S. John Weisnagel

Dietary cod protein improves insulin sensitivity in insulin-resistant men and women: a randomized controlled trial.

OBJECTIVE—The purpose of this article was to compare the effects of cod protein to those of other animal proteins on insulin sensitivity in insulin-resistant human subjects. RESEARCH DESIGN AND METHODS—Insulin sensitivity (M/I) was assessed using a hyperinsulinemic-euglycemic clamp in 19 insulin-resistant subjects fed a cod protein diet and a similar diet containing lean beef, pork, veal, eggs, milk, and milk products (BPVEM) for 4 weeks in a crossover design study. Both diets were formulated to differ only in protein source, thus providing equivalent amounts of dietary fibers and monounsaturated, polyunsaturated (including n-3), and saturated fatty acids (1.1:1.8:1.0). β-Cell function, estimated by oral glucose tolerance test–derived parameters, was also assessed. RESULTS—There was a significant improvement in insulin sensitivity (P = 0.027) and a strong tendency for a better disposition index (β-cell function × M/I) (P = 0.055) in subjects consuming the cod protein diet compared with those consuming the BPVEM diet. When median baseline M/I (4.8 × 10−3 mg · kg−1 · min−1 · pmol−1) was taken into account, an interaction on the 30-min C-peptide–to–30-min glucose ratio, used as an index of β-cell function, was observed between diet and M/I status (P = 0.022). Indeed, this ratio strongly tended to increase in subjects with low M/I consuming the cod protein diet compared with those consuming the BPVEM diet (P = 0.065). CONCLUSIONS—Dietary cod protein improves insulin sensitivity in insulin-resistant individuals and thus could contribute to prevention of type 2 diabetes by reducing the metabolic complications related to insulin resistance.

Prevention of gestational diabetes mellitus: a review of studies on weight management.

Entering pregnancy with overweight, obesity or gaining excessive gestational weight could increase the risk of gestational diabetes mellitus (GDM), which is associated with negative consequences for both the mother and the offspring. The objective of this article was to review scientific evidence regarding the association between obesity and GDM, and how weight management through nutritional prevention strategies could prove successful in reducing the risk for GDM. Studies published between January 1975 and January 2009 on the relationship between GDM, pre‐pregnancy body mass index (BMI), gestational weight gain and nutritional prevention strategies were included in this review. Results from these reports suggest that maternal obesity assessed by pre‐pregnancy BMI is associated with an increased risk of GDM. They also show an association between gestational weight gain and increased risk for GDM. Higher dietary fat and lower carbohydrate intakes during pregnancy appear to be associated with a higher risk for GDM, independent of pre‐pregnancy BMI. Some studies showed that restricting energy and carbohydrates could minimize gestational weight gain. However, a firm conclusion on the most effective nutritional intervention for the control of gestational weight gain and glycaemic responses could not be reached based on available studies. In light of the studies reviewed, we conclude that weight management through nutritional prevention strategies could be successful in reducing the risk of GDM. Further studies are required to identify the most effective diet composition to prevent GDM and excessive gestational weight gain. Copyright

Dietary Cod Protein Reduces Plasma C-Reactive Protein in Insulin-Resistant Men and Women

Chronic low-grade inflammation has been associated with insulin resistance and type 2 diabetes. Recently, we showed that cod protein (CP) improved insulin sensitivity in insulin-resistant subjects. In this study, we investigated the effects of dietary CP compared with those of other animal proteins on plasma concentrations of inflammatory markers, lipids, and lipoproteins in insulin-resistant subjects. Nineteen Caucasian men and women aged 40-65 y, overweight or obese (BMI > 25 kg/m(2)), and insulin resistant, rotated in a crossover design and consumed a CP diet and a similar diet containing lean beef, pork, veal, eggs, milk, and milk products (BPVEM) for 4 wk each. Diets differed only in protein source and thus provided equivalent amounts of dietary fibers, monounsaturated fat, PUFA [including (n-3) fatty acids], and SFA. Blood samples were collected before and after each experimental diet. Notably, the CP diet decreased high-sensitivity C-reactive protein (hsCRP; P = 0.021), whereas the BPVEM diet tended to increase it (P = 0.063), leading to a significant difference between diets (P = 0.041). Changes in plasma interleukin-6, tumor necrosis factor-alpha, and adiponectin concentrations did not differ between diets. Plasma total cholesterol (P = 0.0007), LDL cholesterol (P = 0.014), and apolipoprotein B (P = 0.005) were reduced only by the BPVEM diet. Thus, changes in total cholesterol differed between diets (P = 0.040), whereas changes in LDL cholesterol (P = 0.052) and apolipoprotein B (P = 0.075) tended to differ. Changes in all other lipids and lipoproteins did not differ between diets. Therefore, these results show that CP can lower hsCRP, a marker of inflammation associated with insulin resistance and type 2 diabetes.

Regional body fat distribution and metabolic profile in postmenopausal women

The aim of the study was to examine how body fat distribution variables were associated with metabolic parameters in a sample of 113 postmenopausal women not receiving hormone therapy (56.9 +/- 4.4 years, 28.4 +/- 5.1 kg/m(2)). Body fat distribution variables (visceral adipose tissue [AT], subcutaneous AT, and total midthigh AT) were measured using computed tomography; body fat mass was assessed by hydrostatic weighing; insulin sensitivity was determined with the euglycemic-hyperinsulinemic clamp; fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) concentrations were measured by a 75-g oral glucose load; and (high-sensitivity) C-reactive protein (hs-CRP) was measured using a highly sensitive assay. After controlling for fat mass, visceral AT was positively associated with plasma triglyceride, hs-CRP, FPG, and 2hPG, and negatively associated with high-density lipoprotein cholesterol (HDL-C) and insulin sensitivity. Total midthigh AT was negatively associated with apolipoprotein B, FPG, and 2hPG, and positively associated with insulin sensitivity. Stepwise multiple regression analyses including abdominal visceral AT, subcutaneous AT and total midthigh AT as independent variables showed that abdominal visceral AT best predicted the variance in plasma triglyceride, HDL-C, low-density lipoprotein peak particle size, hs-CRP, FPG, 2hPG, and insulin sensitivity. Abdominal subcutaneous AT was a significant predictor of only insulin sensitivity, whereas total midthigh AT predicted HDL-C, low-density lipoprotein peak particle size, and apolipoprotein B. These multivariate analyses also indicated that total midthigh AT was favorably related to these outcomes, whereas abdominal visceral AT and subcutaneous AT were unfavorably related. These results confirmed that abdominal visceral fat is a critical correlate of metabolic parameters in postmenopausal women. In addition, a higher proportion of AT located in the total midthigh depot is associated with a favorable metabolic profile.

Effects of sitagliptin therapy on markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes

UNLABELLED Inflammation and endothelial dysfunction are increasingly being recognized as key etiological factors in the development of atherosclerosis and subsequent cardiovascular disease. These pro-atherogenic factors are strongly correlated and are often found to co-segregate in patients with type 2 diabetes. The impact of sitagliptin, a selective inhibitor of dipeptidyl peptidase-4, on inflammation and markers of endothelial function remains to be fully characterized. OBJECTIVE The objective of the present study was to examine the effects of treatment with sitagliptin on the plasma levels of various markers of low-grade inflammation and cell adhesion molecules in patients with type 2 diabetes. METHODS AND RESULTS Thirty-six subjects with type 2 diabetes (30 men/6 postmenopausal women with a mean age of 58.1 ± 6.4 years and a body mass index of 30.7 ± 4.9 kg/m²) were recruited into this double-blind, cross-over study using sitagliptin (100mg/d) or placebo, each for a 6-week period, including a 4-week washout period between the two phases. Blood samples were taken at the end of each phase of treatment. Compared with placebo, treatment with sitagliptin significantly reduced the plasma levels of C-reactive protein (CRP) (44.9%, P=0.006), interleukin (IL)-6 (24.7%, P=0.04), IL-18 (7.3%, P=0.004), secreted phospholipase-A₂ (sPLA₂) (12.9%, P=0.04), soluble intercellular adhesion molecule-1 (5.3%, P=0.002), and E-selectin (5.9%, P=0.005). A significant inverse correlation was found between changes in glucagon-like peptide-1 (GLP-1) and changes in CRP levels (r=0.41, P=0.01) following sitagliptin therapy. Sitagliptin therapy had more pronounced effects in subjects with higher levels of inflammatory markers and cell adhesion molecules compared with subjects with lower levels. CONCLUSIONS Treatment with sitagliptin for 6 weeks reduced plasma markers of low-grade inflammation and cell adhesion molecules, most likely by increasing plasma GLP-1 levels and improving glucose-insulin homeostasis. These beneficial effects of sitagliptin might represent a further advantage in the management of diabetes and its proatherogenic comorbidities.

Weight Gain Measures in Women with Gestational Diabetes Mellitus

BACKGROUND Gestational diabetes mellitus (GDM) and excessive gestational weight gain have significant implications for the health of both mother and child. Our objective was to detail gestational weight gain in women in relationship to GDM. METHODS Data were collected by retrospective reviews of medical records in women who delivered between January and December 2007 at the Laval University Medical Center (Quebec, Canada). The analysis included 294 women (55 GDM and 239 controls) for whom gestational weight gain was calculated by the difference between maternal weight measured at delivery, or at the last prenatal visit (≥37th week), and prepregnancy self-reported weight. Gestational weight gain and rate of weight gain were also calculated for each trimester and until GDM screening. Gestational weight gain was compared to the 2009 recommendations by the Institute of Medicine (IOM). Women with GDM were diagnosed and treated according to the Canadian Diabetes Association guidelines. RESULTS Weight gain in the first trimester was significantly higher in GDM patients compared to controls (3.40 ± 0.42 vs. 1.87 ± 0.16 kg, p ≤ 0.01) and was above IOM recommendations, whereas weight gain in the third trimester was significantly lower in GDM patients compared to controls (4.11 ± 0.36 vs. 6.35 ± 0.18 kg, p ≤ 0.0001). Prepregnancy body mass index (BMI) and first trimester weight gain were both significant and independent predictors of GDM (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17, and OR 1.25, 95% CI 1.10-1.42, respectively). CONCLUSIONS First trimester gestational weight gain may need more clinical attention, as it has been identified as an independent and significant risk factor for GDM independent of traditional risk factors, including preconception obesity.

Circulating interleukin-6 concentrations during and after gestational diabetes mellitus.

Objective. Recent studies have shown that high interleukin‐6 (IL‐6) secretion may aggravate insulin resistance in pregnancy and participate in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to determine whether the presence of GDM is associated with elevated IL‐6 concentrations and whether this association remains after delivery, independent of body mass index. Design. Longitudinal study. Setting. Hospital‐based. Sample. Forty‐seven women were screened for GDM with a 75g oral glucose tolerance test at 26.1±3.7 weeks of pregnancy following the Canadian Diabetes Association guidelines (20 GDM, 27 control subjects). Main outcome measures. Interleukin‐6 levels were measured by ELISA at the time of GDM screening and two months post‐partum. Results. Interleukin‐6 concentrations were significantly higher in women with GDM compared with control women at the time of GDM screening (1.47±0.72 vs. 0.90±0.32pg/mL, p≤0.01). Similar results were obtained two months post‐partum, where IL‐6 levels remained significantly higher in women with GDM compared with control women (1.88±0.85 vs. 1.41±0.87pg/mL, p≤0.05). Interleukin‐6 concentrations were significantly correlated with the Matsuda insulin sensitivity index, measured at the two time points (r=–0.60, p≤0.01 and r=–0.34, p≤0.05). The Matsuda insulin sensitivity index was an independent and significant predictor of IL‐6 concentrations at the time of GDM screening, explaining 35.6% of the variance (p≤0.0001) in this variable. IL‐6 concentration measured at GDM screening was identified as an independent and significant predictor of post‐partum IL‐6 concentrations, explaining 28.6% of the variance (p≤0.001). Conclusions. These results show that GDM is associated with elevated IL‐6 levels independent of obesity levels, both during pregnancy and after delivery.

Impact of a lignan-rich diet on adiposity and insulin sensitivity in post-menopausal women

There has been a growing interest in lignans, a class of phyto-oestrogens, because of their potentially favourable effects on human health. The aim of the present study was to compare the metabolic profile of post-menopausal women consuming various amounts of dietary lignans. Phyto-oestrogen intake was assessed using a 3-d dietary record analysed with a Canadian food phyto-oestrogen content data table in 115 post-menopausal women (age 56.8 (SD 4.4) years and BMI 28.5 (SD 5.9) kg/m(2)). Plasma enterolactone (ENL), the major biologically active metabolite of dietary lignans, was determined by time-resolved fluoroimmunoassay. Anthropometrics, abdominal adipose tissue areas (computed tomography), body composition (hydrostatic weighing) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured in all women. Women in the high dietary lignan intake subgroup (n 29) had a significantly lower BMI and total body fat mass, as well as a better glucose disposal rate (GDR; P < 0.05), compared with women in the low lignan intake subgroup (n 28). The majority of women with the highest dietary lignan intake were also in the highest quartile of plasma ENL (59 %). Women in the highest ENL quartile had a significantly lower BMI (26.1 (SD 4.4) v. 30.4 (SD 6.9) kg/m(2), P < 0.05), total body fat mass (24.8 (SD 9.8) v. 33.3 (SD 13.3) kg, P < 0.05), 2 h postload glycaemia (5.5 (SD 0.9) v. 5.7 (sd 0.8) nmol/l, P < 0.05) and a higher GDR (8.3 (SD 2.7) v. 5.5 (SD 2.8), P < 0.01) compared with women in the lowest ENL quartile. In conclusion, women with the highest ENL concentrations had a better metabolic profile including higher insulin sensitivity and lower adiposity measures.

Androgens in the maternal and fetal circulation: association with insulin resistance.

Objective: To examine maternal insulin resistance in relationship with maternal and fetal androgen levels as well as with term placenta mRNA and protein abundance of steroidogenic enzymes implicated in androgen dynamics. Methods: The study included 20 women with gestational diabetes mellitus and 27 controls tested using a 120 min., 75 g oral glucose tolerance test. Maternal and fetal plasma concentrations of total testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone (DHEA) were measured by high-performance gas chromatography and chemical ionization mass spectrometry at 26.1 ± 3.7 weeks of pregnancy. Results: Glycemic response to oral glucose over 120 min. as well as Matsuda insulin sensitivity and HOMA insulin resistance (HOMA-IR) indices were significantly associated with maternal testosterone levels (r = 0.31, r = −0.37 and r = 0.35 respectively, p ≤ 0.05 for all). Among male offspring, a positive association between maternal and fetal testosterone levels was observed (r = 0.43, p ≤ 0.05). Testosterone levels were higher in the cord blood of newborns from insulin-resistant mothers compared to newborns from insulin-sensitive mothers (0.48 ± 0.36 nmol/L vs. 0.29 ± 0.18 nmol/L p ≤ 0.05). No difference was observed in mRNA abundance or protein expression of placental steroidogenic enzymes according to the degree of maternal insulin resistance. Conclusion: Our results demonstrate a possible association between fetal and maternal androgen concentrations in relationship with insulin resistance.

The WHO and NCEP/ATPIII Definitions of the Metabolic Syndrome in Postmenopausal Women: Are They So Different?

BACKGROUND The aim of this study was to examine the metabolic risk profile in postmenopausal women characterized by either the metabolic syndrome (MS) as defined by the World Health Organization (WHO) or the National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII). METHODS One hundred and eight postmenopausal women (56.9 +/- 4.2 years; 28.5 +/- 5.9 kg/m(2)) were examined. Each underwent an oral glucose tolerance test, an euglycemic-hyperinsulinemic clamp, an assessment of body fat distribution by computed tomography, a complete plasma lipid-lipoprotein profile, and standard measurements of inflammatory markers. RESULTS The prevalence of the MS-WHO was 29.6% in our women. Type 2 diabetes was found in 28.1% of women with the MS-WHO. Thirty-one percent of women had the MS-ATP, from which 36.4% had type 2 diabetes. Among the 32 women identified as having MS-WHO, 25 (78.1 %) were also identified as having the MS-ATP. On the other hand, among the 34 women identified as having MS-ATP, 24 (70.0 %) also had MS-WHO (kappa = 0.60). When we subdivided our sample of women as having either isolated MS-WHO, isolated MS-ATP, or combined MS-WHO and MS-ATP, we observed a more deteriorated metabolic risk profile (higher values for visceral adipose tissue, 2-h plasma glucose, and lower HDL-cholesterol concentrations) in women characterized by isolated MS-ATP compared to women with isolated MS-WHO. CONCLUSIONS These results suggest that, in postmenopausal women, the concordance in the identification of subjects with the MS using each of the proposed definitions is only moderate.