The association between time to antibiotics and relevant clinical outcomes in emergency department patients with various stages of sepsis: a prospective multi-center study.

INTRODUCTION: In early sepsis stages, optimal treatment could contribute to prevention of progression to severe sepsis. Therefore, we investigated if there was an association between time to antibiotics and relevant clinical outcomes in hospitalized emergency department (ED) patients with mild to severe sepsis stages. METHODS: This is a prospective multicenter study in three Dutch EDs. Patients were stratified into three categories of illness severity, as assessed by the predisposition, infection, response, and organ failure (PIRO) score: PIRO score 1 to 7, 8 to 14 and >14 points, reflected low, intermediate, and high illness severity, respectively. Consecutive hospitalized ED patients with a suspected infection who were treated with intravenous antibiotics were eligible to participate in the study. The primary outcome measure was the number of surviving days outside the hospital at day 28 which was used as an inverse measure of hospital length of stay (LOS). The secondary outcome measure was 28-day mortality, taking into account the time to mortality. Multivariable Cox regression analysis was used to estimate the association between time to antibiotics and the primary and secondary outcome measures corrected for confounders, including appropriateness of antibiotics and initial ED resuscitation, in three categories of illness severity. RESULTS: Of the 1,168 included patients, 112 died (10%), while 85% and 95% received antibiotics within three and six hours, respectively. No association between time to antibiotics and surviving days outside the hospital or mortality was found. Only in PIRO group 1 to 7 was delayed administration of antibiotics (>3 hours) associated with an increase in surviving days outside the hospital at day 28 (hazard ratio: 1.46, 95% confidence interval: 1.05 to 2.02 after correction for potential confounders). CONCLUSIONS: In ED patients with mild to severe sepsis who received antibiotics within six hours after ED presentation, a reduction in time to antibiotics was not found to be associated with an improvement in relevant clinical outcomes.

Peer support to decrease diabetes-related distress in patients with type 2 diabetes mellitus: design of a randomised controlled trial.

BACKGROUND: Many type 2 diabetes mellitus patients face difficulties self-managing their illness, which can lead to high levels of diabetes-related distress. Diabetes distress may be decreased by peer support, as peers understand and have dealt with similar problems, and can help motivate each other. A recent systematic review concluded that evidence of benefits of peer support in patients with type 2 diabetes mellitus is too inconsistent due to weak theoretical foundation of the interventions. This study describes the design of a trial evaluating the effectiveness of a group-based, peer support programme with a strong theoretical foundation on diabetes-related distress in type 2 diabetes patients. METHODS: This is a parallel group randomised controlled trial of a six session group-based peer support intervention, delivered by peer leaders and group psychotherapists, compared with one educational meeting on diabetes. At least 152 patients with a type 2 diabetes duration of three years or more and between 50 and 70 years of age, recruited via their general practitioner, will be randomised to receive the peer support intervention or one educational meeting. The intervention is developed in line with three key stages of research development of the Medical Research Council framework. The primary outcome measure for this study is diabetes-related distress. Secondary outcomes include self-management behaviour, well-being and health-related quality of life. Perceived social support is a process measure. Outcomes will be measured one month before, and 6, and 12 months after the intervention by means of self-reported questionnaires. Analysis will be on an intention-to-treat basis. DISCUSSION: This article contains a description of the design of a study that will investigate the effect of a group-based, peer support intervention on diabetes-related distress in type 2 diabetes patients. The intervention was developed in recognition of the limited evidence, and the importance of a theoretical foundation and its implementation. Findings will contribute to knowledge in the field of peer support and patient-important outcomes in type 2 diabetes patients. TRIAL REGISTRATION: Dutch Trial Registry: NTR3474.

Comorbidity in adults with hearing difficulties: which chronic medical conditions are related to hearing impairment?

OBJECTIVES: To investigate the occurrence of 27 chronic medical conditions in a cohort of adults with and without hearing impairment, and to examine the association between these conditions and hearing ability. DESIGN: The National Longitudinal Study on Hearing (NL-SH study) is a large prospective study among adults aged 18 to 70 years, conducted via the internet in the Netherlands. Hearing ability was measured with a digits-in-noise test and comorbidity was assessed through self-report. STUDY SAMPLE: Cross-sectional data of 890 hearing-impaired and 975 normally-hearing adults were analyzed. Both descriptive statistics and multinomial logistic regression analyses were conducted. RESULTS: Of the NL-SH participants with insufficient or poor hearing ability, 78.5% reported to suffer from at least one additional chronic condition. This proportion was larger than in the normally-hearing group (68.6% with one or more chronic conditions and 37.7% with two or more). After adjustment for age and gender, 'dizziness causing falling', 'diabetes' and 'arthritis types other than osteoarthritis and rheumatic arthritis' were significantly associated with poor hearing ability. CONCLUSIONS: Our results show that some previously reported associations do not only occur in older age groups, but also in younger cohorts. Comorbidity is relevant in the rehabilitation (multi-disciplinary care) and the clinical encounter.

Meta-analysis suggests that intensive non-biological combination therapy with step-down prednisolone (COBRA strategy) may also 'disconnect' disease activity and damage in rheumatoid arthritis.

BACKGROUND/OBJECTIVE: Treatment of rheumatoid arthritis (RA) with tumour necrosis factor (TNF) antagonists changes the relationship between disease activity and progression of radiological joint damage ('disconnect'): patients who have little or no response of disease activity still show reductions in damage progression. In early RA, the COBRA strategy (combination of methotrexate and sulfasalazine with step-down prednisolone) has been shown to be equivalent to high-dose methotrexate and infliximab in suppressing damage progression (BeSt trial). We investigated whether COBRA treatment can also 'disconnect' disease activity and damage. DESIGN: A meta-analysis combined data from the COBRA trial (COBRA vs sulfasalazine monotherapy) with that of two arms of the BeSt trial (COBRA vs sequential monotherapy). Linear regression related 1-year progression of damage (Sharp van der Heijde score) as a dependent variable with disease activity (time-averaged Disease Activity Score in 44 joints (DAS44) or C-reactive protein (CRP)), treatment strategy (COBRA or control) and their interaction (indicator of a disconnect) as independent variables. The main outcome was the pooled interaction term. RESULTS: Complete data from 60-100% of patients were available. Before pooling, disease activity was the only (strongly) significant independent factor related to damage progression. The pooled interaction term was (weakly) significant: time-averaged DAS44×treatment interaction, one-sided p=0.027; time-averaged CRP×treatment interaction, one-sided p=0.044. CONCLUSIONS: Changes in the relationship between disease activity and damage progression may not be limited to anti-TNF treatment, but a property of early, rapid and deep suppression of joint inflammation, also induced by conventional strategies that include glucocorticoids.

Motivational interviewing and problem solving treatment to reduce type 2 diabetes and cardiovascular disease risk in real life: a randomized controlled trial.

BACKGROUND: Intensive lifestyle interventions in well-controlled settings are effective in lowering the risk of chronic diseases such as type 2 diabetes (T2DM) and cardiovascular diseases (CVD), but there are still no effective lifestyle interventions for everyday practice. In the Hoorn Prevention Study we aimed to assess the effectiveness of a primary care based lifestyle intervention to reduce the estimated risk of developing T2DM and for CVD mortality, and to motivate changes in lifestyle behaviors. METHODS: The Hoorn Prevention Study is a parallel group randomized controlled trial, implemented in the region of West-Friesland, the Netherlands. 622 adults with ≥10% estimated risk of T2DM and/or CVD mortality were randomly assigned and monitored over a period of 12 months. The intervention group (n=314) received a theory-based lifestyle intervention based on an innovative combination of motivational interviewing and problem solving treatment, provided by trained practice nurses in 12 general practices. The control group (n=308) received existing health brochures. Primary outcomes was the estimated diabetes risk according to the formula of the Atherosclerosis Risk In Communities (ARIC) Study, and the estimated risk for CVD mortality according to the Systematic COronary Risk Evaluation (SCORE) formula. Secondary outcomes included lifestyle behavior (diet, physical activity and smoking). The research assistants, the principal investigator and the general practitioners were blinded to group assignment. Linear and logistic regression analysis was applied to examine the between-group differences in each outcome measure, adjusted for baseline values. RESULTS: 536 (86.2%) of the 622 participants (age 43.5 years) completed the 6-month follow-up, and 502 (81.2%) completed the 12-month follow-up. The mean baseline T2DM risk was 18.9% (SD 8.2) and the mean CVD mortality risk was 3.8% (SD 3.0). The intervention group participated in a median of 2 sessions. Intention-to-treat analyses showed no significant differences in outcomes between the two groups at 6 or 12-months follow-up. CONCLUSIONS: The lifestyle intervention was not more effective than health brochures in reducing risk scores for T2DM and CVD or improving lifestyle behavior in an at-risk population. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN59358434.

Comparison of long-term clinical outcome with etanercept treatment and adalimumab treatment of rheumatoid arthritis with respect to immunogenicity.

OBJECTIVE: To compare rates of sustained low and minimal disease activity and remission according to the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) criteria during 3-year followup in rheumatoid arthritis (RA) patients treated with etanercept and adalimumab in routine care. METHODS: Four hundred seven RA patients previously unexposed to tumor necrosis factor antagonists were treated with etanercept (n = 203) or adalimumab (n = 204) and assessed at 3- and later 6-month intervals. Treatment allocation was at the discretion of the treating rheumatologist. Clinical parameters were measured at each time point, as were anti-adalimumab antibodies in adalimumab-treated patients. Achievement of clinical outcome was defined as the occurrence of sustained (at least 12 consecutive months) low disease activity (28-joint Disease Activity Score [DAS28] <3.2), minimal disease activity (DAS28 <2.6), or ACR/EULAR remission based on the Simplified Disease Activity Index (SDAI). Non-overlapping response rates were calculated. RESULTS: Among the adalimumab group, 13% reached sustained low disease activity but not sustained minimal disease activity, 15% reached sustained minimal disease activity but not sustained remission according to the SDAI, and 16% reached sustained ACR/EULAR remission. In the etanercept group the corresponding rates were 16%, 11%, and 12%, respectively (P = 0.42, overall test for linear trend). Adalimumab-treated patients without anti-adalimumab antibodies (n = 150 [74%]) had the best outcomes, and adalimumab-treated patients with anti-adalimumab antibodies the worst, with outcomes in etanercept-treated patients in between (P < 0.0001). Differences were most apparent in the sustained SDAI remission and sustained minimal disease activity categories. For example, 40% of anti-adalimumab antibody-negative patients, 23% of etanercept-treated patients, and 4% of anti-adalimumab antibody-positive patients achieved at least sustained minimal disease activity. CONCLUSION: Overall, etanercept and adalimumab treatment appear similar in inducing a good long-term clinical outcome. However, in the case of adalimumab this is strongly dependent on the presence or absence of anti-adalimumab antibodies.

Using web-based familial risk information for diabetes prevention: a randomized controlled trial.

BACKGROUND: It has been suggested that family history information may be effective in motivating people to adopt health promoting behaviour. The aim was to determine if diabetic familial risk information by using a web-based tool leads to improved self-reported risk-reducing behaviour among individuals with a diabetic family history, without causing false reassurance among those without a family history. METHODS: An online sample of 1,174 healthy adults aged 35-65 years with a BMI ≥ 25 was randomized into two groups receiving an online diabetes risk assessment. Both arms received general tailored diabetes prevention information, whilst the intervention arm also received familial risk information after completing a detailed family history questionnaire. Separate analysis was performed for four groups (family history group: 286 control versus 288 intervention group; no family history: 269 control versus 266 intervention group). Primary outcomes were self-reported behavioural outcomes: fat intake, physical activity, and attitudes towards diabetes testing. Secondary outcomes were illness and risk perceptions. RESULTS: For individuals at familial risk there was no overall intervention effect on risk-reducing behaviour after three months, except for a decrease in self-reported saturated fat intake among low-educated individuals (Beta (b) -1.01, 95% CI -2.01 to 0.00). Familial risk information resulted in a decrease of diabetes risk worries (b -0.21, -0.40 to -0.03). For individuals without family history no effect was found on risk-reducing behaviour and perceived risk. A detailed family history assessment resulted in a greater percentage of individuals reporting a familial risk for diabetes compared to a simple enquiry. CONCLUSIONS: Web-based familial risk information reduced worry related to diabetes risk and decreased saturated fat intake of those at greatest need of preventative care. However, the intervention was not effective for the total study population on improving risk-reducing behaviour. The emphasis on familial risk does not seem to result in false reassurance among individuals without family history. Additionally, a detailed family history questionnaire identifies more individuals at familial risk than a simple enquiry. TRIAL REGISTRATION: NTR1938.

Effects of a cognitive behavioural treatment in patients with type 2 diabetes when added to managed care; a randomised controlled trial.

Effects of a cognitive behavioural treatment (CBT) in type 2 diabetes patients were studied in a randomised controlled trial. Patients were recruited from a diabetes care system (DCS). The intervention group (n = 76) received managed care from the DCS and CBT. The control group (n = 78) received managed care only. Effects on risk of developing coronary heart disease (CHD), clinical characteristics, lifestyle, determinants of behaviour change, quality of life, and depression were assessed after 6 and 12 months. The intervention did not result in a significant reduction of CHD risk (difference between intervention and control group was -0.32 % (95 % CI: -2.27; 1.63). The amount of heavy physical activity increased significantly in the intervention group at 6 months [intervention versus control group was 20.14 min/day (95 % CI: 4.6; 35.70)]. Quality of life and level of depression improved as well. All effects disappeared after 6 months. No effects were found on clinical characteristics.

The effectiveness of a graphical presentation in addition to a frequency format in the context of familial breast cancer risk communication: a multicenter controlled trial.

BACKGROUND: Inadequate understanding of risk among counselees is a common problem in familial cancer clinics. It has been suggested that graphical displays can help counselees understand cancer risks and subsequent decision-making. We evaluated the effects of a graphical presentation in addition to a frequency format on counselees' understanding, psychological well-being, and preventive intentions. DESIGN: Multicenter controlled trial. SETTING: Three familial cancer clinics in the Netherlands. PARTICIPANTS: Unaffected women with a breast cancer family history (first-time attendees). INTERVENTION: Immediately after standard genetic counseling, an additional consultation by a trained risk counselor took place where women were presented with their lifetime breast cancer risk in frequency format (X out of 100) (n = 63) or frequency format plus graphical display (10 × 10 human icons) (n = 91). MAIN OUTCOME MEASURES: understanding of risk (risk accuracy, risk perception), psychological well-being, and intentions regarding cancer prevention. Measurements were assessed using questionnaires at baseline, 2-week and 6-month follow-up. RESULTS: Baseline participant characteristics did not differ between the two groups. In both groups there was an increase in women's risk accuracy from baseline to follow-up. No significant differences were found between women who received the frequency format and those who received an additional graphical display in terms of understanding, psychological well-being and intentions regarding cancer prevention. The groups did not differ in their evaluation of the process of counseling. CONCLUSION: Women's personal risk estimation accuracy was generally high at baseline and the results suggest that an additional graphical display does not lead to a significant benefit in terms of increasing understanding of risk, psychological well-being and preventive intentions. TRIAL REGISTRATION: Current Controlled Trials http://ISRCTN14566836.

Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients.

In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) µmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) µmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.

Helicobacter pylori eradication in patients on long-term treatment with NSAIDs reduces the severity of gastritis: a randomized controlled trial.

BACKGROUND: Maintenance use of nonsteroidal anti-inflammatory drugs (NSAIDs) is often complicated by gastropathy. In non-NSAID users, eradication of Helicobacter pylori is associated with decreased mucosal inflammation, and may halt the progression to atrophy and intestinal metaplasia, but the continuous use of NSAIDs may interfere with these processes. GOAL: To investigate the effect of H. pylori eradication on gastric mucosal histology during long-term NSAID use, with and without gastroprotective therapy. STUDY: Patients were eligible for inclusion if they were on long-term NSAIDs and were H. pylori-positive on serologic testing. Patients were randomly assigned to either eradication or placebo. Gastritis was assessed according to the updated Sydney classification for activity, chronic inflammation, gastric glandular atrophy, intestinal metaplasia, and H. pylori density. RESULTS: Biopsy specimens were available for histology of 305 patients. Of these, 48% were on chronic gastroprotective medication. Significant less active gastritis, inflammation, and H. pylori density was found in the eradication group compared with the placebo group in both corpus and antrum (P<0.001). In the corpus, less atrophy was found in the eradication group compared with the placebo group. CONCLUSIONS: H. pylori eradication in patients on long-term NSAID therapy leads to healing of gastritis despite ongoing NSAID therapy.

Effects of self-monitoring of glucose in non-insulin treated patients with type 2 diabetes: design of the IN CONTROL-trial.

BACKGROUND: Diabetes specific emotional problems interfere with the demanding daily management of living with type 2 diabetes mellitus (T2DM). Possibly, offering direct feedback on diabetes management may diminish the presence of diabetes specific emotional problems and might enhance the patients' belief they are able to manage their illness. It is hypothesized that self-monitoring of glucose in combination with an algorithm how and when to act will motivate T2DM patients to become more active participants in their own care leading to a decrease in diabetes related distress and an increased self-efficacy. METHODS AND DESIGN: Six hundred patients with T2DM (45 < or = 75 years) who receive care in a structured diabetes care system, HbA1c > or = 7.0%, and not using insulin will be recruited and randomized into 3 groups; Self-monitoring of Blood Glucose (SMBG), Self-monitoring of Urine Glucose (SMUG) and usual care (n = 200 per group). Participants are eligible if they have a known disease duration of over 1 year and have used SMBG or SMUG less than 3 times in the previous year. All 3 groups will receive standardized diabetes care. The intervention groups will receive additional instructions on how to perform self-monitoring of glucose and how to interpret the results. Main outcome measures are changes in diabetes specific emotional distress and self-efficacy. Secondary outcome measures include difference in HbA1c, patient satisfaction, occurrence of hypoglycaemia, physical activity, costs of direct and indirect healthcare and changes in illness beliefs. DISCUSSION: The IN CONTROL-trial is designed to explore whether feedback from self-monitoring of glucose in T2DM patients who do not require insulin can affect diabetes specific emotional distress and increase self-efficacy. Based on the self-regulation model it is hypothesized that glucose self-monitoring feedback changes illness perceptions, guiding the patient to reduce emotional responses to experienced threats, and influences the patients ability to perform and maintain self-management skills.

Web-based guided insulin self-titration in patients with type 2 diabetes: the Di@log study. Design of a cluster randomised controlled trial [TC1316].

BACKGROUND: Many patients with type 2 diabetes (T2DM) are not able to reach the glycaemic target level of HbA1c < 7.0%, and therefore are at increased risk of developing severe complications. Transition to insulin therapy is one of the obstacles in diabetes management, because of barriers of both patient and health care providers. Patient empowerment, a patient-centred approach, is vital for improving diabetes management. We developed a web-based self-management programme for insulin titration in T2DM patients. The aim of our study is to investigate if this internet programme helps to improve glycaemic control more effectively than usual care. METHODS/DESIGN: T2DM patients (n = 248), aged 35-75 years, with an HbA1c > or = 7.0%, eligible for treatment with insulin and able to use the internet will be selected from general practices in two different regions in the Netherlands. Cluster randomisation will be performed at the level of general practices. Patients in the intervention group will use a self-developed internet programme to assist them in self-titrating insulin. The control group will receive usual care.Primary outcome is the difference in change in HbA1c between intervention and control group. Secondary outcome measures are quality of life, treatment satisfaction, diabetes self-efficacy and frequency of hypoglycaemic episodes. Results will be analysed according to the intention-to-treat principle. DISCUSSION: An internet intervention supporting self-titration of insulin therapy in T2DM patients is an innovative patient-centred intervention. The programme provides guided self-monitoring and evaluation of health and self-care behaviours through tailored feedback on input of glucose values. This is expected to result in a better performance of self-titration of insulin and consequently in the improvement of glycaemic control. The patient will be enabled to 'discover and use his or her own ability to gain mastery over his/her diabetes' and therefore patient empowerment will increase. Based on the self-regulation theory of Leventhal, we hypothesize that additional benefits will be achieved in terms of increases in treatment satisfaction, quality of life and self-efficacy. TRIAL REGISTRATION: Dutch Trial Register TC1316.

Increased plasma apolipoprotein C-III concentration independently predicts cardiovascular mortality: the Hoorn Study.

BACKGROUND: Hypertriglyceridemia is a cardiovascular risk factor. Apolipoprotein C-III (apoC-III) is an important determinant of the catabolic rate of triglyceride-rich lipoproteins. The aim of this study was to investigate the prognostic value of plasma apoC-III concentrations for cardiovascular mortality. METHODS: We performed this prospective study in 2244 subjects (ages 49-77 years) who participated in the Hoorn Study. During a mean follow-up of 15 years, 504 individuals died: 231 of cardiovascular disease, 180 of cancer, and 93 of other causes. Cardiovascular disease risk factors and plasma apoC-III concentrations were measured at baseline. RESULTS: The age- and sex-adjusted plasma apoC-III concentration was prospectively associated with cardiovascular mortality (P < 0.001). After adjustment for traditional risk factors, including fasting triglycerides, the hazard ratio (95% CI) for cardiovascular death between the highest and the lowest quartile of apoC-III was 1.85 (1.02-3.38). High concentrations of apoC-III did not appear to be associated with noncardiovascular mortality. CONCLUSIONS: In this general population cohort, a high apoC-III concentration in plasma, independently of fasting triglycerides and other traditional risk factors, predicts cardiovascular mortality.

The influence of diabetes mellitus type 1 and 2 on the thickness, shape, and equivalent refractive index of the human crystalline lens.

PURPOSE: To study the influence of diabetes mellitus (DM) types 1 and 2 on the thickness, radius of curvature, equivalent refractive index, and power of the lens. DESIGN: Observational cross-sectional study. PARTICIPANTS AND CONTROLS: One hundred fourteen patients with DM type 1, 112 patients with DM type 2, and 75 control subjects. METHODS: Lens thickness and the anterior and posterior radius of the lens were measured by means of corrected Scheimpflug imaging. Ocular refraction was determined with Hartmann-Shack aberrometry. The equivalent refractive index and the power of the lens were calculated from these parameters. Several systemic parameters (e.g., duration of DM, glycated hemoglobin, and type of medication) and ocular comorbidity (e.g., level of diabetic retinopathy) were recorded. MAIN OUTCOME MEASURES: The thickness, anterior and posterior radii, equivalent refractive index, and power of the lens. RESULTS: The lenses of the patients with DM type 1 were significantly thicker and more convex, compared with those of the control group (P<0.001). Furthermore, there was a significant decrease in the equivalent refractive index of their lenses compared with the control group. No difference in lens parameters was found between the patients with DM type 2 and the control group. In the DM type 1 group, the duration of DM was an important determinant of lens biometry; the independent effects of the duration of DM per year on lens thickness, anterior radius, posterior radius, and equivalent refractive index were respectively 95%, 88%, 207%, and 45% of the effect of age per year. Lens power and ocular refraction were not affected by DM types 1 or 2. CONCLUSIONS: The results of the present study show that DM type 1 has a major impact on lens biometry. Furthermore, the difference in effect of DM types 1 and 2 on lens biometry may indicate a fundamental difference in pathogenesis. The decrease in equivalent refractive index of the lens seemed to compensate for the profound increase in lens convexity in patients with DM type 1, resulting in no significant change in lens power or ocular refraction with the duration of DM.

Comparison of two consecutive fat-rich and carbohydrate-rich meals on postprandial myeloperoxidase response in women with and without type 2 diabetes mellitus.

Patients with type 2 diabetes mellitus (DM2) have an increased risk of cardiovascular disease (CVD). Myeloperoxidase (MPO), expressed in leukocytes and released upon activation, is associated with CVD and endothelial dysfunction. Postprandial leukocyte recruitment and activation with subsequent MPO release may contribute to atherosclerosis and CVD. We hypothesized that MPO may increase in the postprandial state because of postprandial leukocyte recruitment and/or activation, especially in subjects with DM2. One hundred postmenopausal women, aged 50 to 65 years (66 with normal glucose metabolism [NGM] and 34 with DM2), received 2 consecutive fat-rich meals and 2 consecutive carbohydrate-rich meals on separate occasions. Blood samples were taken before (t = 0) and at 2, 4, and 8 hours after breakfast; lunch was given at t = 4. Plasma MPO concentration was measured by sandwich enzyme-linked immunosorbent assay. The number of leukocytes in fasting blood samples was higher in DM2 compared with NGM (6.1 +/- 1.4 and 5.4 +/- 1.2 x 10(9)/L, respectively; P < .05). Baseline MPO concentration did not significantly differ between NGM and DM2 (51.4 +/- 12.9 and 54.5 +/- 18.4 mug/L, respectively; P = .39). Baseline MPO was positively associated with leukocytes (r = 0.20, P < .05) and inversely associated with high-density lipoprotein cholesterol (r = -0.22, P < .05). Leukocytes increased from 5.0 +/- 1.5 to 6.1 +/- 1.5 x 10(9)/L and from 5.8 +/- 1.4 to 6.6 +/- 1.4 x 10(9)/L in NGM and DM2, respectively (both P < .01), after the fat-rich meals. In contrast to our hypothesized increase in MPO, we found a significant decrease in MPO in NGM (both meal types) and DM2 (fat-rich meals only). Our findings provide no support to our initial hypothesis that meal-induced release of MPO might be a mechanism that contributes to CVD risk.

Microvascular disease in type 1 diabetes alters brain activation: a functional magnetic resonance imaging study.

Individuals with type 1 diabetes have mild performance deficits on a range of neuropsychological tests compared with nondiabetic control subjects. The mechanisms underlying this cognitive deterioration are still poorly understood, but chronic hyperglycemia is now emerging as a potential determinant, possibly through microvascular changes in the brain. In 24 type 1 diabetic patients, we tested at euglycemia and at acute hypoglycemia whether the presence of proliferative diabetic retinopathy, as a marker of microvascular disease, adversely affects the ability of the brain to respond to standardized hypoglycemia, using functional magnetic resonance imaging with a cognitive task. Patients with retinopathy, compared with patients without, showed less deactivation (hence, an increased response) in the anterior cingulate and the orbital frontal gyrus during hypoglycemia compared with euglycemia (P < 0.05). Task performance and reaction time were not significantly different for either group. We conclude that microvascular damage in the brain of patients with retinopathy caused this increased brain response to compensate for functional loss.

Endothelial dysfunction and low-grade inflammation explain much of the excess cardiovascular mortality in individuals with type 2 diabetes: the Hoorn Study.

OBJECTIVE: The mechanisms responsible for the increased cardiovascular disease risk that accompanies type 2 diabetes (T2D) remain poorly understood. It is commonly held that endothelial dysfunction and low-grade inflammation can explain, at least in part, why deteriorating glucose tolerance is associated with cardiovascular disease. However, there is no direct evidence for this contention. METHODS AND RESULTS: In this population-based study (n=631), T2D was cross-sectionally associated with both endothelial dysfunction and low-grade inflammation, whereas impaired glucose metabolism (IGM) was associated only with low-grade inflammation. These findings were independent of other risk factors that accompany T2D or IGM. During a follow-up of 11.7 years (median; range 0.5 to 13.2 years), low-grade inflammation was associated with a greater risk of cardiovascular mortality (hazard ratio, 1.43 [95% CI, 1.17 to 1.77] per 1 SD difference). For endothelial dysfunction, the association with cardiovascular mortality was stronger in diabetic (hazard ratio, 1.87 [95% CI, 1.43 to 2.45]) than in nondiabetic individuals (hazard ratio, 1.23 [95% CI, 0.86 to 1.75]; P interaction=0.06). Finally, T2D-associated endothelial dysfunction and low-grade inflammation explained approximately 43% of the increase in cardiovascular mortality risk conferred by T2D. CONCLUSIONS: These data emphasize the necessity of randomized controlled trials of strategies that aim to decrease cardiovascular disease risk by improving endothelial function and decreasing low-grade inflammation, especially for T2D patients.

The influence of chronic diabetes mellitus on the thickness and the shape of the anterior and posterior surface of the cornea.

PURPOSE: To determine the influence of diabetes mellitus (DM) type 1 and type 2 on the thickness, radius of curvature, power, and asphericity of the cornea. METHODS: In this observational cross-sectional study, 102 patients with DM type 1, 101 patients with DM type 2, and 69 healthy subjects were measured by means of Scheimpflug imaging to determine central corneal thickness and the radius and asphericity of the anterior and posterior corneal surfaces. Corneal power was calculated from these parameters. Several systemic parameters (eg, duration of diabetes, glycated hemoglobin, blood glucose levels, and type of medication) and ocular comorbidity (eg, stage of retinopathy) were recorded. RESULTS: Patients with DM type 1 and 2 had significantly smaller posterior corneal radii (P < 0.05) than those of healthy subjects (men: 6.49/6.48/6.64 mm; women: 6.36/6.30/6.49 mm). As a result, the optical power of the posterior corneal surface of the patients with diabetes differed from that of the healthy subjects (P < 0.01; men: DM, -6.2 D; healthy, -6.0 D; women: DM, -6.3 D; healthy, -6.2 D). However, corneal thickness, anterior radius and asphericity, and overall corneal power did not differ significantly between the groups. Furthermore, none of the systemic factors or ocular comorbidity had any influence on the corneal thickness or shape. CONCLUSIONS: DM affects the posterior corneal radius, resulting in a small change in posterior corneal power. However, chronic DM does not seem to significantly influence the overall corneal power.