We report the identification of a mutation in the solute carrier family 5 member 2 (SLC5A2) gene, which encodes sodium-glucose cotransporter 2, in a family with familial renal glucosuria. The proband was a 26-year-old Japanese man referred to the diabetes division with repeated glucosuria without hyperglycemia. His mother, uncle and grandfather also had a history of glucosuria. A heterozygous missense mutation (c.303T>A: p.N101K) in SLC5A2 was identified in the patient and his mother, but not in 200 chromosomes from 100 healthy and unrelated individuals, or in 3,408 Japanese individuals in the Tohoku Medical Megabank. Furthermore, bioinformatics software predicted that this lesion would be pathogenic. We infer that the mutation led to clinically relevant sodium-glucose cotransporter 2 dysfunction. The patient showed no symptoms of hypoglycemia, but continuous glucose monitoring confirmed asymptomatic hypoglycemia.

Aims/Introduction: The slope of estimated glomerular filtration rate (eGFR) decline (eGFR slope) in early-stage type 2 diabetes patients might predict the future risk of endstage renal disease. Type 2 diabetes patients who show rapid progressive eGFR decline are termed rapid decliners. Several studies of rapid decliners have investigated the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with advanced renal dysfunction; however, no studies, to our knowledge, have focused on patients with preserved renal function. Therefore, we investigated the efficacy of SGLT2i in rapid decliners with preserved renal function. Materials and Methods: This study enrolled type 2 diabetes patients with baseline eGFR ≥60 mL/min/1.73 m 2 who had been treated with SGLT2i for ≥3 years. Among these individuals, we defined those with annual eGFR declines ≥5 mL/min/1.73 m 2 per year before SGLT2i administration as rapid decliners. The primary end-point was the change in eGFR slope after SGLT2i administration. Results: Among 165 patients treated with SGLT2i for ≥3 years, 21 patients were rapid decliners with preserved renal function. The mean age and eGFR at SGLT2i administration were 58.6 years and 87.1 mL/min/1.73 m 2 , respectively. The mean annual eGFR slope improved significantly in those administered SGLT2i compared with the control group (-1.00 and -4.36 mL/min/1.73 m 2 per year, respectively; P < 0.001). Notably, the steeper the eGFR slope before starting SGLT2i administration, the larger the improvement of eGFR slope, which was independent of the reduction of albuminuria. Conclusions: Early intervention with SGLT2i may have renoprotective effects in type 2 diabetes patients with rapid decline and preserved renal function.incident dialyses in Japan since 1998, was 16,019 in 2019 3 . To reduce the progression from diabetic kidney disease to endstage renal disease (ESRD), identification and effective screening of high-risk patients, and early therapeutic interventions in these individuals are important [4][5][6] .Recently, it has been found that a certain proportion of patients with diabetes show a rapid progressive decline in renal function from preserved baseline estimated glomerular filtration rate (eGFR; ≥60 mL/min/1.73 m 2 ) [7][8][9][10][11] . It has been suggested that the slope of eGFR decline (eGFR slope) of early-stage

Insulin resistance associated with visceral fat obesity has been suggested to be the pathological basis of metabolic syndrome. Many studies have demonstrated increased oxidant stress in diabetic patients and animal models of diabetes mellitus. In this study, the eŠect of liver hydrolysate administration on the blood glucose was examined in SHR/NDmcrcp (SHR-cp) rats that show spontaneously occurring metabolic syndrome-like abnormalities. The SHR-cp rats were fed diets containing 5％ liver hydrolysate for 12 weeks, and the fasting blood glucose and HbA1c were determined every 3 weeks. After administration of the liver hydrolysate-containing feed for 12 weeks, an oral glucose tolerance test was conducted and the plasma angiotensin II (AngII) concentrations were determined. The liver hydrolysate administration had no eŠect on the blood insulin levels in the oral glucose tolerance test, but signiˆcantly inhibited the d-glucose-induced increases of the blood glucose levels. Furthermore, the liver hydrolysate had almost no eŠect on the fasting blood glucose level, but tended to inhibit the increase of HbA1c. The plasma AngII concentration after the 12-week administration of liver hydrolysate remained signiˆcantly lower than that in the control group. These results indicate that a component of liver hydrolysate inhibits d-glucose-induced increase of the blood glucose level, and may improve insulin resistance. The angiotensin converting enzyme (ACE)-inhibiting eŠect and antioxidant eŠect of liver hydrolysate may be involved in this eŠect.

Although diabetic peripheral neuropathy is the most common diabetic microangiopathic complication, several other neuropathy syndromes can occur in the context of diabetes. We describe a rare case of polyneuropathy associated with diabetic ketoacidosis in a patient with new‐onset type 1 diabetes. A 42‐year‐old man with diabetic ketoacidosis was admitted to our hospital with complications of respiratory and renal failure requiring mechanical ventilation and hemodialysis, respectively. After diabetic ketoacidosis improved from the critical state, he developed upper‐ and lower‐limb paralysis with sensory disturbances and pain, as well as right facial paralysis, left recurrent nerve paralysis, and left hypoglossal nerve paralysis. Autonomic nerve function was also impaired. As the pathophysiology, prevention, and treatment of polyneuropathy associated with diabetic ketoacidosis are unclear, the neurologic function of patients with diabetic ketoacidosis should be closely monitored.