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标题：The Inter- and Intragenerational Impact of Gestational Diabetes on the Epidemic of Type 2 Diabetes
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作者：Nathaniel D. Osgood ; Roland F. Dyck ; Winfried K. Grassmann 等
期刊名称：American journal of public health
印刷版ISSN：0090-0036
出版年度：2011
卷号：101
期号：1
页码：173-179
DOI：10.2105/AJPH.2009.186890
语种：English
出版社：American Public Health Association
摘要：Objectives. We investigated the contribution of gestational diabetes mellitus (GDM) to the historic epidemic of type 2 diabetes mellitus (T2DM) in Saskatchewan. Methods. We constructed a population-level simulation model of the inter- and intragenerational interaction of GDM and T2DM for the period 1956 to 2006. The model was stratified by gender, ethnicity, and age; parameterized with primary and secondary data; and calibrated to match historic time series. Risk of diabetes was sigmoidally trended to capture exogenous factors. Results . Best-fit calibrations suggested GDM may be responsible for 19% to 30% of the cases of T2DM among Saskatchewan First Nations people, but only for approximately 6% of cases among other persons living in Saskatchewan. The estimated contribution of GDM to the growth in T2DM was highly sensitive to assumptions concerning the post-GDM risk of developing T2DM. Conclusions. GDM may be an important driver for the T2DM epidemic in many subpopulations. Because GDM is a readily identifiable, preventable, and treatable condition, investments in prevention, rapid diagnosis, and evidence-based treatment of GDM in at-risk populations may offer substantial benefit in lowering the T2DM burden over many generations. Model-informed data collection can aid in assessing intervention tradeoffs. The rise of the global epidemic of type 2 diabetes mellitus (T2DM) has been particularly rapid and acute among disadvantaged and indigenous populations.¹ In North America, for example, aboriginal peoples experience rates of diabetes several times higher than that among the general population.² Although research has pointed to the influence of rapid environmental and behavioral changes,² as well as possible genetic contributors,³ recent attention has also been directed at the possible role of diabetic pregnancies (gestational diabetes mellitus [GDM] and pre-existing maternal T2DM) in this epidemic. Previous research conducted among Saskatchewan First Nations people has provided indirect evidence to support a temporal contribution of GDM. Similar to many North American aboriginal peoples, Saskatchewan First Nations people suffer from high rates of GDM,^{4 – 8} with First Nations ethnicity being an independent predictor of GDM and with the magnitude of that risk exhibiting distinctive interactions between obesity and ethnicity.⁵ Among Saskatchewan First Nations people, rates of GDM and overweight or obesity appear to have risen many years prior to widespread appearance of T2DM.⁶ High-birthweight (HBW) rates, a frequent complication of GDM, have increased in Saskatchewan's predominantly First Nations communities over several decades.^{8 , 9} Similar to patterns seen among other Aboriginal groups,¹⁰ diabetic Saskatchewan First Nations adults are more likely to have been born with HBW than are their nondiabetic counterparts,⁸ and the HBW–T2DM relationship appears to have strengthened over time.⁸ In a reversal of the pattern seen in other Saskatchewan populations, Saskatchewan First Nations women also suffer from significantly higher rates of T2DM than do their male counterparts, with the disparity particularly pronounced in the childbearing years.¹¹ GDM is associated with serious health consequences for both mother and offspring. There is substantial evidence suggesting that GDM predisposes women to T2DM,^{4 , 12 – 15} with approximately 4% to 10% of GDM cases proceeding on to T2DM within the first 9 months after pregnancy.^{16 – 18} Occurrence of GDM during a pregnancy is also a predictor for GDM in future pregnancies,¹⁷ as well as for other conditions such as cardiovascular disease.¹⁹ Finally, because GDM encourages fetal growth,¹⁴ women with GDM are more likely to require caesarean sections and are at greater risk of complications during birth.²⁰ For children, the consequences of GDM are of equal or greater severity. GDM significantly elevates the risk of macrosomia and risk of fetal injury during delivery. Children of mothers with GDM also tend to have higher adiposity²⁰ and abnormal glucose tolerance.^{21 – 26} Seminal work carried out in the Pima Indian population showed that the children of women with diabetes during pregnancy had increased rates of obesity^{14 , 27 – 29} and T2DM^{30 – 33} by adolescence and early adulthood. Observations from Manitoba, where aboriginal children with diabetes were more likely to have experienced a diabetic intrauterine environment,³⁴ support this finding. Some of these effects appear to be independent of birthweight.²⁷ Findings from animal models³⁵ and from sibling studies,²⁹ the absence of influence of paternal diabetes,^{36 – 38} and an apparent dose–response relationship between gestational glycemic control and risk of diabetes in one's offspring³² suggest that GDM plays a causal role.^{29 , 31 , 39} Evidence is mixed as to the degree to which infants of glycemically well-controlled mothers with GDM remain at risk.^{27 , 40} Although the concept of an intergenerational vicious cycle of diabetic pregnancies leading to progressively increasing rates of T2DM has been demonstrated in animal models³⁵ and is now increasingly cited as a possible contributor to the diabetes epidemic,^{14 , 33 , 41 , 42} this effect has been challenging to observe and measure in diverse human populations. This may be in part because GDM was not broadly diagnosed until the 1980s and because of the long delays associated with intergenerational effects. Studies among the Pima have suggested that GDM has played a dominant role in elevating rates of T2DM among that population.³³ Although these findings have been seminal for providing evidence that a vicious cycle is operating and suggest the importance of the subject, they require translation to understand the degree to which GDM contributes to T2DM rates among other populations. This translation process requires addressing a variety of contextual factors that distinguish the populations of interest, such as differences in age-specific fertility rates, birthweights, population-specific risk factors for GDM, weight profiles through life, and differences in health care systems. Establishing the existence and strength of a link between diabetic pregnancies and the epidemic of T2DM is important because it would contribute to our basic understanding of this devastating chronic disease, provide novel opportunities for primary prevention initiatives, and allow for targeted allocation of health care resources. While awaiting more definitive longitudinal studies, there are prospects for leveraging the large body of evidence regarding the linkages between diverse factors that shape the inter- and intragenerational influences of gestational diabetes on population health (e.g., changing fertility patterns, onset and progression of diabetes, macrosomia and overweight, mortality, and weight gain during and outside of pregnancy). Simulation modeling provides an attractive vehicle both for exploring contributions of GDM to the observed rates and changes in diabetes rates by ethnicity and gender and for lending insight into how focused interventions might reduce this burden. To this end, we investigated the contribution of GDM on the historic epidemic of T2DM in Saskatchewan. Saskatchewan offers a valuable opportunity to examine these factors because of the availability of a long and rich sequence of administrative data,⁴³ the systematic series of studies that have already been conducted related to this subject, and the available interdisciplinary expertise.