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The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 10 4596-4601
Copyright © 2003 by The Endocrine Society

Is Glycosylated Hemoglobin A1c a Surrogate for Metabolic Syndrome in Nondiabetic, First-Degree Relatives of African-American Patients with Type 2 Diabetes?

Kwame Osei, Scott Rhinesmith, Trudy Gaillard and Dara Schuster

The Ohio State University, College of Medicine and Public Health, Columbus, Ohio 43210

Address all correspondence and requests for reprints to: Kwame Osei, M.D., F.A.C.E., F.A.C.P., 491 McCampbell Hall, Columbus, Ohio 43210. E-mail: osei-1{at}medtr.osu.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Glycosylated hemoglobin (Hb)A1c provides a practical assessment of long-term glycemic control in patients with diabetes. However, whether HbA1c has any clinical significance in metabolic syndrome (MS) in nondiabetic subjects remains debatable. Therefore, we examined the impact of different levels of HbA1c on insulin sensitivity (Si), non-insulin-dependent glucose disposal, and blood pressure (BP), as well as lipids and lipoproteins in nondiabetic, first-degree relatives of African-American patients with type 2 diabetes.

The study consisted of 219 nondiabetic, first-degree relatives (offspring and siblings) of African-American patients with type 2 diabetes. To examine the metabolic impact of HbA1c in our population, HbA1c was divided into tertiles (normal range, 3.3–6.4%). The mean HbA1c was 4.7% (range, 3.3–4.8%, n = 74) for tertile 1, 5.4% (range, 4.9–5.6%, n = 73) for tertile 2, and 5.8% (range, 5.7–6.4%, n = 72) for tertile 3. Si and glucose effectiveness (Sg) were determined by the Bergman’s minimal model method. Homeostasis model assessment (HOMA)-insulin resistance and HOMA-ß-cell function were also estimated. BP, body compositional variables, and body fat distribution, as well as fasting serum lipid and lipoprotein concentrations, were determined in each subject.

The mean age, body weight, body mass index, waist and hip circumference, and systolic and diastolic BPs were significantly (P < 0.02–0.001) greater in the subjects in tertile 3 than those in tertiles 1 and 2. The mean fasting serum glucose was significantly (P < 0.01) higher in tertile 3 (95.5 ± 3.2 mg/dl) than in tertile 2 (83.0 ± 2.7 mg/dl) and tertile 1 (78.8 ± 1.5 mg/dl). Mean fasting serum insulin and c-peptide levels tended to be higher in tertile 3 subjects than in those in tertiles 1 and 2, but the mean differences did not reach statistical significance. The mean Si was significantly (P < 0.001) lower in the subjects in tertile 3 [1.66 ± 0.2019 x 10-4·min-1(µU/ml)-1], when compared with those in tertile 1 [2.27 ± 0.20 19 x 10-4·min-1(µU/ml)-1] and tertile 2 [2.61 ± 0.19 x 10-4·min-1(µU/ml)-1]. The mean Sg was significantly (P < 0.02) lower in tertile 3 (1.95 ± 0.12 x 10-2·min-1), when compared with those of tertile 1 (2.27 ± 0.10 x 10-2·min-1) and tertile 2 (2.29 ± 0.11 x 10-2·min-1). In addition, the (HOMA)-insulin resistance was significantly (P < 0.01) higher in tertile 3 (3.62 ± 0.26) than in tertile 1 (2.6 ± 0.21) and tertile 2 (2.55 ± 0.31) HbA1c. In contrast, HOMA-ß-cell function, was not different among tertiles 1, 2, and 3. Mean fasting serum triglycerides, cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels also were not significantly different in subjects in tertile 3, when compared with those in tertiles 1 and 2.

In summary, the present study demonstrates that the upper tertile HbA1c level (tertile 3) reflects some components of MS in the nondiabetic, obese, first-degree relatives of African-Americans who are genetically predisposed to type 2 diabetes. The metabolic abnormalities in the upper tertile 3 subjects included a reduced insulin action (Si) and reduced Sg, as well as elevated systolic and diastolic BPs, but not ß-cell secretion and lipids and lipoproteins. We conclude that the upper tertile of HbA1c should be considered as a major surrogate of MS in high-risk African-Americans who are genetically predisposed to type 2 diabetes.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
RECENTLY, THERE HAS been increasing interest in the metabolic syndrome (MS), or insulin resistance syndrome, which is regarded mostly as a constellation of anthropometric and metabolic parameters that lead to cardiovascular diseases (CVDs) in humans (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). The current definition of MS, by the Adult Treatment Panel III, includes blood pressure (BP) of 135/85 mm Hg, serum triglycerides more than 150 mg/dl, serum high-density lipoprotein cholesterol (HDL-C) levels less than 45 mg/dl in females and less than 40 mg/dl in males, waist circumference more than 88 cm (38 in.) for females and more than 102 cm (40 in.) for males, and fasting glucose more than 110 mg/dl (10, 11, 12). These anthropometric, hemodynamic, and biochemical parameters seem to antecede the development of hypertension and type 2 diabetes and, eventually, CVDs. In this regard, Ford et al. (10) and others (11, 12, 13) examined the Third National Health and Nutrition Examination Survey (NHANES III) data and reported that there is a large pool of the general U.S. population (approximately 50 million; age, 24–75 yr) who have MS. Worthy of note is that, the prevalence of MS varies among different ethnic populations (11, 12, 13). In this regard, the prevalence of MS [as defined by Adult Treatment Panel III and World Health Organization (WHO)] was: 21.6% in African-Americans, 23.8% in white Americans, and 31.9% in Mexican-Americans. The reasons for the ethnic differences are unclear but can be ascribed to differences in rates of obesity, hypertension, glucose intolerance, and body fat distribution patterns.

Although insulin resistance is regarded as the etiological lesion underpinning for MS, the direct measurement of quantitative insulin sensitivity (Si) can be laborious and complex in the general population. In this regard, simple measures, such as fasting serum insulin, have been used as a surrogate of insulin resistance in previous epidemiological studies. Thus, we propose that hemoglobin (Hb)A1c could be an important surrogate for MS for several reasons. First, HbA1c reflects long-term glycemic control in diabetic patients. Second, HbA1c is a significant predictor of long-term complications of diabetes in both cross-sectional and longitudinal studies in both type 1 (14) and type 2 diabetes (15). Third, it has been demonstrated that HbA1c represents both fasting and postprandial glycemic states (16, 17, 18, 19, 20, 21). However, for practical and pragmatic reasons, there is no universal acceptance of HbA1c as a screening or diagnostic tool for diabetes because HbA1c has a 65% sensitivity, but 94% specificity, for the diagnosis of the diabetes (16, 17, 18, 19, 20). Indeed, HbA1c is reported to be higher in nondiabetic African-Americans than white Americans (21). We therefore postulated that HbA1c levels could reflect convergence of multiple metabolic defects (beyond ambient glucose levels) and thus could serve as a surrogate of MS. Thus, if HbA1c value is proven to be predictive of MS, this could provide an easy screening tool for subjects who are potential candidates for lifestyle and/or pharmacological primary prevention of type 2 diabetes and CVDs (22, 23, 24, 25).

African-Americans and other high-risk populations manifest greater prevalence and incidence of type 2 diabetes and its long-term complications, when compared with their white counterparts (26, 27, 28, 29, 30). In addition, our investigators and others have reported alterations in ß-cell function, hepatic insulin extraction, Si, and Sg in African-Americans with normal glucose tolerance (NGT), when compared with their white counterparts (31, 32, 33). Of great interest is that some of these metabolic differences in adults (30, 31, 32, 33, 34, 35, 36) also extend to African-American children and adolescents (37, 38, 39, 40), when compared with their white counterparts. Therefore, we have systematically examined the significance of HbA1c in the MS in nondiabetic, first-degree relatives of African-American patients with type 2 diabetes.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Populations

We undertook an anthropometric and metabolic study to examine the significance of HbA1c and metabolic correlates in 219 (172 females and 47 males; age, 42 ± 2 yr; range, 25–66 yr) first-degree relatives of African-American patients with type 2 diabetes who were residing in Franklin County, Central Ohio. Informed written consent, approved by the institutional review board for human biomedical research at The Ohio State University, Columbus, OH, was obtained from each subject after the risks entailed in the study were thoroughly explained. The subjects had blood drawn for metabolic, biochemical, and hematological parameters after a 10–12 h overnight fasting. Glucose tolerance was determined by the WHO criteria adopted in 1985 (41), which was subsequently replaced by the American Diabetes Association (ADA) Recommendations (42). Because the primary goal of the present study was to provide a more clinically useful and practical approach for screening for diabetes, we used only fasting glucose criteria to define the normal vs. abnormal glucose tolerance status of our subjects. NGT was defined as individuals with fasting serum glucose level less than 110 mg/dl. All subjects with fasting glucose levels greater than 110 mg/dl were excluded. To examine the impact of HbA1c on MS, the anthropometric and metabolic parameters of the subjects were divided according to tertiles of HbA1c as follows: tertile 1 (lowest tertile) = 4.7% (3.3–4.8); tertile 2 (middle tertile) = 5.4% (4.9–5.6%), and tertile 3 (upper tertile) = 5.6%(5.7–6.4%). The baseline clinical characteristics of our African-Americans with varying tertiles of HbA1c are shown in Table 1Go. The following subjects were excluded: 1) those taking medications known to influence glucose and insulin and lipid and lipoprotein metabolism; 2) those individuals with liver, heart, lung, and kidney diseases; 3) those with established diabetes on antidiabetic medications or those with newly diagnosed diabetes identified during screening; and 4) those who participated in endurance exercise or indulged in regular competitive sport. Furthermore, we excluded subjects with known or newly detected hemoglobinopathy, using Hb electrophoresis.


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  		TABLE 1. Baseline clinical characteristics of nondiabetic, high-risk African Americans with NGT, divided as tertiles of HbA1c levels

 
Study Protocol

After a 10–12 h overnight fast, the subjects reported to the General Clinical Research Center (GCRC) of The Ohio State University Medical Center. Body weight and height were measured with the subject wearing a very light gown and without shoes. The body fat distribution was measured as the waist-to-hip circumference ratios (WHR). The waist circumference was measured at the level of the umbilicus (with the subject in standing position) and the hip circumference at the level of the greater trochanter (in the standing position). The body composition (lean body mass and body fat) was measured using a bioelectrical impedance analyzer (43). All the subjects answered a simple questionnaire on physical activity. The activity levels were described as: 1) sedentary (no extra physical activity apart from walking and activity of daily living); 2) moderate (e.g. tennis, brisk walking, swimming, at least three times a week); and 3) strenuous (e.g. weight lifting, wrestling, racket ball, marathon, jogging, at least three times a week). Subjects who participated in an endurance or competitive sport were excluded. Three BPs were determined, by standard methods, with the subjects in supine position (44).

Metabolic studies

All the subjects were admitted to the Clinical Research Center of The Ohio State University after 10–12 h overnight fasting. With the subject in the supine position, two iv needles (heparin lock) were inserted into the forearm veins and kept patent with 0.9% normal saline infusion. One iv line was used to draw blood samples and the other to administer the iv glucose and exogenous insulin as previously described. Blood samples were drawn for serum glucose, insulin, and c-peptide levels as well as lipids and lipoproteins and HbA1c. Based on the fasting serum glucose, categories of glucose tolerance status of the subjects were defined by the WHO criteria (41) before the new ADA Recommendation (42). NGT was defined as individuals with fasting serum glucose level less than 110 mg/dl. All subjects with fasting glucose levels greater than 110 mg/dl were excluded.

Frequently sampled iv glucose tolerance

With the subject in the supine position, four blood samples were obtained at t = -20, -10, -5, and 0 min for basal serum glucose, c-peptide, and insulin concentrations as previously described (45, 46). The average of the four samples was taken as the basal level. Thereafter, 0.3 gm/kg glucose (50 ml of 50% dextrose water) was infused over a 1-min period: at t = 19 min, iv insulin (0.05 U/kg, Humulin; Eli Lilly, Indianapolis, IN) dissolved in 30 ml of 0.9% normal saline was infused over 60 sec. Blood samples were obtained at frequent intervals at t = 2, 3, 4, 5, 6, 8, 10, 12, 16, 19, 22, 24, 25, 27, 30, 40, 60, 70, 90, 120, 140, 150, 160, and 180 min for serum glucose, c-peptide, and insulin concentrations. All the samples were centrifuged at 4 C and the sera frozen and stored at -20 C until assayed.

Analytical methods

Serum glucose concentrations were measured by the hexokinase method using a glucose autoanalyzer (Yellow Spring Instruments, Yellow Spring, OH). The serum insulin and c-peptide levels were determined by a standard double-antibody RIA technique at The Core Laboratories of The Ohio State University Hospitals. The sensitivity of the insulin assay was 2.5 µU/ml. The intra- and interassay coefficients of variation were 6 and 10%, respectively. The lower limit of the c-peptide assay was 0.47 ng/ml, and the intra- and interassay coefficients of variation were 7 and 13%, respectively. The HbA1 was measured by the cationic, microcolumn chromatographic technique (Isolab, Akron, OH). The normal reference range was 4.1–8.0%. Our previous HbA1 assay measured HbA1a, HbA1b, and HbA1c. HbA1c is the major component of HbA1, accounting for at least 80% of the total HbA1 in our assay. Thus, to be consistent with the HbA1c data that have been used in both Diabetes Control and Complications Trial and UK Prospective Diabetes Study, we have converted the HbA1 to HbA1c equivalent. The normal HbA1c range in our population was 3.3–6.4%. The serum cholesterol, HDL-C, and triglycerides were measured using enzymatic methods.

Calculations and statistical analyses

Results are expressed as mean ± SEM, unless stated otherwise. The body mass index (BMI) was calculated as weight (kilograms) divided by height square (meters squared). Obesity was defined as BMI greater than 30 kg/m2 for both females and males. Si and glucose effectiveness (Sg) were calculated using Bergman’s Minmod software program (45, 46). Insulin resistance and ß-cell function were also calculated using homeostasis model assessment (HOMA) (46). The insulin resistance index was also calculated using the homeostasis model assessment-insulin resistance (HOMA-IR) as follows: fasting insulin (µU/ml) x fasting plasma glucose (mmol/ml)/22.5. HOMA-derived, ß-cell function (HOMA %B) was also calculated by the formula: 20 x fasting insulin (µU/ml)/fasting glucose (mmol/ml) - 3.5 (47). The low-density lipoprotein cholesterol (LDL-C) was calculated using Friedwald’s equation: LDL-C = (total cholesterol - HDL-C - triglyceride)/5, for serum triglycerides less than 400 mg/dl.

The nonparametric data were analyzed using {chi}2 and the Mann-Whitney rank test. Statistical analyses were performed using Student’s t test (unpaired) between the group analyses and ANOVA with repeated measures, where appropriate. The Bonferroni method was used for post hoc testing. The relationship of Si and HOMAR-IR and body composition variables was calculated using the least-squares method and step-wise linear regression. For comparison of the mean data with unequal variance, the Newman-Keuls multiple t test was used. P value less than 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Clinical characteristics (Table 1Go)

The clinical characteristics of the African-American subjects divided into tertiles are shown in Table 1Go. The mean HbA1c tertiles were as follows: tertile 1, 4.7% (range, 3.3–4.8%); tertile 2, 5.4% (range, 4.9–5.6%); and tertile 3, 5.8% (range, 5.7–6.4%). The mean age of the subjects in the upper tertile 3 was significantly higher than in tertiles 1 and 2. In addition, the mean body weight, percentage body fat, and BMI were significantly higher, whereas the lean body mass was significantly lower in the upper tertile 3 than in tertile 1. However, the mean waist and hip circumferences, but not the WHR, were significantly higher in upper tertile 3 than lower tertile 1. The mean systolic and diastolic BPs were significantly higher in the upper tertile 3 than in tertiles 1 and 2, although all were within normal limit. Furthermore, the skinfold thickness values were significantly higher in tertile 3 than in tertiles 1 and 2.

Metabolic parameters (Table 2Go)

As shown in Table 2Go, mean fasting serum glucose was significantly (P < 0.01) higher in tertile 3 than in tertiles 1 and 2. However, mean fasting serum c-peptide levels, but not insulin levels, were significantly (albeit weak) higher in the upper tertile 3 than in tertiles 1 and 2. Mean fasting serum triglycerides, cholesterol, LDL-C, and HDL-C levels were not significantly different in the upper tertile 3 than tertiles 1 and 2.


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  		TABLE 2. Metabolic characteristics of nondiabetic, high-risk African Americans with NGT, divided as tertiles (T) of HbA1c levels

 
Minimal model-derived parameters (Table 2Go)

As shown in Table 2Go, the mean Si was significantly lower in tertile 3 than in tertiles 1 and 2. Similarly, the mean Sg was also significantly lower in tertile 3 than in tertiles 1 and 2.

HOMA-derived parameters (Table 2Go)

The mean HOMA-IR was significantly higher in tertile 3 than in tertiles 1 and 2. However, mean HOMA %B was not significantly different among the tertile 3 subjects, when compared with those of tertiles 1 and 2.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Glycosylation of proteins or advanced glycated end products has been implicated as an important pathogenetic mechanism underlying the long-term complications of diabetes. Theoretically, HbA1c could reflect universal tissue protein glycation and might be a much better index for overall biological effects of glucose above and beyond its predictive value for the 3-month averages of circulating glycemic levels. Thus, we postulated that HbA1c could serve as a surrogate of MS. Thus, we examined the anthropometric and metabolic correlates, i.e. cardiovascular risk factors, in nondiabetic, first-degree relatives of African-American patients with type 2 diabetes based on tertiles of HbA1c. Our present study demonstrated that, within normal HbA1c limits, there were several anthropometric and metabolic differences among high-risk African-Americans belonging to the lower and upper HbA1c tertiles. As shown in Table 1Go, in general, the clinical and metabolic characteristics of the subjects in tertiles 1 and 2 of HbA1c were similar. The subjects in upper tertile 3 had mean HbA1c of 5.8% (normal, 3.3–6.4%), which was top normal. We found that African-Americans in the upper tertile 3 of HbA1c had significantly higher fasting glucose (albeit within normal limits) and lower Si (and HOMA-IR) than those in tertiles 1 and 2. In addition, the mean systolic and diastolic BPs were also significantly greater in those in the upper HbA1c tertile than those in tertiles 1 and 2. These differences in the upper tertile 3 and tertiles 1 and 2 of HbA1c could not be explained by the differences in body composition indices, such as body weight, BMI, and WHR. In this regard, we found a weak relationship between serum insulin, insulin resistance, and BP in our nondiabetic African-American subjects who were genetically predisposed to type 2 diabetes in each of the tertiles or as a group These findings were similar to those reported by our investigators (48) and others (49). To the best of our knowledge, the present study is the first in high-risk, nondiabetic African-Americans to examine the relationship between HbA1c on the one hand and fasting serum insulin and insulin resistance and BP on the other hand. We are therefore tempted to conclude that the upper tertile of HbA1c selected out individuals who were perhaps genetically unique to develop MS as currently recommended by ADA. We should note that, because we used only fasting serum glucose levels as the selection criteria for practical purposes, it is possible that some of our subjects could have had impaired glucose tolerance and rarely type 2 diabetes but had a normal HbA1c, especially those in tertile 3.

A major component of the MS is altered lipid and lipoprotein metabolism (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). Specifically, nondiabetic subjects with the MS manifest high serum triglycerides and low HDL-C levels, whereas cholesterol levels tend to be normal (1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13). In our study, the serum triglycerides, LDL-C, HDL-cholesterol, and cholesterol levels were all normal, irrespective of the absolute HbA1c values and tertiles of HbA1c in our high-risk African-Americans. We should note that, even in the presence of impaired glucose tolerance (IGT), type 2 diabetes, and hypertension, African-Americans, in general, tend to have favorable lipid and lipoprotein levels (50, 51, 52). Furthermore, we found no significant relationship between fasting serum insulin and lipids and lipoproteins in our cohort. Thus, our present study showed that the insulin-resistant, high-risk African-Americans in the upper tertile 3 of HbA1c had favorable lipid and lipoprotein profiles, similar to those found in other African-Americans (50, 51, 52) and Afro-Caribbeans (53), when compared with other populations, such as Caucasians.

There is strong evidence to indicate that insulin resistance and obesity are genetically inherited with a strong familial and environmental component (54, 55, 56, 57, 58, 59). In this regard, it is worthy to note that insulin resistance and obesity (especially upper-body fat distribution), with their associated metabolic disorders (such as type 2 diabetes), have a predilection for certain ethnic groups. In this regard, previous studies found greater hyperinsulinemia and insulin resistance in African-Americans (32, 33, 34, 35, 36, 37, 38, 39, 40), Afro-Caribbeans (53), Pima Indians (55), and Mexican-Americans (4), when compared with Caucasians. The ethnic and racial contrast in African-Americans and white Americans extends to the children and adolescents (37, 38, 39, 40). We found that our subjects in the upper tertile 3 of HbA1c were older, with overall, generalized obesity, but without specific upper-body fat distribution (i.e. truncal obesity). However, when obesity and age were accounted for, the differences in insulin resistance and BP persisted, irrespective of HbA1c tertile. We should note that Yates and Laing (21) have reported age-related increases in HbA1c and fasting plasma glucose attributed to a decreased ß-cell function without changes in insulin resistance, as assessed by HOMA, in the Finnish population. These age-associated increases in HbA1c were not seen in the NHANES III population in the United States or in our present study in high-risk African-Americans. The long-term biological significance of these findings in the subjects of tertile 3 of HbA1c in relation to the development of type 2 diabetes and CVDs could not be ascertained in our cross-sectional study. This would require prospective, longitudinal studies in these populations.

A major factor in determining glucose tolerance has been ascribed to glucose disposal by mass action effect per se. This ability of glucose to mediate its own glucose disposal, as well as suppress basal hepatic glucose production at basal insulin level (also referred to as Sg) is considered a major component in maintaining normoglycemia and glucose tolerance in vivo in humans and experimental animals (34, 35, 36, 45, 46). We have previously demonstrated that Sg is slightly reduced in African-Americans with newly diagnosed IGT and diabetes mellitus, when compared with healthy, NGT subjects (31). However, unlike Si, which has a well-defined impact, the role of Sg in MS in healthy, glucose-tolerant, humans remains unknown. Thus, we examined the association of tertiles of HbA1c with Sg in the nondiabetic, African-Americans who are genetically predisposed to type 2 diabetes. Our present study demonstrated that Sg was slightly, but significantly, reduced in those in tertile 3, when compared with those in tertiles 1 and 2. Mean Sg, however, was not different in the African-Americans in tertiles 1 and 2. We have recently demonstrated that a lower Sg predicts the development of IGT and type 2 diabetes with insulin resistance (unpublished personal observation). This was similar to that of offspring of White American patients with type 2 diabetes who developed type 2 diabetes after 25 yr of follow-up in the nondiabetic subjects described by Martin et al. (54). To the best of our knowledge, this was the first report to examine the impact of HbA1c on Sg in African-Americans who are genetically predisposed to type 2 diabetes. We are tempted to conclude that African-American subjects in tertile 3 represent subjects with tissue glucose resistance of uncertain etiology and perhaps attributable to genetic etiology.

Conclusions

The present study demonstrated alterations in multiple factors, including insulin action (Si), tissue glucose sensitivity (Sg), and BP, but not lipid and lipoprotein disorder per se, which were components of MS based on HbA1c level. We found that components of MS could be defined by the upper tertile of HbA1c in high-risk African-Americans. Our present study demonstrated that upper tertile 3 HbA1c (albeit within normal limits) could be considered as a marker or surrogate of MS in nondiabetic, first-degree relatives of African-American patients with type 2 diabetes These multiple defects existed before the development of type 2 diabetes and hypertension in these high-risk subjects. Whether our findings could be extrapolated to nondiabetic African-Americans who are not genetically predisposed to diabetes or other racial and ethnic populations remains to be elucidated. We conclude that measuring random HbA1c (especially those in the third tertile) serves as a surrogate of MS. This is a very convenient and practical (and perhaps cost-effective) approach as a screening tool for high-risk populations for primary diabetes and cardiovascular prevention programs (60). This can be elucidated in long-term, prospective studies from other ethnic population with high propensity for developing type 2 diabetes.


   Acknowledgments
 
We thank the volunteers for the study, the registered nurses, and dietitians in the GCRC, and the Core Laboratory.


   Footnotes
 
This work was supported by National Institutes of Health Grants GCRC-RR0034 and NIDDK DK48127.

Abbreviations: ADA, American Diabetes Association; BMI, body mass index; BP, blood pressure; CVD, cardiovascular disease; GCRC, General Clinical Research Center; Hb, hemoglobin; HDL-C, high-density lipoprotein cholesterol; HOMA, homeostasis model assessment; HOMA %B, HOMA-ß-cell function; HOMA-IR, HOMA-insulin resistance; IGT, impaired glucose tolerance; LDL-C, low-density lipoprotein cholesterol; MS, metabolic syndrome; NGT, normal glucose tolerance; Sg, glucose effectiveness; Si, insulin sensitivity; WHO, World Health Organization; WHR, waist-to-hip circumference ratio.

Received April 18, 2003.

Accepted July 1, 2003.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

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