A qualitative study exploring the factors that influence the uptake of pre-pregnancy care among women with Type 2 diabetes.

AIM: To elicit the views and experiences of women with Type 2 diabetes and healthcare professionals relating to the pregnancy and pre-pregnancy care they have received or provided. METHODS: A qualitative study using in-depth semi-structured interviews with women with Type 2 diabetes (n=30) and healthcare professionals (n=22) from primary and specialist care. Women were purposively sampled to include different experiences of pregnancy and pre-pregnancy care. Data were transcribed verbatim and analysed thematically using Framework Analysis. RESULTS: The median age of the women was 37 years, and most were obese (median BMI 34.9 kg/m2 ), of black or Asian ethnicity (n=24, 80%) and from areas of high deprivation (n=21, 70%). Participating healthcare professionals were from primary (n=14), intermediate (n=4) and secondary (n=4) care. Seven themes expressing factors that mediate reproductive behaviour and care in women with Type 2 diabetes were identified at the patient, professional and system levels. Type 2 diabetes was generally perceived negatively by the women and the healthcare professionals. There was a lack of awareness about the pre-pregnancy care needs for this population, and communication between both groups was unhelpful in eliciting the reproductive intentions of these women. The themes also reveal a lack of systemic processes to incorporate pre-pregnancy care into the care of women with Type 2 diabetes, and consequently, health professionals in primary care have limited capacity to provide such support. CONCLUSION: If the current high levels of unprepared pregnancies in women with Type 2 diabetes are to be reduced, the reproductive healthcare needs of this group need to be embedded into their mainstream diabetes management.

Healthcare professionals' views of group structured education for people with newly diagnosed Type 2 diabetes.

AIM: To determine healthcare professionals' (HCP) views of group structured education for people with newly diagnosed Type 2 diabetes. METHODS: This was a qualitative study using semi-structured interviews to ascertain primary care HCPs' views and experiences of education for people with newly diagnosed Type 2 diabetes. A thematic framework method was applied to analyse the data. Participants were HCPs (N = 22) from 15 general practices in three south London boroughs. RESULTS: All but one HCP viewed diabetes education favourably and all identified that low attendance was a problem. Three key themes emerged from the qualitative data: (1) benefits of diabetes education, including the group mode of delivery, improved patient interactions, saving HCPs' time and improved patient outcomes; (2) factors limiting uptake of education, including patient-level problems such as access and the appropriateness of the programme for certain groups, and difficulties communicating the benefits to patients and integration of education management plans into ongoing diabetes care; and (3) suggestions for improvement, including strategies to improve attendance at education with more localized and targeted marketing and enhanced programme content including follow-up sessions and support for people with pre-existing psychological issues. CONCLUSIONS: Most HCPs valued diabetes education and all highlighted the lack of provision for people with different levels of health literacy. Because there was wide variation in terms of the level of knowledge regarding the education on offer, future studies may want to focus on how to help HCPs encourage their patients to attend.

A prospective randomized controlled study of a virtual clinic integrating primary and specialist care for patients with Type 2 diabetes mellitus.

AIMS: To investigate the effectiveness of a diabetes virtual clinic to enhance diabetes in primary care by developing clinical management plans for patients with suboptimal metabolic control and/or case complexity. METHODS: A prospective study with randomized allocation to virtual clinic or usual care. Patients with Type 2 diabetes (n = 208) were recruited from six general practices in South London. The primary outcome for the study was glycaemic control, secondary outcomes included: lipids, blood pressure, weight (kg and BMI) and renal function (eGFR). Data were collected from participants' records at baseline and 12 months. We also considered process measures including therapy optimization. RESULTS: The 12-month data show equivalence between the virtual clinic and control groups for glycaemic control with both achieving clinically significant reductions in HbA1c of 8 mmol/mol (0.6 ± 1.7%) and 10 mmol/mol (0.8 ± 1.9%), respectively (P = 0.4). The virtual clinic group showed superiority over the intervention group for blood pressure control with a mean reduction in systolic blood pressure of 6 ± 16 mmHg compared with an increased of 2 ± 18 mmHg in the control group (P = 0.008). There were no significant differences between the groups in terms of cholesterol, weight and renal function. Process measures showed an increased level of therapy adjustment in the virtual clinic group. CONCLUSION: The virtual clinic model explored in this study showed a clinically important improvement in glycaemic control. Although this improvement was not superior to that observed in the control participants, this might be attributable to the systemic impact of the virtual clinic on the practice as a whole.

The clinical characteristics at diagnosis of type 2 diabetes in a multi-ethnic population: the South London Diabetes cohort (SOUL-D).

AIMS/HYPOTHESIS: This study aimed to investigate the clinical features of newly diagnosed type 2 diabetes in an urban multi-ethnic cohort. METHODS: A population-based cross-sectional design was used. People diagnosed with type 2 diabetes in the preceding 6 months were recruited from primary care practices in three adjacent inner-city boroughs of South London, serving a population in which 20% of residents are of black African or Caribbean ethnicity. Sociodemographic and biomedical data were collected by standardised clinical assessment and from medical records. Multiple logistic regression methods were used to report associations between ethnicity and diabetes-complication status. RESULTS: From 96 general practices, 1,506 patients were recruited. Their mean age was 55.6 (± 11.07) years, 55% were men, 60% were asymptomatic at diagnosis and 51%, 38% and 11% were of white, black and South Asian/other ethnicity, respectively. Compared with white participants, black and South Asian/other participants were: younger (mean age 58.9 [± 10.09], 52.4 [± 11.19] and 51.5 [± 10.42] years, respectively; p < 0.0001); less likely to have neuropathy (10.1%, 3.6% and 4.4%; p < 0.0001) or report coronary artery disease (12.7%, 4.8% and 7.3%; p < 0.0001). In logistic regression, compared with white participants, black participants had lower levels of macrovascular complications (OR 0.52, 95% CI 0.32, 0.84; p = 0.01). Male sex was independently associated with microvascular disease (OR 1.69, 95% CI 1.26, 2.28; p < 0.0001). CONCLUSIONS/INTERPRETATION: The prevalence of complications at time of diagnosis was lower than expected, especially in black and South Asian/other ethnic groups. However, in multi-ethnic inner-city populations, onset of type 2 diabetes occurred almost 10 years earlier in non-white populations than in white participants, predicating a prolonged morbidity.

Socio-economic and ethnic inequalities in diabetes retinal screening.

OBJECTIVE: We aimed to quantify socio-economic and ethnic inequalities in diabetes retinal screening. METHODS: Data were analysed for the retinal screening programme for three South London boroughs for the 18-month period to February 2009. Sight-threatening diabetic retinopathy (STDR) was defined as the occurrence of diabetic maculopathy, severe non-proliferative or proliferative diabetic retinopathy. Odds ratios were adjusted for sex, age group, duration and type of diabetes, self-reported ethnicity and deprivation quintile by participant postal code. RESULTS: There were 76 351 records obtained but, after excluding duplicate and ineligible records, data were analysed for 59 495 records from 31 484 subjects. There were 7026 (22%) subjects called for appointments who were not screened in the period, with 24 458 (78%) having one or more screening episodes. Non-attendance for screening was highest in young adults aged 18-34 years (32%) and in those aged 85 years or greater (28%). In the most deprived quintile, non-attendance was 23% compared with 21% in the least deprived quintile [odds ratio (OR) 1.37, 95% confidence interval (CI) 1.16-1.61, P < 0.001]. There were 2819 (11.5%) participants with STDR, including 10.8% in the least deprived quintile and 12.2% in the most deprived quintile (OR 1.10, 95% CI 0.95-1.16, P = 0.196). Compared with white Europeans (9.4%), STDR was higher in Africans (15.2%) and African Caribbeans (14.7%), resulting from a higher frequency of diabetic maculopathy. CONCLUSION: Socio-economic inequality in diabetes retinal screening may be smaller than reported in earlier studies. This study suggested an increased frequency of diabetic maculopathy among participants of African origins.

A genetic map of candidate genes and QTLs involved in tomato fruit size and composition.

In order to screen for putative candidate genes linked to tomato fruit weight and to sugar or acid content, genes and QTLs involved in fruit size and composition were mapped. Genes were selected among EST clones in the TIGR tomato EST database (http://www.tigr.org/tdb/tgi/lgi/) or corresponded to genes preferentially expressed in the early stages of fruit development. These clones were located on the tomato map using a population of introgression lines (ILs) having one segment of Lycopersicon pennellii (LA716) in a L. esculentum (M82) background. The 75 ILs allowed the genome to be segmented into 107 bins. Sixty-three genes involved in carbon metabolism revealed 79 loci. They represented enzymes involved in the Calvin cycle, glycolysis, the TCA cycle, sugar and starch metabolism, transport, and a few other functions. In addition, seven cell-cycle-specific genes mapped into nine loci. Fourteen genes, primarily expressed during the cell division stage, and 23 genes primarily expressed during the cell expansion stage, revealed 24 and 26 loci, respectively. The fruit weight, sugars, and organic acids content of each IL was measured and several QTLs controlling these traits were mapped. Comparison between map location of QTLs and candidate gene loci indicated a few candidate genes that may influence the variation of sugar or acid contents. Furthermore, the gene/QTL locations could be compared with the loci mapped in other tomato populations.

A new C-type cyclin-dependent kinase from tomato expressed in dividing tissues does not interact with mitotic and G1 cyclins.

Cyclin-dependent kinases (CDKs) form a conserved superfamily of eukaryotic serine-threonine protein kinases whose activity requires the binding of a cyclin protein. CDKs are involved in many aspects of cell biology and notably in the regulation of the cell cycle. Three cDNAs encoding a C-type CDK, and a member of each B-type CDK subfamily, were isolated from tomato (Lycopsersicon esculentum Mill.) and designated Lyces;CDKC;1 (accession no. AJ294903), Lyces; CDKB1;1 (accession no. AJ297916), and Lyces;CDKB2;1 (accession no. AJ297917). The predicted amino acid sequences displayed the characteristic PITAIRE (CDKC), PPTALRE (CDKB1), and PPTTLRE (CDKB2) motives in the cyclin-binding domain, clearly identifying the type of CDK. The accumulation of all transcripts was associated preferentially with dividing tissues in developing tomato fruit and vegetative organs. In contrast to that of CDKA and CDKBs, the transcription pattern of Lyces;CDKC;1 was shown to be independent of hormone and sugar supply in tomato cell suspension cultures and excised roots. This observation, together with the absence of a patchy expression profile in in situ hybridization experiments, suggests a non-cell cycle regulation of Lyces;CDKC;1. Using a two-hybrid assay, we showed that Lyces;CDKC;1 did not interact with mitotic and G1 cyclins. The role of plant CDKCs in the regulation of cell division and differentiation is discussed with regard to the known function of their animal counterparts.

Structural basis for light activation of a chloroplast enzyme: the structure of sorghum NADP-malate dehydrogenase in its oxidized form.

Some key chloroplast enzymes are activated by light via a ferredoxin-thioredoxin reduction system which reduces disulfide bridges in the enzymes. We describe for the first time the structural basis for the redox activation of a chloroplast enzyme, the NADP-dependent malate dehydrogenase (MDH) from Sorghum vulgare whose structure has been determined and refined at 2.4 A resolution. In addition to the normal structural components of MDHs, the enzyme exhibits extensions at both the N- and C-termini, each of which contains a regulatory disulfide bridge which must be reduced for activation. The N-terminal disulfide motif is inserted in a cleft between the two subunits of the dimer, thereby locking the domains in each subunit. The C-terminal disulfide keeps the C-terminal residues tight to the enzyme surface and blocks access to the active site. Reduction of the N-terminal disulfide would release the stopper between the domains and give the enzyme the necessary flexibility. Simultaneous reduction of the C-terminal disulfide would free the C-terminal residues from binding to the enzyme and make the active site accessible.

An internal cysteine is involved in the thioredoxin-dependent activation of sorghum leaf NADP-malate dehydrogenase.

The chloroplastic NADP-malate dehydrogenase is activated by thiol/disulfide interchange with reduced thioredoxins. Previous experiments showed that four cysteines located in specific N- and carboxyl-terminal extensions were implicated in this process, leading to a model where no internal cysteine was involved in activation. In the present study, the role of the conserved four internal cysteines was investigated. Surprisingly, the mutation of cysteine 207 into alanine yielded a protein with accelerated activation time course, whereas the mutations of the three other internal cysteines into alanines yielded proteins with unchanged activation kinetics. These results suggested that cysteine 207 might be linked in a disulfide bridge with one of the four external cysteines, most probably with one of the two amino-terminal cysteines whose mutation similarly accelerates the activation rate. To investigate this possibility, mutant malate dehydrogenases (MDHs) where a single amino-terminal cysteine was mutated in combination with the mutation of both carboxyl-terminal cysteines were produced and purified. The C29S/C365A/C377A mutant MDH still needed activation by reduced thioredoxin, while the C24S/C365A/C377A mutant MDH exhibited a thioredoxin-insensitive spontaneous activity, leading to the hypothesis that a Cys24-Cys207 disulfide bridge might be formed during the activation process. Indeed, an NADP-MDH where the cysteines 29, 207, 365, and 377 are mutated yielded a permanently active enzyme very similar to the previously created permanently active C24S/C29S/C365A/C377A mutant. A two-step activation model involving a thioredoxin-mediated disulfide isomerization at the amino terminus is proposed.