Background: Cardiovascular diseases (CVDs) are the major cause of mortality and disability in patients with type 2 diabetes mellitus (T2DM). The increased risk of major cardiovascular (CV) events in patients with T2DM causes an estimated 12-year reduction in life expectancy. Despite their heightened CV risks, most T2DM patients do not meet treatment targets for multiple CV risk factors. Moreover, in the UAE, the incidence of cardiometabolic diseases is exceedingly high, impacting young patients and leading to a high burden of premature CV events. Summary: We propose this comprehensive cardiometabolic evaluation to address both glycemic control and early diagnosis of CV complications as well as early implementation of multifactorial intensive therapies that are evidence and guideline based. Widespread utilization and implementation of the guidelines in primary diabetic care, coupled with early referral to a CV or the relevant specialists, will result in a significant reduction of CV events and CV hospitalization in the UAE population. Hence, the Emirates Diabetes and Endocrine Society with the Emirates Cardiac Society collaborated for the first time to develop these recommendations. These will aid in the early identification of CV risk factors in persons with prediabetes and diabetes, as well as their effective assessment and management. These guidelines are aimed not just at primary care physicians but also specialists, perhaps leading to a more collaborative and multidisciplinary approach to the prevention, diagnosis, and treatment of patients with diabetes and CVD. Key Message: The establishment of combined cardiometabolic clinics providing comprehensive assessment and management in every major cardiology and diabetology center, particularly in patients who have already had a CV event, where the combined involvement of a cardiologist and a diabetologist in an intensive multifactorial outpatient program is urgently required to prevent recurrent CV events. In addition, establishing a National Cardiometabolic Registry is an essential element of this recommendation.

Diabetes mellitus (DM) remains one of the most prevalent chronic diseases globally. Cardiovascular disease (CVD) is the most prevalent cause of morbidity and mortality in people with DM [1]. It frequently coexists with other cardiovascular (CV) risk factors such as hypertension, obesity, and dyslipidemia, sometimes known as the metabolic or cardiometabolic syndrome. Several investigators have reported that molecular mechanisms linked to DM raise the risk of CVD on their own. As a result, reducing CV risk factors in patients with DM is crucial for reducing the long-term untoward CV outcomes [2].

Currently, primary care professionals treat 90% of people with type 2 diabetes mellitus (T2DM) [3]. The average visit is too short [4] to comprehensively discuss CV risk factors with patients who are at high risk for CVD and DM. If these risk factors are not timely addressed, they may lead to ischemic heart disease, ischemic stroke, peripheral artery disease, and congestive heart failure, which are the common causes of long-term morbidity and mortality in patients with DM. A paradigm shift can now be observed from a focus on the control of HbA1c (only) to an organ-protective approach with greater emphasis on cardio-renal risk protection based on the data showing significantly improved cardio-renal outcomes with sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists along with tight control of traditional CV risk factors. The European Society of Cardiology (ESC) already in 2019 including evidence from key CV outcome trials (CVOTs) emphasized the need for this approach. The ESC guidelines have been consistently confirmed by other international scientific societies including the recent American Heart Association (AHA) statement (2022) [5]. Based on the above, for the first time, the Emirates Diabetes and Endocrine Society and the Emirates Cardiac Society have come together to create the proposed guidelines. This will help in the early recognition of the CV risk factors in people with prediabetes and diabetes, followed by their proper evaluation and management. These guidelines are not only directed toward the primary care professionals but also the specialists which may further lead to a more collaborative and multidisciplinary approach to the prevention, detection, and management of patients with DM and CVD.

The global burden of noncommunicable diseases (NCDs) is increasing rapidly, and CVD remains the leading cause of death and disability. It is estimated that 85% of CVD deaths are caused by ischemic heart disease and stroke. The risks of CVDs are multifactorial and largely modifiable; the most common are obesity, central obesity/abdominal obesity, hyperglycemia, dyslipidemia, and hypertension [6]. According to the World Health Organization (WHO) predictions and projections, these risk factors are rapidly increasing in the United Arab Emirates (UAE) [7].

Diabetes and Prediabetes

According to the International Diabetes Federation (IDF), more than 73 million adults have been diagnosed with diabetes in the Middle East and North African (MENA) region, which has the highest diabetes prevalence rate (16.2%) in all the IDF regions [8]. Age-adjusted (20–79 years) comparative prevalence of diabetes in the UAE is 16.4%, with diabetes-related expenditure (per person) of 2,109.5 USD [8]. According to Hamoudi et al. [9], prevalence of prediabetes ranged from 8 to 17%. Two large national surveys were conducted in the UAE. In Abu Dhabi, the Weqaya Program (n = 50,138) reported that 17.6% of the population was diagnosed with diabetes [10]. The prevalence of diabetes among UAE nationals was 21% in males and 23% in females. In Dubai, a household health survey indicated that the prevalence of diabetes among Emiratis was 19.3%, among Expat was 12.4%, and the overall prevalence of diabetes in Dubai was 13.7% [11]. An alarming situation is that 40.7% of the diabetic population in the UAE is undiagnosed with diabetes [12]. The prevalence of prediabetes varies widely throughout the literature mainly because of the different diagnostic criteria that are used [13]. The Weqaya program in Abu Dhabi reported the prevalence of prediabetes to be dramatically high, reaching up to 27.1% [14]. It was reported by the IDF that, in the UAE, the prevalence of impaired glucose tolerance was 18.3% [15].

The obesity epidemic was predicted by WHO in 1997, and it has now become a true pandemic, affecting young people [16]. Obesity and overweight are major health problems since they increase the risk of developing diabetes, CVD, hypertension, chronic kidney diseases (CKD), and other complications [16‒18].

In the UAE, the prevalence has doubled from 1989 to 2017, and the current prevalence rate is 31.7% [17, 18]. Another survey reported that approximately one-third of the UAE population was obese and almost 40% was overweight [16]. In the UAE and Gulf Cooperation Council (GCC) nations, an increase in per-capita income and economic growth, coupled with increasing life expectancy, has resulted in increasing rates of obesity and associated NCDs. The levels of inflammatory and oxidative stress markers were highly prevalent among overweight/obese Emirati women, and this may predispose them to increased CV risks at relatively young age [19].

Hypertension

Hypertension is also one of the major NCDs and a public health challenge that increases the risk of developing CVD [20]. The Gulf region has become one of the most affected regions by hypertension, and the prevalence ranges from 26.1% in Saudi Arabia to 37% in Kuwait [20]. Among the UAE population, a cross-sectional study found that 22.4% were hypertensive, and men had higher blood pressure than women [20]. The Weqaya Program in Abu Dhabi showed an overall prevalence of hypertension of 23.1% [14]. According to the Dubai Household Survey (2019) (n = 2,530), 32.5% of adults reported being diagnosed with hypertension (38.37% of males and 16.66% of females) [21].

Metabolic Syndrome

Metabolic syndrome is a multifactorial condition that is characterized by a combination of three or more of the following risk factors: increased waist circumference, high triglycerides, low high-density lipoprotein cholesterol (HDL-C), high blood pressure, and high fasting blood glucose [22] (Fig. 1). Metabolic syndrome alone increases CVDs by twofold even without the presence of DM. According to a cross-sectional population-based study conducted in the UAE, metabolic syndrome prevalence was 37.4% (32.7% in women and 39% in men). The prevalence was 33.6% in the Emirati population, 34.5% in the Arab non-Emirati population, and 40.7% in the Asian population [23]. The young adult population in the UAE has a high prevalence of metabolic syndrome compared to global estimates in the same age group. A cross-sectional national survey showed that the prevalence of diabetes and cardiometabolic risk factors in young men (aged 18–29) in the UAE was high. The age-adjusted prevalence was 4.7% for diabetes, 41.3% for impaired fasting glucose, 5.5% for hypercholesterolemia, 11.5% for hypertriglyceridemia, and 10.4% for hypertension. Overall, 62% presented at least one of these risk factors [24].

Fig. 1.

Clinical manifestations and diagnostic parameters of metabolic syndrome. BG, blood glucose; HDL-C, high-density lipoprotein cholesterol.

Fig. 1.

Clinical manifestations and diagnostic parameters of metabolic syndrome. BG, blood glucose; HDL-C, high-density lipoprotein cholesterol.

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Dyslipidemia

A study examining the lipid control over 5 years in patients with diabetes across primary and tertiary government health sectors in Dubai found that 60.5% of patients achieved LDL levels <100 mg/dL. Non-HDL-C levels <130 mg/dL were achieved in 67.9% of patients in tertiary care in 2012 compared to 60.9% in primary care. UAE nationals had better lipid control across the study duration compared to expatriates [25]. The Weqaya program in Abu Dhabi reported dyslipidemia rates to be high (44.2%), with newly diagnosed individuals having high LDL and low HDL levels. The low HDL levels were reported to be a greater contributor to dyslipidemia than the high LDL levels [14].

Dietary Practices, Physical Activity, and Smoking

A cross-sectional study conducted in 628 randomly selected households in all seven Emirates reported that across all gender-age groups, 43% of girls and 38% of boys (6–10 years) consumed more calories than their estimated energy requirements. Snacking represents a major source of Emirati caloric intake (>20%) of total calories. In addition, caloric beverages account for 8–14% of total calories, emphasizing to pay more attention to educating the public on nutrition. A high prevalence of physical inactivity was observed among the sampled population of Dubai (85.1%), 95.4% of which did not engage in vigorous-intensity activities [26]. According to the UAE Ministry of Health and Prevention 2010 report, the prevalence of smoking any tobacco product was 21.6% among men and 1.9% among women [27].

Obstructive Sleep Apnea

The linkage between obstructive sleep apnea (OSA), obesity, metabolic syndrome, hypertension, left ventricular hypertrophy, and atrial fibrillation is well established. The major barriers to diagnosis and treatment are that many people do not recognize the symptoms and severity of the condition, and HCPs do not regularly ask about the duration and quality of sleep or screen patients for OSA. HCP should ask about symptoms and there should be =1 of the following:

  • Daytime sleepiness, unintentional sleep episodes, unrefreshing sleep, fatigue, or difficulty staying asleep

  • Awakening with breath-holding, gasping, or choking

  • Reports by a bed partner of loud snoring, breathing interruptions, or both in the patient’s sleep

  • The patient and any bed partners, roommates, or housemates are all sources for clinical risk assessment

  • Patients with poorly controlled hypertension (which may be caused or exacerbated by OSA), atrial fibrillation or other arrhythmias, heart failure (which may cause OSA), stroke, or diabetes

  • STOP-BANG score (see the questionnaire, online suppl. Table 1; for all online suppl. material, see https://doi.org/10.1159/000531107)

    • 1.

      Overnight oximetry

    • 2.

      In such cases, to confirm the diagnosis, measurement of neck circumference is required (>17 inches in men, >16 inches in women)

  • Once OSA is suspected, referral to an expert is needed

    • 1.

      Polysomnography for oxygen desaturation, apnea, and hypopnea events

    • 2.

      ENT examination for upper airway obstruction

Obesity

Obesity is defined as an abnormal or excessive fat accumulation that may impair health. Classification of obesity as per BMI is given in online suppl Table 2.

Diet, physical activity, and behavioral therapy are recommended at all levels of BMI, with pharmacologic and surgical interventions recommended for weight management in obesity [28]. Obesity and adverse CVD outcomes with management are illustrated in Figure 2 and online suppl Table 3.

Fig. 2.

Obesity and adverse CVD outcomes with management.

Fig. 2.

Obesity and adverse CVD outcomes with management.

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Nonalcoholic Fatty Liver Disease and NASH

NAFLD has reached epidemic proportions fueled by the increase in the incidence of obesity and T2DM, creating a need for endocrinology and primary care clinicians to become engaged in its early diagnosis and management. This is especially relevant given the fact that the vast majority of persons with T2DM, who may have underlying NAFLD, are predominantly seen by primary care clinicians and endocrinologists but remain undiagnosed and untreated.

The presence of NAFLD has also been associated with microvascular diabetic complications, especially CKD [29]. A meta-analysis including 20 cross-sectional studies with approximately 28,000 individuals reported that NAFLD was associated with a twofold increased prevalence of CKD (odds ratio [OR], 2.12; 95% CI, 1.69–2.66) [30]. In the 13 longitudinal studies included in the meta-analysis, NAFLD was associated with an overall 80% increased risk of incident CKD.

Women with polycystic ovary syndrome (PCOS) are at increased risk of T2DM and NAFLD. A recent meta-analysis among 10,576,383 individuals across 24 countries in nonobese persons with NAFLD, aiming to remove obesity as a confounding factor, found that there was still a much higher incidence rate of new-onset CVD in individuals with NAFLD (18.7 per 1,000 person years; 95% CI, 9.2–31.2). A 2015 analysis of the Framingham Heart Study found that hepatic steatosis was strongly associated with subclinical CVD outcomes, independent of other metabolic risk factors. Based on pathophysiology persons with NAFLD will be at risk of other CMD manifestations, and individuals who have one or more CMD manifestations will be at increased risk of NAFLD. ASCVD is the principal cause of death in patients with NAFLD [31]. NAFLD can be considered a risk enhancer when ASCVD risk is assessed in patients [32].

Clinicians should recommend lifestyle changes in persons with excess adiposity and NAFLD with a goal of at least 5%, preferably 10% weight loss, as more weight loss is often associated with greater liver histologic and cardiometabolic benefit, depending on individualized risk assessments. In summary, exercise has shown to consistently benefit persons with NAFLD, the challenge being long-term adoption. Benefit from increasing physical activity appears to be more linked to the intensity and adherence to the training program rather than the type of exercise. Of note, a decrease in hepatic steatosis with exercise is observed even in the absence of major weight loss [33].

At present, there are no FDA-approved drugs for the treatment of NASH [34]. Therefore, treatment recommendations for persons with T2DM and NASH are centered on the dual purpose of treating hyperglycemia and/or obesity. To offer cardiometabolic benefit in persons with T2DM and NAFLD, clinicians must consider treatment with GLP-1RAs, pioglitazone, or SGLT-2 inhibitors [35]; however, there is no evidence of benefit for treatment of steatohepatitis with SGLT-2 inhibitors [36].

Treatment with GLP-1RAs or bariatric surgery that induces sustained weight loss leads to improvement of common comorbidities in NAFLD, such as hypertension, sleep apnea, atherogenic dyslipidemia, hyperglycemia with frequent resolution of diabetes, and amelioration of the risk of CVD and HCC. Bariatric surgery is considered in patients with NASH and BMI >35 with remission of T2DM, improved dyslipidemias, and risk of ASCVD events [37, 38] (online suppl. Fig. 1).

There is a high prevalence of metabolic syndrome in the UAE, and physicians must remain vigilant about recognizing the phenotype and the associated multi-component risk management. Recognizing the presence of one of these conditions should prompt screening for the others.

Screening and Diagnosis of Cardiometabolic Complications

The ability to accurately identify people at high risk of cardiometabolic events allows for more extensive risk factor treatment to lower the chance of an incident of heart failure (HF) or atherosclerotic cardiovascular disease (ASCVD). Risk variables are used in a variety of ways to assess a person’s both cardiometabolic and CVD risk [39] (Fig. 3, 4). In this consensus, we will use a modified updated risk stratification algorithm initially published by the EDES in their guidelines in 2020.

Fig. 3.

Metabolic syndrome – dysglycemia/prediabetes/OSA – screening and diagnosis.

Fig. 3.

Metabolic syndrome – dysglycemia/prediabetes/OSA – screening and diagnosis.

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Fig. 4.

Biomarkers, electrocardiography, and imaging for clinical assessment of CV damage. hsTnT, High Sensitivity Troponin; NT-ProBNP, N-terminal prohormone BNP; FPG, fasting plasma glucose; PPG, postprandial plasma glucose; CT, computed tomography; CRP, C-reactive protein.

Fig. 4.

Biomarkers, electrocardiography, and imaging for clinical assessment of CV damage. hsTnT, High Sensitivity Troponin; NT-ProBNP, N-terminal prohormone BNP; FPG, fasting plasma glucose; PPG, postprandial plasma glucose; CT, computed tomography; CRP, C-reactive protein.

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Clinical Assessment of CV Damage

  • Recommendations for the use of a biochemical, electrocardiogram, and imaging testing are given for CV risk assessment in asymptomatic patients with diabetes.

  • Routine assessment of microalbuminuria is indicated to identify patients at risk of developing renal dysfunction or at high risk of future CVD [40].

  • Annual resting ECG is indicated in patients with DM diagnosed with hypertension or with suspected CVD [41].

  • Annual biomarkers including NT-proBNP (>125) and High Sensitivity Troponin were used for detection of early stages of CVD; if NT-proBNP is not available, then BNP may be used (>30).

  • Ankle-brachial index (ABI) performed in clinic annually should be considered a risk modifier in CV risk assessment [42].

  • Coronary artery calcium (CAC) score with non-contrast CT directly detects the presence of calcified coronary atherosclerosis in asymptomatic patients with diabetes at moderate risk where the clinical suspicion is increased if additional risk enhancers are present, for example, family history. CAC should be considered a powerful risk modifier in the CV risk assessment of asymptomatic patients with DM at moderate risk [44] and may be repeated in 5 years.

  • Risk scores developed for the general population SCORE, Framingham, and American College of Cardiology (ACC), AHA, and PCE are not recommended for CV risk assessment in patients with DM in the UAE as they underestimate risk, particularly in young patients in the UAE.

Additional RISK Assessment Tools

  • CT coronary angiogram (CTCA) or functional imaging (radionuclide myocardial perfusion imaging, stress cardiac magnetic resonance imaging, or exercise or pharmacological stress echocardiography) may be considered in asymptomatic patients with DM or patients with abnormal ECG for evaluation of coronary artery disease (CAD) [45].

  • Assessment of carotid and/or femoral plaque burden with arterial ultrasonography should be considered as a risk modifier in asymptomatic patients with DM [46].

  • Imaging assessment femoral arteries by cardiac or vascular specialist by CT or magnetic resonance imaging may be considered a risk modifier in symptomatic patients with DM at moderate or high-risk peripheral arterial disease (PAD)/CVD [47].

Comprehensive Multimodality Cardiometabolic Therapies

Lifestyle modification is applicable at all stages of cardiometabolic disorders (CMDs) and needs to be continually reinforced as it impacts all of the risk factors simultaneously.

Lipids

In T2DM, the risk of ASCVD is strongly determined by the presence of target organ damage. Hypertension, dyslipidemia, abdominal obesity, and nonalcoholic fatty liver disease (NAFLD) commonly coexist with T2DM (online suppl. Fig. 2). Dyslipidaemia in T2DM and metabolic syndrome is typically represented by elevation of both fasting and postprandial TG, Apo-B, small dense LDL, and low HDL-C and Apo-A1 levels.

We recommend a diet with low saturated fat, high in fiber and fish; target body mass index of 20–25 kg/m2; waist <37 inches in men and 31.4 inches in women; 3.5–7.0 h of moderate physical activity per week or 30–60 min most days (Fig. 5, 6). In addition to lifestyle modification, we recommend initially a high-intensity statin up to the highest tolerated dose to reach target goals for specific levels of risk.

Fig. 5.

Lifestyle modification for cardiometabolic disorders.

Fig. 5.

Lifestyle modification for cardiometabolic disorders.

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Fig. 6.

Eligible high- and very high-risk diabetic patients.

Fig. 6.

Eligible high- and very high-risk diabetic patients.

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We recommend reassessing the LDL at 4–6 weeks and, if the goal is not reached, switching to statin in combination with ezetimibe. The addition of other agents like proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors (including the siRNA (RNAi) inhibitors) should be considered in patients not achieving the LDL target (on maximally tolerated statin therapy) or patients with “statin intolerance.”

In randomized controlled trials, neither ezetimibe nor the PCSK9 inhibitors have been reported to increase the risk of DM. In patients with ASCVD or other CV risk factors on a statin with controlled LDL cholesterol but persistently elevated triglycerides (135–499 mg/dL), the addition of icosapent ethyl can be considered to reduce CV risk.

Combination of maximum tolerated statin, ezetimibe, and PCSK9-targeted therapies in very high-risk patients (in particular DM with established ASCVD/PAD) to achieve 85% reductions of LDL and target LDL of less than 1.4 achieves a linear reduction in CV events [48]. Utilization of fixed-dose combination of statin and ezetimibe maximizes adherence. In addition, the PCSK9 siRNA inclisiran has shown reduction of LDL and proportionate CV events using a 6-month injection, a strategy that maximizes adherence to lipid lowering [49]. We typically obtain a lipid profile at the initiation of statins or other lipid-lowering therapy, 4–6 weeks after initiation or a change in dose, and annually thereafter, as it may help to monitor the response to therapy and inform medication adherence (online suppl. Fig. 3).

ESC/EASD-2019 [50] guidelines recommend to achieve a minimum 50% reduction from baseline LDL and also achieve the below risk-specific targets:

  • LDL-C <100 mg/dL – patients with T2DM at moderate CV risk

  • LDL-C <70 mg/dL – patients with T2DM at high CV risk

  • LDL-C <55 mg/dL – patients with T2DM at very high CV risk

Hypertension in Patients with Dysglycemia

High blood pressure is the main risk factor for CVD and all-cause mortality. There is ample evidence that blood pressure lowering leads to reduced CVD and total mortality. Hypertension is defined as a sustained blood pressure =130/80 mm Hg. While blood pressure should be confirmed using multiple readings, patients with BP =180/110 mm Hg and CVD could be diagnosed with hypertension at a single visit [51]. Home BP monitoring is recommended to confirm treatment effectiveness [52]. A healthy lifestyle with weight loss when indicated, reducing dietary sodium, increasing dietary potassium intake, and increasing physical activity, preferably as recommended in the Dietary Approaches to Stop Hypertension (DASH)-style eating pattern [53].

Pharmacologic therapy should be started when BP is =130/80 mm Hg, aiming for a target BP of <130/80 mm Hg. However, target BP can be individualized, taking into consideration CV risk, potential drug side effects, and patient preference. Patients with BP =160/100 mm Hg should be started on two drugs, preferably in a single pill to aid adherence. Angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) are the recommended first-line therapy for the treatment of hypertension in people with diabetes and CAD and/or albuminuria. Regular testing for serum creatinine/eGFR and potassium levels should be assured. Other classes of BP medications with evidence-based CV mortality benefits include calcium channel blockers and thiazide-like diuretics [54]. For those not meeting BP targets on three classes of antihypertensive medications (including a diuretic), a mineralocorticoid receptor antagonist (MRA) should be considered.

In diabetic hypertensive patients with sympathetic overdrive manifested by a heart rate >80 associated with metabolic syndrome and obesity, the use of glycemically neutral and highly selective beta-blockers is recommended [55] as elevated heart rate doubles the risk of CV events [56]. In some of these patients, investigations for secondary causes of hypertension may be warranted.

Antiplatelet Therapy and Antithrombotic Therapy

Antiplatelet therapy is recommended for secondary prevention of CV events in patients with diabetes [57]. Historically, antiplatelet therapy with aspirin or clopidogrel in aspirin-allergic patients was used. Adults who are being evaluated for CVD prevention should undergo a thorough risk assessment as delineated previously (particularly high and very high risk) and have a clinician-patient risk discussion before starting on aspirin. In addition, assessing for other risk-enhancing factors can help guide decisions about preventive interventions in selected individuals, as can CAC scanning (online suppl. Fig. 4).

The CV outcomes for people using anti-coagulation strategies (COMPASS) study established the evidence-based role of the addition of aspirin to a “CV” dose of rivaroxaban 2.5 mg in CV residual risk reduction in diabetics (chronic CAD and PAD) as well as diabetics with CKD [58].

Management of CKD and Microalbuminuria as CV Risk Factors

The clinical importance of screening and treating patients with diabetes and CKD/DKD to preserve kidney function and reduce CV risk is highlighted [59]. Proteinuria indicates abnormal excretion of protein by the kidneys, whereas albuminuria refers to an abnormal excretion rate of the specific protein albumin. It is a marker of endothelial dysfunction and increased risk for CV morbidity and mortality, especially, but not exclusively, in high-risk populations such as diabetics and hypertensives [60]. The CKD stages reflect progression of CV risk, as shown in Table 1. Patients with progressive diabetic kidney disease are twice more likely to have CVD events and die of CVD than patients with renal complications [61, 62]. It reflects the urgent need for intensification of multiple protective therapies and increased frequency of testing and referral.

Table 1.

KDIGO 2022, clinical practice guideline for diabetes management in CKD [63]

Table 1.

KDIGO 2022, clinical practice guideline for diabetes management in CKD [63]

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Treatment

People with diabetes and moderately elevated ACR and/or eGFR <60 should be referred to the relevant specialists. ACE inhibitors and ARBs are not recommended for the primary prevention of CKD in patients with diabetes who have normal blood pressure, normal urine albumin-creatinine ratio, and normal eGFR [53]. In the treatment of albuminuria/nephropathy, both ACE inhibitors and ARBs can be used. In T1DM with or without hypertension, with microalbuminuria or clinical albuminuria, ACE inhibitors are the initial agents of choice. In hypertensive T2DM with microalbuminuria or clinical albuminuria, ACE inhibitors or ARBs are the initial agents of choice. If one class is not tolerated, the other should be substituted. Besides optimum blood glucose control, in patients with T2DM and CKD, both SGLT2 and a selective nonsteroidal mineralocorticoid receptor agonist, finerenone, can be used, alone or in combination, early in a wide range of DKD to reduce cardiac events and renal worsening. The use of an SGLT2-inhibitor in patients with an eGFR <60 and =20 mL/min/1.73 m2 or urinary albumin =30 mg/g creatinine is recommended to reduce CKD progression and CV events [64]. In patients with a broad range of diabetic CKD stage, 1–4 with GFR 90-25 mL/min or urine albumin-creatinine ratio 30–300 mg/gm are at significantly increased risk of both CV events and CKD progression or are unable to use an SGLT2-inhibitor, finerenone is recommended to reduce CKD progression and CV events [65, 66]. Both SGLT2-inhibitors and finerenone can be safely used together in DKD [67].

Smoking

Smoking is an important modifiable risk factor for CVD. The number of smokers worldwide has increased to 1.1 billion in 2019, with tobacco smoking causing 7.7 million deaths annually including 1 in 5 deaths in males worldwide [68]. All patients with CVD should be screened for tobacco or electronic cigarette smoking. Minimal counseling on the importance of smoking cessation should be granted to all patients with CVD risk factors to reduce the rate of smoking and subsequent CVD events [53].

The following should be accessible to adults who smoke:

  • Behavioral interventions: behavioral support and very brief advice on quitting smoking

  • Medicinally licensed products: nicotine replacement therapy, bupropion, and varenicline [69]

Hypoglycemia

Hypoglycemia, usually caused by insulin or sulphonylurea therapy, is limiting a key factor in achieving tight glycemic control in patients with diabetes [70]. Severe hypoglycemia causes QT prolongation, which is a strong risk factor for severe ventricular arrhythmias and sudden death [71]. Severe hypoglycemia is one of the predictors of ASCVD in those with T2DM. However, recent CVOTs did not show a link between hypoglycemia and increased CV morbidity or mortality [72, 73]. Nevertheless, educating patients and their caregivers on the prevention, recognition, and prompt treatment of hypoglycemia is important.

Management of Heart Diseases and Vascular Diseases in Dysglycemia Patients

Prevention and treatment of heart failure in patients with impaired glucose metabolism includes the following:

  • a.

    Lifestyle intervention particularly weight loss and cardiac rehabilitation

  • b.

    Pharmacotherapies combining SGLT-2 inhibitor with ARNI or ACE inhibitor, MRA, and ß blockers

  • c.

    Treatment of atrial fibrillation in patients with impaired glucose metabolism for stroke prevention and rate versus rhythm control, where SGLT-2 inhibitor has been shown to decrease atrial fibrillation incidence and progress in DECLARE study

  • d.

    Use of GLP1-RA and metabolic surgery in diabetic patients with obesity and heart failure (in particular HFPEF) has been shown to improve hypertension, sleep apnea, atrial fibrillation burden as well as functional capacity and MRI/ECHO parameters of diastolic dysfunction. Metabolic surgery is associated with a 62% reduced risk of developing heart failure [74]

Coronary Artery Disease and Chronic Coronary Syndrome

A stable chronic coronary syndrome is managed by both disease-modifying agents and symptomatic therapy; disease-modifying agents include dual antiplatelet (aspirin plus clopidogrel), statins, and ACE inhibitors. Symptomatic therapy includes ß-blockers, nitrates, non-dihydropyridine calcium channel blockers, trimetazidine, ivabradine, and ranolazine. Dysglycemia adds more risk to cardiac conditions; in this respect, T2DM increases the percentage of small dense LDL, which is more readily deposited in the blood vessels, and according to the recent evidence, using GLP1 agonist is recommended for the high-risk patients to reduce CV events, especially MI and stroke [76] (online suppl. Fig. 5).

Atrial Fibrillation

In diabetic patients with atrial fibrillation (non-valvular), the risk of embolic stroke is markedly elevated. Thus, for stroke prevention, direct oral anti-coagulants (apixaban 5 mg bid, dabigatran 150 mg bid, edoxaban 60 QD, and rivaroxaban 20 QD) are superior to warfarin with 60% reduced risk of intracranial hemorrhage. However, unlike the other direct oral anti-coagulants, DM patients treated with apixaban bled more (3.0%/year) than did subjects without diabetes (1.9%/year) [77‒80]. Standard dosing is recommended except with significant CKD. Aspirin is not recommended as it is inferior and does not reduce the risk of bleeding [81].

Atrial fibrillation is managed through rate or rhythm control, which can be accomplished through medication or pulmonary vein isolation, and most importantly, upstream management, which addresses the underlying disease and precipitating factors, especially sleep apnea and obesity, which are major triggers of atrial fibrillation recurrence. It is important to note that diabetes is one of the risk factors for stroke [82].

Chronic Heart Failure and Diabetic Cardiomyopathy

Chronic heart failure is the third most common cardiac condition in dysglycemia patients, and it is the least well-recognized and poorly diagnosed, commonly presenting as heart failure with preserved ejection fraction [83]. The symptoms of heart failure in outpatient diabetics are often vague and contribute to the misdiagnosis; however, key symptoms that should be asked about during every visit include exertional fatigue, inability to go one flight upstairs (NYHA functional class-II), lower limb edema, and exertional palpitation. In this situation, NT-proBNP and an ECG should be obtained with a fast-track referral to a cardiologist, and a detailed Echo should be obtained. For an asymptomatic diabetic patient, the ADA has recently recommended annual screening with NT-ProBNP to diagnose the early stages of HF, initiate the guideline-directed therapy for heart failure, and obtain an Echo [5].

Based on aggregate population and clinical trial data, the biomarker thresholds for clinical use in the outpatient diabetic setting include a BNP >50 pg/mL and NT-proBNP >125 pg/mL, and this is an integral part of the new Universal Definition of Heart Failure [84]. Among patients with advancing age, more advanced CKD or atrial fibrillation, including anemia, OSA, pulmonary hypertension, critical illness, and sepsis, may lead to higher concentrations of prognostic biomarkers. Obesity may lower natriuretic peptide concentrations even in the presence of significant HF risk [85]. If a patient has an abnormal NT-proBNP or BNP above the cutoff point, this confirms the presence of heart failure; thus, referral for Echo and cardiology evaluation is recommended; however, based on the evidence, we recommend immediate initiation of SGLT2-inhibitor therapy even prior to ECHO and RAAS inhibitor (ARNI is preferred over ACE inhibitors and ARBs in addition to MRA). Despite all these evidence-based therapies, there is still a gap to work on heart failure as mortality remains high at 50% in 5 years.

Screening for PAD and Diabetic Foot

The presence of diabetic foot and severe peripheral neuropathy both indicate advanced target organ damage, which itself classifies diabetic patients at very high risk for CV events. Simultaneous referral to the specialty for surgical management and limb salvage as well as to cardiology for detailed assessment of associated CVD is recommended. DM patients should have annual ABI screening even if asymptomatic; if abnormal (less than 0.9 in DM), then the multifactorial management will include reclassification to very high risk and need for antiplatelets, as well as lipid-lowering targeting to LDL of 1.4 mol/L/55 mg/dL and intensive glycemic control with the addition of GLP1-RA, which has been shown to reduce amputation [86]. Diabetic-related foot problems continue to increase in number, are costly, may cause significant morbidity, and can be the direct precursor to fatality [87].

Diabetic patients account for up to 50% of all lower-extremity amputations, and most of these amputations are preceded by a foot ulcer. Given the fact that as high as 34% of all diabetics have a lifetime risk of a pedal ulceration, a consistent screening or surveillance approach can be instituted to minimize or marginalize the potential catastrophic sequelae of diabetes related to the feet [88]. Ideally, all diabetic patients should be referred to podiatry for risk stratification for the development of ulceration and other diabetic-related pathologies such as Charcot neuroarthropathy [89]. In the absence of an ability to refer to podiatry, many simple things can and should be done regularly by primary care physicians. Nurses and medical assistants can be trained to perform diabetic pedal screenings or assessments. All diabetic patients should be asked to take both of their footwear for inspection upon each visit to evaluate for following:

Musculoskeletal

Initially, all patients should be asked to stand in order to identify any pedal deformities such as bunions, flatfeet, or hammertoes and any asymmetry between foot, ankle, and leg position.

Vascular

Skin temperature from tibial tuberosity, color return to digits, and, most importantly, the absence or presence of pedal pulses (posterior tibial and dorsalis pedis) are all evaluated to assess for arterial vascular disease. In the absence of palpable pedal pulses, an ABI is often utilized to evaluate for PAD. With more advanced disease and increasing vessel calcification seen in diabetes and end-stage renal disease, a simple ABI is not sensitive to diagnose. If the patient does not have an urgent problem (Table 2), therefore, more detailed noninvasive tests such as pulse volume recordings, toe pressure, or toe brachial indices should be considered with a referral to vascular surgeon and/or vascular medicine specialist, particularly if skin changes are noted [90].

Table 2.

Modified ADA diabetic foot risk classification [90]

PriorityIndicationsTimelineSuggested follow-up
Urgent (active pathology)  • Open wound or ulcerative area, with or without signs of infection• New neuropathic pain or pain at rest• Signs of active Charcot deformity (red, hot, swollen midfoot or ankle)• Vascular compromise (sudden absent DP/PT pulses or gangrene)  Immediate referral/consultation As determined by specialist 
High (ADA risk category 3: the diabetic foot in remission)  • Presence of diabetes with a previous history of ulcer or lower-extremity amputation• Chronic venous insufficiency (skin color change or temperature difference)  Immediate or “next available” outpatient referral Every 1–2 months 
Moderate (ADA risk category 2)  • PAD ± LOPS• DP/PT pulses diminished• Presence of swelling or edema  Referral within 1–3 weeks (if not already receiving regular care) Every 2–3 months 
Low (ADA risk category 1)  • LOPS ± longstanding, nonchanging deformity• Patient requires prescriptive or accommodative footwear  Referral within 1 month Every 4–6 months 
Very low (ADA risk category 0)  • No LOPS or PAD• Patient seeks education on topics such as routine foot care, athletic training, appropriate footwear, or injury prevention  Referral within 1–3 months At least annually for all people with diabetes 
PriorityIndicationsTimelineSuggested follow-up
Urgent (active pathology)  • Open wound or ulcerative area, with or without signs of infection• New neuropathic pain or pain at rest• Signs of active Charcot deformity (red, hot, swollen midfoot or ankle)• Vascular compromise (sudden absent DP/PT pulses or gangrene)  Immediate referral/consultation As determined by specialist 
High (ADA risk category 3: the diabetic foot in remission)  • Presence of diabetes with a previous history of ulcer or lower-extremity amputation• Chronic venous insufficiency (skin color change or temperature difference)  Immediate or “next available” outpatient referral Every 1–2 months 
Moderate (ADA risk category 2)  • PAD ± LOPS• DP/PT pulses diminished• Presence of swelling or edema  Referral within 1–3 weeks (if not already receiving regular care) Every 2–3 months 
Low (ADA risk category 1)  • LOPS ± longstanding, nonchanging deformity• Patient requires prescriptive or accommodative footwear  Referral within 1 month Every 4–6 months 
Very low (ADA risk category 0)  • No LOPS or PAD• Patient seeks education on topics such as routine foot care, athletic training, appropriate footwear, or injury prevention  Referral within 1–3 months At least annually for all people with diabetes 

DP, dorsalis pedis; LOPS, loss of protective sensation; PT, posterior tibial.

Neurologic

Neuropathy seen in diabetes can have a sensory component, a motor component, and/or an autonomic component. Typically, the sensory component is most commonly assessed to determine if there is loss of protective sensation (LOPS). This is most commonly done by evaluating the response of a 10 g monofilament wire to the plantar aspect of multiple digits, metatarsal heads, and heel. If this is not available, an Ipswich test is a reasonable substitute. This test consists of lightly touching the plantar aspect of digits 1, 3, and 5 for 1–2 s. In a metanalysis review of 5 papers, when compared to 10 g monofilament, the sensitivity of the Ipswich test ranged from 51% to 83%, and the specificity range was 96.4%–98% [91].

Dermatologic

The entire skin surface of the foot and ankle should be visualized for any dry skin, hyperkeratosis, fissuring of skin, or ulceration; this includes all of the interdigital areas. Lack of sweating, which can lead to anhidrosis, is a sign of possible autonomic neuropathy. This in conjunction with a patient who says their feet feel “cold” or “warm” (loss of autonomic vascular tone to veins and arteries, respectively) is a strong suggestion of autonomic neuropathy. There is a high crossover between patients with pedal autonomic neuropathy and cardiac autonomic neuropathy [92].

Modified ADA diabetic foot risk classification and IWGDF risk stratification system for foot screening were mentioned in Tables 2 and 3. In patients with advanced vascular disease, i.e., ABI <0.5, SGLT-2 inhibitor can be used with caution after consultation with a CV specialist (Fig. 7).

Table 3.

The IWGDF risk stratification system and corresponding foot screening frequency [88]

CategoryUlcer riskCharacteristicsFrequency
Very low No LOPS and No PAD Once a year 
Low LOPS and PAD Once every 6–12 months 
Moderate LOPS + PAD, or LOPS + foot deformity or PAD + foot deformity Once every 3–6 months 
High  LOPS or PAD, and one or more of the following• History of a foot ulcer• A lower-extremity amputation (minor or major)• End-stage renal disease  Once every 1–3 months 
CategoryUlcer riskCharacteristicsFrequency
Very low No LOPS and No PAD Once a year 
Low LOPS and PAD Once every 6–12 months 
Moderate LOPS + PAD, or LOPS + foot deformity or PAD + foot deformity Once every 3–6 months 
High  LOPS or PAD, and one or more of the following• History of a foot ulcer• A lower-extremity amputation (minor or major)• End-stage renal disease  Once every 1–3 months 

LOPS, loss of protective sensation; PAD, peripheral artery disease.

Screening frequency is based on expert opinion since no evidence is available to support these intervals. When the screening interval is close to a regular diabetes check-up, consider screening the foot at that check-up.

Table 4.

Management of cardiometabolic parameters

Table 4.

Management of cardiometabolic parameters

Close modal
Fig. 7.

Measurement of the ankle-brachial index (ABI) in the outpatient setting.

Fig. 7.

Measurement of the ankle-brachial index (ABI) in the outpatient setting.

Close modal

Multidisciplinary Referral to Address the Comorbidities

URGENT referral of symptomatic patients is essential. This would include the following:

  • Hypertension has difficulty in achieving the target blood pressure

  • ECG changes or chest symptoms suspicious of CAD

  • Palpitations

  • Atrial fibrillation (including asymptomatic) or another arrhythmia

  • Heart failure symptoms such as dyspnea and pedal edema, pulmonary congestion on chest X-ray, or elevated BNP or NT-proBNP

  • Syncope and loss of consciousness

  • Chest pain and dyspnea

  • Claudication symptoms

  • Foot ulcers

  • Asymptomatic patients with very high-risk score and patients who are screen positive need to be referred promptly for therapy intensification and reassessment

  • Asymptomatic patients with ECG abnormalities

Symptoms in sedentary patients are masked due to lack of exertion and reduced activity, thus questioning the patient – do they avoid mild exertion such as stairs due to fatigue, shortness of breath, or having increased tiredness while walking? Shortness of breath while bending down, “bendopnea” during prayer, for example, as well as ankle edema or abdominal bloating are all symptoms of heart failure that should be systematically asked for.

In patients with newly developed complications of diabetes, recognizing that diabetic retinopathy and nephropathy are target organ damage and amplify CV risk as well as DM risk and prompt referral to intensification of evidence-based therapy. The complexity of the patient due to comorbidities or therapy regimen should also trigger early referral to specialists.

The assessment of cardiometabolic disease risk in a person with diabetes or prediabetes in everyday clinical practice is likely to be done by a primary physician, a diabetologist, a cardiologist, a nephrologist, or an ophthalmologist. Hence, awareness of the details of how to screen and how to manage is essential to many HCPs. Indeed, the timely referral to the appropriate specialists is of utmost importance. The multidisciplinary approach in these circumstances with the person with diabetes at the center of the management circle would aid in the provision of the best care and is likely to improve the outcome, as illustrated in Figure 8. Indeed, understanding the skills and the limitations of every HCP in this management circle could not be more emphasized for such complex medical conditions with multiple comorbidities and complex treatment regimens. Different diabetes-related comorbidities and/or different risk factors will need the assessment of various specialists, as illustrated in Figures 9, 10 and Table 4.

Fig. 8.

Multidisciplinary referral to address the comorbidities.

Fig. 8.

Multidisciplinary referral to address the comorbidities.

Close modal
Fig. 9.

Risk factors and diagnosis of diabetic complications.

Fig. 9.

Risk factors and diagnosis of diabetic complications.

Close modal
Fig. 10.

Cardiometabolic screening and management algorithm. *CV risk factors are hypertension (>130/80), smoking, obesity (BMI >30) and dyslipidaemia (LDL >120mg/dl). ***Symptoms or signs of CVD or PAD or CHF chest pain, peripheral edema, dizziness, palpitations, fatigue, effort intolerance, syncope, intermittent claudication, etc.

Fig. 10.

Cardiometabolic screening and management algorithm. *CV risk factors are hypertension (>130/80), smoking, obesity (BMI >30) and dyslipidaemia (LDL >120mg/dl). ***Symptoms or signs of CVD or PAD or CHF chest pain, peripheral edema, dizziness, palpitations, fatigue, effort intolerance, syncope, intermittent claudication, etc.

Close modal

Cardiometabolic Screening and Management Algorithm

This algorithm reflects the risk categories of people with DM living in the UAE; hence, we have included screening in people with prediabetes and minority of people with DM who would be considered low CV risk due to young age and absence of screened risk factors. However, regardless of age, all people with DM or prediabetes should be screened for CMD as per the above.

Holistic approach with evidence-based therapies is tailored to the complications of diabetes that are identified through diagnosis and evaluation process. If a specific complication is identified, the recommended intensified therapies should be initiated. This is regardless of HbA1c level. In addition, regular re-evaluation is needed in order to assess the response and adherence to the therapies (Fig. 11).

Fig. 11.

Risk factors and management of diabetic complications.

Fig. 11.

Risk factors and management of diabetic complications.

Close modal

Cardiometabolic disease spans from obesity to metabolic syndrome and insulin resistance to prediabetes and overt diabetes. The complications of cardiometabolic disease occur even at the earlier stages or accumulate/progress with time. The burden of CMD is extremely high in the UAE, affecting young patients and resulting in a very high incidence of premature CV events. A comprehensive cardiometabolic approach addressing not only the glycemic control but also implementation of multifactorial intensive therapies as well as early diagnosis of CV complications is mandatory. The utilization of evidence-based, guideline recommendations coupled with early referral to the relevant specialist in the outpatient settings will lead to a substantial reduction of CV events and CV hospitalization in the UAE populations. The application of this algorithm as a key performance indicator supported by governmental regulators and insurance providers will ensure widespread implementation as a national public health initiative.

Future Directions

It is crucial to comprehend that the prevalence of cardiometabolic disorders (CMDs) including CVD will lead to an exponential rise in healthcare costs with negative effects on the general economy. A national cardiometabolic registry to assess the burden of CMD and its complications is timely. This could be easily established because all major centers in cardiology and diabetology in the UAE utilize electronic medical records. The rapid implementation of a CMD registry should be prioritized as a matter of great public health importance. Another priority is the creation of cardiometabolic outpatient clinics in every major cardiology and diabetology center where the guideline-based comprehensive assessment and intensive multifactorial intervention would naturally take place for the benefit of our patients.

Gaps in Evidence

  • 1.

    Screening and management of prediabetes and use of agents other than metformin for CV protection (there is indirect evidence from CVOTs in CHF and CKD in nondiabetic subgroups)

  • 2.

    Early (upfront) combination of GLP1-RA and SGLT2-inhibitor in T2DM

  • 3.

    Cardioprotective therapies (especially GLP1-RA) in T1DM with ASCVD

The authors would like to acknowledge the leadership role of the Emirates Diabetes & Endocrine Society and Emirates Cardiac Society in convening the expert group. Cognizant Worldwide Limited provided medical writing.

The authors have no conflicts of interest to declare. None of the authors received any compensation for their contributions to this work. Novo Nordisk UAE did not participate in any of the meetings or the drafting of the manuscript.

The convening of the expert group meetings, medical writing, and editorial assistance were facilitated by an unrestricted grant from Novo Nordisk, UAE, to the Emirates Diabetes & Endocrine Society.

All authors contributed to the writing and review of the manuscript. Mohamed Hassanein, Hani Sabbour, Fatheya Al Awadi, and Wael Almahmeed were the core group for the guidelines, where Mohamed Hassanein jointly with Hani Sabbour are considered the principle editors and joint first authors for the manuscript.

Additional Information

Mohamed Hassanein and Hani Sabbour are equal contributors, and both are first authors.

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.

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