What is the optimal fasting glucose range for minimizing the risk of cardiovascular disease (CVD) in an adult patient with no significant medical history?

Optimal Fasting Glucose Range for Lowest CVD Risk

For adults with no significant medical history, the fasting glucose range associated with the lowest cardiovascular disease risk is 85-99 mg/dL, with levels below 75 mg/dL or above 100 mg/dL conferring increased cardiovascular risk. 1, 2

Evidence-Based Glucose Thresholds

The most robust evidence comes from a prospective cohort study of over 1.1 million Koreans followed for 16 years, which demonstrated J-shaped curves for CVD risk with the nadir at 85-99 mg/dL 1. This finding is corroborated by an urban population study showing fasting glucose <75 mg/dL was associated with the lowest prevalence of cardiovascular risk factors including hypertension, dyslipidemia, and metabolic syndrome 2.

Risk at Lower Glucose Levels

• Fasting glucose <70 mg/dL increases stroke risk by 6% in men (HR 1.06) and 11% in women (HR 1.11) 1
• Levels <70 mg/dL confer a 3.3-fold increased risk of cardiovascular mortality, and 70-79 mg/dL carries a 2.4-fold increased risk compared to 80-109 mg/dL 3
• This U-shaped relationship persists even after adjusting for age, smoking, hypertension, cholesterol, BMI, and prior cardiovascular disease 3

Risk at Higher Glucose Levels

• As fasting glucose increases >100 mg/dL, risks for CVD, ischemic heart disease, myocardial infarction, and thrombotic stroke progressively increase 1
• The relationship between fasting glucose and cardiovascular risk factors shows a continuous trend, with each increment above 75 mg/dL associated with higher prevalence of hypertension, obesity, hypercholesterolemia, and metabolic syndrome 2

Post-Prandial Glucose Matters More Than Fasting

A critical caveat from the ESC/EASD guidelines: post-load (2-hour) glucose is a stronger predictor of CVD mortality than fasting glucose alone 4. The DECODE study of over 22,000 Europeans demonstrated that:

• High 2-hour post-load glucose predicted all-cause, CVD, and CAD mortality after adjustment for other risk factors, but high fasting glucose alone did not 4
• Impaired glucose tolerance (IGT) doubled CVD mortality, while isolated impaired fasting glucose showed no significant increase in mortality 4
• The relationship between 2-hour glucose and mortality was linear, but no such linear relation existed with fasting glucose 4

Clinical Application Algorithm

Step 1: Assess fasting glucose in context

• Target range: 85-99 mg/dL for lowest CVD risk 1
• If <75 mg/dL: investigate for hypoglycemia causes, consider increased stroke risk 1, 2
• If 100-125 mg/dL: recognize progressive CVD risk increase 1

Step 2: Don't rely on fasting glucose alone

• Obtain 2-hour post-load glucose or consider continuous glucose monitoring, as post-prandial hyperglycemia is the stronger CVD predictor 4
• The largest absolute number of excess CVD deaths occurs in subjects with IGT who have normal fasting glucose 4

Step 3: Address modifiable risk factors

• Optimal fasting triglyceride level may be ≤100 mg/dL, as observational studies consistently show lowest CVD risk at the lowest triglyceride levels 4
• The 25% rise in U.S. triglyceride levels over recent decades coinciding with higher caloric intake represents a reversible CVD risk factor 4

Common Pitfalls

Pitfall 1: Assuming "normal" fasting glucose is safe

• Standard laboratory reference ranges (70-100 mg/dL) include the upper range where CVD risk begins to increase 1
• Even fasting glucose of 90-109 mg/dL carries higher risk than 85-99 mg/dL 1

Pitfall 2: Ignoring low glucose levels

• Clinicians often focus only on hyperglycemia, but fasting glucose <70 mg/dL significantly increases cardiovascular and all-cause mortality 3
• This is not simply a marker of frailty—the association persists after extensive multivariate adjustment 3

Pitfall 3: Overlooking post-prandial glucose

• Fasting glucose can be normal while post-load glucose is elevated, and this isolated post-challenge hyperglycemia doubles CVD mortality 4
• The diabetic state diagnosed by 2-hour glucose has higher death rates than diabetes diagnosed by fasting glucose alone 4