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.

Identification of persistent defects in insulin receptor structure and function capillary endothelial cells from diabetic rats.

Insulin actions and receptors were studied in capillary endothelial cells cultured from diabetic BB rats and their nondiabetic colony mates. The endothelial cells from diabetic rats of 2 mo duration had persistent biological and biochemical defects in culture. Compared with normal rats, endothelial cells from diabetic rats grew 44% more slowly. Binding studies of insulin and insulin-like growth factor I (IGF-I) showed that cells from diabetic rats had 50% decrease of insulin receptor binding (nondiabetic: 4.6 +/- 0.7; diabetic: 2.6 +/- 0.4% per milligram protein, P less than 0.01), which was caused by a 50% decrease in the number of binding sites per milligram protein, whereas IGF-I binding was not changed. Insulin stimulation of 2-deoxy-glucose uptake and alpha-aminoisobutyric acid uptake were also severely impaired with a 80-90% decrease in maximal stimulation, in parallel with a 62% decrease in insulin-stimulated autophosphorylation (P less than 0.05). 125I-insulin cross-linking revealed an 140-kD alpha subunit of the insulin receptor similar to that in cells from nondiabetic rats, although bands at greater than 200 kD were also detected. The molecular weight of the insulin receptor beta subunit (by SDS-PAGE) was smaller in cells from diabetic than from normal rats (88-90 vs. 95 kD). Neuraminadase treatment of the partially purified insulin receptors decreased the molecular weight of the insulin receptors from nondiabetic rats to a greater degree than its diabetic counterpart. In contrast, Northern blot analysis of insulin receptor mRNAs using human cDNA probes revealed two species of 9.4 and 7.2 kb with no difference in mRNA abundance between cells from diabetic and nondiabetic rats. We conclude that the exposure of capillary endothelial cells to a diabetic milieu in vivo can cause specific and persistent changes in the insulin receptor and insulin action.

Growth hormone (GH) replacement reduces total body fat and normalizes insulin sensitivity in GH-deficient adults: a report of one-year clinical experience.

The effects of GH replacement on body fat composition and insulin sensitivity were assessed in GH-deficient adults. The patients were randomized into a double-blind, placebo-controlled study of human recombinant GH replacement therapy for 6 months (period 1), followed by an open phase of GH for another 6 months (period 2). Anthropometric variables, body fat composition (fat %), and biochemical parameters were measured during the trial. Measurements of in vivo insulin sensitivity were carried out at the commencement of the study and on completion of the trial by modified insulin suppression test. The modified insulin suppression test was performed both in the morning (AM) and in the afternoon (PM) to further evaluate the PM-AM steady-state plasma glucose (SSPG) pattern. We found that the GH-deficient adults had more body fat and were insulin resistant. Significant reduction in fat % and total body fat mass was found in the active arm of period 1 without alteration of body weight. Besides, we demonstrated, for the first time, the GH replacement for 6 months did not alter the insulin sensitivity, but replacement for a longer period (12 months) normalized not only the AM SSPG level but also the PM-AM SSPG pattern. We also found a positive correlation between SSPG (regardless of AM vs. PM) and fat % and total body fat mass. In conclusion, normalization of insulin sensitivity in GH-deficient adults after replacement of GH may be related to the reduction of total body fat.

Overexpression of vascular endothelin-1 and endothelin-A receptors in a fructose-induced hypertensive rat model.

OBJECTIVE: To examine the temporal relationship between hyperinsulinemia and hypertension in the fructose-hypertensive rat model and to study the function of endothelin-1 (ET-1) in fructose-induced hypertension. DESIGN: Since ET-1 induces insulin resistance in conscious rats, we tested the hypothesis that both hyperinsulinemia and hypertension developed in the fructose-hypertensive rat model might be the sequelae of an elevated tissue content of ET-1 and ET(A) receptors. MATERIALS AND METHODS: Systolic hypertension was induced within 3 weeks in male Sprague-Dawley rats fed on a fructose-rich diet. After continual monitoring of blood pressure and plasma insulin concentrations, the animals were killed at the end of experiment to determine plasma levels of ET-1, the contractile response of aortic rings to ET-1, and ET-1 and ET(A) receptor gene expressions. In a separate experiment, BQ-610 was administered to lower the effect of ET-1 in rats with fructose-induced hypertension. RESULTS: Compared with control rats given normal chow, the fructose-fed rats developed systolic hypertension after 3 weeks of the diet (127+/-3.7 versus 110+/-5.5 mmHg, P < 0.01) and hyperinsulinemia both before (1 07.1+/-32.5 versus 48.5+/-14.3 pmol/l, P < 0.005) and after (96.6+/-63.7 versus 50.4+/-5.6 pmol/l, P< 0.05) they became hypertensive. Although plasma ET-1 levels did not differ between the rat groups, aortic ring contraction-concentration curves, indicating vessel contractility in response to ET-1, were significantly greater in these rats than in controls (F1,72 = 12.34, P< 0.00077). Messenger RNA extracted from the tail arteries and blotted with both ET-1 and ET(A) probes showed that fructose-fed rats had greater ET-1 and ET(A)-receptor gene expression than control rats. Concomitant administration of BQ-610 to rats fed on a fructose diet significantly reduced the hypertension. Conclusions These findings suggest that elevated vascular expression of ET-1 and ET(A) receptor genes may mediate the development of hypertension and hyperinsulinemia in rats fed a fructose-rich diet

Insulin-like growth factor-I receptor increases in aortic endothelial cells from diabetic rats.

Endothelial cells are likely to play an important role in the development of diabetic vascular diseases, since they are exposed directly to the abnormal circulating metabolites of diabetes and may be easily damaged early in the natural course of vascular complications. In this study, aortic endothelial cells were cultured from diabetic BB rats. Their binding and internalization of insulin-like growth factor-I (IGF-I) were measured. IGF-I binding was higher in cells of diabetic rats than of control rats at both 37 degrees C (4.5% +/- 1.6% v 2.74% +/- 0.9% per mg protein, P < .05) and 4 degrees C (20.6% +/- 5.6% v 13.7% +/- 4.6% per mg protein, P < .01). Internalization of IGF-I also increased (1.62% +/- 0.2% v 0.74% +/- 0.15% of total count at 37 degrees C after 60 minutes, P < .05). Cross-linking studies showed that in cells from diabetic rats, the major band of 140 kd corresponding to the alpha-subunit of the IGF-I receptor increased in density by 50% compared with those from control rats. The IGF-I-stimulated tyrosine kinase activity (TKA) of partially purified receptor from cells of diabetic rats, measured using poly-glu-tyr as substrate, was normal. Since the biological effects of IGF-I are initiated by its binding to the IGF-I receptor, which is able to transduce mitogenic and metabolic signals, our results support the hypothesis that the IGF-I receptor is involved in the development of diabetic vascular complications.

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.

Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors.

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake (ISGU) in rat adipocytes was investigated. Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley rats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agonist for ETC receptors, to displace [125I]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 >> ET-3, indicating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 micromol/L, BQ-610, a selective ETA antagonist, displaced [125I]ET-1 from binding to fat cells, whereas IRL-1038, a selective ETB antagonist, did not. Using [3H]2-deoxy-D-1-glucose ([3H]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 completely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was ineffective. Northern blot analysis of adipocyte receptors showed abundant mRNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes.

Exogenous hyperinsulinemia causes insulin resistance, hyperendothelinemia, and subsequent hypertension in rats.

In many clinical and animal studies, hypertension and insulin resistance coexist, but their mechanistic relationship is unclear. We explored the causal link between these two parameters in a rat model with chronic hyperinsulinemia induced with human insulin (1 U/d) released from subcutaneously implanted minipumps. Rats with saline minipumps served as a control. During the first experiment, plasma levels of insulin and glucose and the systolic blood pressure of the two groups were continuously monitored for 17 days. In the subsequent four experiments, rats were killed on days 10 and 13 to measure plasma endothelin-1 (ET-1) levels and the glucose transport into and insulin and ET-1 binding of isolated adipocytes. In one experiment, rats were tested for oral glucose tolerance on days 10 and 13. In another experiment, ET-1 binding to the aortic plasma membrane was also determined. The results showed that rats became hyperinsulinemic throughout the experimental period by the instillation of exogenous insulin. Hyperinsulinemic rats were consistently hypoglycemic during the first day, but they became euglycemic thereafter, indicating an insulin-resistant state. Glucose intolerance was obvious by day 10, but significant hypertension was not detected until the 11th day on insulin infusion. Compared with the saline controls, insulin-infused rats had an increase of plasma ET-1 levels but a decrease of both basal and insulin-stimulated glucose transport into adipocytes. ET-1 binding to adipocytes of the insulin-infused group was elevated significantly from day 10 through day 13. ET-1 binding to the aortic membranes, supposedly downregulated by the increased plasma ET-1 and hypertension, was similar to that found in the controls on day 13. These results imply that hyperinsulinemia in rats could lead to hypertension via the elevation of plasma ET-1 levels together with an unaltered vascular binding of ET-1, which was probably unrelated to the insulin resistance.

Amelioration of insulin resistance and hypertension in a fructose-fed rat model with fish oil supplementation.

In type II diabetic patients, one can detect several pathologic changes including insulin resistance and hypertension. Sprague-Dawley rats fed a fructose-rich diet (group F) exhibited these characteristic abnormalities within 2 weeks and were an excellent laboratory animal model for research on insulin action and development of hypertension. Since fish oils containing omega-3 fatty acids have a beneficial effect in preventing atherosclerotic diseases, we performed repeated experiments to test the effects of fish oil supplementation in group F rats. Compared with control rats on a normal diet (group C), group F consistently developed hypertriglyceridemia without elevated plasma free fatty acid (FFA), fasting hyperinsulinemia together with fasting hyperglycemia (insulin resistance syndrome), and systolic hypertension within 3 weeks. Insulin-stimulated glucose uptake and insulin binding of adipocytes were significantly reduced. Rats fed the same high-fructose diet but supplemented with fish oil (group O) had alleviation of all of these metabolic defects and a normalized insulin sensitivity and blood pressure. beta-Cell function as shown by plasma glucose and insulin responses to oral glucose remained intact in group F and group O. The plasma endothelin-1 (ET-1) level and ET-1 binding to adipocytes were not different among the three groups. Based on these results, we suggest that dietary high fructose induced hypertriglyceridemia and insulin resistance with normal islet function, and that the induced hypertension was not associated with plasma ET-1 abnormalities and was probably caused by other undefined pathologic changes that can be prevented by dietary omega-3 fatty acids.

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.

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.

Technical and clinical evaluation of an electrochemistry glucose meter: experience in a diabetes center.

The Sensorex (Metertech, Taipei, Taiwan), an electrochemical blood glucose meter, is designed for self-monitoring of blood glucose (BG) concentrations in capillary blood through the use of an electrochemical test strip. The intra-assay coefficients of variation of Sensorex were 5.2, 5.4, and 4.7% at BG levels of 46, 154 and 302 mg/dl respectively. The BG concentrations tested by Sensorex were correlated well with those by YSI method (r approximately/= 0.85, P < 0.0001). The intraclass correlation coefficients (rI) between the results obtained by Sensorex and YSI were 0.84 in capillary blood and 0.69 in venous whole blood, which indicated good agreement between both methods. The Sensorex was evaluated by error grid analysis and revealed 'acceptance' results. In field test, the Sensorex results obtained by lay users were in concordance with those by trained technicians (rI = 0.87). Our data show that the Sensorex glucometer is reliable and easy to use. We also demonstrate a practical clinical approach for the evaluation of a novel SMBG system.

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.

Steroid cell tumors of the ovary: clinical, ultrasonic, and MRI diagnosis--a case report.

Steroid cell tumors of the ovary are rare sex-cord neoplasms which account for less than 0.1% of all ovarian tumors. They have been divided into two subtypes according to their cell of origin as follows: stromal luteoma, and Leydig cell tumors, and a third subtype with lineage unknown is a steroid cell tumor, not otherwise specified (NOS). The clinical presentation may take many forms, including pain, abdominal distention and bloating, but perhaps the most interesting and noticeable presentations are those related to the hormonal activity and virilizing properties of the tumor. No radiological features of the steroid cell tumor, NOS have been presented in the literature. This report presents the MRI and ultrasonographic findings of a patient having steroid cell tumor, NOS, of the right ovary with metastasis to the uterus.

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.

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.

Metabolic control and B cell function in patients with diabetes mellitus secondary to chronic pancreatitis.

To investigate the relationship between metabolic control and beta cell functions in chronic pancreatitis, 30 patients were selected for study, including 10 with diabetes mellitus in insulin-dependent state (group 1, Mean age 37.6), 10 with diabetes mellitus in non-insulin-dependent state (group 2, Mean age 47.8), and 10 with normal fasting glucose levels (group 3, Mean age 42.1). Each patient received urine routine, stool fat, renal function, biochemical study such as: serum lipid and glycosylated hemoglobin, eye fundi and X-ray examinations. Beta cell function was measured by C-peptide concentration six minutes after intravenous infusion of 1 mg glucagon. The results showed that the glycosylated hemoglobin concentrations were higher in group 1 than in group 2 or 3 patients (P less than 0.05), and were higher in group 2 than in group 3 patients (P less than 0.001) as well. The cholesterol and triglyceride levels were not significantly different among three groups. Furthermore, eight and two of group 1 and 2 patients manifested pancreatic calcification on abdomen X-ray examination (P less than 0.05). All and eight of group 1 and 2 patients received insulin injection respectively. In addition, group 1 patients were more likely to develop steatorrhea, other associated diseases and uncontrolled plasma glucose levels as compared with group 2 patients. In conclusion, insulin-dependent pancreatic diabetics had more advanced disease process and were therefore more likely to get other associated diseases than noninsulin-dependent pancreatic diabetics.

Insulin-pen: preliminary report on its use for multiple injection regiment in insulin-dependent diabetic patients.

Insulin pens are pen-like devices for multiple injection of insulin. They can cut down the equipment necessary for a multidose regimen and thus make the therapy more convenient and flexible to help improve daily-life quality. It is of interest for us to known whether the average diabetic patients are motivated to achieve better metabolic control by means of insulin-pens. Seven insulin-dependent diabetic patients (male: 3, female: 4, age: 21-34 years) from the Veterans General Hospital participated in the study. None of them had diabetic proliferative retinopathy or proteinuria. They are initially treated with twice daily injection of mixtures of short- and intermediate-acting insulin (run-in period, 8 weeks). A multi-dose regimen with three premeal injections of short-acting insulin with insulin-pen plus one injection of long-acting insulin at bedtime was then used during the study period (12 weeks). Improved in metabolic control as assessed by HbAlc (7.6 +/- 0.9 vs 6.9 +/- 0.8%) and mean blood glucose (175.2 +/- 34 vs 152.3 +/- 28.1 mg/dl) in all patients was found. The frequency and severity of hypoglycemic episodes were not changed. In addition, all patients chose to continue multiple injection using insulin-pen, indicating a high acceptability of such device.

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.