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The incidence and prevalence of diabetes mellitus (DM) continue to grow markedly throughout the world, due primarily to the increase in type 2 DM (T2DM). Although improvements in DM and hypertension management have reduced the proportion of diabetic individuals who develop chronic kidney disease (CKD) and progress to end-stage renal disease (ESRD), the sheer increase in people developing DM will have a major impact on dialysis and transplant needs. This KDIGO conference addressed a number of controversial areas in the management of DM patients with CKD, including aspects of screening for CKD with measurements of albuminuria and estimated glomerular filtration rate (eGFR); defining treatment outcomes; glycemic management in both those developing CKD and those with ESRD; hypertension goals and management, including blockers of the renin–angiotensin–aldosterone system; and lipid management.

Muscle Strength in Type 2 Diabetes Henning Andersen 1 , Søren Nielsen 2 , Carl E. Mogensen 2 and Johannes Jakobsen 1 1 Department of Neurology, Aarhus University Hospital, Aarhus, Denmark 2 Medical Department M (Endocrinology and Diabetes), Aarhus University Hospital, Aarhus, Denmark Address correspondence and reprint requests to Henning Andersen, MD, Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, 8000 Aarhus C, Denmark. E-mail: hande{at}akh.aaa.dk Abstract Motor function in type 2 diabetes is largely unknown. In 36 type 2 diabetic patients and in 36 control subjects matched for sex, age, weight, height, and physical activity, strength of flexors and extensors at elbow, wrist, knee, and ankle was assessed at isokinetic dynamometry. The degree of neuropathy was determined by clinical scores, nerve conduction studies, and quantitative sensory testing. Eventually, all results were summed to obtain a neuropathy rank-sum score (NRSS). The degree of nephropathy and retinal condition were also evaluated. Diabetic patients had a 17 and 14% reduction of strength of ankle flexors ( P < 0.02) and ankle extensors ( P < 0.03), respectively. At the knee, strength of extensors and flexors was reduced by 7% (NS) and 14% ( P < 0.05), respectively. At the elbow and wrist, muscle strength was preserved. The NRSS was related to the strength at the ankle ( r = −0.45, P < 0.01) and knee ( r = −0.42, P < 0.02). Following multiple regression analysis, the NRSS but not the degree of nephropathy or retinopathy was related to strength at the ankle and knee. In conclusion, type 2 diabetic patients may have muscle weakness at the ankle and knee related to presence and severity of peripheral neuropathy. CMAP, compound muscle action potential MNCV, motor nerve conduction velocity NDS, neurological disability score NRSS, neuropathy rank-sum score NSS, neuropathy symptom score SNAP, sensory nerve action potential SNCV, sensory nerve conduction velocity VPT, vibration perception threshold Footnotes Accepted March 15, 2004. Received January 7, 2004. DIABETES

Macular Edema Reflects Generalized Vascular Hyperpermeability in Type 2 Diabetic Patients With Retinopathy Søren T. Knudsen , MD, PHD 1 , Toke Bek , MD, DMSC 2 , Per L. Poulsen , MD, PHD 1 , Marianne N. Hove , MD 2 , Michael Rehling , MD, DMSC 3 and Carl E. Mogensen , MD, DMSC 1 1 Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, Aarhus, Denmark 2 Department of Ophthalmology, Aarhus Kommunehospital, Aarhus, Denmark 3 Department of Clinical Physiology and Nuclear Medicine, Aarhus Kommunehospital, Aarhus, Denmark Abstract OBJECTIVE —Diabetic maculopathy (DMa) is the most prevalent sight-threatening type of retinopathy in type 2 diabetes and a leading cause of visual loss in the western world. The disease is characterized by hyperpermeability of retinal blood vessels and subsequent formation of hard exudates and macular edema, the degree of which can be estimated by measurement of retinal thickness. We examined associations between retinal thickness as evaluated by optical coherence tomography scanning (OCT), glomerular leakage as evaluated by urinary albumin excretion rate (UAE), and general vascular leakage as evaluated by the transcapillary escape rate of albumin (TER alb ) in type 2 diabetic patients with and without DMa. RESEARCH DESIGN AND METHODS —In 20 type 2 diabetic patients with DMa and 20 type 2 diabetic patients without retinopathy matched for age, sex, and duration of diabetes, we performed OCT, fundus photography, fluorescein angiography, and 24-h ambulatory blood pressure measurement. UAE was determined by radioimmunoassay. TER alb was determined as the initial disappearance of intravenously injected 125 I-labeled human serum albumin. RESULTS —Patients with diabetic maculopathy had higher HbA 1c (8.5 ± 1.5 vs. 7.4 ± 1.2%, P < 0.05) and higher total cholesterol (5.8 ± 0.7 vs. 5.2 ± 0.9 mmol/l, P < 0.05) than patients without retinopathy. UAE was higher in the DMa group than in the group with no retinopathy (9.3 ×/÷ 3.1 vs. 3.9 ×/÷ 1.9 μg/min, P < 0.01). There was no difference in TER alb between the two groups (6.0 ± 1.6 vs. 6.6 ± 1.5%, NS). In the group with DMa, OCT, TER alb , and UAE correlated significantly (OCT versus TER alb : r = 0.55, P < 0.05; OCT versus UAE: r = 0.58, P < 0.01; UAE versus TER alb : r = 0.81, P < 0.01). Conversely, there were no correlations between these three parameters in the group without retinopathy. CONCLUSIONS —Macular edema seems to reflect a generalized vascular leakage in type 2 diabetic patients. AMBP, 24-h ambulatory blood pressure BP, blood pressure DMa, diabetic maculopathy OCT, optical coherence tomography scanning TERalb, transcapillary escape rate of albumin UAE, urinary albumin excretion Footnotes Address correspondence and reprint requests to Søren Tang Knudsen, Medical Department M (Diabetes & Endocrinology), Aarhus Kommunehospital, DK-8000 Aarhus C, Denmark. E-mail: stk{at}dadlnet.dk . Received for publication 30 January 2002 and accepted in revised form 23 August 2002. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances. DIABETES CARE

No detailed description available for \"Prevention and Treatment of Diabetic Late Complications\".

OBJECTIVE:--Our current aims were to investigate whether 1) baseline urinary albumin-to-creatinine ratio (UACR) predicted cardiovascular outcomes, 2) changes in UACR differed between treatments, 3) benefits of losartan were related to its influence on UACR, and 4) reduction in albuminuria reduced cardiovascular events. RESEARCH DESIGN AND METHODS--In 1,063 patients with diabetes, hypertension, and left ventricular hypertrophy, UACR was measured for a mean of 4.7 years. The primary composite end point included cardiovascular death, myocardial infarction, and stroke. Cox models were run including and excluding baseline and time-varying UACR. RESULTS:--Increasing baseline albuminuria related to increased risk for cardiovascular events. Reductions in UACR at years 1 and 2 were [approximately]33% for losartan vs. 15% for atenolol (P < 0.001). Benefits of losartan seem to be most prominent in patients with the highest level of baseline UACR, although treatment by albuminuria interaction was only significant for total mortality. Approximately one-fifth of the superiority of losartan was explained by the greater reduction of albuminuria. Risk of the primary end point was related to the in-treatment UACR. CONCLUSIONS:--Lowering of albuminuria in patients with hypertension and diabetes appears to be beneficial and should be the subject of additional study in future clinical trials.

OBJECTIVE:--To assess and compare the long-term effects of the combination of candesartan and lisinopril with high-dose lisinopril on systolic blood pressure in patients with hypertension and diabetes. RESEARCH DESIGN AND METHODS--This was a prospective, randomized, parallel-group, double-blind, double-dummy study with a 12-month follow-up. Drug therapy was either lisinopril 40 mg once daily or dual-blockade treatment with candesartan 16 mg once daily and lisinopril 20 mg once daily. The study comprised 75 type 1 and type 2 diabetic patients aged 35-74 years. The main outcome measures were seated and 24-h ambulatory systolic blood pressure. RESULTS:--Reduction in systolic blood pressure (24-h systolic blood pressure) reduction was obtained in both treatment arms (mean reduction at final follow-up: dual blockade 6 mmHg vs. lisinopril 2 mmHg), but no significant difference was found between dual-blockade and lisinopril 40 mg once daily (P = 0.10). Both treatments were generally well tolerated, and similar low rates of side effects were found in the two groups. CONCLUSIONS:--There was no statistically significant difference between lisinopril 40 mg once daily and lisinopril 20 mg in combination with candesartan 16 mg once daily in reducing systolic blood pressure in hypertensive patients with diabetes.

In summary, 18 weeks of low-dose simvastatin treatment reduced circulating OPG levels in type 2 diabetic patients with microalbuminuria but had no effect on VCAM-1 or ICAM.

Albuminuria, reflecting systemic microvascular damage, and left ventricular (LV) geometric abnormalities have both been shown to predict increased cardiovascular morbidity and mortality. However, the relationship between these markers of cardiovascular damage has not been evaluated in a large hypertensive population. The urine albumin/creatinine ratio (UACR) and echocardiographic measures of LV structure and function were obtained in 833 patients with stage I to III hypertension and LV hypertrophy determined by electrocardiogram (ECG) (Cornell voltage-duration or Sokolow-Lyon voltage criteria) after 14 days of placebo treatment. Patients' mean ages were 66 years, 42% were women, 23% had microalbuminuria, and 5% had macroalbuminuria. Patients with eccentric or concentric LV hypertrophy had higher prevalences of microalbuminuria (average 26%-30% vs 9%, P <.001) and macroalbuminuria (6%-7% vs <1%, P <.001). Furthermore, patients with microalbuminuria and macroalbuminuria had a significantly higher LV mass and lower endocardial and midwall fractional shortening. Patients with abnormal diastolic LV filling parameters had a significantly increased prevalence of microalbuminuria. In univariate analyses, UACR correlated positively to LV mass, systolic blood pressure, age (all P <.001) and pulse pressure/stroke volume and negatively to relative wall thickness (both P <.01) and endocardial (P <.05) and midwall shortening (P <.001) but not to diastolic filling parameters. In multiple regression analysis higher UACR was associated with higher LV mass (beta=.169, P <.001) independently of older age (beta =.095, P <.01), higher systolic pressure (beta=.163), black race (beta=.186), and diabetes (beta=.241, all P <.001). In hypertensive patients with ECG LV hypertrophy, abnormal LV geometry and high LV mass are associated with high UACR independent of age, systolic blood pressure, diabetes, and race, suggesting parallel cardiac and microvascular damage.

Multicenter evaluation of the Micral-Test II test strip, an immunologic rapid test for the detection of microalbuminuria. C E Mogensen , G C Viberti , E Peheim , D Kutter , C Hasslacher , W Hofmann , R Renner , M Bojestig , P L Poulsen , G Scott , J Thoma , J Kuefer , B Nilsson , B Gambke , P Mueller , J Steinbiss and K D Willamowski Medical Department M, Kommunehospital, Aarhus, Denmark. Abstract OBJECTIVE: To assess the performance of the Micral-Test II immunologic test strip for the detection of microalbuminuria, a multicenter evaluation in eight European study sites was performed. RESEARCH DESIGN AND METHODS: Using both the Micral-Test II test strip and the routine method for the determination of albumin concentration, we investigated 2,228 urine samples from diabetic patients. Additionally, interperson variability, color stability, and possible interfering factors (temperature, pH, leucocyturia, erythrocyturia, and drugs) were tested. RESULTS: For a cutoff concentration of 20 mg/l with respect to the routine methods, a sensitivity of 96.7% and a specificity of 71% were calculated for the Micral-Test II test strip. The negative predictive value was 0.95, and the positive predictive value was 0.78, with a prevalence of positive samples (laboratory method) of 52%. The interperson variability of color interpretation showed 93% concordant readings. The interference study showed an influence of oxytetracycline, leading to higher readings. There was no interference from pH. A sample temperature of < 10 degrees C led to lower readings. In the case of samples with massive leucocyturia and erythrocyturia that may delete the chromatographic process, waiting an additional 1-2 min is needed before reading. CONCLUSIONS: The results of the multicenter evaluation show that the Micral-Test II test strip permits an immediate and reliable semiquantitative determination of low albumin concentrations in urine samples with an almost user-independent color interpretation.

In a follow-up study of patients with type 2 diabetes, mortality benefits in those originally assigned to antihypertensive therapy were evident at the end of follow-up, but in-trial glucose differences did not result in long-term benefits in mortality or macrovascular events. Post-trial follow-up studies involving patients with diabetes have previously shown long-term beneficial effects of earlier periods of intensive glucose control, but not blood-pressure lowering, on a range of outcomes, including mortality and macrovascular events. 1 – 3 The Epidemiology of Diabetes Interventions and Complications (EDIC) study, an extension of the Diabetes Control and Complications Trial (DCCT) involving young patients with type 1 diabetes and no history of cardiovascular disease, hypertension, or hypercholesterolemia, showed a lower risk of macrovascular events, as well as a sustained benefit with respect to microvascular complications, beyond the period of intensive glucose control. 1 The post-intervention follow-up of the . . .