BMS 150 Week 13: Type 2 Diabetes Overview

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Questions and Answers

What percentage of diabetes cases are classified as Type II diabetes?

Around 25%

Over 50%

Less than 10%

90% or more (correct)

Which demographic group has a higher prevalence of Type II diabetes?

Middle Eastern populations

Caucasians

Individuals with Asian ancestry

Individuals of Aboriginal descent (correct)

What condition is often a precursor to the development of Type II diabetes in individuals?

Excessive urination

Insulin resistance (correct)

High blood pressure

Hypoglycemia

What is the typical age of diagnosis for Type II diabetes?

Over 30 years Signup and view all the answers

What lifestyle factor can significantly impact the progression of Type II diabetes?

Proper diet and adequate physical activity Signup and view all the answers

What is the primary function of the VLDL lipoprotein in the endogenous pathway?

To carry liver-synthesized lipids to other cells Signup and view all the answers

Which apoproteins are primarily associated with chylomicrons?

ApoB-48, ApoE, and ApoC-II Signup and view all the answers

How does the liver regulate the amount of cholesterol it receives from peripheral tissues?

By downregulating the LDL receptor Signup and view all the answers

What triggers the transformation of monocytes into macrophages during the development of atherosclerosis?

Binding to LDL lipoprotein Signup and view all the answers

What is one consequence of excess cholesterol accumulation in hepatocytes?

Decreased expression of the LDL receptor Signup and view all the answers

What is the primary function of the large intestine?

Convert undigested material into feces and remove water Signup and view all the answers

Which part of the large intestine is the widest and most prone to perforation?

Cecum Signup and view all the answers

Which reflex is associated with the movement of contents from the ileum to the colon?

Gastroileal reflex Signup and view all the answers

What role does mucin play in the function of the large intestine?

Enhances fecal formation and lubrication Signup and view all the answers

What is the primary function of the microbiota present in the large intestine?

Synthesize Vitamin K and Biotin Signup and view all the answers

What anatomical feature separates the rectum from the prostate and seminal vesicles?

Denonvilliers’ fascia Signup and view all the answers

Which artery supplies blood to the proximal rectum?

Superior rectal artery Signup and view all the answers

What type of muscle comprises the external anal sphincter?

Voluntary skeletal muscle Signup and view all the answers

Which of the following is the primary innervation source for the ascending and transverse colon?

Vagus nerve Signup and view all the answers

What structural characteristic distinguishes the mucosa of the rectum from the rest of the large intestine?

Rectal columns of Morgagni Signup and view all the answers

What mechanism does Shigella use to invade neighboring epithelial cells?

Endocytosis Signup and view all the answers

What occurs as a result of Shigella infection in epithelial cells?

Formation of mucosal abscess Signup and view all the answers

What happens to Shigella that enters the bloodstream?

It is phagocytized and destroyed Signup and view all the answers

Which serotypes of Salmonella are primarily responsible for causing typhoid fever?

Typhi and Paratyphi Signup and view all the answers

What outcome occurs with the multiplication of Shigella in the cytosol?

Neighboring epithelial cells are invaded Signup and view all the answers

What is a primary symptom associated with typhoid fever?

Increasing fever Signup and view all the answers

What complication can arise from Campylobacter diarrhea?

Guillain-Barre Syndrome Signup and view all the answers

What is the primary method by which Salmonella induces infection?

Triggers endocytosis in host cells Signup and view all the answers

Which of the following describes how Salmonella can cause bacteremia?

Enters the bloodstream after intestinal infection Signup and view all the answers

What does Salmonella do to the host cells after multiplication?

Kills host cells Signup and view all the answers

Study Notes

Diabetes Epidemiology

25 million Americans have diabetes; one-third are unaware.
54 million adults are classified as pre-diabetic.
Pre-diabetes is indicated by abnormal OGTT results, with a 5-10% annual progression to diabetes.
1.5 million new diabetes cases arise yearly.
Increasing prevalence noted in countries like India and China.
High-risk racial groups include Aboriginal peoples, Hispanics, and those of African ancestry, with a risk increase of 1.5 to 2 times.

Type II Diabetes

Accounts for over 90% of diabetes cases, typically diagnosed after age 30.
Often preceded by insulin resistance and glucose intolerance, sometimes starting in childhood.
Characterized by initial insulin resistance followed by decreasing insulin secretion.
Progression spans years to decades, with 80% of sufferers being obese.
Twin concordance rate between 70-90% suggests significant genetic and environmental influences.

Etiology of Type II Diabetes

Lifestyle choices significantly impact T2DM progression; however, genetics play a larger role compared to Type I.
Monozygotic twins show a 70-90% concordance for Type II diabetes, while Type I shows 30-50%.
Over 70 genes identified influencing insulin secretion and diabetes susceptibility.

Genes Implicated in Type II Diabetes

Each identified gene roughly increases diabetes risk by 5% (RR 1.05).
Key genes include TCF7L2 (transcription factor) and PPAR receptor (nuclear receptor).
Existing genes account for only 10% of overall genetic risk in diabetes cases.

Environmental Risk Factors

Obesity, particularly central obesity, is the primary environmental risk factor leading to insulin resistance.
Exercise is a separate risk factor influencing diabetes risk.

Pathogenesis and Insulin Resistance

Obesity causes reduced glucose utilization, abnormal fat metabolism, and systemic low-grade inflammation.
Central fat strongly correlates with type 2 diabetes.
Insulin resistance is generally a product of multifactorial influences, not single-gene disorders.

Obesity and Satiety Regulation

Satiety signals include leptin, GLP1, CCK, PYY, while hunger is driven by ghrelin.
Regulation occurs through interaction with the hypothalamus.

Visceral Obesity Effects

Visceral obesity exacerbates insulin resistance by increasing insulin release and reducing glucagon secretion.
Chronic high glucose levels cause insulin receptor desensitization.

Non-Esterified Fatty Acids (NEFA) Role

NEFA from central fat increases insulin resistance.
High intracellular NEFA levels cause serine phosphorylation, inactivating insulin receptors.
Adipokines can enhance or reduce insulin sensitivity based on circulating levels.

Insulin Resistance and Dyslipidemia

Insulin-resistant individuals produce more VLDL; liver produces excess triglycerides.
Lipoprotein lipase (LPL) is down-regulated in insulin-resistant states leading to reduced triglyceride clearance.
HDL levels decrease during insulin resistance, mechanisms remain unclear.

Long-term Hyperglycemia Complications

Diabetes leads to both small vessel and large vessel diseases.
Diabetic macrovascular disease is characterized by accelerated atherosclerosis.
Myocardial infarction due to coronary artery atherosclerosis is the most common diabetic mortality cause.
Advanced peripheral vascular disease leads to gangrene, being significantly more common in diabetics.

Clinical Features of Type II Diabetes

Often asymptomatic initially; most patients exhibit obesity.
Diabetic ketoacidosis (DKA) is rare; hyper-osmolar non-ketotic crises may occur.
Patients experience slowly progressing peripheral neuropathy, impaired wound healing, and vision complications.
Acanthosis nigricans appears as an early sign of insulin resistance.

Acanthosis Nigricans

Characterized by hyperpigmented, velvety skin patches, commonly in axillary regions and neck.

General Lipoprotein Physiology

Cholesterol and triglycerides are transported by lipoproteins, which consist of a phospholipid monolayer and apoproteins.
Three main transport pathways:
- Exogenous: Lipids sourced from the digestive tract, distributed after meals.
- Endogenous: Liver-produced apolipoproteins that distribute lipids systemically.
- Reverse cholesterol transport: Removes cholesterol from peripheral tissues back to the liver.

Overview of Lipid Transport

Exogenous Pathway:
- Initial lipoprotein: Chylomicrons (ApoB-48, ApoE, ApoC-II).
- Function: Carry dietary lipids to cells, especially liver and adipose tissue.
- Cleared by liver using an ApoE-dependent mechanism.
Endogenous Pathway:
- Initial lipoprotein: VLDL (ApoB-100, ApoC-II).
- Transforms into IDL and then LDL as triglycerides are cleaved.
- LDL is primarily cleared by LDL receptors in the liver.
Reverse Cholesterol Transport:
- Initial lipoprotein: HDL (ApoA-I, ApoA-II).
- Function: Transfer cholesterol from tissues to liver.
- Contains cholesterol esters and can exchange cholesterol with other lipoproteins.

Regulation of the LDL Receptor

LDL receptor activity is downregulated when hepatocytes have excess cholesterol.
Liver reduces VLDL synthesis and increases cholesterol secretion in bile.
PCSK9 protein can degrade LDL receptors, affecting LDL clearance.

Atherosclerosis

Atheromas develop in large and medium arteries, leading to significant mortality in Western countries.
Key factors in development include endothelial injury, hyperlipidemia, and inflammation.

Atherosclerosis Pathogenesis

Endothelial damage increases permeability and leukocyte adhesion, leading to lipid accumulation.
LDL and oxidized LDL lead to macrophage activation and foam cell formation.
Plaque progression causes further endothelial dysfunction and smooth muscle cell proliferation.

Major Risk Factors for Atherosclerosis

Dyslipidemia: High LDL, low HDL.
Lifestyle: Smoking, inactivity, unhealthy diet.
Medical: Diabetes, hypertension.
Demographics: Family history, age, obesity.

Cardiac Risk and Lipid Labs

LDL categorized based on Canadian values; indirectly measured via equations including total cholesterol and triglycerides.
Total cholesterol and HDL values impact cardiovascular risk assessments, aiming for a TC:HDL ratio under 3.5.

Primary Care Lipid Measurement

Recommendations include fasting serum tests for TC, LDL, HDL, and triglycerides every 1-3 years for at-risk groups.
Utilize the Framingham Risk Score to assess 10-year coronary artery disease risk based on gender, age, cholesterol levels, and other health factors.

Overview of the Large Intestine

Converts undigested material to feces by removing water and adding mucus.
Stores and transports feces while hosting the largest microbial population in the body.
Microbiota produce essential vitamins, such as Vitamin K and Biotin.
Slower motility aids in water and solute absorption.

Anatomy of the Large Intestine

Begins at the ileocecal valve; ends at the anus.
Cecum: Widest part, most susceptible to perforation.
Colon parts:
- Ascending, transverse, descending, and sigmoid colon.
- Hepatic and splenic flexures mark transitions between segments.
Sigmoid colon: Narrowest and most mobile, prone to volvulus.

Rectum and Anal Canal

Rectum: 12-15 cm long, supported by Denonvilliers’ fascia, and innervated by pelvic splanchnic nerves.
Anal Canal: 4 cm in length; transitions from simple columnar to stratified squamous epithelium.
Contains both internal (involuntary) and external (voluntary) anal sphincters.

Vascular Supply

Supplied by branches of the Superior Mesenteric Artery (ileocolic, right colic, middle colic) and Inferior Mesenteric Artery (left colic, sigmoid branches, superior rectal artery).
Venous drainage parallels arterial supply, facilitating efficient blood flow.

Innervation

Sympathetic innervation arises from thoracic and lumbar spinal regions.
Parasympathetic innervation: Vagus nerve for ascending/transverse colon; S2-S4 for descending/sigmoid colon.

Histology of the Large Intestine

Lacks villi, with simple columnar epithelium rich in goblet cells for mucus production.
Deep crypts present, important for lymphocyte proliferation.
Muscularis externa characterized by three longitudinal bands known as Teniae coli.

Digestion and Absorption

Microbiota play a crucial role in digestion, particularly in short-chain fatty acid (SCFA) production.
Primarily absorbs water, Na+, and minerals, along with SCFA produced by microbiota.
Mucin secretion produces a protective mucus layer that aids in lubrication and immune defense.

Motility Patterns

Involves segmentation, peristalsis, and mass action contractions for fecal movement.
Hirschsprung Disease: Congenital absence of ganglia causes severe constipation due to lack of peristalsis.
Gastroileal and Gastrocolic Reflexes: Coordination of movement between GI tracts stimulated by food intake.

Fluid Homeostasis

Absorbs approximately 5 L of water daily, retaining about 200 mL in feces.
Water absorption is enhanced by Na+ uptake occurring differently in various sections of the colon.

Mechanisms of Na+ Absorption

Involves electrogenic and electroneutral mechanisms, including Na+/K+ ATPase activity and exchange processes with H+ and HCO3-.

Defecation Process

Rectal distention triggers reflex contractions indicating the need to defecate.
Internal and external sphincters coordinate voluntary and involuntary control.
Puborectalis muscle adjustment influences the rectoanal angle, facilitating bowel movements.

Inhibition of Defecation

Maintained by tonic activity of both sphincters and the contraction of the puborectalis muscle, preserving fecal continence.

Shigella and Shigellosis

Shigella invades epithelial cells of the colon and triggers endocytosis.
Shigella multiplies within the cytosol and uses actin fibers to move into neighboring cells.
This invasion allows Shigella to evade immune defenses and form mucosal abscesses due to the death of epithelial cells.
Shigella does not typically enter the bloodstream; if it does, it is rapidly phagocytized without causing bacteremia.

Salmonella and Salmonellosis/Typhoid Fever

Causative agent: Salmonella enterica with over 2000 serotypes; Typhi and Paratyphi cause typhoid fever, while Enteridis and Typhimurium lead to nonspecific infections.
Salmonella attaches to small intestine epithelial cells and triggers endocytosis, multiplying inside food vesicles.
Host cell death results in fever, cramps, and diarrhea; bacteria can enter the bloodstream, leading to bacteremia.

Typhoid Fever Symptoms

Symptoms include increasing fever, headache, muscle pains, malaise, and appetite loss lasting over a week.
Characteristic “Rose Spot” rash may appear on the abdomen.
Severe complications: intestinal hemorrhage, perforation, kidney failure, peritonitis.

Campylobacter Diarrhea

Causative agent: Campylobacter jejuni, frequently found in chickens (81% carry it).
Virulence factors allow colonization of jejunum, ileum, and colon.
Incidence: 1.3 million cases per year with a mortality rate of approximately 75.
Complications include Guillain-Barre Syndrome (GBS), Irritable Bowel Syndrome (IBS), and arthritis.

Antimicrobial-Associated Diarrhea

Severe diarrhea can arise from the use of broad-spectrum antibiotics, common in hospitals.
Acute cases involve passing up to 10 watery, foul-smelling stools daily; severe cases may produce blood.

C. difficile and Pathogenesis

Causative agent of antimicrobial-associated diarrhea: Clostridium difficile.
Bacterial gastroenteritis can lead to bacterial intoxication, featuring symptoms like nausea, vomiting, diarrhea, and dehydration.

Helicobacter pylori and Peptic Ulcers

Helicobacter pylori is responsible for ulcer formation by neutralizing stomach acid and invading gastric epithelial cells.
Symptoms include abdominal pain, nausea, and "coffee grounds" vomit.
Long-term complications can include bowel obstructions and internal bleeding.

Dental Caries and Gingivitis

Causative agent of dental caries is Streptococcus mutans, which contributes to plaque formation.
High sucrose diets and frequent snacking are primary causes; 92% of North American adults have had dental caries.
Diagnosis is through visual inspection and X-rays; treatment often involves cavity filling.

Mumps

Caused by Rubulavirus (unenveloped, -ssRNA virus) with entry through upper respiratory mucus membranes.
Symptoms include parotitis, facial pain, fever, headache, and sore throat; incubation period lasts 12-24 days.

Viral Gastroenteritis

Approximately 200 million cases occur daily, with a vast volume of diarrheal water produced akin to water flow over Victoria Falls.
Rotavirus is the leading cause of infant diarrheal illness worldwide, with an RNA genome and infections peaking in winter.
Transmitted through fecal-oral contamination, with as little as 10 infectious particles needed for infection.

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Description

This quiz covers critical information regarding Type 2 diabetes, its epidemiology, and the impact of obesity and insulin resistance. Explore statistics regarding its prevalence in the US and other countries, including the implications of pre-diabetes. Understand key findings and trends to enhance your knowledge of this significant health issue.