Long-Term Intensive Lifestyle Intervention Promotes Improvement of Stage III Diabetic Nephropathy

Abstract

BACKGROUND Diabetic nephropathy (DN) is a potentially fatal complication of diabetes mellitus. While lifestyle changes can reduce diabetes risk, it is unclear whether improved lifestyle can slow or reverse DN progression. This study evaluated whether an intensive lifestyle intervention (IL-I) targeting weight loss and inflammation through increased physical activity and reduced caloric intake can delay DN progression. MATERIAL AND METHODS Patients were randomly divided into 2 groups. Both groups received diet and exercise guidelines, but one (IL-I) received more frequent external support than the other (control). We compared markers of metabolic and cardiovascular health, redox status, inflammation, and renal function between groups at 3 and 6 months. Metabolic and cardiovascular metrics included BMI, blood pressure, blood glycosylated hemoglobin (HbA1c), and serum HDL-cholesterol. Redox status was evaluated by serum superoxide dismutase (SOD) and the lipid oxidation product malondialdehyde (MDA), while inflammation was assessed by serum concentrations of IL-6 and TNF-alpha. Renal function was assessed by urine/serum 8-OHdG, albumin: creatinine ratio (ACR), and the renal fibrosis marker TGF-ß1. RESULTS Both groups demonstrated initial BMI reduction, lower HbA1c, and higher HDL-cholesterol, but changes were significantly larger in the IL-I group at 6 months. Blood pressure at 6 months was reduced only in the IL-I group. The IL-I group also achieved a greater sustained SOD increase and MDA reduction. Finally, only the IL-I group demonstrated significant reductions in urine ACR, serum/urine 8-OHdG, and plasma TGF-ß1. These indicators deteriorated after IL-I was stopped. CONCLUSIONS Lifestyle changes including exercise and diet can delay renal damage and promote improvement from DN.

Figure 1

Effect of long-term intensive lifestyle intervention (IL-I) on metabolic health in diabetic nephropathy (DN) patients. (A–C) Compared to control intervention, IL-I produced a larger and more sustained (A) decrease in BMI (P^a, P^b, and P^d <0.05; P^c <0.01; P^ab >0.05; P^cd <0.05), (B) increase in HDL-cholesterol (P^a and P^b <0.05; P^c <0.01; P^ab and P^d >0.05; P^cd <0.05), and (C) reduction in HbA1c (P^a, P^b, and P^d >0.05; P^c <0.01, P^ab >0.05; P^cd <0.05). (D) The 2 groups both demonstrated a downward trend in blood glucose that did not reach statistical significance (P^a, P^b, P^c, P^d, P^ab, and P^cd >0.05). P^a, 3 months vs. baseline in the IL-I group; P^b, 3 months vs. baseline in the control group; P^ab, IL-I vs. control group at 3 months; P^c, 6 months vs. baseline in the IL-I group; P^d, 6 months vs. baseline in the control group; P^cd, IL-I vs. control group at 6 months.

Figure 2

Effects of IL-I on renal function and blood pressure. (A, B) IL-I reduces (A) systolic blood pressure (P^a, P^b, and P^d >0.05; P^c <0.01; P^ab >0.05; P^cd >0.05) and diastolic blood pressure at 6 months (P^a, P^b, and P^d >0.05; P^c <0.01; P^ab >0.05; P^cd >0.05). (C, D) There were no significant changes in creatinine and blood urea nitrogen at 3 and 6 months (P^a, P^b, P^c, P^d, P^ab, and P^cd >0.05).

Figure 3

Long-term intensive lifestyle intervention enhances antioxidant capacity and reduces inflammation in DN patients. (A, B) Both IL-I and control groups exhibited increased SOD and reduced MDA at 3 and 6 months, but the increase was greater and more sustained in the IL-I group (P^a and P^b <0.05; P^c <0.01; P^ab and P^d >0.05; P^cd <0.05). (B) Both groups also demonstrated reduced MDA at 6 months, but the change was greater in the IL-I group (P^a and P^b <0.05, Pc <0.01, Pd and P^ab >0.05, P^cd <0.01). (C) Both groups showed reduced serum IL-6 at 3 and 6 months (P^a, P^b, and P^d <0.05; P^c <0.01; P^ab >0.05; P^cd <0.05). (D) Both groups exhibited a downward trend in plasma TNF-α, but the difference from baseline did not reach statistical significance (P^a, P^b, P^c, P^d, P^ab, and P^cd >0.05).

Figure 4

Long-term intensive lifestyle intervention improves renal function in diabetic nephropathy. (A, B) IL-I reduced both plasma (A) and 24-h urine (B) 8-OHdG (in A: P^a, P^b, and P^d <0.05; P^c <0.01; P^ab and P^cd >0.05; in B: P^a, P^b, and P^d <0.05; P^c <0.01; P^ab and P^cd >0.05). (C) Both IL-I and control groups demonstrated reduced 24-h urine ACR at 3 and 6 months, but the decrease was larger in the IL-I group (P^a, P^b, and P^ab <0.05; P^c <0.01; P^ab >0.05; P^cd <0.05). (D) IL-I also induced a more sustained reduction in TGF-β1 (P^a, P^b, and P^d >0.05; P^c <0.05; P^ab >0.05; P^cd >0.05).