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October 11, 2021

Blood Glucose Above Optimal Can Break Your Heart

Elevated blood glucose is a classic sign of metabolic dysfunction. It is associated not only with diabetes but with cardiometabolic risk factors such as visceral obesity, high blood pressure, and dyslipidemia,[i] as well as cardiovascular disease itself.

The need to periodically update standard reference intervals to reflect dysfunction is illustrated by updates in the diagnostic guidelines for diabetes.

In 1979, diabetes wasn’t diagnosed until fasting plasma glucose reached 140 mg/dL (7.77 mmol/L) or higher. This means that early asymptomatic dysfunction and outright disease were present but not accounted for due to outdated reference intervals.[ii] [iii]

Even traditional medical practice recognizes that a fasting blood glucose that had previously been defined as “normal” is now categorized as “prediabetes,” with increased likelihood of progressing to overt diabetes. The functional blood chemistry approach addresses levels that are trending toward dysfunction instead of waiting for it to arrive.

Current 2021 ADA Guidelines [iv] [v] [vi] [vii]

Biomarker

Normal

Prediabetes

Diabetes

Fasting plasma glucose (FPG)

(No caloric intake for at least 8 hours)

70 – 99 mg/dL

3.9 – 5.5 mmol/L

100 – 125 mg/dL

5.6 – 6.9 mmol/L

126 mg/dL or higher

7 mmol/L or higher

Hemoglobin A1c

Less than 5.7%

Less than

39 mmol/mol

5.7-6.4%

39-47 mmol/mol

6.5% or higher

48 mmol/mol or higher

Oral Glucose Tolerance Test

2-hour result following 75 g anhydrous glucose dissolved in water

Less than 140 mg/dL

Less than 7.8 mmol/L

140 – 199 mg/dL

7.8 – 11 mmol/L

200 mg/dL or higher

11.1 mmol/L or higher

 

Or random glucose >199 mg/dL

>11 mmol/L

Other

If symptomatic for hyperglycemia

 

 

Random plasma glucose of

200 mg/dL or higher

11.1 mmol/L or higher

Hypoglycemia

 

 

Level 1

54-70 mg/dL

3-3.9 mmol/L

Level 2

Less than 54 mg/dL

3 mmol/L

Prediabetes must be addressed early on. Progressive nutrition and lifestyle changes that bring blood glucose biomarkers into optimal range can help avoid progression to an inevitable diagnosis of diabetes.

Research from 2008 based on 46,578 individuals with “normal” fasting plasma glucose (FPG) less than 100 mg/dL (5.6 mmol/L) revealed:[viii]

  • “Diabetes risk increases as FPG levels increase, even within the currently accepted normal range.”
Four FPG categories were defined:
    • Less than 85 mg/dL (4.7 mmol/L)
    • 85-89 mg/dL (4.7 – 4.9 mmol/L)
    • 90-94 mg/dL (5-5.2 mmol/L)
    • 95-99 mg/dL (5.3-5.5 mmol/L)
  • Subjects with levels 90-99 mg/dL were significantly more likely to progress to diabetes than those with a FPG of 89 mg/dL (4.9 mmol/L) or lower.
  • Those with FPG 90-94 mg/dL were 49% more likely to progress to diabetes.
  • Those with FPG of 95-99 mg/dL had a 2.33 greater chance of progressing to diabetes than those with a FPG below 85 mg/dL (4.7 mmol/L).
  • Each mg/dL (0.56 mmol/L) increased diabetes risk by 6%.

The importance of creating narrower ranges to better identify disease risk is being recognized by the mainstream. For example, defining prediabetes in those with a hemoglobin A1c of 5.7-6.4% instead of 6-6.4% helps identify more individuals at increased risk of cardiovascular disease and, of course full-blown diabetes.[ix]

Optimal Levels can Translate into Optimal Health

Earlier research from 1999 reveals that fasting glucose above 85 mg/dL (4.7 mmol/L) is associated with health risks including increased risk of cardiovascular disease and myocardial infarction. A 22-year follow-up study of healthy non-diabetic men demonstrates that higher than optimal levels of blood glucose may literally be a matter of life and death.[x]

The prospective study, published in Diabetes Care in 1999, revealed that those with a fasting blood glucose of 86-109 mg/dL (4.8–6 mmol/L), the highest glucose quartile defined, had a “significantly higher mortality rate from cardiovascular diseases compared to the three lowest quartiles... even after adjusting for age, smoking habits, serum lipids, blood pressure, forced expiratory volume in 1 s, and physical fitness.”

  • Quartile I 52-73 mg/dL         9-4 mmol/L
  • Quartile II 74-79 mg/dL         1-4.4 mmol/L
  • Quartile III 80-85 mg/dL        44-4.7 mmol/L
  • Quartile IV 86-109 mg/dL       8-6 mmol/L

20 years later…

A 2019 study of 19,630 individuals assessing Long-term Absolute Risk for Cardiovascular Disease Stratified by Fasting Glucose Level, revealed the risk associated with “normal” fasting glucose levels.[xi]

  • Participants had no history of a prior CVD event
  • Incidence for each CVD end point was lowest among those with fasting blood glucose of less than 90 mg/dL (<5.0 mmol/L) and highest among those meeting criteria for diabetes.
  • Conversion of prediabetes to diabetes was associated with a 1.3-3.6 fold increased cardiovascular risk including coronary heart disease and stroke

Recognition of elevated blood glucose as a cardiovascular risk factor has been documented in the literature for decades though its importance has been overlooked:

  • “Subjects with fasting glucose levels in the high normal range of 95–99 mg/dL (5.3-5.5 mmol/L) had an increased CVD risk when compared with levels <80 mg/dL (HR 1.53;CI 95% [1.22–1.91], P < .001).”[xii]
  • “Plots of stroke mortality rates versus blood glucose identified an upward inflection in risk of death from a stroke at about 83 mg/dL (4.6 mmol/L)…An 18 mg/dL (1 mmol/L) increase in blood glucose after this point was associated with a 27% increase in the risk of death from stroke.”[xiii]

As you can see, assessing fasting blood glucose levels through an optimal lens provides the opportunity for early detection of metabolic abnormalities that can otherwise advance to chronic disease. While standard lab values for a “normal” fasting blood glucose range from 65-99 mg/dL (3.6-5.5 mmol/L),[xiv] a healthier, optimal range would be 75-86 mg/dL (4.2- 4.8 mmol/L).

Functional medicine by nature emphasizes the need to consider optimal ranges for patients’ bloodwork in order to optimize prevention. Fortunately, ongoing research and observation is confirming the functional medicine approach to detecting and addressing blood glucose parameters beyond what was traditionally considered normal.[xv] [xvi]

References

[i] American Diabetes Association. “2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020.” Diabetes care vol. 43,Suppl 1 (2020): S14-S31. doi:10.2337/dc20-S002

[ii] Pape J. Diabetes Self-management. (2011). Diagnosing Diabetes.

[iii] “Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. National Diabetes Data Group.” Diabetes vol. 28,12 (1979): 1039-57. doi:10.2337/diab.28.12.1039

[iv] American Diabetes Association. “2. Classification and Diagnosis of Diabetes: Standards of Medical Care in Diabetes-2020.” Diabetes care vol. 43,Suppl 1 (2020): S14-S31. doi:10.2337/dc20-S002

[v] Press release Newest Prediabetes Awareness Campaign by Nation’s Medical Authorities Spreads the Word: 1 in 3 Americans Has Prediabetes, Learn Your Risk For Immediate Release: Wednesday, November 14, 2018

[vi] American Diabetes Association. Understanding A1c. Diagnosis.

[vii] American Diabetes Association. "6. Glycemic Targets: Standards of Medical Care in Diabetes—2021." Diabetes Care 44.Supplement 1 (2021): S73-S84.

[viii] Nichols, Gregory A et al. “Normal fasting plasma glucose and risk of type 2 diabetes diagnosis.” The American journal of medicine vol. 121,6 (2008): 519-24. doi:10.1016/j.amjmed.2008.02.026

[ix] Vistisen, Dorte et al. “Risk of Cardiovascular Disease and Death in Individuals With Prediabetes Defined by Different Criteria: The Whitehall II Study.” Diabetes care vol. 41,4 (2018): 899-906. doi:10.2337/dc17-2530

[x] Bjørnholt, J V et al. “Fasting blood glucose: an underestimated risk factor for cardiovascular death. Results from a 22-year follow-up of healthy nondiabetic men.” Diabetes care vol. 22,1 (1999): 45-9. doi:10.2337/diacare.22.1.45

[xi] Bancks, Michael P et al. “Long-term Absolute Risk for Cardiovascular Disease Stratified by Fasting Glucose Level.” Diabetes care vol. 42,3 (2019): 457-465. doi:10.2337/dc18-1773

[xii] Shaye, Kivity et al. “Fasting glucose levels within the high normal range predict cardiovascular outcome.” American heart journal vol. 164,1 (2012): 111-6. doi:10.1016/j.ahj.2012.03.023

[xiii] Batty, G D et al. “Post-challenge blood glucose concentration and stroke mortality rates in non-diabetic men in London: 38-year follow-up of the original Whitehall prospective cohort study.” Diabetologia vol. 51,7 (2008): 1123-6. doi:10.1007/s00125-008-1005-0

[xiv] Quest Diagnostics Glucose. Fasting.

[xv] Lutfi, Mohamed Faisal, and Ramaze Farouke Elhakeem. “Effect of Fasting Blood Glucose Level on Heart Rate Variability of Healthy Young Adults.” PloS one vol. 11,7 e0159820. 21 Jul. 2016, doi:10.1371/journal.pone.0159820

[xvi] McGlothin, Paul, and Meredith Averill. The CR Way: Using the Secrets of Calorie Restriction for a Longer, Healthier Life. Harper Collins, 2008.

 

Tag(s): Biomarkers

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