Can prolonged fasting of 16 hours cause fasting blood sugar levels to rise?

Prolonged Fasting Can Cause Fasting Blood Sugar Levels to Rise

Yes, prolonged fasting of 16 hours can cause fasting blood sugar levels to rise due to stress hormone responses, particularly cortisol-mediated hepatic glucose production. 1

Physiological Mechanisms Behind Fasting Hyperglycemia

• During prolonged fasting (16+ hours), cortisol is released as part of the body's stress response, which directly stimulates hepatic gluconeogenesis and glycogenolysis, increasing endogenous glucose production even when insulin levels are present 1
• This stress-induced cortisol release leads to peripheral insulin resistance while simultaneously increasing hepatic glucose output, contributing to what's sometimes called "stress diabetes" 1
• The body's metabolic adaptation to prolonged fasting includes increased production of ketones and stress hormones that can counteract insulin's effects, leading to higher blood glucose levels 2

Evidence from Clinical Studies

• Research shows that short-term fasting (2 days) can actually impair glucose tolerance more than prolonged fasting (6 days), with the 2-day fast group showing residual impaired glucose tolerance even after returning to normal diet 2
• This paradoxical effect appears linked to greater perceived stress during short-term fasting, as evidenced by elevated epinephrine response and changes in core temperature 2
• In contrast, prolonged fasting seems to eventually trigger adaptive mechanisms related to improved insulin release and maintained glucose tolerance 2

Fasting Duration and Glucose Regulation

• The 16-hour threshold appears significant, as the 2025 Diabetes Care guidelines specifically identify fasting periods of ≥16 hours as a risk factor in their assessment tool for patients with diabetes 3
• During fasting, endogenous glucose production is initially mediated by hepatic glycogenolysis during the first 8-12 hours, followed by gluconeogenesis, which can lead to higher blood glucose levels as the fast continues 3
• The kidney also plays a role in endogenous glucose production, particularly during prolonged starvation periods 3

Clinical Implications

• Time-restricted eating with fasting windows exceeding 14 hours has been linked to poor cardiometabolic health in several studies 3
• Eating 12 hours out of sync with the light-dark cycle—even with sufficient sleep—increases three-hour postprandial glucose levels by 15% and induces insulin resistance in just four days 3
• For people with diabetes, prolonged fasting periods (≥16 hours) are considered a risk factor that may require closer monitoring 3

Individual Variations

• There is considerable inter-individual variation in how people respond to fasting, with some experiencing more pronounced stress hormone responses than others 2
• In people with untreated type 2 diabetes, a 24-hour fast initially decreased blood glucose levels from elevated to normal range, but then glucose began to rise again after reaching its nadir 4
• In people with type 1 diabetes, a controlled study showed they could safely perform a 36-hour fast with low risk of hypoglycemia, though beta-hydroxybutyrate levels were significantly higher after prolonged fasting 5

Practical Considerations

• For diagnostic testing requiring fasting blood glucose measurements, the standard recommendation is typically 8-12 hours of fasting, not 16+ hours, to avoid the potential confounding effect of stress-induced hyperglycemia 1
• For patients with diabetes who choose to practice intermittent fasting, monitoring blood glucose levels is particularly important during extended fasting periods 3
• Understanding the cortisol-mediated increase in hepatic glucose production is important for interpreting fasting blood glucose results after prolonged fasting periods 1