The cardiovascular System

The cardiovascular system, also known as the circulatory system,  comprises the heart, blood vessels (arteries, veins, and capillaries),  and blood. Its primary function is to circulate blood throughout the  body, delivering oxygen, nutrients, and hormones to cells and tissues  while removing metabolic waste products and carbon dioxide. The heart  acts as the central pump, propelling blood through the blood vessels via  rhythmic contractions. Arteries carry oxygen-rich blood away from the  heart to the body's tissues, while veins return oxygen-depleted blood  back to the heart. Capillaries facilitate the exchange of gases,  nutrients, and waste products between the bloodstream and tissues.  Additionally, the cardiovascular system plays a crucial role in  regulating blood pressure, maintaining fluid balance, and supporting  immune function. Overall, the cardiovascular system is essential for  sustaining life by ensuring adequate oxygen and nutrient delivery to all  cells and tissues of the body. 

 Coronary Artery Disease (CAD): Caused by the buildup of plaque (atherosclerosis) in the coronary arteries, CAD reduces blood flow to the heart muscle, leading to angina (chest pain), heart attacks (myocardial infarctions), and heart failure.

1. Hypertension (High Blood Pressure): Persistent elevation of blood pressure in the arteries, increasing the workload on the heart and blood vessels and raising the risk of heart disease, stroke, and kidney failure.
2. Heart Failure: A condition where the heart is unable to pump blood effectively, leading to symptoms such as shortness of breath, fatigue, and fluid retention.
3. Arrhythmias: Abnormal heart rhythms, including tachycardia (rapid heart rate), bradycardia (slow heart rate), atrial fibrillation, and ventricular fibrillation, which can impair cardiac function and increase the risk of stroke and sudden cardiac death.
4. Peripheral Artery Disease (PAD): Narrowing or blockage of arteries outside the heart, typically in the legs, leading to decreased blood flow, pain, and impaired mobility.
5. Stroke: Occurs when blood flow to the brain is disrupted, either by a blockage (ischemic stroke) or bleeding (hemorrhagic stroke), resulting in neurological deficits and potentially permanent disability or death.
6. Deep Vein Thrombosis (DVT) and Pulmonary Embolism (PE): DVT occurs when blood clots form in deep veins, often in the legs, while PE occurs when these clots break loose and travel to the lungs, causing potentially life-threatening blockages.

yperinsulinemia, insulin resistance, and metabolic syndrome are implicated in various cardiovascular disorders through multiple pathways:

1. Coronary Artery Disease (CAD): Insulin resistance and hyperinsulinemia contribute to atherosclerosis by promoting inflammation, oxidative stress, and endothelial dysfunction, leading to plaque formation and narrowing of coronary arteries.
2. Hypertension: Insulin resistance is associated with increased sympathetic nervous system activity, sodium retention, and endothelial dysfunction, all contributing to elevated blood pressure and the development of hypertension.
3. Heart Failure: Insulin resistance and metabolic abnormalities can impair cardiac metabolism, myocardial function, and remodeling processes, increasing the risk of heart failure development and progression.
4. Arrhythmias: Insulin resistance and hyperinsulinemia may affect cardiac ion channels and electrical conduction, predisposing individuals to arrhythmias such as atrial fibrillation and ventricular tachycardia.
5. Peripheral Artery Disease (PAD): Insulin resistance and metabolic syndrome are risk factors for atherosclerosis and peripheral vascular disease, contributing to reduced blood flow to the legs and increased risk of PAD.
6. Stroke: Insulin resistance and metabolic abnormalities are associated with a prothrombotic state, endothelial dysfunction, and increased risk of atherosclerosis, all contributing to the development of ischemic stroke.
7. Thromboembolic Events: Insulin resistance and hyperinsulinemia may promote platelet aggregation, endothelial dysfunction, and altered coagulation pathways, increasing the risk of deep vein thrombosis (DVT) and pulmonary embolism (PE).

Overall, addressing metabolic abnormalities and promoting insulin sensitivity may help mitigate the risk and severity of cardiovascular disorders associated with hyperinsulinemia, insulin resistance, and metabolic syndrome.

  Increases the risk of hypertension, dyslipidemia, and atherosclerosis, predisposing individuals to heart disease and stroke. 

 Diabetes accelerates atherosclerosis and endothelial dysfunction,  increasing the risk of heart attack and peripheral vascular disease. 

By Jer5150 - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=19669589

 Arrhythmia refers to abnormal heart rhythms, which can manifest as a  heartbeat that is too slow (bradycardia), too fast (tachycardia), or  irregular. Hyperinsulinemia, characterized by elevated levels of insulin  in the blood, can potentially contribute to arrhythmias through various  mechanisms. Insulin resistance, a hallmark of hyperinsulinemia and  metabolic syndrome, is associated with dysregulation of autonomic  nervous system activity, increased sympathetic tone, and altered  electrolyte balance, all of which can predispose individuals to  arrhythmias. Additionally, hyperinsulinemia may promote inflammation,  endothelial dysfunction, and oxidative stress, which can damage cardiac  tissues and disrupt the electrical conduction system of the heart,  leading to arrhythmias. Furthermore, insulin resistance is linked to  obesity, hypertension, and dyslipidemia, all of which are risk factors  for arrhythmias and cardiovascular disease. Therefore, managing  hyperinsulinemia through lifestyle modifications, insulin-sensitizing  medications, and appropriate medical interventions may help reduce the  risk of arrhythmias and their associated complications. 

 Cardiovascular disease (CVD) encompasses a range of conditions affecting  the heart or blood vessels outlined further in other sections , including coronary artery disease, stroke,  heart failure, peripheral artery disease, arrhythmias, and heart valve  disease. Risk factors for CVD include smoking, high blood pressure, high  cholesterol, diabetes, obesity, unhealthy diet, sedentary lifestyle,  and family history. Prevention and management strategies focus on  lifestyle changes, medication, and sometimes surgical interventions.  Early detection and treatment are crucial for improving outcomes and  reducing complications associated with CVD. 

 In summary, hyperinsulinemia, insulin resistance, and metabolic syndrome  all contribute to the development and progression of heart disease by  promoting inflammation, oxidative stress, endothelial dysfunction,  dyslipidemia, and atherosclerosis. Managing these metabolic disturbances  through lifestyle modifications, medication, and other interventions is  crucial for reducing the risk of heart disease and improving  cardiovascular health. 

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 Coronary heart disease (CHD), also known as coronary artery disease  (CAD), occurs when plaque builds up inside the coronary arteries, which  supply oxygen-rich blood to the heart muscle. Hyperinsulinemia,  characterized by elevated levels of insulin in the blood, can contribute  to the development and progression of CHD through several mechanisms.  Insulin resistance, a key feature of hyperinsulinemia and metabolic  syndrome, is associated with dyslipidemia, including high levels of  triglycerides and low levels of HDL cholesterol, which can promote the  formation of atherosclerotic plaques in the coronary arteries.  Additionally, insulin resistance is linked to chronic inflammation,  endothelial dysfunction, and oxidative stress, all of which can  contribute to the initiation and progression of atherosclerosis.  Moreover, hyperinsulinemia may promote vasoconstriction and smooth  muscle cell proliferation in the arterial wall, further narrowing the  coronary arteries and reducing blood flow to the heart muscle,  increasing the risk of angina, myocardial infarction (heart attack), and  other complications of CHD. Therefore, managing hyperinsulinemia  through lifestyle modifications, insulin-sensitizing medications, and  appropriate medical interventions is crucial for preventing and managing  coronary heart disease. 

 This study points to vegetable oils/margarines as clearly implicated in heart disease compared to animal fats  

 "Insulin resistance (IR) is associated with coronary artery disease  (CAD) severity. However, its underlying mechanisms are not fully  understood. Therefore, our study aimed to explore the relationship  between IR and coronary inflammation and investigate the synergistic and  mediating effects of coronary inflammation on the association between  IR and CAD severity. "

 "The patients in the high-TyG index/high PCAT attenuation group had  approximately 3.2 times the odds of multivessel CAD compared with those  in the low-TyG index."

 By BruceBlaus. When using this image in external sources it can be cited as:Blausen.com staff (2014). "Medical gallery of Blausen Medical 2014". WikiJournal of Medicine 1 (2). DOI:10.15347/wjm/2014.010. ISSN 2002-4436. - Own work, CC BY 3.0, https://commons.wikimedia.org/w/index.php?curid=29140359

 Thromboembolic events, including deep vein thrombosis (DVT) and  pulmonary embolism (PE), occur when blood clots form in the veins and  travel to other parts of the body, typically the lungs.  Hyperinsulinemia, characterized by elevated levels of insulin in the  blood, can contribute to the risk of thromboembolic events through  various mechanisms. Insulin resistance, a hallmark of hyperinsulinemia  and metabolic syndrome, is associated with dyslipidemia, chronic  inflammation, endothelial dysfunction, and oxidative stress, all of  which can promote the formation of blood clots. Additionally,  hyperinsulinemia may exacerbate other risk factors for thromboembolic  events, including obesity, immobility, and certain medical conditions  such as cancer and inflammatory disorders. Over time, these processes  can increase the likelihood of clot formation in the veins, particularly  in the deep veins of the legs, which can dislodge and travel to the  lungs, causing a pulmonary embolism. Therefore, managing  hyperinsulinemia through lifestyle modifications, insulin-sensitizing  medications, and appropriate medical interventions is crucial for  reducing the risk of thromboembolic events and their potentially  life-threatening consequences. 

Risk factors for COVID-19 patients with poorer outcomes include  pre-existing conditions: obesity, type 2 diabetes mellitus,  cardiovascular disease (CVD), heart failure, hypertension, low oxygen  saturation capacity, cancer, elevated: ferritin, C reactive protein  (CRP) and D-dimer. A common denominator, hyperinsulinaemia, provides a  plausible mechanism of action, underlying CVD, hypertension and strokes,  all conditions typified with thrombi. The underlying science provides a  theoretical management algorithm for the frontline  practitioners.Vitamin D activation requires magnesium. Hyperinsulinaemia  promotes: magnesium depletion via increased renal excretion, reduced  intracellular levels, lowers vitamin D status via sequestration into  adipocytes and hydroxylation activation inhibition. Hyperinsulinaemia  mediates thrombi development via: fibrinolysis inhibition,  anticoagulation production dysregulation, increasing reactive oxygen  species, decreased antioxidant capacity via nicotinamide adenine  dinucleotide depletion, haem oxidation and catabolism, producing carbon  monoxide, increasing deep vein thrombosis risk and pulmonary emboli.  Increased haem-synthesis demand upregulates carbon dioxide production,  decreasing oxygen saturation capacity. Hyperinsulinaemia decreases  cholesterol sulfurylation to cholesterol sulfate, as low vitamin D  regulation due to magnesium depletion and/or vitamin D sequestration  and/or diminished activation capacity decreases sulfotransferase enzyme  SULT2B1b activity, consequently decreasing plasma membrane negative  charge between red blood cells, platelets and endothelial cells, thus  increasing agglutination and thrombosis.Patients with COVID-19 admitted  with hyperglycaemia and/or hyperinsulinaemia should be placed on a  restricted refined carbohydrate diet, with limited use of intravenous  dextrose solutions. Degree/level of restriction is determined by serial  testing of blood glucose, insulin and ketones. Supplemental magnesium,  vitamin D and zinc should be administered. By implementing refined  carbohydrate restriction, three primary risk factors, hyperinsulinaemia,  hyperglycaemia and hypertension, that increase inflammation,  coagulation and thrombosis risk are rapidly managed.      

By Mark-shea at English Wikipedia - Transferred from en.wikipedia to Commons by Knochen., Public Domain, https://commons.wikimedia.org/w/index.php?curid=30596249

Dyslipidemia refers to abnormal levels of lipids, including cholesterol  and triglycerides, in the blood. While hyperinsulinemia isn't directly  correlated with dyslipidemia, it often coexists with insulin resistance  and metabolic syndrome, both of which are closely associated with  dyslipidemia. Insulin resistance can lead to dysregulation of lipid  metabolism, resulting in increased production of triglycerides and  decreased clearance of cholesterol from the blood. Additionally,  hyperinsulinemia can stimulate the synthesis of fatty acids in the  liver, contributing to elevated levels of triglycerides. Furthermore,  insulin resistance is linked to low levels of high-density lipoprotein  (HDL) cholesterol, often referred to as "good" cholesterol. Managing  hyperinsulinemia through lifestyle changes, medication, or other  interventions can help improve insulin sensitivity and may lead to  improvements in dyslipidemia. However, the relationship between  hyperinsulinemia and dyslipidemia is complex and multifactorial, and  further research is needed to fully understand their interplay. 

 A heart attack, or myocardial infarction (MI), occurs when blood flow to  a part of the heart is blocked, often due to a blood clot forming in a  coronary artery. This blockage deprives the heart muscle of oxygen and  nutrients, leading to tissue damage or death. Hyperinsulinemia, a  condition characterized by abnormally high levels of insulin in the  blood, can contribute to the development of heart disease and increase  the risk of heart attacks. Insulin resistance, a hallmark of  hyperinsulinemia and metabolic syndrome, is associated with  inflammation, endothelial dysfunction, and dyslipidemia, all of which  can promote the formation of atherosclerotic plaques in the arteries.  These plaques can rupture, leading to the formation of blood clots that  can block coronary arteries and trigger a heart attack. Additionally,  hyperinsulinemia can promote the accumulation of visceral fat and  increase levels of circulating free fatty acids, both of which are  associated with insulin resistance and adverse cardiovascular outcomes.  Therefore, managing hyperinsulinemia through lifestyle modifications and  appropriate medical interventions is essential for reducing the risk of  heart attacks and other cardiovascular complications. 

 Metabolic syndrome is associated with adverse cardiovascular outcome,  independently of its associations with diabetes and obesity. A metabolic  profile should form part of the risk assessment in all patients with  coronary disease, not just those who are obese.      

The study recruited over 30,000 men and women aged 40-79 years at  baseline between 1993 and 1998 from 35 participating general practices  in Norfolk. Individuals provided information about behavioural factors,  including diet and physical activity, and attended a baseline health  check including the provision of blood samples for concurrent and future  analysis and the collection of anthropometric data.

The participants have continued to provide follow up data and attend  additional health checks for over 25 years. They provided consent to  future linkage to medical record information and a wide range of  follow-up studies for different disease endpoints have subsequently been  undertaken.

 Heart failure is a condition characterized by the heart's inability to  pump enough blood to meet the body's needs. While hyperinsulinemia isn't  directly linked to heart failure, it often coexists with insulin  resistance and metabolic syndrome, both of which are risk factors for  cardiovascular disease, including heart failure. Insulin resistance can  lead to dysregulation of lipid metabolism, inflammation, and oxidative  stress, all of which can contribute to the development and progression  of heart failure. Additionally, hyperinsulinemia may promote the  development of atherosclerosis, hypertension, and other conditions that  increase the workload on the heart and impair its function over time.  Managing hyperinsulinemia through lifestyle changes, medication, or  other interventions may help reduce the risk of heart failure by  improving insulin sensitivity and addressing underlying metabolic  abnormalities. However, the relationship between hyperinsulinemia and  heart failure is complex, and additional research is needed to fully  understand their interplay. 

Highlights:

- Low carbohydrate diets lead to significant weight loss in patients with diabetic cardiomyopathy.

- Improvements in quality-of-life scores on the low carbohydrate diet may be clinically significant.

- Low carbohydrate diets present a safe dietary pattern for patients with diabetic cardiomyopathy. 

1. González-Islas  D, Orea-Tejeda A, Castillo-Martínez L, et al. The effects of a  low-carbohydrate diet on oxygen saturation in heart failure patients: a  randomized controlled clinical trial. Nutr Hosp. 2017;34(4):792-798.  doi:10.20960/nh.784
2. Nielsen  R, Møller N, Gormsen LC, et al. Cardiovascular Effects of Treatment  With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure  Patients. Circulation. 2019;139(18):2129-2141. doi:10.1161/CIRCULATIONAHA.118.036459
3. Zeybek  C, Celebi A, Aktuglu‐Zeybek C, et al. The effect of low-carbohydrate  diet on left ventricular diastolic function in obese children.  Pediatrics International. 2010;52(2):218-223. doi:10.1111/j.1442-200X.2009.02940.x
4. Solis-Herrera C, Qin Y, Honka H, et al. Effect of elevated plasma ketones on cardiac efficiency. American Heart Journal. 2021;242:163. doi:10.1016/j.ahj.2021.10.045 ABSTRACT
5. Cui  C, Zhou M, Cheng L, et al. Admission hyperglycemia as an independent  predictor of long-term prognosis in non-diabetic patients with acute  myocardial infarction: a retrospective study. Journal of Diabetes Investigation. n/a(n/a). doi:https://doi.org/10.1111/jdi.13468
6. Bejko  J, Bottio T, Caraffa R, et al. Lipid-In, Sugar-Out: Early Results of  Treatment with Additional Ketogenic Parenteral Nutrition in Left  Ventricle Assist Device Patients. In Review; 2021. doi:10.21203/rs.3.rs-649111/v1
7. Deberles  E, Maragnes P, Penniello-Valette M-J, Allouche S, Joubert M. Reversal  of cardiac hypertrophy with a ketogenic diet in a child with  mitochondrial disease and hypertrophic cardiomyopathy. Canadian Journal  of Cardiology. 2020;0(0). doi:10.1016/j.cjca.2020.04.024 ABSTRACT
8. Berezin  AE, Berezin AA, Lichtenauer M. Emerging Role of Adipocyte Dysfunction  in Inducing Heart Failure Among Obese Patients With Prediabetes and  Known Diabetes Mellitus. Front Cardiovasc Med. 2020;7. doi:10.3389/fcvm.2020.583175
9. Monzo  L, Sedlacek K, Hromanikova K, et al. Ketone body metabolism in failing  heart. Metabolism. Published online November 25, 2020:154452. doi:10.1016/j.metabol.2020.154452 ABSTRACT
10. Hirose  K, Nakanishi K, Daimon M, et al. Impact of insulin resistance on  subclinical left ventricular dysfunction in normal weight and  overweight/obese japanese subjects in a general community. Cardiovascular Diabetology. 2021;20(1):22. doi:10.1186/s12933-020-01201-6
11. Kim  D, Roberts C, McKenzie A, George MP. Nutritional ketosis to treat  pulmonary hypertension associated with obesity and metabolic syndrome: a  case report. Pulm Circ. 2021;11(1):2045894021991426. doi:10.1177/2045894021991426
12. Zheng  Y, Xie Z, Li J, et al. Meta-analysis of metabolic syndrome and its  individual components with risk of atrial fibrillation in different  populations. BMC Cardiovasc Disord. 2021;21(1):90. doi:10.1186/s12872-021-01858-1
13. Wesół-Kucharska,  D. (2022) ‘The Effectiveness of the Ketogenic Diet for Leigh Syndrome  with Cardiomiopathy’(sic), 8(16), p. 7. ISSN 2639-8109
14. Gajagowni,  S., Tarun, T., Dorairajan, S., Chockalingam, A., 2022. First Report Of  50-Day Continuous Fasting in Symptomatic Multivessel Coronary Artery  Disease and Heart Failure: Cardioprotection Through Natural Ketosis. Mo  Med 119, 250–254. PMID: 36035583 (highlights importance of monitoring and adequate hydration/electrolytes)

1. Karwi  QG, Biswas D, Pulinilkunnil T, Lopaschuk GD. Myocardial Ketones  Metabolism in Heart Failure: Karwi et al. Role of ketone in heart  failure. Journal of Cardiac Failure. 2020;0(0). doi:10.1016/j.cardfail.2020.04.005 PDF
2. Yurista  SR, Chong C-R, Badimon JJ, Kelly DP, de Boer RA, Westenbrink BD.  Therapeutic Potential of Ketone Bodies for Patients With Cardiovascular  Disease: JACC Focus Seminar. Journal of the American College of Cardiology. Published online February 23, 2021. doi:10.1016/j.jacc.2020.12.065
3. White  H, Heffernan AJ, Worrall S, Grunsfeld A, Thomas M. A Systematic Review  of Intravenous β-Hydroxybutyrate Use in Humans – A Promising Future  Therapy? Frontiers in Medicine. 2021;8. doi:10.3389/fmed.2021.740374
4. Cuenoud  B, Hartweg M, Godin J-P, et al. Metabolism of Exogenous  D-Beta-Hydroxybutyrate, an Energy Substrate Avidly Consumed by the Heart  and Kidney. Front Nutr. 2020;7. doi:10.3389/fnut.2020.00013
5. Abbasi J. Ketone Body Supplementation—A Potential New Approach for Heart Disease. JAMA. Published online June 17, 2021. doi:10.1001/jama.2021.8789
6. Karwi QG, Lopaschuk GD. CrossTalk proposal: Ketone bodies are an important metabolic fuel for the heart. The Journal of Physiology. n/a(n/a). doi:https://doi.org/10.1113/JP281004 ABSTRACT
7. S S, Dp K, Kb M. Implications of Altered Ketone Metabolism and Therapeutic Ketosis in Heart Failure. Circulation. doi:10.1161/CIRCULATIONAHA.119.045033 ABSTRACT – open access 2021
8. Lopaschuk Gary D., Karwi Qutuba G., Tian Rong, Wende Adam R., Abel E. Dale. Cardiac Energy Metabolism in Heart Failure. Circulation Research. 2021;128(10):1487-1513. doi:10.1161/CIRCRESAHA.121.318241 ABSTRACT
9. Lopaschuk  GD, Karwi QG, Ho KL, Pherwani S, Ketema EB. KETONE METABOLISM IN THE  FAILING HEART. Biochimica et Biophysica Acta (BBA) – Molecular and Cell  Biology of Lipids. Published online September 10, 2020:158813. doi:10.1016/j.bbalip.2020.158813 ABSTRACT

 Hypertension, or high blood pressure, is a condition characterized by  elevated pressure in the arteries. While hyperinsulinemia isn't directly  linked to hypertension, it often coexists with insulin resistance and  metabolic syndrome, both of which are risk factors for hypertension.  Insulin resistance can lead to dysregulation of vascular function,  including impaired vasodilation and increased sodium retention, which  can contribute to elevated blood pressure. Additionally,  hyperinsulinemia may stimulate the sympathetic nervous system and  increase the production of vasoconstrictor hormones, further raising  blood pressure. Managing hyperinsulinemia through lifestyle changes,  such as weight loss, physical activity, and dietary modifications, may  help improve insulin sensitivity and reduce the risk of hypertension.  However, the relationship between hyperinsulinemia and hypertension is  complex, and additional research is needed to fully elucidate their  interplay. 

Systematic Reviews, Meta-Analyses and other reviews

1. Evans  CE, Greenwood DC, Threapleton DE, Gale CP, Cleghorn CL, Burley VJ.  Glycemic index, glycemic load, and blood pressure: a systematic review  and meta-analysis of randomized controlled trials. The American Journal of Clinical Nutrition. 2017;105(5):1176-1190. doi:10.3945/ajcn.116.143685
2. Yu  Z, Nan F, Wang LY, Jiang H, Chen W, Jiang Y. Effects of high-protein  diet on glycemic control, insulin resistance and blood pressure in type 2  diabetes: a systematic review and meta-analysis of randomized  controlled trials. Clinical Nutrition. Published online August 15, 2019. doi:10.1016/j.clnu.2019.08.008 
3. Rebholz  CM, Friedman EE, Powers LJ, Arroyave WD, He J, Kelly TN. Dietary  Protein Intake and Blood Pressure: A Meta-Analysis of Randomized  Controlled Trials. American Journal of Epidemiology. 2012;176(suppl_7):S27-S43. doi:10.1093/aje/kws245
4. Mente A, O’Donnell M, Yusuf S. Sodium Intake and Health: What Should We Recommend Based on the Current Evidence? Nutrients. 2021;13(9):3232. doi:10.3390/nu13093232

Trials/Studies

1. Yancy  WS, Westman EC, McDuffie JR, et al. A Randomized Trial of a  Low-Carbohydrate Diet vs Orlistat Plus a Low-Fat Diet for Weight Loss. Arch Intern Med. 2010;170(2):136. doi:10.1001/archinternmed.2009.492 
2. Chiu  S, Bergeron N, Williams PT, Bray GA, Sutherland B, Krauss RM.  Comparison of the DASH (Dietary Approaches to Stop Hypertension) diet  and a higher-fat DASH diet on blood pressure and lipids and  lipoproteins: a randomized controlled trial1–3. The American Journal of Clinical Nutrition. 2016;103(2):341-347. doi:10.3945/ajcn.115.123281Unwin DJ, T
3. Unwin  DJ, Tobin SD, Murray SW, Delon C, Brady AJ. Substantial and Sustained  Improvements in Blood Pressure, Weight and Lipid Profiles from a  Carbohydrate Restricted Diet: An Observational Study of Insulin  Resistant Patients in Primary Care. International Journal of Environmental Research and Public Health. 2019;16(15):2680. doi:10.3390/ijerph16152680
4. Pérez-Guisado  J, Muñoz-Serrano A. A Pilot Study of the Spanish Ketogenic  Mediterranean Diet: An Effective Therapy for the Metabolic Syndrome. Journal of Medicinal Food. 2011;14(7-8):681-687. doi:10.1089/jmf.2010.0137
5. Walker  L, Smith N, Delon C. Weight loss, hypertension and mental well-being  improvements during COVID-19 with a multicomponent health promotion  programme on Zoom: a service evaluation in primary care. BMJ Nutrition, Prevention & Health. Published online February 13, 2021:bmjnph. doi:10.1136/bmjnph-2020-000219 PDF
6. Barrea, L. et al. (2023) ‘Very low-calorie ketogenic diet (VLCKD): an antihypertensive nutritional approach’, Journal of Translational Medicine, 21(1), p. 128. Available at: https://doi.org/10.1186/s12967-023-03956-4.
7. Sun  S, Kong Z, Shi Q, Zhang H, Lei O-K, Nie J. Carbohydrate Restriction  with or without Exercise Training Improves Blood Pressure and Insulin  Sensitivity in Overweight Women. Healthcare. 2021;9(6):637. doi:10.3390/healthcare9060637
8. Shah  S, MacDonald C-J, El Fatouhi D, et al. The associations of the  Palaeolithic diet alone and in combination with lifestyle factors with  type 2 diabetes and hypertension risks in women in the E3N prospective  cohort. Eur J Nutr. Published online April 28, 2021. doi:10.1007/s00394-021-02565-5
9. Kim  D, Roberts C, McKenzie A, George MP. Nutritional ketosis to treat  pulmonary hypertension associated with obesity and metabolic syndrome: a  case report. Pulm Circ. 2021;11(1):2045894021991426. doi:10.1177/2045894021991426 
10. Ballard  KD, Quann EE, Kupchak BR, et al. Dietary carbohydrate restriction  improves insulin sensitivity, blood pressure, microvascular function,  and cellular adhesion markers in individuals taking statins. Nutr Res. 2013;33(11):905-912. doi:10.1016/j.nutres.2013.07.022 ABSTRACT

Association Studies

1. Peng  W, Xie Y, Cao H, et al. Association study of fasting blood glucose and  salt sensitivity of blood pressure in community population: the EpiSS  study. Nutrition, Metabolism and Cardiovascular Diseases. 2021;0(0). doi:10.1016/j.numecd.2021.04.026 PDF
2. He  D, Sun N, Xiong S, Qiao Y, Ke C, Shen Y. Association between the  proportions of carbohydrate and fat intake and hypertension risk:  findings from the China Health and Nutrition Survey. Journal of Hypertension. 2021;Publish Ahead of Print. doi:10.1097/HJH.0000000000002803 ABSTRACT

Fasting

1. Maifeld  A, Bartolomaeus H, Löber U, et al. Fasting alters the gut microbiome  reducing blood pressure and body weight in metabolic syndrome patients. Nature Communications. 2021;12(1):1970. doi:10.1038/s41467-021-22097-0 
2. Grundler  F, Mesnage R, Michalsen A, Wilhelmi de Toledo F. Blood Pressure Changes  in 1610 Subjects With and Without Antihypertensive Medication During  Long‐Term Fasting. J Am Heart Assoc. 2020;9(23). doi:10.1161/JAHA.120.018649
3. Luke  K, Ferona NA, Putri HLAS, et al. THE EFFECT OF RAMADAN FASTING TO BLOOD  PRESSURE IN HYPERTENSIVE PATIENTS: A META-ANALYSIS. Journal of Community Medicine and Public Health Research. 2021;2(2):53-59. doi:10.20473/jcmphr.v2i2.26821 PDF
4. Touyz Rhian M. Gut Dysbiosis–Induced Hypertension Is Ameliorated by Intermittent Fasting. Circulation Research. 2021;128(9):1255-1257. doi:10.1161/CIRCRESAHA.121.319147 ABSTRACT – a commentary on the following pre-clinical study

Mechanisms

1. Barrea, L. et al. (2023) ‘Effects of very low-calorie ketogenic diet on  hypothalamic–pituitary–adrenal axis and renin–angiotensin–aldosterone  system’, Journal of Endocrinological Investigation, 46(8), pp. 1509–1520. Available at: https://doi.org/10.1007/s40618-023-02068-6.
2. da  Silva AA, do Carmo JM, Li X, Wang Z, Mouton AJ, Hall JE. Role of  Hyperinsulinemia and Insulin Resistance in Hypertension: Metabolic  Syndrome Revisited. Can J Cardiol. 2020;36(5):671-682. doi:10.1016/j.cjca.2020.02.066 
3. Yanai  H, Tomono Y, Ito K, Furutani N, Yoshida H, Tada N. The underlying  mechanisms for development of hypertension in the metabolic syndrome. Nutrition Journal. 2008;7(1):10. doi:10.1186/1475-2891-7-10
4. Preuss  HG, Kaats GR, Mrvichin N, Bagchi D. Analyzing Blood Pressure Ascent  during Aging in Non-Diabetics: Focusing on Links to Insulin Resistance  and Body Fat Mass. Journal of the American College of Nutrition. 2021;40(4):317-326. doi:10.1080/07315724.2021.1875339
5. Senarathne, R. et al. (2021) ‘Metabolic syndrome in hypertensive and non-hypertensive subjects’, Health Science Reports, 4(4), p. e454. doi:10.1002/hsr2.454.

By Abdullah Sarhan - Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=75989191

 Hypertriglyceridemia is a condition characterized by elevated levels of  triglycerides in the blood. Triglycerides are a type of fat found in  your blood. They are primarily derived from the fats we eat, but they  are also produced by the body as a form of energy storage. Elevated  triglyceride levels can be a risk factor for cardiovascular diseases,  including heart attacks and strokes. 

Hyperinsulinemia can exacerbate hypertriglyceridemia by promoting the  synthesis of triglycerides, reducing their breakdown, impairing their  clearance, and disrupting lipid metabolism. Managing insulin levels  through lifestyle changes, such as diet and exercise, and in some cases,  medication, can help improve triglyceride levels and reduce the risk of  cardiovascular complications associated with hypertriglyceridemia. 

 Hyperuricemia, an elevated level of uric acid in the blood, can be influenced by insulin resistance, hyperinsulinemia, or metabolic syndrome in several ways:

1. Insulin resistance and uric acid production: Insulin resistance is associated with increased insulin levels, which can stimulate the production of uric acid in the body. Elevated insulin levels inhibit renal uric acid excretion and promote uric acid reabsorption in the kidneys, leading to higher uric acid levels in the blood.
2. Dyslipidemia and uric acid metabolism: Metabolic syndrome often includes dyslipidemia, characterized by elevated triglyceride levels and decreased HDL cholesterol levels. Dyslipidemia can disrupt uric acid metabolism and lead to increased uric acid production, contributing to hyperuricemia.
3. Obesity-related factors: Obesity, a common feature of metabolic syndrome, is strongly associated with hyperuricemia. Adipose tissue produces substances called adipokines, such as leptin and adiponectin, which can influence uric acid metabolism and renal function. Adipokines may promote uric acid production and decrease uric acid excretion, leading to higher uric acid levels in obese individuals.
4. Insulin signaling and renal uric acid handling: Insulin resistance and hyperinsulinemia can affect renal uric acid handling by altering insulin signaling pathways in the kidneys. Insulin resistance may impair the ability of renal tubular cells to reabsorb glucose and uric acid, leading to increased urinary excretion of glucose and decreased excretion of uric acid, contributing to hyperuricemia.
5. Chronic inflammation: Insulin resistance and metabolic syndrome are associated with chronic low-grade inflammation, which may contribute to hyperuricemia. Inflammatory cytokines and adipokines produced by adipose tissue and activated immune cells can influence uric acid metabolism and renal function, leading to elevated uric acid levels in the blood.

Overall, insulin resistance, hyperinsulinemia, and metabolic syndrome can contribute to the development of hyperuricemia through various mechanisms, including increased uric acid production, dyslipidemia, obesity-related factors, altered insulin signaling in the kidneys, and chronic inflammation. Managing these metabolic abnormalities through lifestyle modifications, weight loss, dietary changes, and medication may help reduce uric acid levels and prevent complications associated with hyperuricemia, such as gout and kidney stones.

 The prevalence rate of hyperuricemia remains high in Taiwan, at 21.6% in  men and 9.57% in women. Both metabolic syndrome (MetS) and  hyperuricemia can cause many complications; however, few studies have  evaluated the correlation between MetS and hyperuricemia. Therefore, in  this observational cohort study, we explored associations between  metabolic syndrome (MetS) and its components and new-onset  hyperuricemia. Of 27,033 individuals in the Taiwan Biobank who had  complete follow-up data, we excluded those with hyperuricemia at  baseline (n = 4871), those with gout at baseline (n = 1043), those with no data on baseline uric acid (n = 18), and those with no data on follow-up uric acid (n = 71). The remaining 21,030 participants (mean age 50.8 ± 10.3 years)  were enrolled. We found a significant association between new-onset  hyperuricemia with MetS and the components of MetS  (hypertriglyceridemia, abdominal obesity, low high-density lipoprotein  cholesterol, hyperglycemia, and high blood pressure). Furthermore,  compared to those without any MetS components, those with one MetS  component (OR = 1.816), two MetS components (OR = 2.727), three MetS  components (OR = 3.208), four MetS components (OR = 4.256), and five  MetS components (OR = 5.282) were significantly associated with  new-onset hyperuricemia (all p < 0.001). MetS and its five  components were associated with new-onset hyperuricemia in the enrolled  participants. Further, an increase in the number of MetS components was  associated with an increase in the incidence rate of new-onset  hyperuricemia 

 A persistent cough primarily involves the respiratory system. The respiratory system, also known as the pulmonary system, encompasses the organs and structures involved in breathing and gas exchange, including the lungs, airways (such as the trachea and bronchi), and muscles involved in breathing (such as the diaphragm and intercostal muscles).

A persistent cough can be a symptom of various respiratory conditions, including infections (such as bronchitis or pneumonia), allergies, asthma, chronic obstructive pulmonary disease (COPD), gastroesophageal reflux disease (GERD), or even lung cancer. It is the body's reflex response to irritation or inflammation in the airways, and it serves as a protective mechanism to clear the airways of mucus, irritants, or foreign particles. Therefore, while a persistent cough can sometimes be indicative of issues in other body systems (such as GERD affecting the gastrointestinal system), it is most directly associated with the respiratory system.

 Metabolic issues can contribute to a persistent cough via a number of mechanisms  

Obesity: Metabolic syndrome often involves obesity or excess body weight, which can lead to mechanical compression of the lungs and airways. This compression can result in restricted airflow and increased respiratory effort, potentially causing a chronic cough.

Increased inflammation: Hyperinsulinemia and insulin resistance are associated with chronic low-grade inflammation throughout the body, including in the respiratory system. Elevated levels of inflammatory markers can irritate the airways and contribute to respiratory symptoms such as coughing.

Respiratory infections: Individuals with metabolic syndrome may be at a higher risk of respiratory infections due to impaired immune function and chronic inflammation. Respiratory infections, such as bronchitis or pneumonia, can cause a persistent cough as the body attempts to clear mucus and pathogens from the airways.

Gastroesophageal reflux: Metabolic syndrome is often accompanied by conditions such as gastroesophageal reflux disease (GERD), where stomach acid flows back into the esophagus. This acid reflux can irritate the throat and airways, leading to coughing.

Sleep apnea: Metabolic syndrome is a risk factor for obstructive sleep apnea, a condition characterized by episodes of interrupted breathing during sleep. Chronic coughing can be a symptom of sleep apnea due to irritation of the airways during episodes of airflow obstruction.

Overall, while hyperinsulinemia, insulin resistance, and metabolic syndrome may not directly cause a persistent cough, their impact on obesity, inflammation, immune function, and comorbid conditions can contribute to respiratory issues that manifest as a chronic cough. It's essential for individuals with these conditions to manage them effectively and seek medical  

Background: Metabolic syndrome and insulin resistance are associated with worsened outcomes of chronic lung disease. The triglyceride-glucose index (TyG), a measure of metabolic dysfunction, is associated with metabolic syndrome and insulin resistance, but its relationship to lung health is unknown. 

Research question: What is the relationship of TyG to respiratory symptoms, chronic lung disease, and lung function? 

Study design and methods: This study analyzed data from the National Health and Nutrition Examination Survey from 1999 to 2012. Participants included fasting adults age ≥ 40 years (N = 6,893) with lung function measurements in a subset (n = 3,383). Associations of TyG with respiratory symptoms (cough, phlegm production, wheeze, and exertional dyspnea), chronic lung disease (diagnosed asthma, chronic bronchitis, and emphysema), and lung function (FEV1, FVC, and obstructive or restrictive spirometry pattern) were evaluated, adjusting for sociodemographic variables, comorbidities, and smoking. TyG was compared vs insulin resistance, represented by the homeostatic model assessment of insulin resistance (HOMA-IR), and vs the metabolic syndrome. 

Results: TyG was moderately correlated with HOMA-IR (Spearman ρ = 0.51) and had good discrimination for metabolic syndrome (area under the receiver-operating characteristic curve, 0.80). A one-unit increase in TyG was associated with higher odds of cough (adjusted OR [aOR], 1.28; 95% CI, 1.06-1.54), phlegm production (aOR, 1.20; 95% CI, 1.01-1.43), wheeze (aOR, 1.18; 95% CI, 1.03-1.35), exertional dyspnea (aOR, 1.21; 95% CI, 1.07-1.38), and a diagnosis of chronic bronchitis (aOR, 1.21; 95% CI, 1.02-1.43). TyG was associated with higher relative risk of a restrictive spirometry pattern (adjusted relative risk ratio, 1.45; 95% CI, 1.11-1.90). Many associations were maintained with additional adjustment for HOMA-IR or metabolic syndrome. 

Interpretation: TyG was associated with respiratory symptoms, chronic bronchitis, and a restrictive spirometry pattern. Associations were not fully explained by insulin resistance or metabolic syndrome. TyG is a satisfactory measure of metabolic dysfunction with relevance to pulmonary outcomes. Prospective study to define TyG as a biomarker for impaired lung health is warranted. 

It was the persistent cough that finally got me to a medical appointment.  Just an ongoing small iritation, not quite enough to take seriously which disappeared without trace once blood sugars normnalised 

  A Pulmonary embolism (PE) occurs when a blood clot, typically originating  from the deep veins of the legs (deep vein thrombosis), travels to the  lungs and blocks a pulmonary artery or one of its branches.  Hyperinsulinemia, characterized by elevated levels of insulin in the  blood, can contribute to the risk of pulmonary embolism through various  mechanisms. Insulin resistance, a hallmark of hyperinsulinemia and  metabolic syndrome, is associated with dyslipidemia, chronic  inflammation, endothelial dysfunction, and oxidative stress, all of  which can promote the formation of blood clots. Additionally,  hyperinsulinemia may exacerbate other risk factors for pulmonary  embolism, such as obesity, immobility, surgery, and certain medical  conditions like cancer and inflammatory disorders. Over time, these  processes can increase the likelihood of clot formation in the deep  veins of the legs, which can dislodge and travel to the lungs, causing a  pulmonary embolism. Therefore, managing hyperinsulinemia through  lifestyle modifications, insulin-sensitizing medications, and  appropriate medical interventions is crucial for reducing the risk of  pulmonary embolism and its potentially life-threatening consequences. 

  A stroke occurs when blood flow to a part of the brain is interrupted or  reduced, leading to brain cell damage and potentially permanent  neurological deficits. Hyperinsulinemia, characterized by elevated  levels of insulin in the blood, can contribute to the development and  risk of stroke through several mechanisms. Insulin resistance, a  hallmark of hyperinsulinemia and metabolic syndrome, is associated with  dyslipidemia, chronic inflammation, endothelial dysfunction, and  oxidative stress, all of which can promote the formation of  atherosclerotic plaques in the arteries supplying blood to the brain  (cerebral arteries). Additionally, hyperinsulinemia may exacerbate other  risk factors for stroke, including hypertension, diabetes, and obesity.  Over time, these processes can increase the likelihood of  atherosclerosis, blood clots, or rupture of blood vessels in the brain,  leading to ischemic or hemorrhagic strokes. Therefore, managing  hyperinsulinemia through lifestyle modifications, insulin-sensitizing  medications, and appropriate medical interventions is crucial for  preventing and reducing the risk of stroke and its devastating  consequences. 

" Compared to non-diabetes, T2D had a two-to four-fold higher risk of  recurrent atherosclerotic thrombotic events and vascular complications.  The activation of these events causes even more vasoconstriction and  promotes thrombosis (32).  IR, the key role of T2D, has also attracted the interest of  researchers. A rising number of studies are focusing on the connection  between IR and thrombosis. Researchers found that IR can impair  endothelial cell function and enhance platelet adhesion, activation, and  aggregation, resulting in the formation of thrombosis "

"The pathological condition of insulin resistance prevents the  neuroprotective effects of insulin. Numerous studies have demonstrated  that insulin resistance, as an independent risk factor for ischemic  stroke, accelerates the formation of thrombosis and promotes the  development of atherosclerosis, both of which are major mechanisms of  ischemic stroke. Additionally, insulin resistance negatively affects the  prognosis of patients with ischemic stroke regardless of whether the  patient has diabetes, but the mechanisms are not well studied. We  explored the association between insulin resistance and the primary  mechanisms of brain injury in ischemic stroke (inflammation, oxidative  stress, and neuronal damage), looking for potential causes of poor  prognosis in patients with ischemic stroke due to insulin resistance.  Furthermore, we summarize insulin resistance therapeutic approaches to  propose new therapeutic directions for clinically improving prognosis in  patients with ischemic stroke.      "