The effect of sodium-glucose cotransporter 2 inhibitor (tofogliflozin) on renal tubular damage in diabetic patients without albuminuria.

PURPOSE: The sodium-glucose cotransporter 2 (SGLT2) inhibitors comprise a new class of glucose-lowering drugs for individuals with diabetes. Large-scale clinical trials indicated that SGLT2 inhibitors have both a cardiovascular-protective and renal-protective effects. A reduction in glomerular hyperfiltration and a decrease in albuminuria are suspected as the main causes of SGLT2 inhibitors' renoprotective effect. The effects of SGLT2 inhibitors on tubular damage in non-albuminuric diabetic patients are unclear. METHODS: The SGLT2 inhibitor tofogliflozin (20 mg, 1 × /day) was orally administered to 14 non-albuminuric diabetic patients. Serum and urine samples were collected at baseline (before) and after the start of tofogliflozin treatment. Hemoglobin A1c, hemoglobin, estimated glomerular filtration rate (eGFR), body weight, and blood pressure (BP) were analyzed as clinical parameters at baseline and 1, 3, and 6 months later. Urinary neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl-ß-D-glucosaminidase were measured as tubular damage markers and the urinary 8-hidroxydeoxyguanosine (8-OHdG) values were measured as an oxidative stress marker at baseline and at 1 and 3 months. RESULTS: Compared to baseline, the patients' HbA1c values and body weights were significantly decreased post-tofogliflozin administration, and their eGFR values were decreased at 3 months but recovered at 6 months; the hemoglobin concentrations were significantly increased at 3 and 6 months and the urinary NGAL level tended to be decreased at 3 months. No significant changes in blood urea nitrogen, BP, NAG, urine sodium concentration, or urinary 8-OHdG values occurred. The effect of this SGLT2 inhibitor was not influenced by the use of an angiotensin receptor blocker or dipeptidyl-peptidase 4 inhibitor. CONCLUSION: For individuals with non-albuminuric diabetes, tofogliflozin has a good glucose-lowering effect and might have a tubular-protective effect.

Insulin-derived amyloidosis and poor glycemic control: a case series.

OBJECTIVES: Insulin-derived amyloidosis is a rare skin-related complication of insulin therapy. The purpose of this study was to show the effects of insulin-derived amyloidosis on blood glucose levels, insulin dose requirements, and insulin absorption. METHODS: Seven patients were found to have insulin-derived amyloidosis at the Tokyo Medical University Ibaraki Medical Center. The clinical characteristics and insulin therapy of the 7 patients were investigated. Insulin absorption was studied by comparing the serum insulin levels after insulin injections into insulin-derived amyloidosis sites versus injections into normal sites in 4 patients. RESULTS: When the insulin-derived amyloidosis was discovered, the mean hemoglobin A1c level was 9.3%, and the mean daily insulin dose was 57 units. After changing the injection sites to avoid the insulin-derived amyloidosis, the blood glucose concentrations improved, and the mean daily insulin dose could be reduced to 27 units (P = .035; 53% reduction). The insulin absorption at insulin-derived amyloidosis sites was 34% of that at normal sites (P = .030). CONCLUSIONS: Insulin-derived amyloidosis caused poor glycemic control and increased insulin dose requirements because of impairments in insulin absorption.

A trial to assess the amount of insulin antibodies in diabetic patients by surface plasmon resonance.

OBJECTIVE: To measure the amount and affinity of insulin antibodies, we performed a trial to establish a new method for quantitative and qualitative analysis of these antibodies by using surface plasmon resonance (BIAcore system). METHODS: Real-time detection of insulin antibody interaction and kinetic analysis were performed using the BIAcore system. PATIENTS OR MATERIALS: Eight diabetic patients with insulin antibodies and whose fasting total immunoreactive insulin levels were more than 100 microU/ml were selected. The patients with and without recurrent hypoglycemia were classified into hypoglycemic episode-positive or hypoglycemic episode-negative groups, respectively. Seven diabetic patients without insulin antibodies were selected as controls. RESULTS: In the 8 patients, the concentration of insulin antibodies ranged from 2.91 to 16.3 microg/ml and insulin antibodies were not detected in the control group. The apparent KD (dissociation constant) and kd (the dissociation rate constant) values of the patients were much larger than those seen for the anti-human insulin monoclonal antibody. The KD values were significantly higher in the hypoglycemic episode-positive group than in the hypoglycemic episode-negative group (p<0.05). No significant differences in the concentration, the ka (the association rate constant) and the kd values were noted between the groups. CONCLUSION: The data suggests that insulin antibodies of the patients have an apparently lower affinity status in sera as compared with that for the anti-human insulin monoclonal antibody, and dissociate easily from the immune-complex in the sera, especially in cases where there is recurrent hypoglycemia in the patients. Therefore insulin antibody characteristics are one of the causative factors in hypoglycemic episodes.