Comparison of modified preadmission glucose-lowering regimen with basal/bolus regimen for glucose control on outcome in general medicine wards.

BACKGROUND: It is undecided whether glucose control as advocated by the professional organisations and the glucose-lowering method by itself affects clinical outcome in patients with diabetes mellitus hospitalised in general medical wards. Our aim was to investigate whether a basal/bolus regimen and a modified prehospitalisation regimen have a different impact on the clinical diabetic patients in general medicine wards. METHODS: Glucose control of patients with diabetes hospitalised in two different wards of internal medicine was achieved according to their wards' policy: a modified preadmission regimen (conventional regime) or a basal/bolus regimen (intensive regime). Death and any adverse event were determined during hospitalisation and within 6 months after discharge to assess clinical outcome. RESULTS: Median fasting and daily glucose levels were similar in the conventional (n = 116) and intensive regime (n = 129) groups: 161 mg/dl (inter-quartile range: 138-201) and 176 mg/dl (152-215) vs. 155 mg/dl (133-208) and 173 mg/dl (146-208) respectively. Clinical outcome was not affected by the treatment modality. In the subgroup of patients hospitalised with infection, the median fasting glucose was significantly lower in the interventional compared with the conventional regime: 141 and 172 mg/dl respectively (p = 0.041). However, tighter control was associated with a significantly higher incidence of adverse events within 6 months after discharge: 48.9% and 21.4% respectively (p = 0.047). CONCLUSION: In general medicine wards, modified prehospital hypoglycaemic regimens and a basal/bolus insulin regimen achieve similar glucose control. The clinical outcome was not affected by the modality of glucose control.

Characterization of GLUT5 domains responsible for fructose transport.

The domains responsible for the fructose specificity of GLUT5 were investigated by creating chimeras of GLUT5 with the selective glucose transporter GLUT3, which were expressed in Xenopus oocytes. 3-O-Methylglucose uptake of chimeric GLUT3-5 (M11; GLUT3 to the 11th transmembrane domain, GLUT5 to the carboxyl end) was similar to that of GLUT3, while fructose was not transported. Fructose uptake of chimeric GLUT5-3 (M3-5) to -5 (GLUT3 from the 3rd to 5th transmembrane domains, the rest GLUT5) was similar to that of GLUT5; no glucose was transported. Four chimeras transported neither fructose nor glucose: GLUT3-5 (M5; GLUT3 to the 5th transmembrane domain, GLUT5 to the carboxyl end), GLUT5-3 (M2; GLUT5 to the 2nd transmembrane domain, the rest GLUT3), GLUT5-3 (M3-11) to -5 (GLUT3 between the 3rd and 11th transmembrane domains, the rest GLUT5) and GLUT5-3 (M3-5) to -5-3 (M11; GLUT3 from the 3rd to 5th transmembrane domains and after the 11th transmembrane domain, the rest GLUT5). They, nevertheless, induced full-size proteins that were transported to the cell surface, as demonstrated by exofacial labeling with biotin. To conclude, the GLUT5 domain from the amino-terminus to the third transmembrane domain and that between the 5th and 11th transmembrane stretches seem to be necessary for fructose uptake.

T cell signaling and autoimmune diabetes.

Stimulation of the T-cell lymphocyte surface receptor (TCR) initiates a cascade of intracellular signaling events leading to proliferation, anergy, cytokine secretion, or apoptosis. In prediabetic NOD mice, T cell proliferative hyporesponsiveness has been correlated to decreased TCR-mediated signal transduction along the PKC/p21ras/p42mapk pathway. Limited data regarding T cell signaling defects are available in patients with autoimmune diabetes mellitus. Some but not all investigators have found decreased in vitro proliferative hyporesponsiveness to lectin mitogens or anti-CD3 mAb associated with impaired PKC activation and cytokine production. More recently, defective expression and function of the p21ras cascade was reported in these patients. Taken together, these data suggest that lymphocytes from animals and patients with autoimmune diabetes have defective TCR mediated signaling which may result in aberrant T cell activation and proliferation. This may lead to an imbalance of Th1/Th2 cytokine secretory pattern and thereby promote disease development.

Murine typhus endocarditis.

We have described a 28-year-old male sheepfarmer who had fever, headache, chills, malaise, and aortic insufficiency. Echocardiography revealed a tricuspid aortic valve with a large vegetation on the right cusp, an enlarged left ventricle, and diastolic flutter of the mitral valve. Repeated blood cultures were negative. Seroconversion of IgG and IgM to Rickettsia typhi was found on the 13th day of hospitalization. The patient was treated with tetracycline for 1 year and remained afebrile and free of symptoms for 9 months, when he was lost to follow-up. IgM and IgG fluorescent antibodies to R typhi remained positive during 8 months of the follow-up period. We believe this to be the second reported case of endocarditis due to R typhi and the first not treated surgically.

Hemodynamic characterization of conscious and ketamine-anesthetized bile duct-ligated rats.

The present study was conducted to characterize the hemodynamic alterations in common bile duct-ligated (CBDL) rats under ketamine anesthesia and in the awake restrained state. Hemodynamic studies using the radioactive microspheres technique were performed 17.6 +/- 0.6 (SE) days after bile duct ligation or sham operation. CBDL rats had lower mean arterial pressure, reduced systemic and renal resistance, and increased renal blood flow compared with sham-operated rats. This was found both in the conscious and anesthetized states. Anesthetized CBDL rats had higher portal pressure (13.2 +/- 0.5 vs. 9.2 +/- 0.4 mmHg; P less than 0.001) and lower splanchnic arteriolar resistance (15.4 +/- 1.3 vs 26.8 +/- 4.6 mmHg.ml-1.min.100 g body wt; P less than 0.05) than sham-operated rats. Portosystemic shunting was 52.3 +/- 11.7% in CBDL and negligible in sham-operated rats. The last three parameters could not be measured in conscious animals. Total peripheral resistance was lower in the conscious than in the anesthetized state, diverting a higher fraction of cardiac output at the expense of splanchnic organs and leading to a significant reduction of portal venous inflow in sham-operated but not in CBDL rats [3.36 +/- 0.47 vs. 5.38 +/- 0.65 (P less than 0.05) and 5.33 +/- 0.58 vs. 6.34 +/- 0.37 ml.min-1.100 g body wt-1 (P = NS), respectively]. These findings indicate that CBDL and normal rats respond differently to anesthesia and restraint. Because the restrained state is stressful and studies in anesthetized animals are technically simpler, provide additional information such as portal pressure and portosystemic shunting, and diminish animal suffering, we suggest that hemodynamic studies in rats, using the microsphere technique, should be preferably performed under ketamine anesthesia.

Increased expression of tissue factor and receptor for advanced glycation end products in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus with vascular complications.

The aim of the study was to determine the correlation between the expression of tissue factor (TF) and the receptor for advanced glycation end products (RAGEs) and vascular complications in patients with longstanding uncontrolled type 2 diabetes (T2D). TF and RAGE mRNAs as well as TF antigen and activity were investigated in 21 T2D patients with and without vascular complications. mRNA expression was assessed by reverse transcriptase-polymerase chain reaction (RT-PCR) in nonstimulated and advanced glycation end product (AGE) albumin-stimulated peripheral blood mononuclear cells (PBMCs). TF antigen expression was determined by enzyme-linked immunosorbent assay (ELISA) and TF activity by a modified prothrombin time assay. Basal RAGE mRNA expression was 0.2 +/- 0.06 in patients with complications and 0.05 +/- 0.06 patients without complications (P =.004). Stimulation did not cause any further increase in either group. TF mRNA was 0.58 +/- 0.29 in patients with complications and 0.21 +/- 0.18 in patients without complications (P =.003). Stimulation resulted in a nonsignificant increase in both groups. Basal TF activity (U/10(6) PBMCs) was 18.4 +/- 13.2 in patients with complications and 6.96 +/- 5.2 in patients without complications (P =.003). It increased 3-fold in both groups after stimulation (P =.001). TF antigen (pg/10(6) PBMCs) was 33.7 +/- 28.6 in patients with complications, 10.4 +/- 7.8 in patients without complications (P =.02). Stimulation tripled TF antigen in both groups of patients (P =.001). The RAGE/TF axis is up-regulated in T2D patients with vascular complications as compared to patients without complications. This suggests a role for this axis in the pathogenesis of vascular complications in T2D.