Carl-Magnus Henriksson

Exploring factors that might impact decline of renal function in patients with type 2 diabetes

Type 2 diabetes is a widespread disease with a risk of renal damage. We intend to investigate the association between novel risk factors, such as fluctuations in long-term glucose control, and decline of renal function. Furthermore, we intend to investigate the association between socioeconomic factors, fluctuations in long-term glucose and decline of renal function in type 2 diabetes.

The prevalence of type 2 diabetes in Sweden has been estimated to 4-6 % with a male dominance. Age-standardized prevalence of chronic kidney disease (CKD) has been estimated to around 5%. Type 2 diabetes is associated with increased risk of macrovascular complications (myocardial infarction and stroke) as well as microvascular complications (nephropathy, retinopathy and neuropathy). The main causes for CKD are hypertension and diabetes, albeit risk factors influencing the natural course of CKD are complex and heterogenous. In recent years, studies have indicated that variability in long-term glucose control, independent of high glucose levels, may be an additional risk factor for development of macrovascular as well as microvascular complications. The underlying mechanism is not known, but it has been suggested that variability in glucose control may lead to oxidative stress, endothelial dysfunction, and inflammation, which are known risk factors for microvascular damage. Socioeconomic factors like immigrant background, low educational achievement or low-income level have been shown to correlate to an increased risk for type 2 diabetes. However, very little is known about the association between socioeconomic factors and variability of long-term glucose, a potential risk factor for renal damage.

Aim
To explore factors that might impact decline of renal function in patients with type 2 diabetes and in the general population.

Study 1 To examine the association between variability in long-term glucose control (HbA1c), defined by coefficient of variation, and decline in renal function.

Study 2 Use structural equation modelling to estimate the effect of variability in long-term glucose control and glucose exposure on decline in renal function.

Study 3 Linking of data from LISA to the DiabNorr registry to evaluate the impact of socioeconomic factors such as educational level, unemployment, need for income support or health care support, on variability of long-term glucose control (HbA1c), level of glucose control (exposure) and potential decline in renal function.

Study 4 Comparing the trajectory of renal function (change in GFR) before and after the diagnosis of type 2 diabetes, in screening detected versus symptoms detected patients.

By investigating the correlation between variability in long-term glucose control (HbA1c) and change in renal function, we hope to bring further tools to the primary health care in the detection and treatment of type 2 diabetes and diabetic kidney disease. By surveying the progression of renal function after diagnosis, we may give more specific knowledge to optimize the arrangement of screening, in preventing kidney disease. Primary care has a natural contact surface to all socioeconomic group. In clarifying the socioeconomic factors that increase the risk of glucose variability and correlated decline in renal function, we may aid in a shift of attention to factors with the highest impact.

Umeå University
Main Supervisor: Johan Nilsson Sommar, PhD