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Mounting evidence indicates that adverse activation of the complement system plays a role in the development of diabetic vascular complications. Plasma levels of the complement proteins mannan-binding lectin (MBL) and its associated serine proteases (MASP-1 and MASP-2) are elevated in diabetes. We hypothesized that single nucleotide polymorphisms (SNPs) in the MASP1 gene may contribute to altered plasma levels of the belonging gene products; MASP-1, MASP-3 and mannan-binding lectin-associated protein of 44 kDa (MAp44) in patients with type 2 diabetes. To investigate this, we compared plasma levels of MASP-1, MASP-3 and MAp44 in 100 patients with type 2 diabetes and 100 sex- and age-matched controls. Ten carefully selected SNPs were analysed using TaqMan® genotyping assay. Additionally, we included a streptozotocin-induced diabetes mouse model to directly examine the effect of inducing diabetes on MASP-1 levels. MASP-1 levels were significantly higher among patients with type 2 diabetes compared with healthy controls ( P = 0·017). Five SNPs (rs874603, rs72549254, rs3774275, rs67143992, rs850312) in the MASP1 gene were associated with plasma levels of MASP-1, MASP-3 and MAp44. In the diabetes mouse model, diabetic mice had significantly higher MASP-1 levels than control mice ( P = 0·003). In conclusion, MASP-1 levels were higher among patients with type 2 diabetes and diabetic mice. The mechanism behind this increase remains elusive. [ABSTRACT FROM AUTHOR]

AIMS: Several studies have indicated that low physical activity is associated with increased risk of cardiovascular disease (CVD) and all-cause mortality among patients with diabetes. The association between physical activity and subclinical cardiovascular changes preceding clinical events remains to be elucidated. We investigated the relationship between physical activity and arterial stiffness, an independent predictor of CVD, in patients with type 2 diabetes and controls. METHODS: We included 100 patients with type 2 diabetes and 100 sex- and age-matched controls in a cross-sectional study. Arterial stiffness (carotid-femoral pulse wave velocity, cfPWV) was measured using the SphygmoCor device (AtCor Medical, Sydney, Australia). Physical activity was assessed by an accelerometer (counts per minute (cpm), Actiheart (CamNtech, Cambridge, UK)) worn by the participants for up to 6 days. High vs. low levels of physical activity was defined according to the median level of activity (cpm = 31). RESULTS: Sixty-five patients and 65 controls were included in the final analysis (median age 59 years, 55% men, median diabetes duration 1.9 years). Participants with low physical activity had higher cfPWV compared to participants with high physical activity: (i) Patients and controls combined: 9.3±1.7 m/s vs. 7.8±1.5 m/s, P < 0.001; (ii) Patients with diabetes: 9.5±1.8 m/s vs. 8.3±1.6 m/s, P = 0.02 and C) Controls: 9.0±1.4 m/s vs. 7.7±1.4 m/s, P < 0.01). The difference remained significant after adjustment for other determinants of cfPWV including whole body fat percentage (P < 0.01). No significant interaction between diabetes and the effect of low activity was seen. CONCLUSIONS: Low physical activity is associated with increased arterial stiffness in patients recently diagnosed with type 2 diabetes and in healthy controls. [ABSTRACT FROM AUTHOR]

BACKGROUND The SphygmoCor is used for noninvasive assessment of ascending aortic blood pressure (BP). However, the validity of the SphygmoCor transfer function has not been tested in an exclusively type 2 diabetic patient sample. Calibration with systolic (SBP) and diastolic (DBP) brachial BP has previously been associated with substantial imprecision of central BP estimates. We hypothesized that different noninvasive calibration strategies might improve the accuracy of the estimated ascending aortic BPs. METHODS In 34 patients with type 2 diabetes we estimated ascending aortic SBP and DBP using the SphygmoCor device and compared these data with invasively recorded data. The validity of the transfer function was assessed by calibrating with invasively recorded DBP and mean BP (MBP). The influence of noninvasive calibration strategies was assessed by calibrating with brachial oscillometric SBP+DBP vs. DBP+MBP using a form factor (ff) of 0.33 and 0.40, respectively. RESULTS When calibrating with invasive BP, the difference between estimated and invasively measured ascending aortic SBP and DBP was −2.3±5.6/1.0±0.9mm Hg. When calibrating with oscillometric brachial BPs, the differences were −9.6±8.1/14.1±6.2 mm Hg (calibration with SBP and DBP), −8.3±11.7/13.9±6.1 mm Hg (DBP and MBP; ff = 0.33), and 1.9±12.2/14.1±6.2 mm Hg (DBP and MBP; ff = 0.40), respectively. Calibration with the average of 3 brachial BPs did not improve accuracy. CONCLUSIONS The SphygmoCor transfer function seems valid in patients with type 2 diabetes. Noninvasive calibration with DBP and MBP (ff = 0.40) enables accurate estimation of mean ascending aortic SBP at the group level. However, the wide limits of agreement indicate limited accuracy in the individual patient. CLINICAL TRIALS REGISTRATION Clinical Trials No. NCT01538290. [ABSTRACT FROM PUBLISHER]

Aims To evaluate physical activity in people with newly diagnosed Type 2 diabetes using objective measures. Methods We analysed data from a study aimed at assessing carotid femoral pulse wave velocity in which a piezoelectric accelerometer was worn by 100 people with newly diagnosed Type 2 diabetes and by 100 age- and sex-matched control subjects. Differences in physical activity patterns were investigated. Results Compared with the control group, the people with Type 2 diabetes spent significantly more time engaged in sedentary or lower level activities during the day, with a mean ( sd) time of 926 (44) vs 898 (70) min, P < 0.001). This difference remained significant after correction for differences in BMI between the two groups. Conclusions Using objective measurements, our findings demonstrate that people with newly diagnosed Type 2 diabetes have a more sedentary lifestyle compared with well-matched controls. [ABSTRACT FROM AUTHOR]

OBJECTIVE -- Patients with type 2 diabetes have a high incidence of cardiovascular events including stroke. Increased arterial stiffness (AS) predicts cardiovascular events in the general population. Cerebral white matter lesions (WMLs) are associated with an increased risk of stroke. It is unknown whether AS in patients with type 2 diabetes is associated with WMLs. RESEARCH DESIGN AND METHODS -- We examined 89 patients recently diagnosed with type 2 diabetes (<5 years) and 89 sex- and age-matched controls. AS was assessed with carotid-femoral pulse wave velocity (PWV). WMLs were identified using magnetic resonance imaging and graded qualitatively with the Breteler scale (no/slight changes = 0, moderate changes = 1, severe changes = 2) and semiquantitatively. RESULTS -- The diabetic population had excellent glycemic control (HbA1c, 6.5% [6.2-6.8]; median [interquartile range {IQR}]) and had, compared with the controls, lower office blood pressure (BP) (127 ± 12/79 ± 8 vs. 132 ± 14/84 ± 10 mmHg) and total cholesterol (4.3[3.9-4.7] vs. 5.6 [5.1-6.4]; mmol/L; median [IQR]), (P < 0.01 for all). Despite this, PWV was higher in the patients with diabetes compared with controls (9.3 ± 2.0 vs. 8.0 ± 1.6 m/s; P < 0.0001). PWV was associated with Breteler score (OR 1.36 [95% CI 1.17-1.58]; P < 0.001) and WML volume (OR 1.32 [95% CI 1.16-1.51]; P < 0.001) per 1 m/s increase in PWV. These associations remained significant when adjusted for age, sex, diabetes, 24-h mean arterial BP, BMI, heart rate, and use of antihypertensives and statins (Breteler score: OR 1.28 [95% CI 1.03-1.60]; P < 0.05 and WML volume: OR 1.30 [95% CI 1.06-1.58]; P < 0.05). CONCLUSIONS -- PWV was higher among patients with well-controlled type 2 diabetes compared with controls and was independently associated with WMLs. PWV may represent a clinically relevant parameter in the evaluation of cerebrovascular disease risk in type 2 diabetes. [ABSTRACT FROM AUTHOR]

Patients with type 2 diabetes mellitus are at increased risk of cardiovascular disease (CVD). We examined the predictive ability of 24-hour ambulatory pulse pressure (24-h PP), ambulatory arterial stiffness index (AASI) and diurnal blood pressure (BP) parameters for fatal and non-fatal CVD in patients with type 2 diabetes mellitus. A total of 108 patients with type 2 diabetes mellitus (mean duration 6.6 years) were followed for 9.5 (0.5-14.5) years. At baseline, all patients underwent ambulatory BP monitoring. During follow-up, 45 patients had cardiovascular (CV) events (35 non-fatal and 10 fatal). In bivariate analysis, events during follow-up were predicted by 24-h PP (P<0.01), AASI, 24-h systolic BP and systolic and diastolic night-day BP ratio (P<0.05 for all). In Cox regression analysis adjusted for established risk markers, only 24-h PP and systolic night-day BP ratio predicted CV events, P<0.05 for both. A significant interaction between the two parameters was found, P<0.05; thus, the higher the systolic night-day ratio, the greater the increase in hazard ratio (HR) per mmHg increase in 24-h PP and vice versa. A combined 10 mmHg increase in 24-h PP and 10%-point increase in systolic night-day ratio from the 25th percentile increased the adjusted HR (95% confidence interval) for CV events with 1.29 (0.53; 3.12), whereas a similar increase from the 75th percentile increased the HR with 4.2 (1.54; 11,51). Our study showed that 24-h PP and systolic night-day ratio interact as predictors of CV events in type 2 diabetes patients, and should be considered in conjunction when evaluating the risk of CVD. [ABSTRACT FROM AUTHOR]

. Introduction: Diabetic retinopathy is screened by fundus photography and screening intervals are defined according to general rules to ensure that vision threatening complications are detected even if the progression of the disease is fast. The resulting superfluous examinations of patients with slow disease progression can be reduced by a more exact decision model that allows an adjustment of the screening interval to each patient's individual risk profile. This requires an identification of independent risk factors for reaching treatment end points for diabetic retinopathy. Methods: Clinical data from 5365 patients who had undergone 23 324 examinations at the Department of Ophthalmology, Århus University Hospital between Jan 1st 1994 and Dec 31st 2007 were used to identify independent risk factors for progression of treatment requiring retinopathy. Results: The risk of reaching a treatment end point was in both diabetes types independently affected by retinopathy grade and HbA1c. Furthermore, in type 1 diabetic patients the risk of reaching a treatment end point was independently affected by disease duration and by a recommended control interval of less than 3 months, in spite of correction for retinopathy grade and other studied confounders, whereas in type 2 diabetes this risk was affected by increasing age of diagnosis of the disease. Conclusions: Only a subset of known risk factors for development and progression of diabetic retinopathy should be used to construct a decision model for optimizing screening intervals for diabetic retinopathy. [ABSTRACT FROM AUTHOR]

Aims/hypothesis. The excess mortality in diabetes is mainly due to cardiovascular causes and almost confined to patients with abnormal albuminuria. Compared to healthy subjects, diabetic patients have a prolonged QT interval and increased QT dispersion. In non-diabetic subjects, as well as in Type 1 diabetic patients with overt nephropathy, a prolonged QT interval and increased QT dispersion are associated with cardiac morbidity and mortality. There is an increasing number of studies on effects of beta blocker treatment on QT interval and QT dispersion in non-diabetic subjects. In contrast, there are no studies on the effects of beta blocker treatment on QT interval and QT dispersion in patients with diabetes. The aim of our study was to describe the effects of metoprolol treatment on QT interval and QT dispersion in a group of well-characterised Type 1 diabetic patients with elevated urine albumin excretion. Methods. We studied the effects of 6 weeks of treatment with metoprolol (100 mg once daily, zero order kinetics formulation) in a randomised, placebo-controlled, double blind, crossover trial including 20 Type 1 diabetic patients. Patients were simultaneously monitored under ambulatory conditions with 24-h Holter-monitoring, 24-h ambulatory blood pressure recording and 24-h fractionated urine collections. On days of investigation 12-lead electrocardiograms were recorded and autonomic tests performed. Results. We found strong associations between both daytime and night-time blood pressure and heart-rate-corrected QT interval dispersion (QTc dispersion). Heart rate variability parameters indicating sympathetic and parasympathetic modulation showed strong correlations with heart-rate-corrected QT interval (QTc interval) and with QTc dispersion. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. Conclusions/interpretation. This study is the first to address the QTc interval and QTc dispersion in Type 1 diabetic patients treated with metoprolol. Beta blocker treatment caused a decrease in QTc interval but no change in QTc dispersion. These results may in part explain the pronounced cardioprotective effect of beta blocker treatment in diabetic patients with cardiovascular disease. [ABSTRACT FROM AUTHOR]

Aim: The effect of the angiotensin II receptor antagonist losartan on renal haemodynamics and insulin-mediated glucose disposal was examined in normotensive, normoalbuminuric type 1 diabetic patients using a double-blind, placebo-controlled, cross-over design. Methods: Diurnal blood pressure, glomerular filtration rate (GFR, determined using [125I]-iothalamate), renal plasma flow (RPF, determined using [131I]-hippuran) and urinary albumin excretion rate (UAE) were measured, and a hyperinsulinaemic, euglycaemic clamp with indirect calorimetry was performed in nine patients (age 30 ± 7 years (mean ± s.d.), HbA1c 8.1 ± 1.1%) following 6 weeks' administration of either losartan 50 mg/day or placebo. Results: Diurnal blood pressure was significantly reduced after losartan compared with placebo (122/70 ± 11/8 vs. 130/76 ± 12/6 mmHg, p < 0.05). A significant decline in GFR (133 ± 23 vs. 140 ± 22 ml/min, p < 0.05) and filtration fraction (FF; GFR/RPF) (24.6 ± 3.5 vs. 26.2 ± 3.6%, p < 0.05) was observed in the losartan vs. placebo groups. RPF and UAE did not change. Isotopically determined glucose disposal rates were similar after losartan and placebo in the basal (2.61 ± 0.53 vs. 2.98 ± 0.93 mg/kg/min) and insulin-stimulated states (6.84 ± 2.52 vs. 6.97 ± 3.11 mg/kg/min). However, the glucose oxidation rate increased significantly after losartan vs. placebo in the basal state (1.72 ± 0.34 vs. 1.33 ± 0.18, mg/kg/min, p < 0.01) and during insulin stimulation (2.89 ± 0.75 vs. 2.40 ± 0.62 mg/kg/min, p < 0.03). Basal and insulin-stimulated non-oxidative glucose disposal tended to decrease after losartan; however, this was not significant. Endogenous glucose production and lipid oxidation were unchanged after treatment and similarly suppressed during hyperinsulinaemia. Glycaemic control, total cholesterol, high-density lipoprotein (HDL)-cholesterol and triglycerides were stable in both losartan and placebo groups. Conclusions: Losartan reduces blood pressure, glomerular hyperfiltration and FF, and improves basal and insulin-stimulated glucose oxidation in normotensive, normoalbuminuric type 1 diabetic patients. [ABSTRACT FROM AUTHOR]

Abstract. Poulsen PL, Ebbehøj E, Mogensen CE (Medical Department M (Diabetes & Endocrinology) Aarhus Kommunehospital, Aarhus, Denmark). Lisinopril reduces albuminuria during exercise in low grade microalbuminuric Type 1 diabetic patients: a double blind randomized study. J Intern Med 2001; 249: 433–440. Background. Antihypertensive treatment is presently recommended in most type 1 diabetic patients with microalbuminuria. The long-term effect of angiotensin converting enzymes (ACE) inhibitor (ACE-i) treatment on exercise urinary albumin excretion (E-UAE) and exercise blood pressure (E-BP) in type 1 diabetic patients with low grade microalbuminuria is not well documented. In addition, the possible predictive effect of baseline E-UAE on the progression of overnight UAE remains to be clarified. Design and Methods. In a randomized placebo controlled double blind study the effects of 2 years treatment with either lisinopril (20 mg o.d.) or placebo was evaluated in 21 normotensive type 1 diabetic patients with overnight UAE between 20 and 70 μg min–1. Determinations of E-UAE and E-BP were performed after exercise on an ergometercycle with a load of 70% of estimated maximal VO2 for 20 min. Patients in the placebo and lisinopril groups were similar with regard to age (35.8 ± 11.3 vs. 29.3 ± 8.6 years), duration of diabetes (19.4 ± 8.2 vs. 16.8 ± 5.3 years), and HbA1c (9.0 ± 1.0 vs. 9.4 ± 1.7%). Results. At baseline, E-UAE was similar in the two groups (placebo: 150.1 ×/÷ 3.7, lisinopril: 96.8 ×/÷ 1.8 μg min–1 (geometric mean ×/÷ tolerance factor)). After 2 years treatment E-UAE had increased in the placebo group, whereas E-UAE was reduced in the lisinopril treated patients (placebo: 213.6 ×/÷ 6.9, lisinopril: 48.3 ×/÷ 3.1 μg min–1, P=0.04). The relative increase in E-UAE (E-UAE/Pre-exercise UAE) was similar at baseline in both groups (3.7 ×/÷ 2.3 vs. 2.8 ×/÷ 2.0) but significantly higher in the placebo group after 2 years (4.4 ×/÷ 2.4 compared with 1.6 ×/÷ 1.7 in the lisinopril group, P < 0.01) These changes over two years in relative increase in E-UAE were significantly different (P=0.03). Exercise blood pressure was similar in both groups at baseline and over 2 years increased in the placebo group (from 166.5 ± 15.1–179.9 ± 35.6 mmHg), in contrast to the lisinopril group where E-BP was slightly reduced (from 168.5 ± 20.6–165.1 ± 16.6 mmHg) but the difference in blood pressure over the 2 years did not reach statistical significance. Exercise urinary albumin excretion and E-BP were closely associated (correlation for year 2: r=0.734, P < 0.001), and also changes over the 2 years in E-UAE and E-BP were positively correlated (r=0.53, P=0.01). At year 2, overnight UAE, pre-exercise UAE (pre-E-UAE), E-UAE and E-BP were all closely linked (r-values between 0.6 and 0.9, P-values <0.01). In the prediction of changes in overnight UAE over 2 years, neither baseline E-UAE nor baseline E-BP conveyed explanatory information in comparison with baseline overnight UAE and HbA1c. Conclusions. In type 1 diabetic patients with low-grade microalbuminuria, 2 years of ACE-i treatment with lisinopril significantly reduced E-UAE. Strong correlations were found between E-UAE and E-BP and also changes over 2 years in these parameters were significantly associated. [ABSTRACT FROM AUTHOR]

In order to evaluate the covariation in UAE and BP and to examine the predictive value of each of them for the subsequent development of hypertension and microalbuminuria, we conducted a 4-year prospective study including normoalbuminuric, normotensive type 1 diabetic patents (n = 131), and a 25-year follow-up study (n = 272). In the 4-year study 24h ambulatory blood pressure measurement (AMBP), UAE measurements in 3 overnight urine collections, blood samples (HbA1c and serum creatinine), and heart rate variability tests (short term spectral analysis) were performed once a year. In the 25-year study patients were examined at baseline and 25-year mortality was recorded. Baseline characteristics of normoalbuminuric patients in the 4-year study: 72 males/59 females, age 37.5 ± 12.1 year, diabetes duration 18.6 ± 10.1 year, day-time AMBP 128/80 ± 11/6 mmHg, geometric mean of 3 overnight UAE 5.2 x/% 2.7 µg/min, HbA1c8.4 ± 1.1%. Over 4 years 19 patients reached an endpoint: 12 patients developed hypertension (both clinic BP> 140/90 and day-time AMBP >135/85 at two consecutive visits), one person became microalbuminuric, and two patients developed both hypertension and microalbuminuria. At baseline, patients who subsequently developed hypertension and/or microalbuminuria were characterized by: older age (45 vs. 37 years, p = 0.0002), higher BP values (140/87 vs. 127/79 mmHg, p= 0.0001), higher UAE (6.2 vs. 4.2. µg/min p = 0.01), higher serum creatinine (97 vs. 91 µmol/l, p= 0.03). The annual increase in day-time AMBP was 0.85 ± 0.17/0.35 ± 0.10 mmHg (p= 0.001). The annual increase in night-time AMBP was 0.65 ± 0.17/0.45 ± 0.11 mmHg (p= 0.001) in the 4-year study. BP and albuminuria were dominant risk factors in the 25-year study. In the long-term study the normos showed an increased mortality rate only. after 10 years compared to the background population. After 25 years the mortality risk ratio for normos, micros, and macros was 2.3, 5.8, and 13.3. So with long-term follow-up, the prognosis is also bad even for the normos. Conclusion: The 4-year prospective study reveals hypertension as the major complication in normoalbuminuric type 1 diabetic patients. Only three patients developed microalbuminuria. In this well characterized study, population daytime AMBP increased annually with 0.85 / 0.35 mmHg. However, the long-term mortality-prognosis is not good in the normoalbuminuric patient compared to the background population [ABSTRACT FROM AUTHOR]