Georgios A. Fragkiadakis

Plasma trimethylamine-N-oxide and related metabolites are associated with type 2 diabetes risk in the Prevención con Dieta Mediterránea (PREDIMED) trial

Background The role of trimethylamine-N-oxide (TMAO) in type 2 diabetes (T2D) is currently partially understood and controversial. Objective The aim of this study was to investigate associations between TMAO and related metabolites with T2D risk in subjects at high risk of cardiovascular disease. Design This is a case-cohort design study within the Prevención con Dieta Mediterránea (PREDIMED) study, with 251 incident T2D cases and a random sample of 694 participants (641 noncases and 53 overlapping cases) without T2D at baseline (median follow-up: 3.8 y). We used liquid chromatography-tandem mass spectrometry to measure plasma TMAO, l-carnitine, betaine, lyso-phosphatidylcholine (LPC) and lyso-phosphatidylethanolamine (LPE) species, phosphocholine, α-glycerophosphocholine, and choline at baseline and after 1 y. We examined associations with the use of weighted Cox proportional hazard models, accounting for the weighted case-cohort design by the Barlow method. Results After adjustment for recognized T2D risk factors and multiple testing, individuals in the highest quartile of baseline TMAO and α-glycerophosphocholine had a lower risk of T2D [HR (95% CI): 0.52 (0.29, 0.89) and 0.46 (0.24, 0.89), respectively]. The HR (95% CI) comparing the extreme quartiles of betaine was 0.41 (0.23, 0.74). Similar trends were observed for C16:0 LPC, C18:1 LPC, C18:0 LPC, C20:4 LPC, C22:6 LPC, C18:1 LPC plasmalogen, and C16:0 LPE. After correcting for multiple comparisons, participants in the highest quartile of 1-y changes in oleic acid LPC plasmalogen concentrations had a lower T2D risk than the reference quartile. Conclusion Whether the associations between plasma TMAO and certain metabolite concentrations with T2D risk reflect its pathophysiology or represent an epiphenomenon needs to be elucidated. This trial is registered at http://www.controlled-trials.com as ISRCTN35739639.

Seven Countries Study cohort in Crete, Greece: gluteal adipose-tissue fatty-acid profiles of survivors, at 2010.

OBJECTIVE To analyse the gluteal adipose-tissue fatty-acid profiles from Cretan cohort survivors of the Seven Countries Study (SCS) at 2010 and to compare them with those of survivors assessed in 2000, as well as with literature data on male Cretans at 1965. DESIGN We analysed data concerning the gluteal adipose-tissue fatty acids (analysed by GC) from three studies. SETTING The island of Crete (rural areas and the city of Heraklion). SUBJECTS Twenty-two of the 2010 SCS survivors aged 90 years and over; seventy-eight men aged 80 years of the 2000 SCS survivors; and 280 men assessed in 1965. RESULTS In comparison to 1965 and 2000, the SCS survivors in 2010 had a higher amount of 18:1n-9 (P<0·05) in their gluteal adipose tissue and a lower amount of PUFA (P<0·05). On the other hand, a constant decrease in adipose-tissue 14:1n-5 and 16:1n-7 was recorded between 1965 and 2010 (P<0·001), and between 2000 and 2010 (P<0·05), while 18:2n-6 appeared to decrease between the 1965 and 2010 assessments (P<0·001). CONCLUSIONS Comparison with a 1965 representative Cretan sample and 2000 SCS survivors indicated an increased concentration of oleic acid (known for its protective role against mortality) and a decreased concentration of PUFA (known for their susceptibility to oxidation) in our surviving sample at 2010. These changes may reflect internal physiological processes due to diet change within these years and/or ageing.

Effects of different weight loss percentages on moderate to severe obstructive sleep apnoea syndrome

Lifestyle-induced weight loss studies in patients with obstructive sleep apnoea syndrome (OSAS) have revealed that at least 10% loss of their initial weight may correct or at least improve the symptoms of the syndrome. Obese individuals are encouraged to lose 5–10% of their weight to improve OSAS but data supporting this recommendation are limited, particularly in moderate to severe cases. Whether a 5–10% weight loss range is more beneficial in moderate and/or severe OSAS compared with less weight loss (<5%) is the main focus of this study. We present additional data from a previous study after pooling the patients’ data and subdividing them into three categories according to the weight changes recorded at the 6-month follow-up: 0–4.9% (lowest), 5–9.9% (intermediate) and >10% (highest). One-way analysis of variance was used to assess differences among weight loss categories regarding patients’ characteristics at baseline and betweengroup differences in changes in characteristics during a 6-month period. The Bonferroni correction was used to account for increase in type I error owing to multiple comparisons. There were no significant differences (p > 0.05) among the weight loss categories concerning the baseline characteristics (Table 1). The highest category showed a greater improvement in apnoeahypopnoea index during rapid eye movement (AHI/ REM) and the lowest oxygen saturation compared with the lowest (p < 0.05; Table 2). The latter OSAS parameter also improved significantly more in the highest category than in the intermediate (p < 0.05). The comparison between the lowest and intermediate category did not reveal any significant differences concerning changes in OSAS severity indices (p > 0.05). In the present study, the OSAS parameters with a remarkable difference in their change between different weight loss categories were AHI/REM and lowest arterial oxygen saturation. These are promising findings in OSAS treatment, because compared with non-rapid eye movement (REM) sleep, during REM sleep there is an increase in the duration of apnoea episodes and the lowest oxygen saturation has been independently associated with several metabolic and inflammatory risks. The significant difference in the change in AHI/ REM between the lowest and highest category coexisted with notable differences in the change of waist circumference (WC) and WC/height ratio. Patients with the highest weight loss reduced AHI/REM more than the others possibly because of the greater reduction in abdominal fat and the associated mechanical load. The differences between the aforementioned categories in body changes can be attributed to the adherence concerning prescribed diets and exercise programs. Another finding of this study is that in the lowest category, an increase in apnoea-hypopnoea index (AHI) during REM sleep was recorded despite reductions in abdominal and body fat. Decreases in AHI