Normal Nocturnal Glucose Ranges and Impaired Glucose Tolerance
In individuals with normal glucose tolerance, interstitial glucose concentrations during sleep average 4.29-4.53 mmol/L (77-82 mg/dL), with glucose declining during REM sleep phases, while patients with impaired glucose tolerance (IGT) are defined by fasting plasma glucose <7.0 mmol/L (126 mg/dL) but 2-hour post-load values ≥7.8 mmol/L (140 mg/dL), though specific nocturnal ranges for IGT patients are not established in current guidelines. 1, 2
Normal Nocturnal Glucose Physiology
Sleep Stage-Specific Glucose Patterns
During REM sleep, interstitial glucose concentrations decrease by a mean of 0.028 mmol/L per 5-minute interval compared to NREM sleep, with absolute REM glucose levels averaging 4.29 ± 1.00 mmol/L (77 ± 18 mg/dL) versus 4.53 ± 0.90 mmol/L (82 ± 16 mg/dL) during NREM sleep in subjects with normal glucose tolerance. 2
The decline in glucose during REM sleep occurs in approximately 92% of individuals with normal glucose tolerance, while glucose increases during NREM sleep in about 62% of subjects. 2
This REM-related glucose decline represents a physiological risk factor for nocturnal hypoglycemia, particularly in insulin-treated patients. 2
Diagnostic Criteria for Impaired Glucose Tolerance
WHO and ADA Classification Standards
IGT is diagnosed when fasting plasma glucose is <7.0 mmol/L (126 mg/dL) AND 2-hour post-load plasma glucose is ≥7.8 and <11.1 mmol/L (≥140 and <200 mg/dL) during a 75-gram oral glucose tolerance test performed after an 8-14 hour overnight fast. 1
Normal glucose regulation requires fasting plasma glucose <6.1 mmol/L (110 mg/dL) according to WHO criteria, or <5.6 mmol/L (100 mg/dL) according to 2003 ADA criteria, plus 2-hour post-load glucose <7.8 mmol/L (140 mg/dL). 1
Metabolic Characteristics of IGT
Patients with IGT demonstrate impaired early insulin release as the most consistent metabolic defect, combined with impaired suppression of hepatic glucose release after meals, though fasting glucose production and disposal rates typically remain normal. 3
Postprandial glucose disposal is often normal or increased in IGT due to compensatory hyperglycemia and delayed hyperinsulinemia. 3
Fasting levels of free fatty acids, glycerol, ketone bodies, lactate, and alanine generally remain within normal ranges in IGT patients. 3
Critical Consideration: Alcohol and Nocturnal Glucose
Impact of Evening Alcohol Consumption
In patients with diabetes using insulin or insulin secretagogues, evening alcohol consumption (0.75 g/kg) causes delayed morning hypoglycemia 12-15 hours after ingestion, with blood glucose nadirs reaching 1.9-2.9 mmol/L (34-52 mg/dL), despite normal overnight glucose levels. 4
Alcohol must always be consumed with food to reduce nocturnal and fasting hypoglycemia risk, as recommended by the American Diabetes Association. 1
The mechanism involves reduced nocturnal growth hormone secretion (area under curve reduced from 6.5 to 2.1 μg·L⁻¹·h⁻¹ between midnight and 4:00 AM), which impairs counterregulatory responses. 4
Blood ethanol becomes undetectable by 8:00 AM, yet hypoglycemic effects persist through the following morning, creating a delayed risk window. 4
Practical Monitoring Strategy
For IGT patients who consume alcohol regularly, test blood glucose at four critical timepoints: before bed, at 2:00-3:00 AM, upon waking, and 2 hours after breakfast to detect delayed hypoglycemia patterns. 5
The incidence of hypoglycemia peaks between midnight and 6:00 AM, making this the highest-risk period for nocturnal glucose disturbances. 6
Circadian Effects on Glucose Tolerance
Time-of-Day Glucose Variability
Evening consumption of carbohydrates produces significantly higher and more prolonged glucose elevations compared to identical foods eaten in the morning, with glucose remaining elevated 3-9 hours after an evening meal. 1, 5
Each 1-hour increase in overnight fasting duration is associated with a 0.03 mmol/L decrease in fasting glucose, indicating that late-night eating directly shortens the beneficial fasting period. 1, 5
Post-prandial glucose concentrations are higher at 4:00 PM versus 8:00 AM following identical glucose loads, with this difference becoming more pronounced as glucose tolerance deteriorates. 1
Clinical Implications and Mortality Risk
Long-Term Outcomes in IGT with Sleep Disturbances
IGT patients with sleep disorders have a 2.03-fold increased risk of all-cause mortality (95% CI: 1.24-3.34) compared to those with normal glucose tolerance and no sleep disorders, highlighting the importance of addressing both glucose abnormalities and sleep quality. 7
This mortality risk is comparable whether assessed by sleep disorders or short sleep duration (<7 hours), suggesting both sleep quality and quantity matter. 7
Diabetes patients show elevated mortality risk regardless of sleep disorder status, but the IGT group only demonstrates increased mortality when sleep disturbances are present. 7