Lactoferrin and Diabetes mellitus

We have already described that lactoferrin can have an influence on the formation of belly fat (Lactoferrin and the Metabolic Syndrome). A high accumulation of visceral fat directly affects fat and sugar metabolism in the body.
How might lactoferrin be useful here? What about the other risk factors for metabolic syndrome, and ultimately, the development of type 2 diabetes mellitus?
The diagnosis of diabetes mellitus type 2 is in itself associated with some pathological changes in the body.  Lactoferrin has been shown to have a positive influence on these. Chronic inflammatory processes in the body are also involved. Measurably increased values of pro-inflammatory messengers in the blood are seen as risk factors, as well as a reflection of the existing disease [1,2].
One of the specific risk factors is insulin resistance
Insulin resistance means that the cells of insulin-dependent tissue are less sensitive to insulin. As a result, the pancreas produces more insulin and hyperinsulinemia (high blood insulin) occurs. If this continues long-term, there is a risk that the β-cells of the pancreas down-regulate their function and produce too little insulin.  
In vitro and in vivo studies have shown that lactoferrin improves the insulin sensitivity of cells, even with existing insulin resistance [3,4].
If insulin resistance persists, too little glucose is absorbed by the cells and the glucose level in the blood remains high (hyperglycaemia).
An increased blood glucose level can be both a triggering, and an amplifying factor of chronic inflammation, thereby promoting disease progression [5].
In animal experiments, oral administration of lactoferrin was seen to reduce weight gain, reduce visceral fat levels and regulate blood sugar levels as well as leptin and lipid levels [6].  Sugars interact with Lactoferrin by using binding sites located on the C-lobe of the lactoferrin molecule [7].
In a 2016 study, Lactoferrin was administered to overweight mice.  Glucose metabolism was regulated by the positive modulation of the microbiome and the reduction of inflammation [8].
Taken as a whole, lactoferrin has shown good antidiabetic effects, in vivo and in vitro [9]. 
Also interesting is a demonstrated synergistic effect with metformin, one of the most important drugs in the treatment of type 2 diabetes [10].
In 2018, a study of paediatric patients with diabetes mellitus type 2 also showed an antidiabetic effect of lactoferrin in humans [11]. The study measurements showed a significant improvement in HbA1c (a long-term marker of sugar presence in the blood), body mass index and lipid status (blood fat values).
In addition to the insulin-sensitising effect, an anti-inflammatory effect could also be detected here via a reduction in the pro-inflammatory messengers. 
The antidiabetic effectiveness of lactoferrin can be explained by the improvement of blood sugar levels and fat metabolism, along with the anti-inflammatory component.
The authors suggest regular intake of lactoferrin in type 2 diabetes could ensure better blood glucose control compared to conventional antidiabetic medications alone. 
Lactoferrin presents the possibility of a natural and safe intervention in the prophylaxis and therapy of metabolic disorders in general [11].