The relationship among breakfast time, morningness-eveningness preference and body mass index in Type 2 diabetes.

AIMS: Obesity is prevalent and related to poor outcomes in Type 2 diabetes. Evening preference and late meal times have been shown to be associated with obesity, but data are lacking in people with Type 2 diabetes. This study examined the relationship among meal timing, morningness-eveningness preference and BMI in Type 2 diabetes, using a mediation analysis. METHODS: Some 210 non-shift workers with Type 2 diabetes participated in the study. Morningness-eveningness preference was assessed using a standard questionnaire, the Composite Scale of Morningness (CSM). Meal timing and daily calorie intake were obtained from 1-day food recall. A mediation analysis adjusting for relevant covariables was performed to explore whether morningness-eveningness had a direct effect on BMI, or whether the effect was mediated through the intermediate variable of meal timing. RESULTS: Mean BMI was 28.4 ± 4.8 kg/m2 . A higher BMI was associated with greater evening preference (P = 0.019), and non-significantly associated with late breakfast time (P = 0.053). BMI was not associated with other mealtimes or calorie intake. In addition, evening preference was associated with late breakfast time (P < 0.001). Mediation analysis revealed that breakfast time mediated the association between morningness-eveningness and BMI, i.e. morning preference (CSM ≥ 45) was associated with earlier breakfast time, and lower BMI by 0.37 kg/m2 [coefficient = -0.365, 95% confidence intervals (CI): -0.877, -0.066), whereas the direct relationship between BMI and morningness-eveningness was non-significant. CONCLUSIONS: Late breakfast time mediated the relationship between morningness-eveningness preference and BMI. These results suggest that circadian preference and meal timing are novel and possibly modifiable risk factors for obesity in Type 2 diabetes.

Serum C3 epimer of 25-hydroxyvitamin D and its determinants in adults: a national health examination survey in Thais.

UNLABELLED: A high percentage have detectable C3 epimer of 25-hydroxyvitamin D3 (3-epi-25(OH)D3) in the population of Thai National Health Examination Survey IV. INTRODUCTION: C3 epimers of vitamin D have recently been shown to contribute significantly to 25-hydroxyvitamin D (25(OH)D) levels in an infant population. However, the findings in the general adult population are unclear. Therefore, the purpose of the present study is to determine the percentage of the C3 epimer of 25(OH)D (3-epi-25(OH)D) and its determinants in an adult population. METHODS: A subsample of 1148 sera randomly selected from the Thai National Health Examination Survey IV (2009) samples were measured for serum 25(OH)D2, 25(OH)D3, 3-epi-25(OH)D2, and 3-epi-25(OH)D3 by LC-MS/MS method. The relative 3-epimer contribution (%) was used to express the amount of 3-epimer-25(OH)D3 as a percentage of total 25(OH)D3 (the sum of 25(OH)D3, and 3-epi-25(OH)D3). RESULTS: A high proportion of subjects had detectable 3-epi-25(OH)D3 that was <10 % of the total 25(OH)D levels. Since the level of total 25(OH)D2 is low, only a minority of subjects had detectable 3-epi-25(OH)D2. Multivariate analysis suggested that age, male gender, and rural residence were independently related to the 3-epi-25(OH)D3/total 25(OH)D3 ratio. CONCLUSIONS: A high percentage of Thai adults had detectable 3-epi-25(OH)D3 that was <10 % of the total 25(OH)D levels. Age, gender, and living in a rural area were associated with the relative amount of 3-epi-25(OH)D3 to total 25(OH)D3.

Causal relationship between the AHSG gene and BMD through fetuin-A and BMI: multiple mediation analysis.

UNLABELLED: Using mediation analysis, a causal relationship between the AHSG gene and bone mineral density (BMD) through fetuin-A and body mass index (BMI) mediators was suggested. INTRODUCTION: Fetuin-A, a multifunctional protein of hepatic origin, is associated with bone mineral density. It is unclear if this association is causal. This study aimed at clarification of this issue. METHODS: A cross-sectional study was conducted among 1,741 healthy workers from the Electricity Generating Authority of Thailand (EGAT) cohort. The alpha-2-Heremans-Schmid glycoprotein (AHSG) rs2248690 gene was genotyped. Three mediation models were constructed using seemingly unrelated regression analysis. First, the ln[fetuin-A] group was regressed on the AHSG gene. Second, the BMI group was regressed on the AHSG gene and the ln[fetuin-A] group. Finally, the BMD model was constructed by fitting BMD on two mediators (ln[fetuin-A] and BMI) and the independent AHSG variable. All three analyses were adjusted for confounders. RESULTS: The prevalence of the minor T allele for the AHSG locus was 15.2%. The AHSG locus was highly related to serum fetuin-A levels (P < 0.001). Multiple mediation analyses showed that AHSG was significantly associated with BMD through the ln[fetuin-A] and BMI pathway, with beta coefficients of 0.0060 (95% CI 0.0038, 0.0083) and 0.0030 (95% CI 0.0020, 0.0045) at the total hip and lumbar spine, respectively. About 27.3 and 26.0% of total genetic effects on hip and spine BMD, respectively, were explained by the mediation effects of fetuin-A and BMI. CONCLUSIONS: Our study suggested evidence of a causal relationship between the AHSG gene and BMD through fetuin-A and BMI mediators.

The relationship of fetuin-A and lactoferrin with bone mass in elderly women.

SUMMARY: The relationships of fetuin-A and lactoferrin to bone-related phenotypes were investigated in elderly women. Fetuin-A was associated not only with bone mineral density (BMD) but also with bone resorption marker suggesting an influence of fetuin-A on osteoclasts. INTRODUCTION: The aim of this study is to investigate the relationship of bone-related phenotypes in elderly women with circulating fetuin-A and lactoferrin. METHODS: Eighty-two elderly women were studied. Serum fetuin-A, lactoferrin, C-terminal telopeptide of type I collagen (CTx), total procollagen type 1 amino-terminal propeptide, and plasma intact parathyroid hormone (PTH) were analyzed. BMD of the lumbar spine at L2-4 and at the femoral neck was measured. RESULTS: Serum fetuin-A was significantly associated with L2-4 BMD (r = 0.23, P < 0.05). After controlling for age and body weight, the association remained statistically significant. There was a significant association between serum fetuin-A and serum CTx (r = -0.37, P < 0.001). The association between fetuin-A and L2-4 BMD no longer existed after controlling for serum CTx. There were positive associations of circulating lactoferrin with plasma PTH (r = 0.24, P < 0.05) and serum CTx (r = 0.26, P < 0.05). No association between serum lactoferrin and BMD at the lumbar spine or femoral neck was detected. CONCLUSIONS: Circulating fetuin-A is related to bone mass and bone resorption markers in elderly women. Lactoferrin, in contrast, is associated only with bone resorption markers.

Association of genetic variations near P2 promoter of the hepatocyte nuclear factor-4alpha gene and insulin secretion index in Thais.

This study was aimed to assess the association of the two single nucleotide polymorphisms (SNPs) near P2 promoter (rs1884614 and rs2144908) of hepatocyte nuclear factor-4alpha (HNF4A) with insulin secretion index and type 2 diabetes in Thais. Participants were categorized into three groups; unrelated type 2 diabetes (N = 219), prediabetes subjects (N = 228), and normal glucose tolerant controls (N = 203). Homeostasis model assessment was calculated for individual insulin secretion and insulin sensitivity index. Genotyping of both SNPs was done by allele-specific PCR technique. Difference of SNP allele frequencies between groups were computed using the chi (2)-statistic. Multivariate regression analysis was performed to determine the effect of SNPs on insulin secretion index. The clinical features of all groups were similar. We demonstrated genotype TT at rs1884614, BMI, and waist circumference were significantly associated with insulin secretion index (P = 0.023) but not with diabetes phenotype.

A comparison of teriparatide and calcitonin therapy in postmenopausal Asian women with osteoporosis: a 6-month study.

OBJECTIVE: The number of hip fractures is expected to double in the next 20 years, with current estimates that Asia will account for 37% of these cases. As bone mineral density (BMD) may be used as a measure of fracture risk, we sought to compare the effects of teriparatide with salmon calcitonin treatment on changes in BMD, biochemical bone markers, and safety in postmenopausal Asian women with osteoporosis. METHODOLOGY: A total of 104 patients (n = 47 teriparatide [20 g/day subcutaneously] and n = 57 calcitonin [100 IU/day subcutaneously]) were enrolled in Hong Kong, Singapore, Philippines, Malaysia, and Thailand. Calcium (> or = 500 mg/day) and vitamin D (200-400 IU/day) supplements were taken throughout the 6-month controlled, randomized study. RESULTS: Teriparatide was associated with a 5.03 +/- 4.77% increase in lumbar spine BMD (p < 0.0001, mean +/- SD change from baseline), whereas changes in lumbar spine BMD for patients on calcitonin were not statistically significant (mean change of 0.36 +/- 4.12%, p = 0.16). Comparison of the two groups indicated that teriparatide treatment improved lumbar spine BMD statistically significantly more than calcitonin (p < 0.0001). No statistically significant changes were observed for total hip or femoral neck BMD. Serum bone-specific alkaline phosphatase (BSAP) increased by 55.9% (median change from baseline, p < 0.0001) in the teriparatide group, and remained stable with calcitonin (5.0% change, p = 0.24); osteocalcin increased by 156.15% (median change from baseline, p < 0.0001) with teriparatide, and decreased with calcitonin (-15.25%, p = 0.03). Similar rates of adverse events were observed, with nausea and dizziness the most commonly reported for both groups (teriparatide versus calcitonin, 13.0% versus 23.2% p = 0.21, 10.9% versus 21.4% p = 0.19, respectively). There were no clinically relevant changes observed in laboratory parameters. CONCLUSIONS: Both treatments were similarly tolerated, however teriparatide was associated with greater increases in lumbar spine BMD and bone formation markers, demonstrating the unique mechanism of action and safety of this treatment for osteoporosis in these Asian women.

Thai Osteoporosis Foundation (TOPF) position statements on management of osteoporosis.

The adjusted incidence rate of hip fracture in Thailand has increased more than 31% from 1997 to 2006. Mortality and morbidity after hip fracture are also high. One year mortality after a hip fracture has increased from 18% in 1999 to 21% in 2007. The Thai Osteoporosis Foundation (TOPF) developed the first Clinical Practice Guideline (CPG) in 2002 and keeps updating the CPG since then. This latest version of the CPG is our attempt to provide comprehensive positional statement on the diagnosis, prevention and treatment of osteoporosis in Thailand. The study group who revised this position statement contains experts from the TOPF, Four Royal Colleges of Thailand, includes the Orthopaedic Surgeons, Gynecologists and Obstetricians, Physiatrists, Radiologists and 2 Associations of Endocrinologists and Rheumatologists which have involved in the management of patients with osteoporosis.

Excessive L-thyroxine therapy decreases femoral bone mineral densities in the male rat: effect of hypogonadism and calcitonin.

Excess thyroid hormone decreases bone mineral density (BMD), a potential problem in managing patients with differentiated thyroid carcinoma and nontoxic goiter who require lifelong TSH-suppressive doses of thyroid hormone. We studied the effect of thyroid hormone excess on vertebral and femoral BMD and the role of hypogonadism in modulating this effect in a rat model. The potential role of calcitonin (CT) in preventing thyroid hormone-associated bone loss was also investigated. A total of 40 male Sprague-Dawley rats were divided into four groups. Groups 1 and 2 were orchidectomized (ORX); groups 3 and 4 were sham operated (SO). Groups 1 and 3 received 20 micrograms intraperitoneal L-thyroxine (L-T4) per 100 g body weight daily for 3 weeks; groups 2 and 4 received vehicle IP. Another 40 rats were divided into four groups. Groups 1 and 2 received L-T4, and groups 1 and 3 received CT, 2.5 U per 100 g body weight, subcutaneously (SC) daily for 3 weeks. BMD of the L4 and 5 and the right femur were measured by dual-energy x-ray absorptiometry at baseline and at the end of the study. Orchidectomy decreased femoral (P < 0.05) but not lumbar BMD. The administration of excess L-T4 decreased femoral (cortical) BMD in both SO (P < 0.05) and ORX rats (P < 0.05) without affecting lumbar (trabecular) BMD. CT increased lumbar BMD in both vehicle (P < 0.001) and L-T4-treated rats (P < 0.001). However, CT did not affect femoral BMD in vehicle-treated rats and did not prevent the L-T4-induced femoral bone loss.(ABSTRACT TRUNCATED AT 250 WORDS)

Etidronate inhibits the thyroid hormone-induced bone loss in rats assessed by bone mineral density and messenger ribonucleic acid markers of osteoblast and osteoclast function.

TSH-suppressive doses of thyroid hormone are associated with bone loss. We have previously reported that L-T4 decreases femoral, but not vertebral bone mineral density (BMD) in rats. As bisphosphonates are able to decrease bone resorption, especially in high bone turnover states, we investigated the potential effects of etidronate disodium (EHDP) on L-T4-induced bone loss in the rat model by assessing BMD and gene expression of osteoblast (osteocalcin, osteopontin, type I collagen, and alkaline phosphatase), osteoclast (tartrate-resistant acid phosphatase), and cell growth (histone) markers in the skeleton. L-T4 administered for 20 days decreased BMD in the femur, but had no effect on the lumbar spine. EHDP alone had no effect on femoral or vertebral BMD, but did prevent the L-T4-induced bone loss in the femur. L-T4 increased mRNA levels of alkaline phosphatase, tartrate-resistant acid phosphatase, and histone H4 in the femur, but not in the vertebrae. EHDP, which alone had no effect on gene expression in the femur or vertebrae, inhibited the effect of L-T4 on mRNA markers in the femur. The results demonstrate that EHDP can prevent the L-T4-induced decrease in femoral BMD in rats that is associated with the prevention of changes in mRNA markers of osteoclast and osteoblast function. EHDP and other bisphosphonate compounds may be useful in the prevention of thyroid hormone-induced bone loss in humans.

Differential responses of femoral and vertebral bones to long-term excessive L-thyroxine administration in adult rats.

Recent studies suggest that thyroid-stimulating hormone suppressive doses of thyroid hormone decrease bone mass in humans and growing rats. To determine the long-term effects of excessive L-thyroxine administration on the femur and vertebrae in an adult rat model, 20 male Sprague-Dawley rats (20 weeks old) were randomized into two groups. Group 1 received L-thyroxine (20 micrograms/100 g body weight ip daily), and group 2 received normal saline ip daily for 20 weeks. Femoral and lumbar vertebral bone mineral density measurements were performed at 0, 6, 15, 18 and 20 weeks of treatment. After 20 weeks of treatment, total RNA was isolated from both femoral and lumbar bones. Northern hybridization was performed with 32P-labeled DNA probes for osteocalcin, osteopontin, alkaline phosphatase and tartrate-resistant acid phosphatase. Significant decreases in bone mineral density in the femur of L-thyroxine-treated rats were observed after 15 weeks (p < 0.03). Lumbar bone mineral density was not affected. Both osteoblast (osteocalcin, osteopontin, alkaline phosphatase) and osteoclast (tartrate-resistant acid phosphatase) gene expression markers were increased significantly in the femoral bone (p < 0.001), but not in the lumbar vertebrae of the L-thyroxine-treated rats. We conclude that long-term administration of excessive doses of L-thyroxine to the adult rat preferentially affects femoral but not vertebral bone. This is manifested by decreased bone mineral density as well as increased gene expression markers for osteoblast and osteoclast activity in the femur.

Tumor necrosis factor-alpha decreases thyrotropin-induced 5'-deiodinase activity in FRTL-5 thyroid cells.

Tumor necrosis factor-alpha (TNF-alpha) exerts various effects on many cell types. Acute administration of TNF-alpha to rats decrease hepatic 5'-deiodinase activity (5'D-I) and TNF-alpha has been implicated in the pathogenesis of the low triiodothyronine syndrome in non-thyroidal illness in humans. The thyroid, liver and kidney are rich in 5'D-I. Unlike hepatic and renal 5'D-I, thyroid 5'D-I is regulated by thyrotropin. We have investigated the effects of TNF-alpha on 5'D-I in FRTL-5 cells, a cultured rat thyroid follicular cell line. Tumor necrosis factor-alpha did not significantly affect basal 5'D-I but thyrotropin markedly increased 5'D-I (p < 0.001). This TSH-induced increase in 5'D-I was attenuated by TNF-alpha in a dose-dependent manner (p < 0.001). Enzyme kinetic analysis demonstrated that thyrotropin increased 5'D-I by increasing Vmax (p < 0.01) without significantly affecting Km. Likewise, TNF-alpha decreased the thyrotropin-induced 5'D-I by decreasing Vmax (p < 0.05) but not Km. The effect of TNF-alpha on thyrotropin-induced 5'D-I in FRTL-5 cells is probably mediated through post-thyrotropin-induced generation of cyclic adenosine monophosphate (cAMP) because TNF-alpha inhibited both dibutyryl cAMP (p < 0.001) and forskolin (p < 0.001)-induced increases in 5'D-I without affecting cAMP generation stimulated by thyrotropin. In conclusion, we have demonstrated that TNF-alpha inhibits thyrotropin-induced 5'D-I activity in FRTL-5 cells by pathways distal to the generation of cAMP and that TNF-alpha may play a role in the modulation of the production of triiodothyronine by the thyroid gland. (ABSTRACT TRUNCATED AT 250 WORDS)

Relation of beta3-adrenergic receptor gene mutation to total body fat but not percent body fat and insulin levels in Thais.

A Trp64Arg mutation in the beta3-adrenergic receptor gene has been implicated in the pathophysiology of non-insulin-dependent diabetes mellitus and obesity. However, the findings have been controversial due to the use of different populations and different methods for the estimation of body fat. In the present study, the prevalence of Trp64Arg mutation of the beta3-adrenergic receptor gene was determined and its relation to body fat as assessed by dual-energy x-ray absorptiometry (DEXA) was evaluated in Thai men and women. The effect on insulin sensitivity as assessed by the serum insulin to glucose ratio was also examined. The subjects were 76 men and 135 women aged 20 to 80 years. Body fat and its regional distribution were assessed by DEXA. Mutation in the beta3-adrenergic receptor gene was determined by polymerase chain reaction (PCR)-restriction fragment length polymorphism. Data are expressed as the mean +/- SEM. Fifty-nine subjects (28.0%) had the Trp64Arg mutation in the beta3-adrenergic receptor gene; 54 (25.6%) were heterozygotes and five (2.4%) were homozygotes. The gene frequency of Trp64Arg mutation was 15.2% in these subjects. In women, Trp64Arg mutation was not associated with the difference in total body fat (Trp/Arg or Arg/Arg, 19.4 +/- 1.0 kg; Trp/Trp, 19.2 +/- 0.6 kg) or percent body fat (Trp/Arg or Arg/Arg, 34.6% +/- 1.2%; Trp/Trp, 34.3% +/- 0.6%). In contrast to the findings in women, men with Trp64Arg mutation had lower total body fat after controlling for age (Trp/Arg or Arg/Arg, 13.2 +/- 1.1 kg; Trp/Trp, 15.8 +/- 0.7 kg; P < .05). However, no difference was found in percent body fat (Trp/Arg or Arg/Arg, 20.9% +/- 1.3%; Trp/Trp, 23.3% +/- 0.7%). No difference in the fasting insulin resistance index (FIRI) was found between subjects with and without Trp64Arg mutation. The data suggest that Trp64Arg mutation of the beta3-adrenergic receptor is common in Thais and appears to exert effects on total body fat but not percent body fat in men. Trp64Arg mutation is not associated with insulin resistance as assessed by the FIRI in Thais.

Effect of estrogen replacement on insulin sensitivity, serum lipid and bone resorption marker in hypogonadal males.

Recent reports of osteoporosis in congenital estrogen deficiency in humans from estrogen resistance or aromatase deficiency have called attention to the importance of estrogen in males. It is the purpose of the present study to evaluate the effects of low- dose estrogen on glucose, lipid and bone metabolism in males with hypogonadism. Nine Thai males with primary or secondary hypogonadism were included in the study. Testosterone was discontinued at least 8 weeks before the study. The subjects received 0.3 mg of conjugated equine estrogen (CEE) daily for 4 weeks. Serum C-terminal telopeptide of type 1 collagen (CTX), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG) and parameters related to insulin sensitivity were measured at baseline and 4 weeks after treatment. Insulin sensitivity was assessed by frequent intravenous glucose tolerance test. The mean age of subjects was 35.77 years (22-70 years). Insulin sensitivity index (SI) did not change significantly after the administration of CEE (P=0.09). Likewise, no change in acute insulin response (AIR(glucose)) was detected. However, glucose effectiveness (SG) significantly decreased after CEE (P<0.05). No significant change in serum TC, LDL-C, HDL-C or TG was detected. In regard to bone turnover, serum CTX significantly decreased after CEE administration (P<0.05). We concluded that low-dose estrogen administration in hypogonadal males for 4 weeks causes a decrease in bone turnover and an increase in glucose effectiveness. No effect on serum lipid concentrations or insulin sensitivity and secretion was detected.

Prevention of postmenopausal bone loss by low and conventional doses of calcitriol or conjugated equine estrogen.

OBJECTIVES: Estrogen deficiency is the most common cause of postmenopausal osteoporosis and estrogen replacement is well known to retard postmenopausal bone loss. Calcium supplement alone is generally considered to be insufficient for the prevention of bone loss associated with estrogen deficiency while the role of calcitriol is unclear. In the present study we examined the efficacy different doses of estrogen or calcitriol in the prevention of postmenopausal bone loss in Thais. METHODS: The subjects consisted of 146 Thai women no more than 6 years postmenopausal. The subjects were randomly allocated to receive 750 mg supplemental calcium alone, calcium and conjugated equine estrogen (CEE) at 0.3 or 0.625 mg, calcium and calcitriol at 0.25 or 0.5 microg daily. Those receiving CEE also took 5 mg medrogestone for 12 days each month. BMD at L2-4 and femoral neck were measured at baseline 1 year and 2 years after treatments. Data were expressed as mean +/- S.E. RESULTS: Subjects on supplemental calcium alone had approximately 2.5% decreases in L2-4 (P < 0.05) and femoral BMD (P < 0.01) at 2 years. CEE (0.3 mg) resulted in 3.20 +/- 1.2% increase in vertebral BMD (P < 0.05) while no significant change in BMD was demonstrated at the femoral neck. Likewise, 0.625 mg of CEE induced 5.4 +/- 1.4% increase in vertebral BMD at 2 years (P < 0.001) without change in the femoral BMD. In regard to calcitriol, no significant change in vertebral or femoral BMD was demonstrated with either 0.25 or 0.5 microg calcitriol. CONCLUSION: We concluded that calcitriol is effective in the prevention of early postmenopausal bone loss in Thais. It represents an option for the prevention of osteoporosis in postmenopausal women who are contraindicated for estrogen replacement.

Differential associations of residual estradiol levels with bone mineral density and serum lipids in postmenopausal women with osteoporosis.

OBJECTIVES: To examine the associations of residual endogenous estradiol (E2) to bone mineral density (BMD) and lipid concentrations in elderly women. METHODS: Subjects consisted of 59 elderly postmenopausal women with vertebral or femoral osteoporosis. BMD was measured at L2-4 and femoral neck by dual-energy X-ray absorptiometry (DEXA). Residual E2 concentrations were assessed by a sensitive radioimmunoassay. Data were expressed as mean +/- S.E.M. RESULTS: The age of the subjects was 65.2 +/- 0.8 years with 18.9 +/- 1.0 years postmenopausal. The mean residual E2 concentration was 6.0 +/- 0.5 pg/ml. There was a correlation between E2 levels and BMD at L2-4 (r = 0.32, P < 0.01) while no association was found at the femoral neck. The association between E2 and L2-4 BMD persisted after adjusting for years since menopause and body weight (r = 0.33, P < 0.05). With regard to serum lipid concentrations, no association of serum total cholesterol, LDL-cholesterol, HDL-cholesterol or triglyceride concentrations with residual E2 was found. CONCLUSIONS: Our findings confirm the role of residual endogenous E2 in the determination of bone mass in postmenopausal women with osteoporosis. The effect of residual E2 appears to be skeletal specific and possess no association with serum lipid concentrations.

Change in body weight after hormone replacement therapy in postmenopausal women is dependent on basal circulating leptin.

OBJECTIVE: To address the effect of leptin in the modulation of change in body weight after hormone replacement therapy (HRT), we prospectively examined the responses of body weight and serum leptin after estrogen-progestin replacement in postmenopausal women. PATIENTS: Subjects consisted of 63 postmenopausal women aged 54-82 years on HRT for osteoporosis. DESIGN: Thirty three of the subjects received 0.3 mg of conjugated equine estrogen (CEE) (group 1) while 30 were on 0.625 mg of CEE daily (group 2). All subjects also took 5 mg of medrogestone acetate and 750 mg elemental calcium supplement daily. MEASUREMENTS: Fasting serum leptin was measured by RIA at baseline, 1 and 3 months after treatment. Data were expressed as mean +/- S.E.M. RESULTS: Serum leptin was highly related to body weight both at baseline (r = 0.40, P < 0.001) and after 3 months of HRT (r = 0.42, P < 0.001). When divided the subjects into three equal groups according to baseline leptin levels, it was found that serum leptin significantly decreased in subjects with high baseline leptin at 3 months (-9.4 +/- 5.7%, P < 0.05) while it increased in subjects whose baseline leptin levels were in the lowest tertile at 1 month (33.2 +/- 8.3%, P < 0.001) and 3 month (27.8 +/- 8.3%, P < 0.01). In regards to body weight, those with leptin in the highest tertile demonstrated a reduction of body weight at 3 (-1.9 +/- 0.6%, P < 0.05) and 12 months (-3.2 +/- 0.5%, P < 0.05) after HRT while those whose serum leptin levels were in the lowest and middle tertiles did not demonstrate change in body weight. By repeated measured analysis of variance, it was found that the decrease in body weight in subjects with high serum leptin was independent of the doses of estrogen. CONCLUSION: Postmenopausal hormone replacement does not cause weight gain. However, it results in a small reduction in body weight particularly in subjects with higher basal leptin concentrations.

Diabetes insipidus: another cause of hormonal hyperthermia.

Diabetes insipidus is not generally recognized as a possible cause of etiologically obscure fever. We describe a female patient who presented with fever and polyuria and was shown to have idiopathic partial neurogenic diabetes insipidus. The fever was subsequently demonstrated to be caused by diabetes insipidus per se. The mechanism for the production of fever in this patient was most likely a defect in peripheral heat dissipation secondary to inadequate hydration. We conclude that diabetes insipidus is another cause of hormonal hyperthermia and should be considered in the differential diagnosis of etiologically obscure fever.

Effect of TSH-suppressive doses of levothyroxine on bone mineral density in Thai women.

Thyroid hormone stimulates both osteoblast and osteoclast. However, the effect on osteoclast exceeds that of osteoblast resulting in a decrease in bone mass. TSH-suppressive doses of levothyroxine (L-T4) with otherwise normal thyroid function, so-called subclinical hyperthyroidism, has been reported to cause a reduction in bone mass. However, the sites of bone loss vary among studies. Moreover, the effect of menopausal status on thyroid-hormone-induced bone loss is inconclusive. Ethnic and geographical differences may modify the skeletal response to thyroid hormone. In the present study, we looked at the effect of TSH-suppressive doses of L-T4 on bone mineral density (BMD) in Thai pre- and post-menopausal women. Subjects consisted of 27 Thai females aged between 23-79 years. Eighteen were premenopausal and nine were postmenopausal. All were attending the Thyroid Clinic at Ramathibodi Hospital and had been on at least 150 micrograms/day of L-T4 for the treatment of nodular thyroid diseases for more than 2 years with at least one TSH value during the follow-up period in the suppressive range. None of the subjects had a previous history of Graves' disease. BMD was determined by dual-energy X-ray absorptiometry. Data of 54 age-matched healthy controls were used for comparison. BMD values were converted to Z-scores before analyses. Data were expressed as mean +/- SEM. Compared to controls, postmenopausal women on long-term L-T4 had decreased BMD at anteroposterior spine (-0.69 +/- 0.20 vs 0.05 +/- 0.17, P < 0.01), femoral neck (-0.61 +/- 0.35 vs 0.18 +/- 0.24, P < 0.05), femoral trochanter (-0.64 +/- 0.37 vs 0.13 +/- 0.22, P < 0.05) but not at Ward's triangle. In contrast to the findings in postmenopausal women. there was no significant difference of BMD compared to controls in premenopausal women at the lumbar spine, Ward's femoral neck or femoral trochanter. We conclude that Thai postmenopausal women on long-term TSH-suppressive doses of L-T4 have reduced BMD at various skeletal sites which may increase fracture risks. TSH-suppressive doses of thyroid hormone should only be prescribed when appropriate and no longer than necessary to minimize this adverse effect of excessive doses of thyroid hormone on bone.

Serum vitamin D, parathyroid hormone and biochemical markers of bone turnover in normal Thai subjects.

The sera from 158 healthy Thai volunteers (77 males and 81 females), aged 20-80 years, were studied. The vitamin D status, parathyroid gland activity and the magnitude of bone turnover were assessed by measurement of serum 25-hydroxycholecalciferol (25-OH-D), intact parathyroid hormone (N-tact-PTH), osteocalcin and alkaline phosphatase. The mean serum 25-OH-D, N-tact-PTH, osteocalcin and alkaline phosphatase concentrations in men were 67.4 +/- 31.6 (S.D.) [Range (R): 20.6-147.1 ng/ml], 23.3 +/- 10.3 (R: 5.6-56.6 pg/ml) 3.4 +/- 1.5 (R: 1.2-10.5 ng/ml), and 19.9 +/- 6.6 (R: 7.5-35.7 IU/L), respectively, and the mean levels in women were 42.4 +/- 23.9 (R: 13.8-127.8 ng/ml), 26.1 +/- 11.3 (R: 10.5-68.7 pg/ml), 3.7 +/- 2.1 (R: 0.5-11.5 ng/ml), and 19.5 +/- 6.0 (R: 9.1-41.5 IU/L), respectively. There is no evidence of vitamin D deficiency in ambulatory elderly Thais. Serum N-tact PTH increased with advancing age in both men and women whereas increasing serum osteocalcin and alkaline phosphatase with age were observed only in women. In addition, serum alkaline phosphatase correlated to serum osteocalcin only in women suggesting an increase in bone turnover after menopause. These basic data would be useful for the study of metabolic bone diseases in Thai population.