Manja Reimann

The Finnish Diabetes Risk Score Is Associated with Insulin Resistance and Progression towards Type 2 Diabetes

OBJECTIVE The Finnish Diabetes Risk Score (FINDRISC) questionnaire is a practical screening tool to estimate the diabetes risk and the probability of asymptomatic type 2 diabetes. In this study we evaluated the usefulness of the FINDRISC to predict insulin resistance in a population at increased diabetes risk. DESIGN Data of 771 and 526 participants in a cross-sectional survey (1996) and a cohort study (1997-2000), respectively, were used for the analysis. Data on the FINDRISC and oral glucose tolerance test parameters were available from each participant. The predictive value of the FINDRISC was cross-sectionally evaluated using the area under the curve-receiver operating characteristics method and by correlation analyses. A validation of the cross-sectional results was performed on the prospective data from the cohort study. RESULTS The FINDRISC was significantly correlated with markers of insulin resistance. The receiver operating characteristics-area under the curve for the prediction of a homeostasis model assessment insulin resistance index of more than five was 0.78 in the cross-sectional survey and 0.74 at baseline of the cohort study. Moreover, the FINDRISC at baseline was significantly associated with disease evolution (P < 0.01), which was defined as the change of glucose tolerance during the 3 yr follow-up. CONCLUSIONS The results indicate that the FINDRISC can be applied to detect insulin resistance in a population at high risk for type 2 diabetes and predict future impairment of glucose tolerance.

Arterial Stiffness Profiles: Investigating Various Sections of the Arterial Tree of African and Caucasian People

In Africans, arterial stiffness progression seems more pronounced compared to Caucasians. We compared the arterial stiffness profiles of different age groups and focused on muscular arteries and two more central arterial segments in African and Caucasian people from South Africa. In African (N = 374) and Caucasian (N = 376) participants (20–70 years), we measured carotid-radial (C-R) and carotid-dorsalis pedis (C-DP) pulse wave velocity (PWV) and aortic characteristic impedance (Zao). Major findings were that normotensive and high-normal/hypertensive (HT) Caucasians indicated increased trends of C-R PWV with aging (P = .029 and P = .067), not seen in the African groups (P = .122 and P = .526). Both ethnic groups showed significant increases of C-DP PWV and Zao with aging. High-normal/hypertensive Africans had significantly stiffer arteries than hypertensive Caucasians for almost all age groups, and for all stiffness measures. African C-R PWV correlated significantly with blood pressure (BP), but not with age. Opposite results were observed for Caucasians. In conclusion, the stiffness of muscular arteries is already elevated in young Africans, in both those with normal or elevated BP. This is possibly due to an earlier deterioration during childhood, or perhaps already present from birth. Also, in Caucasians stiffness seems more age-related, while in Africans it seems to be more pressure-related.

An update on preventive and regenerative therapies in diabetes mellitus

Type 1A (immune-mediated) and type 2 diabetes mellitus are two of the most common severe chronic illnesses, affecting over 230 million people worldwide with an estimated global prevalence of 5.1%. Although type 1 and type 2 diabetes differ greatly in modes of pathogenesis, these illnesses share a common pathology and consequences characterized by loss of functional beta-cell mass and subsequent dysregulation of carbohydrate and lipid metabolism. Since therapy for diabetes and the associated complications poses enormous public health and economic burdens, novel preventive and regenerative therapies have emerged in the past decade with the aim to preserve beta-cell mass and delay the onset of diabetes. The goal of this review is to provide a comprehensive overview of current efforts in the fight against diabetes, and attempts to document all strategies that have emerged in clinical studies within the past 25 years. First, strategies to identify individuals at risk, ranging from whole-genome scans to autoantibody screening, will be discussed. Second, novel approaches to prevent or delay the onset of disease will be covered. Particular focus is given on emerging strategies for individuals at risk for type 1 diabetes that target T-cell regulation and induction of tolerance, while new pharmaceutical concepts in combination with lifestyle interventions are discussed within the scope of type 2 diabetes prevention. Lastly, important efforts to halt disease progression with emphasis on beta-cell regeneration are presented.

Should obesity be blamed for the high prevalence rates of hypertension in black South African women

Hypertension is highly prevalent in South Africa, resulting in high stroke mortality rates. Since obesity is very common among South African women, it is likely that obesity contributes to the hypertension prevalence. The aims were to determine whether black African women have higher blood pressures (BPs) than Caucasian women, and whether obesity is related to their cardiovascular risk. African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were included. Correlations between obesity (total body fat, abdominal obesity and peripheral fat) and cardiovascular risk markers (haemodynamic parameters, lipids, inflammatory markers, prothrombotic factors, adipokines, HOMA-IR (homoeostasis model assessment insulin resistance)) were compared between the ethnic groups (adjusted for age, smoking, alcohol and physical activity). Comparisons between low- and high-BP groups were also made for each ethnic group. Results showed that African women had higher BP (P<0.01) with increased peripheral vascular resistance. Surprisingly, African women showed significantly weaker correlations between obesity measures and cardiovascular risk markers when compared to Caucasian women (specifically systolic BP, arterial resistance, cardiac output, fibrinogen, plasminogen activator inhibitor-1, leptin and resistin). Interestingly, the latter risk markers were also not significantly different between low- and high-BP African groups. African women, however, presented significant correlations of obesity with triglycerides, C-reactive protein and HOMA that were comparable to the Caucasian women. Although urban African women have higher BP than Caucasians, their obesity levels are weakly related to traditional cardiovascular risk factors compared to Caucasian women. The results, however, suggest a link with the development of insulin resistance.

Facilitated defensive coping, silent ischaemia and ECG left-ventricular hypertrophy: the SABPA study.

Background: Defensive active coping responses (being-in-control, acceptance of the stressor as reality) have been associated with vascular hyper-responsiveness in urban Africans. However, the association between active coping responses, blood pressure (BP), and ECG-derived left-ventricular hypertrophy (LVH) responses is unknown. Objectives and methods: Associations between BP, silent ischaemia and ECG Cornell product LVH were assessed in 161 African and Caucasian men with active coping responses identified by the Amirkhan Coping Strategy Indicator. BP, ECG and silent ischaemia data were obtained from 24-h ambulatory monitoring. Beat-to-beat BP was continuously recorded during stress testing and fasting resting blood samples obtained for biochemical analyses. Results: Enhanced ß-adrenergic central cardiac responses were evident in active coping Caucasians as opposed to a predomination of &agr;-adrenergic vascular responses in active coping Africans. Active coping African men displayed higher 24-h BP and prevalence of silent ischaemia events compared to the Caucasian men. Regression analyses revealed that &agr;-adrenergic responses were associated with silent ischaemic events, adjusted R2 0.21 [ß 1.07, 95% confidence interval (CI) 0.29–1.85] and that ischaemic events predicted LVH in active coping Africans (adjusted R2 0.12, ß 0.35, 95% CI 0.11–0.59). Receiver-operated characteristic (ROC) analyses indicated a defensive pathway cut point of 16 in Africans as opposed to 32 in Caucasians predicting silent ischaemia with sensitivity/specificity 100/96%. Conclusions: A defensive pathway revealed disturbed vascular function showing dissociation between behavioural and physiological ß-adrenergic active coping responses in Africans. Vascular responsiveness facilitated silent ischaemia events and structural LVH changes which potentially explain the increased risk for incident ischaemic stroke in black Africans.

Defensive coping facilitates higher blood pressure and early sub–clinical structural vascular disease via alterations in heart rate variability: The SABPA study

OBJECTIVES Defensive coping (AC) responses in urban African males have been associated with vascular responsiveness, partly explaining autonomic nervous system dysfunction. We therefore aimed to assess whether AC responses facilitate higher blood pressure and early sub-clinical structural vascular disease via alterations in frequency- and time-domain heart rate variability (HRV) responses. METHODS We included 355 African and Caucasian men and women without pre-existing atrial fibrillation, aged 45 ± 9 years. Significant interaction on main effects (coping × ethnicity × gender) for left carotid intima media thickness far wall (L-CIMTf) and cross sectional wall area values necessitated selection of AC responders above mean via the Coping Strategy Indicator. We collected B-mode ultrasound L-CIMTf, ambulatory BP and-HRV data. Overnight fasting blood was obtained. RESULTS Overall, Africans and AC Africans, mostly men, revealed a poorer lifestyle profile, higher prevalence of hypertensive status, disturbed sympathovagal balance and depressed HRV temporal and geometric patterns compared to the Caucasians (P ≤ 0.05). Moderately depressed non-linear and time-domain HRV (SDNN <100 ms) was prevalent in 28% of Africans compared to 11% of Caucasians. A similar trend was shown for the AC African participants (32%) compared to Caucasians (16%). Only depressed HRV time-domain (SDNN: adj. R(2) = 0.34; β = -0.24; p = 0.08) and vagal-impaired heart rate responses (RMSSD: adj. R(2) = 0.28; β = -0.28; p < 0.05) were associated with higher blood pressure and early structural vascular changes in AC African men. CONCLUSION Defensive coping facilitated autonomic nervous system dysfunction, which was associated with higher blood pressure and sub-clinical structural vascular disease in an African male cohort.

Comprehensive autonomic assessment does not differentiate between Parkinson’s disease, multiple system atrophy and progressive supranuclear palsy

Differential diagnosis of parkinsonian syndromes is a major challenge in movement disorders. Dysautonomia is a common feature but may vary in clinical severity and onset. The study attempted to find a pattern of autonomic abnormalities discriminative for patients with different parkinsonian syndromes. The cross-sectional study included 38 patients with multiple system atrophy (MSA), 32 patients with progressive supranuclear palsy (PSP), 26 patients with idiopathic Parkinson’s disease (IPD) and 27 age-matched healthy controls. Autonomic symptoms were evaluated by a standardized questionnaire. The performance of patients and controls was compared on five autonomic function tests: deep breathing, Valsalva manoeuvre, tilt-table testing, sympathetic skin response, pupillography, and 24-h ambulatory blood pressure monitoring (ABPM). Disease severity was significantly lower in IPD than PSP and MSA. Except for pupillography, none of the laboratory autonomic tests distinguished one patient group from the other alone or in combination. The same was observed on the questionnaire. Receiver operating characteristic curve revealed discriminating performance of pupil diameter in darkness and nocturnal blood pressure change. The composite score of urogenital and vasomotor domains significantly distinguished MSA from IPD patients but not from PSP. Our study supports the observation that even mild IPD is frequently indistinguishable from more severe MSA and PSP. Thus, clinical combination of motor and non-motor symptoms does not exclusively point at MSA. Pupillography, ABPM and the questionnaire may assist in delineating the three syndromes when applied in combination.

Retinal vessel analysis in hypercholesterolemic patients before and after LDL apheresis

OBJECTIVE Changes in the microcirculation per se may precede macrovascular changes, hence, may present a good surrogate for monitoring vascular changes during treatment. Using retinal vascular imaging techniques, we attempted to investigate the microvascular benefit of a single LDL apheresis in hypercholesterolemia. METHODS Twenty-one hypercholesterolemic patients (57+/-15 years) on regular LDL apheresis treatment, seven women and 14 men, were examined for retinal endothelial function before and after a single LDL apheresis. The Dynamic Vessel Analyzer was applied for static and dynamic retinal vessel analysis. Retinal vessel diameter was measured at rest and during flicker light stimulation. Changes in vasodilation are expressed as percent changes over baseline. RESULTS Cholesterol fractions and triglycerides were reduced by 21-74 % by the LDL apheresis procedure. In hypercholesterolemic patients, flicker-induced vasodilation was diminished in both retinal arterioles and venules, but had significantly improved in retinal venules after a single LDL apheresis (p = 0.013). This increase in vasodilatory capacity of retinal venules was linked to a wider basal retinal venular caliber (p = 0.031), but was unrelated to changes in serum lipids (p > 0.05). CONCLUSION In hypercholesterolemia, abnormal retinal autoregulation is improved by a single LDL apheresis. Our findings suggest that venules represent a dynamic component, which is highly responsive to metabolic changes in the microcirculation.

Baroreceptor sensitivity, cardiovascular responses and ECG left ventricular hypertrophy in men: The SABPA study

Abstract Aim. Research has shown a significant relationship between hypertension and attenuated baroreceptor sensitivity (BRS), which in turn reflects alterations of autonomic control of the cardiovascular system. The objective of this study was to compare the BRS of African and Caucasian men and determine possible associations with blood pressure and left ventricular hypertrophy. Materials and methods. Participants included African (n = 82) and Caucasian (n = 100) male teachers, aged between 20 and 65 years, recruited in the North-West Province, South Africa. Ambulatory blood pressure monitoring was conducted for a 22–23-h period and, thereafter, cardiovascular parameters were recorded with a Finometer and 12-lead ECG during rest and while challenging the cardiovascular system with the cold pressor and Stroop color–word conflict tests. Spontaneous BRS was calculated as well as the Cornell product [marker of left ventricular hypertrophy (LVH)]. Results. The African men had significantly lower BRS stress responses. Attenuated BRS coupled to an α-adrenergic response pattern predicted elevation of blood pressure in the African men. BRS reduction did not prove to be a significant predictor of LVH. Conclusion. Lower BRS, especially during stress, may pose a significant health threat for African men regarding earlier development or promotion of α-adrenergic-driven hypertension and greater risk for cardiovascular disease.

Education Research: Cognitive performance is preserved in sleep-deprived neurology residents

Objective: To test the hypotheses that sleep deprivation in neurology residents is associated with performance deficits and that vigilance and cognitive performance is more compromised after overnight on-call duty compared to night shift. Methods: Thirty-eight neurology residents of a university teaching hospital participated in a prospective single-blind comparison study. Residents were recruited according to their working schedule and divided into 3 groups: 24 hours overnight on-call duty, night shift, and regular day shift (controls). All participants underwent serial measurements of sleepiness and cognitive performance in the morning directly after or before their shift. Pupillary sleepiness test and Paced Auditory Serial Addition Test were applied. Perceived sleepiness was assessed by a questionnaire. Results: Sleepiness was increased in residents after night shift and overnight call compared to controls while the type of night duty was not associated with the extent of sleepiness. Sleep-deprived residents did not show any performance deficits on the Paced Auditory Serial Addition Test. Cognitive performance was not associated with sleepiness measures. Conclusions: Night shift and overnight call duty have a similar impact on alertness in neurology residents. Sleep-deprived neurology residents may be able to overcome sleep loss–related performance difficulties for short periods.