Kathryn L. Pedula

Childhood Obesity and Metabolic Imprinting: The Ongoing Effects of Maternal Hyperglycemia

OBJECTIVE—The purpose of this study was to determine how the range of measured maternal glycemia in pregnancy relates to risk of obesity in childhood. RESEARCH DESIGN AND METHODS—Universal gestational diabetes mellitus (GDM) screening (a 50-g glucose challenge test [GCT]) was performed in two regions (Northwest and Hawaii) of a large diverse HMO during 1995–2000, and GDM was diagnosed/treated using a 3-h 100-g oral glucose tolerance test (OGTT) and National Diabetes Data Group (NDDG) criteria. Measured weight in offspring (n = 9,439) was ascertained 5–7 years later to calculate sex-specific weight-for-age percentiles using U.S. norms (1963–1994 standard) and then classified by maternal positive GCT (1 h ≥ 7.8 mmol/l) and OGTT results (1 or ≥2 of the 4 time points abnormal: fasting, 1 h, 2 h, or 3 h by Carpenter and Coustan and NDDG criteria). RESULTS—There was a positive trend for increasing childhood obesity at age 5–7 years (P < 0.0001; 85th and 95th percentiles) across the range of increasing maternal glucose screen values, which remained after adjustment for potential confounders including maternal weight gain, maternal age, parity, ethnicity, and birth weight. The risk of childhood obesity in offspring of mothers with GDM by NDDG criteria (treated) was attenuated compared with the risks for the groups with lesser degrees of hyperglycemia (untreated). The relationships were similar among Caucasians and non-Caucasians. Stratification by birth weight also revealed these effects in children of normal birth weight (≤4,000 g). CONCLUSIONS—Our results in a multiethnic U.S. population suggest that increasing hyperglycemia in pregnancy is associated with an increased risk of childhood obesity. More research is needed to determine whether treatment of GDM may be a modifiable risk factor for childhood obesity.

Lactic Acidosis Rates in Type 2 Diabetes

OBJECTIVE To provide a context for the interpretation of lactic acidosis risk among patients using metformin, we measured rates of lactic acidosis in patients with type 2 diabetes before metformin was approved for use in the U.S. RESEARCH DESIGN AND METHODS Using electronic databases of hospital discharge diagnoses and laboratory results maintained by a large, nonprofit health maintenance organization (HMO), we identified possible lactic acidosis events in three geographically and racially diverse populations with type 2 diabetes. We then reviewed hard-copy clinical records to confirm and describe each event and determine its likely cause(s). RESULTS From <41,000 person-years of experience, we found four confirmed, three possible, and three borderline cases of lactic acidosis. In each case, we identified at least one severe medical condition that could have caused the acidosis. The annual confirmed event rate is similar to published rates of metformin-associated lactic acidosis. CONCLUSIONS Lactic acidosis occurs regularly, although infrequently, among persons with type 2 diabetes, at rates similar to its occurrence among metformin users. The medical conditions with which both metformin-associated and naturally occurring lactic acidosis cooccur are also its potential causes. The observed association between metformin and lactic acidosis may be coincidental rather than causal. This possibility merits further study.

The global diabetes model: user friendly version 3.0

The attributes of Release 3.0 of the user friendly version (UFV) of the global diabetes model (GDM) are described and documented in detail. The GDM is a continuous, stochastic microsimulation model of type 2 diabetes. Suitable for predicting the medical futures of both individuals with diabetes and representative diabetic populations, the GDM predicts medical events (complications of diabetes), survival, utilities, and medical care costs. Incidence rate functions for microvascular and macrovascular complications are based on a combination of published studies and analyses of data describing diabetic members of Kaiser Permanente Northwest Region, a non-profit group-model health maintenance organization. Active risk factors include average blood glucose (HbAlc), systolic blood pressure (SBP), low density lipoprotein cholesterol (LDL), high density lipoprotein cholesterol (HDL), triglycerides, smoking status, and use of prophylactic aspirin. Events predicted include diabetic eye disease, diabetic nephropathy, peripheral neuropathy amputation, myocardial infarction, stroke, peripheral artery disease, congestive heart failure, coronary artery surgery, coronary angioplasty, and death.

Binocular Visual-Field Loss Increases the Risk of Future Falls in Older White Women

OBJECTIVES: To examine the relationship between binocular visual field loss and the risk of incident frequent falls in older white women.

Excess Gestational Weight Gain : Modifying Fetal Macrosomia Risk Associated With Maternal Glucose

OBJECTIVE: To estimate how maternal weight gain and maternal glucose relate to fetal macrosomia risk (greater than 4,000 g) among a population universally screened for gestational diabetes mellitus (GDM). METHODS: Between 1995 and 2003, 41,540 pregnant women in two regions (Northwest/Hawaii) of a large U.S. health plan had GDM screening using the 50-g glucose challenge test; 6,397 also underwent a 3-hour, 100-g oral glucose tolerance test. We assessed the relationship between level of maternal glucose with glucose screening and fetal macrosomia risk after adjustment for potential confounders, including maternal age, parity, and ethnicity and sex of the newborn. We stratified by maternal weight gain (40 lb or fewer compared with more than 40 lb) because excessive maternal weight gain modified results. RESULTS: Among women with both normal and abnormal GDM screenings, increasing level of maternal glucose was linearly related to macrosomia risk (P<.001 for trend in all groups). Women with excessive weight gain (more than 40 lb) had nearly double the risk of fetal macrosomia for each level of maternal glucose compared with those with gestational weight gain of 40 lb or fewer. For example, among women with normal post–glucose challenge test glucose levels (less than 95 mg/dL) and excessive weight gain, 16.5% had macrosomic newborns compared with 9.3% of women who gained 40 lb or fewer. Moreover, nearly one third of women (29.3%) with GDM who gained more than 40 lb had a macrosomic newborn compared with only 13.5% of women with GDM who gained 40 lb or fewer during pregnancy (P=.018). CONCLUSION: Excessive pregnancy weight gain nearly doubles the risk of fetal macrosomia with each increasing level of maternal glucose, even among women with GDM. LEVEL OF EVIDENCE: II

Nulliparity and fracture risk in older women: the study of osteoporotic fractures.

Whether nulliparity increases fracture risk is unclear from prior studies, which are limited by small samples or lack of measured bone mineral density. No study has evaluated whether the effect of parity differs by skeletal site. We prospectively analyzed the relationship of parity to the risk of incident nontraumatic hip, spine, and wrist fractures in 9704 women aged 65 years or older participating in the Study of Osteoporotic Fractures to determine if parity reduces postmenopausal fracture risk, and if so, if this risk reduction is (1) greater at weight‐bearing skeletal sites and (2) independent of bone mineral density. Parity was ascertained by self‐report. Incident hip and wrist fractures were determined by physician adjudication of radiology reports (mean follow‐up, 9.8 years) and spine fractures by morphometric criteria on serial radiographs. The relationship of parity to hip and wrist fracture was assessed by proportional hazards models. Spine fracture risk was evaluated by logistic regression. Compared with parous women, nulliparous women (n = 1835, 19%) had an increased risk of hip and spine, but not wrist, fractures. In multivariate models, parity remained a significant predictor only for hip fracture. Nulliparous women had a 44% increased risk of hip fractures independent of hip bone mineral density (hazards ratio, 1.44; 95% CI, 1.17‐1.78). Among parous women, each additional birth reduced hip fracture risk by 9% (p = 0.03). Additionally, there were no differences in mean total hip, spine, or radial bone mineral density values between nulliparous and parous women after multivariate adjustment. In conclusion, childbearing reduces hip fracture risk by means that may be independent of hip bone mineral density.

WHO absolute fracture risk models (FRAX): Do clinical risk factors improve fracture prediction in older women without osteoporosis?

Bone mineral density (BMD) is a strong predictor of fracture, yet most fractures occur in women without osteoporosis by BMD criteria. To improve fracture risk prediction, the World Health Organization recently developed a country‐specific fracture risk index of clinical risk factors (FRAX) that estimates 10‐year probabilities of hip and major osteoporotic fracture. Within differing baseline BMD categories, we evaluated 6252 women aged 65 or older in the Study of Osteoporotic Fractures using FRAX 10‐year probabilities of hip and major osteoporotic fracture (ie, hip, clinical spine, wrist, and humerus) compared with incidence of fractures over 10 years of follow‐up. Overall ability of FRAX to predict fracture risk based on initial BMD T‐score categories (normal, low bone mass, and osteoporosis) was evaluated with receiver‐operating‐characteristic (ROC) analyses using area under the curve (AUC). Over 10 years of follow‐up, 368 women incurred a hip fracture, and 1011 a major osteoporotic fracture. Women with low bone mass represented the majority (n = 3791, 61%); they developed many hip (n = 176, 48%) and major osteoporotic fractures (n = 569, 56%). Among women with normal and low bone mass, FRAX (including BMD) was an overall better predictor of hip fracture risk (AUC = 0.78 and 0.70, respectively) than major osteoporotic fractures (AUC = 0.64 and 0.62). Simpler models (eg, age + prior fracture) had similar AUCs to FRAX, including among women for whom primary prevention is sought (no prior fracture or osteoporosis by BMD). The FRAX and simpler models predict 10‐year risk of incident hip and major osteoporotic fractures in older US women with normal or low bone mass.

Glaucoma Risk and the Consumption of Fruits and Vegetables Among Older Women in the Study of Osteoporotic Fractures

PURPOSE To explore the association between the consumption of fruits and vegetables and the presence of glaucoma. DESIGN Cross-sectional cohort study. METHODS In a sample of 1,155 women located in multiple centers in the United States, glaucoma specialists diagnosed glaucoma in at least one eye by assessing optic nerve head photographs and 76-point suprathreshold screening visual fields. Consumption of fruits and vegetables was assessed using the Block Food Frequency Questionnaire. The relationship between selected fruit and vegetable consumption and glaucoma was investigated using adjusted logistic regression models. RESULTS Among 1,155 women, 95 (8.2%) were diagnosed with glaucoma. In adjusted analysis, the odds of glaucoma risk were decreased by 69% (odds ratio [OR], 0.31; 95% confidence interval [CI], 0.11 to 0.91) in women who consumed at least one serving per month of green collards and kale compared with those who consumed fewer than one serving per month, by 64% (OR, 0.36; 95% CI, 0.17 to 0.77) in women who consumed more than two servings per week of carrots compared with those who consumed fewer than one serving per week, and by 47% (OR, 0.53; 95% CI, 0.29 to 0.97) in women who consumed at least one serving per week of canned or dried peaches compared with those who consumed fewer than one serving per month. CONCLUSIONS A higher intake of certain fruits and vegetables may be associated with a decreased risk of glaucoma. More studies are needed to investigate this relationship.

The Association of Consumption of Fruits/Vegetables With Decreased Risk of Glaucoma Among Older African-American Women in the Study of Osteoporotic Fractures

PURPOSE To explore the association between consumption of fruits and vegetables and the presence of glaucoma in older African-American women. DESIGN Cross-sectional study. METHODS Disc photographs and suprathreshold visual fields were obtained from the 662 African-American participants in the Study of Osteoporotic Fractures. Masked, trained readers graded all discs, and 2 glaucoma specialists reviewed photographs and visual fields. The Block Food Frequency Questionnaire assessed food consumption. Relationships between selected fruit/vegetable/nutrient consumption and glaucoma were evaluated using logistic regression models after adjusting for potential confounders. RESULTS After excluding women missing Food Frequency Questionnaire and disc data, 584 African-American women (88.2% of total African-American cohort) were included. Glaucoma was diagnosed in at least 1 eye in 77 subjects (13%). Women who ate 3 or more servings/day of fruits/fruit juices were 79% (odds ratio [OR] = 0.21; 95% confidence interval [CI]: 0.08-0.60) less likely to have glaucoma than women who ate less than 1 serving/day. Women who consumed more than 2 servings/week of fresh oranges (OR = 0.18; 95% CI: 0.06-0.51) and peaches (OR = 0.30; 95% CI: 0.13-0.67) had a decreased odds of glaucoma compared to those consuming less than 1 serving/week. For vegetables, >1 serving/week compared to ≤1 serving/month of collard greens/kale decreased the odds of glaucoma by 57% (OR = 0.43; 95% CI: 0.21-0.85). There was a protective trend against glaucoma in those consuming more fruit/fruit juices (P = .023), fresh oranges (P = .002), fresh peaches (P = .002), and collard greens/kale (P = .014). Higher consumption of carrots (P = .061) and spinach (P = .094) also showed some associations. Individual nutrient intake from food sources found protective trends with higher intakes of vitamin A (P = .011), vitamin C (P = .018), and α-carotene (P = .021), and close to statistically significant trends with β-carotene (P = .052), folate (P = .056), and lutein/zeaxanthin (P = .077). CONCLUSION Higher intake of certain fruits and vegetables high in vitamins A and C and carotenoids may be associated with a decreased likelihood of glaucoma in older African-American women. Randomized controlled trials are needed to determine whether the intake of specific nutrients changes the risk of glaucoma.

The Association of Smoking and Alcohol Use with Age-Related Macular Degeneration in the Oldest Old: the Study of Osteoporotic Fractures

PURPOSE To estimate the incidence of age-related macular degeneration (AMD) and the association of smoking and alcohol in a population of older women. DESIGN Prospective cohort study. METHODS Subjects were women who attended the Study of Osteoporotic Fractures year-10 and year-15 follow-up clinic visits and had fundus photographs taken at both visits (n = 1958; 245 Black and 1713 White subjects; mean age at year 10 visit, 78.2 years). Forty-five degree stereoscopic fundus photographs were graded for AMD. Logistic regression was used to test whether risk factors were associated with incident AMD. RESULTS The overall 5-year AMD incidence was 24.1% (95% confidence interval [CI], 21.7 to 26.6) for early and 5.7% (95% CI, 4.6 to 6.8) for late. Early AMD incidence in White subjects ranged from 21.9% in those aged 74 to 79 years to 33.2% in those 80 to 84 years, but was observed at the slightly lower rate of 29.0% in subjects > or =85 years (trend P < .0001). After confounder adjustment, alcohol consumption was significantly associated with an elevated risk of incident early AMD (odds ratio [OR], 1.57; 95% CI, 1.18 to 2.11). There was an increased risk of early AMD among subjects aged 80 years or older who were smoking compared to those younger than 80 years who were not smoking (OR, 5.49; 95% CI, 1.57 to 19.20; P for interaction = .026). CONCLUSIONS The magnitude of the greater-than-additive effect of smoking on the age-adjusted risk of AMD reinforces recommendations to quit smoking even for older individuals.