Dietary Survey of Japanese Individuals with Type 2 Diabetes Mellitus on a Low-Carbohydrate Diet: An Observational Study.

The nutrient intake of persons with diabetes placed on a low-carbohydrate diet remains unclear. This study aimed to assess nutrient intake in persons with type 2 diabetes mellitus treated with a low-carbohydrate diet. The brief-type self-administered diet history questionnaire was used to collect the dietary information of 335 outpatients at Kitasato Institute Hospital, while their clinical characteristics were collected from their electronic medical records. The median age, HbA1c level, and body mass index of the participants were 68 (60-74) years, 49 (45-55) mmol/mol [6.7 (6.3-7.2)%], and 24.0 (21.8-26.7) kg/m2, respectively; median energy intake was 1457 (1153-1786) kcal/day; and protein-energy, fat-energy, and available carbohydrate-energy ratios were 18.6 (15.7-21.4)%E, 36.8 (31.6-43.2)%E, and 34.6 (26.0-42.4)%E, respectively. As the available carbohydrate-energy ratio decreased, the fat-energy ratio increased significantly. The total dietary fibre and salt intake were 7.1 (5.6-8.4) g/1000 kcal and 6.5 (5.6-7.5) g/1000 kcal, respectively. Japanese individuals with type 2 diabetes mellitus placed on a low-carbohydrate diet had a fat-to-energy ratio exceeding 30%, while the fat-energy ratio increased as the carbohydrate-energy ratio decreased.

Interactions between Intestinal Homeostasis and NAD+ Biology in Regulating Incretin Production and Postprandial Glucose Metabolism.

The intestine has garnered attention as a target organ for developing new therapies for impaired glucose tolerance. The intestine, which produces incretin hormones, is the central regulator of glucose metabolism. Glucagon-like peptide-1 (GLP-1) production, which determines postprandial glucose levels, is regulated by intestinal homeostasis. Nicotinamide phosphoribosyltransferase (NAMPT)-mediated nicotinamide adenine dinucleotide (NAD+) biosynthesis in major metabolic organs such as the liver, adipose tissue, and skeletal muscle plays a crucial role in obesity- and aging-associated organ derangements. Furthermore, NAMPT-mediated NAD+ biosynthesis in the intestines and its upstream and downstream mediators, adenosine monophosphate-activated protein kinase (AMPK) and NAD+-dependent deacetylase sirtuins (SIRTs), respectively, are critical for intestinal homeostasis, including gut microbiota composition and bile acid metabolism, and GLP-1 production. Thus, boosting the intestinal AMPK-NAMPT-NAD+-SIRT pathway to improve intestinal homeostasis, GLP-1 production, and postprandial glucose metabolism has gained significant attention as a novel strategy to improve impaired glucose tolerance. Herein, we aimed to review in detail the regulatory mechanisms and importance of intestinal NAMPT-mediated NAD+ biosynthesis in regulating intestinal homeostasis and GLP-1 secretion in obesity and aging. Furthermore, dietary and molecular factors regulating intestinal NAMPT-mediated NAD+ biosynthesis were critically explored to facilitate the development of new therapeutic strategies for postprandial glucose dysregulation.

Intestinal Epithelial NAD+ Biosynthesis Regulates GLP-1 Production and Postprandial Glucose Metabolism in Mice.

Obesity is associated with perturbations in incretin production and whole-body glucose metabolism, but the precise underlying mechanism remains unclear. Here, we tested the hypothesis that nicotinamide phosphoribosyltransferase (NAMPT), which mediates the biosynthesis of nicotinamide adenine dinucleotide (NAD+), a key regulator of cellular energy metabolism, plays a critical role in obesity-associated intestinal pathophysiology and systemic metabolic complications. To this end, we generated a novel mouse model, namely intestinal epithelial cell-specific Nampt knockout (INKO) mice. INKO mice displayed diminished glucagon-like peptide-1 (GLP-1) production, at least partly contributing to reduced early-phase insulin secretion and postprandial hyperglycemia. Mechanistically, loss of NAMPT attenuated the Wnt signaling pathway, resulting in insufficient GLP-1 production. We also found that diet-induced obese mice had compromised intestinal NAMPT-mediated NAD+ biosynthesis and Wnt signaling pathway, associated with impaired GLP-1 production and whole-body glucose metabolism, resembling the INKO mice. Finally, administration of a key NAD+ intermediate, nicotinamide mononucleotide (NMN), restored intestinal NAD+ levels and obesity-associated metabolic derangements, manifested by a decrease in ileal Proglucagon expression and GLP-1 production as well as postprandial hyperglycemia in INKO and diet-induced obese mice. Collectively, our study provides mechanistic and therapeutic insights into intestinal NAD+ biology related to obesity-associated dysregulation of GLP-1 production and postprandial hyperglycemia.

Cardiorenal Protection: Potential of SGLT2 Inhibitors and GLP-1 Receptor Agonists in the Treatment of Type 2 Diabetes.

Recent large clinical trials on sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists, with the aim of verifying cardiovascular safety, have revealed that these medications have a preventative advantage on adverse cardiovascular outcomes, including worsening of heart failure and deterioration of nephropathy, in patients with type 2 diabetes (T2D). These observed benefits do not seem to correlate with the glucose-lowering effect, and the underlying mechanism is being intensively investigated. Given the results from recent studies, the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD) recommend that patients with T2D and clinical cardiovascular disease (CVD) with inadequate glucose control despite treatment with metformin should receive an SGLT2 inhibitor or GLP-1 receptor agonist. In this review we summarize the results of recent cardiovascular outcome trials and discuss the potential clinical advantage of SGLT2 inhibitors and GLP-1 receptor agonists. We also present practical implications of these glucose-lowering agents for reducing the risk of adverse cardiovascular events and progressive renal comorbidity in patients with T2D and CVD.