Weight-related differences in glucose metabolism and free fatty acid production in two South African population groups.

OBJECTIVE: The effects of free fatty acids (FFA), leptin, tumour necrosis factor (TNF) alpha and body fat distribution on in vivo oxidation of a glucose load were studied in two South African ethnic groups. DESIGN AND MEASUREMENTS: Anthropometric and various metabolic indices were measured at fasting and during a 7 h oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis and subcutaneous and visceral fat mass was assessed using a five- and two-level CT-scan respectively. Glucose oxidation was evaluated by measuring the ratio of (13)CO(2) to (12)CO(2) in breath following ingestion of 1-(13)C-labelled glucose. SUBJECTS: Ten lean black women (LBW), ten obese black women (OBW), nine lean white women (LWW) and nine obese white women (OWW) were investigated after an overnight fast. RESULTS: Visceral fat levels were significantly higher (P<0.01) in obese white than black women, despite similar body mass indexes (BMIs). There were no ethnic differences in glucose oxidation however; in the lean subjects of both ethnic groups the area under the curve (AUC) was higher than in obese subjects (P<0.05 for both) and was found to correlate negatively with weight (r=-0.69, P<0.01) after correcting for age. Basal TNF alpha concentrations were similar in all groups. Percentage suppression of FFAs at 30 min of the OGTT was 24+/-12% in OWW and -38+/-23% (P<0.05) in OBW, ie the 30 min FFA level was higher than the fasting level in the latter group. AUC for FFAs during the late postprandial period (120--420 min) was significantly higher in OWW than OBW (P<0.01) and LWW (P<0.01) and correlated positively with visceral fat mass independent of age (r=0.78, P<0.05) in the OWW only. Leptin levels were higher (P<0.01) both at fasting and during the course of the OGTT in obese women from both ethnic groups compared to the lean women. CONCLUSIONS: Glucose oxidation is reduced in obese subjects of both ethnic groups; inter- and intra-ethnic differences were observed in visceral fat mass and FFA production and it is possible that such differences may play a role in the differing prevalences of obesity-related disorders that have been reported in these two populations.

Lactate and glycerol release from adipose tissue in lean, obese, and diabetic women from South Africa.

Abnormalities observed in intermediary metabolism may be related to the pathogenesis of obesity-related diseases such as type 2 diabetes. Glycerol and lactate production was estimated in the sc adipose tissue of two anatomical regions of 10 lean (LW), 10 obese (OW), and 10 matched diabetic (DW) black urban women. This was done with the sc microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from (133)Xe clearance. Biochemical measurements were made in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used to define body composition. DW present with more visceral fat (DW, 138 +/- 5.0; OW, 66.6 +/- 5.0 cm; P < 0.01). This was associated with elevated free testosterone levels (DW, 1.21 +/- 0.1; OW, 0.75 +/- 0.1 nmol/L; P < 0.05). The fasting FFA, glycerol, and lactate levels increased across the three groups (LW < OW < DW). During the oral glucose tolerance test, glucose levels were elevated in DW, with higher insulin levels [0 h: DW, 207 +/- 8.6; OW, 100 +/- 7.2 pmol/L (P < 0.01); 1 h: DW, 410 +/- 15.2; OW, 320 +/- 10.9 pmol/L (P < 0.05)], but with a flat Cpeptide response (1 h: DW, 932 +/- 40; OW, 1764 +/- 40 pmol/L; P < 0.05). Plasma lactate levels increased significantly in LW and OW at 1 h (P < 0.001), but remained lower in LW vs. OW for all time points. ATBF was highest in LW [abdominal, 0 h: DW, 4.5 +/- 0.2; OW, 1.7 mL/100 g.min (P < 0.01); femoral, 0 h: DW, 3.4 +/- 0.2; OW, 1.8 +/- 0.3 mL/100 g.min (P < 0.01)]. ATBF did not increase in DW during the oral glucose tolerance test. Glycerol release (GR) was used to assess the lipolytic rate and was highest in LW in the abdominal area [0 h: LW, 1.7 +/- 0.2; OW, 1.1 +/- 0.2 micromol/kg.min (P < 0.05); DW, 0.78 +/- 0.05 micromol/kg.min (P < 0.05 vs. OW)]. By contrast, GR was higher in the femoral area of OW (0 h: OW, 1.6 +/- 0.2; LW, 1.15 +/- 0.1 micromol/kg.min; P < 0.05). Regional differences were observed for GR in both OW and DW (femoral > abdominal). Lactate release (LR) was low in DW [abdominal, 0 h: DW, 3.5 +/- 0.4; OW, 7.8 +/- 1.0 micromol/kg.min (P < 0.001); femoral, 0 h: DW, 3.1 +/- 0.3; OW, 9.0 +/- 0.9 micromol/kg.min (P < 0.001)]. LR was appropriately low for body fat mass in LW, with a brisk increase between 0 and 1.5 h. A negative correlation exists between GR (abdominal area) and insulin levels in the postabsorptive state (P < 0.0001). In conclusion, 1) the fasting lipolytic rate is associated with insulin levels; 2) OW and DW have more adipose tissue insulin resistance than LW; 3) OW and DW have a brisker lipolysis in the femoral area; and 4) in DW, higher visceral mass is associated with elevated free testosterone and FFA concentrations. Obesity in the black population is therefore characterized by a marked degree of adipose tissue lipolysis. This degree of resistance together with increasing body fat mass may predispose the obese women to developing type 2 diabetes. Once this disease is established, the onset of adipose tissue vascular insulin resistance will sustain ongoing insulin resistance, even in the presence of relative insulinopenia.

Ethnic differences in lipid metabolism in two groups of obese South African women.

There is a higher prevalence of ischemic heart disease (IHD) in South African white than black women. The objective of this study was to determine biochemical explanations for this prevalence. The study group contained 15 obese black women (OBW) and 14 obese white women (OWW), all premenopausal, who were examined after an overnight fast. Anthropometric measurements and blood concentrations of glucose, non-esterified fatty acids (NEFAs), catecholamines, plasminogen activator inhibitor-1, C-peptide, proinsulin, lipograms, cortisol, growth hormone, and post-heparin lipoprotein lipase activity were measured during an oral glucose tolerance test (OGTT). Body composition was measured using bioelectrical impedance analysis, and subcutaneous and visceral fat mass were assessed with CT-scans. Visceral fat area was higher in OWW (139.7 +/- 10.7 cm(2)) than in OBW (72.3 +/- 3.9 cm(2)) (P < 0.01), as were fasting and 3 h triglyceride concentrations (P < 0.05 for all). OWW also had higher NEFA levels than OBW at 3 and 4 h compared with OBW (P < 0.05 for both). Fasting cortisol (266 +/- 24 vs. 197 +/- 19 nmol/l; P < 0.05) was higher in OWW than in OBW. These data demonstrate that OWW have higher visceral fat mass than OBW, which may lead to a more atherogenic fasting and postprandial lipid profile. The higher cortisol levels of the OWW may promote visceral fat deposition.

Evidence for insulin resistance in black women from South Africa.

OBJECTIVE: The rate of glucose disposal was determined in 10 black and 10 white obese nondiabetic urban women from South Africa to assess insulin resistance. DESIGN AND METHODS: Euglycemic hyperinsulinemic clamp and body composition analysis. RESULTS: Age, body mass index (BMI), anthropometric measurements and body composition were similar in both groups of women. A five-level computed tomography (CT) scan showed a similar mean subcutaneous fat mass in both groups of women (black obese women 555 +/- 9.0 vs white obese women 532 +/- 6.0 cm2), but less visceral fat in black obese women (90 +/- 3.0 vs 121 +/- 3.1 cm2; P< 0.05). Black obese women had higher fasting free fatty acid (997 +/- 69 vs 678 +/- 93 micromol/l; P < 0.05) and lactate concentrations (1,462 +/- 94 vs 1,038 +/- 39 micromol/l; P < 0.05), but lower fasting insulin levels (87 +/- 12 vs 155 +/- 9 pmol/l; P < 0.001). Black obese women also had a more favorable HDL: total cholesterol ratio (30.5% vs 23.0%; P< 0.04). The mean glucose disposal rate (M) and disposal expressed as glucose sensitivity index (M/I) were reduced in the black obese women vs white obese women (M: 7.1 +/- 0.8 vs 13.7 +/- 1.0 mmol/kg min(-1) x 100; P< 0.01, and M/I: 0.12 +/- 0.01 vs 0.24 +/- 0.02 mmol/kg x min(-1)/pmol/1 x 1,000; P < 0.01). Only black obese women showed a significant decrease in C-peptide levels during the clamp (2.9 +/- 0.22 vs 1.2 +/- 0.12 nmol/l; P<0.001). During the euglycemic period, the black obese women had higher lactate levels at all time points, but only the white obese women had increased lactate levels (918 +/- 66 to 1,300 +/- 53 micromol/l; P< 0.05). CONCLUSION: Black obese women demonstrate a higher degree of insulin resistance, despite less visceral fat and a higher HDL: total-cholesterol ratio. In addition, endogenous beta-cell secretory function in black obese women appears to be more sensitive to the suppressive effect of exogenous insulin administration. The significant increase in lactate levels in white obese women confirms that they are more insulin sensitive.

Free fatty acids and insulin levels--relationship to leptin levels and body composition in various patient groups from South Africa.

OBJECTIVE: To investigate the relationship between leptin concentrations, various metabolic indices and body composition in six different groups. DESIGN AND MEASUREMENTS: Anthropometric measurements, fasting plasma glucose, serum insulin, C-peptide, FFA and leptin levels were performed. In the obese and diabetic subjects, body composition was analysed with bio-impedance equipment and as a 5 level CT scan. SUBJECTS: Five lipoatrophic diabetes mellitus (LDM) patients, five normal subjects (N), nine white and nine black obese women (WW, BW), and nine white and nine black diabetic women (DWW, DBW) were investigated after an overnight fast. RESULTS: In both ethnic groups there was a positive correlation between leptin and BMI (black group: r=0.8; P<0.0001, white group: r=0.7, P<0.002) and leptin and SC fat mass (black group: r=0.6; P<0.005, white group: r=0.6; P<0.004). CONCLUSIONS: Across the groups, there were positive linear correlations between leptin concentrations, BMI, SC fat mass and FFA levels. Leptin and FFA concentrations are higher and insulin levels lower in both groups of black women compared to the two groups of white women, despite a similar BMI and body fat mass. In the DBW the large increase in visceral fat mass may be indicative of a more complex relationship between compensatory insulin resistance, elevated FFA levels and leptin secretion.

Lactate and glycerol release from the subcutaneous adipose tissue of obese urban women from South Africa; important metabolic implications.

Interstitial glycerol and lactate production was measured in the s.c. adipose tissue of two anatomical regions in 10 obese urban black women (BW) and 10 obese urban white women (WW) matched for age, body mass index, waist-hip ratio, diet, and physical activity. This was done with the s.c. microdialysis technique and combined with adipose tissue blood flow (ATBF) rates calculated from 133Xe clearance. Biochemical measurements were done in the postabsorptive and postprandial state. Bioimpedance and computed tomography scans were used for analyses of body composition. BW responded with lower plasma insulin levels, but higher glucose levels, during the oral glucose tolerance test. BW have higher lactate release from the s.c. adipose tissue, compared with WW, in the postabsorptive state (abdominal: 7.8 +/- 0.9 vs. 2.4 +/- 0.3 micromol/kg x min, P < 0.0001; femoral: 9.1 +/- 0.9 vs. 2.1 +/- 0.3 micromol/kg x min, P < 0.0001) and during the postprandial period (at 1 h, abdominal = 7.3 +/- 0.8 vs. 3.0 +/- 0.4 micromol/kg x min, P < 0.0001, femoral area = 8.1 +/- 1.0 vs. 2.7 +/- 0.4 micromol/kg x min, P < 0.0001; at 2 h, abdominal = 5.7 +/- 0.4 vs. 3.1 +/- 0.3 micromol/kg x min, P < 0.001). The BW also released more glycerol from the sc adipose tissue in the postabsorptive state (abdominal = 1.15 +/- 0.17 vs. 0.65 +/- 0.03 micromol/ kg x min, P < 0.009; femoral = 1.55 +/- 0.19 vs. 0.72 +/- 0.05 micromol/kg x min, P < 0.001) and during the postprandial period (at 1 h, abdominal = 1.05 +/- 0.15 vs. 0.11 +/- 0.02 micromol/kg x min, P < 0.001, femoral = 1.05 +/- 0.12 vs. 0.21 +/- 0.03 micromol/kg x min, P < 0.001; at 2 h, abdominal = 0.31 +/- 0.06 vs. 0.04 +/- 0.01 micromol/kg x min, P < 0.001, femoral = 0.28 +/- 0.07 vs. 0.05 +/- 0.01 micromol/kg x min, P < 0.003). Postprandially, the BW had higher ATBF rates in the abdominal and femoral areas. WW have more visceral fat (150 +/- 2.0 vs. 110 +/- 5.0 cm2, P < 0.05). In conclusion, the insulinopenic BW have a brisker lipolysis and ATBF and release more glycerol and lactate from their sc adipose tissue, both in the postabsorptive state and after an oral glucose tolerance test. These variations in adipose tissue metabolism may contribute to differences observed in the disease profiles of these two groups of women.