Temporal changes in concentrations of lipids and apolipoprotein B among adults with diagnosed and undiagnosed diabetes, prediabetes, and normoglycemia: findings from the National Health and Nutrition Examination Survey 1988–1991 to 2005–2008

  • Earl S Ford1Email author,

    Affiliated with

    • Chaoyang Li2 and

      Affiliated with

      • Allan Sniderman3

        Affiliated with

        Cardiovascular Diabetology201312:26

        DOI: 10.1186/1475-2840-12-26

        Received: 31 October 2012

        Accepted: 13 December 2012

        Published: 30 January 2013

        Abstract

        Background

        Diabetes is characterized by profound lipid abnormalities. The objective of this study was to examine changes in concentrations of lipids and apolipoprotein B among participants stratified by glycemic status (diabetes, undiagnosed diabetes, prediabetes, and normoglycemia) in the United States from 1988–1991 to 2005–2008.

        Methods

        We used data from 3202 participants aged ≥20 years from the National Health and Nutrition Examination Survey (NHANES) III (1988–1991) and 3949 participants aged ≥20 years from NHANES 2005–2008.

        Results

        Among participants of all four groups, unadjusted and adjusted mean concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B, but not triglycerides, decreased significantly. Among participants with prediabetes and normoglycemia, unadjusted and adjusted mean concentrations of high-density lipoprotein cholesterol increased significantly. Adjusted mean log-transformed concentrations of triglycerides decreased in adults with undiagnosed diabetes and prediabetes. During 2005–2008, unadjusted concentrations of apolipoprotein B ≥80 mg/dl were observed in 72.8% of participants with diagnosed diabetes, 87.9% of participants with undiagnosed diabetes, 86.6% of participants with prediabetes, and 77.2% of participants with normoglycemia. The unadjusted use of cholesterol-lowering medications rose rapidly, especially among participants with diabetes (from ~1% to ~49%, P <0.001). The use of fenofibrate, gemfibrozil, and niacin rose significantly only among adults with diagnosed diabetes (from ~2% to ~8%, P = 0.011).

        Conclusion

        Lipid profiles of adults with diabetes improved during the approximately 16-year study period. Nevertheless, large percentages of adults continue to have elevated concentrations of apolipoprotein B.

        Keywords

        Apolipoprotein B Cholesterol Diabetes High-density lipoprotein cholesterol Lipids Prediabetes Triglycerides Fenofibrate Gemfibrozil Niacin

        Background

        During the last several decades, diabetes has emerged as a major public health problem in the United States as the incidence and prevalence of obesity has escalated rapidly [1, 2]. The lifetime probability of developing this disease is approximately 32.8% for men and 38.5% for women [3], and an estimated 25.6 million adults have diabetes [4]. Furthermore, diabetes has an enormous impact on health care costs in the United States; in 2007, for example, the economic costs attributable to this condition were estimated to have been $174 billion [4].

        Much of the toll exacted by diabetes is due to the complications of this disease, notably from cardiovascular disease: as many as 65% of people with diabetes will die of cardiovascular disease, and diabetes approximately doubles the risk of developing cardiovascular disease [5, 6]. This increased risk for cardiovascular morbidity and mortality is largely a function of a number of cardiometabolic abnormalities, including lipid abnormalities. In general, people with diabetes tend to have elevated concentrations of triglycerides and apolipoprotein B, low concentrations of high-density lipoprotein cholesterol, and an elevated number of small dense low-density lipoprotein cholesterol particles [7].

        Previous trend studies have shown some improvement in lipid abnormalities in adults with diabetes including total cholesterol, low-density lipoprotein cholesterol, and non-high-density lipoprotein cholesterol [810]. However, less is known about apolipoprotein B, which some have argued is a superior marker of cardiovascular risk than low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol [11]. Consequently, the objective of the present study was to examine changes in concentrations of lipids with a focus on apolipoprotein B among adults with diagnosed and undiagnosed diabetes from 1988–1991 to 2005–2008. In addition, we examined changes in concentrations of lipids and apolipoprotein B among participants with prediabetes and normoglycemia.

        Research design and methods

        The analyses for the present study were conducted using data from the first phase of the National Health and Nutrition Examination Survey (NHANES) III (1988–1991) and from NHANES 2005–2008. Using a multistage, stratified sampling design, participants were recruited into the survey. After an interview in the home, participants were invited to attend one of three examination sessions: morning, afternoon, or evening. Persons attending the morning session were asked to fast overnight. In the mobile examination center, participants completed additional questionnaires, had a series of examinations, and provided biological specimens including blood. Interview and examination response rates were 86% and 78%, respectively, for NHANES III, 80% and 77%, respectively, for NHANES 2005–2006, and 78% and 75%, respectively, for NHANES 2007–2008. Details about the surveys and their methods have been published previously [12, 13].

        Four groups of participants were defined: those with diagnosed diabetes, those with undiagnosed diabetes, those with prediabetes, and those with normoglycemia. Participants with diagnosed diabetes were identified by responses to the NHANES questions: “Have you ever been told by a doctor that you have diabetes or sugar diabetes?” or “Have you ever been told by a doctor or health professional that you have diabetes or sugar diabetes?”, respectively, in the two surveys. Those who responded “yes” were considered to have diagnosed diabetes. Participants who responded that they may have had "borderline" diabetes or were "prediabetic" were coded as not having diagnosed diabetes. Concentrations of HbA1c were used to establish the glycemic status of the remaining participants without diagnosed diabetes as follows: undiagnosed diabetes: ≥6.5%; prediabetes: 5.7- < 6.5%; and normal: <5.7%.

        High-performance liquid chromatography (HPLC) was used to measure concentrations of HbA1c in NHANES III (Bio-Rad DIAMAT glycosylated hemoglobin analyzer system, Bio-Rad Laboratories, Hercules, CA) and NHANES 2005–2008 (NHANES 2005–2006: Tosoh A1c 2.2 Plus Glycohemoglobin Analyzer, Tosoh Medics, Inc., So. San Francisco, CA; NHANES 2007–2008: Tosoh G 7 HPLC Glycohemoglobin Analyzer, Tosoh Medics, Inc., So. San Francisco, CA). Serum concentrations of total cholesterol, high-density lipoprotein cholesterol, and triglycerides were measured enzymatically on a Hitachi 704 Analyzer (Boehringer Mannheim Diagnostics, Indianapolis, IN) for NHANES III, on a Hitachi 717 or 912 Analyzer (Roche Diagnostics, Indianapolis, IN) for NHANES 2005–2006, and on a Roche Modular P Chemistry Analyzer (Roche Diagnostics, Indianapolis, IN) for NHANES 2007–2008. Measurements of apolipoprotein B for NHANES III were performed by using radial immunodiffusion (Behring Diagnostics, Westwood, MA) and rate immunonephelometrix assay (Beckman Instruments, Brea, CA). Nephelometry was used to measure apolipoprotein B during 2005–2008 (NHANES 2005–2006: Dade Behring BN100 nephelometer, Dade Behring, Deerfield, IL; NHANES 2007–2008: ProSpec nephelometer, Dade Behring GMBH, Marburg, Germany).

        Participants could report up to 16 medications in NHANES III and 20 medications in NHANES 2005–2008. When prescription bottles were available, participants were asked to show them to the interviewers. For our study, we established the following two groups of medications: cholesterol-lowering medications (statins [atorvastatin, fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin], ezetimibe, cholestyramine, probucol, colesevelam, and colestipol) and triglyceride-lowering medications (fenofibrate, gemfibrozil, and niacin). Products containing a cholesterol-lowering medication in the form of a statin and a triglyceride-lowering medication were counted as one of each.

        The following covariates were included in the analyses: age, gender, race or ethnicity (whites, African Americans, Mexican Americans, other), educational status (<high school, high school graduate or equivalent, >high school), and body mass index. Measured weight and height were used to calculate and categorize body mass index levels (<25, 25- < 30, and ≥30 kg/m2).

        For participants with diagnosed diabetes, we also calculated 10-year predicted cardiovascular risk using the UK Prospective Diabetes Study (UKPDS) risk engine that uses the following variables: age at diagnosis of diabetes, gender, race or ethnicity, smoking status, concentration of HbA1c, systolic blood pressure, and ratio of concentrations of total cholesterol to high-density lipoprotein cholesterol [14]. Participants who had smoked at least 100 cigarettes during their lifetime and were currently smoking were designated as current smokers. For systolic blood pressure, we averaged the second and third measurements of systolic blood pressure.

        The analyses were limited to participants aged ≥20 years who attended the morning examination and had fasted ≥8 hours. Pregnant women were excluded. Adjusted mean concentrations of lipids and apolipoprotein B were calculated by using analysis of covariance. Differences in percentages and means were tested by using chi-square tests and t-tests, respectively. In addition, changes in the prevalence of abnormal concentrations of lipids were examined by log-linear regression analysis adjusting for age (continuous) and age, gender, race or ethnicity, educational status, and body mass index (continuous). Data management was done with SAS and estimates were produced with SUDAAN to account for the complex sampling designs of the surveys. Sample sizes reflect unweighted numbers, whereas sampling weights were used to generate estimates.

        Results

        Of the 3840 participants aged ≥20 years in NHANES III who attended the morning examination, 3510 were left after excluding pregnant women and participants who had fasted <8 hours. Additional exclusions of participants who had missing data for variables needed to establish glycemic status and for lipids reduced the sample size to 3225 participants. After covariates with missing values were excluded, 3202 were included in the analyses. In NHANES 2005–2008, 4341 participants attended the morning examination, 4173 remained after excluding pregnant women and participants who had fasted <8 hours, 4020 were left after excluding participants who had missing data for variables needed to establish glycemic status and for lipids, and 3949 were included in the analyses after excluding participants who had covariates with missing values. Changes in covariates by glycemic status are shown in Table 1.
        Table 1

        Unadjusted percentages, medians, or means (standard error) of selected sociodemographic and anthropometric characteristics among adults aged > =20 years, National Health and Nutrition Examination Survey 1988–1991 and 2005-2008

         

        Diagnosed diabetes

         

        Undiagnosed diabetes

         

        Prediabetes

         

        Normal

         
         

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        N

        207

        457

         

        92

        103

         

        566

        850

         

        2337

        2539

         

        Age (years) - median

        59.9 (1.6)

        59.8 (1.1)

        58.6 (2.1)

        61.6 (3.0)

        56.9 (2.2)

        56.5 (0.9)

        38.0 (0.8)

        40.9 (0.8)

        Age (%)

          

        0.783

          

        0.531

          

        0.257

          

        0.001

        20-39 years

        13.3 (4.3)

        10.8 (1.7)

         

        13.2 (4.8)

        6.7 (3.0)

         

        18.0 (2.7)

        14.7 (1.4)

         

        51.5 (1.6)

        46.2 (1.4)

         

        40-59 years

        33.6 (4.8)

        37.3 (2.6)

         

        38.1 (6.5)

        40.8 (6.2)

         

        36.2 (3.3)

        41.2 (1.9)

         

        30.6 (1.5)

        38.8 (1.4)

         

        ≥60 years

        53.1 (3.8)

        51.9 (2.9)

         

        48.7 (6.6)

        52.5 (6.5)

         

        45.9 (4.3)

        44.1 (2.1)

         

        17.9 (1.5)

        15.0 (1.4)

         

        Men (%)

        36.4 (5.7)

        44.4 (3.0)

        0.221

        49.5 (7.9)

        56.6 (6.1)

        0.482

        53.3 (3.1)

        47.9 (2.3)

        0.170

        47.9 (1.3)

        48.8 (1.0)

        0.567

        Race or ethnicity (%)

          

        0.268

          

        0.932

          

        0.020

          

        0.004

        White

        73.4 (4.3)

        65.3 (4.3)

         

        53.3 (6.3)

        55.3 (6.9)

         

        63.9 (5.0)

        66.7 (3.4)

         

        81.1 (2.2)

        73.7 (2.0)

         

        African American

        15.1 (3.6)

        17.3 (2.9)

         

        29.8 (4.9)

        28.3 (4.0)

         

        24.0 (3.1)

        17.4 (2.5)

         

        7.7 (1.0)

        8.3 (1.1)

         

        Mexican American

        8.4 (1.4)

        8.2 (1.4)

         

        8.1 (2.6)

        9.9 (2.7)

         

        4.8 (0.5)

        7.3 (1.3)

         

        4.7 (0.6)

        8.0 (0.9)

         

        Other

        3.1 (2.2)

        9.2 (2.3)

         

        8.8 (5.9)

        6.6 (3.1)

         

        7.3 (2.4)

        8.6 (1.9)

         

        6.5 (1.7)

        9.9 (1.1)

         

        ≥High school graduates (%)

        57.4 (5.5)

        70.4 (2.2)

        0.030

        50.2 (5.4)

        71.7 (4.8)

        0.013

        60.3 (2.8)

        77.7 (1.7)

        <0.001

        79.4 (1.9)

        84.4 (1.2)

        0.034

        Body mass index ≥30 kg/m2 (%)

        38.2 (5.8)

        61.7 (2.8)

        0.001

        60.3 (7.1)

        68.4 (6.2)

        0.378

        28.2 (2.5)

        43.0 (2.0)

        <0.001

        17.4 (1.3)

        27.5 (1.3)

        <0.001

        Body mass index (kg/m2)

        29.6 (0.7)

        32.8 (0.5)

        0.001

        32.6 (1.8)

        34.8 (1.3)

        0.343

        27.6 (0.3)

        30.2 (0.3)

        <0.001

        25.7 (0.2)

        27.5 (0.2)

        <0.001

        HbA1c (%)

        6.8 (0.2)

        7.2 (0.1)

        0.060

        7.8 (0.3)

        7.5 (0.2)

        0.345

        5.9 (<0.1)

        5.9 (<0.1)

        0.024

        5.0 (<0.1)

        5.2 (<0.1)

        <0.001

        *P-value from chi-square test for categorical variables and from t-test for means.

        Among participants with diagnosed diabetes, undiagnosed diabetes, prediabetes, and normoglycemia, significant decreases occurred in concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B (Table 2). Concentrations of high-density lipoprotein cholesterol also increased significantly among participants with prediabetes and normoglycemia in all models and among participants with diagnosed diabetes in the most adjusted model. Log-transformed concentrations of triglycerides decreased significantly among participants with undiagnosed diabetes and prediabetes only in the most adjusted model.
        Table 2

        Unadjusted and least-square adjusted mean concentrations (standard error) of lipids and apolipoprotein B among adults aged ≥20 years, by glycemic status and survey, National Health and Nutrition Examination Surveys 1988–1991 and 2005-2006

         

        Diagnosed diabetes

        Undiagnosed diabetes

        Prediabetes

        Normal

         

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        N

        207

        457

         

        92

        103

         

        566

        850

         

        2337

        2539

         

        Unadjusted

                    

        Total cholesterol (mg/dl)

        215.0 (3.6)

        181.0 (2.3)

        <0.001

        223.0 (5.0)

        200.4 (4.8)

        0.002

        218.0 (1.7)

        202.9 (1.8)

        <0.001

        200.5 (1.4)

        195.0 (0.9)

        0.002

        High-density lipoprotein cholesterol (mg/dl)

        49.1 (1.6)

        50.7 (1.0)

        0.390

        44.9 (1.8)

        47.7 (1.6)

        0.234

        48.0 (0.7)

        53.6 (0.7)

        <0.001

        51.8 (0.7)

        55.7 (0.4)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        135.4 (2.9)

        100.5 (1.8)

        <0.001

        143.3 (3.8)

        121.7 (4.3)

        <0.001

        142.6 (1.8)

        122.3 (1.4)

        <0.001

        124.8 (1.3)

        115.4 (0.9)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        166.0 (4.4)

        130.3 (2.0)

        <0.001

        178.1 (4.6)

        152.7 (4.4)

        <0.001

        170.0 (1.8)

        149.3 (1.8)

        <0.001

        148.8 (1.5)

        139.3 (1.0)

        <0.001

        Triglycerides (mg/dl)†

        153.1 (9.8)

        148.9 (4.0)

        0.687

        173.6 (10.1)

        155.4 (10.1)

        0.207

        137.0 (4.2)

        136.9 (3.6)

        0.985

        119.6 (3.6)

        119.5 (1.7)

        0.974

        Triglycerides (mg/dl)‡

        137.8 (9.7)

        133.0 (3.6)

        0.634

        158.4 (9.2)

        135.0 (9.4)

        0.084

        122.0 (3.5)

        122.1 (2.9)

        0.970

        104.3 (3.2)

        104.6 (1.6)

        0.933

        Apolipoprotein B (mg/dl)

        114.2 (2.7)

        96.3 (1.5)

        <0.001

        120.3 (3.4)

        110.4 (3.1)

        0.035

        115.6 (1.3)

        106.2 (1.2)

        <0.001

        102.0 (0.9)

        98.6 (0.8)

        0.011

        Age-adjusted

                    

        Total cholesterol (mg/dl)

        206.7 (3.5)

        172.3 (2.5)

        <0.001

        215.2 (4.5)

        191.3 (4.7)

        0.001

        211.0 (1.7)

        195.9 (1.8)

        <0.001

        202.9 (1.4)

        197.0 (0.8)

        <0.001

        High-density lipoprotein cholesterol (mg/dl)

        47.5 (1.6)

        49.1 (1.0)

        0.418

        43.4 (1.7)

        46.0 (1.6)

        0.265

        46.7 (0.7)

        52.3 (0.7)

        <0.001

        52.2 (0.7)

        56.0 (0.4)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        130.2 (2.8)

        95.1 (2.0)

        <0.001

        138.5 (3.7)

        116.0 (4.3)

        <0.001

        138.3 (1.8)

        118.0 (1.5)

        <0.001

        126.3 (1.3)

        116.7 (0.8)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        159.2 (4.3)

        123.3 (2.2)

        <0.001

        171.8 (4.3)

        145.2 (4.3)

        <0.001

        164.3 (1.9)

        143.7 (1.8)

        <0.001

        150.7 (1.5)

        141.0 (0.9)

        <0.001

        Triglycerides (mg/dl)†

        145.1 (9.6)

        140.5 (4.2)

        0.662

        166.1 (9.8)

        146.6 (9.7)

        0.160

        130.2 (4.4)

        130.1 (3.5)

        0.993

        121.9 (3.6)

        121.5 (1.6)

        0.912

        Triglycerides (mg/dl)‡

        127.9 (8.9)

        123.0 (3.6)

        0.601

        147.7 (8.3)

        124.3 (8.3)

        0.052

        114.5 (3.3)

        114.7 (2.5)

        0.957

        106.5 (3.2)

        106.5 (1.5)

        1.000

        Apolipoprotein B (mg/dl)

        109.9 (2.7)

        91.9 (1.6)

        <0.001

        116.3 (3.2)

        105.7 (3.1)

        0.024

        112.0 (1.3)

        102.6 (1.2)

        <0.001

        103.2 (0.9)

        99.7 (0.7)

        0.006

        Adjusted for age, gender, race or ethnicity, education, and body mass index

                    

        Total cholesterol (mg/dl)

        205.6 (3.3)

        169.6 (2.5)

        <0.001

        213.0 (4.7)

        187.6 (4.3)

        <0.001

        211.5 (1.8)

        194.7 (1.9)

        <0.001

        203.7 (1.3)

        197.0 (0.8)

        <0.001

        High-density lipoprotein cholesterol (mg/dl)

        48.1 (1.2)

        52.2 (1.0)

        0.010

        46.6 (2.0)

        51.1 (2.1)

        0.128

        46.9 (0.7)

        53.7 (0.7)

        <0.001

        51.2 (0.6)

        56.0 (0.3)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        129.2 (2.6)

        91.8 (1.9)

        <0.001

        135.1 (4.2)

        110.6 (3.8)

        <0.001

        138.0 (1.9)

        116.3 (1.5)

        <0.001

        127.4 (1.3)

        116.8 (0.7)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        157.5 (3.9)

        117.4 (2.2)

        <0.001

        166.4 (5.3)

        136.4 (3.7)

        <0.001

        164.6 (1.9)

        141.0 (1.9)

        <0.001

        152.6 (1.3)

        141.0 (0.8)

        <0.001

        Triglycerides (mg/dl)†

        141.7 (8.2)

        128.2 (4.3)

        0.153

        156.3 (11.5)

        129.6 (11.4)

        0.100

        133.0 (3.8)

        125.2 (3.5)

        0.137

        125.9 (3.2)

        120.9 (1.6)

        0.161

        Triglycerides (mg/dl)‡

        124.4 (7.2)

        111.0 (3.3)

        0.078

        136.3 (10.0)

        108.0 (8.6)

        0.032

        117.5 (2.7)

        110.1 (2.3)

        0.041

        110.2 (2.9)

        105.9 (1.4)

        0.179

        Apolipoprotein B (mg/dl)

        108.7 (2.5)

        88.0 (1.5)

        <0.001

        112.5 (3.4)

        99.7 (2.8)

        0.005

        111.8 (1.5)

        100.8 (1.2)

        <0.001

        104.4 (0.9)

        99.8 (0.6)

        <0.001

        *P-values from linear regression analyses.

        †Untransformed mean.

        ‡Geometric mean.

        A secondary observation of the results shown in Table 2 was that participants with undiagnosed diabetes and prediabetes exhibited worse lipid profiles than participants with diagnosed diabetes. During 2005–2008, unadjusted and adjusted concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B were significantly higher among participants with undiagnosed diabetes and prediabetes than among participants with diagnosed diabetes.

        To estimate the possible impact of improvements in concentrations of total cholesterol and high-density lipoprotein cholesterol may have had on 10-year predicted risk from cardiovascular disease, we estimated risk using the UKPDS risk engine for the adults with diagnosed diabetes during 1988–1994 under two scenarios: 1) using the original data and 2) after reducing the ratio of TC/HDLC by approximately 20% for each participant while holding the values for the other variables that are part of the risk engine constant. The 20% reduction represents the mean improvement in the mean ratio of TC/HDLC from 1988–1994 to 2005–2008. The predicted 10-year risk dropped from 21.2% (95% confidence interval: 15.8—26.5) to 17.3% (95% confidence interval: 12.7—21.9).

        The unadjusted use of cholesterol-lowering medications increased significantly in all groups (P for all comparisons <0.001) and was particularly striking among participants with diagnosed diabetes in whom the use increased from approximately 1% to 49% (Figure 1). The use of medications for lowering concentrations of triglycerides or increasing concentrations of high-density lipoprotein cholesterol also rose but at a less impressive rate. The largest increases were noticed in participants with diagnosed diabetes among whom the unadjusted percentage increased from about 2% to almost 8% (P = 0.011) and in participants with undiagnosed diabetes among whom the percentage increased from 0% to almost 5% (P = 0.147).
        http://static-content.springer.com/image/art%3A10.1186%2F1475-2840-12-26/MediaObjects/12933_2012_Article_602_Fig1_HTML.jpg
        Figure 1

        Percentages (95% confidence interval) of participants aged ≥20 years who reported using cholesterol-lowering medications (panel A) and fenofibrate, gemfibrozil, or niacin (panel B), by survey period and glycemic status, National Health and Nutrition Examination Survey 1988–1991 and 2005–2006. *Results were adjusted for age, gender, race or ethnicity, educational status, and body mass index.

        The analyses that generated the results shown in Table 2 were repeated after excluding participants who were using cholesterol-lowering medications, fenofibrate, gemfibrozil, and niacin (Table 3). Many of the significant improvements in lipid concentration persisted in analyses that excluded participants who used cholesterol-lowering and triglyceride-lowering medications, although the magnitude of the decrease narrowed to some degree in many comparisons.
        Table 3

        Unadjusted and least-square adjusted mean concentrations (standard error) of lipids and apolipoprotein B among adults aged > =20 years, by glycemic status and survey, National Health and Nutrition Examination Survey 1988–1991 and 2005–2006

         

        Diagnosed diabetes

        Undiagnosed diabetes

        Prediabetes

        Normal

         

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        N

        200

        211

         

        91

        67

         

        545

        634

         

        2302

        2290

         

        Unadjusted

                    

        Total cholesterol (mg/dl)

        214.4 (3.7)

        194.6 (3.2)

        <0.001

        224.5 (5.0)

        208.8 (6.0)

        0.051

        217.5 (1.7)

        209.9 (2.2)

        0.008

        199.9 (1.3)

        196.0 (1.2)

        0.034

        High-density lipoprotein cholesterol (mg/dl)

        48.8 (1.6)

        51.2 (1.5)

        0.287

        44.8 (1.8)

        46.3 (2.0)

        0.580

        48.1 (0.7)

        53.5 (0.9)

        <0.001

        51.8 (0.7)

        55.9 (0.5)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        134.7 (3.0)

        113.8 (2.6)

        <0.001

        144.8 (3.9)

        130.0 (5.3)

        0.028

        142.2 (1.8)

        129.8 (1.6)

        <0.001

        124.3 (1.3)

        116.7 (1.1)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        165.6 (4.6)

        143.5 (3.2)

        <0.001

        179.7 (4.5)

        162.5 (5.5)

        0.019

        169.4 (1.8)

        156.4 (2.1)

        <0.001

        148.1 (1.5)

        140.1 (1.2)

        <0.001

        Triglycerides (mg/dl)†

        154.5 (9.8)

        148.1 (7.4)

        0.604

        174.0 (10.4)

        163.2 (11.9)

        0.496

        135.9 (4.3)

        135.8 (3.7)

        0.987

        118.8 (3.6)

        116.9 (1.7)

        0.639

        Triglycerides (mg/dl)‡

        139.1 (9.9)

        131.2 (7.1)

        0.513

        158.3 (9.6)

        140.6 (12.1)

        0.263

        120.9 (3.7)

        120.5 (3.0)

        0.936

        103.8 (3.2)

        102.3 (1.6)

        0.674

        Apolipoprotein B (mg/dl)

        113.8 (2.8)

        103.2 (2.4)

        0.005

        121.7 (3.1)

        116.9 (3.6)

        0.321

        115.1 (1.2)

        109.6 (1.3)

        0.003

        101.6 (0.9)

        98.7 (1.0)

        0.041

        Age-adjusted

                    

        Total cholesterol (mg/dl)

        202.5 (3.7)

        185.8 (3.6)

        0.002

        212.9 (4.4)

        198.4 (6.3)

        0.070

        207.4 (1.8)

        202.1 (2.0)

        0.048

        201.6 (1.2)

        198.5 (1.1)

        0.062

        High-density lipoprotein cholesterol (mg/dl)

        46.9 (1.6)

        49.7 (1.5)

        0.202

        42.9 (1.8)

        44.6 (2.0)

        0.528

        46.5 (0.7)

        52.2 (0.9)

        <0.001

        52.1 (0.7)

        56.3 (0.4)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        126.6 (2.9)

        107.8 (2.9)

        <0.001

        137.0 (3.7)

        122.9 (5.7)

        0.046

        135.3 (1.9)

        124.5 (1.5)

        <0.001

        125.5 (1.3)

        118.4 (1.1)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        155.6 (4.5)

        136.1 (3.6)

        0.001

        170.0 (4.1)

        153.8 (5.7)

        0.028

        160.9 (2.0)

        149.9 (2.0)

        <0.001

        149.5 (1.4)

        142.2 (1.2)

        <0.001

        Triglycerides (mg/dl)†

        145.2 (9.6)

        141.2 (7.6)

        0.743

        164.9 (10.0)

        155.0 (11.5)

        0.518

        127.9 (4.4)

        129.7 (3.6)

        0.755

        120.2 (3.6)

        118.9 (1.7)

        0.750

        Triglycerides (mg/dl)‡

        127.6 (9.0)

        123.1 (6.9)

        0.683

        145.6 (8.5)

        130.4 (11.0)

        0.283

        112.3 (3.4)

        113.9 (2.6)

        0.713

        105.1 (3.2)

        104.2 (1.6)

        0.797

        Apolipoprotein B (mg/dl)

        107.8 (2.7)

        98.7 (2.6)

        0.019

        115.8 (2.9)

        111.6 (3.8)

        0.388

        109.9 (1.4)

        105.7 (1.2)

        0.018

        102.4 (0.9)

        100.0 (0.9)

        0.066

        Adjusted for age, gender, race or ethnicity, education, and body mass index

                    

        Total cholesterol (mg/dl)

        201.7 (3.5)

        183.7 (3.4)

        <0.001

        211.3 (4.7)

        193.9 (6.2)

        0.029

        208.0 (1.9)

        200.7 (2.1)

        0.010

        202.2 (1.2)

        198.4 (1.0)

        0.018

        High-density lipoprotein cholesterol (mg/dl)

        48.0 (1.2)

        52.9 (1.4)

        0.009

        46.8 (2.1)

        51.0 (2.5)

        0.213

        47.0 (0.7)

        53.9 (0.8)

        <0.001

        51.2 (0.6)

        56.3 (0.4)

        <0.001

        Low-density lipoprotein cholesterol (mg/dl)

        125.6 (2.7)

        104.8 (2.8)

        <0.001

        133.7 (4.3)

        116.3 (5.6)

        0.016

        135.0 (2.0)

        122.5 (1.5)

        <0.001

        126.2 (1.2)

        118.5 (0.9)

        <0.001

        Non-high-density lipoprotein cholesterol (mg/dl)

        153.7 (4.0)

        130.8 (3.4)

        <0.001

        164.5 (5.3)

        143.0 (5.9)

        0.009

        160.9 (2.0)

        146.9 (2.0)

        <0.001

        150.9 (1.2)

        142.1 (0.9)

        <0.001

        Triglycerides (mg/dl)†

        140.6 (8.2)

        129.7 (7.4)

        0.324

        154.1 (11.9)

        134.0 (13.2)

        0.258

        129.6 (3.7)

        124.4 (3.8)

        0.319

        123.4 (3.2)

        118.1 (1.6)

        0.141

        Triglycerides (mg/dl)‡

        122.9 (7.3)

        111.7 (6.0)

        0.224

        133.2 (10.3)

        109.4 (10.4)

        0.107

        114.3 (2.7)

        109.0 (2.5)

        0.148

        108.0 (2.8)

        103.4 (1.4)

        0.146

        Apolipoprotein B (mg/dl)

        106.4 (2.6)

        95.0 (2.5)

        0.002

        111.8 (3.2)

        104.2 (4.0)

        0.148

        109.6 (1.5)

        103.5 (1.2)

        0.002

        103.4 (0.9)

        100.0 (0.7)

        0.006

        Participants who reported using cholesterol-lowering medications, fenofibrate, gemfibrozil, and niacin were excluded.

        *P-values from linear regression analyses.

        †Untransformed mean.

        ‡Geometric mean.

        Changes in concentrations of lipids in dichotomized form are presented in Table 4. In all four groups, elevated concentrations of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B decreased significantly after adjustment for age, gender, race or ethnicity, education, and body mass index. Among persons with prediabetes and normoglycemia, low concentrations of high-density lipoprotein cholesterol decreased significantly. A significant decrease in the prevalence of the lipid triad consisting of low concentrations of high-density lipoprotein cholesterol and elevated concentrations of triglycerides and apolipoprotein B was noted among participants with prediabetes and normoglycemia.
        Table 4

        Unadjusted and adjusted percentages (standard error) of lipids and apolipoprotein B among adults aged ≥20 years, by glycemic status and survey, National Health and Nutrition Examination Surveys 1988–1991 and 2005-2006

         

        Diagnosed diabetes

        Undiagnosed diabetes

        Prediabetes

        Normal

         

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        1988-1991

        2005-2008

        P*

        N

        207

        457

         

        92

        103

         

        566

        850

         

        2337

        2539

         

        Unadjusted

                    

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women

        46.4 (5.8)

        37.2 (3.0)

        0.165

        57.5 (8.7)

        34.4 (6.4)

        0.037

        41.8 (2.8)

        24.9 (1.7)

        <0.001

        33.3 (1.7)

        22.4 (1.1)

        <0.001

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women or medication use

        47.9 (5.8)

        40.7 (3.0)

        0.275

        57.5 (8.7)

        37.5 (6.5)

        0.071

        43.4 (3.1)

        26.4 (1.6)

        <0.001

        33.6 (1.6)

        23.0 (1.0)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl

        86.1 (4.7)

        42.9 (2.6)

        <0.001

        91.5 (3.3)

        70.3 (4.9)

        0.001

        90.0 (1.4)

        75.0 (1.7)

        <0.001

        74.4 (1.8)

        66.0 (1.2)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl or medication use

        86.1 (4.7)

        79.1 (2.4)

        0.183

        94.4 (2.4)

        87.0 (4.9)

        0.180

        90.1 (1.4)

        88.4 (1.3)

        0.365

        74.4 (1.8)

        70.6 (1.2)

        0.085

        Non-high-density lipoprotein cholesterol ≥130 mg/dl

        81.9 (5.5)

        43.6 (2.8)

        <0.001

        91.7 (3.4)

        67.5 (5.4)

        <0.001

        85.0 (1.5)

        67.9 (1.9)

        <0.001

        65.2 (1.7)

        57.8 (0.8)

        <0.001

        Triglycerides ≥150 mg/dl

        44.7 (7.0)

        43.9 (2.7)

        0.909

        54.3 (5.8)

        43.0 (6.9)

        0.215

        33.9 (1.9)

        33.2 (2.1)

        0.797

        24.7 (2.3)

        24.7 (1.1)

        0.997

        Triglycerides ≥150 mg/dl or medication use

        46.9 (6.9)

        47.8 (3.0)

        0.905

        54.3 (5.8)

        44.1 (7.1)

        0.271

        35.9 (1.9)

        34.6 (2.0)

        0.625

        24.9 (2.3)

        25.1 (1.0)

        0.936

        Triglycerides ≥150 mg/dl or use of TG-lowering or cholesterol-lowering medications

        47.6 (6.7)

        73.5 (2.9)

        0.001

        54.3 (5.8)

        67.4 (5.9)

        0.121

        36.9 (2.0)

        50.2 (2.1)

        <0.001

        25.3 (2.4)

        30.3 (1.3)

        0.070

        Apolipoprotein B ≥80 mg/dl

        91.1 (3.6)

        72.8 (2.1)

        <0.001

        95.8 (2.8)

        87.9 (4.2)

        0.123

        92.8 (1.3)

        86.6 (1.4)

        0.002

        81.7 (1.3)

        77.2 (1.0)

        0.007

        Lipid triad: definition 1§

        31.4 (6.5)

        21.6 (2.8)

        0.172

        35.7 (7.7)

        23.4 (5.2)

        0.190

        20.7 (1.7)

        13.8 (1.2)

        0.002

        13.1 (1.5)

        9.8 (0.7)

        0.050

        Lipid triad: definition 2ǁ

        33.3 (6.4)

        24.8 (2.7)

        0.228

        35.7 (7.7)

        24.0 (5.3)

        0.212

        23.3 (1.9)

        15.2 (1.1)

        0.001

        13.5 (1.4)

        10.4 (0.7)

        0.056

        Lipid triad: definition 3¶

        33.3 (6.4)

        26.6 (2.8)

        0.342

        35.7 (7.7)

        25.4 (5.8)

        0.287

        23.8 (2.1)

        16.1 (1.1)

        0.002

        13.7 (1.5)

        10.9 (0.7)

        0.102

        Age-adjusted

                    

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women

        51.5 (6.8)

        41.5 (3.3)

        0.180

        63.4 (9.5)

        38.7 (7.4)

        0.042

        45.6 (3.0)

        27.2 (1.9)

        <0.001

        32.4 (1.6)

        21.9 (1.0)

        <0.001

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women or medication use

        52.1 (6.7)

        44.5 (3.3)

        0.293

        62.2 (9.3)

        41.2 (7.3)

        0.078

        46.6 (3.4)

        28.3 (1.8)

        <0.001

        32.8 (1.6)

        22.5 (1.0)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl

        80.9 (4.4)

        40.2 (2.4)

        <0.001

        86.2 (3.3)

        65.5 (4.6)

        0.001

        85.2 (1.4)

        71.1 (1.7)

        <0.001

        75.8 (1.7)

        67.1 (1.2)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl or medication use

        78.1 (4.2)

        71.4 (2.2)

        0.154

        86.1 (2.7)

        78.1 (4.3)

        0.127

        82.8 (1.3)

        81.4 (1.4)

        0.386

        76.6 (1.7)

        72.5 (1.2)

        0.062

        Non-high-density lipoprotein cholesterol ≥130 mg/dl

        74.2 (5.1)

        39.3 (2.6)

        <0.001

        83.6 (3.7)

        60.5 (4.8)

        <0.001

        78.0 (1.6)

        62.5 (1.9)

        <0.001

        67.1 (1.6)

        59.4 (0.8)

        <0.001

        Triglycerides ≥150 mg/dl

        38.6 (6.1)

        37.7 (2.6)

        0.882

        47.4 (4.7)

        36.6 (5.8)

        0.155

        29.8 (2.0)

        29.3 (1.9)

        0.832

        25.8 (2.4)

        25.7 (1.1)

        0.970

        Triglycerides ≥150 mg/dl or medication use

        40.1 (5.9)

        40.6 (2.8)

        0.936

        46.9 (4.7)

        37.2 (5.9)

        0.198

        31.4 (1.8)

        30.3 (1.8)

        0.649

        26.2 (2.3)

        26.3 (1.0)

        0.970

        Triglycerides ≥150 mg/dl or use of TG-lowering or cholesterol-lowering medications

        38.1 (5.4)

        58.4 (2.7)

        0.001

        44.2 (4.4)

        52.9 (4.5)

        0.160

        30.3 (1.9)

        41.6 (1.8)

        <0.001

        27.2 (2.4)

        32.3 (1.3)

        0.075

        Apolipoprotein B ≥80 mg/dl

        85.4 (3.2)

        68.1 (2.1)

        <0.001

        90.2 (2.9)

        81.9 (4.0)

        0.096

        87.8 (1.3)

        82.0 (1.4)

        0.001

        83.3 (1.3)

        78.5 (0.9)

        0.005

        Lipid triad: definition 1§

        30.0 (6.4)

        20.6 (2.8)

        0.174

        34.3 (7.2)

        22.3 (5.1)

        0.179

        20.0 (1.8)

        13.3 (1.1)

        0.002

        13.3 (1.5)

        9.9 (0.7)

        0.048

        Lipid triad: definition 2ǁ

        30.9 (6.2)

        22.9 (2.6)

        0.226

        33.3 (6.9)

        22.0 (4.9)

        0.194

        21.8 (1.8)

        14.2 (1.1)

        <0.001

        13.8 (1.4)

        10.6 (0.7)

        0.053

        Lipid triad: definition 3¶

        30.5 (6.1)

        24.2 (2.7)

        0.336

        32.9 (6.9)

        23.0 (5.3)

        0.262

        22.0 (2.0)

        14.9 (1.1)

        0.002

        14.0 (1.5)

        11.2 (0.7)

        0.098

        Adjusted for age, gender, race or ethnicity, education, and body mass index

                    

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women

        45.8 (5.7)

        34.8 (3.0)

        0.073

        50.6 (10.4)

        31.0 (7.0)

        0.111

        47.6 (2.9)

        25.6 (1.8)

        <0.001

        34.0 (1.8)

        21.9 (1.1)

        <0.001

        High-density lipoprotein cholesterol <40 mg/dl in men, <50 mg/dl in women or medication use

        46.7 (5.6)

        37.6 (3.1)

        0.131

        50.3 (10.0)

        33.3 (7.1)

        0.157

        48.6 (3.2)

        26.7 (1.7)

        <0.001

        34.4 (1.7)

        22.5 (1.0)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl

        79.8 (4.1)

        38.1 (2.3)

        <0.001

        82.2 (3.1)

        60.3 (3.8)

        <0.001

        85.6 (1.7)

        69.2 (1.9)

        <0.001

        77.4 (1.8)

        67.0 (1.2)

        <0.001

        Low-density lipoprotein cholesterol ≥100 mg/dl or medication use

        77.6 (3.9)

        67.8 (2.2)

        0.024

        82.8 (2.6)

        71.8 (4.0)

        0.018

        83.6 (1.6)

        79.3 (1.6)

        0.018

        78.1 (1.8)

        72.4 (1.2)

        0.012

        Non-high-density lipoprotein cholesterol ≥130 mg/dl

        72.1 (4.5)

        35.6 (2.4)

        <0.001

        76.6 (4.0)

        51.9 (3.9)

        <0.001

        79.2 (1.9)

        59.7 (2.0)

        <0.001

        69.8 (1.6)

        59.3 (0.8)

        <0.001

        Triglycerides ≥150 mg/dl

        36.9 (5.3)

        32.6 (2.4)

        0.444

        41.5 (7.2)

        29.2 (6.0)

        0.183

        31.8 (1.9)

        27.7 (1.9)

        0.090

        27.6 (2.4)

        25.3 (1.0)

        0.376

        Triglycerides ≥150 mg/dl or medication use

        38.4 (5.1)

        35.3 (2.6)

        0.558

        41.3 (7.1)

        29.8 (6.1)

        0.209

        33.4 (1.6)

        28.7 (1.7)

        0.025

        28.0 (2.4)

        25.8 (0.9)

        0.399

        Triglycerides ≥150 mg/dl or use of TG-lowering or cholesterol-lowering medications

        37.0 (4.9)

        51.2 (2.8)

        0.009

        40.1 (5.7)

        42.9 (5.2)

        0.707

        32.0 (1.8)

        39.4 (1.8)

        0.001

        28.9 (2.5)

        32.0 (1.2)

        0.255

        Apolipoprotein B ≥80 mg/dl

        84.1 (3.1)

        64.5 (2.0)

        <0.001

        85.8 (3.1)

        75.5 (3.4)

        0.017

        88.2 (1.6)

        80.0 (1.5)

        <0.001

        84.9 (1.2)

        78.5 (0.9)

        <0.001

        Lipid triad: definition 1§

        27.6 (5.6)

        17.7 (2.5)

        0.099

        28.4 (8.0)

        17.6 (5.0)

        0.240

        21.7 (1.8)

        12.7 (1.1)

        <0.001

        14.1 (1.5)

        9.8 (0.7)

        0.013

        Lipid triad: definition 2ǁ

        28.7 (5.5)

        19.7 (2.4)

        0.117

        28.2 (7.6)

        17.5 (4.9)

        0.227

        23.7 (1.8)

        13.6 (1.0)

        <0.001

        14.7 (1.5)

        10.4 (0.7)

        0.012

        Lipid triad: definition 3

        28.3 (5.4)

        20.8 (2.4)

        0.186

        27.9 (7.3)

        18.1 (5.0)

        0.260

        23.7 (1.9)

        14.1 (1.0)

        <0.001

        14.9 (1.5)

        11.1 (0.7)

        0.028

        *P-values for difference of predicted marginal from log-linear regressions.

        Use of fenofibrate, gemfibrozil, and niacin.

        Use of cholesterol-lowering medications as well as fenofibrate, gemfibrozil, and niacin.

        §Definition 1 was based on measured values of concentrations of high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B.

        ǁ Definition 2: use of fenofibrate, gemfibrozil, and niacin was counted as having elevated concentrations of triglycerides and decreased concentrations of high-density lipoprotein cholesterol.

        ¶Definition 3: use of cholesterol-lowering medications, fenofibrate, gemfibrozil, and niacin was counted as having elevated concentrations of triglycerides and use of fenofibrate, gemfibrozil, and niacin was counted as having decreased concentrations of high-density lipoprotein cholesterol.

        Correlation coefficients among concentrations of triglycerides (log-transformed), non-high-density lipoprotein cholesterol, and apolipoprotein B are shown in Table 5. The largest correlation coefficients were noted for non-high-density lipoprotein cholesterol and apolipoprotein B and ranged from 0.90 to 0.95.
        Table 5

        Unadjusted Pearson correlation coefficients among triglycerides, non-high-density lipoprotein cholesterol, and apolipoprotein B among adults aged > =20 years, National Health and Nutrition Examination Survey 2005-2008

        Glycemic status

        Ln(TG) and non-HDLC

        Ln(TG) and apo B

        non-HDLC and apo B

        Diagnosed diabetes

        0.40

        0.40

        0.96

        Undiagnosed diabetes

        0.45

        0.37

        0.95

        Prediabetes

        0.51

        0.45

        0.90

        Normal

        0.51

        0.49

        0.95

        apo B = apolipoprotein B; non-HDLC = non-high-density lipoprotein cholesterol; TG = triglycerides.

        Discussion and conclusion

        Several key points emerged from our analyses. First, the lipid profile of adults with undiagnosed diabetes during 1988–1991 was the worst of the four groups; these participants had the lowest adjusted mean concentration of high-density lipoprotein cholesterol or the highest adjusted mean concentrations of total cholesterol, non-high-density lipoprotein cholesterol, triglycerides, and apolipoprotein B. By 2005–2008, however, this group no longer uniformly had the worst mean concentrations of lipids and apolipoprotein B. Second, unadjusted and adjusted mean concentrations of several lipids improved from 1988–1991 to 2005–2008 among adults in all four groups. Third, some of this improvement was likely a consequence of the increased use of cholesterol-lowering medications and, to a lesser degree, the increased use of triglyceride-lowering medications. Fourth, the age-adjusted prevalence of the atherogenic lipid triad, as we defined it, decreased significantly only among adults with prediabetes and normoglycemia.

        Adults with diabetes experienced the largest absolute decreases in mean concentrations of total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B. All of these lipids have been shown to be directly related to the risk for cardiovascular disease, although a long-running debate about the superiority of one lipid parameter over another in predicting risk of cardiovascular disease remains unresolved [1519]. Thus, the improvement in all of these lipid parameters is encouraging and suggests that the risk for cardiovascular disease, at least from lipids, has declined over time. Previous studies have shown that morbidity and mortality from cardiovascular disease among adults with diabetes have declined in the United States [20, 21].

        The rapidly increasing use of cholesterol-lowering medications is undoubtedly a major contributor to the improvements in these lipids. The increased use of such medications among adults with diabetes has been reported previously [9]. The contribution of other factors is less clear. The intake of dietary fat in the United States has not changed appreciably in recent decades [22], and, thus, it seems unlikely that changes in the intake of this macronutrient provide a ready explanation for the observed reduction in mean concentrations of these lipids. One factor that should have worked against favorable improvements in lipid concentrations is the strong increase in body mass index; increased body mass index generally correlates with increased concentrations of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, apolipoprotein B, and triglycerides as well as decreased concentrations of high-density lipoprotein cholesterol. The fact that improvements in concentrations of various lipids were observed in the face of the rising prevalence of obesity testifies to the presence of other powerful secular trends that were able to offset the potentially deleterious impact of obesity on lipid concentrations.

        In contrast, the mean concentrations of triglycerides did not change significantly among patients with diabetes. The mean concentration of high-density lipoprotein cholesterol increased significantly only when covariates including body mass index were taken into account. Although the use of medications known to influence concentrations of these lipids increased significantly, especially among adults with diagnosed diabetes, the use of these agents is far less common than that of cholesterol-lowering medications. Hence, the use of fenofibrate, gemfibrozil, and niacin is unlikely to have substantially influenced the observed mean concentrations. Dietary practices can affect concentrations of triglycerides. However, the intake of fat has changed little since 1999–2000 whereas the intake of carbohydrates has decreased [22]. Concentrations of high-density lipoprotein cholesterol are influenced by physical activity, alcohol use, and other factors. Trends in physical activity in the United States remain clouded because of inconsistency in recording physical activity in national surveys. Data from the National Health Interview Survey from 1999 to 2010 shows that some improvement in the percentage of adults meeting current guidelines has taken place [23]. A recent analysis of energy expenditure in the workplace concluded that a reduction in energy expenditure has occurred over five decades [24]. Per capita alcohol consumption has increased slightly from a little over 2.1 gallons during 1997–1998 to about 2.3 gallons during 2009 [25].

        Among people with diabetes, changes in glycemic control can also affect lipid parameters. For example, in a study of 73 patients with type 2 diabetes, improved glycemic control was associated with favorable changes in high-density lipoprotein cholesterol, apolipoprotein A1 and the ratio of apolipoprotein A1 to apolipoprotein B [26]. Because data indicate that glycemic control has improved in the United States [10, 27], this development may have contributed to improving the lipid profiles of people with diabetes.

        An interesting observation from our analyses is that adults with undiagnosed diabetes and prediabetes showed evidence of having worse lipid profiles than adults with diagnosed diabetes. The high uptake of cholesterol-lowering medications by adults with diagnosed diabetes likely improved the lipid profile of these adults in comparison with the lipid profiles of adults with undiagnosed diabetes and prediabetes. Nevertheless, mean concentrations of lipids generally changed in a favorable direction among adults with undiagnosed diabetes and prediabetes, although the magnitude of the change was generally smaller than that achieved by adults with diagnosed diabetes. This observation suggests that adults with undiagnosed diabetes and prediabetes are at increased cardiovascular risk from uncontrolled lipid abnormalities and that, once diabetes is diagnosed, adults with previously undiagnosed diabetes will benefit from treatment to manage dyslipidemias.

        Apolipoprotein B is the protein that constitutes the principal structural element of lipoprotein particles for very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and LDL. Two forms of apolipoprotein B have been identified: apolipoprotein B48 and apolipoprotein B100. The latter is generally measured in assays of apolipoprotein B such as the present study. Apolipoprotein B100 is produced in the liver, incorporated into VLDL particles, and subsequently secreted into the circulation where the particle is transformed into LDL. Because there is one molecule of apolipoprotein B per lipoprotein particle, concentrations of apolipoprotein B reflect the number of VLDL, IDL, and LDL particles. Apolipoprotein B is recognized by cell receptors, leading to the uptake of the lipoprotein particle. Numerous studies have shown that concentrations of apolipoprotein B are directly related to cardiovascular risk, and some have argued that apolipoprotein B is a better lipid measure for assessing cardiovascular risk than are other lipid parameters such as low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol [15, 17, 18] although considerable disagreement persists [16, 19]. Because apolipoprotein B is not routinely measured in clinical practice at present, alternative methods to derive estimates of concentrations of apolipoprotein B have been pursued [28].

        In persons with diabetes, a limited number of studies has shown that concentrations of apolipoprotein B predict cardiovascular morbidity and mortality [2932], but not always better than other lipid markers [32]. Concentrations of apolipoprotein B have also been shown to be associated with diabetic retinopathy [33], microalbumiuria [34, 35], carotid atherosclerosis [36, 37], and coronary artery calcification [38]. Thus, the drop in mean concentration of apolipoprotein B in adults with diabetes in the present study, which was consistent with the decreases in mean concentrations of low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, suggests a lessening of cardiovascular risk among people with diabetes. The data suggest that the use of lipid-lowering medications accounted for a substantial portion of the decrease.

        Current guidelines from the American Diabetes Association and the American College of Cardiology Foundation call for reducing concentrations of apolipoprotein B to less than 80 mg/dl in people who have diabetes in addition to at least one additional major risk factor for cardiovascular disease [39]. Elevated concentrations of apolipoprotein B were the most pronounced dyslipidemia among all four groups of adults. Pharmacologic approaches to accomplishing this goal in people with diabetes rely mostly on the use of statins [40]. Insulin treatment in patients with type 2 diabetes has been shown to lower concentrations of apolipoprotein B [41]. Potential nonpharmacological approaches includes increased physical activity and dietary change.

        The findings of the present study are subject to several limitations. First, methods and laboratories used to conduct the lipid measurements changed during the study period. Although strict quality control procedures were implemented in all surveys, direct comparisons were not done. Supportive of the validity of our observations, however, is that the changes in all the atherogenic indices- low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B- were similar. Second, the sample sizes for some of the groups, particularly diagnosed diabetes and undiagnosed diabetes, were small resulting in limited statistical power to detect significant changes in lipid concentrations. The available sample sizes also precluded us from performing stratified analyses by various sociodemographic or other variables.

        In conclusion, mean concentrations of several lipids and apolipoprotein B decreased significantly from 1988–1991 to 2005–2008 among adults with diagnosed diabetes. However, no statistically significant changes in concentrations of triglycerides transpired. The rapid increase in the use of lipid-lowering medications, especially among adults with diagnosed diabetes, likely was a factor in the observed changes. Despite these improvements, sizeable percentages of adults with diabetes continue to have elevated concentrations of low-density lipoprotein cholesterol, triglycerides, and especially apolipoprotein B. Thus, further progress in adequately managing dyslipidemias in adults with diabetes, and thereby lessening their risk for cardiovascular morbidity and mortality, remains to be achieved.

        Disclaimer

        The findings and conclusions in this article are those of the authors and do not represent the official position of the Centers for Disease Control and Prevention.

        Abbreviations

        NHANES: 

        National Health and Nutrition Examination Survey.

        Declarations

        Authors’ Affiliations

        (1)
        Division of Population Health, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention
        (2)
        Division of Behavioral Surveillance, Office of Surveillance, Epidemiology, and Laboratory Services, Centers for Disease Control and Prevention
        (3)
        Mike Rosenbloom Laboratory for Cardiovascular Research, McGill University Health Centre

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        This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.