Plasma SHBG Levels as an Early Predictor of Response to Bariatric Surgery.

BACKGROUND: Obesity is a growing global health problem, and currently, bariatric surgery (BS) is the best solution in terms of sustained total weight loss (TWL). However, a significant number of patients present weight regain (WR) in time. There is a lack of biomarkers predicting the response to BS and WR during the follow-up. Plasma SHBG levels, which are low in obesity, increase 1 month after BS but there is no data of plasma SHBG levels at long term. We performed the present study aimed at exploring the SHBG role in predicting TWL and WR after BS. METHODS: Prospective study including 62 patients with obesity undergoing BS. Anthropometric and biochemical variables, including SHBG were analyzed at baseline, 1, 6, 12, and 24 months; TWL ≥ 25% was considered as good BS response. RESULTS: Weight loss nadir was achieved at 12 months post-BS where maximum SHBG increase was reached. Greater than or equal to 25% TWL patients presented significantly higher SHBG increases at the first and sixth months of follow-up with respect to baseline (100% and 150% respectively, p = 0.025), than < 25% TWL patients (40% and 50% respectively, p = 0.03). Also, these presented 6.6% WR after 24 months. The first month SHBG increase predicted BS response at 24 months (OR = 2.71; 95%CI = [1.11-6.60]; p = 0.028) and TWL in the 12th month (r = 0.330, p = 0.012) and the WR in the 24th (r = - 0.301, p = 0.028). CONCLUSIONS: Our results showed for the first time that increase in plasma SHBG levels within the first month after BS is a good predictor of TWL and WR response after 2 years.

Accuracy of a sequential algorithm based on FIB-4 and ELF to identify high-risk advanced liver fibrosis at the primary care level.

Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease, and liver fibrosis is the strongest predictor of morbimortality. We aimed to assess the performance of a sequential algorithm encompassing the Fibrosis 4 (FIB-4) and Enhanced Liver Fibrosis (ELF) scores for identifying patients at risk of advanced fibrosis. This cross-sectional study included one hospital-based cohort with biopsy-proven NAFLD (n = 140) and two primary care cohorts from different clinical settings: Type 2 Diabetes (T2D) follow-up (n = 141) and chronic liver disease (CLD) initial study (n = 138). Logistic regression analysis was performed to assess liver fibrosis diagnosis models based on FIB-4 and ELF biomarkers. The sequential algorithm retrieved the following accuracy parameters in predicting stages F3-4 in the biopsy-confirmed cohort: sensitivity (85%), specificity (73%), negative predictive value (79%) and positive predictive value (81%). In both T2D and CLD cohorts, a total of 28% of patients were classified as stages F3-4. Furthermore, of all F3-4 classified patients in the T2D cohort, 80% had a diagnosis of liver disease and 44% were referred to secondary care. Likewise, of all F3-4 classified patients in the CLD cohort, 71% had a diagnosis of liver disease and 44% were referred to secondary care. These results suggest the potential utility of this algorithm as a liver fibrosis stratifying tool in primary care, where updating referral protocols to detect high-risk F3-4 is needed. FIB-4 and ELF sequential measurement is an efficient strategy to prioritize patients with high risk of F3-4 in populations with metabolic risk factors.

Human sex hormone-binding globulin is expressed in testicular germ cells and not in sertoli cells.

The human sex hormone-binding globulin ( SHBG) gene contains at least two transcription units. A 4.3 kb human SHBG transcription unit encodes the precursor polypeptide, which is processed and secreted by hepatocytes as plasma SHBG. The proximal promoter of this transcription unit differs from the corresponding sequence in other mammals, in which it is also expressed in Sertoli cells. In particular, its proximal promoter sequence contains a binding site for USF transcription factors that represses its activity in Sertoli cells. Although human SHBG is not expressed in Sertoli cells, human SHBG transcripts containing an alternative exon 1 sequence are present in testicular germ cells. These are the products of an approximately 8 kb human SHBG transcription unit, and they appear to encode an SHBG isoform that is 4 - 5 kDa smaller than plasma SHBG. This sperm SHBG isoform accumulates between the outer acrosomal membrane and the sperm plasma membrane, and it is released during the capacitation reaction. These remarkable differences in human SHBG expression in the testis, when compared to other mammals, force us to reconsider the functional significance of SHBG expression in the testis in relation to male reproduction.

Meiotic arrest and germ cell apoptosis in androgen-binding protein transgenic mice.

The fundamental role of androgen-binding protein (ABP) in spermatogenesis remains obscure after nearly 25 yr since its first characterization. In the present investigation, we used a transgenic mouse model that overexpresses rat ABP to examine the potential involvement of this protein in the regulation of processes occurring during spermatogenesis. Specifically, homozygous or heterozygous transgenic mice were analyzed in terms of spermatogenic progression, DNA fragmentation pattern, and germinal cell ploidy status. All animals homozygous for transgenic ABP exhibited an increased accumulation of primary spermatocytes and cells at metaphase with abnormal morphology and localization within the seminiferous epithelium. Analysis of DNA fragmentation by in situ techniques and agarose gel electrophoresis provided evidence for an increased occurrence of apoptosis in the transgenic animals, principally involving pachytene spermatocytes and cells at metaphase. Flow cytometric analysis of the DNA content of isolated germ cells revealed a reduction in the number of haploid cells, an increase in the number of tetraploid cells, and the appearance of a hypotetraploid cell population, consistent with degenerating primary spermatocytes. In mice heterozygous for the transgene, the effects were less prominent, and the degree to which spermatogenesis was compromised correlated with the levels of ABP messenger RNA in individual animals. The present results are interpreted to suggest that ABP can act as a modulator of spermatogenesis by regulating completion of the first meiotic division of primary spermatocytes.