Determining the optimal screening interval for type 2 diabetes mellitus using a risk prediction model

Abstract

Background: Progression to diabetes mellitus (DM) is variable and the screening time interval not well defined. The American Diabetes Association and US Preventive Services Task Force suggest screening every 3 years, but evidence is limited. The objective of the study was to develop a model to predict the probability of developing DM and suggest a risk-based screening interval.

Methods: We included non-diabetic adult patients screened for DM in the Cleveland Clinic Health System if they had at least two measurements of glycated hemoglobin (HbA1c), an initial one less than 6.5% (48 mmol/mol) in 2008, and another between January, 2009 and December, 2013. Cox proportional hazards models were created. The primary outcome was DM defined as HbA1C greater than 6.4% (46 mmol/mol). The optimal rescreening interval was chosen based on the predicted probability of developing DM.

Results: Of 5084 participants, 100 (4.4%) of the 2281 patients with normal HbA1c and 772 (27.5%) of the 2803 patients with prediabetes developed DM within 5 years. Factors associated with developing DM included HbA1c (HR per 0.1 units increase 1.20; 95%CI, 1.13-1.27), family history (HR 1.31; 95%CI, 1.13-1.51), smoking (HR 1.18; 95%CI, 1.03-1.35), triglycerides (HR 1.01; 95%CI, 1.00-1.03), alanine aminotransferase (HR 1.07; 95%CI, 1.03-1.11), body mass index (HR 1.06; 95%CI, 1.01-1.11), age (HR 0.95; 95%CI, 0.91-0.99) and high-density lipoproteins (HR 0.93; 95% CI, 0.90-0.95). Five percent of patients in the highest risk tertile developed DM within 8 months, while it took 35 months for 5% of the middle tertile to develop DM. Only 2.4% percent of the patients in the lowest tertile developed DM within 5 years.

Conclusion: A risk prediction model employing commonly available data can be used to guide screening intervals. Based on equal intervals for equal risk, patients in the highest risk category could be rescreened after 8 months, while those in the intermediate and lowest risk categories could be rescreened after 3 and 5 years respectively.

Fig 1. Cumulative probability of developing diabetes mellitus.

Cumulative probability of 5% would be reached in 19 months for all patients, in 7 months for patients with HbA1c 6.1–6.4%, and in 26 months for patients with HbA1c 5.7–6.0%. Patients with HbA1c <5.7% won’t reach the 5% threshold within 5 years.

Fig 2. The calibration of the model, which measures the relationship between the model’s predicted probability against the actual probability.

The final model, had a bootstrap bias-corrected c-statistic of 0.809 with a 95% CI (0.795, 0.823). Quintiles of 5-year risk ranged from 0.03–0.49 and were well calibrated.

Fig 3. Cumulative probability of developing diabetes mellitus.

Cumulative probability of 5% would be reached in 8 months for T3 and 35 months for T2. T1 won’t reach the 5% threshold.