Digital intervention increases influenza vaccination rates for people with diabetes in a decentralized randomized trial.

People with diabetes (PWD) have an increased risk of developing influenza-related complications, including pneumonia, abnormal glycemic events, and hospitalization. Annual influenza vaccination is recommended for PWD, but vaccination rates are suboptimal. The study aimed to increase influenza vaccination rate in people with self-reported diabetes. This study was a prospective, 1:1 randomized controlled trial of a 6-month Digital Diabetes Intervention in U.S. adults with diabetes. The intervention group received monthly messages through an online health platform. The control group received no intervention. Difference in self-reported vaccination rates was tested using multivariable logistic regression controlling for demographics and comorbidities. The study was registered at clinicaltrials.gov: NCT03870997. A total of 10,429 participants reported influenza vaccination status (5158 intervention, mean age (±SD) = 46.8 (11.1), 78.5% female; 5271 control, Mean age (±SD) = 46.7 (11.2), 79.4% female). After a 6-month intervention, 64.2% of the intervention arm reported influenza vaccination, vers us 61.1% in the control arm (diff = 3.1, RR = 1.05, 95% CI [1.02, 1.08], p = 0.0013, number needed to treat = 33 to obtain 1 additional vaccination). Completion of one or more intervention messages was associated with up to an 8% increase in vaccination rate (OR 1.27, 95% CI [1.17, 1.38], p < 0.0001). The intervention improved influenza vaccination rates in PWD, suggesting that leveraging new technology to deliver knowledge and information can improve influenza vaccination rates in high-risk populations to reduce public health burden of influenza. Rapid cycle innovation could maximize the effects of these digital interventions in the future with other populations and vaccines.

Community and stakeholders' engagement in the prevention and management of Type 2 diabetes: a qualitative study in socioeconomically disadvantaged suburbs in region Stockholm.

Background: Community-based approaches have been identified as an effective strategy to address the growing burden of noncommunicable diseases (NCDs) worldwide. However, little is known about community as a concept among people living in socioeconomically disadvantaged settings and stakeholders' interactions and engagement in NCDs prevention and management. Objective: The aim of this study was to understand; (1) the meaning of community among people living in socioeconomically disadvantaged suburbs in Region Stockholm and (2) how communities interact and engage with stakeholders at local and regional levels for the prevention and management of type 2 diabetes (T2D). Methods: This qualitative study was conducted in three municipalities in Region Stockholm with a high proportion of migrants. Multiple data collection methods were used, including observations of community activities; interviews with community members, representatives of public authorities and NGOs; and group interviews with healthcare providers. Data were analyzed using content analysis. Results: Community was perceived as living in close proximity with shared beliefs, values and resources. Although they recognized its social and cultural diversity, community members focused more on the commonalities of living in their neighborhood and less on their differences in country of birth and languages spoken. Several mismatches between awareness of community needs and the available skills and resources among stakeholders for T2D prevention were identified. Stakeholders expressed awareness of T2D risk and interest in addressing it in a culturally appropriate manner. Conclusion: Interaction between the communities and stakeholders was limited, as was engagement in T2D prevention and management. This highlights barriers in the collaboration between community, healthcare institutions and other stakeholders which consequently affect the implementation of preventive interventions. Innovative ways to link the community to the healthcare sector and other local government institutions are needed to build the capacity of health systems for T2D prevention in socioeconomically disadvantaged communities.

'What kind of life is this?' Diabetes related notions of wellbeing among adults in eastern Uganda and implications for mitigating future chronic disease risk.

BACKGROUND: Effective prevention and care for type 2 diabetes requires that people link healthy behaviours to chronic disease-related wellbeing. This study explored how people perceive current and future wellbeing, so as to inform lifestyle education. METHODS: Eight focus group discussions and 12 in-depth interviews were conducted in Iganga and Mayuge districts in rural Eastern Uganda among people aged 35-60 years in three risk categories (1) People with diabetes, (2) people at higher risk of diabetes (with hypertension or overweight) and (3) community members without diabetes. RESULTS: People define wellbeing in three notions: 1) Physical health, 2) Socio-economic status and 3) Aspirational fulfilment. Most people hold the narrower view of wellbeing that focuses on absence of pain. Most overweight participants did not feel their condition as affecting their wellbeing. However, for several people with hypertension, the pains they describe indicate probable serious heart disease. Some people with diabetes expressed deep worry and loss of hope, saying that 'thoughts are more bothersome than the illness'. Wellbeing among people with diabetes was described in two perspectives: Those who view diabetes as a 'static' condition think that they cannot attain wellbeing while those who view it as a 'dynamic' condition think that with consistent treatment and healthy lifestyles, they can be well. While many participants perceive future wellbeing as important, people without diabetes are less concerned about it than those with diabetes. Inadequate knowledge about diabetes, drug stock-outs in health facilities, unaffordable healthier food, and contradictory information were cited as barriers to future wellbeing in people with diabetes. CONCLUSIONS: To make type 2 diabetes prevention relevant to healthy people, health education messages should link current lifestyles to future wellbeing. Diabetes patients need counselling support, akin to that in HIV care, to address deep worry and loss of hope.

Urban residential greenness and adiposity: A cohort study in Stockholm County.

BACKGROUND: Increasing evidence suggests that exposure to residential greenness is associated with positive health outcomes among urban populations. However, few studies have considered effects on adiposity development in a longitudinal setting. OBJECTIVES: This study aimed to explore the association between long-term exposure to urban residential greenness and markers of adiposity. METHODS: A cohort of 5126 adults from five municipalities in Stockholm County was examined clinically at baseline (1992-1998) and follow-up (2002-2006) after on average nine years. Time-weighted average exposure to urban greenness was estimated by Normalized Difference Vegetation Index (NDVI) within 100 m, 250 m, and 500 m buffers around the residential addresses of each participant. Multiple linear and Poisson regression models were used to estimate associations between greenness and change in weight and waist circumference as well as risk of overweight, obesity and central obesity. Co-exposures to air pollution, traffic noise and distance to water were also examined. RESULTS: In women, higher levels of residential greenness were associated with a reduced increase in waist circumference during follow-up (ß = -0.11 cm/year, 95% CI -0.14; -0.08 per one interquartile range increase in NDVI) and decreased risk for central obesity (IRR = 0.88: 95% CI 0.79; 0.99) in the 500 m buffer. No associations were observed for men or with regard to weight development or the risk of developing overweight or obesity. Exposure to low NDVI levels in combination with high NOx from road traffic and transportation noise as well as long distance to water rendered statistically significant increases in waist circumference in both sexes. CONCLUSION: Higher long-term exposure to greenness was associated with a reduced increase in waist circumference and lower risk of central adiposity in women but not in men. In both sexes, low NDVI exposure in combination with other environmental risk factors appeared particularly harmful.

Cannabis Use as Risk or Protection for Type 2 Diabetes: A Longitudinal Study of 18 000 Swedish Men and Women.

Aims. Whether or not cannabis use may increase or decrease the risk of type 2 diabetes is not clear. We analyzed the association between cannabis and subsequent type 2 diabetes and if a potential positive or reverse association persisted after controlling for potential confounders. Methods. In this population-based cohort study, 17,967 Swedish men and women (aged 18-84 years), who answered an extensive questionnaire in 2002 (including questions on cannabis use), were followed up for new cases of type 2 diabetes (n = 608) by questionnaire (in 2010) and in health registers during 2003-2011. Odds ratios (ORs) with 95% CIs were estimated in a multiple logistic regression analysis. Potential confounders included age, sex, BMI, physical inactivity, smoking, alcohol use, and occupational position. Results. The crude association showed that cannabis users had a reduced risk of type 2 diabetes OR = 0.68 (95% CIs: 0.47-0.99). However, this inverse association attenuated to OR = 0.94 (95% CIs: 0.63-1.39) after adjusting for age. Conclusions. The present study suggests that there is no association between cannabis use and subsequent type 2 diabetes after controlling for age. To make more robust conclusions prospective studies, with longer periods of follow-up and more detailed information about cannabis use, are needed.

Adenylate cyclase 3: a new target for anti-obesity drug development.

Obesity has become epidemic worldwide, and abdominal obesity has a negative impact on health. Current treatment options on obesity, however, still remain limited. It is then of importance to find a new target for anti-obesity drug development based upon recent molecular studies in obesity. Adenylate cyclase 3 (ADCY3) is the third member of adenylyl cyclase family and catalyses the synthesis of cAMP from ATP. Genetic studies with candidate gene and genome-wide association study approaches have demonstrated that ADCY3 genetic polymorphisms are associated with obesity in European and Chinese populations. Epigenetic studies have indicated that increased DNA methylation levels in the ADCY3 gene are involved in the pathogenesis of obesity. Furthermore, biological analyses with animal models have implicated that ADCY3 dysfunction resulted in increased body weight and fat mass, while reduction of body weight is partially explained by ADCY3 activation. In this review, we describe genomic and biological features of ADCY3, summarize genetic and epigenetic association studies of the ADCY3 gene with obesity and discuss dysfunction and activation of ADCY3. Based upon all data, we suggest that ADCY3 is a new target for anti-obesity drug development. Further investigation on the effectiveness of ADCY3 activator and its delivery approach to treat abdominal obesity has been taken into our consideration.

Particulate matter air pollution components and risk for lung cancer.

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important.

Self-reported non-severe hypoglycaemic events in Europe.

AIMS: Hypoglycaemia presents a barrier to optimum diabetes management but data are limited on the frequency of hypoglycaemia incidents outside of clinical trials. The present study investigated the rates of self-reported non-severe hypoglycaemic events, hypoglycaemia awareness and physician discussion of events in people with Type 1 diabetes mellitus or insulin-treated Type 2 diabetes mellitus. METHODS: People in seven European countries aged >15 years with Type 1 diabetes or insulin-treated Type 2 diabetes (basal-only, basal-bolus and other insulin regimens) were recruited via consumer panels, nurses, telephone recruitment and family referrals. Respondents completed four online questionnaires. The first questionnaire collected background information on demographics and hypoglycaemia-related behaviour, whilst all four questionnaires collected data on non-severe hypoglycaemic events in the preceding 7 days. RESULTS: Analysis was based on 11 440 respondent-weeks from 3827 respondents. All participants completed the first questionnaire and 57% completed all four. The mean number of events/respondent-week was 1.8 (Type 1 diabetes) and 0.4-0.7 (Type 2 diabetes, with different insulin treatments) corresponding to annual event rates of 94 and 21-36, respectively. A total of 63% of respondents with Type 1 diabetes and 49-64% of respondents with Type 2 diabetes, treated with different insulin regimens, who experienced hypoglycaemic events, reported impaired hypoglycaemia awareness or unawareness. A high proportion of respondents rarely or never informed their general practitioner/specialist about hypoglycaemia: 65% (Type 1 diabetes) and 50-59% (Type 2 diabetes). Overall, 16% of respondents with Type 1 diabetes and 26% of respondents with Type 2 diabetes reported not being asked about hypoglycaemia during routine appointments. CONCLUSION: Non-severe hypoglycaemic events are common amongst people with Type 1 diabetes and insulin-treated Type 2 diabetes in real-world settings. Many rarely or never inform their general practitioner/specialist about their hypoglycaemia and the real burden of hypoglycaemia may be underestimated.

Therapeutic properties of VO(dmpp)2 as assessed by in vitro and in vivo studies in type 2 diabetic GK rats.

The bis(1,2-dimethyl-3-hydroxy-4-pyridinonato)oxidovanadium(IV), VO(dmpp)2, has shown anti-diabetic effects by in vitro studies in Wistar (W) rat adipocytes and in vivo in obese Zucker rats. The aim of this work is to confirm the therapeutic properties of VO(dmpp)2 in non-obese type 2 diabetic Goto-Kakizaki (GK) rats. An in vivo study was carried out, treating W and GK rats during 21 days with a daily dose of VO(dmpp)2 (44 µmol/kg). It was shown that VO(dmpp)2 doesn't affect the normal increase of body weight of both W and GK rats, after 8 days of treatment ameliorates glycemia in GK rats (8.4 ± 0.3 vs 10.1 ± 0.2 mM in GK control, P<0.001) but doesn't interfere with glucose levels in W rats and, after 21 days of treatment, improves the glucose intolerant profile of GK rats (13.1 ± 0.5 vs 20.6 ± 0.7 mM/min in GK control, P<0.001), despite no increase of plasma insulin levels during glucose tolerance test. Additionally, it was demonstrated that VO(dmpp)2 significantly enhances [3-(3)H]-glucose uptake by W and GK rat adipocytes (non-toxic concentration of 100 µM: respectively 193 ± 20 and 254 ± 21%, P<0.001, relative to the basal value) showing an efficacy similar to insulin 1.72 nM and better than the same concentration of BMOV (P<0.01). Western blotting revealed that in W and GK rats VO(dmpp)2 significantly promotes IRS2 (P<0.05) and p-AKT expression (P<0.001 and P<0.05, respectively, relative to the respective controls) and in GK animals reduces the increase of PTP1ß expression (P<0.001, relative to GK control).

Identification of ATP synthase as a lipid peroxide protein adduct in pancreatic islets from humans with and without type 2 diabetes mellitus.

CONTEXT: Most current knowledge of pancreatic islet pathophysiology in diabetes mellitus has come from animal models. Even though islets from humans are readily available, only a few come from diabetic donors. We had the uncommon opportunity to acquire islets from humans with type 2 diabetes and used it to perform a study not previously done with human or animal islets. OBJECTIVES: Oxidative stress has been proposed as a mechanism for impaired ß-cell function in type 2 diabetes. Lipid peroxides caused by reactive oxygen species are damaging to body tissues. The objective was to determine whether lipid peroxide-protein adducts occur in pancreatic islets of humans with type 2 diabetes. DESIGN: Immunoblots with two antibodies to hydroxynonenal and 2 other antibodies we generated against reactive small aliphatic compounds were used to detect lipid peroxide-protein adducts in islets of patients with type 2 diabetes and controls. RESULTS: The antibodies reacted strongly to ≥5 islet proteins. The major hydroxynonenal adduct in the islets of type 2 diabetes patients was a 52-kDa protein seen with all 4 antibodies that was also seen in islets of nondiabetic humans, rat islets, and insulinoma cells and in mitochondria of various rat tissues. Nano-LC-MS/MS (liquid chromatography-tandem mass spectrometry) and MALDI-TOF (matrix-assisted laser desorption/ionization-time of flight) analysis identified the protein as the ß-chain of the mitochondrial F-ATP synthase, an enzyme responsible for 95% of ATP formed in tissues. CONCLUSIONS: Lipid peroxide-protein adducts occur in ß-cells in the nondiabetic state and in diabetes. Lipid peroxidation is thought to be damaging to tissues. Analogous to various other unhealthy characteristics, the presence in nondiabetic individuals of lipid peroxide-protein adducts does not necessarily indicate they are not detrimental.

Gynostemma pentaphyllum Tea Improves Insulin Sensitivity in Type 2 Diabetic Patients.

Aims. To evaluate the effect of the traditional Vietnamese herb Gynostemma pentaphyllum tea on insulin sensitivity in drug-naïve type 2 diabetic patients. Methods. Patients received GP or placebo tea 6 g daily for four weeks and vice versa with a 2-week wash-out period. At the end of each period, a somatostatin-insulin-glucose infusion test (SIGIT) was performed to evaluate the insulin sensitivity. Fasting plasma glucose (FPG), HbA(1C), and oral glucose tolerance tests and insulin levels were measured before, during, and after the treatment. Results. FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment compared to placebo treatment (P < 0.001). The levels of FPG in the control group were slightly reduced to 0.2 ± 1.5 versus 1.9 ± 1.0 mmol/L in GP group (P < 0.001), and the effect on FPG was reversed after exchanging treatments. The glycometabolic improvements were achieved without any major change of circulating insulin levels. There were no changes in lipids, body measurements, blood pressure, and no reported hypoglycemias or acute adverse effects regarding kidney and liver parameters. Conclusion. The results of this study suggested that the GP tea exerted antidiabetic effect by improving insulin sensitivity.

Effects of Nordic walking on cardiovascular risk factors in overweight individuals with type 2 diabetes, impaired or normal glucose tolerance.

BACKGROUND: Physical activity remains a valuable prevention for metabolic disease. The effects of Nordic walking on cardiovascular risk factors were determined in overweight individuals with normal or disturbed glucose regulation. METHODS: We included 213 individuals, aged 60 ± 5.3 years and with body mass index (BMI) of 30.2 ± 3.8 kg/m(2); of these, 128 had normal glucose tolerance (NGT), 35 had impaired glucose tolerance (IGT) and 50 had type 2 diabetes mellitus (T2DM). Participants were randomized to unaltered physical activity or to 5 h per week of Nordic walking with poles, for a 4-month period. Dietary habits were unaltered. BMI, waist circumference, blood pressure, glucose tolerance, clinical chemistry, maximal oxygen uptake (peak VO(2)) and self-reported physical activity (questionnaire) were assessed at the time of inclusion and after 4 months. The participants in the exercise-intervention group kept a walking diary. RESULTS: In the NGT exercise group, self-reported physical activity increased markedly, and body weight (-2.0 ± 3.8 kg), BMI (-0.8 ± 1.4 kg/m(2)) and waist circumference (-4.9 ± 4.4 cm) (mean ± SD) decreased. Exercise power output (12.9 ± 9.9 W) and peak VO(2) (2.7 ± 2.8 mL/kg/min) increased in the IGT exercise group. More cardiovascular risk factors were improved after exercise intervention in people with NGT compared with those with IGT or T2DM. Exercise capacity improved significantly in all three groups of participants who reported at least 80% compliance with the scheduled exercise. CONCLUSIONS: Nordic walking improved anthropometric measurements and exercise capacity. However, unsupervised Nordic walking may not provide a sufficient increase in exercise intensity to achieve ultimate health-promoting benefits on the cardiovascular parameters assessed in this study, particularly for those with disturbed glucose regulation.

Antidiabetic Effects of Add-On Gynostemma pentaphyllum Extract Therapy with Sulfonylureas in Type 2 Diabetic Patients.

Aims. To investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum (GP) together with sulfonylurea (SU) in 25 drug-naïve type 2 diabetic patients. Methods. After 4-week treatment with gliclazide (SU), 30 mg daily, all patients were randomly assigned into 2 groups to add on GP extract or placebo extract, 6 g daily, during eight weeks. Results. After 4-week SU treatment, fasting plasma glucose (FPG) and HbA(1C) decreased significantly (P < 0.001). FPG was further reduced after add-on therapy with 2.9 ± 1.7 and 0.9 ± 0.6 mmol/L in the GP and placebo groups, respectively (P < 0.001). Therapy with GP extract also reduced 30- and 120-minute oral glucose tolerance test postload values. HbA(1C) levels decreased approximately 2% units in the GP group compared to 0.7% unit in the placebo group (P < 0.001). Conclusion. GP extract in addition to SU offers an alternative to addition of other oral medication to treat type 2 diabetic patients.

Type 2 diabetes impairs tendon repair after injury in a rat model.

Type 2 diabetes adversely affects the properties of native connective tissue. The underlying mechanisms, however, by which diabetes alters connective tissue metabolism, especially tendon, are poorly defined. The aim of this study was to determine the effect of type 2 diabetes on the mechanical, histological, and molecular properties of the intact and healing Achilles tendon. The right Achilles tendon was transected in 11 male diabetic Goto-Kakizaki (GK) and 10 age- and sex-matched Wistar control rats, while the left Achilles tendon was left intact. At 2 wk postinjury the intact and injured tendons were assessed by biomechanical testing and histology. The gene expression of collagen I and III, biglycan, versican, MMP-13, and MMP-3 was measured by quantitative RT-PCR, and their protein distribution was studied by immunohistochemistry. Intact tendons exhibited only small differences between the groups. In injured tendons, however, a significantly smaller transverse area and lower stiffness was found in diabetic GK compared with Wistar control rats. This correlated with impaired structural organization of collagen fibers and a reduced expression of collagen I and III in the injured tendons of the diabetic GK compared with Wistar control. Moreover, MMP-3 gene expression was downregulated in the injured diabetic GK tendons compared with injured Wistar controls. Our results indicate that in a rat model of diabetes tendon healing is impaired mainly due to altered expression of collagen and MMPs reflecting decreased degradation of matrix proteins and impaired tissue remodeling. Further our data suggest that therapeutic modulation of collagens or MMPs might be targets for new regenerative approaches in operated, injured, or maybe also degenerative tendon diseases in diabetes.

Low serum 25-hydroxyvitamin D level predicts progression to type 2 diabetes in individuals with prediabetes but not with normal glucose tolerance.

AIMS/HYPOTHESIS: Vitamin D deficiency may increase the risk of type 2 diabetes. We therefore investigated whether serum concentrations of 25-hydroxyvitamin D [25(OH)D] would predict the development of prediabetes (impaired fasting glucose, impaired glucose tolerance or the two combined) and type 2 diabetes, either on their own or when combined with serum concentrations of IGF-1 or IGF-binding protein-1 (IGFBP-1), which may interact with 25(OH)D. METHODS: At baseline, participants aged 35-56 years without known type 2 diabetes were examined using OGTTs, 25(OH)D and IGF peptide measurements, and anthropometric and lifestyle data. Participants who had prediabetes or type 2 diabetes at follow-up 8-10 years later were selected as cases; these were then age- and sex-matched to controls with normal glucose tolerance (NGT) at both baseline and follow-up, giving a total of 980 women and 1,398 men. RESULTS: Men but not women in the highest quartile of 25(OH)D level had a decreased OR for developing type 2 diabetes after adjustment for confounders (OR 0.52, 95% CI 0.30, 0.90), an effect accounted for by individuals with prediabetes, but not with NGT, at baseline. In both sexes, progression from prediabetes to type 2 diabetes was reduced by about 25% per 10 nmol/l increase in 25(OH)D. A high IGFBP-1 value was a better predictor of a reduced risk of type 2 diabetes than high 25(OH)D for both sexes, whereas high IGF-1 concentrations predicted a decreased risk only in men. CONCLUSIONS/INTERPRETATION: High serum 25(OH)D concentrations predict a reduced risk of type 2 diabetes in individuals with prediabetes, but not NGT. There were no significant interactions between 25(OH)D and IGFBP-1 or IGF-1 in terms of risk of diabetes. Our data suggest that vitamin D supplementation should be evaluated for the prevention of type 2 diabetes in prediabetic individuals.

Alcohol consumption and risk of pre-diabetes and type 2 diabetes development in a Swedish population.

AIMS: Alcohol is a potential risk factor of Type 2 diabetes. However, more detailed information on effects of alcohol types and early phases of Type 2 diabetes development seems warranted. The aim of this study was to investigate the influence of alcohol consumption and specific alcoholic beverages on the risk of developing pre-diabetes and Type 2 diabetes in middle-aged Swedish men and women. METHODS: Subjects, who at baseline had normal glucose tolerance (2070 men and 3058 women) or pre-diabetes (70 men and 41 women), aged 35-56 years, were evaluated in this cohort study. Logistic regression was performed to estimate the risk [odds ratio (OR) and 95% confidence interval (CI)] to develop pre-diabetes and Type 2 diabetes at 8-10 years follow-up, in relation to self-reported alcohol intake at baseline. Adjustment was performed for several risk factors. RESULTS: Total alcohol consumption and binge drinking increased the risk of pre-diabetes and Type 2 diabetes in men (OR 1.42, 95% CI 1.00-2.03 and OR 1.67, 95% CI 1.11-2.50, respectively), while low consumption decreased diabetes risk in women (OR 0.41, 95% CI 0.22-0.79). Men showed higher risk of pre-diabetes with high beer consumption (OR 1.84, 95% CI 1.13-3.01) and of Type 2 diabetes with high consumption of spirits (OR 2.03, 95% CI 1.27-3.24). Women showed a reduced risk of pre-diabetes with high wine intake (OR 0.66, 95% CI 0.43-0.99) and of Type 2 diabetes with medium intake of both wine and spirits (OR 0.46, 95% CI 0.24-0.88 and OR 0.55, 95% CI 0.31-0.97, respectively), whereas high consumption of spirits increased the pre-diabetes risk(OR 2.41, 95% CI 1.47-3.96). CONCLUSION: High alcohol consumption increases the risk of abnormal glucose regulation in men. In women the associations are more complex: decreased risk with low or medium intake and increased risk with high alcohol intake.

Effects of Nordic walking on health-related quality of life in overweight individuals with type 2 diabetes mellitus, impaired or normal glucose tolerance.

AIMS: To assess the effects of 4 months of increased physical activity on health-related quality of life in overweight individuals with Type 2 diabetes mellitus, normal or impaired glucose tolerance. METHODS: We included 212 individuals without severe physical or cardiovascular impairments aged 61 (57-64) years, with BMI of 29 (27.5-32) kg/m². Numbers are median (25th-75th percentile). Subjects were stratified based on normal glucose tolerance (n = 128), impaired glucose tolerance (n = 34) or Type 2 diabetes mellitus (n = 50). They were randomized into either a control group (n= 125), who maintained unaltered habitual lifestyle, or an exercise intervention group (n = 87), who were directed to engage in Nordic walking with walking poles, 5 h per week over 4 months. Self-reported physical activity and health-related quality of life was assessed at the time of inclusion and after 4 months. RESULTS: Baseline health-related quality of life of this study cohort was similar to, or better than, an age- and sex-matched Swedish population sample, for 12 of 13 scales. Quality of sleep and BMI were improved for participants with normal glucose tolerance after 4 months of Nordic walking, with little or no musculoskeletal pain as compared with control subjects. No correlation was evident between improved quality of sleep and improved BMI. CONCLUSIONS: Quality of sleep improved in the group with normal glucose tolerance following 4 months of Nordic walking. BMI reduction did not account for this improvement. Nordic walking can be introduced in a primary health care setting as a low-cost mode of exercise that promotes weight loss and improved health satisfaction.

Oral contraceptive use and abnormal glucose regulation in Swedish middle aged women.

AIM: To investigate the association between oral contraceptive (OC) use and abnormal glucose regulation in Swedish middle aged women. METHODS: A prospective population-based study including 4794 women, aged 36-56 at baseline. None had previously diagnosed diabetes. At both baseline and follow-up 8 years later, the women were examined by oral glucose tolerance test. Information regarding lifestyle factors and anthropometric measurements were collected. RESULTS: At baseline, current use of OCs was associated with pre (Odds ratio, OR 4.1, 95%CI 2.2-7.8) but not with type 2 diabetes. The association to prediabetes was entirely linked to IGT (OR 7.1, 3.3-15.8) in current users of OCs and in former users (OR 2.1, 1.1-3.9). Women who used OC at baseline had a better cardiovascular disease risk profile; lower body mass index (BMI), more physically active and less smoking. At follow-up, the increased risk did not persist. CONCLUSION: Current use of OC was associated with a four times increased risk of having prediabetes and seven times of having impaired glucose tolerance. No increased risk persisted at the follow-up, suggesting that the risk due to prior use of OC is decreasing with time. The healthier lifestyle in women who used OCs may have contributed to reduced long-term risk of prediabetes.

Herbal extract of gynostemma pentaphyllum decreases hepatic glucose output in type 2 diabetic goto-kakizaki rats.

The aim of the study was to explore the effect of Gynostemma pentaphyllum (GP) extract on hepatic glucose output (HGO) in spontaneously type 2 diabetic Goto-Kakizaki (GK) rats treated orally with GP or placebo extract 1600 mg/kg daily, during three days or three weeks. The three-week treatment of GP, but not three-day treatment, significantly reduced plasma glucose (PG) levels from 9.8 ± 0.6 to 6.8 ± 0.4 mmol/L (p=0.027) in GK rats, whereas PG levels were not significantly decreased in the placebo rats. Glucose tolerance assessed by an intra-peritoneal glucose tolerance test was significantly improved in GP treated compared to placebo treated group (areas under the glucose curves, AUCs, from 0 to 120 min were 1150 ± 200 vs. 1761 ± 87 mmol/L; p=0.013). The glucose response in an intra-peritoneal pyruvate tolerance test from minute 15 to minute 120, the AUC (15-120) was significantly lower in the GP group (415.5 ± 68.0 vs. 641.5 ± 41.8 mmol/L; p<0.05). In liver perfusions, the AUCs for HGO during 18 min (0-18 min) were significantly decreased in GP treated rats compared with control rats (302.8 ± 36.5 vs. 423.5 ± 44.7 µmol, p<0.05). The three-week GP treatment significantly reduced the hepatic glycogen content, but not glycogen synthase activity compared to placebo group (p<0.007). In conclusion, three-week treatment of GP extract exerted anti-diabetic effect in GK rats, reducing plasma glucose levels and HGO, suggesting that GP improves the hepatic insulin sensitivity by suppressing gluconeogenesis.

Glucocorticoid-induced cell death is mediated through reduced glucose metabolism in lymphoid leukemia cells.

Malignant cells are known to have increased glucose uptake and accelerated glucose metabolism. Using liquid chromatography and mass spectrometry, we found that treatment of acute lymphoblastic leukemia (ALL) cells with the glucocorticoid (GC) dexamethasone (Dex) resulted in profound inhibition of glycolysis. We thus demonstrate that Dex reduced glucose consumption, glucose utilization and glucose uptake by leukemic cells. Furthermore, Dex treatment decreased the levels of the plasma membrane-associated glucose transporter GLUT1, thus revealing the mechanism for the inhibition of glucose uptake. Inhibition of glucose uptake correlated with induction of cell death in ALL cell lines and in leukemic blasts from ALL patients cultured ex vivo. Addition of di-methyl succinate could partially overcome cell death induced by Dex in RS4;11 cells, thereby further supporting the notion that inhibition of glycolysis contributes to the induction of apoptosis. Finally, Dex killed RS4;11 cells significantly more efficiently when cultured in lower glucose concentrations suggesting that modulation of glucose levels might influence the effectiveness of GC treatment in ALL. In summary, our data show that GC treatment blocks glucose uptake by leukemic cells leading to inhibition of glycolysis and that these effects play an important role in the induction of cell death by these drugs.