Evaluation of the hypothalamic–pituitary–adrenal axis in a case series of familial partial lipodystrophy

Abstract

BackgroundFamilial partial lipodystrophy (FPL) is a rare genetic disease characterized by body fat abnormalities that lead to insulin resistance (IR). Clinical conditions linked to milder IR, such as type 2 diabetes (T2D) and metabolic syndrome, are associated with abnormalities of the hypothalamic–pituitary–adrenal (HPA) axis, but little is known about its activity in FPL.MethodsPatients meeting the clinical criteria for FPL were subjected to anthropometric, biochemical and hormone analyses. A genetic study to identify mutations in the genes encoding peroxisome proliferator-activated receptor gamma (PPARγ) was performed. Polycystic ovary syndrome and hepatic steatosis were investigated, and the patient body compositions were analyzed via dual X-ray energy absorptiometry (DXA). The HPA axis was assessed via basal [cortisol, adrenocorticotrophic hormone (ACTH), cortisol binding globulin, nocturnal salivary cortisol and urinary free cortisol (UFC)] as well as dynamic suppression tests (cortisol post 0.5 mg and post 1 mg dexamethasone).ResultsSix patients (five female and one male) aged 17 to 42 years were included. In DXA analyses, the fat mass ratio between the trunk and lower limbs (FMR) was > 1.2 in all phenotypes. One patient had a confirmed mutation in the PPARγ gene: a novel heterozygous substitution of p. Arg 212 Trp (c.634C>T) at exon 5. HPA sensitivity to glucocorticoid feedback was preserved in all six patients, and a trend towards lower basal serum cortisol, serum ACTH and UFC values was observed.ConclusionsOur findings suggest that FPL is not associated with overt abnormalities in the HPA axis, despite a trend towards low-normal basal cortisol and ACTH values and lower UFC levels. These findings suggest that the extreme insulin resistance occurring in FPL may lead to a decrease in HPA axis activity without changing its sensitivity to glucocorticoid feedback, in contrast to the abnormalities in HPA axis function in T2D and common metabolic syndrome.

Reporting of Perinatal Outcomes in Probiotic Randomized Controlled Trials. A Systematic Review and Meta-Analysis

“…The included papers dated from 2001 to 2020. Of the studies, 15 were conducted in Iran [ 30 , 31 , 33 , 34 , 35 , 36 , 40 , 46 , 47 , 48 , 50 , 51 , 64 , 70 , 72 ]; 4 trials were conducted in Finland [ 49 , 55 , 56 , 69 ]; 3 in New Zealand [ 66 , 73 , 74 ]; 3 in Australia [ 37 , 38 , 67 ]; 2 each in Canada [ 71 , 75 ], Germany [ 43 , 54 ], Taiwan [ 45 , 68 ], and Ireland [ 58 , 59 ], and the remaining 13 RCTs were conducted in other different countries. Most of the studies recruited healthy pregnant women.…”

“…Regarding the main objectives of the studies, the most common were improving insulin/glucose metabolism (13 studies) [ 30 , 33 , 34 , 40 , 44 , 46 , 50 , 52 , 58 , 64 , 69 , 70 , 72 ]; preventing eczema, allergic disease, or atopic sensitization (10 studies) [ 29 , 37 , 41 , 49 , 53 , 54 , 55 , 65 , 68 , 73 ]; improving oxidative stress status and inflammatory profile (8 studies) [ 14 , 36 , 46 , 47 , 48 , 51 , 64 ]; modifying the mother’s or infant’s microbiota (5 studies) [ 14 , 61 , 63 , 65 , 75 ]; and preventing GBS occurrence (4 studies) [ 45 , 67 , 71 , 74 ]. Other outcomes included bacterial vaginosis, mastitis, pregnancy outcomes, safety assessment, maternal anthropometric measures, infant colic, genetic profile, and infant diarrhea or gut integrity.…”

“…Probiotic/synbiotic administration was only compared to placebo in 37 trials (80%) [ 29 , 30 , 31 , 32 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 58 , 59 , 63 , 64 , 65 , 66 , 68 , 70 , 71 , 72 , 73 , 74 , 75 ], while 5 studies (11%) used a group with no treatment or routine care as a comparison [ 14 , 33 , 34 , 35 , 67 ], and the remaining 4 papers (9%) analyzed other additional comparison groups (i.e., probiotic + vitamin D) [ 48 , 56 , 60 , 69 ]. Microorganisms were administered orally in all of the included studies.…”

“…Microorganisms were administered orally in all of the included studies. Administration vehicles consisted of capsules in most of the cases (35 studies, 76%), with 3 studies using probiotic yoghurt (6.5%) [ 33 , 34 , 70 ]; 3 studies using probiotic powder [ 53 , 60 , 61 ]; and 1 study each using probiotic oil (2.2%) [ 29 ], tablets [ 14 ], and milk [ 41 ]. The two remaining studies (4.3%) did not specify the vehicle used to administer the microorganisms [ 67 , 72 ].…”

Can Metformin Exert as an Active Drug on Endothelial Dysfunction in Diabetic Subjects?

“…Both in diabetic rats [ 191 ], and newly diagnosed diabetic patients [ 192 ], metformin has been shown to restore the activity of paraoxonase 1, an antioxidant associated with circulating HDL that hydrolyzes lipid peroxides in LDL.…”