Non-proteinuric pathways in loss of renal function in patients with type 2 diabetes.

Largely on the basis of data from patients with type 1 diabetes, the natural history of diabetic renal disease has been classified as a sequence of three stages: normoalbuminuria, microalbuminuria, and macroalbuminuria. Progressive decline of glomerular filtration rate (GFR) was thought to parallel the onset of macroalbuminuria (overt nephropathy), whereas glomerular hyperfiltration was deemed a hallmark of early disease. However, researchers have since shown that albuminuria is a continuum and that GFR can start to decline before progression to overt nephropathy.

The effects of GLP-1 analogues, DPP-4 inhibitors and SGLT2 inhibitors on the renal system.

Diabetic nephropathy (DN) affects an estimated 20%-40% of patients with type 2 diabetes mellitus (T2DM). Key modifiable risk factors for DN are albuminuria, anaemia, dyslipidaemia, hyperglycaemia and hypertension, together with lifestyle factors, such as smoking and obesity. Early detection and treatment of these risk factors can prevent DN or slow its progression, and may even induce remission in some patients.

Fatty kidney: emerging role of ectopic lipid in obesity-related renal disease.

The global increase in chronic kidney disease (CKD) parallels the obesity epidemic. Obesity conveys a gradual but independent risk of progression of CKD that seems irrespective of the underlying nephropathy. Obesity has been associated with a secondary focal segmental glomerulosclerosis coined obesity-related glomerulopathy (ORG).

Intensive glucose control improves kidney outcomes in patients with type 2 diabetes.

The effect of intensive glucose control on major kidney outcomes in type 2 diabetes remains unclear. To study this, the ADVANCE trial randomly assigned 11,140 participants to an intensive glucose-lowering strategy (hemoglobin A1c target 6.5% or less) or standard glucose control.

Predictors of mortality of patients newly diagnosed with clinical type 2 diabetes: a 5-year follow up study.

Background: At diabetes diagnosis major decisions about life-style changes and treatments are made based on characteristics measured shortly after diagnosis. The predictive value for mortality of these early characteristics is widely unknown. We examined the predictive value of patient characteristics measured shortly after diabetes diagnosis for 5-year all-cause and cardiovascular mortality with special reference to self-rated general health.

Mistakes, misunderstandings and controversies in diabetes: A review and personal account.

A number of controversies in diabetes have had too little attention. I discuss the following issues: (i) drug therapy; (ii) genetics; (iii) antihypertensive treatment in patients with normoalbuminuria and with abnormal albuminuria; (iv) insulin analogs; (v) cancer in diabetes; (vi) hypophysectomy; (vii) renal biopsy; (viii) low protein diet; and (ix) glycated hemoglobin. A closer look at these items is required in order to have a more realistic picture of diabetes research.

Efficacy and safety of routine blood pressure lowering in older patients with diabetes: results from the ADVANCE trial.

Objective: The efficacy and safety of blood pressure lowering in elderly patients have not been sufficiently investigated in patients with diabetes. Using data from the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation study, we assessed the efficacy and safety of routine blood pressure lowering to prevent major clinical outcomes in elderly patients with type 2 diabetes.

Methods: Eleven thousand one hundred and forty patients aged at least 55 years with type 2 diabetes (mean 66+/-6 years) were randomly assigned to perindopril-indapamide or placebo.

[Microalbuminuria].

Microalbuminuria is common in patients with hypertension and even lower levels of albuminuria reflect subclinical cardiovascular damage which is associated with increased cardiovascular risk. Reduction of albuminuria is associated with improved prognosis independently of reduction of blood pressure and regression of left ventricular hypertrophy. Accordingly, albuminuria--an integrated measure of cardiovascular risk--should be monitored and reduced through intensified antihypertensive treatment in combination with careful correction of other cardiovascular risk factors.

Microalbuminuria and short-term prognosis in patients undergoing cardiac surgery.

Objectives: To examine if preoperative microalbuminuria (MA) is associated with in increased risk of adverse outcomes in patients undergoing elective cardiothoracic surgery, and if adding information on MA could improve the accuracy of the additive EuroSCORE.

Methods: In a follow-up study we included 962 patients undergoing elective cardiothoracic surgery from 1 April 2005 to 30 September 2007 at our department. MA (urine albumin/creatinine ratio between 2.

Albuminuria and kidney function independently predict cardiovascular and renal outcomes in diabetes.

There are limited data regarding whether albuminuria and reduced estimated GFR (eGFR) are separate and independent risk factors for cardiovascular and renal events among individuals with type 2 diabetes. The Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study examined the effects of routine BP lowering on adverse outcomes in type 2 diabetes. We investigated the effects of urinary albumin-to-creatinine ratio (UACR) and eGFR on the risk for cardiovascular and renal events in 10,640 patients with available data.

Lowering blood pressure reduces renal events in type 2 diabetes.

BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study.

The management of the type 2 diabetic patient with hypertension - too late and too little: suggested improvements.

Patients with comorbid hypertension and type 2 diabetes are common, have a greatly increased risk of premature cardiovascular and renal morbidity and mortality, and are likely to increase substantially in number over the next 10-15 years. We suggest the need for more aggressive management strategies for these patients, regardless of their baseline blood pressure, including the early use of combination therapy with blockers of the renin-angiotensin system.

Twelve shifting paradigms in diabetic renal disease and hypertension.

In the last 30 years we have seen considerable progress in the management of patients with diabetes, in particular with diabetic renal disease. A number of paradigms have been broken down, namely the following, as a consequence, clinical care has improved dramatically. .

Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.

Background: In patients with type 2 diabetes, the effects of intensive glucose control on vascular outcomes remain uncertain.

Methods: We randomly assigned 11,140 patients with type 2 diabetes to undergo either standard glucose control or intensive glucose control, defined as the use of gliclazide (modified release) plus other drugs as required to achieve a glycated hemoglobin value of 6.5% or less.

Endothelial perturbation: a link between non-dipping and retinopathy in type 2 diabetes?

Reduced diurnal blood pressure (BP) variation ("non-dipping") is associated with both micro- and macrovascular complications in patients with type 2 diabetes. The relation between endothelial perturbation and diurnal BP variation in diabetic subjects has not previously been studied. Seventy-six subjects, stratified to 4 gender-, age-, and duration-matched groups of 19 subjects each, were studied (group A: non-diabetic subjects; group B to D, type 2 diabetic subjects; group B: no retinopathy; group C: minimal background retinopathy; group D: diabetic maculopathy).

The blood pressure-induced diameter response of retinal arterioles decreases with increasing diabetic maculopathy.

Background: The aim of the study was to compare the diameter response of retinal arterioles and retinal thickness in patients with different stages of diabetic maculopathy during an increase in the arterial blood pressure.

Methods: Four groups each consisting of 19 individuals were studied. Group A consisted of normal individuals and groups B-D consisted of type 2 diabetic patients matched for diabetes duration, age, and gender, and characterized by: Group B no retinopathy, Group C mild retinopathy, Group D maculopathy not requiring laser treatment.

Urinary creatinine concentration is inversely related to glycaemic control and the presence of some diabetic complications in patients with newly diagnosed Type 2 diabetes.

Background: The ratio between urinary albumin concentration (UAC) and urinary creatinine concentration (UCC) is widely used to estimate renal involvement. We examined how UAC and UCC associate with each other, with other risk factors, and with diabetic complications in a population-based sample of Type 2 diabetic patients.

Methods: A freshly voided morning urine specimen was provided by 1,284 consecutive, newly diagnosed diabetic patients aged 40 years or over in general practice.

[Vascular impact of anti-hypertensive treatment and renal protection].

Hypertension contributes to the progression of renal disease by accelerating structural changes in the kidney, leading to a progressive decline in glomerular filtration rate. Hypertension and microvascular changes can create a vicious circle, leading to further renal damage and increases in blood pressure. Prevention of renal damage is a priority, especially in the growing number of patients with diabetic hypertension.

Importance of baseline distribution of proteinuria in renal outcomes trials: lessons from the reduction of endpoints in NIDDM with the angiotensin II antagonist losartan (RENAAL) study.

A key issue in the analysis of outcome trials is the adjustment for baseline covariates that influence the primary outcome. Imbalance of an important covariate between treatment groups at baseline is of considerable concern if one treatment group is favored over another with respect to the hypothesis testing outcome. With the use of the Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan (RENAAL) study database as an example, the influence of baseline proteinuria on the primary composite endpoint, ESRD, and ESRD or death after adjusting for baseline proteinuria as a continuous covariate was examined.

Diabetic renal disease in patients with type 2 diabetes mellitus: new strategies for prevention and treatment.

Over the last 35 years an increasing number of patients with type 2 diabetes mellitus have developed advanced renal disease and the need for dialysis. At present in the US, about 50% of the patients in dialysis units have type 2 diabetes mellitus. The explanation for the increase in the number of patients with type 2 diabetes mellitus in end-stage renal disease programs is not completely clear, but the overall number of patients with this type of diabetes is rapidly increasing - and is expected to continue to increase over the next years.