0

The full content of Annals is available to subscribers

Subscribe/Learn More  >
Articles |

Metabolic Risk Factors Worsen Continuously across the Spectrum of Nondiabetic Glucose Tolerance: The Framingham Offspring Study

James B. Meigs, MD, MPH; David M. Nathan, MD; Peter W.F. Wilson, MD; L. Adrienne Cupples, PhD; and Daniel E. Singer, MD
[+] Article and Author Information

Grant Support: In part by the Earle P. Charlton, Jr. Charitable Foundation and by a subcontract from the National Heart, Lung, and Blood Institute Framingham Heart Study, National Institutes of Health (NIH/NHLBI contract NO1-HC-38083). Requests for Reprints: James B. Meigs, MD, MPH, General Medicine Division, Staniford 50-9, Massachusetts General Hospital, Boston, MA 02114; e-mail jmeigs@sol.mgh.harvard.edu. Current Author Addresses: Drs. Meigs and Singer: General Medicine Division, Staniford 50-9, Massachusetts General Hospital, Boston, MA 02114.


Copyright ©2004 by the American College of Physicians


Ann Intern Med. 1998;128(7):524-533. doi:10.7326/0003-4819-128-7-199804010-00002
Text Size: A A A

Background: Categorical definitions for glucose intolerance imply that risk thresholds exist, but metabolic risk for type 2 diabetes mellitus or cardiovascular disease may increase continuously as glucose intolerance increases.

Objective: To examine the distributions of the following metabolic risk factors across the spectrum of glucose tolerance: overall and central obesity, hypertension, low levels of high-density lipoprotein cholesterol, and increased triglyceride and insulin levels.

Design: Cross-sectional analysis.

Setting: The community-based Framingham Offspring Study.

Participants: 2583 adults without previously diagnosed diabetes.

Measurements: Clinical data; fasting glucose, insulin, and lipid levels; and glucose and insulin levels taken 2 hours after oral challenge were collected from 1991 to 1993. Glucose tolerance was determined by 1980 World Health Organization criteria. Patients with normal glucose tolerance were categorized into quintiles of fasting glucose. The distributions of each metabolic risk factor and the metabolic sum of the six risk factors were assessed across seven categories from the lowest quintile of normal fasting glucose level through impaired glucose tolerance and previously undiagnosed diabetes.

Results: The mean age of patients was 54 years (range, 26 to 82 years); 52.7% of patients were women, Glucose tolerance testing found that 12.7% of patients had impaired glucose tolerance and 4.8% had previously undiagnosed diabetes. Multivariable-adjusted mean measures of risk factors and odds ratios for obesity, elevated waist-to-hip ratio, hypertension, low levels of high-density lipoprotein cholesterol, elevated triglyceride levels, and hyperinsulinemia showed continuous increases across the spectrum of nondiabetic glucose tolerance. Although a threshold effect near the upper range of nondiabetic glucose tolerance could not be ruled out for triglyceride levels in men and for insulin levels 2 hours after oral challenge in men and women, no other metabolic risk factors showed clear evidence of thresholds for increased risk.

Conclusions: Metabolic risk factors for type 2 diabetes mellitus and for cardiovascular disease worsen continuously across the spectrum of glucose tolerance categories, beginning in the lowest quintiles of normal fasting glucose level.

Figures

Grahic Jump Location
Figure 1.
Distribution of hemoglobin A1c levels and of the study population by glucose tolerance categories.1cP

Mean hemoglobin A levels and 95% CIs (error bars) among women (□s and dotted lines) and men (black squares and solid lines) are given for each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously unrecognized diabetes mellitus (DM). The fasting plasma glucose range and number and proportion of men and women in each category are given below the figure. Means are multivariable adjusted. *  < 0.001 for trend from the lowest quintile of normal fasting glucose level to impaired glucose tolerance.

Grahic Jump Location
Grahic Jump Location
Figure 2.
Distribution of obesity and blood pressure by glucose tolerance category.top lefttop rightbottom leftbottom rightP

Mean body mass index ( ), waist-to-hip ratio ( ), systolic blood pressure ( ), and diastolic blood pressure ( ) and 95% CIs (error bars) among women (white squares and dotted lines) and men (black squares and solid lines) are given for each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously undiagnosed diabetes mellitus (DM). Means are multi-variable adjusted. * < 0.001 for trend from the lowest quintile of normal fasting glucose level to impaired glucose tolerance.

Grahic Jump Location
Grahic Jump Location
Figure 3.
Distribution of insulin and lipid levels by glucose tolerance category.top left and top rightbottom rightbottom leftPP

Mean fasting and 2-hour post-oral glucose challenge levels of serum insulin ( ), plasma triglyceride ( ), and plasma high-density lipoprotein cholesterol ( ) and 95% CIs (error bars) among women (white squares and dotted lines) and men (black squares and solid lines) are given for each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously undiagnosed diabetes mellitus (DM). Means are multivariable adjusted. * < 0.001; † = 0.003 for trend from the lowest quintile of normal fasting glucose level to impaired glucose tolerance.

Grahic Jump Location
Grahic Jump Location
Figure 4.
Distribution of high-density lipoprotein (HDL) cholesterol levels by obesity and glucose tolerance category.leftright22P

Mean plasma HDL cholesterol levels and 95% CIs (error bars) among female ( ) and male ( ) participants who were obese (body mass index ≥ 27.3 kg/m in women or ≥ 27.8 kg/m in men [black squares and solid lines]), nonobese (white squares and dotted lines), and obese and nonobese combined (slashed squares and dashed lines) in each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously undiagnosed diabetes mellitus (DM). Means are multivariable adjusted. The values indicate the significance of trends from the lowest quintile of normal fasting glucose level to impaired glucose tolerance.

Grahic Jump Location
Grahic Jump Location
Figure 5.
Multivariable odds ratios for metabolic risk factors by glucose tolerance category.22PPP

Odds ratios and 95% CIs (error bars) for obesity (body mass index ≥ 27.3 kg/m in women or ≥ 27.8 kg/m in men [top left]), elevated waist-to-hip ratio (>0.9 for women and >1.0 for men [top middle]), hypertension (two measurements with diastolic blood pressure > 90 mm Hg, systolic blood pressure > 140 mm Hg, or any use of antihypertensive medication [top right]), low high-density lipoprotein (HDL) cholesterol level (<45 mg/dL in women or <35 mg/dL in men [bottom left]), elevated triglyceride level (>200 mg/dL [bottom middle]), and hyperinsulinemia (fasting insulin level > the 90th percentile of its distribution among Framingham Offspring Study participants with normal glucose tolerance [bottom right]) among women (white squares and dotted lines) and men (black squares and solid lines) are shown for each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously undiagnosed diabetes mellitus (DM). Odds ratios are multivariable adjusted. * < 0.001; † = 0.002; * = 0.008 for trend from the lowest quintile of normal fasting glucose level to impaired glucose tolerance.

Grahic Jump Location
Grahic Jump Location
Figure 6.
Age-standardized distribution of the metabolic sum by glucose tolerance category.22

The proportion of women (W) and men (M) with 2 to 3 (white bars) or 4 to 6 (diagonally striped bars) of the following features: obesity (body mass index ≥ 27.3 kg/m in women or ≥ 27.8 kg/m in men), elevated waist-to-hip ratio (>0.9 for women and >1.0 for men), hypertension (two measurements of diastolic blood pressure > 90 mm Hg, systolic blood pressure > 140 mm Hg, or any use of antihypertensive medication), low high-density lipoprotein cholesterol level (<45 mg/dL in women or <35 mg/dL in men), elevated triglyceride level (>200 mg/dL), or hyperinsulinemia (fasting insulin level greater than the 90th percentile of its distribution among Framingham Offspring Study participants with normal glucose tolerance) are displayed for each glucose tolerance category from the lowest quintile (N1) to the highest quintile (N5) of fasting plasma glucose level among participants with normal glucose tolerance, impaired glucose tolerance (IGT), and previously undiagnosed diabetes mellitus (DM). *P< 0.001 for trend from the lowest quintile of normal fasting plasma glucose level to impaired glucose tolerance.

Grahic Jump Location

Tables

References

Letters

NOTE:
Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Comments

Submit a Comment
Submit a Comment

Summary for Patients

Clinical Slide Sets

Terms of Use

The In the Clinic® slide sets are owned and copyrighted by the American College of Physicians (ACP). All text, graphics, trademarks, and other intellectual property incorporated into the slide sets remain the sole and exclusive property of the ACP. The slide sets may be used only by the person who downloads or purchases them and only for the purpose of presenting them during not-for-profit educational activities. Users may incorporate the entire slide set or selected individual slides into their own teaching presentations but may not alter the content of the slides in any way or remove the ACP copyright notice. Users may make print copies for use as hand-outs for the audience the user is personally addressing but may not otherwise reproduce or distribute the slides by any means or media, including but not limited to sending them as e-mail attachments, posting them on Internet or Intranet sites, publishing them in meeting proceedings, or making them available for sale or distribution in any unauthorized form, without the express written permission of the ACP. Unauthorized use of the In the Clinic slide sets will constitute copyright infringement.

Toolkit

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Advertisement
Related Articles
Related Point of Care
Topic Collections
PubMed Articles

Buy Now

to gain full access to the content and tools.

Want to Subscribe?

Learn more about subscription options

Forgot your password?
Enter your username and email address. We'll send you a reminder to the email address on record.
(Required)
(Required)