5 (3.3-8.0) years. Parathyroidectomy was associated with lower risk of incident diabetes (hazard ratio [HR], 0.68 [95% CI, 0.65-0.71]; P < .001). Results were consistent across multiple sensitivity analyses. Subgroup analyses revealed more prominent protective associations among younger patients (age ≤65 years vs >65 years: HR, 0.64 [95% CI, 0.60-0.68] vs HR, 0.68 [95% CI, 0.63-0.72]; interaction P < .001) and those with more severe PHPT (parathyroid hormone [PTH] > twice the upper limit of normal vs PTH ≤ twice the upper limit of normal: HR, 0.58 [95% CI, 0.53-0.63] vs HR, 0.73 [95% CI, 0.69-0.77]; calcium > 2.8 vs calcium ≤ 2.8 mmol/L : HR, 0.58 [95%CI, 0.54-0.63] vs HR, 0.69 [95%CI, 0.66-0.73]; interaction P < .001). CONCLUSIONS AND RELEVANCE: In this cohort of patients with PHPT, parathyroidectomy was associated with a lower risk of incident diabetes. The association was more prominent in younger patients and those with more severe PHPT. These results may suggest potential additional metabolic benefits of parathyroidectomy in PHPT.