Biomarkers of Glucose Regulation: Non-Fasting Glucose

Optimal Takeaways

Blood glucose levels fluctuate with food intake, rising after a meal and then returning to premeal levels under normal circumstances. The inability to return glucose to a healthy baseline within 1-2 hours indicates glucose dysregulation.

Prolonged postprandial spikes or “excursions” in glucose levels are detrimental and increase the risk of cardiovascular disease and diabetes mellitus.

These excursions may occur without a rise in fasting glucose in the early phases of insulin resistance and diabetes. Therefore, non-fasting postprandial glucose levels should be evaluated periodically and monitored regularly in high-risk individuals. A good rule of thumb is to limit postprandial glucose increases to no more than 40 mg/dL (2.22 mmol/L) above fasting or a peak of 125 mg/dL (6.94 mmol/L).

Low non-fasting glucose may be a sign of hypoglycemia, malabsorption, malnutrition, or hypothyroidism.

Standard Range:: 65 – 139 mg/dL (3.61 – 7.71 mmol/L)

The ODX Range: 75 – 125 mg/dL (4.2 – 6.94 mmol/L)

Low non-fasting postprandial glucose (PPG) may be associated with insulin overdose, insulinoma, malabsorption, hypothyroidism, hypopituitarism, or Addison’s disease (Pagana 2022).

High non-fasting postprandial glucose (PPG) is associated with insulin resistance (Tuan 2019), diabetes mellitus, acute stress, smoking, corticosteroid therapy, diuretic therapy, hyperthyroidism, liver disease, chronic renal failure, Cushing syndrome, glucagonoma, adrenal tumor, acromegaly, or malnutrition (Pagana 2022).

Elevated levels are also a risk factor for endothelial dysfunction, inflammation, oxidative stress, retinopathy, cancer of the pancreas, breast, and colon, all-cause mortality cognitive dysfunction (Madsbad 2016), impaired verticality perception (Razzak 2018), cardiovascular disease, CVD mortality (Wang 2022), and coronary heart disease events (Imano 2012).

Overview

Consumption of food or caloric beverages can significantly affect blood glucose levels. Postprandial glucose levels(PPG) increase for approximately 30 minutes following a meal but then decrease and return to baseline (Razzak 2018). Abnormally high fasting or non-fasting levels suggest impaired glucose tolerance, insulin resistance, or diabetes.

Fasting blood glucose is measured after at least 8 hours since the last caloric intake, “early” non-fasting glucose is measured within 3 hours of the last caloric intake, and “late” non-fasting is measured between 3 and 7.9 hours since the last caloric intake (Wang 2022).

Ideally, glucose levels should return to premeal levels within 2 hours due to the action of insulin. A 2-hour PPG above 140 mg/dL (7.77 mmol/L) is highly suspect for diabetes and should be investigated further with an oral glucose tolerance test (OGGT). A level exceeding 140 mg/dL after one hour may indicate gestational diabetes (Pagana 2022).

Isolated “excursions” of hyperglycemia increase cardiometabolic risk even when not associated with elevated fasting glucose or HbA1C, suggesting that non-fasting glucose levels should be measured as part of a comprehensive assessment. Evaluating non-fasting glucose may be preferred to HbA1C for identifying blood glucose dysregulation. A 2-hour PPG above 160 mg/dL (8.89 mmol/L) was consistently observed in people with type 2 diabetes despite being considered in “good control,” i.e., with an HbA1C below 7% (Bonora 2006).

Non-fasting glucose provides better insight into overall glycemic control than fasting glucose when insulin resistance is a factor. Fasting glucose may be maintained within the standard or even optimal range due to excess insulin secretion. However, insulin resistance decreases glucose uptake by muscle tissue and increases blood glucose levels over time. This causes further release of insulin until pancreatic insulin production progressively declines, leading to overt diabetes mellitus. Non-fasting glucose should be monitored regularly, as postprandial hyperglycemia can occur years before fasting hyperglycemia (Turan 2019).

One group of NHANES subjects diagnosed with prediabetes or normal glucose tolerance based on fasting glucose and HbA1C actually had type 2 diabetes with a 2-hour PPG of 200 mg/dL (11.1 mmol/L) or above. These individuals had significantly higher rates of hypertriglyceridemia, hypertension, microalbuminuria, and elevated ALT. However, a 1-hour PPG of 155 mg/dL (8.6 mmol/L) or higher may be an early indicator of impaired beta cell function, reduced insulin sensitivity, and a significantly increased risk of type 2 diabetes. Researchers suggest this 1-hour PPG cut-off should be used to identify prediabetes and warrants further investigation, including evaluation of fructosamine and 1,5- anhydroglucitol (1,5-AG) (Bergman 2018, 2020).

Implementation of a 1-hour PPG screen may not only identify those at risk of diabetes but may be a predictor of future complications and mortality. This prudent approach can delay or prevent the onset of diabetes and improve the quality of life for those at risk (Manco 2019).

Even tighter glucose control may be needed to prevent progression to T2DM. A review of NHANES data revealed that a single random blood glucose (RBG) of 100 mg/dL (5.6 mmol/L) or above was more strongly associated with undiagnosed diabetes than traditional risk factors, including hypertension, BMI, cardiovascular disease, or family history of diabetes. Mean RBG was 89.9 mg/dL (5.0 mmol/L) in those with no diabetes, 99.1 mg/dL (5.5 mmol/L) with undiagnosed diabetes, and 156 mg/dL (8.7 mmol/L) in those with undiagnosed diabetes (Bowen 2015).

One study of 63 healthy male subjects observed a mean fasting blood glucose of 80.61 mg/dL (4.47 mmol/L) in those fasting for 7-15 hours and a mean PPG of 85.53 mg/dL (4.75 mmol/L) taken within a range of 10 minutes to 6 hours after their last meal. The highest PPG glucose observed was 117 mg/dL ( 6.49 mmol/L) in this healthy non-diabetic cohort (Razzak 2018).

Postprandial hyperglycemia is a risk factor for CVD and associated events, increased carotid intima-media thickness, carotid artery stenosis, microvascular complications, cognitive dysfunction, cancer, and all-cause mortality. Research suggests that a 1% reduction in non-fasting glucose in those with an HbA1C of 6.5% or higher may reduce the relative risk of myocardial infarction by 14% and the risk of microvascular complications by 37%. A 2-hour PPG of 200 mg/dL (11.1 mmol/L) or greater can significantly increase cancer risk as well (Madsbad 2016).   

A higher 1-2 hour PPG is a significant and stronger predictor of CVD events in subjects with type 2 diabetes. A community-based observational study of non-fasting glucose and CVD risk in a cohort of 7,332 subjects found that higher PPG level was an independent predictor of coronary heart disease and myocardial infarction. Non-fasting glucose levels were categorized as non-diabetic, borderline diabetic, and diabetic, with levels of 113.5, 158.56, and 248.65 mg/dL (6.3, 8.8, and 13.8 mmol/L), respectively, in men. Non-fasting glucose levels in women were 111.71, 156.76, and 263.06 mg/dL (6.2, 8.7, and 14.6 mmol/L), respectively. The association between higher non-fasting glucose and cardiac risk remained unchanged when restricted to within 3 hours of a meal (Imano 2012).

A large prospective study of 34,907 individuals found that cardiovascular mortality increased significantly with a late non-fasting glucose of 105 mg/dL (5.83 mmol/L) or above, especially 115 mg/dL (6.38 mmol/L) or above. All-cause mortality began to significantly increase with a late non-fasting glucose of 95 mg/dL (5.27 mmol/L) or above. Late PPG was defined as 3-7.9 hours after caloric intake (Wang 2022).                 

Diabetes mellitus and thyroid disorders often coexist. Thyroid hormones play an essential role in glucose regulation, ultimately facilitated by the balance of the pancreas, brain, liver, intestine, adipose tissue, and muscle tissue. Thyroid hormone influences glucose metabolism by affecting the pancreas, liver, GI tract, skeletal muscles, adipose tissue, and the central nervous system. It can increase post-meal glucose absorption by increasing GI motility and promoting hepatic glucose release via increased glycogenolysis and gluconeogenesis. Not surprisingly, hyperthyroidism is associated with hyperglycemia and diabetes, though both hyperthyroidism and hypothyroidism can affect insulin resistance (Eom 2022).

Hyperthyroidism can contribute to impaired glucose tolerance via hepatic insulin resistance, while hypothyroidism is associated with peripheral insulin resistance and a decreased rate of peripheral blood flow (Ha 2021). However, a complex association exists between hypothyroidism and hypoglycemia, which can occur when skeletal muscle and adipose tissue gluconeogenesis and hepatic glycogenolysis are impaired. This hypoglycemic effect can be exacerbated by adrenal insufficiency (Eom 2022). Stress can increase blood glucose via the release of cortisol and catecholamines and should be managed accordingly (Ranabir 2011).

Once hormone imbalances have been addressed, non-fasting glucose levels can be improved with lifestyle changes, increased physical activity, and nutrition intervention. Walking after meals and even short intervals of activity throughout the day versus being sedentary improves PPG and insulin levels in those who are overweight or obese (Dunstan 2012).

The type and quantity of macronutrients in a meal influence the timing and amount of glucose released into the bloodstream. The order in which foods are consumed during a meal also affects PPG, as demonstrated in a small study of 11 individuals with type 2 diabetes. When protein and vegetables were consumed first and carbohydrates last, PPG and insulin levels decreased significantly. The 1-hour PPG was 199.4 mg/dL (11.07 mmol/L) when 68 grams of carbohydrate were consumed first versus 125.6 mg/dL (6.97 mmol/L) when the same amount of carbohydrate was consumed last. The 2-hour PPG was 169.2 mg/dL (9.39 mmol/L) versus 140.8 mg/dL (7.8 mmol/L) consuming carbohydrates last (Shukla 2015).

Soluble dietary fiber also helps reduce the postprandial glucose response (Cassidy 2018). Even meal timing may affect PPG. A meta-analysis also suggests that postprandial glucose response is lower for the same meal during the day versus at night (Leung 2020).

References

Bonora, E et al. “Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus.” Diabetologia vol. 49,5 (2006): 846-54. doi:10.1007/s00125-006-0203-x

Bowen, Michael E et al. “Random blood glucose: a robust risk factor for type 2 diabetes.” The Journal of clinical endocrinology and metabolism vol. 100,4 (2015): 1503-10. doi:10.1210/jc.2014-4116

Bergman, Michael et al. “Petition to replace current OGTT criteria for diagnosing prediabetes with the 1-hour post-load plasma glucose ≥ 155 mg/dl (8.6 mmol/L).” Diabetes research and clinical practice vol. 146 (2018): 18-33. doi:10.1016/j.diabres.2018.09.017

Bergman, Michael et al. “Review of methods for detecting glycemic disorders.” Diabetes research and clinical practice vol. 165 (2020): 108233. doi:10.1016/j.diabres.2020.108233

Cassidy, Yvonne M., Emeir M. McSorley, and Philip J. Allsopp. "Effect of soluble dietary fibre on postprandial blood glucose response and its potential as a functional food ingredient." Journal of functional foods (2018).

Dunstan, David W et al. “Breaking up prolonged sitting reduces postprandial glucose and insulin responses.” Diabetes care vol. 35,5 (2012): 976-83. doi:10.2337/dc11-1931

Eom, Young Sil et al. “Links between Thyroid Disorders and Glucose Homeostasis.” Diabetes & metabolism journal vol. 46,2 (2022): 239-256. doi:10.4093/dmj.2022.0013

Ha, Jeonghoon et al. “Association of serum free thyroxine and glucose homeostasis: Korea National Health and Nutrition Examination Survey.” The Korean journal of internal medicine vol. 36,Suppl 1 (2021): S170-S179. doi:10.3904/kjim.2019.160

Imano, Hironori et al. “Non-fasting blood glucose and risk of incident coronary heart disease in middle-aged general population: the Circulatory Risk in Communities Study (CIRCS).” Preventive medicine vol. 55,6 (2012): 603-7. doi:10.1016/j.ypmed.2012.09.013

Leung, Gloria K W et al. “Time of day difference in postprandial glucose and insulin responses: Systematic review and meta-analysis of acute postprandial studies.” Chronobiology international vol. 37,3 (2020): 311-326. doi:10.1080/07420528.2019.1683856

Madsbad, Sten. “Impact of postprandial glucose control on diabetes-related complications: How is the evidence evolving?.” Journal of diabetes and its complications vol. 30,2 (2016): 374-85. doi:10.1016/j.jdiacomp.2015.09.019

Manco, Melania et al. “One hour post-load plasma glucose and 3 year risk of worsening fasting and 2 hour glucose tolerance in the RISC cohort.” Diabetologia vol. 62,3 (2019): 544-548. doi:10.1007/s00125-018-4798-5

Pagana, Kathleen Deska, et al. Mosby's Diagnostic and Laboratory Test Reference. 16th ed., Mosby, 2022.

Ranabir, Salam, and K Reetu. “Stress and hormones.” Indian journal of endocrinology and metabolism vol. 15,1 (2011): 18-22. doi:10.4103/2230-8210.77573

Razzak, Rima Abdul et al. “High-normal blood glucose levels may be associated with decreased spatial perception in young healthy adults.” PloS one vol. 13,6 e0199051. 14 Jun. 2018, doi:10.1371/journal.pone.0199051

Shukla, Alpana P et al. “Food Order Has a Significant Impact on Postprandial Glucose and Insulin Levels.” Diabetes care vol. 38,7 (2015): e98-9. doi:10.2337/dc15-0429

Turan, Elif, Recep Tunç, and Yaşar Turan. "Comparison of fasting and postprandial levels of commonly used biochemical and hematological parameters." Archives of Clinical and Experimental Medicine 4.2 (2019): 66-71.    

Wang, Yutang, and Yan Fang. “Late non-fasting plasma glucose predicts cardiovascular mortality independent of hemoglobin A1c.” Scientific reports vol. 12,1 7778. 11 May. 2022, doi:10.1038/s41598-022-12034-6