1. Diabetes Mellitus
Hart,
Nieren & Hypertensie

2. Microalbuminurie bij Diabetes

3. Definitions of Microalbuminuria and Macroalbuminuria
Parameter
Normal
Micro-albuminuria
Macro-albuminuria
Urine AER
(g/min)
< 20
>200
(mg/24h)
< 30
>300
Urine albumin/
Cr# ratio (mg/mmol)
< 3
3 - 30
>30
Definitions of Microalbuminuria and Macroalbuminuria
Measurements of urinary albumin are made from either a timed (4 or 24 hours) urine collection or from a randomly voided “spot” urine. In the former case the urinary albumin concentration is divided by the time of the collection (in minutes) calculate the first parameter. In the latter case, both albumin and creatinine concentrations are measured in the same specimen and a ratio of albumin to creatinine calculated. Numerous studies have demonstrated that the values obtained from both timed and randomly collected specimens correlate well and have the same prognostic significance. Measurements of urine protein concentrations by “dipstick” chemistry are not sufficiently sensitive to identify urine albumin concentrations that meet the criteria for microalbuminuria. Protein in the urine is usually a combination of albumin, globulins, and Tamm-Horsfall protein derived from tubular secretion.
References:
Bianchi S, Bigazzi R, Campese VM. Microalbuminuria in essential hypertension: significance, pathophysiology, and therapeutic implications. Am J Kidney Dis. 1999;34(6):
Keane WF. Proteinuria: its clinical importance and role in progressive renal disease. Am J Kidney Dis. 2000;35(4suppl1):S97-S105.
AER=Albumin excretion rate CR# =creatinine

7. Behandeling van Diabetes moet dus in hoge mate zijn gericht op preventie van cardiovasculaire ziekte

8. Treatment Targets for Diabetic Renal Disease With Hypertension
GLUCOSE
GLUCOSE BP BP
Treatment Targets for Diabetic Renal Disease With Hypertension
The results of clinical trials in diabetic patients at increased risk for cardiovascular and renal events suggest that aggressive control of hypertension may be the most cost-effective in reducing these risks, followed, in rank order, by aggressive management of dyslipidemia, and then by tight blood glucose control.
References:
Agarwal R. Treatment of hypertension in patients with diabetes: lessons from recent trials. Cardiol Rev. 2001;9(1):36-44.
UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:
LIPIDS
LIPIDS

9. Meta Analysis: Lower Systolic BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics
SBP (mmHg)
130
134
138
142
146
150
154
170
180 -2
r = 0.69; P < .05 -4 -6
GFR (mL/min/year)
Untreated
HTN -8
-10
Meta Analysis: Lower Systolic BP Results in Slower Rates of Decline in GFR in Diabetics and Non-Diabetics
Like control of mean arterial blood pressure, lower systolic blood pressure results in slower rates of decline in glomerular filtration rate (GFR) in patients with diabetic and non-diabetic renal disease. The beneficial impact from achieved control of systolic blood pressure (SBP) is demonstrated in this slide, which shows a meta-analysis of the 9 major clinical trials in diabetic and non-diabetic renal diseases. The GISEN Group, Klahr, and Moschio studies are those in non-diabetic subjects. The higher the SBP, the faster the GFR declines; the better the control of SBP, the slower the GFR declines.
References:
Bakris GL, Mangrum A, Copley JB, Vicknair N, Sadler R. Effect of calcium channel or beta-blocker on the progression of diabetic nephropathy in African Americans. Hypertension. 1997;29(3):
Bakris GL, Siomos M, Richardson D, et al. Comparative effects of an ACE inhibitor and an angiotensin receptor blocker on potassium homeostasis in high risk patients. Kidney Int. (in press).
Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):
Herbert LA, Bain RP, Verme D, Cattran D, Whittier FC, Tolchin N, Rohde RD, Lewis EJ. Remission of nephrotic range proteinuria in type 1 diabetes. Collaborative Study Group. Kidney Int. 1994;46(6):
Klahr S, Levey AS, Beck GJ, Caggiula AW, Hunsicker L, Kusek JW, Striker G. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal failure. N Eng J Med. 1994;330(13):
Lebovitz HE, Wiegmann TB, Cnaan A, Shahinfar S, Sica DA, Broadstone V, Schwartz SL, Mengel MC, Segal R, Versaggi JA, et al. Renal protective effects of enalapril in hypertensive NIDDM:Role of baseline albuminuria. Kidney Int Suppl. 1994;Suppl 45:
Parving HH, Hommel E, Damkjaer Nielsen M, Giese J. Effect of captopril on blood pressure and kidney function in normotensive insulin dependent diabetics with nephropathy. BMJ. 1989;299(6698):
Randomised placebo-controlled trial of effect of ramipril on decline in glomerular filtration rate and risk of terminal failure in proteinuric, non-diabetic nephropathy. The GISEN group (Gruppo Italiano di Studi Epidemiologici in Nefrologia). Lancet. 1997;349(9069):
Viberti G, Morgensen CE, Groop LC, Pauls JF. Effect of captopril on progression to clinical proteinuria in patients with insulin-dependent diabetes mellitus and microalbuminuria. JAMA. 1994;271(4):
-12
-14
Parving HH, et al. Br Med J Moschio G, et al. N Engl J Med
Viberti GC, et al. JAMA Bakris GL, et al. Kidney Int
Klahr S, et al. N Eng J Med Bakris GL. Hypertension
Hebert L, et al. Kidney Int The GISEN Group. Lancet
Lebovitz H, et al. Kidney Int
Bakris GL, et al. Am J Kidney Dis. 2000;36(3):

10. Behandeling Microalbuminurie bij DM ~ 2e-doel RR: 120-130/<80 mmHg
ACEi met diureticum (eg. Captopril/HCT of Lisinopril/HCT)
2e middel op indicatie (eg. BB bij angina pectoris)
2-3e middel: Spironolacton, (z.n. + kaliumbeperkt dieet of HCT/chloortalidon of sorbisterit)
3-4e middel: Allopurinol

12. Consultatie van of verwijzing naar de tweede lijn is aangewezen bij
twijfel over de diagnose,
problemen bij de glycemische instelling,
problemen bij behandeling van risicofactoren,
het onvoldoende onder controle krijgen van de gevolgen van complicaties
zwangerschap(swens).
LTA DM-II, 2012

13. From Dr J Vora

14. DM-II Losartan verhoogt de incidentie van microalbuminurie
RR-verlaging < 120 mmHg systolisch induceert meer sterfte
Vitamine-D vermindert microalbuminurie
Intensieve behandeling hyperglycemie in de initiële fase van DM-I/II reduceert nefropathie en CVR
Mortaliteit stijgt bij HbA1c > 85 en < 42 mmol/mol
Intermitterende episodes van acute nierinsufficientie verslechteren de lange termijn prognose

15. Allopurinol initiation and all-cause mortality in the general population
Results Of 5927 allopurinol initiators and 5927 matched comparators, 654 and 718, respectively, died during the follow-up (mean=2.9 years). The baseline characteristics were well balanced in the two groups, including the prevalence of gout in each group (84%). Allopurinol initiation was associated with a lower risk of all-cause mortality (matched HR 0.89 (95% CI 0.80 to 0.99)). When we limited the analysis to those with gout, the corresponding HR was 0.81 (95% CI 0.70 to 0.92).
annrheumdis

16. Urinezuur is een cardiovasculaire risicofactor

17. Allopurinol bij DM Vermindert insuline resistentie Verlaagt CRP
Vertraagt Atherosclerose
Vermindert Microalbuminurie
Vermindert Chronische nierschade
Vermindert Linkerventrikelhypertrofie
Vermindert Oxidatieve stress

18. Allopurinol risico’s Acute allergische reactie 4,7 promille
Gerelateerde mortaliteit 0,4 promille
Heupfractuur Odds Ratio (OR) 1,07
Lager risico op Hartinfarct: OR 0,73 OR 0,52, dosis en duur afhankelijk
Atriumfibrilleren: OR 0,73
JAMA Intern Med. 2015;175(9):1550.
Archives of Osteoporosis , 10:36
annrheumdis
heartjnl
annrheumdis-2012

19. Metformine

20. Metformine risico’s Bij eGFR<15: Mortaliteit OR 1,35
Lactaat acidose 1,6 vs 1,3/100jaar (n.s.)
Bij eGFR > 30 ml/min/1,73m2: nuttig en veilig
Bij eGFR ml/min/1,73m2: waarschijnlijk nuttig en veilig.

21. Effectiveness and safety of metformin in patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register.
BMJ Open Jul 13;2(4).

23. Verschillen tussen ACE-remmers

24. CV Mortality in General Population (GP) & Dialysis Patients, By Race
CV Mortality in General Population (GP) and Dialysis Patients, by Race
These data provide preliminary information on the excess of cardiovascular disease (CV) mortality in end stage renal disease (ESRD) as compared to the general population. In this slide, cardiovascular mortality is defined by death due to arrhythmias, cardiomyopathy, cardiac arrest, myocardial infarction, atherosclerotic heart disease, and pulmonary edema in the general population (GP) [from the National Center for Health Statistics, ICD9 codes 402, 404, 410–414, and 425–429, 1993] compared to ESRD treated by dialysis (US Renal Data System special data request HCFA Form 2746 numbers 23, 26–29, and 31, ). Data are stratified by age, race, and gender. After stratification for age, CVD mortality remains 10 times higher in the dialysis population as compared to the general population, even in the older age groups. Although diabetes is a risk factor in each group, CVD mortality in diabetic patients on dialysis (not shown here) is much higher than in diabetic patients in the general population.
References:
Foley RN, Parfrey PS, Sarnak M. Clinical epidemiology of cardio-vascular disease in chronic renal disease. Am J Kidney Dis. 1998;32(Suppl):S112–S115.
Sarnak MJ, Levey AS. Epidemiology of Cardiac Disease in Dialysis Patients. Semin Dial. 1999;12:69-76.
Sarnak MJ, Levey AS. Semin Dial. 1999;12:69-76.

25. Tot slot, praktisch:

26. Mijn behandelingsstrategie bij: diabetes + chronische nierziekte (≥ microalbuminurie) ± hypertensie
≥3x1uur bewegen/week; roken -; gewicht ; voeding.
Bloeddruk ≤125/75 mmHg
Start met een ACE-remmer, liefst een combinatiepil met een lage dosis diureticum !
+/-Zoutarm dieet (<6 g NaCl/d)
Doseren totdat proteinuria ≤ 0,5 g/dag is
Behandel dislipidemie (LDL <2,5 mmol/L, Trigl ≤ 2,0)
HbA1C < 60 mm/m P C Chang, RZZ
Management of HTN and Chronic Renal Disease (CRD) in Diabetics
The management of hypertension and chronic renal disease in diabetics should be even more aggressive than in the non-diabetic. The goal of anti-hypertensive therapy should be blood pressure values <130/80 mmHg, except in those diabetics who have > 1gm/day of proteinuria. In the latter patients, the goal blood pressure should be <125/75 mmHg. Multiple anti-hypertensive drugs will usually be required to achieve these blood pressure goals. Drugs or drug combinations that are most effective in reducing or abolishing proteinuria should be used, and the doses modified based on frequent determination of urine protein, until the desired effect is achieved. Effective risk factor management of diabetics also includes control of hyperlipidemia and hyperglycemia. Modest dietary protein restriction is recommended for the hypertensive diabetic whose creatinine clearance is already diminished. Sodium restriction is indicated in patients with CRD and impaired ability to excrete sodium. Smoking cessation is key to successful cardiovascular risk reduction.

27. UKPDS: Relationship Between BP Control And Diabetes-Related Deaths
17% decrease per 10 mmHg decrement in BP
p<0.0001 . 5 1 2 3 4 6 7
Hazard ratio
UKPDS: Relationship Between BP Control And Diabetes-Related Deaths
In patients with type 2 diabetes, the risk of diabetic complications is strongly associated with raised blood pressure. UKPDS determined the relationship over time between systolic blood pressure and the risk of macrovascular or microvascular complications in patients with type 2 diabetes. This was a prospective observational study in 23 hospital-based clinics in England, Scotland, and Northern Ireland. There were 4801 white, Asian Indian, and Afro-Caribbean UKPDS patients included in analyses of incidence and 3642 were included in analyses of relative risk. The primary predefined aggregate clinical outcome was any complications or deaths related to diabetes and all cause mortality. Secondary aggregate outcomes were myocardial infarction, stroke, lower extremity amputation (including death from peripheral vascular disease), and microvascular disease (predominantly retinal photocoagulation). Risk reduction associated with a 10 mmHg decrease in updated mean systolic blood pressure adjusted for specific confounders. The incidence of clinical complications was significantly associated with systolic blood pressure, except for cataract extraction. Each 10 mmHg decrease in updated mean systolic blood pressure was associated with reductions in risk of 12% for any complication related to diabetes (95% confidence interval 10% to 14%, P<0.0001), 17% for deaths related to diabetes (12% to 18%, P<0.0001), 11% for myocardial infarction (7% to 14%, P<0.0001), and 13% for microvascular complications (10% to 16%, P<0.0001). No threshold of risk was observed for any end point. Any reduction in blood pressure is likely to reduce the risk of complications, with the lowest risk being in those with systolic blood pressure <120 mmHg.
Reference:
Adler AI, Stratton IM, Neil HA, Yudkin JS, Matthews DR, Cull CA, Wright AD, Turner RC, Holman RR. Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study. BMJ. 2000; 321(7258):  
Mean systolic blood pressure (mmHg)
Adler AI, et al. BMJ. 2000;321:
Reprinted by permission, BMJ Publishing Group.

28. Risk of Ischemic Heart Disease Related to SBP and Microalbuminuria
N=2,085; 10 year follow-up
Risk of Ischemic Heart Disease Related to SBP and Microalbuminuria
The purpose of this study was to analyze prospectively whether the urinary albumin-to-creatinine (A/C) ratio could independently predict ischemic heart disease (IHD) in a population-based cohort. In 1983, urinary albumin and creatinine levels were measured, along with the conventional atherosclerotic risk factors, in 2,085 consecutive participants without IHD, renal disease, urinary tract infection, or diabetes mellitus. The participants were followed up until death, emigration, or December 31, IHD was identified by hospital diagnosis or listed as a cause of death. Seventy-nine individuals developed IHD. Microalbuminuria (MA) was defined as an A/C ratio >90 percentile (>0.65 mg/mmol). When adjusted for other risk factors, the relative risk of IHD associated with MA was 2.3 (95% CI, 1.3 to 3.9, p=0.002), and the 10-year disease-free survival decreased from 97% to 91% (p<0.0001) when MA was present. An interaction between MA and smoking was observed, and the presence of MA more than doubled the predictive effect of the conventional atherosclerotic risk factors for development of IHD. It is concluded that MA is not only an independent predictor of IHD but also substantially increases the risk associated with other established risk factors.
Reference:
Borch-Johnsen K, Feldt-Rasmussen B, Strandgaard S, Schroll M, Jensen JS. Urinary albumin excretion. An independent predictor of ischemic heart disease. Arterioscler Thromb Vasc Biol. 1999;19(8):
Borch-Johnsen K, et al.
Arterioscler Thromb Vasc Biol. 1999;19(8):

29. Relative Importance of CV Risk Factors in Diabetes12
10.0 10 8
6.5
Odds Ratio 6
3.2
Key Fact:
In people with diabetes, smoking is a greater risk factor than diastolic BP or cholesterol levels. It is superseded by microalbuminuria which is an indicator of generalized vascular inflammation and the early sign of endothelial dysfunction.
Routine screening for this prognostic indicator is recommended in patients at risk. 4
2.3 2
Microalbuminuria
Smoking
Diastolic BP
Cholesterol
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.

30. Diabetes and Chronic Renal Disease as CV Risk

31. Behandeling van Diabetes moet dus in hoge mate zijn gericht op preventie van cardiovasculaire ziekte

32. Cardiovasculaire Preventie in Diabetes
The concept of vascular protection has been highlighted in the most recent publication of the guidelines by the Canadian Diabetes Association (CDA). The importance of vascular protection in patients with diabetes is related to the outcome data: cardiovascular events determine morbidity and mortality to a large extent and therefore prevention of these is of the greatest importance.

33. Vascular Protection: Glycaemic Control

34. Glycaemic Control for Vascular Protection:
after all Patients are on ACE Inhibitor, ASA and Lipid Control (statin) 5
Fatal and Non -
Fatal Myocardial Infarction
14% decrease per 1% decrement in HbA1c
p<0.0001
CDA 2003 Glycaemic Targets
A1c  7% for most patients
A1c  6% when safely achievable
Hazard ratio
Glycaemic Control and Macrovascular Complications (Summary Slide)
The CDA guidelines recommend an A1c target of  7% for most patients. A1c levels > 7% are associated with a significantly increased risk of both microvascular and macrovascular complications, regardless of underlying treatment.
Secondary analyses from the DCCT and the UKPDS (as shown here) demonstrated a continuous relationship between A1c and diabetes complications, with no apparent threshold of benefit. In the UKPDS, this relationship was linear, with each 1.0% absolute reduction in mean A1c being associated with a 14% lower rate of myocardial infarctions.
The CDA guidelines therefore recommend an A1c target  6.0% when reasonably and safely achievable, considering in particular the risk of severe hypoglycaemia. 1 . 5 5 6 7 8 9 1 1 1
Updated mean HbA1c
UKPDS 35. BMJ 2000; 321:

35. Vascular Protection: Diabetes and Control of Hypertension

36. Treatment Targets for Diabetic Renal Disease With Hypertension
GLUCOSE
GLUCOSE BP BP
Treatment Targets for Diabetic Renal Disease With Hypertension
The results of clinical trials in diabetic patients at increased risk for cardiovascular and renal events suggest that aggressive control of hypertension may be the most cost-effective in reducing these risks, followed, in rank order, by aggressive management of dyslipidemia, and then by tight blood glucose control.
References:
Agarwal R. Treatment of hypertension in patients with diabetes: lessons from recent trials. Cardiol Rev. 2001;9(1):36-44.
UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:
LIPIDS
LIPIDS

37. CV Mortality Risk Doubles with Each 20/10 mm Hg BP Increment*
SBP/DBP (mm Hg) 1 2 3 4 5 6 7 8
115/75
135/85
155/95
175/105
*Individuals aged years, starting at BP 115/75 mm Hg.
CV, cardiovascular; SBP, systolic blood pressure; DBP, diastolic blood pressure
Lewington S, et al. Lancet. 2002; 60:
JNC VII. JAMA

38. Goal BP Recommendations for Patients with DM or Renal Disease
Organization
Year
Systolic BP
Diastolic BP
American Diabetes Association
2001
<130
<80
National Kidney Foundation
2000
Canadian Hypertension Society
1999
British Hypertension Society
<140
WHO & International
Society of Hypertension
<85
Joint National Committee
(JNC VI)
1997
Goal BP Recommendations for Patients with DM or Renal Disease
Since 1997, 6 international organizations have revised their recommendations for goal blood pressures in diabetes mellitus and renal diseases. Randomized clinical trials and observational studies have demonstrated the importance of blood pressure control to the level of 140/80 down to 125/75 mmHg. The National Kidney Foundation, the American Diabetes Association, and the Canadian Hypertension Society have developed consensus guidelines for blood pressure control to <130/80 mmHg.
References:
American Diabetes Association: Standards of medical care for patients with diabetes mellitus. Diabetes Care. 2001;24(suppl1):33-66.
Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M, Toto R et al. Preserving renal function in adults with hypertension and diabetes: a consensus approach. National Kidney Foundation Hypertension and Diabetes Executive Committees Working Group. Am J Kidney Dis. 2000;36(3):
Ramsay L, Williams B, Johnston G, MacGregor G, Poston L, Potter J, Poulter N, Russell G. Guidelines for management of hypertension: report of the third working party of the British Hypertension Society. J Hum Hypertens. 1999;13(9):
Feldman RD, Campbell N, Larochelle P, Bolli P, Burgess ED, Carruthers SG, Floras JS, Haynes RB, Honos G, Leenen FH, Leiter LA, Logan AG, Myers MG, Spence JD, Zarnke KB Canadian recommendations for the management of hypertension. Task Force for the Development of the 1999 Canadian Recommendations for the Management of Hypertension. CMAJ 1999;161(suppl12):S1-17.
Chalmers J, MacMahon S, Mancia G, Whitworth J, Beilin L, Hansson L et al World Health Organization-International Society of Hypertension Guidelines for the management of hypertension. Guidelines sub-committee of the World Health Organization. Clin Exp Hypertens. 1999;21(5-6):
The sixth report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Arch Intern Med 1997; 157(21):
Renal Disease & Proteinuria >1g
(JNC VI)
125 75

39. From Dr J Vora

40. Management of Chronic Renal Disease: Initial Diet Therapy
For patients with modest renal insufficiency, reduce intake of high biological quality protein* intake of 1 gm/kg body weight/day
For patients with marked renal insufficiency, reduce dietary protein intake to 0.8 gm/kg body weight/day
Restrict dietary sodium intake to 4-6 gm/day
Avoid foods rich in potassium
Management of Chronic Renal Disease: Initial Diet Therapy
These are the recommendations of the National Kidney Foundation for diet therapy of patients with chronic renal disease.
Source: National Kidney Foundation
*high biological quality proteins are those rich in essential amino acids

41. Impact of Blood Pressure Reduction on Mortality in Diabetes
Trial
Conventional
care
Intensive
Risk
reduction
P-value
UKPDS
154/87
144/82
32%
0.019
HOT
144/85
140/81
66%
0.016
Impact of Blood Pressure Reduction on Mortality in Diabetes
Additional support for CV risk reduction in diabetes related to lower ranges of blood pressure values comes from two recent prospective trials. The Hypertension Optimal Treatment (HOT) trial was the first to show the benefit of a lower blood pressure goal in reducing CV events in the subgroup of people with diabetes. In this study, 1,501 diabetic patients were randomized to one of three diastolic blood pressure targets: <90 mmHg, <85 mmHg, or <80 mmHg. Initial anti-hypertensive therapy in this group was with the calcium channel blocker, felodipine; however, 73% of the people randomized to the lowest blood pressure group required approximately 2.7 different anti­hypertensive medications, and most participants in this group also received an ACE inhibitor. Those who achieved the lowest blood pressure goal experienced the lowest rate of CV events. The United Kingdom Prospective Diabetes Study (UKPDS) was the second study to show the long-term benefit of a lower-than-usual blood pressure goal for people with diabetes. In this study, 1,148 type 2 diabetics were randomized to one of two goal blood pressures [<150/85 mmHg (intensively treated group) or <180/105 mmHg (conventional group)]. Average blood pressures for both groups are shown on this slide. The differences were 5 mmHg in diastolic pressure and 10 mmHg in systolic pres­sure. Follow-up was an average of 8.4 years. Those randomized to the intensively treated group had 32% fewer deaths, 44% fewer strokes, 24% fewer diabetes-related endpoints (including amputations), and 37% fewer microvascular complications (including retinal hemorrhages). In the HOT trial, there was also a 4-mmHg difference in the achieved diastolic blood pres­sure between the intensively treated group and other target groups (84.6 versus 81 mmHg). However, these small reductions in blood pressure in both trials resulted in a significantly lower CV event rate and a greater preservation of renal function.
References:
Hansson L, Zanchetti A, Carruthers SG, Dahlof B, Elmfeldt D, Julius S, Menard J, Rahn KH, Wedel H, Westerling S. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. HOT Study Group. Lancet 1998;351(9118):
Efficacy of atenolol and captopril in reducing risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 39. UK Prospective Diabetes Study Group. BMJ 1998;317(7160):
Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group. BMJ. 1998;317(7160):  
Mortality endpoints are:
UK Prospective Diabetes Study (UKPDS) – “diabetes related deaths”
Hypertension Optimal Treatment (HOT) Study – “cardiovascular deaths” in diabetics
Turner RC, et al. BMJ. 1998;317:
Hansson L, et al. Lancet. 1998;351:1755–1762.

42. Diabetes and Hypertension
3.0%
No DM
2.0% DM
Annual
Mortality
1.0%
Hypertension is a frequent co-morbid condition in patients with diabetes. As this slide demonstrates, increase in systolic BP is linearly related to mortality. Moreover, in the setting of diabetes this relationship becomes even more important, thus highlighting the need for comprehensive approach towards management of all risk factors in patients with diabetes as recommended by CDA.
0.0%
<120
120-
140-
160-
180-
>200
139
159
179
199
Systolic BP
Stamler J, et al, Diabetes Care, 1993;16(2):

43. Treatment Targets for Diabetic Renal Disease With Hypertension
GLUCOSE
GLUCOSE BP BP
Treatment Targets for Diabetic Renal Disease With Hypertension
The results of clinical trials in diabetic patients at increased risk for cardiovascular and renal events suggest that aggressive control of hypertension may be the most cost-effective in reducing these risks, followed, in rank order, by aggressive management of dyslipidemia, and then by tight blood glucose control.
References:
Agarwal R. Treatment of hypertension in patients with diabetes: lessons from recent trials. Cardiol Rev. 2001;9(1):36-44.
UK Prospective Diabetes Study Group: Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMJ. 1998;317:
LIPIDS
LIPIDS