Unexpected Acute Hyperglycemia Following Pre-Surgical Discontinuation of SGLT2 Inhibitors in a Type 1 Diabetic Patient.

BACKGROUND Sodium-glucose transporter 2 (SGLT2) inhibitors serve as adjuncts in managing type 1 diabetes. Preoperative guidelines suggest discontinuing SGLT2 inhibitors to avoid associated adverse events. We report an unusual case of acute hyperglycemia following the discontinuation of SGLT2 inhibitors in a patient undergoing surgery, posing substantial challenges to glycemic control. CASE REPORT A 47-year-old female with type 1 diabetes was hospitalized for benign thyroid tumor surgery. She discontinued her SGLT2 inhibitors a day after admission. Unexpectedly, her glycemic control worsened with her mean sensor glucose value spiking from 109 mg/dL on admission to 273.9 mg/dL five days post-discontinuation. Despite increasing insulin doses, glycemic control remained suboptimal. The glucose level improved to a mean sensor value of 160.4 mg/dL only after SGLT2 inhibitors were resumed three days post-surgery. CONCLUSIONS This report highlights a case of acute hyperglycemia following preoperative discontinuation of SGLT2 inhibitors in a patient with type 1 diabetes. Such changes in glucose levels were captured using intermittent continuous glucose monitoring. Given the potential for similar cases during preoperative discontinuation of SGLT2 inhibitors, it is advisable to intensify bolus insulin administration, under continuous glucose monitoring, in patients discontinuing SGLT2 inhibitors before surgery.

Cold Crystallization of Ferrocene-Hinged π-Conjugated Molecule Induced by the Limited Conformational Freedom of Ferrocene.

Crystallization that proceeds above the glass transition temperature upon heating the glassy or amorphous state is referred to as "cold crystallization", which has often been observed in supercooled phases of molecular materials followed by the transition to the thermodynamically stable crystalline phase. Although this behavior is common for the macromolecules with high structural flexibility among segments preserving the wide temperature range of corresponding glassy phases, cold crystallization of small molecules is relatively rare and there is still less knowledge on the design guideline of such molecules. Here we report a ferrocene-hinged molecule DC12 carrying two units of didodecyl-substituted pentathiophenes at the 1,1'-positions. Due to the rotational freedom of the ferrocene unit, DC12 forms amorphous solid on cooling from its isotropic melt. The amorphous state was realized even by slow cooling such as 0.1 °C min-1. The possible reason for the easy formation of the amorphous phase is the coexistence of various conformations of DC12 originating from the open conformers of the ferrocene. On heating from the amorphous phase, DC12 shows cold crystallization with the estimated activation energy of 61 kJ mol-1. The crystalline phase is composed of the closed form of DC12 molecules packed in a lamellar fashion, and the degree of crystallinity is remarkably high compared with the case of macromolecular materials. The crystallization is triggered by the intermolecular interactions among the dodecyl chains and rotational flexibility of the ferrocene unit. This work provides an unprecedented example that ferrocenes act as heat-controllable rotational hinges in condensed phases. Considering that the cold crystallization phenomenon is related to heat-storage materials, the design strategy presented in this work will be novel to realize both easily formed amorphous phases and highly crystalline phases formed through cold crystallization.

Seasonal Variations in the Achievement of Guideline Targets for HbA1c, Blood Pressure, and Cholesterol Among Patients With Type 2 Diabetes: A Nationwide Population-Based Study (ABC Study: JDDM49).

OBJECTIVE: Precise monthly achievement rates for reaching guideline targets for HbA1c, blood pressure (BP), and lipid levels remain unknown. We evaluated achievement rates on a monthly basis in persons with type 2 diabetes mellitus (T2DM) and explored related factors. RESEARCH DESIGN AND METHODS: This retrospective study initially analyzed data on 104,601 persons with T2DM throughout Japan. Patients whose HbA1c, BP, and LDL cholesterol were measured ≥12 times during a 24-month period were included. We evaluated monthly achievement rates. Achieved targets were defined as HbA1c <7%, BP <130/80 mmHg, and LDL cholesterol <100 mg/dL. Achievement of all targets was expressed as the "all ABC achievement." RESULTS: A total of 4,678 patients were analyzed. The achievement rates of all ABC, HbA1c, BP, and LDL cholesterol were lowest in winter, with those for systolic BP (SBP) being particularly low (all ABC, summer 15.6%, winter 9.6%; HbA1c, 53.1%, 48.9%; SBP, 56.6%, 40.9%; LDL cholesterol, 50.8%, 47.2%). In winter, age ≥65 years (odds ratio 0.47 [95% CI 0.34-0.63]) was independently related to decreased achievement rates for SBP, BMI ≥25 kg/m2 (BMI 25-30 kg/m2, 0.45 [0.29-0.70]; BMI ≥30 kg/m2, 0.35 [0.22-0.57]), and diabetes duration ≥10 years (0.53 [0.37-0.76]) were independently related to lower achievement rates for HbA1c. Insulin use and sulfonylurea use were independently associated with the decreased all ABC achievement rates in both summer and winter. CONCLUSIONS: The all ABC achievement rate for guideline targets changed on a monthly basis. Seasonal variations in the all ABC achievement rate should be considered when managing T2DM in ordinary clinical practices.

[Anti-Hu antibody positive sensory neuronopathy causing painful legs and moving toes (PLMT) in a 75-year-old female with small cell lung cancer (SCLC)].

The case is a 75-year-old female. She had dysesthesia in the distal extremities and truncal ataxia, and they had progressed in two months. Neurological examination revealed the findings of segmental dysesthesia in the distal extremities, impaired deep sensations in the trunk and four limbs, and painful legs and moving toes (PLMT). After workup, she was diagnosed with small cell lung cancer and her blood sample was positive for anti-Hu antibody. We concluded that her neurological symptoms were attributable to sensory neuronopathy associated with paraneoplastic syndrome. No cases with PLMT caused by paraneoplastic syndrome have been reported so far. She had chemotherapy to lung cancer and Duloxetine without improvement of PLMT. On the other hand, intravenous immunoglobulin treatment improved lightening pain in the toes without improvement of moving toes.

Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction.

The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy.

Coffee consumption is inversely associated with depressive status in Japanese patients with type 2 diabetes.

Depression has been reported to be more prevalent among diabetic patients than non-diabetic individuals. Although depression and diabetes are causally and bi-directionally related, the influence of food intake frequency on depressive symptoms in diabetic patients has not been fully evaluated. This cross-sectional study analyzed data obtained from 89 patients with type 2 diabetes who completed self-administered questionnaires regarding food intake frequency, diabetic variables, physical activity and depressive states. The prevalence of a "definite" depressive state was 16.9%. The duration of diabetes, hemoglobin A1c levels, diabetic microvascular complications and physical activity levels were similar between depressed and non-depressed patients. Daily intakes of total lipids, n-6 polyunsaturated fatty acids and lipid energy ratios were significantly lower, and the carbohydrate energy ratio was significantly higher in depressed than in non-depressed patients. Coffee consumption was inversely associated with depressive symptoms, but no significant association was found between tea or green tea consumption and depressive symptoms. The logistic regression analysis showed that coffee consumption was an independent predictor of non-depressed status in diabetic patients. This might be due to biologically active compounds containing in coffee other than caffeine.

Highly sensitive and selective analysis of widely targeted metabolomics using gas chromatography/triple-quadrupole mass spectrometry.

In metabolomics studies, gas chromatography coupled with time-of-flight or quadrupole mass spectrometry has frequently been used for the non-targeted analysis of hydrophilic metabolites. However, because the analytical platform employs the deconvolution method to extract single-metabolite information from co-eluted peaks and background noise, the extracted peak is artificial product depending on the mathematical parameters and is not completely compatible with the pure component obtained by analyzing a standard compound. Moreover, it has insufficient ability for quantitative metabolomics. Therefore, highly sensitive and selective methods capable of pure peak extraction without any complicated mathematical techniques are needed. For this purpose, we have developed a novel analytical method using gas chromatography coupled with triple-quadrupole mass spectrometry (GC-QqQ/MS). We developed a selected reaction monitoring (SRM) method to analyze the trimethylsilyl derivatives of 110 metabolites, using electron ionization. This methodology enables us to utilize two complementary techniques-non-targeted and widely targeted metabolomics in the same sample preparation protocol, which would facilitate the formulation or verification of novel hypotheses in biological sciences. The GC-QqQ/MS analysis can accurately identify a metabolite using multichannel SRM transitions and intensity ratios in the analysis of living organisms. In addition, our methodology offers a wide dynamic range, high sensitivity, and highly reproducible metabolite profiles, which will contribute to the biomarker discoveries and quality evaluations in biology, medicine, and food sciences.

GC/MS based metabolomics: development of a data mining system for metabolite identification by using soft independent modeling of class analogy (SIMCA).

BACKGROUND: The goal of metabolomics analyses is a comprehensive and systematic understanding of all metabolites in biological samples. Many useful platforms have been developed to achieve this goal. Gas chromatography coupled to mass spectrometry (GC/MS) is a well-established analytical method in metabolomics study, and 200 to 500 peaks are routinely observed with one biological sample. However, only ~100 metabolites can be identified, and the remaining peaks are left as "unknowns". RESULT: We present an algorithm that acquires more extensive metabolite information. Pearson's product-moment correlation coefficient and the Soft Independent Modeling of Class Analogy (SIMCA) method were combined to automatically identify and annotate unknown peaks, which tend to be missed in routine studies that employ manual processing. CONCLUSIONS: Our data mining system can offer a wealth of metabolite information quickly and easily, and it provides new insights, particularly into food quality evaluation and prediction.

Serial clinical and angiographic follow-up after phosphorylcholine-coated stent implantation.

The efficacy of drug-eluting stents (DES) has been proven, but concerns about late complications after DES have been raised. Polymers that do not increase inflammatory or hypersensitivity reactions which may contribute to late complications are needed for new generation DES. To evaluate the safety and efficacy of phosphorylcholine-polymer coating, we investigated serial clinical and angiographic outcomes after phosphorylcholine-coated stent placement. Seventy-five consecutive patients treated with a BiodivYsio phosphorylcholine-coated stent for de novo lesions at our institute between October 2001 and August 2002 were enrolled. Six-month follow-up angiography was performed in 71 lesions (94.7%), and angiographic restenosis was found in 19 lesions (26.8%). Target lesion revascularization (TLR) was performed in 10 lesions (14.1%). Eighteen-month follow-up angiography was performed in 58 (95.1%) of the remaining 61 lesions (excluding TLR lesions), and angiographic restenosis was found in only 3 lesions. The cumulative MACE-free survival rate was 86.3%, 83.6%, and 78.6% at 6-month, 18-month, and 8-year follow-up, respectively. There were no episodes of stent thrombosis. Late loss decreased significantly from 0.74 ± 0.40 mm (6-months) to 0.51 ± 0.46 mm (18-months) (P < 0.0001). Phosphorylcholine-coated stent implantation was associated with acceptable clinical and angiographic results. Phosphorylcholine-coating may be an ideal polymer for new generation DESs.

Effectiveness of paclitaxel-eluting balloon catheter in patients with sirolimus-eluting stent restenosis.

OBJECTIVES: The aim of this study was to investigate the efficacy of a paclitaxel-eluting balloon (PEB) for the treatment of sirolimus-eluting stent (SES) restenosis. BACKGROUND: Because drug-eluting stents (DES) are being used in increasingly complicated settings, DES restenosis is no longer an uncommon phenomenon, and its optimal treatment is unknown. METHODS: This study was a prospective single-blind randomized trial conducted in 50 patients with SES restenosis. Patients were randomly assigned to a PEB group (n = 25) or a conventional balloon angioplasty (BA) group (n = 25). The primary end point was late lumen loss at 6-month follow-up. Secondary end points included the rate of binary restenosis (in-segment analysis) and major adverse cardiac events (MACE) at 6-month follow-up. RESULTS: At 6-month angiographic follow-up (follow-up rate: 94%), in-segment late lumen loss was lower in the PEB group than in the BA group (0.18 ± 0.45 mm vs. 0.72 ± 0.55 mm; p = 0.001). The incidence of recurrent restenosis (8.7% vs. 62.5%; p = 0.0001) and target lesion revascularization (4.3% vs. 41.7%; p = 0.003) was also lower in the PEB group than in the BA group. The cumulative MACE-free survival was significantly better in the PEB group than in the BA group (96% vs. 60%; p = 0.005). CONCLUSIONS: In patients with SES restenosis, PEB provided much better clinical, angiographic outcomes than conventional BA.