Beyond the clinical model of recovery: recovery of a Chinese immigrant woman with bipolar disorder.

Recovery from serious mental illness can be conceptualised in a number of ways, some more helpful to clients than others. This paper aimed to show that the clinical model of recovery, based on symptom relief, return to function, and freedom from hospitalisation, is a limited one and that a holistic approach is needed. The author has chosen to narrate her own story. She is a Chinese immigrant from Hong Kong to Canada suffering from bipolar illness, who was hospitalised several times and, eventually, achieved full recovery. The recovery of the author illustrates the limitations of the clinical model of recovery. Her story demonstrates the importance of the principles of empowerment, as achieved through self-management, social support, meaningful occupation, and spiritual fulfilment. The empowerment model of recovery is recommended for the use of mental health professionals, with special attention to individual client factors such as culture and gender.

Type 2 diabetes prevalence and incidence among adults in Taiwan during 1999-2004: a national health insurance data set study.

AIM: To evaluate annual prevalence and incidence of Type 2 diabetes and to examine possible trends among adults in Taiwan. METHODS: A retrospective nationwide longitudinal study using the Taiwan National Health Insurance Research Database collected during 1999-2004. Adult patients aged > or = 20 years old with prevalent and incident Type 2 diabetes were identified using ICD-9-CM diagnostic codes. Age-specific and age-direct-standardized annual incidence and prevalence were calculated to describe their trends in different gender and age group and compared using Poisson regression. RESULTS: During the study years, the age-standardized prevalence of Type 2 diabetes increased from 4.7 to 6.5% for men and from 5.3 to 6.6% for women. The increasing trends in prevalence were significant and higher among people aged < 40 and > or = 80 years. The age-standardized incidence rates of Type 2 diabetes per 1000 person-years were approximately 7.6 and remain stable for men, but decreasing from 7.7 to 6.9 for women. However, the incidence increased significantly in younger adults aged < 40 years whose relative incidence (RI with 95% confidence interval) was 1.31 (1.20-1.42) for men and 1.04 (1.01-1.08) for women. The incidence trends for people aged > or = 40 years were decreased for men and women. The differences in incidence trends between age groups and between genders were all statistically significant (all P < 0.001). CONCLUSIONS: This study demonstrated a substantial increasing trend in Type 2 diabetes prevalence during 1999-2004 among adults in Taiwan. Despite the incidence decreased in older people, young men aged 20-40 years were most susceptible to higher incidence of Type 2 diabetes.

Insulin sensitivity and resistin expression in nitric oxide-deficient rats.

AIMS/HYPOTHESIS: The aim of this study was to investigate changes in insulin sensitivity and expression of the gene encoding resistin (Retn) in adipocytes from long-term nitric oxide (NO)-deficient rats. METHODS: Male Sprague-Dawley rats received [Formula: see text]-nitro-L: -arginine methyl ester (L-NAME 0.5 mg/ml) in their drinking water for 4 weeks, while control rats received plain drinking water. During the experimental period, changes in plasma glucose, insulin and C-peptide levels were measured. After administration of L-NAME for 4 weeks, insulin sensitivity was evaluated in vivo and in vitro. An insulin binding assay was also performed to determine the number and binding affinity of insulin receptors in adipocytes. Adipocyte Retn mRNA levels were examined using northern blotting. RESULTS: Successful induction of NO deficiency was demonstrated by an increase in systemic blood pressure. No difference in plasma glucose levels was found between the two groups. Compared with the control rats, plasma insulin and C-peptide levels were significantly decreased in the NO-deficient rats, and insulin sensitivity was significantly increased. Insulin-stimulated glucose uptake and insulin binding capacity, but not binding affinity, were significantly increased in adipocytes isolated from NO-deficient rats. In addition, adipocyte Retn mRNA levels, but not plasma resistin levels, were significantly decreased in NO-deficient rats, and the Retn mRNA levels were negatively correlated with insulin sensitivity. CONCLUSIONS/INTERPRETATION: Insulin sensitivity was increased in NO-deficient rats and this was associated with insulin binding capacity and downregulated Retn expression. These findings suggest that NO plays a regulatory role in metabolism. Dysregulation of NO production may result in the development of metabolic disorders.

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.

Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids.

Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.

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.

Growth inhibition of cultured smooth muscle cells by corrosion products of 316 L stainless steel wire.

The potential cytotoxicity on vascular smooth muscle cells of corrosion products from 316 L stainless steel, one of most popular biomaterials of intravascular stents, has not been highlighted. In this investigation, 316 L stainless steel wires were corroded in Dulbecco's modified eagle's medium with applied constant electrochemical breakdown voltage, and the supernatant and precipitates of corrosion products were prepared as culture media. The effects of different concentrations of corrosion products on the growth of rat aortic smooth muscle cells were conducted with the [3H]-thymidine uptake test and cell cycle sorter. Both the supernatant and precipitates of corrosion products were toxic to the primary culture of smooth muscle cells. The growth inhibition was correlated well with the increased nickel ions in the corrosion products when nickel concentration was above 11.7 ppm. The corrosion products also changed cell morphology and induced cell necrosis. The cell growth inhibition occurred at the G0/G1 to S transition phase. Similar to our recent study of nitinol stent wire, the present investigation also demonstrated the cytotoxicity of corrosion products of 316 L stainless steel stent wire on smooth muscle cells, which might affect the poststenting vascular response.

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.

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.

The cytotoxicity of corrosion products of nitinol stent wire on cultured smooth muscle cells.

Although nitinol is one of most popular materials of intravascular stents, there are still few confirmative biocompatibility data available, especially in vascular smooth muscle cells. In this report, the nitinol wires were corroded in Dulbecco's modified Eagle's medium with constant electrochemical breakdown voltage and the supernatant and precipitates of corrosion products were prepared as culture media. The dose and time effects of different concentrations of corrosion products on the growth and morphology of smooth muscle cells were evaluated with [(3)H]-thymidine uptake ratio and cell cycle sorter. Both the supernatant and precipitate of the corrosive products of nitinol wire were toxic to the primary cultured rat aortic smooth muscle cells. The growth inhibition was correlated well with the increased concentrations of the corrosion products. Although small stimulation was found with released nickel concentration of 0.95 +/- 0.23 ppm, the growth inhibition became significant when the nickel concentration was above 9 ppm. The corrosion products also altered cell morphology, induced cell necrosis, and decreased cell numbers. The cell replication was inhibited at the G0-G1 to S transition phase. This was the first study to demonstrate the cytotoxicity of corrosion products of current nitinol stent wire on smooth muscle cells, which might affect the postimplantation neointimal hyperplasia and the patency rate of cardiovascular stents.

Combined use of insulin and endothelin-1 causes decrease of protein expression of beta-subunit of insulin receptor, insulin receptor substrate-1, and insulin-stimulated glucose uptake in rat adipocytes.

Previously, we reported that insulin-stimulated glucose uptake (ISGU) can be inhibited by endothelin (ET-1). However, the mechanism by which ET-1 impairs ISGU in adipocytes remains unclear. This study investigated the effects of ET-1 on insulin action in rat adipocytes in order to elucidate the molecular mechanism of action of ET-1 on ISGU. The results show that ISGU was increased fivefold after 3-h treatment with 1 nM insulin. Treatment with 100 nM ET-1 had no effect on basal glucose uptake. However, ET-1 inhibited approximately 25% of ISGU and 20% of insulin binding after 3-h treatment in the presence of 1 nM insulin. Expression of the beta-subunit of the insulin receptor (IRbeta) and the insulin receptor substrate-1 (IRS-1) in adipocytes was not significantly affected by 1 nM insulin or by 100 nM ET-1, even after 3-h treatment. However, expressions of IRbeta and IRS-1 were dramatically decreased in a dose- and time-dependent manner when adipocytes were treated with both insulin and ET-1. Approximately 50% of IRbeta and 65% of IRS-1 expression levels were suppressed when adipocytes were simultaneously treated with both 1 nM insulin and 100 nM ET-1 for 3 h. These results suggest that the inhibitory effect of ET-1 on ISGU may be mediated via the insulin receptor and suppression of IRbeta/IRS-1 expression.

A novel mutation in the hepatocyte nuclear factor-1alpha/MODY3 gene in Chinese subjects with early-onset Type 2 diabetes mellitus in Taiwan.

AIMS: The goal of this study was to determine the frequency of mutation in hepatic nuclear factor (HNF)-1alpha, a gene recently implicated as causing maturity-onset diabetes of the young (MODY) and to analyse the respective clinical presentations in an ethnically Chinese population. METHODS: Fifteen unrelated subjects (nine females and six males) aged less than 35 years who had early-onset diabetes were analysed to test the possibility that mutation of the HNF-1alpha gene was responsible for this disorder. Genomic DNA extraction, polymerase chain reaction and DNA sequence analysis were performed accordingly. RESULTS: One patient with MODY had a novel missense mutation in exon 3 of the HNF-1alpha gene (Y218C) in a region of the protein that corresponds to a predicted DNA binding domain. CONCLUSIONS: A Y218C mutation in HNF-1alpha gene was identified in one family in Taiwan.

Insulin sensitivity in normotensive offspring of hypertensive parents.

OBJECTIVES: To investigate the insulin sensitivity in normotensive offspring of hypertensive parents. SUBJECTS: Fifteen young normotensive offspring of hypertensive parents were paired with 15 controls matched for age, sex and body mass index. METHODS: The insulin sensitivity was investigated by 75 g oral glucose tolerance test (OGTT) and modified insulin suppression test. A high-fat mixed meal was administered to observe the changes of TG levels. RESULTS: The plasma glucose and serum insulin responses to oral glucose challenge were comparable between both groups. High-fat mixed meal made no difference in the plasma glucose, serum triglyceride or insulin between the 2 groups. With the modified insulin suppression test, the steady-state plasma glucose levels (SSPG) were higher in the offspring of parents with essential hypertension (138+/-43 mg/dl) than in the control group (95+/-26 mg/dl). The diastolic blood pressure and heart rate of the offspring of hypertensive parents are also higher than the control group. CONCLUSIONS: Insulin resistance exists in young normotensive offspring of hypertensive parents, and the impairment of insulin-mediated glucose uptake in these subjects develop before any alteration of fasting and postprandial triglyceride.

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. METHODS: A double-blind, randomized, placebo-controlled and two-period crossover study. After a 2-month run-in, 19 eligible Type 2 diabetic patients with hypercholesterolaemia were randomized to receive either simvastatin or placebo for 3 months, exchanging their treatment thereafter for another 3 months. Blood samples were taken in month 0 and at monthly intervals to measure serum lipids and indices of glycaemic control. An euglycaemic insulin clamp was performed in months 0, 3 and 6 to assess change of insulin sensitivity. The amount of glucose infused during 90-120 min of the clamp (M), and the mean values of serum insulin during 90-120 min (I) were measured. The M and M/I ratio were used to represent the in vivo insulin sensitivity of the subject. RESULTS: Simvastatin significantly reduced serum total cholesterol (TC) by 23+/-18% and low density lipoprotein-cholesterol (LDL-C) by 30+/-26%. It did not alter glycaemic control. The M-values and M/I ratios were similar in both groups in each period and no drug effect on insulin sensitivity could be identified. CONCLUSIONS: Simvastatin significantly reduced the serum TC and LDL-C levels without alteration of insulin sensitivity in Type 2 diabetic patients with hypercholesterolaemia.

Octreotide effect on hypersecretion of growth hormone in a patient with fibrous dysplasia: a case report.

We report the case of a 17-year-old adolescent boy with polyostotic fibrous dysplasia and hypersecretion of growth hormone (GH). The fasting serum GH, insulin-like growth factor-I (IGF-I), alkaline phosphatase activity and osteocalcin levels were all elevated. The GH secretion was stimulated by thyrotropin-releasing hormone and was not suppressed by an oral glucose test. Magnetic resonance imaging of the sella turcica showed no abnormal findings. The patient was treated with octreotide, 100 micrograms subcutaneous injection three times a day for two weeks to observe the effects of octreotide on growth hormone secretion. GH and IGF-I secretions were suppressed by octreotide therapy, while alkaline phosphatase activity and osteocalcin secretion were partially suppressed. We suggest that the high bone turnover states in this patient may be attributed to both hypersecretion of growth hormone and the polyostotic fibrous dysplasia itself.