CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into available therapies in advanced heart failure 4
Contributing experts 5

CHAPTER 2 BACKGROUND 7
Diabetes mellitus 7
Definition 7
Segmentation of diabetes 8
Type 1 diabetes 8
Type 1.5 diabetes 8
Type 2 diabetes 9
Mechanisms of development of diabetes 9
Genetic or acquired causes 10
Diabetic complications 10
Microvascular complications 12
Retinopathy 12
Neuropathy 14
Nephropathy 17
Macrovascular complications 21
Effect of macrovascular complications on type 2 diabetes treatment 23
End-stage disease considerations 24
Co-morbidities 25
Obesity 25
Effect of obesity on type 2 diabetes treatment 27
Hypertension 27
Dyslipidemia 28

CHAPTER 3 DIABETIC RENAL DISEASE - DEFINITIONS AND OVERVIEW 30
Diabetic renal disease and diabetic nephropathy 30
Etiology of diabetic nephropathy 32
Etiological factors influencing the development of diabetic renal disease 32
Pathogenesis and natural history of renal nephropathy 33
Microalbuminuria 34
Pathophysiological role of hyperglycemia 36
Pathophysiological role of hypertension 37
Macroalbuminuria and end stage renal disease 38
Chronic kidney disease and cardiovascular risk 39
Diagnosis 40

CHAPTER 4 TREATMENT STRATEGIES 46
Pharmacotherapy 46
Glycemic control 47
Managing hypertension 51
Benefits of ACE inhibition 52
Data supporting the renoprotective benefits of ACE inhibitors. 53
Benefits of angiotensin II receptor blockade 57
Renin inhibitors 61
Diuretics 65
Calcium channel blockers 65
Diet and protein restriction 66
Renal replacement 67
Dialysis 68
Hemodialysis 68
Peritoneal dialysis 70
Renal transplantation 71
Cultural issue 73

CHAPTER 5 COMMERCIAL OPPORTUNITIES 74
Battle of the antihypertensives 74
Rationale for the renin-angiotensin combinations 75
Development of new agents 77
APPENDIX 79
Report methodology 79
Bibliography 79
About Datamonitor 83
About Datamonitor Healthcare 83
About the cardiovascular analysis team 84
Disclaimer 85

List of Tables 
Table 1: Framingham Heart Study data on percentage lipid levels in men and women with and without diabetes 29
Table 2: Stages of diabetic nephropathy: cut-off values of urine albumin for diagnosis and main clinical characteristics 36
Table 3: Stages of chronic kidney disease 38
Table 4: Cardiovascular risk according to stages of chronic kidney disease 39
Table 5: Pharmacokinetic profiles of commercially available angiotensin II receptor blockers (ARBs) 59

List of Figures 
Figure 1: Proportion of type 2 diabetics with complications in the seven major markets, 2007 11
Figure 2: Proportion of type 2 diabetics with complications that suffer from microvascular and/or macrovascular complications in the seven major markets, 2007 12
Figure 3: Proportion of type 2 diabetics with retinopathy in the seven major markets, 2007 13
Figure 4: Average time required for the development of diabetic retinopathy in the seven major markets, 2007 14
Figure 5: Proportion of type 2 diabetics with neuropathy in the seven major markets, 2007 16
Figure 6: Average time required for the development of diabetic neuropathy in the seven major markets, 2007 17
Figure 7: Proportion of type 2 diabetics with different stages of nephropathy in the seven major markets, 2007 19
Figure 8: Average time from the diagnosis of diabetes required for the development of different stages of diabetic nephropathy in the seven major markets, 2007 20
Figure 9: Proportion of type 2 diabetics with macrovascular complications in the seven major markets, 2007 22
Figure 10: Average time for the development of macrovascular complications in the seven major markets, 2007 23
Figure 11: Proportion of type 2 diabetics with serious complications (e.g. end-stage renal disease, acute myocardial infarction, amputation), 2007 25
Figure 12: Treatment algorithm for type 2 diabetes, recommended by the 2006 ADA/EASD clinical practice guidelines 50
Figure 13: Mechanism of action of ACE inhibitors 53