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1.  DIETARY ENERGY INTAKE IS ASSOCIATED WITH TYPE 2 DIABETES RISK MARKERS IN CHILDREN 
Diabetes care  2013;37(1):116-123.
Objective
Energy intake, energy density and nutrient intakes are implicated in type 2 diabetes risk in adults, but little is known about their influence on emerging type 2 diabetes risk in childhood. We examined these associations in a multi-ethnic population of children.
Research Design and Methods
Cross-sectional study of 2017 children predominantly of white European, South Asian and black African-Caribbean origin aged 9-10 years who had a detailed 24 hour dietary recall, measurements of body composition and provided a fasting blood sample for measurements of plasma glucose, HbA1c and serum insulin; HOMA insulin resistance was also derived.
Results
Energy intake was positively associated with insulin resistance. After the removal of 176 participants with implausible energy intakes (unlikely to be representative of habitual intake), energy intake was more strongly associated with insulin resistance, and was also associated with glucose and fat mass index. Energy density was also positively associated with insulin resistance and fat mass index. However, in mutually adjusted analyses, the associations for energy intake remained while those for energy density became non-significant. Individual nutrient intakes showed no associations with type 2 diabetes risk markers.
Conclusions
Higher total energy intake was strongly associated with high levels of insulin resistance and may help to explain emerging type 2 diabetes risk in childhood. Studies are needed to establish whether reducing energy intake produces sustained favourable changes in insulin resistance and circulating glucose levels.
doi:10.2337/dc13-1263
PMCID: PMC3966263  PMID: 23939542
2.  Pesticide Exposure and Self-Reported Gestational Diabetes Mellitus in the Agricultural Health Study 
Diabetes care  2007;30(3):529-534.
OBJECTIVE
To examine the association between pesticide use during pregnancy and gestational diabetes mellitus (GDM) among wives of licensed pesticide applicators.
RESEARCH DESIGN AND METHODS
Using data from the Agricultural Health Study (AHS), we estimated the association between self-reported pesticide-related activities during the first trimester of the most recent pregnancy and GDM among 11,273 women whose pregnancy occurred within 25 years of enrollment.
RESULTS
A total of 506 (4.5%) women reported having had GDM. Women who reported agricultural pesticide exposure (mixing or applying pesticides to crops or repairing pesticide application equipment) during pregnancy were more likely to report GDM (odds ratio [OR] 2.2 [95% CI 1.5–3.3]). We saw no association between residential pesticide exposure (applying pesticides in the home and garden during pregnancy) and GDM (1.0 [0.8–1.3]). Among women who reported agricultural exposure during pregnancy, risk of GDM was associated with ever-use of four herbicides (2,4,5-T; 2,4,5-TP; atrazine; or butylate) and three insecticides (diazinon, phorate, or carbofuran).
CONCLUSIONS
These findings suggest that activities involving exposure to agricultural pesticides during the first trimester of pregnancy may increase the risk of GDM.
doi:10.2337/dc06-1832
PMCID: PMC3902103  PMID: 17327316
4.  Quality of Diabetes Care in U.S. Academic Medical Centers 
Diabetes care  2005;28(2):337-442.
Objective
To assess both standard and novel diabetes quality measures in a national sample of U.S. academic medical centers.
Research Design and Methods
This retrospective cohort study was conducted from 10 January 2000 to 10 January 2002. It involved 30 U.S. academic medical centers, which contributed data from 44 clinics (27 primary care clinics and 17 diabetes/endocrinology clinics). For 1,765 eligible adult patients with type 1 or type 2 diabetes with at least two clinic visits in the 24 months before 10 January 2002, including one visit in the 6 months before 10 January 2002, we assessed measurement and control of HbA1c, blood pressure, and cholesterol and corresponding medical regimen changes at the most recent clinic visit.
Results
In this ethnically and economically diverse cohort, annual testing rates were very high (97.4% for HbA1c, 96.6% for blood pressure, and 87.6% for total cholesterol). Fewer patients were at HbA1c goal (34.0% <7.0%) or blood pressure goal (33.0% <130/80 mmHg) than lipid goals (65.1% total cholesterol <200 mg/dl, 46.1% with LDL cholesterol <100 mg/dl). Only 10.0% of the cohort met recommended goals for all three risk factors. At the most recent clinic visit, 40.4% of patients with HbA1c concentrations above goal underwent adjustment of their corresponding regimens. Among untreated patients, few with elevated blood pressure (10.1% with blood pressure >130/80 mmHg) or elevated LDL cholesterol (5.6% with LDL >100 mg/dl) were started on corresponding therapy. Patients with type 2 diabetes were no less likely to be intensified than patients with type 1 diabetes.
Conclusions
High rates of risk factor testing do not necessarily translate to effective metabolic control. Low rates of medication adjustment among patients with levels above goal suggest a specific and novel target for quality improvement measurement.
PMCID: PMC3829636  PMID: 15677789
5.  Clinical Predictors of Disease Progression and Medication Initiation in Untreated Patients with Type 2 Diabetes and A1C Less Than 7% 
Diabetes care  2007;31(3):10.2337/dc07-1934.
Objective
Many patients with early diabetes remain untreated. Our objectives were to identify clinical predictors of 1) worsening glycemic control and 2) medical treatment initiation in response to worsening glycemic control among patients with type 2 diabetes.
Research Design and Methods
We identified 5,804 type 2 diabetic patients seen at least twice between June 2005 and June 2006 within our 12-clinic primary care network. We examined predictors of diabetes progression (A1C ≥7% or initiation of hypoglycemic agent) over a 1-year follow-up period in 705 patients who had A1C <7% and were not on glucose-lowering medications at baseline. In the 200 patients in this group who progressed, we examined predictors of medical therapy initiation.
Results
In multivariate analyses, baseline A1C (P < 0.0001), younger age (P = 0.04), and weight gain (P = 0.03) were independent predictors of progression after adjusting for race, sex, and baseline HDL levels. Each decade of increasing age reduced the risk of progression by 15%. Each 1-lb increase in weight was associated with a 2% increased odds of progression. Likelihood of medication initiation among progressors decreased by 40% (P = 0.02) with every decade of age and decreased by 2.3% (P = 0.02) with each 1-mg/dl decrease in LDL level from baseline after adjusting for race, sex, and weight change.
Conclusions
Among untreated primary care patients with type 2 diabetes and A1C < 7%, younger patients and those with weight gain were more likely to have diabetes progression and should be the focus of aggressive diabetes management.
doi:10.2337/dc07-1934
PMCID: PMC3829640  PMID: 18083790
6.  How Doctors Choose Medications to Treat Type 2 Diabetes 
Diabetes care  2007;30(6):10.2337/dc06-2499.
OBJECTIVE
Glycemic control remains suboptimal despite the wide range of available medications. More effective medication prescription might result in better control. However, the process by which physicians choose glucose-lowering medicines is poorly understood. We sought to study the means by which physicians choose medications for type 2 diabetic patients.
RESEARCH DESIGN AND METHODS
We surveyed 886 physician members of either the Society of General Internal Medicine (academic generalists, response rate 30%) or the American Diabetes Association (specialists, response rate 23%) currently managing patients with type 2 diabetes. Respondents weighed the importance of 15 patient, physician, and nonclinical factors when deciding which medications to prescribe for type 2 diabetic subjects at each of three management stages (initiation, use of second-line oral agents, and insulin).
RESULTS
Respondents reported using a median of five major considerations (interquartile range 4–6) at each stage. Frequently cited major considerations included overall assessment of the patient’s health/comorbidity, A1C level, and patient’s adherence behavior but not expert guidelines/hospital algorithms or patient age. For insulin initiation, academic generalists placed greater emphasis on patient adherence (76 vs. 60% of specialists, P < 0.001). These generalists also identified patient fear of injections (68%) and patient desire to prolong noninsulin therapy (68%) as major insulin barriers. Overall, qualitative factors (e.g., adherence, motivation, overall health assessment) were somewhat more highly considered than quantitative factors (e.g., A1C, age, weight) with mean aggregate scores of 7.3 vs. 6.9 on a scale of 0–10, P < 0.001.
CONCLUSIONS
The physicians in our survey considered a wide range of qualitative and quantitative factors when making medication choices for hyperglycemia management. The apparent complexity of the medication choice process contrasts with current evidence-based treatment guidelines.
doi:10.2337/dc06-2499
PMCID: PMC3829641  PMID: 17337497
7.  Long-Term Effects on Medical Costs of Improving Depression Outcomes in Patients With Depression and Diabetes 
Diabetes care  2008;31(6):10.2337/dc08-0032.
OBJECTIVE
The purpose of this study was to examine the 5-year effects on total health care costs of the Pathways depression intervention program for patients with diabetes and comorbid depression compared with usual primary care.
RESEARCH DESIGN AND METHODS
The Pathways Study was conducted in nine primary care practices of a large HMO and enrolled 329 patients with diabetes and comorbid major depression. The current study analyzed the differences in long-term medical costs between intervention and usual care patients. Participants were randomly assigned to a nurse depression intervention (n = 164) or to usual primary care (n = 165). The intervention included education about depression, behavioral activation, and a choice of either starting with support of antidepressant medication treatment by the primary care doctor or problem-solving therapy in primary care. Interventions were provided for up to 12 months, and the main outcome measures are health costs over a 5-year period.
RESULTS
Patients in the intervention arm of the study had improved depression outcomes and trends for reduced 5-year mean total medical costs of –$3,907 (95% CI –$15,454 less to $7,640 more) compared with usual care patients. A sensitivity analysis found that these cost differences were largely explained by the patients with depression and the most severe medical comorbidity.
CONCLUSIONS
The Pathways depression collaborative care program improved depression outcomes compared with usual care with no evidence of greater long-term costs and with trends for reduced costs among the more severely medically ill patients with diabetes.
doi:10.2337/dc08-0032
PMCID: PMC3810023  PMID: 18332158
8.  Long-Term Mortality in Nationwide Cohorts of Childhood-Onset Type 1 Diabetes in Japan and Finland 
Diabetes care  2003;26(7):2037-2042.
Objective
This study compares mortality from type 1 diabetes in Japan and Finland and examines the effects of sex, age at diagnosis, and calendar time period of diagnosis on mortality.
Research Design and Methods
Patients with type 1 diabetes from Japan (n = 1,408) and Finland (n = 5,126), diagnosed from 1965 through 1979, at age <18 years, were followed until 1994. Mortality was estimated with and without adjustment for that of the general population to assess absolute and relative mortality using Cox proportional hazard models.
Results
Overall mortality rates in Japan and Finland were 607 (95% CI 510–718) and 352 (315–393), respectively, per 100,000 person-years; standardized mortality ratios were 12.9 (10.8–15.3) and 3.7 (3.3–4.1), respectively. Absolute mortality was higher for men than for women in Finland, but relative mortality was higher for women than for men in both cohorts. Absolute mortality was higher in both cohorts among those whose diabetes was diagnosed during puberty, but relative mortality did not show any significant difference by age at diagnosis in either cohort. In Japan, both absolute and relative mortality were higher among those whose diagnosis was in the 1960s rather than the 1970s.
Conclusions
Mortality from type 1 diabetes was higher in Japan compared with Finland. The increased risk of death from type 1 diabetes seems to vary by sex, age at diagnosis, and calendar time period of diagnosis. Further investigation, especially on cause-specific mortality, is warranted in the two countries.
PMCID: PMC3752687  PMID: 12832309
9.  Age, BMI, and Race Are Less Important Than Random Plasma Glucose in Identifying Risk of Glucose Intolerance 
Diabetes care  2008;31(5):884-886.
OBJECTIVE
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.
RESEARCH DESIGN AND METHODS
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).
RESULTS
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.
CONCLUSIONS
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.
doi:10.2337/dc07-2282
PMCID: PMC3685424  PMID: 18310308
10.  A Prospective Study of the Association Between Quantity and Variety of Fruit and Vegetable Intake and Incident Type 2 Diabetes 
Diabetes Care  2012;35(6):1293-1300.
OBJECTIVE
The association between quantity of fruit and vegetable (F&V) intake and risk of type 2 diabetes (T2D) is not clear, and the relationship with variety of intake is unknown. The current study examined the association of both quantity and variety of F&V intake and risk of T2D.
RESEARCH DESIGN AND METHODS
We examined the 11-year incidence of T2D in relation to quantity and variety of fruit, vegetables, and combined F&V intake in a case-cohort study of 3,704 participants (n = 653 diabetes cases) nested within the European Prospective Investigation into Cancer and Nutrition-Norfolk study, who completed 7-day prospective food diaries. Variety of intake was derived from the total number of different items consumed in a 1-week period. Multivariable, Prentice-weighted Cox regression was used to estimate hazard ratios (HRs) and 95% CIs.
RESULTS
A greater quantity of combined F&V intake was associated with 21% lower hazard of T2D (HR 0.79 [95% CI 0.62–1.00]) comparing extreme tertiles, in adjusted analyses including variety. Separately, quantity of vegetable intake (0.76 [0.60–0.97]), but not fruit, was inversely associated with T2D in adjusted analysis. Greater variety in fruit (0.70 [0.53–0.91]), vegetable (0.77 [0.61–0.98]), and combined F&V (0.61 [0.48–0.78]) intake was associated with a lower hazard of T2D, independent of known confounders and quantity of intake comparing extreme tertiles.
CONCLUSIONS
These findings suggest that a diet characterized by a greater quantity of vegetables and a greater variety of both F&V intake is associated with a reduced risk of T2D.
doi:10.2337/dc11-2388
PMCID: PMC3357245  PMID: 22474042
12.  Disparities in HbA1c Levels Between African-American and Non-Hispanic White Adults With Diabetes 
Diabetes care  2006;29(9):2130-2136.
OBJECTIVE
Among individuals with diabetes, a comparison of HbA1c (A1C) levels between African Americans and non-Hispanic whites was evaluated. Data sources included PubMed, Web of Science, the Cumulative Index to Nursing and Allied Health, the Cochrane Library, the Combined Health Information Database, and the Education Resources Information Center.
RESEARCH DESIGN AND METHODS
We executed a search for articles published between 1993 and 2005. Data on sample size, age, sex, A1C, geographical location, and study design were extracted. Cross-sectional data and baseline data from clinical trials and cohort studies for African Americans and non-Hispanic whites with diabetes were included. Diabetic subjects aged <18 years and those with pre-diabetes or gestational diabetes were excluded. We conducted a meta-analysis to estimate the difference in the mean values of A1C for African Americans and non-Hispanic whites.
RESULTS
A total of 391 studies were reviewed, of which 78 contained A1C data. Eleven had data on A1C for African Americans and non-Hispanic whites and met selection criteria. A meta-analysis revealed the standard effect to be 0.31 (95% CI 0.39–0.25). This standard effect correlates to an A1C difference between groups of ~0.65%, indicating a higher A1C across studies for African Americans. Grouping studies by study type (cross-sectional or cohort), method of data collection for A1C (chart review or blood draw), and insurance status (managed care or nonmanaged care) showed similar results.
CONCLUSIONS
The higher A1C observed in this meta-analysis among African Americans compared with non-Hispanic whites may contribute to disparity in diabetes morbidity and mortality in this population.
doi:10.2337/dc05-1973
PMCID: PMC3557948  PMID: 16936167
13.  Youth Type 2 Diabetes 
Diabetes care  2005;28(3):638-644.
OBJECTIVE
This study evaluates insulin sensitivity, pancreatic β-cell function (BCF), and the balance between the two in youth with type 2 diabetes and assesses the relationship of diabetes duration and HbA1c to insulin sensitivity and BCF.
RESEARCH DESIGN AND METHODS
The subjects were 14 adolescents with type 2 diabetes and 20 obese control subjects of comparable age, BMI, body composition, and puberty. Insulin sensitivity was evaluated with a 3-h hyperinsulinemic (80 mU · m−2 · min−1) euglycemic clamp. First-phase insulin secretion (FPIS) and second-phase insulin secretion (SPIS) were evaluated with a 2-h hyperglycemic (12.5 mmol/l) clamp. Fasting glucose rate of appearance was determined with the use of [6,6-2H2]glucose.
RESULTS
Fasting glucose rate of appearance was higher in type 2 diabetic patients than in obese control subjects (16.5 ± 1.1 vs. 12.3 ± 0.5 µmol · kg−1 · min−1; P = 0.002). Insulin sensitivity was lower in type 2 diabetic patients than in obese control subjects (1.0 ± 0.1 vs. 2.0 ± 0.2 µmol · kg−1 · min−1 per pmol/l; P = 0.001). Fasting insulin was higher in type 2 diabetic patients than in obese control subjects (289.8 ± 24.6 vs. 220.2 ± 18.0 pmol/l; P = 0.007), and FPIS and SPIS were lower (FPIS: 357.6 ± 42.0 vs. 1,365.0 ± 111.0 pmol/l; SPIS: 652.2 ± 88.8 vs. 1,376.4 ± 88.8 pmol/l; P < 0.001 for both). The glucose disposition index (GDI = insulin sensitivity × FPIS) was ~86% lower in type 2 diabetic patients than in obese control subjects. HbA1c correlated with FPIS (r = −0.61, P = 0.025) with no relationship to insulin sensitivity.
CONCLUSIONS
Despite the impairment in both insulin sensitivity and BCF in youth with type 2 diabetes, the magnitude of the derangement is greater in BCF than insulin sensitivity when compared with that in obese control subjects. The inverse relationship between BCF and HbA1c may either reflect the impact of deteriorating BCF on glycemic control or be a manifestation of a glucotoxic phenomenon on BCF. Future studies in youth type 2 diabetes should target the natural course of β-cell failure and means of retarding and/or preventing it.
PMCID: PMC3428068  PMID: 15735201
15.  A Prospective Study of Cardiorespiratory Fitness and Risk of Type 2 Diabetes in Women 
Diabetes care  2007;31(3):550-555.
OBJECTIVE
The purpose of this study was to determine the independent and joint associations of cardiorespiratory fitness (CRF) and BMI with the incidence of type 2 diabetes in women.
RESEARCH DESIGN AND METHODS
An observational cohort of 6,249 women aged 20–79 years was free of baseline cardiovascular disease, cancer, and diabetes. CRF was measured using a maximal treadmill exercise test. BMI was computed from measured height and weight. The incidence of type 2 diabetes was identified primarily by 1997 American Diabetes Association criteria.
RESULTS
During a 17-year follow-up, 143 cases of type 2 diabetes occurred. Compared with the least fit third, the multivariate (including BMI)-adjusted hazard ratio (HR) (95% CI) was 0.86 (0.59–1.25) for the middle third and 0.61 (0.38–0.96) for the upper third of CRF. For BMI, the multivariate (including CRF)-adjusted HR (95% CI) was 2.34 (1.55–3.54) for overweight individuals and 3.70 (2.12–6.44) for obese individuals, compared with normal-weight patients. In the combined analyses, overweight/obese unfit (the lowest one-third of CRF) women had significantly higher risks compared with normal-weight fit (the upper two-thirds of CRF) women.
CONCLUSIONS
Low CRF and higher BMI were independently associated with incident type 2 diabetes. The protective effect of CRF was observed in individuals who were overweight or obese, but CRF did not eliminate the increased risk in these groups. These findings underscore the critical importance of promoting regular physical activity and maintaining normal weight for diabetes prevention.
doi:10.2337/dc07-1870
PMCID: PMC3410433  PMID: 18070999
16.  A prospective study of the association between quantity and variety of fruit and vegetable intake and incident type 2 diabetes 
Diabetes care  2012;35(6):1293-1300.
Objective
The association between quantity of fruit and vegetable intake and risk of type 2 diabetes (T2D) is not clear, and the relationship with variety of intake is unknown. The current study examined the association of both quantity and variety of fruit and vegetable intake and risk of T2D.
Research Design and Methods
We examined the 11-year incidence of T2D in relation to quantity and variety of fruit, vegetables and combined fruit and vegetable intake in a case-cohort study of 3,704 participants (n=653 T2D cases) nested within the European Prospective Investigation into Cancer and Nutrition-Norfolk Study, who completed 7-day prospective food diaries. Variety of intake was derived from the total number of different items consumed in a one week period. Multivariable Prentice-weighted Cox regression was used to estimate hazard ratios (HR) and 95% CI.
Results
Greater quantity of combined fruit and vegetable intake was associated with 21% lower hazard of T2D (HR 0.79; 0.62-1.00) comparing extreme tertiles, in adjusted analyses including variety. Separately, quantity of vegetable intake (HR 0.76; 0.60-0.97), but not fruit, was inversely associated with T2D in adjusted analysis. Greater variety in fruit (HR 0.70; 0.53-0.91), vegetable (HR 0.77; 0.61-0.98), and combined fruit and vegetable (HR 0.61; 0.48-0.78) intake was associated with a lower hazard of T2D, independent of known confounders and quantity of intake comparing extreme tertiles.
Conclusions
These findings suggest that a diet characterised by greater quantity of vegetable and greater variety of both fruit and vegetable intake is associated with a reduced risk of T2D.
doi:10.2337/dc11-2388
PMCID: PMC3357245  PMID: 22474042
18.  Metabolic Syndrome and Onset of Depressive Symptoms in the Elderly 
Diabetes Care  2011;34(4):904-909.
OBJECTIVE
Given the increasing prevalence of both metabolic syndrome (MetS) and depressive symptoms during old age, we aimed to examine prospectively the association between MetS and the onset of depressive symptoms according to different age-groups in a large, general elderly population.
RESEARCH DESIGN AND METHODS
This was a prospective cohort study of 4,446 men and women aged 65–91 years who were free of depression or depressive symptoms at baseline (the Three-City Study, France). MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. New onset of depressive symptoms (the Center for Epidemiologic Studies Depression Scale score ≥16 and use of antidepressant treatment) was assessed at 2- and 4-year follow-ups.
RESULTS
After adjusting for a large range of potential confounders, we observed MetS to be associated with 1.73-fold (95% CI 1.02–2.95) odds for new-onset depressive symptoms in the youngest age-group (65–70 years at baseline), independently of cardiovascular diseases. No such association was seen in older age-groups.
CONCLUSIONS
Our findings suggest that the link between MetS and depressive symptoms evidenced until now in middle-aged people can be extended to older adults but not to the oldest ones. Additional research is needed to examine if a better management of MetS prevents depressive symptoms in people aged 65–70 years.
doi:10.2337/dc10-1644
PMCID: PMC3064049  PMID: 21346185
19.  Salsalate Improves Glycemia and Inflammatory Parameters in Obese Young Adults 
Diabetes care  2007;31(2):289-294.
OBJECTIVE
— Sedentary lifestyle and a western diet promote subacute-chronic inflammation, obesity, and subsequently dysglycemia. The aim of the current study was to evaluate the efficacy of the anti-inflammatory drug salsalate to improve glycemia by reducing systemic inflammation in obese adults at risk for the development of type 2 diabetes.
RESEARCH DESIGN AND METHODS
— In a double-masked, placebo controlled trial, we evaluated 20 obese nondiabetic adults at baseline and after 1 month of salsalate or placebo.
RESULTS
— Compared with placebo, salsalate reduced fasting glucose 13% (P < 0.002), glycemic response after an oral glucose challenge 20% (P < 0.004), and glycated albumin 17% (P < 0.0003). Although insulin levels were unchanged, fasting and oral glucose tolerance test C-peptide levels decreased in the salsalate-treated subjects compared with placebo (P < 0.03), consistent with improved insulin sensitivity and a known effect of salicylates to inhibit insulin clearance. Adiponectin increased 57% after salsalate compared with placebo (P < 0.003). Additionally, within the group of salsalate-treated subjects, circulating levels of C-reactive protein were reduced by 34% (P < 0.05).
CONCLUSIONS
— This proof-of-principle study demonstrates that salsalate reduces glycemia and may improve inflammatory cardiovascular risk indexes in overweight individuals. These data support the hypothesis that subacute-chronic inflammation contributes to the pathogenesis of obesity-related dysglycemia and that targeting inflammation may provide a therapeutic route for diabetes prevention.
doi:10.2337/dc07-1338
PMCID: PMC3226794  PMID: 17959861
20.  Breast-Feeding and Risk for Childhood Obesity 
Diabetes care  2006;29(10):2231-2237.
OBJECTIVE
We sought to evaluate whether maternal diabetes or weight status attenuates a previously reported beneficial effect of breast-feeding on childhood obesity.
RESEARCH DESIGN AND METHODS
Growing Up Today Study (GUTS) participants were offspring of women who participated in the Nurses’ Health Study II. In the present study, 15,253 girls and boys (aged 9–14 years in 1996) were included. Maternal diabetes and weight status and infant feeding were obtained by maternal self-report. We defined maternal overweight as BMI ≥25 kg/m2. Childhood obesity, from self-reported height and weight, was based on the Centers for Disease Control and Prevention definitions as normal, at risk for overweight, or overweight. Maternal status categories were nondiabetes/normal weight, nondiabetes/overweight, or diabetes. Logistic regression models used generalized estimating equations to account for nonindependence between siblings.
RESULTS
For all subjects combined, breast-feeding was associated with reduced overweight (compared with normal weight) in childhood. Compared with exclusive use of formula, the odds ratio (OR) for exclusive breast-feeding was 0.66 (95% CI 0.53– 0.82), adjusted for age, sex, and Tanner stage. Results did not differ according to maternal status (nondiabetes/normal weight OR 0.73 [95% CI 0.49 –1.09]; nondiabetes/overweight 0.75 [0.57– 0.99]; and diabetes 0.62 [0.24 –1.60]). Further adjustment for potential confounders attenuated results, but results remained consistent across strata of maternal status (P value for interaction was 0.50).
CONCLUSIONS
Breast-feeding was inversely associated with childhood obesity regardless of maternal diabetes status or weight status. These data provide support for all mothers to breast-feed their infants to reduce the risk for childhood overweight.
doi:10.2337/dc06-0974
PMCID: PMC3210833  PMID: 17003298
21.  Distinct Component Profiles and High Risk Among African Americans With Metabolic Syndrome 
Diabetes care  2008;31(6):1248-1253.
Objective
Health of African Americans is seriously threatened by unremitting epidemics of diabetes and cardiovascular disease (CVD). However, the role of metabolic syndrome in the African-American population has not been investigated widely. This study examined the prevalence of metabolic syndrome and assessed its cross-sectional relationship to CVD in the Jackson Heart Study (JHS) cohort.
Research Design and Methods
A total of 5,302 participants aged ≥21 years who were recruited at baseline during 2000–2004 were analyzed for this study. Adjusted odds ratios (ORs) were estimated in a logistic regression analysis for coronary heart disease (CHD) and cerebrovascular disease (CBD) in those with and without coexisting metabolic syndrome. Diabetic participants were excluded.
Results
Among those aged 35–84 years, metabolic syndrome prevalence was 43.3% in women and 32.7% in men. Elevated blood pressure (70.4%), abdominal obesity (64.6%), and low HDL cholesterol (37.2%) were highly prevalent among those with metabolic syndrome. Prevalence rates for CVD, CHD, and CBD were 12.8, 8.7, and 5.8%, respectively. After adjustment for age and sex, metabolic syndrome was associated with increased age- and sex-adjusted ORs for CVD (OR 1.7 [95% CI 1.4–2.1]), CHD (1.7 [1.4–2.2]), and CBD (1.7 [1.3–2.3]) compared with those without CVD, CHD, or CBD.
Conclusion
Metabolic syndrome prevalence in the JHS is among the highest reported for population-based cohorts worldwide and is significantly associated with increased ORs for CVD, CHD, and CBD. Abdominal obesity, increased blood pressure, and low HDL cholesterol (without triglyceride elevation) are surprisingly prominent. A high prevalence of low HDL emerges as a leading contributor to metabolic syndrome among African Americans in this large African-American cohort.
doi:10.2337/dc07-1810
PMCID: PMC3209804  PMID: 18332154
22.  Overall Diet History and Reversibility of the Metabolic Syndrome Over 5 Years 
Diabetes Care  2010;33(11):2339-2341.
OBJECTIVE
We examined the impact of adherence to the Alternative Healthy Eating Index (AHEI), a set of dietary guidelines targeting major chronic diseases, on metabolic syndrome (MetS) reversion in a middle-aged population.
RESEARCH DESIGN AND METHODS
Analyses were carried out on the 339 participants (28% women, mean age 56.4 years) from the Whitehall II study with MetS as defined by the National Cholesterol Education Program Adult Treatment Panel III criteria. Reversion was defined as not having MetS after 5 years of follow-up (158 case subjects).
RESULTS
After controlling for potential confounders, adherence to AHEI was associated with MetS reversion (odds ratio 1.88 [95% CI 1.04–3.41]), predominantly in participants with central obesity and in those with high triglyceride.
CONCLUSIONS
Our findings support the benefit of adherence to AHEI dietary guidelines for individuals with MetS, especially those with central obesity or high triglyceride levels.
doi:10.2337/dc09-2200
PMCID: PMC2963491  PMID: 20671094
24.  Serum Insulin, Obesity, and the Incidence of Type 2 Diabetes in Black and White Adults 
Diabetes care  2002;25(8):1358-1364.
OBJECTIVE
In this study, we tested the hypothesis that fasting serum insulin is higher in nonobese black adults than in white adults and that high fasting insulin predicts type 2 diabetes equally well in both groups.
RESEARCH DESIGN AND METHODS
At the baseline examination (1987–1989) of the Atherosclerosis Risk in Communities Study, fasting insulin and BMI were measured in 13,416 black and white men and women without diabetes. Participants were examined at years 3, 6, and 9 for incident diabetes based on fasting glucose and American Diabetes Association criteria.
RESULTS
Fasting insulin was 19.7 pmol/l higher among nonobese (BMI <30 kg/m2) black women compared with white women (race and obesity interaction term, P < 0.01). There were no differences among men. Among nonobese women, the relative risk for developing diabetes was similar between racial groups: 1.4 (95% CI 1.2–1.5) and 1.3 (1.2–1.4) per 60 pmol/l increase in insulin (P < 0.01) for black and white women, respectively (interaction term, P = 0.6). Findings were similar among men. Adjusting for established risk factors did not attenuate this association.
CONCLUSIONS
Nonobese black women have higher fasting insulin levels than nonobese white women, and fasting insulin is an equally strong predictor of diabetes in both groups. These results suggest one mechanism to explain the excess incidence of diabetes in nonobese black women but do not explain the excess among black men. Future research should evaluate additional factors: genetic, environmental, or the combination of both, which might explain higher fasting insulin among black women when compared with white women.
PMCID: PMC3132185  PMID: 12145235
25.  Antidepressant Use Before and After the Diagnosis of Type 2 Diabetes 
Diabetes Care  2010;33(7):1471-1476.
OBJECTIVE
To examine antidepressant use before and after the diagnosis of diabetes.
RESEARCH DESIGN AND METHODS
This study was a longitudinal analysis of diabetic and nondiabetic groups selected from a prospective cohort study of 151,618 men and women in Finland (the Finnish Public Sector Study, 1995–2005). We analyzed the use of antidepressants in those 493 individuals who developed type 2 diabetes and their 2,450 matched nondiabetic control subjects for each year during a period covering 4 years before and 4 years after the diagnosis. For comparison, we undertook a corresponding analysis on 748 individuals who developed cancer and their 3,730 matched control subjects.
RESULTS
In multilevel longitudinal models, the odds ratio for antidepressant use in those who developed diabetes was 2.00 (95% CI 1.57–2.55) times greater than that in nondiabetic subjects. The relative difference in antidepressant use between these groups was similar before and after the diabetes diagnosis except for a temporary peak in antidepressant use at the year of the diagnosis (OR 2.66 [95% CI 1.94–3.65]). In incident cancer case subjects, antidepressant use substantially increased after the cancer diagnosis, demonstrating that our analysis was sensitive for detecting long-term changes in antidepressant trajectories when they existed.
CONCLUSIONS
Awareness of the diagnosis of type 2 diabetes may temporarily increase the risk of depressive symptoms. Further research is needed to determine whether more prevalent use of antidepressants noted before the diagnosis of diabetes relates to effects of depression, side effects of antidepressant use, or a common causal pathway for depression and diabetes.
doi:10.2337/dc09-2359
PMCID: PMC2890343  PMID: 20368411

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