Diabetes, insulin treatment, and cancer risk:what is the evidence?

Diabetes, in particular type 2, is associated with an increased incidence of cancer. Although the mortality attributable to cancer in type 2 diabetes is overshadowed by that due to cardiovascular disease, emerging data from epidemiologic studies suggest that insulin therapy may confer added risk for cancer, perhaps mediated by signaling through the IGF-1 (insulin-like growth factor-1) receptor. Co-administered metformin seems to mitigate the risk associated with insulin. A recent series of publications in Diabetologia addresses the possibility that glargine, the most widely used long-acting insulin analogue, may confer a greater risk than other insulin preparations, particularly for breast cancer. This has led to a heated controversy. Despite this, there is a consensus that the currently available data are not conclusive and should not be the basis for any change in practice. Further studies and more thorough surveillance of cancer in diabetes are needed to address this important issue.

Increased serum kallistatin levels in type 1 diabetes patients with vascular complications

Kallistatin, a serpin widely produced throughout the body, has vasodilatory, anti-angiogenic, anti-oxidant, and anti-inflammatory effects. Effects of diabetes and its vascular complications on serum kallistatin levels are unknown.

Low clusterin levels in high-density lipoprotein associate with insulin resistance, obesity, and dyslipoproteinemia

To determine whether obesity and insulin resistance associate with changes in the protein content of high-density lipoprotein (HDL) in 2 different groups of men by using targeted proteomics.

Strawberries decrease atherosclerotic markers in subjects with metabolic syndrome

Strawberries have been reported to be potent antioxidants and reduce cardiovascular risk factors, such as elevated blood pressure, hyperglycemia, dyslipidemia, and inflammation in limited studies. We hypothesized that freeze-dried strawberry supplementation will improve blood pressure, impaired glucose, dyslipidemia, or circulating adhesion molecules in obese subjects with metabolic syndrome, thereby lowering cardiovascular risk factors in these subjects. Twenty-seven subjects with metabolic syndrome (2 males and 25 females; body mass index, 37.5 +/- 2.15 kg/m(2); age, 47.0 +/- 3.0 years [means +/- SE]) consumed 4 cups of freeze-dried strawberry beverage (50 g freeze-dried strawberries approximately 3 cups fresh strawberries) or equivalent amounts of fluids (controls, 4 cups of water) daily for 8 weeks in a randomized controlled trial. Anthropometrics and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screen and 8 weeks of the study. Strawberry supplementation significantly decreased total and low-density lipoprotein cholesterol (5.8 +/- 0.2 to 5.2 +/- 0.2 mmol/L and 3.5 +/- 0.2 to 3.1 +/- 0.1 mmol/L, respectively [means +/- SE], P <.05) and small low-density lipoprotein particles using nuclear magnetic resonance-determined lipoprotein subclass profile vs controls at 8 weeks (794.6 +/- 94.0 to 681.8 +/- 86.0 nmol/L [means +/- SE], P <.05). Strawberry supplementation further decreased circulating levels of vascular cell adhesion molecule-1 vs controls at 8 weeks (272.7 +/- 17.4 to 223.0 +/- 14.0 ng/mL [means +/- SE], P <.05). Serum glucose, triglycerides, high-density lipoprotein cholesterol, blood pressure, and waist circumference were not affected. Thus, short-term freeze-dried strawberry supplementation improved selected atherosclerotic risk factors, including dyslipidemia and circulating adhesion molecules in subjects with metabolic syndrome, and these results need confirmation in future trials.

Dose-dependent effects of the once-daily GLP-1 receptor agonist lixisenatide in patients with Type 2 diabetes inadequately controlled with metformin:a randomized, double-blind, placebo-controlled trial

To evaluate the dose-response relationship of lixisenatide (AVE0010), a glucagon-like peptide-1 (GLP-1) receptor agonist, in metformin-treated patients with Type 2 diabetes.

Blueberries decrease cardiovascular risk factors in obese men and women with metabolic syndrome

Among all fruits, berries have shown substantial cardio-protective benefits due to their high polyphenol content. However, investigation of their efficacy in improving features of metabolic syndrome and related cardiovascular risk factors in obesity is limited. We examined the effects of blueberry supplementation on features of metabolic syndrome, lipid peroxidation, and inflammation in obese men and women. Forty-eight participants with metabolic syndrome [4 males and 44 females; BMI: 37.8 +/- 2.3 kg/m(2); age: 50.0 +/- 3.0 y (mean +/- SE)] consumed freeze-dried blueberry beverage (50 g freeze-dried blueberries, approximately 350 g fresh blueberries) or equivalent amounts of fluids (controls, 960 mL water) daily for 8 wk in a randomized controlled trial. Anthropometric and blood pressure measurements, assessment of dietary intakes, and fasting blood draws were conducted at screening and at wk 4 and 8 of the study. The decreases in systolic and diastolic blood pressures were greater in the blueberry-supplemented group (- 6 and - 4%, respectively) than in controls (- 1.5 and - 1.2%) (P lt 0.05), whereas the serum glucose concentration and lipid profiles were not affected. The decreases in plasma oxidized LDL and serum malondialdehyde and hydroxynonenal concentrations were greater in the blueberry group (- 28 and - 17%, respectively) than in the control group (- 9 and - 9%) (P lt 0.01). Our study shows blueberries may improve selected features of metabolic syndrome and related cardiovascular risk factors at dietary achievable doses.

Green tea minimally affects biomarkers of inflammation in obese subjects with metabolic syndrome

Green tea (Camellia sinensis) has shown to exert cardioprotective benefits in observational studies. The objective of this clinical trial was to assess the effects of green tea on features of metabolic syndrome and inflammation in obese subjects.

LDL-containing immune complexes in the DCCT/EDIC cohort:associations with lipoprotein subclasses

Immune complexes containing modified LDL (LDL-IC) and NMR-determined Total LDL particle concentrations are significantly associated with intima-media thickness (IMT). We analyzed the associations between concentrations of NMR-determined lipoprotein subclasses and LDL-IC in the DCCT/EDIC cohort. LDL-IC concentrations in women and men of the DCCT/EDIC cohort did not differ significantly and were positively associated with Total LDL particle concentrations in men and women (r=0.34, r=0.32, respectively; P

Green tea supplementation affects body weight, lipids, and lipid peroxidation in obese subjects with metabolic syndrome

To compare the effects of supplementation of green tea beverage or green tea extracts with controls on body weight, glucose and lipid profile, biomarkers of oxidative stress, and safety parameters in obese subjects with metabolic syndrome.

Berries:emerging impact on cardiovascular health

Berries are a good source of polyphenols, especially anthocyanins, micronutrients, and fiber. In epidemiological and clinical studies, these constituents have been associated with improved cardiovascular risk profiles. Human intervention studies using chokeberries, cranberries, blueberries, and strawberries (either fresh, or as juice, or freeze-dried), or purified anthocyanin extracts have demonstrated significant improvements in LDL oxidation, lipid peroxidation, total plasma antioxidant capacity, dyslipidemia, and glucose metabolism. Benefits were seen in healthy subjects and in those with existing metabolic risk factors. Underlying mechanisms for these beneficial effects are believed to include upregulation of endothelial nitric oxide synthase, decreased activities of carbohydrate digestive enzymes, decreased oxidative stress, and inhibition of inflammatory gene expression and foam cell formation. Though limited, these data support the recommendation of berries as an essential fruit group in a heart-healthy diet.

Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo

The oxidation of LDLs is considered a key step in the development of atherosclerosis. How LDL oxidation contributes to atherosclerosis remains poorly defined. Here we report that oxidized and glycated LDL (HOG-LDL) causes aberrant endoplasmic reticulum (ER) stress and that the AMP-activated protein kinase (AMPK) suppressed HOG-LDL-triggered ER stress in vivo.

Know your diabetes risk project:Student pharmacists educating adults about diabetes risk in a community pharmacy setting

To determine the feasibility of educating adults about their risk of prediabetes/diabetes in a community pharmacy, to determine the common risk factors for prediabetes/diabetes in adults visiting a community pharmacy, and to assess any association between risk factors and age.

Activation of the Wnt pathway plays a pathogenic role in diabetic retinopathy in humans and animal models

Although Wnt signaling is known to mediate multiple biological and pathological processes, its association with diabetic retinopathy (DR) has not been established. Here we show that retinal levels and nuclear translocation of beta-catenin, a key effector in the canonical Wnt pathway, were increased in humans with DR and in three DR models. Retinal levels of low-density lipoprotein receptor-related proteins 5 and 6, coreceptors of Wnts, were also elevated in the DR models. The high glucose-induced activation of beta-catenin was attenuated by aminoguanidine, suggesting that oxidative stress is a direct cause for the Wnt pathway activation in diabetes. Indeed, Dickkopf homolog 1, a specific inhibitor of the Wnt pathway, ameliorated retinal inflammation, vascular leakage, and retinal neovascularization in the DR models. Dickkopf homolog 1 also blocked the generation of reactive oxygen species induced by high glucose, suggesting that Wnt signaling contributes to the oxidative stress in diabetes. These observations indicate that the Wnt pathway plays a pathogenic role in DR and represents a novel therapeutic target.

Freeze-dried strawberry powder improves lipid profile and lipid peroxidation in women with metabolic syndrome:baseline and post intervention effects

Strawberry flavonoids are potent antioxidants and anti-inflammatory agents that have been shown to reduce cardiovascular disease risk factors in prospective cohort studies. Effects of strawberry supplementation on metabolic risk factors have not been studied in obese populations. We tested the hypothesis that freeze-dried strawberry powder (FSP) will lower fasting lipids and biomarkers of oxidative stress and inflammation at four weeks compared to baseline. We also tested the tolerability and safety of FSP in subjects with metabolic syndrome. FSP is a concentrated source of polyphenolic flavonoids, fiber and phytosterols.

Insulin-like growth factor binding protein-3 mediates vascular repair by enhancing nitric oxide generation

Insulin-like growth factor binding protein (IGFBP)-3 modulates vascular development by regulating endothelial progenitor cell (EPC) behavior, specifically stimulating EPC cell migration. This study was undertaken to investigate the mechanism of IGFBP-3 effects on EPC function and how IGFBP-3 mediates cytoprotection following vascular injury.