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Cardiovascular Risk Factors in Confirmed Prediabetic Individuals: Does the Clock for Coronary Heart Disease Start Ticking Before the Onset of Clinical Diabetes?
Abstract
Although type II diabetes is associated with both microvascular and macrovascular complications, duration of diabetes and severity of glycemia are strongly associated only with the former. Since prediabetic individuals are hyperinsulinemic, and since hyperinsulinemia may be a cardiovascular risk factor, we hypothesized that prediabetic individuals might have an atherogenic pattern of risk factors even before the onset of clinical diabetes, thereby explaining the relative lack of an association of macrovascular complications with either glycemic severity or disease duration. We documented the cardiovascular risk factor status of 614 initially nondiabetic Mexican Americans who later participated in an 8-year follow-up of the San Antonio Heart Study, a population-based study of diabetes and cardiovascular disease. Individuals who were nondiabetic at the time of baseline examination, but who subsequently developed type II diabetes (ie, confirmed prediabetic subjects, n = 43), had higher levels of total and lowdensity lipoprotein cholesterol, triglyceride, fasting glucose and insulin, 2-hour glucose, body mass index, and blood pressure, and lower levels of high-density lipoprotein cholesterol than subjects who remained nondiabetic (n = 571). Most of these differences persisted after adjustment for obesity and/or level of glycemia, but were abolished after adjustment for fasting insulin concentration. When subjects with impaired glucose tolerance at baseline (n = 106) were eliminated, the more atherogenic pattern of cardiovascular risk factors was still evident (and statistically significant) among initially normoglycemic prediabetic subjects. These results indicate that prediabetic subjects have an atherogenic pattern of risk factors (possibly caused by obesity, hyperglycemia, and especially hyperinsulinemia), which may be present for many years and may contribute to the risk of macrovascular disease as much as the duration of clinical diabetes itself. (JAMA. 1990;263:2893-2898)
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“The risk of progressing from prediabetes to overt T2D are greatest for those persons with a history of GDM, strong family history of T2D, progressive increments in glycemia within the prediabetes range, and who meet criteria for a combination of IFG, IGT, or metabolic syndrome (any 2 out of 3).9,805,806”
From American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update. (2022) · cites this paper as [805]
In the citing paper
“In this regard, elevated TG and insulin resistance may both impair HDL function37-39 and predate the development of diabetes.40”
From Is Isolated Low High-Density Lipoprotein Cholesterol a Cardiovascular Disease Risk Factor?: New Insights From the Framingham Offspring Study (2016) · cites this paper as [40]
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“High triglyceride levels that accompany either normal or impaired fasting glucose predict the development of T2DM, 166,167 and therefore, hypertriglyceridemic states should prompt surveillance to rule out T2DM.”
From Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association (2011) · cites this paper as [166]
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Metadata
- Authors
- Haffner, S. M.
- Corresponding author
- Haffner, Steven M.
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 1990-06-06
- Volume
- 263
- Issue
- 21
- Pages
- 2893
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W4297681290
- Cited by
- 668
- References
- 0
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 14 · 2023: 9 · 2022: 18 · 2021: 12 · 2020: 23 · 2019: 15 · 2018: 16 · 2017: 14 · 2016: 17 · 2015: 25 · 2014: 21 · 2013: 16 · 2012: 22
- FWCI
- 6.93
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Function and Risk Factors
- Keywords
- prediabetes, type 2 diabetes, cardiovascular risk factors, hyperinsulinemia, atherogenic lipid profile, impaired glucose tolerance, macrovascular complications, Mexican Americans, San Antonio Heart Study, fasting insulin, obesity, disease duration
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