Unit 4: Diabetes Mellitus

What is diabetes mellitus (DM)?

A group of metabolic disorders characterized by chronic hyperglycemia.

What pancreatic cells produce glucagon?

Alpha cells in the islets of Langerhans.

What pancreatic cells produce insulin?

Beta cells in the islets of Langerhans.

What is insulin’s overall effect on blood glucose?

Decreases blood glucose levels by promoting glucose uptake and storage.

What is glucagon’s overall effect on blood glucose?

Increases blood glucose levels by promoting glycogen breakdown and gluconeogenesis.

What stimulates insulin release after a meal?

An increase in blood glucose

How does insulin decrease blood glucose?

It decreases hepatic glucose production and increases glucose uptake into peripheral tissues.

What does insulin do to glucagon secreation?

Decreases glucagon secretion by inhibiting its release from the alpha cells of the pancreas.

What does insulin do to lipolysis?

Decrease due to hibiting lipolysis by promoting the storage of fats in adipose tissue.

What is glucagon’s major action during fasting?

It stimulates the liver to produce/release glucose, helping prevent hypoglycemia

What is the main pathophysiology of Type 1 diabetes?

Autoimmune destruction of pancreatic B-cells resulting in absolute insulin deficiency

Does a patient with T1D eventually make adequate endogenous insulin?

No. Progressive B-cell destruction causes an absolute insulin deficiency.

What is believed to trigger T1D?

An environmental trigger in a genetically susceptible person initates B-cell autoimmunity.

What are the major autoantibodies associated with T1D?

• IAA (insulin autoantibodies)

• GAD65

• IA-2

• ZnT8

Do T1D autoantibodies directly destroy B-cells?

No. They are primarily markers of B-cell autoimmunity and do not directly cause destruction. Instead, they indicate the presence of an autoimmune response against the pancreatic beta cells.

Approximately how much B-cell destruction occurs before T1D hyperglycemia becomes apparent?

about 60-90%

What is the “honeymoon phase” of T1D?

A temporary period after diagonosis when remaining B-cells still produce some insulin, causing lower insulin requirements.

What is the main pathophysiology of Type 2 diabetes?

Insulin resistance + progressive B-cell dysfunction/impaired insulin secretion

Does the pancreas still produce insulin in T2D?

Yes, especially early in the disease, but tissures are insulin resistant and B-cell function progressively declines.

What happens to hepatic glucose production in T2D?

It is increased

What happens to renal glucose reabsorption in T2D?

It is increased, leading to higher levels of glucose in the urine.

What happens to the incretin effect in T2D?

It is decreased/impaired

What happens to glucagon secretion in T2D?

There is inappropriate/excess glucagon secretion, contributing to hyperglycemia.

What is receptor desensitization?

A decreased response to continued receptor stimulation. This can result from prolonged exposure to agonists, leading to reduced receptor sensitivity and altered signaling.

How does receptor desensitization relate to insulin resistance?

Tissues become less responsive to insulin, so more insulin is required to produce the same effect.

What is the easiest way to distinguish T1D from T2D pathophysiologically?

T1D = No/absolute lack of insulin from B-cell destruction.

T2D= insulin resistance + progressive B-cell failure.

What are the major risk factors of T1D?

Genetic susceptibility, autoimmune factors, and environmental triggers.

Does a patient need a family history of Type 1 to develop Type 1?

No. Many patients have no identifiable family history

What is a major modifiable risk factor for T2D?

Overweight/obesity

What are common T2D risk factors?

• Obesity

• Family history

• Physical inactivity

• Prediabetes

• Hypertension

• Dyslipidemia

• Gestational diabetes history

• CVD

What are the classic “3 P’s” of diabetes?

Polyuria, polydipsia, polyphagia.

What is polyuria?

Frequent/excessive urination

What is polydipsia?

Excessive thirst

What is polyphagia?

Excessive hunger

Why does hyperglycemia casue polyuria?

Glucose enters the urine and pulls water with it by osmotic diuresis

Why does diabetes cause polydipsia?

Fluid loss from polyuria causes dehydration which increases thirst and leads to excessive thirst.

What is the typical onset of T1D?

Abrupt, usually developing over days to weeks

What is the typical onset of T2D?

Gradual, often over months to years

Are patients with T2D always symptomatic when diagnosed?

No, T2D is frequently asymptomatic or causes only mild symptoms.

Why can patients with T2D already have complications when diagnosed?

T2D can remain undiagnosed for years because of its gradual onset.

Which hyperglycemic emergency is characteristic of T1D?

Diabetic ketoacidosis (DKA) is the hyperglycemic emergency characteristic of Type 1 Diabetes , resulting from a severe shortage of insulin, leading to high blood sugar levels and the production of ketones. Life threatening

Which hyperglycemic emergency is characteristic of T2D?

Hyperglycemic hyperosmolar state (HHS) is the hyperglycemic emergency characteristic of Type 2 Diabetes, typically occurring in older adults with uncontrolled blood sugar levels, leading to severe dehydration and high blood glucose concentrations. Life threatening

What are the 3 major microvascular complications of diabetes?

Retinopathy, nephropathy, neuropathy

What organ is damaged by diabetic retinopathy?

Eyes/retina

What organ is damaged by diabetic nephropathy?

Kidneys

What does diabetic neuropathy damage?

Nerves

What are major macrovascular complications of diabetes?

Coronary disease (heart disease)/MI (heart attack), stroke, and peripheral arterial disease

What causes the chronic complications of diabetes?

Long-term hyperglycemia damages blood vessels and nerves

What are the major acute complications of diabetes?

Hypoglycemia, DKA, and HHS

Memory trick for microvascular complications?

R-N-N: Retina, Nephron, Nerves

What fasting plasma glucose indicated prediabetes?

100-125 mg/dL

What fasting plasma glucose is normal?

<100 mg/dL

What fasting plasma glucose indicates diabetes?

>126 mg/dL

How long must a patient fast for a fasting plasma glucose test?

At least 8 hours without caloric intake

What A1C indicates diabetes?

>6.5%

What A1C is considered normal?

5.7 - 6.4%

What A1C is considered normal?

<5.7%

What 2-hour OGTT result indicates diabetes?

>200 mg/dL

What 2-hour OGTT result indicates prediabetes?

140-199 mg/dL

What 2-hour OGTT result is normal?

<140 mg/dL

What random plasma glucose can diagnose diabetes in a pateint with classic symptoms or hyperglycemic crisis?

>200 mg/dL

If unequivocal hyperglycemia is absent, how is a diabetes diagnosis confirmed?

Two abnormal test results are required

Approximately what period does A1C reflect?

The previous 2-3 months of glycemic exposure in the bloodstream.

What is the usual preprandial glucose goal?

80 - 130 mg/dL

What is the usual peak postprandial glucose goal?

< 180 mg/dL

What is the usual A1C goal for many nonpregnant adults with diabetes?

< 7%

What blood glucose level is considered hypoglycemia?

< 70 mg/dL

What serious neurologic effects can severe hypoglycemia cause?

• Shakiness

• Loss of consciousness

• Coma

• Potentially death

What is the 15 - 15 rule?

Give 15 g fast-acting carbohydrate and recheck in another 15 minutes

What are common symptoms of hypoglycemia?

• Shakiness

• Sweating

• Hunger

• Palpitations

• Anxiety

• Dizziness

• Weakness

• Confusion

What should you do if BG is still <70 mg/dL after the 15-15 rule?

Repeat the 15-15 rule and consider administering glucagon if symptoms persist.

What should be used for severe hypoglycemia when a patient cannot safely swallow?

Glucagon

Should you give food or drink by mouth to an unconscious hypoglycemic patient?

No. Use glucagon/emergency treatment because of aspiration risk

Why is insulin required in Type 1?

T1D causes absolute insulin deficiency from B-cell destruction

What is basal insulin?

Background insulin that controls glucose between meals and while fasting.

What is bolus/prandial insulin?

Insulin used to cover meals

What is correction insulin?

Bolus insulin used to correct elevated BG

What type of insulin regimen does T1D require?

Basal + Bolus insulin

What does MDI stand for?

Mulitple Daily Injections

What does CSII stand for?

COntinuous Subcutaneous Insulin Infusion (Insulin pump)

What are the main categories of insulin?

• Ultra- rapid

• Rapid

• Short-acting

• Intermediate

• Long-acting

• Inhaled insulin is also available but not used often

What is an example of short-acting insulin?

Regular insulin

What is an example of intermediate-acting insulin?

NPH insulin

What are examples of rapid acting insulin?

• Aspart

• Lispro

• Glulisine

What are examples of long-acting basal insulin?

• Glargine

• Degludec

Which insulin has an onset of about 30-60 minutes, peak of 2-4 hours, and duration of 5-8 hours?

Regular insulin

Which insulin has an onset of about 2-4 hours, peak of 4-10 hours, and a duration of 10-24 hours?

NPH insulin

Which insulin is considered peakless and lasts about 20-24 hours?

Insulin glargine U-100

Which insulin has a duration of approximately 42 hours?

Insulin degludec

What is the most common and serious adverse effect of insulin?

Hypoglycemia

What other major adverse effect occurs with insulin?

Weight gain

Why is insulin considered a high-alert medication?

An insulin error has an increased risk of causing significant patient harm

What is the typical average daily insulin requiremet in T1D according to the assigned DiPrio reading?

About 0.5-1 units/kg/day

How is the initial TDD commonly divided?

About 50% basal + 50% meal coverage

A 60 kg patient is started at 0.5 units/kg/day. What is the TDD?

30 units/day

A patient’s TDD is 30 units. Approximately how much should be basal?

15 units/day

A patient’s TDD is 30 units. Approximately how much is available for meal coverage?

15 units/day

What formula do use to estimate the carbohydrate to insulin ratio?

500 / TDD

What does a carbohydrate-to-insulin ratio of 1:15 mean?

1 unit of insulin covers approximately 15 g of carbohydrate

If TDD = 50 units, what is the estimated C:1 ratio using the 500 rule?

500 / 50 = 10 —> about 1 unit per 10 g of carbs