Transforming Medical Paradigms: A Cutting-Edge Review of Genomic and Robotic Medical and Surgical Approaches in the Battle Against Diabetes, Hypertension, and Cardiovascular Issues

This article provides an in-depth review of the current state of management for diabetes, hypertension, and cardiovascular disease, focusing on advancements from genomics to robotics. It explores the role of genomic markers in personalized medicine, offering tailored treatment options for these chronic conditions. The article also examines the efficacy of various pharmacological and surgical interventions, including bariatric surgery for diabetes and device-based treatments for hypertension. A comparative analysis is presented to evaluate the cost-effectiveness and patient outcomes between medical and surgical approaches. The review concludes that while personalized medicine and minimally invasive surgical techniques show promise, more high-quality comparative research is needed. The ultimate goal is to integrate these emerging technologies within a framework of evidence-based medicine to improve patient outcomes and health equity.


Introduction And Background
Interconnected medical conditions, such as diabetes, hypertension, and cardiovascular disease (CVD), have a profound impact on global health.Type 2 diabetes, in particular, is characterized by chronic hyperglycemia and insulin resistance, which lead to vascular complications.Several underlying mechanisms contribute to these issues, including the formation of advanced glycation end products (AGEs), oxidative stress, and the activation of the AGE-receptor for AGEs (RAGE) axis [1].
CVD remains the leading cause of morbidity and mortality among individuals with diabetes.While rigorous glycemic control has its benefits, it is not without drawbacks [2].Hypertension and dyslipidemia are often comorbid with type 2 diabetes and serve as significant risk factors for atherosclerotic cardiovascular disease (ASCVD).Effective management of these risk factors can halt or slow the progression of ASCVD [3].
The relationship between diabetes and hypertension is further complicated by shared risk factors such as endothelial dysfunction, vascular inflammation, atherosclerosis, and obesity.These factors exacerbate the cardiovascular complications associated with diabetes.Notably, the prevalence of hypertension is higher among individuals with diabetes compared to those without the condition [4].This narrative review aims to offer a comprehensive overview of the latest medical and surgical approaches for treating diabetes, hypertension, and cardiovascular events.This encompasses everything from genomic discoveries to advancements in robotic technologies.The objectives are multi-faceted: to review recent genomic studies on the genetic etiology and biomarkers of cardiovascular diseases, hypertension, and diabetes; to summarize current pharmaceutical treatments for glycemic, blood pressure, and cardiovascular event control; to describe significant advancements in surgical methods; to consider the growing roles of robotic surgery, artificial intelligence, and digital health; to identify areas for further research and innovation; and to offer recommendations for personalized treatment strategies aimed at improving patient outcomes.

Review Genomics and personalized medicine
Genomic Markers in Diabetes TCF7L2: Variants in the Transcription Factor 7-Like 2 (TCF7L2) gene represent the most significant genetic risk factor for type 2 diabetes, as evidenced by a meta-analysis involving over 30,000 individuals [5].These variants are linked to impaired insulin secretion, suggesting that patients carrying this genetic marker may benefit from early initiation of insulin therapy.
PPARG: Polymorphisms in the Peroxisome Proliferator-Activated Receptor Gamma (PPARG) gene, a nuclear receptor crucial for glucose and lipid metabolism, have a notable impact on insulin sensitivity.Specifically, the P12A variant offers protective effects against the progression of type 2 diabetes [6].Therefore, medications like thiazolidinediones, which target PPARG, may be particularly effective for patients with this variant.
KCNJ11: Variants in the Potassium Inwardly Rectifying Channel, Subfamily J, Member 11 (KCNJ11) gene, which encodes a pancreatic beta-cell potassium channel, influence insulin secretion [7].Patients with these variants tend to respond more favorably to sulfonylurea drugs that target the encoded KATP channel, guiding the selection of these therapeutic agents.
TCF2: Polymorphisms in the Transcription Factor 2 (TCF2) gene, which regulates proinsulin processing, elevate the risk of type 2 diabetes by impairing insulin secretion [8].For patients with TCF2 abnormalities, enhancing endogenous insulin secretion through both pharmaceutical and lifestyle interventions appears to be the optimal management strategy.
CDKAL1: Variants in the CDK5 Regulatory Subunit Associated Protein 1-Like 1 (CDKAL1) gene, involved in cell cycle regulation, compromise beta-cell function and increase the risk of type 2 diabetes [9].Patients with these variants may benefit more from therapies aimed at improving beta-cell function and mass, such as GLP-1 agonists.
IGF2BP2: A specific variant in the Insulin-Like Growth Factor 2 mRNA Binding Protein 2 (IGF2BP2) gene is linked to both insulin resistance and impaired insulin secretion [10].Patients with this variant tend to have a poor response to metformin, suggesting the need for alternative first-line medications.

Genomic Markers in Hypertension
ADD1: Variants in the Adducin 1 (ADD1) gene, which plays a role in renal sodium reabsorption, have been linked to an elevated risk of hypertension [11].Studies have shown that sodium restriction can significantly lower blood pressure in individuals carrying these ADD1 variants.
AGT: Polymorphisms in the Angiotensinogen (AGT) gene, responsible for encoding a precursor of the vasoconstrictor angiotensin II, are associated with a predisposition to hypertension [12].Patients with these AGT variants may particularly benefit from angiotensin receptor blockers like losartan, which directly counteract the effects of elevated angiotensin II levels.
CYP11B2: Variants in the Cytochrome P450 Family 11 Subfamily B Member 2 (CYP11B2) gene, which encodes aldosterone synthase, play a role in blood pressure regulation [13].Mineralocorticoid receptor antagonists, such as spironolactone, may be especially effective in treating hypertension in patients with CYP11B2 variants that affect aldosterone synthesis.
WNK1: Abnormalities in the expression of WNK Lysine Deficient Protein Kinase 1 (WNK1) can lead to monogenic hypertension through their effects on renal electrolyte transport [14].Hypertension linked to WNK1 appears to be uniquely responsive to thiazide diuretics due to the associated electrolyte transport abnormalities.
NPPA: The rs5068 variant in the Natriuretic Peptide A (NPPA) gene, which encodes atrial natriuretic peptide, offers protective effects against hypertension [15].This NPPA rs5068 variant is associated with a reduced need for antihypertensive medications, guiding a more conservative approach to prescribing.NEDD4L: Variants in the Neural Precursor Cell Expressed, Developmentally Down-Regulated 4-Like (NEDD4L) gene influence blood pressure by altering sodium reabsorption [16].Sodium-wasting diuretics like amiloride may be effective in normalizing sodium reabsorption in patients with these NEDD4L variants.

Genomic Markers in Cardiovascular Events
9p21: Variants in the 9p21 genomic region are associated with an increased risk for conditions such as myocardial infarction, coronary artery disease, and aneurysms, primarily through their effects on vascular cell proliferation [17].Patients carrying these 9p21 variants may benefit more from aggressive management of modifiable risk factors like LDL cholesterol and blood pressure.
KIF6: The KIF6 719Arg variant in the Kinesin Family Member 6 gene is linked to an elevated risk of coronary heart disease [18].This particular KIF6 variant has been shown to respond more effectively to statin therapy for the prevention of coronary heart disease.
LPA: Variants in the Lipoprotein(a) gene (LPA) influence Lp(a) levels and the risk of atherosclerotic cardiovascular disease [19].For individuals with these LPA variants, Lipoprotein apheresis may be a more effective treatment for lowering Lp(a) levels and cardiovascular risk when conventional drug therapies are ineffective.
PCSK9: Loss-of-function mutations in the Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) gene result in lower LDL cholesterol levels and offer protection against cardiovascular events [20].These PCSK9 loss-of-function mutations indicate a better response to PCSK9 inhibitor drugs like alirocumab and evolocumab for lowering LDL cholesterol.
APOA5: Rare variants in the Apolipoprotein A5 (APOA5) gene disrupt triglyceride metabolism and increase susceptibility to ischemic heart disease [21].These APOA5 variants are associated with a poorer response to standard triglyceride-lowering therapies, suggesting the need for newer agents like icosapent or pemafibrate.
MTHFR: The MTHFR 677C>T variant impacts folate metabolism and increases susceptibility to vascular diseases [22].Patients with the MTHFR 677TT variant may benefit from increased folate intake to lower homocysteine levels and reduce vascular risk.

Pharmacological Treatment
Metformin: Metformin stands as the preferred initial oral medication for managing type 2 diabetes, owing to its proven efficacy, safety, and cost-effectiveness [23].
Sulfonylureas: Second-line agents like glipizide and glimepiride fall under the category of sulfonylureas, which function by stimulating insulin secretion and are commonly used in the treatment of type 2 diabetes.
Thiazolidinediones: Drugs such as pioglitazone and rosiglitazone belong to the thiazolidinedione class and work by improving insulin sensitivity.They may also contribute to the durability of glycemic control.
GLP-1 receptor agonists: Injectable GLP-1 analogs, including liraglutide and semaglutide, serve to lower glucose levels and promote weight loss, offering a dual benefit.
SGLT2 inhibitors: SGLT2 inhibitors, such as empagliflozin and canagliflozin, function by reducing glucose reabsorption in the kidneys, thereby aiding in glycemic control.
Insulin therapy: The administration of exogenous insulin is indispensable for the management of type 1 diabetes and often becomes necessary in the later stages of type 2 diabetes.

Lifestyle Modification
Physical activity: It is recommended that individuals engage in at least 150 minutes of moderate-intensity aerobic activity per week, supplemented by resistance training two to three days per week.This regimen aims to enhance glycemic control, cardiovascular health, weight management, and overall well-being [24].
Weight management: A modest weight loss of 5-10%, achieved through caloric restriction and increased physical activity, can yield significant improvements in hyperglycemia and other cardiovascular risk factors, particularly in overweight or obese patients.
Diet: Medical nutrition therapy is advised for optimizing glycemic control, lipid profiles, and blood pressure.This involves limiting the intake of refined carbohydrates and added sugars while emphasizing high-fiber foods, lean proteins, and healthy fats.
Smoking cessation: All patients who smoke should be strongly encouraged to quit, given the elevated cardiovascular risks associated with both smoking and diabetes.
Stress management: The adoption of healthy coping strategies for stress, such as relaxation techniques, can positively impact diabetes management.

Pharmacological Treatment
Thiazide diuretics: Thiazide diuretics, such as chlorthalidone and hydrochlorothiazide, are often the preferred initial agents for most patients.Their preference is based on their proven efficacy, costeffectiveness, and favorable outcomes data [25].
ACE inhibitors: Angiotensin-converting enzyme (ACE) inhibitors, including lisinopril and enalapril, serve as effective first-line options.They are particularly beneficial for patients with diabetes or heart failure.
Angiotensin receptor blockers: Angiotensin receptor blockers (ARBs) like losartan and valsartan offer benefits similar to ACE inhibitors but generally come with fewer side effects.
Calcium channel blockers: Non-dihydropyridine calcium channel blockers (CCBs), such as diltiazem and verapamil, are useful as add-on medications.They are especially beneficial for older patients who may require additional blood pressure control.
Beta-blockers: Beta-blockers, like metoprolol, are effective in reducing blood pressure but generally have more limited effects on long-term outcomes compared to other classes of antihypertensive medications.

Lifestyle Modification
Weight loss: Reducing body weight has been shown to lower blood pressure in overweight and obese patients diagnosed with hypertension.
Dietary sodium reduction: Limiting daily sodium intake to no more than 2400 mg is recommended for achieving optimal blood pressure reduction.
DASH diet: The Dietary Approaches to Stop Hypertension (DASH) diet, which is rich in fruits, vegetables, nuts, and low-fat dairy while being low in fats and sweets, has demonstrated antihypertensive effects [26].
Physical activity: Engaging in aerobic exercise for a minimum of 90-150 minutes per week has been shown to lower blood pressure and enhance the effectiveness of pharmacological treatments.
Moderation of alcohol: For those who consume alcohol, limiting intake to a maximum of two drinks daily for men and one drink for women can contribute to blood pressure reduction.
Smoking cessation: Quitting smoking not only lowers blood pressure but also eliminates the additional cardiovascular risks associated with smoking.
Stress management: Employing stress management techniques, such as meditation, may assist in controlling blood pressure levels.

Pharmacological Treatment
Antiplatelet agents: Antiplatelet medications, such as aspirin and P2Y12 inhibitors (e.g., clopidogrel, prasugrel), play a crucial role in preventing recurrent ischemic events in patients with atherosclerotic disease [27].
Beta-blockers: Beta-blockers serve as a standard therapy for treating heart failure and reducing mortality following a myocardial infarction.
ACE inhibitors/ARBs: Angiotensin-converting enzyme (ACE) inhibitors like enalapril and angiotensin receptor blockers (ARBs) like losartan are frontline therapies for managing heart failure and post-myocardial infarction care.
Statins: High-intensity statin therapy, including drugs like atorvastatin and rosuvastatin, effectively lowers LDL cholesterol levels and reduces the risk of recurrent cardiovascular events.
Anticoagulants: Anticoagulant medications are indispensable for managing thrombotic events such as deep vein thrombosis (DVT), pulmonary embolism (PE), and atrial fibrillation-related strokes.
Nitrates: Nitrates like isosorbide mononitrate alleviate angina symptoms in patients with coronary artery disease through vasodilation.
Calcium channel blockers: Non-dihydropyridine calcium channel blockers (CCBs), such as diltiazem, are effective in managing heart rate in atrial fibrillation and relieving angina symptoms.

Lifestyle Modification
Smoking cessation: Quitting smoking is crucial for lowering the risk of recurrent cardiovascular events and mortality, especially in patients with a history of cardiovascular disease (CVD).
Weight management: A gradual weight loss of 5-10% in overweight or obese patients can significantly reduce cardiovascular risk factors such as blood pressure, lipid levels, and glucose levels.
Dietary pattern: Adopting a diet rich in fruits, vegetables, whole grains, lean proteins, nuts, legumes, and healthy oils -akin to the Mediterranean diet -offers protective benefits against CVD.
Sodium reduction: Limiting daily sodium intake to between 1500 and 2000 mg can effectively lower blood pressure and subsequently reduce the risk of CVD.
Physical activity: Engaging in 150-300 minutes of moderate exercise per week, such as brisk walking, contributes to weight loss, glucose control, blood pressure reduction, and overall cardiovascular health.
Stress management: Mind-body practices like meditation, yoga, tai chi, or breathing exercises may have beneficial effects on cardiovascular health.

Bariatric Surgery
Bariatric surgery (e.g., Roux-en-Y gastric bypass, sleeve gastrectomy, biliopancreatic diversion) is a notable solution for obesity-related type 2 diabetes [28].Controlled trials prove it surpasses medical therapy by achieving better glycemic control, remission, weight loss, and cardiovascular benefits.Yet, challenges encompass perioperative risks, nutritional deficiencies, and lifestyle changes, with declining remission rates over time.Financial and accessibility barriers limit wider use.While effective for suitable candidates, multidisciplinary care is essential due to individual complications and needs [29].More research on longterm outcomes is needed.

Pancreatic Transplant
Pancreatic transplantation restores insulin production in type 1 diabetes through the whole pancreas or islet cell transplant [30].Success achieves insulin independence and improves glycemic control, reducing complications and enhancing life quality.Challenges include immunosuppression, surgical risks, organ scarcity, and graft failure risks.Limited eligibility exists, despite effectiveness in restoring euglycemia without insulin.Risks, rejection, and limitations restrict wider use, though organ advancements may broaden feasibility for more patients [31].

Renal Denervation
Renal denervation lowers blood pressure by ablating renal sympathetic nerves in hypertension patients.
Trials reveal blood pressure reduction, aiding resistant hypertension cases and even reducing medication needs.Yet, effectiveness varies across trials, some showing no significant benefit.The procedure remains investigational with unclear long-term effects and safety concerns like renal artery stenosis [32].Renal denervation holds promise for hypertension management, but more data on patient selection, techniques, and long-term outcomes are needed to define its role definitively.

Carotid Baroreceptor Stimulation
Carotid baroreceptor stimulation uses an implantable device to activate the carotid baroreflex, reducing blood pressure by inhibiting vasoconstriction and sympathetic activity.Studies show sustained blood pressure reduction and safety, potentially lowering medication needs.Surgical risks exist, and not all patients respond.Long-term durability and impact on cardiovascular outcomes remain uncertain while costs are high.Despite the promise of treating resistant hypertension, clinical trials are necessary to define its role [33].

Surgical interventions for cardiovascular events
Coronary Artery Bypass Grafting (CABG) Coronary artery bypass grafting (CABG) surgically bypasses arterial blockages, restoring blood flow to the heart.CABG reduces mortality and heart attack risk, especially in complex cases, offering more lasting revascularization than PCI.Yet, risks include bleeding, arrhythmias, infection, and graft issues, with prolonged recovery.Higher costs than PCI exist.CABG suits complex cases where PCI isn't viable, backed by strong evidence for event reduction [34].Surgery's invasiveness must balance individual risk factors carefully.

Heart Transplant
Heart transplantation replaces a failing heart with a healthy donor heart, offering gold-standard treatment for end-stage heart failure.It enhances symptoms, exercise capacity, and life quality in select refractory patients.Challenges encompass organ scarcity, surgical risks, high immunosuppression costs, and potential rejection or graft vasculopathy [35].Rigorous candidate screening is crucial.Heart transplantation remains lifesaving for severe heart failure, yet availability limits its use.Better donor allocation and graft failure management could broaden feasibility.

Robotic Surgery in Diabetes
Robotic systems like da Vinci enable minimally invasive bariatric and metabolic procedures for diabetes linked to obesity.Compared to open surgery, they bring benefits such as less blood loss, shorter hospital stays, and similar outcomes in weight loss and diabetes remission.Yet, drawbacks exist: high costs, limited availability, and longer operation times.Specialized training is needed due to a lack of tactile feedback.Risks involve complications like bleeding, infection, leaks, and potential device-related issues.Despite challenges, robotic bariatric surgery holds potential for diabetes management, but high costs hinder wider use.Research is vital to establish safety and long-term efficacy [36].

Robotic Surgery in Hypertension
Robotic platforms are used for minimally invasive hypertension treatments like renal denervation and baroreceptor activation.They offer the benefits of smaller incisions, quicker recovery, and improved visualization [37].Challenges include costs, limited availability, learning curve, and unproven efficacy.General risks like bleeding and infection apply, alongside device malfunction and stimulation issues.Despite hurdles, robotic systems show potential for precise, minimally invasive hypertension procedures, though utility remains uncertain due to costs and expertise demands.

Robotic Surgery in Cardiovascular Events
Robotic platforms enhance cardiovascular procedures like CABG and mitral valve repair, offering benefits such as minimal invasiveness, reduced pain, and quicker recovery [38].Challenges include learning curve, costs, and limited data on long-term effectiveness.Similarities exist in clinical outcomes like mortality and stroke risk, while technical issues like anastomoses difficulties and device malfunction persist.Though enabling minimally invasive complexity, adoption is hindered by costs, lack of superiority proof, and expertise demands.

Prospects in the field of robotic surgeries for diabetes, hypertension, and cardiovascular diseases
Advancements in robotic surgery enhance diabetes and cardiovascular treatment.Robotics improve bariatric surgery, aiding diabetes remission.Innovations in catheter navigation and renal systems for hypertension promise safer, fully robotic procedures.Complex cardiovascular surgeries will benefit from enhanced robotic platforms and training [39].The future holds minimally invasive metabolic and cardiovascular treatments, though comparative data against traditional methods is crucial for acceptance and implementation.
In the realm of treating diabetes, hypertension, and cardiovascular events, a comparative analysis between medical and surgical approaches offers valuable insights into cost-effectiveness and patient outcomes.For diabetes, although bariatric surgery entails higher upfront costs compared to medications, it proves to be more cost-effective in the long run.This surgical approach achieves superior glycemic control and higher rates of diabetes remission [40].On the other hand, hypertension is generally better managed through medications, which serve as the first-line treatment.These medications are more cost-effective than emerging surgical techniques like renal denervation, which currently lack conclusive data to support their clinical benefits [41].When it comes to cardiovascular events, revascularization procedures like coronary artery bypass grafting (CABG) may be costly initially but yield improved outcomes compared to medical therapy alone, especially for high-risk patients with multi-vessel disease.In summary, diabetes currently appears to be the most amenable to surgical intervention while hypertension is better managed medically.For cardiovascular events, the optimal treatment strategy is guided by the individual patient's clinical context.Further research is needed to provide more comprehensive comparative data.

Conclusions
This review provides a comprehensive overview of the current advancements in the management of diabetes, hypertension, and cardiovascular disease, ranging from genomics to robotics.Personalized medicine, guided by genomic profiling, is increasingly influencing treatment choices, especially in diabetes and cardiovascular disease.However, for genomics to fully realize its potential, more research is needed to identify additional variants and establish evidence-based guidelines.Bariatric surgery has shown promise in treating diabetes while pharmacological approaches remain the cornerstone for hypertension management.Device-based interventions and surgical revascularization offer new avenues but require further validation through randomized trials.
The overarching theme is a shift toward more integrative, individualized, and minimally invasive treatments, supported by innovations in molecular genetics and robotics.However, the integration of these emerging tools must be rooted in evidence-based medicine, patient-centered care, and equitable access.As technology continues to advance, high-quality comparative research is essential for translating these innovations into meaningful improvements in patient outcomes and health equity.This is particularly crucial given the increasing global burden of chronic diseases like diabetes, hypertension, and cardiovascular disease.