Insulinsensitive and resistant Variants in Type Diabetes in African Americans

Type 2 diabetes in African Americans is a heterogeneous disorder with insulin-sensitive and insulin-resistant variants identified using the eu-glycemic insulin clamp method (77). In contrast, most studies (66,78,79) with few exceptions (80,81,82) report Type 2 diabetes to be a disorder of insulin resistance. The two variants are notably different in terms of cardiovascular risk factors and body composition (72,83,84). The insulinsensitive variant has low lipid levels while the insulin-resistant variant has higher lipid levels.

The relationship of insulin action to obesity was studied: most obese African American Type 2 diabetes subjects (BMI > 30 kg/m2) were insulin-resistant, but below this level, they were equally likely to be insulin-resistant as insulin-sensitive (85). Further body composition studies using 23 scan computed tomographic techniques showed among modestly obese to lean diabetics (BMI 26.3 men

Table 9A.4 Association of plasma insulin or insulin resistance to the components of the metabolic syndrome X in black subjects

Plasma insulin

Insulin resistance

Blood pressure

Glucose intolerance

Trig

HDL-chol

Central obesity SSST/waist/WHR

Comments

Fontbonne

Associations found in groups based on high and low

Telecom (48)

X

Yes

Yes

Yes

Yes

plasma insulin level

Freedman (54)

X

Yes

Yes

Children and adolescents-selected by extremes of plasma

Jiang

X

No

VLDL and LDL cholestrol levels

Bogalusa (73)

Ref (54): X-sectional data, association with central fat not

seen in thin or sexually immature children; Ref (73): 6-year

longitudinal data

McKeigue (56)

X

Yes

Yes

Yes

Yes

Association reported for mean only

Nabulsi (51)

X

No

Yes

Yes

Yes

Associations stronger for lean versus obese subjects

Folsom

X

Yes

ARIC (76)

Folsom (50)

X

Yes

Yes

Yes

Association of % body fat and CV risk factors not

Manolio

Yes Yes

explained entirely by plasma insulin levels

CARDIA (57)

X

Karter

X

X

Yes

IRAS (60)

Chaturved (49)

X

Yes

Cruikshank (55)

X

No

Yes

Falkner (65)

X

X

Yes

Young lean hypertensive and normotensive men

Saad (61)

X

X

No

Young modestly obese US men

Association found in whites but not blacks

Osei (74)

X

No

No

Yes

lst-degree non-diabetic relatives of Type 2 diabetic subjects

Gaillard (75)

X

No

Yes

Yes*

No

lst-degree relatives of Type 2 diabetes US blacks n = 200

*association only in highest insulin quintile

Chaiken (71)

X

No

Yes

Yes*

Diabetic subjects *men only

Banerji (84,86)

X

Yes

Yes

Diabetic subjects

Central obesity = total visceral fat measured by computed

tomography

Trig = serum trigylceride levels WHR = waist to hip ratio

HDL-chol = serum HDL-cholesterol levels

SSST =

subscapular

or skinfold thickness

and 27.7 women), insulin-sensitive subjects had significantly lower visceral or intraabdominal adipose tissue volume compared with the insulin-resistant variants (84). In contrast, there were no differences in subcutaneous adipose tissue volume. Comparing men and women with Type 2 diabetes, total visceral adipose tissue volume was not different while total or subcutaneous adipose tissue was 2-fold greater in women (84). Insulin-mediated glucose disposal, derived using euglycemic clamp studies, was inversely related to visceral adipose tissue in both men and women while there was no such relationship with subcutaneous adipose tissue, Figure 9A.5. Increased visceral adipose tissue was related to increased liver fat (measured by CT density) (86). Liver fat content may alter the dynamics of hepatic insulin clearance (87) and thus, insulin resistance and hyperinsulinemia may both be the result of increased visceral adipose tissue and hepatic fat. Whether insulin sensitivity or visceral adipose tissue is genetically or environmentally determined is not known; however, differences in HLA-DQ subtyping in the resistant and sensitive variants (88) suggest a genetic component.

Insulin-sensitive subjects have low plasma LDL-cholesterol and triglyceride levels compared to insulin-resistant subjects, suggesting markedly different cardiovascular disease outcomes (72,83). Serum triglyceride is inversely related to insulin mediated glucose disposal levels, visceral fat and liver fat (86). The presence of insulin-resistant and insulin-sensitive diabetic subtypes with differing cardiovascular risk factors is consistent with the lower serum triglyceride levels and higher HDL-cholesterol levels found among African Americans and Afro Caribbeans compared to whites (48,51,56,69) and their lower rates of cardiovascular disease (6,55).

Several studies estimate the frequency of insulinsensitive compared to insulin-resistant subtypes. Chaiken reports that 30% or 27 of 90 unselected African American clinic-based Type 2 diabetes subjects with a BMI < 30 kg/m2, were insulinsensitive (euglycemic insulin clamp technique) (71). Ginsberg showed that following treatment of hyperglycemia, some African Americans Type 2 diabetes subjects were normally insulin-sensitive (89). In contrast, a small subset of the IRAS population-based study showed that only 11% of African American Type 2 diabetes subjects with a BMI < 30 kg/m2 (n = 60) were insulin-sensitive, using the FSIVGTT-S1 (44).

Whether differences in frequency of insulin sensitivity among studies of African Americans

Figure 9A.5 Relationship of insulin-mediated glucose disposal (mg.kg lean body mass (LBM)-1.min-1) during a 1 mU.kg-1.min-1 euglycemic insulin clamp with adipose tissue distribution in black men (filled squares) and women (open triangles) with Type 2 diabetes

Panel A: Glucose disposal and total visceral adipose tissue volume (ml/m2 body surface area, BSA); equation for line shown is y = -4.15 ln(x) + 38.86. Correlation coefficient = -0.58, p = 0.0001 Panel B: Glucose disposal and total subcutaneous adipose tissue volume (ml/m2 body surface area, BSA), correlation coefficient = -0.27, p = not significant

Source: Reproduced from (84) by permission.

with Type 2 diabetes are due to differences in amounts of visceral adipose tissue, inherent population differences or technique is not known. Insulin action measured by the FSIVGTT-S1 may not be equivalent to euglycemic insulin clamp technique in diabetic subjects (45). Therefore, based on the evidence, one can conclude that above a BMI of 30, African Americans with diabetes are likely to be insulin-resistant and below this, up to 30% are likely to be insulin-sensitive.

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