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BSTETRICS

oes frank diabetes in first-degree relatives of a pregnantoman affect the likelihood of her developing gestationaliabetes mellitus or nongestational diabetes?

atherine Kim, MD, MPH; Tiebin Liu, MSPH; Rodolfo Valdez, PhD, MSc; Gloria L. Beckles, MD, MSc

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BJECTIVE: We sought to examine the associations between patternsf family histories of diabetes and a history of gestational diabetes mel-

itus (hGDM).

TUDY DESIGN: Parous women participating in the National Health andutrition Examination Survey III (n � 4566) were classified as havingGDM only, diagnosed diabetes, or neither. Family history of diabetesas categorized as: maternal only, paternal only, biparental, and siblingnly. The covariate-adjusted prevalence and odds of having hGDM were

estational diabetes mellitus or nongestational diabetes? Am J Obstet Gynecol 2009

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76.e1 American Journal of Obstetrics & Gynecology DECEMBER 2009

ESULTS: Compared to women without a family history of diabetes,omen with a maternal (odds ratio [OR], 3.0; 95% confidence interval

CI], 1.2–7.3), paternal (OR, 3.3; 95% CI, 1.1–10.2), or sibling (OR,.1; 95% CI, 1.6–30.9) history of diabetes had greater odds of hGDM,fter adjustment for age and race/ethnicity.

ONCLUSION: Women with a sibling history of diabetes were moreikely to have hGDM than women with other family history patterns.

stimated. Key words: family history, gestational diabetes, sibling

ite this article as: Kim C, Liu T, Valdez R, et al. Does frank diabetes in first-degree relatives of a pregnant woman affect the likelihood of her developing
;201:576.e1-6.
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estational diabetes mellitus (GDM)is defined as glucose intolerance first

dentified during pregnancy.1 Womenith GDM are at increased risk for futureiabetes,2 but not all women with GDMventually develop diabetes.2 Women whoave isolated GDM, or GDM without sub-equent frank diabetes, could have differ-

rom the Departments of Medicine andbstetrics and Gynecology, University ofichigan Medical School, Ann Arbor, MI

Dr Kim); and the National Office of Publicealth Genomics (Mr Liu and Dr Valdez)

nd the Division of Diabetes Translation (Dreckles), Centers for Disease Control andrevention, Atlanta, GA.

eceived April 16, 2009; revised June 9, 2009;ccepted June 29, 2009.

eprints not available from the authors.

upported by K23DK071552 from the Nationalnstitute of Diabetes and Digestive and Kidneyiseases (Dr Kim) and by the Centers forisease Control and Prevention (Drs Valdeznd Beckles, and Mr Liu).

he findings and conclusions in this article arehose of the authors and do not necessarilyepresent the official positions of the fundinggency or of the Centers for Disease Controlnd Prevention.

002-9378/$36.002009 Mosby, Inc. All rights reserved.

nt familial transmission patterns thanomen who develop permanent glucose

ntolerance. However, studies of familialransmission of GDM are relatively fewnd small, and the results conflict.3-7

In comparison, a family history of di-betes increases the risk of diabetes in aose-response manner: the risk is higherhen both parents are affected thanhen only one is affected.8-13 Moreover,aternal diabetes may9,12 or may not8,11

onfer greater risk of diabetes in the off-pring than paternal diabetes. Studiesocumenting greater maternal risk mayave had greater rates of maternal glu-ose intolerance during pregnancy; suchxcess risk may be partially incurredn utero or during early childhoodevelopment.14

Using the National Health and Nutri-ion Examination Survey (NHANES) III,population-based survey, we examined

he patterns of a family history of diabe-es among parous, nonpregnant women.

e compared family histories of diabe-es in women with an isolated history ofDM (hGDM) vs women with diag-osed diabetes vs unaffected women. Weished to answer the following ques-

ions. (1) Does a maternal-only historyf diabetes increase risk of hGDM com-

history of diabe- a

es? (2) Does a biparental history of dia-etes increase risk of hGDM beyondaving a single parent affected by diabe-es? (3) Does a sibling-only history of di-betes increase risk of hGDM? (4) Dohese associations differ from familialransmission patterns in women with di-gnosed diabetes?

ATERIALS AND METHODStudy populationhe study population was obtained fromHANES III, a survey conducted using aultistage sampling design to make the

ample representative of the noninstitu-ionalized civilian population in thenited States between 1988-1994. A de-

ailed description of the objectives andata collection procedures of theHANES III has been reported previ-usly.15 Briefly, each NHANES waveonsists of a detailed standardized med-cal examination in a mobile examina-ion unit and an interview to obtainnformation on sociodemographic char-cteristics and other variables. For thisrticle, we excluded women who wereulliparous, pregnant at the time of dataollection, or had missing data regardingregnancy status or previous diabetes orGDM diagnoses or family history of di-
betes, for a total sample of 4566 parous

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omen. As we analyzed a public-use de-dentified dataset, this study was de-lared institutional review board exempty our university.

ain outcome measuresomen were classified as having diag-

osed diabetes, isolated hGDM, or nei-her condition. At the time of theHANES interview, women were asked

he following questions. (1) Have youver been told by a doctor that you haveiabetes or sugar diabetes? (2) Were youregnant when you were told you hadiabetes? (3) Other than during preg-ancy, has a doctor ever told you thatou have diabetes or sugar diabetes?ased on these questions, women werelassified as having diagnosed diabetes ifhey reported a diagnosis of diabetes out-ide of pregnancy (n � 214).1 Womenere classified as having isolated hGDM

hGDM without a diagnosis of diabetes)f they reported having a diagnosis of di-betes during pregnancy but not at theime of interview (n � 84). Women werelassified as unaffected if they had nei-her hGDM nor diagnosed diabetes (n �268). Since we were focused on theomen with hGDM only without cur-

ent diagnosed diabetes, women whoad both diabetes and hGDM (n � 29)ere classified as having diagnosed dia-etes. In the NHANES III, it is not pos-ible to combine participants with diag-osed and undiagnosed diabetes for risknalysis, since the denominator to esti-ate undiagnosed diabetes is different

rom the one to estimate diagnosed dia-etes; undiagnosed diabetes was assessed

n a subsample of nondiabetic personsho were randomly assigned to a morn-

ng fasting examination, whereas diag-osed diabetes was assessed for the entireample. Therefore, we did not use fastinglucose levels to assess diabetes status.nformation on the tests used to makehe original diagnosis of GDM was notvailable in the NHANES.

xposure assessmentamily history of diabetes was obtainedrom the NHANES question, “Includingiving and deceased, were any of your bi-logical relatives, that is, blood relatives,

ncluding grandparents, parents, broth- N

rs, and sisters, ever told by a health pro-essional that they had diabetes? Whichamily member?” Maternal-only (n �13), paternal-only (n � 393), biparen-al (both parents affected) (n � 139),nd sibling-only (�1 siblings affectedut neither parent affected) (n � 214)istory of diabetes were mutually exclu-ive categories. Women who had a par-nt and a sibling affected were classifiedccording to their parental history; thus,omen with a mother and a sibling af-

ected were classified as maternal only,omen with a father and a sibling af-

ected were classified as paternal only,nd women with 2 parents and a siblingffected were classified as having a bipa-ental family history.

Information on age, sex, race/ethnic-ty, education, and household incomeas collected by interview.15 The pov-

rty-income ratio (PIR) was calculatedsing self-reported family income, fam-

ly size, and the poverty threshold valueroduced annually by the US Census Bu-eau.16 Measurements of height, weight,nd waist circumference were performedn a standardized manner, and body

ass index (BMI) was calculated aseight in kilograms divided by height ineters, squared.

tatistical analysisll analyses accounted for the complex,ultistage, stratified, cluster-sampling

esign of NHANES III by using sampleeights, strata, and primary samplingnits provided by the survey manual asart of the public data set. First, we com-ared family history patterns amongomen with diabetes, hGDM, and nei-

her condition. For continuous vari-bles, we conducted analysis of variance,nd for categorical variables, we con-ucted �2 tests. Second, using multivari-ble logistic regression models, we calcu-ated the odds ratios (ORs) and 95%onfidence intervals for hGDM and di-gnosed diabetes. Finally, we used theodels to calculate the adjusted preva-

ence for hGDM and diagnosed diabe-es.17 Multivariable models were con-tructed in consecutive stages. The firstets of models adjusted for age (model 1)nd age and race/ethnicity (model 2).
ext, we added BMI and waist circum- h
DECEMBER 2009 Americ

erence, measures of central obesitymodel 3). The final set of models alsodjusted for education and PIR (model). Statistical analyses were conductedsing software (SUDAAN 9.0; Researchriangle Institute, Research Triangleark, NC).

ESULTS

he characteristics of women in ourample are illustrated in Table 1. The

ajority of women reported not havingny first-degree relative with diabetes.ompared to women with a family his-

ory of diabetes, women without a familyistory were younger, more likely to beon-Hispanic white, better educated,

hinner, and less likely to be impover-shed. Among women with hGDM, 50%eported no family history of diabetes,1% reported a maternal history only,4% reported a paternal history only, 2%eported a biparental history, and 13%eported a sibling history (P � .001).mong women with diabetes, 43% re-orted no family history, 23% reported aaternal history only, 15% reported a

aternal history only, 11% reported a bi-arental history, and 8% reported a sib-

ing history (P � .001). Among womenith neither condition, 74% reported no

amily history, 13% reported maternalistory only, 8% reported a biparentalistory, and 2% reported a sibling his-ory (P � .001).

In unadjusted analyses, women withaternal-only and paternal-only histo-

ies reported similar prevalences ofGDM and diagnosed diabetes, whichere higher than those for women with-ut any family history (Table 1). Womenho reported a biparental history of di-

betes did not have an increased preva-ence of hGDM compared to womenithout such a history; however, womenith a biparental history had a preva-

ence of diagnosed diabetes that was 2-8imes that of women in the other groups.

omen who reported a sibling-only his-ory of diabetes had a significantly higherrevalence of hGDM and diagnosed di-betes than those without a family
istory.
an Journal of Obstetrics & Gynecology 576.e2

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aternal-only and paternal-nly diabetesfter adjustment for age and race/eth-icity (Table 2), women with a maternal-nly history had a 3-fold increased oddsf hGDM and women with a paternal-nly history had a similar increased oddsf hGDM compared to women without aamily history. The odds of hGDM wereomewhat attenuated after adjustment,ith the association between paternal-nly history and hGDM losing signifi-

TABLE 1Unadjusted characteristics by diab

Characteristics

Family

No hist(n � 3

Age, y 38.7 (0...................................................................................................................

Race/ethnicity, n (%)..........................................................................................................

Non-Hispanic white 74.1 (1..........................................................................................................

Non-Hispanic black 13.1 (1..........................................................................................................

Mexican American 5.2 (0..........................................................................................................

Other 7.6 (1...................................................................................................................

Education, n (%)..........................................................................................................

�High school 20.9 (1..........................................................................................................

High school 40.6 (1..........................................................................................................

�High school 37.9 (1..........................................................................................................

Unknown 0.6 (0...................................................................................................................

PIR quartiles, n (%) (n � 4177)..........................................................................................................

�1.49 24.7 (1..........................................................................................................

1.49 to �2.72 25.9 (1..........................................................................................................

2.72 to �4.20 25.7 (1..........................................................................................................

�4.20 23.7 (2...................................................................................................................

BMI (kg/m2), n (%)..........................................................................................................

�25 52.9 (1..........................................................................................................

25-29.9 24.6 (1..........................................................................................................

�30 22.6 (1...................................................................................................................

Waist circumference, cm (%) 86.8 (0...................................................................................................................

Diabetes status, n (%)..........................................................................................................

Neither hGDM nor DM 97.1 (0..........................................................................................................

hGDM only 0.8 (0..........................................................................................................

Diagnosed diabetes 2.1 (0...................................................................................................................

BMI, body mass index; DM, diabetes mellitus; hGDM, historyMeans (SE) or percentages (SE) are shown.

Kim. Family history and GDM. Am J Obstet Gynecol 200

ance in models including BMI and waist e

76.e3 American Journal of Obstetrics & Gynecolo

ircumference. Similarly, women withmaternal-only history had a 2.6-fold

ncreased odds of diagnosed diabetesompared to women without familyistory, and women with a paternal-nly history had similar increased oddsf diagnosed diabetes (Table 3). Thedds of diagnosed diabetes were alsoomewhat attenuated after adjust-

ent, most notably after adjustmentor BMI and waist circumference, andess so after additional adjustment for

s family historytory status

)Maternal only(n � 713)

Paternal only(n � 393)

41.4 (0.6) 41.2 (0.7).........................................................................................................................

.........................................................................................................................

62.3 (2.8) 70.0 (3.5).........................................................................................................................

17.1 (1.4) 12.6 (1.4).........................................................................................................................

8.3 (1.1) 6.6 (0.8).........................................................................................................................

12.3 (2.8) 10.8 (3.5).........................................................................................................................

.........................................................................................................................

29.3 (3.1) 22.1 (4.0).........................................................................................................................

36.7 (2.6) 38.3 (4.8).........................................................................................................................

33.8 (2.9) 39.3 (4.0).........................................................................................................................

0.1 (0.1) 0.3 (0.2).........................................................................................................................

.........................................................................................................................

32.9 (3.4) 23.5 (3.3).........................................................................................................................

24.8 (3.5) 33.9 (4.0).........................................................................................................................

23.4 (2.6) 25.8 (3.5).........................................................................................................................

18.9 (2.5) 16.8 (2.7).........................................................................................................................

.........................................................................................................................

35.7 (2.7) 42.4 (3.9).........................................................................................................................

25.6 (2.3) 23.7 (3.8).........................................................................................................................

38.7 (3.0) 33.9 (4.3).........................................................................................................................

93.8 (1.0) 91.4 (1.4).........................................................................................................................

.........................................................................................................................

92.0 (1.5) 91.7 (1.7).........................................................................................................................

1.8 (0.5) 1.9 (0.8).........................................................................................................................

6.2 (1.5) 6.4 (1.4).........................................................................................................................

stational diabetes mellitus; PIR, poverty-income ratio.

ducation and PIR. a

gy DECEMBER 2009

iparental diabetesfter adjustment for age and race/eth-icity (Table 2), women with a biparen-

al history did not have a marked in-rease in odds of hGDM either before orfter adjustment for other factors. Inontrast, women with a biparental his-ory had a 9.6 increased odds of diag-osed diabetes compared to womenithout any family history, more thanouble the odds of maternal-only his-ory (Table 3). The odds of diagnosed di-

iparentaln � 139)

Sibling only(n � 214) P value

0.5 (1.1) 42.6 (1.1) � .001..................................................................................................................

� .001..................................................................................................................

8.4 (4.6) 60.0 (4.1)..................................................................................................................

8.0 (3.6) 20.3 (2.9)..................................................................................................................

0.6 (2.3) 6.5 (1.1)..................................................................................................................

2.9 (2.0) 13.2 (3.7)..................................................................................................................

.003..................................................................................................................

9.1 (4.4) 37.9 (6.2)..................................................................................................................

8.5 (5.8) 36.1 (6.0)..................................................................................................................

2.1 (6.4) 25.9 (5.5)..................................................................................................................

0.3 (0.2) 0.1 (0.1)..................................................................................................................

.003..................................................................................................................

3.9 (7.3) 37.1 (5.3)..................................................................................................................

5.9 (8.1) 23.2 (4.7)..................................................................................................................

7.9 (5.7) 26.6 (5.4)..................................................................................................................

2.2 (4.7) 13.1 (4.3)..................................................................................................................

� .001..................................................................................................................

5.9 (5.9) 32.6 (4.3)..................................................................................................................

2.4 (5.6) 27.4 (3.7)..................................................................................................................

1.8 (7.2) 40.0 (5.0)..................................................................................................................

6.5 (2.1) 95.0 (1.4) � .001..................................................................................................................

..................................................................................................................

1.8 (5.3) 88.6 (3.3)..................................................................................................................

1.1 (0.6) 3.9 (2.6)..................................................................................................................

7.1 (5.0) 7.5 (3.0) � .001..................................................................................................................

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ly by adjustment for BMI and waistircumference.

ibling-only diabetesfter adjustment for age and race/eth-icity (Table 2), women with a sibling-nly history had markedly increaseddds of hGDM compared to womenithout any family history, more thanouble the odds of maternal-only his-ory. These associations were attenuatedfter adjustment for BMI and waist cir-umference, but actually strengthenedith further adjustment for education

nd PIR. Women with a sibling-only his-ory had increased odds of diagnosed di-betes compared to women without anyamily history (Table 3). These associa-ions were most attenuated by adjust-

ent for BMI and waist circumference.

OMMENTn this cross-sectional study of parousomen in the United States, we found

hat a family history of diabetes was as-ociated with increased odds of hGDM.

TABLE 2Associations between family histor

Models and adjustmentsNo hist(n � 3

Model 1: adjusted for age..........................................................................................................

OR (95% CI) 1.0..........................................................................................................

Prevalence of hGDM (SE) 0.7 (0.2...................................................................................................................

Model 2: adjusted for age,race/ethnicity

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


Model 3: adjusted for age,race/ethnicity, BMI, waistcircumference

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


Model 4: adjusted for age,race/ethnicity, BMI, waistcircumference, education,PIR

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


BMI, body mass index; CI, confidence interval; hGDM, historyReference group: no family history of diabetes among first-de


ore specifically, we found that a mater- c

al-only history of diabetes and a pater-al-only history of diabetes similarlyoubled or tripled the odds of hGDMompared to no family history. Havingoth parents affected with diabetes didot seem to increase the odds of hGDMompared to having 1 parent affectedith diabetes, although it increased thedds of diabetes. We also found that sib-

ing-only history of diabetes conferreduch greater odds of hGDM than hav-

ng a parent affected. Finally, maternal-nly history did not seem to confer ex-ess risk for either hGDM or diagnosediabetes beyond paternal risk.

aternal-only and paternal-nly diabetes historyther reports examining hGDM have

lso found that both maternal-only andaternal-only diabetes histories conferreater hGDM risk.3-6 In these other re-orts, the degree of excess risk with ma-ernal-only history compared to pater-al-only history ranges from little toone,4,6 as in our report, to mildly in-

nd gestational diabetes

)Maternal only(n � 713)

Paternal onl(n � 393)

.........................................................................................................................

3.1 (1.3–7.6) 3.3 (1.1–10.5.........................................................................................................................

2.2 (0.7) 2.3 (1.0).........................................................................................................................

.........................................................................................................................

3.0 (1.2–7.3) 3.3 (1.1–10.2.........................................................................................................................

2.0 (0.7) 2.3 (1.0).........................................................................................................................

.........................................................................................................................

2.8 (1.1–7.0) 2.9 (0.8–10.3.........................................................................................................................

1.9 (0.7) 2.0 (1.0).........................................................................................................................

.........................................................................................................................

2.7 (1.0–7.3) 2.8 (0.8–10.0.........................................................................................................................

2.0 (0.7) 2.0 (1.0).........................................................................................................................

stational diabetes mellitus; OR, odds ratio; PIR, poverty-income rrelatives.

reased,5 to double.3 Excess risk with a t


aternal-only history would imply in-rauterine, mitochondrial, or other epi-enetic influences. Reports may conflictor several reasons. First, 1 feature of oureport is that women with hGDM didot also have diagnosed diabetes; ourrevious reports show that few had ele-ated glucose levels.18 Women with dia-etes may have excess maternal risk,9,12

o it is possible that other reports alsoncluding women with hGDM who latereveloped diabetes as well as womenith hGDM who actually had undiag-osed preconception diabetes mightave shown increased maternal risk forhis reason. Another possibility is that

aternal risk may be mediated differ-ntly than paternal risk. We found thathe association between paternal-onlyistory and hGDM was no longer signif-

cant after adjustment for BMI, but thessociation between maternal-only his-ory and hGDM remained robust, sug-esting maternal-only history may affectlucose metabolism through alternateathways aside from BMI. Finally, ma-

Biparental(n � 139)

Sibling only(n � 214)

..................................................................................................................

2.1 (0.5–8.6) 7.2 (1.8–29.0)..................................................................................................................

1.4 (0.8) 4.7 (3.1)..................................................................................................................

..................................................................................................................

1.9 (0.5–7.6) 7.1 (1.6–30.9)..................................................................................................................

1.2 (0.7) 4.7 (3.2)..................................................................................................................

..................................................................................................................

1.6 (0.4–6.6) 6.9 (1.6–29.4)..................................................................................................................

1.0 (0.6) 4.6 (3.1)..................................................................................................................

..................................................................................................................

1.8 (0.4–7.6) 7.3 (1.9–28.0)..................................................................................................................

1.2 (0.8) 4.9 (3.1)..................................................................................................................

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he mother had dysglycemia during herregnancy; maternal glucose intoleranceccurring after the pregnancy should not

ead to in utero changes, and reports mayave had mothers with differing ages ofnset of diabetes.Maternal-only history may be more

ikely to be ascertained than paternal-nly history, due to biases such as longer

ife span in women, reduced health carese among fathers, incidence of diabetest a later age in fathers compared toothers, or greater awareness of moth-

r’s history than father’s history.9 As weid not find evidence of excess maternalransmission in the current report, theseiases may be of less importance, butould possibly explain the contrast withther reports.

iparental history of diabetess in other reports of family history ofiabetes and risk for diabetes (as op-osed to hGDM), we found that bipa-ental history significantly increases off-pring risk of diabetes compared to

TABLE 3Associations between family historModels andadjustments

No histor(n � 310

Model 1: adjusted for age..........................................................................................................

OR (95% CI) 1.0..........................................................................................................

Prevalence of DM (SE) 2.2 (0.4)...................................................................................................................

Model 2: adjusted forage, race/ethnicity

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


Model 3: adjusted forage, race/ethnicity, BMI,waist circumference

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


Model 4: adjusted forage, race/ethnicity, BMI,waist circumference,education, PIR

..........................................................................................................

OR (95% CI) 1.0..........................................................................................................


BMI, body mass index; CI, confidence interval; DM, diabetes mReference group: no family history of diabetes among first-de


ingle-parent history.8-10,12,13 In the Fra- d

76.e5 American Journal of Obstetrics & Gynecolo

ingham Offspring Study, biparentaliabetes was associated with a 6-fold in-rease in odds of diabetes, almost doublehe odds of either parent alone (odds ra-io [OR], 6.1; 95% confidence intervalCI], 2.9 –13.0). In contrast, we foundhat biparental history of diabetes wasot associated with hGDM beyond a ma-

ernal-only history, consistent with a re-ort by McLean et al3 but different fromreport by Williams et al.4 Again, sinceur report examined women withGDM only, it is possible that the excessisk associated with biparental historyas due to inclusion of women with pre-iously undiagnosed diabetes or hGDMho were at excess risk for diabetes. In

ddition, due to the definition of hGDM,he prevalence of hGDM and diabetesxists in equilibrium. Women with a bi-arental history might have greater riskf earlier onset diabetes compared toomen with other types of familyistory, and thus the odds of hGDMith a biparental history were relatively

nd diabetesMaternal only(n � 713)

Paternal only(n � 393)

.........................................................................................................................

2.7 (1.6–4.7) 2.9 (1.6–5.2).........................................................................................................................

5.6 (1.2) 5.9 (1.3).........................................................................................................................

.........................................................................................................................

2.6 (1.5–4.5) 2.9 (1.6–5.2).........................................................................................................................

5.4 (1.2) 6.0 (1.3).........................................................................................................................

.........................................................................................................................

2.1 (1.1–3.9) 2.6 (1.4–4.7).........................................................................................................................

4.7 (1.1) 5.7 (1.1).........................................................................................................................

.........................................................................................................................

2.1 (1.1–3.8) 2.3 (1.3–4.3).........................................................................................................................

4.8 (1.2) 5.4 (1.1).........................................................................................................................

us; OR, odds ratio; PIR, poverty-income ratio.relatives.

ecreased. t

gy DECEMBER 2009

ibling history of diabetess in our article, others have found thataternal history and paternal history of

iabetes were associated with similardds of hGDM, but the odds of hGDM

ncreased most markedly when a siblingas affected.4 In addition, we found that

he odds of hGDM with a sibling-onlyistory actually increased with adjust-ent for measures of current and early-

ife influences such as education andIR. This suggests that these environ-ental factors obscure the association

etween sibling-only history and hGDMiagnosis, and that sibling-only historyay be a greater risk factor than previ-

usly documented.

trengths and limitationstrengths of this article include a largeumber of participants, a nationally rep-esentative population-based sample,nformation on multiple potential con-ounders including BMI and central ad-posity, and comparison with familial

Biparental(n � 139)

Sibling only(n � 214)

..................................................................................................................

10.0 (4.4–22.7) 3.0 (1.3–7.0)..................................................................................................................

16.9 (4.9) 6.0 (2.4)..................................................................................................................

..................................................................................................................

9.6 (4.1–22.1) 2.7 (1.1–6.2)..................................................................................................................

16.4 (4.9) 5.4 (2.2)..................................................................................................................

..................................................................................................................

8.0 (3.1–20.5) 1.7 (0.6–4.7)..................................................................................................................

14.1 (4.2) 3.8 (1.8)..................................................................................................................

..................................................................................................................

7.8 (3.0–20.1) 1.5 (0.5–4.5)..................................................................................................................

14.1 (4.2) 3.5 (1.8)..................................................................................................................

y ay7)

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ellitgree

9.

ransmission patterns of diabetes. How-

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ver, NHANES is cross sectional, and weere unable to calculate relative risks (aspposed to OR) of diabetes and hGDM,hich would have required a much

arger number of subjects. We deliber-tely distinguished between women withGDM only and women with diagnosediabetes, so our results do not apply tohe women with hGDM who later devel-ped diabetes. The hGDM and familyistory of diabetes were ascertained byarticipant self-report. If GDM screen-

ng were associated with self-report ofamily history of diabetes, this would ar-ificially increase association with familyistory. Similarly, if diagnosed diabetesere associated with family history of di-

betes, this would artificially increase as-ociation with family history. We did notave more specific information abouthe timing and criteria used to diagnoseDM and postpartum testing, whichay have resulted in misclassification,

lthough it is difficult to state how thisffected the estimates of association.

These biases may be less important forhis study as the ORs we obtained wereimilar to other reports that directly val-dated family history for diabetes as wells the diagnosis of GDM. It is possiblehat the estimate of maternal transmis-ion for diagnosed diabetes was biased tohe null by the inclusion of adults withype 1 diabetes, for whom maternal intero transmission may be less influen-

ial.19 Optimally, we would have deter-ined whether the mother had glucose

ntolerance at the time of the pregnancyo more exactly pinpoint the degree of

aternal risk. To our knowledge, no re-orts of GDM and only 2 reports exam-

ning diabetes have been able to examinege of onset.8,19 Thus, our estimates ofxcess maternal transmission may have
een biased toward the null. l
We conclude that family history of di-betes increases the odds of hGDM. Ma-ernal-only family history of diabetesnd paternal-only family history diabe-es both increase risk of diagnosed diabe-es and hGDM, but the odds of hGDMid not increase with the number of af-

ected family members. In particular,omen with a sibling history of diabetesere more likely to have hGDM com-ared to other family history patterns.hese results suggest that women whoevelop GDM but not diabetes may haveifferent family history transmissionatterns than women with diabetes. Fur-her research distinguishing geneticransmission among these 2 groups ofomen, with particular focus on siblingistory, may help risk stratify GDMomen at high risk for developing futureiabetes, and thus target them for pre-ention interventions. f

EFERENCES. Metzger B, Buchanan T, Coustan D, et al.ummary and recommendations of the fifth in-

ernational workshop-conference on gesta-ional diabetes mellitus. Diabetes Care 2007;0:S251-60.. Kjos S, Peters R, Xiang A, Henry O, Montoro, Buchanan T. Predicting future diabetes in

atino women with gestational diabetes. Diabe-es 1995;44:586-91.. McLean M, Chipps D, Cheung N. Mother tohild transmission of diabetes mellitus: doesestational diabetes program type 2 diabetes inhe next generation? Diabet Med 2006;3:1213-5.. Williams M, Qiu C, Dempsey J, Luthy D. Fa-ilial aggregation of type 2 diabetes and

hronic hypertension in women with gestationaliabetes mellitus. J Reprod Med 2003;48:55-62.. Harder T, Franke K, Kholhoff R, Plagemann. Maternal and paternal family history of diabe-

es in women with gestational diabetes or insu-in-dependent diabetes mellitus type 1. Gynecolbstet Invest 2001;51:160-4.. Mclellan J, Barrow B, Levy J, et al. Preva-

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pring study. Diabetes 2000;49:2201-7.. Karter A, Rowell S, Ackerson L, et al. Excessaternal transmission of type 2 diabetes. Dia-etes Care 1999;22:938-43.0. Harris M, Flegal K, Cowie C, et al. Preva-

ence of diabetes, impaired fasting glucose, andmpaired glucose tolerance in US adults: thehird national health and nutrition examinationurvey. Diabetes Care 1998;21:518.1. Mitchell B, Kammerer C, Reinhart L, Stern, Maccluer J. Is there an excess in maternal

ransmission of NIDDM? Diabetologia 1995;8:314-7.2. Mitchell B, Valdez R, Hazuda H, Haffner S,onterrosa A, Stern M. Differences in the prev-

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ions of obesity and parental diabetes. Am Jpidemiol 1981;113:144-56.4. Dabelea D. The predisposition to obesitynd diabetes in offspring of diabetic mothers.iabetes Care 2007;30:S169-74.5. National Center for Health Statistics.HANES III reference manuals and reports.yattsville, MD: Centers for Disease Controlnd Prevention; 1996.6. Wu T, Dorn J, Donahue R, Sempos C, Tre-isan M. Associations of serum C-reactive pro-ein with fasting insulin, glucose, and glycosy-ated hemoglobin. Am J Epidemiol 2002;55:65-71.7. Graubard B, Koren E. Predictive marginsith survey data. Biometrics 1999;55:652-99.8. Kim C, Cheng Y, Beckles G. Cardiovascularisease risk profiles in women with histories ofestational diabetes but without current diabe-es. Obstet Gynecol 2008;112:875-83.9. Pettitt D, Lawrence J, Beyer J, et al. Asso-iation between maternal diabetes in utero andge of offspring’s diagnosis with type 2 diabe-
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