Correlation of Significantly Decreased Serum Circulating Mesencephalic Astrocyte-Derived Neurotrophic Factor Level With an Increased Risk of Future Cardiovascular Disease in Adult Patients With Growth Hormone Deficiency

Ren, Zhijian; Wang, Yunting; Chen, Qing; Long, Jiangchuan; Zhang, Rui; Wu, Xun; Qian, Wenjie; Chen, Yue; Liu, Dongfang; Ren, Wei

doi:10.3389/fendo.2021.671126

Cited by 7 publications

(6 citation statements)

References 39 publications

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“…Although several authors associate GHD in adults with insulin resistance, this association is not well established in the literature. Conversely, a recent study has shown that adult patients with GHD are more sensitive to insulin than the control group matched for age, sex, and BMI through HOMA-IR [22,23]. In our study, using the HEC, we found no differences in SI between patients with AOGHD and the matched control group.…”

Section: Discussioncontrasting

confidence: 90%

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

et al. 2022

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Introduction: The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. Materials and Methods: In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. Results: COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Conclusions: Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

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Section: Discussioncontrasting

confidence: 90%

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

et al. 2022

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“…In healthy adults, lower levels of IGF-1 were associated with lower fasting blood glucose, insulin and C-peptide levels 27 . Previous studies have revealed that diabetes is a common comorbidity in AGHD and is a major contributor to cardiovascular risk 28 . In our study, fasting blood glucose was also remarkably elevated in AO AGHD patients.…”

Section: Discussionmentioning

confidence: 99%

Metabolic Profile and Echocardiographic Evaluation in Adults with Growth Hormone Deficiency

Yang

Wang

et al. 2022

Horm Metab Res

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Adult growth hormone deficiency (AGHD) is associated with increased cardiovascular risks. The primary endpoint of this retrospective cohort study was to compare metabolic profile and echocardiographic parameters in childhood-onset (CO) and adulthood-onset (AO) AGHD patients. 26 patients with CO AGHD (19 males, 26.8±8.5 years) and 41 patients with AO AGHD (23 males, 35.1±6.8 years) were included. The standard deviation score of insulin-like growth factor-1 (IGF-1 SDS), metabolic profile, liver sonography and echocardiographic parameters were compared. The IGF-1 SDS were significantly lower in CO AGHD patients (p<0.05). AO AGHD patients showed much profound glycolipid aberrations, elevated C-reactive protein levels (p=0.012), and proportionally higher prevalence of non-alcoholic fatty liver disease (95.2% vs.8.3%, p<0.001). In all subjects, IGF-1 SDS was negatively related to low-density lipoprotein cholesterol, and positively related to total cholesterol and lipoprotein a (Lpa). There were significant differences between the two group with regard to the correlations between IGF-1 SDS and high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, LPa, uric acid and creatinine (all p for interaction<0.05). CO AGHD patients exhibited smaller heart, but similar ventricular ejection fraction compared to AO AGHD patients. AGHD may be a group of heterogenous entity based on the onset ages of disease. AO patients had prominent metabolic disorders, while CO patients had smaller heart but similar cardiac performance. Whether growth hormone replacement therapy will equally benefit both CO and AO AGHD patients needs further investigations.

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“…In the serum, MANF levels are increased in conditions such as ischemic stroke, drug-induced liver injury, hyperlipidemia, obesity, and types 1 and 2 diabetes (53,61,64,66,69,73). In contrast, decreased levels of MANF in the serum have been reported in adult patients with growth hormone deficiency, major depressive disorder, nonalcoholic steatohepatitis, and polycystic ovary syndrome (56,62,68,70). Expression of CDNF has been investigated in different disease conditions, but not as extensively as MANF.…”

Section: Cdnf and Manf Expression In Human Diseasesmentioning

confidence: 99%

CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson’s disease

Pakarinen

Lindholm

2023

Front. Psychiatry

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Parkinson’s disease (PD) is a progressive neurodegenerative disease characterized by gradual loss of midbrain dopamine neurons, leading to impaired motor function. Preclinical studies have indicated cerebral dopamine neurotrophic factor (CDNF) and mesencephalic astrocyte-derived neurotrophic factor (MANF) to be potential therapeutic molecules for the treatment of PD. CDNF was proven to be safe and well tolerated when tested in Phase I-II clinical trials in PD patients. Neuroprotective and neurorestorative effects of CDNF and MANF were demonstrated in animal models of PD, where they promoted the survival of dopamine neurons and improved motor function. However, biological roles of endogenous CDNF and MANF proteins in the midbrain dopamine system have been less clear. In addition to extracellular trophic activities, CDNF/MANF proteins function intracellularly in the endoplasmic reticulum (ER), where they modulate protein homeostasis and protect cells against ER stress by regulating the unfolded protein response (UPR). Here, our aim is to give an overview of the biology of endogenous CDNF and MANF in the brain dopamine system. We will discuss recent studies on CDNF and MANF knockout animal models, and effects of CDNF and MANF in preclinical models of PD. To elucidate possible roles of CDNF and MANF in human biology, we will review CDNF and MANF tissue expression patterns and regulation of CDNF/MANF levels in human diseases. Finally, we will discuss novel findings related to the molecular mechanism of CDNF and MANF action in ER stress, UPR, and inflammation, all of which are mechanisms potentially involved in the pathophysiology of PD.

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Correlation of Significantly Decreased Serum Circulating Mesencephalic Astrocyte-Derived Neurotrophic Factor Level With an Increased Risk of Future Cardiovascular Disease in Adult Patients With Growth Hormone Deficiency

Cited by 7 publications

References 39 publications

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity

Metabolic Profile and Echocardiographic Evaluation in Adults with Growth Hormone Deficiency

CDNF and MANF in the brain dopamine system and their potential as treatment for Parkinson’s disease

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