Different expression of Tn and sialyl-Tn antigens between normal and diseased human gastric epithelial cells.

Thomsen-Friedenreich antigen (T antigen) has been supposed to be a cancer-specific carbohydrate antigen. We have previously shown that one third of the Japanese population normally expressed T antigen in gastric surface epithelia and the other two thirds expressed fucosyl-T antigen. Their sialylation and blocked-synthesis were associated with diseased conditions. In the present study, we studied gastric surface epithelial expression of monosaccharide antigen Tn, i.e., a precursor of T antigen, and sialyl-Tn. Normal fundic and pyloric epithelia, respectively, expressed Tn supranucleally and cytoplasmically, but did not express sialyl-Tn. In the intestinal metaplasias and intestinal-type adenomas, goblet cells expressed sialyl-Tn in their vacuoles, and absorptive cells expressed Tn apically. In gastric-type adenomas, Tn, but not sialyl-Tn, was detected. Intestinal-type cancers expressed Tn and sialyl-Tn more often than the diffuse-type cancers. Five cancers did not express Tn, sialyl-Tn, or the T-related antigens. In these, four were diffuse-type cancers. We concluded that: a) normal gastric epithelial cells express Tn; b) metaplastic differentiation is associated with sialylation of Tn and c) expression of Tn and sialyl-Tn is depressed in the gastric cancers. </p

Marked Hypertriglyceridemia in a Patient with type 2 Diabetes Receiving SGLT2 Inhibitors

A 43-year-old male with type 2 diabetes, under treatment with 5 mg/day of dapagliflozin, was referred to our hospital with upper left abdominal pain and marked hypertriglyceridemia (triglycerides [TGs], 5,960 mg/dl). He was also on a low-carbohydrate diet that promoted ketosis under sodium glucose cotransporter 2 (SGLT2) inhibitor administration. Polyacrylamide gel electrophoresis revealed a remarkable increase in very-low-den-sity lipoprotein, a TG-rich lipoprotein particle synthesized in the liver using free fatty acids derived from adi-pose tissue. Although SGLT2 inhibitors generally improve the lipid profile, under certain conditions such as a low-carbohydrate diet, they may adversely exacerbate the lipid profile via ketosis

Rationale, design and baseline characteristics of the effect of canagliflozin in patients with type 2 diabetes and microalbuminuria in the Japanese population: The CANPIONE study

Aim To evaluate the effect of canagliflozin, a sodium-glucose co-transporter-2 (SGLT2) inhibitor, on albuminuria and the decline of estimated glomerular filtration rate (eGFR) in participants with type 2 diabetes and microalbuminuria. Methods The CANPIONE study is a multicentre, randomized, parallel-group and open-labelled study consisting of a unique 24-week preintervention period, during which the rate of eGFR decline before intervention is estimated, followed by a 52-week intervention and a 4-week washout period. Participants with a geometric mean urinary albumin-to-creatinine ratio (UACR) of 50 and higher and less than 300 mg/g in two consecutive first-morning voids at two different time points, and an eGFR of 45 ml/min/1.73m2 or higher, are randomly assigned to receive canagliflozin 100 mg daily or to continue guideline-recommended treatment, except for SGLT2 inhibitors. The first primary outcome is the change in UACR, and the second primary outcome is the change in eGFR slope. Results A total of 258 participants were screened and 98 were randomized at 21 sites in Japan from August 2018 to May 2021. The mean baseline age was 61.4 years and 25.8% were female. The mean HbA1c was 7.9%, mean eGFR was 74.1 ml/min/1.73m2 and median UACR was 104.2 mg/g. Conclusions The CANPIONE study will determine whether the SGLT2 inhibitor canagliflozin can reduce albuminuria and slow eGFR decline in participants with type 2 diabetes and microalbuminuria

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Introduction Given an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methods We registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.Results Of the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (&gt;90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.Conclusions Alogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting