Endogenous estradiol in elderly individuals: cognitive and noncognitive associations.

OBJECTIVE: To investigate an association between endogenous estradiol (E(2)) levels and cognition and behavior in elderly individuals. PATIENTS: We studied 135 community-based men and women aged 52 to 85 years in urban Bangkok, Thailand; 72 had dementia and 63 did not. MATERIALS AND METHODS: Dementia was diagnosed using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria after appropriate investigations. Blood samples for assay were collected in the morning after 6 hours of fasting. Levels of E(2) were measured by radioimmunoassay (double antibody technique). The Thai version of the Mini-Mental State Examination was used to assess cognition; the Neuropsychiatric Inventory was used to assess neuropsychiatric symptoms; and the Functional Assessment Questionnaire was used to assess instrumental activities of daily living. RESULTS: There was no correlation between age and level of E(2) in either men or women. Individuals with lower estrogen levels had more behavioral disturbances (men: r = -0.467, n = 45; P =.001; women: r = -0.384, n = 90; P<.001) and worse cognition (men: r = 0.316, n = 45; P =.03; women: r = 0.243, n = 90; P =.02) and function (men: r = -0.417, n = 45; P =.004; women: r = -0.437, n = 90; P<.001). The threshold level of endogenous E(2) in elderly individuals for the risk of developing dementia was less than 15 pg/mL (<55 pmol/L) in men and less than 1 pg/mL (<4 pmol/L) in women. CONCLUSION: Lower E(2) levels are correlated with poor cognitive, behavioral, and functional status in older individuals.

Evaluation of the new fasting plasma glucose cutpoint of 7.0 mmol/l in detection of diabetes mellitus in the Thai population.

To determine whether a fasting plasma glucose (FPG) cutpoint of 7.0 mmol/l can be appropriately used for detection of diabetes mellitus (DM) in the Thai population, different FPG cutpoints were evaluated for their efficacy in the diagnosis of DM. A plasma glucose level of > or = 11.1 mmol/l at 2 h after a 75-g oral glucose tolerance test (OGTT) was used as the gold standard criterion for diagnosis of DM. OGTT was performed in 496 subjects who were at risk of developing diabetes. They were 120 males and 376 females, 14-76 years old (mean +/- S.D. = 45.0 +/- 12.2 years). Plasma glucose level was determined in NaF preserved plasma using the glucose oxidase method. Diagnosis of DM was made in 22.8% of cases by the gold standard criterion as compared to 4.2% by using FPG values of > or = 7.8 mmol/l. The sensitivity of the FPG cutpoint of 7.8 mmol/l was 18.6%. Diagnosis of DM using FPG > or = 7.0 mmol/l improved the sensitivity to 33.6% with a positive predictive value of 100% and highest Youden's index of 0.836. The receiver operating characteristic curve of FPG revealed the best cutpoint to lie between 5.6-6.0 mmol/l. A FPG cutpoint of < 6.0 mmol/l over-estimated the prevalence of diabetes. DM and impaired glucose tolerance were noted in 65.6 and 29.5% of the subjects who had FPG values between 6.0 and 6.9 mmol/l, respectively. We conclude that FPG cutpoint of 7.0 mmol/l is applicable to a high risk Thai population for detection of DM. OGTT is recommended for definitive determination of glucose tolerance status in those individuals with FPG values between 6.0 and 6.9 mmol/l.

Behavior in self-care of the foot and foot ulcers in Thai non-insulin dependent diabetes mellitus.

A cross sectional study was conducted to examine behavior in self-care of the foot and foot ulcers in Thai non-insulin dependent diabetic patients. Fifty-five patients with foot ulcers (ulcer group; 42 females and 13 males) and 110 patients without foot ulcers (control group; 83 females and 27 males) were evaluated for self foot-care behavior using a questionnaire consisting of questions about foot inspection, foot cleaning, nail-care, and the use of footwear which possessed a total score of 20. The results showed that a mean total self foot-care score of the ulcer group was significantly lower than that of the control group (14.50 +/- 3.35 vs 15.74 +/- 2.31; p < 0.01). The patients with foot ulcers had lower mean scores in all of the four self foot-care categories than did those without foot ulcers. However, only the difference in foot cleaning score was statistically significant (7.35 +/- 0.21 vs 7.88 +/- 0.11; p < 0.05). A univariate analysis has shown that the risk of developing foot ulcers was significantly associated with a total self foot-care score of less than 15 with an odd ratio of 2.6 and a 95 per cent confidence interval of 1.3-5.6. Regarding the behavior in self foot ulcer-care, 45.5 per cent of the diabetic patients with foot ulcers had neglected them and 54.5 per cent had inappropriately cared for their ulcers. In conclusion, Thai non-insulin dependent diabetic patients with foot ulcers understood less about self foot-care practice than did those without foot ulcers. Incorrect self foot-care behavior particularly foot cleaning is associated with an increased risk of foot ulceration. In addition, diabetic patients should be advised about the correct self-care of their feet and foot ulcers in order to prevent foot ulceration and its complications.

Efficacy of using basal plasma adrenocorticotropic hormone-radioimmunoassay (ACTH-RIA) level in the identification of the cause of Cushing's syndrome.

Basal (8.00 a.m.) plasma ACTH-radioimmunoassay (ACTH-RIA) levels were studied in 32 cases of endogenous Cushing's syndrome (17 Cushing's disease, 13 adrenocortical tumors, and 2 ectopic ACTH syndrome) and 11 normal volunteers. There were overlaps in the ranges of plasma ACTH-RIA levels among patients with Cushing's disease, adrenocortical tumors, and normal volunteers but not ectopic ACTH syndrome. By using different plasma ACTH-RIA levels as cut-off points in differentiating ACTH-dependent from ACTH-independent Cushing's syndrome, the level of 30 pg/ml had the highest diagnostic efficacy with a 94.7 per cent sensitivity, a 84.6 per cent specificity and a 90.6 per cent diagnostic accuracy.

Factors associated with diabetic foot ulceration in Thailand: a case-control study.

A case-control study was conducted to determine factors involved in foot ulceration in Thai non-insulin-dependent (Type 2) diabetic patients. Fifty-five patients with foot ulcers (42 females and 13 males) and 110 patients without foot ulcers (83 females and 27 males) were evaluated for 26 factors possibly associated with foot ulceration. The results showed that diabetic patients with foot ulcers had significantly lower diabetic knowledge and foot-care practice scores; poorer glycaemic control, renal function, and visual function, and higher prevalence of retinopathy and peripheral neuropathy than diabetic patients without foot ulcers, whereas there were no differences in peripheral vascular status between both groups, each having a low prevalence. Multiple logistic regression analyses indicated that the risk of developing foot ulcers was associated with only three factors which were peripheral nerve status as determined by somatosensory evoked potentials (OR = 1.67; 95% CI 0.31 -8.97), visual acuity (OR = 0.223 per unit decrease in decimal visual acuity; 95% CI = 0.005, 0.39) and fasting plasma glucose level (OR = 1.01 per mmol l-1 increase; 95% CI = 1.00, 1.02). We conclude that peripheral neuropathy, visual impairment, and poor glycaemic control, but not peripheral vascular insufficiency, are the major independent risk factors associated with foot ulceration in Thai diabetic patients.

Angiotensin converting enzyme gene polymorphism in healthy Thais and patients with non-insulin dependent diabetes mellitus.

Insertion/deletion (I/D) polymorphism of the angiotensin converting enzyme (ACE) gene has been shown to be associated with various cardiovascular disorders in diabetic and non-diabetic patients. Its association with the development of non-insulin dependent diabetes mellitus (NIDDM) has been raised. This study was aimed to examine I/D polymorphism of ACE gene in healthy Thai subjects and patients with NIDDM. The I/D ACE genotypes were determined by polymerase chain reaction technique. Healthy unrelated subjects were 151 males and 147 females, 17-70 year old (mean +/- SD = 37.5 +/- 10.4). The unrelated diabetic patients were 42 males and 66 females, 20-79 years of age (mean +/- SD = 54.7 +/- 12.0). In healthy subjects, the ACE genotypes were DD 10.1 per cent, ID 39.2 per cent and II 50.7 per cent. Diabetic patients had similar distribution of ACE genotypes. The frequency of I and D alleles in diabetic patients was 0.69 and 0.31, similar to 0.70 and 0.30, respectively, in healthy subjects (p = 0.69). The frequency of I and D alleles in healthy Thai subjects was similar to the Japanese (I = 0.66 & D = 0.34) but different from Caucasians (I = 0.44-0.46 & D = 0.54-0.56). We conclude that I/D ACE gene polymorphisms may possess a racial difference. The similar frequency of both alleles in diabetic patients and healthy subjects suggests that there is no association between I/D polymorphism of ACE gene and diabetes mellitus in Thai individuals.

Nocturnal 8 mg dexamethasone suppression test: a practical and accurate test for identification of the cause of endogenous Cushing's syndrome.

The efficacy of a nocturnal 8 mg dexamethasone suppression test (nocturnal DST) was compared with that of the standard high-dose dexamethasone suppression test (standard DST) in identifying the cause of endogenous Cushing's syndrome in 10 proven cases with Cushing's disease, 20 with adrenal tumours, and one with ectopic ACTH syndrome. The nocturnal test compared serum cortisol concentration at 8 am before and after administration of a single dose of 8 mg dexamethasone at 11 pm. Suppression of serum cortisol level to < 50% of the baseline value indicated a diagnosis of Cushing's disease, while a lack of suppression below that limit indicated one of the other two causes of Cushing's syndrome: glucocorticoid-secreting adrenal tumour or ectopic ACTH syndrome. The nocturnal DST had a sensitivity of 90%, a specificity of 100%, an accuracy of 96.8%, a positive predictive value of 100%, and a negative predictive value of 95.5%. These values are comparable to the efficacy of the standard DST in distinguishing Cushing's disease from glucocorticoid-secreting adrenocortical tumour or ectopic ACTH syndrome. Furthermore, this rapid test does not require hospitalisation or urine collection like the standard DST. The nocturnal 8 mg dexamethasone suppression test is practical, fairly reliable, and an effective alternative with which to identify the cause of endogenous Cushing's syndrome.

Effects of alpha-glucosidase inhibitor (acarbose) combined with sulfonylurea or sulfonylurea and metformin in treatment of non-insulin-dependent diabetes mellitus.

The effects of alpha-glucosidase inhibitor (acarbose) were studied in 36 patients with non-insulin-dependent diabetes mellitus (NIDDM), aged 34-67 years with a mean duration of diabetes of 8.8 +/- 0.9 years. They were poorly controlled with diet plus sulfonylurea alone or plus sulfonylurea combined with metformin drugs. Acarbose, 100 mg three times daily, was additionally given to these patients for six months. Results showed small but significant decreases (P < 0.001) in postprandial blood glucose level. Glycosylated hemoglobin level was lowered significantly (P < 0.001) and was normalised (level of < 8%) in 17 per cent of the patients. Fasting serum triglycerides level decreased significantly (P < 0.01), whereas, no significant changes in serum total cholesterol and HDL cholesterol levels were seen. Body weight also decreased significantly (P < 0.001) at the end of acarbose trial. Flatulence was the major side effect of acarbose found in 42 per cent of the patients but it was well-tolerated and may be transient and self-limited. We concluded that the addition of acarbose to the therapeutic regimens of diet therapy plus sulfonylurea or plus sulfonylurea combined with metformin drugs led to significant improvement of glycemic control. Acarbose may be a safe and valuable adjunct to diet and sulfonylurea and metformin treatments in obese, poorly-controlled patients with NIDDM.

Comparison of anti-human insulin antibodies detection by commercial enzyme-linked immunosorbent assay kit, displacement enzyme-linked immunosorbent assay and radioimmunoassay, in Thai diabetic patients.

Antibodies specific to human insulin, in sera of Thai diabetic patients and normal healthy individuals, were detected by a commercial enzyme-linked immunosorbent assay (ELISA) kit, displacement ELISA and radioimmunoassay (RIA). Among 36 insulin-treated patients, the antibodies were detected in 22, 23 and 20 individuals, by RIA, commercial ELISA kit and displacement ELISA, respectively. Among those who had never previously received insulin therapy, RIA showed positive results in 5/11 patients with insulin-dependent diabetes mellitus (IDDM) and 1/2 patients with fibrocalculous pancreatic diabetes (FCPD); but were negative in all 26 patients with non-insulin-dependent diabetes mellitus (NIDDM) and 30 normal healthy individuals. The commercial ELISA kit could detect such insulin autoantibodies (IAA) in 4/11 IDDM, 3/26 NIDDM, 2/2 FCPD patients and 4/30 normal controls; while the displacement ELISA showed positive IAA detection in 5/11 IDDM, 2/26 NIDDM, 2/2 FCPD and 2/30 normal controls. By using RIA as the 'gold standard', the commercial ELISA kit had 92.86% sensitivity, 87.01% specificity, 88.57% accuracy, 72.22% positive predictive value and 97.10% negative predictive value; while these indices for the displacement ELISA were 85.71%, 90.01%, 89.52%, 77.42% and 94.59%, respectively.

Pituitary function in thalassemic patients and the effect of chelation therapy.

This study examined anterior pituitary function and the effect of chelation therapy in 31 patients with beta-thalassemia/HbE disease. Patients were divided into those receiving chelation therapy by deferoxamine and those receiving no such therapy (control group). Pituitary function studies were repeated in both groups 18 months later. The results showed decreased pituitary responses following stimulation in 22 patients. Among these, gonadotropin and PRL responses were most affected. After 18 months, serum ferritin levels had significantly decreased in the deferoxamine group. PRL and GH responses were improved in 3 patients receiving chelation therapy without changes in other hormone responses. In contrast, no changes in pituitary responses were shown in the control group at the end of follow-up. There were 6 drop-outs (4 in the control and 2 in the deferoxamine group) and 3 deaths (2 in the control and 1 in the deferoxamine group) during 18 months. In conclusion, gonadotropin and PRL deficiencies occur most frequently in thalassemic patients. Chelation therapy for 18 months markedly reduced serum ferritin level and might preserve or improve PRL and GH secretions, but seems to have no beneficial effects on other pituitary hormone reserves.

C-peptide secretion in calcific tropical pancreatic diabetes.

Serum C-peptide levels were measured during a glucagon stimulation test in ten normal nonobese controls and 54 diabetic patients with recent onset of diabetes under 30 years of age. Diabetic patients were comprised of 13 CTPD, 23 IDDM, and 18 NIDDM. As similar to IDDM patients, serum C-peptide concentrations did not rise significantly (P greater than 0.05) in response to glucagon administration in CTPD-patients. Mean baseline and peak serum C-peptide concentrations in CTPD-patients were significantly lower (P less than 0.001) than the values in normal controls and NIDDM patients, but were significantly higher (P less than 0.05) than those in IDDM patients. We conclude that CTPD patients have partial C-peptide reserve, which may protect against ketosis and contribute to ketosis resistance in CTPD. Our results also suggest that CTPD patients require insulin treatment. Neither baseline nor peak C-peptide levels after glucagon could discriminate CTPD from IDDM and CTPD from NIDDM.