The Aggressive Diabetic Kidney Disease in Youth-Onset Type 2 Diabetes: Pathogenetic Mechanisms and Potential Therapies

Abstract

Youth-onset Type 2 Diabetes Mellitus (T2DM) represents a major burden worldwide. In the last decades, the prevalence of T2DM became higher than that of Type 1 Diabetes Mellitus (T1DM), helped by the increasing rate of childhood obesity. The highest prevalence rates of youth-onset T2DM are recorded in China (520 cases/100,000) and in the United States (212 cases/100,000), and the numbers are still increasing. T2DM young people present a strong hereditary component, often unmasked by social and environmental risk factors. These patients are affected by multiple coexisting risk factors, including obesity, hyperglycemia, dyslipidemia, insulin resistance, hypertension, and inflammation. Juvenile T2DM nephropathy occurs earlier in life compared to T1DM-related nephropathy in children or T2DM-related nephropathy in adult. Diabetic kidney disease (DKD) is T2DM major long term microvascular complication. This review summarizes the main mechanisms involved in the pathogenesis of the DKD in young population and the recent evolution of treatment, in order to reduce the risk of DKD progression.

Role of Zinc in Diabetic Kidney Disease

“…Kidney biopsy is of pivotal importance for a correct diagnosis but also for defining prognosis, especially in the presence of heavy proteinuria or its rapid onset [ 53 ]. A timely correction of risk factors for DKD progression and a personalized therapeutic approach are fundamental in decreasing the impact of its complications and to reduce the risk of ESRD [ 54 , 55 ]. Different therapeutic approaches have been proposed for DKD treatment, including pharmaceutical and nutraceutical approaches [ 56 , 57 , 58 ].…”

The analysis of risk factors for diabetic kidney disease progression: a single-centre and cross-sectional experiment in Shanghai

“…6 In addition, aggressive DKD in youth-onset type 2 diabetes should also receive great attention; it has a rising incidence, is genetically predisposed, is closely associated with obesity, hyperglycaemia, hyperlipidemia, insulin resistance, hypertension and inflammation, and represents a major worldwide burden. 7 Several important clinical indicators have been discovered in research as independent risk factors that affect the incidence risk of DKD for patients with T2DM, such as disease course, body mass index (BMI), triglycerides (TGs), systolic blood pressure (SBP) and haemoglobin A1c (HbA1c). 8 That means DKD is related to certain factors such as poor glycaemic control, dyslipidaemia and hypertension in T2DM.…”

Incretins in the Therapy of Diabetic Kidney Disease

“…The young population with T2D presents many additional risk factors of kidney failure, such as obesity, dyslipidaemia, hypertension and inflammation. The main mechanisms involved in the pathogenesis and progression of the DKD in young people are insulin resistance and impaired insulin secretion [69]. Moreover, puberty has a possible influence on the progression of DKD lesions, increasing the production and activity of transforming growth factor-β (TGF-β), a key factor in the development of diabetic renal hypertrophy and nephropathy [70].…”