A consensus statement from the Japan Diabetes Society: A proposed algorithm for pharmacotherapy in people with type 2 diabetes - 2nd edition (English version).

This algorithm was issued for the appropriate use of drugs for the treatment of type 2 diabetes mellitus in Japan. The revisions include safety considerations, fatty liver disease as a comorbidity to be taken into account and the position of tirzepatide.

E4BP4 in macrophages induces an anti-inflammatory phenotype that ameliorates the severity of colitis.

Macrophages are versatile cells of the innate immune system that work by altering their pro- or anti-inflammatory features. Their dysregulation leads to inflammatory disorders such as inflammatory bowel disease. We show that macrophage-specific upregulation of the clock output gene and transcription factor E4BP4 reduces the severity of colitis in mice. RNA-sequencing and single-cell analyses of macrophages revealed that increased expression of E4BP4 leads to an overall increase in expression of anti-inflammatory genes including Il4ra with a concomitant reduction in pro-inflammatory gene expression. In contrast, knockout of E4BP4 in macrophages leads to increased proinflammatory gene expression and decreased expression of anti-inflammatory genes. ChIP-seq and ATAC-seq analyses further identified Il4ra as a target of E4BP4, which drives anti-inflammatory polarization in macrophages. Together, these results reveal a critical role for E4BP4 in regulating macrophage inflammatory phenotypes and resolving inflammatory bowel diseases.

Diffuse Large B-cell Lymphoma Complicated with Anti-3-hydroxy-3-methylglutaryl-Coenzyme A Reductase Immune-mediated Necrotizing Myopathy: A Case Report.

A 75-year-old woman presented with significant muscle weakness after statin use. A muscle biopsy revealed necrotizing myopathy, and the patient tested positive for serum anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) antibodies, leading to a diagnosis of anti-HMGCR immune-mediated necrotizing myopathy (IMNM). Computed tomography revealed intraperitoneal lymphadenopathy, which was diagnosed as a diffuse large B-cell lymphoma. Immunostaining confirmed HMGCR expression in the lymphoma cells. The patient received chemotherapy and achieved complete remission of the lymphoma, along with nearly complete recovery from IMNM. Although the etiologies of IMNM and lymphoma remain unclear, HMGCR expression in lymphoma cells is likely to be associated with the development of IMNM.

A consensus statement from the Japan Diabetes Society (JDS): a proposed algorithm for pharmacotherapy in people with type 2 diabetes-2nd Edition (English version).

The Japan Diabetes Society (JDS) adopted a sweeping decision to release consensus statements on relevant issues in diabetes management that require updating from time to time and launched a "JDS Committee on Consensus Statement Development." In March 2020, the committee's first consensus statement on "Medical Nutrition Therapy and Dietary Counseling for People with Diabetes" was published. In September 2022, a second consensus "algorithm for pharmacotherapy in people with type 2 diabetes" was proposed. In developing an algorithm for diabetes pharmacotherapy in people with type 2 diabetes, the working concept was that priority should be given to selecting such medications as would appropriately address the diabetes pathology in each patient while simultaneously weighing the available evidence for these medications and the prescribing patterns in clinical practice in Japan. These consensus statements are intended to present the committee's take on diabetes management in Japan, based on the evidence currently available for each of the issues addressed. It is thus hoped that practicing diabetologists will not fail to consult these statements to provide the best available practice in their respective clinical settings. Given that the persistent dual GIP/GLP-1 receptor agonist tirzepatide was approved in April 2023, these consensus statements have been revised1). In this revision, specifically, tirzepatide was added to the end of [likely involving insulin resistance] of "Obese patients" in Step 1: "Select medications to address the diabetes pathology involved" in Fig. 2. While the sentence, "Insulin insufficiency and resistance can be assessed by referring to the various indices listed in the JDS 'Guide to Diabetes Management.' was mentioned in the previous edition as well, "While insulin resistance is analogized based on BMI, abdominal obesity, and visceral fat accumulation, an assessment of indicators (e.g., HOMA-IR) is desirable" was added as information in order to more accurately recognize the pathology. Regarding Step 2: "Give due consideration to safety," "For renal excretion" was added to the "Rule of thumb 2: Avoid glinides in patients with renal impairment." The order of the medications in "rule of thumb 3: Avoid thiazolidinediones and biguanides in patients with heart failure (in whom they are contraindicated)." to thiazolidinediones then biguanides. In the description of the lowest part of Fig. 2, for each patient failing to achieve his/her HbA1c control goal, "while reverting to step 1" was changed to "while reverting to the opening" and "including reassessment if the patient is indicated for insulin therapy" was added. In the separate table, the column for tirzepatides was added, while the two items, "Characteristic side effects" and "Persistence of effect" were added to the area of interest. The revision also carried additional descriptions of the figure and table such as tirzepatides and "Characteristic side effects" in the statement, and while not mentioned in the proposed algorithm figure, nonalcoholic fatty liver disease (NAFLD) is covered from this revision for patients with comorbidities calling for medical attention. Moreover, detailed information was added to the relative/absolute indication for insulin therapy, the Kumamoto Declaration 2013 for glycemic targets, and glycemic targets for older people with diabetes. Again, in this revision, it is hoped that the algorithm presented here will not only contribute to improved diabetes management in Japan, but will continue to evolve into a better algorithm over time, reflecting new evidence as it becomes available.