Structural and immunoendocrine remodeling in gut, pancreas and thymus in weaning rats fed powdered milk diets rich in Maillard reactants.

Western diet is extending worldwide and suspected to be associated with various metabolic diseases. Many food products have skim milk powder added to it and, during processing, lactose reacts with milk proteins and Maillard reaction products (MRPs) are formed. Dietary MRPs are suggested risk factors for metabolic dysregulation, but the mechanisms behind are still enigmatic. Here we describe that weaning rats fed diets rich in MRPs are affected in both their immune and endocrine systems. Marked structural changes in pancreas, intestine and thymus are noted already after 1 week of exposure. The pancreatic islets become sparser, the intestinal mucosa is thinner, and thymus displays increased apoptosis and atrophy. Glucagon- like peptide-1 (GLP-1) seems to play a key role in that the number of GLP-1 expressing cells is up-regulated in endocrine pancreas but down-regulated in the intestinal mucosa. Further, intestinal GLP-1-immunoreactive cells are juxta positioned not only to nerve fibres and tuft cells, as previously described, but also to intraepithelial CD3 positive T cells, rendering them a strategic location in metabolic regulation. Our results suggest dietary MRPs to cause metabolic disorders, dysregulation of intestinal GLP-1- immunoreactive cells, arrest in pancreas development and thymus atrophy.

Low sun exposure habits is associated with a dose-dependent increased risk of hypertension: a report from the large MISS cohort.

In prospective observational cohort studies, increasing sun exposure habits have been associated with reduced risk of cardiovascular mortality. Our aim was to assess possible observational mechanisms for this phenomenon. A written questionnaire was answered by 23,593 women in the year 2000 regarding risk factors for melanoma, including factors of possible interest for hypertension, such as detailed sun exposure habits, hypertension, marital status, education, smoking, alcohol consumption, BMI, exercise, and chronic high stress. Hypertension was measured by the proxy "use of hypertension medication" 2005-2007, and high stress by "need of anti-depressive medication". Sun exposure habits was assessed by the number of `yes' to the following questions; Do you sunbath during summer?, During winter vacation?, Do you travel south to sunbath?, Or do you use sun bed? Women answering 'yes' on one or two questions had moderate and those answering 'yes' on three or four as having greatest sun exposure. The main outcome was the risk of hypertension by sun exposure habits adjusted for confounding. As compared to those women with the greatest sun exposure, women with low and moderate sun exposure were at 41% and 15% higher odds of hypertension (OR 1.41, 95% CI 1.3‒1.6, p < 0.001 and OR 1.15, 95% CI 1.1‒1.2, p < 0.001), respectively. There was a strong age-related increased risk of hypertension. Other risk factors for hypertension were lack of exercise (OR 1.36), a non-fair phenotype (OR 1.08), chronic high stress level (OR 1.8), and lack of university education (OR 1.3). We conclude that in our observational design sun exposure was associated with a dose-dependent reduced risk of hypertension, which might partly explain the fewer deaths of cardiovascular disease with increasing sun exposure.

Pregnancy-associated plasma protein-A2 levels are increased in early-pregnancy gestational diabetes: a novel biomarker for early risk estimation.

AIM: To determine whether pregnancy-associated plasma protein-A2 levels are increased in early pregnancies complicated by gestational diabetes and whether gestation age influences levels. The possible use of pregnancy-associated plasma protein-A2 as a pre-screening biomarker to reduce the need for performing oral glucose tolerance tests in pregnant women was also investigated. METHODS: Pregnant women were diagnosed with gestational diabetes in early pregnancy after a 2-hour 75 g oral glucose tolerance test in the catchment area of Skåne University Hospital, Lund, Sweden during 2011-2015 (n = 99). Age- and BMI-matched pregnant women without diabetes were recruited at similar gestational ages from maternal healthcare centres in the same geographical area during 2014-2015 to act as controls (n = 100). Circulating pregnancy-associated plasma protein-A2 was analysed in participant serum using commercially available enzyme-linked immunosorbent assay kits. RESULTS: Circulating pregnancy-associated plasma protein-A2 was increased in women diagnosed with gestational diabetes [13.5 (9.58-18.8) ng/ml] compared with controls [8.11 (5.74-11.3) ng/ml; P < 0.001]. Pregnancy-associated plasma protein-A2 was associated with gestational diabetes independent of age, BMI, C-peptide and adiponectin (P < 0.001). Pregnancy-associated plasma protein-A2 as a pre-screening biomarker to identify women at a decreased risk of gestational diabetes resulted in a negative predictive value of 99.7%, with a sensitivity of 96% and a specificity of 30% at a cut-off level of 6 ng/ml. CONCLUSIONS: This is the first study to show increased pregnancy-associated plasma protein-A2 levels in gestational diabetes. Pregnancy-associated plasma protein-A2 also shows promise as a pre-screening biomarker with the potential to reduce the need for performing oral glucose tolerance tests in early pregnancy. Future prospective cohort studies in a larger group of both high- and low-risk women are, however, needed to further confirm this observation.

Skim milk powder with high content of Maillard reaction products affect weight gain, organ development and intestinal inflammation in early life in rats.

BACKGROUND: The intestinal tract is important for development of immune tolerance and disturbances are suggested to trigger autoimmune disorders. The aim of this study was to explore the effect of Maillard products in skim milk powder obtained after long storage, compared to fresh skim milk powder. METHODS: Young rats were weaned onto a diet based on skim milk powder with high concentration of Maillard products (HM-SM, n = 18) or low (C-SM, n = 18) for one week or four weeks. Weekly body weight and feed consumption were noted. At the end, organ weights, intestinal histology, permeability and inflammatory cytokines were evaluated. RESULTS: Rats fed with HM-SM had after one week, 15% less weight gain than controls, despite equal feed intake. After one week thymus and spleen were smaller, intestinal mucosa thickness was increased and acute inflammatory cytokines (IL-17, IL-1ß, MCP-1) were elevated. After four weeks, cytokines associated with chronic intestinal inflammation (fractalkine, IP-10, leptin, LIX, MIP-2, RANTES and VEGF) were increased in rats fed with HM-SM compared to C-SM. CONCLUSION: High content of Maillard products in stored milk powder caused an intestinal inflammation. Whether this is relevant for tolerance development and future autoimmune diseases remains to be explored.

Overweight, hyperglycemia and tobacco use are modifiable risk factors for onset of retinopathy 9 and 17years after the diagnosis of diabetes - A retrospective observational nation-wide cohort study.

BACKGROUND: The aims of this study were to estimate the risk for diabetic retinopathy (DR) and to identify risk factors. We investigated a nationwide population-based cohort with diabetes diagnosed at age 15-34years. PATIENTS AND METHODS: Of 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) 444 (56%) patients with retinal photos available for classification of retinopathy participated in a follow-up study 15-19 (median 17) years after diagnosis. Mean age was 42.3±5.7years, BMI 26.1±4.1kg/m2, 62% were male and 91% had type 1 diabetes. A sub-study was performed in 367 patients with retinal photos from both the 9 and 17year follow up and the risk for development of retinopathy between 9 and 17years of follow up was calculated. RESULTS: After median 17years 324/444 (73%, 67% of T1D and 71% of T2D), had developed any DR but only 5.4% proliferative DR. Male sex increased the risk of developing retinopathy (OR 1.9, 95% CI 1.2-2.9). In the sub-study obesity (OR 1.2, 95% CI 1.04-1.4), hyperglycemia (OR 2.5, 95% CI 1.6-3.8) and tobacco use (OR 2.9, 95% CI 1.1-7.3) predicted onset of retinopathy between 9 and 17years after diagnosis of diabetes. CONCLUSION: The number of patients with severe retinopathy after 17years of diabetes disease was small. The risk of developing retinopathy with onset between 9 and 17years after diagnosis of diabetes was strongly associated to modifiable risk factors such as glycemic control, obesity and tobacco use.

Avoidance of sun exposure as a risk factor for major causes of death: a competing risk analysis of the Melanoma in Southern Sweden cohort.

OBJECTIVE: Women with active sunlight exposure habits experience a lower mortality rate than women who avoid sun exposure; however, they are at an increased risk of skin cancer. We aimed to explore the differences in main causes of death according to sun exposure. METHODS: We assessed the differences in sun exposure as a risk factor for all-cause mortality in a competing risk scenario for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 (aged 25-64 years at the start of the study). We obtained detailed information at baseline on sun exposure habits and potential confounders. The data were analysed using modern survival statistics. RESULTS: Women with active sun exposure habits were mainly at a lower risk of cardiovascular disease (CVD) and noncancer/non-CVD death as compared to those who avoided sun exposure. As a result of their increased survival, the relative contribution of cancer death increased in these women. Nonsmokers who avoided sun exposure had a life expectancy similar to smokers in the highest sun exposure group, indicating that avoidance of sun exposure is a risk factor for death of a similar magnitude as smoking. Compared to the highest sun exposure group, life expectancy of avoiders of sun exposure was reduced by 0.6-2.1 years. CONCLUSION: The longer life expectancy amongst women with active sun exposure habits was related to a decrease in CVD and noncancer/non-CVD mortality, causing the relative contribution of death due to cancer to increase.

Patients presenting at the emergency department with acute abdominal pain are less likely to be admitted to inpatient wards at times of access block: a registry study.

BACKGROUND: Also known as access block, shortage of inpatient beds is a common cause of emergency department (ED) boarding and overcrowding, which are both associated with impaired quality of care. Recent studies have suggested that access block not simply causes boarding in EDs, but may also result in that patients are less likely to be admitted to the hospital from the ED. The present study's aim was to investigate whether this effect remained for patients with acute abdominal pain, for which different management strategies have emerged. Access block was defined in terms of hospital occupancy and the appropriateness of ED discharges addressed as 72 h revisits to the ED. METHODS: As a registry study of ED administrative data, the study examined a population of patients who presented with acute abdominal pain at the ED of a 420-bed hospital in southern Sweden during 2011-2013. Associations between exposure and outcomes were addressed in contingency tables and by logistic regression models. RESULTS: Crude analysis revealed a negative association between access block and the probability of inpatient admission (38.6 % admitted at 0-95 % occupancy, 37.8 % at 95-100 % occupancy, and 35.0 % at ≥ 100 % occupancy) (p < .001). No significant associations between exposure and 72 h revisits emerged. Multivariable models indicated an odds ratio of inpatient admission of 0.992 (95 % CI: 0.986-0.997) per percentage increase in hospital occupancy. CONCLUSIONS: Study findings indicate that patients with acute abdominal pain are less likely to be admitted to the hospital from the ED at times of access block and that other management strategies are employed instead. No association with 72 h revisits was seen, but future studies need to address more granular outcomes in order to clarify the safety aspects of the effect.

The risk for diabetic nephropathy is low in young adults in a 17-year follow-up from the Diabetes Incidence Study in Sweden (DISS). Older age and higher BMI at diabetes onset can be important risk factors.

AIMS: The main objective of this study was to estimate the occurrence of diabetic nephropathy in a population-based cohort of patients diagnosed with diabetes as young adults (15-34 years). METHODS: All 794 patients registered 1987-1988 in the Diabetes Incidence Study in Sweden (DISS) were invited to a follow-up study 15-19 years after diagnosis, and 468 (58%) participated. Analysis of islet antibodies was used to classify type of diabetes. RESULTS: After median 17 years of diabetes, 15% of all patients, 14% T1DM and 25% T2DM, were diagnosed with diabetic nephropathy. Ninety-one percent had microalbuminuria and 8.6% macroalbuminuria. Older age at diagnosis (HR 1.05; 95% CI 1.01-1.10 per year) was an independent and a higher BMI at diabetes diagnosis (HR 1.04; 95% CI 1.00-1.09 per 1 kg/m²), a near-significant predictor of development of diabetic nephropathy. Age at onset of diabetes (p = 0.041), BMI (p = 0.012) and HbA1c (p < 0.001) were significant predictors of developing diabetic nephropathy between 9 and 17 years of diabetes. At 17 years of diabetes duration, a high HbA1c level (OR 1.06; 95% CI 1.03-1.08 per 1 mmol/mol increase) and systolic blood pressure (OR 1.08; 95% CI 1.05 1.12 per 1 mmHg increase) were associated with DN. CONCLUSIONS: Patients with T2DM diagnosed as young adults seem to have an increased risk to develop diabetic nephropathy compared with those with T1DM. Older age and higher BMI at diagnosis of diabetes were risk markers for development of diabetic nephropathy. In addition, poor glycaemic control but not systolic blood pressure at 9 years of follow-up was a risk marker for later development of diabetic nephropathy.

Avoidance of sun exposure is a risk factor for all-cause mortality: results from the Melanoma in Southern Sweden cohort.

BACKGROUND: Sunlight exposure and fair skin are major determinants of human vitamin D production, but they are also risk factors for cutaneous malignant melanoma (MM). There is epidemiological evidence that all-cause mortality is related to low vitamin D levels. METHODS: We assessed the avoidance of sun exposure as a risk factor for all-cause mortality for 29 518 Swedish women in a prospective 20-year follow-up of the Melanoma in Southern Sweden (MISS) cohort. Women were recruited from 1990 to 1992 and were aged 25 to 64 years at the start of the study. We obtained detailed information at baseline on their sun exposure habits and potential confounders. Multivariable flexible parametric survival analysis was applied to the data. RESULTS: There were 2545 deaths amongst the 29 518 women who responded to the initial questionnaire. We found that all-cause mortality was inversely related to sun exposure habits. The mortality rate amongst avoiders of sun exposure was approximately twofold higher compared with the highest sun exposure group, resulting in excess mortality with a population attributable risk of 3%. CONCLUSION: The results of this study provide observational evidence that avoiding sun exposure is a risk factor for all-cause mortality. Following sun exposure advice that is very restrictive in countries with low solar intensity might in fact be harmful to women's health.

Plasma alkylresorcinols C17:0/C21:0 ratio, a biomarker of relative whole-grain rye intake, is associated to insulin sensitivity: a randomized study.

BACKGROUND/OBJECTIVES: Few studies have used biomarkers of whole-grain intake to study its relation to glucose metabolism. We aimed to investigate the association between plasma alkylresorcinols (AR), a biomarker of whole-grain rye and wheat intake, and glucose metabolism in individuals with metabolic syndrome (MetS). SUBJECTS/METHODS: Participants were 30-65 years of age, with body mass index 27-40 kg/m(2) and had MetS without diabetes. Individuals were recruited through six centers in the Nordic countries and randomized to a healthy Nordic diet (ND, n=96), rich in whole-grain rye and wheat, or a control diet (n=70), for 18-24 weeks. In addition, associations between total plasma AR concentration and C17:0/C21:0 homolog ratio as an indication of the relative whole-grain rye intake, and glucose metabolism measures from oral glucose tolerance tests were investigated in pooled (ND+control) regression analyses at 18/24 weeks. RESULTS: ND did not improve glucose metabolism compared with control diet, but the AR C17:0/C21:0 ratio was inversely associated with fasting insulin concentrations (P=0.002) and positively associated with the insulin sensitivity indices Matsuda ISI (P=0.026) and disposition index (P=0.022) in pooled analyses at 18/24 weeks, even after adjustment for confounders. The AR C17:0/C21:0 ratio was not significantly associated with insulin secretion indices. Total plasma AR concentration was not related to fasting plasma glucose or fasting insulin at 18/24 weeks. CONCLUSIONS: The AR C17:0/C21:0 ratio, an indicator of relative whole-grain rye intake, is associated with increased insulin sensitivity in a population with MetS.

Assessment of beta-cell function in young patients with type 2 diabetes: arginine-stimulated insulin secretion may reflect beta-cell reserve.

OBJECTIVE: Simple methods for the evaluation of dynamic b-cell function in epidemiological and clinical studies of patients with type 2 diabetes (T2D) are needed. The aim of this study was to evaluate the dynamic beta-cell function in young patients with T2D with different disease durations and treatments. METHODS: Overall, 54 subjects with T2D from the Diabetes Incidence Study in Sweden (DISS) and 23 healthy control participants were included in this cross-sectional study. Beta-cell function was assessed by intravenous (i.v.) administration of arginine followed by i.v. glucose. The acute insulin and C-peptide responses to arginine (AIRarg and Ac-pepRarg, respectively) and to glucose (AIRglu and Ac-pepRglu, respectively)were estimated.Homeostasis model assessment of b-cell function(HOMA-b) andCpeptide assessments were also used for comparisons between patients with T2D and control participants. RESULTS: AIRarg and Ac-pepRarg, but not AIRglu and Ac-pepRglu, could differentiate between patients with different disease durations. AIRglu values were 89% (P < 0.001) lower and AIRarg values were 29% (P < 0.01) lower in patients with T2D compared with control participants. HOMA-b and fasting plasma C-peptide levels did not differ between the T2D and control groups. CONCLUSION: In young patients with T2D, the insulin secretory response to i.v. glucose is markedly attenuated, whereas i.v. arginine-stimulated insulin release is better preserved and can distinguish between patients with different disease duration and antidiabetic therapies. This suggests that the i.v. arginine stimulation test may provide an estimate of functional beta-cell reserve.

Variability in the CIITA gene interacts with HLA in multiple sclerosis.

The human leukocyte antigen (HLA) is the main genetic determinant of multiple sclerosis (MS) risk. Within the HLA, the class II HLA-DRB1*15:01 allele exerts a disease-promoting effect, whereas the class I HLA-A*02 allele is protective. The CIITA gene is crucial for expression of class II HLA molecules and has previously been found to associate with several autoimmune diseases, including MS and type 1 diabetes. We here performed association analyses with CIITA in 2000 MS cases and up to 6900 controls as well as interaction analysis with HLA. We find that the previously investigated single-nucleotide polymorphism rs4774 is associated with MS risk in cases carrying the HLA-DRB1*15 allele (P=0.01, odds ratio (OR): 1.21, 95% confidence interval (CI): 1.04-1.40) or the HLA-A*02 allele (P=0.01, OR: 1.33, 95% CI: 1.07-1.64) and that these associations are independent of the adjacent confirmed MS susceptibility gene CLEC16A. We also confirm interaction between rs4774 and HLA-DRB1*15:01 such that individuals carrying the risk allele for rs4774 and HLA-DRB1*15:01 have a higher than expected risk for MS. In conclusion, our findings support previous data that variability in the CIITA gene affects MS risk, but also that the effect is modulated by MS-associated HLA haplotypes. These findings further underscore the biological importance of HLA for MS risk.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

Age-dependent variation of genotypes in MHC II transactivator gene (CIITA) in controls and association to type 1 diabetes.

The major histocompatibility complex class II transactivator (CIITA) gene (16p13) has been reported to associate with susceptibility to multiple sclerosis, rheumatoid arthritis and myocardial infarction, recently also to celiac disease at genome-wide level. However, attempts to replicate association have been inconclusive. Previously, we have observed linkage to the CIITA region in Scandinavian type 1 diabetes (T1D) families. Here we analyze five Swedish T1D cohorts and a combined control material from previous studies of CIITA. We investigate how the genotype distribution within the CIITA gene varies depending on age, and the association to T1D. Unexpectedly, we find a significant difference in the genotype distribution for markers in CIITA (rs11074932, P=4 × 10(-5) and rs3087456, P=0.05) with respect to age, in the collected control material. This observation is replicated in an independent cohort material of about 2000 individuals (P=0.006, P=0.007). We also detect association to T1D for both markers, rs11074932 (P=0.004) and rs3087456 (P=0.001), after adjusting for age at sampling. The association remains independent of the adjacent T1D risk gene CLEC16A. Our results indicate an age-dependent variation in CIITA allele frequencies, a finding of relevance for the contrasting outcomes of previously published association studies.

Prevalence of zinc transporter 8 antibodies in gestational diabetes mellitus.

AIMS: Gestational diabetes mellitus affects approximately 7% of all pregnant women. Some of these women develop autoantibodies that are generally characteristic of Type 1 diabetes. Autoantibodies targeting glutamic acid decarboxylase and tyrosine phosphatase-like protein are the most frequently reported. A recently identified autoantigen in Type 1 diabetes is zinc transporter 8. Some reports suggest that the frequency of zinc transporter 8 antibodies is as high as glutamic acid decarboxylase antibodies in Type 1 diabetes and thus a good diagnostic marker for autoimmune diabetes. There are currently no reports of zinc transporter 8 antibodies in gestational diabetes. The aim of this pilot study was to investigate the frequency of zinc transporter 8 antibodies in patients at clinical onset of gestational diabetes mellitus. METHODS: Subjects included in this pilot study were all diagnosed with gestational diabetes at Skåne University Hospital, Lund, Sweden, 2009-2010 (n = 193). Sera samples were analysed for antibodies using a commercial enzyme-linked immunosorbent assay according to the manufacturers' instructions. RESULTS: We found that 19/193 patients with gestational diabetes, diagnosed in 2009-2010, were positive for at least one autoantibody. Glutamic acid decarboxylase was the most common single autoantibody (52.6%; 10/19), followed by zinc transporter 8 (21.1%; 4/19) and tyrosine phosphatase-like protein (15.8%; 3/19). Combinations of two or more antibodies were rare (10.5%; 2/19). CONCLUSIONS: In this study, we found that zinc transporter 8 added 2.1% (4/193) of autoantibody positivity in women with gestational diabetes who were negative for glutamic acid decarboxylase and tyrosine phosphatase-like protein antibodies. Glutamic acid decarboxylase was still the most prevalent autoantibody in gestational diabetes, but, as zinc transporter 8 was present even in the absence of glutamic acid decarboxylase, this autoantibody could be an important independent marker of autoimmunity in gestational diabetes.

Genetic prediction of postpartum diabetes in women with gestational diabetes mellitus.

AIMS: To examine whether genetic variants that predispose individuals to type 2 diabetes (T2D) could predict the development of diabetes after gestational diabetes mellitus (GDM). METHODS: 13 SNPs (FTO rs8050136, CDKAL1 rs7754840 and rs7756992, CDKN2A/2B rs10811661, HHEX rs1111875, IGF2BP2 rs1470579 and rs4402960, SLC30A8 rs13266634, TCF7L2 rs7903146, PPARG rs1801282, GCK rs1799884, HNF1A rs1169288, and KCNJ11 rs5219) were genotyped in 793 women with GDM after a median follow-up of 57 months. RESULTS: After adjustment for age and ethnicity, the TCF7L2 rs7903146 and the FTO rs8050136 variants significantly predicted postpartum diabetes; hazard ratio (95% confidence interval 1.29 (1.01-1.66) and 1.36 (1.06-1.74), respectively (additive model) versus 1.45 (1.01-2.08) and 1.56 (1.06-2.29) (dominant model)). Adjusting for BMI attenuated the effect of the FTO variant, suggesting that the effect was mediated through its effect on BMI. Combining all risk alleles to a weighted risk score was significantly associated with the risk of postpartum diabetes (hazard ratio 1.11, 95% confidence interval 1.05-1.18, p=0.00016 after adjustment for age and ethnicity). CONCLUSIONS: The TCF7L2 rs7903146 and FTO rs8050136 polymorphisms, and particularly a weighted risk score of T2D risk alleles, predict diabetes after GDM. Further studies in other populations are needed to confirm our results.

Effects of rose hip intake on risk markers of type 2 diabetes and cardiovascular disease: a randomized, double-blind, cross-over investigation in obese persons.

BACKGROUND/OBJECTIVES: In studies performed in mice, rose hip powder has been shown to both prevent and reverse high-fat diet-induced obesity and glucose intolerance as well as reduce plasma levels of cholesterol. The aim of this study was to investigate whether daily intake of rose hip powder over 6 weeks exerts beneficial metabolic effects in obese individuals. SUBJECTS/METHODS: A total of 31 obese individuals with normal or impaired glucose tolerance were enrolled in a randomized, double-blind, cross-over study in which metabolic effects of daily intake of a rose hip powder drink over 6 weeks was compared with a control drink. Body weight, glucose tolerance, blood pressure, blood lipids and markers of inflammation were assessed in the subjects. RESULTS: In comparison with the control drink, 6 weeks of daily consumption of the rose hip drink resulted in a significant reduction of systolic blood pressure (-3.4%; P=0.021), total plasma cholesterol (-4.9%; P=0.0018), low-density lipoprotein (LDL) cholesterol (-6.0%; P=0.012) and LDL/HDL ratio (-6.5%; P=0.041). The Reynolds risk assessment score for cardiovascular disease was decreased in the rose hip group compared with the control group (-17%; P=0.007). Body weight, diastolic blood pressure, glucose tolerance, and plasma levels of high-density lipoprotein (HDL) cholesterol, triglycerides, incretins and markers of inflammation did not differ between the two groups. CONCLUSIONS: Daily consumption of 40 g of rose hip powder for 6 weeks can significantly reduce cardiovascular risk in obese people through lowering of systolic blood pressure and plasma cholesterol levels.

Immunoglobulin subclass profiles of anti-idiotypic antibodies to GAD65Ab differ between type 1 diabetes patients and healthy individuals.

Previously we reported the presence of anti-idiotypic antibodies (anti-Id)-specific to autoantibodies against GAD65 (GAD65Ab) in healthy individuals while the activity of anti-Id directed to GAD65Ab in type 1 diabetes (T1D) patients was significantly lower. These anti-Id recognize the antigen-binding site of GAD65Ab, thus preventing their binding to GAD65. Here, we characterized the IgG subclass profile of these anti-Id (GAD65Ab specific) and of the associated GAD65Ab themselves. The IgG subclass response of anti-Id in healthy individuals (n = 16) was IgG3-dominated, while in T1D patients (n = 8) IgG1 was the major IgG subclass. The GAD65Ab bound by anti-Id in both healthy individuals (n = 38) and GAD65Ab-negative T1D patients (n = 35) showed a predominant rank order of IgG1 > IgG2 > IgG4 > IgG3. However, the frequency of GAD65Ab of the IgG4 subclass was significantly higher in T1D patients (P < 0.05). We conclude that the IgG subclass profile of anti-Id (GAD65Ab specific) in healthy individuals differs from that in T1D patients. These differences may provide insights into the development of these antibodies.

Hyperbaric oxygen therapy improves health-related quality of life in patients with diabetes and chronic foot ulcer.

AIMS: Adjunctive treatment with hyperbaric oxygen therapy has recently been shown to improve ulcer healing in patients with chronic diabetic foot ulcer. The aim of the present study is to evaluate whether hyperbaric oxygen therapy improves the health related quality of life in these patients. METHODS: Prospective randomized placebo-controlled double-blinded study setting using SF-36. RESULTS: A total of 75 patients were included in the study; 38 were randomized to hyperbaric oxygen therapy and 37 to placebo (hyperbaric air). The overall mean physical and mental summary scores for the entire study population at baseline were 29.6 ± 8.8 and 47.5 ± 12.4, respectively. There was a significant difference between baseline and 1 year follow-up responses to the mental summary score and two of the eight (SF-36) (?) domains in the -hyperbaric oxygen group, whereas no significant improvement of health related quality of life was seen in the placebo group. Comparing quality of life in patients who healed their ulcer (healers) with those who did not (non-healers), post-treatment levels of the mental health summary score, social functioning and role limitations due to physical and emotional health were significantly improved in healers. No differences were seen in any SF-36 (?) domain in non-healers. CONCLUSIONS: Hyperbaric oxygen therapy improves long-term health related quality of life in patients with chronic diabetic foot ulcers, possibly attributable to better ulcer healing.

Relationship between ulcer healing after hyperbaric oxygen therapy and transcutaneous oximetry, toe blood pressure and ankle-brachial index in patients with diabetes and chronic foot ulcers.

AIMS/HYPOTHESIS: The randomised, double-blind, placebo-controlled Hyperbaric Oxygen Therapy (HBOT) in Diabetic Patients with Chronic Foot Ulcers (HODFU) study showed beneficial effect of HBOT. As this treatment is expensive and time-consuming, being able to select patients for therapy would be very useful. The aim of this study was to evaluate whether circulatory variables could help in predicting outcome of HBOT. METHODS: All HODFU study participants who completed therapy, predefined as receiving at least 36 out of 40 scheduled HBOT/placebo sessions, were included in this study (n = 75). Baseline transcutaneous oximetry (TcPO2), toe blood pressure (TBP) and ankle-brachial index (ABI) were measured. Ulcer healing rate was registered at the 9-month follow-up visit. An ulcer was considered healed when it was completely epithelialised and remained so at the 12-month follow-up. RESULTS: In the HBOT group TcPO2 were significantly lower for patients whose ulcer did not heal as compared with those whose ulcers healed. A significantly increased healing frequency was seen with increasing TcPO(2) levels in the HBOT group (TcPO2/healing rate: <25 mmHg/0%; 26-50 mmHg/50%; 51-75 mmHg/73%; and >75 mmHg/100%). No statistically significant relation between the level of TBP or ABI and healing frequency was seen. CONCLUSIONS/INTERPRETATION: Our results indicate that TcPO2 in contrast to ABI and TBP correlates to ulcer healing following HBOT. We suggest HBOT as a feasible adjunctive treatment modality in diabetic patients with chronic non-healing foot ulcers when basal TcPO2 at the dorsum of the foot is above 25 mmHg. TRIAL REGISTRATION: NCT00953186 FUNDING: Mrs Thelma Zoegas Foundation and Faculty of Medicine, Lund University.