Markers Of Insulin Sensitivity Research Articles

Complement C3 Is the Strongest Predictor of Whole-Body Insulin Sensitivity in Psoriatic Arthritis.

ObjectivesTo evaluate the correlation between inflammatory measures and whole-body insulin sensitivity in psoriatic arthritis (PsA) patients.MethodsFor the present study, 40 nondiabetic PsA patients were recruited. A standard oral glucose tolerance test (OGTT) was performed. The insulin sensitivity index (ISI), insulinogenic index (IGI) and oral disposition index (ODI) were calculated from dynamic values of glucose and insulin obtained during OGTT.ResultsIn our study population, mean ISI was 3.5 ± 2.5, median IGI was 1.2 (0.7–1.8), mean ODI 4.5 ± 4.5. In univariate correlation analysis, ISI correlated inversely with systolic blood pressure (sBP) (R = -0.52, p = 0.001), diastolic blood pressure (dBP) (R = -0.45, p = 0.004) and complement C3 (R = -0.43, p = 0.006) and ODI correlated inversely with sBP (R = -0.38, p = 0.02), dBP (R = -0.35, p = 0.03) and complement C3 (R = -0.37, p = 0.02). No significant correlations were found between analyzed variables and IGI. In a stepwise multiple regression, only complement C3 entered in the regression equation and accounted for approximately 50% of the variance of ISI. Using a receiver operating characteristic (ROC) curve we identified the best cut-off for complement C3 of 1.32 g/L that yielded a sensitivity of 56% and a specificity of 96% for classification of insulin resistant patients.ConclusionsIn conclusion, our data suggest that serum complement C3 could represent a useful marker of whole-body insulin sensitivity in PsA patients.

Endothelial Function in Youth: A Biomarker Modulated by Adiposity-Related Insulin Resistance

To investigate the physical and metabolic determinants of endothelial dysfunction, an early marker of subclinical atherosclerosis, in normal weight and overweight adolescents with and without type 2 diabetes mellitus. A cross-sectional study of 81 adolescents: 21 normal weight, 25 overweight with normal glucose tolerance, 19 overweight with impaired glucose regulation, and 16 with type 2 diabetes mellitus underwent evaluation of reactive hyperemia index (RHI) and augmentation index (AIx) at heart rate 75 bpm by peripheral arterial tonometry; oral glucose tolerance test, lipid profile, and hyperinsulinemic-euglycemic clamp to measure insulin sensitivity; and dual energy X-ray absorptiometry scan and abdominal magnetic resonance imaging for percentage of body fat and abdominal fat partitioning. Participants across tertiles of RHI (1.2 ± 0.02, 1.5 ± 0.02, and 2.0 ± 0.05, P < .001) had similar age, sex, race, lipid profile, and blood pressure. Body mass index z-score, percentage body fat, abdominal fat, and hemoglobin A1c decreased, and insulin sensitivity increased from the first to third tertile. RHI was inversely related to percentage body fat (r = -0.29, P = .008), total (r = -0.37, P = .004), subcutaneous (r = -0.39, P = .003), and visceral (r = -0.26, P = .04) abdominal fat. AIx at heart rate 75 bpm was higher (worse) in the lower RHI tertiles (P = .04), was positively related to percentage body fat (r = 0.26, P = .021), and inversely related to age, insulin sensitivity, and inflammatory markers (tumor necrosis factor-α and plasminogen activator inhibition-1). Childhood obesity, particularly abdominal adiposity, is associated with endothelial dysfunction manifested by worse reactive hyperemia and higher AIx. Insulin resistance appears to mediate this relationship.

Potential Intervention of α- Lipoic Acid and Carnitine on Insulin Sensitivity and Anti-Inflammatory Cytokines Levels in Fructose-Fed Rats, a Model of Metabolic Syndrome

ABSTRACTThe objective of this work was to evaluate the beneficial effect of α-lipoic acid (ALA) and L-carnitine (CAR) on insulin sensitivity and anti-inflammatory markers in animal model of metabolic syndrome (MS), high fructose (HF)-fed rats. Forty male rats were randomly divided into four groups (n = 10). Group 1(control rats, G1), animals were allowed to drink 0.2% gum acacia (GA, p.o) and were fed a modified diet containing 65% cornstarch. The remaining rats were induced MS by feeding the same diet + free access to 10% fructose (w/v) in 0.2% GA (HF, MS) for 4 weeks. After 4 weeks of HF feeding, the rats were further divided into three subgroups; G2: HF (MS) in 0.2% GA, G3: HF (MS)+CAR (200 mg/kg/day) in 0.2% GA and G4: HF (MS)+ALA (200 mg/kg/day) in 0.2% GA, respectively. All ingredients were administered orally by guava daily for four weeks. A significant increase in serum glucose, insulin and Homeostasis Model Assessment-Insulin Resistance (HOMA-IR) levels was observed after four weeks of HF feeding compared to control rats. Administration of ALA and CAR reversed the increase of the mentioned parameters. In HF rats, the increase of serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels were significantly lowered, while the reduction of the serum high-density lipoprotein cholesterol (HDL-C) was alleviated after administration of CAR and ALA. The reduction of the serum adiponectin level was significantly increased after administration of CAR and ALA. These data suggested that CAR and/or ALA had a beneficial role in the prevention of MS associated with development of type 2 diabetes.

Associations of 25-hydroxyvitamin D with markers of inflammation, insulin resistance and obesity in black and white community-dwelling adults

AimsVitamin D is a fat-soluble vitamin classically known for its role in calcium absorption and bone health. Growing evidence indicates that vitamin D deficiency may be associated with inflammation, insulin resistance, and obesity. However, prior studies examining the association of vitamin D with metabolic risk factors had relatively low representation of individuals of black race, limiting their ability to characterize associations of vitamin D and parameters of metabolic health in black vs. white individuals. MethodsWe examined associations of 25-hydroxyvitamin D (25(OH)D) concentrations with markers of inflammation (interleukin [IL]-6, IL-10, high sensitivity C-reactive protein [hsCRP]), insulin sensitivity (adiponectin, resistin, HOMA-IR), and obesity (body mass index [BMI], waist circumference) in 1042 participants from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a large national cohort of black and white adults 45 years or older. ResultsIn unadjusted analyses, lower 25(OH)D concentrations were associated with higher IL-6 and hsCRP concentrations; lower adiponectin concentrations; higher HOMA-IR; and higher BMI and waist circumference (P < 0.05 for all). After adjustment for sociodemographic, clinical, lifestyle, and laboratory variables, lower 25(OH) D concentrations remained associated with lower adiponectin concentrations, higher IL–6 concentrations, higher HOMA-IR, and higher BMI and waist circumference (P < 0.05 for all). The magnitude of these associations did not differ by race (Pinteraction > 0.1). ConclusionsLower 25(OH)D concentrations are associated with disturbances in metabolic health in both blacks and whites. Whether correcting vitamin D deficiency could offer a beneficial therapy for disease prevention requires further study.

Sfrp5 associates with beta-cell function in humans.

Secreted frizzled-related protein (Sfrp)5 improves insulin sensitivity, but impairs beta-cell function in rodents. However, the relationship between Sfrp5, insulin sensitivity and secretion in humans is currently unclear. Therefore, the aim of the study was to characterize the associations between serum Sfrp5 and indices of insulin sensitivity and beta-cell function from dynamic measurements using oral glucose tolerance tests (OGTT) in humans. This study enrolled 194 individuals with nonalcoholic fatty liver disease (NAFLD), who were diagnosed based on ultrasound and liver transaminases and underwent a frequent sampling 75-g OGTT. Fasting serum Sfrp5 was measured by ELISA. Associations were assessed with several indices of insulin sensitivity and beta-cell function derived from glucose, insulin and C-peptide concentrations during the OGTT. Circulating Sfrp5 associated inversely with the insulinogenic index based on C-peptide (rs = -0·244, P = 0·001), but not with the insulinogenic index based on insulin levels (rs = -0·007, P = 0·926) after adjustment for age, sex and body mass index. Sfrp5 inversely correlated only with QUICKI as a marker of insulin sensitivity in the model adjusted for age and sex (rs = -0·149, P = 0·039). These associations were not influenced by the additional adjustment for hepatic steatosis index. The inverse association of serum Sfrp5 with beta-cell function suggests a detrimental role of Sfrp5 for insulin secretion also in humans. The severity of NAFLD does not appear to affect this relationship. The weak association between serum Sfrp5 and insulin sensitivity was partially explained by body mass.

Naturally occurring mitochondrial-derived peptides are age-dependent regulators of apoptosis, insulin sensitivity, and inflammatory markers.

Mitochondria are key players in aging and in the pathogenesis of age-related diseases. Recent mitochondrial transcriptome analyses revealed the existence of multiple small mRNAs transcribed from mitochondrial DNA (mtDNA). Humanin (HN), a peptide encoded in the mtDNA 16S ribosomal RNA region, is a neuroprotective factor. An in silico search revealed six additional peptides in the same region of mtDNA as humanin; we named these peptides small humanin-like peptides (SHLPs). We identified the functional roles for these peptides and the potential mechanisms of action. The SHLPs differed in their ability to regulate cell viability in vitro. We focused on SHLP2 and SHLP3 because they shared similar protective effects with HN. Specifically, they significantly reduced apoptosis and the generation of reactive oxygen species, and improved mitochondrial metabolism in vitro. SHLP2 and SHLP3 also enhanced 3T3-L1 pre-adipocyte differentiation. Systemic hyperinsulinemic-euglycemic clamp studies showed that intracerebrally infused SHLP2 increased glucose uptake and suppressed hepatic glucose production, suggesting that it functions as an insulin sensitizer both peripherally and centrally. Similar to HN, the levels of circulating SHLP2 were found to decrease with age. These results suggest that mitochondria play critical roles in metabolism and survival through the synthesis of mitochondrial peptides, and provide new insights into mitochondrial biology with relevance to aging and human biology.

Differences in homeostatic model assessment (HOMA) values and insulin levels after vitamin D supplementation in healthy men: a double-blind randomized controlled trial.

Vitamin D is thought to play a role in glucose metabolism. The aim of the present study was to determine the effect of vitamin D supplementation on markers of insulin sensitivity and inflammation in men without diabetes with vitamin D deficiency/insufficiency. In this 1-year double-blind randomized controlled trial, 130 men aged 20-65 years (mean age 47.52 ± 11.84 years) with serum 25-hydroxyvitamin D levels <50 nmol/l (mean 38.89 ± 8.64 nmol/l) were randomized to treatment (100 000 IU vitamin D bimonthly) or placebo. Anthropometric measurements, demographic questionnaires, and blood indices (fasting glucose, insulin, high-sensitivity C-reactive protein, lipids) were collected and repeated after 6 and 12 months. The compliance rate was 98.5%. Multivariate models, adjusted for baseline levels, age, body mass index, sun exposure, physical activity and LDL, showed significant differences in insulin and homeostatic model assessment of insulin resistance (HOMA-IR) values between groups. Levels of insulin and HOMA-IR values remained steady during the study period in the treatment group but increased by 16% in the control group (p = 0.038 and p = 0.048, respectively). Vitamin D supplementation administered for 12 months in healthy men maintained insulin levels and HOMA-IR values relative to the increase in the control group. Further studies are needed to establish the long-term effect of vitamin D supplementation on the risk of diabetes.

SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

Insulin-Like Growth Factor Binding Protein 1 Predicts Insulin Sensitivity And Insulin Area-Under-The-Curve In Obese, Nondiabetic Adolescents

To compare fasting insulin-like growth factor binding protein 1 (IGFBP-1) to other fasting indices as a surrogate marker of insulin sensitivity and resistance calculated from a 3-hour oral glucose tolerance test (oGTT). Fasting IGFBP-1 and oGTT were performed at 0 (n = 77), 52 (n = 54), and 100 (n = 38) weeks in a study investigating metformin treatment of obesity in adolescents. Insulin area-under-the-curve (IAUC) and the composite insulin sensitivity index (CISI) calculated from the oGTT were compared to fasting IGFBP-1, homeostasis model assessment-insulin resistance, and corrected insulin release at the glucose peak (CIRgp). IGFBP-1 and the ratio of IGFBP-1 to fasting insulin were significantly correlated with indices based on timed sampling, including IAUC, CISI, and CIRgp. In addition, a significant effect of IGFBP-1, but not IGFBP-1 to insulin at time zero, was observed for IAUC and CISI. Our results indicate that fasting IGFBP-1 may be a useful marker of insulin sensitivity and secretion.

Arsenic exposure is associated with diminished insulin sensitivity in non-diabetic Amish adults.

Substantial evidence supports an association between diabetes and arsenic at high exposure levels, but results are mixed at low exposure levels. The aetiology of diabetes involves insulin resistance and β-cell dysfunction. However, only a few epidemiologic studies have examined measures of insulin resistance and β-cell function in relation to arsenic exposure, and no studies have tested for associations with the oral glucose tolerance test (OGTT). We examined the association between urinary total arsenic and OGTT-based markers of insulin sensitivity and β-cell function. We studied 221 non-diabetic adults (mean age = 52.5years) from the Amish Family Diabetes Study. We computed OGTT-based validated measures of insulin sensitivity and β-cell function. Generalized estimating equations accounting for sibship were used to estimate associations. After adjusting for age, sex, waist-to-hip ratio and urinary creatinine, an interquartile range increase in urinary total arsenic (6.24µg/L) was significantly, inversely associated with two insulin sensitivity measures (Stumvoll metabolic clearance rate = -0.23mg/(kgmin), (95% CI: -0.38, -0.089), p = 0.0015; Stumvoll insulin sensitivity index = -0.0029µmol/(kgminpM), (95% CI: -0.0047, -0.0011), p = 0.0015). Urinary total arsenic was also significantly associated with higher fasting glucose levels (0.57mg/dL (95% CI: 0.06, 1.09) per interquartile range increase, p = 0.029). No significant associations were found between urinary total arsenic and β-cell function measures. This preliminary study found that urinary total arsenic was associated with insulin sensitivity but not β-cell function measures, suggesting that low-level arsenic exposure may influence diabetes risk through impairing insulin sensitivity. Copyright © 2015 John Wiley & Sons, Ltd.

Increased levels of serum granzyme-B is associated with insulin resistance and increased cardiovascular risk in adolescent polycystic ovary syndrome patients

ObjectivesOur aim was to determine serum perforin and granzyme-B levels in adolescent PCOS patients, and to investigate whether they are associated with some of the insulin sensitivity, obesity and cardiovascular (CV) risk markers and metabolic syndrome. Study designA case–control study was carried out including a total of 172 adolescents (83 PCOS patients and 89 age-matched healthy controls). Participants were recruited consecutively. Homeostasis model assessment (HOMA-IR), lipid parameters, and anthropometric measurements were determined. Serum perforin and granzyme B levels were measured by commercially available ELISA kits. HOMA-IR>3.16 was considered to indicate the presence of insulin resistance. Logistic regression analysis was applied for the predictive value of granzyme-B for increased CV risk in PCOS patients. ResultsAs body mass index (BMI) of the PCOS patients was significantly higher than the controls (median 24.6kg/m2 and 21.4kg/m2, respectively, p<0.001) all parameters were evaluated after adjustment for BMI. Adolescents with PCOS had significantly higher levels of fasting glucose, insulin, HOMA-IR and granzyme-B when compared with controls. According to the results of logistic regression analysis, granzyme-B levels were found to be significantly associated with increased HOMA-IR (OR=6.120, 95% CI: 2.352–15.926, p<0.001) in adolescent PCOS patients. Additionally, elevated levels of serum granzyme-B were predictive for increased CV risk in PCOS patients (OR=0.237, 95% CI: 0.091–0.616, p=0.003). ConclusionsIncreased levels of serum granzyme-B are independently associated with insulin resistance and also with increased CV risk in adolescent polycystic ovary syndrome patients.

Insulin Sensitivity and Secretion in Obese Type 2 Diabetic Women after Various Bariatric Operations

Objective: To compare the effects of biliopancreatic diversion (BPD) and laparoscopic gastric banding (LAGB) on insulin sensitivity and secretion with the effects of laparoscopic gastric plication (P). Methods: A total of 52 obese women (age 30-66 years) suffering from type 2 diabetes mellitus (T2DM) were prospectively recruited into three study groups: 16 BPD; 16 LAGB, and 20 P. Euglycemic clamps and mixed meal tolerance tests were performed before, at 1 month and at 6 months after bariatric surgery. Beta cell function derived from the meal test parameters was evaluated using mathematical modeling. Results: Glucose disposal per kilogram of fat free mass (a marker of peripheral insulin sensitivity) increased significantly in all groups, especially after 1 month. Basal insulin secretion decreased significantly after all three types of operations, with the most marked decrease after BPD compared with P and LAGB. Total insulin secretion decreased significantly only following the BPD. Beta cell glucose sensitivity did not change significantly post-surgery in any of the study groups. Conclusion: We documented similar improvement in insulin sensitivity in obese T2DM women after all three study operations during the 6-month postoperative follow-up. Notably, only BPD led to decreased demand on beta cells (decreased integrated insulin secretion), but without increasing the beta cell glucose sensitivity.

Surrogate measures of insulin sensitivity when compared to euglycemic hyperinsulinemic clamp studies in Asian Indian men without diabetes

AimFasting surrogate measures of insulin sensitivity are increasingly used in research and clinical practice. To assess the reliability of these measures, we aimed to evaluate multiple fasting surrogate measures simultaneously in non-diabetic subjects in comparison with the euglycemic hyperinsulinemic clamp study. MethodsSixteen normoglycemic male South Indian subjects were studied. After an overnight fast, blood samples were collected for glucose, insulin and lipid profile measurements, and stepped euglycemic hyperinsulinemic clamp studies were performed on all subjects. Steady state glucose infusion rates (M value) during low and high insulin phases of the clamp were calculated. Correlation of M value with surrogate markers of insulin sensitivity was performed. Predictive accuracy of surrogate indices was measured in terms of Root Mean Squared Error (RMSE) and leave-one-out cross-validation-type RMSE of prediction using a calibration model. ResultsM values showed a strong and significant correlation (p<0.01) with the following surrogate markers: Fasting insulin (r=−0.714), Fasting glucose to insulin ratio (FGIR, r=0.747) and Raynaud index (r=0.714). FGIR had a significantly lower RMSE when compared with HOMA-IR and QUICKI. ConclusionsAmong the surrogate measures, FGIR had the strongest correlation with M values. FGIR was also the most accurate surrogate measure, as assessed by the calibration model.

A Dietary Supplement Containing Cinnamon, Chromium and Carnosine Decreases Fasting Plasma Glucose and Increases Lean Mass in Overweight or Obese Pre-Diabetic Subjects: A Randomized, Placebo-Controlled Trial.

BackgroundPreventing or slowing the progression of prediabetes to diabetes is a major therapeutic issue.ObjectivesOur aim was to evaluate the effects of 4-month treatment with a dietary supplement containing cinnamon, chromium and carnosine in moderately obese or overweight pre-diabetic subjects, the primary outcome being change in fasting plasma glucose (FPG) level. Other parameters of plasma glucose homeostasis, lipid profile, adiposity and inflammatory markers were also assessed.MethodsIn a randomized, double-blind, placebo-controlled study, 62 subjects with a FPG level ranging from 5.55 to 7 mmol/L and a body mass index ≥25 kg/m2, unwilling to change their dietary and physical activity habits, were allocated to receive a 4-month treatment with either 1.2 g/day of the dietary supplement or placebo. Patients were followed up until 6 months post-randomization.ResultsFour-month treatment with the dietary supplement decreased FPG compared to placebo (-0.24±0.50 vs +0.12±0.59 mmol/L, respectively, p = 0.02), without detectable significant changes in HbA1c. Insulin sensitivity markers, plasma insulin, plasma lipids and inflammatory markers did not differ between the treatment groups. Although there were no significant differences in changes in body weight and energy or macronutrient intakes between the two groups, fat-free mass (%) increased with the dietary supplement compared to placebo (p = 0.02). Subjects with a higher FPG level and a milder inflammatory state at baseline benefited most from the dietary supplement.ConclusionsFour-month treatment with a dietary supplement containing cinnamon, chromium and carnosine decreased FPG and increased fat-free mass in overweight or obese pre-diabetic subjects. These beneficial effects might open up new avenues in the prevention of diabetes.Trial RegistrationClinicalTrials.gov NCT01530685

Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism.

Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test the hypothesis that CRF modifies the association between PAEE and glucose metabolism. We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake) was estimated using a submaximal 8 min step test. The associations were examined by linear regression analysis. Results were adjusted for relevant confounders. PAEE and CRF were reduced in individuals with i-IGT, combined IFG + IGT and screen-detected diabetes mellitus, but were not significantly different in individuals with i-IFG compared with those with normal glucose tolerance. When adjusting CRF for PAEE and vice versa, PAEE and CRF were both associated with lower fasting and 2 h insulin and higher peripheral insulin sensitivity. CRF was additionally associated with lower fasting and 2 h glucose and higher insulin sensitivity and beta cell function. There was no interaction between CRF and PAEE for any markers of glucose metabolism. Only CRF, not PAEE, appears to be independently associated with plasma glucose levels and beta cell function, suggesting that CRF may be particularly important for glycaemic control.

Effects of Inhibiting Dipeptidyl Peptidase-4 (DPP4) in Cows with Subclinical Ketosis.

The inhibition of dipeptidyl peptidase-4 (DPP4) via specific inhibitors is known to result in improved glucose tolerance and insulin sensitivity and decreased accumulation of hepatic fat in type II diabetic human patients. The metabolic situation of dairy cows can easily be compared to the status of human diabetes and non-alcoholic fatty liver. For both, insulin sensitivity is reduced, while hepatic fat accumulation increases, characterized by high levels of non-esterified fatty acids (NEFA) and ketone bodies.Therefore, in the present study, a DPP4 inhibitor was employed (BI 14332) for the first time in cows. In a first investigation BI 14332 treatment (intravenous injection at dosages of up to 3 mg/kg body weight) was well tolerated in healthy lactating pluriparous cows (n = 6) with a significant inhibition of DPP4 in plasma and liver. Further testing included primi- and pluriparous lactating cows suffering from subclinical ketosis (β-hydroxybutyrate concentrations in serum > 1.2 mM; n = 12). The intension was to offer effects of DPP4 inhibition during comprehensive lipomobilisation and hepatosteatosis. The cows of subclinical ketosis were evenly allocated to either the treatment group (daily injections, 0.3 mg BI 14332/kg body weight, 7 days) or the control group. Under condition of subclinical ketosis, the impact of DPP4 inhibition via BI 14332 was less, as in particular β-hydroxybutyrate and the hepatic lipid content remained unaffected, but NEFA and triglyceride concentrations were decreased after treatment. Owing to lower NEFA, the revised quantitative insulin sensitivity check index (surrogate marker for insulin sensitivity) increased. Therefore, a positive influence on energy metabolism might be quite possible. Minor impacts on immune-modulating variables were limited to the lymphocyte CD4+/CD8+ ratio for which a trend to decreased values in treated versus control animals was noted. In sum, the DPP4 inhibition in cows did not affect glycaemic control like it is shown in humans, but was able to impact hyperlipemia, as NEFA and TG decreased.

Retraction Note to: Different Aspects of Sartan + Calcium Antagonist Association Compared to the Single Therapy on Inflammation and Metabolic Parameters in Hypertensive Patients

This study aims to evaluate the effects of an angiotensin receptor blocker (ARB)/calcium channel blocker combination on blood pressure control, lipid profile, insulin sensitivity, and inflammation markers. We randomized 276 hypertensive patients to olmesartan 20 mg, amlodipine 10 mg, or a single pill containing an olmesartan/amlodipine combination 20/5 mg for 12 months. We evaluated the following: body weight, systolic and diastolic blood pressure, fasting plasma glucose, fasting plasma insulin (FPI), M value, lipid profile, adiponectin (ADN), high sensitivity C-reactive protein (Hs-CRP), monocyte chemoattractant protein-1 (MCP-1), and macrophage migration inhibitory factor-1β (MIP-1β). Olmesartan/amlodipine combination better reduced blood pressure, FPI, homeostasis model assessment index, and increased M value and ADN compared to olmesartan and amlodipine monotherapies. Olmesartan/amlodipine significantly decreased Hs-CRP, MCP-1, and MIP-1β. In this multicenter, randomized, double-blind, clinical study, ARB/calcium antagonist combination resulted to be more effective than single monotherapies in reducing blood pressure, in improving insulin sensitivity, and in reducing inflammation parameters in patients with stage I essential hypertension.

Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial

Epidemiologic data suggest that low serum 25-hydroxyvitamin D [25(OH)D] increases insulin resistance and the risk of type 2 diabetes. Few interventional trials have assessed the effect of vitamin D on insulin metabolism, and published results are discordant. The goal of this study was to perform a detailed assessment of the effect of ergocalciferol administration on glucose and insulin metabolism in healthy people with low total 25(OH)D(total). This was a 12-wk, double-blinded, randomized controlled trial. We enrolled 90 healthy volunteers aged 18-45 y with serum 25(OH)D ≤20 ng/mL (by immunoassay) and administered 50,000 IU ergocalciferol/wk or placebo for 12 wk. Primary endpoints were change in first-phase insulin response and insulin sensitivity as measured by intravenous glucose tolerance test. Secondary endpoints included change in homeostasis model assessment of insulin resistance; fasting glucose, insulin, and lipids; body mass index (BMI); and blood pressure. On-study 25(OH)D(total) was assessed by liquid chromatography-tandem mass spectrometry. In the treated group, 25(OH)D(total) rose from 18 ± 7 to 43 ± 12 ng/mL (P < 0.001) with no change in the placebo group. Despite this increase, at 12 wk, there were no between-group differences in either insulin response or insulin sensitivity; nor were there differences in any measured secondary endpoints. There was no evidence of effect modification by sex, race, glucose tolerance status, baseline 25(OH)D(total), or BMI. In healthy persons with low 25(OH)D(total), ergocalciferol administration for 12 wk normalizes 25(OH)D(total) but does not improve insulin secretion, insulin sensitivity, or other markers of metabolic health.

Improved glycemic control due to sitagliptin is not related to cortisol or the surrogate marker IGFBP-1 for hepatic insulin sensitivity

ImportanceElevated cortisol levels and dysregulated insulin-like growth factor binding protein-1 (IGFBP-1; a marker of hepatic insulin sensitivity) are both related to insulin resistance and glucose abnormalities. It is unknown whether improvement in these parameters is related to improved glucose metabolism during treatment with sitagliptin. ObjectiveTo determine whether improved insulin sensitivity and beta-cell function during treatment with sitagliptin is related to lower cortisol levels and/or improved regulation of IGFBP-1 in patients with recent acute coronary syndrome (ACS) and newly discovered glucose abnormalities. DesignSamples were taken from The BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction (BEGAMI) trial, a double-blinded, placebo-controlled randomized clinical trial on the efficacy and safety of sitagliptin for patients with ACS and newly discovered glucose abnormalities. SettingCardiology departments (cardiac ICU and outpatient clinic) in two hospitals in Stockholm, Sweden. ParticipantsSubjects hospitalized (or recently hospitalized) for ACS, in whom an oral glucose tolerance test revealed previously unknown glucose abnormalities. InterventionsSubjects were randomized to sitagliptin 100mg once daily (n=34) or placebo (n=37) for twelve weeks. Oral glucose tolerance test (OGTT) and randomization occurred after stabilization median 7days after ACS. Main outcomes and measuresFasting serum cortisol and IGFBP-1 were analyzed before OGTT, around 8a.m., and after at 10a.m. The latter time point was chosen as the spread in cortisol levels around is small then, allowing improved chances to detect differences between groups. ResultsGlucose tolerance and insulin sensitivity improved in both groups, while HbA1c and indices of β-cell function improved only in the sitagliptin group as reported previously. Both groups displayed decreased cortisol levels around 10a.m. (from 338±21 to 278±14nmol/L, p=0.038, in the sitagliptin group; from 343±17 to 302±15nmol/L, p=0.017, in the placebo group), and improved correlation between fasting log-IGFBP-1 and insulin. Conclusions and relevanceThese findings suggest that a stress-related elevation in cortisol may have negative impact on glucose tolerance in patients with recent ACS. However, improved glycemic control with sitagliptin does not appear to be related to changes in cortisol levels or hepatic insulin sensitivity as assessed by IGFBP-1.

Dietary Advanced Glycation End Products Consumption as a Direct Modulator of Insulin Sensitivity in Overweight Humans: A Study Protocol for a Double-Blind, Randomized, Two Period Cross-Over Trial.

BackgroundAdvanced glycation end products (AGEs) are formed during the processing, storage, and cooking of foods. As part of a western diet, AGEs are consumed in excess and impair glucose metabolism in patients with type 2 diabetes. In the absence of diabetes, AGE-mediated decreases in insulin sensitivity and signaling have been postulated. However, randomized studies to test this relationship in humans are limited.ObjectiveThe primary aim of this trial is to determine whether dietary consumption of AGEs will decrease insulin sensitivity in healthy overweight adults. A secondary aim is to determine the effects of dietary AGEs on insulin secretion, circulating soluble receptor for AGEs (sRAGE), and inflammation markers.MethodsOverweight, but otherwise healthy, non-diabetic adults (N=20) aged 18-50 years old will complete a randomized cross-over design intervention study alternating low and high (4-fold increase) AGE diets (2-week duration). At baseline, participants will undergo a medical review including an intravenous glucose tolerance test (IVGTT), a hyperinsulinemic-euglycemic clamp, and anthropometric measures and questionnaires assessing diet, physical activity, and general wellness. Each test diet will be followed for 14 days, followed by a 4-week washout period before commencement of the second alternate dietary period. Energy, macronutrient, and AGE intake will be calculated for each dietary period. Additionally, the AGE content of foods used in the study will be measured by ultra performance liquid chromatography mass spectrometry. All measurements will be repeated at the beginning and end of each dietary period. Primary and secondary outcomes will be expressed as a change over the dietary period for insulin sensitivity, secretion, anthropometric parameters, sRAGE, and inflammation markers and compared by paired t test and analysis of variance (ANOVA).ResultsThe study will be completed in early 2016.ConclusionThe proposed trial will provide much needed clinical evidence on the impact of excess dietary AGE consumption on insulin sensitivity and will indicate whether lowering dietary AGE intake can improve insulin sensitivity and/or secretion, thereby decreasing risk for type 2 diabetes.Trial RegistrationClinicaltrials.gov NCT00422253; https://clinicaltrials.gov/ct2/show/NCT00422253 (Archived by Webcite at http://www.webcitation.org/6ZXLhT89c)