Immunoreactive Insulin Levels Research Articles

L-Asparaginase diabetes mellitus in rabbits: differing effects of two different schedules of L-asparaginase administration.

The diabetogenic effect of daily injections of 1000 i.u./kg body wt. E coli L-asparaginase was studied in male New Zealand white rabbits and compared with the diabetogenic effect of a single bolus of 10,000 I.U. E coli L-asparaginase/kg body wt. to determine whether the schedule of administration of the drug altered the diabetic syndrome produced. A daily injection of 1000 i.u. L-asparaginase/kg. body wt. was continued for 30 days. During this time glucose levels in rabbits allowed free access to food rose steadily, reaching levels of 717 +/- 63 mg/dl the day after the last injection. Levels of immunoreactive insulin fell, reaching their nadir, 53 +/- 4 pg/ml (approximately 50% of baseline) at 25 days. Glucose levels declined when therapy was discontinued, but remained significantly above control levels 46 days after insulin injections were stopped. (Glucose levels in L-asparaginase-treated groups vs. those in controls on day 46 after discontinuation: 116 +/- 3 vs. 104 +/- 1 mg/dl; P less than 0.0025.) Levels of immunoreactive insulin rose when therapy ended, reaching control levels 17 days after discontinuation. In contrast, a single bolus injection of 10,000 I.U. L-asparaginase/kg resulted in hyperglycemia with hyperinsulinemia. These data suggest that L-asparaginase can induce either a hypoinsulinemic or a hyperinsulinemic diabetic syndrome depending on the schedule of administration of the L-asparaginase and that a mild abnormality in glucose homeostasis persists after discontinuation of L-asparaginase therapy.

Factors responsible for age-related elevation in fasting plasma glucose: a cross-sectional study in Japanese men

To evaluate the factors associated with age-related increase in fasting plasma glucose (FPG) in Japanese men with normal fasting glucose, we measured FPG, fasting immunoreactive insulin, glycated hemoglobin, total cholesterol, triglyceride, and high-density lipoprotein cholesterol levels in health check examinees. Subjects with FPG less than 6.1 mmol/L together with glycated hemoglobin less than 5.6% were enrolled in the study. The homeostasis model assessment of insulin resistance (HOMA-IR) and HOMA- β were used as the indices of insulin sensitivity and insulin secretion, respectively. Fasting plasma glucose increased significantly with age ( r = 0.30, P < .0001), and HOMA- β decreased significantly with age ( r = 0.24, P < .0001). The HOMA-IR had no significant relation with age ( r = 0.06, not significant), whereas body mass index and serum triglyceride were associated with HOMA-IR ( r = 0.49, P < .0001 and r = 0.33, P < .0001, respectively). Thus, in Japanese male subjects with normal fasting glucose, it is suggested that the FPG increment with age is associated with decreased β-cell function rather than with insulin resistance. Further analyses were performed by comparing 3 groups: low FPG (FPG <5.0 mmol/L), high FPG (5.0 ≤ FPG < 5.6 mmol/L), and mild impairment of fasting glycemia (mild IFG) (5.6 ≤ FPG < 6.1 mmol/L). The insulin levels in mild IFG and high FPG were significantly higher than in low FPG ( P < .001), but those in mild IFG were similar to those in high FPG. Analysis of the 3 subgroups revealed that, whereas insulin sensitivity was impaired more in high FPG, there was little compensatory increase in insulin in mild IFG, suggesting that β-cell function is already deteriorated when the FPG level is greater than 5.6 mmol/L.

Treatment of insulin dependent diabetes mellitus with intravascular transplantation of pancreatic islet cells without immunosuppressive therapy

To evaluate intravascular xenotransplantation of macroencapsulated pancreatic islet cells in the process of the treatment of diabetes mellitus type 1 without immunosuppressive therapy. Xenogenic intravascular transplantation was performed in 19 patients with diabetes mellitus (type 1) having high insulin demand and frequent hypo- and hyperglycemic comas without immunosuppressive therapy. The culture was obtained from 3rd trimester rabbit fetuses. Cell culture suspension was encapsulated into microporous macrocapsule made of nylon and grafted into the deep femoral artery or the forearm cubital vein after performing arteriovenous anastomosis. For 2 years after transplantation, positive results were observed in 14 recipients (73.7%). The total decrease of insulin demand was 60-65%, and hypo- and hyperglycemic comas disappeared completely, while C-peptide and immunoreactive insulin levels significantly increased, reversely correlating with the fructosamin level, as a protein glycation marker. Xenotransplantation of pancreatic islet cells with their subsequent grafting into the vascular lumen creates double immune isolation and allows overcoming acute and chronic graft rejection without immuno-suppressive therapy. It considerably decreases insulin demand, compensates hypo- and hyperglycemic conditions, makes the course of diabetes stable, and improves the quality of the patients' life.

Evaluation of the Hemodialysis‐induced Changes in Plasma Glucose and Insulin Concentrations in Diabetic Patients: Comparison Between the Hemodialysis and Non‐hemodialysis Days

Often, well-controlled plasma glucose levels but high hemoglobin A(1c) levels have been observed at prehemodialysis in diabetic patients. The present study aimed to evaluate this difference between fasting glucose and hemoglobin A(1c) levels. We investigated hemodialysis-induced alterations in the plasma glucose and insulin levels. Based on their glycemic control level at inclusion, subjects were divided into poor control (hemoglobin A(1c)> or =7.0%; n = 8) and good control groups (hemoglobin A(1c) <7.0%; n = 8). We measured their plasma glucose and immunoreactive insulin levels at arterial and venous sites at three time points (predialysis, 2 h and 4 h after starting dialysis); we also studied their daily plasma glucose profiles. In both the groups, the V-site plasma glucose and immunoreactive insulin levels were significantly decreased compared to the A-site levels at each time point. The A-site plasma immunoreactive insulin levels 4 h after dialysis were significantly decreased compared to the levels 2 h after dialysis. Comparison between hemodialysis and non-hemodialysis days revealed that the plasma glucose levels decreased significantly during hemodialysis and significantly increased between predinner and bedtime in the poor control group. The present study confirmed that hemodialysis decreased the plasma glucose and immunoreactive insulin levels. In the poor control group, hyperglycemia appeared posthemodialysis; this was attributed partly to the hemodialysis-induced decrease in the plasma immunoreactive insulin levels. These results suggest that although diet therapy has been effective in diabetic hemodialysis patients, hemodialysis caused hyperglycemia by absolute or relative plasma immunoreactive insulin deficiency.

Plasma Insulin is Removed by Hemodialysis: Evaluation of the Relation Between Plasma Insulin and Glucose by Using a Dialysate With or Without Glucose

The aim of the present study was to evaluate the alteration in plasma immunoreactive insulin (IRI) and glucose concentrations due to hemodialysis (HD) treatment by using a dialysate with or without glucose in HD patients. We divided the patients into three groups: non-diabetic patients (n-DM group), well-controlled diabetic patients (HbA(1c) <7.0% [w-DM group]), and poorly-controlled diabetic patients (HbA(1c) > or = 7.0% [p-DM group]). Using a dialysate with a glucose concentration of 100 mg/dL (glu(+)-dialysate) and a glucose-free dialysate (glu(-)-dialysate), we studied the daily profiles of plasma glucose in the three groups. We measured the levels of plasma glucose and IRI at three time points (predialysis and 2 h and 4 h after the initiation of dialysis) at pre(A) and postdialyzer (V) sites in HD patients. There was a significant increase in the daily profiles of the plasma glucose level from the time before dinner until bedtime in both the w-DM and p-DM groups, when comparing the values on an HD day with those on a non-HD day. In the p-DM group, the use of the glu(-)-dialysate resulted in a significant hyperglycemia in the evening hours when compared with the use of the glu(+)-dialysate. In the DM group, the use of the glu(+)-dialysate resulted in a significant decrease in the plasma glucose and IRI levels during HD. However, in the n-DM group, there was no difference in the plasma glucose levels during HD. On the other hand, the use of a glucose-free dialysate led to a significant decrease in the plasma glucose and IRI levels during HD in all groups. The plasma IRI levels decreased significantly between the A and V sites at each point in all groups irrespective of the glucose concentration of the dialysate. The present study confirmed that the concentration of not only glucose but also IRI had decreased during the passage of the plasma through the dialyzer. In HD patients with diabetes, the glucose content of the hemodialysis solution plays an important role in preventing acute hypoglycemia and hyperglycemia on HD days.

Recurrent Hypoglycemia in a Hemodialysis Patient Related to Propoxyphene Treatment

There are various etiologies for hypoglycemia in patients with chronic renal failure, and its pathogenesis is complex. Concomitant use of medications is the most common cause. We report a rare case of an 82-year-old woman with type 2 diabetes mellitus in end-stage renal disease undergoing maintenance hemodialysis, who experienced recurrent symptomatic hypoglycemia during treatment with propoxyphene for pain relief. Hypoglycemia occurred simultaneously with elevated levels of serum immunoreactive insulin and C-peptide. After discontinuing propoxyphene, hypoglycemia mitigated and the level of insulin returned to normal range. Our case reminds us that propoxyphene-induced hypoglycemia should not be ignored, especially in hemodialysis patients with cold sweats, agitation and depressed consciousness.

Hepatic iron accumulation may be associated with insulin resistance in patients with chronic hepatitis C

Insulin resistance and hepatic iron overload are frequently demonstrated in hepatitis C virus (HCV)-related liver diseases. We investigated the relationship between insulin resistance and hepatic iron deposition in patients with chronic HCV infection. Insulin resistance was evaluated using the homeostasis model assessments for insulin resistance (HOMA-IR) in 56 non-diabetic non-obese patients with biopsy proven chronic hepatitis C. The relationship between insulin resistance and serum ferritin levels or the grade of hepatic iron deposition was assessed. The levels of plasma immunoreactive insulin (IRI) and HOMA-IR were significantly correlated with serum ferritin levels and the grade of hepatic iron deposition (P = 0.003).Although IRI and HOMA-IR increased in parallel with the development of hepatic fibrosis, insulin resistance (HOMA-IR > 2) was observed in 11 (26.2%) of 42 patients even without severe fibrosis (F0-2). Among patients without severe fibrosis, IRI and HOMA-IR were significantly higher in patients with iron deposits than in those without iron deposits. Hepatic iron overload may be associated with insulin resistance in patients with chronic hepatitis C, especially in patients with mild to moderate fibrosis.

Effects of a sperminated gelatin on the nasal absorption of insulin

The effects of a sperminated gelatin (SG), which was prepared as a candidate absorption enhancer by the addition of spermine to gelatin, on the nasal absorption of insulin, were examined in rats. The AUC of immuno-reactive insulin levels in the plasma after nasal administration of insulin were increased 5.3-fold by addition of 0.2% SG, and the plasma glucose levels fell in a manner dependent on the insulin levels. In Calu-3 cell monolayer permeation experiments, SG showed significant enhancing effects on 5(6)-carboxyfluorescein (CF), FITC-dextran (MW 4400, FD4) and insulin. Evaluation of the tight junctions in the Calu-3 cell monolayers based on the Renkin molecular sieving function suggests that the pore occupancy/length ratio of the permeation pathways for water-soluble molecules in the tight junctions increases, while the equivalent cylindrical pore radius is not changed by SG treatment. SG may transform the true tight junctions, which act as a barrier for water-soluble molecules, into pathways for CF and FD4 to increase their number. SG is a good candidate for a safe absorption enhancer to produce a slight modification of the permeability of the paracellular pathway of mucosal membranes, while retaining the sieving property of the epithelial membranes.

Colestimide Lowers Plasma Glucose Levels and Increases Plasma Glucagon-like Peptide-1 (7-36) Levels in Patients with Type 2 Diabetes Mellitus Complicated by Hypercholesterolemia

Colestimide has been reported to lower blood glucose levels in patients with type 2 diabetes complicated by hypercholesterolemia. To examine the mechanism by which colestimide decreases plasma glucose levels in the above patients. A total of 16 inpatients with type 2 diabetes complicated by hypercholesterolemia received colestimide for 1 week after their plasma glucose levels stabilized. We measured plasma glucose, serum immunoreactive insulin (IRI), serum lipid, plasma glucagon, and plasma glucagon-like peptide-1 (GLP-1) levels. These variables at baseline and 1 week of colestimide administration were compared. Preprandial plasma glucose levels (baseline: 132 +/- 33 mg/dL vs. completion: 118 +/- 43 mg/dL, P=0.073) tended to decrease after colestimide administration, while 1-hr postprandial plasma glucose levels (baseline: 208 +/- 49 mg/dL vs. completion: 166 +/- 30 mg/dL, P<0.001) and 2-hr postprandial plasma glucose levels (baseline: 209 +/- 56 mg/dL vs. completion: 178 +/- 39 mg/dL, P=0.015) decreased significantly at 1 week of colestimide administration. The 2-hr postprandial plasma GLP-1 level was significantly (P=0.015) higher at 1 week of colestimide administration as compared with the baseline level, while there were no significant changes in preprandial and 1-hr postprandial plasma GLP-1 levels. The GLP-1-increasing activity of colestimide may explain, at least in part, the mechanism of its blood glucose-lowering activity in patients with type 2 diabetes complicated by hypercholesterolemia.

Effects of Hachimi-jio-gan (Ba-Wei-Di-Huang-Wan) on Hyperglycemia in Streptozotocin-Induced Diabetic Rats

The present study investigated the effects of Hachimi-jio-gan (HJ) on diabetic hyperglycemia in streptozotocin (STZ)-induced diabetic rats. After STZ administration, rats had free access to pellets containing 1% HJ extract powder for four weeks. HJ markedly suppressed hyperglycemia in STZ-induced diabetic rats at three and four weeks after the start of administration. There were also significant increases in serum and pancreatic immunoreactive insulin levels in STZ and HJ co-administering rats. However, in the present study, the number of beta cells in the pancreatic Langerhans' islets did not increase. Next, in order to investigate the action mechanism besides the glycemic control action of insulin, the expression of glucose transporter 2 (GLUT2) protein, which is involved in glucose uptake and release in the liver, was investigated. GLUT2 protein expression was increased by STZ administration but was normalized after four weeks of HJ administration. Therefore, irrespective of the structural changes in pancreatic beta-cells due to STZ, HJ increased insulin production and secretion by the pancreas and significantly suppressed GLUT2 synthesis in the liver. Amylase secretion from the pancreas was measured to assess pancreatic secretion. Amylase activity was decreased by STZ but was increased by HJ. Therefore, the effects of HJ on STZ-induced hyperglycemia in rats could be summarized as follows: besides increasing insulin synthesis and release, HJ normalizes GLUT2 protein expression in the liver to suppress hyperglycemia. Hence, the results of the present study suggest for the first time that HJ affects not only the production and secretion of insulin, but also the release of glucose from the liver.

Postprandial lipemia and insulinemia in obese females with cholelithiasis

The authors studied the pattern of fatty tissue distribution in the body and revealed changes In the baseline and postprandial levels of serum lipids and insulin In females with cholelithiasis (CL) obese. Ninety-five females were examined. These included 41 patients with CL and obesity, 20 patients with the normal body mass index and CL, and 34 obese females without CL. The pattern of abdominal adipose tissue distribution was determined by computed tomography. The serum levels of major lipids and immunoreactive insulin (IRI) were measured at the baseline and 3 and 9 hours after administration of fat emulsion (130 g of fat per 2 m2 of body surface). There was a significant predominance of the area of visceral adipose tissue (VFT) at the level of the gallbladder. In the groups of CL patients, the percent of VFT of the total abdominal adipose tissue was higher than that in obese patients without CL. During a dietary fat load test, a persistent postprandial hypertriglyceridemia and no increases in the levels of high-density lipoprotein cholesterol were observed in CL female patients irrespective of whether systemic obesity was present or absent. In the group of CL patients without signs of obesity, there were high baseline concentrations of IRI and no significant increase in IRI levels in response to the administration of fat emulsion.

Alterations in regulation of energy homeostasis in cyclic nucleotide phosphodiesterase 3B–null mice

Cyclic nucleotide phosphodiesterase 3B (PDE3B) has been suggested to be critical for mediating insulin/IGF-1 inhibition of cAMP signaling in adipocytes, liver, and pancreatic beta cells. In Pde3b-KO adipocytes we found decreased adipocyte size, unchanged insulin-stimulated phosphorylation of protein kinase B and activation of glucose uptake, enhanced catecholamine-stimulated lipolysis and insulin-stimulated lipogenesis, and blocked insulin inhibition of catecholamine-stimulated lipolysis. Glucose, alone or in combination with glucagon-like peptide-1, increased insulin secretion more in isolated pancreatic KO islets, although islet size and morphology and immunoreactive insulin and glucagon levels were unchanged. The beta(3)-adrenergic agonist CL 316,243 (CL) increased lipolysis and serum insulin more in KO mice, but blood glucose reduction was less in CL-treated KO mice. Insulin resistance was observed in KO mice, with liver an important site of alterations in insulin-sensitive glucose production. In KO mice, liver triglyceride and cAMP contents were increased, and the liver content and phosphorylation states of several insulin signaling, gluconeogenic, and inflammation- and stress-related components were altered. Thus, PDE3B may be important in regulating certain cAMP signaling pathways, including lipolysis, insulin-induced antilipolysis, and cAMP-mediated insulin secretion. Altered expression and/or regulation of PDE3B may contribute to metabolic dysregulation, including systemic insulin resistance.

Medical Treatment of Benign Insulinoma Using Octreotide LAR: A Case Report

In some patients with insulinoma, surgery is not possible due to either difficulties in detecting the tumor or advanced age. These patients need medical treatment for hypoglycemia. We report a case of benign insulinoma using the long-acting octreotide formulation, octreotide long-acting repeatable (octreotide LAR), as a medical therapy. A 67-year-old woman was referred to our hospital for examinations of hypoglycemia. A blood sample taken during a hypoglycemic episode revealed low plasma glucose concentration, hyperinsulinemia and a high C-peptide level. An abdominal CT scan demonstrated a hypervascular tumor in the body of pancreas. She was diagnosed with insulinoma. As the patient refused surgical resection of the pancreas tumor, we started to use the somatostatin analogue, octreotide, for treatment of hypoglycemia. After the treatment her plasma glucose levels were elevated and serum immunoreactive insulin (IRI) levels were decreased. For long-term treatment, we changed the treatment from daily subcutaneous injection of octreotide to monthly intramuscular administration of octreotide LAR. This treatment was also effective and hypoglycemic attacks disappeared. Both plasma glucose levels and serum IRI levels were improved. Our case demonstrated that octreotide LAR was useful for long-term medical treatment of insulinoma.

Effect of cerebrocrast, a new long‐acting compound on blood glucose and insulin levels in rats when administered before and after STZ‐induced diabetes mellitus

Insulin-dependent diabetes mellitus (IDDM) is an autoimmune disease that is characterized by selective destruction of insulin secreting pancreatic islets beta-cells. The formation of cytokines (IL-1beta, IL-6, TNF-alpha, etc.) leads to extensive morphological damage of beta-cells, DNA fragmentation, decrease of glucose oxidation, impaired glucose-insulin secretion and decreased insulin action and proinsulin biosynthesis. We examined the protective effect of a 1,4-dihydropyridine (DHP) derivative cerebrocrast (synthesized in the Latvian Institute of Organic Synthesis) on pancreatic beta-cells in rats possessing diabetes induced with the autoimmunogenic compound streptozotocin (STZ). Cerebrocrast administration at doses of 0.05 and 0.5 mg/kg body weight (p.o.) 1 h or 3 days prior to STZ as well as at 24 and 48 h after STZ administration partially prevented pancreatic beta-cells from the toxic effects of STZ, and delayed the development of hyperglycaemia. Administration of cerebrocrast starting 48 h after STZ-induced diabetes in rats for 3 consecutive days at doses of 0.05 and 0.5 mg/kg body weight (p.o.) significantly decreased blood glucose level, and the effect remained 10 days after the last administration. Moreover, in these rats, cerebrocrast evoked an increase of serum immunoreactive insulin (IRI) level during 7 diabetic days as compared to both the control normal rats and the STZ-induced diabetic control rats. The STZ-induced diabetic rats that received cerebrocrast had a significantly high serum IRI level from the 14th to 21st diabetic days in comparison with the STZ-induced diabetic control. The IRI level in serum as well as the glucose disposal rate were significantly increased after stimulation of pancreatic beta-cells with glucose in normal rats that received cerebrocrast, administered 60 min before glucose. Glucose disposal rate in STZ-induced diabetic rats as a result of cerebrocrast administration was also increased in comparison with STZ-diabetic control rats. Administration of cerebrocrast in combination with insulin intensified the effect of insulin. The hypoglycaemic effect of cerebrocrast primarily can be explained by its immunomodulative properties. Moreover, cerebrocrast can act through extrapancreatic mechanisms that favour the expression of glucose transporters, de novo insulin receptors formation in several cell membranes as well as glucose uptake.

Association of metabolic syndrome risk factors with selected markers of oxidative status and microinflammation in healthy omnivores and vegetarians

Conditions predisposing to metabolic syndrome (MetS) are associated with increased oxidative stress and inflammation. We studied, in vegetarians (n = 90) and omnivores (n = 46), the impact of the dietary regimen on the occurrence of MetS risk factors (RFs: BMI, blood pressure, glucose metabolism and lipid profile) in relation to oxidative status (advanced glycation end products (AGEs), advanced oxidation protein products (AOPPs), malondialdehyde, ferric reducing ability of plasma, vitamins A, E, C, beta-carotene and superoxide dismutase activity) and microinflammation (C-reactive protein, leukocytes and neopterin). The proportion of subjects without/positive for one or two MetS RFs was comparable between the groups. From the components of MetS only immunoreactive insulin levels differed significantly (95% CI: omnivores: 5.0-7.1 microU/mL, vegetarians: 4.5-5.4, p = 0.03). Omnivores had lower AOPP (omnivores: 0.29-0.36 micromol/g albumin, vegetarians: 0.36-0.52, p = 0.01) and beta-carotene levels than vegetarians, they consumed more calories, proteins, fat and saturated fatty acids, and less fibres, beta-carotene and vitamin C. Multiple regression analysis revealed vitamin E and AOPP levels as the most important independent determinants of MetS RFs. The vegetarian diet seems to exert beneficial effects on MetS RFs associated microinflammation. Whether the vegetarian diet may counteract the deleterious effects of elevated AOPPs and AGEs, remains to be elucidated.

Clinical features of insulin-like growth factor-II producing non-islet-cell tumor hypoglycemia

In some patients with non-islet-cell tumor hypoglycemia (NICTH), a high molecular weight form of IGF-II (big IGF-II) derived from tumors is present in the circulation and might be associated with recurrent hypoglycemia. In this study, in order to survey the clinical characteristics of patients with IGF-II producing NICTH, we analyzed the medical records of 78 patients with NICTH (M/F 44/34, age 62 ± 1.8, range; 9–86 years.) whose serum contained a large amount of big IGF-II. Hepatocellular carcinoma and gastric carcinoma were the most common causes of NICTH. The diameters of the tumors were more than 10 cm in 70% of the patients. Basal immunoreactive insulin (IRI) levels were less than 3 μU/dl in 79% of the patients. Hypoglycemic attack was the onset of disease in 31 of 65 cases (48%), but the tumor was revealed prior to the occurrence of hypoglycemia in 34 cases (52%). Twenty-five of 47 (53%) patients had decreased serum potassium levels. These data suggested that hypoinsulinemic hypoglycemia associated with the presence of a large tumor supports the diagnosis of IGF-II producing NICTH. Hypokalemia was associated with hypoglycemia in some patients. The BMI (21.4 ± 0.6 kg/m 2) and serum total protein levels (6.6 ± 0.1 g/dl) were preserved at the occurrence of first hypoglycemic attack suggesting that malnutrition might not be the main cause of hypoglycemia in most patients.

Effect of nateglinide on the size of LDL particles in patients with type 2 diabetes

The objective of the present study was to evaluate the efficacy of nateglinide in controlling blood glucose levels and regulating lipid metabolism in patients with type 2 diabetes by focusing attention particularly on low-density lipoprotein (LDL) particle size. The subjects were 23 patients with type 2 diabetes who were given nateglinide, 90 to 270 mg/d. Laboratory studies were conducted at treatment initiation and 3 mo later. Despite a decline that occurred in the level of fasting plasma glucose before and after administration of nateglinide, no significant difference was recognized. Hemoglobin A1c decreased significantly from 6.37+/- 0.75% to 5.91+/-0.64% (P<.001). A significant decline was also seen in the fasting level of immunoreactive insulin, from 9.82+/-5.69 microU/mL to 8.59+/-4.05 microU/mL (P<.05), and in the homeostasis model assessment for insulin resistance, from 3.06+/-1.83 to 2.55+/-1.26 (P<.05). Regarding lipids, triglycerides significantly decreased from 140.7+/-61.8 mg/dL to 117.3+/-34.7 mg/dL )P<.05). The significant reduction in migration index value, which was used as an index to LDL particle size, from 0.374+/-0.034 to 0.357+/-0.035 (P<.05), confirmed that LDL particle size had increased. The results of the present study show that nateglinide is effective in controlling blood glucose and improving insulin resistance, hypertriglyceridemia, and LDL particle size in patients with mild type 2 diabetes. These effects suggest that nateglinide may effectively control coronary artery disease in this population.

Blood levels of true insulin and immunoreactive insulin in evaluating beta-cell function with arginine stimulation test

To investigate the difference between serum true insulin (TI) and immunoreactive insulin (IRI) in evaluating islet beta-cell function and insulin resistance. The arginine stimulation test was performed in 141 individuals, including 35 with normal glucose tolerance (NGT) and 106 with type 2 diabetes (T2DM). Plasma glucose (PG), TI, IRI and proinsulin (PI) levels were measured; the incremental value of TI/PG, (TI+PI)/PG and IRI/PG (delta TI/PG, delta(TI+PI)/PG and deltaIRI/PG) and the area under curve of TI/PG, (TI+PI)/PG and IRI/PG (AUC [TI/PG], AUC[(TI+PI)/PG] and AUC [IRI/PG]) after arginine stimulation were calculated to evaluate beta-cell function. There were positive correlations of delta TI/PG with delta (TI+PI)/PG and delta IRI/PG in both NGT and T2DM patients (r=0.68 - 0.99, P<0.01). The similar correlations of AUC [TI/PG] with AUC [(TI+PI)/PG] and AUC [IRI/PG] were also shown (r=0.62 - 0.99, P<0.01). delta TI/PG was correlated with AUC [TI/PG] in two groups (NGT r=0.96, T2DM r=0.82, P<0.01). HOMA-IRTI, HOMA-IR(TI+PI) and HOMA-IRIRI in T2DM were higher than those in NGT (P<0.01). After arginine stimulation T2DM subjects mainly presented insulin resistance and decreased insulin secretion. The determination of TI may be more accurate than IRI in evaluating beta-cell function and insulin resistance.

The effect of fluvastatin on plasma adiponectin levels in dyslipidaemia

There is controversy about the effects of statins on insulin resistance and plasma adiponectin. The aim of this study was to investigate the effects of fluvastatin treatment on these parameters in a group of dyslipidaemic patients who had no confounding factors for insulin resistance or alterations in plasma adiponectin. Forty-nine patients [27 males, 22 females; mean age 47.2 +/- 10.3 years; body mass index (BMI) 29.64 +/- 3.2 kg/m2] with dyslipidaemia and 20 controls (six males, 14 females; mean age 45.3 +/- 9.31 years; BMI 30.07 +/- 4.04 kg/m2) were enrolled. All patients were treated initially with therapeutic lifestyle changes (TLC) for 6 weeks. Six out of 49 subjects were excluded from the study. Then, 24 out of 43 patients with high blood cholesterol despite TLC were allocated to fluvastatin 80 mg daily plus TLC, and the remaining 19 patients with normal cholesterol were subjected to TLC alone for additional 12 weeks. Plasma adiponectin, immunoreactive insulin levels, BMI, waist circumference, blood pressure, lipids, and glucose were determined. The insulin sensitivity index was quantified using the homeostasis model assessment (HOMA). TLC caused significant improvement in plasma insulin (P = 0.02) and elevation in plasma adiponectin (P = 0.02). Fluvastatin treatment decreased total cholesterol and low density lipoprotein (LDL)-cholesterol significantly (P = 0.01 and P = 0.02, respectively). No significant effect of fluvastatin was observed on plasma insulin or adiponectin or on the HOMA index. Fluvastatin does not improve plasma adiponectin levels and insulin sensitivity, despite its beneficial effects on lipid levels. Our data, however, were limited by the fact that a more accurate method of assessing insulin sensitivity, the euglycaemic-hyperinsulinaemic glucose clamp technique, was not used.

Effects of Gatifloxacin on Serum Glucose Concentration in Normal and Diabetic Rats

To clarify the mechanisms of gatifloxacin (GFLX)-induced hypoglycemia and hyperglycemia, the effect of GFLX on serum glucose levels was investigated in normal and diabetic rats. Rats received an intravenous injection of GFLX and their arterial blood was sampled periodically. Diabetic rats were produced by the intraperitoneal injection of streptozotocin and nicotinamide. In normal rats, the serum glucose concentration was decreased by GFLX at 25 and 50 mg/kg, while it was elevated 0.25 h after the injection of 100 mg/kg of GFLX. Serum immunoreactive insulin (IRI) levels increased as the dose of GFLX increased. The serum epinephrine concentration rose rapidly after the injection of GFLX at 50 and 100 mg/kg. In diabetic rats, the serum glucose concentration was actually increased by GFLX at 50 mg/kg. The baseline concentration of IRI was lower and the degree of the elevation caused by GFLX was smaller in diabetic rats. Both diabetic and control rats showed an increase in the serum epinephrine concentration after the injection of 50 mg/kg of GFLX. In conclusion, GFLX-induced secretion of insulin and epinephrine would contribute to the abnormalities in glucose homeostasis. The response of serum glucose to GFLX may differ between diabetic and normal rats due to the alteration of insulin secretion.