Advanced glycation end products are not associated with bone mineral density, trabecular bone score, and bone turnover markers in adults with and without type 1 diabetes: a cross-sectional study.

It is unclear if AGEs are involved in the bone fragility of type 1 diabetes (T1D). We evaluated whether skin AGEs by skin autofluorescence and serum AGEs (pentosidine, carboxymethyl-lysine [CML]) are independently associated with BMD by DXA (lumbar spine, hip, distal radius), trabecular bone score (TBS), serum bone turnover markers (BTMs: CTX; P1NP; osteocalcin), and sclerostin in participants with and without T1D. Linear regression models were used, with interaction terms to test effect modification by T1D status. In participants with T1D, correlations between skin and serum AGEs as well as between AGEs and 3-year HbA1C were evaluated using Spearman's correlations. Data are mean ± SD or median (interquartile range). We included individuals who participated in a cross-sectional study and had BMD and TBS assessment (106 T1D/65 controls, 53.2% women, age 43 ± 15 yr, BMI 26.6 ± 5.5 kg/m2). Participants with T1D had diabetes for 27.6 ± 12.3 yr, a mean 3-yr HbA1C of 7.5 ± 0.9% and skin AGEs of 2.15 ± 0.54 arbitrary units. A subgroup of 65 T1D/57 controls had BTMs and sclerostin measurements, and those with T1D also had serum pentosidine (16.8[8.2-32.0] ng/mL) and CML [48.0 ± 16.8] ng/mL) measured. Femoral neck BMD, TBS, and BTMs were lower, while sclerostin levels were similar in participants with T1D vs controls. T1D status did not modify the associations between AGEs and bone outcomes. Skin AGEs were significantly associated with total hip and femoral neck BMD, TBS, BTMs, and sclerostin before, but not after, adjustment for confounders. Serum AGEs were not associated with any bone outcome. There were no significant correlations between skin and serum AGEs or between AGEs and 3-yr HbA1C. In conclusion, skin and serum AGEs are not independently associated with BMD, TBS, BTMs, and sclerostin in participants with relatively well-controlled T1D and participants without diabetes.

Marginal Impact of Brown Seaweed Ascophyllum nodosum and Fucus vesiculosus Extract on Metabolic and Inflammatory Response in Overweight and Obese Prediabetic Subjects.

The objective of the present study was to test whether a brown seaweed extract rich in polyphenols combined with a low-calorie diet would induce additional weight loss and improve blood glucose homeostasis in association with a metabolic and inflammatory response in overweight/obese prediabetic subjects. Fifty-six overweight/obese, dysglycemic, and insulin-resistant men and women completed a randomized, placebo-controlled, double-blind, and parallel clinical trial. Subjects were administrated 500 mg/d of either brown seaweed extract or placebo combined with individualized nutritional advice for moderate weight loss over a period of 12 weeks. Glycemic, anthropometric, blood pressure, heart rate, body composition, lipid profile, gut integrity, and oxidative and inflammatory markers were measured before and at the end of the trial. No effect was observed on blood glucose. We observed significant but small decreases in plasma C-peptide at 120 min during 2 h-OGTT (3218 ± 181 at pre-intervention vs. 2865 ± 186 pmol/L at post-intervention in the brown seaweed group; 3004 ± 199 at pre-intervention vs. 2954 ± 179 pmol/L at post-intervention in the placebo group; changes between the two groups, p = 0.002), heart rate (72 ± 10 at pre-intervention vs. 69 ± 9 (n/min) at post-intervention in the brown seaweed group; 68 ± 9 at pre-intervention vs. 68 ± 8 (n/min) at post-intervention in the placebo group; changes between the two groups, p = 0.01), and an inhibition in the increase of pro-inflammatory interleukin-6 (IL-6) (1.3 ± 0.7 at pre-intervention vs. 1.5 ± 0.7 pg/L at post-intervention in the brown seaweed group; 1.4 ± 1.1 at pre-intervention vs. 2.2 ± 1.6 pg/L at post-intervention in the placebo group; changes between the two groups, p = 0.02) following brown seaweed consumption compared with placebo in the context of moderate weight loss. Although consumption of brown seaweed extract had no effect on body weight or blood glucose, an early attenuation of the inflammatory response was observed in association with marginal changes in metabolic parameters related to the prevention of diabetes type 2.

Impact of a High Intake of Dairy Product on Insulin Sensitivity in Hyperinsulinemic Adults: A Crossover Randomized Controlled Trial.

BACKGROUND: Dairy product intake has been associated with decreased risk of type 2 diabetes (T2D) in cohort studies. However, results from clinical trials on T2D-related risk factors remain inconclusive. OBJECTIVE: The aim of this clinical trial was to evaluate the impact of high dairy product intake (HD) (≥4 servings/d) for 6 wk, compared with an adequate dairy product intake (AD) (≤2 servings/d), on glycemic and insulinemic parameters, insulin sensitivity, insulin secretion, and ß-cell function in hyperinsulinemic adults. METHODS: In this crossover clinical trial, hyperinsulinemic adults were randomly assigned to HD or AD for 6 wk, then crossed over after a 6-wk washout period. Serum glucose, insulin, C-peptide, HOMA-IR, Matsuda index, insulinogenic index, and disposition index were measured and analyzed using a repeated-measures mixed model adjusted for age, sex, and BMI. Anthropometric measures were collected and food intake was evaluated using a validated FFQ. RESULTS: Nineteen men and 8 women completed the study (mean ± SD age: 55 ± 14 y; BMI: 31.3 ± 3.3 kg/m2. Dairy product intake was 5.8 servings/d in the HD condition and 2.3 servings/d in the AD condition after 6 wk. No difference was observed between HD and AD after 6 wk for all outcomes. CONCLUSIONS: HD does not affect glycemic and insulinemic parameters, insulin sensitivity, insulin secretion, and ß-cell function over AD in hyperinsulinemic adults. Additional larger and longer studies assessing T2D-related risk factors are required. This trial was registered at clinicaltrials.gov as NCT02961179.

Increased Dairy Product Intake Alters Serum Metabolite Profiles in Subjects at Risk of Developing Type 2 Diabetes.

SCOPE: Metabolomics is increasingly used to identify biomarkers of diet or chronic diseases, such as type 2 diabetes. Yet, metabolite signatures following dairy intake in hyperinsulinemic subjects have not been identified. The objective is to evaluate the effects of a high dairy diet (HD) for 6 weeks (4 servings or more per day), compared with an adequate dairy diet (AD) (2 servings or less per day), on serum metabolite profiles in hyperinsulinemic adults. METHODS AND RESULTS: In this crossover trial, subjects are randomized to HD or AD for 6 weeks. Serum metabolites are assessed using GC/MS. Twenty-six subjects completed the study. Levels of pentadecanoic acid, tyrosine and lathosterol are increased in HD, while 1,5-anhydrosorbitol, myo-inositol, 3-aminoisobutyric acid and beta-sitosterol are decreased (p < 0.05). Sorbitol levels are increased after AD, while hexanoic acid, lauric acid, l-kynurenine, methionine, and benzoic acid levels are reduced (p < 0.05). Histidine, caprylic acid, nonanoic acid, decanoic acid, lauric acid, heptadecanoic acid, and benzoic acid levels are increased in HD compared to AD, while malic acid levels are increased in AD compared with HD (p < 0.05). CONCLUSION: Higher dairy products intake modifies metabolite profiles in hyperinsulinemic subjects.

Visceral adipose tissue accumulation and cardiovascular disease risk profile in postmenopausal women with impaired glucose tolerance or type 2 diabetes.

OBJECTIVE: Women with impaired glucose tolerance (IGT) and type 2 diabetes (T2D) are more at risk of cardiovascular disease. The aim of this study was to test the hypothesis that increased visceral adipose tissue (VAT) could explain to a large extent alterations in the cardiovascular disease risk profile of postmenopausal women with IGT or T2D. DESIGN, PATIENTS AND MEASUREMENTS: Sixty-two women with normal glucose tolerance (NGT), 33 with IGT and 18 with de novo diagnosed T2D were tested. The sample was further divided into five groups: (i) NGT-low VAT (<130 cm(2) ); (ii) NGT-high VAT (≥130 cm(2)); (iii) IGT-low VAT (<130 cm(2) ); (iv) IGT-high VAT (≥130 cm(2) ) and (v) T2D. RESULTS: Women with T2D, women with IGT-high VAT and those with NGT-high VAT all had lower insulin sensitivity as determined by the euglycaemic-hyperinsulinaemic clamp (M_I), higher triglyceride (TG), lower HDL(2)-cholesterol (chol) levels and higher levels of high-sensitivity C-reactive protein than women with NGT-low VAT. Only differences in M_I and early insulin response (EIR) were observed between women with IGT-high VAT and those with NGT-high VAT (lower values in IGT-high VAT). Women with T2D had lower M_I and EIR as well as higher plasma TG and lower plasma Apo A1 and HDL-chol concentrations than women with NGT-high VAT. CONCLUSIONS: Our results suggest that increase in VAT accumulation usually found in women with IGT explains to a large extent the deterioration in their plasma lipid-lipoprotein and inflammatory profile. However, factors other than VAT are involved in explaining the high TG-low HDL dyslipidaemia observed in women with T2D.

Discordances among different tools used to estimate cardiovascular risk in postmenopausal women.

BACKGROUND: New cardiovascular disease (CVD) risk factors are being recognized and suggested to be included in CVD risk stratification. High-sensitivity C-reactive protein (hs-CRP) and the metabolic syndrome (MetS) are among these risk factors. However, CVD risk classification may be divergent when using different approaches. OBJECTIVES: To compare differences in CVD risk estimation using the Framingham risk score (FRS), hs-CRP and the presence of the MetS in a group of 109 postmenopausal women in primary CVD prevention. METHODS: The FRS and presence of the MetS were determined. CVD risk was evaluated with a cardiovascular point scoring system based on Framingham covariables and hs-CRP values (Women's Health Study [WHS] model). The estimated CVD risks based on hs-CRP levels and the WHS model were compared with the FRS. RESULTS: Using the FRS, 99% of women (n=108) were determined to have a low CVD risk. The MetS was identified in 39.4% (n=43) of the women. When hs-CRP was used alone to estimate CVD risk, 37.6% (n=41) of women were classified as being at low, 33.9% (n=37) at moderate and 28.4% (n=31) at high CVD risk. With the WHS model, 83.5% (n=91), 14.7% (n=16) and 1.8 % (n=2) of women were classified as being at low, moderate and high CVD risk, respectively. CONCLUSIONS: A substantial number of postmenopausal women showing evidence of the MetS were not identified by the FRS, even though women with the MetS are at higher risk of CVD. Estimation of risk by hs-CRP is significantly divergent when using conventional hs-CRP cutoff values compared with an integrated use in the WHS model.

Relation of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor-alpha, and fibrinogen to abdominal adipose tissue, blood pressure, and cholesterol and triglyceride levels in healthy postmenopausal women.

The associations of inflammatory markers (high-sensitivity C-reactive protein [hs-CRP], interleukin-6 [IL-6], tumor necrosis factor-alpha, and fibrinogen) with anthropometric and metabolic variables were examined in a sample of 112 postmenopausal women not receiving hormone therapy. Body fat distribution was measured by computed tomography, and insulin sensitivity was determined by an euglycemic-hyperinsulinemic clamp. hs-CRP (0.10 < or = r(2) < or =0.37) and IL-6 (0.06 < or = r(2) < or =0.31) were significantly associated with anthropometric and metabolic variables, including visceral and subcutaneous adipose tissue, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein (HDL) cholesterol, and insulin sensitivity (p <0.05). Women with greater hs-CRP concentrations showed deterioration in their metabolic risk profiles, including abdominal obesity, greater triglyceride and lower HDL cholesterol concentrations, and lower insulin sensitivity compared with women with lower hs-CRP levels. Fifty-nine percent of women with high hs-CRP concentrations had the metabolic syndrome as recently defined by the Third Report of the National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. After adjustment for visceral adipose tissue, most of the differences in the plasma lipid-lipoprotein profile were eliminated between women with high hs-CRP levels and women with low hs-CRP levels, whereas some differences in blood pressure variables, insulin sensitivity, and inflammatory markers (IL-6 and fibrinogen) remained significant. In conclusion, these results suggest that increased visceral adipose tissue levels appear to be a determinant covariable of the association between high hs-CRP concentrations and alteration in the metabolic profile.