No abstract

Clinical studies have shown a relationship between diabetic retinopathy and vascular endothelial growth factor (VEGF) levels in ocular fluid. Advanced glycation end products (AGEs) have been implicated in diabetes complications, including diabetic retinopathy. Nepsilon-(carboxymethyl) lysine (CML) is a glycoxidation product that may be a marker of oxidative stress. In this study, we used enzyme-linked immunosorbent assays to determine the levels of VEGF, non-CML AGE and CML in the aqueous humor and serum of 82 Japanese patients with type 2 diabetes and 60 non-diabetic subjects. VEGF, non-CML AGE, and CML concentrations in aqueous humor and serum were then compared with the severity of diabetic retinopathy. Immunohistochemical detection analysis of non-CML AGE and CML was also performed using retinal tissues from patients with progressive diabetic retinopathy. Aqueous levels of VEGF, non-CML AGE and CML increased along with the progression of diabetic retinopathy compared to age-matched controls. After coagulation therapy, the VEGF, non-CML AGE, and CML levels were significantly reduced. Immunostaining showed diffuse co-localization of non-CML AGE and CML around microvessels and in the glial cells of proliferative membranes from patients with progressive diabetic retinopathy. These findings suggest that glycation and glycoxidation reactions (or oxidation, as revealed by CML) may contribute to both the onset and progression of diabetic retinopathy.

Background: To explore the efficacy and safety of switching from once-daily basal insulin therapy to once-daily pre-meal injection insulin degludec/insulin aspart (IDegAsp) with respect to the glycemic control of participants with type 2 diabetes mellitus (T2DM). Methods: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, participants on basal insulin therapy were switched to IDegAsp (IDegAsp group; n=30) or continued basal insulin (Basal group; n=29). The primary endpoint was the superiority of IDegAsp in causing changes in the daily blood glucose profile, especially post-prandial blood glucose concentration after 12 weeks. Results: Blood glucose concentrations after dinner and before bedtime were lower in the IDegAsp group, and the improvement in blood glucose before bedtime was significantly greater in the IDegAsp group than in the Basal group at 12 weeks (−1.7±3.0 mmol/L vs. 0.3±2.1 mmol/L, P<0.05). Intriguingly, glycemic control after breakfast was not improved by IDegAsp injection before breakfast, in contrast to the favorable effect of injection before dinner on blood glucose after dinner. Glycosylated hemoglobin significantly decreased only in the IDegAsp group (58 to 55 mmol/mol, P<0.05). Changes in daily insulin dose, body mass, and recorded adverse effects, including hypoglycemia, were comparable between groups. Conclusion: IDegAsp was more effective than basal insulin at reducing blood glucose after dinner and before bedtime, but did not increase the incidence of hypoglycemia. Switching from basal insulin to IDegAsp does not increase the burden on the patient and positively impacts glycemic control in patients with T2DM.

This multicentre, prospective, randomized, open‐label, blinded‐endpoint, parallel‐group, short‐term (4–5 weeks) controlled trial was conducted to investigate the superiority of the effect of reducing mean amplitude of glycaemic excursions (MAGE) during meal tolerance tests (MTTs) for the combination of dipeptidyl peptidase‐4 (DPP‐4) inhibitor and sodium‐glucose co‐transporter‐2 (SGLT2) inhibitor compared with SGLT2 inhibitor monotherapy. Ninety‐nine patients with type 2 diabetes who were taking teneligliptin (20 mg/d) were randomized to one of the following two groups: those who switched to 100 mg/d of canagliflozin (SWITCH group) or those who added 100 mg/d of canagliflozin (COMB group). MAGE in the COMB group was significantly decreased compared with that in the SWITCH group (COMB 117.5 ± 39.8 to 92.2 ± 28.0 mg/dL vs SWITCH 110.7 ± 29.8 to 104.2 ± 27.6 mg/dL; P<0.01). Mean blood glucose decreased significantly during MTTs in both groups, although the extent of the reduction was significantly greater in the COMB group (COMB 142.3 ± 28.7 to 119.5 ± 25.1 mg/dL vs SWITCH 146.4 ± 25.5 to 135.5 ± 22.4 mg/dL; P < 0.01). SGLT2 inhibitor combined with DPP‐4 inhibitor therapy strongly reduced glycaemic fluctuation compared with SGLT2 inhibitor monotherapy.

With the expansive use of immune checkpoint inhibitors, the frequency of immune‐related adverse events, including autoimmune type 1 diabetes, has been exponentially increased. The anti‐programmed death‐ligand 1 antibody, avelumab, has recently been approved for metastatic Merkel cell carcinoma therapy. Here, we report a patient that developed fulminant type 1 diabetes during avelumab treatment. An 81‐year‐old woman with no history of diabetes received avelumab for metastatic Merkel cell carcinoma. Elevated plasma glucose level (483 mg/dL), hemoglobin A1c level (7.5%) and ketosis were observed after 10 courses of avelumab without any symptoms related to hyperglycemia. As the laboratory tests showed insulin depletion, we diagnosed her with fulminant type 1 diabetes induced by avelumab. This is the first reported case of avelumab‐induced type 1 diabetes, illustrating the necessity for close monitoring of glycemic control during avelumab therapy, as well as other immune checkpoint inhibitors.