The combination of soluble tumor necrosis factor receptor type 1 and fibroblast growth factor 21 exhibits better prediction of renal outcomes in patients with type 2 diabetes mellitus.

PURPOSE: Numerous biomarkers of diabetic kidney disease (DKD) are associated with renal prognosis but head-to-head comparisons are lacking. This study aimed to examine the association of soluble tumor necrosis factor receptor type 1 (sTNFR1), fibroblast growth factor 21 (FGF-21), endocan, N-terminal pro-brain natriuretic peptide (NT-pro-BNP), and renal outcomes of patients with or without clinical signs of DKD. METHODS: A total of 312 patients were enrolled in a prospective observational study that excluded individuals with estimated glomerular filtration rates (eGFR) < 30 mL/min/1.73 m2. Composite renal outcomes included either a > 30% decline in eGFR and worsening albuminuria or both from consecutive tests of blood/urine during a 3.5-year follow-up period. RESULTS: Higher sTNFR1 and FGF-21, rather than endocan and NT-pro-BNP, levels were associated with renal outcomes but the significance was lost after adjusting for confounders. However, sTNFR1 levels ≥ 9.79 pg/dL or FGF-21 levels ≥ 1.40 pg/dL were associated with renal outcomes after adjusting for the confounders (hazard ration [HR] 2.76, 95% confidence interval [CI] 1.36-5.60, p = 0.005 for sTNFR1 level; HR 1.95, 95% CI 1.03-3.69, p = 0.03 for FGF-21 level). The combination of both levels exhibited even better association with renal outcomes than did either one alone (adjusted HR 4.45, 95% CI 1.86-10.65, p = 0.001). The results were consistent among patients with preserved renal function and normoalbuminuria. CONCLUSION: Both sTNFR1 and FGF-21 levels were associated with renal outcomes of in patients with type 2 diabetes, and the combination of the abovementioned markers exhibits better predictability.

Prehypertension is associated with insulin resistance.

BACKGROUND: Prehypertension, a new category of blood pressure (BP) classification introduced by The Seven Report of the Joint National Commission (JNC-7) on High BP for individuals with systolic BP in the range of 120-139 mmHg or diastolic BP between 80 and 89 mmHg, is a strong predictor for the development of hypertension. Insulin resistance (IR) has been proposed to be a key feature of metabolic abnormalities of hypertension and may precede the elevation of BP. AIM: The purpose of the study is to evaluate whether prehypertension is associated with IR. DESIGN: This is a cross-sectional study. METHODS: Anthropometric and BP measurements were performed in 83 prehypertensive subjects and 192 normotensives. All subjects received a 75-g oral glucose tolerance test (OGTT) for the measurements of IR. RESULTS: The prehypertensive subjects were more obese and had higher levels of fasting triglycerides and 2-h insulin than the normotensives. The subjects with prehypertension were more insulin resistant than the counterparts, indicated by lower insulin sensitivity index, ISI(0,120), values. While there was no difference between the two groups in insulin response of OGTT after adjustments for confounders, the prehypertension group maintained significant between-group differences in glucose response even when the incremental insulin levels were added to covariates for adjustments. DISCUSSION: Our data show that prehypertension is associated with IR. The subjects with prehypertension have clinical characteristics of the IR syndrome. It seems that the prehypertension group cannot handle oral glucose challenge as well as the normotension, probably a consequence of IR in prehypertension.

Diagnosis of insulin resistance in hypertensive patients by the metabolic syndrome: AHA vs. IDF definitions.

BACKGROUND: Subjects with the metabolic syndrome are accompanied by insulin resistance (IR). However, it is not clear how well the newly defined metabolic syndrome identifies IR specifically in hypertensive subjects. AIMS: The purpose of the study was to evaluate the performance of the metabolic syndrome, defined by the American Heart Association (AHA) and the International Diabetes Federation (IDF) definitions, in identifying IR in hypertension. METHODS: The analysis is a cross-sectional study. Totally, 228 hypertensive patients and 92 non-diabetic normotensive controls who received insulin suppressive tests for direct evaluation of their insulin sensitivity were included from the Stanford Asia and Pacific Program for Hypertension and IR. McNemar's tests were used to compare sensitivity and specificity of the AHA-defined with the IDF-defined metabolic syndrome in diagnosis of IR. RESULTS: The sensitivity of the metabolic syndrome for IR in hypertension was 89.7% and the specificity 45.9% by the AHA definition. Using the IDF definition, the sensitivity was 77.6%, and the specificity increased to 63.5%. The diagnostic power of individual components of the syndrome was also modest. The predictive discrimination of wider waist circumference was similar to that of the AHA-defined metabolic syndrome. CONCLUSIONS: Use of the metabolic syndrome by the AHA definition provided good sensitivity, but low specificity to diagnose IR in hypertension. The IDF definition improved in false-positive rate, but it was still not specific enough to identify IR in hypertension.

Glucose tolerance status and cognitive impairment in early middle-aged women.

AIMS: To examine the effect of glucose tolerance status on cognitive performance in early middle-aged women. METHODS: We conducted a matched, case-control study from a population-based cohort in Kinmen, Taiwan. Women aged 40-54 years were recruited. Participants were classified into one of three groups: normal, impaired glucose tolerance (IGT) or diabetes mellitus. Cognitive measures used were the Rey Auditory-Verbal Learning Test, visual memory, verbal fluency, Trail Making Test, and digit spans. RESULTS: Seven hundred and twenty eligible women underwent both the cognitive and oral glucose tolerance tests. The 72 women (10%) who had diabetes mellitus were compared with 68 women with IGT and 144 with normal glucose tolerance. All groups were matched for age and education level. Mean scores on cognitive testing did not differ between the three groups, except for the forward digit spans test. After adjustment for menopausal status, psychological stress scores and other cardiovascular variables, glucose tolerance status was no longer a significant predictor for forward digit span scores. CONCLUSIONS: Glucose tolerance status was not associated with cognitive performance in middle-aged women.

Surrogate estimates of insulin sensitivity in subjects with hypertension.

The purpose of the study is to compare surrogate estimates of insulin sensitivity with a directly measured insulin sensitivity index, steady-state plasma glucose (SSPG) from insulin suppression test (IST), in subjects with hypertension. Two hundred and twenty-eight hypertensive patients who received IST for SSPG were included for analysis. Estimates from fasting measurements alone, homeostasis model assessment for insulin resistance (HOMA-IR) and quantitative insulin sensitivity check index (QUICKI)), and indices from fasting and/or 2 h samples (ISI(0,120) and ISI(TX)) were calculated. In addition to Pearson and partial correlations, variance-component models were used to test the relationship between surrogate estimates of insulin sensitivity and SSPG. A large proportion of variance owing to covariates in the variance-component models indicated the goodness of model fit, irrespective of the independence among variables. SSPG was positively correlated with logarithmic transformation (Log) (HOMA-IR) and negatively correlated with QUICKI, Log (ISI(0,120)) and ISI(TX) (all P<0.0001). Log (ISI(0,120)) seemed to have a better correlation with SSPG (r=-0.72) than other measures in partial correlation. The proportion of variance owing to all covariates of Log (ISI(0,120)) and ISI(TX) were larger than those of Log (HOMA-IR) and QUICKI in the variance-component models. After adjustments for demographic and obesity covariates, the proportion of variance explained by Log (ISI(0,120)) were largest among the surrogate measures in the variance-component models. Our results showed that ISI(0,120) and ISI(TX) correlated better with SSPG than those used fasting measures alone (HOMA-IR and QUICKI). Log (ISI(0,120)) currently showing the strongest association with SSPG than other estimates is adaptable for use in large studies of hypertension.

Prevalence and awareness of diabetes and mean fasting glucose by age, sex, and region: results from the Nutrition and Health Survey in Taiwan, 1993-1996.

AIMS: The objective of this study was to evaluate the prevalence and awareness of diabetes mellitus (DM) in Taiwan. METHODS: The Nutrition and Health Survey in Taiwan for people aged > or = 4 years was conducted between 1993 and 1996, using a multistaged, stratified, and clustered sampling scheme. RESULTS: The prevalence of DM, defined by fasting whole blood glucose > or = 6.1 mmol/l or diagnosed DM subjects taking hypoglycaemic drugs, was 3.7% in men > or = 19 years and 6.3% in women. Corresponding to age groups 19-44, 45-64 and > or = 65 years, the prevalence was 1.5%, 7.9% and 7.8% in men and 0.5%, 12.3% and 19.6% in women, respectively. People in mountainous areas and in Peng-Hu islands had the highest prevalence, but the lowest awareness rates among seven survey strata (regions). Women from metropolitan cities had the lowest DM prevalence and body mass index (BMI) values, but the highest rate of DM awareness among all strata. This phenomenon was not apparent in men. The age, sex, and regional patterns of DM prevalence were consistent with those of BMI. CONCLUSIONS: The prevalence of DM in Taiwan in 1993-1996 was relatively high, given a mean BMI of 23 kg/m2 in adults. Gender and regional differences were apparent in DM prevalence and awareness and in mean BMI.

Sagittal abdominal diameter is associated with insulin sensitivity in Chinese hypertensive patients and their siblings.

The purpose of the study is to observe the relation between anthropometric measurements, focusing on sagittal abdominal diameter (SAD), and insulin sensitivity indices in Chinese hypertensive patients and their siblings. In total, 907 participants, 537 hypertensive and 370 nonhypertensive, from 311 Taiwanese families were drawn from the Stanford Asia and Pacific Program for Hypertension and Insulin Resistance for the study. The participants received anthropometric measurements and 75-g oral glucose tolerance tests after an overnight fast. Fasting insulin, homeostasis model assessment for insulin resistance (HOMA-IR), and the insulin sensitivity index ISI(0,120) were chosen as surrogate measures of insulin sensitivity. In addition to Pearson and partial correlations, we used generalized estimating equations (GEEs) to examine the association between anthropometric measurements and insulin sensitivity indices. A small deviance in the GEEs indicates the goodness of model fit, irrespective of the independence among variables. The hypertensive patients were older in age, wider in waist circumference (WC), larger in body mass index (BMI) and SAD, and more insulin resistant than the nonhypertensive counterparts. The logarithmic transformation of fasting insulin, HOMA-IR, and ISI(0,120) significantly correlated with SAD, WC, and BMI before and after adjustments for age and sex. The deviances of SAD in the GEEs were similar to those of WC in all subjects, while BMI had smaller deviances than SAD and WC in the hypertensive patients. Our results suggest that the performance of SAD in predicting insulin sensitivity is comparable with WC in Chinese hypertensive patients and their siblings. BMI, however, seems to have better association with insulin sensitivity than SAD and WC in the patients with hypertension.

Surrogate estimates of insulin sensitivity in Chinese diabetic patients and their offspring.

AIMS: To evaluate the relationship between surrogate measures of insulin sensitivity and results from euglycaemic insulin clamp in Chinese diabetic patients and their offspring. METHODS: The study included 59 volunteers from 20 diabetic families. Each participant completed a 75-g oral glucose tolerance test (OGTT) and a euglycaemic insulin clamp. We tested the correlation of surrogate measures of insulin sensitivity with M-values and M/I ratios (the amount of glucose infused during 90-120 min of the clamp was defined as M, and the mean values of plasma insulin during 90-120 min as I) from the euglycaemic insulin clamp. These measures included fasting insulin (FPI), insulin at 120 min of OGTT, insulin area under the curve of OGTT, fasting glucose-to-insulin ratio, homeostasis model assessment for insulin sensitivity (HOMA-IR and HOMA %S) and the Matsuda-DeFronzo index from OGTT. RESULTS: The Matsuda-DeFronzo index closely correlated to M-value and M/I in 21 diabetic, 38 non-diabetic individuals and the 59 participants overall (with M-value, r = 0.68, 0.84 and 0.84; with M/I, r = 0.71, 0.72 and 0.75, respectively, all P < 0.001). Without OGTT, HOMA %S was a good surrogate index for diabetic (correlated to M-value and M/I, r = 0.71 and 0.68, P = 0.001) and for non-diabetic subjects (to M-value, r = 0.73; to M/I, r = 0.55, both P < 0.001). FPI was as good as HOMA %S and Matsuda-DeFronzo index. CONCLUSIONS: The Matsuda-DeFronzo index, HOMA %S and FPI are good surrogate estimates of insulin sensitivity in Chinese diabetic subjects and their offspring.

Waist circumference predicts insulin resistance in offspring of diabetic patients.

The purpose of the study was to identify a good abdominal obesity index for insulin resistance in offspring of diabetic patients. A total of 74 non-diabetic subjects (male =36; female =38) were recruited from a diabetic family study. The waist circumference (W), waist-hip ratio (WHR) and conicity index were used as the abdominal obesity indices. The body mass index (BMI) and indices obtained from bioelectric impedance analysis (BIA) (body fat percentage, fat mass and fat mass index) were used as overall obesity indices. Fasting plasma insulin (FPI), homeostasis model assessment for insulin resistance (HOMA-IR) and Matsuda-Defronzo index from oral glucose tolerance test were chosen as the insulin sensitivity indices. We correlated obesity indices with insulin resistance indices with age and family adjusted. W was closely correlated in both sexes of subjects with Matsuda-DeFronzo index (male, r=-0.661,p<0.001; female, r=-0.419,p=0.026), FPI (male, r=0.614,p=0.001; female, r=0.503,p=0.006) and HOMA-IR (male, r=0.609,p=0.001; female, r=0.472,p=0.011). WHR and its log transformation predicted insulin resistance only in males. BMI as an overall obesity index was in good correlation with Matsuda-DeFronzo index (male, r=-0.646,p<0.001; female, r=-0.469,p=0.012), FPI (male, r=0.711,p<0.001; female, r=0.464,p=0.013) and HOMA-IR (male, r=0.708,p<0.001; female, r=0.469,p=0.012). Overall obesity indices from BIA were similar to BMI to predict insulin resistance. In conclusion, W is a good abdominal obesity predictor of insulin resistance in offspring of diabetic patients in Taiwan.

Exacerbation of insulin resistance and postprandial triglyceride response in newly diagnosed hypertensive patients with hypertriglyceridaemia.

The purpose of the study is to examine the differences in insulin resistance and postprandial triglyceride (TG) response between hypertensive patients with or without hypertriglyceridaemia. The study is a comparative cohort study with matching. Thirty-one newly diagnosed hypertensive patients without any medication were recruited from a health survey. The participants were further divided into two groups: those with fasting TG <2.26 mmol/L, and those with TG between 2.26 and 5.65 mmol/L. Both groups were matched in age, sex, body mass index and waist circumference. Each patient received a 75-g oral glucose tolerance test, an insulin suppression test, and a 1000 kcal high fat mixed meal test. The hypertriglyceridaemic hypertensive patients had significantly higher fasting insulin, 2-h plasma glucose, 2-h insulin, and steady-state plasma glucose (SSPG) (13.16 +/- 1.87 vs 9.76 +/- 3.18 mmol/L). They also had a greater postprandial TG response to the challenge of mixed meal (DeltaAUC 20.76 +/- 10.06 vs 7.97 +/- 3.18 mmol 8 h/L). The postprandial TG response was closely correlated (r = 0.72-0.95, P < 0.0001) with fasting TG in all hypertensive patients. Both fasting TG levels and postprandial TG response were significantly (P < 0.05) correlated with SSPG. In conclusion, the hypertensive patients with hypertriglyceridaemia were more insulin resistant than those without it. Exacerbation of postprandial hypertriglyceridaemia was identified in these patients. The TG response to the challenge of high fat meal was significantly correlated with fasting TG and insulin resistant in them. The results provide a rationale for the alleviation of insulin resistance and hypertriglyceridaemia in these atherosclerosis-prone hypertensive patients.

Glucose suppresses the enhancement by free fatty acids on thrombin- stimulated production of prostacyclin in cultured aortic endothelial cells.

BACKGROUND: Prostacyclin (PGI2) is a potent vasodilator and inhibitor of platelet aggregation. It may reduce in diabetic patients to contribute to the platelet hyperaggregability and acceleration of atherosclerosis. While the major clinical manifestation of diabetes mellitus is increased blood levels of glucose, elevation of free fatty acids (FFA) levels in the circulation has also been reported. METHODS: Cultured rat aortic endothelial cells were treated with media containing high concentration of FFA (oleic acid 0.5 mM, palmitic acid 0.25 mM, linoleic acid 0.25 mM, stearic acid 0.06 mM, arachidonic acid 0.04 mM, total 1.1 mM, and the molar ratio of FFA/albumin < 2), glucose (22 mM) or both. Then the PGI2 release was studied by measuring 6-keto-PGF1alpha in the media. RESULTS: We found that high concentration of FFA increased the PGI2 production at basal (1.227 +/- 0.031 vs 0.762 +/- 0.028 ng/mg protein, n = 6, p = 0.002) and when stimulated by 0.5 unit/ml of thrombin (2.708 +/- 0.115 vs 1.337 +/- 0.225 ng/mg protein, n = 6, p = 0.002). Two-day treatment with high-glucose did not affect PGI2 production. However, in the presence of high-glucose, the enhancement by high FFA of thrombin stimulated PGI2 production disappeared (high-glucose 1.461 +/- 0.312 ng/mg, normal-glucose 2.708 +/- 0.115 ng/mg, n = 6, p = 0.002). CONCLUSIONS: The interaction between glucose and FFA can reduce PGI2 production in thrombin-stimulated state. Our findings further support their role in the pathogenesis of platelet hyperaggregability and acceleration of atherosclerosis in diabetes.

Undiagnosed glucose intolerance encountered in clinical practice: reappraisal of the use of the oral glucose tolerance test.

BACKGROUND: In 1997, the Expert Committee of the American Diabetes Association (ADA) revised the diabetes mellitus (DM) diagnostic criteria to facilitate the diagnosis of DM on the basis of fasting plasma glucose (PG). The major purpose of the study is to evaluate if oral glucose tolerance test (OGTT) is still needed after the revision of criteria. METHODS: From September 1994 to March 1995, 247 ambulatory subjects referred by clinicians for 75-g OGTT were recruited for the study. Fasting and 2-h PG and serum insulin concentrations were determined. Additional fasting blood samples were collected for the measurement of HbA1c. We used the receiver operating characteristic (ROC) curve to locate a cut-point of fasting PG corresponding to 2-h PG of 200 mg/dl. RESULTS: The optimal fasting PG level depicted by ROC curve was more than 105 mg/dl, giving 80.6% sensitivity and 85.6% specificity for the diagnosis of DM in clinical setting. If fasting PG > or = 126 mg/dl was employed, the specificity was 98.3% but the sensitivity went down to 42.6%. High rates of glucose intolerance would remain undiagnosed in subjects with fasting PG less than 126 mg/dl (41.6% of them being IGT and 38.6% DM), if the OGTT was exempted from clinical practice. HbA1c more than 6.2% could be a clue to recognize undiagnosed DM, but was unable to separate impaired glucose tolerance (IGT) from non-DM. CONCLUSIONS: In the population studied, undiagnosed glucose intolerance can still be encountered in a large number of subjects with fasting PG less than 126 mg/dl. OGTT is still indispensable in clinical setting for the diagnosis of DM and IGT after the revision of diagnostic criteria.

Genetic variation in the human urea transporter-2 is associated with variation in blood pressure.

The kidney, by regulating the volume of fluid in the body, plays a key role in regulating blood pressure (BP). The kidney uses primarily sodium and, to a lesser extent, urea to maintain the appropriate volume of fluid. Genetic variation in proteins that determine sodium reabsorption and excretion is known to significantly influence BP. However, the influence of genetic variation in urea transporters on BP has not been examined. We determined therefore whether nucleotide variation in the kidney-specific human urea transporter, HUT2, is associated with variation in BP. After determining the genomic structure of the coding sequence, seven single nucleotide polymorphisms (SNPs) were identified. Two of the SNPs result in Val/Ile and Ala/Thr amino acid substitutions at positions 227 and 357 in the HUT2 open reading frame, respectively. Another SNP is silent and four others are in introns or the 3' untranslated region. Over 1000 hypertensive and low-normotensive individuals of Chinese origin were typed for five of these SNPs using a high-throughput genotyping method. The Ile227 and Ala357 alleles were associated with low diastolic BP in men but not women, with odds ratios 2.1 [95% confidence interval (CI) 1.5-2.7, P < 0.001] and 1.5 (95% CI 1.2-1.8, P < 0.001), respectively. There was a similar trend for systolic BP, and odds ratios for the Ile227 and Ala357 alleles were 1.7 (95% CI 1.2-2.3, P = 0.002) and 1.3 (95% CI 1.1-1.6, P = 0.007), respectively, in men.

Comparison of official coders versus physician panel in assignment of underlying cause of death.

BACKGROUND AND PURPOSE: In outcome analyses of clinical trials and mortality follow-up studies, the underlying cause of death (UCOD) is commonly assigned either by official coders or by a panel of physicians. We evaluated the validity of UCOD assigned by official coders by comparison with the assignments of a panel of physicians who reviewed the available medical records of the deceased. METHODS: The comparisons focused on deaths occurring from October 1995 through June 1998 in a series of residents in a veterans home. Because of limited resources, only the first 104 deaths that occurred during the study period were included. Agreement rate, sensitivity, specificity, and kappa statistics were calculated to assess the consistency of coder versus physician panel assignment of UCOD by selected main causes of death. For 32 of the 104 deaths, the panel concluded that the information obtained from medical records was insufficient to determine the UCOD, and the following analyses were confined to the other 72 deaths. RESULTS: For the 72 deaths considered by the panel to have sufficient information to determine UCOD, all four physicians agreed on a single UCOD in 50 (69%) cases, while three or four agreed in 66 (92%) cases. A consensus was reached in cases with disagreement. The two procedures completely agreed in 40 (56%) of the deaths. For general category UCOD, the kappa value was high for cancer (0.83) and cardiovascular disease (CVD, 0.73) but only moderate for pulmonary disease (PD, 0.60). When the UCOD assigned by the panel was used as the gold standard, official coders showed relatively low sensitivity for correct determination of UCOD in cases of CVD (0.76) compared with cancer (0.86) and PD (0.80). CONCLUSIONS: Given the high inter-physician consistency and the relatively low sensitivity of official coders in assigning CVD as the UCOD, we conclude that the use of clinical review panels would provide more accurate UCOD assignments for use in outcome analyses in mortality follow-up studies and clinical trials in Taiwan.

Abnormal cardiovascular reflex tests are predictors of mortality in Type 2 diabetes mellitus.

AIMS: To determine whether diabetic autonomic neuropathy is an important factor contributing to mortality in Type 2 diabetes mellitus. METHODS: Between 1989 and 1993, 431 men and 181 women with Type 2 diabetes were given diabetic autonomic neuropathy cardiovascular reflex (CVR) tests. These subjects were followed for the subsequent 5--9 years to assess mortality rates. RESULTS: The prevalence rate of abnormal CVR tests was 46.1% in patients with the history of diabetes less than 5 years and up to 69.4% when the history of diabetes exceeded 20 years. During the follow-up period from 1 January 1989 to 31 December 1997 (mean 7.7 years), a total of 135 participants died. The 8-year survival rate for patients with abnormal CVR tests was 63.6% in males and 76.4% in females, compared with 80.9 and 93.3% for patients with normal CVR tests. The results were grouped as: group 1, normal CVR tests without postural hypotension (PHT); group 2, normal CVR tests with PHT; group 3, abnormal CVR tests without PHT; and group 4, abnormal CVR tests with PHT. The 8-year survival rate was 85.4% in group 1, 80.9% in group 2, 74.5% in group 3 and 61.1% in group 4. CONCLUSION: Type 2 diabetic patients with abnormal CVR tests may have increased mortality, and those combined with postural hypotension have higher mortality than those without. Abnormal CVR tests may be important predictors of mortality in Type 2 diabetes mellitus.

Undiagnosed diabetes mellitus in Taiwanese subjects with impaired fasting glycemia: impact of female sex, central obesity, and short stature.

AIMS: To study the extent and determinants of undiagnosed diabetes mellitus (DM) in Taiwanese subjects with impaired fasting glycemia (IFG) defined by the newly proposed WHO criteria. METHODS: Oral glucose tolerance tests were carried out for 306 IFG subjects identified from 6632 adult participants of two large scale community-based studies: Nutrition and Health Survey in Taiwan (1993-1996) and the Cardiovascular Disease Two-township Study (1994-1997). Similar protocols were used in these two studies to collect data on glycemic status, anthropometric measurements, and other data used in the present study. RESULTS: Subjects with IFG had a non-trivial undiagnosed diabetes mellitus rate (30% in men and 42% in women) and a high rate of glucose intolerance and undiagnosed DM combined (75% in men and 86% in women). Women with IFG had a 1.6 fold higher risk (p = 0.04) for undiagnosed DM and a 2.1 fold higher risk (p = 0.01) for glucose intolerance and DM when compared to men. There were more women than men with an elevated body mass index in undiagnosed DM patients. Among IFG subjects, undiagnosed DM patients were significantly (p < 0.05) older, more centrally obese and shorter than their normal IFG counterparts, irrespective of gender. In men, height was independent of age and waist circumference in predicting undiagnosed DM (p = 0.037). CONCLUSIONS: A high proportion of impaired glucose tolerance and undiagnosed DM was found in subjects with IFG. Its public health impact should not be overlooked. Central obesity, female sex, and short stature were associated with undiagnosed DM status in IFG subjects.

A comparison of insulin suppression tests performed with somatostatin and octreotide with particular reference to tolerability.

To evaluate the tolerability of insulin suppression test (IST) using octreotide instead of somatostatin, we compared the steady-state plasma glucose (SSPG) values and the safety during and after the test in 17 normal volunteers. The subject received IST twice (with somatostatin or with octreotide) in random order. During the test, all subjects were infused with regular insulin and glucose simultaneously for 180 min. In addition, either somatostatin or octreotide was infused intravenously over the same period of time. Plasma glucose, insulin and C-peptide were measured. The subject response to the test was recorded during and one day after the test by a structured questionnaire. The SSPG and the steady-state plasma insulin (SSPI) values reached during IST were similar, irrespective of the use of somatostatin or octreotide. There was a positive correlation between the SSPG values obtained from both methods (r = 0.67, P = 0.003). However, the mean intra-individual coefficient of variation is 17.9% for SSPG. The SSPG levels, no matter from which method, correlated positively with the 2-h insulin after oral glucose challenge. Most adverse events (especially gastrointestinal discomfort) occurred after the test, and increased much more after using octreotide than somatostatin (P = 0.002 by chi 2 test). In conclusion, the SSPG values measured by IST using octreotide or somatostatin are similar in normal healthy subjects. Yet, the octreotide method has more adverse events after the test.

Using semi-automated oscillometric blood pressure measurement in diabetic patients and their offspring.

To determine whether a semi-automatic oscillometric blood pressure (BP) monitor Dinamap 1846SX (DIN) can replace the standard mercury sphygmomanometer (SMS) for BP measurements in diabetic patients and their offspring, we compared SMS with DIN in 105 diabetic patients and their families. Their mean age was 50.6 (range 24-86) years, of whom 41 had diabetes mellitus (DM), 32 impaired glucose tolerance and 32 non-DM. After resting quietly for 10 min, their right arm BP were measured twice with each device at random and with 1-min intervals between each measurement. Agreement between measurements was tested by plotting the differences between the methods against means and by intraclass correlation coefficient (r(I)). The DIN was also evaluated by the criteria of American Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society (BHS) criteria and clinical criteria of O'Brien. All measurements by DIN [first readings or averaged readings of duplicate measurements of systolic BP (SBP) or diastolic BP (DBP)] satisfied the AAMI criteria and had good agreement with SMS (r(I)=. 951 for SBP and r(I)=.905 for DBP). The first readings of systolic BP measured by DIN vs. SMS failed to satisfy the criteria by O'Brien and reached BHS grade C level. Other measurements passed the limits of O'Brien and reached BHS grade A or B. In conclusion, averaged readings of duplicate BP measurements by DIN are interchangeable with that by SMS in Chinese diabetic patients and their offspring. Only one single DIN measurement is not acceptable for clinical application.

Linoleic acid and oleic acid increase the endothelin-1 binding and action in cultured rat aortic smooth muscle cells.

An increase in circulating non-esterified fatty acids (NEFA) has been observed in patients with poorly controlled diabetes mellitus. To investigate whether fatty acids will affect the endothelin-1 (ET-1) receptor and thus contribute to the acceleration of atherosclerosis in diabetic patients, cultured rat aortic smooth muscle cells (SMC) were maintained in media containing higher (similar to those in diabetic patients) concentrations of oleic acid (OA) or linoleic acid (LA). The ET-1 binding and ET-1-stimulated thymidine uptake were then examined. We found that cells treated with OA (500 micromol/L) or LA (250 micromol/L) showed a significant increase in ET-1 receptor amount as demonstrated by Scatchard analysis (Bmax: 7.40 +/- 1.04 v 2.71 +/- 0.54 fmol/mg and 5.00 +/- 1.00 v 3.32 +/- 0.70 fmol/mg, respectively). No change in binding affinity was found. Moreover, both the basal and ET-1-stimulated thymidine uptake were enhanced by treatment with either LA (basal, 11,367 +/- 4,117 cpm/mg; LA, 13,933 +/- 4,003 cpm/mg; ET-1 (10(-8)), 16,931 +/- 4,412 cpm/mg; LA +/- ET-1 (10(-8)), 28,855 +/- 5,217 cpm/mg) or OA (basal, 4,912 +/- 1,193 cpm/mg, OA, 8,027 +/- 1,318 cpm/mg; ET-1 (10(-8)) 9,947 +/- 2,520 cpm/mg; OA + ET-1 (10(-8)), 16,761 +/- 1,740 cpm/mg). This enhancement in thymidine uptake was associated with an increase in cell number. Because ET-1 and its receptor are involved in atherogenesis, our findings suggested that increase in circulating NEFA may contribute to the acceleration of atherosclerosis in diabetic patients. Further studies to confirm its role in the vascular wall are warranted.