Peripheral and hepatic insulin antagonism in hyperthyroidism.

Eight hyperthyroid and eight normal subjects underwent 2-h oral glucose tolerance tests (OGTT) and euglycemic clamp studies to assess the presence of peripheral and hepatic insulin antagonism in hyperthyroidism. Although the mean total glucose area during the OGTT was similar in the hyperthyroid patients and normal subjects [16.4 +/- 0.8 (+/- SE) vs. 15.8 +/- 0.7 mmol/L.h], the mean insulin area was significantly elevated in the hyperthyroid group (1413 +/- 136 vs. 1004 +/- 122 pmol/L.h; P less than 0.05). Basal hepatic glucose production was measured during the second hour of a primed [3-3H]glucose infusion. A two-insulin dose euglycemic clamp study with [3-3H]glucose and somatostatin (500 micrograms/h) was carried out during the next 6 h. The insulin infusion rate was 0.05 mU/kg.min during the third, fourth, and fifth hours and 0.60 mU/kg.min during the sixth, seventh, and eighth hours. Hepatic glucose production and glucose utilization were measured during the final 0.5 h of each clamp period. Serum C-peptide concentrations were measured in the initial sample and in the last sample of each clamp period. The mean equilibrium serum insulin concentrations were similar in both groups during the final 0.5 h of the low (90 +/- 8 vs. 79 +/- 6 pmol/L) and high (367 +/- 11 vs. 367 +/- 15 pmol/L) insulin infusion rates. Basal serum C-peptide levels were significantly increased in the hyperthyroid patients (596 +/- 17 vs. 487 +/- 43 pmol/L; P less than 0.05) but were suppressed equally in both groups at the end of both clamp periods. The MCRs of insulin were similar in the hyperthyroid and normal subjects during the low (6.7 +/- 1.1 vs. 5.6 +/- 0.5 mL/kg.min) and high (11.9 +/- 0.4 vs. 12.1 +/- 0.5 mL/kg.mm) insulin infusion rates. Glucose production was significantly increased in the hyperthyroid patients during the basal state (17.6 +/- 0.9 vs. 11.5 +/- 0.5 mumol/kg.min; P less than 0.001) and remained elevated during the final 0.5 h of the low (12.1 +/- 1.1 vs. 5.9 +/- 1.7; P less than 0.01) and high (3.2 +/- 1.2 vs. 0.5 +/- 0.3; P less than 0.05) insulin infusion rates. Peripheral insulin action, assessed by Bergman's sensitivity index, was significantly decreased in the hyperthyroid patients (7.4 +/- 2.2 vs. 15.6 +/- 2.1 L/kg min-1/pmol/L; P less than 0.02). In conclusion, hyperthyroidism is characterized by 1) hyperinsulinemia after oral glucose loading, 2) increased basal hepatic glucose production, 3) impairment of insulin-mediated suppression of hepatic glucose production, and 4) antagonism to insulin-stimulated peripheral glucose utilization.

Effect of thyroxine administration on serum thyrotropin receptor antibody and thyroglobulin levels in patients with Graves' hyperthyroidism during antithyroid drug therapy.

Graves' hyperthyroidism is due primarily to overproduction of antibodies to thyrotropin receptors (TR-ab), which stimulate the thyroid gland and cause hyperthyroidism. Antibody production during antithyroid drug therapy is an important determinant of the course of the disease. We therefore observed the changes of serum TR-ab, thyroglobulin (Tg) and thyroid hormone levels in response to administration of L-thyroxine (T4) in Graves' hyperthyroid patients during antithyroid drug therapy. Serum levels of TR-ab, Tg and other thyroid hormones were measured by radioimmunoassay (RIA) during either methimazole treatment alone or in combination with thyroxine in 60 Graves' hyperthyroid patients. The patients initially were treated with 30 mg of methimozole daily for 3 months, which was then reduced to 15 mg daily for the following 3 months. All patients were euthyroid 6 months after the start of antithyroid therapy and the TR-ab level decreased from 61 +/- 11% (+/- SD) to 28 +/- 7% (p < 0.01). Patients then were divided into three groups: group A (N = 25), whose TR-ab level was 10% or more (the cut-off value for positivity), received 0.1 mg of T4 and 10 mg of methimazole daily for 6 months; group B (N = 15), whose TR-ab level also was 10% or more and was age- and thyroid function-matched with group A, received only 10 mg of methimazole daily for 6 months; group C (N = 20), with a TR-ab level of less than 10%, received 10 mg of methimazole alone daily for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Increased urinary excretion of sulfated 3,3',5-triiodothyronine in patients with nodular goiters receiving suppressive thyroxine therapy.

Increased serum 3,3',5-triiodothyronine sulfate (T3S) levels have been detected in various pathophysiologic states. However, little is known about T3S concentrations in other biological fluids. By employing a highly sensitive, specific, and reproducible radioimmunoassay (RIA), we measured T3S in the serum and urine of 20 premenopausal women with benign nodular goiters before and after administration of thyroxine for 6 months (T4; 3.2 micrograms/kg/day). Serum T3 concentrations did not change significantly after treatment (2.0 vs. 1.7 nmol/L; p > 0.05). However, the mean serum T4 and free T4 concentrations were significantly higher after treatment (138 vs. 88 nmol/L and 28 vs. 17 pmol/L; p < 0.01, respectively). Serum thyroid stimulating hormone (TSH) levels were significantly reduced after T4 treatment (0.13 vs. 0.66 mU/L, p < 0.01) and the serum levels of T3S were significantly increased after treatment (82 vs. 45 pmol/L; p < 0.01). A good correlation was observed between increased serum T3S and T4 concentrations (r = 0.66; p < 0.001). The sulfoconjugate of T3 was significantly increased in creatinine-corrected urine after treatment (606 vs. 253 pmol/umol Cr.; p < 0.01). There was a significant correlation between increased creatinine-corrected urine T3S and increased serum free T4 (r = 0.65; p < 0.001). In summary, significant increases in serum and urine T3S levels were noted in T4-treated patients with subnormal serum TSH and borderline elevated T4. We thus conclude that the sulfation pathway may play a role in the homeostasis of thyroid hormone metabolism in T4-treated subjects with relative hyperthyroxinemia. In addition, the creatinine-corrected urine concentrations of T3S may serve as an index for the evaluation of T4-treated patients with elevated levels of T4.

Insulin secretion and insulin action in Taiwanese with type 2 diabetes.

In contrast to the United State, type 2 diabetes appears to be a common occurrence in non-obese Asians. In order to evaluate the possibility that this epidemiologic difference was indicative of a basic metabolic phenomenon, estimates of insulin secretion and insulin action were generated in 32 Chinese males, 16 with type 2 diabetes and 16 with normal glucose tolerance. Half of the individuals in each diagnostic category were obese (body mass index greater than 28 kg/m2) and half were non-obese (less than 26 kg/m2). Plasma glucose responses to a 75-g oral glucose challenge were significantly higher in patients with type 2 diabetes, but did not vary significantly within either group as a function of obesity. Plasma insulin concentrations were lower than normal when patients with type 2 diabetes were compared to their weight-matched controls. In addition, the absolute insulin values also varied as a function of body weight, with higher plasma insulin concentrations observed in the obese individuals. Insulin action was estimated by determination of the steady-state plasma insulin (SSPI) and glucose (SSPG) concentrations during the last 60 min of a continuous 180-min intravenous infusion of somatostatin, crystalline insulin, and glucose. Under these conditions endogenous insulin secretion is suppressed, SSPI concentrations are similar in all individuals, and SSPG concentrations provide a quantitative estimate of insulin-stimulated glucose disposal. The results of these studies indicated that patients with type 2 diabetes had significantly elevated SSPG concentrations as compared to normals, and this was true whether the diabetic subjects were obese or non-obese.(ABSTRACT TRUNCATED AT 250 WORDS)

A new reversed phase, paired ion thin-layer chromatographic method for steroid sulfate separations.

The sulfoconjugated steroids estrone sulfate (ES) and dehydroepiandrosterone sulfate (DS) were separated in the reversed phase mode on polyamide-coated TLC plates. Baseline resolution was obtained between tritiated ES and DS standards when run with a mobile phase of 20% acetonitrile in 5mM aqueous triethylamine, triethanolamine, tris-hydroxymethylaminomethane, tributylamine or ammonia. ES and DS showed no mobility in the absence of an ion-pair reagent. The radioactive peaks were detected and integrated non-destructively by scanning. Quantitation was confirmed by elution of cut-out peak areas and liquid scintillation counting. Similar results were obtained with washed ethanol extracts of serum labeled with tritiated ES and DS. The extracts were defatted on the plate with hexane: ethyl acetate (1:1) prior to the reversed phase development.

A new partition thin-layer chromatographic method for steroid separations.

TLC plates with a 25 mu thick polyamide stationary phase were modified for the separation of neutral steroids by impregnation with propylene glycol. A mixture of tritiated 5 alpha-androstan-3 alpha,17 beta-diol, testosterone, 17 beta-hydroxy-5 alpha-androstan-3-one and 4-androstene-3,17-dione was applied to the plate and developed in a toluene mobile phase to a height of 13.6 cm. This resulted in complete resolution of the 4 compounds as detected by a gas flow scanner or imaging analyzer. Cutting and elution of peak areas with methanol resulted in quantitative recovery of all four steroids. The thinness of the layer also permitted a 3-5% counting efficiency on scanning, resulting in good quantitation of recovery without liquid scintillation counting. The high sorptive capacity of the polyamide layer also enabled extracts of normal human serum to be defatted on the TLC plate by development with pure hexane prior to the toluene step. The new method thus offers several advantages over existing methods for steroid separations and should be adaptable to separations of other relatively non-polar compounds.

[Microalbuminuria in insulin-dependent diabetes mellitus: a comparison of specimen collection, analytic methods and relationship with glycemic control and blood pressure].

The excretion of small quantities of urinary albumin (microalbuminuria = urinary albumin excretion rate, UAER = 20-200 micrograms/min) may predict renal function in both insulin-dependent and noninsulin-dependent diabetes. We compared radioimmunoassay with the immunoturbidimetric method to detect early increases in urine albumin concentration. More problems have been encountered in deciding which method of collecting urine best differentiate between early onset diabetic nephropathy and normality. Random urine samples collected at clinics are convenient but show wide variations in concentration and the effects of exercise. Such variations may be overcome by using a rest period and correcting for urine creatinine concentration. We studied 21 IDDM patients (12 female, 9 male), aged 13-33 years old (mean 21) and 11 nondiabetics (6 female, 5 male), aged 15-30 years old (mean 23). All gave negative results on testing with Albustix at clinic visits. All subjects passed urine immediately after they got up in the morning. The results disclosed: (1) The correlation coefficient of albumin excretion (micrograms/ml) in the urine collected overnight with that collected over 24 hours was good (r = 0.89, p less than 0.001). (2) When the albumin excretion rate of the urine collected overnight was expressed as microgram albumin/mg creatinine, the correlation was also as good as the 24-hr urine albumin excretion (microgram albumin/mg creatinine) (r = 0.87, p less than 0.001). (3) The results of our study support the use of urine samples collected overnight, corrected for creatinine, to estimate microalbuminuria.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of thyroxine-suppressive therapy and its relation to serum thyroglobulin levels in solitary nontoxic thyroid nodules.

Patients with nontoxic thyroid nodules are often treated with thyroxine (T4) in order to reduce the size of the nodule, but the efficacy of thyrotropin-suppressive therapy with thyroxine remains uncertain. In this study, 35 patients with a solitary thyroid nodule were given thyroxine (0.1 mg/day) for three months. High resolution (7.5 MHz) sonography was used to measure the size of the nodules before and after thyroxine therapy. The volume of the nodules in 12 patients (34.3%, responders) decreased by more than 50% after thyroxine therapy. In this group, the mean serum thyroglobulin (Tg) level decreased significantly (from 424 to 107 ng/mL, p < 0.001). In the nonresponders, the mean serum Tg level did not change significantly after thyroxine therapy (291 vs 261 ng/mL, p > 0.05). The mean serum total T4 and free T4 concentrations increased significantly in both groups after thyroxine therapy (p < 0.01), the serum total triiodothyronine (T3) level did not change (p > 0.05), and the serum thyrotropin level (TSH) and T3/T4 ratio decreased markedly (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Maturation of hepatic desulfation activity in developing rats.

The present study was carried out to further characterize the maturation of desulfation activity in developing rats. High levels of 3,3',5-triiodothyronine sulfate (T3S) were found in rat fetal serum whereas 3,3',5-triiodothyronine (T3) levels were low. The ratio of T3S/T3. was dramatically reversed in the rat maternal circulation. Maternal rats had higher desulfation activity than did near-term fetuses. Desulfation of T3S to T3 by microsomes of fetal and maternal livers were studied by incubating microsomes with T3S as a substrate. Desulfated T3 was measured by radioimmunoassay. The Km and Vmax values for desulfation of T3S to T3 by hepatic microsomes in different age groups were compared. Little desulfation activity was found in hepatic microsomal preparations from fetal rats compared with newborn rats. There was a trend of increasing desulfation activity in rats after birth until 1 month of age, although this was not significant. A surge of desulfating activity was observed between the 1- and 2-month old groups. The K(m) values for T3S desulfation activity were similar in all age groups. The Vmax values for the T3S to T3 desulfation activity progressively increased after birth until 2 months of age. The Vmax of the latter group, however, was comparable to that of the maternal group. These results suggest that the maturation of desulfation activity in the microsomal preparations from rat livers is completed by 2 months of age and is mainly due to increased enzyme capacity. Sulfation-desulfation of T3 may play a role in the thyroid hormone regulation of developing mammals.

Effects of lovastatin and gemfibrozil in subjects with high ratios of total cholesterol to high-density lipoprotein cholesterol.

Insulin resistance is associated with hypertriglyceridemia, low serum high-density lipoprotein cholesterol (HDL-C) concentrations and high serum total cholesterol (TC) to HDL-C ratios. Several reports have demonstrated that either lovastatin or gemfibrozil may favorably lower serum lipid concentrations. However, their effects on insulin sensitivity are unknown. The primary aim of this study was to compare the effects of lovastatin and gemfibrozil on insulin sensitivity and serum leptin concentrations in subjects with high TC/HDL-C ratios. We enrolled 25 nondiabetic patients, similar in terms of age and weight with TC/HDL-C ratios greater than 5. Thirteen subjects were treated with lovastatin 20 mg per day, and 12 received gemfibrozil 300 mg twice per day. Plasma lipids, glucose, and leptin were measured, and a 75-g oral glucose tolerance test (OGTT) and a modified insulin suppression test were performed before and after 3 months of treatment. The study showed the mean plasma TC, low-density lipoprotein cholesterol (LDL-C) concentrations, and TC/HDL-C ratio were significantly reduced in the lovastatin-treated group, but no obvious effects on plasma triglyceride (TG) and HDL-C were noted. In the gemfibrozil group, plasma TG and HDL-C were markedly lowered, but no significantly different effects in other plasma lipids were found. Gemfibrozil did not affect steady-state plasma glucose (SSPG) concentrations, whereas lovastatin significantly increased SSPG concentrations. Neither drug affected the serum leptin concentration during the OGTT. We conclude that lovastatin significantly lowers plasma TC and LDL-C ratio, and TC/HDL-C concentrations and adversely affects insulin sensitivity, while gemfibrozil markedly reduces plasma TG concentrations without altering insulin sensitivity in subjects with high TC/HDL-C ratios.

Sympathoadrenal reactions during asphyxia in hypoglycemia and hyperglycemia of cats.

In 26 cats anesthetized with alpha-chloralose and urethane, cardiovascular changes during asphyxia in hypoglycemia and hyperglycemia were studied. Systemic hypoglycemia (serum glucose decrease from 148 to 31 mg/100 ml) was produced by i.v. injection of insulin 20 U/kg, followed by continuous I.V. infusion of 10 U/kg/hr. Systemic hyperglycemia (serum glucose increase from 187 to 657 mg/100 ml) was produced by I.V. infusion of 25% glucose at a rate of 1.5 gm/kg/hr. During hypo- or hyperglycemia, resting mean systemic arterial pressure (MSAP) and heart rate did not change significantly. Brain transection at various levels, i.e., midcollicular decerebration, ponto-medullary or medulla-spinal transection progressively decreased the resting MSAP, but not the heart rate. The most apparent reduction was at the medulla-spinal junction. After induction of systemic hypo- or hyperglycemia, plasma catecholamine concentrations increased significantly. Further increase occurred during asphyxia. Increases of MSAP and plasma catecholamine concentrations during asphyxia were attenuated after midcollicular decerebration and decreased further after subsequent ponto-medullary and medulla-spinal transections. Increases in plasma catecholamines during asphyxia were greater in hypoglycemic than those in hyperglycemic state. The increase in plasma catecholamine persisted in hypoglycemic animals during asphyxia after midcollicular decerebration and ponto-medullary transections. As the terminal stage of asphyxia approached spasmodic contractions of urinary bladder occurred. Bladder contractions were abolished after intracerebroventricular (lateral) injection of insulin (0.25 unit/kg). In conclusion, asphyxia produced very marked cardiovascular and plasma catecholamine responses during hypo- or hyperglycemia and more so during the former condition. These reactions depend mainly on the neural mechanisms of medullary structures. Neural structures rostral to the midcollicular level are not essential.

Evaluation of intraoperative cardiovascular responses to closed repair for pectus excavatum.

OBJECTIVE: Closed repair of pectus excavatum (PE), also known as the Nuss procedure, has become more popular recently, and whether this operation results in true cardiac improvement as opposed to postoperative physical rehabilitation or a psychological effect deserves examination. METHODS: Ten PE patients (8 males, 2 females) aged 4 to 54 years (average, 19.6+/-14 years) were prospectively evaluated using preoperative computed tomography (CT) scan, pulmonary function studies, electrocardiogram and transthoracic echocardiographic (TTE) evaluation of cardiac function. The same studies were repeated at 3 months post bar placement. In addition, intraoperative transesophageal echocardiogram (TEE) was done to measure the procedure-related values of the cardiac chamber and functional indices before and after turning of the pectus bar. RESULTS: Statistically significant changes in the pectus index, obtained by dividing the internal transverse distance of the thorax by the vertebral-sternal distance at the most depressed portion of the deformity, were noted after surgery, decreasing from 5.06+/-1.46 to 3.55+/-0.48 (P<0.05). Most patients with previously abnormal electrocardiograms showed a normal pattern after surgical repair (P<0.05). Five subjects in the PE group (50%) showed mitral valve prolapse in TTE and 4 of them had mitral regurgitation. However, these valve patterns could not be corrected after surgical repair of the chest wall deformity (P=0.25). The cardiac chamber and the function of the right ventricle were evaluated by intraoperative TEE and showed significantly increased values after retrosternal dissection and post-turning of the pectus bar. CONCLUSION: The data of this study supports the concept that closed repair directly contributes to hemodynamic improvement.

Thoracoscopic diaphragmatic repair for refractory hepatic hydrothorax: application of pleural flap and mesh onlay reinforcement.

BACKGROUND: Management of hepatic hydrothorax is difficult, and no radical treatment has been established. Based on accumulating evidence that diaphragmatic defects contribute to hepatic hydrothorax, we developed a diaphragmatic repair method for the management of this complex condition. METHODS: From October 2003 to March 2005, 10 patients (age, 32 - 83 years; 6 men and 4 women) with refractory hepatic hydrothorax (Child-Pugh class B-C) underwent thoracoscopic pleura (n = 7) or mesh (n = 3) onlay reinforcement to repair the diaphragmatic defects on which this study focuses, and all patients have since been under follow-up in a prospective observation study. RESULTS: After a mean of 7.7 months of follow-up examinations, no local recurrence occurred in all patients. Two patients died of hemorrhage from esophageal varices two months postoperatively. All patients had a better postoperative pulmonary function. CONCLUSION: The use of pleura and mesh onlay reinforcement of the diaphragm is an encouraging treatment for refractory hepatic hydrothorax.

Modified Nuss operation for pectus excavatum: design for decreasing cardiopulmonary complications.

BACKGROUND: Thoracoscopic Nuss operation of funnel chest is increasingly performed. However, it has a high rate of complications. This study developed some modifications to facilitate Nuss operations with the intention of reducing several major complications. METHODS: Patients who presented for surgical repair of pectus excavatum from July 2003 through June 2004 had a preoperative computed tomography (CT) scan, pulmonary function tests, and cardiac echo before and two months after the modified Nuss operation. The following modifications of the standard Nuss procedure were implemented: (1) One small subxyphoid incision was made to guide the plate implantation and to decrease cardiopulmonary complications. (2) Thoracic muscles were dissected off the ribs to provide muscle pockets. (3) Shorter thick stainless-steel AO bars were selected to avoid thoracic outlet syndrome and restriction. (4) The bars were fixed to adjacent ribs by 4-0 stainless steel wires into the submuscular pockets. (5) No thoracoscope routinely used. (6) No chest tubes were placed to decrease chest pain or for cosmetic purposes. RESULTS: 15 patients aged between 4 and 32 years (mean, 18.6 +/- 7.8) underwent evaluation. Preoperative CT index was 4.14 +/- 0.86. The average operating time was 95.7 +/- 27.0 min. There was no bar dislocation, prolonged pain, or neuralgia. Echocardiography showed no pericarditis and no pneumothorax occurred after placement of the intrathoracic bar. CONCLUSION: A small subxiphoid incision makes bar implantation easier and has reduced the incidence of major complications in this early experience with 15 patients.

Effect of orlistat in overweight poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study.

The aim of the study was to assess the adjunctive effects of orlistat on weight loss and the influence of weight reduction on glycaemic control in overweight Chinese female type 2 diabetic patients. A randomised, placebo-controlled, double-blind, 12-week study was conducted. Chinese female type 2 diabetic patients, overweight (body mass index > 25 kg/m(2)), poorly controlled glucose levels [glycosylated haemoglobin (HbA1c) > 8%], were randomly assigned to two groups. In addition to their oral hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a placebo and the other (n = 30) received orlistat 120 mg t.i.d. for 12 weeks. Comparing the changes that occurred after 12 weeks in the orlistat and placebo groups, the former showed significantly greater reduction in bodyweight (2.5 vs. 0.4 kg; p < 0.05), fasting plasma insulin level (p < 0.01), 2-h postprandial blood glucose after glucose challenge (p < 0.01), insulin resistance (p < 0.01), HbA1c (p < 0.05), total cholesterol and triglyceride levels (p < 0.05, respectively). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of orlistat to oral hypoglycaemic agents resulted in a significant weight reduction and improvement of metabolic control in overweight Chinese female type 2 diabetic patients.

The effect of thyroxine-suppressive therapy in patients with solitary non-toxic thyroid nodules -- a randomised, double-blind, placebo-controlled study.

The efficacy of thyroxine (T(4)) for solitary non-toxic thyroid nodule remains uncertain. In this study, 60 patients with solitary non-toxic thyroid nodule were divided randomly into two groups. Group I (n = 30) received thyroxine 100 microg/day for 6 months and group II (n = 30) received placebo. The volume of the thyroid nodules in 11 patients decreased more than 50% after thyroxine therapy (36.7%, responders). In these 11 patients, the mean serum thyroglobulin level decreased significantly (340 +/- 115 to 162 +/- 86 microg/l, p < 0.01). Compared with the non-responders (n = 19, 63.3%), the serum thyroglobulin level before treatment was significantly higher (340 +/- 115 vs. 220 +/- 102 microg/l, p < 0.05). Thyroxine-suppressive therapy is proved as a useful tool in reducing nodule size in some patients with solitary thyroid nodules. The patients with a higher serum thyroglobulin level generally respond better to thyroxine-suppressive therapy.

Metabolic characteristics in individuals with impaired glucose homeostasis.

We sought to clarify whether impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or both (IFG/IGT) represent the most severe impairment in insulin resistance (IR) and insulin secretion. Among the 159 Chinese subjects, 21 were diagnosed as having IFG, 103 as having IGT and 35 as having both. IR and beta-cell function were assessed using homeostatic model assessment (HOMA) and an insulin-suppression test (IST). No differences were evident between the groups in blood pressure, body mass index, plasma insulin fasting levels and lipid profiles. However, plasma 2-h insulin levels were higher in the IGT and IFG/IGT groups. Beta-cell functions were not different between these groups. But, the result of glucose tolerance was different, in which the IFG/IGT and IFG groups displayed higher insulin sensitivity than IGT via HOMA instead of no difference via IST in the three patient groups.

Effects of sibutramine in overweight, poorly controlled Chinese female type 2 diabetic patients: a randomised, double-blind, placebo-controlled study.

To assess the efficacy of sibutramine 15 mg once daily as weight reduction in overweight and obese (body mass index > 25 kg/m2) Chinese female type 2 diabetic patients and to evaluate the influence of weight loss on diabetic control, a randomised, double-blind, placebo-control, 12-week study was conducted. Chinese female type 2 diabetic patients, poorly controlled glucose levels and HbA(1C) > 8% were randomly assigned to two groups. In addition to their hypoglycaemic agents (maximal doses of sulphonylureas and metformin), one group (n = 30) received a sibutramine 15 mg once daily for 12 weeks, and the other (n = 30) received placebo for the same period. Comparing the changes that occurred after 12 weeks in the sibutramine and placebo groups, the former showed significantly greater reduction in body weight (2.5 vs. 0.1 kg, p < 0.05), fasting plasma insulin level (28.8 vs. 2.4 pmol/l, p < 0.01), 2-h postprandial blood glucose after standard test meal (3.2 vs. 1.1 mmol/l, p < 0.01), insulin resistance (5.1 vs. 0.2, p < 0.01), HbA1C (1.7% vs. 0.2%, p < 0.05), triglyceride (0.43 vs. 0.12 mmol/l, p < 0.05) and total cholesterol (0.52 vs. 0.08 mmol/l, p < 0.05). No significant differences were found between treatment groups in blood pressure and heart rate. The addition of sibutramine to diet and oral hypoglycaemic therapy resulted in significant weight loss and improvement in metabolic parameters in the treatment group. Sibutramine should be considered for use alongside diet and oral hypoglycaemic therapy in Chinese overweight and obese women with poorly controlled type 2 diabetes.

The relationships between insulin resistance and components of metabolic syndrome in Taiwanese Asians.

Metabolic syndrome (MetS) is a complicated clinicopathological entity with clustering of cardiovascular and metabolic risk factors, which includes central obesity, hypertension, dyslipidemia and glucose intolerance. There were many studies investigating a wide variety of clinical and pathophysiological aspects of this syndrome. However, the cutoffs of the components of MetS are not yet being evaluated by measured the insulin resistance (IR) directly. In this study, we enrolled 564 (male/female: 250/314) middle-aged healthy subjects. Each of the male and the female group was further divided into four subgroups (group 1 to group 4). Group 4 had the top 25 percentile of most severe IR determined by insulin suppression test. We then obtain the mean values of each component of the MetS in group 4 and compared them with the definitions of World Health Organization, National Cholesterol Education Program Adult Treatment Panel III, European Study Group of Insulin Resistance and International Diabetes Federation. The means of the blood pressure (BP) (male, 125/81; female, 125/80 mmHg) and the triglyceride (TG) (male, 1.6; female, 1.4 mmol/l) in group 4 were lower, and the fasting plasma glucose (6.2 mmol/l) was higher than the cutoffs of the other four sets of the criteria. The means of the high-density lipoprotein cholesterol (male, 0.9; female, 1.03 mmol/l) and the body mass index (male, 26.9; female 26.1 kg/m(2)) in group 4 were consistent with the cutoffs of other four groups and also the Taiwan Health Department criteria. In conclusion, we suggest to lower the cutoffs of the BP from 140/90 to 125/80 mmHg, TG from 1.7 to 1.6 mmol/l for males and 1.4 mmol/l for females for MetS definition, at least in Taiwan. This may help to early detect subjects under high risk of future coronary heart disease and diabetes. Still, these newly proposed cutoffs need larger-scale epidemiological studies to confirm.

Sibutramine improves insulin sensitivity without alteration of serum adiponectin in obese subjects with Type 2 diabetes.

AIM: To evaluate the effect of sibutramine on weight loss, insulin sensitivity and serum adiponectin levels in obese patients with Type 2 diabetes. METHODS: This study is a randomized, double-blind, placebo-controlled parallel comparison study of sibutramine 15 mg/day and placebo. Forty-eight eligible obese patients with Type 2 diabetes (age between 30 and 75 years with body mass index > or = 27 kg/m(2)) were randomly assigned to receive either placebo (n = 24) or sibutramine (15 mg/day) (n = 24) for 6 months. Fifteen subjects in each group underwent meal tests and modified insulin suppression tests before and after 6 months' treatment. RESULTS: After 6 months of sibutramine treatment statistically significant changes from baseline were observed for body weight (85.4 +/- 2.5 vs. 82.9 +/- 2.4 kg, P < 0.005) and body mass index (32.0 +/- 0.7 vs. 31.4 +/- 0.6 kg/m(2), P < 0.05) without a significant alteration of waist-hip ratio (W/H), blood pressure, heart rate, glycaemic parameters or lipid profiles. The steady-state plasma glucose (SSPG) level during the modified insulin suppression test was significantly reduced in the sibutramine group (17.33 +/- 2.92 vs. 14.29 +/- 4.19 mmol/l, P < 0.05) despite similar steady-state plasma insulin (SSPI) concentrations. In addition, serum adiponectin and C-reactive protein (CRP) levels remained unchanged, although modest weight reduction was achieved after sibutramine treatment. There were also no significant correlations between changes in serum adiponectin and reduction of SSPG or body weight. Daily ambient plasma insulin and glucose concentrations in response to a test meal were not significantly different in subjects receiving sibutramine treatment. CONCLUSIONS: We conclude that treatment with sibutramine 15 mg once daily effectively reduces weight and enhances insulin sensitivity without alteration of serum adiponectin levels in obese patients with Type 2 diabetes.