Postprandial blood glucose is a strong predictor of HbA1c levels and cardiovascular mortality (1–3). The treatment of postprandial hyperglycemia has become prominent with the recent availability of oral hypoglycemic agents that specifically target the postmeal glucose rise. The aim of this study was to examine the relationship between the fasting blood glucose level and the magnitude of the postprandial glucose rise in type 2 diabetes. Specifically, if the fasting blood glucose level is a determinant of the postprandial glucose excursion, then correction of fasting hyperglycemia should precede attempts at limiting postprandial hyperglycemia.
All results are expressed as means ± SD. A total of 21 subjects (11 men and 10 women) with non-insulin-requiring type 2 diabetes and average glycemic control (HbA1c 7.3 ± 1.4%) were recruited. The subjects were aged 59.4 ± 11.1 years, were moderately obese (BMI 31.3 ± 5.5 kg/m2), and had been diagnosed with diabetes for 8.7 ± 8.8 years. Two of the patients were treated with diet and exercise alone, and the remaining 19 were taking one or two oral hypoglycemic agents for diabetes control (n = 13 for sulfonylureas, n = 6 for metformin, and n = 3 for thiazolidinediones).
Subjects were admitted overnight to the General Clinical Research Center for stabilization. At 2200, subjects ate a 5-kcal/kg American Diabetes Association (ADA) snack and then fasted until morning. The volunteers’ diabetes medications were withheld on the morning of the study. Between 0800 and 0815, the subjects ate a standardized 8-kcal/kg ADA breakfast. The breakfast was prepared in the metabolic kitchen and consisted of an English muffin, bacon, a scrambled egg, and a noncaffeinated beverage. Blood was drawn for analysis at −0.05, 0, 0.5, 1, 2, 3, and 4 h relative to the test meal. Plasma glucose was analyzed using the glucose oxidase method. The glucose excursion at each time point was expressed as the change from the fasting plasma glucose level. Area under the curve (AUC) for the glucose excursion was calculated using the linear trapezoidal rule. The relationship between the fasting plasma glucose level and the postprandial glucose excursions was analyzed using linear regression.
The average fasting plasma glucose was 7.4 ± 2.4 mmol/l (135 ± 43 mg/dl), with a range of 4.3–14.3 mmol/l (78–259 mg/dl). The fasting plasma glucose level was strongly correlated with the 30-min (r = 0.86, P < 0.001), 1-h (r = 0.9, P < 0.001), 2-h (r = 0.89, P < 0.001), 3-h (r = 0.84, P < 0.001), and 4-h (r = 0.89, P < 0.001) absolute postmeal plasma glucose levels and with the integrated AUC (r = 0.93, P < 0.001) for the absolute postmeal plasma glucose levels (not baseline corrected). Furthermore, the fasting plasma glucose level had a strong positive correlation with the 1-h (r = 0.55, P = 0.01), 2-h (r = 0.7, P < 0.001), 3-h (r = 0.59, P = 0.005), and 4-h (r = 0.6, P = 0.004) glucose excursions from baseline. Overall, the correlation between the fasting plasma glucose and the AUC for the postprandial glucose excursion was highly significant (r = 0.71, P < 0.001).
We conclude that the fasting plasma glucose level predicts the degree of postmeal hyperglycemia and the magnitude of the postmeal glucose excursion from baseline. It is not surprising that the uncorrected postmeal glucose levels are strongly related to the premeal baseline glucose concentration. However, the observation that the prandial glycemic excursion from baseline is predicted by the fasting plasma glucose level is more relevant to decisions regarding diabetes therapy. The premeal glucose concentration accounts for 50% of the variability in the postmeal glucose rise in subjects with non-insulin-requiring diabetes. The remaining variability in glycemic responses after a standardized meal could be explained by relatively fixed factors, such as the renal threshold for glycosuria, endogenous insulin reserves, and the gastric emptying time.
The strength of this study is that participants had a wide range of fasting blood glucose levels with HbA1c values close to targets recommended by the ADA. The subjects enrolled in this study were taking standard oral hypoglycemic agents, including sulfonylureas, metformin, and thiazolidinediones, until the morning of the study and were tested after a standardized meal. Our results extend a recently published study that employed nonstandardized meals and variable medications (4). In that study, the investigators found a weaker correlation between the fasting and absolute postbreakfast glucose levels (r = 0.64, P < 0.01). A small number of studies have shown equivalent reductions in HbA1c regardless of whether treatments were used to specifically correct fasting or postprandial hyperglycemia (5–7). The outcomes of these studies suggest a carry over beneficial effect on premeal glucose levels when postmeal and nocturnal hyperglycemia is reduced with meal-based therapies. To date, no published studies have compared the glycemic response to a standardized meal in subjects with type 2 diabetes where each subject was studied at varying levels of fasting glucose.
The importance of the current study to health care providers is that it shows that the postmeal glucose excursion is directly related to overnight fasting blood glucose concentration. Data from this study suggest that, in order to improve overall glycemic control, fasting hyperglycemia should be corrected before starting specific treatment for postprandial hyperglycemia in subjects with non-insulin-requiring type 2 diabetes. Because correction of fasting hyperglycemia may be easier to achieve (in some patients) than correction of postprandial hyperglycemia, this strategy may result in improved overall glycemic control at reduced medication cost.
References
Address correspondence to Mary F. Carroll, MD, University of New Mexico Health Sciences Center, Department of Internal Medicine, 5-ACC, 2211 Lomas Blvd. NE, Albuquerque, NM 87131. E-mail: mcarroll@salud.unm.edu.
This research was supported by the University of New Mexico General Clinical Research Center (NIH NCCR GCRC Grant no. 5 Mo1-RR00997)