Association of Impaired Awareness of Hypoglycemia with Driving Safety and Hypoglycemia Problem-solving Abilities among Patients with Type 1 Diabetes in Japan: The PR-IAH Study.

Objective Patients with type 1 diabetes (T1D) and impaired awareness of hypoglycemia (IAH) are at an elevated risk of experiencing automobile accidents. We therefore investigated the association of IAH with driving safety and hypoglycemia problem-solving abilities in adults with T1D. Methods This cross-sectional survey used Gold's method in adult patients with T1D at the National Hospital Organization (NHO) Hospital from February 14, 2020, to October 31, 2021. The participants were divided into control and IAH groups. The data included information on demographics, worries and distress regarding hypoglycemia, hypoglycemia problem-solving abilities, and adverse driving events. Patients We enrolled 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%) from NHO collaborating centers in Japan. Results Among a total of 233 participants (mean age: 48.5±12.8 years old, mean hemoglobin A1c level: 7.6%±0.9%), the prevalence rate of IAH was 11.6% [95% confidence interval (CI): 7.8-16.4%]. IAH was significantly associated with near-miss car accidents (odds ratio: 5.41; 95% CI:1.64-17.80). Diabetic peripheral neuropathy was associated with an increased risk of IAH, while treatment with continuous subcutaneous insulin infusion was not associated with a decreased risk of IAH. The average hypoglycemia problem-solving perception, detection control, and seeking preventive strategies scores in the IAH group were significantly reduced compared with those in the control group. Conclusion IAH was associated with an increased risk of near-miss car accidents among adults with T1D. Furthermore, good hypoglycemia problem-solving abilities were associated with a decreased risk of IAH.

Protective and risk factors of impaired awareness of hypoglycemia in patients with type 1 diabetes: a cross-sectional analysis of baseline data from the PR-IAH study.

BACKGROUND: Hypoglycemia in type 1 diabetes (T1D) is associated with mortality and morbidity, especially when awareness of hypoglycemia is impaired. This study aimed to investigate the protective and risk factors for impaired awareness of hypoglycemia (IAH) in adults with T1D. METHODS: This cross-sectional study enrolled 288 adults with T1D (mean age, 50.4 ± 14.6 years; male, 36.5%; diabetes duration, 17.6 ± 11.2 years; mean HbA1c level, 7.7 ± 0.9%), who were divided into IAH and non-IAH (control) groups. A survey was conducted to assess hypoglycemia awareness using the Clarke questionnaire. Diabetes histories, complications, fear of hypoglycemia, diabetes distress, hypoglycemia problem-solving abilities, and treatment data were collected. RESULTS: The prevalence of IAH was 19.1%. Diabetic peripheral neuropathy was associated with an increased risk of IAH (odds ratio [OR] 2.63; 95% confidence interval [CI] 1.13-5.91; P = 0.014), while treatment with continuous subcutaneous insulin infusion and hypoglycemia problem-solving perception scores were associated with a decreased risk of IAH (OR, 0.48; 95% CI, 0.22-0.96; P = 0.030; and OR, 0.54; 95% CI, 0.37-0.78; P = 0.001, respectively). There was no difference in continuous glucose monitoring use between the groups. CONCLUSION: We identified protective factors in addition to risk factors for IAH in adults with T1D. This information may help manage problematic hypoglycemia. TRIAL REGISTRATION: University hospital Medical Information Network (UMIN) Center: UMIN000039475). Approval date 13 February 2020.

Euglycemic diabetic ketoacidosis in a patient with type 2 diabetes mellitus 3 days after initiating sodium-glucose cotransporter 2 inhibitor while on an extremely low carbohydrate diet: A case report.

This paper presents a case with type 2 diabetes mellitus on a very-low-carbohydrate diet who developed euglycemic diabetic ketoacidosis (EDKA) 3 days after starting sodium-glucose cotransporter 2 inhibitors (SGLT2i). When initiating SGLT2i, healthcare providers should confirm the implementation of a low-carbohydrate diet and provide intensive guidance to prevent EDKA.

Case of subcutaneous insulin resistance syndrome treated with ultra-rapid insulin lispro.

Subcutaneous insulin resistance syndrome is a rare condition that causes difficulty in glycemic control due to severe resistance to subcutaneous insulin injections. We herein present a case of a 40-year-old woman with type 2 diabetes mellitus who had been diagnosed with subcutaneous insulin resistance syndrome since the age of 29 years, and had been persistently treated with continuous subcutaneous insulin infusion using a mixture of insulin lispro and heparin. The patient was switched from insulin lispro plus heparin to ultra-rapid insulin lispro; given that it contains treprostinil and citrate, it is expected to have similar effects as heparin, and shows similar glucose-lowering effects and insulin absorption. Our results suggest that treatment with ultra-rapid insulin lispro is effective for subcutaneous insulin resistance syndrome.

Activation of liver X receptor inhibits osteopontin and ameliorates diabetic nephropathy.

Osteopontin is a proinflammatory cytokine and monocyte chemoattractant implicated in the pathogenesis of diabetic nephropathy. Synthetic agonists for liver X receptors (LXRs) suppress the expression of proinflammatory genes, including osteopontin, but whether LXR activation modulates diabetic nephropathy is unknown. We administered the LXR agonist T0901317 to mice with streptozotocin-induced diabetes and evaluated its effects on diabetic nephropathy. The LXR agonist decreased urinary albumin excretion without altering blood glucose levels and substantially attenuated macrophage infiltration, mesangial matrix accumulation, and interstitial fibrosis. LXR activation suppressed the gene expression of inflammatory mediators, including osteopontin, in the kidney cortex. In vitro, LXR activation suppressed osteopontin expression in proximal tubular epithelial cells by inhibiting AP-1-dependent transcriptional activation of the osteopontin promoter. Taken together, these results suggest that inhibition of renal osteopontin by LXR agonists may have therapeutic potential for diabetic nephropathy.

Serum vaspin concentrations are closely related to insulin resistance, and rs77060950 at SERPINA12 genetically defines distinct group with higher serum levels in Japanese population.

CONTEXT: Vaspin is an adipokine with insulin-sensitizing effects identified from visceral adipose tissues of genetically obese rats. OBJECTIVE: We investigated genetic and nongenetic factors that define serum concentrations of vaspin. DESIGN, SETTING AND PARTICIPANTS: Vaspin levels were measured with RIA in Japanese subjects with normal fasting plasma glucose (NFG; n = 259) and type 2 diabetes patients (T2D; n = 275). Single nucleotide polymorphisms (SNP) at SERPINA12 (vaspin) gene locus were discovered, and five SNP were genotyped in the subjects with varied body mass index (n = 1138). RESULTS: The level of serum vaspin in 93% of the samples was found to vary from 0.2 to nearly 2 ng/ml in NFG subjects (n = 259) and from 0.2 to nearly 3 ng/ml in T2D patients (n = 275) (Vaspin(Low) group), whereas a significant subpopulation (7%) in both groups displayed much higher levels of 10-40 ng/ml (Vaspin(High) group). In the Vaspin(Low) group, serum vaspin levels in T2D were significantly higher than healthy subjects (0.99 ± 0.04 vs. 0.86 ± 0.02 ng/ml; P < 0.01). Both in T2D and genotyped Japanese population, serum vaspin levels closely correlated with homeostasis model of assessment for insulin resistance rather than anthropometric parameters. By genotyping, rs77060950 tightly linked to serum vaspin levels, i.e. CC (0.6 ± 0.4 ng/ml), CA (18.4 ± 9.6 ng/ml), and AA (30.5 ± 5.1 ng/ml) (P < 2 × 10(-16)). Putative GATA-2 and GATA-3 binding consensus site was found at rs77060950. CONCLUSIONS: Serum vaspin levels were related to insulin resistance, and higher levels of serum vaspin in 7% of the Japanese population are closely linked to minor allele sequence (A) of rs77060950.

Indigenous utilization of termite mounds and their sustainability in a rice growing village of the central plain of Laos.

BACKGROUND: The objective of this study was to investigate the indigenous utilization of termite mounds and termites in a rain-fed rice growing village in the central plain of Laos, where rice production is low and varies year-to-year, and to assess the possibility of sustainable termite mound utilization in the future. This research was carried out from 2007 to 2009. METHODS: The termites were collected from their mounds and surrounding areas and identified. Twenty villagers were interviewed on their use of termites and their mounds in the village. Sixty-three mounds were measured to determine their dimensions in early March, early July and middle to late November, 2009. RESULTS: Eleven species of Termitidae were recorded during the survey period. It was found that the villagers use termite mounds as fertilizer for growing rice, vegetable beds and charcoal kilns. The villagers collected termites for food and as feed for breeding fish. Over the survey period, 81% of the mounds surveyed increased in volume; however, the volume was estimated to decrease by 0.114 m3 mound(-1) year(-1) on average due to several mounds being completely cut out. CONCLUSION: It was concluded that current mound utilization by villagers is not sustainable. To ensure sustainable termite utilization in the future, studies should be conducted to enhance factors that promote mound restoration by termites. Furthermore, it will be necessary to improve mound conservation methods used by the villagers after changes in the soil mass of mounds in paddy fields and forests has been measured accurately. The socio-economic factors that affect mound utilization should also be studied.

Activation of peroxisome proliferator-activated receptor delta inhibits streptozotocin-induced diabetic nephropathy through anti-inflammatory mechanisms in mice.

OBJECTIVE: Activation of the nuclear hormone receptor peroxisome proliferator-activated receptor (PPAR)-δ has been shown to improve insulin resistance, adiposity, and plasma HDL levels. Several studies have reported that activation of PPARδ is atheroprotective; however, the role of PPARδ in renal function remains unclear. Here, we report the renoprotective effects of PPARδ activation in a model of streptozotocin-induced diabetic nephropathy. RESEARCH DESIGN AND METHODS: Eight-week-old male C57BL/6 mice were divided into three groups: 1) nondiabetic control mice, 2) diabetic mice, and 3) diabetic mice treated with the PPARδ agonist GW0742 (1 mg/kg/day). GW0742 was administered by gavage for 8 weeks after inducing diabetes. RESULTS: GW0742 decreased urinary albumin excretion without altering blood glucose levels. Macrophage infiltration, mesangial matrix accumulation, and type IV collagen deposition were substantially attenuated by GW0742. The gene expression of inflammatory mediators in the kidney cortex, such as monocyte chemoattractant protein-1 (MCP-1) and osteopontin (OPN), was also suppressed. In vitro studies demonstrated that PPARδ activation increased the expression of anti-inflammatory corepressor B-cell lymphoma-6, which subsequently suppressed MCP-1 and OPN expression. CONCLUSIONS: These findings uncover a previously unrecognized mechanism for the renoprotective effects of PPARδ agonists and support the concept that PPARδ agonists may offer a novel therapeutic approach for the treatment of diabetic nephropathy.

The usefulness of super-selective computed tomography angiography (CTA) for diagnosing and localizing a small insulinoma.

Localization of insulinomas by preoperative imaging is critical for successful surgical resection. However, the visualization and localization of small insulinomas by recent imaging modalities still remains a challenge. Here, we report a 77-year-old woman with a small insulinoma successfully localized by performing arterial stimulation and venous sampling (ASVS), and subsequent super-selective CTA (SSCTA). It was not visualized by routine non-invasive imaging tests such as digital subtraction angiography (DSA). The small size (1.0 cm) of the surgically removed tumor supports the usefulness of SSCTA for localizing very small insulinomas.

Activation of microglia by endotoxin suppresses the secretion of glial cell line-derived neurotrophic factor (GDNF) through the action of protein kinase C alpha (PKCalpha) and mitogen-activated protein kinases (MAPKS).

The ability of microglia to produce/secrete glial cell line-derived neurotrophic factor (GDNF) in vitro was examined. Immunoblotting analysis revealed that nonstimulated microglia release limited amounts of GDNF with molecular sizes of 14 and 17 kDa. However, the secreted amounts significantly decreased when the microglia were activated with the endotoxin lipopolysaccharide (LPS). Comparison of the amounts of GDNF in the cells and the conditioned medium between the nonstimulated microglia and LPS-stimulated microglia clarified that the secretion of GDNF, but not its production, is strongly suppressed when the microglia are activated with LPS. The inhibitor experiments suggested that the GDNF secretion is depressed by a signaling cascade associated with protein kinase C alpha (PKCalpha) and/or mitogen-activated protein kinases (MAPKs). As expected from the above results, a PKC activator suppressed the secretion of GDNF in nonstimulated microglia. Taken together, these results demonstrated that microglia have the ability to produce and secrete GDNF in vitro, and that the secretion is suppressed by stimulation with endotoxin, probably due to a signaling mechanism involving PKCalpha and/or MAPKs.

Enzymatic in situ saccharification of cellulose in aqueous-ionic liquid media.

The enzymatic saccharification of a model cellulosic substrate, Avicel PH-101, using an ionic liquid (IL), 1-ethyl-3-methylimidazolium diethylphosphate, was explored. After mixing the IL solution of cellulose with different volumes of 10 mM citrate buffer (pH 5.0), cellulase was directly added to the aqueous-IL mixture at 40 degrees C. When the volume of IL to water was greater than 3:2, little cellulase activity was observed. However, decreasing the volume ratio markedly enhanced enzymatic activity: an IL to water ratio of 1:4 (v/v) resulted in over 70% of the starting amount of cellulose (10 mg/ml) being converted to glucose and cellobiose.

Increased enantioselectivity and remarkable acceleration of lipase-catalyzed transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid.

Several types of imidazolium salt ionic liquids were prepared derived from poly(oxyethylene)alkyl sulfate and used as an additive or coating material for lipase-catalyzed transesterification in an organic solvent. A remarkably increased enantioselectivity was obtained when the salt was added at 3-10 mol % versus substrate in the Burkholderia cepacia lipase (lipase PS-C)-catalyzed transesterification of 1-phenylethanol by using vinyl acetate in diisopropyl ether or a hexane solvent system. In particular, a remarkable acceleration was accomplished by the ionic liquid coating with lipase PS in an iPr(2)O solvent system while maintaining excellent enantioselectivity; it reached approximately 500- to 1000-fold acceleration for some substrates with excellent enantioselectivity. A similar acceleration was also observed for IL 1-coated Candida rugosa lipase. MALDI-TOF mass spectrometry experiments of the ionic-liquid-coated lipase PS suggest that ionic liquid binds with lipase protein.

Differential suppression of endotoxin-inducible inflammatory cytokines by nuclear factor kappa B (NFkappaB) inhibitor in rat microglia.

The molecular mechanism by which the deleterious cytokines interleukin 1 beta (IL-1beta) and tumor necrosis factor alpha (TNFalpha) are induced in endotoxin-stimulated microglia was investigated from the viewpoint of signal transduction. Neither cytokine is produced in nonstimulated rat microglia, but both are remarkably induced by stimulation with endotoxin lipopolysaccharide (LPS). LPS-inducible IL-1beta was significantly suppressed by pretreatment with the nuclear factor kappa B (NFkappaB) inhibitor ammonium pyrrolidine dithiocarbamate (APDC), but TNFalpha was not. APDC was actually confirmed to suppress the degradation of IkappaBalpha and IkappaBbeta in microglia, indicating a role for the inhibitor of NFkappaB activation. Taken together, these results suggest that the induction of IL-1beta and TNFalpha in endotoxin-stimulated microglia is differentially regulated at the level of NFkappaB activation.