Effect of free fatty acids on insulin secretion, insulin sensitivity and incretin effect - a narrative review.

Deleterious effects of free fatty acids, FFAs, on insulin sensitivity are observed in vivo studies in humans. Mechanisms include impaired insulin signaling, oxidative stress, inflammation, and mitochondrial dysfunction, but the effects on insulin secretion are less well known. Our aim was to review the relationship of increased FFAs with insulin resistance, secretion and mainly with the incretin effect in humans. Narrative review. Increased endogenous or administered FFAs induce insulin resistance. FFAs effects on insulin secretion are debatable; inhibition and stimulation have been reported, depending on the type and duration of lipids exposition and the study subjects. Chronically elevated FFAs seem to decrease insulin biosynthesis, glucose-stimulated insulin secretion and ß-cell glucose sensitivity. Lipids infusion decreases the response to incretins with unchanged incretin levels in volunteers with normal glucose tolerance. In contrast, FFAs reduction by acipimox did not restore the incretin effect in type-2 diabetes, probably due to the dysfunctional ß-cell. Possible mechanisms of FFAs excess on incretin effect include reduction of the expression and levels of GLP-1 (glucagon like peptide-1) receptor, reduction of connexin-36 expression thus the coordinated secretory activity in response to GLP-1, and GIP (glucose-dependent insulinotropic polypeptide) receptors downregulation in islets cells. Increased circulating FFAs impair insulin sensitivity. Effects on insulin secretion are complex and controversial. Deleterious effects on the incretin-induced potentiation of insulin secretion were reported. More investigation is needed to better understand the extent and mechanisms of ß-cell impairment and insulin resistance induced by increased FFAs and how to prevent them.

High serum TSH levels are associated with depression in the elderly.

In order to investigate the association between elevated serum TSH levels and depression in the elderly, we conducted a population-based study of 451 over 60-year-old outpatients of a general University Hospital. Patients were divided into Group I (GI) (248 individuals) with high serum TSH levels, but otherwise no important condition or disease, and Group II (GII) (203 patients) with no previous diagnosis of thyroid or mood disease, referred to the hospital because of nonthyroidal severe diseases. All patients were clinically examined and classified according to DMS-IV for mood disturbance and had serum TSH, free T4 levels and antithyroid antibodies measured. High serum TSH levels (11.6+/-14.8 mU/l) were observed in 65/203 (32%) patients of GII. Among these patients, 42/65 (65%) had normal free T4 concentrations (1.23+/-0.98 ng/dl), no clinical manifestation of hypothyroidism and thus were considered to present subclinical hypothyroidism. Depression was observed in 24 cases from GI (9.7%) and 29 from GII (14.3%) and was frequent in the subclinical hypothyroid patients (49%). Our results suggest that mood disturbances are frequent in the elderly with elevated serum TSH levels, but they do not differ in the primary hypothyroid and the nonthyroidal sick patients.