Fasting plasma glucose and risk factor assessment: Comparing sensitivity and specificity in identifying gestational diabetes in urban black African women.

BACKGROUND: Identifying women with gestational diabetes mellitus (GDM) allows interventions to improve perinatal outcomes. A fasting plasma glucose (FPG) level ≥5.1 mmol/L is 100% specific for a diagnosis of GDM. The International Association of Diabetes and Pregnancy Study Groups acknowledges that FPG <4.5 mmol/L is associated with a low probability of GDM. OBJECTIVES: The validity of selective screening based on the presence of risk factors was compared with the universal application of FPG ≥4.5 mmol/L to identify women with GDM. FPG ≥4.5 mmol/L or the presence of one or more risk factors was assumed to indicate an intermediate to high risk of GDM and therefore the need for an oral glucose tolerance test (OGTT). METHODS: Consecutive black South African (SA) women were recruited to a 2-hour 75 g OGTT at 24 - 28 weeks' gestation in an urban community health clinic. Of 969 women recruited, 666 underwent an OGTT, and of these 589 were eligible for analysis. The glucose oxidase laboratory method was used to measure plasma glucose concentrations. The World Health Organization GDM diagnostic criteria were applied. All participants underwent a risk factor assessment. The χ2 test was used to determine associations between risk factors and a positive diagnosis of GDM. The sensitivity and specificity of a positive diagnosis of GDM were calculated for FPG ≥4.5 mmol/L, FPG ≥5.1 mmol/L, and the presence of one or more risk factors. RESULTS: The prevalence of overt diabetes mellitus and GDM was 0.5% and 7.0%, respectively. Risk factor-based selective screening indicated that 204/589 (34.6%) of participants needed an OGTT, but 18/41 (43.9%) of positive GDM diagnoses were missed. Universal screening using the FPG threshold of ≥4.5 mmol/L indicated that 152/589 (25.8%) of participants needed an OGTT, and 1/41 (2.4%) of positive diagnoses were missed. An FPG of ≥5.1 mmol/L identified 36/41 (87.8%) of GDM-positive participants. The sensitivity and specificity of the presence of one or more risk factors were 56% and 67%, respectively. The sensitivity and specificity of FPG ≥4.5 mmol/L were 98% and 80%, respectively. CONCLUSIONS: Universal screening using FPG ≥4.5 mmol/L had greater sensitivity and specificity in identifying GDM-affected women and required fewer women to undergo a resource-intensive diagnostic OGTT than risk factor-based selective screening. A universal screening strategy using FPG ≥4.5 mmol/L may be more efficient and cost-effective than risk factor-based selective screening for GDM in black SA women.

Women's accounts of the gestational diabetes experience ­ a South African perspective

Background. Considering the perspectives of African women affected by gestational diabetes mellitus (GDM) may facilitate the development of culturally sensitive interventions to address this public health concern. Objective. To identify the personal experiences, challenges, coping strategies and health decisions made by urban indigenous South African women affected by GDM. Methods. The experiences of urban African women (n=10) previously affected by GDM were documented during focus group discussions. The Diabetes Conversation Map educational instrument was used to facilitate discussions. Sessions were audio-recorded, transcribed and thematically analysed. Results. Participants experienced shock and fear on diagnosis of GDM, but family support and sharing their experiences with their peers provided relief from anxiety. They were aware of the inconsistent implementation of GDM diagnostic procedures at tertiary hospitals and community health clinics, which exacerbated their confusion. Despite their initial difficulty in adjusting to a diet perceived as unpalatable, adopting a healthier lifestyle was considered a positive consequence of a GDM diagnosis. Healthy lifestyle changes were partially retained post partum and were reported to have a positive effect on other family members. The participants had little awareness of their long-term risk of developing diabetes mellitus and the need for regular follow-up screening. Unexpectedly, the majority of participants concurred that being HIV-positive would be less stressful than living with diabetes. Conclusion. Participants viewed being HIV-positive as preferable to having GDM, which may reflect the distress caused by inadequate pretest counselling, inconsistent health information, inconsistent screening practices and suboptimal support from healthcare professionals

Fatty acid and phorbol ester-mediated interference of mitogenic signaling via novel protein kinase C isoforms in pancreatic beta-cells (INS-1).

It is possible that activation of protein kinase C (PKC) isoforms by free fatty acids (FFA) plays a role in the failure of pancreatic beta-cell mass expansion to compensate for peripheral insulin resistance in the pathogenesis of type-2 diabetes. The effect of lipid moieties on activation of conventional (PKC-alpha and -beta1), novel (PKC-delta) and atypical (PKC-zeta) PKC isoforms was evaluated in an in vitro assay, using biotinylated neurogranin as a substrate. Oleoyl-Coenzyme A (CoA) and palmitoyl-CoA, but not unesterified FFA, significantly increased the activity of all PKC isoforms (P< or =0.05), particularly that for PKC-delta. It was found that FFA (0.4 mM oleate/complexed to 0.5% bovine serum albumin) inhibited IGF-I-induced activation of protein kinase B (PKB) in the pancreatic beta-cell line (INS-1), but this was alleviated in the presence of the general PKC inhibitor (Gö6850; 1 microM). To further investigate whether conventional or novel PKC isoforms adversely affect beta-cell proliferation, the effect of phorbol ester (phorbol 12-myristate 13-acetate; PMA)-mediated activation of these PKC isoforms on glucose/IGF-I-induced INS-1 cell mitogenesis, and insulin receptor substrate (IRS)-mediated signal transduction was investigated. PMA-mediated activation of PKC (100 nM; 4 h) reduced glucose/IGF-I mediated beta-cell mitogenesis (>50%; P< or =0.05), which was reversible by the general PKC inhibitor Gö6850 (1 microM), indicating an effect of PKC and not due to a non-specific PMA toxicity. PMA inhibited IGF-I-induced activation of PKB, correlating with inhibition of IGF-I-induced association of IRS-2 with the p85 regulatory subunit of phosphatidylinositol-3 kinase. However, in contrast, PMA activated the mitogen-activated protein kinases, Erk1/2. Titration inhibition analysis using PKC isoform inhibitors indicated that these PMA-induced effects were via novel PKC isoforms. Thus, FFA/PMA-induced activation of novel PKC isoforms can inhibit glucose/IGF-I-mediated beta-cell mitogenesis, in part by decreasing PKB activation, despite an upregulation of Erk1/2. Thus, activation of novel PKC isoforms by long-chain acyl-CoA may well contribute to decreasing beta-cell mass in the pathogenesis of type-2 diabetes, similar to their inhibition of insulin signal transduction which causes insulin resistance.

Automated entry of hospital infection surveillance data.

OBJECTIVE: To assess the accuracy of an automated data entry system employing optical scanning technology and to provide an analysis of its costs as compared to manual data entry. DESIGN: The accuracy and cost of automated data entry of 100 surgical-wound infection surveillance questionnaires was compared to manual entry. SETTING: The Surgical Directorate, The Royal Hospitals, Belfast, Northern Ireland. RESULTS: The use of optical scanning technology greatly improved the speed and accuracy of data entry. The time spent by the keyboard operator on data entry was reduced substantially. For each surgical-wound infection questionnaire automatically processed, there was a saving in clerical time equivalent to $0.63. The automated data entry process resulted in a 22-fold productivity increase compared to manual data entry with validation. After validation, an error rate of < 0.2 errors per 1,000 responses was detected in automatically entered data compared to a rate of 12.4 errors per 1,000 responses for manually entered data. The automated system, including validation, provided a seven-fold productivity increase compared to "quick-and-dirty" manual data entry without validation. CONCLUSION: Hospital information technology systems may achieve total integration of data management, but realistically this would appear to be very much in the future. Until then, in view of the accuracy and substantial savings in time and money, we recommend the use of automated data entry technology. This system would be especially useful where data are transported from outlying hospitals to a central receiving center for collation and analysis.

mRNA translation in yeast during entry into stationary phase.

The expression of some Saccharomyces cerevisiae genes is induced as cells enter stationary phase. Their mRNAs are translated during a period in the growth cycle when the translational apparatus is relatively inert, thereby raising the possibility that these mRNAs compete effectively for a limiting pool of translation factors. To test this idea, the translation of mRNAs carrying different 5'-leaders was compared during exponential growth and after entry into stationary phase upon glucose starvation. Closely related sets of lacZ mRNAs, carrying 5'-leaders from the PYK1, PGK1, RpL3, Rp29, HSP12, HSP26 or THI4 mRNAs, were studied. These mRNAs displayed differing translational efficiencies during exponential growth, but their relative translatabilities were not significantly affected by entry into stationary phase, indicating that they compete just as effectively under these conditions. Polysome analysis revealed that the wild-type PYK1, ACT1 and HSP26 mRNAs are all translated efficiently during stationary phase, when the translational apparatus is relatively inert. Also, significant levels of the translation initiation factors eIF-2alpha, eIF-4E and eIF-4A were maintained during the growth cycle. These data are consistent with the idea that, while translational activity decreases dramatically during entry into stationary phase, yeast cells maintain excess translational capacity under these conditions.

Differential activation of protein kinase B and p70(S6)K by glucose and insulin-like growth factor 1 in pancreatic beta-cells (INS-1).

It has been shown that IGF-1-induced pancreatic beta-cell proliferation is glucose-dependent; however, the mechanisms responsible for this glucose dependence are not known. Adenoviral mediated expression of constitutively active phosphatidylinositol 3-kinase (PI3K) in the pancreatic beta-cells, INS-1, suggested that PI3K was not necessary for glucose-induced beta-cell proliferation but was required for IGF-1-induced mitogenesis. Examination of the signaling components downstream of PI3K, 3-phosphoinositide-dependent kinase 1, protein kinase B (PKB), glycogen synthase kinase-3, and p70-kDa-S6-kinase (p70(S6K)), suggested that a major part of glucose-dependent beta-cell proliferation requires activation of mammalian target of rapamycin/p70(S6K), independent of phosphoinositide-dependent kinase 1/PKB activation. Adenoviral expression of the kinase-dead form of PKB in INS-1 cells decreased IGF-1-induced beta-cell proliferation. However, a surprisingly similar decrease was also observed in adenoviral wild type and constitutively active PKB-infected cells. Upon analysis of extracellular signal-regulated protein kinase 1 and 2 (ERK1/ERK2), an increase in ERK1/ERK2 phosphorylation activation by glucose and IGF-1 was observed in kinase-dead PKB-infected cells, but this phosphorylation activation was inhibited in the constitutively active PKB-infected cells. Hence, there is a requirement for the activation of both ERK1/ERK2 and mammalian target of rapamycin/p70(S6K) signal transduction pathways for a full commitment to glucose-induced pancreatic beta-cell mitogenesis. However, for IGF-1-induced activation, these pathways must be carefully balanced, because chronic activation of one (PI3K/PKB) can lead to dampening of the other (ERK1/2), reducing the mitogenic response.