High prevalence of comorbidities in older adult patients with type 2 diabetes: a cross-sectional survey

Abstract

Background

Diabetes is a global health problem, and its incidence and complications increase with the duration of the disease and over time. This increase in complications in older patients can lead to disability and a lower quality of life. This study aimed to investigate the rate of diabetes control and complications in older adults.

Method

This was a cross-section of an ongoing cohort of patients with type 2 diabetes mellitus (T2DM) aged 65 years and older. The clinical and laboratory characteristics of older adult patients with T2DM in good and intermediate health conditions were collected between 2010 and 2022.

Results

A total of 2,770 older adult patients with T2DM were enrolled, including 1,530(55.3%) female and 1,240 (44.7%) male participants. Metabolic syndrome, hypertension, and coronary artery disease were the most common comorbidities, affecting 1,889 (71.4%), 1,495 (54.4%), and 786 (29.2%) patients, respectively. Albuminuria was present in 626 (22.6%) patients, while retinopathy was detected in 408 (14.7%) patients, including 6% with proliferative retinopathy. Most patients were treated with oral antidiabetic agents (88.9%), with metformin being the most prescribed medication (85.6%). Statins were prescribed to 71.8% of the patients. The most prescribed antihypertensive medications were angiotensin receptor blockers and angiotensin-converting enzyme inhibitors, prescribed to 54% and 15% of patients, respectively. The hemoglobin A1c (HbA1c) goal (HbA1c < 7.5%) was achieved in 1,350 (56.4%) patients, and the low-density lipoprotein cholesterol (LDL-C) goal (LDL < 100) was achieved in 1,165 (45.6%) patients. Blood pressure control (BP < 140/90) was achieved in 1,755 (65.4%) patients. All three goals were achieved in 278 (10.3%) patients. There were no significant differences in clinical laboratory results and the patients’ characteristics based on gender.

Conclusion

The rate of progression of complications in older adult patients is higher than the effectiveness of the treatment, indicating the need for increased social support for this age group.

Background

Diabetes is one of the most concerning global public health complications and is a leading cause of increased mortality and reduced life expectancy in all societies. The global prevalence of diabetes in people aged 65 years and older is estimated to be 19.3% (135.6 million), and it is projected to reach 19.6% (276.2 million) by 2045. Currently, evaluations by the International Diabetes Federation reveal that one in every five people with diabetes is over 65 years old. A significant regional difference has been reported in the prevalence of diabetes among people aged 65 years and older. The Middle East and North Africa region, which includes Iran, ranks second in global diabetes incidence. In 2019, the incidence of diabetes in individuals aged 65 years and older in this region was estimated at 24.2% (8.4 million). This figure is projected to increase to 25.2% (25.2 million) by 2045 [1, 2].

Older adults with diabetes have a higher risk of cardiovascular complications and many geriatric syndromes due to the aging process and vascular changes. Cardiovascular disease is known as one of the major causes of disability and mortality in older adults. Insulin resistance and elevated blood glucose increase the risk of cardiovascular events as a primary consequence of type 2 diabetes mellitus (T2DM) in this age group. Approximately 61% of all healthcare costs associated with diabetes are related to people over 65 years of age [3]. In Iran, the prevalence of T2DM in older adults is estimated to be 14.4%, the same as the global average. However, there is a paucity of data on the demographics and characteristics of T2DM in older adults in Iran. In a population-based study conducted in the USA, researchers assessed the frequency of type 1 and type 2 diabetes (T2D). Their findings revealed that T2DM is more commonly observed in older adults than younger individuals.

The management of diabetes in older adults is challenging due to the extensive variability in clinical presentation, psychosocial factors, available social support, living situations, and resource availability. In a study conducted in Iran, ABC goal achievement was reported across different age groups. Among younger groups, such as those aged 20–49 and 50–65, ABC achievement was 21.7% and 22.9%, respectively, between 2012 and 2014. For older groups, such as those aged 65–74 years and older than 74 years, ABC achievement during the same period was 27.3% and 20.6%, respectively [4]. Another study by the same institute compared ABC goal achievement across all age categories between 2010 and 2014 and 2015–2019, reporting higher but still suboptimal results [5]. According to a study conducted in Canada between 2007 and 2017, ABC goal achievement increased from 11.53 to 14.54%, with moderate and vigorous physical activity having significant effects on goal achievement [6]. In a nationwide cross-sectional study in China, 8,401 adults were enrolled, and over a 2-year period, 4.4% of them achieved all three ABC goals [7]. In a Brazilian national health study, 465 adults were enrolled, and the achievement rates were reported as 46% for A1C, 51.4% for blood pressure, and 40% for LDL-C. The achievement of all three goals was attained by 12.5% [8]. On the other hand, recent guidelines do not consider reaching ABC goals as a criterion for successful treatment in older adults and recommend a unique, individualized approach without strict control over all three ABC goals [9].

Older patients are more likely to suffer from disorders such as metabolic syndrome, hypertension, and coronary artery disease (CAD) despite the availability of preventive measures, diagnostic screenings, and treatments. Given the lack of studies on diabetes-associated complications in the aged population in this region, this research aimed to evaluate the characteristics of T2D, the rate of diabetes-related complications, and the effectiveness of treatments in adults over 65. This large population-based study will provide important new insights into the characteristics of T2D in older adults over 65 in an Iranian population, as the Iranian population pyramid is shifting toward an older demographic in future years. Based on this investigation, it may be possible to revise screenings and improve treatments for older people based on their living areas.

Materials and methods

Patient selection

The data were obtained from an ongoing cohort of patients with T2DM treated at the Diabetes Clinic of Vali-Asr Hospital, affiliated with Tehran University of Medical Sciences. A total of 2,770 patients with diabetes aged over 65 years were recruited for this study. T2DM was diagnosed according to the American Diabetes Association (ADA) guidelines. The population was mainly homogenous, middle class, with an elementary-to-high school education, and most were retired or housewives without a defined physical activity routine. They had access to healthcare facilities and insurance. Their health condition level according to ADA standards of care for older adults, were good and intermediate [10]. Before enrollment, written informed consent was obtained from all patients. The ethics committee of Tehran University of Medical Sciences approved the study protocol, which complied with the principles of the Declaration of Helsinki. The exclusion criteria included patients in poor health according to ADA guidelines and hospitalized and disabled patients.

Patient characteristics and measurements

Patient characteristics, including age, gender, height, weight, waist circumference, smoking status, duration of diabetes, medications, and laboratory measurements, including fasting blood glucose, HbA1c, total cholesterol, triglycerides, LDL, high-density lipoprotein, and serum creatinine, were extracted from medical records. Body mass index (kg/m²) was calculated as weight (kg) divided by height squared (m²). The estimated glomerular filtration rate was calculated using the Cockcroft-Gault formula: ([140-age] * [weight in kg] * [0.85 if female]) / (72 * [serum creatinine in mg/dL]) for each participant. Systolic and diastolic blood pressure measurements were performed in the seated position after 10 min of rest, using a calibrated Omron M7 sphygmomanometer (Hoofddrop, the Netherlands), ensuring that the calves covered at least 80% of the patients’ arms. The measurement was repeated after 15 min, and the average was reported. CAD was defined as a history of percutaneous coronary intervention, coronary artery bypass graft, acute coronary syndrome, or myocardial infarction. All demographic information is shown in Table 1.

Table 1 Demographic information of all patients

A (HbA1c), B (blood pressure), and C (LDL-C) goals were defined as HbA1c < 7.5%, blood pressure < 140/90 mmHg, and LDL < 100 mg/dL for CAD-negative patients, and LDL < 70 mg/dL for CAD-positive patients, respectively.

Statistical analysis

The statistical software IBM SPSS version 24 and Stata software version 17 (Statacorp, LLC) were used for statistical analysis. Continuous variables were presented as mean ± standard deviation, and comparisons were performed using an independent sample t-test. Categorical variables were presented as numbers and percentages and were compared using Fisher’s exact test. One-way analysis of variance and x² test were used as appropriate for between-group comparisons. Statistical significance was defined as a p-value of less than 0.05. Backward selection logistic regression analysis with α = 0.2 was used to identify potential independent predictors of goal achievement. The restricted cubic spline is shown in Fig. 1. The results demonstrated the relationship between CAD incidence and age.

Fig. 1

Association between CAD with age in older adults, allowing for nonlinear effect, with 95% CIs. The restricted cubic spline was designed with 4 knots according to CAD. Curves show ORs compared with the chosen reference of age 70 years. The prevalence of coronary artery disease (CAD) progressively increases with age until 73 years, beyond which there is no meaningful correlation

Results

In the present study, 2,771 patients with T2DM aged over 65 years were enrolled, including 1,531 (55.3%) female and 1,240 (44.7%) male participants. The clinical and laboratory characteristics of the patients are shown in Table 1. The mean age of the study population was 70.32 ± 4.27 years, and the duration of diabetes was 11.72 ± 8.72 years. The number of patients who smoked was 117 (6.2%), and hypertension was present in 1,495 (54.4%) participants. In addition, the number of statin-treated patients was 1,749 (71.8%), and metabolic syndrome was diagnosed in 1,889 (71.4%) participants.

Coronary artery disease was present in 786 (29.2%) of the patients. A total of 279 (14.1%) patients had a history of CABG. In addition, 348 (14.7%) patients had retinopathy, including 143 (6%) patients with proliferative diabetic retinopathy. Albuminuria was present in 392 (22.6%) of the patients.

Achievement of an HbA1c goal of ≤ 7.5% was observed in 1,350 (56.4%) of the participants. A total of 576 (21.9%) patients had an HbA1c level between 7.5% and 8%, and 699 (26.6%) had an HbA1c level greater than 8%. Achievement of the blood pressure goal was observed in 1,755 (65.4%) of the patients, while the LDL-C goal was achieved in 1,165 (45.6%) patients. Achievement of all three goals (A, B, and C) was observed in 278 (10.3%) of the participants. Logistic regression analysis to evaluate predictors of achieving all three goals showed that male gender [OR: 2.026, CI: 1.14–3.6, p = 0.01], older age [OR: 1.082, CI: 1.03–1.13, p = 0.001], duration of diabetes [OR: 0.94, CI: 0.92–0.97, p = 0.001], metabolic syndrome [OR: 0.36, CI: 0.23–0.56, p = 0.001], and ASCVD risk score [OR: 0.82, CI: 0.77–0.81, p = 0.001] were significant independent predictors of achieving all three goals.

Evaluation of gender differences revealed significant differences between males and females older than 65 years in age, duration of diabetes, BMI, eGFR, FBS, 2Hpp, HbA1c, cholesterol, TG, HDL, LDL, AIP, smoking status, hypertension, albuminuria, metabolic syndrome, and coronary artery disease. However, there were no significant differences in the rates of HbA1c target achievement [53.5% in females vs. 48.9% in males, p = 0.6], the achievement of the LDL goal [45.3% in females vs. 45.9% in males, p = 0.791], and the achievement of the blood pressure goal between males and females [65.9% in females vs. 64.8% in males, p = 0.55].

Discussion

This real-world, cross-sectional study was designed to focus on diabetes-related demographic information in 2,771 adults older than 65 years with T2DM, with a mean duration of 11.72 years, in the Iranian population exhibiting overall health categories of healthy and intermediate health status. In each of the following sections, we will explain the findings based on the type of complication and in order of prevalence.

Coronary artery disease and hypertension

In this study, coronary artery disease was present in 29.2% of the patients, with 14.1% having a history of CABG. Patients with diabetes had a greater risk of all cardiovascular complications, and this risk increased significantly with age, as shown in Fig. 1. Diabetes and aging have synergistic effects on the vascular system by increasing the wall thickness and stiffness of blood vessels and decreasing vessel compliance. These changes can lead to additional vascular complications [11]. A study conducted by Sattar et al. demonstrated that the impact of age and diabetes duration on mortality was 1.6 times greater in patients diagnosed with diabetes for more than ten years [12]. There is a significant difference in the occurrence of coronary artery disease between males and females, with male participants appearing to be more affected. Several reasons contribute to this, including cultural and social roles of men in the community that impose greater stress on them, lower physical activity levels compared to women, and higher consumption of cigarettes and opium among men. Meanwhile, women tend to be caregivers and pay more attention to their health [13,14,15].

Hypertension is the primary and most frequent macrovascular complication in patients with T2D. It was present in 54.4% of our study participants, with 35.6% of these patients having a systolic blood pressure greater than 140 mmHg. Sims et al. reported a 17% co-occurrence of diabetes and hypertension in older adults, indicating a significant increase [16].

In a study by Gonzalez-Juanatey et al. in 2001, 74% of patients with T2D and CAD had hypertension. In our study, 65.4% of the patients had a blood pressure of less than 140 mmHg [17]. Carlberg et al. revealed that a systolic goal of 140 mmHg can decrease the incidence of cardiovascular complications, and intense therapeutic plans may lead to increased cardiovascular mortality [18].

All antihypertensive drugs can be used in older adults with diabetes, but they should be chosen and combined based on the patient’s lifestyle and other health conditions. Thiazide diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel blockers (CCBs) should be considered as initial therapies for these patients. In this study, angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) were the most commonly prescribed drugs due to their high availability in drugstores throughout the country and lower risk of falls for this age group. Diuretics are prescribed less frequently because of adverse effects such as glucose intolerance and hypotension. In other countries, such as the United States, ACEIs, CCBs, and thiazides are the most commonly prescribed drugs. In European countries, ACEIs, ARBs, and CCBs are the most frequently prescribed. In the MENA region, diuretics and beta-blockers are used more often than in other countries due to the limited availability and higher cost of newer medications. However, the main goal is to control blood pressure itself.

Shepherd et al. revealed that primary prevention with statins could only decrease the incidence of ischemic heart disease and CAD, while secondary prevention with statins may decrease all cardiovascular-related mortalities [19]. Ginsberg’s HN study showed that patients who were treated with statins had 15% fewer cardiovascular complications [20].

The mean levels of LDL and triglycerides were reported to be approximately 100 and 159 mg/dL, respectively. Statin use was reported by 71.8% of the participants. Nearly all of our patients used atorvastatin because of its better availability in Iran and lower price compared to other lipid-lowering drugs. The Endocrine Society guidelines suggest statin therapy to reduce the absolute risk of CVD [21]. Van Hateren et al. mentioned that as the duration of diabetes increases to more than 8 years, a higher lipid profile rate will be predictive of cardiovascular mortality [22].

Although this study detected a significant difference between males and females in HDL-C levels, for a more accurate and detailed review, HDL levels under 40 for male participants and under 50 for female participants were assessed. The results still showed that more women in older ages were affected by lower HDL levels. Various studies have shown that female participants have higher levels of HDL-C than male participants. In a recent study from this center by Mokhtarpour et al., the impact of gender on diabetes complications was assessed. In that study, there was a significant difference between male and female participants, but female participants had higher levels of HDL-C. These data were from the same center, with participants of similar culture and socioeconomic status as this study, and the only difference is age, which suggests that we should put more effort into addressing HDL-C levels in older adults [23].

Metabolic syndrome

Metabolic syndrome is one of the most common diabetes-related complications that has synergy with aging and diabetes in the older adult population. In this study, metabolic syndrome was reported as the most prevalent complication, accounting for 71.4% of all the complications evaluated. Globally, the prevalence of metabolic syndrome in the general adult population varies from 12.5 to 31.4% [24]. In a study conducted in Mexico, the prevalence of metabolic syndrome in nondiabetic older adults varied widely from 36 to 52%. A diabetic care study found that the prevalence of metabolic syndrome in older adults with diabetes was 28.1% according to the ATP III criteria. Orcses et al. revealed that the prevalence of metabolic syndrome among older adults in Ecuador is 66% [25]. Another study in China revealed that metabolic syndrome was diagnosed in 1 in every 2 older adults, and for those over 70 years old, the propensity grows [26]. In this study, this percentage was higher than we predicted and will increase over time with the growth of the older adult population in Iran and its prevalence with age.

According to the NCEP ATP III modified by AHA/NHLBI criteria [27], 22% of the patients had two, 28% had three, and 44% had four or more metabolic syndrome components. We evaluated the relationship between age and metabolic syndrome and found that it increased with age. There is an important association between two specific metabolic syndrome criteria and mortality rates in older adults with T2DM. In a study conducted by Mozaffarian et al., there was a higher mortality rate in older adults who had metabolic syndrome with elevated fasting glucose levels and/or hypertension [28]. Another study revealed that metabolic syndrome itself, without any relation to a specific component, can increase the mortality rate by 2 to 5-fold.

The high prevalence of metabolic syndrome is one of the major causes of cardiovascular complications and mortality in older adults. In the Italian Longitudinal Study on Aging, there was a significant association between metabolic syndrome and chronic heart disease, in addition to a high correlation between metabolic syndrome and diabetes [29]. Wang et al. stated that metabolic syndrome had a significant association with an increased risk of MI, stroke, and CVD mortality, independent of CVD risk factors, in Chinese older adults [30]. The results of different studies are controversial. Sattar et al. revealed that metabolic syndrome and its components have weak or no correlation with vascular disease risk in geriatrics [31]. On the other hand, Monami et al. reported in their analysis that age and metabolic syndrome are independent of each other, and more than 70% of patients with metabolic syndrome have a higher mortality rate in future years [32].

In conclusion, the high prevalence of metabolic syndrome among older adults with T2DM in this study highlights the need for early detection and management of this complication. As metabolic syndrome is associated with increased cardiovascular complications and mortality, clinicians should consider this when developing therapeutic plans and strategies for individualized care.

HbA1c

In this study, we found that approximately half of the participants had HbA1c levels either below 6.5 or above 8. Previous studies have shown that an HbA1c level of less than 6.5 is not beneficial for lowering the risk of cardiovascular complications in T2DM and can increase the possibility of hypoglycemia, which may lead to a higher rate of frailty and impotence in this population group. There is a J-shaped nonlinear relationship between HbA1c level and all-cause mortality, and a U-shaped nonlinear relationship between HbA1c and heart failure in the group of cardiovascular complications [33]. An HbA1c level of more than 8 can increase all cardiovascular-related complications and mortality, while low levels of HbA1c (< 6.5) can also cause the same result, leading to a decreased risk. Half of the study patients were at higher risk of cardiovascular complications resulting from intensive or poor glycemic control. On the other hand, we should be conscious of the effect of age on HbA1c levels. Although HbA1c is the gold standard laboratory test for assessing long-term glycemic control in patients, multiple conditions can cause falsely higher or lower results of HbA1c, such as decreased RBC count and anemia [34]. There is a controversial perspective about the impact of age on HbA1c levels, but most studies agree that all clinicians should consider this effect to individualize therapeutic plans based on each patient’s complications. It will be even more crucial if clinicians aim to prevent mild or intense glycemic control and remain cautious when using HbA1c results to guide therapeutic plans.

Diabetic kidney disease

In 22.6% of the study’s participants, diabetic kidney disease was more prevalent in the female population. Barzilay et al. revealed in their study that participants with albuminuria are more likely to be hospitalized for any underlying cause [35]. revealed that there is a correlation between albuminuria and disability in older adults with diabetes, and approximately one in every five older adults can suffer from a higher likelihood of hospitalization and disability [36].

Retinopathy

In this study, 14.7% of the patients had retinopathy, including 6% with proliferative retinopathy. The prevalence of diabetic retinopathy was estimated to be 41.9% in a meta-analysis and review conducted in 2017 [37]. Furthermore, due to the progression of aging, patients may have difficulty noticing changes in their vision, which can delay their visits to ophthalmology clinics. Voigt et al. revealed in their study that the occurrence of proliferative retinopathy in the first 10 years after a diabetes diagnosis is rare, and it is notable that, in older ages, a serial ophthalmology consultation can reduce the development of this complication [38]. The incidence of retinopathy in our study was lower than projected in other studies. This phenomenon may be attributed to low insurance coverage, limited access to hospitals with ophthalmology clinics, and insufficient social support, all of which reduce the likelihood of receiving routine eye exams.

Blood glucose lowering treatment

The ADA suggests in geriatric diabetes management that every physician should set therapeutic goals based on the patient’s overall health category to minimize complications and achieve better control. Deintensification and simplification are key components of these treatments [2]. In this study, 88.9% of the participants used antidiabetic oral agents, which is one of the most straightforward treatment plans for this age group. A total of 6.8% of the patients were receiving insulin, followed by combination therapy of insulin and antidiabetic oral agents (4.3%), which could be one of the intangible regimens at this age. Insulin regimens alone are not popular in older adults due to the difficulty of regular, timely, and precise injections, and the increased risk of falls and hypoglycemia [3]. As recommended by guidelines, every insulin therapy regimen should be revised with a simple, individualized plan that has a tolerable level of complexity, suited to older patients’ self-management abilities [21].

Various studies worldwide have focused limited attention and research on adults over 65 years old, despite the increasing incidence of diabetes-related complications and aging being global concerns. According to Iran’s population pyramid, there will be a significant increase in the older adult population in the next 30 years, and the prevalence of diabetes will rise accordingly. Therefore, more attention, care, and better individualized therapeutic plans are needed for older adults to reduce diabetes-related mortalities and complications.

Conclusion

The findings of the article will help inform the development of interventions to improve the prevention, diagnosis, and management of T2D in older adults in the Iranian population.

Limitations

This study has several limitations. Like any other cross-sectional study, the role of residual confounders cannot be ruled out. The poor health category in overall geriatric health categories was not included in the study. Additionally, the mortality rate was not assessed. In this study, the lifestyle changes due to the physician’s recommendations, such as diet and physical activity changes, were not evaluated. Hence, these shortcomings can be addressed in future studies.

Strengths

This study has considerable strengths. The substantial number of participants enhanced the accuracy and depth of our understanding of the older adult population. The majority of clinical characteristics were obtained from patients through standardized measurements and medical assessments.