The study population included 2866 participants, with an average age of 58.6 years, 43.3% men and 56.7% women. Among the participants 31.8% were born in Israel. According to their computerized medical records 31.2% were smokers, 78% had hyperlipidemia and 63.7% had hypertension. In the study population 89.2% used ACE inhibitors or ARB’s, 93.8% used Statins and 42.5% used Insulin. Each participant had an average of 20.9 HbA1C measures in their computerized medical record during the 11 years of follow up. The mean HbA1C value of the study population was 7.8%. We found 632 patients (22%) with a high variability, considered “HbA1C variability group”, whereas 2234 (78%) who had a low variability of HbA1C were called “No HbA1C variability group”.
Table 1 shows baseline demographic and clinical characteristics of the two study groups. In both groups, patients had more than 20 measures of HbA1C during the study period, without significant difference. In the “HbA1C variability” group (“variability group”) there was a statistically significant higher percentage of smokers and BMI ≥ 30 as opposed to the “No HbA1C variability” group. There was no statistically significant difference in the percentage of hypertension, hyperlipidemia and there was a borderline significance in the percentage of ischemic heart disease. We also compared the number of visits in diabetic specialized clinics as an indication of the disease severity. In “Clalit” health services most diabetic patients are treated in primary care clinics by family physicians and nurses and only patients with a more complicated disease are referred to diabetic clinics. In the “HbA1C variability” group 28.6% had more than 5 visits in the diabetes clinic during the study follow up, as opposed to 22.9% in the “No HbA1C variability” group (p = 0.003).
Table 2 shows the differences in the medications used by participants. In the “HbA1C variability group” we found a statistically significant higher use of insulin and ACE inhibitors, compared to the “no variability” group. There was no difference in the use of diabetic oral treatment or the use of statins, which was high in both groups.
Figure 1 shows the percentage of participants with balanced laboratory tests (the mean of all results during the study period): fasting glucose, LDL and HDL cholesterol and triglycerides. In all categories the percentage of participants with balanced laboratory results was lower in the “HbA1C variability group all the differences between the groups were statistically significant, p < 0.001.
We subdivided HbA1C into four categories (Fig. 2) and found that in the “HbA1C variability group” 79.8% were with a mean HbA1C above 8% while in the “No HbA1C variability group” 76.4% were with mean HbA1C lower than 7.9%, the difference between the groups was statistically significant, p < 0.001.
Figure 3 displays the frequency of HbA1c variability at different values of HbA1c represented as a trend, showing that the highest frequency of variability was between values of 8.1–8.5 of HbA1c.
Table 3 shows the mean laboratory results during the study period—comparing the two groups: All blood tests were significantly worse in the variability group: glucose, LDL cholesterol, triglycerides, HDL cholesterol, microalbuminuria/creatinine ratio and HbA1C (mean and median) (all p < 0.001).
In the multivariate analysis we included variables with clinical importance or statistical significance (Table 4). The analysis shows that HbA1C variability was associated with insulin usage (OR = 4.1, p < 0.001), younger age (OR = 0.939, p < 0.001) and Ischemic heart disease (OR = 1.258, p = 0.03). HbA1C variability was also associated with BMI ≥ 30, almost statistically significant (OR = 1.206, p = 0.06). Gender was statistically insignificant.