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Niina Matikainen, Marja-Riitta Taskinen, Sanna Stennabb, Nina Lundbom, Antti Hakkarainen, Kirsi Vaaralahti, and Taneli Raivio

Background

Elevated levels of circulating fibroblast growth factor 21 (FGF21) are commonly encountered in type 2 diabetes, dyslipidemia, and non-alcoholic fatty liver disease, all of which share exaggerated postprandial lipemia as a common proatherogenic feature. How FGF21 responds to an oral fat load in man is unknown.

Methods

We measured liver fat contents and subcutaneous and visceral fat volumes in 47 healthy subjects, who also underwent an oral fat load with measurements of plasma FGF21 and free fatty acid (FFA). Triglyceride (TG), apolipoprotein B-48 (apoB-48), and apoB-100 concentrations were measured in triglyceride-rich lipoprotein (TRL) fractions.

Results

When compared with fasting levels, the concentration of FGF21 decreased significantly at 4 h (P<0.05) and tended to return to fasting levels at 8 h after an oral fat load. Fasting and postprandial FGF21 correlated significantly with liver fat as well as with TRLs in the chylomicron and especially in very low-density lipoprotein 1 (VLDL1) and VLDL2 fractions representing remnant particles, but not with FFA. Subjects with increased liver fat (>5%, n=12) showed impaired suppression of FGF21 at 4 h (P<0.05) and at 8 h (P=0.01) and demonstrated higher postprandial TG area under the curve in plasma and TRL fractions (P≤0.032) compared with those with normal liver fat (≤5%, n=35).

Conclusions

We observed a significant decrease of FGF21 concentration after an oral fat load. Fasting and postprandial FGF21 levels were closely related to large VLDL and remnants, but not to plasma FFA. Our pilot findings suggest that the postprandial accumulation of TRL remnants and liver fat may modulate postprandial FGF21 levels.

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Minna Soinio, Anna-Kaarina Luukkonen, Marko Seppänen, Jukka Kemppainen, Janne Seppänen, Juha-Pekka Pienimäki, Helena Leijon, Tiina Vesterinen, Johanna Arola, Eila Lantto, Semi Helin, Ilkka Tikkanen, Saara Metso, Tuomas Mirtti, Ilkka Heiskanen, Leena Norvio, Mirja Tiikkainen, Tuula Tikkanen, Timo Sane, Matti Välimäki, Celso E Gomez-Sanchez, Ilkka Pörsti, Pirjo Nuutila, Pasi I Nevalainen, and Niina Matikainen

Objective

Endocrine Society guidelines recommend adrenal venous sampling (AVS) in primary aldosteronism (PA) if adrenalectomy is considered. We tested whether functional imaging of adrenal cortex with 11C-metomidate (11C-MTO) could offer a noninvasive alternative to AVS in the subtype classification of PA.

Design

We prospectively recruited 58 patients with confirmed PA who were eligible for adrenal surgery.

Methods

Subjects underwent AVS and 11C-MTO-PET without dexamethasone pretreatment in random order. The lateralization of 11C-MTO-PET and adrenal CT were compared with AVS in all subjects and in a prespecified adrenalectomy subgroup in which the diagnosis was confirmed with immunohistochemical staining for CYP11B2.

Results

In the whole study population, the concordance of AVS and 11C-MTO-PET was 51% and did not differ from that of AVS and adrenal CT (53%). The concordance of AVS and 11C-MTO-PET was 55% in unilateral and 44% in bilateral PA. In receiver operating characteristics analysis, the maximum standardized uptake value ratio of 1.16 in 11C-MTO-PET had an AUC of 0.507 (P = n.s.) to predict allocation to adrenalectomy or medical therapy with sensitivity of 55% and specificity of 44%. In the prespecified adrenalectomy subgroup, AVS and 11C-MTO-PET were concordant in 10 of 19 subjects with CYP11B2-positive adenoma and in 6 of 10 with CYP11B2-positivity without an adenoma.

Conclusions

The concordance of 11C-MTO-PET with AVS was clinically suboptimal, and did not outperform adrenal CT. In a subgroup with CYP11B2-positive adenoma, 11C-MTO-PET identified 53% of cases. 11C-MTO-PET appeared to be inferior to AVS for subtype classification of PA.