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Patients with diabetes mellitus having insulin antibodies (InsAb) with properties of high binding capacity and low affinity, which are observed in insulin autoimmune syndrome (IAS), are known to have greater plasma glucose fluctuations. Glycated albumin (GA) and the GA/HbA1c ratio have been demonstrated to reflect plasma glucose fluctuations. Hence, we hypothesized that GA or the GA/HbA1c ratio in diabetic patients having InsAb with properties of high binding capacity and low affinity may be higher than those in InsAb-negative diabetic patients, and we verified this hypothesis. Subjects were 12 diabetic patients who had InsAb noted while being treated with insulin and were subjected to Scatchard analysis and whose InsAb had properties similar to those of patients with IAS (affinity constant K1 < 0.24 x 1/10(-8) M, number of binding sites R1 ≥ 11.5 x 10(-8) M) [four cases of type 1 diabetes (T1D) and eight cases of type 2 diabetes (T2D)]. The control group consisted of T1D and T2D cases matched to the T1D and T2D cases, respectively, according to sex, age, BMI, and HbA1c. GA and the GA/HbA1c ratio were compared between both groups. GA and the GA/HbA1c ratio in InsAb-positive patients was significantly higher than that in the control group for both T1D and T2D patients. Diabetic patients having InsAb with properties of high binding capacity and low affinity had higher GA and the GA/HbA1c ratio than those of InsAb-negative patients. Greater plasma glucose fluctuations were suggested in InsAb-positive diabetic patients.

Bariatric surgery has been shown to have a variety of metabolically beneficial effects for patients with type 2 diabetes (T2D), and is now also called metabolic surgery. At the 2nd Diabetes Surgery Summit held in 2015 in London, the indication for bariatric and metabolic surgery was included in the “algorithm for patients with type T2D”. With this background, the Japanese Society for Treatment of Obesity (JSTO), the Japan Diabetes Society (JDS) and the Japan Society for the Study of Obesity (JASSO) have formed a joint committee to develop a consensus statement regarding bariatric and metabolic surgery for the treatment of Japanese patients with T2D. Eventually, the consensus statement was announced at the joint meeting of the 38th Annual Meeting of JSTO and the 41st Annual Meeting of JASSO convened in Toyama on March 21, 2021. In preparing the consensus statement, we used Japanese data as much as possible as scientific evidence to consider the indication criteria, and set two types of recommendation grades, “recommendation” and “consideration”, for items for which recommendations are possible. We hope that this statement will be helpful in providing evidence-based high-quality care through bariatric and metabolic surgery for the treatment of obese Japanese patients with T2D. Supplementary Information The online version contains supplementary material available at 10.1007/s13340-021-00551-0.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors often increase the hematocrit. It remains unclear whether this increase would be observed in all patients administered SGLT2 inhibitors, however. We therefore used the data from the previous study and investigated time-dependent alterations of various outcomes related to erythrocytes, erythropoiesis, and clinical outcome in type 2 diabetes subjects (n = 89) treated with ipragliflozin for 16 weeks. Among a total of 89 participants, 71 subjects (80.0% of total participants) showed the elevation of the hematocrit and 18 subjects (20.0% of total participants) did not at 16 weeks. Although the hematocrit levels at baseline were significantly lower in hematocrit-elevated group than non-elevated group, they reached the same levels 4 weeks after the onset of treatment. Binomial logistic regression analysis demonstrated that a lower baseline hematocrit level was related to the elevation of hematocrit at 16 weeks. Optimal cutoff hematocrit levels at baseline to predict hematocrit elevation were 46.9% (male) and 41.7% (female) in ROC analysis. Random intercept model analysis revealed the serum erythropoietin level increased in both hematocrit-elevated and non-elevated groups, whereas only the former group showed an increase in the percentage of reticulocytes during the first 4 weeks. These results suggest that the ipragliflozin-induced increase in hematocrit which is affected by the baseline hematocrit level is attributable to the responsiveness to, but not to the production of, erythropoietin. Collectively, Ht elevation observed in administration of SGLT2 inhibitors can result from erythropoietin-induced erythropoiesis, which is determined by the pre-treatment Ht level. Trial registration: This trial has been registered with University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR no. 000015478).

Whereas the genetic basis of insulin sensitivity is determined by variation in multiple genes, mutations of single genes can give rise to profound changes in such sensitivity. Mutations of the insulin receptor gene (INSR)—which trigger type A insulin resistance, Rabson–Mendenhall, or Donohue syndromes—and those of the gene for the p85α regulatory subunit of phosphoinositide 3-kinase (PIK3R1), which give rise to SHORT syndrome, are the most common and second most common causes, respectively, of single-gene insulin resistance. Loss-of-function mutations of the genes for the protein kinase Akt2 (AKT2) or for TBC1 domain family member 4 (TBC1D4) have been identified in families with severe insulin resistance. Gain-of-function mutations of the gene for protein tyrosine phosphatase nonreceptor type 11 (PTPN11), which negatively regulates insulin receptor signaling, give rise to Noonan syndrome, and some individuals with this syndrome manifest insulin resistance. Gain-of-function mutations of the gene for the p110α catalytic subunit of phosphoinositide 3-kinase (PIK3CA) have been identified in individuals with segmental overgrowth or megalencephaly, some of whom also manifest spontaneous hypoglycemia. A gain-of-function mutation of AKT2 was also found in individuals with recurrent hypoglycemia. Loss-of-function mutations of the gene for phosphatase and tensin homolog (PTEN), another negative regulator of insulin signaling, give rise to Cowden syndrome in association with exaggerated metabolic actions of insulin. Clinical manifestations of individuals with such mutations of genes related to insulin signaling thus provide insight into the essential function of such genes in the human body.

Evidence suggests that sensor augmented pump (SAP) therapy is superior to conventional continuous subcutaneous insulin infusion (CSII) for achieving glycemic control in patients with type 1 diabetes. However, the clinical benefit of SAP therapy in East Asians has not yet been demonstrated.The effect of switching from conventional CSII to SAP therapy on glycemic profile was examined in 18 Japanese patients with type 1 diabetes. The glycemic profile of the patients was determined by retrospective continuous glucose monitoring (CGM) within 1 month before the treatment switch, whereas that at 6 and 12 months after the switch was evaluated with the CGM function of the SAP device. Hemoglobin A1c levels were also measured before and after the switch to SAP therapy.The duration of hypoglycemia was significantly decreased at both 6 and 12 months after the change in treatment (6.6 ± 4.5, 3.2 ± 4.1, and 3.0 ± 2.8 min/h for before and 6 and 12 months, respectively), as was the HbA1c level at 12 months (7.8 ± 1.0 and 7.4 ± 0.9%, respectively). The duration of hyperglycemia did not differ between before and after the treatment switch. The decline in HbA1c level at 12 months after the switch to SAP was negatively correlated with age.Switching from conventional CSII to SAP therapy was associated with a decrease in both the duration of hypoglycemia and the level of HbA1c in Japanese patients with type 1 diabetes.

Fear of iatrogenic hypoglycemia associated with insulin therapy or oral hypoglycemic agents may prevent patients from achieving appropriate control of blood glucose levels. Such episodes also often impair quality of life and can be fatal. Hypoglycemia-induced hemiplegia is a neurological sign that is thought to result from selective neuronal vulnerability to low blood glucose and is readily reversed by glucose administration. A differential diagnosis of such hypoglycemia-induced hemiplegia relative to ischemic cerebrovascular conditions is important given the substantial differences in prognosis. We now report a case of hemiplegia induced by hemodynamic change in association with hypoglycemia, with this condition being differentiated clinically from typical hypoglycemia-induced hemiplegia. An 85-year-old woman presented with left-sided hemiplegia that was rapidly resolved by intravenous glucose administration. Magnetic resonance imaging revealed no acute changes in the brain parenchyma, whereas diffusion-weighted images typically show high-intensity areas in cases of hypoglycemia-induced hemiplegia. Magnetic resonance angiography revealed advanced stenosis of the right internal carotid artery. Furthermore, whereas single-photon emission computed tomography showed no abnormality in blood flow at rest, it revealed marked impairment of blood flow in the right hemicerebrum after loading with acetazolamide, consistent with the advanced arteriosclerosis. The impaired cerebral flow reserve was thus likely exacerbated by hypoglycemia and evoked transient hemiplegia. As far as we are aware, this is the first report of a hypoglycemia-induced transient ischemic attack in the presence of underlying arteriosclerosis. The cerebrovascular state of patients with hemiplegia and hypoglycemia should thus be appropriately assessed to prevent future cerebral infarction.