Risk of type 2 diabetes according to regular use of proton pump inhibitors (PPIs)
| Cases/person-years | HR (95% CI) | |||
| Age and period-stratified model | Multivariable adjusted model 1* | Multivariable adjusted model 2† | ||
| NHS | ||||
| Non-regular PPI user | 3864/758043 | 1.00 (Reference) | 1.00 (Reference) | 1.00 (Reference) |
| Regular PPI user | 862/123249 | 1.63 (1.51 to 1.76) | 1.27 (1.18 to 1.37) | 1.22 (1.12 to 1.33) |
| NHS II | ||||
| Non-regular PPI user | 3457/866393 | 1.00 (Reference) | 1.00 (Reference) | 1.00 (Reference) |
| Regular PPI user | 1174/135042 | 2.16 (2.01 to 2.33) | 1.36 (1.26 to 1.47) | 1.27 (1.17 to 1.38) |
| HPFS | ||||
| Non-regular PPI user | 607/210398 | 1.00 (Reference) | 1.00 (Reference) | 1.00 (Reference) |
| Regular PPI user | 141/34346 | 1.44 (1.20 to 1.74) | 1.22 (1.01 to 1.47) | 1.12 (0.91 to 1.38) |
| Pooled | ||||
| Non-regular PPI user | 7928/1834834 | 1.00 (Reference) | 1.00 (Reference) | 1.00 (Reference) |
| Regular PPI user | 2177/292637 | 1.74 (1.37 to 2.20) | 1.31 (1.24 to 1.38) | 1.24 (1.17 to 1.31) |
*Multivariable adjusted model 1: additionally adjusted for race (white or other), family history of diabetes (yes or no), BMI (continuous), pack-years of smoking (0, 10–20, 20+, missing), alcohol intake per day (0, 0–2, 2–5, >5 g), physical activity (in quintiles), overall diet quality (AHEI score <30, 30.1–60, or >60), total calories (in quintiles), multivitamin use (yes or no), hypertension (yes or no), hypercholesterolaemia (yes or no), cancer (yes or no), menopausal status and postmenopausal hormone use (premenopausal, postmenopausal (never, past, current menopausal hormone use, or unknown), or missing), number of parity (0, 1–2, 3+ children), breastfeeding (no, 1–2 years, 2+ years, or missing), any use of antibiotics (yes or no), regular use of non-steroidal anti-inflammatory drugs (yes or no), and any use of steroids (yes or no).
†Multivariable adjusted model 2: additionally adjusted for gastro-oesophageal reflux disease (yes or no), gastric or duodenal ulcer (yes or no), upper gastrointestinal tract bleeding (yes or no) and regular use of histamine-2 receptor antagonists (yes or no).
HPFS, Health Professionals Follow-up Study; NHS, Nurses' Health Study.