Differences in bone mineral density and lifestyle factors of postmenopausal women living in Bangkok and other provinces.

Decreased bone mineral density (BMD) with age is an increasing health problem, especially for postmenopausal women. Multiple factors have been reported to affect BMD including both genetic and environmental factors such as calcium intake and physical activity. For Thailand, people residing in different regions may differ in BMD due to these factors. However, there is a paucity of data concerning this issue. The objectives of this study were to identify the lifestyle factors which may influence BMD and to investigate the association between BMD and these factors in postmenopausal women who have been living in Bangkok and other provinces in Thailand. Subjects consisted of 466 postmenopausal women aged 46-90 years including 236 Bangkokians (116 early postmenopausals and 120 late postmenopausals) and 230 non-Bangkokians (134 early postmenopausals and 96 late postmenopausals). All were healthy and ambulatory. BMD was measured by dual energy X-ray absorptiometry (DEXA, Expert XL). Calcium intake was assessed by food-frequency questionnaire. Data were expressed by mean + /- SEM. There were 22 per cent (n=52), 5.9 per cent (n=14), and 4.2 per cent (n=10) of postmenopausal Bangkokians while 13.9 per cent (n=32), 4.3 per cent (n=10), and 2.2 per cent (n=5) of postmenopausal non-Bangkokians who had low BMD at spine, femoral neck, and at both sites, respectively. Spine BMD (SPBMD) and femoral neck BMD (FNBMD) increased significantly across the quartiles of calcium intake in both groups of subjects (P<0.05) and a significant difference was found between the lowest and the highest quartiles of calcium intake (P<0.05). Moreover, BMD at both regions was shown to be correlated with calcium intake, exercise and sunlight exposure in these subjects (P<0.001). Further analysis revealed higher BMD at spine (0.992 + 0.02 vs 0.945 +/- 0.02 g/cm2, P<0.05) and at femur (0.780 +/- 0.01 vs 0.740 +/- 0.01 g/cm2, P<0.05), calcium intake (348.9 +/- 12.7 vs 316.3 +/- 8.0 mg/day, P<0.05), exercise (2.8 +/- 0.1 vs 2.4 +/- 0.1 h/wk, P<0.001) and sunlight exposure (2.9 +/- 0.06 vs 1.9 +/- 0.04 h/day, P<0.001) were found in late postmenopausal women in other provinces than their counterparts in Bangkok. Nevertheless, no significant difference of BMD at both sites, calcium intake and exercise was found in the early postmenopausal groups of these two areas. CONCLUSIONS: There were significant differences in BMD and lifestyle factors between late postmenopausal women in Bangkok and other provinces. Environmental factors especially calcium intake, exercise and sunlight exposure, may influence BMD in late postmenopausal Thai women.

A simple prediction rule and a neural network model to predict pancreatic beta-cell reserve in young adults with diabetes mellitus.

In the present study we developed and assessed the performance of a simple prediction rule and a neural network model to predict beta-cell reserve in young adults with diabetes. Eighty three young adults with diabetes were included in the study. All were less than 40 years old and without apparent secondary causes of diabetes. The subjects were randomly allocated to 2 groups; group 1 (n = 59) for developing a prediction rule and training a neural network, group 2 (n = 24) for validation purpose. The prediction rule was developed by using stepwise logistic regression. Using stepwise logistic regression and modification of the derived equation, the patient would be insulin deficient if 3(waist circumference in cm) + 4(age at diagnosis) < 340 in the absence of previous diabetic ketoacidosis (DKA) or < 400 in the presence of previous DKA. When tested in the validation set, the prediction rule had positive and negative predictive values of 86.7 per cent and 77.8 per cent respectively with 83.3 per cent accuracy while the ANN model had a positive predictive value of 88.2 per cent and a negative predictive value of 100 per cent with 91.7 per cent accuracy. When testing the performance of the prediction rule and the ANN model compared to the assessment of 23 internists in a subgroup of 9 diabetics whose age at onset was less than 30 years and without a history of DKA, the ANN had the highest ability to predict beta-cell reserve (accuracy = 88.9), followed by the prediction rule (accuracy = 77.8%) and assessments by internists (accuracy = 60.9%). We concluded that beta-cell reserve in young adults with diabetes mellitus could be predicted by a simple prediction rule or a neural network model. The prediction rule and the neural network model can be helpful clinically in patients with mixed clinical features of type 1 and type 2 diabetes.

Diabetes mellitus in young Thai adults.

The purposes of the present study were to 1) find the prevalence of various types of diabetes; 2) determine the prevalence of glutamate decarboxylase autoantibody (anti-GAD) and 3) identify clinical characteristics which may help in predicting insulin deficiency in young Thai adults with diabetes. Subjects consisted of 93 adults with diabetes mellitus aged 15-40 years. In each subject, basal and post glucagon C-peptide levels were determined by radioimmunoassay. Anti-GAD was measured by radioimmunoassay and mitochondrial 3243 tRNA(Leu(UUR)) gene mutation was detected by PCR-RFLP. Data were expressed as mean +/- SEM. The mean age of subjects was 31.0 +/- 0.7 years with age at diagnosis of 25.6 +/- 0.9 years. Thirty nine (41.9%) were males and 54 (58.1%) were females. Pancreatic calcification was found in 7 (7.5%) of the patients while 2 (2.2%) were identified as having Wolfram syndrome. Four (4.3%) had nonketotic diabetes with affected family members in multiple generations consistent with MODY. Mitochondrial 3234 tRNA(Leu(UUR)) gene mutation was detected in only one patient. After excluding 14 subjects with pancreatic calcification, Wolfram's syndrome, MODY or mitochondrial gene mutation, 45 (57.0%) were found to be insulin-deficient and 34 (43.0%) were insulin-sufficient based on post-glucagon C-peptide levels. Using stepwise logistic regression analysis, it was found that younger age at diagnosis (p<0.001), smaller waist circumference (p<0.01), previous history of DKA (p<0.01) was significantly associated with insulin deficiency. After excluding patients with DKA, younger age at diagnosis of diabetes (p<0.05) and lower BMI (p<0.01) were related to insulin deficiency. Concerning the role of autoimmunity, it was found that 13 (28.3%) of insulin-deficient subjects were positive for anti-GAD while 4 (11.8%) of those who were insulin-sufficient had positive results. Of the 54 patients currently on insulin, 42 (77.8%) are insulin deficient and 14 (25.9%) have positive anti-GAD. There were 10 (18.5%) who were both insulin sufficient and negative for anti-GAD suggesting that insulin therapy may not be required. We concluded that about half of young Thai adults with diabetes are not insulin-deficient and treatment with insulin may be unnecessary. The prevalence of glutamate decarboxylase antibody and mitochondrial 3234 tRNA(Leu(UUR)) gene mutation is low and as yet undefined factors are accountable for insulin deficiency in a significant number of patients.

Correlation of apolipoprotein E gene polymorphism to serum lipid concentrations in healthy Thais.

This study determined the genotype distribution of apolipoprotein E (apo E) gene and its relation to serum lipids in 217 healthy Thais consisting of 79 males and 138 females. Serum total cholesterol (TC), HDL-cholesterol (HDL-C) and triglyceride (TG) concentrations were determined by enzymatic-colorimetric methods, while serum LDL-cholesterol (LDL-C) levels were calculated using Friedewald formula. Apo E genotypes were determined by PCR-RFLP. Out of 217 subjects, apo E genotype frequencies were 5.5 per cent for E2/E2, 12.4 per cent for E2/E3, 81.1 per cent for E3/E3 and 0.9 per cent for E4/E4. In men, advancing age was associated with increased serum TC (r = 0.28, P < 0.05) and LDL-C (r = 0.27, P < 0.01). Subjects having the E2 allele had lower TC (r = -0.27, P < 0.05) and LDL-C. (r = -0.25, P < 0.05). Age and apo E genotypes were not associated with HDL-C and TG in men. In women, increasing age was related to higher serum TC (r = 0.45, P < 0.001), LDL-C (r = 0.44, P < 0.001), TG (r = 0.40, P < 0.001) and lower HDL-C (r = -0.36, P < 0.001). The presence of E2 allele was related to lower TC (r = -0.24, P < 0.001), LDL-C (r = -0.26, P < 0.001), TG (r = -0.15, P < 0.05) and higher HDL-C (r = 0.20, P < 0.01) independent of age and menopausal status. We concluded that the epsilon 4 allele of apo E gene is rare in Thais. The presence of the epsilon 2 allele is associated with a more favorable lipid profile and there is a sexual dimorphism concerning the effect of apo E genotype on serum HDL-C and TG.

Renal osteodystrophy in Ramathibodi Hospital: histomorphometry and clinical correlation.

The spectrum and clinical relevance of renal osteodystrophy in Thai dialysis patients are unknown. A study was conducted on the prevalence and clinico-pathological correlation of renal osteodystrophy in chronic dialysis patients who attended Ramathibodi Renal Transplant Clinic between September 1996 and March 1998. All possible volunteers were enrolled irrespective of musculoskeletal symptoms. Fifty six dialysis patients, including 17 (30.4%) CAPD and 39 (69.6%) hemodialysis patients, participated in this study. Serum calcium, phosphate, iPTH, and bone specific alkaline phosphatase were determined. Transiliac crest bone specimens were measured with an average of 30 fields/specimen by a specific computer program for bone histomorphometry (Osteomeasure), and were also studied for dynamic by double tetracycline label. Bone mineral density (BMD) was also determined by DEXA scan. The type of bone pathology was based on Fournier's criteria for renal osteodystrophy. The mean +/- SEM for age was 45.52 +/- 1.74 years, dialysis duration 42.26 +/- 5.54 (range 1-156) months, calcium phosphate product 52.31 +/- 2.77, and iPTH 307.73 +/- 62.04 pg/ml. The following types of renal osteodystrophy were found: adynamic bone 23 (41.1%), hyperparathyroid 16 (28.6%), mixed type 11 (19.6%), mild lesion 3 (5.4%), osteomalacia 2 (3.6%), and osteosclerosis 1 (1.8%) cases. Two cases of aluminum related bone disease were found. The distribution of different bone diseases was not affected by mode of dialysis or vitamin D supplement, but it was affected by dialysis duration. High turnover bone diseases were associated with longer dialysis duration (63.19 +/- 8.9 vs 23 +/- 4.73 months), higher iPTH (541.53 +/- 109.32 vs 87.77 +/- 15.76 pg/ml), and higher bone specific alkaline phosphatase (25.43 +/- 5.04 vs 9.62 +/- 1.34 mg/ml) when compared to low turnover bone diseases, p < 0.05. Intact PTH of greater than 200 pg/ml was a good predictor for high turnover bone diseases (74% sensitivity and 96% specificity). BMD at torch and wards areas varied inversely with dialysis duration (r = -0.3 and r = -0.4, respectively; p < 0.05). Chronic dialysis patients had a greater tendency of bone loss compared to the general Thai population. There was no difference in BMD between CAPD and hemodialysis patients or different types of bone lesions. CONCLUSION: Significant bone diseases are common among Thai chronic dialysis patients. Adynamic bone disease is the most common bone lesion followed by hyperparathyroid and mixed type. The spectrum of bone diseases is affected mainly by dialysis duration. Intact PTH is a good predictor of high turnover bone disease. Greater bone loss than in the general population is common in our patients and is also accentuated by longer dialysis duration.

Correlation between serum insulin and features of metabolic syndrome in Thais.

Several clinical and metabolic abnormalities, i.e. central obesity, hypertension, impaired glucose tolerance or diabetes and dyslipidemia often cluster together and are commonly found in patients with atherosclerotic cardiovascular disease. Hyperinsulinemia and insulin resistance are often evident in subjects with these metabolic abnormalities, so called insulin resistance or metabolic syndrome. In the present study, we looked into the correlations between serum insulin or index of insulin sensitivity and various clinical and metabolic abnormalities. Subjects consisted of 103 males and 118 females. Oral glucose tolerance test was performed on all subjects. Homeostasis model assessment of insulin sensitivity (HOMA-S) was used to determine insulin sensitivity. In males, HOMA-S was found to be significantly correlated with BMI, plasma glucose, insulin, triglycerides and waist circumference. Male subjects in the highest quartile of HOMA-S also had significantly higher systolic blood pressure compared to those in the lowest quartile. In females, HOMA-S was significantly correlated with BMI, blood pressure, plasma glucose, insulin, triglycerides, HDL-cholesterol, waist circumferences and waist-hip ratio. However, after adjustment for BMI, correlation between HOMA-S and blood pressure in women was no longer statistically significant. We, therefore, concluded that correlations between serum insulin or index of insulin sensitivity with certain metabolic abnormalities also existed in Thai subjects. Some of these correlations seem to be at least in part dependent on obesity.

Serum leptin concentrations in relation to body fat, gender, sex hormones and metabolic covariates in Thais.

In the present study, the relation of serum leptin to adiposity, gender and metabolic covariates in normal Thais was examined. Subjects consisted of 224 individuals aged between 20-79 years. Eighty two were men while 142 were women. Data were expressed as mean +/- SEM. Serum leptin was associated with total body fat assessed by dual-energy X-ray absorptiometry in both men (r = 0.80, P < 0.0001) and women (r = 0.73, P < 0.0001). Compared to women, serum leptin concentrations was lower in men (P < 0.0001). The difference still persisted after controlling the adiposity. Compared to premenopausal women, postmenopausal women had higher serum leptin independent of adiposity (P < 0.0001). In men, serum free testosterone was negatively associated with serum leptin (r = -0.36, P < 0.001) while there was no association between serum estradiol and leptin. The relation between serum FT and leptin in men no longer persisted after controlling for adiposity. Body fat was associated with fasting insulin levels in both men (r = 0.26, P < 0.05) and women (r = 0.18, P < 0.05). However, the association between fasting insulin levels and body fat in both men and women no longer existed after adjusting for leptin. We concluded that serum leptin concentrations are associated with total body adiposity and serum leptin may mediate the effect of body fat on insulin sensitivity. There appears to be a sexual dimorphism of serum leptin unrelated to sex hormone status and the amount of body fat.

Impediment of the progressions of microalbuminuria and hyperlipidemia in normotensive type 2 diabetes by low-dose ramipril.

In a randomized, double-blind, placebo-controlled study, we investigated in normotensive type 2 diabetics with microalbuminuria the effect of ramipril, an ACE inhibitor, on urine albumin excretion and serum lipids. A total of 1,882 patients were screened for urine microalbumin consecutively by dipstick test, Rapi Tex-Albumin test and RIA. The final 28 normotensive and microalbuminuric patients were assigned to receive either ramipril (1.25 mg/d, n = 16) or placebo (n = 12) for 12 weeks. Throughout the study, both groups had no changes in blood pressure, fasting plasma glucose, HbA1C, serum creatinine and electrolytes and no difference in creatinine clearance. At week 12 only the placebo group showed the significant increment of urine albumin excretion and triacylglycerol (30.6 +/- 38.3 to 39.0 +/- 19.7 and 167 +/- 64 to 208 +/- 77 mg/dl, respectively) but the decrement of HDL-cholesterol (46 +/- 16 to 35 +/- 6 mg/dl). During a 3 month period, increased urine albumin excretion was observed in normotensive type 2 diabetes with microalbuminuria who received only placebo. We conclude that ramipril may arrest the progression of albumin excretion and had favorable effects on serum lipids. Ramipril was safe and well-tolerated without untoward side effects during the study period.

Prediction of low bone mineral density in postmenopausal women by artificial neural network model compared to logistic regression model.

Measuring bone mineral density (BMD) is currently the best modality to diagnose osteoporosis and predict future fractures. The use of risk factors to predict BMD and fracture risk has been considered to be inadequate for precise diagnostic purpose, but it may be helpful as a screening tool to determine who actually needs BMD assessment. Recently, artificial neural network (ANN), a nonlinear computational model, has been used in clinical diagnosis and classification. In the present study, we evaluated the risk factors associated with low BMD in Thai postmenopausal women and assessed the prediction of low BMD using an ANN model compared to a logistic regression model. The subjects consisted of 129 Thai postmenopausal women divided into 2 groups, 100 subjects in the training set and the remaining 29 subjects in the validation set. The subjects were classified as having either low BMD or normal BMD by using BMD value 1 SD lower than the mean value of young adults as the cutoff point. Decreased body weight, decreased hip circumference and increased years since menopause were found to be associated with low BMD at the lumbar spine by logistic regression. For the femoral neck, increased age and decreased urinary calcium were associated with low BMD. The models had a sensitivity of 85.0 per cent, a specificity of 11.1 per cent and an accuracy of 62.0 per cent for the diagnosis of low BMD at the lumbar spine when tested in the validation group. For the femoral neck, the sensitivity, specificity and accuracy were 90.5 per cent, 12.5 per cent, and 69.0 per cent, respectively. Models based on ANN correctly classified 65.5 per cent of the subjects in the validation group according to BMD at the lumbar spine with a sensitivity of 80.0 per cent and a specificity of 33.3 per cent while it correctly classified 58.6 per cent of the subjects at the femoral neck with a sensitivity of 76.2 per cent and a specificity of 12.5 per cent. There was no significant difference in terms of accuracy, sensitivity and specificity in the prediction of low BMD at the lumbar spine or the femoral neck between ANN model and logistic regression model. We concluded that ANN does not perform better than convention statistical methods in the prediction of low BMD. The less than perfect performance of the prediction rules used in the prediction of low BMD may be due to the lack of adequate association between the commonly used risk factors and BMD rather than the nature of the computational models.

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.

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.