Search tips
Search criteria

Results 1-25 (57)

Clipboard (0)

Select a Filter Below

more »
Year of Publication
more »
1.  We Can Change the Natural History of Type 2 Diabetes 
Diabetes Care  2014;37(10):2668-2676.
As diabetes develops, we currently waste the first ∼10 years of the natural history. If we found prediabetes and early diabetes when they first presented and treated them more effectively, we could prevent or delay the progression of hyperglycemia and the development of complications. Evidence for this comes from trials where lifestyle change and/or glucose-lowering medications decreased progression from prediabetes to diabetes. After withdrawal of these interventions, there was no “catch-up”—cumulative development of diabetes in the previously treated groups remained less than in control subjects. Moreover, achieving normal glucose levels even transiently during the trials was associated with a substantial reduction in subsequent development of diabetes. These findings indicate that we can change the natural history through routine screening to find prediabetes and early diabetes, combined with management aimed to keep glucose levels as close to normal as possible, without hypoglycemia. We should also test the hypothesis with a randomized controlled trial.
PMCID: PMC4170125  PMID: 25249668
2.  Educational attainment, MRI changes and cognitive function in older postmenopausal women from the Women’s Health Initiative Memory Study 
The relationship between neuropathology and clinically manifested functional and cognitive deficits is complex. Clinical observations of individuals with greater neuropathology who function better than some individuals with less neuropathology are common and puzzling. Educational attainment, a proxy for ‘cognitive reserve’, may help to explain this apparent contradiction. The objective of this study is to determine if educational attainment is correlated with cognitive decline, brain lesion volume and total brain atrophy. One thousand three hundred ninety of the 7,479 community-dwelling women 65 years of age and older enrolled in the Women’s Health Initiative Memory Study, two parallel randomized, placebo-controlled clinical trials comparing unopposed and opposed post-menopausal hormone therapy with placebo, were studied. Study participants received annual assessments of global cognitive function with the Modified Mini Mental State exam. One thousand sixty-three participants also received a supplemental neurocognitive battery and neuroimaging studies. Magnetic resonance imaging was used to calculate total ischemic lesion and brain volumes. Incident cases of probable dementia and mild cognitive impairment were centrally adjudicated. After adjustment for total lesion and total brain volumes (atrophy), higher educational attainment predicted better cognitive performance (p<0.001). Following conversion to dementia/MCI, higher education predicted steeper declines in cognitive function (p<0.001). Thus, higher educational attainment was associated with a delay in diagnosis of dementia/MCI in the face of a growing neuropathological load.
PMCID: PMC4544866  PMID: 24552037
cognition; MRI; cognitive reserve; aging; women; WHIMS
3.  Comparative Definitions for Moderate-Severe Ischemia in Stress Nuclear, Echocardiography, and Magnetic Resonance Imaging 
JACC. Cardiovascular imaging  2014;7(6):593-604.
The lack of standardized reporting of the magnitude of ischemia on noninvasive imaging contributes to variability in translating the severity of ischemia across stress imaging modalities. We identified the risk of coronary artery disease (CAD) death or myocardial infarction (MI) associated with ≥10% ischemic myocardium on stress nuclear imaging as the risk threshold for stress echocardiography and cardiac magnetic resonance. A narrative review revealed that ≥10% ischemic myocardium on stress nuclear imaging was associated with a median rate of CAD death or MI of 4.9%/year (interquartile range: 3.75% to 5.3%). For stress echocardiography, ≥3 newly dysfunctional segments portend a median rate of CAD death or MI of 4.5%/year (interquartile range: 3.8% to 5.9%). Although imprecisely delineated, moderate-severe ischemia on cardiac magnetic resonance may be indicated by ≥4 of 32 stress perfusion defects or ≥3 dobutamine-induced dysfunctional segments. Risk-based thresholds can define equivalent amounts of ischemia across the stress imaging modalities, which will help to translate a common understanding of patient risk on which to guide subsequent management decisions.
PMCID: PMC4128344  PMID: 24925328
cardiac imaging; ischemia; prognosis
4.  Hormone Therapy Dose, Formulation, Route of Delivery, and Risk of Cardiovascular Events in Women: Findings from the WHI Observational Study 
Menopause (New York, N.Y.)  2014;21(3):260-266.
Research comparing hormone therapy (HT) doses, regimens, and routes of delivery in relation to cardiovascular disease (CVD) outcomes have been limited. This study directly compared different estrogen doses, routes of delivery, and HT formulations in postmenopausal women in relation to the risk of coronary heart disease (CHD), stroke, CVD mortality, total CVD, and all-cause mortality.
The Women’s Health Initiative Observational Study (WHI-OS) is a multi-center prospective cohort study conducted at 40 US sites. Analyses included 93,676 postmenopausal women, aged 50-79 years at study entry and recruited September 1994 - December 1998, with annual follow-up through August 14, 2009.
Average follow-up was 10.4 years. In direct comparisons, oral estradiol was associated with lower hazard ratios (HRs) for stroke than oral conjugated equine estrogens (CEE) (HR 0.64; 95% CI 0.40, 1.02), but statistical power was limited. Similarly, transdermal estradiol was associated with a moderate but non-significant lower risk of CHD compared to oral CEE (HR 0.63; 95% CI 0.37, 1.06). For other outcomes, comparisons revealed no appreciable differences by estrogen doses, formulations, or routes of delivery. Absolute risks of CVD events and all-cause mortality were markedly lower in younger, compared to older, women.
In direct comparisons, various HT doses and regimens were associated with similar rates of cardiovascular events and all-cause mortality. However, oral estradiol may be associated with a lower risk of stroke and transdermal estradiol with a lower risk of CHD, compared to conventional-dose oral CEE. Additional research is needed to confirm these hypotheses.
PMCID: PMC3872264  PMID: 24045672
Menopause Hormone Therapy; Cardiovascular disease; Stroke
5.  Prevalence and Incident Prehypertension and Hypertension in Postmenopausal Hispanic Women: Results from the Women’s Health Initiative 
American Journal of Hypertension  2014;27(3):372-381.
There is a paucity of research on prehypertension and incident hypertension among postmenopausal Hispanic women. The overall objective is to determine the multiple risk factors associated with the prevalence of hypertension status at baseline and incident hypertension at year 3 in postmenopausal Hispanic women.
For the analyses in this paper, we included a total of 4,680 Hispanic women who participated in the Women’s Health Initiative (WHI), a randomized clinical trial and observational study, at baseline (1994–1998) and at third-year follow-up and for whom blood pressure was measured at year 3 (n = 3,848). Multivariable logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) of hypertension status, defined as systolic blood pressure ≥140mm Hg and/or diastolic blood pressure ≥90mm Hg, to assess the odds of incident hypertension at year 3 of follow-up in association with the factors included in the baseline models.
At year 3 of follow-up, 27.3% of Hispanic women who were normotensive at baseline had progressed to prehypertension, and 9.0% had become hypertensive. Among the prehypertensive participants at baseline, 30.4% had progressed to hypertension. Compared with normotensive Hispanic women, hypertensive participants had a higher number of cardiovascular risk factors: body mass index ≥30kg/m2 (OR = 3.76; 95% CI = 3.01–4.71), a family history of diabetes, stroke, and/or myocardial infarction (OR = 1.12; 95% CI 1.03–1.23), treated hypercholesterolemia (OR = 1.57; 95% CI = 1.23–1.99), treated diabetes (OR = 2.04; 95% CI = 1.40–2.97), and a history of cardiovascular disease (OR = 2.04; 95% CI = 1.58–2.64).
Hispanic women seem to experience an increased risk of incident hypertension in later adulthood. On a practical level, recommendations for preventive care and population-wide adoption of health behaviors, such as community-focused campaigns to engage in physical activity, may contribute to reductions in hypertension risk factors.
Trial Number NCT00000611
PMCID: PMC3915745  PMID: 24480867
blood pressure; cardiovascular risk; Hispanic; hypertension; postmenopausal; women; Women’s Health Initiative
6.  CHD Events in the WHI Hormone Trials: Effect Modification by Metabolic Syndrome A Nested Case/Control Study within the WHI RCTs 
Menopause (New York, N.Y.)  2013;20(3):254-260.
Our objective was to determine if metabolic syndrome (MetS), or its components, modified the effect of HT on risk of CHD events in the Women’s Health Initiative (WHI) clinical trials.
We performed a nested case/control study of incident CHD events during the first 4 years of follow up in the WHI HT trials (estrogen plus progestin [E+P] and estrogen-alone [E-alone]). There were 359 incident cases of CHD during follow up. After excluding women with cardiovascular disease (CVD) (n=90), diabetes or hypertension at baseline (n=103), 166 CHD cases were matched to 524 controls on age, randomization date, and hysterectomy status. MetS classification required at least 3 of 5 ATPIII criteria. Analyses by Chi-square, t-tests for heterogeneity and logistic regression were performed. Postmenopausal women (n=27,347) ages 50 to 79 from 40 US clinical centers participated.
Daily conjugated equine estrogens (0.625 mg) and medroxyprogesterone acetate (2.5mg) (EPT) or conjugated equine estrogens (0.625 mg) (ET) was compared to placebo. The Main Outcome Measure was the odds for CHD with HT use vs. placebo by MetS status.
MetS modified the risk of CHD events with HT. In the pooled analysis, with MetS, risk was increased with HT vs. placebo (OR=2.26[95% CI, 1.26, 4.07]), whereas women without MetS were not found to have increased risk for a CHD event with HT (OR=0.97 [95% CI, 0.58, 1.61]) (p for interaction = 0. 03). Results were similar in the EPT and ET trials, when examined separately. The constellation of MetS variables was more predictive of risk from HT than Mets components assessed individually. When patients with diabetes or hypertension were included in the analysis we could not detect statistically significant effect modification.
MetS at baseline, in women without prior CVD, diabetes, or hypertension at baseline, identified women more likely to have had adverse coronary outcomes on HT. CHD risk stratification is recommended prior to initiating HT. The basis for the greater risk of CHD events with HT among patients with the metabolic syndrome requires further study.
PMCID: PMC4279916  PMID: 23435021
WHI; CHD; HT; Metabolic syndrome; Effect Modification
7.  Melatonin supplementation to treat the metabolic syndrome: a randomized controlled trial 
Supplemental melatonin may ameliorate metabolic syndrome (MetS) components, but data from placebo-controlled trials are lacking.
We conducted a double-blind, placebo-controlled, crossover, Phase II randomized pilot clinical trial to estimate the effects of melatonin supplementation on MetS components and the overall prevalence of MetS. We randomized 39 subjects with MetS to receive 8.0 mg oral melatonin or matching placebo nightly for 10 weeks. After a 6-week washout, subjects received the other treatment for 10 more weeks. We measured waist circumference, triglycerides, HDL cholesterol, fasting glucose, and blood pressure (BP) in each subject at the beginning and end of both 10-week treatment periods. The primary outcome was the mean 10-week change in each MetS component, and a secondary outcome was the proportion of subjects free from MetS, after melatonin versus placebo.
The mean 10-week change for most MetS components favored melatonin over placebo (except fasting glucose): waist circumference -0.9 vs. +1.0 cm (p = 0.15); triglycerides -66.3 vs. -4.2 mg/dL (p = 0.17); HDL cholesterol -0.2 vs. -1.1 mg/dL (p = 0.59); fasting glucose +0.3 vs. -3.1 mg/dL (p = 0.29); systolic BP -2.7 vs. +4.7 mmHg (p = 0.013); and diastolic BP -1.1 vs. +1.1 mmHg (p = 0.24). Freedom from MetS tended to be more common following melatonin versus placebo treatment (after the first 10 weeks, 35.3% vs. 15.0%, p = 0.25; after the second 10 weeks, 45.0% vs. 23.5%, p = 0.30). Melatonin was well-tolerated.
Melatonin supplementation modestly improved most individual MetS components compared with placebo, and tended to increase the proportion of subjects free from MetS after treatment.
Trial registration
PMCID: PMC4416300  PMID: 25937837
Melatonin; Metabolic syndrome; Randomized controlled trial
8.  All-Cause, Cardiovascular, and Cancer Mortality Rates in Postmenopausal White, Black, Hispanic, and Asian Women With and Without Diabetes in the United States 
American Journal of Epidemiology  2013;178(10):1533-1541.
Using data from the Women's Health Initiative (1993–2009; n = 158,833 participants, of whom 84.1% were white, 9.2% were black, 4.1% were Hispanic, and 2.6% were Asian), we compared all-cause, cardiovascular, and cancer mortality rates in white, black, Hispanic, and Asian postmenopausal women with and without diabetes. Cox proportional hazard models were used for the comparison from which hazard ratios and 95% confidence intervals were computed. Within each racial/ethnic subgroup, women with diabetes had an approximately 2–3 times higher risk of all-cause, cardiovascular, and cancer mortality than did those without diabetes. However, the hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups. Population attributable risk percentages (PARPs) take into account both the prevalence of diabetes and hazard ratios. For all-cause mortality, whites had the lowest PARP (11.1, 95% confidence interval (CI): 10.1, 12.1), followed by Asians (12.9, 95% CI: 4.7, 20.9), blacks (19.4, 95% CI: 15.0, 23.7), and Hispanics (23.2, 95% CI: 14.8, 31.2). To our knowledge, the present study is the first to show that hazard ratios for mortality outcomes were not significantly different between racial/ethnic subgroups when stratified by diabetes status. Because of the “amplifying” effect of diabetes prevalence, efforts to reduce racial/ethnic disparities in the rate of death from diabetes should focus on prevention of diabetes.
PMCID: PMC3888272  PMID: 24045960
diabetes; health disparities; menopause; mortality; obesity; women's health
9.  Sex Hormone Levels and Risk of Breast Cancer With Estrogen Plus Progestin 
Although high endogenous sex hormone levels and estrogen plus progestin (E+P) therapy are associated with increased breast cancer risk, it is unknown whether pretreatment levels of sex hormones modify E+P effect on breast cancer.
We conducted a nested case–control study within the Women’s Health Initiative randomized clinical trial of E+P. The trial enrolled 16608 postmenopausal women aged 50 to 79 years with intact uterus and no breast cancer history. During a mean of 5.6 years of follow-up, 348 incident breast cancer case subjects were identified and matched with 348 control subjects. Case and control subjects had their sex hormone levels measured at baseline (estrogens, testosterone, progesterone, and sex hormone–binding globulin [SHBG]) and year 1 (estrogens and SHBG) using sensitive assays. All statistical tests were two-sided.
Statistically significant elevations in breast cancer risk were seen with greater pretreatment levels of total estradiol (P trend = .04), bioavailable estradiol (P trend = .03), estrone (P trend = .007), and estrone sulfate (P trend = .007). E+P increased all measured estrogens and SHGB at year 1 (all P < .001). The effect of E+P on breast cancer risk was strongest in women whose pretreatment levels of total estradiol, bioavailable estradiol, and estrone were in the lowest quartiles. For example, the odds ratio for E+P relative to placebo was 2.47 (95% confidence interval [CI] = 1.28 to 4.79) in the lowest total estradiol quartile, compared with 0.96 (95% CI = 0.44 to 2.09) in the highest total estradiol quartile; P interaction = .04).
Women with lower pr-treatment endogenous estrogen levels were at greater risk of breast cancer during E+P therapy compared with those with higher levels. Further studies are warranted to confirm these findings.
PMCID: PMC3787910  PMID: 24041978
10.  Evidence of Reduced β-Cell Function in Asian Indians With Mild Dysglycemia 
Diabetes Care  2013;36(9):2772-2778.
To examine β-cell function across a spectrum of glycemia among Asian Indians, a population experiencing type 2 diabetes development at young ages despite low BMI.
One-thousand two-hundred sixty-four individuals without known diabetes in the Diabetes Community Lifestyle Improvement Program in Chennai, India, had a 75-g oral glucose tolerance test, with glucose and insulin measured at 0, 30, and 120 min. Type 2 diabetes, isolated impaired fasting glucose (iIFG), isolated impaired glucose tolerance (iIGT), combined impaired fasting glucose and impaired glucose tolerance, and normal glucose tolerance (NGT) were defined by American Diabetes Association guidelines. Measures included insulin resistance and sensitivity (homeostasis model assessment of insulin resistance [HOMA-IR], modified Matsuda Index, 1/fasting insulin) and β-cell function (oral disposition index = [Δinsulin0–30/Δglucose0–30] × [1/fasting insulin]).
Mean age was 44.2 years (SD, 9.3) and BMI 27.4 kg/m2 (SD, 3.8); 341 individuals had NGT, 672 had iIFG, IGT, or IFG plus IGT, and 251 had diabetes. Patterns of insulin resistance or sensitivity were similar across glycemic categories. With mild dysglycemia, the absolute differences in age- and sex-adjusted oral disposition index (NGT vs. iIFG, 38%; NGT vs. iIGT, 32%) were greater than the differences in HOMA-IR (NGT vs. iIFG, 25%; NGT vs. iIGT, 23%; each P < 0.0001). Compared with NGT and adjusted for age, sex, BMI, waist circumference, and family history, the odds of mild dysglycemia were more significant per SD of oral disposition index (iIFG: odds ratio [OR], 0.36; 95% CI, 0.23–0.55; iIGT: OR, 0.37; 95% CI, 0.24–0.56) than per SD of HOMA-IR (iIFG: OR, 1.69; 95% CI, 1.23–2.33; iIGT: OR, 1.53; 95% CI, 1.11–2.11).
Asian Indians with mild dysglycemia have reduced β-cell function, regardless of age, adiposity, insulin sensitivity, or family history. Strategies in diabetes prevention should minimize loss of β-cell function.
PMCID: PMC3747932  PMID: 23596180
11.  Relations of Depressive Symptoms and Antidepressant Use to Body Mass Index and Selected Biomarkers for Diabetes and Cardiovascular Disease 
American journal of public health  2013;103(8):e34-e43.
We investigated whether depressive symptoms and antidepressant use are associated with biomarkers for glucose dysregulation and inflammation, body mass index (BMI), and waist circumference.
Postmenopausal women were recruited into the Women’s Health Initiative from 1993 to 1998, and data were collected at regular intervals through 2005. We used multiple linear regression models to examine whether depressive symptoms and antidepressant use are associated with BMI, waist circumference, and biomarkers.
Analysis of data from 71 809 women who completed all relevant baseline and year 3 assessments showed that both elevated depressive symptoms and antidepressant use were significantly associated with higher BMI and waist circumference. Among 1950 women, elevated depressive symptoms were significantly associated with increased insulin levels and measures of insulin resistance. Analyses of baseline data from 2242 women showed that both elevated depressive symptoms and antidepressant use were associated with higher C-reactive protein levels.
Monitoring body habitus and other biomarkers among women with elevated depression symptoms or taking antidepressant medication may be prudent to prevent diabetes and cardiovascular disease.
PMCID: PMC3791588  PMID: 23763394
12.  Hyperglycemia, Insulin Resistance, Impaired Pancreatic β-Cell Function, and Risk of Pancreatic Cancer 
Obesity and diabetes mellitus are associated with an increased risk of pancreatic cancer. These associations may be secondary to consequences of peripheral insulin resistance, pancreatic β-cell dysfunction, or hyperglycemia itself. Hemoglobin A1c (HbA1c) is a measure of hyperglycemia, whereas plasma insulin and proinsulin are markers of peripheral insulin resistance, and the proinsulin to insulin ratio marks pancreatic β-cell dysfunction.
This was a prospective, nested case-control study of 449 case patients and 982 control subjects with prediagnostic blood samples and no diabetes history from five prospective US cohorts followed through 2008. Two or three control subjects were matched to each case patient by year of birth, cohort, smoking, and fasting status. Pancreatic cancer risk was assessed by prediagnostic HbA1c, insulin, proinsulin, and proinsulin to insulin ratio with multivariable-adjusted logistic regression. All P values were two-sided.
The highest vs lowest quintiles of HbA1c, insulin, and proinsulin were associated with with an increased risk for pancreatic cancer (odds ratio [OR] = 1.79; 95% confidence interval [CI] = 1.17 to 2.72, P trend = .04 for HbA1c; OR = 1.57; 95% CI = 1.08 to 2.30; Ptrend = .002 for insulin; and OR = 2.22; 95% CI = 1.50 to 3.29; P trend < .001 for proinsulin). Proinsulin to insulin ratio was not associated with pancreatic cancer risk. Results were similar across studies (all P heterogeneity > .29). In cancers developing 10 or more years after blood collection, the associations with insulin and proinsulin became stronger (highest vs lowest quintile, OR = 2.77; 95% CI = 1.28 to 5.99 for insulin and OR = 3.60; 95% CI = 1.68 to 7.72 for proinsulin). In mutually adjusted models including HbA1c, insulin, and proinsulin, only proinsulin remained statistically significant ( highest vs lowest quintile, OR = 2.55; 95% CI = 1.54 to 4.21; Ptrend < .001).
Among participants from five large prospective cohorts, circulating markers of peripheral insulin resistance, rather than hyperglycemia or pancreatic β-cell dysfunction, were independently associated with pancreatic cancer risk.
PMCID: PMC3714020  PMID: 23847240
13.  Screening for Diabetes and Prediabetes Should Be Cost-Saving in Patients at High Risk 
Diabetes Care  2013;36(7):1981-1987.
Although screening for diabetes and prediabetes is recommended, it is not clear how best or whom to screen. We therefore compared the economics of screening according to baseline risk.
Five screening tests were performed in 1,573 adults without known diabetes—random plasma/capillary glucose, plasma/capillary glucose 1 h after 50-g oral glucose (any time, without previous fast, plasma glucose 1 h after a 50-g oral glucose challenge [GCTpl]/capillary glucose 1 h after a 50-g oral glucose challenge [GCTcap]), and A1C—and a definitive 75-g oral glucose tolerance test. Costs of screening included the following: costs of testing (screen plus oral glucose tolerance test, if screen is positive); costs for false-negative results; and costs of treatment of true-positive results with metformin, all over the course of 3 years. We compared costs for no screening, screening everyone for diabetes or high-risk prediabetes, and screening those with risk factors based on age, BMI, blood pressure, waist circumference, lipids, or family history of diabetes.
Compared with no screening, cost-savings would be obtained largely from screening those at higher risk, including those with BMI >35 kg/m2, systolic blood pressure ≥130 mmHg, or age >55 years, with differences of up to −46% of health system costs for screening for diabetes and −21% for screening for dysglycemia110, respectively (all P < 0.01). GCTpl would be the least expensive screening test for most high-risk groups for this population over the course of 3 years.
From a health economics perspective, screening for diabetes and high-risk prediabetes should target patients at higher risk, particularly those with BMI >35 kg/m2, systolic blood pressure ≥130 mmHg, or age >55 years, for whom screening can be most cost-saving. GCTpl is generally the least expensive test in high-risk groups and should be considered for routine use as an opportunistic screen in these groups.
PMCID: PMC3687271  PMID: 23393215
14.  Lessons learned from MPI and physiologic testing in randomized trials of stable ischemic heart disease: COURAGE, BARI 2D, FAME, and ISCHEMIA 
There is a preponderance of evidence that, in the setting of an acute coronary syndrome, an invasive approach using coronary revascularization has a morbidity and mortality benefit. However, recent stable ischemic heart disease (SIHD) randomized clinical trials testing whether the addition of coronary revascularization to guideline-directed medical therapy (GDMT) reduces death or major cardiovascular events have been negative. Based on the evidence from these trials, the primary role of GDMT as a front line medical management approach has been clearly defined in the recent SIHD clinical practice guideline; the role of prompt revascularization is less precisely defined. Based on data from observational studies, it has been hypothesized that there is a level of ischemia above which a revascularization strategy might result in benefit regarding cardiovascular events. However, eligibility for recent negative trials in SIHD has mandated at most minimal standards for ischemia. An ongoing randomized trial evaluating the effectiveness of randomization of patients to coronary angiography and revascularization as compared to no coronary angiography and GDMT in patients with moderate-severe ischemia will formally test this hypothesis. The current review will highlight the available evidence including a review of the published and ongoing SIHD trials.
PMCID: PMC3954506  PMID: 23963599
Myocardial perfusion imaging; ischemia; coronary artery disease; clinical trials
15.  Diabetes and risk of pancreatic cancer: a pooled analysis from the pancreatic cancer cohort consortium 
Cancer causes & control : CCC  2012;24(1):13-25.
Diabetes is a suspected risk factor for pancreatic cancer, but questions remain about whether it is a risk factor or a result of the disease. This study prospectively examined the association between diabetes and the risk of pancreatic adenocarcinoma in pooled data from the NCI pancreatic cancer cohort consortium (PanScan).
The pooled data included 1,621 pancreatic adenocarcinoma cases and 1,719 matched controls from twelve cohorts using a nested case–control study design. Subjects who were diagnosed with diabetes near the time (<2 years) of pancreatic cancer diagnosis were excluded from all analyses. All analyses were adjusted for age, race, gender, study, alcohol use, smoking, BMI, and family history of pancreatic cancer.
Self-reported diabetes was associated with a forty percent increased risk of pancreatic cancer (OR = 1.40, 95 % CI: 1.07, 1.84). The association differed by duration of diabetes; risk was highest for those with a duration of 2–8 years (OR = 1.79, 95 % CI: 1.25, 2.55); there was no association for those with 9+ years of diabetes (OR = 1.02, 95 % CI: 0.68, 1.52).
These findings provide support for a relationship between diabetes and pancreatic cancer risk. The absence of association in those with the longest duration of diabetes may reflect hypoinsulinemia and warrants further investigation.
PMCID: PMC3529822  PMID: 23112111
Diabetes; Risk factor; Cohort consortium; Pancreatic cancer
16.  Determinants of Racial/Ethnic Disparities in Incidence of Diabetes in Postmenopausal Women in the U.S. 
Diabetes Care  2012;35(11):2226-2234.
To examine determinants of racial/ethnic differences in diabetes incidence among postmenopausal women participating in the Women’s Health Initiative.
Data on race/ethnicity, baseline diabetes prevalence, and incident diabetes were obtained from 158,833 women recruited from 1993–1998 and followed through August 2009. The relationship between race/ethnicity, other potential risk factors, and the risk of incident diabetes was estimated using Cox proportional hazards models from which hazard ratios (HRs) and 95% CIs were computed.
Participants were aged 63 years on average at baseline. The racial/ethnic distribution was 84.1% non-Hispanic white, 9.2% non-Hispanic black, 4.1% Hispanic, and 2.6% Asian. After an average of 10.4 years of follow-up, compared with whites and adjusting for potential confounders, the HRs for incident diabetes were 1.55 for blacks (95% CI 1.47–1.63), 1.67 for Hispanics (1.54–1.81), and 1.86 for Asians (1.68–2.06). Whites, blacks, and Hispanics with all factors (i.e., weight, physical activity, dietary quality, and smoking) in the low-risk category had 60, 69, and 63% lower risk for incident diabetes. Although contributions of different risk factors varied slightly by race/ethnicity, most findings were similar across groups, and women who had both a healthy weight and were in the highest tertile of physical activity had less than one-third the risk of diabetes compared with obese and inactive women.
Despite large racial/ethnic differences in diabetes incidence, most variability could be attributed to lifestyle factors. Our findings show that the majority of diabetes cases are preventable, and risk reduction strategies can be effectively applied to all racial/ethnic groups.
PMCID: PMC3476929  PMID: 22833490
17.  A Prospective Study of Leukocyte Telomere Length and Risk of Type 2 Diabetes in Postmenopausal Women 
Diabetes  2012;61(11):2998-3004.
Telomere length (TL) has been implicated in the pathogenesis of age-related disorders. However, there are no prospective studies directly investigating the role of TL and relevant genes in diabetes development. In the multiethnic Women’s Health Initiative, we identified 1,675 incident diabetes case participants in 6 years of follow-up and 2,382 control participants matched by age, ethnicity, clinical center, time of blood draw, and follow-up duration. Leukocyte TL at baseline was measured using quantitative PCR, and Mendelian randomization analysis was conducted to test whether TL is causally associated with diabetes risk. After adjustment for matching and known diabetes risk factors, odds ratios per 1-kilobase increment were 1.00 (95% CI 0.90–1.11) in whites, 0.95 (0.85–1.06) in blacks, 0.96 (0.79–1.17) in Hispanics, and 0.88 (0.70–1.10) in Asians. Of the 80 single nucleotide polymorphisms (SNPs) in nine genes involved in telomere regulation, 14 SNPs were predictive of TL, but none were significantly associated with diabetes risk. Using ethnicity-specific SNPs as randomization instruments, we observed no statistically significant association between TL and diabetes risk (P = 0.52). Although leukocyte TL was weakly associated with diabetes risk, this association was not independent of known risk factors. These prospective findings indicate limited clinical utility of TL in diabetes risk stratification among postmenopausal women.
PMCID: PMC3478524  PMID: 22829448
18.  Ethnic heterogeneity in glucoregulatory function during treatment with atypical antipsychotics in patients with schizophrenia✩  
Journal of psychiatric research  2008;42(13):1076-1085.
Atypical antipsychotics induce weight gain and are linked to increased diabetes risk, but their relative impact on factors that elevate disease risk are unknown.
We performed a 6-month, randomized, double-blind study to evaluate the effects of risperidone and olanzapine in patients with schizophrenia. At baseline and weeks 6 and 24, we quantified: (1) total adiposity by DEXA, (2) visceral adiposity by abdominal CT, and (3) insulin sensitivity (SI) and (4) pancreatic function (“disposition index”, DI) by intravenous glucose tolerance test.
At baseline, groups (risperidone: n = 28; olanzapine: n = 31) were overweight or obese by body mass index (risperidone: 28.4 ± 5.4, olanzapine: 30.6 ± 7.0 kg/m2). Both drugs induced weight gain (p < 0.004). Total adiposity was increased by olanzapine at 6 weeks (p = 0.0006) and by both treatments at 24 weeks (p < 0.003). Visceral adiposity was increased by olanzapine and risperidone by 24 weeks (p < 0.003). SI did not deteriorate appreciably, although a downward trend was observed with risperidone. Given known ethnic differences in adiposity and SI, we performed secondary analysis in African American and Hispanic subjects. In this subset, olanzapine expanded both total and visceral adiposity (p < 0.02); no increase was observed with risperidone. There were modest downward trends for SI with both treatments. By week 24, olanzapine-treated subjects exhibited diminished DI (p = 0.033), indicating inadequate pancreatic compensation for insulin resistance.
This is the first prospective study in psychiatric patients that quantified antipsychotic effects on the multiple metabolic processes that increase diabetes risk. Results indicate that ethnic minorities may have greater susceptibility to antipsychotic-induced glucoregulatory complications.
PMCID: PMC3769976  PMID: 18295798
Risperidone; Olanzapine; Schizophrenia; Diabetes; Minorities
19.  Sagittal Abdominal Diameter and Visceral Adiposity 
Obesity surgery  2013;23(7):874-881.
In the context of increasing obesity prevalence, the relationship between large visceral adipose tissue (VAT) volumes and type 2 diabetes mellitus (T2DM) is unclear. In a clinical sample of severely obese women (mean body mass index [BMI], 46 kg/m2) with fasting normoglycemia (n=40) or dysglycemia (impaired fasting glucose+diabetes; n=20), we sought to determine the usefulness of anthropometric correlates of VAT and associations with dysglycemia.
VAT volume was estimated using multi-slice computer tomography; anthropometric surrogates included sagittal abdominal diameter (SAD), waist circumference (WC) and BMI. Insulin sensitivity (Si), and beta-cell dysfunction, measured by insulin secretion (AIRg) and the disposition index (DI), were determined by frequently sampled intravenous glucose tolerance test.
Compared to fasting normoglycemic women, individuals with dysglycemia had greater VAT (P<0.001) and SAD (P=0.04), but BMI, total adiposity and Si were similar. VAT was inversely associated with AIRg and DI after controlling for ancestry, Si, and total adiposity (standardized beta, −0.32 and −0.34, both P<0.05). In addition, SAD (beta=0.41, P=0.02) was found to be a better estimate of VAT volume than WC (beta=0.32, P=0.08) after controlling for covariates. Receiver operating characteristic analysis showed that VAT volume, followed by SAD, outperformed WC and BMI in identifying dysglycemic participants.
Increasing VAT is associated with beta-cell dysfunction and dysglycemia in very obese women. In the presence of severe obesity, SAD is a simple surrogate of VAT, and an indicator of glucose dysregulation.
PMCID: PMC3750719  PMID: 23408092
Obesity; Type 2 diabetes; Waist circumference; Anthropometry; Intra-abdominal fat; Insulin resistance; Sagittal abdominal diameter
20.  Diabetes, Metformin, and Breast Cancer in Postmenopausal Women 
Journal of Clinical Oncology  2012;30(23):2844-2852.
Emerging evidence suggests that metformin may reduce breast cancer incidence, but reports are mixed and few provide information on tumor characteristics. Therefore, we assessed associations among diabetes, metformin use, and breast cancer in postmenopausal women participating in Women's Health Initiative clinical trials.
Patients and Methods
In all, 68,019 postmenopausal women, including 3,401 with diabetes at study entry, were observed over a mean of 11.8 years with 3,273 invasive breast cancers diagnosed. Diabetes incidence status was collected throughout follow-up, with medication information collected at baseline and years 1, 3, 6, and 9. Breast cancers were confirmed by review of central medical records and pathology reports. Cox proportional hazards regression, adjusted for breast cancer risk factors, compared breast cancer incidence in women with diabetes who were metformin users or nonusers with breast cancer incidence in women without diabetes.
Compared with that in women without diabetes, breast cancer incidence in women with diabetes differed by diabetes medication type (P = .04). Women with diabetes receiving medications other than metformin had a slightly higher incidence of breast cancer (hazard ratio [HR], 1.16; 95% CI, 0.93 to 1.45), and women with diabetes who were given metformin had lower breast cancer incidence (HR, 0.75; 95% CI, 0.57 to 0.99). The association was observed for cancers positive for both estrogen receptor and progesterone receptor and those that were negative for human epidermal growth factor receptor 2.
Metformin use in postmenopausal women with diabetes was associated with lower incidence of invasive breast cancer. These results can inform future studies evaluating metformin use in breast cancer management and prevention.
PMCID: PMC3826090  PMID: 22689798
21.  Diabetes Management in Urban African Americans: Review of a Public Hospital Experience 
Ethnicity & disease  2008;18(3):336-341.
To review characteristics of an urban (primarily African American) diabetes patient population and discuss experience with treatment strategies, we summarize key retrospective and prospective analyses conducted during 15 years.
Severe socioeconomic and personal barriers to diabetes care were often seen in the population. An atypical presentation of diabetic ketoacidosis was observed and extensively studied. A structured diabetes care delivery program was implemented more than three decades ago. A better understanding of how to provide simpler but effective dietary education and factors that affect lipid levels were elucidated. The phenomenon of clinical inertia was described, and methods were developed to facilitate the intensification of diabetes therapy and improve glycemic control.
Structured diabetes care can be successfully introduced into a public health system and effective diabetes management can be provided to an under-served population that can result in improved metabolic outcomes. Lessons learned on diabetes management in this population can be extended to similar clinical settings.
PMCID: PMC3688048  PMID: 18785449
African Americans; Diabetes Mellitus; Urban Health Services
22.  Age, BMI, and Race Are Less Important Than Random Plasma Glucose in Identifying Risk of Glucose Intolerance 
Diabetes care  2008;31(5):884-886.
Age, BMI, and race/ethnicity are used in National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and American Diabetes Association (ADA) guidelines to prompt screening for pre-diabetes and diabetes, but cutoffs have not been evaluated rigorously.
Random plasma glucose (RPG) was measured and 75-g oral glucose tolerance tests were performed in 1,139 individuals without known diabetes. Screening performance was assessed by logistic regression and area under the receiver operating characteristic curve (AROC).
NIDDK/ADA indicators age >45 years and BMI >25 kg/m2 provided significant detection of both diabetes and dysglycemia (both AROCs 0.63), but screening was better with continuous-variable models of age, BMI, and race and better still with models of age, BMI, race, sex, and family history (AROC 0.78 and 0.72). However, screening was even better with RPG alone (AROCs 0.81 and 0.72). RPG >125 mg/dl could be used to prompt further evaluation with an OGTT.
Use of age, BMI, and race/ethnicity in guidelines for screening to detect diabetes and pre-diabetes may be less important than evaluation of RPG. RPG should be investigated further as a convenient, inexpensive screen with good predictive utility.
PMCID: PMC3685424  PMID: 18310308
24.  Education, Income, and Incident Heart Failure in Post Menopausal Women: The Women’s Health Initiative Hormone Therapy trials 
To estimate the effect of education and income on incident heart failure (HF) hospitalization among post-menopausal women.
Investigations of socioeconomic status (SES) have focused on outcomes after HF diagnosis, not associations with incident HF. We used data from the Women’s Health Initiative Hormone Trials to examine the association between SES levels and incident HF hospitalization.
We included 26,160 healthy, post-menopausal women. Education and income were self-reported. ANOVA, Chi-square tests, and proportional hazards models were used for statistical analysis, with adjustment for demographics, co-morbid conditions, behavioral factors, and hormone and dietary modification assignments.
Women with household incomes <$20,000/year had higher HF hospitalization incidence (57.3/10,000 person-years) than women with household incomes >$50,000/year (16.7/10,000 person-years; p<0.01). Women with less than a high school education had higher HF hospitalization incidence (51.2/10,000 person-years) than college graduates and above (25.5/10,000 person-years; p<0.01). In multivariable analyses, women with the lowest income levels had 56% higher risk (HR 1.56, 95% CI 1.19 to 2.04) than the highest income women; women with the least amount of education had 21% higher risk for incident HF hospitalization (HR 1.21, 95% CI 0.90 to 1.62) than the most educated women.
Lower income is associated with an increased incidence of HF hospitalization among healthy, post-menopausal women, whereas multivariable adjustment attenuated the association of education with incident HF.
PMCID: PMC3635103  PMID: 21939829
heart failure; socioeconomic status; women
25.  Serum 25-Hydroxyvitamin D and Physical Performance in Postmenopausal Women 
Journal of Women's Health  2011;20(11):1603-1608.
Impairments in physical performance increase sharply with age. Low serum 25-hydroxyvitamin D (25-OHD) levels may be a modifiable risk factor for physical performance decline.
Five hundred thirty-two participants in the Women's Health Initiative Clinical Trial (WHI CT) were among a 25% randomly selected subsample of women who participated in performance-based measures of physical performance at baseline, year 1, year 3, and year 6. A physical performance summary score was derived from three tests: timed walk, chair-stand, and grip strength. Levels of 25-OHD were measured at baseline. We used the generalized estimating equations (GEE) method to examine repeated measures of physical performance as a function of follow-up time since baseline according to 25-OHD concentration.
In 6 years of follow-up, participants with serum 25OHD ≥75 nmol/L had significantly higher scores for physical performance (β=2.64, 95% confidence interval [CI] 0.90-4.39) compared with the reference category (<35 nmol/L) after adjustment for age, chronic conditions, body mass index (BMI), race/ethnicity, time spent walking outside, trial arm, clinic latitude, and season of blood draw. However, the rate of decline in physical performance did not differ by level of 25OHD.
Higher baseline serum 25-OHD was associated with better physical performance but did not reduce decline in physical performance over the 6-year period.
PMCID: PMC3216069  PMID: 21923280

Results 1-25 (57)