OBJECTIVETo investigate the effect of a tight control of blood glucose by intensive insulin therapy on human sepsis, and to explore the potential mechanism of the intensive insulin therapy.

METHODSEligible patients were randomized by a blinded pharmacist to receive tight control of blood glucose by intensive insulin therapy (maintenance of blood glucose at a level between 4.4 and 6.1 mmol/L) or to receive conventional treatment (maintenance of glucose at a level between 10.0 and 11.1 mmol/L). The expression of HLA-DR on peripheral monocytes was measured in 54 patients by flow cytometry on 24 h, 3 d, 5 d, 7 d, 10 d and 14 d of intensive care in parallel with serum c-reactive protein (CRP), severity of the disease (APACHE II score, SOFA score) and clinical data collection.

RESULTSPatients receiving intensive insulin therapy were less likely to require prolonged mechanical ventilation. Tight control of blood glucose significantly reduced the number of days during which leukopenia or leukocytosis and the days with hypo- or hyperthermia (P < 0.05). Hypoglycemia occurred in 3 patients (10.7%) in the tight control of blood glucose group. There were no instance of hemodynamic deterioration or convulsions. Compared with the conventional treatment, tight control of blood glucose also increased the HLA-DR expression of peripheral monocytes, and there were significantly difference on 3 d, 5 d and 7 d (P < 0.05). Whereas it suppressed the elevated serum CRP concentrations, there was significantly difference on 7 d (P < 0.05).

CONCLUSIONSTight control of blood glucose by intensive insulin therapy expedited healing of human sepsis, and increased the HLA-DR expression of peripheral and suppressed the elevated serum CRP. So, it is necessary to use insulin to strict control the glucose levels in human sepsis.

Blood Glucose ; metabolism ; C-Reactive Protein ; metabolism ; HLA-DR Antigens ; biosynthesis ; Humans ; Hyperglycemia ; drug therapy ; etiology ; metabolism ; Hypoglycemic Agents ; therapeutic use ; Insulin ; therapeutic use ; Sepsis ; complications

BACKGROUND/AIMS: This multicenter, open-labeled, randomized trial was performed to compare the effects of rosuvastatin 10 mg and atorvastatin 10 mg on lipid and glycemic control in Korean patients with nondiabetic metabolic syndrome. METHODS: In total, 351 patients who met the modified National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria for metabolic syndrome with low-density lipoprotein cholesterol (LDL-C) levels > or = 130 mg/dL were randomized to receive either rosuvastatin 10 mg (n = 173) or atorvastatin 10 mg (n = 178) for over 6 weeks. RESULTS: After 6 weeks of treatment, greater reductions in total cholesterol (- 35.94 +/- 11.38 vs. - 30.07 +/- 10.46%, p < 0.001), LDL-C (48.04 +/- 14.45 vs. 39.52 +/- 14.42%, p < 0.001), non-high-density lipoprotein cholesterol (- 42.93 +/- 13.15 vs. - 35.52 +/- 11.76%, p < 0.001), and apolipoprotein-B (- 38.7 +/- 18.85 vs. - 32.57 +/- 17.56%, p = 0.002) levels were observed in the rosuvastatin group as compared to the atorvastatin group. Overall, the percentage of patients attaining the NCEP ATP III goal was higher with rosuvastatin as compared to atorvastatin (87.64 vs. 69.88%, p < 0.001). Changes in glucose and insulin levels, and homeostasis model assessment of insulin resistance index were not significantly different between the two groups. The safety and tolerability of the two agents were similar. CONCLUSIONS: Rosuvastatin 10 mg was more effective than atorvastatin 10 mg in achieving NCEP ATP III LDL-C goals in patients with nondiabetic metabolic syndrome, especially in those with lower NCEP ATP III target level goals.
Blood Glucose/metabolism ; Cholesterol, LDL/blood ; Female ; Fluorobenzenes/*administration & dosage ; Hemoglobin A, Glycosylated/metabolism ; Heptanoic Acids/*administration & dosage ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage ; Hypercholesterolemia/blood/complications/*drug therapy ; Hyperglycemia/blood/complications/*drug therapy ; Insulin/blood ; Male ; Metabolic Syndrome X/blood/complications/*drug therapy ; Middle Aged ; Pyrimidines/*administration & dosage ; Pyrroles/*administration & dosage ; Sulfonamides/*administration & dosage ; Treatment Outcome

Hepatocyte growth factor (HGF) is a potent mitogen and promoter of proliferation of insulin producing beta cells of pancreatic islets. To study the role of HGF, an adenoviral vector carrying the human HGF (Ad.hHGF) gene was transfected into the streptozotocin-induced diabetic mice and evaluated the effect on the blood glucose metabolism and the insulin-secreting beta cells of pancreatic islets. Ad.hHGF gene transfection resulted in amelioration of hyperglycemia and prolongation of survival period in the diabetic mice. Concomitantly adenoviral- mediated hHGF gene therapy slightly increased serum insulin concentration and the expression of insulin in the pancreatic islet. Although the proliferation of beta-cell mass was not noticeable, the beneficial effect of HGF is significant to an almost deteriorated pancreatic islets. Taken together, these data suggest that the Ad.hHGF gene therapy into diabetic mice may prevent the further destruction and present as a beneficial remedy for type 1 diabetic patients.
Adenoviridae/*genetics/physiology ; Animals ; Blood Glucose/analysis ; Body Weight ; Diabetes Mellitus, Experimental/blood/genetics/*metabolism/*therapy ; *Gene Therapy ; Hepatocyte Growth Factor/genetics/*metabolism ; Humans ; Hyperglycemia/blood/complications/genetics/*therapy ; Insulin/blood ; Islets of Langerhans/metabolism/*pathology ; Male ; Mice ; Mice, Inbred BALB C ; Recombinant Proteins/genetics/metabolism ; Survival Rate

Hypoxic damage is one of the major causes of islet graft failure and VEGF is known to play a crucial role in revascularization. To address the effectiveness of a cationic lipid reagent as a VEGF gene carrier, and the beneficial effect of VEGF-transfected islets on glycemic control, we used effectene lipid reagent in a transfection experiment using mouse islets. Transfection efficiencies were highest for 4 microgram/microliter cDNA and 25 microliter effectene and cell viabilities were also satisfactory under this condition, and the overproduction of VEGF mRNA and protein were confirmed from conditioned cells. A minimal number of VEGF-transfected islets (100 IEQ/animal) were transplanted into streptozotocin (STZ)-induced diabetic mice. Hyperglycemia was not controlled in the islet transplantation (IT)-alone group (0/8) (non- diabetic glucose mice number/total recipient mice number) or in the IT-pJDK control vector group (0/8). However, hyperglycemia was completely abrogated in the IT-pJDK-VEGF transduced group (8/8), and viable islets and increased VEGF-transfected grafts vascularization were observed in renal capsules.
Animals ; Body Weight ; Cell Survival ; Diabetes Mellitus, Experimental/*complications/metabolism ; Disease Models, Animal ; Glucose/pharmacology ; Glucose Tolerance Test ; Hyperglycemia/complications/*metabolism/*therapy ; Insulin/secretion ; Islets of Langerhans/blood supply/cytology/secretion ; *Islets of Langerhans Transplantation ; Liposomes/*administration & dosage/chemistry ; Male ; Mice ; Mice, Inbred BALB C ; Neovascularization, Physiologic ; RNA, Messenger/genetics/metabolism ; Research Support, Non-U.S. Gov't ; Streptozocin ; Transfection ; Vascular Endothelial Growth Factors/biosynthesis/*genetics/*metabolism/secretion

OBJECTIVETo investigate the effects of the treatment of supplementing qi, nourishing yin, and promoting blood flow (SQNYPBF) on the serum levels of CRP, TNF-alpha, IL-1 and IL-6, as well as the expression of HLA-DR in the peripheral monocytes in septic patients suffering from stress-induced hyperglycemia.

METHODSIn the prospective randomized controlled study, eighty-five stress-induced hyperglycemia patients with sepsis were randomly assigned to the experimental group (45 cases) and the control group (40 cases). On the basis of routine therapies, including anti-infection, nutrition support, and the glucose control with insulin pump, patients in the experimental group additionally received the treatment of SQNYPBF (They were intravenously dripped with Shenmai Injection and Sulfotanshinone Sodium Injection, once daily, for 7 successive days). The serum levels of CRP, TNF-alpha, IL-1, and IL-6 and the HLA-DR expression of the peripheral monocytes were detected using ELISA before treatment and on the 8th day of the treatment. The total dose and the duration of insulin used, the morbidity of hypoglycemia, the APACHE II scores, and the mortality within 28-day hospitalization were compared between the two groups.

RESULTSThe total dose of insulin used, the duration of insulin used, the morbidity of hypoglycemia, the APACHE II score on the 8th day of treatment, and the mortality within 28-day hospitalization significantly decreased in the experimental group, when compared with the control group (P < 0.05, P < 0.01). There was no difference in the expression of HLA-DR, the serum levels of CRP, TNF-alpha, IL-1, or IL-6 before treatment between the two groups (P > 0.05). After treatment the serum levels of CRP, TNF-alpha, IL-1, and IL-6 significantly decreased (P < 0.05) and the expression of HLA-DR significantly increased in the two groups (P < 0.05). Better effects were shown in the experimental group (P < 0.05, P < 0.01).

CONCLUSIONSQNYPBF combined intensive insulin therapy could better improve the sepsis patients' immunity, decrease the plasma glucose level and duration, increase their survival rate, and improve their prognosis.

APACHE ; Aged ; C-Reactive Protein ; analysis ; Female ; HLA-DR Antigens ; metabolism ; Humans ; Hyperglycemia ; drug therapy ; etiology ; Interleukin-1 ; blood ; Interleukin-6 ; blood ; Male ; Medicine, Chinese Traditional ; methods ; Middle Aged ; Oxidative Stress ; Prospective Studies ; Sepsis ; complications ; drug therapy ; metabolism ; Tumor Necrosis Factor-alpha ; blood

Dietary fiber improves hyperglycemia in patients with type 2 diabetes through its physicochemical properties and possible modulation of gut hormone secretion, such as glucagon-like peptide 1 (GLP-1). We assessed the effect of dietary fiber-enriched cereal flakes (DC) on postprandial hyperglycemia and gut hormone secretion in patients with type 2 diabetes. Thirteen participants ate isocaloric meals based on either DC or conventional cereal flakes (CC) in a crossover design. DC or CC was provided for dinner, night snack on day 1 and breakfast on day 2, followed by a high-fat lunch. On day 2, the levels of plasma glucose, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and insulin were measured. Compared to CC, DC intake exhibited a lower post-breakfast 2-hours glucose level (198.5±12.8 vs. 245.9±15.2 mg/dL, P<0.05) and a lower incremental peak of glucose from baseline (101.8±9.1 vs. 140.3±14.3 mg/dL, P<0.001). The incremental area under the curve (iAUC) of glucose after breakfast was lower with DC than with CC (P<0.001). However, there were no differences in the plasma insulin, glucagon, GLP-1, and GIP levels. In conclusion, acute administration of DC attenuates postprandial hyperglycemia without any significant change in the representative glucose-regulating hormones in patients with type 2 diabetes (ClinicalTrials.gov. NCT 01997281).
Adult ; Aged ; Area Under Curve ; Blood Glucose/*analysis ; Cross-Over Studies ; Diabetes Mellitus, Type 2/complications/diagnosis/*diet therapy ; Dietary Fiber/*therapeutic use ; Female ; Gastric Inhibitory Polypeptide/blood ; Glucagon/blood ; Glucagon-Like Peptide 1/*blood ; Hemoglobin A, Glycosylated/analysis ; Humans ; Hyperglycemia/complications/diagnosis ; Insulin/blood ; Intestines/metabolism ; Male ; Middle Aged ; ROC Curve