History of Public Health

• From the beginning of recorded time through the first half of the twentieth century, people got sick and died quickly, and young especially died young and quick.
• Some people had chronic infections like tuberculosis, leprosy, syphilis, or trichinosis.
• In the Middle Ages, people went to barber surgeons for treatments like vein cutting
• Sanitaria became the first chronic care facilities, while madhouses handled mental health issues
• The first effective prevention started when Edward Jenner discovered vaccination against smallpox in the 1790s
• In 1854, John Snow isolated the Broad Street pump as the source of a London cholera epidemic, inventing the field of epidemiology
• Joseph Lister advocated for sterilizing surgical instruments and handwashing in 1883
• Preventing infections at the public health level was a success with hygiene, quarantine, sanitation, and immunization
• Tuberculosis and typhus were combatted through societal hygiene changes
• Government intervention was necessary for public health to reach the populace
• The Industrial Revolution introduced sweatshops, accidents, sickness, and nutritional deficiencies
• Canning food became popular in the late 1800's but so did lead poisoning
• Government regulation is ultimately required for effective change in curtailing acute and chronic diseases
• In 1940, Albert Alexander was the first human to receive penicillin for a severe acute facial infection
• In 1947, bacterial species began developing resistance to penicillin
• Modern medicine continues to chase targeted therapy but cures continue to elude society

Modern Medicine 2.0

• There is a critical mass of drug-resistant bacteria that can share intelligence between species
• Viral diseases are now more dangerous and harder to control than bacteria, like HIV in 1979, hantavirus in 1993, Ebola in 2014, and coronavirus in 2020
• High-tech screening of drugs, Big Data informatics, and genetic editing using CRISPR-Cas9 attempt to target therapy to the individual and the pathology
• Therapies for genetic diseases, such as severe combined immunodeficiency disease, hold promise
• Viruses are also being researched to program an individual's own immune cells to kill cancers
• At UCSF, stem cells are harvested and differentiated into pancreatic beta-cells to cure Type 1 diabetes
• Targeted cures may not address what reduces life span and health worldwide, and is increasing morbidity, costing big dollars, and breaking healthcare
• Metabolic syndrome encompasses the cluster of NCDs that cost 75% of healthcare dollars in the US, and half of the healthcare dollars around the world
• Metabolic syndrome diseases do not have one gene or pathway to target, and are multifactorial diseases with multiple morbidities.
• Insulin resistance is the primary defect in metabolic syndrome an underlying cause of most troubles
• Insulin resistance manifests differently, with variable cholesterol and blood pressure
• Leptin and Ghrelin play a role in the hunger satiety system, with insulin doing double duty to tell the body to "store" and tell the brain to "stop eating."
• Obesity is a Red Herring and everyone thinks that first you gain weight, and then you get sick.
• The key to remaining healthy is people have lots of subcutaneous fat, very little ectopic fat (fat in cells that shouldn't have fat), normal metabolic function, and low insulin levels.
• Approximately 40% of normal weight people also have metabolic syndrome
• TOFI describes people who are thin on the outside, fat on the inside
• Ectopic fat determines the odds of developing diabetes or heart disease

Cholesterol and Risk Factors

• High LDL-C isn't really so bad, and once younger people are removed and just look at older people high LDL-C levels correlate with longevity
• Nine times out of ten patients gets a prescription for a statin, which inhibits cholesterol synthesis for high LDL-C levels
• LDL-C levels haven't changed appreciably despite governmental recommendations to eat low-fat and despite a high prescription rate of statins, at a population level
• Individuals are suffering heart attacks with lower LDL-Cs because the standard fasting lipid profile, cholesterol assumes that all LDL particles are the same
• Eighty percent of circulating LDL species, large buoyant, or type A LDL are increased by dietary fat consumption
• Statins are reducing the large buoyant LDL but not doing anything about the small dense LDL, therefore the risk of a first heart attack remains unchanged
• Up to 20 perfect of statin users demonstrated some form of side effect, often quite serious like increase in glucose intolerance in the risk for both diabetes and weight gain, etc.
• Triglycerides high the age ratio for triglycerides and heart disease is 1.8
• Hypertension is the #1 risk factor for death globally, with each 5-point rise in blood pressure increasing a death risk by 10 percent
• Patients with mild hypertension show no benefit from blood pressure reduction whatsoever in terms of cardiovascular disease, stroke, and death

Food and Blood Pressure

• The UK documented a 40 percent reduction in stroke between 2006 and 2012 via the government forcing food companies to reduce the amount of salt allowed in processed foods
• High insulin levels increase blood pressure, even with relatively low sodium intake and many people are insulin resistant.
• Sugar raises your blood pressure more than salt, and reducing your blood pressure
• If you take processed food out, you've lowered salt and sugar, and you wouldn't need the medicine
• One hundred% of a fructose load enters the liver, fructose leads to loss of phosphates from ATP
• Fructose generating of uric acid, which reduces nitric oxide, your blood vessels relaxing agent, which leads to hypertension.
• Type 1 diabetes is due to insulin deficiency, an autoimmune destruction of the pancreas, and is usually associated with children
• Type 2 is due to insulin resistance, the key driver of metabolic syndrome and usually associated with adults
• The diabetes biomarker hemoglobin Alc tests for chronically high blood glucose levels
• The potential side effects of meds, can include dizziness, drowsiness, heartburn, gastrointestinal distress, and seizures

Insulin and Diabetes

• Insulin is real bad in this story and it's own risk factor
• Kahn's lab constructed eight separate tissue-specific insulin receptor knockout IRKO models
• Pathology development varies with the liver and the brain IRKO mice developing high blood glucose, and only the brain IRKO mouse became obese and developed metabolic syndrome.
• Insulin is both good lowers blood glucose to prevent microvascular disease and bad increases the smooth muscle around the coronary arteries or in the kidney, leading to narrowing
• The dichotomous effect of insulin has been seen in every intensive blood glucose control study
• Blood glucose has become so important to Modern Medicine with CGMs to lower their glucose excursions and therefore improve their metabolic control
• In the US, the total expenditure in diabetic drugs, monitors, and treatment reached $ 350 billion last year, which is 10 percent of the overall healthcare expenditure
• Modern Medicine works downstream of the problem by treating the symptoms, rather than working upstream to treat the cause