Normal Fasting Plasma Glucose and Risk of Type 2 Diabetes Diagnosis

Center for Health Research, Kaiser Permanente Northwest, Portland, OR 97227-1098, USA.
The American journal of medicine (Impact Factor: 5). 06/2008; 121(6):519-24. DOI: 10.1016/j.amjmed.2008.02.026
Source: PubMed


The study compares the risk of incident diabetes associated with fasting plasma glucose levels in the normal range, controlling for other risk factors.
We identified 46,578 members of Kaiser Permanente Northwest who had fasting plasma glucose levels less than 100 mg/dL between January 1, 1997, and December 31, 2000, and who did not previously have diabetes or impaired fasting glucose. After assigning subjects to 1 of 4 categories (<85, 85-89, 90-94, or 95-99 mg/dL), we followed them until they developed diabetes, died, or left the health plan, or until April 30, 2007. We used Cox regression analysis to estimate the risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension.
Subjects developed diabetes at a rate of less than 1% per year during a mean follow-up of 81.0 months. Each milligram per deciliter of fasting plasma glucose increased diabetes risk by 6% (hazard ratio [HR] 1.06, 95% confidence interval [CI], 1.05-1.07, P < .0001) after controlling for other risk factors. Compared with those with fasting plasma glucose levels less than 85 mg/dL, subjects with glucose levels of 95 to 99 mg/dL were 2.33 times more likely to develop diabetes (HR 2.33; 95% CI, 1.95-2.79; P < .0001). Subjects in the 90 to 94 mg/dL group were 49% more likely to progress to diabetes (HR 1.49; 95% CI, 1.23-1.79; P <.0001). All other risk factors except sex were significantly associated with a diabetes diagnosis.
The strong independent association between the level of normal fasting plasma glucose and the incidence of diabetes after controlling for other risk factors suggests that diabetes risk increases as fasting plasma glucose levels increase, even within the currently accepted normal range.

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    • "IFG often coexists with other metabolic syndrome components and is included in the definition of the metabolic syndrome in epidemiological studies; nevertheless, the temporal association of other cardiometabolic risk factors, particularly elevated TGs with IFG has not been well examined. As people with normal fasting glucose can also have elevated TGs and other cardiometabolic risk factors (13,14), it is reasonable to assume that those with higher TGs and other cardiometabolic risk factors may have a greater risk of developing IFG. Elevated TGs have been used in diabetes risk prediction models (15–18), but little is known about whether elevated TG levels also increase the risk for IFG independently of central obesity, HDL-C, and elevated blood pressure (BP). "
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    ABSTRACT: OBJECTIVE Elevated plasma triglycerides (TGs) have been included in diabetes risk prediction models. This study examined whether elevated TGs predict risk for impaired fasting glucose (IFG).RESEARCH DESIGN AND METHODS This study used the baseline and longitudinal follow-up data from the Multi-Ethnic Study of Atherosclerosis (MESA). The analysis included non-Hispanic whites, African Americans, Hispanics, and Chinese Americans 45-84 years of age who had fasting glucose <100 mg/dL at baseline, and who did not have clinically evident cardiovascular disease or diabetes. Cox proportional regression models were used to examine the association of elevated TGs with incidence of IFG adjusting for central obesity, low HDL cholesterol, elevated blood pressure, baseline fasting glucose, and BMI. Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity of elevated TGs in predicting IFG were calculated.RESULTSThe incidence rate of developing IFG was 59.1 per 1,000 person-years during the median 4.75 years of follow-up. African Americans and Hispanics had a higher incidence rate of IFG compared with non-Hispanic whites among people with normal TG concentrations. Elevated TGs (>150 mg/dL) at baseline were independently associated with the incidence of IFG with an adjusted hazard ratio of 1.19 (95% CI 1.04-1.37). However, its predictive value for identifying people at risk for IFG was poor, with <57% AUC. Interactions of elevated TGs with race/ethnicity in predicting IFG were not statistically significant.CONCLUSIONS Elevated TGs were moderately associated with risk for IFG, and it was a poor risk prediction tool for IFG.
    Full-text · Article · Oct 2012 · Diabetes care
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    • "Literatures suggest that the extent of glucose levels may be related to the subsequent development of diabetes even among healthy individuals. For example, two large-scale epidemiological studies have demonstrated a clear diabetes risk gradient in glycemic levels within what was previously considered the " normal " profile (i.e., an fasting plasma glucose (FPG) level of 100 mg/dL and a Hemoglobin A1c (HbA1c) level of 6.0% [1] [2]). In addition to the evidence that the strong independent association is observed between the level of normal fasting plasma glucose (NFG) and the incidence of diabetes, another study demonstrated the powerful effects of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) on the development of diabetes [3]. "
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    ABSTRACT: Scant data exists on glucose profile variability in healthy individuals. Twenty-nine healthy subjects without diabetes (86% male; mean age, 38 years) were measured by a CGM system and under real-life conditions. The median percentage of time spent on the blood glucose >7.8 mmol/L for 24 hrs was greater than 10% in both NFG and IFG groups. When subjects were divided into either NFG group (i.e., FPG levels of <5.6 mmol/L; n = 22) or IFG group (FPG levels of 5.6-6.9 mmol/L; n = 7), all CGM indicators investigated but GRADE scores, including glucose variability measures, monitoring excursions, hyperglycemia, hypoglycemia, and 24-hour AUC, did not differ significantly between the two groups. GRADE score and its euglycemia% were significantly different between the two groups. Among various CGM indicators, GRADE score may be a sensitive indicator to discriminate glucose profiles between subjects with NFG and those with IFG.
    Full-text · Article · Dec 2011
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    • "It is hoped that new genetic [26] [27] or nongenetic causative factors, like the epigenetic regulation of the expression of genes involved in the maintenance of PG homeostasis, will emerge. Since PG is both a predictor of T2DM [13] [14] and the basis for its medical definition, it was attractive to study the variation of PG as a quantitative trait (QT) in the general population. The causality of QT variation such as PG is known to be a mixing of genetic, epigenetic [28], and environmental factors. "
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    ABSTRACT: Type 2 Diabetes Mellitus (T2DM) is a metabolic disorder influenced by interactions between genetic and environmental factors. Epigenetics conveys specific environmental influences into phenotypic traits through a variety of mechanisms that are often installed in early life, then persist in differentiated tissues with the power to modulate the expression of many genes, although undergoing time-dependent alterations. There is still no evidence that epigenetics contributes significantly to the causes or transmission of T2DM from one generation to another, thus, to the current environment-driven epidemics, but it has become so likely, as pointed out in this paper, that one can expect an efflorescence of epigenetic knowledge about T2DM in times to come.
    Full-text · Article · Nov 2011 · Journal of nutrition and metabolism
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