Abstract
Hyperglycemia significantly contributes to the development and progression of metabolic diseases. Managing postprandial blood glucose fluctuations is of particular importance for patients with hyperglycemia, but safe and effective means of reducing blood glucose levels are still lacking. Five diets with varying macronutrient ratios and omega-3 fatty acid amounts were tested for their blood glucose-lowering effects in male C57BL/6J mice. The diets with potent blood glucose-lowering effects were further investigated for their underlying mechanisms and their beneficial effects on hyperglycemia models. Mice given the low-carbohydrate, high-protein, and high-omega-3 (LCHP+3) diet exhibited a rapid reduction of the blood glucose levels that remained consistently low, regardless of feeding. These effects were associated with reduced amino acid gluconeogenesis, due to the inhibition of hepatic alanine transaminase (ALT). Furthermore, the LCHP+3 intervention was effective in reducing the blood glucose levels in several disease conditions, including type 1 diabetes mellitus, hormone-induced hyperglycemia, and diet-induced metabolic syndrome. Our findings identify the LCHP+3 diet as a potent blood glucose-lowering diet that suppresses postprandial blood glucose fluctuations through the inhibition of gluconeogenesis and may have great clinical utility for the management of metabolic diseases with hyperglycemia.
Highlights
Hyperglycemia, a condition in which blood glucose levels are abnormally high, is a central factor in the development of type 2 diabetes mellitus (T2DM) and increases the risk of cardiovascular disease, cancer, and all-cause mortality [1,2,3,4]
All three diets low in carbohydrates (LCHF+3, LCHP, LCHP+3) lowered the random blood glucose levels when compared with the Control diet (Figure 1B), the LCHP+3 group exhibited a faster decrease in random blood glucose levels after three days of intervention, and its lowest random blood glucose levels were sustained throughout the experimental period (Figure 1C)
These results indicate that the LCHP+3 diet is able to quickly and effectively lower the blood glucose levels, and that the supplementation of omega-3 to the LCHP diet is instrumental in minimizing postprandial glucose spikes
Summary
Hyperglycemia, a condition in which blood glucose levels are abnormally high, is a central factor in the development of type 2 diabetes mellitus (T2DM) and increases the risk of cardiovascular disease, cancer, and all-cause mortality [1,2,3,4]. Glucose-lowering therapies such as anti-diabetic drugs reduce the risk of hyperglycemia and improve the outcomes for patients but have some adverse effects [6,7,8,9,10]. Previous studies have shown that a low-carbohydrate, high-protein dietary intervention can reduce fasting plasma glucose and 24 h glucose response in non-diabetic and T2DM patients [13,14]. Given the detrimental impact of the postprandial glucose spike, a diet capable of eliminating or significantly reducing postprandial glucose fluctuations can greatly benefit health conditions requiring glycemic control, such as diabetes and cancer
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