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.

Hepatic insulin and glucagon receptors in pregnancy: their role in the enhanced catabolism during fasting.

The response to dietary deprivation in late pregnancy, as compared to the non-pregnant condition, is more rapid and profound in terms of mobilization of fuels frm peripheral tissues as well as hepatic ketogenesis and gluconeogenesis ("accelerated starvation"). We examined the potential role of hepatic insulin and glucagon receptors in mediating these changes by comparing 48-h fasted 18-day pregnant and age-matched nongravid rats. Molar ratios for insulin:glucagon in peripheral and portal blood were significantly higher in the pregnant rats. Insulin binding to purified liver plasma membrane receptors, when appropriately corrected for differences in insulin degradation by the membrane system, was marginally diminished in the pregnant animals. Glucagon binding and adenylate cyclase activation by glucagon was indistinguishable in the two groups of animals. On the basis of portal vein hormone concentrations and the values for receptor binding, liver insulinization relative to glucagonization appears to be unchanged or slightly increased in the fasted pregnant rat compared to the fasted nongravid rat. Thus, it seems unlikely that much of the "accelerated starvation" response in late pregnancy can be ascribed to diminished insulin and/or increased glucagon availability at the hepatocellular level. Instead, it is hypothesized that postreceptor events play the major role in sustaining the intrahepatic realignments of established fasting in late pregnancy.

Insulin receptors and insulin resistance in human pregnancy: evidence for a postreceptor defect in insulin action.

Pregnancy is accompanied, in its later stages, by physiological resistance to the action of insulin. We studied the potential contribution of altered insulin receptors to this phenomenon in 12 healthy pregnant women during their third trimester. For comparison, we studied the same women again several weeks postpartum. We also used a group of randomly chosen nonpregnant subjects as a control population. Women in this control group were studied during the luteal phase of the menstrual cycle. Plasma insulin and insulin to glucose ratios were significantly higher in the pregnant women. Insulin binding to peripheral blood monocytes was higher in pregnancy than postpartum in the majority of women, and as a group, the pregnant subjects showed significantly higher insulin binding than the nongravid subjects. This appeared to be due to a greater number of receptor sites per cell. We found no correlation between plasma insulin and insulin binding in pregnancy. We conclude that the insulin resistance of pregnancy is not attended by impaired binding of insulin to cellular receptors, at least in the monocyte. Our data suggest that the defect in insulin action lies at a site distal to the receptor.

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.

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. World Health Organization.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.