Markers of "prediabetes" independently raise mortality risk

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Markers of "Prediabetes" Seen to Independently Raise Mortality Risk CME

News Author: Steve Stiles
CME Author: Laurie Barclay, MD

Complete author affiliations and disclosures, and other CME information, are available at the end of this activity.

Release Date: June 25, 2007; Valid for credit through June 25, 2008
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from Heartwire — a professional news service of WebMD

June 25, 2007 — Markers of impaired glucose metabolism in nondiabetics were independently related to increased risks of all-cause and cardiovascular death in a large population-based study. The follow-up time, averaging only about five years, suggests that such indicators of "prediabetes" may represent significant mortality risk factors in their own right, not simply predictors of a later high-risk condition, the investigators speculate.

In the Australian Diabetes, Obesity, and Lifestyle Study (AusDiab), 65% of all cardiovascular deaths occurred in people with previously known or newly identified diabetes or otherwise impaired glucose metabolism at baseline, report Elizabeth LM Barr (International Diabetes Institute, Caulfield, Victoria, Australia) and colleagues.

Compared with participants initially with normal glucose tolerance and after researchers controlled for traditional CV risk factors, the group writes, those with impaired fasting glucose metabolism or impaired glucose tolerance showed a significant 50% to 60% increase in the risk of death from any cause. The risk of CV death was more than doubled among those initially with impaired fasting glucose (fasting plasma glucose ≥ 6.1 and < 7.0 mmol/L with two-hour plasma glucose < 7.8 mmol/L).

Taken together, "these findings suggest that strategies to prevent premature mortality, particularly cardiovascular-disease death, need to be targeted not only to people with diabetes mellitus but also toward people with milder forms of abnormal glucose metabolism." The group's report was published online June 18, 2007, in Circulation.

In the analysis encompassing 10,428 participants, 298 (2.86%) died over a median of 5.2 years. Of the 260 deaths for which a cause was known, a third were due to CV disease. Of the 88 cardiovascular deaths, 57 (65%) were among the participants initially with previously recognized or new diabetes or impaired fasting glucose levels or tolerance, all of which — except for newly diagnosed diabetes — were significant independent risk factors for death from any cause.
Mortality Risks, HR (95% CI), by Baseline Metabolic Status Compared to 7662 Participants Initially With Normal Glucose Tolerance*
Endpoint IFG
(n = 610) IGT
(n = 1298) NDM
(n = 433) KDM
(n = 425)
All-cause mortality 1.6 (1.0 -2.4) 1.5 (1.1 - 2.0) 1.3 (0.9 - 2.0) 2.3 (1.6 - 3.2)
CV mortality 2.5 (1.2 - 5.1) 1.2 (0.7 - 2.2) 1.8 (0.9 - 3.6) 2.6 (1.4 - 4.7)

*Adjusted for age, sex, previously reported CV disease, waist circumference, lipid-lowering medication use, total cholesterol:high-density lipoprotein cholesterol ratio, and smoking status. All-cause mortality also adjusted for hypertension (BP ≥ 140/90 or antihypertensive drug use). CV mortality also adjusted for diastolic blood pressure.
DM = diabetes mellitus; FPG = fasting plasma glucose; PG = plasma glucose; normal glucose tolerance = FPG < 6.1 mmol/L and 2-hour PG < 7.8 mmol/L; IFG = impaired FPG (≥ 6.1 and < 7.0 mmol/L with 2-hour PG < 7.8 mmol/L); IGT = impaired glucose tolerance (2-hour PG ≥ 7.8 and < 11.1 mmol/L with FPG < 7.0 mmol/L); NDM = newly diagnosed DM (no physician-diagnosed DM but FPG ≥ 7.0 mmol/L or 2-hour PG ≥ 11.1 mmol/L); KDM = known DM (physician-diagnosed DM and on hypoglycemic medication, or had FPG ≥ 7.0 mmol/L or 2-hour PG ≥ 11.1 mmol/L).

Those initially with known diabetes or impaired glucose tolerance had independently elevated risks of non-CV death: HR 2.3 (95% CI, 1.5-3.6) and 1.6 (1.1-2.3), respectively. Of the 172 deaths with a known non-CV cause, 59% were attributed to "malignant neoplasm," the authors write.

Noting that the risk of all-cause mortality, but not CV-mortality, reached significance for those initially with impaired glucose tolerance, Barr et al write that even with the small sample size, "it is possible to infer that in the present study cohort, impaired glucose tolerance may increase the risk of cancer mortality."

Often in prior studies tracking mortality associated with impaired glucose metabolism in nondiabetics, the group notes, it has been difficult to distinguish any risk from baseline glucose abnormalities from risk directly related to diabetes developing later. In the current study, the glucose-related markers predicted mortality "after only a relatively short period of follow-up," suggesting that later diabetes onset "was not a major pathway to death and that impaired fasting glucose and impaired glucose tolerance are genuine risk factors for mortality and not just precursors of diabetes mellitus."

The AusDiab report says the study received financial support from Abbott Australasia, Alphapharm, AstraZeneca, Aventis Pharma, Bio-Rad Laboratories, Bristol-Myers Squibb, Eli Lilly Australia, GlaxoSmithKline, Merck Sharp & Dohme, Multiplex, Novartis Pharmaceuticals, Novo Nordisk Pharmaceuticals, Pfizer, Roche Diagnostics Australia, and Sanofi-Synthelabo. Coauthor Dr Timothy A Welborn (University of Western Australia, Nedlands) has received speaker payments from Novo Nordisk Pharmaceuticals, Eli Lilly, Sanofi-Synthelabo, Aventis Pharma, and Servier, and is an consultant and advisor to the boards of Abbott Australasia, Roche Diagnostics Australia, Sanofi-Synthelabo, and Aventis Pharma.

Circulation. Published online June 18, 2007.
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