Diabetes Mellitus: Glucose Metabolism & Regulation

Diabetes Mellitus (DM)

• Affects how the body uses energy nutrients
• Alters glucose metabolism, hormonal regulation, insulin's role, and glucose regulators with regard to glucose metabolism

Glucose Regulation

• Produced from endogenous glycogen stores in muscle/liver
• Supplied through bloodstream from GI tract and liver
• Regulated by insulin, neural activity, exercise, and stress

Glucose Metabolism

• Exercise lowers insulin levels while increasing glucagon/catecholamine levels, leading to glycogenolysis
• Stress raises blood glucose due to corticosteroids and catecholamines
• Insulin lowers glucose levels by allowing glucose to enter cells for use
• Neural: High glucose stimulates insulin release; glucagon regulated by SNS in response to hypoglycemia
• Glucagon release tells the liver to release glycogen when glucose levels are low

Insulin

• The pancreas makes insulin
• Released when glucose levels are high
• Regulates protein and fat metabolism
• Stimulated by glucose
• Mediates glucose uptake into cells
• Lowers amino acid release by skeletal muscle
• Prevents muscle breakdown to conserve energy/glucose
• Prevents fat breakdown and promotes lipid formation
• Stimulates insulin-like growth factor, leading to somatomedin production, to facilitate growth during periods of high glucose

Insulin Role

• Fed state: glucose from food intake triggers insulin release
• Amylin increases feelings of fullness
• Amylin blocks gastric emptying and decreases hunger
• Postprandial rise in blood glucose stimulates insulin production
• 1st phase: brief insulin increase

Glucose Production

• 2nd phase (insulin synthesis): sustained presence of glucose
• Insulin presence starts glucose spread into muscle and fat tissue
• Prevents liver glucose production
• Increased glucose from food/liver results in high blood sugar
• Fasting state: relies on glycogenolysis and gluconeogenesis

Glucose Level Control

• Glycogenolysis: breakdown of stored liver glycogen
• Gluconeogenesis: glucose production from amino acids
• Insulin levels fall, preserving glycogen
• Lipolysis: breakdown of fat from adipose tissue yields free fatty acids for energy, stimulated by declining insulin

Factors That Increase Glucose Levels

• Corticosteroids: stimulate gluconeogenesis and counter hypoglycemia
• Growth Hormone (GH): promotes glucose level increase to support growth
• Catecholamines: from stress, increase glucose via glycogenolysis and gluconeogenesis

Glucose Intolerance Disorders

• Type 1 Diabetes Mellitus (T1DM), Type 2 Diabetes Mellitus (T2DM), Gestational Diabetes Mellitus (GDM), and Metabolic Syndrome

Type 1 DM (T1DM)

• No insulin production
• Acute onset usually within days
• Beta cell destruction leads to absolute insulin deficiency
• Autoimmune etiology, with genetic/environmental factors, body attacks beta cells
• The liver continuously releases glucose, raising blood sugar

Type 1 DM Manifestations

• Ketoacidosis
• Polydipsia (excessive thirst)
• Polyphagia (extreme hunger)
• Polyuria (excessive urination)
• Weight loss
• High blood sugar and lack of insulin cause ketoacidosis.
• The body breaks down fats/muscles for energy, leading to ketosis, and ketones appear in urine

Type 2 DM (T2DM)

• Insulin produced, but tissues are resistant to it
• Most prevalent and common
• Elevated fasting glucose levels
• Slow glucose level increase due to developing insulin resistance
• Familial risk factor, obesity
• Relative insulin deficiency, tissues resistant to insulin

Type 2 DM Manifestations

• Polydipsia
• Polyuria
• Weight gain
• Blurry vision
• Infections
• Rarely ketoacidosis
• Family history screenings

Gestational Diabetes Mellitus (GDM)

• Like Type 2, develops during pregnancy
• Requires 2-3x more insulin
• Body unable to keep up with insulin demands
• Untreated results in stillbirth or macrosomia (large baby)
• Resolves after birth, risk of later developing Type 2 DM

Metabolic Syndrome

• High risk of cardiovascular disease and DM
• Requires aggressive treatment of high cholesterol, blood pressure, and glucose levels
• Increased waist circumference, sedentary lifestyle, high blood sugar/triglycerides, hypertension

Diabetes Treatment and Prevention

• Keep A1C low and blood sugar controlled
• Goal A1C < 5.7
• Diet change: low fat, low cholesterol
• Exercise

Diabetes Type 1 vs Type 2

• Onset: Type 1 any age, Type 2 adults
• Weight: Type 1 underweight, Type 2 obese
• Immune-mediated: Type 1 yes, Type 2 no
• Ketoacidosis: Type 1 yes, Type 2 no
• Insulin secretion: Type 1 no, Type 2 yes
• Beta cell function: Type 1 no, Type 2 yes
• HLA-linkage: Type 1 yes, Type 2 no

Acute and Chronic Complications of Diabetes Mellitus

• Infection
• Hyper/hypoglycemia
• Somogyi and Dawn phenomena
• Micro/macrovascular complications
• Healing

Hyperglycemia

• Not enough insulin
• Too much food intake
• Not enough exercise

Hypoglycemia

• Insufficient food intake
• Unplanned activity
• Inappropriate medication dose/use

Hypoglycemia Symptoms (low glucose)

• Pallor
• Shaky, sweaty
• Sleepiness
• Headache
• Weakness, dizziness
• Confusion
• Hunger

Hyperglycemia Symptoms (high glucose)

• Thirst
• Increased urination
• Aching
• Increased respiratory rate
• Nausea/vomiting
• Fatigue

Somogyi Effect

• Insulin-induced hypoglycemia
• Increased insulin dose at bedtime causes overnight glucose drop, triggering a compensatory increase in glucagon and epinephrine

Dawn Phenomenon

• Growth hormone increases overnight, raising glucose levels

Diabetes Education and Age Considerations

• Pediatrics: achieve normal growth/development, avoid acute/chronic complications, address psychosocial issues, educate on self-care
• Older Adults: increased Type 2 DM prevalence; prevent/manage acute/chronic issues, address psychosocial issues, educate on self-care

Endocrine Disorders - Primary vs. Secondary

• Primary: problem at the main gland; example: thyroid gland
• Secondary: problem at hormone release site; example: pituitary, not thyroid

Main Pituitary Hormones

• Antidiuretic Hormone (ADH): Increases body fluid volume, reduces urine output
• Oxytocin
• Growth Hormone: tissue growth/repair
• Prolactin: breast tissue development/lactation
• Gonadotropins: stimulate estrogen/progesterone/testosterone; Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH)
• Thyroid Stimulating Hormone (TSH)
• Adrenocorticotropic Hormone (ACTH): stimulates cortisol/adrenal androgen production

Thyroid Hormones

• Secreted by the thyroid in response to pituitary TSH
• T3 and T4; T4 is most abundant
• Too much/little of either alters growth, metabolic rate, and development

Steroid Hormones

• Made in adrenal glands, responding to pituitary hormones
• Adrenal glands sit atop kidneys
• Secrete epinephrine/norepinephrine for SNS stimulation
• Produce glucocorticoids (cortisol), mineralocorticoids (aldosterone), sex steroids (androgens)
• Regulate stress response, sugar, salt, sex; made on demand

Endocrine Disorders

Growth Hormone (GH)

• Excess and deficiency

Thyroid Hormone

• Hyper and hypo

Adrenocortical Hormone

• Addison, Cushings, Conn

Parathyroid

• Hyper and hypo

Antidiuretic Hormone Disorders

• DI and SIADH

Growth Hormone Function

• Increases lean body mass
• Increases glucose from liver
• Energy needed for BS (blood sugar)
• Responsible for growth
• Released from pituitary

Growth Hormone Deficiency

• Etiology
  • Prolonged labor, breech delivery, midline craniocerebral defects midline tumors, chronic illness, malnutrition
• Patho:
  • In children: decreased linear growth (not as tall)
  • Adults: decreased BS, decreased muscle mass, increased cholesterol, increased risk
• Manifestations
  • In children: delayed dental status, growth below 3rd percentile, thin hair/nails
  • Adults: delayed bone formation, decreased muscle mass, delayed puberty

GH Excess

• Patho
  • In children: increased growth, increased weight
  • In adults: hyperplasia, (increases cell production in organ) acromegaly
• Manifestations:
  • In children: increase in ring size, shoe size
  • In adults: increase BS = risk for DM, thickness of bones, intracranial pressure

Thyroid Hormone

• Metabolism regulator
• T3 and T4

Thyroid Stimulating Hormone (TSH)

• Signals thyroid to increase T3 and T4 release

Hypothyroidism (HIPPO)

• Etiology:
  • Dysfunction of thyroid gland (Primary)
  • Defects in TSH producton (Secondary)
• Patho
  • Lack of neg feedback (↑TSH) from 3/4
  • Autoimmune Disorder that causes hypothyroidism (Hoshmioto Thyroidits)
• Manifestations:
  • Newborn: infant screening, dull, thick tongue, poortone, bradycardia, hoarse/weak cry
  • Children: same symptomology as adults, delayed growth/development, early puberty
  • General: decreased metabolic rate, decreased appetite, weakness, wt, gain, lethargy
• Treatment:
  • Thyroid replacement
  • Blood levels monitoring
  • Overtreatment leads to Osteoporsis

Hyperthyroidism/Graves Disease/Chihuahua

• Etiology:
  • Primary, T3 and T4 are high and TSH is low
  • Excessive TSH production (Secondary)
• Patho: increased SNS and metabolic rate
• Manifestation: insomnia, irritability, restlessness, palpatations, tremors, heat intolerance and inability to concentrations
• Treatment: Beta-blockers treat acute symptoms, drugs to block production and help with palpatations and tachycardia

Adrenocorticoid Disorders

• Produces cortisol, aldosterone, cateholamines

Cortisol

• Increases BS/Glucose through the use of liver for energy, an anti-inflammation, decreases immune response

Aldosterone

• Retention of Na and water to lead to more fluid volume overload (↑FVO), ↑ Na, ↓ K

Addison's Disease

• Adrenal Cortical Insufficiency

• Etiology:

  • Destruction of cortex causes idiopathic and abrupt medication withdrawl

• Patho: Loss of function

• Manifestations: anorexia, n/v, ↓ Fv, ↓BP↓Na↑ K

• Tx:

  • Replace deficient hormones by use or adrenal cortex
  • higher day dose

Cushing's Syndrome

• Hypercortisolism

• Etiology:

  • Too much prednisone use causing body to have excessive ACTH production

• Manifestations: Moon face, wt. gain and body fat esp the face and back.

• Treatment:

  • Reduce exogenous cortiocosterioid if applicable by taper

Tumors

• Can cause thinning skin that decreases muscle mass, weakness and glucose intolerance but hyperglycemia leads to adrenal gland removal
• Leads to lifelong cortical replacement

Conn's Disease

• (hyperaldosteronism)

• Caused by RAAS from both Heart and kidney

• Patho:

  • Increases aldosterone, sodium, decreases Potassium

Parathyroid Hormone

• Regulates phosphorus and calcium for ↓ PTH = ↓ and vice versa

Hypoparathyroid

• Etiology:
  • Autoimmune or neck surgery
• Manifestations:
  • EKG changes with parenthesia, cramps and laryngospasm, tetany, ↑ phosphate
• Patho:
  • PTH levels can fall and also calcium levels

Hyperparathyroid

• Etiology:
  • Tumor overproduces
• Patho:
  • Overproduction can lead to chronic renal failure due to increase in calcium levels
• Manifestation:
  • EKG changes with parenthesia, lethargy and kidney stones = Fracture risk

Antiduretic Hormone

• Causes the body to hold water an determines volume and osmolarity

Diabetes Insipidus - Low ADH

• -Etiology
• Kidney unable to Kidney unable to Central from pituitary due to release Patho: Decreases both blood pressure but causes fluid deficiets because of increase urination
• Manifestitations: polyuria, polydispia and High sodium levels with a urine specific level of <1.010

Syndrome of Inappropriate Antidiuretic Hormone (SIADH) - High ADH

• Etiology: Tumor and related to Tuberculous
• Manifestations: hyponatremia, weakness, muscle cramps, high BP with fluid overload
• Patho: Causes hyponatermia and low fluid decrease and can become a risk for seizures

Fluid and Electrolytes - Homeostasis in the Body

Hydrostatic Pressure

• From force of heart = main force which helps the normal capillary wall

Oncontic Pressure

• Holds vessels and fluids in the body

Osmolarity/Osmolality

• Movement of electrolyte from high to low points

Tonicity

• Isontic (Normal amount of fluid) Hypotonic and Hypertonic (High osmolarity for electrolyte volume)

IV FLuids

Hypotonic IV

• Loves water due to lower salt productons and diluted the concentration of fluids
  • Cell gets big after use and never used with ICP

Isonotic, Hypertonic and D5W

• Normal Saline from Blood (Isotonic)
• Rarely used and for cerebral edma (Hypertonic)
• Detrose 5% Water used

Fluid Volume Deficiet

• Dehyrdation , ↑ Urinary Output, fever , low intake
• Manifestiations: prolonged cap refill and dry mucus with tachycardia
• Labs: elevated BUN creatine

Fluid Overload

• Low HCT blood volume, Edema cause high BP JVD

Body Fluid Spacing

Third Spacing

• Fluids trapped don't do anything
• Manifestitians : Resembles both Fluid Overload/Deficiet

Fluid Volume Status and In Pediatric

• Kidneys are less mature and risk for water loss
• Adults recognizes thirst with less bodily water and take more medication

Potassium

• Maintains heart and muscle contractions (3.5-5.0)

Hyerplakemia

• Tight

• Heart: HoT and Bradycardia

• GI and Neuro issues causing paralysis

• Manifestattions: Muscles become weak

Hypokalemia:

• low
• Heart and Muscle become slow, muscles get weak and GI decreases due to the intestine paralyzed- Obstruction

Sodium

• • Regulates balance in BP volume and PH levels
• High sodium Skin causes edema and patient gets thirst

Hyponatremia-

• • depressed levels: patients have seizures and rapid rest problems

• Sheriff regulates CA levels

Magnum

High Magnesium

• Calms and Quiets
• High levels are calm and low causes people BuckWilde

Calcium - Strong Heart

• High = patients swollen, slow and groan in pain with possible constipation
• Calcium Went on vacation. No Heart Beat

Genetic Key Points:

• Gene: at a site on a chromosome
• Allele: 2 characteristics on a gene
• Homo: same levels
• Actuak express: Phenotype and genotype

Inheritance

• Mutation that shows inherited changes
• Domiant and have effect parent
• Marfran syndrome:
• Brain: Huntington disease
• PKU and cystic for fibrosis
• Chromo that causes:
• Klinfelter syndrome
• Tumner

Genetic Information

• Adverse issues during uterine development
• Pre natal diagonsis for problems with the use of family history
• Enuresis for def of vassopression from ADHD

Blatter

-Urinary problem disrupt communcation and is from defects

• Over and full with Incontinence

Risk factors - Bladder cancer

• Cucasians most at risk with increase in older age caused by smoking
• Manifestion. Heme issues happen

STI (Sexually Transmitted Infections)

STI

• -Discuss infection
• HSV, HPV, Gonorrhea, Chlamydia, and syphilis

HSV

• can be cold sores from transmission
• Cause Herpes and are caused by the tongue Treatment - self treatment

HPV

• warts externaly removed with cervical monitor for cervical cancer

Gonnorrhea

• Infection of the epithelial site treated for possible secondary sites for infection Manifestatittiosn. Dysuria and bleeding Men: swelling at the infection site
• Treatment- needs deterred since infection for differation.

Syphilis- phase of process to start beginnings of chancre) that happens quick

• Treated quickly
• Condom C-Seciton

Reporductive

• Fertile into advanced age
• Testroene decreases with weeker contractions

Reproductive

Can’t achieve from hormones

• 13,Prostate Prostitis : causes inflaion for chills and lower back Hyoerpasia- increase in testrone decreasing force on strea
• Unknown cause for metasis

Abnormal locartions- caused by stream that effect

• Bifida

Testicular

• Causes torision from injury with inflammation
• Test with bacteria

Reproductive - Female

STI - Amnorrhea

• No preiroid and low blood or increase with pain
• Cyrocele can occer

Pregnancy

• hypertension, hyperemesis, and placenta previa, and abruptio placenta
• Increase Bp and preclamsia are biggest issues

Urinary

• Functions - filters

• Vitmain

• Erythoporietin - Produces

• Regulate balance

-Urine samples for tests

• UTIs,

• Cystitis

• Kidney problems

• Repereted infections atrophy over time

• Cystitis (lower urinary)

• Caused by e-coli and sex

Hyeronophrisis

• Cause issues and kidney damage
• Treated : through antibiotics

Genetic Disorder

• Polycistis - Expands and leads to failure and damage
• Can lead to failure
• Manifestations:
• Pain and pressure
• Glomerlus problems

Glumulus

• Glumuers damage from system infections

Nephoric System

• From streoph with infections and increases sodium problems

AKI

• Kydney problems are indicated to retenotion of nitrogen and creatinie

Nephrosis

Progressive but is developed over time

• Medictations problems can caused kindeys -Older patients are senstivie
• Causes:

High BP and loss of nephroms in blood

Dyaslis

• Hemodialysis , to get the blood clean

Diayliss

• Memrbane is instill into

Important points

• Hypertension, hyperemesis, and placenta previa
• Sex infections with bladder and bacteria
• Testrosteron. Decresses
• Renal is linked to hypertension .