Effect of Calcium Hydroxy-Methyl-Butyrate-Enriched Diabetes-Specific Oral Nutritional Supplementation on Patients with Heterogeneous Diabetes Mellitus Population with Disease Related Malnutrition Assessed with AI-Assisted Ultrasound Imaging

<b>Background/Objectives</b>: Sarcopenia is common in patients with diabetes mellitus. The use of branched-chain amino acids may influence muscle mass. The aim of this study is to evaluate the effect of a diabetes-specific formula enriched with calcium hydroxy-methyl-butyrate (CaHMB) on muscle mass in patients with diabetes and high risk of malnutrition. <b>Methods</b>: A prospective observational study in 95 patients divided into two cohorts of patients with diabetes, treated with a tailored diet, dietary counseling, and diabetes-specific oral nutritional supplements (ONSs) administered between meals: one enriched with CaHMB (CaHMB Diabetes ONS) 44 (46.32%) patients; and another without CaHMB (Diabetes-Specific ONS) 51 (53.68%) patients. Anthropometric parameters, bioimpedance, artificial intelligence (AI)-assisted ultrasound of the rectus femoris muscle (PIIXMED^TM), and handgrip strength were assessed. Evaluations were conducted at baseline and after 3 months. <b>Results</b>: The mean age was 71.05 (10.67) years; 56.8% were male. After three months, both groups increased their nutritional intake with no differences in dietary protein content between groups. The CaHMB group showed a greater increase in muscle mass as measured by ultrasound, both in muscle area (CaHMB ONS: +5.84 (-3.3 ± 21.58)% vs. Diabetes-Specific ONS: -9.34% (-25.78 ± 12.02)%; <i>p</i> < 0.01) and muscle thickness (CaHMB ONS: +9.17 (-4.40 ± 21.05)% vs. Diabetes-Specific ONS -6.30 (-18.57 ± 12.56)%; <i>p</i> < 0.01). The CaHMB ONS group showed a higher likelihood of increased muscle mass compared to the Diabetes-Specific ONS, with an odds ratio (OR) of 9.31 (95%CI: 2.16-40.13) for thickness and 3.96 (95%CI: 1.11-14.13) for area, adjusted for gender, age, serum albumin, and baseline glycated hemoglobin. <b>Conclusions</b>: Supplementation with Ca-HMB in patients with diabetes and high risk of malnutrition showed significant improvements in muscle mass as assessed by AI-assisted ultrasound. Both groups increased nutritional intake, but only the CaHMB group showed specific benefits in muscle parameters.