'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.

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.

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.

Genetic analysis of non-insulin dependent diabetes mellitus in the GK rat.

Non-insulin dependent diabetes mellitus (NIDDM) is a major public health problem, but its aetiology remains poorly understood. We have performed a comprehensive study of the genetic basis of diabetes in the Goto-Kakizaki (GK) rat, the most widely used animal model of non-obese NIDDM. The genetic dissection of NIDDM using this model has allowed us to map three independent loci involved in the disease. In addition, we identify a major factor affecting body weight, but not glucose tolerance, on chromosome 7 and map a further 10 regions that are suggestive for linkage. We conclude that NIDDM is polygenic and fasting hyperglycaemia and postprandial hyperglycaemia clearly have distinct genetic bases.

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.

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.

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.

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.

Antidiabetic effect of Gynostemma pentaphyllum tea in randomly assigned type 2 diabetic patients.

The aim of the study was to investigate the antidiabetic effect of the traditional Vietnamese herb Gynostemma pentaphyllum in 24 drug-naïve type 2 diabetic patients. All patients were randomized to authenticated Gynostemma pentaphyllum tea or placebo tea, 6 g daily, during twelve weeks and received information regarding diet and exercise. Fasting plasma glucose, insulin levels, and glycosylated hemoglobin (HbA(1C)) were measured before, during, and after the treatment. Oral glucose tolerance tests were performed every four weeks. After 12-week treatment, fasting plasma glucose levels totally decreased to an extent of 3.0+/-1.8 mmol/l in the Gynostemma pentaphyllum tea group as compared to a decrease of 0.6+/-2.2 mmol/l in the control group (p<0.01). HbA(1C) levels after 12 weeks decreased approximately 2% units in the Gynostemma pentaphyllum group compared to 0.2% unit in the controls (p<0.001). Change in Homeostasis Model Assessment-Insulin Resistance between baseline and twelfth week indicated that insulin resistance decreased significantly in the Gynostemma pentaphyllum group (-2.1+/-3.0) compared with that (+1.1+/-3.3) in the control group (p<0.05). There were no hypoglycemias, or adverse effects regarding kidney and liver parameters or gastrointestinal function. In addition, lipid profiles, glucagon, cortisol levels, body measurements, and blood pressure were not different between the groups. This study shows a prompt improvement of glycemia and insulin sensitivity, and thereby provides a basis for a novel, effective, and safe approach, using Gynostemma pentaphyllum tea, to treat type 2 diabetic patients.

Decreased levels of metabolic enzymes in pancreatic islets of patients with type 2 diabetes.

AIMS/HYPOTHESIS: Glucose-stimulated insulin secretion is defective in patients with type 2 diabetes. We sought to acquire new information about enzymes of glucose metabolism, with an emphasis on mitochondrial enzymes, by comparing pancreatic islets of type 2 diabetes patients with those of non-diabetic controls. METHODS: Expression of genes encoding 13 metabolic enzymes was estimated with microarrays and activities of up to nine metabolic enzymes were measured. RESULTS: The activities of the mitochondrial enzymes, glycerol phosphate dehydrogenase, pyruvate carboxylase (PC) and succinyl-CoA:3-ketoacid-CoA transferase (SCOT) were decreased by 73%, 65% and 92%, respectively, in the diabetic compared with the non-diabetic islets. ATP citrate lyase, a cytosolic enzyme of the mitochondrial citrate pyruvate shuttle, was decreased 57%. Activities of propionyl-CoA carboxylase, NADP-isocitrate dehydrogenase, cytosolic malic enzyme, aspartate aminotransferase and malate dehydrogenase were not significantly different from those of the control. The low activities of PC and SCOT were confirmed with western blots, which showed that their protein levels were low. The correlation of relative mRNA signals with enzyme activities was good in four instances, moderate in four instances and poor in one instance. In diabetic islets, the mRNA signal of the islet cell-enriched transcription factor musculoaponeurotic fibrosarcoma oncogene homologue A, which regulates expression of islet genes, including the PC gene, was decreased to 54% of the control level. PC activity and protein levels in the non-diabetic islets were significantly lower than in islets from non-diabetic rodents. CONCLUSIONS/INTERPRETATION: Low levels of certain islet metabolic enzymes, especially mitochondrial enzymes, are associated with human type 2 diabetes.

Factors determining normalization of glucose intolerance in middle-aged Swedish men and women: a 8-10-year follow-up.

AIMS: To examine factors in middle-aged Swedish men and women predicting the conversion from a state of abnormal glucose regulation to normal glucose tolerance (NGT) after 8-10 years. METHODS: At baseline 3128 men and 4821 women, aged 35-56 years, without previously diagnosed diabetes underwent an oral glucose tolerance test and completed a questionnaire. At follow-up, 2383 men and 3329 women were re-examined. The study group consisted of 156 men and 124 women with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), or both at baseline. RESULTS: The rate of reversal to NGT from IFG or IGT was similar regardless of gender. In participants having IFG or IGT, reversal to NGT was predicted by low fasting and 2-h insulin, homeostasis model assessment of insulin resistance and of pancreatic beta cell function, body mass index and waist circumference without differences between gender and baseline glucose tolerance group. Low 2-h glucose, however, predicted reversal to NGT in men with IFG at baseline, but not in men with IGT at baseline, or in women with either IFG or IGT at baseline. Men reverting to NGT had higher coffee consumption and women had higher baseline leisure-time physical activity. In multiple logistic regression, including all participants, low fasting and 2-h glucose remained independent predictors of reverting to NGT. CONCLUSIONS: Factors predicting reversal to NGT were measures correlated with low insulin resistance, but also lower insulin secretion, perhaps indicating a lower pancreatic beta cell workload in those who reverted. In men, but not in women, low 2-h glucose was of predictive value.

Screening of the hypoglycemic effect of eight Vietnamese herbal drugs.

The prevalence of type 2 diabetes in developing countries is increasing. In Vietnam, several plants are thought to be useful for the treatment of type 2 diabetes. This study has been performed to screen the hypoglycemic effects of eight Vietnamese herbs used in traditional medicine for the treatment of diabetes. Blood glucose levels were measured before and several times after oral or i.p. administration of the ethanol-based plant extracts in normal mice. The extracts that reduced blood glucose both orally and i.p. were also studied in glucose tolerance tests in mice. Gynostemma pentaphyllum Makino (Cucurbitaceae) at doses of 200 and 300 mg/kg i.p. or 1500 mg/kg orally reduced blood glucose in mice (P < 0.001 for all compared to control group using NaCl 0.9%). Similarly, Anemarrhena asphodeloides Bunge (Liliaceae) at 200 and 300 mg/kg i.p. (P < 0.001 vs. control group) and 1500 mg/kg orally reduced blood glucose 4 h after administration (P < 0.001). Angiopteris evecta Forst. Hoffn. (Marattiaceae) 300 mg/kg i.p. and 1500 mg/kg orally strongly reduced blood glucose levels (P < 0.001 vs. control groups). All three extracts when dosed at 1000 mg/kg orally suppressed the rise in blood glucose in normal mice during a glucose tolerance test. We have found three herbs that reduced blood glucose and inhibited increases in blood glucose after a glucose challenge in normal mice.

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.

Genetic variation of the adenylyl cyclase 3 (AC3) locus and its influence on type 2 diabetes and obesity susceptibility in Swedish men.

OBJECTIVE: Our previous study using the Goto-Kakizaki rat implicates that the adenylyl cyclase 3 (AC3) is a candidate gene for genetic study of metabolic disorders. The present study aimed to investigate the susceptibility of genetic variation of the AC3 gene in type 2 diabetes (T2D) patients and obese subjects. SUBJECTS AND METHODS: Variation screening in the putative promoter and validation of single nucleotide polymorphisms (SNPs) covering the AC3 gene were performed. In total, 630 Swedish men, including 243 T2D patients (BMI from 18.4 to 45.6 kg m(-2)), 199 obese subjects with normal glucose tolerance (NGT, BMI> or =30 kg m(-2)) and 188 control subjects (NGT, BMI< or =26 kg m(-2)), were genotyped. RESULTS: A novel variant -17A/T in the promoter was identified, but no significant association of this polymorphism with T2D was found. SNPs rs2033655 C/T and rs1968482 A/G were found to be significantly associated with obesity when T2D patients had BMI> or =30 kg m(-2) (P=0.003 and 0.005). The significance was borderline in T2D patients with BMI<30 kg m(-2) (P=0.051 and 0.084) and disappeared in T2D patients with BMI< or =26 kg m(-2). Importantly, analysis in obese subjects with NGT demonstrated that these two polymorphisms were strongly associated with obesity per se (P=0.028 and 0.003). Furthermore, analyses for diplotypes (haplotypic genotypes) predicted an association with BMI in obese subjects. CONCLUSIONS: The present study provides the first evidence that AC3 polymorphisms confer the risk susceptibility to obesity in Swedish men with and without type 2 diabetes.

Psychological distress and risk of pre-diabetes and Type 2 diabetes in a prospective study of Swedish middle-aged men and women.

AIMS: To determine the role of psychological distress as a predictor of pre-diabetes and Type 2 diabetes. METHODS: This cohort study comprised 2127 Swedish middle-aged men and 3100 women with baseline normal glucose tolerance measured by oral glucose tolerance test. At follow-up 8-10 years later, 245 men and 177 women had pre-diabetes [impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and IFG + IGT] and Type 2 diabetes was detected in 103 men and 57 women. Baseline psychological distress was measured by an index of five questions concerning anxiety, apathy, depression, fatigue and insomnia. Odds ratios (ORs) were estimated for pre-diabetes and Type 2 diabetes in association with total psychological distress. In addition, ORs of the single-item questions were calculated. RESULTS: In men, adjusted ORs (95% confidence interval) in the highest index group of psychological distress compared with the lowest group were 1.9 (1.2-2.8) and 2.2 (1.2-4.1) for pre-diabetes and Type 2 diabetes, respectively. Corresponding estimates in women were 1.2 (0.7-2.1) and 0.5 (0.2-1.2). In the middle symptoms groups, adjusted ORs in men were 1.1 (0.8-1.4) for pre-diabetes and 1.2 (0.7-2.0) for Type 2 diabetes and in women 1.8 (1.1-3.0) and 0.7 (0.3-1.4). When analysed separately, the associations with each of the five single factors were similar. CONCLUSIONS: The results indicate that psychological distress, including symptoms of anxiety, apathy, depression, fatigue and insomnia, increases the risk of pre-diabetes and Type 2 diabetes in Swedish middle-aged men. Increased risks were not present in women, except for pre-diabetes in the middle index group.

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.

B cell insensitivity in a rat model of non-insulin-dependent diabetes. Evidence for a rapidly reversible effect of previous hyperglycemia.

In perfused pancreas of rats rendered diabetic by streptozotocin injection (STZ) during neonatal age the insulin response to 27 mM glucose was significant but impaired. It was unaffected by the alpha adrenergic blocker phentolamine. When 27 mM mannoheptulose was added simultaneously with 27 mM glucose, insulin release was inhibited, but less promptly than in pancreases from non-diabetic rats. When mannoheptulose was introduced 15 min after starting perfusion with 27 mM glucose, inhibition was apparent in non-diabetic rats, but not in STZ. In non-diabetic rats perfusion without glucose for 40 min failed to affect the subsequent response to 27 mM glucose. Conversely, in STZ, glucose omission enhanced 3.7-fold the response to 27 mM glucose. Insulin release in response to 3-isobutyl-1-methylxanthine (IBMX) was more marked in STZ than in non-diabetic rats. After glucose omission the IBMX-induced response was, however, reduced (67%) in STZ, but not significantly (7%) in non-diabetic rats. Thus, glucopenia in vitro sensitizes B cells of STZ to glucose, but desensitizes them to IBMX. Abnormal responsiveness may be linked to metabolic consequences of B cell fuel abundance.

Pancreatic beta cells are important targets for the diabetogenic effects of glucocorticoids.

Abnormalities contributing to the pathogenesis of non-insulin-dependent diabetes mellitus include impaired beta cell function, peripheral insulin resistance, and increased hepatic glucose production. Glucocorticoids are diabetogenic hormones because they decrease glucose uptake and increase hepatic glucose production. In addition, they may directly inhibit insulin release. To evaluate that possible role of glucocorticoids in beta cell function independent of their other effects, transgenic mice with an increased glucocorticoid sensitivity restricted to their beta cells were generated by overexpressing the glucocorticoid receptor (GR) under the control of the insulin promoter. Intravenous glucose tolerance tests showed that the GR transgenic mice had normal fasting and postabsorptive blood glucose levels but exhibited a reduced glucose tolerance compared with their control littermates. Measurement of plasma insulin levels 5 min after intravenous glucose load demonstrated a dramatic decrease in acute insulin response in the GR transgenic mice. These results show that glucocorticoids directly inhibit insulin release in vivo and identify the pancreatic beta cell as an important target for the diabetogenic action of glucocorticoids.

Diabetic Goto-Kakizaki rats display pronounced hyperglycemia and longer-lasting cognitive impairments following ischemia induced by cortical compression.

Hyperglycemia has been shown to worsen the outcome of brain ischemia in several animal models but few experimental studies have investigated impairments in cognition induced by ischemic brain lesions in hyperglycemic animals. The Goto-Kakizaki (GK) rat naturally develops type 2 diabetes characterized by mild hyperglycemia and insulin resistance. We hypothesized that GK rats would display more severe cerebral damage due to hyperglycemia-aggravated brain injury and, accordingly, more severe cognitive impairments. In this study, recovery of motor and cognitive functions of GK and healthy Wistar rats was examined following extradural compression (EC) of the sensorimotor cortex. For this purpose, tests of vestibulomotor function (beam-walking) and combined tests of motor function and learning (locomotor activity from day (D) 1 to D5, operant lever-pressing from D14 to D25) were used. EC consistently reduced cerebral blood flow in both strains. Anesthesia-challenge and EC resulted in pronounced hyperglycemia in GK but not in Wistar rats. Lower beam-walking scores, increased locomotor activity, impairments in long-term habituation and learning of operant lever-pressing were more pronounced and observed at later time-points in GK rats. Fluoro-Jade, a marker of irreversible neuronal degeneration, revealed consistent degeneration in the ipsilateral cortex, hippocampus and thalamus at 2, 7 and 14 days post-compression. The amount of degeneration in these structures was considerably higher in GK rats. Thus, GK rats exhibited marked hyperglycemia during EC, as well as longer-lasting behavioral deficits and increased neurodegeneration during recovery. The GK rat is thus an attractive model for neuropathologic and cognitive studies after ischemic brain injury in hyperglycemic rats.