Abstract
Background: Type 2 Diabetes is the most common form of diabetes mellitus, accounting for 90% of all types of diabetes. Diet is one of the important factors affecting the progression of the disease.
 Methods: In this study, we used urinary protein profile to evaluate the progression of pre-diabetic to diabetic state. Urinary protein profile of pre-diabetic rats with various diet conditions and with or without metformin treatment were compared to those of healthy rats and diabetic rats.
 Results: It was shown that there were distinct bands that could differentiate the healthy rats from the diabetic ones, namely the protein bands at MW 350 kDa, 280 kDa and 85 kDa (for healthy rats), and protein bands at MW 170 kDa, 51 kDa and 46 kDa (for diabetic rats). In addition, the differentially excreted proteins at MW 62 kDa and 25 kDa (between healthy and diabetic rats) could also be used as indicators. Using the unique band indicators, the pre-diabetic urinary profile was shown to be similar to that of healthy rats. However, by using the differential protein indicators, the band intensity of the 62 kDa, 25 kDa and 17 kDa bands of pre-diabetic rats, with normal diet and metformin treatment, was more similar to that of the healthy rats with normal diet. However, the profile of pre-diabetic rats with high fat diet (with or without metformin treatment) and of pre-diabetic rats (with normal diet without metformin treatment) were more similar to that of diabetic rats.
 Conclusion: Using this protein profiling comparison method, it was demonstrated that early metformin treatment and controlled diet intake are important in delaying the progression of the pre-diabetic to diabetic state.
Highlights
Diabetes is one of the most common noncommunicable diseases globally
Urinary protein was concentrated and purified using salting out technique, without concentrating the urine, since it was too dilute to visualize the protein on SDS-PAGE
We found that band 62 kDa was excreted in high quantities in diabetic and prediabetic rats and healthy rats fed with High-fat diet (HFD)
Summary
Diabetes is one of the most common noncommunicable diseases globally. It affects 451 million people worldwide and is estimated to incrementally reach 693 million in the year 2045 1. Pre-diabetic patients with elevated blood glucose levels are at high risk to develop diabetes 2. Urinary protein profile of pre-diabetic rats with various diet conditions and with or without metformin treatment were compared to those of healthy rats and diabetic rats. Using the unique band indicators, the pre-diabetic urinary profile was shown to be similar to that of healthy rats. By using the differential protein indicators, the band intensity of the 62 kDa, 25 kDa and 17 kDa bands of pre-diabetic rats, with normal diet and metformin treatment, was more similar to that of the healthy rats with normal diet. Conclusion: Using this protein profiling comparison method, it was demonstrated that early metformin treatment and controlled diet intake are important in delaying the progression of the pre-diabetic to diabetic state
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