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Biomedical subjects

S Goya Wannamethee

Publications and source records attributed to S Goya Wannamethee.

At least 19 recordsLinked to original sources
PubMed2006

Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease.

BACKGROUND AND AIM: Leptin, an adipocyte-derived protein, regulating food intake and metabolism has been implicated in the development of coronary heart disease. We have examined the relationship between leptin and vascular risk factors including insulin resistance, metabolic, inflammatory and haemostatic risk factors. METHODS AND RESULTS: The study was carried out in 3640 non-diabetic men aged 60-79 years drawn from general practices in 24 British towns and who were not on warfarin. Leptin was strongly positively correlated with waist circumference (r=0.58; p<0.0001). Leptin concentrations decreased significantly with increasing physical activity and were lowered in cigarette smokers and elevated in men with pre-existing coronary heart disease and stroke; alcohol intake showed no association with leptin concentration. After adjustment for waist circumference and these lifestyle factors, increased leptin was independently associated with significant increases in insulin resistance, triglycerides, inflammatory markers (interleukin-6, C-reactive protein, fibrinogen, plasma viscosity), coagulation factor VIII, endothelial markers von Willebrand factor, tissue plasminogen activator, and fibrin D-dimer levels; and a decrease in HDL-cholesterol. No association was seen between leptin and blood pressure, total cholesterol, glucose or white cell count after adjusting for waist circumference. Further adjustment for insulin resistance abolished the relationships between leptin and triglycerides and HDL-cholesterol, weakened the associations with the haemostatic factors although they remained significant, but made minor differences to the associations with inflammatory markers. CONCLUSION: Plasma leptin is associated with insulin resistance, inflammation and disturbances in haemostasis independent of waist circumference, suggesting possible pathways by which leptin may influence risk of cardiovascular disease.

Aged↗
PubMed2006

Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis.

BACKGROUND: It has been suggested that a high dietary intake and high circulating concentrations of vitamin C may protect against ischemic heart disease. OBJECTIVES: The objective was to examine the associations between dietary and plasma vitamin C concentrations, fruit and vegetable intakes, and markers of inflammation and hemostasis associated with cardiovascular disease in older men free of cardiovascular disease. DESIGN: This cross-sectional study examined 3258 men aged 60-79 y with no physician diagnosis of myocardial infarction, stroke, or diabetes and who were drawn from general practices in 24 British towns. Fruit and vegetable intakes and dietary vitamin C were assessed by using a food-frequency questionnaire. RESULTS: Plasma vitamin C, fruit intake, and dietary vitamin C intake were significantly and inversely associated with mean concentrations of C-reactive protein, an acute phase reactant, and tissue plasminogen activator (t-PA) antigen, a marker of endothelial dysfunction, even after adjustment for confounders. Vegetable intake was correlated significantly (inversely) only with t-PA. For plasma vitamin C (highest versus lowest quartile), the adjusted odds of elevated C-reactive protein and t-PA (highest tertile versus lowest tertile) were 0.56 (95% CI: 0.44, 0.71) and 0.79 (0.62, 1.00); for fruit intake, the corresponding odds ratios were 0.76 (0.60, 0.95) and 0.76 (0.61, 0.95). Plasma (but not dietary) vitamin C also showed inverse associations with both fibrinogen concentrations and blood viscosity. No associations were seen with von Willebrand factor or factor VIII. CONCLUSION: The findings suggest that vitamin C has antiinflammatory effects and is associated with lower endothelial dysfunction in men with no history of cardiovascular disease or diabetes.

Acute-Phase Proteins↗
PubMed2006

Modifiable lifestyle factors and the metabolic syndrome in older men: Effects of lifestyle changes.

OBJECTIVES: To examine the influence of lifestyle factors and changes in these factors on risk of the metabolic syndrome in elderly men. DESIGN: Cross-sectional and longitudinal analyses of cohort study. SETTING: General practices in 24 British towns. PARTICIPANTS: Three thousand fifty-one men aged 60 to 79 with no diabetes mellitus or diagnosis of coronary heart disease. MEASUREMENTS: Lifestyle factors (smoking, physical activity, alcohol intake, body weight, dietary fat and carbohydrate intake) including recent changes in the previous 3 years (physical activity and body weight); metabolic syndrome. RESULTS: After adjustment for each of the other modifiable lifestyle factors, overweight/obesity and physical inactivity were associated with a significantly higher risk of the metabolic syndrome, as were cigarette smoking and a high-carbohydrate diet (>57% of energy). Alcohol intake and dietary fat intake were not related to the metabolic syndrome. Long-term ex-smokers showed similar risk to never smokers. Taking up physical activity and losing weight in the previous 3 years were associated with a reduction in risk of the metabolic syndrome. CONCLUSION: Overweight/obesity, physical inactivity, a high-carbohydrate diet, and cigarette smoking are associated with higher risk of the metabolic syndrome in elderly men. Modification of lifestyle factors, even later in life, has considerable potential for primary prevention of the metabolic syndrome.

Aged↗
PubMed2005

Reasons for intentional weight loss, unintentional weight loss, and mortality in older men.

BACKGROUND: We have examined the relationship between intentional and unintentional weight loss and the reasons underlying intention to lose weight and all-cause mortality and mortality due to cardiovascular disease (CVD) and non-CVD causes in older men. METHODS: Prospective study of 4869 men aged 56 to 75 years drawn from general practices in 24 British towns, who in 1996 completed questionnaires about intentional and unintentional weight loss over the preceding 4 years and were followed up for a subsequent 7 years. RESULTS: Unintentional but not intentional weight loss was associated with a significant increase in risk of all-cause mortality compared with men who reported no weight change, even after adjustment for lifestyle characteristics and preexisting disease (adjusted relative risk [RR], 1.71; 95% confidence interval [CI], 1.33-2.19; and RR, 1.00; 95% CI, 0.91-1.10, respectively). Men who lost weight intentionally as a result of personal choice showed significant benefit in all-cause mortality (RR, 0.59; 95% CI, 0.34-1.00; P = .05), which was largely owing to a significant reduction in mortality from non-CVD causes (RR, 0.36; 95% CI, 0.15-0.87). The benefit in these men was most apparent in markedly overweight men (BMI [calculated as weight in kilograms divided by the square of height in meters] > or = 28) and in younger men (age < 65 years). Men who lost weight intentionally owing to ill health or physician's advice showed an increased risk of all-cause mortality (RR, 1.37; 95% CI, 0.96-1.94). No harm or benefit was seen for CVD mortality, irrespective of reasons for intentional weight loss. CONCLUSION: Intentional weight loss carried out for personal reasons is associated with a significant reduction in all-cause mortality in markedly overweight men, and the data suggest that the earlier the intervention, the greater the chance of benefit.

Age Factors↗
PubMed2005

Lifestyle and cardiovascular disease in middle-aged British men: the effect of adjusting for within-person variation.

AIMS: To examine the effect that within-person variation has on the estimated risk associations between cigarette smoking, physical inactivity, and increased body mass index (BMI) and the development of cardiovascular disease (CVD) in middle-aged British men. METHODS AND RESULTS: In total, 6452 men aged 40-59 with no prior evidence of CVD were followed for major CVD events (fatal/non-fatal myocardial infarction or stroke) and all-cause mortality over 20 years; lifestyle characteristics were ascertained at regular points throughout the study. A major CVD event within the first 20 years was observed in 1194 men (18.5%). Use of baseline assessments of cigarette smoking and physical activity in analyses resulted in underestimation of the associations between average cumulative exposure to these factors and major CVD risk. After correction for within-person variation, major CVD rates were over four times higher for heavy smokers (> or =40 cigarettes/day) compared with never smokers and three times higher for physically inactive men compared with moderately active men. Major CVD risk increased by 6% for each 1 kg/m(2) increase in usual BMI. If all men had experienced the risk levels of the men who had never regularly smoked cigarettes, were moderately active, and had a BMI of < or =25 kg/m(2) (6% of the population), 66% of the observed major CVD events would have been prevented or postponed (63% before adjustment for within-person variation). Adjustment for a range of other risk factors had little effect on the results. Similar results were obtained for all-cause mortality. CONCLUSION: Failure to take account of within-person variation can lead to underestimation of the importance of lifestyle characteristics in determining CVD risk. Primary prevention through lifestyle modification has a great preventive potential.

Body Mass Index↗
PubMed2005

Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease.

AIMS: To examine the associations between cigarette smoking, pipe/cigar smoking, and years since quitting smoking, and inflammatory and haemostatic markers. METHODS AND RESULTS: A study in 2920 men aged 60-79 with no history of myocardial infarction, angina, stroke, or diabetes, and who were not on warfarin, from general practices in 24 British towns. After adjustment for other major cardiovascular risk factors, compared with never smokers, current cigarette smokers showed significantly higher levels of C-reactive protein (2.53 vs. 1.35 mg/L), white cell count (7.92 vs. 6.42 x 10(9)/L), and fibrinogen (3.51 vs. 3.13 g/L). They also showed higher levels of haematocrit, blood and plasma viscosity, tissue plasminogen activator antigen, and fibrin D-dimer, and lower levels of albumin. Primary pipe/cigar smokers showed levels similar to never smokers. Ex-cigarette smokers and secondary pipe/cigar smokers showed intermediate levels although secondary pipe/cigar smokers showed higher odds of having elevated white cell count and fibrinogen than ex-cigarette smokers. Most inflammatory and haemostatic levels improved within 5 years of smoking cessation but took over 20 years to revert to levels of never smokers. CONCLUSION: These findings suggest that activation of inflammation and haemostasis may be potential mechanisms by which cigarette and pipe/cigar smoking increase cardiovascular risk.

Adult↗
PubMed2005

The metabolic syndrome and insulin resistance: relationship to haemostatic and inflammatory markers in older non-diabetic men.

AIMS: We have examined the cross-sectional relationship between insulin resistance, the metabolic syndrome and haemostatic and inflammatory markers. METHODS AND RESULTS: We carried out the study in 2722 non-diabetic men aged 60-79 years with no history of coronary heart disease or stroke and who were not on warfarin treatment, drawn from general practices in 24 British towns. Insulin resistance (HOMA) was significantly associated with increased inflammatory markers (C-reactive protein (CRP), white cell count), coagulation factors VII-IX, von Willebrand factor (VWF) and tissue plasminogen activator (t-PA) antigens (markers of endothelial dysfunction) and blood viscosity after adjustment for age, smoking, physical activity, alcohol intake and waist circumference. Relationships with fibrinogen and fibrin D-dimer were weak. The relationship between HOMA and CRP was abolished after adjustment for t-PA. The prevalence of the metabolic syndrome was similar using World Health Organization (WHO) and National Cholesterol Education Program definitions (26.7% and 27.0%) but associations between the metabolic syndrome and increased haemostatic markers, particularly for raised factor VIII and VWF were stronger using WHO criteria. CONCLUSION: Insulin resistance and the metabolic syndrome showed significant associations with markers of haemostasis and inflammation, which may be relevant to their associations with cardiovascular disease.

Aged↗
PubMed2005

From a postal questionnaire of older men, healthy lifestyle factors reduced the onset of and may have increased recovery from mobility limitation.

BACKGROUND AND OBJECTIVE: We have examined predictors of the onset of and recovery from mobility limitation and the association between lifestyle changes in later life and mobility status. STUDY DESIGN AND SETTING: From a cohort of 7,735 men recruited at ages 40-59 years (1978-1980), 5,075 men completed follow-up postal questionnaires in 1992 (Q92), then aged 52-73 years, and again in 1996 (Q96). Mobility limitation was defined as reported difficulty in any one or more of the following: getting outdoors, walking 400 yards, or climbing stairs. RESULTS: Lifestyle factors (smoking, obesity, physical inactivity, and heavy drinking) and manual worker social class were significantly and independently associated with onset of mobility limitation and with the exception of physical activity remained significant after further adjustment for chronic diseases. Smoking cessation and taking up physical activity in later life are associated with reduced onset of mobility limitation. Among men with mobility limitation at Q92 (n=645), light or moderate levels of physical activity were associated with significantly increased odds of recovery at Q96 (light activity, OR=2.43, 95% CI 1.48, 4.00; moderate activity, OR=2.57, 95% CI 1.31, 5.02). CONCLUSION: Maintaining and adopting a healthy lifestyle in later life reduces the onset of mobility limitation in old age. Maintaining physical activity may improve recovery.

Adult↗
PubMed2005

Measures of adiposity in the identification of metabolic abnormalities in elderly men.

BACKGROUND: Body mass index (BMI; in kg/m(2)) is considered a poor indicator of overall and abdominal obesity in the elderly. OBJECTIVES: Our goal was to determine which simple anthropometric measurements [BMI, waist-to-hip ratio (WHR), waist circumference (WC), percentage body fat (%BF), or fat mass (FM)] are most closely associated with metabolic risk factors and insulin resistance in elderly men. DESIGN: This was a cross-sectional study of 2924 men aged 60-79 y with no history of coronary heart disease, stroke, or diabetes who were drawn from general practices in 24 British towns. RESULTS: BMI and WC were the measures most strongly associated with the metabolic syndrome (>/=3 of the following: hypertension, low HDL cholesterol, high triacylglycerols, or high blood glucose) and insulin resistance. For a 1-SD increase in BMI, WC, WHR, %BF, and FM, the odds ratios (95% CIs) of having the metabolic syndrome after adjustment for age, socioeconomic status, smoking status, and physical activity were as follows: BMI, 1.61 (1.44, 1.79); WC, 1.65 (1.48, 1.81); WHR, 1.49 (1.34, 1.66); %BF, 1.41 (1.25, 1.59); and FM, 1.53 (1.38, 1.70). For insulin resistance, the odds ratios (95% CIs) were as follows: 2.48 (2.22, 2.77), 2.46 (2.19, 2.65), 1.75 (1.59, 1.93), 1.79 (1.60, 2.00), and 2.10 (1.88, 2.34), respectively. In normal-weight (BMI < 25) and overweight (BMI 25-29.9) men, the presence of the metabolic syndrome and insulin resistance increased with increasing WC; this did not occur in obese men. CONCLUSIONS: BMI and WC are the simple measures of adiposity most strongly associated with metabolic abnormalities in elderly men. Our findings suggest that WC can be used as a complementary measurement to identify health risks in normal-weight and overweight elderly persons.

Adipose Tissue↗
PubMed2005

Body fat distribution, body composition, and respiratory function in elderly men.

BACKGROUND: Most population studies have reported weak or nonsignificant associations between body mass index (BMI; in kg/m2) and lung function. OBJECTIVE: This study focused on the distinct effects of fat distribution and body composition on lung function and examined these relations in elderly men. DESIGN: The study was a cross-sectional evaluation of 2744 men aged 60-79 y who were free of cardiovascular disease and cancer and were drawn from general practices in 24 British towns. Anthropometric and body-composition [including fat mass (FM), fat-free mass (FFM), and percentage body fat (%BF) evaluated with bioelectric impedance] measurements were made, and lung function was examined by using spirometry. RESULTS: Height-standardized forced expiratory volume in 1 s (FEV1) was diminished only in lean (BMI < 22.5) and obese (BMI > or = 30) men, but forced vital capacity (FVC) tended to decrease with increasing BMI (P < 0.01). All other measures of adiposity [ie, waist circumference (WC), waist-hip ratio (WHR), FM, and %BF] were significantly and inversely related to FEV1 and FVC after adjustment for confounders, including age and cigarette smoking (all: P < 0.05). This was seen both in nonobese (BMI < 30) and obese men. FFM was positively associated with FEV1 (P = 0.03) and to a lesser extent with FVC. Higher BMI and FFM were both associated with reduced odds of a low FEV1-FVC ratio (ie, <70%). CONCLUSION: Total body fat and central adiposity are inversely associated with lung function, but increased FFM reflecting increases in muscle mass is associated with increased lung function and lower odds of low FEV1:FVC in the elderly.

Adipose Tissue↗
PubMed2005

Overweight and obesity and weight change in middle aged men: impact on cardiovascular disease and diabetes.

CONTEXT: The benefit of weight reduction for cardiovascular disease (CVD) outcomes remains uncertain. OBJECTIVE: To examine the effects of baseline body mass index on major CVD outcomes and diabetes over a 20 year follow up, and of weight change in the first five years over the subsequent 15 years. DESIGN AND SETTING: A prospective study of British men followed up for 20 years. PARTICIPANTS: Men aged 40-59 years with no diagnosis of CVD or diabetes (n = 7176) of whom 6798 provided full information on weight change five years later. OUTCOME MEASURES: Major CVD events (fatal and non-fatal myocardial infarction and stroke, angina, "other" CVD deaths) and diabetes. RESULTS: During the 20 year follow up there were 1989 major CVD events and 449 incident cases of diabetes in the 7176 men. Risk of major CVD and diabetes increased significantly with increasing overweight and obesity. During the 15 year follow up, weight gain was associated with increased risk of CVD and diabetes. Weight loss was associated with lower risk of diabetes than the stable group irrespective of initial weight. No significant cardiovascular benefit was seen for weight loss in any men, except possibly in considerably overweight (BMI 27.5-29.9 kg/m(2)) younger middle aged men (RR = 0.42; 95% CI 0.22 to 0.81). CONCLUSION: Long term risk of CVD and diabetes increased significantly with increasing overweight and obesity. Weight loss was associated with significant reduction in risk of diabetes but not CVD, except possibly in considerably overweight younger men. Duration and severity of obesity seem to limit the cardiovascular benefits of weight reduction in older men.

Adult↗
PubMed2005

Serum uric acid and risk of coronary heart disease.

Many large epidemiological studies confirmed a positive association between raised serum uric acid (SUA) levels and risk of coronary heart disease (CHD) or cardiovascular disease (CVD) in the general population, among hypertensive patients and those with established CHD, stroke, diabetes and heart failure. There is much controversy concerning the role of SUA as an independent risk factor for CHD as SUA is related to many of the established risk factors for cardiovascular disease including hypertension, dyslipidaemia, obesity and pre-existing disease. The epidemiological evidence suggests that SUA is an independent predictor of CVD in subjects with hypertension and established vascular disease but not in healthy subjects. This evidence suggests that the influence of SUA on CHD is explained by the secondary association of SUA with other established etiological risk factors (hypertension, dyslipidaemia, hyperinsulinaemia, obesity and pre-existing disease). There is no evidence so far to indicate that lowering SUA levels with drug treatment has a beneficial effect on CVD outcome. In summary, there is little support for an independent causal role for SUA in the development of CHD. However, SUA may provide useful prognostic information in subjects with hypertension and vascular disease.

Coronary Disease↗
PubMed2004

Serum albumin and risk of stroke, coronary heart disease, and mortality: the role of cigarette smoking.

OBJECTIVE: Lower levels of serum albumin are associated with increased risk of all-cause and cardiovascular mortality as well as with coronary heart disease and stroke incidence. These relationships have been examined with specific focus on the role of cigarette smoking. STUDY DESIGN AND SETTING: A prospective study of 7,690 British men aged 40-59 years, with 16.8 years mean follow-up. RESULTS: Cigarette smoking was strongly and inversely associated with serum albumin concentrations that reverted to levels seen in never smokers after 5 years' cessation. Only in current and former smokers were there significant inverse relationships between serum albumin and risk of major CHD and stroke events even after adjustment for potential confounders. Only in current smokers was a significant inverse relationship seen between serum albumin and mortality from cardiovascular disease, cancer, and all causes. CONCLUSION: The inverse association between serum albumin concentration and disease outcome appears to be related to the effects of cigarette smoking on serum albumin concentration.

Adult↗
PubMed2004

Alcohol intake and 8-year weight gain in women: a prospective study.

OBJECTIVE: To examine prospectively the relationship between alcohol and 8-year weight gain in women. RESEARCH METHODS AND PROCEDURES: A prospective study of 49,324 women 27 to 44 years old who did not have a history of cardiovascular disease, cancer, or diabetes, who were not pregnant during the study period, and who reported weights in 1991 and 1999. RESULTS: In cross-sectional analyses, there was a significant inverse relationship between alcohol and BMI even after adjustment for dietary factors and a wide range of confounders. In multivariate prospective analyses, a nonlinear relationship was seen between alcohol and weight gain (>or=5 kg) in all women. Compared with nondrinkers, the adjusted relative odds [95% confidence interval (CI)] of weight gain according to grams per day were 0.94 (0.89, 0.99) for those consuming 0.1 to 4.9 g/d, 0.92 (0.85,0.99) for 5 to 14.9 g/d, 0.86 (0.76, 0.78) for 15 to 29.9 g/d, and 1.07 (0.89,1.28) for those consuming 30+ g/d (p < 0.0001 for quadratic trend). Women who continued to drink heavily and those who became heavy drinkers showed similar increased odds of weight gain. The increased odds of weight gain associated with heavy drinking (30+ g/d) were most marked in the younger women (<35 years) (odds ratio 1.64; 5% CI 1.03 to 2.61). In African-American women, light drinking was associated with increased odds of weight gain compared with nondrinkers (odds ratio = 2.43; 95% CI 1.22 to 4.82). DISCUSSION: Our data suggest that light to moderate drinking (up to 30 g/d) is not associated with weight gain in women except possibly in African-American women. Heavier drinking may promote weight gain in women.

Adult↗
PubMed2004

Overweight and obesity and the burden of disease and disability in elderly men.

OBJECTIVE: To examine the prevalence of disease burden and disability associated with overweight and obesity in men aged 60-79 y and to assess whether the current WHO weight guidelines are appropriate in the elderly. DESIGN: Cross-sectional survey 20 y after enrollment. SETTING: General practices in 24 British towns. PARTICIPANTS: In total, 4232 men aged 60-79 y (77% of survivors) with measured weight and height. MAIN OUTCOME MEASURES: Cardiovascular (CV) risk factors, prevalence of diabetes, cardiovascular disease, cancer, disability and regular medication. RESULTS: In total, 17% of the men were obese (body mass index (BMI) >/=30 kg/m(2)) and a further 52% were overweight (BMI 25-29.9 kg/m(2)). Prevalence of hypertension, low HDL-cholesterol, high triglycerides and insulin resistance and the prevalence of most disease outcomes increased with increasing degrees of overweight/obesity. Men in the normal weight range (18.5-24.9 kg/m(2)) had the lowest prevalence of ill health. Compared with normal weight men, obese men showed a two-fold risk of major CVD (odds ratio (OR)=1.96, 95% CI 1.44-2.67) and locomotor disability (OR=2.26, 95% CI 1.66, 3.09) and were nearly three times as likely to have diabetes, CV interventions or to be on CV medication. Over 60% of the prevalence of high insulin resistance was attributable to overweight and obesity as was over a third of diabetes and hypertension, a quarter of locomotor disability and a fifth of major CVD. CONCLUSION: In elderly men, overweight and obesity are associated with a significantly increased burden of disease, in particular CV-related disorders and disability. The current guidelines for overweight and obesity appear to be appropriate in elderly men.

Aged↗
PubMed2003

Alcohol drinking patterns and risk of type 2 diabetes mellitus among younger women.

OBJECTIVE: To examine the relationship between alcohol consumption and the incidence of type 2 diabetes mellitus among relatively young and middle-aged women. METHODS: In a prospective study, 109 690 women, aged 25 to 42 years, without a history of coronary heart disease, stroke, cancer, or diabetes mellitus completed a detailed lifestyle and medical history questionnaire in 1989. During 10 years of follow-up, we documented 935 incident cases of type 2 diabetes mellitus. RESULTS: We found a nonlinear relationship between alcohol consumption and risk of type 2 diabetes mellitus after adjustment for multiple confounders, including body mass index, smoking, physical activity, and family history of diabetes mellitus (quadratic trend P =.003). Compared with lifelong abstainers, the adjusted relative risks (95% confidence intervals) were 0.80 (0.66-0.96) for those consuming 0.1 to 4.9 g/d, 0.67 (0.50-0.89) for those consuming 5.0 to 14.9 g/d, 0.42 (0.20-0.90) for those consuming 15.0 to 29.9 g/d, and 0.78 (0.34-1.78) for those consuming 30.0 g/d or more. Further adjustment for dietary factors, including glycemic load, trans-fatty acid, polyunsaturated fat, and total fiber intake, did not appreciably alter these findings. The inverse association with light to moderate drinking was most apparent in women who reported wine or beer drinking. Women who reported 30.0 g/d or more of liquor intake showed a significantly increased risk of diabetes mellitus compared with those who did not report liquor intake (adjusted relative risk, 2.50; 95% confidence interval, 1.00-6.23). CONCLUSION: Light to moderate alcoholic beverage consumption may be associated with a lower risk of type 2 diabetes mellitus among women aged 25 to 42 years, although this benefit may not persist at higher levels.

Adult↗