Associations of Insulin Levels and Insulin Resistance With Urine Glucose Excretion Independent of Blood Glucose in Chinese Adults With Prediabetes and Newly Diagnosed Diabetes

Abstract

Several studies have demonstrated that renal glucose reabsorption is increased in patients with type 2 diabetes. However, the increased renal glucose reabsorption may contribute to the progression of hyperglycemia. Therefore, promoting urine glucose excretion (UGE) by suppression of renal glucose reabsorption is an attractive approach for the treatment of diabetes. Insulin resistance is identified as a major characteristic in the pathogenesis of type 2 diabetes. Thus, our aim was to evaluate the association of UGE with serum insulin levels and insulin resistance in subjects with glucose abnormalities, including prediabetes and newly diagnosed diabetes (NDD). The present study included 1129 subjects, 826 individuals with prediabetes and 303 individuals with NDD. Urine samples were collected within 2 h of oral glucose loading for the measurement of glucose. Fasting serum insulin was measured. Homeostatic model assessment of insulin resistance (HOMA-IR) was assessed. Multiple linear regression analysis and multivariate logistic regression analysis were performed to determine the association of UGE with insulin levels and HOMA-IR. A negative association between serum insulin levels and UGE was observed. The relationship remained significant after adjustment for potential confounders, including age, gender, blood pressure and glucose (β = -5.271, 95% CI: -9.775 to -0.767, p = 0.022). Furthermore, multivariable logistic regression model showed that increased insulin levels were associated with a decreased risk for high UGE after multivariable adjustment. In addition, similar correlation was also observed between HOMA-IR and UGE. HOMA-IR was negatively correlated with UGE after controlling for potential confounders. Moreover, an independent inverse relationship between HOMA-IR and the risk of high UGE was found (OR = 0.85, 95% CI: 0.78–0.93, p < 0.001). In conclusion, insulin levels and HOMA-IR were negatively correlated with UGE after adjusting for potential confounders. Subjects with increased insulin levels or IR were at a decreased risk of high UGE independent of blood glucose. The study suggests that insulin might affect UGE through other ways, in addition to the direct blood glucose-lowering effect, thereby resulting in reduced UGE.

Hyperosmolar hyperglycaemic state (HHS) as the first manifestationof type 2 diabetes in a child

“…However, one must remember that insulin receptor is present in renal tubular cells, and insulin stimulates sodium reabsorption in renal proximal tubules. Thus, the renal threshold for glucose reabsorption is higher in individuals with type 2 diabetes mellitus because of the enhanced sodium-glucose cotransporter 2 (SGLT2) expression in the course of hyperinsulinaemia and insulin resistance; this was demonstrated in a recent study by Chen et al in patients with prediabetes and newly diagnosed type 2 diabetes, where insulin levels and insulin resistance were negatively associated with UGE, independent of blood glucose [12]. Reduction in UGE may contribute to the progression of hyperglycaemia.…”

Impact of magnesium sulfate therapy in improvement of renal functions in high fat diet-induced diabetic rats and their offspring

“…Researchers reported some medication like empagliflozin improves T2D and reduces blood glucose levels by inhibiting selective sodium glucose co‐transporter 2 and increasing urinary glucose excretion 35 . DeFronzo et al showed that renal glucose reabsorption increases in T2D patients 36 . So, the suppression of renal glucose reabsorption is a powerful method to treat diabetes.…”

Basal glucose excretion in dogs: The impact of feeding, obesity, sex, and age

“…The elimination of insulin receptors expressed on renal tubular cells, 23 reduces SGLT 2 expression and increases UG excretion 24 . Human patients with increased insulin concentrations are more likely to have low UG concentrations independent of blood glucose concentrations 25 . As insulin increases postprandially, and peak blood glucose concentrations do not exceed the so‐called “renal threshold” in healthy dogs, 26 a drop in postprandial UG concentrations was expected.…”

“…The rationale for comparing UG concentrations between lean and obese dogs was twofold. Obesity causes significant structural, biochemical, hemodynamic, and functional changes in the canine kidneys, 25 possibly impairing glucose handling. Secondly, although dogs are protected from type 2 diabetes mellitus even after years of naturally occurring obesity, they can develop obesity‐induced insulin resistance and compensatory hyperinsulinemia 27,28 .…”