Psychosocial aspects of diabetes technology.

AIM: To identify key psychosocial research in the domain of diabetes technology. RESULTS: Four trajectories of psychosocial diabetes technology research are identified that characterize research over the past 25 years. Key evidence is reviewed on psychosocial outcomes of technology use as well as psychosocial barriers and facilitating conditions of diabetes technology uptake. Psychosocial interventions that address modifiable barriers and psychosocial factors have proven to be effective in improving glycaemic and self-reported outcomes in diabetes technology users. CONCLUSIONS: Psychosocial diabetes technology research is essential for designing interventions and education programmes targeting the person with diabetes to facilitate optimized outcomes associated with technology uptake. Psychosocial aspects of diabetes technology use and related research will be even more important in the future given the advent of systems for automated insulin delivery and the increasingly widespread digitalization of diabetes care.

Comparative characteristics of older people with type 1 diabetes treated with continuous subcutaneous insulin infusion or insulin injection therapy: data from the German/Austrian DPV registry.

AIM: To compare clinical characteristics and outcomes in adults with type 1 diabetes aged ≥ 60 years using continuous subcutaneous insulin infusion (CSII) vs. insulin injection therapy. Further, to determine the percentage of older adults with type 1 diabetes using CSII. RESEARCH DESIGN AND METHODS: Retrospective study using data of the Diabetes Prospective Follow-up Registry (DPV). Including percentage CSII use from 2008 to 2018, and the characteristics of 9547 individuals extracted from the DPV in March 2019 (N = 1404 CSII; N = 8143 insulin injection therapy). Wilcoxon rank sum tests were used for continuous variables and chi-square tests for categorical variables to compare clinical characteristics of people using CSII vs. insulin injection therapy. Adjusted analyses used generalized linear models to compare diabetes-related outcomes. RESULTS: CSII usage has increased in older adults (from 12% in 2008 to 23% in 2018). After adjustment, CSII was associated with lower HbA1c [60.7 mmol/mol (7.7 ± 0.1%) vs. 62.8% (7.9 ± 0.1%)], lower daily insulin dose (0.49 ± 0.02 vs. 0.61 ± 0.01 IU/kg), fewer days in hospital (8.1 ± 0.12 vs. 11.2 ± 0.11 days/person-year), fewer severe hypoglycaemic events (0.16 ± 0.02 vs. 0.21 ± 0.03 events/person-year) and fewer diabetic ketoacidosis (0.06 ± 0.01 vs. 0.08 ± 0.01 events/person-year). Individuals on CSII showed lower rates of microalbuminuria and also have a diagnosis of depression and neuropathy. CONCLUSIONS: A growing number of older adults are using insulin pumps. Older age in itself should not be seen as a contraindication for CSII.

Focus group study to identify the central facets of fear of hypoglycaemia in people with Type 2 diabetes mellitus.

AIMS: To determine key worries about hypoglycaemia among insulin-using adults with Type 2 diabetes using a focus group approach. METHODS: Thirteen focus groups were conducted in three diabetes outpatient care units and one peer support group was set up, in Germany. A total of 64 insulin-dependent adults with Type 2 diabetes (36.5% women, mean age 65.2 ± 11.0 years) discussed their worries about hypoglycaemia. The qualitative results were assigned into thematic categories using a bottom-up coding procedure. Participants completed the Hypoglycaemia Fear Survey and demographic measures were recorded. The results of the Hypoglycaemia Fear Survey were contrasted with the focus group findings to evaluate how accurately the Hypoglycaemia Fear Survey comprehensively captures features of fear of hypoglycaemia in Type 2 diabetes. RESULTS: Eight themes were identified: 'unconsciousness/death'; 'aloneness/ helplessness', 'fear of hurting somebody'; 'shame'; 'loss of physical control'; 'long-term complications'; 'diabetes self-management issues'; and 'impaired awareness'. A total of 30 participants (46.9%) scored ≥3 on at least one item of the Hypoglycaemia Fear Survey worry subscale, indicating elevated worries. The Hypoglycaemia Fear Survey comprehensively captured all identified themes. Self-efficacy with regard to diabetes self-management seemed to play an important role in fear of hypoglycaemia in Type 2 diabetes. CONCLUSIONS: Given that even subclinical worries can have negative effects on quality of life and diabetes self-management, emphasis should be placed on diabetes education; in particular, to help patients to develop self-efficacy concerning diabetes self-management. The Hypoglycaemia Fear Survey comprehensively captures hypoglycaemia worries in Type 2 diabetes. Additional assessment of self-efficacy might be beneficial to identify people at risk of developing hypoglycaemia worries.

Evidence of estrogenic endocrine disruption in smallmouth and largemouth bass inhabiting Northeast U.S. national wildlife refuge waters: A reconnaissance study.

Intersex as the manifestation of testicular oocytes (TO) in male gonochoristic fishes has been used as an indicator of estrogenic exposure. Here we evaluated largemouth bass (Micropterus salmoides) or smallmouth bass (Micropterus dolomieu) form 19 National Wildlife Refuges (NWRs) in the Northeast U.S. inhabiting waters on or near NWR lands for evidence of estrogenic endocrine disruption. Waterbodies sampled included rivers, lakes, impoundments, ponds, and reservoirs. Here we focus on evidence of endocrine disruption in male bass evidenced by gonad histopathology including intersex or abnormal plasma vitellogenin (Vtg) concentrations. During the fall seasons of 2008-2010, we collected male smallmouth bass (n=118) from 12 sites and largemouth bass (n=173) from 27 sites. Intersex in male smallmouth bass was observed at all sites and ranged from 60% to 100%; in male largemouth bass the range was 0-100%. Estrogenicity, as measured using a bioluminescent yeast reporter, was detected above the probable no effects concentration (0.73ng/L) in ambient water samples from 79% of the NWR sites. Additionally, the presence of androgen receptor and glucocorticoid receptor ligands were noted as measured via novel nuclear receptor translocation assays. Mean plasma Vtg was elevated (>0.2mg/ml) in male smallmouth bass at four sites and in male largemouth bass at one site. This is the first reconnaissance survey of this scope conducted on US National Wildlife Refuges. The baseline data collected here provide a necessary benchmark for future monitoring and justify more comprehensive NWR-specific studies.

[Diabetes and dementia]. / Diabetes und Demenz.

Diabetes mellitus is a known risk factor for cognitive dysfunction and dementia. Chronic hyperglycemia, genetic predisposition, arterial hypertension, hyperlipoproteinemia, micro- and macrovascular diseases, and depression play a major role in the development of cognitive dysfunction. Both pathophysiology of diabetes and dementia and the specifics of diabetes therapy in patients with dementia are presented in this review.

[French validation of the anger reactions and goals scale (RBC)]. / Validation française de l'échelle des réactions et des buts liés à la colère (RBC).

BACKGROUND: The study presents the French validation of a German scale (AERZ) [Diagnostica 49 (2003) 97-109, revised Eur J Pers (2009)] measuring anger regulation. The French validation (RBC scale) comprises two subscales measuring seven anger reactions and seven anger goals. Disentangling dimensions related to anger reactions and anger goals, respectively, is the main advantage of this scale. In addition to seven cognitive-behavioral anger reactions (i.e., venting, rumination, submission, feedback, distraction, humor and downplaying the incident's negative impact), the RBC scale also addresses the cognitive representations underlying anger reactions by exploring anger goals (i.e., enforcing personal standards, enforcing social standards, downregulating affect, avoiding conflicts, protecting one's reputation, weighing costs and gaining revenge). METHOD: The original scale was translated following the scientific guidelines and recommendations for cultural adaptation of instruments. The adapted French version was tested with a sample of students (n=184, 70.7% were females) from the University of Luxembourg (M=21.31, S.D.=1.93). Students filled in a questionnaire composed of the RBC scale, the SF-36 quality of life scale and the STAXI-II anger instrument. The RBC scale comprises 56 items; reactions are assessed on a 4 point Likert scale from "almost never" (1) to "always" (4), whereas goals are assessed on a 4 point Likert scale from "not at all" (1) to "completely" (4). RESULTS: Factor analysis revealed a seven-factor solution for the anger reactions subscale (that explained 63.13% of the common variance) and a six-factor solution for the anger goals subscale (that explained 57.45% of the common variance). The original factorial structure was examined in confirmatory factor analysis. For the anger reactions subscale, a good model fit was found, with chi(2)(329)=546.38, p<0.1, CFI=0.87, RMSEA=0.06. For the anger goals subscale, a satisfactory model fit was observed, with chi(2)(335)=658.52, p<0.1, CFI=0.78, RMSEA=0.07 revealing a six-factorial structure that differed from the original version in the combination of two dimensions ("downregulating affect" and "protecting one's reputation"). The RBC scale's internal consistencies were found satisfactory with Cronbach's alphas ranging from 0.60 to 0.83 for the various dimensions. Part-whole correlations ranged from r(it)=0.27 to 0.80. Gender differences showed that female participants used significantly more rumination strategies and emotional regulation, whereas male students demonstrated greater humor in anger situations. Significant correlations between RBC and STAXI-II confirmed the construct validity of the RBC scale. Criteria validity was analyzed using the predictive value of the RBC dimensions on the quality of life subscales of the SF-36. CONCLUSION: The present results support the validity, the reliability and the sensitivity of the 56 items scale on anger regulation and its use in psychological research. Although our findings need to be replicated and the test-retest validity is subject to future verification, the present validation of the RBC scale offers a multidimensional inventory for measuring anger reactions and anger goals. This inventory may be used, for example, as a diagnostic tool or for testing the effectiveness of anger management interventions.

Intervention studies to foster resilience - A systematic review and proposal for a resilience framework in future intervention studies.

Psychological resilience refers to the phenomenon that many people are able to adapt to the challenges of life and maintain mental health despite exposure to adversity. This has stimulated research on training programs to foster psychological resilience. We evaluated concepts, methods and designs of 43 randomized controlled trials published between 1979 and 2014 which assessed the efficacy of such training programs and propose standards for future intervention research based on recent developments in the field. We found that concepts, methods and designs in current resilience intervention studies are of limited use to properly assess efficacy of interventions to foster resilience. Major problems are the use of definitions of resilience as trait or a composite of resilience factors, the use of unsuited assessment instruments, and inappropriate study designs. To overcome these challenges, we propose 1) an outcome-oriented definition of resilience, 2) an outcome-oriented assessment of resilience as change in mental health in relation to stressor load, and 3) methodological standards for suitable study designs of future intervention studies. Our proposals may contribute to an improved quality of resilience intervention studies and may stimulate further progress in this growing research field.

Microdialysis-based 48-hour continuous glucose monitoring with GlucoDay: clinical performance and patients' acceptance.

BACKGROUND: This study was designed to assess clinical performance and patients' acceptance of the minimally invasive microdialysis-based continuous glucose monitoring system Gluco- Day() (Menarini Diagnostics, Florence, Italy) with a targeted monitoring time of 48 h. METHODS: An inpatient sample of 28 patients with diabetes was studied. The analysis of clinical performance was performed using mean absolute differences (MAD) (in percent), Pearson correlations, the Bland-Altman analysis, and Clarke Error Grid Analysis (EGA). GlucoDay glucose values were compared with laboratory standard blood glucose measurements (glucohexokinase assay). The patients' acceptance of the monitoring device was assessed via two self-report scales (pain during application and discomfort while wearing device). RESULTS: A mean (+/- SD) monitoring time of 45.7 +/- 3.3 h with a total of 484 paired readings could be achieved. A correlation of r (average) = 0.91 and a MAD of 19.9% indicated satisfactory to good clinical performance. Of the paired readings, 95.5% fell into the acceptable A and B zones of the EGA. Rather wide 95% limits of agreement were revealed in the Bland-Altman analysis. Whereas virtually no pain was experienced during sensor application, discomfort associated with wearing the device was rather high. All of the participants, however, stated that they would wear the device again. CONCLUSIONS: Satisfactory to good performance of the GlucoDay monitor was observed, indicating the device to be suitable for routine clinical use. In particular, however, the discomfort experienced during wearing requires further improvements in its usability.

Dipeptidyl peptidase IV (DPP-IV) from pig kidney cleaves analogs of bovine growth hormone-releasing factor (bGRF) modified at position 2 with Ser, Thr or Val. Extended DPP-IV substrate specificity?

The literature reported DPP-IV substrate specificity includes oligopeptides with a penultimate Pro, Hyp or Ala residue. Bovine GRF is a substrate for DPP-IV and is rapidly degraded by the enzyme via removal of its N-terminal Tyr-Ala. Incubation of selected GRF analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series with a porcine-kidney-derived DPP-IV in PBS (pH 7.4) resulted in cleavage at the X2-Asp3 bond. The extent of enzymatic hydrolysis varied with X2 as reflected in the following relative cleavage rates: Ala2 (100%), Ser2 (4%), Thr2 (2.5%), Val2 (0.53%), Ile2 (0%). These cleavages were sequestered when similar experiments were performed in the presence of the DPP-IV-specific inhibitor N-epsilon-(p-NO2-benzyloxycarbonyl)-Lys-Pro-OH. A side reaction, buffer-induced deamidation of Asn8, contributed less than 5% of the total substrate degradation. Although our finding qualitatively extends the DPP-IV substrate specificity to also include N-terminal X-Ser, X-Thr and X-Val sequences, quantitatively, relatively fast cleavages of the GRFs with Ala2 make the latter preferred substrates for DPP-IV. The data presented here indicates that the observed GRF(3-29) fragment formation upon incubation of Ser2- and Thr2-substituted bGRF analogs in bovine plasma could have been DPP-IV-related.

Position 2 and position 2/Ala15-substituted analogs of bovine growth hormone-releasing factor (bGRF) with enhanced metabolic stability and improved in vivo bioactivity.

In order to prepare GRF analogs with high activity in vivo, a strategy was undertaken to stabilize the peptide to dipeptidylpeptidase IV (DPP-IV), a protease found in plasma which inactivates native human and bovine GRF by cleavage of the Ala2-Asp3 bond. Replacement of the Ala2 residue with Ser, Thr, or Gly in [Leu27]bGRF(1-29)NH2 resulted in peptides greatly stabilized against proteolysis in plasma, but having low inherent GH-releasing activity when tested in bovine pituitary cell cultures. Replacement of Gly15 with Ala15 was marginally effective in improving the in vitro bioactivity of this group of peptides. When tested for GH-hormone release in steers, however, the Thr2,Ala15 analog was four times more potent than bGRF(1-44)NH2. Eleven additional analogs from the [X2,Ala15,Leu27]bGRF(1-29)NH2 series were synthesized and evaluated for metabolic stability in bovine plasma and for GH releasing activity in steers in vivo and in rat pituitary cells in vitro. Two compounds, [Val2,Ala15,Leu27]dGRF(1-29)NH2 and [Ile2,Ala15,Leu27]-bGRF(1-29)NH2, had increased GH-releasing activity in steers over that of [Thr2,Ala15,Leu27]-bGRF(1-29)NH2 and over a previously reported super-potent analog, [desNH2Tyr1,D-Ala2,Ala15]-hGRF(1-29)NH2.

Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife.

An expert meeting was organized by the World Health Organization (WHO) and held in Stockholm on 15-18 June 1997. The objective of this meeting was to derive consensus toxic equivalency factors (TEFs) for polychlorinated dibenzo-p-dioxins (PCDDs) and dibenzofurans (PCDFs) and dioxinlike polychlorinated biphenyls (PCBs) for both human, fish, and wildlife risk assessment. Based on existing literature data, TEFs were (re)evaluated and either revised (mammals) or established (fish and birds). A few mammalian WHO-TEFs were revised, including 1,2,3,7,8-pentachlorinated DD, octachlorinated DD, octachlorinated DF, and PCB 77. These mammalian TEFs are also considered applicable for humans and wild mammalian species. Furthermore, it was concluded that there was insufficient in vivo evidence to continue the use of TEFs for some di-ortho PCBs, as suggested earlier by Ahlborg et al. [Chemosphere 28:1049-1067 (1994)]. In addition, TEFs for fish and birds were determined. The WHO working group attempted to harmonize TEFs across different taxa to the extent possible. However, total synchronization of TEFs was not feasible, as there were orders of a magnitude difference in TEFs between taxa for some compounds. In this respect, the absent or very low response of fish to mono-ortho PCBs is most noticeable compared to mammals and birds. Uncertainties that could compromise the TEF concept were also reviewed, including nonadditive interactions, differences in shape of the dose-response curve, and species responsiveness. In spite of these uncertainties, it was concluded that the TEF concept is still the most plausible and feasible approach for risk assessment of halogenated aromatic hydrocarbons with dioxinlike properties.

Pharmacology of FMRFamide-related peptides in helminths.

Nervous systems of helminths are highly peptidergic. Species in the phylum Nematoda (roundworms) possess at least 50 FMRFamide-related peptides (FaRPs), with more yet to be identified. To date, few non-FaRP neuropeptides have been identified in these organisms, though evidence suggests that other families are present. FaRPergic systems have important functions in nematode neuromuscular control. In contrast, species in the phylum Platyhelminthes (flatworms) apparently utilize fewer FaRPs than do nematodes; those species examined possess one or two FaRPs. Other neuropeptides, such as neuropeptide F (NPF), play key roles in flatworm physiology. Although progress has been made in the characterization of FaRP pharmacology in helminths, much remains to be learned. Most studies on nematodes have been done with Ascaris suum because of its large size. However, thanks to the Caenorhabditis elegans genome project, we know most about the FaRP complement of this free-living animal. That essentially all C. elegans FaRPs are active on at least one A. suum neuromuscular system argues for conservation of ligand-receptor recognition features among the Nematoda. Structure-activity studies on nematode FaRPs have revealed that structure-activity relationship (SAR) "rules" differ considerably among the FaRPs. Second messenger studies, along with experiments on ionic dependence and anatomical requirements for activity, reveal that FaRPs act through many different mechanisms. Platyhelminth FaRPs are myoexcitatory, and no evidence exists of multiple FaRP receptors in flatworms. Interestingly, there are examples of cross-phylum activity, with some nematode FaRPs being active on flatworm muscle. The extent to which other invertebrate FaRPs show cross-phylum activity remains to be determined. How FaRPergic nerves contribute to the control of behavior in helminths, and are integrated with non-neuropeptidergic systems, also remains to be elucidated.

Importance of the proline residue to the functional activity and metabolic stability of the nematode FMRFamide-related peptide, KPNFIRFamide (PF4).

PF4 has previously been shown to have potent inhibitory effects on myoactivity of somatic muscle strips from the nematode. Ascaris suum. This study examined the bioactivity and metabolic stability of position 2- and position 5-modified analogues of PF4. Although the analogues [Leu5]PF4,[Ala2]PF4, [Gly2]PF4, [Ala2,Leu5]PF4, and [Gly2,Leu5]PF4 all had qualitatively similar inhibitory effects on A. suum somatic muscle strips, their effects were quantitatively distinguishable and had the order of potency: PF4 = [Leu5]PF4 > > [Ala2]PF4 = [Ala2,Leu5]PF4 > > [Gly2]PF4 = [Gly2,Leu5]PF4, Leu5 for Ile5 substitutions in PF4 did not alter the activity of this peptide: however, Gly2/Ala2 for Pro2 substitutions reduced, but did not abolish, peptide activity. Peptide stability studies revealed that [Gly2]PF4(2-7) and -(3-7) and [Ala2]PF4(2-7), -(3-7), and -(4-7) fragments were generated following exposure to A. suum somatic muscle strips. However, the parent peptide (PF4) was not metabolized and appeared to be resistant to the sequential cleavages of native aminopeptidases. Observed analogue metabolism appeared to be due to the activity of released aminopeptidases as identical fragments were generated by incubation in medium that had been exposed to somatic muscle strips and from which the strips had been removed prior to peptide addition. It was found that the muscle stretching and bath mixing characteristics of the tension assay led to more effective release of soluble enzymes from muscle strips and thus greater peptide degradation. These studies reveal that Pro2 in PF4 is not essential for the biological activity of this peptide; however, it does render the peptide resistant to the actions of native nematode aminopeptidases.

Isolation and preliminary biological characterization of KPNFIRFamide, a novel FMRFamide-related peptide from the free-living nematode, Panagrellus redivivus.

A novel FMRFamide-related heptapeptide, Lys-Pro-Asn-Phe-Ile-Arg-Phe-NH2 (KPNFIRFamide), was isolated and characterized from acid ethanol extracts of the free-living nematode, Panagrellus redivivus. Whole-worm extracts contained > or = 9 pmol KPNFIRFamide/g wet weight. A synthetic replicate of this peptide induced a rapid relaxation of tone and inhibited spontaneous contractility in isolated innervated and denervated body-wall muscle strips of the parasitic nematode, Ascaris suum. KPNFIRFamide (0.1 nM) induced measurable relaxations in 50% of the muscle preparations examined. Concentrations > or = 0.3 nM induced relaxation in 100% of muscle preparations examined. The relaxation was short-lived at concentrations of peptide > or = 1 microM and displayed a profile typical of receptor desensitization. These data suggest the occurrence of a closely related peptide in A. suum and add further evidence to the concept of primary structural conservation of FaRPs within the nematodes.

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetes.

Emotional changes during experimentally induced hypoglycaemia in type 1 diabetic patients were investigated using a hyperinsulinaemic glucose clamp. In the experimental group (n=11), blood glucose was stabilised at euglycaemia (5.6 mmol/l, phase 1), then lowered to 2.5 mmol/l (phase 2) and raised to 5.6 mmol/l (phase 3). In the control group (n=11), euglycaemia was maintained during all phases. Hypoglycaemia elicited the expected endocrine, symptomatic and neuroglycopenic effects. During hypoglycaemia negative mood states increased significantly, whereas positive mood states decreased. Hypoglycaemia prolonged rating time of emotional stimuli (drawn from IAPS) significantly. The arousal ratings of the slides were higher during hypoglycaemia. Valence and dominance ratings were not affected. Epinephrine and norepinephrine release correlated with a higher arousal rating and a decrease in positive mood states. Deterioration in neuropsychological tasks correlated with an increase in negative mood states. Experimental induction of hypoglycaemia can offer a new research model to study emotional processes.

Retinoids in eggs and embryos of birds fed fish from the Great Lakes.

Retinoids were analyzed in 11-day chick embryos and eggs from white Leghorn hens (Gallus domesticus) fed environmentally-derived polychlorinated biphenyls (PCB) in carp (Cyprinus carpio) from Saginaw Bay. The yolks and the embryos contained all-trans-retinol, 3,4-didehydroretinol and retinyl esters. There was no significant difference in the total retinoid content in the yolks of 11-day incubated eggs among hens fed for 7 weeks diets containing 0.5-6.6 mg PCB/kg diet. However, the proportional amount of retinols in the high (6.6 mg) PCB group was significantly less than that in low (0.5 mg) PCB controls, while the amount of retinyl palmitate in the high PCB group was significantly greater than that in the controls. Retinoids in the embryos were not affected by any of the PCB levels fed to hens for 7 weeks prior to laying the eggs. The 50% reduction in the molar ratio of retinols to retinyl palmitate in the yolks of eggs as the result of the high PCB level fed to hens for 7 weeks can serve as an indicator for chronic exposure to PCB contamination at the level of 6.6 mg or higher PCB/kg diet.

Continuous glucose monitoring reveals associations of glucose levels with QT interval length.

BACKGROUND: QTc interval lengthening during hypoglycemia is discussed as a mechanism linked to sudden death in diabetes patients and the so-called "dead in bed syndrome." Previous research reported a high interindividual variability in the glucose-QTc association. The present study aimed at deriving parameters for direction and strength of the glucose-QTc association on the patient level using combined Holter electrocardiogram (ECG) and continuous glucose monitoring. METHODS: Twenty type 1 diabetes patients were studied: mean (SD, range) age, 43.6 (10.8, 22-65) years; gender male (n [%]), 10 (50.0%); mean (SD) hemoglobin A1C, 8.5% (1.0%); and impaired hypoglycemia awareness (n [%]), six (30.0%). Continuous interstitial glucose monitoring and Holter ECG monitoring were performed for 48 h. Hierarchical (mixed) regression modeling was used to account for the structure of the data. RESULTS: Glucose levels during nighttime were negatively associated with QTc interval length if the data structure was accounted for (b [SE] = -0.76 [0.17], P = 0.000). Exploratory regression analysis revealed hypoglycemia awareness as the only predictor of the individual strength of the glucose-QTc association, with the impaired awareness group showing less evidence for an association of low glucose with QTc lengthening. CONCLUSIONS: Mixed regression allows for deriving parameters for the glucose-QTc association on the patient level. Consistent with previous studies, we found a large interindividual variability in the glucose-QTc association. The finding on impaired hypoglycemia awareness patients has to be interpreted with caution but provides some support for the role of sympathetic activation for the QTc-glucose link.

The effect of an education programme (HyPOS) to treat hypoglycaemia problems in patients with type 1 diabetes.

BACKGROUND: In a randomized, prospective multi-centre trial, the effect of a specific training programme (HyPOS) for patients with hypoglycaemia problems was compared with a control group (CG), receiving a standardized education programme aiming at avoidance of hypoglycaemia by optimization of insulin therapy. METHODS: A total of 164 type 1 diabetes patients (age 46.0 +/- 12.5 yrs, HbA(1c) 7.3 +/- 1.0%, 50% male) were randomized. Hypoglycaemia awareness was measured by the hypoglycaemia awareness questionnaire (HAQ) and by a visual analogue scale (VAS). There were no baseline differences. RESULTS: After a 6-month follow-up, hypoglycaemia awareness significantly improved in HyPOS compared to that in the CG (Delta HAQ 0.7 [95% CL 0.1-1.2], p = 0.024, Delta VAS 0.8 [95% CL 0.2 - 1.2], p = 0.015). In HyPOS, the threshold for detection of low blood glucose (Delta 0.2 mmol/L [95% CL 0.03 - 0.04], p = 0.02) and the treatment of low blood glucose (Delta 4.6 g [95% CL 1.6 - 7.6], p = 0.03) increased significantly. The number of undetected hypogylcaemic episodes (Delta - 1.4 episodes per week [95% CL 0.4-2.5], p = 0.01) and the rate of mild hypoglycaemia dropped significantly in HyPOS (Delta 2.1% [95% CL 0.5-5.3], p = 0.015). The numbers of severe (Delta 0.3 events per patient per year [95% CL - 0.04-1.0], p = 0.037) and very severe hypoglycaemic episodes (Delta 0.3 events per patient per year [95% CL - 0.1-0.7], p = 0.09) were lower in HyPOS, but these differences were not significant. CONCLUSION: Compared to the CG, HyPOS demonstrates additional benefits in terms of improving impaired hypoglycaemia awareness, reducing mild hypoglycaemia, detecting low blood glucose, and treating low blood glucose.