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Background: The role of dietary Glycemic Index (GI), independently of fiber intake, in modulating cardiovascular disease (CVD) risk among non-diabetic individuals has not been fully elucidated. Objective: To evaluate the effects of a low- versus a high-GI diet, based on a Mediterranean dietary pattern, on cardiometabolic risk factors in individuals at high CVD risk, participating in the MEDGI-Carb intervention study. Subjects and methods: 160 individuals, aged 30–69 years, BMI 25–37 kg/m2, with a waist circumference >102 cm (males) or >88 cm (females) and one feature of the metabolic syndrome, participated in a multi-national (Italy, Sweden, USA) randomized controlled parallel group trial. Participants were assigned to a low GI (< 55) or high-GI MedDiet (> 70) for 12 weeks. The diets were isoenergetic and similar for available carbohydrate (270 g/d) and fiber (35 g/d) content. Fasting metabolic parameters were evaluated in the whole cohort, while an 8-h triglyceride profile (after standard breakfast and lunch) was evaluated only in the Italian cohort. Results: Blood pressure and most fasting metabolic parameters improved at the end of the dietary intervention (time effect, p < 0.05 for all); however, no differences were observed between the low- and the high-GI MedDiet groups (time x group effect; p > 0.05 for all). Conversely, the low-GI diet, compared with high-GI diet, significantly reduced the 8-h triglyceride profile (p < 0.017, time*group effect) that was measured only in the Italian cohort. However, it induced a reduction of plasma triglycerides after lunch (tAUC) that was of only borderline statistically significance (p = 0.065). Conclusions: Consuming a low-GI in comparison with a high-GI MedDiet does not differentially affect the major cardiometabolic risk factors at fasting in individuals at increased cardiometabolic risk. Conversely, it could reduce postprandial plasma triglycerides. Clinical trial registry number: NCT03410719, (https://clinicaltrials.gov). [ABSTRACT FROM AUTHOR]

To address the unmet need for scalable solutions for lifestyle treatment, we developed a new digital method to promote behavioral change. Here we report that patients with type-2 diabetes in Sweden (n = 331) exposed to the intervention have significantly improved HbA1c during a median follow-up of 1038 days (4 mmol/mol compared with matched controls; P = 0.009). This is paralleled by reduced body weight, ameliorated insulin secretion, increased physical activity, and cognitive eating restraints. Participants with high BMI and insulin resistance have an even larger response, as have non-risk allele carriers for the FTO gene. The findings open a new avenue for scalable lifestyle management with sustained efficacy and highlight a previously unrecognized opportunity for digital precision treatment based on genetics and individual pathophysiology. ClinicalTrials.gov NCT04624321. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance has been shown to be related to a higher risk of several cancers, but the association with prostate cancer (PCa) has been inconsistent. Methods: We investigated prediagnostic markers of insulin resistance in men in four cohorts in Sweden, in relation to PCa risk (total, non‐aggressive and aggressive) and PCa death using multivariable‐adjusted Cox regression. The number of men, PCa cases and PCa deaths was up to 66,668, 3940 and 473 for plasma glucose and the triglyceride‐glucose (TyG) index, and up to 3898, 586 and 102 for plasma insulin, glycated haemoglobin (HbA1c) and leptin. Results: Higher HbA1c was related to a lower risk of non‐aggressive PCa but no significant associations were found for insulin resistance markers with the risk of aggressive or total PCa. In PCa cases, higher glucose and TyG index were related to a higher risk of PCa death (hazard ratio [HR] per higher standard deviation, 1.22, 95% CI 1.00–1.49 and 1.24, 95% CI 1.00–1.55), which further increased when restricting the analyses to glucose and TyG index measures taken <10 years before the PCa diagnosis (HR, 1.70, 95% CI 1.09–2.70 and 1.66, 95% CI 1.12–2.51). No associations were observed for other markers in relation to PCa death. Conclusions: The results of this study showed no associations of insulin resistance markers with the risk of clinically relevant PCa, but higher glucose and TyG index were associated with poorer survival from PCa. The lack of association for other insulin resistance markers may be due to their smaller sample size. [ABSTRACT FROM AUTHOR]

Aim: To assess the hypothesis that low internal health locus of control (IHLC) and psychological distress (PD) are associated with insulin resistance. Materials and methods: In 2002–2005, a random population sample of 2,816 men and women aged 30–74 years participated (76%) in two municipalities in southwestern Sweden. This study included 2,439 participants without previously known diabetes or cardiovascular disease. IHLC was measured by a global scale and PD was measured by the 12-item General Health Questionnaire. Insulin resistance was estimated using HOMA-ir. General linear models were used to estimate differences in HOMA-ir between groups with low IHLC, PD, and both low IHLC and PD, respectively. Results: Five per cent (n = 138) had both PD and low IHLC, 62 per cent of participants (n = 1509) had neither low IHLC nor PD, 18 per cent (n = 432) had PD, and 15 per cent (n = 360) low IHLC. Participants with both low IHLC and PD had significantly higher HOMA-ir than participants with neither low IHLC nor PD (Δ = 24.8%, 95%CI: 12.0–38.9), also in the fully adjusted model (Δ = 11.8%, 95%CI: 1.5–23.0). Participants with PD had significantly higher HOMA-ir (Δ = 12%, 95%CI: 5.7–18.7), but the significance was lost when BMI was included in the model (Δ = 5.3%, 95%CI:0.0–10.8). Similarly, participants with low IHLC had significantly higher HOMA-ir (Δ = 10.1%, 95%CI: 3.5–17.0) but the significance was lost in the fully adjusted model (Δ = 3.5%, 95%CI: -1.9–9.3). Conclusions: Internal health locus of control (IHLC) and psychological distress (PD) were associated with insulin resistance. Especially individuals with both PD and low IHLC may need special attention. [ABSTRACT FROM AUTHOR]

The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI: 1.04–1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09–1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance. Follistatin promotes in type 2 diabetes (T2D) pathogenesis in model animals and is elevated in patients with T2D. Here the authors report that plasma follistatin associates with increased risk of incident T2D in two longitudinal cohorts, and show that follistatin regulates insulin-induced suppression lipolysis in cultured human adipocytes. [ABSTRACT FROM AUTHOR]

Background: Middle Eastern immigrants to Europe represent a high risk population for type 2 diabetes. We compared prevalence of novel subgroups and assessed risk of diabetic macro‐ and microvascular complications between diabetes patients of Middle Eastern and European origin. Methods: This study included newly diagnosed diabetes patients born in Sweden (N = 10641) or Iraq (N = 286), previously included in the All New Diabetes in Scania cohort. The study was conducted between January 2008 and August 2016. Patients were followed to April 2017. Incidence rates in diabetic macro‐ and microvascular complications were assessed using cox‐regression adjusting for the confounding effect of age at onset, sex, anthropometrics, glomerular filtration rate (eGFR) and HbA1c. Findings: In Iraqi immigrants versus native Swedes, severe insulin‐deficient diabetes was almost twice as common (27.9 vs. 16.2% p < 0.001) but severe insulin‐resistant diabetes was less prevalent. Patients born in Iraq had higher risk of coronary events (hazard ratio [HR] 1.84, 95% CI 1.06–3.12) but considerably lower risk of chronic kidney disease (CKD) than Swedes (HR 0.19; 0.05–0.76). The lower risk in Iraqi immigrants was partially attributed to better eGFR. Genetic risk scores (GRS) showed more genetic variants associated with poor insulin secretion but lower risk of insulin resistance in the Iraqi than native Swedish group. Interpretation: People with diabetes, born in the Middle East present with a more insulin‐deficient phenotype and genotype than native Swedes. They have a higher risk of coronary events but lower risk of CKD. Ethnic differences should be considered in the preventive work towards diabetes and its complications. [ABSTRACT FROM AUTHOR]

Background: Physical activity (PA) during childhood is important for preventing future metabolic syndrome (MetS). To examine the relationship between PA and MetS in more detail, accurate measures of PA are needed. Previous studies have only utilized a small part of the information available from accelerometer measured PA. This study investigated the association between measured PA and MetS in children with a new method for data processing and analyses that enable more detailed interpretation of PA intensity level. Methods: The association between PA pattern and risk factors related to MetS was investigated in a cross- sectional sample of children (n = 2592, mean age 10.9 years, 49.4% male) participating in the European multicenter I. Family study. The risk factors examined include body mass index, blood pressure, high-density lipoprotein cholesterol, insulin resistance and a combined risk factor score (MetS score). PA was measured by triaxial accelerometers and raw data was processed using the 10 Hz frequency extended method (FEM). The PA output was divided into an intensity spectrum and the association with MetS risk factors was analyzed by partial least squares regression. Results: PA patterns differed between the European countries investigated, with Swedish children being most active and Italian children least active. Moderate intensity physical activity was associated with lower insulin resistance (R2 = 2.8%), while vigorous intensity physical activity was associated with lower body mass index (R2 = 3.6%), MetS score (R2 = 3.1%) and higher high-density lipoprotein cholesterol (R2 = 2.3%). PA of all intensities was associated with lower systolic- and diastolic blood pressure, although the associations were weaker than for the other risk factors (R2 = 1.5% and R2 = 1.4%). However, the multivariate analysis implies that the entire PA pattern must be considered. The main difference in PA was observed between normal weight and overweight children. Conclusions: The present study suggests a greater importance of more PA corresponding to an intensity of at least brisk walking with inclusion of high-intense exercise, rather than a limited time spent sedentary, in the association to metabolic health in children. The methods of data processing and statistical analysis enabled accurate analysis and interpretation of the health benefits of high intensity PA that have not been shown previously. [ABSTRACT FROM AUTHOR]

Context: This study applied the Swedish novel data-driven classification in Chinese newly diagnosed diabetic patients and validated its adoptability.Objective: This study aimed to validate the practicality of the Swedish diabetes regrouping scheme in Chinese adults with newly diagnosed diabetes.Design: Patients were classified into 5 subgroups by K-means and Two-Step methods according to 6 clinical parameters.Setting: Ambulatory care.Patients: A cross-sectional survey of 15 772 patients with adult-onset newly diagnosed diabetes was conducted in China from April 2015 to October 2017.Intervention: None.Main Outcome Measures: Six parameters including glutamate decarboxylase antibodies (GADA), age of onset, body mass index (BMI), glycated hemoglobin A1c (HbA1c), homoeostatic model assessment 2 estimates of β-cell function (HOMA2-B) and insulin resistance (HOMA2-IR) were measured to calculate the patient subgroups.Results: Our patients clustered into 5 subgroups: 6.2% were in the severe autoimmune diabetes (SAID) subgroup, 24.8% were in the severe insulin-deficient diabetes (SIDD) subgroup, 16.6% were in the severe insulin-resistance diabetes (SIRD) subgroup, 21.6% were in the mild obesity-related diabetes (MOD) subgroup and 30.9% were in the mild age-related diabetes (MARD) subgroup. When compared with the Swedish population, the proportion of SIDD subgroup was higher. In general, Chinese patients had younger age, lower BMI, higher HbA1c, lower HOMA2-B and HOMA2-IR, and higher insulin use but lower metformin usage than the Swedish patients.Conclusion: The Swedish diabetes regrouping scheme is applicable to adult-onset diabetes in China, with a high proportion of patients with the severe insulin deficient diabetes. Further validations of long-term diabetes complications remain warranted in future studies. [ABSTRACT FROM AUTHOR]

Aim: The aim of this observational study was to investigate relationships between physiological levels of glucometabolic biomarkers and cognitive test results in a population‐based setting. Methods: Cross‐sectional data were obtained from the Swedish population‐based Malmö Diet and Cancer Study Re‐examination 2007–2012 comprising 3001 older people (mean age 72 years). Through oral glucose tolerance testing (OGTT), fasting and post‐load levels of serum insulin, plasma glucagon, serum glucose‐dependent insulinotropic peptide (GIP) and plasma glucagon‐like peptide‐1 (GLP‐1) were measured. Insulin resistance and insulin sensitivity levels were calculated. In 454 participants, advanced glycation end products (AGEs) were estimated through skin autofluorescence. Associations between biomarkers and two cognitive tests, the Mini‐Mental State Examination (MMSE) and A Quick Test of Cognitive Speed (AQT) respectively, were explored in multiple regression analyses. Results: Positive associations following adjustments for known prognostic factors were found between MMSE scores and insulin sensitivity (B = 0.822, P = 0.004), 2‐h plasma glucagon (B = 0.596, P = 0.026), 2‐h serum GIP (B = 0.581, P = 0.040) and 2‐h plasma GLP‐1 (B = 0.585, P = 0.038), whereas negative associations were found between MMSE scores and insulin resistance (B = −0.734, P = 0.006), fasting plasma GLP‐1 (B = −0.544, P = 0.033) and AGEs (B = −1.459, P = 0.030) were found. Conclusions: Higher levels of insulin sensitivity, GIP and GLP‐1 were associated with better cognitive outcomes, but AGEs were associated with worse outcomes, supporting evidence from preclinical studies. Glucagon was linked to better outcomes, which could possibly reflect neuroprotective properties similar to the related biomarker GLP‐1 which has similar intracellular properties. Longitudinal and interventional studies are needed to further evaluate neuromodulating effects of these biomarkers. Abstract presented at the European Association for the Study of Diabetes (EASD) 2019, Barcelona, Spain What's new?: Preclinical studies suggest that insulin and incretin hormones exert neuroprotective effects in the brain and that advanced glycation end products (AGEs) are linked to Alzheimer's disease. Glucagon has not been studied in relation to cognition, but has similar intracellular properties to the incretin hormone glucagon‐like peptide‐1.This cross‐sectional population‐based study supports previous evidence that insulin and incretin hormones may be neuroprotective and that AGEs may have negative effects on cognition. Furthermore, glucagon was positively associated with cognitive test results, which is a novel finding.These results contribute with new information to the important research field of diabetes‐related cognitive impairment. [ABSTRACT FROM AUTHOR]

Background/Objective: Impaired fasting glycemia (IFG) reflects an intermediate hyperglycemia in the fasting state. Which fasting glucose level that actually is associated with impaired insulin‐glucose homeostasis in children and adolescents with obesity is unknown. The aim of this study was to investigate how insulin and glucose homeostasis in children and adolescents with obesity in Sweden varies within different fasting glucose levels in the non‐diabetic range. Subjects: The subjects, n = 333, were divided into three groups based on their fasting glucose level. Normoglycemic range: up to 5.5 mmol/L (n = 268); the exclusive range the American Diabetes Association (ADA) has for IFG diagnosis: 5.6‐6.0 mmol/L (n = 44); and IFG according to World Health Organization: 6.1‐6.9 mmol/L (n = 21). The three groups were of similar age, degree of obesity, fasting insulin levels, sex, and migrant background distribution. Methods: We used an insulin‐modified frequent sample intravenous glucose tolerance test to study acute insulin response (AIR), insulin sensitivity (SI), and disposition index (DI) in children and adolescents with obesity. The main outcome measures were AIR, SI, and DI in three groups based on fasting glucose level. Results: Fasting glucose levels ranging from 5.6 to 6.0 mmol/L were not associated with a lower AIR, SI, or DI compared with the normoglycemic range. However, glucose levels ranging from 6.1 to 6.9 mmol/L were associated with lower AIR and lower DI, but no statistical differences in SI were present. Conclusions: IFG in the exclusive ADA range was not associated with disturbed glucose metabolism. This suggests that IFG contributes to adverse metabolic profile in children differently to what has been described previously in adult obese populations. [ABSTRACT FROM AUTHOR]

Aim: Metabolic syndrome represents a cluster of risk factors for cardiovascular disease, and we investigated whether otherwise healthy 6-year-olds showed metabolic alterations.Methods: This study followed up a representative Swedish population-based cohort of full-term infants recruited on the maternity ward at Hallands Hospital Halmstad, Sweden, from 2008 to 2011. They were examined at a mean of 6.6 years of age (range 6.5-6.9) using various measures for signs of metabolic syndrome.Results: One key measure showed that 55 (26%) of the 212 children had one or more risk factors for metabolic syndrome requiring action. The 37 who were obese (3%) or overweight (14%) were significantly more likely to be insulin resistant than the normal weight group (28% versus 5%, p < 0.001) and have high triglycerides (8% versus 0%, p < 0.001). Children with high waist circumferences had higher systolic (p = 0.01) and diastolic (p = 0.02) blood pressure than those with normal waist circumferences. Waist circumference identified children at high risk of metabolic syndrome better than body mass index.Conclusion: A significant percentage of 6-year-old children showed abnormal metabolic profiles, including insulin resistance, which increased their risk of cardiovascular disease. Waist circumference was a stronger marker for metabolic alterations than body mass index. [ABSTRACT FROM AUTHOR]

Background: What we eat as infants and children carries long-term consequences. Apart from breastfeeding, the composition of the complementary diet, i.e. the foods given to the infant during the transition from breast milk/infant formula to regular family foods affects the child's future health. A high intake of protein, a low intake of fruits, vegetables and fish and an unfavorable distribution between polyunsaturated and saturated fats are considered to be associate with health risks, e.g. obesity, type 2 diabetes and dyslipidemia later in life.Methods: In a randomized, controlled study from 6 to 18 months of age we will compare the currently recommended, Swedish complementary diet to one based on Nordic foods, i.e. an increased intake of fruits, berries, vegetables, tubers, whole-grain and game, and a lower intake of sweets, dairy, meat and poultry, with lower protein content (30% decrease), a higher intake of vegetable fats and fish and a systematic introduction of fruits and greens. The main outcomes are body composition (fat and fat-free mass measured with deuterium), metabolic and inflammatory biomarkers (associated with the amount of body fat) in blood and urine, gut microbiota (thought to be the link between early diet, metabolism and diseases such as obesity and insulin resistance) and blood pressure. We will also measure the participants' energy and nutrient intake, eating behavior and temperament through validated questionnaires, acceptance of new and unfamiliar foods through video-taped test meals and assessment of cognitive development, which we believe can be influenced through an increased intake of fish and milk fats, notably milk fat globule membranes (MFGM).Discussion: If the results are what we expect, i.e. improved body composition and a less obesogenic, diabetogenic and inflammatory metabolism and gut microbiota composition, a more sustainable nutrient intake for future health and an increased acceptance of healthy foods, they will have a profound impact on the dietary recommendations to infants in Sweden and elsewhere, their eating habits later in life and subsequently their long-term health.Trial Registration: NCT02634749 . Registration date 18 December 2015. [ABSTRACT FROM AUTHOR]

Background: An Okinawa-based Nordic diet with moderately low carbohydrate content and high fat and protein content has been shown to improve anthropometry and metabolism in type 2 diabetes. Objective: The objectives of this study were to measure plasma or serum levels of hormones regulating energy metabolism and metabolic control, that is, cholecystokinin (CCK), Cortisol, C-peptide, ghrelin, glucagon, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin, leptin, plasminogen activator inhibitor-1 (PAI-1), polypeptide YY (PYY), resistin, and visfatin after this diet intervention, and to determine partial correlations between hormonal levels and anthropometric and metabolic responses. Design: A total of 30 patients (17 women) with type 2 diabetes, mean age 57.5 ± 8.2 years, and body mass index (BMI) 29.9 ± 4.1 kg/m2 were served the diet for 12 weeks. Fasting hormones were measured by Luminex and enzyme--linked immunosorbent assay (ELISA) before study start and after 12 and 28 weeks, along with anthropometric and metabolic parameters. Result: The levels of CCK (P = 0.005), cortisol (P = 0.015), C-peptide (P = 0.022), glucagon (P = 0.003), GLP-1 (P = 0.013), GIP (P < 0.001), insulin (P = 0.004), leptin (P < 0.001), and PYY (P < 0.001) were lowered after dietary intervention. These reduced levels only remained for PYY at week 28 (P = 0.002), when also ghrelin (P = 0.012) and visfatin (P = 0.021) levels were reduced. Changes of glucose values correlated with changed levels of C-peptide and PYY (P < 0.001), insulin (P = 0.002), and PAI-1 (P = 0.009); changes of triglyceride values with changed levels of C-peptide, insulin, and PYY (P < 0.001) and PAI-1 (P = 0.005); changes of insulin resistance with changes of leptin levels (P = 0.003); and changes of BMI values with changed levels of C-peptide, insulin, and leptin (P < 0.001). Conclusions: Okinawa-based Nordic diet in type 2 diabetes has significant impact on the endocrine profile, which correlates with anthropometric and metabolic improvements. [ABSTRACT FROM AUTHOR]

Background: The progression of cardiovascular disease (CVD) and atherosclerosis is slow and develops over decades. In the cross-sectional Swedish Lifestyle, Biomarker, and Atherosclerosis study, 834 young, self-reported healthy adults aged 18.0-25.9 years have been studied to identify early risk factors for atherosclerosis.Purpose: The aims of this study were to 1) assess selected cardiometabolic biomarkers, carotid intima-media thickness (cIMT) as a marker of subclinical atherosclerosis, and lifestyle-related indicators (food habits, handgrip strength, and oxygen uptake, VO2 max); 2) analyze the associations between cIMT and lifestyle factors; and 3) identify subjects at risk of CVD using a risk score and to compare the characteristics of subjects with and without risk of CVD.Method: Blood samples were taken in a fasting state, and food habits were reported through a questionnaire. cIMT was measured by ultrasound, and VO2 max was measured by ergometer bike test. The risk score was calculated according to Wildman.Result: cIMT (mean ± standard deviation) was 0.50±0.06 mm, and VO2 max values were 37.8±8.5 and 42.9±9.9 mL/kg/min, in women and men, respectively. No correlation was found between aerobic fitness expressed as VO2 max (mL/kg/min) and cIMT. Using Wildman's definition, 12% of the subjects were classified as being at risk of CVD, and 15% had homeostasis model assessment of insulin resistance. A total of 35% of women and 25% of men had lower high-density lipoprotein cholesterol than recommended. Food habits did not differ between those at risk and those not at risk. However, aerobic fitness measured as VO2 max (mL/kg/min) differed; 47% of the subjects at risk had low aerobic fitness compared to 23% of the nonrisk subjects (P<0.001).Conclusion: High aerobic fitness is associated with low CVD risk in Swedish young adults. The high prevalence of young adults observed with unfavorable levels of high-density lipoprotein cholesterol and homeostasis model assessment of insulin resistance raises concerns about future CVD risk. [ABSTRACT FROM AUTHOR]

Antioxidant vitamins C and E are inversely associated with type 1 diabetes (T1D). We investigated if antioxidants are also associated with latent autoimmune diabetes in adults (LADA), with low (LADA low ) and high (LADA high ) autoantibody levels, type 2 diabetes (T2D), and estimates of beta cell function (HOMA-B) and insulin resistance (HOMA-IR). We used Swedish case-control data with incident cases of LADA ( n = 584) and T2D ( n = 1989) and matched population-based controls ( n = 2276). Odds ratios (OR) and 95% confidence intervals (CI) were calculated per one standard deviation higher beta-carotene, vitamin C, vitamin E, selenium, and zinc intakes. Two-sample Mendelian randomization (MR) analyses assessed causality between genetically predicted circulating antioxidants and LADA, T1D, and T2D, using summary statistics from genome-wide association studies. Among the antioxidants, vitamins C and E were inversely associated with LADA high (OR 0.84, CI 0.73, 0.98 and OR 0.80, CI 0.69, 0.94 respectively), but not with LADA low or T2D. Vitamin E was also associated with higher HOMA-B and lower HOMA-IR. MR analyses estimated an OR of 0.50 (CI 0.20, 1.25) for the effect of vitamin E on T1D, but did not support causal relationships between antioxidants and either LADA or T2D. In conclusion, vitamin E may have a protective effect on autoimmune diabetes, possibly through preserved beta cell function and less insulin resistance.

Objective: Smoking and Swedish smokeless tobacco (snus) are associated with latent autoimmune diabetes in adults (LADA) and type 2 diabetes (T2D). Our aim was to investigate whether genetic susceptibility to T2D, insulin resistance (IR), and insulin secretion (IS) aggravate these associations., Research Design and Methods: We used data from two population-based Scandinavian studies with case subjects with LADA (n = 839) and T2D (n = 5,771), matched control subjects (n = 3,068), and 1,696,503 person-years at risk. Pooled, multivariate relative risks (RR) with 95% CI were estimated for smoking/genetic risk scores (T2D-GRS, IS-GRS, and IR-GRS), and ORs for snus or tobacco/GRS (case-control data). We estimated additive (proportion attributable to interaction [AP]) and multiplicative interaction between tobacco use and GRS., Results: The RR of LADA was elevated in high IR-GRS heavy smokers (≥15 pack-years; RR 2.01 [CI 1.30, 3.10]) and tobacco users (≥15 box/pack-years; RR 2.59 [CI 1.54, 4.35]) compared with low IR-GRS individuals without heavy use, with evidence of additive (AP 0.67 [CI 0.46, 0.89]; AP 0.52 [CI 0.21, 0.83]) and multiplicative (P = 0.003; P = 0.034) interaction. In heavy users, there was additive interaction between T2D-GRS and smoking, snus, and total tobacco use. The excess risk conferred by tobacco use did not differ across GRS categories in T2D., Conclusions: Tobacco use may confer a higher risk of LADA in individuals with genetic susceptibility to T2D and insulin resistance, whereas genetic susceptibility does not seem to influence the increased T2D incidence associated with tobacco use., (© 2023 by the American Diabetes Association.)

Purpose: To study prevalence of diabetic retinopathy (DR) at diagnosis (DRAD) and to estimate contributing risk by sociodemographic, cardiovascular and metabolic characteristics present in patients recently diagnosed with type 2 diabetes (T2D) or latent autoimmune diabetes in the adult (LADA).Methods: Patients (n=2174) recently diagnosed T2D (93%) or LADA (7%) were included upon arrival for their baseline DR screening. Fundus photographs of 4902 eyes were graded by a senior ophthalmologist according to the International Diabetic Retinopathy Disease Severity Scale. Official registers held by Statistics Sweden provided sociodemographic variables. The National Patient Register and Swedish Prescribed Drug Register were used to assess cardiovascular risk. Beta cell function (HOMA2%b) and insulin sensitivity (HOMA2%s) were estimated from fasting (f) C-Peptide using the homeostasis model assessment (HOMA) 2 calculator. Odds ratios (OR) for DRAD were estimated using generalized estimating equation models.Results: The prevalence of DRAD was 12% (7% mild and 5% moderate) and of diabetic macular edema it was 11% (all within vascular arch). The prevalence did not significantly differ between T2D and LADA. Due to sample size, the regression analysis of LADA patients did not yield any significant estimates. In T2D low educational level (≤9years) increased risk for DRAD by 44% (OR 1.44; 95% CI 1.07-1.93) and <50% beta-cell function adjusted for HbA1c and insulin sensitivity at diagnosis increased the risk by 77% (OR 1.77; 95% CI 1.28-2.44). For every unit increase in BMI, risk for DRAD decreased by 3% (OR 0.97; 95% CI 0.95-0.99).Conclusions: DRAD prevalence in patients recently diagnosed with T2D or is 12%. Low educational level and low beta cell function at diagnosis are risk factors for DRAD. Estimation of beta cell function from (f)C-Peptide and (f)P-Glucose may be a valuable tool in identifying patients at risk for DRAD. [ABSTRACT FROM AUTHOR]

Purpose: Specific combinations of dietary fiber (DF) have been observed to result in improved glucose tolerance at a subsequent standardized breakfast. Arabinoxylan oligosaccharides (AXOS) are considered as DF with prebiotic potential, but so far no studies have investigated their metabolic effects in humans. This randomized cross-over study evaluated the overnight impact of breads containing AXOS-rich wheat bran extract and resistant starch (RS, Hi-Maize), separately or combined, on glucose tolerance, related metabolic parameters and markers of gut fermentation in healthy subjects. Methods: Evening reference and test products were: (1) reference white wheat flour bread (WWB), WWB supplemented with (2) AXOS and RS (WWB + AXOS + RS), (3) an increased content of either AXOS (WWB + hiAXOS) or (4) RS (WWB + hiRS). At the subsequent standardized breakfast, blood was sampled for 3 h to monitor glucose, insulin, nonesterified fatty acids, glucagon-like peptide (GLP)-1 and GLP-2. Breath hydrogen (H) and short chain fatty acids (SCFA) were measured as markers of gut fermentation, and subjective appetite was rated using visual analog scales. Results: Dose-dependent decreases in glucose responses were observed with increased AXOS over the duration of 3 h. Insulin sensitivity index was improved in the morning after the WWB + hiAXOS evening meal. An increase in breath H concentration and circulating SCFA was observed in the morning after both evening meals containing AXOS. Conclusion: The present study indicates that AXOS have the potential of improving glucose tolerance in an overnight perspective and suggested mechanisms are improved insulin sensitivity and increased gut fermentation. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the potential short-term benefits associated with reductions in HbA1c levels, and understanding any immediate improvements in health related quality-of-life (HRQoL) through better glycaemic control may help inform diabetes management decisions. This time-trade-off (TTO) study investigated the short-term impact on HRQoL associated with three different aspects of diabetes management; HbA1c change, body weight change, and the complexity of treatment regimen.Methods: The study was designed in three stages: Stage 1) Qualitative telephone interviews with people with type 2 diabetes (T2D) in Denmark who had experienced a decrease in their HbA1c level. Stage 2) A validation survey with people with T2D in Denmark to obtain quantifiable knowledge on the short-term effects of a change in HbA1c levels. Stage 3) TTO survey using health states based on results from stage 2. Respondents were either adults with T2D (Sweden) or from the general public (UK and Denmark) and were separately asked to evaluate seven health states through an internet-based survey.Results: Results from 4060 respondents were available for the TTO analysis (UK n = 1777; Denmark n = 1799, Sweden n = 484). 'Well-controlled diabetes' was associated with utilities of 0.85-0.91 and 'not well-controlled diabetes' with utilities of 0.71-0.80 in all countries. Difference in utilities per HbA1c percentage point was smallest in Sweden and largest in Denmark (between 0.025-0.034 per HbA1c percentage point respectively). The treatment management health state associated with the lowest disutility was the once-daily insulin regimen. The disutility associated with per kg of weight change ranged from 0.0041-0.0073.Conclusions: Changes in HbA1c levels, insulin regimen and body weight are all likely to affect HRQoL for patients with T2D. A change in HbA1c is likely to have a short-term impact in addition to the effect on the development of long term diabetes complications. A treatment which has a simple regimen with fewer injections, and/or the need for less planning, and that causes weight loss or less weight gain, compared with other treatments, will have a positive impact on HRQoL. [ABSTRACT FROM AUTHOR]

Objective: Eligibility criteria for bariatric surgery in diabetes include BMI ≥35 kg/m(2) and poorly controlled glycemia. However, BMI does not predict diabetes remission, and thus, predictors need to be identified.Research Design and Methods: Seven hundred twenty-seven patients were included in a database merged from the Swedish Obese Subjects (SOS) study and two randomized controlled studies, with 415 surgical and 312 medical patients in total. Bariatric operations were divided into gastric only (GO) and gastric plus diversion (GD).Results: Sixty-four percent of patients in the surgical arm and 15.0% in the medical arm experienced diabetes remission (P < 0.001). GO yielded 60% remission, and GD yielded 76% remission. The best predictors of diabetes remission were lower baseline glycemia and shorter diabetes duration. However, when operation type was considered, GD predicted a higher likelihood of remission and greater weight loss. Patients in remission (responders) lost more weight (25% vs. 17%) and waist circumference (18% vs. 13%) and experienced better insulin sensitivity than nonresponders.Conclusions: Surgery is more effective than medical treatment in achieving diabetes remission and tighter glycemic control. Shorter diabetes duration, lower fasting glycemia before surgery, and GD versus GO procedures independently predict higher rates of remission, whereas baseline HbA1c and waist circumference predict improved glycemic control. The results show the advantage of an early operation together with better controlled glycemia on diabetes remission independently of BMI. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is a precursor of type 2 diabetes (T2D), and improved risk prediction and understanding of the pathogenesis are needed. We used a novel high-throughput 92-protein assay to identify circulating biomarkers for HOMA of IR in two cohorts of community residents without diabetes (n = 1,367) (mean age 73 ± 3.6 years). Adjusted linear regression identified cathepsin D and confirmed six proteins (leptin, renin, interleukin-1 receptor antagonist [IL-1ra], hepatocyte growth factor, fatty acid-binding protein 4, and tissue plasminogen activator [t-PA]) as IR biomarkers. Mendelian randomization analysis indicated a positive causal effect of IR on t-PA concentrations. Two biomarkers, IL-1ra (hazard ratio [HR] 1.28, 95% CI 1.03-1.59) and t-PA (HR 1.30, 1.02-1.65) were associated with incident T2D, and t-PA predicted 5-year transition to hyperglycemia (odds ratio 1.30, 95% CI 1.02-1.65). Additional adjustment for fasting glucose rendered both coefficients insignificant and revealed an association between renin and T2D (HR 0.79, 0.62-0.99). LASSO regression suggested a risk model including IL-1ra, t-PA, and the Framingham Offspring Study T2D score, but prediction improvement was nonsignificant (difference in C-index 0.02, 95% CI -0.08 to 0.12) over the T2D score only. In conclusion, proteomic blood profiling indicated cathepsin D as a new IR biomarker and suggested a causal effect of IR on t-PA. [ABSTRACT FROM AUTHOR]

Objective: Study of prevalence of gout with concomitant diseases.Methods: Study population included all living persons in Stockholm County, Sweden, on January 1st 2013 (N=2,124,959). A diagnosis of gout was identified during 2013-2014, with information of diabetes mellitus and insulin resistance, hypertension, chronic heart failure, chronic kidney disease, alcohol abuse, and malignancies. Age-adjusted odds ratios (ORs) with 95% confidence intervals (95% CI) for women and men with gout, using individuals without gout as referents, were calculated.Results: Age-adjusted odds of co-morbidities among individuals with gout vs. those without gout were: diabetes mellitus and insulin resistance 3.97 (95% CI 3.65-4.31) in women and 1.88 (95% CI 1.78-1.99) in men; hypertension 4.02 (95% CI 3.69-4.37) in women and 3.21 (95% CI 3.06-3.37) in men; chronic heart failure 4.72 (95% CI 4.31-5.19) in women and 2.84 (95% CI 2.66-3.04) in men; chronic kidney disease 2.08 (95% CI 1.50-2.87) in women and 2.39 (95% CI 2.15-2.66) in men; alcohol abuse 8.98 (95% CI 8.15-9.80) in women and 4.38 (95% CI 4.10-4.69) in men; and malignancies 1.32 (95% CI 1.17-1.48) in women and 1.13 (95% CI 1.06-1.21) men.Conclusion: Gout is a warning sign for concomitant diseases, e.g. alcoholism, diabetes, cardiovascular diseases, and cancer. KEY MESSAGES. [ABSTRACT FROM AUTHOR]

Aim: The predictive effect of various insulin resistance indexes for risk of cardiovascular diseases (CVD) or type 2 diabetes (T2DM) is still unclear.Methods: One thousand and forty-nine 71-years-old male subjects from the Swedish ULSAM study, mean follow-up 9 years. All subjects performed the euglycemic insulin clamp for M/I [glucose disposal/mean insulin], and 75-g oral glucose tolerance test for Ceder-IR: 1/glucose uptake rate/[mean glucose×log mean insulin]; Matsuda-IR: 1/10,000/square root [glucose0×insulin0×glucose120×insulin120]; Belfiore-IR: 1/([glucose0+glucose120]/normal mean glucose×[insulin0+insulin120]/normal mean insulin)+1); and HOMA-IR: [glucose0×insulin0]/22.5.Results: Bland-Altman plots showed best agreement between M/I versus Belfiore-IR and Ceder-IR with mean difference near zero, -0.21 to -0.46, while -0.68 to -0.77 for the other indexes. ISI-Ceder was the strongest predictor for incident nonfatal/fatal ischemic heart disease (CHD) or CVD at Cox regression in all subjects, and for incident T2DM at logistic regression in 1024 subjects with no baseline T2DM, with significantly higher hazard ratios or odds ratios than with all other indexes, also with best model fit, after adjusting for clinical characteristics and the traditional cardiovascular risk factors, including metabolic syndrome for CVD risk.Conclusion: Ceder-IR performed strongest as independent predictor for incidences of CHD/CVD and T2DM. [ABSTRACT FROM AUTHOR]

Aims: Non-alcohol fatty liver disease (NAFLD) is a strong risk factor for insulin resistance and type 2 diabetes. The prevalence of NAFLD varies across populations of different ethnic backgrounds but the prevalence in Middle Eastern populations, which are at high risk of type 2 diabetes, is largely unknown. Using fatty liver index (FLI) as a proxy for NAFLD the aim was to calculate the odds of NAFLD (FLI≥70) given country of origin and further to investigate the associations between ISI and FLI.Methods: In 2010-2012 we conducted a population-based study of individuals aged 30-75 years born in Iraq or Sweden, in whom anthropometrics, fasting blood samples and oral glucose tolerance tests were performed and sociodemography and lifestyle behaviors characterized.Results: A higher proportion of Iraqis (N=1085) than Swedes (N=605) had a high probability of NAFLD (FLI≥70, 32.5 vs. 22.6%, p<0.001, age- and sex-adjusted data) and ISI was more severely impaired (70.7 vs. 95.9%, p<0.001). Independently of traditional risk factors for NAFLD, being born in Iraqi increased the risk of FLI≥70 (OR 1.59: 95% CI 1.15, 2.20). Furthermore, country of birth presented a stronger association between ISI and FLI≥70 in Iraqis than in Swedes (P(interaction)=0.019).Conclusions: Our data indicate that immigrants from Iraq are at higher risk of NAFLD. The finding that country of birth modifies the relationship of FLI with ISI, suggests that liver fat may be a stronger determinant of impaired insulin action and increased risk of type 2 diabetes in Iraqis than in Swedes. [ABSTRACT FROM AUTHOR]

Objective In this cohort of severely obese children and adolescents in Sweden we investigate the prevalence of impaired fasting glucose ( IFG), impaired glucose tolerance, ( IGT) and silent type 2 diabetes ( T2D), in relation to insulin resistance, insulin secretion, disposition index and cardio respiratory fitness. Methods A total of 134 obese children and adolescents [57 females, 77 males, age 13.7 ± 2.7, body mass index ( BMI) standard deviation score ( SDS) 3.6 ± 0.6] consecutively referred to the National Childhood Obesity Centre performed an oral glucose tolerance test ( OGTT), frequently sampled intravenous glucose tolerance test (fs- IVGTT), dual X-ray absorptiometry ( DEXA), bicycle ergometer test and fasting levels of glucose, insulin and c-peptide were obtained and homeostatic model of insulin resistance (HOMA-IR) was calculated. Results Isolated impaired fasting glucose (i-IFG) were present in 35.8 and 6% had isolated IGT. Combined IGT and IFG were present in 14.2%. The subjects with combined IGT/ IFG had significantly lower acute insulin response (AIR) compared with subjects who had normal glucose metabolism or i- IFG (p < 0.05). Among the prepubertal children (n = 24), 25% (6/24) had i- IFG and 25% (6/24) had IGT/ IFG and it was predominantly males. Disposition index was the major determinant of 2-h glucose levels (β = −0.49, p = 0.0126). No silent diabetes was detected. Conclusion In this cohort of severely obese children and adolescents the prevalence of prediabetes was very high. IFG was two times higher in this cohort of severely obese children than in a recently published unselected cohort of obese children in Sweden. In spite of the high prevalence of prediabetes, no subjects with silent diabetes were found. [ABSTRACT FROM AUTHOR]

Middle Eastern immigrants are at high-risk for insulin resistance. Fatty acid composition (FAC) plays an important role in the development of insulin resistance but has not been investigated in people of Middle Eastern ancestry. Here, the aim was to assess the FAC in visceral and subcutaneous adipose tissue (VAT and SAT) in healthy Iraqi- and Swedish-born men using a magnetic resonance imaging (MRI) method.This case-control study included 23 Iraqi- and 15 Swedish-born middle-aged men, without cardiometabolic disease. Using multi-echo MRI of the abdomen, the fractions of saturated, monounsaturated, and polyunsaturated fatty acids (fSFA, fMUFA, and fPUFA) were estimated in VAT and SAT. SAT was further analyzed in deep and superficial compartments (dSAT and sSAT).In all depots, fPUFA was significantly higher and fSFA significantly lower in Iraqi men, independently of age and BMI. In both Iraqi- and Swedish-born men, higher fPUFA and lower fMUFA were found in sSAT vs. dSAT. Among Iraqi men only, higher fPUFA and lower fMUFA were found in SAT vs. VAT.Iraqi-born men presented a more favorable abdominal FAC compared to Swedish-born men. This MRI method also revealed different FACs in different abdominal depots. Our results may reflect a beneficial FAC in Middle Eastern immigrants.

Aims Assessing the association between BMI and risk of coronary heart disease (CHD), cardiovascular disease (CVD) and mortality in patients with type 2 diabetes, also with regard to higher or lower levels of the ratio triglycerides-to-HDL-cholesterol (TG:HDL). Methods 54,061 patients with BMI ≥ 18.5 kg/m 2 , mean age and duration 61.5 ± 8 and 6.9 ± 6 years, 59% males, 14% with CVD history, from the Swedish National Diabetes Register, followed for mean 4.8 years. Results Adjusting at Cox regression for non-BMI-linked (age, sex, smoking, CVD history) and BMI-linked (blood lipids, blood pressure, HbA1c, albuminuria) covariates, hazard ratios (HR) for fatal/nonfatal CHD and CVD were mainly increased with prominent obesity (BMI ≥ 35 kg/m 2 ), 1.19 ( p = 0.01) and 1.17 ( p = 0.009), compared to normal weight (BMI 18.5–24.9 kg/m 2 ), although increased also with obesity (BMI 30–34.9 kg/m 2 ), 1.34 and 1.30 ( p < 0.001), when adjusting only for non-BMI-linked covariates. Stratifying by 75th percentile of TG:HDL, with normal weight and TG:HDL < 1.9 as reference, obese and prominently obese with TG:HDL ≥ 1.9 had considerably increased HR around 1.7 for fatal/nonfatal CHD and 1.6 for CVD ( p < 0.001), while obese and prominently obese with TG:HDL < 1.9 only had HR 1.2–1.3 for CHD and CVD ( p 0.003–<0.01). Conclusion Obese T2D patients with high TG:HDL, associated with increased insulin resistance, had considerably increased risk of CHD and CVD. [ABSTRACT FROM AUTHOR]

Background: Nitrate, which is an inorganic anion abundant in vegetables, increases the efficiency of isolated human mitochondria. Such an effect might be reflected in changes in the resting metabolic rate (RMR) and formation of reactive oxygen species. The bioactivation of nitrate involves its active accumulation in saliva followed by a sequential reduction to nitrite, nitric oxide, and other reactive nitrogen species. Objective: We studied effects of inorganic nitrate, in amounts that represented a diet rich in vegetables, on the RMR in healthy volunteers. Design: In a randomized, double-blind, crossover study, we measured the RMR by using indirect calorimetry in 13 healthy volunteers after a 3-d dietary intervention with sodium nitrate (NaNO3) or a placebo (NaCl). The nitrate dose (0.1 mmol ⋅ kg-1 ⋅ d-1) corresponded to the amount in 200-300 g spinach, beetroot, lettuce, or other vegetable that was rich in nitrate. Effects of direct nitrite exposure on cell respiration were studied in cultured human primary myotubes. Results: The RMR was 4.2% lower after nitrate compared with placebo administration, and the change correlated strongly to the degree of nitrate accumulation in saliva (r² = 0.71). The thyroid hormone status, insulin sensitivity, glucose uptake, plasma concentration of isoprostanes, and total antioxidant capacity were unaffected by nitrate. The administration of nitrite to human primary myotubes acutely inhibited respiration. Conclusions: Dietary inorganic nitrate reduces the RMR. This effect may have implications for the regulation of metabolic function in health and disease. [ABSTRACT FROM AUTHOR]

Background. Hypercortisolism and type 2 diabetes (T2D) share clinical characteristics. We examined pioglitazone's effects on the GH-IGF-I and HPA axes in men with varying glucose intolerance. Methods. 10 men with T2D and 10 with IGT received pioglitazone 30-45 mg for 12 weeks. OGTT with microdialysis in subcutaneous adipose tissue and 1 µg ACTH-stimulation test were performed before and after. Glucose, insulin, IGF-I, IGFBP1, and interstitial measurements were analyzed during the OGTT. Insulin sensitivity was estimated using HOMA-IR. Results. HOMA-IR improved in both groups. IGF-I was initially lower in T2D subjects (P=0.004) and increased during treatment (-1.4 ± 0.5 to -0.5 ± 0.4 SD; P=0.007); no change was seen in IGT (0.4 ± 39 SD before and during treatment). Fasting glycerol decreased in T2D (P=0.004), indicating reduced lipolysis. Fasting cortisol decreased in T2D (400 ± 30 to 312 ± 25 nmol/L; P=0.041) but increased in IGT (402 ± 21 to 461 ± 35 nmol/L; P=0.044). Peak cortisol was lower in T2D during treatment (599 ± 32 to 511 ± 43, versus 643 ± 0.3 to 713 ± 37 nmol/L in IGT; P=0.007). Conclusions. Pioglitazone improved adipose tissue and liver insulin sensitivity in both groups. ?is may explain increased IGF-I in T2D. Pioglitazone affected cortisol levels in both groups but differently, suggesting different mechanisms for improving insulin sensitivity between T2D and IGT. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance negatively affects the outcome of surgery in patients with type 2 diabetes. This association is often believed to be present in other patient populations as well, but studies are lacking on the influence of preoperative insulin resistance on the clinical course of surgery in non-diabetic patients. Methods: Sixty non-diabetic patients with a mean age of 68 years underwent a 75-min intravenous glucose tolerance test (IVGTT) one day before and after elective hip replacement surgery. Patients were regarded to be either insulin resistant (< median insulin sensitivity) or not (> median insulin sensitivity). Hypotensive events occurring in the postoperative care unit and complications in the orthopedic ward were recorded. Fatigue and well-being were assessed via questionnaires. Results: A total of 52 patients were included in the final analysis. Insulin resistance before surgery was associated with a lower risk of arterial hypotension in the postoperative care unit (systolic pressure < 80 mmHg; P < 0.05) and with fewer complications in the orthopedic ward (mean 1.9 versus 1.2 per operation, P < 0.01), particularly with respect to nausea/vomiting (P < 0.04) and arterial hypotension (P < 0.05). Fewer of these patients had more than one complication (23% versus 58%, P < 0.001), while no statistical link between preoperative insulin resistance and fatigue or well-being was evident. Insulin resistance, when measured one day postoperatively, did not correlate with the number of complications. Conclusions: Preoperative insulin resistance offers some benefit in the postoperative period and early convalescence in non-diabetic patients who undergo hip replacement surgery. [ABSTRACT FROM AUTHOR]

Background/aim: Obesity is characterized by a low-grade inflammation in white adipose tissue (WAT), which promotes insulin resistance. Low serum levels of 1α,25-dihydroxycholecalciferol (DHCC) associate with insulin resistance and higher body mass index although it is unclear whether vitamin D supplementation improves insulin sensitivity. We investigated the effects of DHCC on adipokine gene expression and secretion in adipocytes focusing on two key factors with pro-inflammatory [monocyte chemoattractant protein-1 (MCP-1/ CCL2)] and anti-inflammatory [adiponectin ( ADIPOQ)] effects. Methods: Pre-adipocytes were isolated from human subcutaneous WAT and cultured until full differentiation. Differentiated adipocytes were either pre-treated with DHCC (10 M) and subsequently incubated with tumor necrosis factor-α (TNFα, 100 ng/mL) or concomitantly incubated with TNFα/DHCC. MCP1 and adiponectin mRNA expression was measured by RT-PCR and protein release by ELISA. Results: DHCC was not toxic and did not affect adipocyte morphology or the mRNA levels of adipocyte-specific genes. TNFα induced a significant increase in CCL2 mRNA and protein secretion, while DHCC alone reduced CCL2 mRNA expression (~25%, p < 0.05). DHCC attenuated TNFα-induced CCL2 mRNA expression in both pre-incubation (~15%, p < 0.05) and concomitant (~60%, p < 0.01) treatments. TNFα reduced ADIPOQ mRNA (~80%) and secretion (~35%). DHCC alone decreased adiponectin secretion to a similar degree (~35%, p < 0.05). Concomitant treatment with DHCC/TNFα for 48 h had an additive effect, resulting in a pronounced reduction in adiponectin secretion (~70%). Conclusions: DHCC attenuates MCP-1 and adiponectin production in human adipocytes, thereby reducing the expression of both pro- and anti-inflammatory factors. These effects may explain the difficulties so far in determining the role of DHCC in insulin sensitivity and obesity in humans. [ABSTRACT FROM AUTHOR]

Abstract: The objective was to study obesity and insulin resistance in relation to leisure time physical activity (LTPA) and occupational physical activity (OPA) in a Swedish population, with particular focus on sex differences. Using a cross-sectional design, waist circumference, body mass index (BMI), glucose/insulin metabolism, blood pressure, heart rate, self-reported education, smoking, alcohol consumption, LTPA, and OPA were assessed in 1745 men and women (30-74 years) randomly chosen from 2 municipalities in southwestern Sweden. In both men and women, LTPA was inversely associated with BMI, waist circumference, and the homeostasis model assessment of insulin resistance (HOMA-IR), respectively. These associations remained statistically significant after adjustments for age, OPA, education, alcohol consumption, smoking, and study area, and also for BMI in the analyses concerning waist circumference and HOMA-IR. A statistically significant interaction term (P = .030), adjusted for multiple confounders, revealed a stronger association between LTPA and HOMA-IR in women compared with men. Occupational physical activity was positively associated with BMI (P < .001), waist circumference (P < .001), and HOMA-IR (P = .001), however, only in women. These associations remained when adjusting for multiple confounders. The sex differences were confirmed by statistically significant interaction terms between sex and OPA in association with BMI, waist circumference, and HOMA-IR, respectively. The observed sex differences regarding the strength of the association between LTPA and insulin resistance, and the positive association between OPA and obesity and insulin resistance found solely in women, warrant further investigation. Although exploration of the metabolic effects of OPA appears to be needed, thorough measurement of potential confounders is also vital to understand contextual effects. [Copyright &y& Elsevier]

Objective:To examine the associations of insulin resistance at childhood with adiposity changes over a 6-year period (from 9 to 15 years) in a sample of 659 Swedish and Estonian children (52.7% girls) participating in the European Youth Heart Study.Research, Design and Methods:We measured weight, height, waist circumference, biceps, triceps, subscapular, suprailiac, and medial calf skinfolds, and we calculated body mass index (BMI), sum of five skinfolds, and body fat percentage. Fasting plasma glucose and insulin were measured and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Changes in puberty stage, sex, centre and the corresponding baseline adiposity values were used as confounders in all analysis.Results:HOMA-IR at childhood was significantly and positively associated with changes in BMI (β=0.265; P=0.024), sum of five skinfolds (β=0.3445; P=0.003), body fat percentage (β=1.042; P=0.016) and waist circumference (β=0.806; P=0.002) from childhood to adolescence. These relationships persisted when overweight children were excluded from the analysis. BMI, sum of five skinfolds, body fat percentage and waist circumference at childhood were not significantly associated with changes in HOMA-IR (P for all >0.1).Conclusions:These results give further support to the concept that lower insulin sensitivity at childhood may predict subsequent total and central adiposity gain at adolescence. These findings enhance the role of insulin sensitivity as a target of obesity prevention already from the first decades of life. [ABSTRACT FROM AUTHOR]

Adamsson V, Reumark A, Fredriksson I-B, Hammarström E, Vessby B, Johansson G, Risérus U (Uppsala University, Uppsala; Lantmännen R&D, Stockholm; Bollnäs Heart Clinic, Mitt Hjärta, Bollnäs; Halmstad University, Halmstad, Sweden). Effects of a healthy Nordic diet on cardiovascular risk factors in hypercholesterolaemic subjects: a randomized controlled trial (NORDIET). J Intern Med 2011; : 150-159. The aim of this study was to investigate the effects of a healthy Nordic diet (ND) on cardiovascular risk factors. In a randomized controlled trial (NORDIET) conducted in Sweden, 88 mildly hypercholesterolaemic subjects were randomly assigned to an ad libitum ND or control diet (subjects' usual Western diet) for 6 weeks. Participants in the ND group were provided with all meals and foods. Primary outcome measurements were low-density lipoprotein (LDL) cholesterol, and secondary outcomes were blood pressure (BP) and insulin sensitivity (fasting insulin and homeostatic model assessment-insulin resistance). The ND was rich in high-fibre plant foods, fruits, berries, vegetables, whole grains, rapeseed oil, nuts, fish and low-fat milk products, but low in salt, added sugars and saturated fats. The ND contained 27%, 52%, 19% and 2% of energy from fat, carbohydrate, protein and alcohol, respectively. In total, 86 of 88 subjects randomly assigned to diet completed the study. Compared with controls, there was a decrease in plasma cholesterol (−16%, P < 0.001), LDL cholesterol (−21%, P < 0.001), high-density lipoprotein (HDL) cholesterol (−5%, P < 0.01), LDL/HDL (−14%, P < 0.01) and apolipoprotein (apo)B/apoA1 (−1%, P < 0.05) in the ND group. The ND reduced insulin (−9%, P = 0.01) and systolic BP by −6.6 ± 13.2 mmHg (−5%, P < 0.05) compared with the control diet. Despite the ad libitum nature of the ND, body weight decreased after 6 weeks in the ND compared with the control group (−4%, P < 0.001). After adjustment for weight change, the significant differences between groups remained for blood lipids, but not for insulin sensitivity or BP. There were no significant differences in diastolic BP or triglyceride or glucose concentrations. A healthy ND improves blood lipid profile and insulin sensitivity and lowers blood pressure at clinically relevant levels in hypercholesterolaemic subjects. [ABSTRACT FROM AUTHOR]

The article explores the correlation among fatty acid intake, body weight, diabetes and metabolic syndrome based on various international studies from 1993 to 2009. Five randomized studies and two meta-analyses showed that low-fat diet, physical activity and weight loss reduce the cases of diabetes by 50%. Researcher B. Krachler and colleagues found that decrease in saturated fatty acid (SFA) intakes do not reduce the obesity rates in Sweden. Other studies found that substituting SFA with n-6 polyunsaturated fatty acids (PUFA) reduce insulin sensitivity.

The article presents the results of a study on the link between meal regularity with metabolic syndrome and insulin resistance in 60-year old men and women in Stockholm, Sweden. It was associated with higher y-glutamyl transferase concentrations. It was also an independent predictor of waist circumference, trigylcerides, y-glutamyl transferase, homeostatic model assessment-2 (HOMA-) index and a borderline for high-density lipoprotein (HDL)-cholesterol in serum. For insulin resistants, it was found to be a predictor of metabolic syndrome.

Background:Insulin resistance and diabetes mellitus have been reported in the spinal cord injured (SCI). The group exhibits risk factors, as decreased physical activity, as well as episodes of stimulation of sympathetic nervous system below the level of lesion known to stimulate lipolysis, which in turn could induce insulin resistance. However, data are inconsistent, which might indicate the presence of protective mechanisms.Objective:To investigate the glucose uptake in spastic paralysed SCI legs compared to able-bodied. To investigate regional differences between glucose handling in the arm and leg.Study design:Experimental controlled study.Settings:Institution of Clinical Neuroscience and Physiology, Spinal Injures Unit, Sahlgrens University Hospital, Goteborg, Sweden.Methods:Nine SCI subjects (2 C7, 7 T1–T4 ASIA A: 8, ASIA B: 1) were compared to 10 weight- and age-matched controls. Plasma flow in arm and leg was analysed by venous occlusion strain gauge plethysmography, and plasma derived from artery and veins in the arm and leg was analysed for glucose, insulin and lactate during fasting resting conditions.Results:Glucose uptake was higher in SCI legs compared to controls. There was no difference in insulin uptake or lactate production. Plasma flow was higher in SCI legs compared to controls. Controls showed a higher glucose uptake and lactate production in arm than leg.Conclusions:Spasticity may counteract the risk of diabetes by inducing an insulin-independent glucose uptake. The regional difference in metabolism in able-bodied make it hazardous to do generalizations to whole body metabolism from arm or leg measurements.Spinal Cord (2008) 46, 103–106; doi:10.1038/sj.sc.3102083; published online 19 June 2007 [ABSTRACT FROM AUTHOR]

Objective. To explore the association between abdominal obesity and insulin resistance in patients with type 2 diabetes. Design. A cross-sectional observational study. Setting. Primary care in Skara, Sweden. Subjects. A total of 198 men and 186 women with type 2 diabetes who consecutively completed an annual check-up in 1992–1993. Main outcome measures. Abdominal obesity was defined according to criteria for the metabolic syndrome using the waist circumference (WC): >102 cm for men and >88 cm for women. Insulin resistance was estimated using the Homeostasis Model Assessment (HOMA), and was dichotomized by the 75th percentile (IR). Results. Abdominal obesity was found in 66 men (33%), and in 106 women (57%). Pearson's correlation coefficients between components of the metabolic syndrome and IR were statistically significant for WC, waist–hip ratio, serum triglycerides, and HDL cholesterol, and were higher for WC (0.40) than for waist–hip ratio (0.23) in both genders (p < 0.001). The association between WC and IR was challenged by successively entering other components of the metabolic syndrome into the model in a logistic regression. In the final model, adjusting for differences in age, systolic blood pressure, HbA1c, serum triglycerides, HDL cholesterol, and microalbuminuria, the association remained statistically significant both in men (OR 8.6, 95% CI 3.0–25.2, p < 0.001), and in women (OR 5.6, 95% CI 1.7–18.1, p&VeryThinSpace;=&VeryThinSpace;0.004). Conclusions. WC provides a feasible measure for insulin resistance in the vast majority of subjects with type 2 diabetes. It is convenient and less expensive than direct means and could be used as a proxy for insulin resistance in population studies. [ABSTRACT FROM AUTHOR]

Objective:To study the possibility of improving blood lipids, glucose tolerance and insulin sensitivity in women with impaired glucose tolerance and a history of gestational diabetes by merely changing the glycaemic index (GI) and dietary fibre (DF) content of their bread.Design:Randomized crossover study where test subjects were given either low GI/high DF or high GI/low DF bread products during two consecutive 3-week periods, separated by a 3-week washout period. An intravenous glucose tolerance test followed by a euglycaemic–hyperinsulinaemic clamp was performed on days 1 and 21 in both the high- and low-GI periods, to assess insulin secretion and insulin sensitivity. Blood samples were also collected on days 1 and 21 for analysis of fasting levels of glucose, insulin, HDL-cholesterol and triacylglycerols (TG).Setting:Lund University, Sweden.Subjects:Seven women with impaired glucose tolerance.Results:The study shows that a modest dietary modification, confined to a lowering of the GI character and increasing cereal DF of the bread products, improved insulin economy as judged from the fact that all women lowered their insulin responses to the intravenous glucose challenge on average by 35% (0–60 min), in the absence of effect on glycaemia. No changes were found in fasting levels of glucose, insulin, HDL-cholesterol or TG.Conclusion:It is concluded that a combination of low GI and a high content of cereal DF has a beneficial effect on insulin economy in women at risk of developing type II diabetes. This is in accordance with epidemiological data, suggesting that a low dietary GI and/or increased intake of whole grain prevent against development of type II diabetes.Sponsorship:Supported by grants from Cerealia Research Foundation.European Journal of Clinical Nutrition (2006) 60, 334–341. doi:10.1038/sj.ejcn.1602319; published online 19 October 2005 [ABSTRACT FROM AUTHOR]

OBJECTIVE:Obesity is frequently associated with insulin resistance, dyslipidemia, hypertension and an increased risk of cardiovascular disease, reflected in elevated markers of inflammation, in particular C-reactive protein (CRP). To what extent the insulin resistance or the obesity per se contributes to increased CRP levels is unclear. In morbidly obese patients, gastric bypass surgery causes marked changes in body weight and improves metabolism, thereby providing informative material for studies on the regulation of inflammatory markers.DESIGN:Prospective, surgical intervention study of inflammatory markers in morbidly obese subjects.SUBJECTS:In total, 66 obese subjects with mean age 39 y and mean body mass index (BMI) 45 kg/m2 were studied prior to and 6 and 12 months following Roux-en-Y gastric bypass (RYGBP) surgery.MEASUREMENTS:Serum concentrations of high sensitivity CRP, serum amyloid A (SAA) and interleukin-6 (IL-6), as well as markers of glucose and lipid metabolism.RESULTS:Prior to surgery, CRP levels were elevated compared to the reference range of healthy, normal-weight subjects. CRP correlated with insulin sensitivity, as reflected by the homeostatic model assessment (HOMA) index, but not BMI, when corrected for age and gender. Surgery reduced BMI from 45 to 31 kg/m2 and lowered CRP, SAA and IL-6 levels by 82, 57 and 50%, respectively, at 12 months. The reduction in CRP was inversely related to HOMA at baseline independently of the change in body weight (r=−0.36, P=0.005). At 12 months, 140 and 40% reductions in CRP were seen in subjects with HOMA < 4 (insulin sensitive) and HOMA>9 (insulin resistant) despite similar reductions in BMI. Reductions in SAA and IL-6 tended to parallel the changes in CRP, but were less informative.CONCLUSION:In morbidly obese subjects, gastric bypass surgery lowers energy intake, reduces inflammatory markers and improves insulin sensitivity. Despite a marked reduction in body weight, only a small effect on CRP levels was seen in insulin-resistant patients, indicating that flexibility of circulating CRP levels is primarily dependent upon insulin sensitivity rather than energy supply.International Journal of Obesity (2005) 29, 1275–1280. doi:10.1038/sj.ijo.0803000; published online 12 July 2005 [ABSTRACT FROM AUTHOR]

The objective of this work was to test the clustering of classic Cardiovascular disease (CVD) risk factors, known as the metabolic syndrome (e.g., increased blood pressure, insulin resistance, hypercholesterolemia combined with low levels of high-density lipoprotein, and abdominal fatness), as a mediator of the association between cynicism and CVD. Data were used from the Swedish Adoption/Twin Study of Aging (SATSA) (n = 1944 individuals, average age 62 years, 58% female). The crosssectional association of cynicism with CVD was significant (standardized β = 0.08, p < .01). In a longitudinal model, cynicism measured in 1984 was associated with CVD measured in 1987 (standardized β = 0.06, p < .01). In a third model, a latent construct "metabolic syn- drome" significantly partially mediated this relationship. Cynicism (measured 1984) predicted the metabolic syndrome (measured 19861988) (standardized β = 0.20, p < .05) and the metabolic syndrome predicted CVD (measured 1987) (standardized β = 0.18, p < .001); cynicism no longer significantly predicted CVD. Results were adjusted for baseline CVD, smoking, and age. These findings suggest that a clustering of CVD risk factors partially mediate the association between cynicism and CVD in an older population. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present study was to identify predictors of weight loss in obese men participating in a 2-year behaviour modification programme.Design: Longitudinal, clinical intervention study of a behaviour modifying weight loss program.Setting: University Hospital, Stockholm, Sweden.Subjects: Forty-four obese men (age, 42.7 +/- 1.1 years: BMI, 37.1 +/- 0.6 kg m(-2), mean +/- SEM) followed for 2 years.Interventions: Behaviour modification weight loss programme.Main Outcome Measures: Associations between plasma leptin and thyroid function tests, insulin resistance by homeostatic model assessment (HOMA), dietary recall and anthropometrically determined body composition.Results: At baseline, there were significant correlations between plasma leptin and body mass index (BMI), fat-free mass (FFM) and insulin resistance. Median weight loss over 2 years was 4.9 kg (range, -27.2 to +11.9). Baseline serum leptin concentrations adjusted for BMI (leptin/BMI ratio) were significantly correlated with 2-year weight change (r = 0.34, P = 0.04). A subset of seven of the 44 men gained weight over the 2 years. These 'gainers' differed significantly in initial leptin/BMI ratio (0.62 +/- 0.07) compared with the 37 'losers' (0.42 +/- 0.03, P < 0.05). In a multiple regression model, baseline leptin, insulin and age predicted 22% of the variance in weight change with no additional significant contribution from BMI, FFM, waist:hip ratio, thyroid function tests or energy intake. There was a strong correlation between the change in leptin concentrations and the change in insulin resistance from baseline to 2-year follow-up (r = 0.54; P < 0.001).Conclusion: Baseline plasma leptin concentrations predicted long-term weight loss. Inappropriate leptin secretion or disposal, corrected for BMI, was associated with failure to maintain weight loss in obese men in a behaviour modification weight loss programme. [ABSTRACT FROM AUTHOR]

Aims: Our aim was to study the incidence of type 2 diabetes in a population-based cohort of Swedish and Iraqi born individuals, focussing on traditional risk factors, insulin action, insulin secretion and ethnicity., Materials and Methods: The cohort consisted of 1164 Iraqi and 693 Swedish-born citizens. We investigated the association between new-onset type 2 diabetes and the predictors including lifestyle factors, metabolic risk markers, country of birth, insulin sensitivity and secretion assessed by Matsuda index with Cox regression., Results: Eighty-nine individuals were diagnosed with type 2 diabetes with a mean follow-up of 7.5 years. Both lower insulin sensitivity (ISI, HR 0.02 [0.01-0.08]) as well as insulin secretion (CIR, HR 0.13 [0.07-0.24]) at baseline predicted type 2 diabetes onset, independent of traditional risk factors. Our results were not modified by country of birth. Regarding traditional risk factors, WHR (1.05 [1.00-1.09]), blood glucose (3.27 [2.35-4.55]), LDL/HDL (1.46 [1.20-1.78]) and diastolic blood pressure (1.04 [1.00-1.07]) predicted diabetes incidence in the full model., Conclusions: Both impaired insulin sensitivity index and corrected insulin response predicted type 2 diabetes onset, independent of traditional risk factors. We conclude that insulin secretion and action might be useful additional predictors for type 2 diabetes in populations of European and Middle Eastern ethnicities., (© 2021 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Background and Aims: Insulin resistance contributes to the development of type 2 diabetes (T2D) and is also a cardiovascular risk factor. The aim of this study was to investigate the potential association between insulin resistance measured by estimated glucose disposal rate (eGDR) and risk of stroke and mortality thereof in people with T2D., Materials and Methods: Nationwide population based observational cohort study that included all T2D patients from the Swedish national diabetes registry between 2004 and 2016 with full data on eGDR and categorised as following: < 4, 4-6, 6-8, and ≥ 8 mg/kg/min. We calculated crude incidence rates and 95% confidence intervals (CIs) and used multiple Cox regression to estimate hazard ratios (HRs) to assess the association between the risk of stroke and death, according to the eGDR categories in which the lowest category < 4 (i.e., highest grade of insulin resistance), served as a reference. The relative importance attributed of each factor in the eGDR formula was measured by the R 2 (± SE) values calculating the explainable log-likelihoods in the Cox regression., Results: A total of 104 697 T2D individuals, 44.5% women, mean age of 63 years, were included. During a median follow up-time of 5.6 years, 4201 strokes occurred (4.0%). After multivariate adjustment the HRs (95% CI) for stroke in patients with eGDR categories between 4-6, 6-8 and > 8 were: 0.77 (0.69-0.87), 0.68 (0.58-0.80) and 0.60 (0.48-0.76), compared to the reference < 4. Corresponding numbers for the risk of death were: 0.82 (0.70-0.94), 0.75 (0.64-0.88) and 0.68 (0.53-0.89). The attributed relative risk R 2 (± SE) for each variable in the eGDR formula and stroke was for: hypertension (0.045 ± 0.0024), HbA1c (0.013 ± 0.0014), and waist (0.006 ± 0.0009), respectively., Conclusion: A low eGDR (a measure of insulin resistance) is associated with an increased risk of stroke and death in individuals with T2D. The relative attributed risk was most important for hypertension., (© 2021. The Author(s).)

Context: Roux-en-Y gastric bypass surgery (RYGB) markedly improves glycemia in patients with type 2 diabetes (T2D), but underlying mechanisms and changes over time are incompletely understood., Objective: Integrated assessment of neuroendocrine and metabolic changes over time in T2D patients undergoing RYGB., Design and Setting: Follow-up of single-center randomized study., Patients: Thirteen patients with obesity and T2D compared to 22 healthy subjects., Interventions: Blood chemistry, adipose biopsies, and heart rate variability were obtained before and 4, 24, and 104 weeks post-RYGB., Results: After RYGB, glucose-lowering drugs were discontinued and hemoglobin A1c fell from mean 55 to 41 mmol/mol by 104 weeks (P < 0.001). At 4 weeks, morning cortisol (P < 0.05) and adrenocorticotropin (P = 0.09) were reduced by 20%. Parasympathetic nerve activity (heart rate variability derived) increased at 4 weeks (P < 0.05) and peaked at 24 weeks (P < 0.01). C-reactive protein (CRP) and white blood cells were rapidly reduced (P < 0.01). At 104 weeks, basal and insulin-stimulated adipocyte glucose uptake increased by 3-fold vs baseline and expression of genes involved in glucose transport, fatty acid oxidation, and adipogenesis was upregulated (P < 0.01). Adipocyte volume was reduced by 4 weeks and more markedly at 104 weeks, by about 40% vs baseline (P < 0.01)., Conclusions: We propose this order of events: (1) rapid glucose lowering (days); (2) attenuated cortisol axis activity and inflammation and increased parasympathetic tone (weeks); and (3) body fat and weight loss, increased adipose glucose uptake, and whole-body insulin sensitivity (months-years; similar to healthy controls). Thus, neuroendocrine pathways can partly mediate early glycemic improvement after RYGB, and adipose factors may promote long-term insulin sensitivity and normoglycemia., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.)

Background: Diabetes and insulin resistance is an emerging issue in people with HIV. HIV-related mortality and morbidities have decreased markedly over the last few decades, while co-morbidities including type 2 diabetes (T2D) have increased., Setting: This study investigated the incidence of T2D and insulin resistance in a cohort of HIV-patients on effective treatment., Methods: Prevalence and baseline predictors of T2D were assessed in a cohort of 570 HIV-positive patients 50 years or older. Patients without diabetes (n = 505) were followed prospectively over a median period of 7.25 year (2012-2020) until T2D development, death or end of the study. T2D was defined as repeated fasting glucose values ≥7.0 mmol/L. Insulin resistance was defined as HOMA-IR ≥3.0. Predictors of T2D development (HIV-related parameters, lipids, hypertension, central obesity, inflammation, smoking and use of statins) were assessed using logistic regression analysis., Results: 30% (153/505) had insulin resistance. During follow up (3485 patient-years) 9% (43/505) developed T2D and 7% (36/505) insulin resistance. Thus, at follow up the prevalence of either T2D or insulin resistance was 46% (232/505). T2D incidence was 1.2/100 patient-years. In multivariate analysis, after adjustment for age, T2D development was associated with baseline insulin resistance, hypertriglyceridemia, central obesity and statin treatment, but no HIV-related factors., Conclusion: The incidence of T2D in this cohort of patients with well controlled HIV-infection was high. The predictive factors associated with the development of T2D were not unique for HIV positive patients. The findings underline the importance of lifestyle changes in avoidance of T2D in people with HIV., Competing Interests: The authors have declared that no competing interests exist.