The aim of this study was to determine the effective waist circumference (WC) reduction rate in avoiding the development of type 2 diabetes mellitus (T2DM) in <55 years and ≥55 years Japanese men with abdominal obesity. The study subjects were 795 men with WC ≥85 cm, fasting plasma glucose <126 mg/dL, 2-hr plasma glucose on 75 g of oral glucose tolerance test <200 mg/dL, and HbA1c 5.6-6.4 % (38-40 mmol/mol) at baseline who underwent general health checkups more than twice between April 2007 and May 2015. They were divided into 5 groups based on the change in WC during the observation period (WC gain group, and four groups stratified according the rate of WC loss). The subjects were also divided into the <55 years and ≥55 years (at baseline) subgroups. The cumulative incidence rate of T2DM was analyzed and compared among the groups. The cumulative incidence rates of the largest WC loss quartile (≥5.45 %) in all age, of the largest WC loss quartile (≥5.60 %) and second largest WC loss quartile (3.44-5.59 %) in the <55 years subgroup, and of the largest WC loss quartile (≥5.37 %) in the ≥55 years subgroup were significantly lower than that of the gain group (p<0.001, p=0.009, 0.012, and 0.012, respectively). WC reduction rate of at least about 3 % in the younger (<55 years) and at least about 5 % in the older (≥55 years) non-diabetic Japanese men with abdominal obesity can effectively reduce the chance of development of T2DM.

ContextLow serum adiponectin (Ad) level is an important risk factor for the development of type 2 diabetes mellitus (T2DM).ObjectiveTo determine whether the changes in Ad in subjects with low baseline serum Ad levels can reduce the rate of development of T2DM.Design/Setting/ParticipantsWe performed a large-scale longitudinal study of 7052 healthy Japanese men who underwent general health checkups more than twice between April 2007 and May 2015 at the Physical Check up Center, Sumitomo Hospital. The participants were divided into quartile groups according to baseline Ad level. Subjects of the lowest baseline Ad group (≤5.2 μg/mL) were subdivided into quartile subgroups according to the percent change in Ad (%ΔAd) and into two subgroups according to endpoint Ad (>5.2 and ≤5.2 μg/mL).Main Outcome MeasuresThe cumulative incidence rate of T2DM.ResultsThe cumulative incidence rate of T2DM of the lowest baseline Ad group (≤5.2 μg/mL) was significantly higher than the other quartile groups. The cumulative incidence rates of T2DM were significantly lower in the largest (≥21.5%) and the second largest (9.3% to 21.4%) %ΔAd-increased subgroups compared with the %ΔAd-decreased subgroup (P < 0.001 and P = 0.005, respectively). The cumulative incidence rates of T2DM were significantly lower in the endpoint Ad >5.2 μg/mL subgroup than in the ≤5.2 μg/mL subgroup (P < 0.001).ConclusionsIncreases in serum Ad levels of at least ~10% or >5.2 μg/mL can potentially reduce the risk of development of T2DM in Japanese men with low baseline Ad levels who are at a high risk of developing T2DM.

Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from 3 cases with ICI-related T1D, and their histopathological data were compared those from 3 patients who had received ICI therapy but did not develop T1D (non-T1D) and 7 normal glucose-tolerant subjects as controls. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β-cell area decreased and the α-cell area increased compared to non-T1D and controls. The number of CD3- positive cells around islets increased in ICI-related T1D and non-T1D compared with controls, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and controls. The expression ratios of PD-L1 on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD- L1 expression was observed in most cells of pancreatic islets in controls. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β cell vulnerability. In addition, we showed that absence of PD-L1 expression on β cells, genetic susceptibility and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset.

<p>  </p> <p>Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from 3 cases with ICI-related T1D, and their histopathological data were compared those from 3 patients who had received ICI therapy but did not develop T1D (non-T1D) and 7 normal glucose-tolerant subjects as controls. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β‐cell area decreased and the α‐cell area increased compared to non-T1D and controls. The number of CD3-positive cells around islets increased in ICI-related T1D and non-T1D compared with controls, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and controls. The expression ratios of PD-L1 on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD-L1 expression was observed in most cells of pancreatic islets in controls. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β cell vulnerability. In addition, we showed that absence of PD-L1 expression on β cells, genetic susceptibility and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset.</p>

<p>  </p> <p>Immune checkpoint inhibitors (ICIs) could cause type 1 diabetes (T1D). However, the underlying mechanism remains unclear. We immunohistochemically analyzed pancreatic specimens from 3 cases with ICI-related T1D, and their histopathological data were compared those from 3 patients who had received ICI therapy but did not develop T1D (non-T1D) and 7 normal glucose-tolerant subjects as controls. All ICI-related T1D patients had susceptible HLA haplotypes. In ICI-related T1D, the β‐cell area decreased and the α‐cell area increased compared to non-T1D and controls. The number of CD3-positive cells around islets increased in ICI-related T1D and non-T1D compared with controls, while the number of CD68-positive cells around islets increased in ICI-related T1D compared with non-T1D and controls. The expression ratios of PD-L1 on islets decreased in non-T1D and almost completely disappeared in ICI-related T1D, while PD-L1 expression was observed in most cells of pancreatic islets in controls. This study, therefore, indicates that ICI therapy itself could reduce PD-L1 expression on islets in all subjects, which may be related to β cell vulnerability. In addition, we showed that absence of PD-L1 expression on β cells, genetic susceptibility and infiltration of macrophages as well as T lymphocytes around islets might be responsible for T1D onset.</p>