Type 2 diabetes is a progressive disease that requires ongoing increases in doses and complexity of hypoglycemic pharmacotherapy [
Although most studies have shown glycemic reduction to be associated with a significant improvement in diabetes control [
This study therefore used routinely collected data from a clinical information system for diabetes at Isfahan Endocrine and Metabolism Research Center, Iran, over a mean 8.4 year to describe patterns of long-term glycemic change in patients with type 2 diabetes receiving routine care and identifies factors associated with glycemic change.
Our investigation was conducted in Isfahan, a very large area situated in central Iran, located on 1,590meter height above sea level, between latitudes 30 and 34 degrees north of the equator and longitude 49–55 degrees east, with a population of almost four and half million (4,559,256 in 2006 (men 2,335,399, women 2,223,857)) and a high proportion of young people. The total area is 107,029 Km2. The climate is dry temperate and quite wide temperature differences between the summer and the winter with a mean daily temperature of 3.0°C in January and February, 29.0°C in July and August, and 16.5°C in September and October. The population structure and socioeconomic status of Isfahan are similar to the rest of the country. Private physicians and hospitals, district health centers and government, and university hospitals and clinics provide the health services. 15 endocrinologists and 3 diabetes center serve the study area. Residency in remote and mountain areas and economical status may affect accessibility to the endocrinological expertise.
The recruitment methods and examination procedures of the Isfahan Endocrine and Metabolism Research Center out patient clinics have been described before [
All patients were referred for nutritional and weight management program after the start of the therapy by qualified nutritionists to evaluate the patient and if necessary recommend weight management program. A computerized patient registry provided data on patient characteristics, medications, and laboratory values.
Between 1992 and 2010, a total of 14,243 patients with type 1 and type 2 diabetes were registered in the system. Women with diabetes diagnosed only during pregnancy were excluded. However, this study uses data only for 4,582 (1,725 (37.6%) men and 2,857 (62.4%) women) patients with type 2 diabetes who had at least one subsequent review since registration at baseline and for whom complete data were available. Attendees at the follow-up visit did not differ significantly from nonattendees regarding baseline GHb and high-density lipoprotein (HDL) cholesterol. However, nonattendees who were older (52.8 year versus 49.3 year,
Predictors of GHb (measured by spectrophotometer) change were assessed using the following data from the patient’s registration consultation: gender, age at diagnosis, age, educational level, duration of diabetes (the time between diagnosis and the baseline examination), BMI (weight/height2 (kg/m2)), smoking status (never, current), FPG, serum creatinine, triglyceride, cholesterol, HDL (measured using standardized procedures), LDL (calculated by the Friedwald equation [
Height and weight were measured with subjects in light clothes and without shoes using standard apparatus. Weight was measured to the nearest 0.1 kg on a calibrated beam scale. Height was measured to the nearest 0.5 cm with a measuring tape. Height was assessed at baseline only. A physician measured the systolic and diastolic BPs of seated participants after subjects had been seated for 10 minutes by using a mercury sphygmomanometer and standard techniques. All clinical measurements at baseline and follow-ups were made using the same standardized protocol.
The study protocol was approved by the Institutional Review Board of Isfahan University of Medical Sciences, Iran.
GHb is recognized as the measure of glycemic control. Percent of GHb change was determined by taking the difference between the baseline and last measured GHb and divided that by patient’s baseline GHb. A GHb level of <7% was used to indicate optimal glycemic control; this benchmark was established by the American Diabetes Association (ADA) as the recommended target [
Statistical methods used included the Student’s
Patients had mean (SD) duration of diabetes 5.0 (5.1) years and mean age of 49.3 (9.6) years at baseline. The average time of follow-up was 8.4 (4.2) years (range 1–18 year). The average follow-up visits were 20.9 (18.0) times (range 2–114 visits). 22.7% of men and 1.6% of women were smoking at the baseline. The age-adjusted mean (SD) BMI was 26.8 (3.9) kg/m2 in men and 29.1 (4.5) in women.
Population characteristics at baseline and last follow-up visit are presented in Table
Characteristics of 4,852 patients with type 2 diabetes mellitus at baseline and last follow-up visit.
Characteristics | Mean (SE) | Difference (95% CI) | |
---|---|---|---|
Baseline | Last follow-up | ||
Age (yr) | 49.3 (0.17) | 56.2 (0.19) | −7.1 (−7.25, −6.91)* |
Age at diagnosis (yr) | 44.3 (0.14) | — | — |
Duration of diabetes (yr) | 5.0 (0.08) | — | — |
Follow-up duration (yr) | — | 8.4 (0.06) | — |
Number of follow-up visit | — | 20.9 (0.27) | — |
GHb change (%) | — | 5.7 (0.36) | — |
Weight (kg) | 71.7 (0.18) | 73.2 (0.18) | −1.5 (−1.69, −1.28)* |
Height (cm) | 159.4 (0.14) | — | — |
BMI (kg/m2) | 28.2 (0.07) | 28.8 (0.07) | −0.6 (−0.69, −0.52)* |
Systolic BP (mmHg) | 122.4 (0.26) | 123.0 (0.28) | −0.6 (−1.11, 0.06) |
Diastolic BP (mmHg) | 75.0 (0.18) | 77.4 (0.16) | −2.4 (−2.85, −2.01)* |
Fasting plasma glucose (mg/dL) | 184.6 (1.02) | 155.7 (0.87) | 28.9 (26.57, 31.23)* |
GHb (%) | 8.7 (0.03) | 7.9 (0.03) | 0.8 (0.74, 0.87)* |
Creatinine ( |
0.90 (0.009) | 1.03 (0.007) | −0.13 (−0.15, −0.11)* |
Triglyceride (mg/dL) | 218.7 (2.19) | 173.1 (1.53) | 45.6 (41.58, 49.50)* |
Cholesterol (mg/dL) | 213.9 (0.71) | 185.3 (0.60) | 28.6 (27.17, 30.13)* |
High-density lipoprotein (mg/dL) | 44.9 (0.22) | 44.8 (0.23) | 0.1 (−0.40, 0.54) |
Low-density lipoprotein (mg/dL) | 128.3 (0.84) | 104.4 (0.64) | 23.9 (22.08, 25.70)* |
Gender % | |||
Men | 37.6 | — | — |
Women | 62.4 | — | — |
Therapeutic regimen % | |||
Diet | 20.9 | 11.4 | 9.5 (8.06, 11.10)* |
Oral agent | 67.7 | 48.7 | 19.0 (17.1, 21.00)* |
Insulin | 8.3 | 13.8 | −5.5 (−6.80, −4.24)* |
Insulin and oral agent | 3.1 | 26.1 | −23.0 (−24.50, −21.70)* |
Education % | |||
Less than high school | 58.7 | — | — |
High school | 30.0 | — | — |
College graduate | 11.3 | — | — |
Smoking % | |||
Nonsmoker | 90.4 | — | — |
Current smoker | 9.6 | — | — |
Glycated hemoglobin % | |||
<7% | 25.4 | 35.6 | −10.2 (−12.00, −8.28)* |
7%–9.5% | 43.4 | 46.4 | −3.0 (−5.07, −0.10)* |
>9.5% | 31.2 | 18.0 | 13.2 (11.40, 14.90)* |
Weight category % | |||
Normal weight (BMI < 25.0 kg/m2) | 23.4 | 19.9 | 3.5 (1.79, 5.22)* |
Overweight (BMI 25–29.9 kg/m2) | 45.7 | 44.1 | 1.6 (−0.42, 3.72) |
Obese (BMI ≥ 30.0 kg/m2) | 30.9 | 36.0 | −5.1 (−7.12, −3.19)* |
The mean (SD) GHb was 8.7% (2.3) at baseline and 7.9% (1.9) at the study end and decreased by mean of 0.8% (95% confidence interval (CI) 0.74, 0.87) over mean 8.4 years (
On the other hand, of the 1,163 patients who had GHb <7.0% at baseline 418 (35.9%) subsequently worsen to GHb >7.0%. Of the 1,987 patients with GHb 7.0%–9.5% at initial registration, 263 (13.2%) subsequently progress to GHb >9.5%. This was lower than the rates of worsening seen for GHb <7.0%.
Table
Age-adjusted comparison of baseline variables by glycemic control group in 4,852 patients with type 2 diabetes mellitus.
Characteristics | Mean (SE) | ||
---|---|---|---|
GHb < 7.0% | GHb 7.0%–9.5% | GHb ≥ 9.5% | |
Number (%) | 1164 (25.4) | 1988 (43.4) | 1430 (31.2) |
Age (yr) | 49.5 (0.24) | 49.3 (0.21) | 48.7 (0.33) |
follow-up (yr) | 7.6 (0.10) | 8.8 (0.09) | 9.1 (0.15)*** |
Number of follow-up visit | 19.9 (0.44) | 22.7 (0.38) | 18.3 (0.62)*** |
Duration of diabetes (year) | 4.2 (0.12) | 5.3 (0.10) | 5.7 (0.17)*** |
Weight (kg) | 72.3 (0.30) | 71.4 (0.27) | 71.0 (0.43)* |
Height (cm) | 159.9 (0.23) | 159.1 (0.20) | 159.2 (0.32)* |
BMI (kg/m2) | 28.3 (0.11) | 28.2 (0.10) | 28.1 (0.16) |
Systolic BP (mmHg) | 121.6 (0.41) | 122.7 (0.36) | 123.2 (0.57)* |
Diastolic BP (mmHg) | 74.5 (0.30) | 75.2 (0.26) | 75.4 (0.43) |
Fasting blood glucose (mg/dL) | 167.1 (1.66) | 187.1 (1.46) | 213.1 (2.34)*** |
GHb (%) | 7.7 (0.05) | 8.9 (0.05) | 10.2 (0.07)*** |
Creatinine ( |
0.91 (0.02) | 0.90 (0.01) | 0.90 (0.02) |
Triglyceride (mg/dL) | 209.4 (3.67) | 219.7 (3.20) | 234.8 (5.15)*** |
Cholesterol (mg/dL) | 209.6 (1.19) | 214.8 (1.04) | 220.1 (1.67)*** |
GHb change (%) | −11.6 (0.60) | 4.1 (0.46) | 22.0 (0.54)*** |
HDL (mg/dL) | 44.7 (0.37) | 45.0 (0.32) | 45.2 (0.60) |
LDL (mg/dL) | 125.0 (1.37) | 129.8 (1.20) | 132.0 (2.28)** |
Gender % | |||
Men | 39.9 | 36.3 | 36.8 |
Women | 60.1 | 63.7 | 63.2 |
Therapeutic regimen % | |||
Diet | 28.2 | 17.7 | 15.0*** |
Oral agent | 64.6 | 69.8 | 68.4*** |
Insulin | 7.2 | 12.4 | 16.6*** |
Education % | |||
Less than high school | 51.7 | 61.8 | 64.9*** |
High school | 32.3 | 28.2 | 29.9*** |
College graduate | 16.0 | 10.0 | 5.2*** |
Smokers % | 9.1 | 9.9 | 9.9 |
Weight category % | |||
Normal weight (BMI < 25 kg/m2) | 21.8 | 23.0 | 26.9* |
Overweight (BMI 25–29.9 kg/m2) | 48.1 | 45.7 | 41.1* |
Obese (BMI > 30 kg/m2) | 30.1 | 31.3 | 32.0* |
Age-adjusted means were calculated using general linear models. Comparison across all three groups. *
The average 8.4-year GHb change for the entire population was 5.7 (95% CI: 5.0, 6.4) percentage points. The age-adjusted mean change in GHb varied by level of baseline GHb (Figure
Glycated hemoglobin (GHb) change after 8.4-year follow-up by GHb category.
Table
Age-adjusted associations of patient characteristics at baseline with percent of glycated hemoglobin (GHb) change at average 8.4 year, Isfahan, Iran.
Variables | Age-adjusted mean (SE) percent GHb change | |||
---|---|---|---|---|
Entire group | GHb < 7.0% | GHb 7.0%–9.5% | GHb > 9.5% | |
Number (%) | 4582 (100.0) | 1164 (25.4) | 1988 (43.4) | 1430 (31.2) |
Gender | ||||
Men | 7.1 (1.59) | −11.2 (1.01) | 5.7 (0.77) | 22.7 (0.87)* |
Women | 4.9 (0.45) | −11.7 (0.74) | 3.2 (0.57) | 21.6 (0.69)* |
Age at registration (yr) | ||||
|
3.8 (0.92) | −11.5 (1.52) | 3.5 (1.23) | 19.6 (1.52)* |
40–49 | 4.1 (0.58) | −11.7 (0.95) | 2.5 (0.76) | 21.1 (0.91)* |
50–59 | 6.7 (0.60) | −11.2 (1.04) | 4.9 (0.77) | 22.7 (0.89)* |
60–69 | 9.2 (1.10) | −13.8 (2.14) | 6.7 (1.39) | 24.5 (1.55)* |
|
10.3 (2.02) | −7.2 (3.51) | 7.4 (2.51) | 25.2 (2.82)* |
Age at diagnosis (yr) | ||||
|
4.5 (1.59) | −13.8 (2.90) | 1.9 (2.14) | 19.3 (2.31)* |
30–59 | 5.5 (0.38) | −11.3 (0.63) | 3.7 (0.49) | 22.0 (0.58)* |
|
9.1 (1.54) | −15.3 (2.69) | 11.5 (1.92) | 23.9 (2.33)* |
Duration of diabetes (yr) | ||||
|
4.6 (0.47) | −11.4 (0.72) | 4.9 (0.60) | 22.6 (0.78)* |
5–7 | 6.3 (0.83) | −11.7 (1.50) | 3.0 (1.04) | 21.5 (1.18)* |
8–11 | 7.4 (1.07) | −14.6 (2.15) | 2.8 (1.35) | 22.5 (1.44)* |
|
9.3 (1.03) | −10.1 (2.57) | 2.9 (1.40) | 20.3 (1.33)* |
Fasting blood glucose (mg/dL) | ||||
|
0.9 (1.70) | −9.2 (2.02) | 2.5 (2.59) | 26.5 (3.45)* |
100–125 | −0.2 (1.00) | −12.2 (1.25) | 5.5 (1.37) | 26.7 (2.41)* |
|
7.0 (0.39) | −11.6 (0.74) | 3.9 (0.50) | 21.5 (0.56)* |
Systolic BP (mmHg) | ||||
|
5.6 (0.40) | −10.7 (0.65) | 4.0 (0.52) | 21.6 (0.61)* |
140–159 | 7.2 (0.97) | −15.1 (1.82) | 5.3 (1.19) | 23.5 (1.42)* |
|
5.7 (1.57) | −19.4 (2.85) | 2.4 (1.86) | 23.4 (2.09)* |
Diastolic BP (mmHg) | ||||
|
4.6 (0.67) | −9.9 (1.05) | 5.5 (0.93) | 18.6 (1.07)* |
70–90 | 6.3 (0.48) | −10.9 (0.83) | 3.9 (0.60) | 22.8 (0.72)* |
|
5.4 (0.89) | −16.7 (1.51) | 3.3 (1.10) | 23.7 (1.26)* |
Therapeutic regimen | ||||
Diet alone | 2.8 (0.79) | −10.0 (1.14) | 6.8 (1.04) | 20.9 (1.72)* |
Oral agent | 6.5 (0.43) | −11.6 (0.75) | 3.3 (0.54) | 22.9 (0.62)* |
Insulin | 6.8 (1.07) | −17.5 (2.23) | 3.5 (1.46) | 18.9 (1.37)* |
Education | ||||
Less than high school | 7.1 (0.48) | −13.9 (0.89) | 3.9 (0.59) | 22.6 (0.66)* |
High school | 2.7 (0.66) | −11.4 (1.04) | 3.6 (0.90) | 18.8 (1.16)* |
College graduate | 6.3 (0.99) | −6.2 (1.33) | 7.4 (1.27) | 28.0 (1.83)* |
Smoking | ||||
Nonsmoker | 7.3 (0.48) | −13.7 (0.91) | 4.2 (0.60) | 22.7 (0.68)* |
Current-smoker | 8.3 (1.47) | −10.4 (3.08) | 3.5 (2.01) | 21.3 (2.04)* |
Age-adjusted means were calculated using general linear models. Category definitions are based on ADA and HEDIS cut-offs [
Percent of GHb change was slightly positively correlated with age (
The percent of GHb change was also analyzed with multivariate regression analysis. Age (
The strength and statistical significance of the relationship of baseline characteristics to GHb >9.5% were also tested by multiple logistic regression. Findings of this analysis show that younger age (OR 0.99, 95% CI: 0.98, 0.99), higher FPG (OR 1.002, 95% CI: 1.001, 1.004), GHb (OR 1.35, 95% CI: 1.30, 1.41) at baseline, and higher follow-up duration (OR 1.10, 95% CI: 1.07, 1.13) significantly increased and treatment with oral agent (OR 0.57, 95% CI: 0.37, 0.88) and with insulin (OR 0.48, 95% CI: 0.29, 0.79), higher education (OR 0.48, 95% CI: 0.33, 0.70), and number of follow-up visits (OR 0.97, 95% CI: 0.96, 0.97) significantly decreased the risk of having GHb values >9.5% compared with GHb
Findings of logistic regression analysis to determine predictors of poor glycemic control in 4,852 patients with type 2 diabetes mellitus.
Characteristics | OR (95% CI) |
---|---|
Age (yr) | 0.99 (0.98, 0.99)* |
BMI (kg/m2) | 1.02 (0.99, 1.04) |
Systolic BP (mmHg) | 1.00 (0.99, 1.04) |
Fasting plasma glucose (mg/dL) | 1.002 (1.001, 1.004)*** |
GHb (%) | 1.35 (1.30, 1.41)*** |
Duration of diabetes (yr) | 1.01 (0.99, 1.03) |
follow-up (yr) | 1.10 (1.07, 1.13)*** |
Number of follow-up visit | 0.97 (0.96, 0.97)** |
Creatinine ( |
0.96(0.83, 1.12) |
Triglyceride (mg/dL) | 1.00 (1.00, 1.001) |
Cholesterol (mg/dL) | 1.00 (0.99, 1.002) |
Gender | |
Men | 1.00 |
Women | 1.02 (0.85, 1.24) |
Therapeutic regimen | |
Diet | 1.00 |
Oral agent | 0.57 (0.37, 0.88)* |
Insulin | 0.48 (0.29, 0.79)** |
Education | |
Less than high school | 1.00 |
High school | 1.12 (0.91, 1.37) |
College graduate | 0.48 (0.33, 0.70)*** |
Poor glycemic control is defined as a GHb level of >9.5% based on Health Care Effectiveness Data and Information Set (HEDIS) [
In this large cohort study of patients with type 2 diabetes who received routine care we observed that 35.6% of patients with type 2 diabetes achieved the clinical goals for diabetes during average 8.4 years. These findings suggest that a considerable proportion of patients with type 2 diabetes in Isfahan, Iran, are not well controlled. The estimate of poor GHb control, defined as GHb >9.5%, in our study cohort was 31.2% at baseline and 18.0% at the study end. This is much lower than 32.7% reported by McBean et al. among American elderly managed care beneficiaries [
Although interventional studies have shown that GHb reduction produces improvement in microvascular complications due to this disease, few cohort studies describe the clinical course of GHb changes after diagnosis of type 2 diabetes in patients receiving routine care [
We found that BMI was not predictive of poor glycemic control. Obesity was not related to poor glycemic control, probably because patients with type 2 diabetes, including patients in good glycemic control who have gained weight and patients with poor glycemic control who have lost weight due to disease process. A study among public-hospital patients with type 2 diabetes demonstrated no relationship between BMI and degree of glycemic control [
The reasons for relationship between age, gender, and GHb level are unclear. Younger age was associated with poorer glycemic control because their duration of diabetes was greater than those diagnosed at older ages. Longer duration of diabetes is known to be associated with poor glycemic control [
Our analysis also showed that treatment with oral agent and insulin at baseline was associated with a better glycemic control. This is expected, because patients with more sever hyperglycemia are more likely to have been prescribed oral agent and/or insulin compared with patients with milder hyperglycemia.
We found that long-term GHb change was an increase with number of follow-up visits. These patients are more likely to consult a physician on a regular basis and, therefore, are more likely to be offered appropriate treatment.
Our findings are consistent with previously published findings that education was associated with better glycemic control [
The strengths of this study include the large size, long-term follow-up, sample consisting of both men and women of a wide age range, and detailed information on potential confounding factors. Selection and information bias were unlikely because of the prospective design and high rate of follow-up. These real-life data reflect actual treatment pattern and allow for observation of patients over time. Several limitations of this study should be considered when interpreting our results. We used patient GHb only at the baseline and at last follow-up visits. We could not rule out the possibility of residual confounding because of unmeasured or inaccurately measured covariates. Our study was limited by possible selection bias by restricting the study to patients alive during the whole study period. The possibility exists that the people with diabetes who had the most severe disease or who were in the least good control died before the end of the study and were not included in the sample. This may result in overly optimistic estimates of glycemic control. Loses to follow-up are the major source of bias in longitudinal studies. The slight difference between attendees and nonattendees with regard to age, BP, lipid profile, FPG, duration of diabetes, and BMI might restrict generalizability of our findings. This is the first report of diabetes outcomes measures in routine care in a developing country and provides new data from Iran which has been underrepresented in past studies.
In conclusion, this study highlights the difficult challenges physicians face when treating their patients with type 2 diabetes, such as the low frequency of achieving a clinically significant amount of GHb reduction. Although this population of Iranian type 2 diabetes had small glycemic change over mean 8.4 years and more than 64.4% of the patients have GHb values higher than 7.0%, type 2 diabetes in Isfahan, Iran received an acceptable level of treatment for hyperglycemia, though not optimal.
The authors declared no conflict of interests.
The authors are grateful to Mr. Majid Abyar for computer technical assistance. This study was supported partially by a grant from the Isfahan Endocrine and Metabolism Research Center