Oxidative and inflammatory status in Type 2 diabetes patients with periodontitis

Aim: To determine the impact of periodontitis on oxidative/inflammatory status and diabetes control in Type 2 diabetes. Materials and Methods: A comparative study of 20 Type 2 diabetes patients with periodontitis [body mass index (BMI) 31+5], 20-age/gender-matched, non-periodontitis Type 2 diabetes controls (BMI 29+6) and 20 non-diabetes periodontitis controls (BMI 25+4) had periodontal examinations and fasting blood samples collected. Oxidative stress was determined by plasma small molecule antioxidant capacity (pSMAC) and protein carbonyl levels; inflammatory status by total/differential leucocytes, fibrinogen and high sensitivity C-reactive protein (hsCRP); diabetes status by fasting glucose, HbA1c, lipid profile, insulin resistance and secretion. Statistical analysis was performed using SPSS. Results: pSMAC was lower (p=0.03) and protein carbonyls higher (p=0.007) in Type 2 diabetes patients with periodontitis compared with those without periodontitis. Periodontitis was associated with significantly higher HbA1c (p=0.002) and fasting glucose levels (p=0.04) and with lower ß-cell function (HOMA-ß; p=0.01) in diabetes patients. Periodontitis had little effect on inflammatory markers or lipid profiles, but Type 2 diabetes patients with periodontitis had higher levels of hsCRP than those without diabetes (p=0.004) and the lowest levels of HDL-cholesterol of all groups. Conclusion: Periodontitis is associated with increased oxidative stress and compromised glycaemic control in Type 2 diabetes patients.

Editorial : which weight loss diet?

Full editorial: A recent study evaluating the long-term (2 yr) weight reducing efficacy of different types of diets – high or low in carbohydrates (CHOs), protein or fat - confirmed that it is calorie deficit not dietary composition that determines the loss and maintenance of body weight.1 Is there any advantage in following a specific weight loss diet? Short-term use of nutritionally complete commercially available (very) low calorie diets has benefited people with diabetes when  supported by education programmes.2 Initial weight loss has been encouraging with some fad diets eg the Atkins and the South Beach diets, but these diets are difficult to maintain and there are safety issues regarding their short- and long-term use – especially in people with diabetes.3 The types of macronutrients consumed can have a considerable impact on glycaemic control and energy metabolism. Although a low CHO diet additionally enhances initial weight loss by reducing cellular water content, if fat is not proportionally reduced the diet may not benefit the lipid profile for vascular disease risk. High fat and high protein diets – which are simultaneously low in CHOs – increase vulnerability to hypoglycaemia in people taking insulin secretagogues or on insulin therapy, and may promote excess fat metabolism and ketogenesis, particularly in people vulnerable to lack of insulin. Very low protein diets are not recommended as lean body mass tends to be reduced in diabetes. Altering the macronutrient balance has implications for the micronutrient mix: deficiencies are higher if more foods are excluded and conversely specific micronutrient excess can occur with some fad diets. The altered nutrient mix affects intestinal fauna and flora, and gut motility and glycaemic control are influenced by the quantity and type of fibre consumed. Support programmes help individuals achieve long term weight loss and there is mounting evidence that community schemes which educate and promote lifestyle changes may stem the rising tide of obesity and consequent type 2 diabetes.4 Consuming smaller portions of a balanced diet (and adjusting antidiabetic medications accordingly) will create an energy deficit to promote healthy weight loss. Increased movement/exercise will enhance this energy deficit. Knowledge (eg 1g fat has 2.25 times more energy than 1g CHO) allows sensible food choices and compensation for inclusion of small volumes of  ‘naughty but nice’ foods. Ultimately weight control requires self control. References 1. Sacks FM, Bray GA, Carey VJ et al. Comparison of weight-loss diets with different compositions of fat, protein, and carbohydrates. N Engl J Med 2009;360:859–73. 2. Bennett P. Obesity, diabetes and VLCD. Br J Diabetes Vasc Dis 2004;4:328–30. 3. Baldwin EJ. Fad diets in diabetes. Br J Diabetes Vasc DIs 2004;4:333–7. 4. Romon M, Lommoz A, Tafflet M et al. Downward trends in the prevalence of childhood overweight in the setting of 12-year school- and community-based programmes. Public Health Nutr 2008; Dec 28, 1–8 [Epub ahead of print].

Treatment with metformin

Metformin is an anti-hyperglycaemic agent widely used in the treatment of type 2 diabetes. It counters insulin resistance through insulin-dependent and -independent effects on cellular nutrient and energy metabolism, improving glycaemic control without weight gain and without increasing the risk of hypoglycaemia. Metformin can also benefit several risk factors for vascular disease independently of glycaemic control. In subjects with metabolic syndrome, metformin improves prognosis. It decreases progression of impaired glucose tolerance to type 2 diabetes, assists weight reduction especially in conjunction with lifestyle management and exerts other potentially favourable cardiovascular effects. For example, metformin can modestly improve the lipid profile in some dyslipidaemic individuals, reduce pro-inflammatory cytokines and monocyte adhesion molecules and decrease advanced glycation end products. Metformin can also improve parameters of endothelial function in the macro- and micro-vasculature, indicating lower athero-thrombotic risk, but it does not appear to reduce blood pressure. In normoglycaemic individuals with risk factors for diabetes and in women with polycystic ovary syndrome there is evidence that metformin can defer or prevent the development of diabetes. Thus, metformin offers beneficial effects to delay the onset and reverse or reduce the progression of many of the metabolic features and cardiovascular risk factors associated with metabolic syndrome.

A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL

Lipidome profile of fluids and tissues is a growing field as the role of lipids as signaling molecules is increasingly understood, relying on an effective and representative extraction of the lipids present. A number of solvent systems suitable for lipid extraction are commonly in use, though no comprehensive investigation of their effectiveness across multiple lipid classes has been carried out. To address this, human LDL from normolipidemic volunteers was used to evaluate five different solvent extraction protocols [Folch, Bligh and Dyer, acidified Bligh and Dyer, methanol (MeOH)-tert-butyl methyl ether (TBME), and hexane-isopropanol] and the extracted lipids were analyzed by LC-MS in a high-resolution instrument equipped with polarity switching. Overall, more than 350 different lipid species from 19 lipid subclasses were identified. Solvent composition had a small effect on the extraction of predominant lipid classes (triacylglycerides, cholesterol esters, and phosphatidylcholines). In contrast, extraction of less abundant lipids (phosphatidylinositols, lyso-lipids, ceramides, and cholesterol sulfates) was greatly influenced by the solvent system used. Overall, the Folch method was most effective for the extraction of a broad range of lipid classes in LDL, although the hexane-isopropanol method was best for apolar lipids and the MeOH-TBME method was suitable for lactosyl ceramides. Copyright © 2013 by the American Society for Biochemistry and Molecular Biology, Inc.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.

Age-associated changes in long-chain fatty acid profile during healthy aging promote pro-inflammatory monocyte polarization via PPARγ

Differences in lipid metabolism associate with age-related disease development and lifespan. Inflammation is a common link between metabolic dysregulation and aging. Saturated fatty acids (FAs) initiate pro-inflammatory signalling from many cells including monocytes; however, no existing studies have quantified age-associated changes in individual FAs in relation to inflammatory phenotype. Therefore, we have determined the plasma concentrations of distinct FAs by gas chromatography in 26 healthy younger individuals (age < 30 years) and 21 healthy FA individuals (age > 50 years). Linear mixed models were used to explore the association between circulating FAs, age and cytokines. We showed that plasma saturated, poly- and mono-unsaturated FAs increase with age. Circulating TNF-α and IL-6 concentrations increased with age, whereas IL-10 and TGF-β1 concentrations decreased. Oxidation of MitoSOX Red was higher in leucocytes from FA adults, and plasma oxidized glutathione concentrations were higher. There was significant colinearity between plasma saturated FAs, indicative of their metabolic relationships. Higher levels of the saturated FAs C18:0 and C24:0 were associated with lower TGF-β1 concentrations, and higher C16:0 were associated with higher TNF-α concentrations. We further examined effects of the aging FA profile on monocyte polarization and metabolism in THP1 monocytes. Monocytes preincubated with C16:0 increased secretion of pro-inflammatory cytokines in response to phorbol myristate acetate-induced differentiation through ceramide-dependent inhibition of PPARγ activity. Conversely, C18:1 primed a pro-resolving macrophage which was PPARγ dependent and ceramide dependent and which required oxidative phosphorylation. These data suggest that a midlife adult FA profile impairs the switch from proinflammatory to lower energy, requiring anti-inflammatory macrophages through metabolic reprogramming.