Progression rates from HbA1c 6.0-6.4% and other prediabetes definitions to type 2 diabetes: a meta-analysis.

AIMS/HYPOTHESIS: Precise estimates of progression rates from 'prediabetes' to type 2 diabetes are needed to optimise prevention strategies for high-risk individuals. There is acceptance of prediabetes defined by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), but there is some controversy surrounding HbA1c-defined prediabetes ranges, with some favouring 6.0-6.4% (42-46 mmol/mol). Comparing progression rates between groups might aid this issue, thus we aimed to accurately estimate progression rates to diabetes from different prediabetes categories. METHODS: Meta-analysis of prospective observational studies in which participants had prediabetes at baseline (ADA-defined IFG [5.6-6.9 mmol/l], WHO-defined IFG [6.1-6.9 mmol/l], IGT (7.8-11.0 mmol/l) or raised HbA1c [6.0-6.4%/42-46 mmol/mol]) and were followed up for incident diabetes. Incidence rates were combined using Bayesian random effects models. RESULTS: Overall, 70 studies met the inclusion criteria. In the six studies that used raised HbA1c, the pooled incidence rate (95% credible interval) of diabetes was 35.6 (15.1, 83.0) per 1,000 person-years. This rate was most similar to that for ADA-defined IFG (11 studies; 35.5 [26.6, 48.0]) and was non-significantly lower than WHO-defined IFG (34 studies; 47.4 [37.4, 59.8]), IGT (46 studies, 45.5 [37.8, 54.5]) and IFG plus IGT (15 studies, 70.4 [53.8, 89.7]). Similar results were seen when the data were analysed by the criteria used to diagnose diabetes. CONCLUSIONS/INTERPRETATION: This study provides evidence that progression rates differ by prediabetes definition, which has implications for the planning and implementation of diabetes prevention programmes. HbA1c 6.0-6.4% might identify people at a lower diabetes risk than other prediabetes definitions, but further research is needed.

Implementation of the automated Leicester Practice Risk Score in two diabetes prevention trials provides a high yield of people with abnormal glucose tolerance.

AIMS/HYPOTHESIS: The Leicester Practice Risk Score (LPRS) is a tool for identifying those at high risk of either impaired glucose regulation (IGR), defined as impaired glucose tolerance and/or impaired fasting glucose, or type 2 diabetes from routine primary care data. The aim of this study was to determine the yield from the LPRS when applied in two diabetes prevention trials. METHODS: Let's Prevent Diabetes (LPD) and Walking Away from Diabetes (WAD) studies used the LPRS to identify people at risk of IGR or type 2 diabetes from 54 general practices. The top 10% at risk within each practice were invited for screening using a 75 g OGTT. The response rate to the invitation and the prevalence of IGR and/or type 2 diabetes in each study were calculated. RESULTS: Of those invited 19.2% (n = 3,449) in LPD and 22.1% (n = 833) in WAD attended. Of those screened for LPD 25.5% (95% CI 24.1, 27.0) had IGR and 4.5% (95% CI 3.8, 5.2) had type 2 diabetes, giving a prevalence of any abnormal glucose tolerance of 30.1% (95% CI 28.5, 31.6). Comparable rates were seen for the WAD study: IGR 26.5% (95% CI 23.5, 29.5), type 2 diabetes 3.0% (95% CI 1.8, 4.2) and IGR/type 2 diabetes 29.5% (95% CI 26.4, 32.6). CONCLUSIONS/INTERPRETATION: Using the LPRS identifies a high yield of people with abnormal glucose tolerance, significantly higher than those seen in a population screening programme in the same locality. The LPRS is an inexpensive and simple way of targeting screening programmes at those with the highest risk.

Aberrant production of leukotriene C4 by macrophages from autoimmune-prone mice.

Eicosanoids have been implicated in the pathogenesis of autoimmune diseases. In this study, peritoneal macrophages from autoimmune-prone mice were examined for their capacity to produce proinflammatory 5-lipoxygenase metabolites. The results indicate that enhanced production of leukotriene C4 is a common feature of murine autoimmunity and suggest further that aberrations in 5-lipoxygenase activity may play a role in the development of lupus.

Determinants of age at menarche in the UK: analyses from the Breakthrough Generations Study.

BACKGROUND: Early menarche increases breast cancer risk but, aside from weight, information on its determinants is limited. METHODS: Age at menarche data were collected retrospectively by questionnaire from 81,606 women aged 16-98, resident in the UK and participating in the Breakthrough Generations Study. RESULTS: Menarche occurred earlier in women who had a low birthweight (P(trend)<0.001), were singletons (P<0.001), had prenatal exposure to pre-eclampsia (P<0.001) or maternal smoking (P=0.01), were not breastfed (P(trend)=0.03), were non-white (P<0.001), were heavy (P(trend)<0.001) or tall (P(trend)<0.001) compared with their peers at age 7 and exercised little as a child (P(trend)<0.001). Menarcheal age increased with number of siblings (P<0.001) independently of birth order, and had an inverse association with birth order after adjustment for sibship size (P<0.001). In a multivariate model, birthweight, ethnicity, weight, height, exercise, sibship size and birth order remained significant, and maternal age at birth became significant (positive association, P<0.001). CONCLUSION: Age at menarche was influenced by both pre- and post-natal factors, and these factors may affect breast cancer risk through this route.

Structure of somatomedin-binding protein: alkaline pH-induced dissociation of an acid-stable, 60,000 molecular weight complex into smaller components.

The association of somatomedin (Sm) peptides with their specific serum binding proteins (SmPBs) and the preservation of SmBP integrity are both pH dependent. Acid extracts of human plasma Cohn fraction IV-4 chromatographed at pH 5.0 after incubation with [125I]iodoinsulin-like growth factor I yield predominantly a 60,000 molecular weight complex of specifically bound radiolabeled peptide. Alkaline exposure (pH 8.0) of either the initial acid extract of Cohn fraction IV-4 or the isolated 60,000 molecular weight chromatographic peak shifts the recovery of bound [125I]iodoinsulin-like growth factor I on rechromatography to two smaller complexes of approximately 46,000 and 30,000 molecular weight. These results support the existence of two or more forms of human plasma SmBP that may possess a common 30,000 molecular weight component.

Measuring the effect of a worksite-based nutrition intervention on food consumption.

Although current dietary guidelines focus on a combination of specific nutrients and food items, most effective dietary interventions focus on patterns of dietary intake and take into account the relationships among nutritional factors. In a controlled nutrition intervention conducted at 16 workplaces, a self-administered health habits questionnaire (HHQ) including a 67-item version of a semiquantitative food frequency questionnaire (FFQ) was distributed prior to a 15-month intervention and again after it. Principal components analysis (PCA) was used to reduce this large set of highly correlated FFQ food items to a smaller set of maximally uncorrelated components (PCs). Of the eight discrete food-based eating patterns targeted in the Treatwell intervention, six were highly correlated ([r[ > or = 0.48) with at least one PC each. This indicates a high level of concordance between a priori intervention targets and actual behavior. Based on log-transformed preintervention FFQ measures, our results showed that a very high proportion (0.55) of the variance in the FFQ data was explained by the PCs. A significantly greater increase in consumption of total vegetables and a larger decrease in dietary intake of ground and processed meats were observed among intervention companies. A comparison PCA conducted on intervention and control companies after the intervention indicated that patterns of intake were very stable over time.

Substance P and opioid interaction on stimulated and non-stimulated guinea pig ileum.

In the past, substance P (SP) has been suggested to be both an opiate agonist and an antagonist. It therfore seemed appropriate to examine potential interactions of SP and opioids on guinea pig ileum. On non-stimulated ileal strips SP caused a dose responsive increase in contraction. Pretreatment of the tissue with morphine (3, 30, 300, 3000 nM), enkephalin (1.42, 14.2, 142, 1420 nM), naloxone (5nM), or atropine (0.144 micron) did not significantly alter the spasmogenic effect of SP. On stimulated guinea pig ileum, whereas morphine and enkephalin inhibited the electrically induced twitch, SP adminstration resulted in contraction of the tissue. Additionally, neither strongly effective non sub-threshold doses of SP antagonized the effects of the narcotics. These data are discussed in terms of separate receptors mediating the effects of the opiates and SP on guinea pig ileum.

Fat-free mass is maintained in women following a moderate diet and exercise program.

Weight-loss programs usually result in fat-free mass (FFM) loss along with body-fat (BF) loss. This study examined which combination of diet + exercise would maintain FFM. Forty-four overweight, inactive women completed 20 wk of a randomized intervention: control (C, N = 6), diet only (D, N = 10), diet + cycling (DC, N = 8), diet + resistance training (DR, N = 11), or diet + resistance training + cycling (DRC, N = 9) group. FFM and %BF were determined from hydrostatic weighting. Exercise sessions were attended 3 d.wk-1, with a mean duration of 30 min per session. Caloric intake was reduced 628 kcal.d-1 (+/- 59). Chi squares and ANOVA showed no baseline differences between groups for socioeconomic status, age, body composition, aerobic capacity, or strength. One-way ANOVA of change with Student-Newman Keul multiple range post-hoc tests (P < 0.05) were used to analyze pre to post differences for %BF, body mass (BM), FFM, VO2max, and strength. D, DC, DR, and DRC lost significant BM (-3.7 to -5.4 kg) in comparison with C (+ 1.5 kg). All groups maintained FFM but only DRC significantly lowered %BF (-4.7%) in comparison with C. DRC and DC significantly increased VO2max. Strength 1RM (triceps extension, arm curl, leg extension, chest press) increased significantly for both DR and DRC. Results suggest that moderate levels of caloric restriction, aerobic cycle exercise, and/or resistance training are equally effective in maintaining FFM while encouraging body mass loss.

Brief communication. Generalization of [DAla2]-enkephalinamide but not of substance P to the morphine cue.

Rats were trained to discriminate morphine (7.5 mg/kg, IP) from saline in a two bar positively reinforced lever pressing paradigm on a FR4 schedule. Morphine (IP) showed a naloxone reversible dose-related generalization to the training dose. [DAla2]-Methionine enkephalinamide (DAE) at 1 mg/kg and Substance P (SP) at 0.1 and 0.25 mg/kg showed vehicle appropriate responding after IP injection. DAE (5 mg/kg) disrupted responding completely; SP (0.5 and 0.1 mg/kg) disrupted responding in 50% of the rats. The disruption caused by IP injection of DAE was not naloxone reversible. Intraventricular injection of morphine (5 microgram/rat) and DAE (5 microgram/rat) produced generalization to the opiate cue. The effect of DAE was reversed by naloxone (1 mg/kg, SC). SP (500 and 750 ng/rat, IVT) produced saline-like responding; 1 microgram/rat disrupted responding completely. These data demonstrate that morphine and enkephalin, but not Substance P, share similar discriminative properties.

Employee advisory boards as a vehicle for organizing worksite health promotion programs.

PURPOSE: The purpose of this article is to describe the "employee advisory board model" applied in the Treatwell program, a worksite nutrition intervention program. DESIGN: The employee advisory boards of five of the seven intervention worksites participating in the Treatwell program were surveyed. Results were compared with results of employee surveys conducted in these five worksites. SETTING: The five worksites included in this study are among 16 participating worksites from Massachusetts and Rhode Island. SUBJECTS: Of the 95 board members represented in the five worksites, 88% responded to the survey. This article also presents results from the 698 respondents of the five intervention worksites where the board surveys were conducted. INTERVENTION: The boards in each worksite participated in planning, promoting, and implementing this program in each worksite. MEASURES: Respondents to the board survey were asked about their participation on and satisfaction with the board and factors they thought contributed to its effectiveness. A survey of all employees included information on demographics and program participation. RESULTS: Board members reported that they were highly satisfied with the board's functioning. Board member hours spent on Treatwell activities were directly related to the proportion of employees aware of the program. (r = .82). The boards' effectiveness was limited by conflicting priorities between the job and board responsibilities. CONCLUSION: The employee advisory board model provides promise for increasing worker awareness of worksite health promotion programs through enhanced worker ownership.

How to make sure your older patients are getting enough zinc.

Older patients with inadequate dietary habits tend to be at risk for mild to moderate zinc deficiency. Symptoms that can be of particular concern include slow wound healing, increased risk of infection, and a loss of acuity in taste and smell. The diagnosis of zinc deficiency is based on a review of the patient's eating habits; laboratory testing is not generally useful in the clinical setting. Most older adults can achieve an adequate zinc intake by eating a variety of foods each day, including meat, fish, and poultry. Supplementation is appropriate in cases of known or suspected frank zinc deficiency.

Hypercholesterolemia. Dietary advice for patients regarding meat.

The contribution of beef, pork, lamb, and veal to total fat, saturated fat, and cholesterol intake must be evaluated from a total-diet standpoint. The hidden fats in snack foods and other processed foods contribute significantly to total fat and cholesterol intake. Patients with hypercholesterolemia can include a moderate amount of meat in their cholesterol-lowering diet provided they choose lean cuts of meat, trim visible fat, pay attention to portion size, and use low-fat cooking methods. Substituting skinless chicken or fish for meat may make sense from the standpoint of personal preference and dietary variety but does not confer additional benefits in terms of reducing blood cholesterol levels.

Fruit and vegetable intake and the association with glucose parameters: a cross-sectional analysis of the Let's Prevent Diabetes Study.

BACKGROUND: Dietary recommendations for the prevention of type 2 diabetes mellitus include the message to consume 400 g fruit and vegetables per day. Measurement of habitual diet is inherently difficult, yet errors due to self-report can be eliminated by the use of nutritional biomarkers. The aim of this study was to determine plasma vitamin C concentrations as a biomarker for fruit and vegetable intake in individuals identified at high risk of diabetes. Fruit and vegetables may confer benefit via their antioxidant capacity, thus we also measured urinary F2-isoprostanes as a marker for oxidative stress. SUBJECTS/METHODS: Participants recruited from a high-risk population as part of a diabetes prevention trial provided fasting blood samples and a spot urine sample for the quantification of plasma vitamin C and F2-isoprostanes, respectively. We compared glycaemic parameters by the increments of the standard deviation of plasma vitamin C using multiple regression models. RESULTS: Mean plasma vitamin C of participants was 39.3 µmol/l (s.d. 21.8). In the unadjusted model, 1 s.d. plasma vitamin C was significantly and inversely associated with HbA1c, fasting and 2 h blood glucose (P ≤ 0.0001). Relationships remained significant after adjustment for demographic variables and confounding factors. No significant association was observed between plasma vitamin C and urinary F2-isoprostanes. CONCLUSION: The data adds to the evidence that small lifestyle changes may influence glucose regulation. The role that fruit and vegetables independently have should be investigated further.

Investigating endothelial activation and oxidative stress in relation to glycaemic control in a multiethnic population.

AIM: An exploration of ethnic differences in measures of oxidative stress and endothelial activation in relation to known cardiovascular risk factors within South Asians (SA) and White Europeans (WE) residing in the UK. METHODS: 202 participants within a UK multiethnic population provided biomedical and anthropometric data. Human urinary 2,3-dinor-8-iso-prostaglandin-F1α and plasma ICAM-1 were quantified as measures of oxidative stress and endothelial activation, respectively. RESULTS: 2,3-Dinor-8-iso-prostaglandin-F1α levels were significantly higher in the SA group compared to WE group (10.36 (95% CI: 9.09, 11.79) versus 8.46 (7.71, 9.29), P = 0.021) after adjustment for age, gender, smoking status, body weight, HbA1c, and medication. Oxidative stress was positively associated with HbA1c (ß = 1.08, 95% CI:1.02, 1.14, P = 0.009), fasting (ß = 1.06, 95% CI: 1.02, 1.10, P = 0.002), and 2 hr glucose (ß = 1.02, 95% CI: 1.00, 1.04, P = 0.052). In each adjusted model, SA continued to have elevated levels of oxidative stress compared to WE. ICAM-1 levels were significantly higher in the composite IGR group compared to the normoglycaemic group (P < 0.001). No ethnic differences in ICAM-1 were observed. CONCLUSION: These results suggest that SA are more susceptible to the detrimental effects of hyperglycaemia-induced oxidative stress at lower blood glucose thresholds than WE. Further research into the potential mechanisms involved is warranted.