HbA_1c and Glycemic Profile, Basal- and Post-Treatment With Miglitol, in an Area With a Mediterranean Diet

HbA_1c is the main indicator in the metabolic control of diabetic patients. It it has been used as a guide in therapeutic intervention studies on type 1 diabetic patients, as in the Diabetes Control and Complications Trial (1), and type 2 diabetic patients, as in the U.K. Prospective Diabetes Study (2). These studies have shown that an HbA_lc decrease is followed by a reduction in the appearance of microvascular and neuropathic complications. The relative impact of fasting glycemia and the glycemic levels at other times of the day on the HbA_lc value is therefore of considerable interest when trying to increase control at the times of the day when this impact is at its highest level. Fasting glycemia has traditionally been considered the main HbA_lc marker (3–6). Recently, however, the validity of this has been questioned (7),and it has even been suggested that the main marker is the postprandial glycemic level (8). On the other hand, postprandial glycemia has been described as being more related to the development of macroangiopathy than fasting glycemia (9,10), which increases interest in its relative contribution to the HbA_lc value.

We carried out an observational, prospective, open, nonrandomized, multicenter study comprised of 3,354 recently diagnosed (at least 3 months) patients with type 2 diabetes. Our aim was to identify the impact of glycemia (fasting and at other times of the day) on the HbA_lc values in a Spanish type 2 diabetic population, with typical Mediterranean nutritional habits, who were being treated with different types of oral antidiabetic drugs, before and after treatment with miglitol, a drug that basically controls postprandial glucose absorption. All patients were treated with diet and either oral antidiabetic drugs (74%) or insulin (19%), and were considered to be noncontrolled according to the European Diabetes Policy Group criteria. Patients were excluded if they were <40 years of age, pregnant or breast-feeding, or had type 1 diabetes or diabetes secondary to pancreatopathy, a BMI <25 kg/m² with clinical decompensation (fasting glycemia >250 mg/dl or ketosis), serum creatinine >150 mmol/l, gastrointestinal disease, and comprehension difficulties that could prevent collaboration.

In each case, we recorded the anthropometric data and basal HbA_lc (high-performance liquid chromatography) together with a capillary glycemia profile at four times (fasting glycemia at 8 h, preprandial glycemia at 14 h, postprandial glycemia at 15 h, and late postprandial glycemia at 19 h) on or around the same day as the HbA_1c reading, for which Glucocard/Glucocard Memory was administered. The patients were specifically asked not to make significant changes to their diet, physical activity, or pharmacological treatment on the day the analyses were taken. Treatment with miglitol was then started, as follows: 1st week 50 mg/day, 2nd week 100 mg/day in two doses, 3rd week 150 mg/day in three doses, and finally a maintenance dose of 300 mg/day in three doses. Analyses of the same characteristics were taken after 12 months of treatment. Linear and multiple regression analyses were applied to the data to examine the relation between the glycemic profile parameters and the HbA_1c at each time. The multiple regression analysis provided the standardized partial regression coefficients of each variable for comparative purposes. A receiver-operating characteristic curve analysis provided the sensitivity, specificity, and positive predictive value of the glycemic profile values for predicting deficient control of the HbA_1c.

In the basal assessment, preprandial glycemia showed significantly lower values than fasting glycemia (166.7 ± 47 vs. 172.6 ± 39.4 SD, P < 0.001), whereas early postprandial glycemic values were significantly higher (209.3 ± 53.1 vs. 172.6 ± 39.4 SD, P < 0.001). Glycemia 5 h after the meal showed no statistically significant difference from fasting glycemia. After 12 months of follow-up, preprandial glycemia showed similar values than fasting glycemia (133. ± 35.9 vs. 136.6 ± 30.4 SD, NS), whereas early postprandial glycemic values were significantly higher (165.8 ± 38.1 vs. 136.6 ± 30.4 SD, P < 0.001). When compared with the basal assessement, both early and late postprandial glycemic levels were significantly reduced at 12 months (209.3 ± 53.1 vs. 165.8 ± 38.1 SD, P < 0.001) and (171.4 ± 47.2 vs. 139.8 ± 31.7 SD, P < 0.001).

Throughout the study, the four parameters of the glycemic profile showed a similar, statistically significant, correlation with the HbA_1c (fasting r = 0.39, preprandial r = 0.37, early postprandial r = 0.34, late postprandial r = 0.33; P < 0.001). The multiple standardized regression coefficients of the glycemic profile with the HbA_lc throughout the study show that fasting glucose was the best HbA_1c marker (standarized regression coefficient 0.21, P < 0.001).

The HbA_lc value at each time was estimated from the multiple linear regression of the capillary glycemia. Predicted HbA_lc values were classified as good control (<7.5%) and bad control (>7.5%), and they were compared with the real HbA_lc analytical values. The sensitivity and specificity analyses again identified fasting glycemia as the best HbA_lc predictor either at baseline or after 12 months (sensitivity 71%, specificity 61%, positive predictive value 61%). The specificity improved with the treatment. This was basically due to the fact that more patients were controlled as the study progressed.

According to the results of our study obtained from a large number of patients, we can conclude that the most extreme glycemic profile values have the least impact on HbA_lc levels, and that fasting glycemia has the most impact. This is probably because it is included in the period that contains more glycemic values equal to the average, and consequently has a greater impact on the global glycemic profile. However, the above does not prevent the association of postprandial glycemic spikes, which could be risk factors for the development of macroangiopathy (10).