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β-cell function in black South African women: exploratory associations with insulin clearance, visceral and ectopic fat.

ABSTRACT: The role of ectopic fat, insulin secretion and clearance in the preservation ofβ-cell function in black African women with obesity who typically present with hyperinsulinaemia is not clear. We aim to examine the associations between disposition index (DI, an estimate of β-cell function), insulin secretion and clearance and ectopic fat deposition. This is a cross-sectional study of 43 black South African women (age 20-35 years) with obesity (BMI 30-40 kg/m2) and without type 2 diabetes that measured the following: DI, insulin sensitivity (SI), acute insulin response (AIRg), insulin secretion rate (ISR), hepatic insulin extraction and peripheral insulin clearance (frequently sampled i.v. glucose tolerance test); pancreatic and hepatic fat, visceral adipose tissue (VAT) and abdominal s.c. adipose tissue (aSAT) volume (MRI), intra-myocellular (IMCL) and extra-myocellular fat content (EMCL) (magnetic resonance spectroscopy). DI correlated positively with peripheral insulin clearance (β 55.80, P = 0.002). Higher DI was associated with lower VAT, pancreatic fat and soleus fat, but VAT explained most of the variance in DI (32%). Additionally, higher first phase ISR (P = 0.033) and lower hepatic insulin extraction (P = 0.022) were associated with lower VAT, independent from SI, rather than with ectopic fat. In conclusion, peripheral insulin clearance emerged as an important correlate of DI. However, VAT was the main determinant of a lower DI above ectopic fat depots. Importantly, VAT, but not ectopic fat, is associated with both lower insulin secretion and higher hepatic insulin extraction. Prevention of VAT accumulation in young black African women should, therefore, be an important target for beta cell preservation.

SUBMITTER: Fortuin-de Smidt MC

PROVIDER: S-EPMC8183622 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCross-sectional studies in South Africa (SA) have shown that black SA women, despite being more insulin resistant, have less visceral adipose tissue (VAT) and more subcutaneous adipose tissue (SAT) than white women. This study aimed to investigate whether baseline and/or change in body fat and its distribution predict type 2 diabetes (T2D) risk in middle-aged black SA women, 13 years later.MethodsWe studied 142 black SA women who are the caregivers of the Birth-to-Twenty plus cohort, and who had normal glucose tolerance (NGT) at baseline. At baseline and follow-up, fasting blood samples, basic anthropometry and dual-energy X-ray absorptiometry-derived body composition were measured. At follow-up, an oral glucose tolerance test was completed. The WHO diabetes diagnostic criteria were used to define NGT, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), impaired glucose metabolism (IGM) and T2D.ResultsAt follow-up, 64% of participants remained NGT, whereas 25% developed IGM, and 11% developed T2D. The IGM and the T2D groups were combined for statistical analyses. At baseline, trunk fat mass (FM), VAT but not SAT (measures of central FM) were higher in the IGM/T2D group than the NGT group (p < 0.0001). In contrast, the IGM/T2D group had lower leg %FM at baseline than the NGT group (p < 0.0001). Baseline trunk FM (Odds ratio per 1 kg increase (95% confidence interval, 1.95 (1.43-2.67))), and VAT (OR per 10 cm2 increase, 1.25 (1.10-1.42)), and the change in VAT (1.12 (1.03-1.23)) were associated with greater odds of developing IGM/T2D, whereas baseline leg FM (OR per 1 kg increase, 0.55 (0.41-0.73)) were associated with reduced IGM/T2D risk at follow-up (p < 0.05).ConclusionsRelative fat redistribution, with VAT accumulation, predicted the development of IGM/T2D 13 years before its onset. Prevention of central obesity is a key factor to reduce the risk of developing T2D among middle-aged urban black SA women.

Project description:BACKGROUND:Disruption of the hypothalamic-pituitary-adrenal (HPA) axis, a neuroendocrine system associated with the stress response, has been hypothesized to contribute to obesity development. This may be mediated through epigenetic modulation of HPA axis-regulatory genes in response to metabolic stressors. The aim of this study was to investigate adipose tissue depot-specific DNA methylation differences in the glucocorticoid receptor (GR) and its co-chaperone, FK506-binding protein 51?kDa (FKBP5), both key modulators of the HPA axis. METHODS:Abdominal subcutaneous adipose tissue (ASAT) and gluteal subcutaneous adipose tissue (GSAT) biopsies were obtained from a sample of 27 obese and 27 normal weight urban-dwelling South African women. DNA methylation and gene expression were measured by pyrosequencing and quantitative real-time PCR, respectively. Spearman's correlation coefficients, orthogonal partial least-squares discriminant analysis and multivariable linear regression were performed to evaluate the associations between DNA methylation, messenger RNA (mRNA) expression and key indices of obesity and metabolic dysfunction. RESULTS:Two CpG dinucleotides within intron 7 of FKBP5 were hypermethylated in both ASAT and GSAT in obese compared to normal weight women, while no differences in GR methylation were observed. Higher percentage methylation of the two FKBP5 CpG sites correlated with adiposity (body mass index and waist circumference), insulin resistance (homeostasis model for insulin resistance, fasting insulin and plasma adipokines) and systemic inflammation (c-reactive protein) in both adipose depots. GR and FKBP5 mRNA levels were lower in GSAT, but not ASAT, of obese compared to normal weight women. Moreover, FKBP5 mRNA levels were inversely correlated with DNA methylation and positively associated with adiposity, metabolic and inflammatory parameters. CONCLUSIONS:These findings associate dysregulated FKBP5 methylation and mRNA expression with obesity and insulin resistance in South African women. Additional studies are required to assess the longitudinal association of FKBP5 with obesity and associated co-morbidities in large population-based samples.

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β-cell function in black South African women: exploratory associations with insulin clearance, visceral and ectopic fat.

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