Diabetic Glomerulosclerosis
Diabetes mellitus is a major cause of renal morbidity and mortality and diabetic nephropathy is one of the leading causes of chronic kidney failure in the United States. End – stage kidney disease occurs in as many as 30% of insulin-dependent type I diabetics and accounts for 20% of deaths in patients younger than 40 years. By far the most common lesions involve the glomeruli and are associated clinicallyh with three glomerular syndromes, including non nephrotic proteinuria, nephrotic syndrome, and chronic renal failure. However, also affects the arterioles, causing arteriolar sclerosis; increases susceptibility to the development of pyelonephritis, and particularly papillary necrosis; and causes a variety of tubular lesions. The term diabetic nephropathy is applied to the conglomerate of lesions that often occur concurrently in the diabetic kidney.

Proteinuria, sometimes in the nephrotic range occurs in about 50% of both type 1 and type 2 diabetics. It is usually discovered 12 to 22 years after the clinical appearance of and (particularly in type 1 diabetics) often heralds the progressive development of chronic renal failure ending in death or end stage disease within a period of 4 to 5 years. The morphologic changes in the glomeruli include (1)capillary basement membrane thickening (2) diffuse diabetic glomerulosclerosis, and (3) nodular glomerulosclerosis.

The pathogenesis of diabetic glomerulosclerosis is intimately linked with that og generalized diabetic microangiopathy.

The bulk of evidence suggests that diabetic glomerulosclerosis is caused by the metabolic defect that is the insulin deficiency or the resultant hyperglycemia or some other aspects of glucose intolerance.

Biochemical alterations in diabetic GBM are significant and include increased amount and synthesis of collagen type IV and fibronectin and decreased synthesis of proteoglycan heparan sulfate.

Nonenzymatic glycosylation of proteins, known to occur in diabetics and giving rise to advanced glycosylation and products, may contribute to the glomerulopathy. The mechanisms by which advanced glycosylation end products cause their effects.

One hypothesis implicates hemodynamic changes in the initiation or progression of diabetic glomerulosclerosis. It is well known that early onset type I diabetics have an increased GFR increased glomerular filtration area increased glomerular capilary pressure and glomerular hypertrophy . Hemodynamic alterations and glomerular hypertrophy also occur in experimental streptozotocin induced in rats, in which they are associated with proteinuria and can be reversed by diabetic control. It has been speculated that the subsequent morphologic alterations in the mesangium are somehow influenced by the glomerular hypertrophy and hemodynamic changes, akin to the adaptive responses to ablation of renal mass.

To sum up, two processes seem to play a role in the fullyu developed diabetic glomerular lesions: a metabolic defect possibly linked to advanced glycosylation and products, that accounts for the thickened GBM and increased mesangial matrix that occur in all patients; and hemodynamic effects associated with glomerular hypertrophy which leads to glomerulosclerosis in about 40% of patients.

Clinical Course

The clinical manifestations of diabetic glomerulosclerosis are linked to those of diabetes. The increased GFR typical of early onset type 1 diabetics

Five years on: delivering the diabetes national service...
This report highlights progress over the first five years of...
PBS Phase 3 Diabetes Population Prevalence Model
This is a spreadsheet model that generates expected total...
National Diabetes Audit
This report presents the main findings from the third year...
Diabetes in the NHS
A report on commissioning and providing specialist services...
Two new tools to help diabetes networks develop and improve...
Two new tools have been released by the National Diabetes...
Prevention of Type 2 Diabetes: role of diabetes networks
Nearly two-thirds of Type 2 diabetes cases could be...
Making every young person with diabetes matter
A new Factsheet has been put together to set out the...
Improving services for people with diabetes
The Healthcare Commission has published 'Managing diabetes:...
Diabetes fact sheet to help health professionals
The National Diabetes Support Team has published a fact...
Working together for better diabetes care: clinical case for...
The National Director for Diabetes sets out how services are...
Making every Young Person with Diabetes Matter
The Making every Young Person with Diabetes Matter report,...
National survey of people with diabetes
Presents the results of a national survey of people with...
'The way ahead: the local challenge: Improving diabetes...
The Diabetes National Service Framework set out the first...
'Insulin pump services - report of the Insulin Pumps Working...
This report sets out the findings of the Insulin Pumps...
A pragmatic cluster randomised controlled trial of a...
Following the introduction of a computerised diabetes...
Essential Elements in Developing a Diabetic Retinopathy...
Workbook designed to inform and assist SHAs and PCTs...
Diabetes: State of the Nations 2006
Major report which shows the overall state of diabetes...
Toolkit for Long Term Conditions
This toolkit provides advice and support on all aspects of...
Hyperglycemic Crises in Adult Patients With Diabetes
This consensus statement outlines precipitating factors and...
Structured patient education: role of Diabetes Networks
Supplement to "Beyond Boundaries: A guide to Diabetes...

is associated with microalbuminuria defined as urinary albumin excretion of 30 to 300 mg/day of albumin. Microalbuminuria and increased GFR are important predictors of future overt diabetic nephropathy in these patients. Overt proteinuria then develops which may be mild and asymptomatic initially but gradually increased to nephrotic levels in some patients. This is followed by progressive loss GFR leading to end stage renal failure within a period of 5 years.

Systemic hypertension may precede the development proteinuria and renal insufficiency. Indeed the risk of renal disease in type 1 diabetics is associated with a genetic predisposition to hypertension, possibility related to polymorphisms in the genes encoding proteins of the renin angiotension system. Hypertension in turn increases the susceptibility to developing diabetic nephropathy in the presence of poor hyperglycemic control.

Although the prevalence of protenuria is comparable in type 1 and type 2 diabetics, the lesions are more heterogeneous and less predictable in type 2 diabetics. Indeed 20 to 50% of type 2 patients undergoing renal biopsy have other glomerular diseases (eg., membranous glomerulonephritis). End stage renal disease results in only 10% to 20% of patients with type 2 diabetes.

For more information about disease and disorders visit www.treatdiabetes.net