Study on the correlation between "fibroblast growth factor 21" and "urinary glucose excretion" in patients with type 2 diabetes

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With the widespread application of SGLT2 inhibitors in diabetic patients, related research exploring the clinical significance of urinary glucose excretion has attracted the attention of the academic community
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In order to explore the relationship between fibroblast growth factor 21 and urinary glucose excretion in patients with type 2 diabetes, the team of Professor Ji Linong, Department of Endocrinology, Peking University People’s Hospital, tested the level of urinary glucose excretion and serum FGF21 levels in inpatients with type 2 diabetes, and collected relevant clinical information.
Data, the statistical method of multi-factor logistic regression was used to analyze the correlation between FGF21 and UGE, and the research results were published in the Journal of Diabetes and Its Complications
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Urinary glucose excretion (UGE) is mainly regulated by the sodium-glucose cotransporter (SGLT)-2 on the proximal convoluted tubules of the kidney, while the decrease in UGE in patients with type 2 diabetes is associated with insulin resistance
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SGLT2 inhibitors can improve the obesity and hypertension of type 2 diabetic patients by increasing urinary sugar excretion, thereby reducing cardiovascular and renal risks
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With the wide application of SGLT2 inhibitors in diabetic patients, related research exploring the clinical significance of UGE has attracted the attention of the academic community
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Fibroblast growth factor 21 (FGF21) is a hormone with "endocrine" properties that can regulate glucose and lipid metabolism.
It is elevated in many metabolic diseases including type 2 diabetes, obesity, chronic kidney disease and other people
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Previous studies have found that it can reduce the expression of SGLT2 on the kidneys of diabetic mice and increase UGE, and the use of SGLT2 inhibitors in mouse models can increase the level of FGF21.

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So far, the relationship between FGF21 and UGE is not clear, and the relevant population research evidence is also very limited
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In order to explore the relationship between FGF21 and UGE in patients with type 2 diabetes, the team of Professor Ji Linong, Department of Endocrinology, Peking University People’s Hospital, tested the urine glucose excretion level and serum FGF21 level of inpatients with type 2 diabetes, collected relevant clinical data, and used multi-factor logistic regression.
The statistical method of FGF21 and UGE were used for correlation analysis
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The research results were officially published in the Journal of Diabetes and Its Complications in January 2021
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Dr.
Zhang Rui from the Department of Endocrinology, Peking University People's Hospital is the first author, and Professor Ji Linong and Chief Physician Cai Xiaoling are the co-corresponding authors
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The researchers screened a total of 2066 hospitalized type 2 diabetic patients, and assessed the level of urinary glucose excretion by simultaneously measuring the fasting blood glucose and urine glucose of type 2 diabetic patients during their hospitalization
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When the fasting blood glucose is less than 8.
9mmol/L, the positive urine glucose indicates increased urine glucose excretion (HUGE), and when the fasting blood glucose is more than 10mmol/L, there is still no glucose in the urine, which indicates decreased urine glucose excretion (LUGE)
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 According to the above criteria, this study finally included 70 HUGE patients and 61 LUGE patients, and detected their fasting serum FGF21 levels for subsequent correlation analysis
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The results of the study The results of the study showed that compared with the HUGE group, patients in the LUGE group had higher BMI and serum FGF21 levels, and the difference between the two groups was statistically significant
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Multivariate logistic regression analysis showed that high FGF21 levels were significantly related to UGE reduction, and the correlation between the two was still statistically significant after adjusting for the corresponding confounding factors in different regression models (Table)
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Note: Model 1, adjusted for age and gender, OR=1.
811 (1.
176, 2.
790); Model 2, adjusted for age, gender, fasting blood glucose, eGFR, insulin treatment and BMI, OR=1.
724 (1.
067, 2.
787); Model 3, Corrected for age, gender, fasting blood glucose, eGFR, insulin therapy and HOMA-IR, OR=1.
748 (1.
106, 2.
762)
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Experts comment on Professor Ji Linong.
In this study, by detecting the UGE level and FGF21 level of hospitalized patients with type 2 diabetes, using a multi-factor logistic regression analysis method, after adjusting for the influence of many confounding factors, it was found that high FGF21 level was associated with low UGE
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This study is one of the few cross-sectional studies to explore the relationship between FGF21 levels and UGE levels in patients with type 2 diabetes, and provides new population research clues for further understanding of the role of FGF21 in the occurrence and development of type 2 diabetes
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In recent years, many studies have suggested that there is a close connection between SGLT2 and FGF21 pathways
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Animal experiments have found that FGF21 analogs can reduce the expression of SGLT2 in the proximal tubules of diabetic mice and increase UGE, which suggests that FGF21 may improve blood sugar by increasing UGE
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At the same time, FGF21 levels in obese mice also increased after using SGLT2 inhibitors, and the weight loss and lipolysis mediated by SGLT2 inhibitors showed the characteristics of FGF21 level-dependent
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The research team found in patients with type 2 diabetes that elevated serum FGF21 and decreased urinary glucose excretion are independent of other confounding factors such as obesity or insulin resistance, which suggests that the state of decreased urinary glucose excretion may be related to FGF21 resistance
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Finally, combining the previous research evidence and the new findings of this study, the researchers also raised a new scientific question, namely whether the improvement of fat metabolism by SGLT2 inhibitors through FGF21-related pathways is related to the state of urinary glucose excretion.

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In the future, more research is needed to further explore the relationship between FGF21, SGLT2 and UGE, and deepen our understanding of FGF21's regulation of glucose and lipid metabolism
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