The Effects of Synbiotic Supplementation on Metabolic Status in Women With Polycystic Ovary Syndrome: a Randomized Double-Blind Clinical Trial

Probiotics and Antimicrobial Proteins - Data on the effects of synbiotic supplementation on glycemic control, lipid profiles, and atherogenic index of plasma (AIP) of women with polycystic ovary...     

Optimal Waist Circumference for Prediction of Metabolic Syndrome in Young Korean Women With Polycystic Ovary Syndrome

The International Diabetes Federation consensus proposed an ethnically specific criteria of waist circumference (WC) for central obesity, but, the nationwide definition is still debated in Korea. For the detection of the optimal WC cutoff value, the nonadipose components of the metabolic syndrome (MS) were defined by modification of revised 2003 Rotterdam consensus as having two or more risk factors such as hypertension, hyperglycemia, and dyslipidemia without consideration of abdominal obesity. By using receiver‐operating characteristic (ROC) curve analysis, cutoff points of WC and visceral fat area (VFA) for prediction of MS were 80 cm and 53.1 cm². WC cutoff points corresponding to VFA >53.1 and 100 cm² were 73.3 and 77.8 cm. The sensitivity and specificity of currently used value of WC 88 cm were 41.9 and 91.5%, suggesting that it could be too high in Korean population. Central obesity defined as WC >80 cm was significantly associated with nonadipose components of MS after adjustment for age, BMI, cholesterol, triglycerides, fasting insulin, and free testosterone levels. Central obesity with WC of >80 cm predicted the presence of nonadipose MS (odds ratio 16.6; 95% confidence interval (CI) 6.5–42.6). It was also significant (odds ratio 14.7; 95% CI 3.4–64.3) when we applied the WC value of 70 cm instead of 80 cm. In conclusion, WC of 80 and 70 cm could be appropriate cutoff points to identify the MS and visceral adiposity in Korean women with polycystic ovary syndrome (PCOS), respectively. Therefore, PCOS women with a WC over 70 cm should be closely monitored for the development of MS.     

The Pathophysiology and Clinical Aspects of Hypercalcemic Disorders

For the purposes of this review, the vast and increasingly complex subject of hypercalcemic disorders can be broken down into the following categories: (1) Physiochemical state of calcium in circulation. (2) Pathophysiological basis of hypercalcemia. (3) Causes of hypercalcemia encountered in clinical practice: causes indicated by experience at the University of California, Los Angeles; neoplasia; hyperparathyroidism; nonparathyroid endocrinopathies; pharmacological agents; possible increased sensitivity to vitamin D; miscellaneous causes. (4) Clinical manifestations and diagnostic considerations of hypercalcemic disorders. (5) The management of hypercalcemic disorders: general measures; measures for lowering serum calcium concentration; measures for correcting primary causes—the management of asymptomatic hyperparathyroidism.     

Differences in Daily Rhythms of Wrist Temperature Between Obese and Normal-Weight Women: Associations With Metabolic Syndrome Features

The circadian rhythm of core body temperature is associated with widespread physiological effects. However, studies with other more practical temperature measures, such as wrist (WT) and proximal temperatures, are still scarce. The aim of this study was to investigate whether obesity is associated with differences in mean WT values or in its daily rhythmicity patterns. Daily patterns of cortisol, melatonin, and different metabolic syndrome (MetS) features were also analyzed in an attempt to clarify the potential association between chronodisruption and MetS. The study was conducted on 20 normal-weight women (age: 38?±?11 yrs and BMI: 22?±?2.6?kg/m²) and 50 obese women (age: 42?±?10 yrs and BMI: 33.5?±?3.2?kg/m²) (mean?±?SEM). Skin temperature was measured over a 3-day period every 10?min with the “Thermochron iButton.” Rhythmic parameters were obtained using an integrated package for time-series analysis, “Circadianware.” Obese women displayed significantly lower mean WT (34.1°C?±?0.3°C) with a more flattened 24-h pattern, a lower-quality rhythm, and a higher intraday variability (IV). Particularly interesting were the marked differences between obese and normal-weight women in the secondary WT peak in the postprandial period (second-harmonic power [P2]), considered as a marker of chronodisruption and of metabolic alterations. WT rhythmicity characteristics were related to MetS features, obesity-related proteins, and circadian markers, such as melatonin. In summary, obese women displayed a lower-quality WT daily rhythm with a more flattened pattern (particularly in the postprandial period) and increased IV, which suggests a greater fragmentation of the rest/activity rhythm compared to normal-weight women. These 24-h changes were associated with higher MetS risk. (Author correspondence: garaulet@um.es)     

Severe Metabolic Acidemia in Infants: Clinical and Therapeutic Aspects

A study of 10 infants in severe metabolic acidemia (pH below 7) led to the conclusion that the clinical signs—hyperventilation, coma or lethargy, peripheral vascular collapse, a significantly palpable liver, and abdominal distension—may all be directly related to the metabolic acidemia. In five of 10 infants, an initial erroneous diagnosis of congestive heart failure or pneumonia was made. Dramatic clinical improvement followed correction of the acidemia with rapid intravenous administration of sodium bicarbonate. This rapid administration of sodium bicarbonate was safe, provided hypocalcemia was recognized and treated in its early stages. In severe metabolic acidemia the measurement of blood bicarbonate alone does not reflect adequately the magnitude of the acid-base derangement and repeated measurements of hydrogen ion concentration, Pco₂ and bicarbonates are needed to evaluate and treat such infants correctly.     

Premicroalbuminuria in Women with Polycystic Ovary Syndrome: A Metabolic Risk Marker

ObjectiveTo determine the relationship between urinary albumin excretion and features of the metabolic syndrome in women with polycystic ovary syndrome (PCOS).MethodsWe retrospectively analyzed the medical records of 189 premenopausal women (mean age ± SD, 28.9 ± 7.7 years) with PCOS and 81 control patients (mean age ± SD, 37.9 ± 8.6 years) from a single endocrinology practice. Exclusion criteria were diabetes, heart disease, kidney disease, use of lipid-lowering agents, and use of antihypertensive agents (except spironolactone). The urine albumin-to-creatinine ratio (ACR) was measured in a random single-voided urine sample. Premicroalbuminuria was defined as an ACR > 7 mg/g.ResultsThe prevalence of ACR > 7 mg/g was 31.2% in the PCOS group (N = 189) and 35.8% in the control group (N = 81). The metabolic syndrome was noted in 16.3% (27 of 166) of patients with PCOS and in 2.9% (2 of 69) of control subjects. Nine percent of patients with PCOS who had an ACR ≤ 7 mg/g but 30.9% of those with an ACR > 7 mg/g had the metabolic syndrome. Patients with PCOS who had an ACR > 7 mg/g had significantly higher blood pressure and alanine aminotransferase levels than did those with an ACR ≤ 7 mg/g. In the patients with PCOS who had an ACR ≤ 7 mg/g versus those who had an ACR > 7 mg/g, no significant difference was found in frequency of use of metformin, spironolactone, or oral contraceptives.ConclusionIn women with PCOS, an ACR > 7 mg/g was strongly associated with the metabolic syndrome, high blood pressure, and elevated alanine aminotransferase levels. It may be useful to consider ACR > 7 mg/g as an associated sign of the presence of metabolic syndrome in women with PCOS. (Endocr Pract. 2008;14: 193-200)     

Physical Activity and the Metabolic Syndrome in a Tri-ethnic Sample of Women

Objective: To determine the association of moderate-intensity physical activity (PA), vigorous-intensity PA, and maximal treadmill duration with the metabolic syndrome among African-American (n = 49), Native-American (n = 46), and white (n = 51) women (ages, 40 to 83 years), enrolled in the Cross-Cultural Activity Participation Study. Research Methods and Procedures: The metabolic syndrome was defined as three or more of the following risk factors: waist circumference >88 cm, blood pressure ≥130/85 mm Hg, fasting glucose ≥110 mg/dL, hypertriglyceridemia (≥150 mg/dL), and high-density lipoprotein-cholesterol <50 mg/dL. PA was determined from detailed PA records that included all PA performed during two consecutive 4-day periods. Maximal treadmill duration was determined from a graded exercise test. Women were categorized into quartiles of moderate-intensity PA, vigorous-intensity PA, and maximal treadmill duration. Multiple logistic regression was used to estimate odds ratios of the metabolic syndrome as a function of the four PA categories, adjusted for age, ethnicity, study site, menopausal status, and use of hormone-replacement therapy. Results: The adjusted odds ratio for the metabolic syndrome was 0.18 (95% confidence interval, 0.33 to 0.90) for women in the highest category of moderate-intensity PA compared with women in the lowest category (p = 0.01 for trend). Similar associations were observed for the metabolic syndrome with vigorous-intensity PA (p = 0.01 for trend) and maximal treadmill duration (p = 0.0004 for trend). Discussion: Higher levels of moderate and vigorous-intensity PA and greater maximal treadmill duration were inversely associated with the metabolic syndrome among an ethnically diverse sample of women.     

Cardiac Metabolic Pathways Affected in the Mouse Model of Barth Syndrome

Cardiolipin (CL) is a mitochondrial phospholipid essential for electron transport chain (ETC) integrity. CL-deficiency in humans is caused by mutations in the tafazzin (Taz) gene and results in a multisystem pediatric disorder, Barth syndrome (BTHS). It has been reported that tafazzin deficiency destabilizes mitochondrial respiratory chain complexes and affects supercomplex assembly. The aim of this study was to investigate the impact of Taz-knockdown on the mitochondrial proteomic landscape and metabolic processes, such as stability of respiratory chain supercomplexes and their interactions with fatty acid oxidation enzymes in cardiac muscle. Proteomic analysis demonstrated reduction of several polypeptides of the mitochondrial respiratory chain, including Rieske and cytochrome c1 subunits of complex III, NADH dehydrogenase alpha subunit 5 of complex I and the catalytic core-forming subunit of F₀F₁-ATP synthase. Taz gene knockdown resulted in upregulation of enzymes of folate and amino acid metabolic pathways in heart mitochondria, demonstrating that Taz-deficiency causes substantive metabolic remodeling in cardiac muscle. Mitochondrial respiratory chain supercomplexes are destabilized in CL-depleted mitochondria from Taz knockdown hearts resulting in disruption of the interactions between ETC and the fatty acid oxidation enzymes, very long-chain acyl-CoA dehydrogenase and long-chain 3-hydroxyacyl-CoA dehydrogenase, potentially affecting the metabolic channeling of reducing equivalents between these two metabolic pathways. Mitochondria-bound myoglobin was significantly reduced in Taz-knockdown hearts, potentially disrupting intracellular oxygen delivery to the oxidative phosphorylation system. Our results identify the critical pathways affected by the Taz-deficiency in mitochondria and establish a future framework for development of therapeutic options for BTHS.     

Prevalence of the Metabolic Syndrome across Cardiorespiratory Fitness Levels in Women

Objectives : To determine the prevalence of the metabolic syndrome across age strata and cardiorespiratory fitness (CRF) levels in women. Research Methods and Procedures : 7104 women underwent a physical examination, including a maximal treadmill exercise test. Participants were divided into CRF quintiles according to age. The metabolic syndrome was identified using Adult Treatment Panel‐III Guidelines. Tests for trend were performed on demographic variables across CRF quintiles, as well as prevalence of the metabolic syndrome across CRF quintiles, age strata, and maximal workload achieved [maximal metabolic equivalent (MET) level]. Results : The overall prevalence of the metabolic syndrome was 6.5%. Age‐ and smoking‐adjusted prevalence was lower across quintiles of CRF (19.0%, 6.7%, 6.0%, 3.6%, and 2.3% for quintiles I to V, respectively, p for trend = 0.001). Smoking‐adjusted prevalence of the metabolic syndrome was higher across age strata (2.4%, 2.7%, 6.4%, 8.7%, 15.3%, and 16.1% for ages 20 to 29, 30 to 39, 40 to 49, 50 to 59, 60 to 69, and 70 to 80, respectively, p for trend = 0.001). Prevalence of the metabolic syndrome in the different age groups for women who achieved a maximal MET level of 11 or higher was one‐third to one‐fourth that of women who achieved lower maximal MET levels. Discussion : Prevalence of the metabolic syndrome was markedly lower across progressively higher levels of CRF in women of different age strata. Because regular physical activity improves components of the metabolic syndrome, modest increases in CRF among low fit women may ameliorate the metabolic syndrome in some instances.     

Racial Differences in Adipocyte Size and Relationship to the Metabolic Syndrome in Obese Women

Objective: To determine whether racial differences exist in the relationship of the abnormalities defining the metabolic syndrome (MS) to regional adiposity and fat cell size (FCS) in obese postmenopausal women. Research Methods and Procedures: We determined the relationship of metabolic variables associated with the MS to regional body composition and abdominal (ABD) and gluteal (GLT) FCS in 25 white (CAU) and 25 African‐American (AF‐AMER) older women matched for age (58 ± 5 years; mean ± SD) and BMI (35 ± 4 kg/m²). Results: MS was present in 36% of the AF‐AMER and 57% of the CAU women. There were no differences in total body, trunk, gluteofemoral fat mass or regional FCS, but AF‐AMER women had 22% lower visceral fat, 24% higher insulin, and 31% lower triglyceride levels than CAU women (p < 0.05). Multiple regression analysis with body fat, visceral ABD fat area, and FCS as independent variables showed that GLT FCS was independently correlated with 2‐hour insulin (r = 0.56), triglyceride (r = 0.62), and high‐density lipoprotein cholesterol (r = ?0.72) levels in AF‐AMER women but not in CAU women, where only systolic blood pressure correlated with subcutaneous ABD fat area (r = 0.57) (p < 0.05). Discussion: The associations between GLT FCS and metabolic dysfunction in obese AF‐AMER but not CAU women suggest that central obesity is a less valid predictor of the MS in obese postmenopausal AF‐AMER women than in CAU women and that GLT FCS may be a more sensitive indicator of risk for the MS in AF‐AMER women.     

Increased Cortisol Bioavailability,Abdominal Obesity,and the Metabolic Syndrome in Obese Women

Objective: This study was conducted to obtain a detailed profile of hypothalamo‐pituitary‐adrenal (HPA) axis activity and reactivity and its differential relationships with body fat distribution and total fat mass in premenopausal obese women. Research Methods and Procedures: Cortisol responses to stimulation (awakening, food intake, exercise) and suppression (0.25 mg dexamethasone), cortisol metabolism, and tissue sensitivity to glucocorticoids were studied in 53 premenopausal obese women grouped according to their waist‐to hip ratio: women with abdominal body fat distribution (A‐BFD; n = 31) and women with peripheral fat distribution (P‐BFD; n = 22). Results: Comparatively, A‐BFD women had 1) lower awakening salivary cortisol levels; 2) increased salivary responsiveness to a standardized lunch; 3) similar pituitary sensitivity to dexamethasone but decreased sensitivity of monocytes to dexamethasone; 4) similar 24‐hour urinary free cortisol but increased 24‐hour urinary ratio of cortisone‐to‐cortisol; and 5) no difference in corticosteroid binding protein parameters. Discussion: Although abdominal obesity is not very different from generalized obesity in terms of HPA function, subtle variations in HPA axis activity and reactivity are evidenced in A‐BFD premenopausal obese women.     

Traditional Anthropometric Parameters Still Predict Metabolic Disorders in Women With Severe Obesity

It is well established that fat distribution rather than the total quantity of fat is the major determinant of cardiovascular risk in overweight subjects. However, it is not known whether the concept of fat distribution still makes sense in severely obese subjects. Particularly, the role of visceral fat accumulation and/or of adipocyte hypertrophy in insulin resistance (IR) has not been studied in this population. Therefore, the aim of this study was to clarify the determinants of metabolic disorders in severely obese women. We performed a cross‐sectional study in 237 severely obese women (BMI >35 kg/m²). We assessed total body fat mass and fat distribution by anthropometric measurements (BMI and waist‐to‐hip ratio (WHR)) and by dual‐energy X‐ray absorptiometry (DXA). In 22 women, we measured subcutaneous and visceral adipocyte size on surgical biopsies. Mean BMI was 44 ± 7 kg/m² (range 35–77), mean age 37 ± 11 years (range 18–61). Lipid parameters (triglycerides, high‐density lipoprotein cholesterol) and IR markers (fasting insulin and homeostasis model assessment (HOMA) index) correlated with fat distribution, whereas inflammatory parameters (C‐reactive protein, fibrinogen) correlated only with total fat mass. An association was observed between android fat distribution and adipocyte hypertrophy. Visceral adipocyte hypertrophy was associated with both IR and hypertension, whereas subcutaneous fat‐cell size was linked only to hypertension. Our results obtained in a large cohort of women showed that fat distribution still predicts metabolic abnormalities in severe obesity. Furthermore, we found a cluster of associations among fat distribution, metabolic syndrome (MS), and adipocyte hypertrophy.     

The Metabolic Syndrome and Behavioral Correlates in Obese Patients With Binge Eating Disorder

This study examined the frequency of the metabolic syndrome (MetSyn) and explored behavioral eating‐ and weight‐related correlates in obese patients with binge eating disorder (BED). Ninety‐three treatment‐seeking obese BED patients (22 men and 71 women) with and without the MetSyn were compared on demographic features and a number of current and historical eating and weight variables. Sixty percent of the obese patients with BED met criteria for the MetSyn, with men and whites having significantly higher rates than women and African Americans, respectively. Patients with vs. without coexisting MetSyn did not differ significantly in self‐reported frequency of binge eating or severity of eating disorder psychopathology. Multivariate hierarchical logistic regression analysis revealed that, after controlling for gender, ethnicity, and BMI, fewer episodes of weight cycling and regular meal skipping were significant predictors of the MetSyn. These findings suggest that lifestyle behaviors including weight loss attempts and regular meal consumption may be potential targets for prevention and/or treatment of the MetSyn in obese patients with BED.     

Evaluation of Oxidative Stress in Overweight Subjects With or Without Metabolic Syndrome

Although oxidative stress is considered the underlying mechanism by which dysfunctional metabolism occurs in obese subjects, there are few studies on oxidative stress in overweight subjects. The objective of this study was to verify the influence of metabolic syndrome (MetS) on oxidative stress and antioxidant defense in overweight subjects. There were 123 subjects (50 in the control group and 73 in the overweight group) chosen to participate in this cross‐sectional study. The control group included 50 healthy individuals with a BMI between 20 and 24.9 kg/m² and without MetS. The overweight group included 73 subjects with a BMI between 25 and 29.9 kg/m². Overweight subjects were divided into two groups: with MetS (29 subjects) and without MetS (44 subjects). Control group and overweight group subjects without MetS showed no differences in oxidative stress parameters and total antioxidant capacity (TRAP). Overweight subjects with MetS had higher hydroperoxide concentrations measured by chemiluminescence compared to the control group (P < 0.05), higher hydroperoxide and hydrogen peroxide concentrations determined by ferrous oxidation‐xylenol orange assay compared to overweight subjects without MetS (P < 0.001), and higher advanced oxidation protein product (AOPP) concentrations (P < 0.001) compared to the other groups. AOPP was directly correlated with uric acid concentrations. Overweight subjects with MetS had lower TRAP concentrations compared to the control group (P < 0.001). In conclusion, this study showed that overweight subjects with MetS, in contrast to overweight subjects without MetS, have a redox imbalance characterized by increased plasma oxidation and reduced antioxidant capacity.     

Sheehan Syndrome in Costa Rica: Clinical Experience With 60 Cases

ObjectiveTo describe the clinical and hormonal characteristics of patients with Sheehan syndrome.MethodsWe performed a 20-year cohort study (1969 to 1989) of patients with Sheehan syndrome who were cared for in the endocrinology unit of the México Hospital in San José, Costa Rica. Medical history, physical examination findings, and laboratory test results were documented and reviewed.ResultsSixty patients with a diagnosis of Sheehan syndrome were identified. Mean age at diagnosis was 45.8 ± 10.6 years. The average time between the previous obstetric event and Sheehan syndrome diagnosis was 13 years. Thirteen patients (22%) had a home birth. The median parity was 7. The most frequent obstetric antecedents were history of obstetric hemorrhage in 49 (82%), shock in 28 (47%), blood transfusion in 26 (43%), and peripartum hysterectomy in 4 (7%). The most common symptoms included asthenia and adynamia in 51 (85%), amenorrhea in 44 (73%), loss of axillary or pubic hair in 40 (67%), and agalactia in 40 (67%). The most common findings on physical examination were absence of axillary hair in 56 (93%) and pubic hair in 56 (93%), dry skin in 49 (82%), and pallor in 42 (70%). When a combined pituitary test was performed, 38 of 38 patients (100%) had human growth hormone deficiency, 29 of 30 patients (97%) had adrenal insufficiency, 8 of 10 patients (80%) had hypothyroidism, 8 of 12 patients (67%) had hypogonadism, and 9 of 13 patients (69%) had prolactin deficiency. Despite early onset of symptoms, Sheehan syndrome was diagnosed relatively late in these 60 patients. Hemorrhage during the last delivery, especially if severe and/or associated with shock or transfusion, was the most important obstetric antecedent event. Absence of amenorrhea or presence of postpartum lactation did not exclude the diagnosis. Abnormal responses of human growth hormone to insulin tolerance testing and of prolactin to thyrotropin-releasing hormone confirm the diagnosis.ConclusionsIdentification of patients affected with Sheehan syndrome is critical to avoid delays in diagnosis and treatment. Appropriate replacement therapy is capable of yielding complete remission of symptoms. (Endocr Pract. 2011;17:337-344)     

The Relationship of Ectopic Lipid Accumulation to Cardiac and Vascular Function in Obesity and Metabolic Syndrome

Storage of lipid in ectopic depots outside of abdominal visceral and subcutaneous stores, including within the pericardium and liver, has been associated with obesity, insulin resistance, and cardiovascular risk. We sought to determine whether anatomically distinct ectopic depots were physiologically correlated and site‐specific effects upon cardiovascular function could be identified. Obese subjects (n = 28) with metabolic syndrome but without known atherosclerotic disease and healthy controls (n = 18) underwent magnetic resonance imaging (MRI) and proton MR spectroscopy (MRS) to quantify pericardial and periaortic lipid volumes, cardiac function, aortic compliance, and intrahepatic lipid content. Fasting plasma lipoproteins, glucose, insulin, and free‐fatty acids were measured. Pericardial and intrahepatic (P < 0.01) and periaortic (P < 0.05) lipid volumes were increased in obese subjects vs. controls and were strongly and positively correlated (P ≤ 0.01) but independent of BMI (P = NS) among obese subjects. Intrahepatic lipid was associated with insulin resistance (P < 0.01) and triglycerides (P < 0.05), whereas pericardial and periaortic lipid were not (P = NS). Periaortic and pericardial lipid positively correlated to free‐fatty acids (P ≤ 0.01) and negatively correlated to high‐density lipoprotein (HDL) cholesterol (P < 0.05). Pericardial lipid negatively correlated to cardiac output (P = 0.03) and stroke volume (P = 0.01) but not to left ventricular ejection fraction (P = 0.46). None of the ectopic depots correlated to aortic compliance. In conclusion, ectopic storage of lipid in anatomically distinct depots appeared tightly correlated but independent of body size. Site‐specific functional abnormalities were observed for pericardial but not periaortic lipid. These findings underscore the utility of MRI to assess individual differences in ectopic lipid that are not predictable from BMI.     

Dietary Patterns and the Metabolic Syndrome in Obese and Non‐obese Framingham Women**

Objectives: To examine the relationship between habitual dietary patterns and the metabolic syndrome (MetS) in women and to identify foci for preventive nutrition interventions. Research Methods and Procedures: Dietary patterns, nutrient intake, cardiovascular disease (CVD), and MetS risk factors were characterized in 1615 Framingham Offspring‐Spouse Study (FOS) women. Dietary pattern subgroups were compared for MetS prevalence and CVD risk factor status using logistic regression and analysis of covariance. Analyses were performed overall in women and stratified on obesity status; multivariate models controlled for age, apolipoprotein E (APOE) genotypes, and CVD risk factors. Results: Food and nutrient profiles and overall nutritional risk of five non‐overlapping habitual dietary patterns of women were identified including Heart Healthier, Lighter Eating, Wine and Moderate Eating, Higher Fat, and Empty Calories. Rates of hypertension and low high‐density lipoprotein levels were high in non‐obese women, but individual MetS risk factor levels were substantially increased in obese women. Overall MetS risk varied by dietary pattern and obesity status, independently of APOE and CVD risk factors. Compared with obese or non‐obese women and women overall with other dietary patterns, MetS was highest in those with the Empty Calorie pattern (contrast p value: p < 0.05). Discussion: This research shows the independent relationship between habitual dietary patterns and MetS risk in FOS women and the influence of obesity status. High overall MetS risk and the varying prevalence of individual MetS risk factors in female subgroups emphasize the importance of preventive nutrition interventions and suggest potential benefits of targeted behavior change in both obese and non‐obese women by dietary pattern.