Improvement of mild retinopathy in type 2 diabetic patients correlates with narrowing of retinal arterioles. A prospective observational study.

PURPOSE: Diabetic retinopathy is one of the leading causes of blindness in the Western world. The disease is characterized by morphological lesions secondary to disturbances in retinal blood flow assumed to be related to disturbances in retinal autoregulation. However, there is a need for elucidating the relation between disturbances in diameter regulation of retinal vessels and the development of diabetic retinopathy in longitudinal studies. METHODS: Sixty-four patients with type 2 diabetes mellitus were subjected to measurement of pressure autoregulation of retinal arterioles using the Dynamic Vessel Analyzer (DVA) and measurement of retinal thickness using OCT scanning, and after a mean of 6.8 years, 42 of the patients were re-examined. The vascular response was compared in patients in whom retinopathy had disappeared, was unchanged, or had worsened. RESULTS: At baseline, hemoglobin A1c (HbA1c) was significantly higher in the patients who would later experience worsening of diabetic retinopathy than in the other groups, but had been reduced at the follow-up examination. During the follow-up period, the resting diameter of retinal arterioles decreased significantly in the patients who experienced improvement in diabetic retinopathy but was unchanged in the other groups, whereas both the diameter response of retinal arterioles to isometric exercise and retinal thickness increased non-significantly with worsening of retinopathy. CONCLUSIONS: The development of diabetic retinopathy is related to the diameter of retinal arterioles. Future clinical intervention studies should aim at investigating the effects of normalizing arteriolar diameters in diabetic retinopathy.

Acute hyperinsulinemia increases the contraction of retinal arterioles induced by elevated blood pressure.

Diabetic retinopathy is accompanied by disturbances in retinal blood flow, which is assumed to be related to the diabetic metabolic dysregulation. It has previously been shown that normoinsulinemic hyperglycemia has no effect on the diameter of retinal arterioles at rest and during an increase in the arterial blood pressure induced by isometric exercise. However, the influence of hyperinsulinemia on this response has not been studied in detail. In seven normal persons, the diameter response of retinal arterioles to an increased blood pressure induced by isometric exercise, to stimulation with flickering light, and to the combination of these stimuli was studied during euglycemic normoinsulinemia (protocol N) on one examination day, and euglycemic hyperinsulinemia (protocol H) on another examination day. Isometric exercise induced significant contraction of retinal arterioles at all examinations, but during a repeated examination the diameter response was significantly reduced in the test persons following the N protocol and increased in the persons following the H protocol. Flicker stimulation induced a significant dilatation of retinal arterioles at all examinations, and the response was significantly higher during a repeated examination, irrespective of the insulin level. Repeated exposure to isometric exercise reduces contraction, whereas repeated exposure to flickering light increases dilatation of retinal arterioles in vivo. Hyperinsulinemia increases contraction of retinal arterioles induced by isometric exercise.

Plasma levels of the arterial wall protein fibulin-1 are associated with carotid-femoral pulse wave velocity: a cross-sectional study.

BACKGROUND: The arterial system in diabetic patients is characterized by generalized non-atherosclerotic alterations in the vascular extracellular matrix causing increased arterial stiffness compared with subjects without diabetes. The underlying pathophysiology remains elusive. The elastin-associated extracellular matrix protein, fibulin-1, was recently found in higher concentrations in the arterial wall and in plasma in patients with long duration type 2 diabetes. Furthermore, plasma fibulin-1 independently predicted total mortality and was associated with pulse pressure, an indirect measure of arterial stiffness. Whether plasma fibulin-1 is associated with arterial stiffness at earlier phases of type 2 diabetes has not been determined. METHODS: In this cross-sectional study, we examined 90 patients with recently diagnosed type 2 diabetes (< 5 years) and 90 gender- and age-matched controls. Plasma fibulin-1 was measured immunochemically. Arterial stiffness was assessed by carotid-femoral Pulse Wave Velocity (PWV). Differences in means were assessed by t-tests. Associations were assessed by multivariate regression analyses. RESULTS: Plasma fibulin-1 levels were lower in the diabetic group compared with the control group, 93 ± 28 vs 106 ± 30 µg/mL, p = 0.005. In unadjusted analysis of the total study sample, plasma fibulin-1 was not associated with PWV, p = 0.46. However, with adjustment for the confounders age, gender, mean blood pressure, heart rate, body mass index, diabetes and glomerular filtration rate, a 10 µg/mL increase in plasma fibulin was associated with 0.09 ± 0.04 m/s increase in PWV, p < 0.05. In subgroup analysis, plasma fibulin-1 was associated with PWV in the diabetes group, (0.16 ± 0.07 m/s increase in PWV per 10 µg/mL increase in plasma fibulin-1, p<0.05), but not controls, ß = 0.021 ± 0.057 m/s per 10 µg/mL, p = 0.70. The association remained significant in the diabetes group after adjustment for covariates, p < 0.05. CONCLUSIONS: Plasma fibulin-1 is independently associated with PWV. Yet, as the plasma level of fibulin-1 was lower in patients with recently diagnosed type 2 diabetes than in healthy controls, plasma fibulin-1 levels are not a simple marker of the degree of arterial stiffening. Further studies are needed to determine the exact role of fibulin-1 in arterial stiffness and cardiovascular risk in patients with type 2 diabetes.

[Acute benzodiazepine withdrawal delirium].

In this case report we describe a life-threatening episode of delirium in a 51-year-old man. The condition was triggered by an abrupt withdrawal of benzodiazepines. The patient had been taking multiple sedatives for several years but a large proportion of the drugs were not available in Denmark. His general practitioner substituted and prescribed oxazepam and zolpidem for ten days. Afterwards the patient did not have access to benzodiazepines and developed a severe benzodiazepine withdrawal delirium. He was treated with diazepam and olanzapine with gradual dose reduction.

Real-world use of once-weekly semaglutide in patients with type 2 diabetes: pooled analysis of data from four SURE studies by baseline characteristic subgroups.

INTRODUCTION: This post hoc pooled analysis of four real-world studies (SURE Canada, Denmark/Sweden, Switzerland and UK) aimed to characterize the use of once-weekly (OW) semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), in patients with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: The Semaglutide Real-world Evidence (SURE) studies had a duration of ~30 weeks. Changes in glycated hemoglobin (HbA1c) and body weight (BW) were analyzed for the overall population and the following baseline subgroups: GLP-1RA-naïve/GLP-1RA switchers; body mass index <25/≥25-<30/≥30-<35/≥35 kg/m2; age <65/≥65 years; HbA1c <7%/≥7-≤8%/>8-≤9%/>9%; T2D duration <5/≥5-<10/≥10 years. Data for patients achieving treatment targets were analyzed in the overall population and the baseline HbA1c ≥7% subgroup. RESULTS: Of 1212 patients, 960 were GLP-1RA-naïve and 252 had switched to semaglutide from another GLP-1RA. In the overall population, HbA1c was reduced from baseline to end of study (EOS) by -1.1% point and BW by -4.7 kg; changes were significant for all subgroups. There were significantly larger reductions of HbA1c and BW in GLP-1RA-naïve versus GLP-1RA switchers and larger reductions in HbA1c for patients with higher versus lower baseline HbA1c. At EOS, 52.6% of patients in the overall population achieved HbA1c <7%. No new safety concerns were identified in any of the completed SURE studies. CONCLUSIONS: In this pooled analysis, patients with T2D initiating OW semaglutide showed significant improvements from baseline to EOS in HbA1c and BW across various baseline subgroups, including patients previously treated with a GLP-1RA other than semaglutide, supporting OW semaglutide use in clinical practice. TRAIL REGISTRATION NUMBERS: NCT03457012; NCT03631186; NCT03648281; NCT03876015.

Improving frequency of urinary albumin testing in type 2 diabetes in primary care - An analysis of cross-sectional studies in Denmark.

BACKGROUND: To ensure high quality standards in chronic care of type 2 diabetes, it is paramount to ensure regular measurement of clinical risk factors. For prevention of diabetic kidney disease, testing for albuminuria and kidney function is vital. The majority of individuals with type 2 diabetes in Denmark are treated in general practice, and given the recent development of kidney-protective treatments, a renewed focus on renal risk factors is important. OBJECTIVE: To assess the frequency of albuminuria and kidney function testing in general practice in Denmark and describe developments over the last decade. The proportion of patients with the recommended annual measurements of albuminuria and kidney function was the primary variable. METHODS: We used data from subjects with type 2 diabetes in three cross-sectional general practice studies from 2009 to 2017. RESULTS: Data from 5592 individuals were available. Almost all subjects (96-99%) in the studies had annual measurement of kidney function performed. During the combined observation period there was a clear increase in the proportion of subjects that had albuminuria measured, from 57.2% to 68.0% to 82.8%. CONCLUSION: The regular assessment of renal risk factors in individuals with type 2 diabetes attending primary care in Denmark has seemingly improved over the last decade. This provides the required base for renal risk assessment and appropriate therapy selection.

Real-world use of once-weekly semaglutide in patients with type 2 diabetes: Results from the SURE Denmark/Sweden multicentre, prospective, observational study.

AIMS: As part of the SURE programme, SURE Denmark/Sweden aimed to study the real-world use of once-weekly (OW) semaglutide in adults with type 2 diabetes (T2D) in Denmark/Sweden. METHODS: SURE Denmark/Sweden was an ∼30-week, prospective, multicentre, open-label, observational study, enrolling adults with T2D and ≥1 documented HbA1c value ≤12 weeks before initiating semaglutide at their physician's discretion. Primary (change in HbA1c) and secondary (including change in body weight, glycaemic and weight-loss target achievement) endpoints were assessed between baseline and end of study (EOS). RESULTS: Of the 331 patients initiating semaglutide, 282 (85%) completed the study on treatment. For the latter, estimated mean changes [95% confidence interval] in HbA1c and body weight between baseline and EOS were -1.2 [-1.3; -1.1]%-points (-13 [-14; -12] mmol/mol) and -5.4 [-6.0; -4.7] kg (both p < 0.0001), respectively, with similar results in Denmark and Sweden. At EOS, 67.5% of patients achieved HbA1c <7%; 49.4% achieved a weight reduction of ≥5%. Reported adverse events were consistent with the known safety profile of semaglutide. CONCLUSIONS: In routine clinical practice in Denmark/Sweden, use of OW semaglutide was associated with glycaemic and weight-loss benefits in a wide range of adults with T2D, supporting real-world use. CLINICALTRIALS. GOV IDENTIFIER: NCT03648281.

Risk factor management of type 2 diabetic patients in primary care in the Scandinavian countries between 2003 and 2015.

AIMS: To observe and report population demography, comorbidities, risk factor levels and risk factor treatment in a sample of individuals treated for type 2 diabetes in primary care in Norway, Sweden and Denmark. METHODS: Retrospective observational cohort using extraction of data from electronic medical records linked with national health care registries. RESULTS: Sixty primary care clinics participated with annual cross-sectional data (2003 to 2015). In 2015 the sample consisted of 31,632 individuals. Mean age (64.5-66.8 years) and proportion of women (43-45%) were similar. The prevalence of cardiovascular disease in 2015 was 40.7%, 41.6% and 38.0% for Norway, Sweden and Denmark, respectively and 84% to 89% of patients were receiving a pharmacological anti-diabetic treatment. More Danish patients reached targets for HbA1c and LDL cholesterol, while more patients in Sweden and Denmark met the blood pressure target of <130/80 mmHg as compared to Norway. CONCLUSIONS: In three comparable public primary health care systems we found a high prevalence of cardiovascular disease and differences in risk factor treatment and attainment of risk factor goals. With recent guideline changes there is potential for further prevention of diabetes complications in primary care in the future.

Ambulatory blood pressure, endothelial perturbation, and microvascular complications in type 2 diabetes.

Diabetic vascular complications constitute leading causes of blindness, renal failure, and cardiovascular morbidity and mortality world-wide. We studied haemodynamic and structural abnormalities associated with the development of microvascular complications and evaluated the effect of intervention with antihypertensive agents on these risk factors and complications in type 2 diabetic patients (T2DM). Retinal thickness, urinary albumin excretion rate, and transcapillary escape rate of albumin were strongly associated in T2DM patients with maculopathy, suggesting that macular oedema is a marker of generalised vascular hyperpermeability in T2DM. Plasma from T2DM patients with maculopathy stimulated the expression of E-selectin in cultured endothelial cells. Reduced nocturnal blood pressure decline ("non-dipping") and elevated pulse pressure (PP) were associated with micro- and macrovascular complications and predicted progression of nephropathy in T2DM subjects. Non-dipping and elevated PP were associated with increased plasma levels of markers of endothelial activation in T2DM patients, suggesting that endothelial perturbation could represent a pathophysiological link between these haemodynamic risk factors and the development of vascular complications in T2DM. 4 months treatment with losartan 50 mg o.d. did not ameliorate macular oedema in T2DM patients with maculopathy. 12 months dual blockade of the renin-angiotensin system with candesartan and lisinopril reduced ambulatory PP levels compared with high-dose lisinopril monotherapy in hypertensive T2DM subjects.

Can diabetic polyneuropathy and foot ulcers in patients with type 2 diabetes be accurately identified based on ICD-10 hospital diagnoses and drug prescriptions?

Purpose: We examined whether diabetic polyneuropathy (DPN) and diabetic foot ulcers in type 2 diabetes can be accurately identified using International Classification of Diseases, 10th revision discharge diagnosis codes, surgery codes, and drug prescription codes. Methods: We identified all type 2 diabetes patients in the Central Denmark region, 2009-2016, who had ≥1 primary/secondary diagnosis code of "diabetes with neurological complication" (E10.4-E14.4), "diabetic polyneuropathy" (G63.2), or "polyneuropathy, unspecified" (G62.9). Patients with potential painful DPN and non-painful DPN were identified based on prescription history for serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, or gabapentinoids. Likewise, type 2 diabetes patients with potential foot ulcers were identified based on diagnosis or surgery codes. We used medical record review as the reference standard and calculated positive predictive values (PPVs). Results: Of 53 randomly selected patients with potential painful DPN, 38 were classified as having DPN when validated against medical records; of these, 18 also had neuropathic pain, yielding a PPV of 72% (95% CI: 58-83%) for DPN and 34% (95% CI: 22-48%) for painful DPN. Likewise, among 54 randomly selected patients with potential non-painful DPN, 30 had DPN based on medical record data; of these, 27 had non-painful DPN, yielding PPVs of 56% (95% CI: 41-69%) and 50% (95% CI: 36-64%), respectively. Secondary E-chapter codes often denoted stroke or mononeuropathies, rather than DPN. Excluding secondary E-chapter codes from the algorithm increased the PPV for DPN to 78% (95% CI: 63-89%) for the painful DPN cohort and to 74% (95% CI: 56-87%) for the non-painful DPN cohort. Of 53 randomly selected patients with potential diabetic foot ulcer, only 18 diagnoses were confirmed; PPV=34% (95% CI: 22-48%). Conclusion: G-chapter and primary E-chapter diagnosis codes can detect type 2 diabetes patients with hospital-diagnosed DPN, and may be useful in epidemiological research. In contrast, our diabetic foot ulcer algorithm did not perform well.

Venous thromboembolism and risk of cancer in patients with diabetes mellitus.

AIM: Venous thromboembolism (VTE) has long been regarded as a marker of underlying malignancy in the general population. Patients with diabetes mellitus are at increased risk of developing VTE, but it is unclear whether VTE in diabetes patients is also a harbinger of occult cancer. METHODS: From Danish medical health databases, we identified all diabetes patients (N=8783) with a first-time diagnosis of VTE during 1978-2011. We followed the patients until a first-time diagnosis of cancer, emigration, death, or study end, whichever came first. We calculated one-year absolute cancer risk and overall and site-specific standardized incidence ratios (SIRs) for cancer based on national cancer incidence. RESULTS: During the total study period 878 cancers were observed. The one-year absolute cancer risk was 4.1% and the corresponding SIR was 3.28 (95% confidence interval [CI]: 2.94-3.64). The highest SIRs were observed for cancers of the gallbladder and biliary tract (SIR 13.59; 6.77-24.31), the pancreas (SIR 10.16; 6.85-14.50), the ovary (SIR 9.85; 5.63-16.00), and the liver (SIR 9.39; 4.30-17.84). After the first year of follow-up, the overall cancer SIR associated with VTE and diabetes decreased to 1.05 (95% CI: 0.97-1.15). CONCLUSIONS: VTE may be a marker of underlying cancer in patients with diabetes mellitus.

A Cancer That Went Up in Smoke: Pulmonary Reaction to e-Cigarettes Imitating Metastatic Cancer.

e-Cigarettes have gained worldwide popularity as a substitute for smoking, but concern has been raised regarding the long-term effects associated with their use. We report a case of a 45-year-old female consumer of e-cigarettes who presented with 4 months of abdominal pain and fever. Initial imaging discovered multiple pulmonary nodules and liver lesions suspicious of widespread metastases; however, an extensive evaluation found no evidence of malignancy. Results of a lung biopsy revealed an area with multinucleated giant cells suggestive of a foreign body reaction to a lipophilic material. Upon cessation of e-cigarette use (known as vaping), the lung nodules disappeared, and the liver lesions regressed. Our case report suggests that vaping can induce an inflammatory reaction mimicking metastatic cancer.

Prevalence of cancer in Danish patients referred to a fast-track diagnostic pathway is substantial.

INTRODUCTION: Danish patients diagnosed with cancer who present with unspecific signs and symptoms are diagnosed with unfavourable delay, which has led to the establishment of a national fast-track (cancer) pathway. The aim of this study was to estimate the prevalence of cancer and other diagnoses in patients referred to this programme at Aarhus University Hospital from general practitioners. Furthermore, we aimed to characterise the patient cohort, assess survival and estimate the predictive values of symptoms, signs and biochemical abnormalities. METHODS: From 1 March 2011 to 31 December 2013, data of interest were consecutively collected from the electronic patient record by two medical doctors. RESULTS: Overall, 18% (58/323) had cancer, but the prevalence decreased from 22% in 2011 to 16% in 2013. Haematological cancers and cancers originating from the digestive system were the predominant cancer diagnoses. Patients diagnosed with cancer unfortunately had a high mortality suggesting that we diagnose cancer in the late, non-curable stages. Patients referred to the fast-track pathway had a median of four symptoms, most commonly weight loss and fatigue. In one fourth of the patients, a final diagnosis was not reached at discharge. For the rest (n = 185), gastrointestinal conditions, infectious and rheumatological diseases were most common. The predictive value of the presenting symptoms was poor. Age and biochemical markers considered as unspecific markers of cancer were better predictors. Anaemia was seen in 71% versus 34% of patients with/without diagnosed cancer, respectively. CONCLUSIONS: Unspecific signs and symptoms that may be indicative of cancer represent a clinical challenge. A fast-track (cancer) pathway is a new option for patients not entitled to enter an organ-specific programme.

[Detection of occult cancer in patients with idiopathic venous thrombosis]. / Udredning for uerkendt cancer hos patienter med idiopatisk venøs trombose.

Idiopathic venous thrombosis (VTE) is frequently associated with underlying malignancy. Thus, it is tempting to search for underlying cancer in these patients. However, extensive screening is cost-intensive and no survival benefit has been demonstrated. Based on a review of the literature, we recommend the performance of a thorough medical history and physical examination in addition to basic biochemical screening and a chest X-ray in patients with idiopathic VTE. Only specific symptoms or findings should lead to a more extensive work-up.

A classification model for predicting eye disease in newly diagnosed people with type 2 diabetes.

Diabetic retinopathy may be present at the time type 2 diabetes is diagnosed, and initial screening encompassing an eye examination performed by an ophthalmologist or optometrist is therefore recommended. However, proper screening for retinopathy may be challenging in many parts of the world. We hypothesized that simple, commonly available patient characteristics can be used to identify patients at high risk for having retinopathy. We investigated data from multiple years extracted from the National Health and Nutrition Examination Survey which holds information about blood glucose and eye examinations. Individuals with hitherto undiagnosed diabetes were classified according to the presence or absence of retinopathy. Linear classification was used to predict which patients had retinopathy at the time of diagnosis. A total of 266 individuals with undiagnosed diabetes were identified from the cohorts. Of these, 222 individuals had no sign of retinopathy, whereas 44 had mild or moderate non-proliferative retinopathy. Using information regarding HbA1c, BMI, waist circumference, age, systolic blood pressure, urinary albumin, and urinary creatinine, we were able to construct a model that predicts the presence of retinopathy with a positive predictive value of 22% and a negative predictive value of 99%. Only one true positive (1/44) with mild non-proliferative retinopathy was falsely classified. A classification model using readily available patient information and routine biochemical measures can be used to identify patients at high risk of having retinopathy at the time their diabetes is diagnosed. The model may be used to identify high-risk patients for retinopathy screening.

Elevated levels of mannan-binding lectin in patients with type 1 diabetes.

The hepatic protein mannan-binding lectin (MBL) activates the complement system on binding to carbohydrate patterns and is involved in first-line defense against invading microorganisms. Emerging evidence indicates that in some situations MBL may cause inexpedient complement activation and tissue injury through binding to endothelial glycosylations. MBL levels are suppressed by insulin treatment in critically ill patients, and, hypothetically, hepatic portal hypoinsulinemia could lead to increased levels of MBL in patients with type 1 diabetes. We measured MBL and C-reactive protein (CRP) levels in 132 normoalbuminuric type 1 diabetic patients and 66 healthy age- and sex-matched controls. The median MBL concentration was higher in diabetic patients than in healthy controls [1290 micro g/liter (interquartile range, IQR 354-2961 micro g/liter) vs. 970 micro g/liter (IQR 277-1607 micro g/liter), P = 0.025], whereas CRP concentrations were similar among patients and controls [1.42 mg/liter (IQR 0.95-2.21) vs. 1.21 mg/l (IQR 0.74-2.13), NS]. In diabetic subjects, CRP levels correlated with poor glycemic control as indicated by hemoglobin A(1c) and daily insulin dose, which was not the case with MBL. MBL concentrations were positively correlated with urinary albumin excretion (r = 0.22; P = 0.013) and increased with increasing urinary albumin excretion tertile (P = 0.036). In conclusion, our data demonstrate that circulating MBL concentrations are significantly elevated in patients with type 1 diabetes and suggest a possible role of MBL in the pathogenesis of renovascular complications in diabetes.

Pulse pressure and diurnal blood pressure variation: association with micro- and macrovascular complications in type 2 diabetes.

BACKGROUND: In nondiabetic subjects pulse pressure (PP) is an independent predictor of cardiovascular disease and microalbuminuria. Reduced circadian blood pressure (BP) variation is a potential risk factor for the development of diabetic complications. We investigated the association between retinopathy, nephropathy, macrovascular disease, PP, and diurnal BP variation in a group of type 2 diabetic patients. METHODS: In 80 type 2 diabetic patients we performed 24-h ambulatory BP (AMBP) and fundus photographs. Urinary albumin excretion was evaluated by urinary albumin/creatinine ratio. Presence or absence of macrovascular disease was assessed by an independent physician. RESULTS: Forty-nine patients had no detectable retinal changes (grade 1), 13 had grade 2 retinopathy, and 18 had more advanced retinopathy (grades 3-6). Compared to patients without retinopathy (grade 1), patients with grades 2 and 3-6 had higher PP and blunted diurnal BP variation: night PP 55 +/- 10 mm Hg, 64 +/- 10 mm Hg, 61 +/- 15 mm Hg, P < .05 and systolic night/day ratio 89.3% +/- 7%, 94.6% +/- 8%, and 92.0% +/- 6%, P < .05 (grade 1, 2, and 3-6, respectively). Comparing nephropathy groups (45 normo-, 19 micro-, and 15 macroalbuminuric patients) results were similar: night PP 54 +/- 9 mm Hg, 57 +/- 10 mm Hg, and 70 +/- 15 mm Hg, P < .001 and systolic night/day ratio 88.9% +/- 7%, 92.0% +/- 7%, and 94.9% +/- 7%, P < .02. Likewise, compared to patients without macrovascular disease (n = 55), patients with this complication (n = 25) had higher AMBP values: night PP 57 +/- 12 mm Hg v 63 +/- 11 mm Hg, P < .05 and systolic night/day ratio 89.2% +/- 6% v 94.1% +/- 9%, P < .01. CONCLUSIONS: Increased PP and blunted diurnal BP variation are hemodynamic abnormalities associated with micro- and macrovascular complications in type 2 diabetes.

Invasive validation of arteriograph estimates of central blood pressure in patients with type 2 diabetes.

BACKGROUND: Central blood pressure (BP) has attracted increasing interest because of a potential superiority over brachial BP in predicting cardiovascular morbidity and mortality. Several devices estimating central BP noninvasively are now available. The aim of our study was to determine the validity of the Arteriograph, a brachial cuff-based, oscillometric device, in patients with type 2 diabetes. METHODS: We measured central BP invasively and compared it with the Arteriograph-estimated values in 22 type 2 diabetic patients referred to elective coronary angiography. RESULTS: The difference (invasively measured BP minus Arteriograph-estimated BP) in central systolic BP (SBP) was 4.4±8.7 mm Hg (P = 0.03). The limits of agreement were ±17.1 mm Hg. CONCLUSIONS: Compared with invasively measured central SBP, we found a systematic underestimation by the Arteriograph. However, the limits of agreement were similar to the previous Arteriograph validation study and to the invasive validation studies of other brachial cuff-based, oscillometric devices. A limitation in our study was the large number of patients (n = 14 of 36) in which the Arteriograph was unable to analyze the pressure curves. In a research setting, the Arteriograph seems applicable in patients with type 2 diabetes. CLINICAL TRAIL REGISTRATION: ClinicalTrials.gov ID NCT01538290.

Targeting nocturnal hypertension in type 2 diabetes mellitus.

Several studies in different populations have suggested that nighttime blood pressure (BP) is a stronger predictor of cardiovascular events than daytime BP. Consequently, treatment strategies to target nighttime BP have come into focus. The aim of the present study was to investigate the effect of change of administration time of antihypertensive drugs. We included 41 patients with type 2 diabetes mellitus and nocturnal hypertension (nighttime systolic BP >120 mm Hg) in an open-label, crossover study. Patients were randomized to 8 weeks of either morning or bedtime administration of all of the individual's once-daily antihypertensive drugs, followed by 8 weeks of switched dosing regimen. Bedtime administration of antihypertensive drugs resulted in a significant reduction in nighttime (7.5 mm Hg; P<0.001) and 24-hour (3.1 mm Hg; P=0.014) systolic BP, with a nonsignificant reduction in daytime (1.3 mm Hg; P=0.336) systolic BP. We did not find morning BP surge to be different between dosing regimens. Levels of C-reactive protein were significantly lower with bedtime administration, which may indicate an effect on low-grade inflammation. We found no difference in urinary albumin excretion, regardless of albuminuria status. Urinary sodium/creatinine was significantly increased and urinary osmolality significantly reduced with bedtime administration, which can be interpreted as increased nocturnal natriuresis. In patients with type 2 diabetes mellitus and nocturnal hypertension, administration of once-daily antihypertensive drugs at bedtime may be favorable. The increased nocturnal natriuresis may reflect increased effect of bedtime-administered thiazides and renin-angiotensin system inhibitors, suggesting a potential mechanism of the observed effects on BP with chronotherapeutic intervention.