New data shows that intensive treatment of diabetes may lower coexistent hypertension and delay renal dialysis by up to 20 years

New data shows that intensive treatment of diabetes may lower coexistent hypertension and delay renal dialysis by up to 20 years   DailyUpdates 6th April: According to WHO, there are some 130 million diagnosed diabetics in the world and the long term consequences of diabetes such as diabetic nephropathy are becoming increasingly frequent and unmet components of diabetes care.  In a recent study Glasgow Royal Infirmary researchers report that intensive treatment slowed progression of renal disease within 2 years in patients with established diabetic nephropathy and predict that this approach may delay the onset of dialysis by as long as 20 years.   According to WHO, there are some 130 million diagnosed diabetics in the world, a figure that is predicted to increase to 300 million by 2025. The market for diabetes therapeutics is also rising with global sales reportedly topping $8.1 billion for the 12 months to September 2000, a 19% increase over the previous 12 months (for a full analysis of diabetes therapeutics and market opportunities click here). Further increases are inevitable and the market for diabetes medications could exceed $20 billion by 2006. Oral antidiabetic drugs, the leading class of drugs used to treat the disease, accounted for almost 63% of sales.   In addition to day to day control of hyperglycemia the endocrinologist is faced with the challenge of long-term, complications of diabetes as well as the treatment of other conditions that coexist with diabetes. For example, around 60-65% of diabetics also have hypertension and consequently the development of single treatment modalities that target both diabetes and hypertension is a concept currently attracting considerable attention (for an analysis of the potential of cross indication therapeutics click here).    With respect to long-term complications, the diabetic microvascular complication, nephropathy, is one of the most serious and is a condition with high unmet therapeutic needs. It is linked with significant increases in morbidity and mortality risk, and is the most common cause of end-stage renal disease in the US and Europe (for a full analysis of diabetic nephropathy click here).

The prevalence of nephropathy (encompassing microalbuminuria, proteinuria and end-stage renal disease) is 48% in seven countries representing 18.6m type 2 patients. The main focus of therapy in diabetic nephropathy is on tight control of blood pressure and either ACE or ARB therapy is recommended as a first line renoprotective anti-hypertensive therapy. Existing anti-hypertensive therapies can however only delay the progression of diabetic nephropathy. Research elucidating the etiology and pathways of diabetic microvascular disease has revealed new targets for drug design. Within the next 10 years the most promising compounds will come from the ARI, PKC-beta and AGE inhibitor classes.

Intensive glycemic control prevents or retards microalbuminuria, an early sign of nephropathy, in patients with type 2 diabetes.  In their April Quarterly Journal of Medicine journal article, Joss et al determine the effect of intensive vs. standard medical management over a two year period on the rate of progression of renal failure in patients with diabetic nephropathy. The Glasgow Royal Infirmary group's prospective randomized controlled study divided patients with type 2 diabetes and nephropathy into an intensive group (n = 47) or control group (n = 43). Treatment targets were the same for both groups, but the intensive group were seen as often as required to meet the targets. The primary end-point was the rate of progression of renal disease in the second year.

The results of this study demonstrate that during follow-up, the intensive group had lower mean systolic and diastolic blood pressures as well as cholesterol levels. Median rate of progression of renal failure in the intensive group fell from 0.44 ml/min/month in the first year to 0.14 ml/min/month in the second year, compared to 0.49 ml/min/month and 0.53 ml/min/month in the control group. Patients in the intensive group spent significantly less time in hospital.

This important study highlights the benefits of intensive treatment as this approach both limited co-existent hypertension and slowed progression of renal disease within 2 years in patients with established diabetic nephropathy. Indeed the authors predict that onset of dialysis would be delayed by 20 years in the intensive group compared with the control group.

Source DailyUpdates 6th April; for a full abstract of the original papers see   QJM. 2004 Apr;97(4):219-27

Recommended further reading:

• Diabetic Nephropathy: Prevalence, Progression, Prevention and Potential
• Diabetes 2003
• Markets in Geriatric Medicine: Type II Diabetes
• Potential for Cross-Risk Factor Combinations: Targeting Hypertension, Dyslipidemia and Diabetes

In this edition of DailyUpdates, LeadDiscovery also highlights the potential of monomeric recombinant TCR ligand as a treatment of multiple sclerosis...ryanodine receptors as a target for novel insulinotropic therapeutics...the role of IL-4 in asthma...and much more.