Reduced postprandial bone resorption and greater rise in GLP-1 in overweight and obese individuals after an α-glucosidase inhibitor: a double-blinded randomized crossover trial.

When taken with a meal, α-glucosidase inhibitors (α-GI) reduce the rise in postprandial glucose and increase glucagon-like peptide-1 (GLP-1), and this may lower bone turnover. In this study, a salacinol-type α-GI increased GLP-1 and markedly reduced postprandial bone resorption compared to placebo, suggesting it could have implications for bone health. INTRODUCTION: Animal and clinical trials indicate that α-glucosidase inhibitors attenuate postprandial glycemic indices and increase secretion of GLP-1. In addition, GLP-1 acts on bone by inhibiting resorption. The goal in this study was to determine if a salacinol α-GI alters postprandial bone turnover and can be explained by changes in serum GLP-1. METHODS: In this double-blind, placebo-controlled crossover study, healthy overweight/obese adults (body mass index 29.0 ± 3.8 kg/m2; 21-59 years; n = 21) received a fixed breakfast and, in random order, were administered Salacia chinensis (SC; 500 mg) or placebo. A fasting blood sample was taken before and at regular intervals for 3 h after the meal. Serum was measured for bone turnover markers, C-terminal telopeptide of type I collagen (CTX) and osteocalcin, and for glycemic indices and gut peptides. RESULTS: Compared to placebo, SC attenuated the bone resorption marker, CTX, at 60, 90, and 120 min (p < 0.05) after the meal, and decreased osteocalcin, at 180 min (p < 0.05). As expected, SC attenuated the postprandial rise in glucose compared with placebo, whereas GLP-1 was increased at 60 min (p < 0.05) with SC. Serum GLP-1 explained 41% of the variance for change in postprandial CTX (p < 0.05). CONCLUSION: This study indicates that attenuating postprandial glycemic indices, with an α-GI, markedly decreases postprandial bone resorption and can be explained by the rise in GLP-1. Future studies should determine whether longer term α-GI use benefits bone health.

Three doses of vitamin D, bone mineral density, and geometry in older women during modest weight control in a 1-year randomized controlled trial.

The effects of higher than recommended vitamin D doses on bone mineral density (BMD) and quality are not known. In this study, higher intakes, in postmenopausal women undergoing weight control over 1 year, had no effect on areal or volumetric BMD but prevented the deterioration in cortical bone geometry. INTRODUCTION: Studies examining how bone responds to a standard dose of vitamin D supplementation have been inconsistent. In addition, the effects of higher doses on BMD and quality are not known. Postmenopausal women undergoing weight control to improve health outcomes are particularly at risk for bone loss and might benefit from supplemental vitamin D intake above the recommended allowance. METHODS: This 1-year-long, randomized, double-blind controlled study addresses whether vitamin D supplementation, in healthy overweight/obese older women, affects BMD and bone structural parameters. In addition, bone turnover and serum total, free, and bioavailable 25-hydroxyvitamin D (25OHD) responses to one of three daily levels of vitamin D3 (600, 2000, 4000 IU) with 1.2 Ca g/day during weight control were examined. RESULTS: Fifty-eight women (age, 58 ± 6 years; body mass index, 30.2 ± 3.8 kg/m2, serum 25OHD, 27.3 ± 4.4 ng/mL) were randomized to treatment. After 1 year, serum 25OHD concentrations increased to 26.5 ± 4.4, 35.9 ± 4.5, and 41.5 ± 6.9 ng/mL, in groups 600, 2000, and 4000 IU, respectively, and differed between groups (p < 0.01). Weight change was similar between groups (-3.0 ± 4.1 %). Cortical (Ct) thickness of the tibia changed by -1.5 ± 5.1 %, +0.6 ± 3.2 %, and +2.0 ± 4.5 % in groups 600, 2000, and 4000 IU, respectively, and each group was significantly different from each other (p < 0.05). CONCLUSION: The decline in Ct thickness was prevented with higher vitamin D3 supplementation, but there were no other significant changes due to treatment over 1 year. Whether these findings translate to changes in biomechanical properties leading to reduced fracture risk should be addressed in future studies.

Influence of vitamin D and estrogen receptor gene polymorphisms on calcium absorption: BsmI predicts a greater decrease during energy restriction.

Low calcium absorption is associated with low bone mass and fracture. In this study, we use gold standard methods of fractional calcium absorption (FCA) to determine whether polymorphisms of intestinal receptors, vitamin D receptor (VDR) and estrogen receptor α (ESR1), influence the response to energy restriction. Fractional calcium absorption was measured using dual stable isotopes ((42)Ca and (43)Ca) in women given adequate calcium and vitamin D and examined at baseline and after 6 weeks of energy restriction or no intervention. After genotyping, the relationship between VDR and ESR1 genotypes/haplotypes and FCA response was assessed using several genetic models. One-hundred and sixty-eight women (53 ± 11 years of age) were included in this analysis. The ESR1 polymorphisms, PvuII and XbaI and VDR polymorphisms (TaqI, ApaI) did not significantly influence FCA. The BB genotype of the VDR polymorphism, BsmI, was associated with a greater decrease in FCA than the Bb/bb genotype. Multiple linear regression showed that the BsmI polymorphism or the VDR haplotype, BAt, in addition to changes in weight and vitamin D intake explained ~16% of the variation in changes in FCA. In conclusion, the reduction in calcium absorption due to energy restriction is greatest for those with the BB genotype. Previous candidate gene studies show that VDR polymorphisms are associated with higher risk for osteoporosis, and the current study supports the notion that the BsmI polymorphism in intestinal VDR may be contributing to alterations in bone health.

Hormonal and dietary influences on true fractional calcium absorption in women: role of obesity.

UNLABELLED: The goal in this study was to examine the hormonal and dietary predictors of true fractional Ca absorption (TFCA) in adult women and to determine whether TFCA differs due to body weight. Results showed that TFCA is higher in obese individuals and dietary fat, estradiol, and 1,25-dihydroxy vitamin D are the most significant positive predictors of TFCA in adult women. INTRODUCTION: Calcium absorption is an important determinant of calcium balance and is influenced by several factors. Previous studies have identified that age, intake of protein, fat and fiber, and hormones such as 1, 25-dihyroxyvitamin D (1,25(OH)(2)D(3)) influence absorption. The determinants of TFCA using the double isotope method, the gold standard estimate of absorption, have not been examined previously in adult women nor has the role of obesity been addressed. METHODS: In this study, we examined the hormonal and dietary predictors of TFCA in adult women with a wide range of age, body weights, and nutrient intake. TFCA was measured using dual stable isotope ((42)Ca and (43)Ca) technique. Serum was analyzed for bone-regulating hormones, and dietary information was obtained through food records. The independent dietary factors and hormonal predictors (25-hydroxyvitamin D, 1,25(OH)(2)D(3), parathyroid hormone, and estradiol) of TFCA were analyzed using multiple regression analysis. RESULTS: Two hundred twenty-nine women aged 54 ± 11 years old (24-75 years) and with BMI of 31 ± 7.0 kg/m(2) were eligible and were categorized into tertiles of body mass index (BMI) into leaner, overweight, and obese. In the entire group of women, total fat intake, estradiol, and 1,25(OH)(2)D(3) are significant positive predictors (p < 0.05). As expected, age is a significant negative predictor of TFCA (R (2) = 26%). TFCA is higher in obese women compared to non-obese women (p < 0.05). CONCLUSION: Together, these data show that dietary fat is the most significant positive predictor of TFCA which may have implications for dietary intake for non-obese individuals who are more likely to have lower and potentially compromised Ca absorption.

Obesity alters cortical and trabecular bone density and geometry in women.

UNLABELLED: The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone using quantitative computed tomography. A higher body mass index (BMI) was positively associated with trabecular and cortical bone parameters, and serum parathyroid hormone, and negatively associated with cortical volumetric bone mineral density (vBMD) and serum 25-hydroxy-vitamin D. When BMI is greater than 35 kg/m(2), adiposity affects vBMD and may explain the higher fracture risk in this population without low BMD. INTRODUCTION: The influence of adult obesity on the trabecular and cortical bone, geometry, and strength has not been fully addressed. The goal in this study was to determine the relationship between body mass index and trabecular and cortical bone mass and geometry, over a wide range of body weights. METHODS: We examined 211 women (25-71 years; BMI 18-57 kg/m(2)) who were classified into three categories of BMI (kg/m(2)) including normal-weight (BMI<25), overweight and obese-class I (BMI 25-35) and obese-class II-III (BMI>35), and also by menopausal status. Volumetric bone mineral density (mg/cm(3)), trabecular, and cortical components as well as geometric characteristics at the 4%, 38%, and 66% from the distal tibia were measured by peripheral quantitative computed tomography, and serum was analyzed for parathyroid hormone (PTH) and 25-hydroxy-vitamin D (25OHD). RESULTS: Higher BMI was associated with greater values of trabecular bone and cortical BMC and area and PTH (r>0.39, p<0.001), but lower cortical vBMD and 25OHD (r>-0.27, p<0.001). When controlling for lower leg muscle area, fat area was inversely associated with cortical vBMD (r=-0.16, p<0.05). Premenopausal obese women with both higher BMI and PTH had lower cortical vBMD (r<-0.40, p<0.001). While age is a predictor for most bone variables, fat mass explains more variance for vBMD, and lean mass and 25OHD explain greater variance in geometric and strength indices (p<0.05). CONCLUSIONS: Severe obesity (BMI>35) increases trabecular vBMD and in the presence of a higher PTH is associated with a lower cortical vBMD without compromising bone geometry and strength. Whether or not a lower cortical vBMD in obesity influences fracture risk over time needs to be further explored.

Obese children should be screened for hypercholesterolemia.

Screening only those with a positive family history misses many children with hypercholesterolemia. This study investigated whether sensitivity improved by adding obesity as a criterion when screening children for cholesterol. During a two-year period screenings were conducted on 506 inner-city subjects aged 5-19. Demographic, clinical, and dietary information was also recorded. Mean age of participants was 11 +/- 4 years; 52 percent were female, 53 percent black, 39 percent Hispanic, and 8 percent other. Mean cholesterol level was 4.14 mmol/l (160 mg/dl). In multivariate analysis obesity was an independent risk factor for hypercholesterolemia, F = 13.14, p < 0.001. The sensitivity of obesity as a screening tool for hypercholesterolemia was better than that for positive family history (42 vs. 24 percent, respectively). Combining the two improved the sensitivity to 49 percent. The authors recommend expanding the indications for screening children to include obesity, in addition to positive family history of hypercholesterolemia or premature cardiovascular disease.

Diagnosis and treatment of primary hyperaldosteronism.

OBJECTIVE: To characterize the clinical and laboratory features of primary aldosteronism and to evaluate which diagnostic tests can discriminate surgically curable forms of this syndrome. DESIGN: Retrospective analysis of the following data from 82 patients with primary aldosteronism: blood pressure, serum electrolytes, urinary aldosterone and electrolytes, computed tomographic scans, plasma renin and aldosterone before and during upright posture, atrial natriuretic peptide, and adrenal vein aldosterone and cortisol. Clinical outcomes assessed after treatment included blood pressure, serum electrolytes, and plasma renin activity. RESULTS: Drug therapy was discontinued before diagnostic tests were done in 56 of 82 patients (34 with adenomas and 22 with hyperplasia). Compared with patients with hyperplasia, those with adenomas had higher systolic (184 mm Hg and 161 mm Hg, respectively; P < 0.001) and diastolic blood pressures (112 mm Hg and 105 mm Hg; P = 0.03), lower serum potassium levels (3.0 mmol/L and 3.5 mmol/L; P < 0.001), and higher serum CO2 (P = 0.001), atrial natriuretic peptide (P = 0.008), and urinary 18-methyl oxygenated cortisol metabolite levels (P = 0.02). In patients with adenomas, aldosterone secretion lateralized to one adrenal gland and did not increase during the postural stimulation test; preoperative urinary aldosterone levels were correlated with diastolic pressures (r = 0.58; P = 0.001). Hypertension was "cured" postoperatively in approximately 35% of patients with adenomas and those with hyperplasia (P > 0.2) but was "improved" more frequently in those with adenomas (P = 0.002). Cured patients from both groups were younger than those not cured (mean ages, 43 years and 54 years, respectively; P = 0.002) and had lower preoperative mean plasma renin activity (0.17 ng/mL per hour and 0.50 ng/mL per hour; P < 0.001). All patients with adenomas in whom aldosterone secretion lateralized were either cured or improved. CONCLUSION: Of the 51 patients with primary aldosteronism who had adrenalectomy (43 patients with adenomas and 8 with hyperplasia), those most likely to be cured were younger and had lower plasma renin activity. In patients with adenomas who were cured or improved, aldosterone secretion was more likely to lateralize. Tests that distinguished adenomas from adrenal hyperplasia included the postural stimulation test, urinary excretion rates of 18-oxocortisol and 18-hydroxycortisol, and adrenal vein sampling.

The association between daily blood pressure and catecholamine variability in normotensive working women.

Using ambulatory blood pressure monitors and timed urine collection techniques, blood pressure and the rates of urinary catecholamine excretion were compared across the work, home, and sleep environments of 45 women who perceived their work environment as most stressful (work stressed) and 35 women who perceived their home environment as equally or more stressful (home stressed) on the day of monitoring. The work-stressed women had higher systolic pressure at work (121 vs. 115; p < 0.05). There were no significant differences in diastolic pressure or the absolute levels of the catecholamines between the groups. However, the percent changes in blood pressure and catecholamines from work or home to sleep were significantly correlated in the work-stressed but not the home-stressed women (r values from 0.25 to 0.45, p < 0.05). The work-stressed and home-stressed women differed in their proportional make-up of several demographic characteristics, including having children (percentage of home-stressed women with children > work-stressed) (p < 0.05), ethnicity (percent of black home-stressed > work-stressed) (p < 0.01), and family history of hypertension (percentage of work-stressed > home-stressed) (0.05 < p < 0.10). These differences, in part, may have determined the daily patterns of perceived stress in the two groups of women. Overall, these findings suggest that work stress and/or the sociodemographic characteristics that may influence the perception of work stress may drive a daylong sympathetic response that increases blood pressure in working women.

The impact of anticipation of job loss on psychological distress and worksite blood pressure.

The impact of occupational stressful life events on psychological distress and blood pressure was examined among employees of a major New York City brokerage firm undergoing massive layoffs. One hundred thirty-nine employees of the firm, who had participated in a blood pressure screening in 1986, were rescreened during the period of layoffs within their company in 1989. About two-thirds of the 139 employees reported being "somewhat" or "very" anxious or upset in 1989 during the period of layoffs, and psychological distress was significantly elevated among those employees reporting possible or definite layoff or job change and/or difficulty in obtaining a comparable job. However, we found no increase in overall blood pressure level, and no effect of anticipation of job loss on 1989 blood pressure when controlling for 1986 blood pressure level, age, body mass index, work hours, and other demographic variables. On the other hand, employment in a department sold to another employer on the day of screening, as well as employment in a clerical job title, were both associated with significant increases in diastolic blood pressure of about 5 mm Hg.

Echocardiographic left ventricular mass and electrolyte intake predict arterial hypertension.

OBJECTIVE: To identify predictors of arterial hypertension. PATIENTS: One hundred thirty-two normotensive adults from a large employed population. METHODS: Echocardiography, standard blood tests, and 24-hour urine collection, at baseline and after an interval of 3 to 6 years (mean, 4.7 +/- 0.8 years). RESULTS: At follow-up, 15 subjects (11%; 7 men, 8 women) had a systolic blood pressure greater than 140 mm Hg or a diastolic blood pressure greater than 90 mm Hg or both (mean, 143 +/- 7 and 87 +/- 6 mm Hg, respectively). At baseline, subjects who developed hypertension had a greater left ventricular mass index than those who did not (92 +/- 25 compared with 77 +/- 19 g/m2 body surface area; P less than 0.005) and higher 24-hour urinary sodium/potassium excretion ratio (3.6 +/- 1.7 compared with 2.6 +/- 1.4; P less than 0.04); there were no differences in race, initial age, systolic or diastolic blood pressure, coronary risk factors, or plasma renin activity. The likelihood of developing hypertension rose from 3% in the lowest quartile of sex-adjusted left ventricular mass index to 24% in the highest quartile (P less than 0.005); a parallel trend was less regular for quartiles of the sodium/potassium excretion ratio (P less than 0.04). In multivariate analyses, follow-up systolic pressures in all subjects and in the 117 who remained normotensive were predicted by initial age, systolic blood pressure, black race, and sex-adjusted left ventricular mass index; final diastolic blood pressure was predicted by its initial value, plasma triglyceride levels, urinary sodium/potassium ratio, low renin activity, black race, and plasma glucose level. CONCLUSIONS: Echocardiographic left ventricular mass in normotensive adults is directly related to the risk for developing subsequent hypertension. Left ventricular mass improves prediction of future systolic pressure, whereas diastolic pressure is more related to initial metabolic status. Black race is also an independent determinant of higher subsequent blood pressure.

The role of behavioral factors in white coat and sustained hypertension.

Studies using ambulatory monitoring of blood pressure have indicated that patients with persistently elevated clinic pressures may be subdivided into two groups, those in whom ambulatory pressure is also elevated (persistent hypertension), and those in whom it is normal (white coat hypertension). The role of behavioral factors in contributing to these two types is discussed. Studies of white coat hypertension suggest that it is not characterized by any generalized physiological abnormality, and that target-organ damage is mild and the prognosis relatively benign. It may represent a conditioned response to the physician. Behavioral factors can significantly influence the diurnal profile of blood pressure, as shown by a comparison of ambulatory pressures recorded on working and non-working days, and in women who experience varying levels of occupational and domestic stress. The role of behavioral factors in the development of sustained hypertension (defined as an upward resetting of the diurnal profile), however, is much less clear. A cross-sectional study of normotensive and hypertensive men has shown that men employed in high-strain jobs are more likely to show a sustained elevation of blood pressure.

A validation study of the instromedix Baro-Graf QD home blood pressure monitor.

The purpose of this study was to assess the accuracy of the Instromedix Baro-Graf QD home blood pressure monitor. Forty subjects were divided among three blood pressure (BP) groups: low (BP less than 110/70, N = 11); medium (BP 110/70 to 140/90, N = 17) and high (BP greater than 140/90, N = 12). Five seated readings were taken per subject. We examined the differences between simultaneous auscultatory and machine readings and assessed the machine's accuracy using ANOVA and correlation analysis. The results show that the device, while highly accurate, tended to become less so as pressure increased. However, its accuracy was superior compared to most other devices we have tested, and because of features, such as a computer memory that stores events and blood pressure over time, this monitor will likely be a useful tool for clinical trials of long term blood pressure change.

The effect of work environments on blood pressure: evidence from seven New York organizations.

The prevalence of hypertension defined according to National Health and Nutrition Examination Survey II (NHANES II) criteria (140/90 mmHg and/or taking antihypertensive medication) was analyzed cross-sectionally at seven worksites in New York City (n = 4274; 2616 men and 1648 women), in order to assess whether exposure to different work environments and occupations contributes to blood pressure variation. The prevalence of hypertension across worksites was 26% among men and 12% among women. Blood pressure was significantly different across worksites even after controlling for known risk factors using analysis of covariance. Of the variation in systolic pressure, 34% was predicted significantly by eight variables; after adjusting for upper-arm circumference, age and body mass index, higher pressures were associated with worksite differences (9.0 mmHg), being male (7.2 mmHg), lacking a high-school education (4.3 mmHg), having a clerical occupation (2.9 mmHg) and being unmarried (1.8 mmHg). Similar results for diastolic pressure suggest that researchers should consider worksite and job characteristics as important predictors of blood pressure differences in working populations.

The relationship between 'job strain,' workplace diastolic blood pressure, and left ventricular mass index. Results of a case-control study.

To determine whether "job strain" (defined as high psychological demands and low decision latitude on the job) is associated with increased workplace diastolic blood pressure and the left ventricular mass index, we conducted a case-control study at seven urban work sites of 215 employed men aged 30 to 60 years without evidence of coronary heart disease. After comprehensive blood pressure screening of male employees (N = 2556) at the work site, 87 cases of hypertension and a random sample of 128 controls were studied. In a multiple logistic regression model, job strain was significantly related to hypertension, with an estimated odds ratio of 3.1, after adjusting for age, race, body-mass index, type A behavior, alcohol intake, smoking, work site, 24-hour urine sodium excretion, education, and physical demand level of the job. Controlling for the above variables in subjects aged 30 to 40 years with job strain, we found that the echocardiographically determined left ventricular mass index was, on average, 10.8 g/m2 greater than in subjects without job strain. We conclude that job strain may be a risk factor for both hypertension and structural changes of the heart in working men.

Do laboratory tests of blood pressure reactivity predict blood pressure changes during everyday life?

This study was undertaken to examine whether blood pressure reactivity measured in the controlled setting of a laboratory could be correlated with blood pressure changes occurring during daily life. The subjects were 164 untreated hypertensives with mild hypertension, all of whom had a 24-hour ambulatory blood pressure recording, during which their activities were unrestricted. One hundred thirteen performed a treadmill exercise test, and 51 performed two active coping tasks (playing a video game or mental arithmetic). Blood pressure was monitored at baseline and during the tasks. Significant correlations were observed between the absolute levels of pressure measured during the laboratory tests and ambulatory monitoring, but these were higher for the active coping tasks (r = 0.53 to 0.75) than the exercise testing (r = 0.26 to 0.46) and were no higher for pressures measured during the tasks than at baseline. Correlations between the changes of blood pressure during the laboratory tasks and the changes occurring during ambulatory monitoring were analyzed in three ways, using simple, multiple, and canonical correlations. In no case were these correlations substantively significant. We conclude that blood pressure reactivity measured in the laboratory may not be readily generalized to changes of pressure in everyday life, as measured by noninvasive ambulatory recorders.