Aims/Background: Diabetes is a serious health condition requiring a range of interventions and self-management education to reduce the risk of complications. The aim of the present study was to assess the care management of people with diabetes in medical practice in Tunisia and its efficiency on HbA1c target. 

Materials and methods: The International Diabetes Management Practices Study (IDMPS) is an international, multicentre, non-interventional observational study on care management of diabetes. The data collected from Tunisia in 2016 during the 7th wave was analysed, including 423 patients (people with type1: n=127, with type 2: n=296).

Results: The recommended target of HbA1c <7% was achieved by only 15.5% of type 1 diabetes patients and 24.7% of type 2 diabetes patients. The majority of type 2 diabetes patients (63.3%) received only OGLD (oral glycaemic lowering drug) therapy alone. For type 1 diabetes patients, receiving insulin treatment, more than two-thirds experienced symptomatic episodes of hypoglycemia in the past 3 months, against 24.6% for type 2 diabetes patients. Hospitalizations due to diabetes were reported during the past 12 months for 22.0% and 6.8% of type 1 and type 2 diabetes patients, respectively. 

Conclusions/interpretation: The clinical burden of diabetes in Tunisia is unsettling, highlighting the need for more awareness of the disease and its complications. Clinicians probably need to be more careful about intensification of the treatment, even to some therapeutic inertia for type 2 diabetes patients, and global cardiovascular risk approach including the triple pooled targets as recommended in the last guidelines.

IDF: International Diabetes Federation

IDMPS: International Diabetes Management Practices Study 

LDL-CS: Low-Density Lipoprotein-Cholesterol

MENA: Middle East and North Africa

OGLD: Oral Glycaemic Lowering Drug

SBP/DBP: Systolic Blood Pressure/Diastolic Blood Pressure

What is already known about this subject? 

• The Middle East and North Africa (MENA) region, including Tunisia, records in 2021 the second highest increase in diabetes among all world regions.
• The burden of diabetes in Tunisia is found to be underestimated with a proportion of more than 40% of undiagnosed diabetes.
• Previous IDMPS waves conducted in Tunisia had reported poor glycemic control in diabetic patients.

What is the key question? 

• What is the current care management of diabetic patients in medical practice in Tunisia and what are the predictive factors of reaching the target HbA1c for these patients?

What are the new findings? 

• Most diabetic patients still do not meet recommended glycemic and HbA1c targets.
• Among patients who do not achieve glycemic goals as targeted, the reasons for non-achievement were mostly the lack of titration of insulin (57.1%), the second main reason was the lack of diabetes education (49.5%). 
• Inappropriate management of insulin therapy was highly demonstrated.

How might this impact on clinical practice in the foreseeable future?

• The worrying outcomes will raise awareness for the establishment of an effective healthcare strategy in Tunisia to improve the quality of care for diabetic patients, including the strengthening of therapeutic education programs.

Diabetes is a major health issue that has shown alarming increases across the world, driven by increasing obesity, sedentary lifestyle, and population aging [1]. According to estimates, more than a half a billion people are living with diabetes worldwide and the prevalence of type 2 diabetes is set to increase from its present level of 537 million (2021) to 783 million by the year 2045 [2]. This rise is predicted to occur virtually in every nation, with the greatest increases expected in developing countries. Furthermore, the Middle East and North Africa (MENA) region has the second highest increase of all regions reviewed by the International Diabetes Federation (IDF), with a diabetes prevalence of 18.1% in 2021, the number of people with diabetes is expected to increase by 87% by 2045. However, the prevalence of diabetes in the MENA region may be underestimated, with a proportion of undiagnosed diabetes close to 37.6% (27.3 million) [3]. 

Diabetic patients are at risk of developing serious complications, which if not well managed, can result in hospitalizations and even premature death. It turns out that diabetes and its complications caused 428,600 deaths in adults aged less than 60 years in 2021 (24.5% of all-cause mortality) in MENA region [3].

In addition, diabetes also imposes a significant economic impact on countries, health systems and individuals with an estimated annual cost of diagnosed diabetes in 2017 of $327 billion, including $237 billion in direct medical costs and $90 billion in reduced productivity [4]. Indirect costs including loss of production (labour-force drop out from disability), mortality, absenteeism and presenteeism (reduced productivity when at work).

The Diabetes Control and Complications Trial (DCCT) in subjects with type 1 diabetes and the United Kingdom Prospective Diabetes Study (UKPDS) in subjects with type 2 diabetes have supported the position that early treatment of diabetes with tight glycemic control can reduce the morbidity and mortality of the disease by decreasing its chronic complications [5,6]. Therefore, the goal of treatment for patients with diabetes is to achieve metabolic goals, thus preventing or delaying complications and optimizing quality of life. Moreover, this should be personalized according to individual preferences, values, and goals [7].

International diabetes societies (ADA, EASD) have made global recommendations aiming to achieve optimal levels of glycemic control HbA1c lessthan 7% (53 mmol/mol) for nonpregnant adult without hypoglycemia. However, less stringent HbA1c goals lessthan 8% (64 mmol/mol) may be appropriate for patients with limited life expectancy, or where the harms of treatment are greater than the benefits [8,9]. However, it turns out that several patients are still not well controlled and do not achieve the HbA1c goal, a fact that seems to be related to all the insulin therapy issues, from initiation of insulin therapy to proper insulin titration [10]. Therefore, there is a need to better assess the current practices in diabetes management and put in place some actions to improve the quality of care of these patients.

The standardization of the data collection process and the data analysis will justify international comparisons. This very large database will provide supportive data for international recommendations in terms of insulin therapy, in order to improve quality of medicine usage. It will also support future exploratory research.

In this article, we focused on Tunisian data collected during the 7th wave of the IDMPS to assess the management of diabetic patients in medical practice in Tunisia and the predictive factors of reaching the target HbA1c for these patients.

Study design and recruitment of patients

This is an international, multicentre, non-interventional, observational on management care study of people with type 1 or type 2 diabetes mellitus. The study was composed of a cross-sectional study to assess current practices in the management of subjects with type 1 and type 2 diabetes mellitus. The cross-sectional phase was composed of yearly surveys of 2 weeks duration each.

The IDMPS study is composed of yearly surveys (cross-sectional studies and/or longitudinal studies). The first wave of the study was performed in 2005. Six waves have already been performed. This cross-sectional study has been implemented for the seventh wave, which was carried out in 24 countries. In total, 4 regions were defined: Africa (Algeria, Cameroon, Madagascar, Democratic Republic of Congo, Egypt, Tunisia, Morocco, South Africa, Senegal, Ivory Coast, Nigeria, Kenya), Eurasia (Ukraine, Russia), Middle East (Iran, Iraq, Jordan, Kuwait, Lebanon, Pakistan, UAE, Saudi Arabia), and South Asia (Bangladesh, India). 

As variables collected during each study were analysed on a yearly basis, by country, and in an independent manner, the Statistical Analysis Plan (SAP) was updated before each analysis. 

All the patients who met the eligibility criteria of the cross-sectional study were included. The eligible population considered is: treated with insulin (T1DM only), with type of diabetes recorded (Type1 or type 2), and without missing data concerning the treatment of diabetes (“Does the patient receive oral glycaemic lowering drug (Yes/No)” and “Is the patient currently treated with insulin (Yes/No)”). 

Exclusion criteria were: patients enrolled in ongoing clinical trials, or those undergoing temporary insulin therapy (due to other medical issues including gestational diabetes, pancreatic cancer or surgery at baseline).

Survey data was collected by physicians on a standardized IDMPS case report form. The analysis population was constituted after database cleaning.

The sample size was determined on a country basis, based on the primary objective, which was to assess the management of care of T2DM patients, and on the relative precision that was expected. 

Based on the assumption that insulin was the least prescribed therapy in terms of proportions, the sample size was determined in order to establish the frequency of insulin-treated patients. It was estimated to give an estimation of proportions with an absolute precision of 20% and a confidence interval of 95%. 

n = p (1-p) x (εα/ e)²

with: n = the per country sample size, p = the estimated proportion of type 2 DM patients treated with insulin, εα = 1.96 for α = 5 %, e = the absolute precision (20%) x p = the relative precision.

Ethics

The IDMPS study protocol was approved, all followed procedures were compliant with the appropriate regulatory and ethical committees of the participating countries and centers, as well as those in Tunisia.

Study objectives

The purpose of this diabetes registry is to collect, analyse and disseminate data on people living with diabetes mellitus to improve the quality of care of these patients.

The primary objective of the study was to assess the management of care of people with type 2 diabetes in current medical practice.

The secondary study objectives were: to assess the management of care of patients with type 1 diabetes in current medical practice, and to evaluate the predictive factors for reaching target HbA1c in patients with type 1 and type 2 diabetes.

Statistical analysis

Quantitative variables are described by: the number of missing data, extreme values, mean, standard deviation, median and quartiles. Qualitative variables are described by: the number of missing data, the different modalities of the variable, the corresponding numbers and percentages, and the 95% confidence interval (95% CI).

The modality “Unknown” was considered as missing data regarding “Yes/No/Unknown” answers.

Several comparative analyses were performed. The relationship between categorical variables was investigated using the Chi2 test or Fisher's exact test, depending on the expected values. For categorical variables, comparisons of means were made using the Student t-test or the Wilcoxon/Mann-Whitney test, depending on the normality of the distribution.

Statistical analysis was carried out using SAS® software version 9-2. There was no intermediate analysis.

Study population

In Tunisia, 423 diabetes mellitus patients were recruited in the 7th wave of IDMPS. All of them met the eligibility criteria for analysis, distributed in 127 T1DM patients and 296 T2DM patients (Table 1).

* Health insurance is defined as National Public Health Insurance and/or Private Health Insurance.

Table 1: Patient demography by type of diabetes

30 physicians included at least one patient in the study: 21 (70%) were specialists (endocrinologists or diabetologists) and 9 were non-specialists (4 (13.3%) General practitioners and 5 (16.7%) internists/cardiologists). All patients met the eligibility criteria for analysis (inclusion/exclusion criteria met, without any other reason of exclusion), distributed in 127 T1DM patients and 296 T2DM patients. All patients were included in the eligible population for analysis.

Characteristics of people with type 1 diabetes

Demographic and clinical features of the T1DM cohort (N = 127) are presented in Tables 1 and 2. The average duration of diabetes was 15.29 ± 10.17 years.

Hospitalizations due to diabetes were reported for 22% of patients during the past 12 months.

Treatment of people with T1DM, attainment of targets and self-care

Most people with T1DM (95.3%) were treated with insulin while only 6.3% received OGLD therapy (Table 3). 85.8% received either basal + prandial insulin (Table 4); while 9.4% received basal alone and 3.9% premix alone. The average duration of insulin therapy was approximately 15.18 ± 10.16 years. 85.7% of T1DM patients had a glucose meter.

HbA1c mean was 8.94%. 15.5% of them achieved the glycaemic target HbA1c lessthan 7 %. Glycaemic goals as targeted by the treating physician were achieved in 15.9% of patients. Comparing the last HbA1c measurement with the HbA1c target value considered by the physician, 9.5% of patients had an HbA1c below the targeted value.

Characteristics of people with type 2 diabetes

Demographic and clinical features of the T2DM cohort (N = 296) are exposed in Tables 1 and 2. The average duration of diabetes was 11.74 ± 8.17 years. Diabetes-related complications were experienced by 49.1% of patients: microvascular complications in 41.6% and macrovascular complications in 14.8%. 6.8% had been hospitalized due to their diabetes in the previous 12 months.

Treatment of people with T2DM, attainment of targets and self-care

Regarding lifestyle, 38.6% of the people with T2DM followed healthy diet and exercise plan. Concerning treatment, 171 (63.3%) patients received only OGLD therapy alone, while 99 (36.66%) patients received a combination of OGLD with insulin, and 25 (9.25%) patients received insulin treatment alone.

For those treated with OGLD drugs only, 56.2% were treated with Metformin + sulfonylureas (+/- others), and 27.8% with Metformin alone. For those who received insulin therapy, basal prandial combination was the most frequently (52.0%) used regimen. Basal alone (32.0%) and Premix alone (12.0%) were the following most preferred regimens respectively. For those who received insulin and OGLD drugs, basal alone was the most frequently (52.5%) used regimen, followed by basal prandial combination (36.4%) and premix alone (10.1%).

In T2DM, the premixed insulin dose was higher than basal/ basal+ prandial regimen, mean basal insulin dose was 34.01 IU (0.41 IU/kg), the mean prandial insulin dose was 18.42 IU (0.21 IU/kg) and the mean premixed insulin dose was 54.43 IU (0.67 IU/kg). Self-adjustment of insulin was performed in 23.6% of patients. 

56.1% patients had a glucose meter. Self-management of both blood glucose and insulin was performed in 20.0% of patients. 82.4% of T2DM patients ever received diabetes education and 77.2% were involved in an educational program provided by the physician or his/her clinical staff.

HbA1c mean was 8.16%. Only 24.7% of the T2DM patients achieved the glycemic target HbA1c lassthan 7%, and 26.6% the glycemic goals as targeted by the treating physician. Table 5 summarizes the glycemic control according to insulin regimen. The mean value at the last measurement of HbA1c for patients with insulin therapy was lower with the basal regimen or basal+ postprandial regimen than with the premix regimen: 8.73, 8.62 and 9.44 respectively. Among the patients who did not achieve glycemic goals as targeted, the reasons for non-achievement were mostly the lack of titration of insulin (57.1%) and the lack of diabetes education (49.5%).

Table 2: Clinical profile of patients by type of diabetes

Table 3: Oral glucose-lowering drugs treatment by type of diabetes

Table 4: Current insulin treatment by type of diabetes

Table 5: Glycaemic control per current insulin treatment by type of diabetes

Hypoglycemia 

More than one out of three people living with diabetes mellitus has shown signs of hypoglycemia during the last three months, mainly in patients treated with insulin, 67.7% for T1DM, 24.6% for T2DM (33.3% in patients treated with insulins and 41.8% in patients treated with OGLD plus insulin treatment). One in ten patients experienced severe hypoglycemia in the past of 12 months, mainly in patients treated with insulin, 27.2% for T1DM and 12.5% for T2DM (Table 6). In 95.2% of cases, one of the causes is an inappropriate management of insulin therapy, whether it is the timing of the injection or the adaptation of doses: in case of physical exercise in 42.5% of cases, or relative to food intake, particularly for T2DM patients, in whom it is overestimated by one patient in three (33.3%). Thus, 11.4% required hospitalization due to the diabetes during last 12 months and in 14.6% of cases reason of hospitalization was hypoglycemia.

Table 6: Symptomatic episodes of hypoglycemia

Adherence to insulin therapy and support programs

11.1% of diabetic patients interrupted their insulin treatment, for durations ranging from 2 to 20 months, with an average of 1.68 months for T1DM patients and 4.36 months for T2DM patients with OGLD plus insulin treatment. The main causes for this non-adherence were impact on social life for 58.6% of patients, the fear of hypoglycemia for 27.6%, episodes of hypoglycemia for 24.1%, lack of experience in insulin management for 31% and lack of support for 24.1% of patients (Table 7). 

* A patient may have several reasons of discontinuation.

Table 7: Adherence to insulin therapy by type of diabetes

While 81.2% of clinicians consider patients may benefit from any support and that support programs exist, reaching 83.9% of diabetic people, the impact on insulin therapy management remains insufficient, as well as on dietary habits and physical activity level: 61.4% of patients did not modify them.

63.4% of people with type 2 diabetes had associated hypertension and 60.8% dyslipidemia.

A positive point to note: Tunisians seems to be little smokers. 65% have never smoked, 16.8% have stopped when the diagnosis was announced and therefore 18.2% continue to smoke despite knowing their diabetes. 

Regarding the high cardiovascular risk, the triple targets pooled together HbA1c lessthan 7%, and normal blood pressure (SBP/DBP: 130/80mmHg) and LDL‐CS lessthan 100 mg/dL is strongly recommended. In Tunisia, these triple targets were reached by only 2.4% of the people T2DM. The non-achievement of the triple targets was due to HbA1c level ≥ 7% in 78.8%, abnormal blood pressure for 76.4% and LDL level ≥ 100 mg/dL for 50.8%.

According to the IDF 2021 estimates, the prevalence of diabetes in Tunisia reaches 10.8% among adults aged 20 to 79 years. However, this percentage does not reflect the real situation in the country with a proportion of 40.2% of undiagnosed diabetes [3]. Diabetic patients are at risk of developing complications that reduce quality of life, undue stress on families, and can even be life-threatening if not well managed, thus the need for stringent disease management and individualized medical care [11].

The findings of the present IDMPS wave 7 reveal a worrying clinical burden of diabetes in Tunisia, with the presence of a high cardiovascular risk in diabetic patients, particularly related to the non-achievement of the recommended target value of HbA1c, of blood pressure and of LDL by most of diabetic patients. These outcomes are consistent with the reports of the Tunisian national coronary heart disease registry, where diabetes is significantly associated with coronary heart disease, mostly in women: 50.5% vs 28.7% in men [12].

In Tunisia, according to IDMPS wave 7 results, only 24.7% of the people with T2DM reached the recommended target value of HbA1c < 7>

In the people with T2DM, those treated with insulin alone or with OGLD alone were more likely to have an HbA1c < HbA1c>

In insulin-treated patients, the glycaemic goals as targeted by the treating physician were achieved in 26.6% of the people with T2DM. Among the patients who do not achieve glycaemic goals as targeted, the reasons for non-achievement were mostly first the lack of titration of insulin (57.1%), probably due to fear from hypoglycemia more than one in three patients with diabetes mellitus has shown signs of hypoglycemia during the last three months (37.4%), mainly in patients treated with insulin, one of the causes expressed by the patients is an inappropriate management of insulin therapy. In another local registry (Hypo G study) [16] whose objective was to assess the proportion of the people with T2MD with hypoglycemia in inadequately controlled with basal insulin with high risk of hypoglycemia, 73% of them presented a hypoglycaemia event during the last month. 

The results of Hypo G study may join IDMPS wave 7 results regarding hypoglycaemia as main issue for optimisation of insulin treatment and achievement of glycemic control. Although more than 8 out of 10 patients with diabetes mellitus participated in support programs, it seems that the level of knowledge and acquisition of self-care skills is still insufficient. These data should raise questions about the quality of these programs. Moreover, we must note that the majority of these programs are carried out in less than 2 hours. 

Consequently, physicians should ask their patients about hypoglycemia at each visit to try to find the principal reasons involved and implement a therapeutic strategy to decrease this risk. Also, there is a need to provide more patient support and patient education to improve patient knowledge in diabetes complication and self-care skills in insulin management [17,18]. 

Conclusion

After comparison with the international recommendations (EASD, ADA, and IDF), it appeared that the clinical burden of diabetes in Tunisia is unsettling especially because of the non-achievement of the recommended target value of HbA1c by most patients, highlighting the need for better education of patients and more awareness of the disease particularly its complications. Moreover, clinicians probably also need to explain to them that reaching glycemic targets requires adaptation of treatment, often leading to treatment intensification and insulin optimization taking account minimisation of hypoglycemia risk. Furthermore, the high cardiovascular risk of Tunisian diabetic patients, glycemic targets need to be extended to a more global approach, including the control of any associated hypertension or dyslipidemia.

Limitations 

The information presented in the study is reflective of patients accessing healthcare at the selected study site and may not be representative of the general diabetes population. Due to the descriptive nature of the data, it was not possible to determine the specific impact of variables such as medication change over time. Nevertheless, the data provide some valuable insights into diabetes management in Tunisia.

Declarations

Acknowledgement

The authors would like to thank Charfi Nadia, Professor in endocrinology university of Sfax Tunisia and Ramzy Hala, employee of Sanofi and potential shareholder of Sanofi for their great support and contribution to the study.

The authors would like to thank all the physicians and People who participated in this study.

Editorial assistance and medical writing were provided by Better Being Health SARL, Marrakech, Morocco, and was funded by Sanofi.

Availability of data and materials

"Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized, and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi’s data sharing criteria, eligible studies, and process for requesting access can be found at: https://www.vivli.org/.

The IDMPS study protocol was approved, all followed procedures were compliant with the appropriate regulatory and ethical committees of the participating countries and centers, as well as those in Tunisia.

The study was sponsored and funded by Sanofi.

All participants provided written informed consent before entering the study.

The author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Abid Mohamed declares that there is no conflict of interest. Ben Aissa Emna is an employee of Sanofi and potential shareholder of Sanofi.

Both authors Professor Mohamed ABID and Emna BEN AISSA have enssured the study concept, design, data analysis and interpretation of the current manuscript.

Drafting and critical revision of the manuscript was provided by scientific writing agency Better Being Health SARL based in Morocco.

The authors assume full responsibility for the present study, and state having approved the latest version of the manuscript for publication.