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Mild Glucose Intolerance In Pregnancy May
Be Associated With Cardiovascular Risk
  "Perhaps the cause of the failure of intensive glycemic control regimens, particularly insulin, sulphonylureas and glitazones, is that they inevitably increase weight in already obese people, by an average of 6 kg in the UKPDS trial,12 which is frequently cited as showing the benefits of intensive insulin control.....Weight gain may be key. The newer incretin-like agents (derived from gut hormones supressing glucagon and allowing improved insulin action) can now be trialed to test whether weight gain has been the cause of glycemic control's failure to prevent vascular disease so far."

"Our findings raise the possibility that, in addition to women with gestational diabetes, at least a subset of women with a lesser degree of antepartum dysglycemia may also benefit from closer cardiovascular surveillance.....Because antepartum screening for gestational

diabetes is currently performed in clinical care, it may be convenient and potentially cost-effective if this testing could be secondarily used to detect women at risk of cardiovascular disease, for whom preventive action may be particularly beneficial."

"After adjustment for age, year of delivery, residence location (rural v. urban), income, comorbidity, pre-existing hypertension and gestational hypertension (model A), the Cox proportional hazard ratios (HRs) for cardiovascular disease among women with gestational diabetes and those who received an oral glucose tolerance test were 1.66 (95% confidence interval [CI] 1.30-2.13, p < 0.001) and 1.19 (95% CI 1.02-1.39, p = 0.03) (Table 2), respectively, compared with the women who did not have an oral glucose tolerance test. Compared with women who did not have an oral glucose tolerance test, the absolute risk differences were 0.16% for women with gestational diabetes and 0.05% for those who received an oral glucose tolerance test. After further adjustment adjustment for the subsequent development of diabetes (model B), the HRs for cardiovascular disease were attenuated (gestational diabetes group HR 1.25, 95% CI 0.96-1.62, p = 0.1; oral glucose tolerance test group HR 1.16 (95% CI 0.99-1.36, p = 0.06) (Table 3)."

Even in the absence of gestational diabetes, women who receive an oral glucose tolerance test in pregnancy (typically after abnormal results of a glucose challenge test) may have an increased incidence of subsequent cardiovascular disease. These data raise the possibility that mild glucose intolerance in pregnancy may identify a population of women who are at increased risk of cardiovascular disease in the future. Further study is needed to determine whether findings on antepartum glucose tolerance screening may provide previously unrecognized insight into the risk of vascular disease in young women."

Canadian Medical Association Journal LINKS TO pdfs

Mild glucose intolerance in pregnancy and risk of cardiovascular disease
Ravi Retnakaran, Baiju R. Shah August 24, 2009
COMMENTARY: Pregnancy glycemia to vascular risk: nonglycemic diabetes?

Mild Glucose Intolerance In Pregnancy May Be Associated With Cardiovascular Risk

24 Aug 2009 -

Mild glucose intolerance in pregnancy may be an early identifier of women who are at increased risk of heart disease in the future, found a new study published in CMAJ (Canadian Medical Association Journal.)

In a large population-based cohort study, researchers from the University of Toronto and the Institute for Clinical Evaluative Sciences (ICES) studied data on 435,696 women in Ontario, Canada, who gave birth between April, 1994 and March, 1998. All women were followed until March 31, 2008. The study excluded women with pre-existing diabetes.

As cardiovascular disease is the leading cause of death in Canadian women, it is important to identify early predictors of future vascular risk. While women with gestational diabetes have a higher risk of cardiovascular disease than those without, it previously has not been known whether mild glucose intolerance in pregnancy is associated with heart disease. The study sought to answer this question.

Gestational diabetes is a condition leading to temporarily high blood sugars during pregnancy. It is an important risk factor for future type 2 diabetes. Women are generally screened for gestational diabetes with a glucose challenge test in the late second trimester. If the result is abnormal, they go on to have an oral glucose tolerance test to confirm the diagnosis.

"Women who had an abnormal glucose challenge test but then did not have gestational diabetes had an increased risk of future cardiovascular disease compared to the general population, but a lower risk than women who actually did have gestational diabetes," writes Dr. Baiju Shah, Institute for Clinical and Evaluative Sciences and coauthor.

They suggest that "in women with glucose intolerance during pregnancy, type 2 diabetes and vascular disease may develop in parallel, which is consistent with the "common soil" hypothesis for these conditions."

Current screening procedures for gestational diabetes might also provide a means for the early identification of women who are at risk for developing heart disease later in life.

In a related commentary, Dr. J. Kennedy Cruickshank and Dr. Moulinath Banerjee of the Manchester Royal Infirmary, University of Manchester, UK write that "what the study by Retnakaran and Shah shows is that we all have a great deal to learn from sub-clinical blood vessel changes in younger women who are likely overweight during pregnancy."

They suggest that diabetes research should focus on the blood vessel rather than glycemia.

Glucose Intolerance in Pregnancy May Predict CV Future

By Crystal Phend, Senior Staff Writer, MedPage Today

August 24, 2009

Action Points

* Explain to interested patients that gestational diabetes is linked to future risk of diabetes and cardiovascular risk, and that these results suggest the same may be true for lesser degrees of glycemic problems in pregnancy.

* Note that the study was based on administrative and insurance databases without direct monitoring of clinical events or test measurements.

Mild glucose intolerance in pregnancy -- even if it doesn't rise to gestational diabetes -- may modestly predict future cardiovascular risk, according to a retrospective, population-based study.

Women in that category had a 19% higher risk of cardiovascular disease over the subsequent 12.3 years than those without glucose intolerance (P=0.03), according to Ravi Retnakaran, MD, and Baiju R. Shah, MD, PhD, both of the University of Toronto.

As expected, those found to have gestational diabetes had an even higher future cardiovascular risk compared with normoglycemic women (adjusted hazard ratio 1.66, P<0.001), the investigators reported online in the CMAJ.

Both groups of women may benefit from closer cardiovascular surveillance, they wrote.

Recent research by the same group showed that even mild degrees of glucose dysregulation in pregnancy strongly predict future diabetes risk.

Since many scientists believe type 2 diabetes and cardiovascular disease arise from a "common soil," the researchers turned their attention to future cardiovascular risk.

They used administrative and universal healthcare insurance databases in Ontario to look at outcomes for women ages 20 to 49 who gave birth from 1994 through 1998, excluding those with pregestational diabetes.

In the course of standard obstetric care, Canadian women are typically screened in the late second trimester with a 50 g glucose challenge test. If the results are abnormal, they're referred for a diagnostic oral glucose tolerance test.

Among the 349,977 women who didn't require a diagnostic test -- suggesting normal glucose challenge test results -- the rate of cardiovascular events (hospitalization for acute MI, coronary bypass or angioplasty, stroke, or carotid endarterectomy) was 1.9 per 10,000 person-years over 12.3 years of follow-up.

By comparison, the rate was 2.3 events per 10,000 person-years in the 71,831 women who got the oral glucose tolerance test but did not have gestational diabetes.

Among the 13,888 women who were diagnosed with gestational diabetes, the rate was 4.2 per 10,000 person years.

The absolute risk for women with gestational diabetes was 0.16% higher than for women without an oral glucose tolerance test. It was 0.05% higher for those who received an oral glucose tolerance test but did not have gestational diabetes.

Further adjustment for subsequent development of diabetes attenuated the association to nonsignificance (HR 1.25 for gestational diabetes, P=0.1, and HR 1.16 for oral glucose tolerance test only, P=0.06).

Together with the relatively low underlying cardiovascular risk and longtime frame over which macrovascular disease develops in this population, these results suggest that diabetes and vascular disease may develop in parallel, rather than diabetes coming first in these women, the researchers said.

An accompanying editorial agreed that the "results add weight to the debate over 'the chicken or the egg' and the 'common soil' hypotheses about vascular disease and diabetes -- that is, is type 2 diabetes a vascular disease before it becomes glycemia?"

But editorialists J. Kennedy Cruickshank, MB, MD, and Moulinath Banerjee, MD, PhD, both of Manchester Royal Infirmary at the University of Manchester in England, suggested that the subclinical blood vessel changes in these young women may be more important than glycemia itself.

The researchers cautioned that the study was limited by lack of data on lipid levels and other postpartum cardiovascular risk factors, as well as possible misclassification bias since referral for a glucose tolerance test was used as a surrogate for an abnormal glucose screening test as opposed to having the results of the actual screening test.

Retnakaran and Shah both reported support from the Canadian Institutes of Health Research, the Canadian Diabetes Association, and the University of Toronto Banting and Best Diabetes Centre. The Institute for Clinical Evaluative Sciences is funded in part by the Ontario Ministry of Health and Long-Term Care.

The researchers and editorialists reported no conflicts of interest.

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