Association of DiaRem Score With Cure of Type 2 Diabetes Following Bariatric Surgery

There is great anticipation for the predicted impact that the Precision Medicine Initiative will have on health outcomes.¹ However, we do not need to wait to sequence the DNA of the proposed 1 million–person cohort for this initiative; we can make significant strides in improving the precision of care delivery now. There are sufficient data in existing electronic health record systems that can be used to facilitate tailored treatment decisions. For example, the DiaRem score, a validated score generated from data readily available in the medical record, can be used for patients with type 2 diabetes to predict whether bariatric surgery will lead to short-term remission of diabetes.^2–4 Herein, we examine whether this score can be used to predict patients for whom bariatric surgery will result in cure of type 2 diabetes.⁵

Methods

We conducted electronic health record reviews up to 8 years after Roux-en-y gastric bypass (RYGB) surgery at Geisinger Medical Center for 407 patients with type 2 diabetes. These patients had RYGB surgery between June 2001 and December 2010. We conducted data analysis in October 2015. The sample was a subset of patients from the original validation study of DiaRem who had at least 5 years of electronic health record data postoperatively.² For each patient, we determined their preoperative DiaRem score (a weighted score, ranging from 0–22 points, based on age, insulin dependence, diabetes medication use, and hemoglobin A_1c [HbA_1c] level) and the extent of their diabetes remission based on American Diabetes Association criteria after RYGB surgery^{2, 5} (Table). Complete remission was defined as return to normal glycemic measures (HbA_1c level <5.7% of total hemoglobin [to convert to proportion of total hemoglobin, multiply by 0.01]; fasting glucose level <100 mg/dL [to convert to millimoles per liter, multiply by 0.0555]) and no treatment for 1 year.⁵ Patients were classified as cured if complete remission lasted at least 5 years, based on a published consensus statement.⁵ Partial remission was defined as hyperglycemia below diagnostic thresholds for diabetes (HbA_1c level <6.5% of total hemoglobin; fasting glucose level <125 mg/dL) and no active treatment or procedures for 1 year.⁵ Patients were classified as having prolonged partial remission if partial remission lasted at least 5 years.⁵ Patients were stratified into groups by DiaRem score (scores of 0–2, 3–7, 8–12, 13–17, and 18–22 points). The percentage of patients within each stratum who were cured and who achieved prolonged partial remission were compared using Cochran-Armitage trend tests. This study was approved by the Geisinger Institutional Review Board and participants provided written informed consent.

Table.

Descriptive Profile of the 407 Patients Included in the Analysis

Characteristic	Value (N = 407)
Age, mean (SD) [range], y	51.1 (9.5) [22–72]
Sex, No. (%)
Male	101 (25)
Female	306 (75)
Race/ethnicity, No. (%)
Non-Hispanic white	394 (97)
Non-Hispanic black	6 (1)
Hispanic	6 (1)
Other or unknown	1 (<1)
BMI, mean (SD) [range]	48.5 (7.9) [35–76]
Preoperative fasting glucose, mean (SD) [range], mg/dL	135.1 (59.3) [44-371]
Preoperative hemoglobin A1c, mean (SD) [range], % of total hemoglobin	7.4 (1.6) [4.5–14.1]
Diabetes medications, No. (%)
Biguanides	314 (77)
Sulfonylureas	127 (31)
Nonmetformin insulin-sensitizing agent	125 (31)
Insulin	152 (37)
DiaRem scorea
Mean (SD)	8.3 (6.4)
Grouped by points, No. (%) of patients
0–2	100 (25)
3–7	126 (31)
8–12	43 (11)
13–17	105 (26)
18–22	33 (8)

Abbreviation: BMI, body mass index (calculated as weight in kilograms divided by height in meters squared).

SI conversion factors: To convert fasting glucose to millimoles per liter, multiply by 0.0555; to convert hemoglobin A_1c to proportion of total hemoglobin, multiply by 0.01.

^aThe DiaRem score is calculated by summing the following 4 scores: age (<40 years is scored as 0 points; 40–49 years, 1 point; 50–59 years, 2 points; and ≥60 years, 3 points); hemoglobin A_1c level (<6.5% of total hemoglobin is scored as 0 points; 6.5%–6.9% of total hemoglobin, 2 points; 7.0%–8.9% of total hemoglobin, 4 points; and ≥9.0% of total hemoglobin, 6 points); other diabetes drugs (metformin only is scored as 0 points; sulfonylureas and insulin-sensitizing agent other than metformin, 3 points); and treatment with insulin (no is scored as 0 points; yes, 10 points).

Results

The 407 patients who under went RYGB (mean [SD] age, 51.1 [9.5] years; 75% female) had a median follow-up of 7.1 years (interquartile range, 5.8–8.0 years) (Table). Of the 407 patients, 144 (35%) experienced 1 or more years of complete remission and another 97 (24%) had partial remission lasting at least 1 year. Cure of diabetes was found in 83 patients (20%), and another 102 (25%) had prolonged partial remission. For remissions of any duration, the proportion of patients achieving remission decreased as DiaRem scores increased (P < .001) (Figure). Among the 100 patients with a score from 0 to 2, 82 (82%) experienced prolonged partial remission compared with none of the 33 patients with a score of 18 or higher. Fifty of the 100 patients (50%) with a score of 0 to 2 were cured of diabetes compared with none of the 33 patients with a score of 18 or higher.

Figure. Proportion of Patients With Remission and Cure of Type 2 Diabetes Following Roux-en-Y Gastric Bypass by DiaRem Score.

Partial remission indicates no medications, hemoglobin A_1c (HbA_1c) level less than 6.5% of total hemoglobin (to convert to proportion of total hemoglobin, multiply by 0.01), fasting glucose level less than 125 mg/dL (to convert to millimoles per liter, multiply by 0.0555), and no active treatment or procedures for at least 1 year. Prolonged partial remission indicates no medications, HbA_1c level less than 6.5% of total hemoglobin, fasting glucose level less than 125 mg/dL, and no active treatment or procedures for at least 5 years. Complete remission indicates no medications, HbA_1c level less than 5.7% of total hemoglobin, fasting glucose level less than 100 mg/dL, and no active treatment or procedures for at least 1 year. Diabetes cure indicates no medications, HbA_1c level less than 5.7% of total hemoglobin, fasting glucose level less than 100 mg/dL, and no active treatment or procedures for at least 5 years.

Discussion

Precision medicine does not have to be complicated. The DiaRem score is an algorithm based only on age, medication use, and HbA_1c level that can predict the likelihood that a patient with type 2 diabetes will be cured by surgery. We previously demonstrated that the DiaRem score predicts remission lasting at least 12 months. However, more than one-third of patients with remission will have relapse within 5 years. We now show that the DiaRem score predicts who will be cured by surgery, defined as complete remission lasting at least 5 years. The recent efforts to build larger cohorts, gather more data, and develop new analytical capabilities do not preclude continued exploration into how existing data assets can be used to improve the precision of care today.