Li-Chuan Hsiao

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

SUMMARY

Waist circumference predicts metabolic cardiovascular risk in postmenopausal Chinese women.

Objective The purpose of the study is to compare the differences in metabolic cardiovascular risk factors among postmenopausal Chinese women with or without abdominal obesity. Design The study is a cross-sectional, population-based, comparative cohort study. Each participant received anthropometric measurements and a 75-g oral glucose tolerance test after an overnight fast. The homeostasis model assessment for insulin resistance and the insulin sensitivity index, ISI0,120, were used as measures of insulin resistance. A “metabolic cardiovascular risk score” was calculated from fasting insulin, glucose, lipids, and blood pressure. General linear models (GLM) were fit to examine the relation of waist circumference (WC) to insulin resistance and metabolic risk scores. Results According to the International Obesity Task Force obesity criteria for Asians, 57 women had abdominal obesity (WC ≥ 80 cm), and 58 had WCs less than 80 cm. The two groups were comparable in demographic variables and body mass index (BMI). The women with larger WCs were more insulin-resistant than their counterparts. The metabolic risk scores were significantly higher in women with abdominal obesity than in those without it. The results from the GLM showed that WC was an independent predictor of insulin resistance and metabolic risk scores after controlling for demographic variables (0.06- and 0.29-unit increases in homeostasis model assessment for insulin resistance and metabolic risk scores per 1 cm change in WC). Moreover, BMI neither correlated with metabolic risk scores nor affected the WC effects on insulin resistance and metabolic risk scores in the GLM. Conclusions Postmenopausal Chinese women with adbominal obesity may carry higher metabolic cardiovascular risk than those without it. It is WC, not BMI, that predicts metabolic cardiovascular risk factors in these women.

Is Hyperuricemia Another Facet of the Metabolic Syndrome

Background: Hyperuricemia is commonly associated with obesity, glucose intolerance, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease. The resemblance of the metabolic syndrome and hyperuricemia has led to the suggestion that hyperuricemia is a part of the metabolic syndrome. The purpose of this study is to examine the contribution of uric acid (UA) as an additional component of the metabolic syndrome in middle‐aged men. Methods: In total, 393 male participants, aged 45‐60 years, were recruited from a professional health evaluation program. Anthropometric measurements and blood pressure (BP) were taken after an overnight fast. Fasting blood samples were collected for the measurements of glucose, UA, and lipid profile. Logistic regression models were fitted to examine the relationship between UA and the diagnosis of metabolic syndrome. Factor analysis was performed to explore the relationship between UA and the components of the metabolic syndrome. Results: The diagnosis of the metabolic syndrome was significantly associated with waist circumference (WC), glucose, triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C), systolic BP, and liver enzyme levels, but not associated with UA levels. The sensitivity of hyperuricemia (serum UA = 7.0 mg/dL) for the diagnosis of the metabolic syndrome was 58.0% and the specificity was 55.3%. In factor analysis, UA aggregated with body mass index, WC, glucose, log TG, and HDL‐C as a metabolic factor. Systolic and diastolic BP were loaded on a second factor separately. The model loaded with UA explained a similar proportion of the total variance (56.9%), as did the model loaded without UA (62.5%). Conclusion: Our results suggest that the contribution of UA as an additional component of the syndrome seems to be insignificant. We propose that hyperuricemia might not be an important facet for the understanding of the underlying structure of the metabolic syndrome.

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.

Lack of effect of simvastatin on insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia: results from a double-blind, randomized, placebo-controlled crossover study.

Aims To evaluate the effects of simvastatin on serum lipids and insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.

Acipimox attenuates hypertriglyceridemia in dyslipidemic noninsulin dependent diabetes mellitus patients without perturbation of insulin sensitivity and glycemic control

Hyperlipidemia, hypertriglyceridemia in particular, is a common feature in patients with noninsulin dependent diabetes mellitus (NIDDM) and may associate with insulin insensitivity. Acipimox, being widely prescribed for treating hypertriglyceridemia, is also used in NIDDM patients for their dyslipidemia. In the present study, we evaluated the effect of acipimox in Chinese NIDDM patients with hypertriglyceridemia. A total of 16 patients enrolled in a double-blind, randomized, placebo-controlled and two-period crossover study. After an 8 week run-in period, patients were randomly assigned into two groups receiving either acipimox (250 mg, twice daily) or placebo treatment. A total of 12 weeks later, these two groups switched their treatment for an additional 12 weeks. Blood samples were collected at the end of the run-in period and then at 4-week intervals in the whole study for lipid profile. A modified insulin suppression test was performed at the ends of the run-in period, 12-week and 24-week treatment to assess changes in insulin sensitivity. Our results showed that acipimox significantly lowered serum total triglyceride while compared to those by placebo. However, no difference was observed in serum non-esterified fatty acid, low-density lipoprotein cholesterol, total cholesterol (TC), high density lipoprotein-cholesterol (HDL-C) and HDL-C/ TC ratio between the two groups. Furthermore, glycemic indices and insulin sensitivity were similar during the base-line, placebo or acipimox periods. Taken together, our data suggest that acipimox significantly lowered TG without perturbation of insulin sensitivity in hypertriglyceridemic NIDDM patients.

Clinical and biochemical indicators of homeostasis model assessment-estimated insulin resistance in postmenopausal women.

Background: Homeostasis model assessment of insulin resistance (HOMA‐IR) is a surrogate estimate of directly measured insulin resistance that been robustly proven to be associated with diabetes and cardiovascular disease. The purpose of this study was to evaluate the use of several simple indicators to identify postmenopausal women with insulin resistance estimated by HOMA‐IR. Methods: We recruited 262 naturally postmenopausal women without overt diabetes for the study. HOMA‐IR values were calculated from fasting glucose and insulin levels. Multiple linear regression analyses were carried out to detect determinants of HOMA‐IR. Insulin resistance was conventionally defined as the upper quartile of the HOMA‐IR values. The diagnostic power of clinical and biochemical markers for insulin resistance was assessed using receiver operating characteristic curves. Results: Some 90% of the women with HOMA‐IR ≥ 2.8 (75th percentile as cutoff) showed abnormal glucose metabolism and 45% of them had silent diabetes (odds ratio 6.09, 95% CI 3.17 – 11.73 vs. those with HOMA‐IR < 2.8). Results revealed that uric acid, body mass index, waist circumference, alanine aminotransferase, triglycerides, and high‐density lipoprotein cholesterol were important determinants of HOMA‐IR in these women. Using uric acid ≥ 5.0 mg/dL as a cutoff point, we could diagnose insulin resistance with 75.4% sensitivity and 73.1% specificity. Conclusion: Postmenopausal women with HOMA‐IR‐estimated insulin resistance were at high risk of glucose abnormalities in this study. High HOMA‐IR values were significantly associated with six clinical and biochemical indicators. Among these, high serum uric acid levels seemed to be a useful marker identifying postmenopausal women with insulin resistance. This study was registered at clinicaltrials.gov as NCT00945271.

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 (ΔAUC 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.

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.

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.