Investigation about the change of the peak plantar pressure with the severity of diabetic peripheral neuropathy

Diabetic peripheral neuropathy (DPN) is associated with progressive loss of sensation, restriction of lower limb joint range of motion, and gait alternation. These impairments are significant risk for diabetic plantar ulcer. The aim of the present study is to evaluate the relationship between neuropathy and plantar pressure profilel in diabetic patients with different degrees of peripheral neuropathy. Twenty-four patients of type2 diabetes with DPN were enrolled and classified into 3 groups according to DPN severity, and simultaneously estimated sensory and motor nerve conduction velocity (SCV, MCV), toe and ankle joint range of motion, and peak plantar pressure. Plantar area was divided into 4 regions: toe, forefoot, midfoot and rearfoot. To prevent the extreme variation, patients with plantar callus were excluded. SCV, MCV, toe and ankle joint range of motion, and peak plantar pressure of toe and forefoot were correlated with DPN severity, Moreover, the peak pressure ratio of toe to forefoot was significantly increased in proportion to DPN severity and the restriction of toe joint range of motion. These results indicate that except patients with plantar callus. increasing degrees of DPN restricts the toe joint flexibility and the relative peak plantar pressure of toe rises in accordance with DPN severity

Pemafibrate Dramatically Ameliorated the Values of Liver Function Tests and Fibrosis Marker in Patients with Non-Alcoholic Fatty Liver Disease

[Background] Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease related to metabolic syndrome, which can progress to liver cirrhosis. Standard medication has not been established. Pemafibrate is a selective peroxisome proliferatoractivated receptor (PPAR) α modulator. We retrospectively evaluated the efficacy of pemafibrate in patients with NAFLD. [Methods] We retrospectively enrolled 17 patients (ten men, seven women; median age, 63 years; range, 27?81 years). They were all proven to have fatty liver through imaging and had little or no history of drinking (ethanol consumption of < 20 g/day for women and < 30 g/day for men). They were administered pemafibrate from October 2018 to June 2020. [Results] After administration, serum triglyceride (TG) tended to be decreased (300.5 ± 22.5 to 239.5 ± 34.3 mg/dL, P = 0.06). Serum high-density lipoprotein (HDL) cholesterol and low density lipoprotein (LDL) cholesterol levels did not change. ALT was significantly decreased (-47.4%) for six months (57.5 ± 8.8 to 30.3 ± 5.8 U/L, P < 0.01). The values of serum GGT significantly decreased (-48.7%) for sixth months (63.9 ± 10.3 to 32.8 ± 6.6 U/L, P < 0.01). Aspartate aminotransferase (AST) to platelet ratio (APRI), a fibrosis marker, also was significantly decreased in the sixth month (0.7 ± 0.1 to 0.4 ± 0.1, P < 0.05). Body mass index (BMI) and hemoglobin A1c (HbA1c) showed no significant change. [Conclusion] Pemafibrate dramatically ameliorated the values of liver function tests and APRI in patients with NAFLD

Normal meal tolerance test is preferable to the glucagon stimulation test in patients with type 2 diabetes that are not in a hyperglycemic state: Comparison with the change of C-peptide immunoreactivity

Aims/Introduction: The aim of the present study was to evaluate the properties of the glucagon stimulation test (GST) and the normal meal tolerance test (NMTT) in patients with type 2 diabetes. Materials and Methods: We enrolled 142 patients with type 2 diabetes, and carried out a GST and a NMTT. We carried out the NMTT using a calorie-controlled meal based on an intake of 30 kcal/kg ideal bodyweight/day. We calculated the change in C-peptide immunoreactivity (ΔCPR) by subtracting fasting CPR from the CPR 6 min after the 1-mg glucagon injection (GST) or 120 min after the meal (NMTT). Results: Mean ΔCPR for the GST was 2.0 ng/mL, and for the NMTT was 3.1 ng/mL. A total of 104 patients had greater ΔCPR in the NMTT than the GST, and the mean ΔCPR was significantly greater in the NMTT than the GST (P < 0.05). To exclude any influence of antidiabetic drugs, we examined 42 individuals not taking antidiabetic agents, and found the mean ΔCPR was significantly greater in the NMTT than the GST (GST 2.4 ng/mL, NMTT 4.3 ng/mL; P < 0.05). To consider the influence of glucose toxicity, we carried out receiver operating characteristic analyses with fasting plasma glucose and glycated hemoglobin. The optimal cut-off levels predicting GST ΔCPR to be larger than NMTT ΔCPR were fasting plasma glucose 147 mg/dL and glycated hemoglobin 9.0% (fasting plasma glucose: sensitivity 0.64, specificity 0.76, area under the curve 0.73; glycated hemoglobin: sensitivity 0.56, specificity 0.71, area under the curve 0.66). Conclusions: The NMTT is a reliable insulin secretion test in patients with type 2 diabetes, except for those in a hyperglycemic state

Screening Criteria of Diabetes Mellitus and Impaired Glucose Tolerance of the Japanese Population in a Rural Area of Japan: The Tottori-Kofu Study

We performed the Tottori-Kofu Study to develop an early detection method of the Japanese with diabetes mellitus (DM) and impaired glucose tolerance (IGT), using simple predictors such as fasting plasma glucose (FPG) and other risk information obtainable from basic medical check-ups. In 2005, 734 residents of Kofu Town received a basic medical check-up including blood examination. Some of them meeting the following criteria further underwent the oral glucose tolerance test (OGTT): 5.5 mmol/L (100 mg/dL) ? FPG < 7.0 mmol/L (126 mg/dL); or FPG < 5.5 mmol/L, HbA1c ? 5.5%, BMI ? 25 kg/m2, triglyceride ? 1.69 mmol/L (150 mg/dL), hypertension treatment and family history of DM. Among the 734, only 4 persons with FPG ? 7.0 mmol/L were newly diagnosed as having DM, and 17 persons with FPG ? 6.1 mmol/L (110 mg/dL) were diagnosed with impaired fasting glucose. Among 220 persons who received the OGTT, 115 had normal glucose tolerance, 85 had IGT and 20 had DM. When the above-mentioned criteria were added to FPG levels, additional 67 persons with abnormal glucose tolerance were found. The optimal level to detect IGT and DM was 5.2 mmol/L (93 mg/dL) for FPG and 5.3% for HbA1c. Of persons only with the single risk factor of hypertension treatment, 39.3% had IGT. In conclusion, the results indicate that FPG of 5.2 mmol/L (93 mg/dL), HbA1c of 5.3% and hypertension treatment are useful in detecting early stages of IGT and DM

Screening Criteria of Diabetes Mellitus and Impaired Glucose Tolerance of the Japanese Population in a Rural Area of Japan: The Tottori-Kofu Study

We performed the Tottori-Kofu Study to develop an early detection method of the Japanese with diabetes mellitus (DM) and impaired glucose tolerance (IGT), using simple predictors such as fasting plasma glucose (FPG) and other risk information obtainable from basic medical check-ups. In 2005, 734 residents of Kofu Town received a basic medical check-up including blood examination. Some of them meeting the following criteria further underwent the oral glucose tolerance test (OGTT): 5.5 mmol/L (100 mg/dL) ? FPG < 7.0 mmol/L (126 mg/dL); or FPG < 5.5 mmol/L, HbA1c ? 5.5%, BMI ? 25 kg/m2, triglyceride ? 1.69 mmol/L (150 mg/dL), hypertension treatment and family history of DM. Among the 734, only 4 persons with FPG ? 7.0 mmol/L were newly diagnosed as having DM, and 17 persons with FPG ? 6.1 mmol/L (110 mg/dL) were diagnosed with impaired fasting glucose. Among 220 persons who received the OGTT, 115 had normal glucose tolerance, 85 had IGT and 20 had DM. When the above-mentioned criteria were added to FPG levels, additional 67 persons with abnormal glucose tolerance were found. The optimal level to detect IGT and DM was 5.2 mmol/L (93 mg/dL) for FPG and 5.3% for HbA1c. Of persons only with the single risk factor of hypertension treatment, 39.3% had IGT. In conclusion, the results indicate that FPG of 5.2 mmol/L (93 mg/dL), HbA1c of 5.3% and hypertension treatment are useful in detecting early stages of IGT and DM

Coenzyme Q10 suppresses apoptosis of mouse pancreatic β-cell line MIN6

Abstract Background In mitochondrial diabetes, apoptosis of β-cells caused by mitochondrial stress plays an important role in impaired insulin secretion. Several studies have reported that coenzyme Q10 (CoQ10) has therapeutic effects on mitochondrial diabetes, but no reports have examined the fundamental effectiveness or mechanism of CoQ10 in mitochondrial diabetes. We previously reported in a Japanese article that CoQ10 has protective effects on pancreatic β-cells against mitochondrial stress using mouse pancreatic β-cell line MIN6 and staurosporine (STS). Here, we report that CoQ10 protects MIN6 cells against apoptosis caused by STS and describe the more detailed apoptotic cascade. Methods Apoptosis of MIN6 cells was induced by 0.5 µM STS treatment for specific periods with or without 30 μM CoQ10. The apoptosis cascade in MIN6 cells was then investigated using WST-8 assays, annexin-V staining, western blotting, and DNA degradation analysis. Results Sixteen hours of 0.5 μM STS treatment led to 47% cell viability, but pretreatment with 30 μM CoQ10 resulted in significantly higher viability of 76% (P < 0.01). CoQ10 also prevented translocation of phosphatidylserine from the inner leaflet to the outer leaflet of the cell membrane. CoQ10 prevented cytochrome c release from mitochondria and activation of caspase-3. Conclusion We concluded that CoQ10 protects pancreatic β-cells through anti-apoptotic effects against STS treatment

Disordered Cell Integrity Signaling Caused by Disruption of the kexB Gene in Aspergillus oryzae

We isolated the kexB gene, which encodes a subtilisin-like processing enzyme, from a filamentous fungus, Aspergillus oryzae. To examine the physiological role of kexB in A. oryzae, we constructed a kexB disruptant (ΔkexB), which formed shrunken colonies with poor generation of conidia on Czapek-Dox (CD) agar plates and hyperbranched mycelia in CD liquid medium. The phenotypes of the ΔkexB strain were restored under high osmolarity in both solid and liquid culture conditions. We found that transcription of the mpkA gene, which encodes a putative mitogen-activated protein kinase involved in cell integrity signaling, was significantly higher in ΔkexB cells than in wild-type cells. The ΔkexB cells also contained higher levels of transcripts for cell wall-related genes encoding β-1,3-glucanosyltransferase and chitin synthases, which is presumably attributable to cell integrity signaling through the increased gene expression of mpkA. As expected, constitutively increased levels of phosphorylated MpkA were observed in ΔkexB cells on the CD plate culture. High osmotic stress greatly downregulated the increased levels of both transcripts of mpkA and the phosphorylated form of MpkA in ΔkexB cells, concomitantly suppressing the morphological defects. These results suggest that the upregulation of transcription levels of mpkA and cell wall biogenesis genes in the ΔkexB strain is autoregulated by phosphorylated MpkA as the active form through cell integrity signaling. We think that KexB is required for precise proteolytic processing of sensor proteins in the cell integrity pathway or of cell wall-related enzymes under transcriptional control by the pathway and that the KexB defect thus induces disordered cell integrity signaling

MpkA-Dependent and -Independent Cell Wall Integrity Signaling in Aspergillus nidulans▿ †

Cell wall integrity signaling (CWIS) maintains cell wall biogenesis in fungi, but only a few transcription factors (TFs) and target genes downstream of the CWIS cascade in filamentous fungi are known. Because a mitogen-activated protein kinase (MpkA) is a key CWIS enzyme, the transcriptional regulation of mpkA and of cell wall-related genes (CWGs) is important in cell wall biogenesis. We cloned Aspergillus nidulans mpkA; rlmA, a TF gene orthologous to Saccharomyces cerevisiae RLM1 that encodes Rlm1p, a major Mpk1p-dependent TF that regulates the transcription of MPK1 besides that of CWGs; and Answi4 and Answi6, homologous to S. cerevisiae SWI4 and SWI6, encoding the Mpk1p-activating TF complex Swi4p-Swi6p, which regulates CWG transcription in a cell cycle-dependent manner. A. nidulans rlmA and mpkA cDNA functionally complemented S. cerevisiae rlm1Δ and mpk1Δ mutants, respectively, but Answi4 and Answi6 cDNA did not complement swi4Δ and swi6Δ mutants. We constructed A. nidulans rlmA, Answi4 and Answi6, and mpkA disruptants (rlmAΔ, Answi4Δ Answi6Δ, and mpkAΔ strains) and analyzed mpkA and CWG transcripts after treatment with a β-1,3-glucan synthase inhibitor (micafungin) that could activate MpkA via CWIS. Levels of mpkA transcripts in the mutants as well as those in the wild type were changed after micafungin treatment. The β-glucuronidase reporter gene controlled by the mpkA promoter was expressed in the wild type but not in the mpkAΔ strain. Thus, mpkA transcription seems to be autoregulated by CWIS via MpkA but not by RlmA or AnSwi4-AnSwi6. The transcription of most CWGs except α-1,3-glucan synthase genes (agsA and agsB) was independent of RlmA and AnSwi4-AnSwi6 and seemed to be regulated by non-MpkA signaling. The transcriptional regulation of mpkA and of CWGs via CWIS in A. nidulans differs significantly from that in S. cerevisiae