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Fasting Glucose and Mortality

Jan 27, 2018
 

Study to examine the association between fasting glucose and mortality by age in patients with diabetes.

A study looked at 360,000 adults with diabetes during 2001-2004 and followed them until 2013. The results showed a U-curve association and fasting glucose levels associated with the lowest mortality were 90-130 mg/dl., except for those ages 18-44 years (80-95mg/dl)

Multivariable-adjusted hazard ratios of fasting glucose <65, 65–74, 75–84, 140–169, 170–199, and ≥200 mg/dL were 1.46, 1.12, 1.09, 1.12, 1.31, and 1.78, respectively, compared with 85–99 mg/dL.

Fasting glucose levels are a fundamental element of managing diabetes to help patients achieve good glycemic control. Precise estimates of the age-specific relative risks of death associated with fasting glucose may help determine better glucose targets for the management of diabetes. However, little is known about the associations of the full range of fasting glucose with all-cause mortality and the optimal range for survival according to then age when a person is diagnosed with diabetes.

Fasting serum glucose and total cholesterol were assayed using enzymatic methods. Blood pressure, smoking history, alcohol use, and known prevalent diabetes status at baseline were collected. Fasting glucose concentrations were categorized into 10 groups. HRs were calculated using Cox proportional hazards models stratified by age at baseline after adjustment for age at baseline, sex, smoking status, alcohol use, physical activity, BMI, systolic blood pressure, and total cholesterol.

The results showed that during a mean 10.5 years of follow-up, 62,034 adults with known diabetes died. At baseline, the mean age was 56.8 years and the mean fasting glucose level was 148.5 mg/dL. Men with diabetes had 3.04 mg/dL higher mean fasting glucose levels than women with diabetes (149.78 vs. 146.75 mg/dL). The sex difference in mean glucose levels peaked at 32–35 years, when men had a level 15 mg/dL higher than women. In people with diabetes, U-curve associations between fasting glucose and all-cause mortality were found with a nadir at 100–109 mg/dL in categorical analysis and 107 mg/dL in spline analysis. In populations with diabetes, multivariable adjusted hazard ratios (HRs) of mortality associated with fasting glucose levels of 65, 65–74, 75–84, 140–169, 170–199, and 200 mg/dL were 1.46, 1.12, 1.09, 1.12, 1.31, and 1.78, respectively, compared with 85–99 mg/dL, in comparison with 1.20, 1.06, 1.02, 1.51, 1.74, and 2.29 in people without known diabetes. In the 18–44 years age group, in persons with diabetes, the HRs associated with 100–109, 110–125, and 126–139 mg/dL were 1.35, 1.48, and 1.96, respectively, compared with 85–99 mg/dL. In persons with diabetes ages 65–99 years, fasting glucose levels of 100 mg/dL were associated with excess mortality compared with 100–109 mg/dL. When the range with an excess risk of 5% was considered the optimal range for survival, the optimal ranges in persons with diabetes ages 18–44, 45–64, and 65–99 years were 65–99, 85–139, and 85–139 mg/dL in the categorical analysis and 80–95, 95–135, and 90–130 mg/dL in the analysis, respectively.

In conclusion, U-curve associations were found between fasting glucose and all-cause mortality in those with diabetes regardless of age. In individuals with prevalent diabetes, at younger ages (18–44 years old), overall associations and fasting glucose range for minimal mortality (;80–95 mg/dL) were similar to those of individuals without known prevalent diabetes. However, in middle-aged and elderly adults with prevalent diabetes, the range for lowest mortality shifted upward to 90–130 mg/dL. The population with diabetes had more extreme HRs related to hypoglycemia (65 mg/dL) than individuals without known diabetes. The risk of death associated with hypoglycemia generally exceeded that of levels 170–199 mg/dL, while low-normal levels (65–84 mg/dL) showed a risk comparable with that of fasting glucose 140–169 mg/dL. The finding of 3.0 mg/dL higher fasting glucose levels in men than in women was similar between individuals with and without known prevalent diabetes, despite the substantial difference in the pattern of the mean fasting glucose levels according to sex and age.

However, few studies have shown U-curve associations of fasting glucose in diabetes, perhaps due to lack of studies with a sufficient number of subjects. The observed U-curve associations provide evidence supporting that patients with diabetes should be carefully monitored to avoid fasting glucose 65–84 mg/dL in addition to hypoglycemia (65 mg/dL), considering the greater excess mortality for hypoglycemia at 65 mg/dL than a fasting glucose of 170–199 mg/dL and a comparable risk between levels 65–84 and 140–169 mg/dL. The results further suggest that tight glucose control has more beneficial effects at younger ages than at older ages.

The age-specific findings were generally concordant not only with the Diabetes Control and Complications Trial (DCCT), the Epidemiology of Diabetes Interventions and Complications (EDIC) study, and the UK Prospective Diabetes Study (UKPDS) and its follow-up study that reported a reduction in all-cause mortality in the intensive glucose treatment group.

Practice Pearls:

  • It was concluded that optimal fasting glucose range for survival is higher in adults with instead of without known prevalent diabetes, except, perhaps, younger adults.
  • Tight glucose control may lessen premature death in younger adults with diabetes.
  • Hypoglycemia (<65 mg/dL) was associated with higher mortality versus fasting glucose 170–199 mg/dL, while fasting glucose of 65–84 mg/dL had risks comparable with those at levels 140–169 mg/dL in diabetes.

 

 

Reference:

Sang-Wook Yi, Sangkyu Park, Yong-ho Lee, Beverley Balkau and Jee-Jeon Yi    Diabetes Care 2018 Jan; dc171872. https://doi.org/10.2337/dc17-1872