Oliver Kuss1,2,3  · Michael Roden3,4,5  · Sabrina Schlesinger1,3  · Annika Hoyer6

Received: 27 May 2024 / Accepted: 23 November 2024 / Published online: 12 December 2024 © The Author(s) 2024

Abstract

Aims Two prerequisites must be met for the precision treatment approach to be beneficial for treated individuals. First, there must be treatment heterogeneity; second, in case of treatment heterogeneity, clinical predictors to identify people who would benefit from one treatment more than from others must be available. There is an established meta-regression approach to assess these two prerequisites that relies on measuring the variability of a clinical outcome after treatment in placebo-controlled randomised trials. We recently applied this approach to the treatment of type 2 diabetes for the clinical outcomes of glycaemic control and body weight and repeat it for the clinical outcome of all-cause mortality.

Methods We performed a meta-regression analysis using digitalized individual participant information on time to death from 10 large cardiovascular outcome trials (7563 deaths from 99,746 participants) on DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2 inhibitors with respect to the variability of all-cause mortality and its potential predictors after treatment.

Results The adjusted difference in log(SD) values of time to death between the verum and placebo arms was −0.036 (95%- CI: −0.059; −0.013), showing larger variability of time to death in the placebo arms. No clinical predictors were found to explain treatment heterogeneity.

Conclusions This analysis suggests that the potential of the precision treatment approach in type 2 diabetes is low, at least with regard to improvement of all-cause mortality in population with high cardiovascular risk. This extends our previous findings for the clinical outcomes of glycaemic control and body weight.

Keywords Dipeptidyl peptidase-4 inhibitors · Glucagon-like peptide 1 · HbA1c · Meta-regression · Precision medicine · Sodium–glucose transporter 2 inhibitors · Type 2 diabetes mellitus

Annunziata Lapolla1  · Maria Grazia Dalfrà1  · Giuseppe Marelli2  · Mario Parrillo3  · Laura Sciacca4  · Maria Angela Sculli5  · Elena Succurro6  · Elisabetta Torlone7  · Ester Vitacolonna8

Received: 18 September 2024 / Accepted: 27 December 2024 / Published online: 22 January 2025 © Springer-Verlag Italia S.r.l., part of Springer Nature 2025

Abstract

Proper nutrition is essential during pregnancy to ensure an adequate supply of nutrients to the foetus and adequate maternal weight gain. In pregnancy complicated by diabetes (both gestational and pre-gestational), diet in terms of both the intake and quality of carbohydrates is an essential factor in glycaemic control. Maternal BMI at conception defines the correct weight increase during gestation in order to reduce maternal-foetal complications related to hypo- or hyper-nutrition. The recommendations presented here, which are based on national and international guidelines and the most recently published data on nutrition in physiological pregnancy and pregnancy complicated by hyperglycaemia and/or obesity, are designed to help healthcare professionals prescribe suitable eating patterns to safeguard the health of the mother and the foetus.

Yuta Yamamoto1  · Katsuya Narumi2  · Naoko Yamagishi1  · Yasunori Yonejima3  · Ken Iseki2  · Masaki Kobayashi2  · Yoshimitsu Kanai1

Received: 22 July 2024 / Accepted: 24 January 2025 / Published online: 3 February 2025 © The Author(s) 2025

Abstract

Aims The oral administration of linoleic acid immediately before glucose tolerance test (OGTT) ameliorated postprandial hyperglycemia via GPR120 pathway in normal and type 1 diabetes (T1DM) rats. Linoleic acid could promote inflammatory mediators, but 10-hydroxy-cis-12-octadecenoic acid (HYA) converted from linoleic acid by Lactobacillus plantarum has higher GPR120 agonistic activity without promoting inflammatory mediators. This study examined whether the oral-admin-istration of HYA immediately before OGTT also ameliorated the postprandial hyperglycemia in normal rats and T1DM rats injected with bolus insulin.

Methods Normal and T1DM male Sprague-Dawley rats received HYA immediately before OGTT. Other T1DM rats were given HYA and Humulin R immediately before OGTT. We measured the concentration of glucose, insulin, glucagon-like peptide 1 (GLP-1) and cholecystokinin in blood before and after OGTT. We also measured the amount of glucose in the gastric tract after OGTT, and the amount of uptake of methyl-α-D-glucopyranoside in CACO-2 cells.

Results Postprandial hyperglycemia was ameliorated by HYA in normal rats, and the postprandial blood glucose levels were slowly elevated by HYA in the T1DM model rats. HYA partially inhibited the uptake of methyl-α-D-glucopyranoside in CACO-2 cells. HYA slowed gastric motility and increased the plasma GLP-1 and cholecystokinin levels in normal rats. HYA also ameliorated the postprandial hyperglycemia in T1DM rats given bolus insulin.

Conclusion Oral administration of HYA immediately before OGTT ameliorated postprandial hyperglycemia through inhibi-tion of glucose absorption and slowing of gastric motility in normal rats. Furthermore, this beneficial effect of HYA was also revealed in T1DM rats injected with bolus insulin.

Keywords HYA · Postprandial hyperglycemia · GLP-1 · CCK · Type 1 diabetes mellitus

Lin Liao1  · Qiming Xu2  · Jie Xu3  · Jie Chen1  · Wenrui Liu1  · Wenhao Chen1  · Yunqing Tang1  · Lianxiang Duan1  · Yue Guo1  · Ziyang Liu1  · Pengyu Tao2  · Yu Cao2  · Jianrao Lu1  · Jing Hu1,4

Received: 14 June 2024 / Accepted: 31 January 2025 / Published online: 13 February 2025 © The Author(s) 2025

Abstract

Aims One of the primary pathological features in the early stages of diabetic nephropathy is mesangial cell (MC) hypertro-phy in the glomerulus. Considering the role of E3 ubiquitin ligases in regulating MC hypertrophy, the aim of this study was to identify the functional ubiquitin protein ligase E3 component N-recognin 5 (UBR5) during MC hypertrophy under high glucose conditions.

Methods Human MCs (HMCs) transduced with UBR5 silencing or overexpression vector were treated with high glucose, AKT inhibitor, or glycolysis inhibitor. Cell proliferation, cell cycle, hypertrophy and glycolysis were evaluated in the HMCs after indicated treatment. m6A methylated RNA immunoprecipitation, luciferase reporter assay, and RNA immunoprecipi-tation were performed to determine the regulation of UBR5 by Wilms tumor 1-associating protein (WTAP)/insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) induced m6A modification. Western blot was performed to determine the protein expression levels.

Results UBR5 expression was upregulated in db/db mice and in high glucose-induced HMCs. UBR5 silencing inhibited high glucose-induced HMC cell cycle arrest, cell hypertrophy, and glycolysis. UBR5 facilitated HMC hypertrophy and gly colysis by promoting the phosphorylation levels of AKT. Additionally, the promoting effect of glycolysis on cell hypertrophy were also elucidated. Further investigation into upstream regulators revealed that WTAP promoted m6A modification of UBR5 through the m6A reader IGF2BP1.

Conclusions Our study unveils a novel mechanism involved in high glucose-induced cell hypertrophy, offering new insights into the understanding and treatment of early pathological mechanisms in diabetic nephropathy.

Keywords High glucose · Hypertrophy · Glycolysis · UBR5, AKT phosphorylation