Angiotensin-converting-enzyme inhibitors for impaired glucose tolerance--is there still hope?
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Biomedical subjects
Publications and source records attributed to Caren G Solomon.
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BACKGROUND: Although gestational diabetes mellitus (GDM) has been associated with substantial adverse health outcomes for both mothers and offspring, few modifiable risk factors for GDM have been identified. METHODS: We conducted a prospective cohort study among women in the Nurses' Health Study II to assess whether the amount, type, and intensity of pregravid physical activity and sedentary behaviors are associated with GDM risk. The analysis included 21,765 women who reported at least 1 singleton pregnancy between 1990 and 1998. Physical activity and sedentary behaviors were assessed through validated questionnaire. RESULTS: We documented 1428 incident GDM cases. After controlling for body mass index, dietary factors, and other covariates, there was a significant inverse association between vigorous activity and the risk of GDM. The multivariate relative risk (RR) comparing the highest with the lowest quintile of vigorous activity was 0.77 (95% confidence interval [CI], 0.69-0.94) (P = .002 for trend). Among women who did not perform vigorous activity, brisk walking pace was associated with significantly lower GDM risk (RR, 0.66; 95% CI, 0.46-0.95) compared with an easy pace. Women who spent 20 h/wk or more watching television but did not perform vigorous activity had a significantly higher GDM risk than women who spent less than 2 h/wk watching television and were physically active (multivariate RR, 2.30; 95% CI, 1.06-4.97). CONCLUSION: Our prospective study provides strong evidence that regular physical activity before pregnancy is associated with lower GDM risk.
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BACKGROUND: Changes in estradiol and progesterone during the human menstrual cycle may impact vascular and cardiac function. Renin-angiotensin-aldosterone system (RAAS) hormones increase during the luteal phase of the menstrual cycle and may antagonize the vascular effects of estradiol. This study was designed to investigate central arterial changes, cardiac function, and RAAS activity in response to gonadal steroid variations during the menstrual cycle. METHODS: We studied 15 women during the follicular and midluteal phases with determination of estradiol, progesterone, hormones of the RAAS, and spot urine sodium and creatinine levels. Central pulsatile hemodynamics was evaluated using calibrated carotid tonometry and central aortic Doppler flow. Systolic ejection period (SEP) and systolic pressure time integral (SPTI) were computed from carotid pressure waveforms. RESULTS: Levels of estradiol, progesterone, and RAAS hormones were higher in the luteal phase. SEP and SPTI were lower during the luteal phase, whereas central and peripheral blood pressures and measures of arterial stiffness were unchanged between the two phases. The urine sodium-to-creatinine ratio was similar at both phases. CONCLUSION: Central arterial stiffness does not differ between the follicular and midluteal phases of the menstrual cycle in healthy women, despite significant changes in estradiol and progesterone levels. Systole was shortened during the midluteal phase. RAAS activation during the luteal phase may be responsible for a lack of the expected estradiol-mediated reduction in arterial stiffness between the two phases of the menstrual cycle. Because load was unchanged, the decrease in SEP and SPTI may represent a direct effect of estrogen, progesterone, or RAAS activation on ventricular function.
OBJECTIVE: We aimed to examine whether pregravid dietary fiber consumptions from cereal, fruit, and vegetable sources and dietary glycemic load were related to gestational diabetes mellitus (GDM) risk. RESEARCH DESIGN AND METHODS: This study was a prospective cohort study among 13,110 eligible women in the Nurses' Health Study II. GDM was self-reported and validated by medical record review in a subsample. RESULTS: We documented 758 incident GDM cases during 8 years of follow-up. After adjustment for age, parity, prepregnancy BMI, and other covariates, dietary total fiber and cereal and fruit fiber were strongly associated with GDM risk. Each 10-g/day increment in total fiber intake was associated with 26% (95% CI 9-49) reduction in risk; each 5-g/day increment in cereal or fruit fiber was associated with a 23% (9-36) or 26% (5-42) reduction, respectively. Dietary glycemic load was positively related to GDM risk. Multivariate relative risk for highest versus lowest quintiles was 1.61 (1.02-2.53) (P for trend 0.03). The combination of high-glycemic load and low-cereal fiber diet was associated with 2.15-fold (1.04-4.29) increased risk compared with the reciprocal diet. CONCLUSIONS: These findings suggested that prepregnancy diet might be associated with women's GDM risk. In particular, diet with low fiber and high glycemic load was associated with an increased risk. Future clinical and metabolic studies are warranted to confirm these findings.
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CONTEXT: A history of gestational diabetes (GDM) significantly increases the risk of developing type 2 diabetes, an independent risk factor for cardiovascular disease (CVD). It is not known whether nondiabetic women with prior GDM are also at increased risk of CVD. OBJECTIVE: The aim of this study was to compare biochemical and hemodynamic surrogate markers of CVD in nondiabetic women with and without a history of GDM who were at least 1 yr post delivery. DESIGN: This was a single center cross-sectional study. SETTING: The study was performed in an academic referral center. SUBJECTS: Forty-eight premenopausal healthy women with a history of GDM (n = 25) or a history of normal pregnancy (n = 23) were studied in the follicular phase of the menstrual cycle. MAIN OUTCOME MEASURES: The main outcome measures were: 1) inflammatory markers associated with CVD including C-reactive protein, IL-6, and plasminogen activator inhibitor-1; 2) the adipokine adiponectin; and 3) conduit vessel stiffness. RESULTS: When compared to normal controls, women with prior GDM had higher mean levels of C-reactive protein (3.58 +/- 3.86 vs. 0.52 +/- 0.16 mg/liter; P < 0.001), IL-6 (1.81 +/- 1.04 vs. 0.99 +/- 0.52 pg/ml; P = 0.001), plasminogen activator inhibitor-1 (29.6 +/- 17.6 vs. 16.5 +/- 14.0 ng/ml; P = 0.001), and lower levels of adiponectin (8.9 +/- 3.9 vs. 15.9 +/- 7.3 microg/ml; P = 0.001). Women with prior GDM also had significantly (P </= 0.04) increased peripheral vascular resistance (1658 +/- 290 vs. 1462 +/- 340 dyne.sec/cm(5)), decreased stroke volume (65 +/- 13 vs. 75 +/- 14 ml/beat), and decreased cardiac output (70 +/- 12 vs. 74 +/- 13 ml/sec) when compared to controls, after adjusting for body mass index. CONCLUSIONS: Nondiabetic women with prior GDM have evidence of subclinical inflammation, hypoadiponectinemia, and early vascular dysfunction; this population may be at increased risk of developing CVD.
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OBJECTIVE: We assessed the association between magnesium intake and fasting insulin levels in a large cohort of women. METHODS: Female nurses free of diabetes, cardiovascular diseases and cancer from the Nurses Health Study provided blood samples between 1989-1990. We selected a sub-sample of 219 women for this analysis. Magnesium intake was assessed by a food frequency questionnaire in 1990 and categorized into quartiles. Cross-sectional geometric means of fasting insulin concentrations by quartiles of magnesium intake were obtained with Generalized Linear Model and adjusted for several risk factors and lifestyle characteristics. RESULTS: After adjustment for age, body mass index (BMI), total energy, physical activity, hours per week spent sitting outside work, alcohol intake, smoking, and family history of diabetes, magnesium intake was inversely associated with fasting insulin concentration. The multivariate adjusted geometric mean for women in the lowest quartile of magnesium intake was 11.0 microU/mL and 9.3 microU/mL among those in the highest quartile of magnesium intake (p for trend = 0.04). The inverse association remained when we considered magnesium from only food sources. CONCLUSION: Higher magnesium intake is associated with lower fasting insulin concentrations among women without diabetes. Because lower fasting insulin concentrations generally reflect greater insulin sensitivity, these findings provide a mechanism through which higher dietary magnesium intake may reduce the risk of developing type 2 diabetes mellitus.
New-onset hypertension (which includes preeclampsia and gestational hypertension) is a common and morbid complication of pregnancy. Many features of the insulin resistance syndrome have been associated with this condition. These include hypertension, hyperinsulinemia, glucose intolerance, obesity, and lipid abnormalities. Other accompanying abnormalities may include elevated levels of leptin, TNFalpha, tissue plasminogen activator, plasminogen activator inhibitor-1, and testosterone. The documentation of these features before the onset of hypertension in pregnancy suggests that insulin resistance or associated abnormalities may have a role in this disorder. Furthermore, the recognition that features of the insulin resistance syndrome persist many years after pregnancy among women with this condition raises the possibility that these women may have increased risk for future cardiovascular disease. These observations suggest that interventions to reduce insulin resistance may reduce the risk of both hypertension in pregnancy and later life cardiovascular complications, and warrant further study.
OBJECTIVE: Hyperinsulinemia may promote mammary carcinogenesis. Insulin resistance has been linked to an increased risk of breast cancer and is also characteristic of type 2 diabetes. We prospectively evaluated the association between type 2 diabetes and invasive breast cancer incidence in the Nurses' Health Study. RESEARCH DESIGN AND METHODS: A total of 116,488 female nurses who were 30-55 years old and free of cancer in 1976 were followed through 1996 for the occurrence of type 2 diabetes and through 1998 for incident invasive breast cancer, verified by medical records and pathology reports. RESULTS: During 2.3 million person-years of follow-up, we identified 6,220 women with type 2 diabetes and 5,189 incident cases of invasive breast cancer. Women with type 2 diabetes had a modestly elevated incidence of breast cancer (hazard ratio [HR] = 1.17; 95% CI 1.01-1.35) compared with women without diabetes, independent of age, obesity, family history of breast cancer, history of benign breast disease, reproductive factors, physical activity, and alcohol consumption. This association was apparent among postmenopausal women (1.16; 0.98-1.62) but not premenopausal women (0.83; 0.48-1.42). The association was predominant among women with estrogen receptor-positive breast cancer (1.22; 1.01-1.47). CONCLUSIONS: Women with type 2 diabetes may have a slightly increased risk of breast cancer.
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BACKGROUND: Although the association between smoking and increased risk of coronary heart disease (CHD) is well established in the general population, this relationship is less well-defined among individuals with diabetes. OBJECTIVE: To assess the relationship between cigarette smoking and risk of CHD among women with type 2 diabetes mellitus in the Nurses' Health Study cohort. METHODS: The Nurses' Health Study, a prospective cohort study of 121,700 US female registered nurses surveyed in 11 states and followed up from July 1, 1976, through July 1, 1996, involved a total of 6547 women diagnosed as having type 2 diabetes mellitus. Incident cases of CHD were our main outcome measure in this study. RESULTS: We documented 458 incident cases of CHD (200 fatal CHD-related cases and 258 nonfatal myocardial infarctions) during 20 years (68,227 person-years) of follow-up. We found a dose-response relationship between current smoking status and risk of CHD among diabetic women. Compared with never smokers, the relative risks (RRs) for CHD were 1.21 (95% confidence interval [CI], 0.97-1.51) for past smokers, 1.66 (95% CI, 1.10-2.52) for current smokers of 1 to 14 cigarettes per day, and 2.68 (95% CI, 2.07-3.48) for current smokers of 15 or more cigarettes per day in multivariate analyses (P<.001 for trend). The multivariate RR of CHD among diabetic women who had stopped smoking for more than 10 years was similar to that among diabetic women who were never smokers (RR, 1.01; 95% CI, 0.73-1.38). In secondary analyses involving diabetic and nondiabetic women, the multivariate-adjusted RR of CHD for those with diabetes who currently smoked (> or = 15 cigarettes per day) compared with those who never smoked was 7.67 (95% CI, 5.88-10.01). CONCLUSIONS: Cigarette smoking is strongly associated with an increased risk of CHD among women with type 2 diabetes mellitus. Furthermore, quitting smoking seems to decrease this excess risk substantially; women with diabetes should be strongly advised against smoking.CK
Cross-sectional studies suggest that women who have irregular menstrual cycles and hyperandrogenism may be at increased risk for cardiovascular disease (CVD). However, prospective data are lacking on the relationship between menstrual cycle irregularity and subsequent CVD risk. The objective of this study was to assess prospectively the risk for coronary heart disease (CHD) and stroke associated with a history of irregular menstrual cycles. The study design was a prospective cohort study of 82,439 female nurses who provided information in 1982 on prior menstrual regularity (at ages 20-35 yr) and were followed through 1996 for cardiovascular events. Incident reports of nonfatal myocardial infarction, fatal CHD, and nonfatal and fatal stroke were made. Medical records were reviewed for confirmation. During 14 yr (1,155,915 person-yr) of follow-up, there were 1417 incident cases of CHD and 838 incident cases of stroke, including 471 cases of ischemic stroke. Compared with women reporting a history of very regular menstrual cycles, women reporting usually irregular or very irregular cycles had an increased risk for nonfatal or fatal CHD [age-adjusted relative risks (RR), 1.25 and 1.67, respectively; 95% confidence intervals (CI), 1.07-1.47 and 1.35-2.06, respectively]. Increased risks for CHD associated with prior cycle irregularity remained significant after adjustment for body mass index and several potential confounders. There was a nonsignificant increase in overall stroke risk (RR, 1.30; 95% CI = 0.97-1.74) and in ischemic stroke risk (RR, 1.40; 95% CI = 0.97-2.04) associated with very irregular cycles. Menstrual cycle irregularity may be a marker of metabolic abnormalities predisposing to increased risk for CVD.