Efficacy and safety of patient‐directed titration of once‐daily pre‐dinner premixed biphasic insulin aspart 70/30 injection in Japanese type 2 diabetic patients with oral antidiabetic drug failure: STEP‐AKITA study

Aims/Introduction: To clarify clinical characteristics related to optimal glycemic control achieved after adding once‐daily pre‐dinner biphasic insulin aspart 70/30 (BIAsp 30) in Japanese type 2 diabetic (T2D) patients with oral antidiabetic drug (OAD) failure. Materials and Methods: Under this regimen, we evaluated changes in HbA_1c levels and daily self‐monitoring blood glucose (BG) profiles, as well as the incidences of hypoglycemia and retinopathy progression. The patients adjusted BIAsp 30 dosages themselves every 3–4 days according to a pre‐determined algorithm to achieve fasting BG levels of 101–120 mg/dL. HbA_1c levels were expressed as Japan Diabetes Society values. Results: Of 29 enrolled patients, 22 (HbA_1c levels, 8.5 ± 1.5% [mean ± SD]) and 20 patients completed the 16‐ and 24‐week follow‐up, respectively. At 16 weeks 68.2 and 45.5%, and at 24 weeks 80.0 and 35% of patients had achieved HbA_1c levels of <7.0 and <6.5%, respectively. The patients who had achieved optimal glycemic control, including daytime postprandial BG profiles after treatment, had lower post‐breakfast BG excursions at baseline, shorter diabetes durations and younger age. No severe hypoglycemic episodes were recorded. Progression of retinopathy was observed in 3 of the 29 enrolled patients. Conclusions: Lower post‐breakfast BG excursions, shorter diabetes duration and younger age in Japanese T2D patients with OAD failure might warrant optimal glycemic control with safety after adding once‐daily pre‐dinner BIAsp 30 initiating regimen. (J Diabetes Invest, doi: 10.1111/j.2040‐1124.2010.00062.x, 2010)     

Sulfated glycoprotein biosynthesis in human gastric mucosal biopsies

Sulfated mucus glycoprotein biosynthesis by human gastric mucosal biopsies was studied. Human gastric healthy specimens and cancer specimens were obtained from antral and corpus normal mucosal areas by biopsy. A comparison was made of the biosynthesized sulfated mucus glycoproteins assessed by the incorporation of 35S-sulfate and 14C-glucosamine into the specimens using an organ culture technique. A significant uptake of 35S-sulfate or 14C-glucosamine into the mucus glycoproteins was demonstrated in all specimens. 14C-glucosamine incorporation into the glycoproteins was almost the same for all biopsies. The synthesis of sulfated glycoprotein in healthy antral mucosa was about four times that in corpus mucosa. Significantly raised levels in sulfated glycoprotein biosynthesis were found in cancer specimens, being about 30 and 13 times higher in antrum and corpus mucosa than that of healthy specimens, respectively.     

The significance of low serum pepsinogen levels to detect stomach cancer associated with extensive chronic gastritis in Japanese subjects

Serum pepsinogen levels were measured in 137 stomach cancer patients and compared with those of 288 normal cancer-free subjects. The serum pepsinogen levels of stomach cancer patients, especially pepsinogen I and the pepsinogen I/pepsinogen II ratio were significantly lower than those of normal controls and correlated well with the extent of chronic gastritis associated with the cancerous stomach. These results were in good accordance with the results of previous studies indicating that the cancer derived from the stomach where chronic gastritis/intestinal metaplasia is extensive. The high sensitivity and specificity of this non-invasive serum test to detect chronic gastritis suggested the possibility of its application to the mass screening of stomach cancer.     

Symmetrical drug-related intertriginous and flexural exanthema caused by valacyclovir

Drug-related eruptions that appear only on intertriginous or flexural folds and in gluteal areas have recently been termed symmetrical drug-related intertriginous and flexural exanthema (SDRIFE). We report a case of a 56-year-old woman with acute erythematous rash in the intertriginous areas after treatment with the L-valine ester of acyclovir, valacyclovir. Oral-challenge tests resulted in erythematous pruritic rash in the intertriginous area by valacyclovir. The patient was diagnosed as having SDRIFE due to valacyclovir.     

Blockade of pancreatic islet-derived ghrelin enhances insulin secretion to prevent high-fat diet-induced glucose intolerance

The gastric hormone ghrelin and its receptor, growth hormone secretagogue receptor (GHSR), are expressed in pancreas. Here, we report that ghrelin is released from pancreatic islets to regulate glucose-induced insulin release. Plasma concentrations of ghrelin, as well as insulin, were higher in pancreatic veins than in arteries. GHSR antagonist and immunoneutralization of endogenous ghrelin enhanced glucose-induced insulin release from perfused pancreas, whereas exogenous ghrelin suppressed it. GHSR antagonist increased plasma insulin levels in gastrectomized and normal rats to a similar extent. Ghrelin knockout mice displayed enhanced glucose-induced insulin release from isolated islets, whereas islet density, size, insulin content, and insulin mRNA levels were unaltered. Glucose tolerance tests (GTTs) in ghrelin knockout mice showed increased insulin and decreased glucose responses. Treatment with high-fat diet produced glucose intolerance in GTTs in wild-type mice. In ghrelin knockout mice, the high-fat diet-induced glucose intolerance was largely prevented, whereas insulin responses to GTTs were markedly enhanced. These findings demonstrate that ghrelin originating from pancreatic islets is a physiological regulator of glucose-induced insulin release. Antagonism of the ghrelin function can enhance insulin release to meet increased demand for insulin in high-fat diet-induced obesity and thereby normalize glycemic control, which may provide a potential therapeutic application to counteract the progression of type 2 diabetes.     

Gel filtration of Vitamin B12 binders and intrinsic factor from human gastric juice on sephadex columns

Summary and Conclusions Normal gastric juice-bound Vitamin B₁₂ was excluded from all Sephadex columns, including G-200. Fractions excluded from the G-75, G-100, and G-200 column, exhibited intrinsic-factor activity on urinary excretion test.Since materials excluded from Sephadex G-200 supposedly have a molecular weight of over 200,000, one may assume that the intrinsic-factor-related B₁₂ binders, as well as intrinsic factor itself, have a molecular weight in this high range, or that they polymerize or form a complex with other macromolecular gastric materials of this size range.Supported by Research Grant-in-Aid AM-00068 (12) from the National Institute of Arthritis and Metabolic Diseases, and the American Cancer Society [P-305 (F)].