Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 170
Filter
1.
J Chem Phys ; 160(24)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38912674

ABSTRACT

Simulations of photochemical reaction dynamics have been a challenge to the theoretical chemistry community for some time. In an effort to determine the predictive character of current approaches, we predict the results of an upcoming ultrafast diffraction experiment on the photodynamics of cyclobutanone after excitation to the lowest lying Rydberg state (S2). A picosecond of nonadiabatic dynamics is described with ab initio multiple spawning. We use both time dependent density functional theory (TDDFT) and equation-of-motion coupled cluster singles and doubles (EOM-CCSD) theory for the underlying electronic structure theory. We find that the lifetime of the S2 state is more than a picosecond (with both TDDFT and EOM-CCSD). The predicted ultrafast electron diffraction spectrum exhibits numerous structural features, but weak time dependence over the course of the simulations.

2.
J Chem Phys ; 158(20)2023 May 28.
Article in English | MEDLINE | ID: mdl-37212413

ABSTRACT

We present efficient analytical gradients of property-based diabatic states and couplings using a Lagrangian formalism. Unlike previous formulations, the method achieves a computational scaling that is independent of the number of adiabatic states used to construct the diabats. The approach is generalizable to other property-based diabatization schemes and electronic structure methods as long as analytical energy gradients are available and integral derivatives with the property operator can be formed. We also introduce a scheme to phase and reorder diabats to ensure their continuity between molecular configurations. We demonstrate this for the specific case of Boys diabatic states obtained from state-averaged complete active space self-consistent field electronic structure calculations with GPU acceleration in the TeraChem package. The method is used to test the Condon approximation for the hole transfer in an explicitly solvated model DNA oligomer.

3.
J Am Chem Soc ; 144(43): 19668-19672, 2022 Nov 02.
Article in English | MEDLINE | ID: mdl-36251402

ABSTRACT

The X-ray absorption spectrum (XAS) of the hydrated electron (e(aq)-) has been simulated using time-dependent density functional theory with a quantum mechanics/molecular mechanics description. A unique XAS peak at 533 eV is observed with an energy and intensity in quantitative agreement with recent time-resolved experiments, allowing its assignment as arising from water O1s transitions to the singly occupied molecular orbital (SOMO) in which the excess electron resides. The transitions acquire oscillator strength due to the SOMO comprising an admixture of a cavity-localized orbital and water 4a1 and 2b2 antibonding orbitals. The mixing of antibonding orbitals has implications for the strength of couplings between e(aq)- and intramolecular modes of water.

4.
J Chem Phys ; 155(7): 071103, 2021 Aug 21.
Article in English | MEDLINE | ID: mdl-34418944

ABSTRACT

We introduce Active Orbital Preservation for Multiconfigurational Self-Consistent Field (AOP-MCSCF), an automated approach to improving the consistency of active space orbitals over multiple molecular configurations. Our approach is based on maximum overlap with a reference set of active space orbitals taken from a single geometry of a chromophore in the gas phase and can be used to automatically preserve the appropriate orbitals of the chromophore across multiple thermally sampled configurations, even when the chromophore is solvated by quantum-mechanically treated water molecules. In particular, using the singular value decomposition of a Molecular Orbital (MO) overlap matrix between the system and reference, we rotate the MOs of the system to align with the reference active space orbitals and use the resulting rotated orbitals as an initial guess to a MCSCF calculation. We demonstrate the approach on aqueous p-hydroxybenzylidene-imidazolinone (HBI) and find that AOP-MCSCF converges to the "correct" orbitals for over 90% of 3000 thermally sampled configurations. In addition, we compute the linear absorption spectrum and find excellent agreement with new experimental measurements up to 5.4 eV (230 nm). We show that electrostatic contributions to the solvation energy of HBI largely explain the observed state-dependent solvatochromism.

5.
Horm Metab Res ; 53(3): 204-206, 2021 Mar.
Article in English | MEDLINE | ID: mdl-33652492

ABSTRACT

Currently, we are experiencing a true pandemic of a communicable disease by the virus SARS-CoV-2 holding the whole world firmly in its grasp. Amazingly and unfortunately, this virus uses a metabolic and endocrine pathway via ACE2 to enter our cells causing damage and disease. Our international research training programme funded by the German Research Foundation has a clear mission to train the best students wherever they may come from to learn to tackle the enormous challenges of diabetes and its complications for our society. A modern training programme in diabetes and metabolism does not only involve a thorough understanding of classical physiology, biology and clinical diabetology but has to bring together an interdisciplinary team. With the arrival of the coronavirus pandemic, this prestigious and unique metabolic training programme is facing new challenges but also new opportunities. The consortium of the training programme has recognized early on the need for a guidance and for practical recommendations to cope with the COVID-19 pandemic for the community of patients with metabolic disease, obesity and diabetes. This involves the optimal management from surgical obesity programmes to medications and insulin replacement. We also established a global registry analyzing the dimension and role of metabolic disease including new onset diabetes potentially triggered by the virus. We have involved experts of infectious disease and virology to our faculty with this metabolic training programme to offer the full breadth and scope of expertise needed to meet these scientific challenges. We have all learned that this pandemic does not respect or heed any national borders and that we have to work together as a global community. We believe that this transCampus metabolic training programme provides a prime example how an international team of established experts in the field of metabolism can work together with students from all over the world to address a new pandemic.


Subject(s)
COVID-19 , Diabetes Mellitus , Education, Medical, Continuing , Obesity , Pandemics , SARS-CoV-2 , COVID-19/epidemiology , COVID-19/therapy , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy , Humans , Obesity/epidemiology , Obesity/therapy
6.
J Chem Theory Comput ; 17(3): 1497-1511, 2021 Mar 09.
Article in English | MEDLINE | ID: mdl-33538588

ABSTRACT

We explore the convergence of the many-body expansion for a prototypical hole-transfer reaction between Zn(0) and Zn(I) in a condensed-phase environment. Poor convergence of state energies is seen when the adiabatic representation is used, which can be understood from the fragment single-point calculations at low orders of the many-body expansion incorrectly localizing charges compared to the full system, thus leading to qualitative errors in the electronic structure of the adiabatic states between fragments. Using a charge-localized representation of the electronic Hamiltonian, we introduce a diabatic many-body expansion method with quantitative accuracy for ground- and excited-state potential energy surfaces of a charge-transfer reaction. Combining with a multiconfigurational self-consistent field affords a fragmentation approach that scales quadratically with system size while retaining chemical accuracy (<1 kcal/mol) in total energies compared to full system calculations.

7.
Biochim Biophys Acta Gen Subj ; 1864(6): 129534, 2020 06.
Article in English | MEDLINE | ID: mdl-31954797

ABSTRACT

BACKGROUND: We re-evaluate our RNA-As-Graphs clustering approach, using our expanded graph library and new RNA structures, to identify potential RNA-like topologies for design. Our coarse-grained approach represents RNA secondary structures as tree and dual graphs, with vertices and edges corresponding to RNA helices and loops. The graph theoretical framework facilitates graph enumeration, partitioning, and clustering approaches to study RNA structure and its applications. METHODS: Clustering graph topologies based on features derived from graph Laplacian matrices and known RNA structures allows us to classify topologies into 'existing' or hypothetical, and the latter into, 'RNA-like' or 'non RNA-like' topologies. Here we update our list of existing tree graph topologies and RAG-3D database of atomic fragments to include newly determined RNA structures. We then use linear and quadratic regression, optionally with dimensionality reduction, to derive graph features and apply several clustering algorithms on our tree-graph library and recently expanded dual-graph library to classify them into the three groups. RESULTS: The unsupervised PAM and K-means clustering approaches correctly classify 72-77% of all existing graph topologies and 75-82% of newly added ones as RNA-like. For supervised k-NN clustering, the cross-validation accuracy ranges from 57 to 81%. CONCLUSIONS: Using linear regression with unsupervised clustering, or quadratic regression with supervised clustering, provides better accuracies than supervised/linear clustering. All accuracies are better than random, especially for newly added existing topologies, thus lending credibility to our approach. GENERAL SIGNIFICANCE: Our updated RAG-3D database and motif classification by clustering present new RNA substructures and RNA-like motifs as novel design candidates.


Subject(s)
Computational Biology , Nucleic Acid Conformation , RNA/genetics , Algorithms , Cluster Analysis , Databases, Factual , Gene Library , Humans , Linear Models , Models, Molecular , RNA/ultrastructure
8.
J Diabetes Res ; 2019: 7891359, 2019.
Article in English | MEDLINE | ID: mdl-31781667

ABSTRACT

BACKGROUND: Understanding ethnic differences in beta cell function has important implications for preventative and therapeutic strategies in populations at high risk of type 2 diabetes (T2D). The existing literature, largely drawn from work in children and adolescents, suggests that beta cell function in black African (BA) populations is upregulated when compared to white Europeans (WE). METHODS: A systematic literature search was undertaken in June 2018 to identify comparative studies of beta cell function between adults (>age 18 years) of indigenous/diasporic BA and WE ethnicity. All categories of glucose tolerance and all methodologies of assessing beta cell function in vivo were included. RESULTS: 41 studies were identified for inclusion into a qualitative synthesis. The majority were studies in African American populations (n = 30) with normal glucose tolerance (NGT)/nondiabetes (n = 25), using intravenous glucose stimulation techniques (n = 27). There were fewer studies in populations defined as only impaired fasting glucose/impaired glucose tolerance (IFG/IGT) (n = 3) or only T2D (n = 3). Although BA broadly exhibited greater peripheral insulin responses than WE, the relatively small number of studies which measured C-peptide to differentiate between beta cell insulin secretion and hepatic insulin extraction (n = 14) had highly variable findings. In exclusively IGT or T2D cohorts, beta cell insulin secretion was found to be lower in BA compared to WE. CONCLUSIONS: There is inconsistent evidence for upregulated beta cell function in BA adults, and they may in fact exhibit greater deficits in insulin secretory function as glucose intolerance develops.


Subject(s)
Black People , Blood Glucose/metabolism , Diabetes Mellitus, Type 2/ethnology , Insulin Resistance/ethnology , Insulin-Secreting Cells/metabolism , Insulin/blood , White People , Adult , Biomarkers/blood , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/physiopathology , Female , Humans , Male , Middle Aged , Prognosis , Risk Factors , Young Adult
9.
Diabet Med ; 36(11): 1512-1513, 2019 11.
Article in English | MEDLINE | ID: mdl-31631419
10.
Diabet Med ; 36(11): 1329-1335, 2019 11.
Article in English | MEDLINE | ID: mdl-31418474

ABSTRACT

Pharmacological, technological and educational approaches have advanced the treatment of Type 1 diabetes in the last four decades and yet diabetic ketoacidosis (DKA) continues to be a leading cause of admission in Type 1 diabetes. This article begins by reviewing the contemporary epidemiological evidence in DKA. It highlights a rise in DKA episodes in the last two decades, with DKA continuing to be the leading cause of death in young people with Type 1 diabetes, and that DKA episodes are a marker for subsequent all-cause mortality. It also summarizes the limited evidence base for DKA prevention and associations with psychopathology. To emphasize the importance of this group with high-risk Type 1 diabetes and the degree to which they have been overlooked in the past two decades, the article summarizes the research literature of recurrent DKA during 1976-1991 when it was extensively investigated as part of the phenomenon of 'brittle diabetes'. This period saw numerous basic science studies investigating the pathophysiology of recurrent DKA. Subsequently, research centres published their experiences of brittle diabetes research participants manipulating their treatment under research conditions. Unfortunately, the driver for this behaviour and whether it was indicative of other people with ketoacidosis was not pursued. In summary, we suggest there has been a stasis in the approach to recurrent DKA prevention, which is likely linked to historical cases of mass sabotage of brittle diabetes research. Further investigation is required to clarify possible psychological characteristics that increase the risk of DKA and thereby targets for DKA prevention.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetic Ketoacidosis/prevention & control , Hospitalization/statistics & numerical data , Medication Adherence/statistics & numerical data , Mental Disorders/diagnosis , Cause of Death , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/mortality , Diabetes Mellitus, Type 1/psychology , Diabetic Ketoacidosis/etiology , Diabetic Ketoacidosis/mortality , Diabetic Ketoacidosis/psychology , Health Services Research , Humans , Medication Adherence/psychology , Mental Disorders/epidemiology , Mental Health , Recurrence , Risk Factors
11.
Occup Med (Lond) ; 69(5): 322-328, 2019 Aug 22.
Article in English | MEDLINE | ID: mdl-31087077

ABSTRACT

BACKGROUND: The effect of depression on both employment and productivity in type 2 diabetes (T2D) is poorly understood. AIMS: We tested whether depressive symptoms at diagnosis of T2D are associated with change in employment status and productivity over 2-year follow-up. METHODS: In a prospective analysis of working-age (18-63 years) people with newly diagnosed T2D recruited from primary care, we tested the association between depressive symptoms at diagnosis of T2D (baseline) and employment rates over 2 years. Using the Patient Health Questionnaire-9, depressive symptoms were measured categorically (depression caseness score ≥10) and continuously. In those employed, we measured changes in presenteeism and absenteeism using the World Health Organization (WHO) Health and Work Performance Questionnaire in univariate and multivariate models, respectively, including and excluding part-time workers. RESULTS: Of 1202 people aged 18-63 at baseline, 982 (82%) provided employment information; the mean age was 50.3 (SD 8.1) years, 44% were female, 59% of non-white ethnicity and 16% had depression. After adjustment for age, sex, ethnicity, socio-economic status, diabetes control and depression treatment, depression caseness was associated with worsening unemployment over 2 years only in full-time workers (odds ratio 0.43 (95% CI 0.20, 0.96), P < 0.05). In those employed full-time or part-time, total depressive symptoms were associated with worsening presenteeism over 2 years after full adjustment (ß = -2.63 (95% CI -4.81, -0.45), P < 0.05), despite no association with worsening absenteeism. CONCLUSIONS: In newly diagnosed T2D, depressive symptoms demonstrate an association with worsening employment rate and decline in work productivity over 2-year follow-up.


Subject(s)
Depression/complications , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/psychology , Employment/statistics & numerical data , Absenteeism , Adult , Female , Humans , Longitudinal Studies , Male , Middle Aged , Presenteeism/statistics & numerical data , Prospective Studies , Surveys and Questionnaires
12.
Diabet Med ; 2018 Jun 08.
Article in English | MEDLINE | ID: mdl-29882990

ABSTRACT

AIM: To explore reasons for the poor uptake of accredited diabetes self-management education (DSME) in adults with Type 1 diabetes. METHODS: The study was set in an urban population in South London, UK. A cross sectional survey gathered demographic, diabetes service-use data, psychological scores and reasons for non-attendance at locally-available DSME. In addition, 56 healthcare professionals were surveyed. RESULTS: Responses to surveys were returned by 496 adults with Type 1 diabetes (33% response rate), of whom 263 had attended DSME (53%). Multivariable analysis adjusted for significant variables identified four key variables influencing attendance. Non-attendance was associated with men (OR 0.55 CI 0.37-0.84, p = 0.005), lower educational attainment (OR 0.45 CI 0.28-0.73, p = 0.001), higher glycated haemoglobin (OR 1.74 CI 1.03-2.94, p = 0.04) and healthcare professional encouragement to attend (OR 1.7 CI 1.28-2.3, p = 0.001). The most frequently reported barriers to attendance were work (37%) and time (14%) commitments. Only 49% of healthcare professionals (HCPs) correctly identified the most likely barriers. Those HCPs who had observed courses believed more in their efficacy, with higher uptake within their clinic population. CONCLUSIONS: Social determinants of health, particularly educational attainment and gender, increase health inequalities by influencing decisions to attend evidence-based education courses. Healthcare professional communication is paramount to encourage attendance, and observation of a course may facilitate this.

13.
Diabet Med ; 35(3): 306-316, 2018 03.
Article in English | MEDLINE | ID: mdl-29044708

ABSTRACT

The inability to achieve optimal diabetes glucose control in people with diabetes is multifactorial, but one contributor may be inadequate control of postprandial glucose. In patients treated with multiple daily injections of insulin, both the dose and timing of meal-related rapid-acting insulin are key factors in this. There are conflicting opinions and evidence on the optimal time to administer mealtime insulin. We performed a comprehensive literature search to review the published data, focusing on the use of rapid-acting insulin analogues in patients with Type 1 diabetes. Pharmacokinetic and pharmacodynamic studies of rapid-acting insulin analogues, together with postprandial glucose excursion data, suggest that administering these 15-20 min before food would provide optimal postprandial glucose control. Data from clinical studies involving people with Type 1 diabetes receiving structured meals and rapid-acting insulin analogues support this, showing a reduction in post-meal glucose levels of ~30% and less hypoglycaemia when meal insulin was taken 15-20 min before a meal compared with immediately before the meal. Importantly, there was also a greater risk of postprandial hypoglycaemia when patients took rapid-acting analogues after eating compared with before eating.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/administration & dosage , Insulins/administration & dosage , Blood Glucose/metabolism , Clinical Studies as Topic , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Humans , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/pharmacology , Insulin Aspart/administration & dosage , Insulin Aspart/pharmacokinetics , Insulin Aspart/pharmacology , Insulin Glargine/administration & dosage , Insulin Glargine/pharmacokinetics , Insulin Glargine/pharmacology , Insulin Lispro/administration & dosage , Insulin Lispro/pharmacokinetics , Insulin Lispro/pharmacology , Insulins/pharmacokinetics , Insulins/pharmacology , Postprandial Period/physiology
14.
Diabet Med ; 34(10): 1456-1460, 2017 10.
Article in English | MEDLINE | ID: mdl-28763121

ABSTRACT

AIM: Most guidelines provide people with Type 1 diabetes with pre- and post-meal capillary blood glucose (CBG) targets to achieve optimal glycaemic control. We evaluated the proportion of daily CBG readings between 4 and 10 mmol/l in people achieving different HbA1c levels. METHOD: We analysed CBG data from routine pump/meter downloads from 201 adults treated with continuous subcutaneous insulin infusion (CSII) at a single hospital clinic. Exclusion criteria were CSII < 6 months, < 3 CBG/day, pregnancy, haemoglobinopathy and continuous sensor use. People were categorized into three groups based on HbA1c : < 58 mmol/mol, < 7.5% (n = 58); 58-74 mmol/mol, 7.5-8.9% (n = 107); and ≥ 75 mmol/mol, ≥ 9.0% (n = 36). RESULTS: Participants had a mean age of 43 ± 13 years and mean HBA1c of 64 mmol/mol (8.0 ± 1.1%). 47% of people started CSII for raised HbA1c , 25% due to hypoglycaemia and the rest during pregnancy. Downloads contained a mean of 22 ± 6.8 days of data per participant. CBG frequency was similar between the three groups (5.6 ± 2.0, 5.6 ± 1.9 and 5.4 ± 1.2 CBG/day; P = 0.468). The proportion of CBG readings between 4 and 10 mmol/l (72-180 mg/dl) was 57.3 ± 25.4%, 50.6 ± 11.1% and 39.9 ± 16.5% (P < 0.0001); < 4 mmol was 13.8%, 8.8% and 4.4% (P < 0.0001) and > 10 mmol/l was 28.9 ± 16.5%, 40.6 ± 12.1% and 55.6 ± 17.9% (P < 0.0001) in the three groups respectively. CONCLUSIONS: Participants achieving HBA1c < 58 mmol/mol (< 7.5%) had ~ 60% of CBG readings in range (4-10 mmol/l), with up to 30% of readings > 10 mmol/l. This target of achieving 60% or more readings within target, and being permissive with up to 30% readings > 10 mmol/l may be a novel target for people with diabetes, and may reduce anxiety associated with readings out of range.


Subject(s)
Blood Glucose/analysis , Blood Glucose/drug effects , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/drug therapy , Goals , Insulin/administration & dosage , Adult , Blood Glucose Self-Monitoring/standards , Capillaries/chemistry , Circadian Rhythm , Female , Glycated Hemoglobin/analysis , Humans , Insulin/pharmacology , Insulin Infusion Systems , Male , Middle Aged , Pregnancy , Pregnancy in Diabetics/blood , Pregnancy in Diabetics/drug therapy , Reference Values , Retrospective Studies
15.
Diabet Med ; 34(6): 828-833, 2017 06.
Article in English | MEDLINE | ID: mdl-28196291

ABSTRACT

AIM: To investigate the factors influencing uptake of structured education for people with Type 1 diabetes in our local population in order to understand why such uptake is low. METHODS: We conducted a cross-sectional database study of adults with Type 1 diabetes in two south London boroughs, analysed according to Dose Adjustment For Normal Eating (DAFNE) attendance or non-attendance. Demographics, glycaemic control and service use, with subset analysis by ethnicity, were compared using univariate analysis. An exploratory regression model was used to identify influencing factors. RESULTS: The analysis showed that 73% of adults had not attended the DAFNE programme. For non-attenders vs attenders, male gender (59 vs 48%; P = 0.002), older age (39 vs 35 years; P < 0.001), non-white ethnicity (30 vs 20%; P = 0.001) and coming from an area of social deprivation (index of multiple deprivation score 31 vs 28; P < 0.001) were associated with non-attendance. The difference in gender (88% men vs 70% women; P < 0.001) and age (43 vs 34 years) persisted in the non-white group. Regression analysis showed that higher baseline HbA1c level (odds ratio 1.96; P = 0.004), younger age (odds ratio 0.98; P = 0.001) and lower social deprivation (odds ratio 0.52; P = 0.001) was associated with attendance. CONCLUSION: Socio-economic status and factors perceived as indicating greater severity of disease (HbA1c ) influence attendance at DAFNE. More work is necessary to understand the demography of non-attenders to aid future service design and alternative engagement strategies for these groups.


Subject(s)
Diabetes Mellitus, Type 1/epidemiology , Patient Education as Topic , Patient Participation/statistics & numerical data , Adult , Blood Glucose/metabolism , Cross-Sectional Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/therapy , Ethnicity , Female , Humans , London/epidemiology , Male , Middle Aged , Patient Acceptance of Health Care/ethnology , Patient Acceptance of Health Care/statistics & numerical data , Patient Education as Topic/methods , Patient Education as Topic/statistics & numerical data , Patient Participation/psychology , Socioeconomic Factors
16.
Prim Care Diabetes ; 10(2): 156-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26137918

ABSTRACT

We aimed to investigate the association between incretin-based therapies and 1-year change in depressive symptoms in a cohort of 1735 patients with newly diagnosed type 2 diabetes. The incretin group experienced significant reduction in depressive symptoms compared to controls. This was independent of HbA1c and may be mediated by an anti-inflammatory mechanism.


Subject(s)
Antidepressive Agents/therapeutic use , Depression/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Incretins/therapeutic use , Adult , Affect/drug effects , Aged , Biomarkers/blood , C-Reactive Protein/metabolism , Case-Control Studies , Depression/blood , Depression/diagnosis , Depression/psychology , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/diagnosis , Female , Humans , Incretins/adverse effects , Inflammation Mediators/blood , London , Male , Middle Aged , Prospective Studies , Time Factors , Treatment Outcome
17.
Diabet Med ; 32(11): 1453-9, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26213236

ABSTRACT

AIM: To evaluate the sustainability of the benefits of continuous subcutaneous insulin infusion therapy in routine practice in a cohort of adults with diabetes. METHODS: The clinical records of all adults starting continuous subcutaneous insulin infusion over 12 years at our centre were included in this study. Baseline and mean annual HbA(1c) levels were recorded. The frequency of mild-to-moderate and severe hypoglycaemia and hypoglycaemia awareness were analysed in a subgroup. RESULTS: Adequate data were available from 327 patients, of whom 71% were female. The patients' mean ± sd age was 41 ± 14 years, the mean ± sd (range) follow-up for continuous subcutaneous insulin infusion was 4.3 ± 2.7 (1-12) years. The mean ± sd HbA(1c) concentration fell by 8 ± 5 mmol/mol (0.7 ± 0.5%) at year 1 [to 63 ± 12 mmol/mol from 70 ± 18 mmol/mol (7.9 ± 1.1% from 8.6 ± 1.6%); P < 0.0005], sustained to year 5. In patients with initial poor control, HbA(1c) dropped by 12 ± 11 mmol/mol (1.1 ± 1.0%; P < 0.0005) at year 1, sustained to year 6. The percentage of patients with ≥ 5 mild to moderate hypoglycaemic episodes per week fell from 29 to 12% (n = 163; P = 0.006). In the subgroup (n = 87; follow-up 2.5 ± mean ± sd 1.1 years), the frequency of severe hypoglycaemia fell from 0.6 ± 1.7 episodes per patient per year to 0.3 ± 0.9 (P = 0.047). Of 24 patients with impaired awareness of hypoglycaemia (Gold score ≥ 4), the mean ± sd Gold score improved from 4.9 ± 0.9 to 3.8 ± 1.7 (P = 0.011). Nine people regained awareness. No deterioration in HbA(1c) was seen in the hypoglycaemia-prone groups. CONCLUSIONS: The benefits of continuous subcutaneous insulin infusion with regard to improving glycaemic control and reducing hypoglycaemia frequency, along with improvement in hypoglycaemia awareness without deterioration in glycaemic control, can be sustained over several years in clinical practice.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hyperglycemia/prevention & control , Hypoglycemia/prevention & control , Hypoglycemic Agents/administration & dosage , Insulin Infusion Systems , Insulin/administration & dosage , Adult , Cohort Studies , Combined Modality Therapy , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diet therapy , Diet, Diabetic , Female , Follow-Up Studies , Glycated Hemoglobin/analysis , Health Knowledge, Attitudes, Practice , Hospitals, University , Humans , Hyperglycemia/physiopathology , Hypoglycemia/physiopathology , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , London , Male , Middle Aged , Patient Education as Topic , Retrospective Studies , Severity of Illness Index
18.
Diabet Med ; 32(8): 1071-6, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25982032

ABSTRACT

AIM: This study investigates the relationship between basal insulin regimen and glycaemic outcomes 12 months after skills-based structured education in the UK Dose Adjustment for Normal Eating (DAFNE) programme for Type 1 diabetes mellitus. METHOD: Retrospective analysis of data from 892 DAFNE participants from 11 UK centres. RESULTS: Mean HbA1c 12 months after DAFNE was lower in those using twice- rather than once-daily basal insulin after correcting for differences in baseline HbA1c , age and duration of diabetes; difference -2 (95% CI -3 to -1) mmol/mol [-0.2 (-0.3 to -0.1)%], P = 0.009. The greatest fall in HbA1c of -5 (-7 to -3) mmol/mol [-0.4 (-0.6 to -0.3)%], P < 0.001 occurred in those with less good baseline control, HbA1c  ≥ 58 mmol/mol, who switched from once- to twice-daily basal insulin. There was no difference in the 12-month HbA1c between users of glargine, detemir and NPH insulin after correcting for other variables. Relative risk of severe hypoglycaemia fell by 76% and ketoacidosis by 63% 12 months after DAFNE. The rate of severe hypoglycaemia fell from 0.82 to 0.23 events/patient year in twice-daily basal insulin users. In the group with greatest fall in HbA1c , the estimated relative risk for severe hypoglycaemia in twice-daily basal insulin users versus once daily at 12 months was 1.72 (0.88-3.36, P = 0.110). CONCLUSION: After structured education in adults with Type 1 diabetes mellitus, use of basal insulin twice rather than once daily was associated with lower HbA1c , independent of insulin type, with significant reductions in severe hypoglycaemia and ketoacidosis in all groups.


Subject(s)
Diabetes Mellitus, Type 1/drug therapy , Hypoglycemic Agents/administration & dosage , Insulin, Long-Acting/administration & dosage , Patient Education as Topic , Self Care , Adult , Blood Glucose/metabolism , Cohort Studies , Diabetes Mellitus, Type 1/metabolism , Diabetic Ketoacidosis/prevention & control , Female , Glycated Hemoglobin/metabolism , Humans , Hypoglycemia/chemically induced , Hypoglycemic Agents/adverse effects , Insulin Detemir/administration & dosage , Insulin Detemir/adverse effects , Insulin Glargine/administration & dosage , Insulin Glargine/adverse effects , Insulin, Isophane/administration & dosage , Insulin, Isophane/adverse effects , Insulin, Long-Acting/adverse effects , Logistic Models , Male , Middle Aged , Retrospective Studies , Treatment Outcome
19.
Diabet Med ; 32(5): 601-8, 2015 May.
Article in English | MEDLINE | ID: mdl-25615888

ABSTRACT

AIMS: To explore the psychosocial experiences of closed-loop technology and to compare ratings of closed- and open-loop technology for adults with Type 1 diabetes taking part in a randomized crossover study. METHODS: Adults (aged > 18 years) on insulin pump therapy were recruited to receive a first phase of either real-time continuous glucose monitoring with overnight closed-loop or real-time continuous glucose monitoring alone (open-loop) followed by a second phase of the alternative treatment in random order, at home for 4 weeks, unsupervised. Participants were invited to share their views in semi-structured interviews. The impact of the closed-loop technology, positive and negative aspects of living with the device overnight, along with the hopes and anxieties of the participants, were explored. RESULTS: The participants in the trial were 24 adults with a mean (sd) age of 43 (12) years, of whom 54% were men. The mean (range) interview duration was 26 (12-46) min. Content and thematic analysis showed the following key positive themes: improved blood glucose control (n = 16); reassurance/reduced worry (n = 16); improved overnight control leading to improved daily functioning and diabetes control (n = 16); and improved sleep (n = 8). The key negative themes were: technical difficulties (n = 24); intrusiveness of alarms (n = 13); and size of equipment (n = 7). Of the 24 participant, 20 would recommend the closed-loop technology. CONCLUSIONS: Closed-loop therapy has positive effects when it works in freeing participants from the demands of self-management. The downside was technical difficulties, particularly concerning the pump and 'connectivity', which it is hoped will improve. Future research should continue to explore the acceptability of the closed-loop system as a realistic therapy option, taking account of user concerns as new systems are designed. Failure to do this may reduce the eventual utility of new systems.


Subject(s)
Ambulatory Care , Diabetes Mellitus, Type 1/drug therapy , Insulin Infusion Systems/classification , Insulin Infusion Systems/psychology , Insulin/administration & dosage , Insulin/therapeutic use , Self Care , Adult , Anxiety/epidemiology , Blood Glucose/metabolism , Cross-Over Studies , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/psychology , Female , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/therapeutic use , Incidence , Interview, Psychological , Male , Middle Aged , Patient Satisfaction , Psychology , Surveys and Questionnaires , Treatment Outcome
20.
Diabet Med ; 32(1): 120-8, 2015 Jan.
Article in English | MEDLINE | ID: mdl-25081181

ABSTRACT

AIM: To determine the reasons for non-attendance at structured education sessions among people with a recent diagnosis of Type 2 diabetes. METHODS: This was a qualitative study using semi-structured interviews to elicit the main themes explaining non-attendance. A thematic framework method was applied to analyse the data. People who had not attended structured education were recruited from a population cohort of newly diagnosed Type 2 diabetes from South London (the South London Diabetes cohort study), UK. RESULTS: A sample of 30 people was interviewed. Three main themes emerged from the qualitative data explaining non-attendance at structured education: (1) lack of information/perceived benefit of the programme (e.g. not being informed about the course by their health professional); (2) unmet personal preferences (e.g. parking, timing); and (3) shame and stigma of diabetes (e.g. not wishing to tell others of diabetes diagnosis). CONCLUSION: This is the first time that reasons for non-attendance have been explored in depth among people who have newly diagnosed Type 2 diabetes. Novel reasons identified included non-attendance because of shame and stigma of diabetes. To improve uptake at structured education we need to: consider how health professionals in primary care communicate with their patients on the subject of structured diabetes education; offer alternatives to the traditional group education format; and understand that diabetes is associated with health-related stigma, which may affect participation.


Subject(s)
Diabetes Mellitus, Type 2/psychology , Patient Compliance/psychology , Patient Education as Topic , Social Stigma , Adult , Cohort Studies , Communication Barriers , Female , Health Knowledge, Attitudes, Practice , Humans , London/epidemiology , Male , Middle Aged , Patient Acceptance of Health Care , Patient Compliance/statistics & numerical data , Pilot Projects , Primary Health Care , Qualitative Research , Self Care , Social Perception , Surveys and Questionnaires
SELECTION OF CITATIONS
SEARCH DETAIL
...