OBJECTIVE: This randomized controlled trial evaluated the differential effects of aerobic training (AT), resistance training (RT), and combined training (CT) on biphasic insulin secretion and glucose effectiveness (GE) in patients with Type 2 diabetes mellitus (T2DM). METHODS: Forty-five male T2DM patients (mean age 55.24 +/- 8.17 years; disease duration: 12.51 +/- 6.46 years; baseline HbA1c: 7.1% +/- 1.0%) were randomized to 12-week AT (n = 11), RT (n = 11), CT (n = 11), or control (n = 12) groups. AT involved progressive aerobic exercise (25 to 45 min at 70% to 75% maximum heart rate, thrice weekly). RT comprised nine multijoint exercises (2 to 3 sets, 8 to 12 repetitions, thrice weekly). CT combined the full AT protocol with a modified RT regimen (one set, twice weekly). First-phase insulin secretion (FPIS), second-phase insulin secretion (SPIS), and GE were quantified using validated models pre- and postintervention. RESULTS: Adjusting for baseline values, age, and diabetes duration, ANCOVA revealed significant between-group differences in FPIS (F [3, 38] = 8.64, p < 0.001, eta 2 0.406), SPIS (F [3, 38] = 6.93, p < 0.001, eta 2 0.354), and GE (F [3, 38] = 5.57, p = 0.003, eta 2 0.305). CT elicited the greatest improvements: FPIS (53.4% +/- 12.7%, p < 0.001), SPIS (38.9% +/- 11.2%, p < 0.001), and GE (12.8% +/- 4.6%, p = 0.001) versus control. AT enhanced FPIS (32.6% +/- 10.3%, p = 0.001) and SPIS (21.7% +/- 8.9%, p = 0.042), while RT improved FPIS (28.5% +/- 9.8%, p = 0.006), SPIS (27.5% +/- 9.4%, p = 0.012), and GE (10.7% +/- 4.3%, p = 0.004). Regression analysis identified baseline beta-cell function (beta -0.31, p = 0.020), adiposity reduction (beta -0.36, p = 0.008), and glycemic improvement (beta -0.42, p = 0.003) as predictors of FPIS gains (R2 0.537). CONCLUSIONS: CT outperforms single-modality training in enhancing biphasic insulin secretion and GE in T2DM, supporting multimodal exercise as a cornerstone of diabetes management to improve beta-cell function and glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov identifier: IRCT2016042227529N1.

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