Abstract and Introduction
Purpose: This study aimed to determine the separated and combined effects of metformin and resistance exercise on glycemic control, insulin sensitivity, and insulin-like growth factor 1 (IGF-1) in overweight/obese individuals with prediabetes and type 2 diabetes mellitus.
Methods: Fourteen adults with a body mass index of 32.1 ± 4.1 kg·m−2, insulin resistance (HOMA-2 1.6 ± 0.6), and poor glycemic control (glycated hemoglobin, 6.9% ± 0.9%; 51.9 ± 10.7 mmol·mol−1) while taking metformin (1561 ± 470 g·d−1) were recruited. Participants underwent four 72-h long experimental trials in a randomized counterbalanced order, either 1) taking metformin (MET), 2) replacing metformin by placebo pills (PLAC), 3) taking placebo and undergoing a resistance training bout (RT + PLAC), and 4) taking metformin and undergoing the same RT bout (RT + MET). Interstitial fluid glucose concentration was frequently sampled to obtain 72-h glucose area under the curve (GAUC) and the percentage hyperglycemic glucose readings (>180 mg·dL−1; GPEAKS). Insulin sensitivity (i.e., HOMA-2) and IGF-1 were also assessed.
Results: HOMA-2 was not affected by treatments. GAUC and GPEAKS were similarly reduced below PLAC during RT + MET and MET (all P < 0.05). In contrast, RT + PLAC did not affect glucose concentration. Metformin decreased serum IGF-1 concentrations (P = 0.006), and RT did not reverse this reduction.
Conclusions: A bout of full-body RT does not interfere or aid on metformin's blood glucose–lowering actions in individuals with prediabetes and type 2 diabetes mellitus.
Reduction in hyperglycemic peaks is a primary therapeutic target for the prevention (i.e., in prediabetic individuals) and treatment of type 2 diabetes mellitus (T2DM). Recent technological advances in biomedicine allow for the use of wireless glucose sensors, which are placed subcutaneously, and permit the identification of hyperglycemic peaks in real time. With the use of these sensors, T2DM patients can have immediate feedback of dietary and physical activity effects on their glucose control. This technology is useful in short-term (several days long) field research studies that assess the effect of lifestyle therapy on glucose control in T2DM patients. Using this technology, we have studied the combined effects of antidiabetic medicines and aerobic exercise on reducing the prevalence of hyperglycemic peaks in T2DM.
The most prevalent oral pharmacological treatment for prediabetes and T2DM is a biguanide named metformin. Metformin improves glycemic control, reducing blood glucose in the fasting and postprandial states. Controversy on metformin's mechanism in humans remains, which may involve reductions in gluconeogenesis and hepatic glucose production and/or increases skeletal muscle glucose uptake due to energy imbalance. Of concern, metformin seems to interfere with the acute and chronic insulin-sensitizing effects of exercise. Moreover, it suggested that metformin also interferes with exercise adaptations of aerobic (i.e., cardiorespiratory fitness increases;) and resistance training (RT; i.e., hypertrophy;). Conversely, a bout of aerobic exercise does not interfere with the blood glucose–lowering effects of metformin and even enhances metformin reductions of hyperglycemic peaks.
We have recently reported that substituting portions of aerobic by RT lowers fasting glucose concentrations in obese/overweight individuals with impaired fasting glucose. RT could improve glucose tolerance and insulin sensitivity in skeletal muscle through both the non–insulin-dependent (i.e., AMPK-mediated) and insulin-dependent pathways (e.g., insulin-like growth factor 1 (IGF-1) expression and subsequent GLUT4 translocation).[11,12] On the other hand, metformin may inhibit the insulin-dependent pathway of glucose uptake (i.e., IGF-1/PI3K/AKT pathway) because Walton et al. found that metformin blunts muscle hypertrophy through inhibition of mammalian target of rapamycin (mTORC1), which is the downstream target of IGF-1. However, to our knowledge, the only study analyzing the interaction between metformin and RT in T2DM individuals reported that 22 wk of RT did not significantly lower glycated hemoglobin (HbA1c), whereas aerobic training did. Thus, it is unclear if RT improves the insulin resistance of diabetic individuals.
Besides being an anabolic hormone, IGF-1 functions in coordination with insulin to regulate glucose homeostasis. IGF-1 increases intracellular calcium concentrations, which lead to the activation of multiple anabolic calcium-dependent pathways, including calcineurin and its downstream signaling targets that enhance glycemic control. Interestingly, metformin intake reduces serum IGF-1 concentrations,[17,18] which in diabetic patients could even reduce insulin signalling. In this study, we wanted to observe if a bout of RT would prevent the reductions on IGF-1 induced by metformin and if that will further enhance metformin's antidiabetic actions.
We aimed to determine the interactions between metformin and a bout of RT in a sample of prediabetic and T2DM individuals. To achieve this goal, we compared the separated and combined effects of metformin and one bout of RT on 72-h glycemic control, insulin sensitivity, and IGF-1. We hypothesized that a bout of RT would better the actions of metformin on the glycemic control of T2DM individuals through preventing the reductions of IGF-1.
Med Sci Sports Exerc. 2022;54(7):1043-1050. © 2022 American College of Sports Medicine