Induction of Type 2 Diabetes Mellitus with Antihypertensive Therapy: Is There Any Role of Alpha Adducin, ACE, and IRS-1 Gene?

Abstract

Hypertension and diabetes are related disorders that share common pathophysiological pathways and occur together. Although hypertension itself is a risk factor for developing diabetes, prolonged use of first-line antihypertensive therapy has also been reported to induce diabetes. Genetic polymorphism of genes affecting salt sensitivity and insulin resistance can have a role in antihypertensive therapy-induced diabetes. Polymorphism of the alpha adducin gene, angiotensin-converting enzyme gene, and insulin receptor substrate 1 gene has been found to be associated with new incident diabetes in hypertensive patients via salt sensitivity and insulin resistance. Many studies have, however, revealed a negative correlation with this hypothesis and have shown no role of antihypertensive therapy in diabetes induction. Therefore, more detailed experimental studies are needed to reach a final conclusion.

Prevalence and Risk Factors of Essential Hypertension and New Onset of Diabetes in Essential Hypertension in Rural Population of Haryana

“…Not only hypertension is considered as one of the risk factors for developing diabetes but also antihypertensive therapy also been found associated with new onset of diabetes in essential hypertension patients [10]. Therefore, a high prevalence of hypertension is dangerous in either way and poses health problems in the mankind.…”

“…Co-existence of hypertension and diabetes at a single time in an individual is 75% more dangerous than either a single disease which increases the risk of another cardiovascular disease such as coronary heart disease, nephropathy, retinopathy and stroke [8,9]. In addition, certain antihypertensive therapies (especially beta-blockers (BBs), diuretics, angiotensinconverting enzyme inhibitors (ACEIs) and calcium channel blockers (CCBs)) on prolonged use (for 3 y or more) are also reported to induce type 2 diabetes or glucose dysregulation in hypertensive patients under the influence of polymorphic alleles of certain genes [10]. Even it is very hard to control hypertension in patients who have developed diabetes and a combination of antihypertensive therapies is needed to take control over high blood pressure [11].…”

Insulin receptor substrate-1 gene polymorphism and lipid panel data in type 2 diabetic patients with comorbid obesity and/or essential hypertension

“…Some of these mechanisms involve excessive activation of RAAS. Emergence of oxidative stress is resulting from overproduction of reactive oxygen species (ROS), inflammation, impaired vasodilatation pathways mediated by insulin, overly active sympathetic nervous system, dysfunction of the innate and adaptive immune responses, and dysregulated renal sodium balance (Lastra et al 2014;Gupta and Jhawat 2017;Colussi et al 2020). A key pathogenic factor linking both T2DM and hypertension is the obesity.…”

Angiotensin Converting Enzyme Gene Insertion/Deletion Polymorphism Is Not Responsible for Antihypertensive Therapy Induced New Onset of Type 2 Diabetes in Essential Hypertension

“…16–18 The metabolic disturbances (glucose turnover) associated with salt sensitivity and insulin resistance under the influence of genes polymorphism may be affected by different antihypertensive drugs such as ACE inhibitors, diuretics, and BBs and induce new onset of diabetes in hypertensive patients. 19…”