Calculated Right Adrenal Vein Aldosterone Levels in Patients Undergoing Adrenal Vein Sampling: The Potential to Lateralize Despite Unsuccessful Selection of the Right Adrenal Vein.

PURPOSE: The aim of this study was to use calculated aldosterone level in the right adrenal vein (RAV) (cAldoRAV) rather than measured level for identifying the dominant side of aldosterone secretion in patients with primary aldosteronism undergoing adrenocorticotropic hormone-stimulated adrenal venous sampling (AVS). MATERIALS AND METHODS: Patients with primary aldosteronism who had successful AVS (selectivity index, >3) were studied. Based on the assumption that cortisol production from both adrenal glands is equal, aldosterone level in the RAV was calculated using the data from the left adrenal vein and inferior vena cava. The aldosterone level in the left adrenal vein (AldoLAV) compared with the cAldoRAV (AldoLAV:cAldoRAV ratio) was then used to determine the dominant side of aldosterone secretion compared with standard AVS interpretation using lateralization index (LI). LI ≥4 indicated unilateral disease, and LI ≤3 indicated bilateral disease. The LI between 3 and 4 was diagnosed as indeterminate. RESULTS: Sixty-eight patients with concordant results between AVS and adrenal imaging study (32 were left-sided, 22 were right-sided, and 14 were bilateral) were selected for studying diagnostic performance. The AldoLAV:cAldoRAV ratio with the cutoff values of ≥3 and ≤0.33 could identify unilateral diseases (left-sided and right-sided disease, respectively) with 92.6% sensitivity and 100% specificity. CONCLUSIONS: The calculated AldoLAV:cAldoRAV ratio can determine the dominant side of aldosterone secretion with high sensitivity and specificity when compared with standard AVS interpretation of measured levels. It provides an option for identification of unilateral and bilateral disease in select patients in whom right adrenal vein selection is unsuccessful.

Progression of insulin resistance in individuals with type 1 diabetes: A retrospective longitudinal study on individuals from Thailand.

AIMS: To investigate temporal changes in glycaemic control and weight contributing to insulin resistance (IR), in Thai individuals with type 1 diabetes (T1D). METHODS: Longitudinal data of 69 individuals with T1D were retrospectively collected over a median follow-up of 7.2 years. The estimated glucose disposal rate (eGDR), a marker of IR, was calculated using an established formula. Individuals were assigned as insulin-sensitive T1D (the latest eGDR≥8 mg/kg/min), or insulin-resistant T1D/double diabetes (the latest eGDR<8 mg/kg/min). Generalised linear mixed model was employed to compare the temporal patterns of HbA1c, BMI, and eGDR between the two groups. RESULTS: 26 insulin-resistant T1D had a gradual decline in eGDR, corresponding with increased weight and HbA1c. In contrast, 43 insulin-sensitive T1D had stable insulin sensitivity with an improvement in HbA1c over time, associated with a modest weight gain. Fluctuations of glucose levels were observed during the early diabetes course leading to unstable eGDR, thus limiting the use of eGDR to classify insulin-resistant T1D. CONCLUSION: T1D individuals who eventually develop IR are likely to experience early increasing IR over time. In contrast, those who ultimately do not have IR, maintain their insulin sensitivity throughout their course at least in the medium term.

Using plasma aldosterone concentrations at 1 h of saline infusion test for the diagnosis of primary aldosteronism.

OBJECTIVE: Saline infusion test (SIT) requires 2 l of isotonic saline for intravenous infusion over 4 h to suppress plasma aldosterone concentration (PAC). To shorten the procedure time and minimize the volume load, we study the performance of SIT at 1, 2 and 4 h for diagnosing primary aldosteronism. METHODS: This is a cross-sectional study. PAC was measured before and 1, 2 and 4 h after saline infusion at a rate of 500 ml/h in patients suspected to have primary aldosteronism. Primary aldosteronism was diagnosed based on 4 h PAC, adrenal imaging and/or adrenal venous sampling (AVS). RESULTS: Of the 93 patients, 32 had primary aldosteronism. The area under the receiver operating characteristic (ROC) curve of the 1, 2 and 4 h PAC were not statistically different. All of the nonprimary aldosteronism group had a 1 h PAC lower than 15 ng/dl and all of the primary aldosteronism group had a 1 h PAC higher than 5 ng/dl. Nearly 30% of the nonprimary aldosteronism and primary aldosteronism groups had a 1 h PAC between 5 and 15 ng/dl (equivocal range) and could be discriminated by using percentage suppression of 1 h PAC from baseline. Using 1 h PAC of more than 15 ng/dl together with percentage suppression of 1 h PAC from baseline of less than 60 when 1 h PAC was 5-15 ng/dl, primary aldosteronism could be detected with a sensitivity of 93.7% and specificity of 96.7%. CONCLUSION: The 1 h SIT has a similar diagnostic performance to the standard SIT. Using 1 h PAC together with percentage suppression from baseline when 1 h PAC is equivocal, primary aldosteronism can be diagnosed with good accuracy.

Glucose Interference in Serum and Urine Samples with Various Creatinine Concentrations Measured by the Jaffe Kinetic Method.

Background: The effect of glucose interference on creatinine measurement by Jaffe kinetic method differs between serum and urine specimens. We investigated the effects of creatinine concentration and specimen dilution on glucose interference with urine creatinine measurement. Methods: Leftover serum and urine specimens were collected and stored at -20°C until study. Serum specimens were mixed to make 5 glucose concentrations ranging from <5.6 to 27.8 mmol/L, each group consisting of 5 levels of creatinine concentration ranging from <45 to 354 µmol/L. Urine specimens were divided into 5 groups of creatinine concentration ranging from <1,769 to >7956 µmol/L, each sample was spiked with glucose powder to produce 5 aliquots with glucose concentrations ranging from 0 to 666 mmol/L. Urine samples were automatically diluted 1:20 before analysis. Percent interference of creatinine measurement by Jaffe kinetic method was calculated using enzymatic method as the reference. Results: A total of 148 serum samples and 335 urine samples were analyzed. In serum, glucose interference with Jaffe creatinine measurement was found if creatinine concentrations were 177 µmol/L or less, corresponding to 3,540 µmol/L or less in urine specimens prior to 1:20 dilution. The degree of interference was greater when glucose concentration was higher or creatinine concentration was lower. Conclusions: When creatinine concentration and specimen dilution were considered, the effects of glucose interference on Jaffe creatinine measurement were similar in serum and urine specimens, and was found when creatinine concentrations in serum or diluted urine were 177 µmol/L or less.

Overestimation of glomerular filtration rate calculated from creatinine as compared with cystatin C in patients with type 2 diabetes receiving sodium-glucose cotransportor 2 inhibitors.

AIM: The aim of this cross-sectional study is to compare creatinine-based estimated glomerular filtration rate (eGFRcr) and cystatin C-based estimated glomerular filtration rate (eGFRcys) between patients with type 2 diabetes receiving and not receiving sodium-glucose cotransporter 2 (SGLT2) inhibitors. METHODS: The plasma specimens from 90 patients with type 2 diabetes who had been receiving SGLT2 inhibitors for at least 24 weeks (SGLT2 inhibitors group) were selected. Meanwhile, the plasma specimens from age-, sex- and BMI-matched patients with type 2 diabetes not receiving SGLT2 inhibitors (non-SGLT2 inhibitors group) in 1:1 matching were also selected for comparison. eGFRcr and eGFRcys were calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: When compared with the non-SGLT2 inhibitors group, eGFRcr was significantly higher in the SGLT2 inhibitors group (70.54 ± 24.87 vs. 79.95 ± 19.57 mL/min/1.73 m2 , p = 0.014) while eGFRcys was not different (66.32 ± 24.98 vs 69.17 ± 20.10 ml/min/1.73 m2 , p = 0.401). Based on eGFRcr, the chronic kidney disease (CKD) stage in the SGLT2 inhibitors group was lower than that in the non-SGLT2 inhibitors group, but it was not different when CKD stage was classified by eGFRcys. The difference between eGFRcr and eGFRcys (eGFRcr-cys) was significantly higher in the SGLT2 inhibitors group (4.22 ± 11.20 vs. 10.78 ± 10.42 ml/min/1.73 m2 , p < 0.001). In male patients, there was significant correlation between the eGFRcr-cys and duration of receiving SGLT-2 inhibitors (r = 0.398, p = 0.004). This correlation was not found in female patients. CONCLUSIONS: There was a discrepancy between eGFRcr and eGFRcys in patients with type 2 diabetes receiving SGLT2 inhibitors when compared with those not receiving SGLT2 inhibitors.

Performance of the unilateral AV/IVC index in primary hyperaldosteronism subtype prediction: A validation study in a single tertiary centre.

BACKGROUND: Failure of cannulation of the right adrenal vein is frequent during AVS for investigation of primary aldosteronism (PA). The aldosterone:cortisol ratio of either adrenal vein compared with the inferior vena cava (AV/IVC index) has been proposed to differentiate between unilateral and bilateral disease, and aid in lateralization of unilateral disease. METHODS: Sixty-two patients with unilateral or bilateral PA identified by either successful bilateral (45 patients) or unilateral (17 patients) adrenal vein cannulation, and with biochemical remission following surgery were enrolled into the analysis. The diagnostic performances of the previously identified AV/IVC index cut-offs of ≥5.5 to predict ipsilateral disease and ≤0.5 to predict contralateral disease were validated using data from the entire cohort. RESULTS: Fifty-three patients had unilateral PA and 9 patients bilateral PA. The area under ROC curve (AUROC) of the AV/IVC cut-off ≤0.5 for identifying unilateral aldosterone secretion from the contralateral adrenal was 0.95 (95% CI; 0.88-0.99), whereas the AUROC of the AV/IVC cut-off ≥5.5 for identifying unilateral aldosterone secretion from ipsilateral adrenal was 0.96 (95% CI; 0.92-0.99). The AV/IVC index cut-off value of 0.5 had 93% sensitivity and 91% specificity, and the AV/IVC index cut-off value of 5.5 had 21% sensitivity and 100% specificity. The optimal AV/IVC cut-offs to achieve 100% specificity for our cohort were >2.4 and <0.1 to predict ipsilateral and contralateral disease. CONCLUSION: Our data confirm that the AV/IVC index is a potential tool for subtype classification and lateralization in patients with PA in the setting of failed bilateral, but successful unilateral, adrenal vein cannulation during AVS.

Phytosterols and inulin-enriched soymilk increases glucagon-like peptide-1 secretion in healthy men: double-blind randomized controlled trial, subgroup study.

OBJECTIVE: The study aimed to determine the effect of phytosterols and inulin on plasma glucose, insulin, and GLP-1 levels among healthy men after consuming phytosterols and inulin-enriched soymilk for 8 weeks. RESULTS: A total of 26 men at least 20 years old were randomly assigned into the 2 g/day of phytosterols and 10 g/day of inulin-enriched soymilk (intervention) group or into the standard soymilk (control) group. In the intervention group, the area under the curve of Glucagon-like peptide-1 secretion increased significantly, compared to its baseline (p = 0.003). The area under the curve of insulin secretion also increased but it did not meet statistical significance (p = 0.118). The area under the curves of plasma glucose were similar between pre- and post-test (p = 0.348). In the control group, none of the primary results significantly changed compared to their baseline levels. Trial registration Thai Clinical Trial Registry: TCTR20160319001 date: March 19, 2016, retrospectively registered.

A genome-wide association study identifies novel susceptibility genetic variation for thyrotoxic hypokalemic periodic paralysis.

Several lines of evidence have pointed out that genetic components have roles in thyrotoxic hypokalemic periodic paralysis (TTPP). In this study, for the first time we performed genome-wide association study (GWAS) in male hyperthyroid subjects in order to identify genetic loci conferring susceptibility to TTPP. We genotyped 78 Thai male TTPP cases and 74 Thai male hyperthyroid patients without hypokalemia as controls with Illumina Human-Hap610 Genotyping BeadChip. Among the SNPs analyzed in the GWAS, rs312729 at chromosome 17q revealed the lowest P-value for association (P=2.09 × 10(-7)). After fine mapping for linkage disequilibrium blocks surrounding the landmark SNP, we found a significant association of rs623011; located at 75 kb downstream of KCNJ2 on chromosome 17q, reached the GWAS significance after Bonferroni's adjustment (P=3.23 × 10(-8), odds ratio (OR)=6.72; 95% confidence interval (CI)=3.11-14.5). The result was confirmed in an independent cohort of samples consisting of 28 TTPP patients and 48 controls using the same clinical criteria diagnosis (replication analysis P=3.44 × 10(-5), OR=5.13; 95% CI=1.87-14.1; combined-analysis P=3.71 × 10(-12), OR=5.47; 95% CI=3.04-9.83).

The role of liquid simethicone in enhancing endoscopic visibility prior to esophagogastroduodenoscopy (EGD): A prospective, randomized, double-blinded, placebo-controlled trial.

BACKGROUND: Simethicone improves endoscopic visibility and diagnostic accuracy during colonoscopy and capsule endoscopy. Nevertheless, there have been limited data on its usefulness in esophagogastroduodenoscopy (EGD). OBJECTIVE: To evaluate the effectiveness of simethicone on enhancing endoscopic visibility in patients undergoing EGD. MATERIAL AND METHOD: 121 patients were randomized to take 2 ml ofeither liquid simethicone or placebo in 60 ml of water at 15-30 minutes before EGD. The severity scores of foam and bubbles at the esophagus, stomach and duodenum were compared. RESULTS: Simethicone improved endoscopic visibility by diminishing mean cumulative (6.83 +/- 2.4 vs. 11.05 +/- 2.6, p < 0.001) and local scores offoam and bubbles at all areas, and decreased the number and timing ofadjunctive simethicone washing (17.5% vs. 74.1%, p < 0.001 and 0 vs. 19 seconds, p < 0.001). Simethicone increased endoscopist and patient satisfaction significantly without having adverse effects. CONCLUSION: Using simethicone before EGD enhances endoscopic visibility, reduces adjunctive simethicone washing and increases endoscopist and patient satisfaction.

Contribution of skeletal muscle mass on sex differences in 2-hour plasma glucose levels after oral glucose load in Thai subjects with normal glucose tolerance.

Women have higher 2-hour plasma glucose levels after oral glucose challenge than men. The smaller skeletal muscle mass in women may contribute to the higher postload glucose levels. The objective of this study was to test the hypothesis that the different amount of skeletal muscle mass between men and women contributed to sex difference in postload plasma glucose levels in subjects with normal glucose tolerance. Forty-seven Thai subjects with normal glucose tolerance, 23 women and 24 age- and body mass index-matched men, were studied. Body fat, abdominal fat, and appendages lean mass were measured by dual-energy x-ray absorptiometry. Skeletal muscle insulin sensitivity was determined by euglycemic-hyperinsulinemic clamp. First-phase insulin secretion and hepatic insulin sensitivity were determined from oral glucose tolerance data. beta-Cell function was estimated from the homeostasis model assessment of %B by the homeostasis model assessment 2 model. Correlation and linear regression analysis were performed to identify factors contributing to variances of postload 2-hour plasma glucose levels. This study showed that women had significantly higher 2-hour plasma glucose levels and smaller skeletal muscle mass than men. Measures of insulin secretion and insulin sensitivity were not different between men and women. Male sex (r = -0.360, P = .013) and appendages lean mass (r = -0.411, P = .004) were negatively correlated with 2-hour plasma glucose, whereas log 2-hour insulin (r = 0.571, P < .0001), total body fat (r = 0.348, P = .016), and log abdominal fat (r = 0.298, P = .042) were positively correlated with 2-hour plasma glucose. The correlation of 2-hour plasma glucose and sex disappeared after adjustment for appendages lean mass. By multivariate linear regression analysis, log 2-hour insulin (beta = 18.9, P < .0001), log 30-minute insulin (beta = -36.3, P = .001), appendages lean mass (beta = -1.0 x 10(-3), P = .018), and hepatic insulin sensitivity index (beta = -17.3, P = .041) explained 54.2% of the variance of 2-hour plasma glucose. In conclusion, the higher postload 2-hour plasma glucose levels in women was not sex specific but was in part a result of the smaller skeletal muscle mass. The early insulin secretion, hepatic insulin sensitivity, and skeletal muscle mass were the significant factors negatively predicting 2-hour postload plasma glucose levels in Thai subjects with normal glucose tolerance.

Comparison the Carpenter and Coustan thresholds with the new thresholds obtained from Thai pregnant women for the diagnosis of gestational diabetes.

AIMS: To determine the threshold of plasma glucose levels calculated from the mean+2SDs for diagnosing gestational diabetes mellitus (GDM) in Thai women. METHODS: Thai pregnant women without pre-existing diabetes were invited into the study. A 100-g oral glucose tolerance test (OGTT) was performed in all participants during their second or third trimesters, regardless of the results of 50-g glucose challenge test. RESULTS: Seven hundred and ninety seven women with singleton pregnancy participated in the study. The distribution of 1-, 2-, and 3-h plasma glucose levels of the 100-g OGTT was Gaussian. The rounded cut-off point values calculated from the mean+2SDs were 90, 195, 170, and 155 mg/dl, respectively for fasting, 1-, 2-, and 3-h plasma glucose. With the Carpenter and Coustan thresholds, 52 women (6.5%, 95%CI 4.9-8.5%) were diagnosed as GDM. Of these, when tested with the new thresholds, 30 had normal glucose tolerance and 22 were diagnosed as GDM. CONCLUSION: By using mean+2SDs of plasma glucose levels of the 100-g OGTT as the threshold for diagnosing GDM, the thresholds at 1, 2, and 3h obtained from Thai women were 15 mg/dl higher than those of the Carpenter and Coustan thresholds.

Insulin resistance in women with a history of severe pre-eclampsia.

AIM: This study investigated whether post-partum insulin resistance existed in women with a history of severe pre-eclampsia. METHODS: The euglycemic hyperinsulinemic clamp technique was used to assess insulin sensitivity at least 6 months after delivery in 13 women who had had severe pre-eclampsia and 26 age- and body mass index-matched controls who had had normal pregnancy. RESULTS: The mean (+/-SD) durations after delivery were 2.6 +/- 1.6 years and 4.5 +/- 2.8 years in the pre-eclampsia and control groups, respectively. The systolic blood pressure was significantly higher in the pre-eclampsia group (118 +/- 11 mmHg vs 109 +/- 12 mmHg, P = 0.028). Although the body mass indices were not different among the groups (25.8 +/- 3.1 kg/m(2) vs 24.6 +/- 3.9 kg/m(2)), the waist and waist-to-hip ratio were significantly higher in the women with prior pre-eclampsia. The pre-eclampsia group had lower insulin sensitivity index than the controls (5.4 +/- 2.5 mg/kg/min/mU/L vs 8.1 +/- 4.0 mg/kg/min/mU/L, P = 0.036). Serum triglyceride levels were significantly higher in the pre-eclampsia group (153 +/- 74 mg/dL vs 82 +/- 37 mg/dL, P < 0.01). High-density lipoprotein-cholesterol levels tended to be lower in the pre-eclampsia group (42.1 +/- 9.7 mg/dL vs 48.2 +/- 9.6 mg/dL, P = 0.07). CONCLUSION: Women with a history of severe pre-eclampsia had characteristics of metabolic syndrome and had lower insulin sensitivity compared with those who had had normal pregnancy. These may explain an increased risk of cardiovascular disease in women with pre-eclampsia.

Insulin resistance in subjects with a history of thyrotoxic periodic paralysis (TPP).

BACKGROUND: Hyperinsulinaemia has been suggested as an important factor for developing hypokalaemic paralysis in patients with thyrotoxic periodic paralysis (TPP). Since hyperinsulinaemia is a common feature of insulin resistance, there may be a causal relationship between insulin resistance and TPP. OBJECTIVE: To compare insulin sensitivity between subjects with a history of TPP and others with a history of thyrotoxicosis without periodic paralysis. METHODS: Insulin sensitivity measured by euglycaemic hyperinsulinaemic clamp and 75-g oral glucose tolerance test (OGTT) were performed nonselectively in 10 subjects with a history of TPP (TPP group) and 10 age- and sex-matched subjects with a history of simple thyrotoxicosis (control group). All participants had euthyroidism and fasting plasma glucose of < 5.55 mmol/l at the time of the study. RESULTS: Body mass index and waist circumference of the TPP group were higher than that of the control group. One of 10 (10%) subjects in the TPP group and 6 of 10 (60%) in the control group had BMI of < 23 kg/m2. Areas under the curve (AUC) of plasma glucose after OGTT were comparable, while the AUC of serum insulin of the TPP group was higher than in the control group. The TPP group had lower insulin sensitivity than the control group. CONCLUSION: The subjects with a history of TPP were more obese and had lower insulin sensitivity than those with a history of simple thyrotoxicosis. Insulin resistance with compensatory hyperinsulinaemia may be a key feature of the pathogenesis of TPP.

Association between circadian rhythm of blood pressure and glucose tolerance status in normotensive, non-diabetic subjects.

AIMS: To examine whether circadian rhythm of blood pressure (BP) is associated with glucose tolerance status in normotensive, non-diabetic subjects. METHODS: A cross-sectional study recruited normotensive and non-diabetic subjects, aged 35-79 years. A 75 g oral glucose tolerance test (OGTT) and 24-h ambulatory blood pressure monitoring (24-h ABPM) were performed. RESULTS: Among 31 impaired glucose tolerance (IGT) and 36 normal glucose tolerance (NGT) study subjects, the mean (+/-S.D.) diurnal-nocturnal differences of average systolic BP (SBP) were 7.1+/-6.9 and 9.9+/-6.2 mmHg, respectively (p=0.086). In a linear mixed-effects regression model, however, taking each measurement of BP as the outcome, nighttime reduction of SBP in the IGT group was 7.19 mmHg, which was significantly smaller compared to a reduction of 9.80 mmHg in the NGT group (p-value for IGT: nighttime interaction=0.0014). The prevalence of non-dipping BP pattern was 77.4% in the IGT group which was significantly higher than 52.8% of the NGT group (p=0.036). Logistic regression revealed a significant effect of IGT for predicting non-dipping pattern with an adjusted odds ratio of 3.71 (95% CI: 1.09, 12.66, p=0.029). CONCLUSIONS: Among normotensive, non-diabetic subjects, the decreased nocturnal BP reduction was associated with impaired glucose tolerance status.

Differences in postload plasma glucose levels between 100-g and 75-g oral glucose tolerance tests in normal pregnant women: a potential role of early insulin secretion.

OBJECTIVE: To demonstrate a role of early insulin secretion on plasma glucose levels after different amounts of oral glucose loads in pregnant women. MATERIAL AND METHOD: Forty-one pregnant women with normal glucose tolerance according to the Carpenter and Coustan' s criteria and 25 non-pregnant women (control group) with normal glucose tolerance according to the World Health Organization criteria were enrolled. Each subject was randomly scheduled to perform both the 100-g and 75-g OGTT within a 1-week interval. Venous blood was drawn at fasting, 30-, 60-, 120-, and 180-minute intervals during both tests for determination of plasma glucose and serum insulin levels. RESULTS: The mean (+/- SE) ages of the pregnant and control groups were 33.3 +/- 0.9 and 31.8 +/- 1.4 years, respectively. The mean gestational age at the time of performing OGTT of the pregnant group was 28.7 +/- 0.6 weeks. In the non-pregnant group, the plasma glucose concentrations were not different between 75-g and 100-g OGTT whereas the serum insulin levels at the 30 and 180 minutes of the 100-g OGTT were significantly higher than those of the 75-g OGT. In the pregnant group, both plasma glucose and serum insulin concentrations at the 120 and 180 minutes of the 100-g OGTT were significantly higher than those of the 75-g OGT. CONCLUSION: The limited ability of early insulin secretion to increase when glucose load increased in the pregnant women could explain the high plasma glucose levels at 2 and 3 hours of 100-g OGTT compared to those of 75-g OGTT.

Correlation between change in serum homocysteine levels during hyperinsulinemia and insulin sensitivity.

OBJECTIVE: To study the correlation between the changes in homocysteine (Hcy) levels during hyperinsulinemia and insulin sensitivity. MATERIAL AND METHOD: Forty-five subjects who underwent hyperinsulinemic euglycemic clamp were studied. Twenty-five subjects had normal glucose tolerance, seven had impaired glucose tolerance, and 13 had type 2 diabetes mellitus. Serum Hcy was measured before (Hcy 0) and at 120 minutes (Hcy 120) of glucose clamp. The change in Hcy levels during hyperinsulinemia was expressed as absolute difference between Hcy 0 and Hcy 120 (deltaHcy) and percentage difference over Hcy 0 (%deltaHcy). Insulin sensitivity index (ISI) was used to correlate with variables of interest. RESULTS: The ISI was not correlated with Hcy 0 and Hcy 120 but was correlated with deltaHcy and %deltaHcy. The deltaHcy and %deltaHcy were not significantly different between subjects with normal and abnormal glucose tolerance, whereas they were significantly different between subjects whose ISI were above and below the mean value. CONCLUSION: Although the change in Hcy levels during hyperinsulinemia was correlated with insulin sensitivity, the Hcy levels per se were not found to be correlated with insulin sensitivity. The change in Hcy levels during hyperinsulinemia was significantly different in subjects whose ISI was above and below the mean value but not in subjects with normal and abnormal glucose tolerance. This indicated that insulin resistance, not the glucose tolerance status, affected Hcy metabolism.

Gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais.

To determine gender differences of regional abdominal fat distribution and their relationships with insulin sensitivity in healthy and glucose-intolerant Thais, 44 subjects, 22 men and 22 body mass index-matched women, with normal and abnormal glucose tolerance, which included subjects with impaired glucose tolerance and diabetes, were studied. Total body fat and total abdominal fat (TAF) at L1-L4 were measured by dual-energy x-ray absorptiometry. Regional abdominal fat, which consists of sc abdominal fat and visceral abdominal fat, was determined by single-slice computerized tomography of the abdomen at L4-L5 disc space level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp and expressed as glucose infusion rate (GIR). With comparable body mass index, visceral abdominal fat was most strongly correlated with GIR after adjustment with percent total body fat in both healthy (r = -0.8155; P = 0.007) and glucose-intolerant women (r = -0.7597; P = 0.011), whereas TAF was most strongly correlated with GIR in both healthy (r = -0.8114; P = 0.008) and glucose-intolerant men (r = -0.6194; P = 0.101). By linear regression analysis, visceral abdominal fat accounted for 35.0% (beta = -3.53 x 10(-2); P = 0.001) of GIR variance in women, whereas TAF accounted for 39.3% (beta = -1.28 x 10(-4); P < 0.0001) of GIR variance in men. We conclude that there are gender differences in the relationships of regional abdominal fat and insulin sensitivity in slightly obese healthy and glucose-intolerant Thais, the difference of which may possibly be in part due to the difference of abdominal fat patterning between genders.

Regional abdominal fat distribution in lean and obese Thai type 2 diabetic women: relationships with insulin sensitivity and cardiovascular risk factors.

To determine the relationships of body fat distribution and insulin sensitivity and cardiovascular risk factors in lean and obese Thai type 2 diabetic women, 9 lean and 11 obese subjects, with respective mean age 41.7 +/- 6.3 (SD) and 48.0 +/- 8.5 years, and mean body mass index (BMI) 23.5 +/- 1.8 and 30.3 +/- 3.7 kg/m2, were studied. The amount of total body fat (TBF) and total abdominal fat (AF) were measured by dual-energy x-ray absorptiometer, whereas subcutaneous (SAF) and visceral abdominal fat areas (VAF) were measured by computerized tomography (CT) of the abdomen at the L4-L5 level. Insulin sensitivity was determined by euglycemic hyperinsulinemic clamp. Cardiovascular risk factors, which included fasting and post-glucose challenged plasma glucose and insulin, systolic (SBP) and diastolic blood pressure (DBP), lipid profile, fibrinogen, and uric acid, were also determined. VAF was inversely correlated with insulin sensitivity as determined by glucose infusion rate (GIR) during the clamp, in both lean (r=-0.8821; P=.009) and obese subjects (r=-0.582; P=.078) independent of percent TBF. SAF and TBF were not correlated with GIR. With regards to cardiovascular risk factors, VAF was correlated with SBP (r=0.5279; P=.024) and DBP (r=0.6492; P=.004), fasting insulin (r=0.7256; P=.001) and uric acid (r=0.4963; P=.036) after adjustment for percent TBF. In contrast, TBF was correlated with fasting insulin (r=0.517; P=.023), area under the curve (AUC) of insulin (r=0.625; P=.004), triglyceride (TG) (r=0.668; P=.002), and uric acid (r=0.49; P=.033). GIR was not correlated with any of cardiovascular risk factors independent of VAF. In conclusion, VAF was a strong determinant of insulin sensitivity and several cardiovascular risk factors in both lean and obese Thai type 2 diabetic women.

Relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women.

In order to study the relationships of body fat distribution, insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai men and women, 32 healthy, non-diabetic subjects, 16 men and 16 women, with respective mean age 28.4+/-6.6 (S.D.) and 32.8+/-8.9 years, mean BMI 21.0+/-2.8 and 21.2+/-3.7 kg/m(2), were measured for total body fat and abdominal fat by dual energy X-ray absorptiometry (DEXA), anthropometry and insulin sensitivity by euglycemic hyperinsulinemic clamp. Cardiovascular risk factors included fasting and post-glucose challenge plasma glucose and insulin, blood pressure, lipid profile, fibrinogen and uric acid. For similar age and BMI, men had a lower amount and percent of total body fat, but had a higher proportion of abdominal/total body fat than women. In men, insulin sensitivity, as determined by glucose infusion rate during euglycemic hyperinsulinemic clamp, was inversely correlated with total body fat, abdominal fat, BMI and waist circumference, whereas only total body fat, but not abdominal fat, BW and hip circumference were inversely correlated with insulin sensitivity in women. No cardiovascular risk factors, except area under the curve (AUC), of plasma insulin in women correlated with insulin sensitivity when adjusted for total body fat. After age adjustment, total body fat was better correlated with fasting and AUC of plasma glucose and insulin in men and with systolic blood pressure as well as triglyceride levels in women. Only HDL-C in men was better correlated with abdominal fat. In conclusion, there were sex-differences in body fat distribution and its relationship with insulin sensitivity and cardiovascular risk factors in lean, healthy non-diabetic Thai subjects. Total body fat was a major determinant of insulin sensitivity in both men and women, abdominal fat may play a role in men only. Body fat, not insulin sensitivity, was associated with cardiovascular risk factors in these lean subjects.

Novel insulin sensitivity index derived from oral glucose tolerance test.

The euglycemic hyperglycemic clamp is generally regarded as a reference method for assessing insulin sensitivity. However, this method is laborious and expensive. The oral glucose tolerance test (OGTT), the most commonly used method for evaluating whole body glucose tolerance, has often been used to assess insulin sensitivity. In the previous studies the correlation between the insulin sensitivity index (ISI) obtained from the OGTT (ISI(OGTT)) and those obtained from the glucose clamp (ISI(Clamp)) may not be satisfactory. This is because the glucose clamp study is designed for measuring peripheral glucose utilization, whereas plasma glucose responses during the OGTT are the results of peripheral glucose utilization and hepatic glucose production. Based on this problem, we developed a new equation, ISI(OGTT), [1.9/6 x body weight (kg) x fasting plasma glucose (mmol/liter) + 520 - 1.9/18 x body weight x area under the glucose curve (mmol/h.liter) - urinary glucose (mmol)/1.8] / [area under the insulin curve (pmol/h.liter) x body weight], which would represent peripheral glucose utilization only. We tested our equation with ISI(Clamp) and also compared with others. Thirty-three healthy volunteers (16 males) with normal glucose tolerance underwent a 75-g, 3-h OGTT on the morning of d 1 and a glucose clamp on the morning of d 2. Their mean (+/-SD) age and body mass index were 30.8 +/- 8.3 yr and 22.0 +/- 3.9 kg/m(2), respectively. The mean (+/-SD) glucose disposal rate and ISI determined by glucose clamp were 27.46 +/- 16.55 micro mol/kg.min and 7.39 +/- 2.72 micro mol/kg.min/pmol.liter, respectively. Pearson's correlation coefficient between our ISI(OGTT) and ISI(Clamp) was 0.869 (P < 0.0001) which was stronger than those corresponding values calculated from HOMA, QUICKI, Belfiore, Cederholm, Gutt, Matsuda, and Stumvoll, the respective values of which were 0.404, 0.434, 0.643, 0.533, 0.584, 0.734, and 0.508. In conclusion, the ISI(OGTT) derived from our equation is more suitable than others in assessing insulin sensitivity in subjects with normal glucose tolerance. Further studies in subjects with impaired glucose tolerance and diabetes mellitus should be performed to confirm the validity of this equation.