Week 13: Diabetes

What is insulin?

• peptide hormone & main anabolic hormone of the body

• produced by beta cells in pancreas

What is insulin’s role in glucose regulation?

• insulin tells GLUT4 transporter to facilitate diffusion of glucose into the cell

• without insulin, glucose continues to circulate in the blood

Where is GLUT4 found?

plasma membrane of

• skeletal muscle

• cardiac muscle

• adipose

After entering cells, what is glucose converted to?

• glycogen (long term energy storage)

• triglycerides

Describe what glucose homeostasis looks like

• insulin is secreted by beta cells when high levels of glucose are detected

  • increase in glucose uptake & cell metabolism

  • decrease in blood glucose levels

• glucagon is secreted by alpha cells when low levels of glucose are detected

  • stimulates endogenous glucose production (glycogenolysis & gluconeogenesis)

Describe the most common parameter used to measure blood glucose levels

• describe the different ranges & goal for diabetics

Hemoglobin A1c (HbA1c)

• measures amount of glucose attached to hemoglobin

• ranges include:

  • normal = 5.7%

  • pre-diabetes = 5.7-6.4%

  • diabetes = 6.4% and up

  • can be impacted by other factors such as kidney failure, opioid use, blood loss, & stage of pregnancy

• diabetics aim for 7% to indicate good blood glucose management

What is Type I Diabetes?

• an autoimmune disease

  • highly specific destruction of beta cells by cytotoxic T lymphocytes

• 60-80% of beta cells are destroyed at the time of diagnosis

What is the main therapeutic currently used to treat T1D?

• synthetic insulin

  • originally: porcine insulin was used, but the immune system eventually mounts an allergic response

  • solution: recombinantly generated human insulin, which is tolerated by the immune system

• insulin is NOT a cure

Describe the current FDA-approved therapy for T1D

Teplizumab

• originally investigated to prevent immune rejection of kidney transplants

• postpones onset of T1D by at least two years

• daily infusion for two weeks

• hella expensive ($193,900 for full therapy)

What is Metabolic Syndrome?

• diagnosed when 3+ of risk factors for atherosclerosis and T2D

  • elevated fasting glucose levels

  • elevated triglycerides

  • reduced HDL cholesterol

  • hypertension

  • obesity

  • elevated waist circumference

  • insulin resistance

What exactly is insulin resistance?

normal levels of insulin no longer have an impact on glucose transport into cells & blood sugar levels

Describe the vicious cycle that insulin resistance creates

• eat carbs

• secrete insulin

• cells resist insulin

• sugar stores as fat

• cells remain unfed

• feel hangry

• eat carbs again!!

at this point:

• there is an overproduction of insulin (but not enough to maintain normal blood glucose levels)

• buildup of TGs in non-adipose tissue, leading to inflammation & normal cell death

What are the risk factors that lead to insulin resistance?

• obesity

• inactivity

• genetics

• environmental factors

  • bisphenol A

  • inorganic arsenic

  • pesticides

• aging

• medications

What disease is considered the liver’s eventual manifestation of metabolic syndrome?

Non Alcoholic Fatty Liver Disease, which occurs due to constant deposition of lipids as a result of insulin resistance

Describe the progression to liver failure

• healthy liver

• stage 1: inflammation

  • when body fights an infection or heals an injury

• stage 2: fibrosis

  • liver tissue starts to scar & doesn’t work as well

• stage 3: cirrhosis

  • extensive scarring and loss of function

  • symptoms such as jaundice begin

• stage 4: liver failure

  • liver function has ceased & urgent medical care is required

Pharmaceuticals to Manage Metabolic Syndrome

• name the drug classes & their general MOA

• Statins & Cholesterol Absorption Inhibitors

  • lowers LDL cholesterol levels

• Insulin Sensitizing Agents

  • increase body’s sensitivity to insulin

• GLP-1 Receptor Agonists & DPP-4 Inhibitors

  • enhance natural insulin secretion

• SGLT2 Inhibitors

  • block glucose reabsorption in kidneys

Describe 4 Nutritional Approaches to Manage/Prevent Metabolic Syndrome

• Mediterranean Diet

• Low glycemic index foods

  • low GI = better, fewer drastic spikes/dips in blood sugar

  • high GI = less desirable, dramatic spikes/dips in blood sugar

• therapeutic foods

  • blueberries (shown to improve IR & reduce LDL/BP)

  • apple cider vinegar (reduce post-eating fluxes in glucose & insulin levels)

• cooking techniques

  • avoid maillard reaction components

Describe 2 supplements used to manage/treat metabolic syndrome

• biotin (vitamin B7)

  • must be given at 10x physiological concentration to see efficacy

  • proposed MOAs include upregulation of GLUT4 expression, influences production of insulin from beta cells, reduces glucose output by liver

• ginseng

  • proposed MOA is reduction in inflammation, which improves insulin response

  • low bioavailability

  • many ginseng products are contaminated with toxic metals

  • can interact with prescription drugs such as Warfarin

What is Type II Diabetes?

• typically manifests as a result of lifestyle choices

• characterized by:

  • decreased insulin production

  • beta cell dysfunction

  • decreased uptake of glucose in response to insulin

Describe 4 lifestyle interventions to treat T2D

• smoking cessation

• exercise

• nutrition (Mediterranean diet)

• mind/body therapy

  • mindfulness

  • CBT

  • biofeedback

Describe 2 supplements used to manage T2D

• cinnamon

  • MOA: improves insulin receptor function & reduces inflammation

  • Precautions: inflammation of mouth & lips + rash

• silymarin (active ingredient in milk thistle)

  • Precautions: laxative effect, whole ground seeds have higher conc. than extract

Describe 2 supplements that have high risks for T2D

• selenium

  • has insulin-like actions

  • use as a supplement for other disease states has led to development of T2D by those patients

• B vitamins

  • caution when giving to patients with diabetic neuropathy due to increased cardiac events

Which of the following are snake oils?

• french lilac/galega officinalis

• fenugreek

• white mulberry/morus alba

• milk thistle

• chinese goldthread/coptis chinensis

• ivy gourd

• chromium

french lilac, while mulberry, chromium