Ravi Retnakaran1, Baiju R Shah2. 1. Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON, Canada; Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, ON, Canada; Division of Endocrinology, University of Toronto, Toronto, ON, Canada. 2. Division of Endocrinology, University of Toronto, Toronto, ON, Canada; Institute for Health Policy Management and Evaluation, University of Toronto, Toronto, ON, Canada; Institute for Clinical and Evaluative Sciences, Toronto, ON, Canada; Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada. Electronic address: baiju.shah@ices.on.ca.
Abstract
BACKGROUND: In studies to date, gestational diabetes has consistently been associated with an increased future risk of cardiovascular disease, irrespective of the antepartum screening protocol or diagnostic criteria by which gestational diabetes is diagnosed. We reasoned that the resultant heterogeneity in the severity of dysglycaemia in women with gestational diabetes suggests that the relationship between gestational glycaemia and subsequent cardiovascular disease probably extends into the non-diagnostic range. Thus, we hypothesised that glucose screening in pregnancy would identify future risk of cardiovascular disease in women who did not have gestational diabetes. METHODS: We did a population-based cohort study using information from health-care administrative databases from the Ministry of Health and Long Term Care of Ontario (Canada). We identified all women in Ontario who had a 50 g oral glucose challenge test in pregnancy between 24 and 28 weeks gestation with a livebirth delivery between July 1, 2007, and Dec 31, 2015. Women who had a history of diabetes before pregnancy or had been previously hospitalised for cardiovascular disease were excluded. Women with a 1-h post-challenge plasma glucose concentration of 11·1 mmol/L or greater were considered to have gestational diabetes, as were women with a reading between 7·8 and 11·0 mmol/L inclusive for whom diabetes was recorded as a diagnosis on the delivery hospital record. The study population was divided into six groups based on the results of the glucose challenge test (≤4·8 mmol/L; 4·9-5·5 mmol/L; 5·6-6·2 mmol/L; 6·3-6·9 mmol/L; 7·0-7·9 mmol/L; and ≥8·0 mmol/L). The primary outcome was cardiovascular disease (a composite of hospitalisation for myocardial infarction, acute coronary syndrome, stroke, coronary artery bypass grafting, percutaneous coronary intervention, or carotid endarterectomy). All women were followed up from the index pregnancy until cardiovascular disease event, death, migration, or Sept 30, 2017, whichever came first. FINDINGS: 259 164 women were identified as eligible for this study: 13 609 who had gestational diabetes, and 245 555 women without gestational diabetes. The women were followed up over a median 3·9 years (IQR 2·8-5·6) for the development of cardiovascular disease. Each 1 mmol/L increment in the glucose challenge test result was associated with a 13% higher risk of cardiovascular disease (after adjustment for age, ethnicity, income, and rurality, adjusted hazard ratio [HR] 1·13, 95% CI 1·04-1·22). This relationship persisted after excluding women with gestational diabetes (1·14, 1·01-1·28). In women without gestational diabetes, those with an abnormal glucose challenge test result (≥7·8 mmol/L) and those with a result between 7·2 and 7·7 mmol/L had an increased risk of cardiovascular disease (HR 1·94, 95% CI 1·29-2·92; and 1·65, 0·99-2·76, respectively), compared with those with a result of 7·1 mmol/L or less (overall p=0·003). INTERPRETATION: The relationship between gestational glycaemia and subsequent risk of cardiovascular disease extends into the normoglycaemic range. Accordingly, glucose screening in pregnancy could identify future risk of cardiovascular disease in women who do not have gestational diabetes. FUNDING: None.
BACKGROUND: In studies to date, gestational diabetes has consistently been associated with an increased future risk of cardiovascular disease, irrespective of the antepartum screening protocol or diagnostic criteria by which gestational diabetes is diagnosed. We reasoned that the resultant heterogeneity in the severity of dysglycaemia in women with gestational diabetes suggests that the relationship between gestational glycaemia and subsequent cardiovascular disease probably extends into the non-diagnostic range. Thus, we hypothesised that glucose screening in pregnancy would identify future risk of cardiovascular disease in women who did not have gestational diabetes. METHODS: We did a population-based cohort study using information from health-care administrative databases from the Ministry of Health and Long Term Care of Ontario (Canada). We identified all women in Ontario who had a 50 g oral glucose challenge test in pregnancy between 24 and 28 weeks gestation with a livebirth delivery between July 1, 2007, and Dec 31, 2015. Women who had a history of diabetes before pregnancy or had been previously hospitalised for cardiovascular disease were excluded. Women with a 1-h post-challenge plasma glucose concentration of 11·1 mmol/L or greater were considered to have gestational diabetes, as were women with a reading between 7·8 and 11·0 mmol/L inclusive for whom diabetes was recorded as a diagnosis on the delivery hospital record. The study population was divided into six groups based on the results of the glucose challenge test (≤4·8 mmol/L; 4·9-5·5 mmol/L; 5·6-6·2 mmol/L; 6·3-6·9 mmol/L; 7·0-7·9 mmol/L; and ≥8·0 mmol/L). The primary outcome was cardiovascular disease (a composite of hospitalisation for myocardial infarction, acute coronary syndrome, stroke, coronary artery bypass grafting, percutaneous coronary intervention, or carotid endarterectomy). All women were followed up from the index pregnancy until cardiovascular disease event, death, migration, or Sept 30, 2017, whichever came first. FINDINGS: 259 164 women were identified as eligible for this study: 13 609 who had gestational diabetes, and 245 555 women without gestational diabetes. The women were followed up over a median 3·9 years (IQR 2·8-5·6) for the development of cardiovascular disease. Each 1 mmol/L increment in the glucose challenge test result was associated with a 13% higher risk of cardiovascular disease (after adjustment for age, ethnicity, income, and rurality, adjusted hazard ratio [HR] 1·13, 95% CI 1·04-1·22). This relationship persisted after excluding women with gestational diabetes (1·14, 1·01-1·28). In women without gestational diabetes, those with an abnormal glucose challenge test result (≥7·8 mmol/L) and those with a result between 7·2 and 7·7 mmol/L had an increased risk of cardiovascular disease (HR 1·94, 95% CI 1·29-2·92; and 1·65, 0·99-2·76, respectively), compared with those with a result of 7·1 mmol/L or less (overall p=0·003). INTERPRETATION: The relationship between gestational glycaemia and subsequent risk of cardiovascular disease extends into the normoglycaemic range. Accordingly, glucose screening in pregnancy could identify future risk of cardiovascular disease in women who do not have gestational diabetes. FUNDING: None.
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