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.

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.

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.

Nocturnal physiological and biochemical changes in sudden unexplained death syndrome: a preliminary report of a case control study.

Sudden nocturnal deaths among "healthy" workers in Southeast Asia have been termed "sudden unexplained nocturnal death syndrome (SUNDS)" or "sudden unexplained death syndrome (SUDS)". The pathogenesis is still unknown. The paucity of publications on nocturnal monitoring and scientific data stimulated us to perform this study, which included biochemical tests and physiological monitoring during the night in 11 males north-eastern Thai workers. Group 1 (G1) consisted of 5 subjects with neither a previous history of near-SUDS (NSUDS) nor a familial history of SUDS (FHSUDS). Group 2 (G2) consisted of 6 subjects with a family history of either SUDS or NSUDS. Two subjects in G2 presented with NSUDS. Two-day nocturnal monitoring included blood sugar, electrolytes, and respiratory parameters. 24-hour Holter ECGs were monitored for 2 days. The subjects underwent exercise stress tests on the 2nd day of this study. Significant nocturnal hypoxia was more common in G2 than G1 and this abnormality was aggravated by exercise. There were no significant findings in sleep apnea (apnea indices) or in nocturnal biochemical changes, eg blood sugar, electrolytes, thiamine. The recordings of the Holter-ECGs were within normal limits in both groups. We conclude that nocturnal hypoxia might be the primary abnormality in SUDS, and this abnormality was aggravated by the day-time exercise. The cause of nocturnal hypoxia requires further studies.

An evaluation of glycosylated hemoglobin measurement by a colorimetric method as a screening test for gestational diabetes mellitus.

To assess the potential value of glycosylated hemoglobin measurement (HbA1) in screening for gestational diabetes mellitus (GDM), HbA1 by a colorimetric method, plasma glucose level 1 hr after 50 g oral glucose loading, and 3-hr 100 g oral glucose tolerance test (3-hr OGTT) were performed in 334 pregnant women at Ramathibodi Hospital. These subjects carried high risk factors of GDM. Gestational ages varied from 24 to 38 wks. Twenty-four cases were diabetic (7.2%) by O'Sullivan and Mahan's criteria (1964). As a screening test to select subjects for 3-hr OGTT, plasma glucose level 1 hr after 50 g oral glucose load (plasma glucose level 7.8 mmol/L and above) has sensitivity: 87.50 per cent, specificity: 64.19 per cent. HbA1 level of 5.60 per cent (upper 95% confidence limit of the mean) and above yield sensitivity: 66.67 per cent, specificity: 61.29 per cent. Thus, glycosylated hemoglobin measurement as a screening test for GDM is not as effective as the conventional 50 g oral glucose loading test.

Increased insulin secretion in subjects with impaired glucose tolerance.

In order to assess the relative roles of insulin deficiency and insulin resistance in the pathogenesis of impaired glucose tolerance (IGT), simultaneous measurement of serum immunoreactive insulin (IRI) and serum immunoreactive C-peptide (IRC) responses during 75 g oral glucose tolerance test were performed in 44 normal-weight adults with IGT (27 men, mean age +/- SEM = 46.1 +/- 1.9 year; 17 women, aged 49.1 +/- 3.3 year) and 44 control subjects (27 men, aged 45.5 +/- 2.1 year; 17 women, aged 47.9 +/- 3.0 year). Subjects with IGT had consistently higher 120-m IRI levels in comparison to corresponding age, sex, and BMI-matched control subjects, i.e. mean +/- SEM = 118.8 +/- 13.7 vs 57.0 +/- 6.9 microU/ml (male, P = 0.0002), and 116.3 +/- 11.8 vs 43.3 +/- 5.8 microU/ml (female, P = 0.0000). Similarly, 120-m IRC levels were higher in subjects with IGT, i.e. 2.12 +/- 0.26 vs 1.35 +/- 0.15 pmol/ml (male, P = 0.0262), and 3.13 +/- 1.01 vs 1.54 +/- 0.19 pmol/ml (female, P = 0.0080). Our findings indicate that increased insulin secretion is present in subjects with IGT, suggesting that insulin resistance is the predominant factor in the pathogenesis of IGT.

Impaired glucose tolerance in Thai adults: serum insulin profiles after a 75 gram oral glucose load.

Serum immunoreactive insulin (IRI) profiles after ingestion of a 75 g oral glucose load were measured in 150 Thai adults (50 men and 100 women, aged 15-71 years) with impaired glucose tolerance (IGT), and 133 control subjects (49 men and 84 women, aged 19-72 years). There were no significant differences in fasting and 30-minute serum IRI levels between subjects with IGT and corresponding age-, sex-, and body mass index (BMI)-matched controls, while subjects with IGT had consistently higher 120-minute serum IRI levels. Early serum insulin responses, as measured by ratio of increment in serum IRI level to that of plasma glucose level 30 minutes after glucose load (delta IRI 30/delta PG 30), were generally low or normal. However, when subjects with IGT are considered individually, there was marked heterogeneity in serum insulin responses, as judged by 120-minute serum IRI, delta IRI 30/delta PG 30, and ratio of sum of serum IRI levels during oral glucose tolerance test (0, 1/2, and 2 hour) to that of plasma glucose levels (sigma IRI/sigma PG). Most of the cases, i.e. 52, 76.7 and 69.3 per cent using previous criteria respectively, had normal insulin responses. We conclude that, 1) Thai adults with IGT generally have higher 120-minute serum IRI levels compared with corresponding age-, sex-, and BMI-matched controls, 2) early serum insulin responses as measured by delta IRI 30/delta PG 30 are generally low or normal, and 3) there is marked heterogeneity in serum insulin responses among these subjects.