Fasting Plasma Glucose Below 100mg/dL and Risk of Type 2 Diabetes Diagnosis

The study compares the risk of incident diabetes associated with fasting plasma glucose levels in the normal range below 100mg/dL, controlling for other risk factors. Subjects with glucose levels of 95 to 99 mg/dL were 2.33 times more likely to develop diabetes.

Looking in back in time, the ADA’s definition for diabetes was a fasting blood sugar of over 180mg/dL. Then it was changed to 140mg/dL. And now it is 126mg/dL.  But now instead of lowering it to 100mg/dL., we gave it a new name called pre-diabetes.  But from this study we see we might have to lower it even further to catch it even earlier.  But the medical community will argue, what is the cost benefit?

They 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), they were followed until they developed diabetes, died, or left the health plan, or until April 30, 2007. The Cox regression analysis was used to estimate the risk of incident diabetes, adjusted for age, sex, body mass index, blood pressure, lipids, smoking, cardiovascular disease, and hypertension.
The ADA currently recommends the use of fasting glucose tests to diagnose diabetes. Thus, from the standpoint of US clinical practice, monitoring fasting plasma glucose in at-risk patients is necessary. In the present study, all subjects had apparently normal fasting glucose levels that did not suggest diabetes risk by the current definition. However, those who developed diabetes had other adverse characteristics that may help identify their increased risk, namely, high BMI, hypertension, and poor lipid profiles. The univariate comparisons of these risk factors across fasting plasma glucose categories among those who developed diabetes yielded no significant differences. Thus, a consistent profile of predictive characteristics emerged that may assist clinicians in identifying patients for targeted diabetes screening. Although widespread screening with oral glucose tolerance tests is burdensome, performing this test on patients with the high-risk profile we identified might be an appropriate course of action. In addition to this risk profile, smoking increased the risk of diabetes by 36% independently of other factors, a result consistent with previous studies that have found an association between smoking and diabetes.14, 15, 16, 17 Patients with this high-risk profile would likely benefit from lifestyle modifications known to reduce diabetes risk.18, 19, 20

The results of the study showed that 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, (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.

In a study conducted on the island of Mauritius, Shaw et al10 concluded that the risk of diabetes (when diagnosed by fasting plasma glucose alone) starts to increase at a fasting plasma glucose level of greater than 5.2 mmol/L (∼94 mg/dL).10 Our results suggest that the threshold is lower. In our data, a fasting plasma glucose level of 90 to 94 mg/dL conferred a 49% greater risk of developing diabetes compared with a level less than 85 mg/dL. Furthermore, although the HR of 1.08 in the 85 to 89 mg/dL category did not reach statistical significance, it was nonetheless elevated, suggesting that the upper portion of this range may also carry additional risk. This is consistent with the study of young Israeli men, which found significantly greater risk at the level of 87 to 90 mg/dL (relative to<81 mg/dL).11

Up to 70% of individuals with abnormal glucose regulation, defined as impaired fasting glucose or impaired glucose tolerance, may ultimately progress to diabetes.2 Whether diabetes risk is best identified by fasting or post-challenge glucose tests remains controversial, but it is agreed that impaired fasting glucose and impaired glucose tolerance do not define the same individuals.12 Because no subjects in the current study had impaired fasting glucose, it is likely that some of those who progressed to diabetes had impaired glucose tolerance. This would not be surprising given the higher sensitivity of impaired glucose tolerance in predicting progression to diabetes.13 Indeed, the lowering of the criterion for impaired fasting glucose from 110 to 100 mg/dL was done primarily to equalize the population risk of developing diabetes between impaired fasting glucose and impaired glucose tolerance states.4, 12

Our study has several limitations. First, we defined diabetes as the entry into the electronic medical record of a diagnosis or by a single fasting plasma glucose level greater than 125 mg/dL. Neither of these criteria necessarily defines clinically confirmed diabetes. Oral glucose tolerance tests, which may be a stronger predictor of diabetes, were not available for our subjects. Among those who developed diabetes by our criteria, however, the mean hemoglobin A1c at diagnosis was more than 7%, a level that strongly suggests that abnormal glucose metabolism has been maintained for several months. Second, because of the observational design, we cannot conclude that higher fasting plasma glucose within the normal range actually causes diabetes; we can only report the strong independent association. Third, it is possible that risk factors we could not include, such as insulin resistance and family history of diabetes, would have accounted for the reported difference in diabetes incidence across fasting plasma glucose categories. We also did not assess the use of drugs known to affect glucose levels (eg, thiazide diuretics, glucocorticosteroids) as covariates. Fourth, we did not randomly select participants for fasting plasma glucose testing. Although most of our results were ascertained from routine lipid screening, the study was nonetheless limited to patients who sought health care. Thus, whether our study sample is representative of all individuals with normal fasting plasma glucose levels cannot be determined.

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.

The debate over the “correct” cut-point for defining impaired fasting glucose has not been settled. Our results demonstrate that increased risk of diabetes extends well below the ADA’s current maximum limit of normal plasma glucose of 99 mg/dL. Although impaired fasting glucose may be a useful construct, seemingly normal fasting plasma glucose levels also provide information regarding the future risk of diabetes, especially in conjunction with other known risk factors.
American journal of medicine Volume 121, Issue 6, Pages 519-524 (June 2008)

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