Sex differences in insulin sensitivity and insulin response with increasing age in black South African men and women.

AIMS: Black Africans are disproportionally affected by type 2 diabetes, but the pathophysiology is poorly understood. The study aimed to examine the effect of sex and age on insulin sensitivity and insulin response in black South African adults. METHODS: This cross-sectional study included a random sample of 179 men and 260 women aged 25-74years with normal glucose tolerance from 5 peri-urban townships in Cape Town, SA. Insulin sensitivity (insulin sensitivity index, ISI0,120) and response (insulinogenic index, IGI), and the disposition index (DI, ISI0,120×IGI), derived from an oral glucose tolerance test, were measured. RESULTS: Although men were older (median [interquartile range]: 39 [30-48] vs. 35 [29-44], P=0.021) and had significantly lower BMI than women (22.6 [20.0-25.3] vs. 31.0 [25.9-35.7] kg/m2, P=0.001), DI was not different (P=0.740), but ISI0,120 was higher (P=0.007) and IGI was lower (P=0.074) in men than women, adjusting for age and BMI. With increasing age, DI (ß (95%CI): -24.4 (-36.3 to -12.5), P<0.001) and IGI (ß (95%CI): -4.9 (-7.5 to -2.2), P<0.001) decreased similarly in both sexes, but ISI0,120 did not change (ß (95%CI): 0.005 (-0.20 to 0.03), P=0.675). CONCLUSION: Black South African women with normal glucose tolerance have lower insulin sensitivity than their male counterparts, but increase their insulin response to maintain normoglycemia. With increasing age, insulin sensitivity remains unchanged, but the insulin response decreases at a similar rate in men and women.

Ethnic differences in hepatic and systemic insulin sensitivity and their associated determinants in obese black and white South African women.

AIMS/HYPOTHESIS: There is evidence to suggest that ectopic fat deposition in liver and skeletal muscle may differ between black and white women resulting in organ-specific differences in insulin sensitivity. Accordingly, the aim of the study was to examine ethnic differences in hepatic and peripheral insulin sensitivity, and the association with hepatic and skeletal muscle lipid content, and skeletal muscle gene expression. METHODS: In a cross-sectional study including 30 obese premenopausal black and white women, body composition (dual energy x-ray absorptiometry), liver fat and skeletal muscle (soleus and tibialis anterior) fat accumulation (proton-magnetic resonance spectroscopy), skeletal muscle gene expression, insulin sensitivity (two-step isotope labelled, hyperinsulinaemic-euglycaemic clamp with 10 mU m(-2) min(-1) and 40 mU m(-2) min(-1) insulin infusions), and serum adipokines were measured. RESULTS: We found that, although whole-body insulin sensitivity was not different, obese white women presented with lower hepatic insulin sensitivity than black women (% suppression of endogenous glucose production [% supp EGP], median [interquartile range (IQR)]: 17 [5-51] vs 56 [29-100] %, p = 0.002). While liver fat tended to be lower (p = 0.065) and skeletal muscle fat deposition tended to be higher (p = 0.074) in black compared with white women, associations with insulin sensitivity were only observed in black women (% supp EGP vs liver fat: r = -0.57, p < 0.05 and % supp EGP vs soleus fat: r = -0.56, p < 0.05). CONCLUSIONS/INTERPRETATION: These findings may suggest that black women are more sensitive to the effects of ectopic lipid deposition than white women.

The role of adipose tissue in insulin resistance in women of African ancestry.

Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry.

Reduced gluteal expression of adipogenic and lipogenic genes in Black South African women is associated with obesity-related insulin resistance.

CONTEXT: Black South African women are less insulin sensitive than their White counterparts, despite less central and greater peripheral fat deposition. We hypothesized that this paradox may be explained, in part, by differences in the adipogenic capacity of sc adipose tissue (SAT). OBJECTIVE: Our objective was to measure adipogenic and lipogenic gene expression in abdominal and gluteal SAT depots and determine their relationships with insulin sensitivity (S(I)) in South African women. PARTICIPANTS AND DESIGN: Fourteen normal-weight [body mass index (BMI) <25 kg/m(2)] Black, 13 normal-weight White, 14 obese (BMI >30 kg/m(2)) Black, and 13 obese White premenopausal South African women participated in this cross-sectional study. MAIN OUTCOMES: S(I) (frequently sampled i.v. glucose tolerance test) in relation to expression of adipogenic and lipogenic genes in abdominal and gluteal SAT depots. RESULTS: With increasing BMI, Black women had less visceral fat (P = 0.03) and more abdominal (P = 0.017) and gynoid (P = 0.041) SAT but had lower S(I) (P < 0.01) than White women. The expression of adipogenic and lipogenic genes was proportionately lower with obesity in Black but not White women in the gluteal and deep SAT depots (P < 0.05 for ethnicity × BMI effect). In Black women only, the expression of these genes correlated positively with S(I) (all P < 0.05), independently of age and fat mass. CONCLUSIONS: Obese Black women have reduced SAT expression of adipogenic and lipogenic genes compared with White women, which associates with reduced S(I). These findings suggest that obesity in Black women impairs SAT adipogenesis and storage, potentially leading to insulin resistance and increased risk of type 2 diabetes.

Differential effects of abdominal adipose tissue distribution on insulin sensitivity in black and white South African women.

Black South African women are more insulin resistant than BMI-matched white women. The objective of the study was to characterize the determinants of insulin sensitivity in black and white South African women matched for BMI. A total of 57 normal-weight (BMI 18-25 kg/m(2)) and obese (BMI > 30 kg/m(2)) black and white premenopausal South African women underwent the following measurements: body composition (dual-energy X-ray absorptiometry), body fat distribution (computerized tomography (CT)), insulin sensitivity (S(I), frequently sampled intravenous glucose tolerance test), dietary intake (food frequency questionnaire), physical activity (Global Physical Activity Questionnaire), and socioeconomic status (SES, demographic questionnaire). Black women were less insulin sensitive (4.4 +/- 0.8 vs. 9.5 +/- 0.8 and 3.0 +/- 0.8 vs. 6.0 +/- 0.8 x 10(-5)/min/(pmol/l), for normal-weight and obese women, respectively, P < 0.001), but had less visceral adipose tissue (VAT) (P = 0.051), more abdominal superficial subcutaneous adipose tissue (SAT) (P = 0.003), lower SES (P < 0.001), and higher dietary fat intake (P = 0.001) than white women matched for BMI. S(I) correlated with deep and superficial SAT in both black (R = -0.594, P = 0.002 and R = 0.495, P = 0.012) and white women (R = -0.554, P = 0.005 and R = -0.546, P = 0.004), but with VAT in white women only (R = -0.534, P = 0.005). In conclusion, body fat distribution is differentially associated with insulin sensitivity in black and white women. Therefore, the different abdominal fat depots may have varying metabolic consequences in women of different ethnic origins.