A comprehensive review of oral glucosamine use and effects on glucose metabolism in normal and diabetic individuals

Glucosamine (GlcN) is a widely utilized dietary supplement that is used to promote joint health. Reports that oral GlcN supplementation at usual doses adversely affects glucose metabolism in subjects with impaired glucose tolerance have raised concerns that GlcN should be contraindicated in individuals with diabetes and those at risk for developing it. This review addresses its potential, when used at typical doses, to affect glucose metabolism and insulin sensitivity in healthy individuals and those with diabetes or ‘pre-diabetes’. Publicly available scientific information and data on GlcN were systematically compiled using the electronic search tool, Dialog®, and reviewed with special emphasis on human studies. In long-term clinical trials, including those containing subjects with type 2 diabetes or ‘pre-diabetes’, GlcN produced a non-significant lowering of fasting blood glucose concentrations in all groups of subjects treated for periods of up to 3 years. Owing to limitations in study design, conclusions based on studies that report adverse affects of GlcN on insulin sensitivity and glucose tolerance in pre-diabetic subjects are suspect. However, no definitive long-term studies of GlcN use for individuals with pre-diabetes are available. Nevertheless, based on available evidence, we conclude that GlcN has no effect on fasting blood glucose levels, glucose metabolism, or insulin sensitivity at any oral dose level in healthy subjects, individuals with diabetes, or those with impaired glucose tolerance

Distribution patterns of intramyocellular and extramyocellular fat by magnetic resonance imaging in subjects with diabetes, prediabetes and normoglycaemic controls

AIMS: Intramuscular fat contributes to peripheral insulin resistance and type 2 diabetes mellitus (T2DM). Intra- and extramyocellular lipids (IMCLs&EMCLs) may be quantified by magnetic resonance imaging (MRI) and serve as imaging biomarkers in impaired glucose metabolism. MATERIALS & METHODS: Subjects from a population-based cohort were classified with T2DM, prediabetes or normoglycemic controls. Total myosteatosis, IMCLs and EMCLs were quantified by Multi-echo Dixon MRI as proton-density fat-fraction (PDFF in %) in abdominal skeletal muscle. RESULTS: Among 337 included subjects (median age 56.0years (IQR:49.0-64.0years), 56.4% males, median BMI:27.2kg/m2 ) 129(38.3%) were classified with an impaired glucose metabolism (T2DM: 49(14.5%); prediabetes: 80(23.7%)). IMCLs were significantly higher than EMCLs in subjects without obesity (5.7%(IQR: 4.8-7.0%) vs. 4.1%(IQR: 2.7-5.8%), p<0.001), whereas the amount of IMCLs and EMCLs was shown to be equal and significantly higher in subjects with obesity (both 6.7%, p<0.001). Subjects with prediabetes and T2DM had significantly higher amounts of IMCLs and EMCLs as compared to normoglycemic controls (p<0.001). In univariable analysis, prediabetes and T2DM were significantly associated with both, IMCLs (prediabetes: β:0.76, 95%-CI:0.28-1.24, p=0.002; T2DM: β:1.56, 95%-CI:0.66-2.47, p<0.001) and EMCLs (prediabetes: β:1.54, 95%-CI:0.56-2.51, p=0.002; T2DM: β:2.15, 95%-CI:1.33-2.96, p<0.001). After adjustment for age and gender, the association of IMCLs with prediabetes attenuated (p=0.06), whereas for T2DM, both IMCLs and EMCLs remained significantly and positively associated (p<0.02). CONCLUSION: There are significant differences in the amount and distribution ratio of IMCLs and EMCLs between subjects with T2DM, prediabetes and normoglycemic controls. These patterns of intramuscular fat distribution by MRI might therefore serve as imaging biomarkers in both normal and impaired glucose metabolism

Subacute endotoxemia induces adipose inflammation and changes in lipid and lipoprotein metabolism in cats

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10-1000 ng/kg(-1) · h(-1)) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and β-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR

Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation

apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state