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Health Tool
Tabitha A. Harrison, MPH, Lucia A. Hindorff, MPH, Helen Kim, MPH, Roberta C. M. Wines, MPH,
Deborah J. Bowen, PhD, Barbara B. McGrath, PhD, Karen L. Edwards, PhD
Abstract: Given the substantial morbidity and mortality associated with type 2 diabetes, it is
important that public health seek ways to delay or prevent the onset of this condition. Risk
factors for type 2 diabetes are well established and include underlying genetic susceptibil-
ity. Despite this knowledge, as well as significant advances in understanding the human
genome, the prevalence of type 2 diabetes continues to rise at an alarming rate. Because
type 2 diabetes is a complex condition involving a combination of genetic and environ-
mental factors, DNA testing for susceptibility genes is not yet warranted. However, because
family history reflects genetic susceptibility in addition to other factors, it may be a useful
public health tool for disease prevention. When evaluating family history as a public health
tool, several important issues need to be considered, including the analytic and clinical
validity and the clinical utility of using family history as a screening tool. These issues as well
as a review of the epidemiologic evidence evaluating family history as a risk factor will be
reviewed.
Overall, a family history approach appears to be a promising new public health tool to
fight the growing epidemic of diabetes in the United States. Adequate levels of funding to
further evaluate this approach and to develop appropriate tools should be made available
for research activities focused on this important area. (Am J Prev Med 2003;24(2):
152–159) © 2003 American Journal of Preventive Medicine
T
ype 2 diabetes is a significant public health
Risk factors for type 2 diabetes are well established2
problem, accounting for substantial morbidity
and include age, race and ethnicity, obesity, and lack of
and premature mortality in the United States.
physical activity. The frequency of diabetes is greater
The estimated annual direct and indirect economic
among individuals with hypertension or dyslipidemia
costs of managing type 2 diabetes and its sequelae are
and in women with a prior history of gestational
$98 billion.1 The prevalence of type 2 diabetes among
diabetes. Evidence for genetic susceptibility to type 2
adults varies by age and ethnicity,2 and it continues to
diabetes is also well established.6 –10 However, the ge-
rise at an alarming rate among youth.3 Importantly, the
netics of type 2 diabetes is complex, and it is unlikely
public health burden of type 2 diabetes may be under-
that single major genes will account for a substantial
estimated because approximately 33% to 50% of indi-
viduals with type 2 diabetes (about 8 million) remain proportion of the disease.
undiagnosed and untreated.2,4 Furthermore, it is esti- The American Diabetes Association (ADA) recently
mated that diagnosis and treatment may be delayed 4 to issued a position statement that included a review of
7 years; as a result, many patients with diabetes will four randomized controlled trials,11–13 which showed
that simple lifestyle modifications such as a healthy diet,
increased physical activity, or pharmacologic interven-
From the Department of Epidemiology (Harrison, Hindorff, Kim, tions can significantly decrease the incidence of diabe-
Edwards), Institute for Public Health Genetics (Wines, Edwards), tes in high-risk populations.14 Evidence from these
Department of Health Services (Bowen), School of Public Health and
Community Medicine, University of Washington, Seattle, Washing- studies suggests that preventing or delaying the onset of
ton; Public Health Sciences Division, Fred Hutchinson Cancer Re- type 2 diabetes is possible. However, population screen-
search Center (Bowen), Seattle, Washington; Psychosocial and Com- ing for diabetes, even in high-risk populations, is not
munity Health, School of Nursing, University of Washington
(McGrath), Seattle, Washington currently recommended by the ADA.15 Thus, develop-
Address for correspondence and reprint requests to: Karen L. ing and evaluating strategies to identify at-risk individuals
Edwards, PhD, Department of Epidemiology, Box 357236, School of
Public Health and Community Medicine, University of Washington, who may benefit from targeted interventions are im-
Seattle WA 98195. E-mail: keddy@u.washington.edu. portant and challenging public health responsibilities.
Cohort
Knowler17b,c U.S., Pima Indians 3137 3.9 (p⬍0.001) 2.3 (p⫽0.04)
Shaten18b U.S., men (all races) 5905 2.0 (1.5–2.6)
Burchfiel19b,c,d U.S., Japanese- 7210 1.7 (1.3–2.3)
American men
Bjornholt20b,c,e Norway, Oslo men 1947 2.5 (1.6–4.1) 1.4 (0.7–3.1) 4.0 (1.2–13.0)
Meigs21,b U.S., whites 2527 3.4 (2.3–4.9) 3.5 (2.3–5.2) 6.1 (2.9–13.0)
Case–control
Erasmus22 South Africa, blacks 1798 4.1 (3.0–5.5)
Cross-sectional
Mitchell23b,f U.S., Mexican Men 2116 3.4 (2.3–5.1) 3.5 (2.2–5.6) 3.7 (1.7–8.1)
Americans and
non-Hispanic whites
Women 2798 2.0 (1.5–2.8) 1.4 (0.8–2.2) 2.6 (1.4–4.8)
Lin24 Taiwan, Pu-Li 745 2.6 (1.1–5.7) 0.5 (0.0–2.9)
Lin24 Taiwan, Chinshan ⬎60 years 3548 1.2 (0.4–3.1) 0.6 (0.0–3.3)
50–59 years 3524 1.6 (0.4–4.4) 2.8 (0.5–9.1)
40–49 years 3517 4.4 (1.7–10.1) 2.2 (0.3–8.9)
Sargeant25 United Kingdom, 6473 2.3 (1.7–3.1)
Norfolk
Thorand26b Germany, Augsburg 13,428 2.8 (2.3–3.5) 2.7 (2.0–3.7)
a
Other refers to either parent except for Erasmus et al.22 (any first-, second-, or third-degree relative) and Lin et al.24 (any immediate family
member).
b
Adjusted for age.
c
Adjusted for body mass index.
d
Additional adjustment for subscapular/tricepts ratio, physical activity, glucose, triglyercides, hematocrit, and systolic blood pressure.
e
Additional adjustment for fasting glucose, glucose disappearance rate, fitness, triglycerides.
f
Adjusted for ethnicity.
Family history information may serve as a unique and between family history of diabetes in any relative and
useful tool for public health and preventive medicine.16 clinically diagnosed diabetes.
Because family history reflects both genetic and envi- The following is a summary of ten studies, including
ronmental factors, it may serve as a better predictor of five cohort studies,17–21 one case– control study,22 and
diabetes risk than either factor alone. If this is the case, four cross-sectional studies23–26 that report on the
family history could then be used to identify individuals association between positive family history and type 2
at different levels of risk or to influence health promot- diabetes. Table 1 gives a summary of the estimated risks
ing behaviors. Further, prevention efforts could be reported in these studies according to family history of
extended to family members who may be at increased diabetes.
risk or who may be influential in helping to modify a A long-term follow-up study conducted among a
relative’s health behavior. population of Pima Indians17 showed that participants
The purposes of this paper are to review the epide- with one parent affected with diabetes were 2.3 times
miologic evidence about family history as a risk factor more likely to develop diabetes than participants who
for type 2 diabetes, to assess the analytic and clinical did not have affected parents (p⫽0.039), and partici-
validity and the clinical utility of family history informa- pants with two affected parents were 3.9 times as likely
tion as a screening tool for type 2 diabetes, to identify to develop diabetes (p⫽0.0003). Among participants
gaps in knowledge in these areas, and to illustrate the who had only one parent with diabetes, having a
importance of ethnic and cultural considerations when mother with diabetes was more common than having a
collecting and using family history information. father with diabetes, but this finding was not statistically
significant (p⫽0.15).
Men participating in the control group of the Multi-
Family History as a Risk Factor for Type 2 Diabetes
ple Risk Factor Intervention Trial18 with a parental
To assess the quality and consistency of the scientific history of diabetes were at twofold increased risk of
literature evaluating the relationship between family developing diabetes compared with men with no pa-
history of diabetes and risk of type 2 diabetes, we rental history of diabetes (age-adjusted relative risk
conducted a PubMed search, using the terms “family [RR]⫽2.01, 95% confidence interval [CI]⫽1.54 –2.64).
history,” “parental history,” and “diabetes.” We limited Further adjustments for race and medical and lifestyle
our review to studies that examined the association risk factors diminished the risk associated with family