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Carbohydrate and Lipid Metabolism Research Group (M.-T.v.d.M., B.I.J.), Departments of Chemical Pathology (N.J.C., I.P.G.), Radiology (G.P.S.), and Nuclear Medicine (I.H.B.), Johannesburg Hospital and University of the Witwatersrand Medical School, Johannesburg 2193, South Africa; and Department of Internal Medicine, University of Goteborg, Sahlgren’s Hospital (P.N.L.), S-41345 Goteborg, Sweden
Address all correspondence and requests for reprints to: Dr. M.-T. van der Merwe, Department of Medicine, University of the Witwatersrand Medical School, 7 York Road, Parktown 2193, South Africa. E-mail: 014jhp{at}chiron.wits.ac.za
Abstract
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 133Xe 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 µmol/kg·min (P < 0.05); DW, 0.78 ± 0.05 µmol/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 µmol/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 µmol/kg·min (P < 0.001); femoral, 0 h: DW, 3.1 ± 0.3; OW, 9.0 ± 0.9 µmol/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.
OBESITY IS CHARACTERIZED by alterations in metabolic function that result from an increase in body fat mass as well as the visceral distribution of adipose tissue (1, 2). It has become clear that these metabolic alterations may be closely involved with the development of important comorbid diseases, e.g. type 2 diabetes and ischemic heart disease (3, 4). In contrast to the considerable knowledge about the biochemical background to these alterations, relatively little is understood about the influence of ethnic variability on these changes (5), and although a strong clinical association exists between obesity and type 2 diabetes, questions remain about the relationship between obesity and adipose tissue insulin resistance in diabetes (6).
In South Africa the prevalence of obesity is on the order of 50% for urban women between the ages of 45–65 yr (7). Recent studies performed by us have focused on investigating metabolic differences that could explain the prevalence of various comorbid diseases of obesity in two of our ethnic populations (8, 9). In particular, industrialized urban black women still exhibit a low incidence and mortality due to ischemic heart disease (IHD), whereas type 2 diabetes within this population group is increasing rapidly (10, 11). Previous research findings in urban black women (BW), showed less visceral fat compared with white urban women matched for body mass index (BMI) and body composition (8, 9), a brisker in vivo adipose tissue lipolysis (9), a higher postabsorptive FFA and leptin concentrations with relative insulinopenia (8, 9, 18), a higher proportion of proinsulin conversion to insulin with minimal loss in PC-2 proinsulin processing efficiency,2 and a higher degree of in vitro and in vivo adipose tissue insulin resistance (8, 12). In addition, diabetic BW have impaired hepatic insulin clearance (13).
The above data highlighted the need to conduct a more detailed investigation of adipose tissue metabolism in lean, obese, and diabetic urban BW. The aim of this study was therefore to analyze intermediary metabolism in relation to body composition, sc adipose tissue blood flow, lipolytic rate, and insulin resistance and to relate these findings to the high incidence of type 2 diabetes and the low incidence of ischemic heart disease in urban BW.
Subjects and Methods
Subjects
Ten lean, 10 obese, and 10 obese type 2 diabetic urban BW were studied. They were matched for age (lean and obese), level of habitual activity, number of offspring (no more than three), and socio-economic background. The women followed a westernized diet, with less than 30% of calories obtained from fat. The duration of obesity was 5–8 yr, and the time since the onset of diabetes was 3–5 yr. Weight stability was documented in the 2 obese groups before the investigations. The diabetic patients were well controlled (hemoglobin A1, <7%) on oral agents (sulfonylureas with or without metformin), and no urinary ketones were present on the morning of their investigation. The diabetic patients did not take any medication after 1900 h the previous evening and remained fasting until the next morning. None of the women was postmenopausal or taking an oral contraceptive. All of the patients gave informed consent, and the study was approved by the committee for research on human subjects of the University of the Witwatersrand.
The exclusion criteria included diseases of the major organs and a history of bulimia. None of the women smoked, and they were not allowed to consume alcohol for 7 days before their investigations. No vigorous exercise was allowed for 12 h before the test date. The metabolic investigations were started at 0700 h in the morning after an overnight fast of 10 h, and the tests were conducted during the first 10 days of the follicular phase of their menstrual cycles.
Body composition analyses
These tests were performed on a separate day, approximately 10 days before the metabolic investigations.
Computed tomography (CT) scan measurements. In the week before their investigation a five-level CT scan was performed (SR 7000, Philips, Rotterdam, The Netherlands) as previously described (9). The women fasted for 10 h overnight. The scan parameters were 10-mm slice thickness, 120 kV, 250 mA, 2 s, and 340- to 480-mm field of view, depending on the size of the subject. Photographic images were taken during resting expiration. The five levels were derived from two scanograms and included a CT scan slice at the level of the diaphragm, the umbilicus, L4–L5 lumbar disc, the widest diameter of the pelvis, and midthigh (the total distance from iliac crest to acetabulae and from acetabulae to knee joint, divided by 2). The first scanogram included the diaphragm, umbilicus (marked with a metallic coin), iliac crest, and symphysis pubis, with a maximum length of 500 mm from the umbilicus. The second scanogram extended from the symphysis pubis to the knees. The widest parasagittal diameter was measured at the level of L4–L5. The fat areas were calculated with a region of interest seeding program on a Philips Gyroview workstation (fat values were chosen between -30 and -130 Hounsfield Units). The areas of sc and visceral fat were calculated separately, and the anatomical boundaries were as described by Kvist et al. (14, 15). Visceral fat was measured at the top three levels.
Bioimpedance analyses. This was performed while subjects were fasting in the morning. The Bodystat machine (Bodytrach Pty. Ltd., Stellenbosch, South Africa) was used to assess body composition for fat and muscle tissue (kilograms; percentage) (9). The bioimpedance equations are based on the South African population as a whole [fat free mass (kg) = aH2/z + bH2/wt + cH + d age + e, where H is height, wt is body mass, z is whole body impedance, and a, b, c, d, and e are regression coefficients, validated by the Dunn nutritional center, University of Cambridge, UK].
Microdialysis and blood tests
The patients were studied in the supine position in a room kept at 25 C. One polyethylene catheter was inserted iv in the forearm and placed under a heating pad to ensure sampling of arterialized venous blood (16). At the onset of the study we measured fasting plasma glucose, insulin, FFA, glycerol, and lactate levels. Two microdialysis catheters (0.4 x 30 mm, F4HPS, 5000 molecular weight cut-off, Fresenius, Berlin, Germany) were inserted into sc adipose tissue, 5 cm lateral to the umbilicus and at the level of the midfemur. The insertion was made through a fine cannula (Jelco 16SDD, Criticon, Johannesburg, South Africa) (17), and the inlet nylon tubing of the microdialysis catheter was connected to a precision pump (CMA/100, Carnegie Pty Ltd., Stockholm, Sweden). No local anesthetic was required. For initial equilibration the microdialysis catheters were perfused for 60 min at a rate of 2.5 mL/min with an isotonic saline solution containing 2.5 mmol/L glucose, 25 µmol/L glycerol, and 250 µmol/L lactate to prevent depletion of tissue concentrations (17).
In vivo calibration for the microdialysis catheters
The equilibration calibration technique has been described in detail previously (17). Two 10-min samples were collected for each perfusion concentration, and after the oral glucose tolerance test (OGTT) the samples were collected at 15-min intervals at the level of the final concentration. The net change in the glycerol and lactate concentrations in the outgoing dialysate were calculated. The linear relationship between the concentrations of glycerol and lactate in the ingoing perfusate and the net change in these concentrations in the outgoing dialysate could then be used to calculate the absolute interstitial concentrations for these substances by means of regression analyses by determining the point of no net influx of substrate into perfusate (17).
OGTT
A standard 75-g OGTT was performed at approximately 1400 h. Arterialized postprandial blood samples were taken at four time points over the next 2 h.
Subcutaneous blood flow
Blood flow was measured to be able to determine lactate and
glycerol release (GR) per 100 g adipose tissue/min. An injection
of 3–6 megabecquerels 133Xe in 0.1 mL sterile
saline was given 5 mm under the skin in the sc adipose tissue,
contralateral to the two microdialysis sites. After 60 min, xenon
clearance was monitored at 20 frames/min for a period of 180 min, of
which 120 min were post-OGTT. The energy window was set at 81 keV
± 10%. Initial counts per site were about 10,000 in the 3-min missing
period to enable reliable measurements for 3–4 h. The Elscint 415 ECT
-camera (Elscint, Jaffa, Israel) was used for acquisition of
the data, with the detector placed at 30–50 cm from the
133Xe depot (frame size, 128 x 128 pixels;
zoom factor, 1; collimator, 3). The counts were plotted on a
logarithmic-linear diagram as a function of time. Adipose tissue blood
flow (ATBF) was then calculated with the equation: ATBF = 
x k x 100, where is the tissue to blood partition
coefficient for xenon at equilibrium, and k is the slope of the washout
curve. Experimental values of k were estimated by performing least
squares regression analysis. A mean value of 10.0 mL/g was used for
the partition coefficient (18). In addition, this
value of 10.0 mL/g was chosen for the abdominal and femoral areas in
both groups of women (19), as no difference in cell size
was documented during in vitro cell studies in these four
areas (see Footnote 1). Control experiments have previously shown a
24% mean relative error of 133Xe clearance
measured at two corresponding sites (18).
Biochemical analyses
Glucose was measured with an enzymatic colorimetric method
(GOD-PAP, Roche Molecular Biochemicals, Mannheim,
Germany), insulin levels were measured with an enzyme-amplified
sensitivity immunoassay (EASIA-Medgenix Diagnostics, Antwerp,
Belgium; normal range, 13.8–172.5 pmol/L), and C peptide was
measured by RIA (Medgenix Diagnostics; normal range, 110-1270 pmol/L).
FFA levels were measured with a Half-Micro test (Roche Molecular Biochemicals). Fasting blood samples were also analyzed for
progesterone (Amerlite Progesterone Assay, Amersham Pharmacia Biotech, Little Chalfont, UK; enhanced luminescence with normal
range of 5.84–96.0 nmol/L in the luteal phase), free testosterone
(Enzymun-Test, Roche Molecular Biochemicals; enzyme-linked
immunosorbent assay with a normal range of 0–2.1 nmol/L), and sex
hormone-binding globulin (125I; Farmos
Diagnostica, Helsinki, Finland; immunoradiometric assay kit with
normal range of 20–120 nmol/L). In addition, we assayed epinephrine,
norepinephrine, and dopamine levels in the postabsorptive state. These
samples were taken 1 h after insertion of the iv cannula when the
subjects were recumbent and relaxed. Samples were placed on ice
instantly and centrifuged within 10 min. High performance liquid
chromatography with electrochemical detection was used for analyses,
and normal ranges are as follows: norepinephrine, 100–800 pg/L;
epinephrine, 10–80 pg/L; and dopamine, 10–150 pg/L. The glycerol
contents in adipose tissue dialysate and plasma were determined with a
radiometric phosphorous method (20). Glycerokinase was
obtained from Roche Molecular Biochemicals, and
[-32P]ATP was purchased from NEN Life Science Products (Boston, MA). Plasma lactate was analyzed
within 14 days according to a fluorometric method described by Loomis
(21). The specimens were centrifuged within the hour, and
serum was stored at -70 C until analyzed in a single batch to avoid
interassay variation.
Estimation of glycerol and lactate release (measured as micromoles per 100/min)
According to Fick’s principle, arterialized venous plasma (A)
and capillary venous plasma concentrations of lactate and glycerol (V)
and plasma flow rate (Q) were entered into the equations: 1) EF =
I - Ax (1 - e-PS/Q); and 2) E =
EF x Q, where PS is the permeability surface product area
(adopted to be 
5 mL/100 g/min for glycerol and lactate)
(21), EF is the extraction factor, and E is
extraction.
Statistical analysis
Data are expressed as the mean ± SEM. Significance for multiple samples was established by one-way ANOVA. Statistical significance of parametric data was assessed by Student’s paired and unpaired t tests. Nonparametric data (e.g. blood flow, tissue levels, and release values) were assessed by signed rank test for paired samples. Absolute interstitial levels were calculated by linear regression analysis with the least squares method, and linear correlations were tested with Pearson’s correlation coefficient. Results were deemed significant at P < 0.05.
Results
Clinical features and body composition (Table 1
)
BMI and anthropometric measurements were lower in lean (LW) vs. obese (OW) women. Body composition of the OW and diabetic women (DW) were well matched. However, the DW had a higher visceral fat accumulation (138.0 ± 5.0 vs. 66.6 ± 5.0 cm2; P < 0.01). This was associated with a significantly higher waist circumference in the DW (110.0 ± 5.0 vs. 90.6 ± 3.0 cm; P < 0.05)
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)FFA, glycerol, lactate, insulin, and C peptide concentrations increased across the three groups (LW < OW < DW). LW had a more favorable lipid profile, and for all three groups of women the high density lipoprotein/total cholesterol ratio was above the protective 20% for ischemic heart disease (7). Only the DW had an elevated glucose concentration. The DW also had significantly elevated free testosterone concentrations, associated with lower sex hormone-binding globulin levels. No differences were observed in the fasting catecholamine concentrations.
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During the 75-g OGTT, the glucose concentrations in the DW were significantly higher for all time points compared with those in OW and LW [1 h: DW, 12.1 ± 1.0; OW, 8.2 ± 0.5; LW, 7.9 ± 0.5 mmol/L (P < 0.05); 2 h: DW, 13.3 ± 0.7; OW, 7.5 ± 0.4; LW, 7.2 ± 0.6 mmol/L (P < 0.01)]. This was associated with higher 1-h insulin concentrations in DW than OW (410 ± 50 vs. 361 ± 30 pmol/L; P < 0.05), but with a very flat C peptide response in the DW (1 h: DW, 932 ± 133; OW, 1764 ± 120 pmol/L; P < 0.05). The LW had both lower insulin [1 h, 278 ± 29 pmol/L (P < 0.01); 2 h, 222 ± 30 pmol/L (P < 0.01)] and C peptide (1 h, 1265 ± 133 pmol/L; P < 0.01) responses compared with OW.
For all time points the glycerol and FFA concentrations were highest in the DW and lowest in the LW. Both indexes showed a significant reduction by 120 min (by ANOVA, P < 0.001; glycerol at 2 h: LW, 24.1 ± 1.8; OW, 35.1 ± 2.4; DW, 36.8 ± 2.8 µmol/L; FFA at 2 h: LW, 132 ± 27; OW, 251 ± 39; DW, 425 ± 46 µmol/L). Plasma lactate levels had increased significantly by 1 h post-OGTT in the LW (1287 ± 120 µmol/L; P < 0.001) and OW (1918 ± 115 µmol/L; P < 0.001), whereas no significant increase was observed in DW. For all time points the LW had lower lactate concentrations compared with those in OW.
Subcutaneous ATBF rates (Table 3)
In the abdominal region blood flow increased significantly by 90 and 120 min in LW and by 60 min in OW. Virtually no increase was noted in the DW. Likewise, in the femoral region, blood flow increased significantly by 90 min in the LW and by 60 and 90 min in the OW. The DW again demonstrated a poor vasodilatory response, with an insignificant increase in blood flow. For both anatomical regions, blood flow was highest in the LW. The OW had a higher blood flow in the femoral vs. abdominal region.
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Interstitial glycerol concentrations (Table 4) were highest in the DW, with no
regional differences observed in any of the three groups of women.
Glycerol levels decreased significantly 2 h post-OGTT in both
anatomical regions. Interstitial lactate concentrations (Table 4)
increased in the LW in both regions by 1 h post-OGTT. By contrast,
the significantly higher lactate levels in the OW showed little
elevation, in keeping with a higher degree of adipose tissue insulin
resistance. Likewise, the DW illustrated no incremental rise in lactate
concentrations. No regional differences were observed.
Interstitial-arterial differences for glycerol (Table 5) were highest in the DW at fasting and
significantly so in the femoral area at 1 and 2 h post-OGTT.
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Interstitial GR was used to accurately reflect the lipolytic rate. This was highest in the postabsorptive state in the abdominal area in the LW (abdominal area, 1.7 ± 0.2; femoral area, 1.2 ± 0.2 µmol/kg·min; P < 0.05), in keeping with their degree of insulinopenia. Logarithmic regression analysis showed a negative correlation between the fasting insulin concentration and postabsorptive GR (abdominal), with the highest GR taking place at an insulin concentration below 50 pmol/L. In the femoral region, the OW had a greater degree of resistance to the antilipoplytic effect of insulin, with more GR (abdominal area, 1.1 ± 0.2; femoral area, 1.7 ± 0.1 µmol/kg·min; P < 0.05). Likewise, the DW had higher GR in the femoral area from 1–2 h post-OGTT.
Discussion
Numerous studies have shown that the clinical onset of type 2
diabetes in high risk populations is preceded by a period of insulin
resistance. It is believed that both genetic and acquired factors
contribute to the insulin resistance (22), and among the
most important of these is obesity (i.e. 80% of people
with type 2 diabetes are obese) (23). In addition,
lipolysis is the process most sensitive to the action of insulin, with
a more than 90% effect taking place well within the physiological
range (24). In obese and type 2 diabetic subjects, the
plasma insulin EC50 for suppression of lipolysis
is increased 2- to 3-fold, indicating that adipose tissue is at least
as resistant to the action of insulin as muscle and liver
(25). As failure to adequately turn off lipolysis directly
affects liver and muscle metabolism, it is tempting to speculate that
adipose tissue may be a primary site for the development of generalized
insulin resistance (25). We decided to study intermediary
and adipose tissue metabolism more definitively in a broader spectrum
of BW, because our previous findings showed a greater degree of whole
body insulin resistance in South African BW compared with white women
(8, 12, 26). In addition, the rapid increase in type 2
diabetes among the black population may be causally linked with an
increase in body fat mass.
In South Africa, it has previously been shown that obese BW have less visceral fat than white women for a comparable BMI (8, 9, 13). During this study we found a larger amount of visceral fat accumulation in black DW compared with OW. It would therefore appear as if the development of type 2 diabetes is associated with a relative worsening of one of the components of the plurimetabolic syndrome. The association found in women between visceral adiposity and elevated testosterone levels was previously observed by Evans et al. (27). A cross-sectional association also exists among excess visceral adiposity, higher serum insulin levels, and insulin resistance (28, 29). This appeared to be the case in the black DW as well, in whom higher insulin concentrations were documented than in the OW. This could have been aggravated by diminished hepatic insulin clearance caused by the higher fasting FFA levels (30).
Systemically elevated FFA levels may also induce insulin resistance in both muscle and liver through various mechanisms (31, 32, 33). Furthermore, recent data suggested that chronically elevated FFA levels will cause an additional longitudinal impairment of ß-cell function in humans (34, 35). The relative insulinopenic state of the black Southn African population may reflect a reduction in their ß-cell mass, previously observed by Joffe et al. (36, 37). In this study the DW had a diminished ß-cell reserve, and a very poor C peptide response was documented during the OGTT. In contrast to the classical hyperinsulinemia documented in people of European descent, increased adiposity in the black population is associated with a poor ß-cell response, leading to rapid exhaustion of their secretory capacity (see Footnote 1). A putative reduction in the ß-cell mass could be linked to transient periods of protein-energy malnutrition during infancy or in utero (38, 39). However, there is considerable controversy about a hypothesis that discounts a genetic contribution to type 2 diabetes mellitus. Dunger et al. recently reported that size at birth could be influenced by a common genetic variation in insulin gene expression or in a neighboring gene, such as insulin-like growth factor II (40).
The prevalence of certain obesity-related disorders differs between black and white urban women in South Africa: mortality from ischemic heart disease remains rare in obese black South Africans (8/100,00 vs. 55/100,000), whereas hypertension and type 2 diabetes are more common (41, 42, 43). This may be related to the adverse lipid profile observed in the white population during both fasting and the late postprandial phase (44). A striking feature of this study was the favorable lipid profile and high density lipoprotein to total cholesterol ratio that was present in all three groups of black women, even when they were obese and diabetic (7, 8, 9). This together with lower amounts of visceral fat (8, 9) may offer them a degree of protection against atherosclerosis, but not against insulin resistance per se (26). Similar observations were made by Lovejoy et al. when studying African-Americans (45). In South Africa, obese white women were found to have higher cortisol levels than obese BW (46). Because visceral fat is known to have a higher level of expression of glucocorticoid receptors than other fat depots, this could lead to increased cortisol-associated metabolic activity and fat accumulation (47). Furthermore, the diabetic women have a mean age of 40 yr, and their age-related susceptibility to develop visceral adiposity may therefore have added to their susceptibility to develop type 2 diabetes (48). It therefore seems that in a country undergoing rapid industrialization, both glucose and lipid toxicity play a role in the pathogenesis of comorbid diseases of obesity; however, different ethnic groups are not necessarily affected by both to the same degree, raising the need for very specific primary health care guidelines.
Both the obese and diabetic BW showed a marked degree of adipose tissue insulin resistance, as evident by the insignificant increase in lactate release after the glucose load. Both groups of women also had higher postabsorptive plasma and interstitial lactate concentrations compared with the lean BW, suggestive of an associated insulin resistance as previously described by Lovejoy et al. (49). It therefore appears that basal lactate levels are inversely related to insulin sensitivity, whereas the rate of lactate production following a glucose load was directly related to insulin sensitivity (49). Furthermore, both glucose and lactate metabolism is primarily linked to the degree of insulin resistance and not just to the degree of obesity (50). A higher degree of insulin sensitivity could therefore explain the lactate released in a group of Caucasian obese type 2 diabetics studied by Jansson et al. (51).
Previous measurements with microdialysis in sc adipose tissue have shown that adipose tissue is a significant source of lactate production (50, 53). Adipose tissue lactate production (found to be particularly high in our obese BW) serves as an important gluconeogenic precursor for hepatic glucose production and glycogen synthesis. As such, it may have important metabolic implications in glucose homeostasis in the obese black population, in whom the incidence of type 2 diabetes is increasing rapidly. This operative mechanism seems to be particularly relevant in the initiation of glucose impairment in the obese BW, and advanced insulin resistance at various organ levels may well sustain ongoing hyperglycemia once the patients are diabetic. The decrease in the postprandial lactate interstitial-arterial difference in the OW indicate an additional source of lactate production other than adipose tissue, most likely muscle tissue. Recent studies of rats indicate that insulin resistance and vasodilation in muscle, induced by ß-adrenergic stimulation, were followed by increased interstitial concentrations of glucose and lactate without alterations in interstitial insulin despite an increased insulin secretion rate (54).
The influence of insulin on GR is 2-fold. Firstly, the antilipolytic effect of insulin is the main regulator of lipolysis before and during an OGTT (55). Secondly, insulin acts as an endothelium-dependent vasodilator, the effect of which will be diminished in insulin resistance (56). It is therefore conceivable that adipose tissue insulin resistance would elevate GR, whereas vascular insulin resistance would diminish it. In the postabsorptive state, the present study showed a negative correlation between the GR and fasting insulin concentrations, but in the abdominal area only. This would imply a lesser degree of insulin resistance in the abdominal region in OW and DW compared with that in the femoral region. These results are in keeping with our previous findings of more femoral insulin resistance in BW during both in vivo and in vitro studies (8, 12). The exact mechanism underlying this regional difference in degree of adipose tissue insulin resistance needs future clarification, but factors to be considered would include insulin receptor number, binding affinities, and local tissue concentrations of sex steroids (57). Whether the GR in our DW purely reflects this causal linkage between insulin and degree of suppression of lipolysis or whether it is a modified manifestation of the poor vasodilatory response to the glucose load remains debatable. Changes in local blood flow could alter interstitial concentrations independently of the actual production by the adipocytes (58). Furthermore, it is notable that GR expressed per kg fat mass does not reflect whole body lipolysis, and once the interstitial-arterial differences were corrected for total kilograms fat mass, the DW had higher values than the OW, in keeping with being more insulin resistant. Jansson et al. previously suggested that no primary defect was evident in postabsorptive adipose tissue metabolism in well controlled diabetics at a much lower BMI (51). This may not necessarily be the case for diabetics at a BMI above 35 or when they were studied during the postprandial period.
In summary, the postabsorptive lipolytic rate of abdominal adipose tissue in urban BW is strongly influenced by their fasting insulin concentrations. In this anatomical region, the compensatory hyperinsulinemia associated with obesity and diabetes can partially compensate for adipose tissue lipolysis. In contrast to the LW, OW and DW appear to have a marked degree of adipose tissue insulin resistance, particularly in the femoral region. The higher visceral fat mass in the DW is associated with higher FFA and testosterone levels. In addition, the severity of insulin resistance observed in the OW appear to also manifest as endothelium-related vascular insulin resistance in the diabetic patients. Even though there is no general agreement on the definition of the metabolic syndrome, there is increasing evidence that insulin resistance (also at the adipocyte level) is the most frequent factor underlying the individual components of the syndrome (59). Thus, the management of people with the metabolic syndrome should also include strategies for the improvement of all clinical components. As such, obesity and its related insulin resistance should not be viewed as a benign condition among the black population (60). Intervention with weight management may in the long run prove to be the most efficient way to prevent a further escalation in the prevalence of diabetes mellitus, especially if a putative thrifty genotype is already operative in this population (61).
Acknowledgments
We thank Jenny Pieters for typing the manuscript, Ann Fennel for outstanding technical assistance, and Darren Boyd for performing part of the statistical analyses. We are also grateful to Marion Herz at Presentation Graphics.
Footnotes
1 The chemical analyses were supported in part by the
SAIMR. 
2 Punyadeera, C., M. T. Van der Merwe,
N. J. Crowther, M. Toman, and I. P. Gray, submitted for
publication.
Received August 3, 2000.
Revised March 12, 2001.
Accepted March 16, 2001.
References
This article has been cited by other articles:
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  E. L. Ding, Y. Song, V. S. Malik, and S. Liu Sex Differences of Endogenous Sex Hormones and Risk of Type 2 Diabetes: A Systematic Review and Meta-analysis JAMA, March 15, 2006; 295(11): 1288 - 1299. [Abstract] [Full Text] [PDF]
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