Gobchai Puavilai

Diagnostic criteria for diabetes mellitus and other categories of glucose intolerance: 1997 criteria by the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus (ADA), 1998 WHO Consultation criteria, and 1985 WHO criteria

To compare 1997 ADA diagnostic criteria for diabetes mellitus and other categories of glucose intolerance/1998 WHO Consultation criteria versus 1985 WHO criteria, we analyzed data from a 75-g oral glucose tolerance test (OGTT) performed on 1051 high-risk subjects without medical history of diabetes at Diabetes Screening Clinic, Ramathibodi Hospital, Thailand. There were 372 males and 679 females, aged (mean +/- S.D.) = 50.3 +/- 12.55 years, BMI = 25.62 +/- 4.39 kg/m2. If fasting plasma glucose (FPG) was used as recently recommended then 54.1, 20.4, and 25.5% of cases were classified as normal, impaired fasting glucose (IFG), and diabetic, respectively. In diagnosing diabetes using a full OGTT based on the 1985 WHO criteria as the reference test, FPG > or = 7 mmol/l had a sensitivity of 57.7%, specificity of 97.4%, positive predictive value of 94.0%, and negative predictive value of 76.4%; 53.7% of subjects with IFG had 2-h plasma glucose > or = 11.1 mmol/l. The 1997 ADA/1998 WHO Consultation criteria and 1985 WHO criteria for a full OGTT yield similar overall results. FPG ( > or = 7 mmol/l) was not sensitive for diagnosing diabetes. Moreover, about half of the subjects with IFG were actually diabetic. Therefore, OGTT remains a valuable test in diagnosing diabetes and classifying various categories of glucose intolerance.

Oestrogen-receptor-α gene polymorphism affects response in bone mineral density to oestrogen in post-menopausal women

An oestrogen‐receptor‐α (ERα) gene polymorphism has been variably reported to be related to bone mass. To investigate whether this ERα gene polymorphism is associated with a functional difference, we assessed the response in bone mineral density (BMD) to oestrogen therapy in post‐menopausal women in relation to ERα gene polymorphism.

Serum testosterone and its relation to bone mineral density and body composition in normal males

OBJECTIVE Bone mineral density (BMD) declines with age in both men and women, predisposing the elderly to osteoporosis and fractures. Although there are extensive data about post‐menopausal osteoporosis, there is relatively little information concerning the decrease in BMD with age in normal men, particularly the contribution of declining gonadal function with age to BMD. In the present study, we investigated the effect of age on the pituitary‐gonadal axis in normal males and its relation to BMD and body composition.

Risk of calcium oxalate nephrolithiasis after calcium or combined calcium and calcitriol supplementation in postmenopausal women

Abstract: Although calcium supplementation can cause hypercalciuria, the risk of nephrolithiasis has been shown to decrease rather than increase among subjects who had a higher calcium intake. Hypercalciuria is also a well-established side effect of calcitriol administration. However, the risk of nephrolithiasis is not well defined. The present study was undertaken to prospectively determine the effect of calcium with or without calcitriol on physicochemical risk factors associated with calcium oxalate nephrolithiasis in Thai postmenopausal women with osteoporosis. Subjects consisted of 53 Thai women more than 10 years postmenopausal who were randomly allocated to receive 750 mg of calcium carbonate supplement alone (n= 28) or 750 mg of calcium carbonate plus 0.5 mg calcitriol (n= 25) daily. Mean ± SEM for age was 65.3 ± 1.1 years, body weight 53.5 ± 1.3 kg. Urine samples for biochemical assays were collected at baseline and 3 months after treatment. Supersaturation for calcium oxalate stone formation was assessed from the 24 h urine constituents by the Tiselius’s index, AP(CaOx). Three months of calcium supplement alone resulted in a modest, but not significant, increase in urinary calcium (baseline, 2.90 ± 0.43 mmol/day; after treatment 3.58 ± 0.54 mmol/day) with no change in urinary oxalate, citrate or magnesium. In contrast, calcium together with calcitriol caused a significant increase in urinary calcium (baseline, 2.87 ± 0.41 mmol/day; after treatment, 4.08 ± 0.57 mmol/day; p<0.05). No significant change in other urine constituents after treatment with calcium and calcitriol was detected. Therefore, AP(CaOx) did not significantly increase either after calcium alone (baseline, 1.17 ± 0.39; after treatment, 1.36 ± 0.28) or after calcium plus calcitriol (baseline, 1.09 ± 0.17; after treatment, 1.09 ± 0.19). However, after treatments, 12 subjects (23%) – 6 receiving calcium supplement alone and 6 receiving calcium plus calcitriol supplement – had high AP(CaOx) values (greater than the upper limit of 95% CI for AP(CaOx) derived from non-stone-forming Thai women). The post-treatment/baseline ratio was 3.21 ± 0.74 for urinary calcium, 1.01 ± 0.19 for urinary oxalate, and 2.23 ± 0.42 (median 1.15) for AP(CaOx). The post-treatment/baseline ratio of calcium, but not for urinary oxalate, had a significant correlation with the post-treatment/baseline ratio of AP(CaOx). Our findings suggest that the alteration in the risk of calcium oxalate nephrolithiasis based on urinary composition is related to the alteration in urinary calcium. The risk of calcium oxalate nephrolithiasis does not increase significantly after calcium or combined calcium and calcitriol supplement in the majority of postmenopausal women with osteoporosis.

Vitamin D receptor gene polymorphism is associated with urinary calcium excretion but not with bone mineral density in postmenopausal women

Polymorphism of vitamin D receptor (VDR) gene has been found to be associated with serum osteocalcin (OC) levels and bone mineral density (BMD) in Caucasian identical twins and unrelated postmenopausal women. Being ethnically different and living in a geographic area with adequate vitamin D status due to abundant sunshine exposure, it is unclear whether VDR gene polymorphism will affect bone mass in Thai population. In the present study, we investigated the association between VDR gene polymorphism and bone metabolism in Thai postmenopausal women. Subjects consisted of 84 postmenopausal women. Bsm I, Taq I and Apa I polymorphisms of VDR gene were determined by PCR-RFLP. B, T and A represent the absence of the corresponding restriction sites while b, t and a indicate the presence of the restriction sites. Data were expressed as mean ± SE. Sixty-six subjects (78.6%) had bb genotype while 18 (21.4%) had Bb genotype. None of the subjects was found to have BB genotype. Taq I restriction site was in linkage disequilibrium to the Bsm I site. For Apa I polymorphism, 33 (39.3%), 42 (50.0%) and 9 (10.7%) of the subjects had aa, Aa and AA genotypes, respectively. There was no significant difference in serum intact OC levels and BMD at various skeletal sites among subjects with different genotypes. Despite the lack of difference in BMD and intact OC levels, subjects with bb genotype had higher 24-hour urinary calcium excretion than those with Bb genotype (bb, 6.1 ±0.3 mmol/day; Bb, 4.4±0.6 mmol/day; p<0.05). The effect of Bsm I VDR genotype was still significant (p<0.05) after dietary calcium intake was controlled using analysis of covariance. Despite the difference in urinary calcium levels, there was no significant difference in fractional excretion of calcium among subjects with different Bsm I-related genotypes, suggesting that the effect of the VDR gene polymorphism on urinary calcium excretion is more likely due to the effect on intestinal calcium absorption rather than renal tubular calcium reabsorption. We conclude that VDR genotype distributions in Thai postmenopausal women are different from those reported in Caucasians. VDR gene polymorphism does not appear to be associated with BMD or bone turnover in Thai postmenopausal women. However, Bsm I VDR polymorphism may have physiologic role in calcium homeostatasis by modulating intestinal calcium absorption.

Risk of calcium oxalate nephrolithiasis in postmenopausal women supplemented with calcium or combined calcium and estrogen

BACKGROUND Recent studies showed that postmenopausal women lost less bone mass when supplemented with calcium or estrogen therapy. However, the safety of the treatments in terms of the risk of calcium oxalate stone formation is unknown. We therefore conducted this study to determine the alteration in calcium oxalate supersaturation after calcium supplement or after combined calcium and estrogen therapy in postmenopausal osteoporotic women. METHODS Fifty-six postmenopausal women were enrolled in this study. All subjects were more than 10 years postmenopausal with vertebral or femoral osteoporosis by bone mineral density criteria. They were randomly allocated to receive either 625 mg of calcium carbonate (250 mg of elemental calcium) at the end of a meal three times a day (group A, n=26) or calcium carbonate in the same manner plus 0.625 mg/day of conjugated equine estrogen and 5 mg medrogestone acetate from day 1-12 each month (group B, n=30). The age (mean +/- S.E.M.) was 66.3 +/- 1.2 and 65.1 +/- 1.1 years, weight 54.1 +/- 1.2 and 55.3 +/- 2.1 kg, in group A and group B, respectively. Urine specimens (24-h) were collected at baseline and 3 months after treatment for the determination of calcium oxalate saturation by using Tiseliuss index (AP(CaOx)) and calcium/citrate ratio. RESULTS After 3 months of treatment, there was no significant alteration from baseline for urinary excretion of calcium, citrate and oxalate. Urinary phosphate excretion was significantly reduced (6.3 +/- 0.7 vs. 5.1 +/- 0.7 mmol/day for group A and 8.2 +/- 0.9 vs. 5.8 +/- 0.7 mmol/day for group B, P<0.05), whereas net alkaline absorption was significantly elevated (10.1 +/- 3.6 vs. 20.1 +/- 4.4 meq/day for group A and 4.8 +/- 3.2 vs. 19.9 +/- 3.6 meq/day for group B, P<0.05). Calcium/citrate ratio and AP(CaOx) determined at baseline were not different from the corresponding values after treatment in both groups; calcium/citrate: 10.1 +/- 3.1 vs. 10.1 +/- 2.5 for group A and 9.3 +/- 1.8 vs. 11.9 +/- 2.5 for group B and AP(CaOx): 1.1 +/- 0.1 vs. 1.3 +/- 0.2 for group A and 1.2 +/- 0.2 vs. 1.1 +/- 0.1 for group B. There were eight and nine patients with high AP(CaOx), or >2, at baseline and after treatment, respectively. CONCLUSIONS Calcium supplement with a meal or combined calcium supplement and estrogen therapy is not associated with a significant increased risk of calcium oxalate stone formation in the majority of postmenopausal osteoporotic patients. Determination of urinary saturation for calcium oxalate after calcium and estrogen supplements, especially at the initial phase of treatment, may be helpful in the avoidance of nephrolithiasis.

Association of a T262C transition in exon 1 of estrogen-receptor-α gene with skeletal responsiveness to estrogen in post-menopausal women

Polymorphic genetic markers of estrogen-receptor-α (ERα) gene studied so far in osteoporosis reside in non-coding region with uncertain functional significance. The purpose of the present study was to search for nucleotides changes in the exon 1 and 5′ regulatory region of ERα gene, to study the nature of their linkages to the previously reported Pvull polymorphism in intron 1 and their functional significance in post-menopausal osteoporosis. Direct sequencing of exon 1 and promotor region of ERα gene revealed a synonymous nucleotide substitution from T to C at position 262, 29 nucleotides downstream from the putative start codon. No nucleotide change was found in the promotor region. Linkage disequilibrium between the T262C polymorphism and the Pvull polymorphism in intron 1 of ERα gene was demonstrated in 129 post-menopausal women (p<0.001). After treating 96 post-menopausal with 0.3 mg or 0.625 mg conjugated equine estrogen (CEE) for 2 yr, vertebral bone mineral density (BMD) increased regardless of the T262C genotype. However, with regard to femoral neck BMD, only those subjects that were homozygous for the T262C polymorphism had an increase in femoral BMD (+5.9±1.4%, mean±SE; p<0.0001). Using analysis of covariance to assess the effects of the T262C polymorphism, the intronic Pvull polymorphism, doses of CEE and the corresponding baseline BMD on the changes in vertebral or femoral BMD after treatments, it was found that the change in vertebral BMD was related only to the baseline BMD (p<0.05). The change in femoral BMD was independently related to the T262C polymorphism (p<0.01) and the baseline femoral BMD (p<0.01). No effect of the Pvull polymorphism or the doses of CEE on femoral BMD was demonstrated. We concluded that the previously described intronic Pvull polymorphism of ERα gene is in linkage disequilibrium with a T262C polymorphism in exon 1. This T262C polymorphism appears to be more directly related to the skeletal response after long-term treatment with estrogen.

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.

Random capillary plasma glucose measurement in the screening of diabetes mellitus in high-risk subjects in Thailand

To assess the usefulness of random capillary plasma glucose (RCPG) measurement in screening for diabetes mellitus in high-risk subjects, a RCPG measurement and a 75-g oral glucose tolerance test (OGTT) were performed in 684 women and 164 men, aged 16-76 years (mean+/-SD: 41.9+/-11.3 years). Risk factors included family history of diabetes in first degree relatives (53.8%), obesity (BMI > or =27 kg/m(2)) in 37.9%, dyslipidemia (78.4%), hypertension, i.e. BP > or =140/90 mmHg (28.5%), and history of gestational diabetes mellitus (16.6%). According to the 1997 ADA/1998 WHO Consultation criteria for a full OGTT, 118 cases (13.9%) were found to have diabetes. Each of 19 cases with RCPG > or =13.3 mmol/l had diabetes according to OGTT, 4.7% of 427 cases with RCPG<6.1 mmol/l had diabetes. Among 402 subjects with RCPG between 6.1 and <13.3 mmol/l, 19.7% were found to have diabetes. Thus, 446 (52.6%) of 848 subjects would have been saved from OGTT if RCPG was used as a screening test, in comparison to 33.1% if the cutpoints for RCPG (12.2 and 5.5 mmol/l) recommended by WHO Study Group (1985)/WHO Consultation (1998) were applied. Therefore, RCPG measurement is a useful screening test for the screening of diabetes mellitus in high-risk subjects.

Relation of β3-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.