Terezie Pelikanova

Vegetarian diet improves insulin resistance and oxidative stress markers more than conventional diet in subjects with Type 2 diabetes

Diabet. Med. 28, 549–559 (2011)

Insulin secretion and insulin action related to the serum phospholipid fatty acid pattern in healthy men

In order to decide whether the phospholipid fatty acid pattern is related to variables determining glucose tolerance, 11 healthy volunteers with normal glucose tolerance were studied. The relationship was evaluated between the proportions of individual fatty acids (FA) in serum phospholipids and (1) insulin secretion, determined by fasting and postglucose plasma insulin levels, and (2) in vivo insulin action, assessed as metabolic clearance rates of glucose during euglycemic clamp studies at two insulin concentrations of approximately 70 microU/mL (MCRglu70) and 500 microU/mL (MCRglu500). It was found that both insulin secretion and insulin action are significantly related to the ratio of omega-6 class essential FA to saturated FA in serum phospholipids. An increase of this ratio is associated with a decrease in total insulin response (r = -0.84, P less than .01), and an increase in MCRglu70 (r = .66, P less than .05) and MCRglu500 (r = .82, P less than .01). The data presented support the hypothesis that phospholipid FA composition might play a role in blood glucose regulation.

Insulin sensitivity and counter-regulatory hormones in hypothyroidism and during thyroid hormone replacement therapy.

Abstract We examined insulin sensitivity and secretion, together with the levels of selected glucoregulatory hormones, in 15 female patients with severe hypothyroidism (H) and during subsequent thyroid hormone replacement therapy (HRT) using the euglycaemic hyperinsulinaemic clamp technique. Insulin action, as evaluated by glucose disposal, the insulin sensitivity index, and fasting post-hepatic insulin delivery rate were established. The basal levels of insulin, C-peptide and counter-regulatory hormones were measured in basal condition. In H, glucose disposal (p<0.01), the insulin sensitivity index (p<0.01) and post-hepatic insulin delivery rate (p<0.05) were significantly lower than during HRT. No significant changes in the levels of fasting insulin and C-peptide were observed. The levels of counter-regulatory hormones in patients with H were significantly higher than during HRT (glucagon, p<0.05; epinephrine, p<0.01; cortisol, p<0.05; growth hormone, p<0.05). In H, an inverse correlation between insulin sensitivity and insulin secretion was observed (p<0.05). Cortisol was the most important factor affecting the variability of insulin sensitivity values, regardless of thyroid function (p=0.0012). In conclusion, H altered both insulin sensitivity and the levels of selected counter-regulatory hormones. The situation was restored by HRT, as manifested not only by normalisation of insulin sensitivity, secretion and levels of glucoregulatory hormones, but also by improvement of their relationships.

Fatty acid composition of serum lipids and erythrocyte membranes in type 2 (non-insulin-dependent) diabetic men

The fatty acid (FA) composition of serum lipids and erythrocytes was studied in 21 men with non-insulin-dependent diabetes mellitus (NIDDM) and in 14 normal subjects matched for age, sex, body weight, and dietary intake. Lower levels of linoleic acid and higher levels of highly unsaturated FA (daughter) of n-3 and n-6 family FA, reflected in a higher unsaturation index, were found in serum phospholipids (S-PL), in phospholipids of erythrocyte membranes (ery-PL), and in serum cholesterolesters (S-CHE). The unsaturation index of serum phospholipids significantly correlated with glycosylated hemoglobin A1c (P less than .05) and blood glucose levels after glucose load (P less than .001). The results suggest that elongation and desaturation of essential FA (linoleic acid in particular) are increased. The above changes may be associated with accelerated atherosclerosis in type 2 diabetics.

Fatty acid binding proteins in adipose tissue: A promising link between metabolic syndrome and atherosclerosis?

Adipocyte/macrophage fatty acid binding protein (A-FABP) has been shown to be closely associated with metabolic syndrome, obesity and development of atherosclerosis. Moreover, A-FABP has been recently suggested as a potential therapeutic target of these abnormalities in animal models. The present review aims to summarize current knowledge on A-FABP functions and regulations both in animal models and humans, since the role of A-FABP in human physiology and disease has not been presently clarified.

Metabolic Effects of Omega-3 Fatty Acids in Type 2 (Non-Insulin-Dependent) Diabetic Patients

The metabolic effects of a 3-week dietary supplement of a fish oil concentrate was examined in mildly obese, normotriglyceridemic men with non-insulin-dependent diabetes mellitus (NIDDM) treated with hypoglycemic agents (n = 20). Patients were randomized into two groups, receiving 15 ml per day of fish oil (Martens Oil, Norway) containing 3.1 g of omega-3 fatty acids (FA) (n = 10) or placebo (n = 10). Whereas fish oil led to the expected increase in the ratio of omega-3 to omega-6 FA in serum phospholipids, reflecting the increase in omega-3 FA intake, it did not alter fasting or mixed meal stimulated blood glucose, plasma insulin, and C-peptide concentrations. No changes in insulin action were noted, estimated by the metabolic clearance rates of glucose at plasma insulin levels of approximately 100 microU/ml and 1,400 microU/ml during a hyperinsulinemic, isoglycemic clamp; no changes were seen in insulin binding to erythrocytes. We conclude that during short-term administration, no adverse effects of low dose fish oil on glucose homeostasis were found in mildly obese NIDDM patients treated with oral hypoglycemic agents.

Intramyocellular lipid quantification from 1H long echo time spectra at 1.5 and 3 T by means of the LCModel technique

To introduce a method of independent determination of CH2 and CH3 components of intramyocellular lipids (IMCLs) by using long TE for spectra measurement and LCModel for spectra evaluation, to test this technique in controls and insulin‐resistant subjects, and to compare results at 1.5 and 3 T.

Docosahexaenoic acid-derived fatty acid esters of hydroxy fatty acids (FAHFAs) with anti-inflammatory properties

White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids—lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.

Vegetarian diet in type 2 diabetes – improvement in quality of life, mood and eating behaviour

work reasonably well in identifying those with undiagnosed diabetes and HbA1c/fasting glucose defined high risk. The implementation of this approach will have considerable workload implications for primary care, with up to half of those screened needing biochemical tests and 15% needing management of diabetes or high risk glycaemia. It is striking that, while the risk scores identify similar people, only half of those identified as high risk by one biochemical test would be considered to have high risk if assessed by the alternative test. There may be benefit in standardizing the approach in future.

Effect of ACE inhibition and angiotensin AT1 receptor blockade on renal and blood pressure response to L-arginine in humans.

Objective Nitric oxide (NO) may contribute to the actions of angiotensin converting enzyme (ACE) inhibitors. In contrast, angiotensin type 1 (AT1) receptor blockers (AT1B) have been considered to act exclusively by inhibiting angiotensin II actions. However, recent experimental findings suggest that AT1B actions may be also partly mediated by NO. In this study, we explored whether ACE inhibitors and AT1B modulate hemodynamic responses to L-arginine (L-arg), a NO precursor. Methods Systemic (Finapres) and renal hemodynamic responses to L-arg (200 mg/kg body weight), associated with markers of systemic and renal NO production, were assessed before (control) and after 3 weeks of randomized pretreatment with the ACE inhibitor ramipril (5 mg/day for 3 weeks) or the AT1B losartan (50 mg/day for 3 weeks) in nine healthy male subjects (33 ± 2 years; body mass index 25.5 ± 0.5 kg/m2). Results Control L-arg did not influence mean arterial pressure (MAP) (92 ± 5 versus 90 ± 5 mmHg; not significant). In contrast, L-arg decreased MAP when administered after pretreatment with ramipril (89 ± 5 versus 83 ± 4 mmHg; P < 0.01) or losartan (90 ± 44 versus 86 ± 4; P < 0.05). Control L-arg infusion had no effect on renal plasma flow (RPF) (paraminohippuric acid clearance) and renal vascular resistance (RVR), whereas the glomerular filtration rate (GFR) (inulin clearance) decreased (98 ± 4 versus 89 ± 5 ml/min; P < 0.05), resulting in a decrease in filtration fraction (P < 0.05). After ramipril, L-arg induced renal vasodilation as indicated by significant changes in RPF (576 ± 41 versus 669 ± 21 ml/min; P < 0.01) and RVR (P < 0.05). The GFR did not change statistically after ramipril pretreatment (91 ± 3 versus 97 ± 4 ml/min; not significant); however, the trend was different as compared with control (F = 5.7, P < 0.05). L-Arg-induced renal vasodilation was also observed after losartan (RPF, 637 ± 34 versus 706 ± 40 ml/min; P < 0.05). Enhanced renal and systemic responses to L-arg after ACE inhibitor and AT1B were associated with a rise in plasma L-citrulline levels, which was greater than after control L-arg (P < 0.05). However, other indicators of NO activity such as plasma and urinary cyclic guanosine 3′,5′-monophosphate, and nitrates, remained unchanged throughout all experiments. Conclusion The results indicate that ACE inhibitors and AT1B have a potential to enhance L-arg-induced vasodilation both in systemic and renal vascular beds. However, these hemodynamic responses were not associated with convincing changes in indicators of systemic or renal NO activity, suggesting a contribution of NO-independent vasodilator mechanisms.