Table 1.
Hyperglycemia and Endometrial Cancer.
| Author | Design | Population | Measure | Results |
|---|---|---|---|---|
| NNHSS Cohort * [24] | Prospective Cohort | 24,460 women 130 EC cases |
Non-fasting blood glucose | Overweight women 2.45 times more likely to be diagnosed with EC with baseline non-fasting serum glucose ≥5.6 mmol/L (RR, 95%CI 1.11–5.42). No difference in risk found in women with normal BMI. |
| EPIC Cohort [25] | Nested case-control | 284 EC cases 546 matched control subjects |
Pre-diagnosis blood glucose | Post-menopausal women 2.6 times more likely to be diagnosed with EC with higher baseline blood glucose (RR, 95%CI 1.46–4.66, p < 0.001). No difference in risk found in pre- or peri-menopausal women. |
| WHIOS Cohort [26] | Prospective Cohort | 250 EC cases 465 randomly-selected controls § |
Fasting blood glucose | Fasting serum glucose levels were not associated with EC. |
| Me-Can Cohort * [27] | Prospective Cohort | 290,000 women 917 EC cases |
Non-fasting blood glucose | Higher baseline serum glucose associated with EC in the two highest BMI quintiles (RR = 1.17, 95%CI 1.09–1.25). No association seen in lowest BMI quintiles. |
| AMORIS Cohort [28] | Prospective Cohort | 230,737 women | Blood glucose (fasting and non-fasting) | Women with impaired glucose metabolism (6.1–6.9 mmol/L) were at 2 times increased risk of EC diagnosis than women with normal glucose metabolism (<6.1 mmol/L). Women with diabetes mellitus (≥7 mmol/L or recorded diagnosis) were 1.75 times more like to be subsequently diagnosed with EC (HRs, 95%CI 1.11–3.60 and 0.82–3.75 respectively) |
| Alberta Population [29] | Case-Control | 541 EC cases 961 age-matched controls |
Fasting blood glucose | Small association between higher baseline blood glucose and EC diagnosis (OR = 1.15, 95%CI 1.00–1.31) |
| SEER Medicare database [30] | Case-Control | 16,323 EC cases 100,751 controlsAll women ≥65 years old |
Impaired fasting glucose as recorded in medical notes, including type 2 diabetes diagnosis | EC risk was associated with impaired fasting glucose (OR = 1.38, 95%CI 1.29–1.42) |
| Vasterbotten Intervention Project [31] | Prospective Cohort | 33,293 women 117 EC cases with blood glucose measurements |
Fasting blood glucose and blood glucose 2 h post 75g glucose load | Significant increasing trend in EC risk with increasing quartiles of fasting and post-load blood glucose with top versus bottom quartile RR of 1.86 (1.09–3.31, p = 0.019) and 1.82 (1.07–3.23, p = 0.028) respectively. |
| Modesitt et al. 2012 [32] | Case-control | 38 morbidly obese women ≥50 years old scheduled for hysterectomy 22 with EC |
Fasting blood glucose on morning of surgery | Significantly higher mean blood glucose in EC cases than controls (6.64 mmol/L cases vs. 5.04 mmol/L controls, p = 0.049) |
| Shou et al. 2010 [33] | Retrospective cohort | 123 EC cases 90 age-matched controls |
Fasting blood glucose | Significantly more cases than controls with blood glucose ≥ 5.6 mmol/L (50.4% vs. 27.8%, p < 0.05). |
| Zhan et al. 2013 [34] | Case-control | 206 EC cases 350 controls |
Pre-operative fasting blood glucose or type 2 diabetes diagnosis | Significantly higher mean blood glucose in EC cases than controls (6.2 vs. 5.4 mmol/L, p < 0.001). |
| Ozdemir et al. 2015 [35] | Case-control | 199 women undergoing endometrial curettage for abnormal uterine bleeding 146 with normal endometrium 53 with hyperplasia or carcinoma |
Fasting blood glucose | Significantly higher mean blood glucose in cases than controls (125.8 vs. 97.8 mg/dL, p < 0.001). Odds ratio of endometrial pathology according to fasting glucose level >88 mg/dL (4.9 mmol/L) was 0.11 (95%CI 0.03–0.3, p < 0.001). |
| Nead et al., 2015 [21] | Mendelian Randomization (MR) analysis | 1287 case patients and 8273 control participants from EC studies in Australia and UK | Genetically-predicted fasting glucose levels using 36 genetic variants associated with fasting glucose | Genetically-predicted higher fasting glucose levels were not associated with EC (OR = 1.00, 95% CI = 0.67 to 1.50, p = 0.99). |
| Karaman et al., 2015 [36] | Case-control, retrospective | 35 surgically staged EC patients 40 healthy controls |
HbA1c levels within 3 months of hysterectomy | Significantly higher mean HbA1c in cases than controls (6.19% vs. 5.61%, p = 0.027). |
| Miao Jonasson et al., 2012 [37] | Prospective Cohort | 25,476 patients with type 2 diabetes 183 cases of female genital cancer |
Baseline HbA1c | No increased risk of female genital cancers with HbA1c ≥7.5% versus <7.5% No endometrial cancer-specific data. |
| Traviar et al., 2007 [38] | Prospective Cohort | 25,814 women 13 EC cases Patients with a previous diagnosis of diabetes mellitus were excluded |
Baseline HbA1c | 4.05 –fold increase with baseline HbA1c 6.0–6.9% (HR, 95%CI 1.10–14.88) and 5.07 –fold increase with baseline HbA1c ≥7.0% in EC risk (HR, 95%CI 1.20–21.31) compared to HbA1c <6.0% |
| Levran et al., 1984 [39] | Case-control | 22 EC cases 939 controls of similar weight |
HbA1 1-10 years after diagnosis | HbA1 was significantly increased in cases compared to controls (p < 0.01) |
* overlapping populations. § Diabetics and patients with blood glucose > 125 mg/dL (~6.9 mmol/L) were excluded from study; Blue shaded rows indicate studies showing a relationship between EC risk and increased blood glucose levels, whereas uncolored rows show no association between these factors.