Introduction

The estimated global prevalence of diabetes by the IDF had increased from 151 million adults in year 2000 to 451 million (8.4%) in 2017 [1] and expected to reach 693 million (9.9%) in 2045 [1]. About 50% of the diabetic people do not know that they have diabetes [1]. According to the IDF diabetes Atlas, 9th edition, 2019, three out of each four diabetics (352 million people) had been recorded to be in the working age group and in 2019, the highest age-standardized prevalence of diabetes was 12.2%, expected to reach 13.3%, and 13.9% in 2030 and 2045; respectively in Middle East and North Africa (MENA) region [2].

The prevalence of diabetes was estimated to be 11.4% (4.5 million) in Iran in the fourth round of the periodic National Survey of Risk Factors for Non-communicable Diseases project in 2011, and more than one quarter of them were not previously detected [3]. By 2030, 9.2 million Iranians will have diabetes [4].

Type 2 diabetes (T2DM) accounts for more than 85% of the clinically registered Iranian diabetic patients [5]. This chronic progressive disease, especially if not well managed, has substantial consequences, including microvascular and macrovascular complications leading to repeated hospitalization and premature death. Globally, diabetes is one of the top 10 causes of death, and is associated with 11.3% of global deaths from all causes among the 20–79 years age group. A recent systematic review and meta-analysis showed that the estimated prevalence of diabetic foot ulcer, cardiovascular disease, retinopathy, neuropathy and nephropathy in Iranian diabetics were 3%, 33%, 36%, 38%, and 43%, respectively [6]. It has also been observed that most type 2 diabetics have one or more comorbidities influencing the self-care of diabetes and its progression, which needs to be considered in their care [7].

More than 66% of type 2 diabetic patients had HbA1c above 7% in a recent study conducted in three Iranian provinces [8]. In a study on 348 diabetic patients, poor glycemic control, low medication adherence, and inadequate self-care activities were observed with mean HbA1c of 8.39 ± 2.03 and 33% of patients had levels higher than 9% [9].

The high prevalence of diabetes and its complications imposes a significant burden on health care resources and costs and the main step to avoid these complications is to achieve glycemic control. Self-care is an essential factor for diabetes control [10] and self-care training has shown positive impacts on both quality of life and control among women [11]. The economic burden of diabetes in Iran is predicted to increase markedly in the coming decades [4]. According to findings of a qualitative study in Iran, removing perceived self-care barriers, improving medical welfare and social support [10] could help in better glycemic control. Identification and implementation of effective plans to prevent and manage diabetes should be considered as a public health priority.

The quality of care for diabetes in Iran seems to be improving. Between 2005 and 2011, diabetes awareness improved and the rate of cases with undiagnosed diabetes dropped nearly 50% from 45.7% to 24.7% [3]. Besides, a substantial increase in the use of anti-hyperglycemic [12, 13], anti-hyperlipidemic and antihypertensive medications have been reported through 2011[12]; however, by then, the utilization of diabetes medicines was still relatively low despite the affordability of essential diabetes medications [13]. The current understanding of the quality of care is incomplete.

Therefore, in this comprehensive population-based study, we planned to investigate the current status of diabetes care in a representative sample of Iranian adults with type 2 diabetes at the national level. Treatment goal achievements in type 2 diabetics, diabetes care service utilization, and prevalence of diabetes complications and psychosocial effects of diabetes were assessed.

Materials and methods

The DiaCare was a nationwide observational, population-based survey to determine diabetes care status among diabetic type 2 subjects in Iran. This study was conducted between 2018 and 2020 in all thirty- one provinces of Iran.

Study population and sampling framework

The target population contained diabetic subjects aged 35–75 years in urban and rural areas across the country.

The inclusion criteria were diagnosis of type 2 diabetes according to ADA recommendations [14] at least 3 months before study entry in individuals aged between 35 and 75 years, able to understand and complete questionnaires, and signed patient informed consent form. While individuals suffering from other types of diabetes (e.g. gestational diabetes and type 1 diabetes), people with obvious cognitive impairment, non-Iranian households, current temporary insulin therapy, and absence at the time of the interview, were not included.

We used different sampling methods for selecting primary sampling units (clusters) like as systematic random sampling, stratify sampling and also cluster sampling. Sample size was equal subjects in each province, and divided between urban/ rural areas using the proportion to the population of areas in the provinces.

In order to calculate the number of statistical units in each cluster we used the following equation:

$$\mathrm{Deff}=1\hspace{0.17em}+\hspace{0.17em}\mathrm{\rho cs }(\mathrm{M}\hspace{0.17em}-\hspace{0.17em}1)$$

Where

Deff:

Design Effect

M:

optimal size of each cluster = 12 = [0.03 × 4] (the proportion of the expenses to reach every statistical unit to expenses of data gathering for every member of the cluster was estimated to be 4)

ρ cs:

interclass correlation coefficient estimated to be 0.03 based on experts' opinion

So, by calculation

$$\mathrm{Deff}= 1+ 0.03\;(12-1) = 1.33$$

The sample size of the study was described based on the equation:

$$\mathrm{Ncs }=\mathrm{ Nsrs }\times \mathrm{ Deff}$$
N cs:

the real sample size for cluster sampling

N srs:

the determined sample size for simple random sampling

Deff:

Design Effect = 1.33

Sampling range:

total number of inhabitants in a region / Number of clusters in a region

About 384 participants were needed for estimation of 0.25 proportions in an unlimited population of each province with an absolute error of 5% and a confidence interval of 95% using a cluster simple sampling method with a design effect of 1.33 [15].

With a sample size of 384 subjects and a loss rate (f) of 10%, the sample size was 432 subjects in each province (or 36 clusters of 12 subjects from 4 age and sex groups), 3 subjects in each age and sex groups, a total of 13,392 subjects at national level in 31 provinces. This was the maximum sample size that helped to achieve a good estimate of the primary aims of the study.

Clusters were the primary sampling units (PSU) and to find the first household in each cluster, a systematic random sampling approach was used. A cumulative list of households within each region was provided with unique ten-digit postal codes.

The sampling interval was determined by dividing the total number of households within each region by the number of clusters in the region. The first household of the primary cluster was identified through randomly selecting a number between 1 to a much less than or equal to the sampling interval. The primary household of the second cluster was located through adding the sampling interval to the random number. For next clusters (cluster three, cluster 4, cluster 5, and so on.), identified the primary household via adding the sampling range to the running total of adding the sampling interval to the random number.

The right side neighbors (clockwise direction) of the first household in every cluster had been decided on as the rest households of that cluster. Households that were not Iranian or no longer present at the time of interview for 3 times of referral were excluded from the survey. In each household, the person(s) with type 2 diabetes identified. If more than one person had diabetes in a household, the participant was selected through a predefined random method. Stratification was conducted on selecting 3 equal age and sex strata in each cluster as mentioned previously.

The study protocol was reviewed and approved by the Ethics Committee of the Endocrinology and Metabolism Research Institute (EMRI) of the Tehran University of Medical Sciences (TUMS) (Ethic Code: IR.TUMS.EMRI.REC.1396.00165).

Measurements

Questionnaire

After finding eligible participants, the aim of the study were described and they were invited to the nearest health center and written informed consent was gained from members. Data were gathered by an interviewer in the form of a questionnaire. The final questionnaire results were obtained from several questionnaires with formerly assessed validity and reliability [16,17,18]. The whole process was supervised and managed with the aid of a group of healthcare specialists.

The final questionnaire consists 105 questions in 9 sections including the following:

  • Demographic characteristic of patients

  • Social-economic status (SES)

  • Diabetes Care Services Utilization

  • Family history about diabetes

  • Drug history

  • Information about the diagnosis of Diabetes and treatment

  • Diabetic complications

  • Diet, physical activity, smoking

  • Self-reported questionnaire about PHQ (Patient Health Questionnaire)

Physical measurements

Anthropometrical measurements were obtained from the participants putting on light clothes and after taking of their shoes. Bodyweight was measured on a scale located on flat floor with an accuracy of 0.1 kg and height was measured without shoes to the nearest 0.1 cm. Waist circumference was measured using of a non-elastic tape at a point midway between the anterior superior iliac spine and the lowest rib in the mid-expiration phase, in the standing position. Hip circumference was measured over the biggest part of the buttocks.

Blood pressure (BP) was measured in the sitting position on the right arm by a mercury sphygmomanometer with the suitable cuff size. It was measured 2 times at five min intervals, and the mean was registered.

Blood sampling and laboratory assessments

A blood sample was taken after 8–12 h of fasting and also a first morning void urine sample was collected from each study participant. Laboratory measurements consisted of fasting blood glucose (mg/dl), triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), serum cholesterol, urea, creatinine, HbA1c, and also urine albumin to creatinine ratio. Blood samples were centrifuged at a health care center or laboratory of each province, allocated, and sent to the central laboratory in the Endocrinology and Metabolism Research Institute (EMRI), for analysis within 36 h after sampling. All samples were analyzed when internal quality control met the acceptable criteria.

Data management

The process of data management involved converting the data collected using data collection tools, most commonly Case Report Forms (CRFs), into electronic data that can then be statistically analyzed.

This consists of the following stages:

  • Completion and collection of the paper CRFs

  • Database Management Systems

  • Data entry

  • Data Validation and data cleaning

Paper CRFs were completed at the site by the investigator. Copies of CRFs were kept at the sites according to the protocol. Completed CRFs were collected after Monitoring visits. Paper CRFs were stored securely at all times and only be accessible by authorized personnel e.g. in a locked filing cabinet in a locked office. Then, CRFs were transferred to a Research center for data entry by courier to ensure safe delivery. After collecting CRFs at the site, the next step was to develop the database to store the data. The database management software used by the Research center was network login and user ID protected to prevent unauthorized access to the data and allowed different levels of database access control (e.g. Database, Table, and record). Double data entry by two persons was carried out without interpretation or modification, followed by comparing both datasets. Moreover, a third person was responsible for a confirmatory verification or a visual check, that the entered data matched the records in CRF hard copies.

All information in the original records and certified copies of original records about activities conducted as part of a clinical study that was necessary for reconstruction and evaluation of the study were called “Source Data”. Source Data Verification (SDV) for all required data was carried out by the Research center Monitoring Unit during site monitoring visits. Data validation was carried out at various stages during the study. SDV involved checking the data entered the CRFs against that in the source records.

When data were entered into the database by the data entry group, the database had software that enabled automatic data entry checks. The final dataset was ‘locked’ and password-protected to ensure access was restricted for final analysis and report. The Data Manager provided a copy of the final locked dataset to the sponsor before the statistical analysis was performed.

Statistical methods and Analysis Plans

Weighting methods

Provinces and sampling clusters were considered as strata and primary sample units (PSU), respectively. Since the sampling has been done during 1397 and 1398, as a reference population to define weights we used the average population of these two consecutive years, based on the predicted population by the Iranian statistical society. For each participant, two weights were defined: 1) gender weight, and 2) location weight. Weight of gender was calculated as the ratio of the total number of female/ or male aged 35–75 yrs. to the corresponding country’s number. Likewise, the location’s weight was calculated as the ratio of all 35–75 yrs. residents of urban/ or rural in the province to the sum of the country. Since every 12 related participants labeled as a cluster, to capture the correlation between nearby subjects clustering effect was also considered.

Endpoint evaluation

In each province, the proportion of patients with controlled HbA1c, FBS, or achieved triple targets, with 95% CI that was calculated based on the cluster robust standard error, were reported in genders, different age groups, and residence of living (Urban/ Rural). A country level analysis of outcomes was calculated via survey proportion, adjusted for gender, age, and the area of residents.

Definitions

In this paper, we reported the primary and secondary endpoints of the study in the total country. Therefore in this part, we defined these variables.

  • Primary objective

  • To assess the current status of diabetes control in adult people with type 2 diabetes of Iran:

  • Controlled HbA1c: HbA1c level ≤ 7%

  • Controlled FBG: FBG = 80-130 mg/d

  • Triple target: HbA1c < 7% + Normal blood pressure (SBP/DBP < 140/90 mmHg) + Low Density lipoprotein- Cholesterol (LDL- C) < 100 mg/dl

  • Secondary objective(s)

  • To assess the Diabetic Care Services Utilization:

  • Access to health care included: Access to insurance, Physician Access, Pharmacy Access, and Lab Access

  • To assess the prevalence of diabetic complications (Diabetic feet/Neuropathy and nephropathy):

  • Neuropathy: The United Kingdom Screening Test (UKST) was applied to score for symptoms of peripheral sensory neuropathy. Maximum signs score was 10, graded as follows: Normal 0-2; Mild 3-5; Moderate 6-8; Severe 9-10 [19].

  • The diabetic foot was defined based on having moderate or severe neuropathy or having an amputation.

  • Diabetic Nephropathy: random urine albumin creatinine ratio < 30 mg/g Normal; 30-300 mg/g Micro; and > 300 mg/g Macro-albuminuria. The presence of micro- or macro-diabetic nephropathy was considered [20]

  • Kidney disease status: Normal: Estimated glomerular filtration rate (GFR) > 90 mL/min/1.73 m2); Stage 2: GFR = 60-89 mL/min/1.73 m2; Stage 3: GFR = 30-59 mL/min/1.73 m2; Stage 4: GFR = 15-29 mL/min/1.73 m2); Stage 5: GFR < 15 mL/min/1.73 m2 [21].

  • End- Stage of Renal Disease (ESRD): Patients on dialysis, or those living with a kidney transplant, or having GFR < 15 mL/min/1.73 m.2

  • To evaluate the psychological impact of diabetes:

  • Patient Health Questionnaire (PHQ): This questionnaire examines disorders including Somatoform disorders, Major depressive disorders, other depressive disorders, Panic disorders, Anxiety disorders, Bulimia nervosa, Binge eating disorders, and Alcohol abuse [22].

  • Quality of Life (SF-12)[17].

Analysis Plan

Quantitative data were described as mean and standard deviation (SD) for normally distributed data, based on the Shapiro–Wilk test, while non-normal variables were presented as median (interquartile range: P25-P75). Categorical data were expressed as numbers and percentages. Total country summary statistics were survey adjusted and provincial levels were reported as No. and percentage. To account for the survey effect, between groups (male/female or urban/rural) comparisons, in the total country, were done by regression for survey data.

In maps, the percentage of achieved goals were divided into 5 equal groups (Quintiles), and provinces were categorized based on these cut points. Based on the standard latest shape files of Iran, data were plotted.

All statistical analysis was done by STATA (StataCorp. 2015. Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.), and P-value less than 0.05 was considered as statistical significance.

Results

According to the protocol of the study, 13,392 patients with diabetes type 2 living in 31 provinces should enter the study. Overall, 13,334 people with type 2 diabetes in 31 provinces of Iran completed the survey (response rate: 99.6%). In total 13,321 participants, 6683(50.17%) women and 6638(49.83%) men were included in our analysis. Thirteen recruited patients refused after the consenting process and did not respond. The characteristics of the study participants are presented in Table 1. The mean age (SD) of the total participants was 54.86 (9.44) years and 71.50% were from the urban areas. The median diabetes duration was 72 months and the mean (SD) HbA1c was 8.53(0.09) percent. Also, this table shows that 13.66% of diabetic patients have achieved the triple target of management in the whole country. While 28.74% of people had controlled HbA1c and 33.40% of them had controlled FBG.

Table 1 Characteristics of participants according to gender: The DiaCare study
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Figure 1 shows the proportions of patients with achieved diabetes control among adult people with type 2 diabetes in different provinces of Iran. The dark blue color indicates the provinces that have better control of HbA1c, FBG, and triple targets than others.

Fig. 1
figure 1

Proportions of patients with achieved diabetes control among adult people with type 2 diabetes in different provinces of Iran: The DiaCare study

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Table 2 shows that the best proportion of achieved diabetic control was in controlled FBG and the lowest percentage was in achieving the triple target. Also, patients lived in rural areas had less controlled HbA1c (23.93% vs. 29.48%), controlled FBG (29.50% vs. 34.20%) and controlled triple targets (10.45% vs. 14.32%) than those living in urban areas.

Table 2 Evaluation of patients with Achieved diabetes control in adult people with type 2 diabetes of Iran: The DiaCare study
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In terms of access to health care, more than 92 percent of participants had access to a physician, pharmacy, and laboratory. However, 54% of people had access to a glucometer and used it almost twice a week to measure their blood sugar (Table 3).

Table 3 Access to Health Care of participants according to gender: The DiaCare study
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Table 4 described that diabetic neuropathy and diabetic foot were more common in women than men, while ESRD was more common in men than women. In total, 37.29% of patients had diabetic foot and 49.54% of them had diabetic nephropathy. As regards kidney disease status, most of the participants 54.01% were in stage 2 of chronic kidney disease; 59.84% of women compared to 48.08% of men. ESRD represented 7.13% of the sample population, 9.55% of men and 4.73% of women.

Table 4 Evaluation of diabetic complications in the DiaCare study
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In Table 5, we evaluated the psychological effects of diabetes according to a self-reported questionnaire. Among women, somatoform disorder (22.8 vs. 6.72), major depression (9.99 vs. 2.90), panic disorder (3.59 vs. 1.93) and anxiety disorder (8.31 vs. 3.99) were more than men (all P < 0.001). While the percentage of men with alcohol abuse was about 8 times more than women (12.65 vs. 1.63).

Table 5 Evaluation of Patient Health status among diabetic patients in the DiaCare study
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Adverse Drug Reactions (ADRs) to any anti-diabetic treatment were not recorded from the sites during the course of the study.

Discussion

This comprehensive population-based study shows the current status of diabetes care in a representative sample of Iranian adults with type 2 diabetes at the national level. We presented the impact of gender, age groups, and urban versus rural residency on diabetes treatment goal achievements. Moreover, health care accessibility, prevalence of diabetic complications, and psychological status of diabetics were also provided.

Overall control

We observed controlled HbA1c and FBG respectively in 28.74% and 33.40% of type 2 diabetic patients in Iran at the national level. However, only 13.66% of them achieved the triple target of management. The proportions varied between different regions and provinces. Controlled HbA1c ranged from 14 to 38%, controlled FBG from 24 to 41%, and triple goal achievement from 6 to 15% in different provinces. So, an overall substantial proportion of diabetics were not well managed and controlled. In a similar study originated from Iran’s national non-communicable diseases risk factor surveillance survey of 2005, conducted to depict the first national picture of the quality of care provided for known diabetic patients in Iran, it was shown that about 97% of the patients had poor control according to their most recent HbA1c levels; however, at that time only 6.4% of participants had an HbA1c test during the year before questioning [23]. Previous studies have shown inadequate glycemic control in about 75% of patients in the UK, European countries, and developing countries [24,25,26]. Only 3.6% of type 2 diabetic patients from 17 developing countries attained all three recommended targets (blood pressure, LDL cholesterol, and HbA1c) according to the International Diabetes Management Practice Study in 2008 [26]. A target HbA1c level < 7% is recommended for most patients with type 2 diabetes; however, a more relaxed or more stringent target should be aimed at patients according to their age, presence or absence of comorbidities, life expectancy, risk of hypoglycemia, or present complications [27] and individualizing glycemic targets might increase the proportions of patients considered adequately controlled. Despite the availability of new medications and technologies, still, a substantial number of individuals are not at their glycemic goal pointing to the importance of medication adherence [28]. Failure to achieve glycemic control target could be multi-factorial, including poor medications, lack of knowledge regarding diabetic management and self-care, diabetes duration, lower education level, and poor economic status among all [8, 29, 30].

Men and women

Although regarding triple target achievement men had better status, the proportion was dramatically low in both genders; 12.76% among women and 14.56% among men. However, our findings showed that glycemic control (HbA1c and FBG) was poorer among men. This gender difference, however, was not similar in all regions and age groups. Women of all ages were more likely to have controlled FBG compared with men and controlled HbA1c was more likely in women compared with men in all age groups except 55 to 64 years, in whom men were more likely to meet the control of HbA1c. Better triple target achievement was observed in men of all age groups except 35 to 44 years. In reports of other countries, usually, women had the poorer conditions. Despite lower levels of FBG and HbA1c at the time of diagnosis in women, after 1 year of diabetes management, a small but significant difference was observed in target HbA1c achievement, in favor of men [31]. Indian women had poorer glycemic control [32]. A significant gender-based disparity was observed on cost-related medication non-adherence among diabetic patients according to US National Health Interview Survey data (2011 to 2014) [33]. However, in a recent study in Saudi Arabia, both genders exhibited comparable HbA1c levels, but men were less likely to have hypertension and more likely to have hyperlipidemia [34]. The risk of hypoglycemia is higher in longstanding diabetes and the elderly which could contribute to lower levels of HbA1c in elderly. A higher incidence of hypoglycemia was shown in men with longstanding diabetes [35].

Urban and rural

Overall, higher proportions of treatment target achievement were observed in those living in urban areas compared to rural. However, the gender gap was different between rural and urban areas. Although urban women had better control of HbA1c and FBG, in rural areas, men were more likely to have glycemic control. This may point to greater gender inequality in rural areas. However, regarding triple target, men had better status compared with women in both urban and rural areas. Conversely, in the rural-provincial general adult population in Denmark, poorly controlled diabetes were observed more commonly in men [36]. In rural areas of Iran, the diabetes treatment coverage rate was 67% based on self-report [37]. Iranian rural primary health workers (Behvarzes) are trained to identify and refer high-risk groups. Behvarz worker density, but not physician density, was significantly associated with diabetes treatment coverage rate and was found to be the only variable predictor of technical efficiency [37]. Therefore, the primary health care system may extend the diabetes treatment coverage by expanding the number and scope of its Behvarzes to also address blood pressure and to improve performance in areas with few primary care personnel [37, 38].

Age

Better FBG was observed among older groups. Age is found to be a major independent predictor for better glycemic control in previous studies with OR of about 0.5 [39, 40] which could partly be explained by the higher risk of hypoglycemia in older age groups.

Strengths

Most previous studies were hospital-based or clinic-based. The strengths of the present population-based study include the large and representative sample of diabetic patients from the whole country, including urban and rural areas; detailed data collection on disease management; lab findings measured by reliable methods in a single central laboratory. Finally, the sex and age- stratified analysis provided an accurate snapshot to identify gaps in the quality of care.

Limitations

First, patients in the range of 35–75 years were recruited due to resource limitation which could decrease our external validity and our results can only be generalized to patients in this range. Second, type 2 diabetic patients were identified based on self-report leaving behind undiagnosed patients unaware of their disease which includes half of the diabetic patients according to the IDF reports. Therefore, study results can be only generalized to known diabetic patients. Besides, we used HbA1c level < 7% as an index of good glycemic control for all participants without individualization of glycemic targets. This might underestimate the number of patients considered adequately controlled [27].

Conclusions

This population-based study provided representative information about diabetes care in Iran. Glycemic control was observed in about a quarter of patients and only a minority of patients met the triple target criteria (13.66). Overall, middle-aged patients, men, and rural residents were less likely to achieve glycemic control. However, triple goal achievement were slightly better in men. The high prevalence of diabetes and low proportion of diabetes control in Iran implies that it is necessary to identify factors associated with poor treatment goal achievements. Besides, general improvements in management and care of diabetes are mandatory.