Are glomerular volume differences between type 1 and type 2 diabetic patients pathologically significant?

Abstract

The observation that patients with type 2 diabetes tend to have larger glomeruli than patients with type 1 diabetes was first made more than 10 years ago. It has also been noted that type 2 diabetic patients with nephropathy often have more heterogeneous renal function and structure than type 1 patients. However, whether these observations are linked or have any bearing on the progression of nephropathy in the two types of diabetes remains uncertain. Here we put forward several hypotheses as to why glomerular volume in type 1 differs from that in type 2 diabetes. We suggest that although type 1 and type 2 diabetic patients appear to progress through similar stages of diabetic nephropathy, the route they take may differ. Differences in the way in which the glomeruli respond to the diabetic milieu may enable some type 2 diabetic patients to preserve their filtration surface in the face of an expanding mesangium.

Cellular and physiological effects of C-peptide

“…On the other hand, patients with Type 2 diabetes are generally over the age of 40 and have evidence of age-related glomerulosclerosis, together with other propagators of renal disease, such as hypertension, obesity and dyslipidaemia. Thus nephropathy in Type 2 diabetes reflects a heterogeneous combination of kidney diseases precipitated by a mixture of mechanisms that may modify and overwhelm the typical renal responses to hyperglycaemia and the features of pure diabetic nephropathy [71]. Consequently, it has been suggested that, in terms of responses to treatment, Type 1 and Type 2 diabetic patients should be considered separately.…”

C-peptide reverses TGF-β1-induced changes in renal proximal tubular cells: implications for treatment of diabetic nephropathy

“…Also, in the majority of individuals with type 1 diabetes, chronic hyperglycemia and its consequences are the only evident causes of nephropathy, whereas in type 2 diabetes nephropathy more typically reflects a combination of heterogeneous renal insults caused by a mixture of mechanisms that may alter and overcome renal responses to hyperglycemia and the features of pure diabetic nephropathy (36,51). Consequently, commentators suggest that in terms of responses to treatment, type 1 and type 2 diabetic subjects should be considered independently (36,51). More study of C-peptide (patho)physiology in type 2 diabetes is required to clarify these issues.…”

Associations between structural and functional changes to the kidney in diabetic humans and mice

“…Mesangial matrix formation rather than proliferation of mesangial cells corresponds most closely with declining GFR (Steffes et al, 1992). Growth of the mesangial matrix component of the mesangium is the main contributor to glomerular enlargement in Type 1 diabetic patients (White et al, 2007). The enlarged diabetic glomerulus shown in Figure 3 contains increased mesangium and fewer open capillaries than normal.…”