Diabetes Basics

What causes hyperglycemia in diabetes physiologically, and what can chronic hyperglycemia cause?

Decreased insulin secretion, reduced insulin sensitivity, or both;

chronic hyperglycemia can cause organ and nerve damage

Where is insulin produced and what is its main effect?

Pancreatic beta (β) cells → promotes glucose uptake into tissues → ↓ blood glucose

What happens to glucose after insulin promotes its removal from the blood?

Used by muscle for immediate energy, stored in the liver as glycogen, or stored in adipose tissue for later use

What is glycogen?

The storage form of glucose used as a quick glucose reserve

(counterbalance for insulin, aka insulins antithesis)

Where is glucagon produced and what is its main effect?

Pancreatic alpha (α) cells → ↑ blood glucose

How does glucagon respond to low blood glucose?

Stimulates glycogenolysis → glycogen breakdown → ↑ blood glucose

If glycogen levels are depleted, how does glucagon respond to low blood glucose?

Glucagon stimulates lipolysis → fat breakdown → hepatic ketone production for an alternative energy source

How does the body counteract low blood glucose? (explain the pathophysiology)

↓ BG → hypothalamus activates SNS → adrenal medulla releases EPI; glucagon + EPI stimulate hepatic glucose release → ↑ BG

How does the body counteract high blood glucose? (explain the pathophysiology)

↑ BG→ pancreatic beta cells secrete insulin → insulin promotes blood glucose absorption into the tissues (liver and muscle for storage or immediate use)

What causes type 1 diabetes (T1D)?

Autoimmune destruction of pancreatic beta cells → absolute insulin deficiency

What happens when insulin cannot be produced in T1D?

Glucose cannot be used by muscle for energy → body goes into starvation mode → fat is metabolized → ketones are produced for energy → high ketones can cause DKA

What findings help differentiate T1D from T2D?

islet autoantibodies (autoimmune markers) and C-peptide (released by the pancreas only when insulin is)

If islet autoantibodies like GAD or IA-2 are present, which type of diabetes is indicated?

Type 1

If C-peptide levels are very low or absent, which type of diabetes is indicated?

Type 1

What is the biggest risk factor of T1D?

family history

What are examples of islet autoantibodies associated with T1D?

Glutamic acid decarboxylase (GAD) and islet antigen 2 (IA-2) antibodies

How is T1D treated and what additional screening is recommended?

Insulin is required; screen for other autoimmune disorders such as thyroid disorders and celiac disease

Why do type 1 diabetes REQUIRE insulin treatment?

because they cannot make it on their own!

What is teplizumab (Tzield) used for?

Monoclonal antibody FDA-approved to delay onset of symptomatic T1D

What causes type 2 diabetes (T2D)?

Insulin resistance and relative insulin deficiency from progressive pancreatic beta-cell dysfunction due to damage

What are major risk factors for T2D?

(what can damage the pancreatic beta cells?)

Obesity, unhealthy diet, physical inactivity, family history, and other comorbid conditions

How is T2D generally managed?

Lifestyle modifications alone or combined with medications (oral or injectable)

What is prediabetes and how can progression to diabetes be reduced?

increased risk of developing diabetes, when the BG is above normal but below the diabetes threshold

diet and exercise reduce progression

Which medication can be used to prevent or delay progression of diabetes in a pre-diabetic patient?

metformin!!!

When should metformin especially be considered to prevent or delay T2D in patients with prediabetes?

BMI ≥35 kg/m²,

fasting glucose ≥110 mg/dL,

A1C ≥6%,

age 25–59 years,

or history of gestational diabetes

What additional management is recommended for patients with prediabetes?

Annual diabetes screening + treatment of modifiable cardiovascular disease risk factors

What are the two types of diabetes encountered during pregnancy?

Preexisting diabetes and gestational diabetes mellitus (GDM)

What is a OGTT test and what is its purpose?

oral glucose tolerance test; determines how well glucose is tolerated by measuring the BG level 2 hours after drinking a liquid with alot of sugar

When and how is gestational diabetes mellitus (GDM) routinely screened?

OGTT at 24–28 weeks gestation; screen earlier if high risk

How is hyperglycemia during pregnancy managed?

Lifestyle modifications first; if medication is needed, insulin is 1st line, metformin and glyburide are alternatives

What are important risks of hyperglycemia during pregnancy?

Fetal macrosomia (large infant) + increased risk of obesity and diabetes later in life for both mother and child

What demographic and lifestyle factors increase the risk of prediabetes and T2D?

Age, physical inactivity, poor/unhealthy diet, and overweight

What BMI is considered a risk factor for prediabetes and T2D?

BMI ≥25 kg/m² or ≥23 kg/m² in Asian Americans

Which race/ethnicity groups are at higher risk for prediabetes and T2D?

African American, Asian American, Latino/Hispanic American, Native American, and Pacific Islander

(basically all the big ones besides Caucasians)

What personal and family history factors increase the risk of prediabetes and T2D?

History of gestational diabetes or a first-degree relative (parent/sibling) with diabetes

What metabolic and cardiovascular findings (labs) increase the risk of prediabetes and T2D?

A1C ≥5.7%

HDL <35 mg/dL and/or TG >250 mg/dL

hypertension (BP ≥130/80 mmHg or treated)

What medical and social history increase the risk of prediabetes and T2D?

CVD history and smoking history

What conditions associated with insulin resistance increase the risk of prediabetes and T2D?

PCOS and metabolic dysfunction-associated steatotic liver disease (MASLD)

What are the classic symptoms of hyperglycemia?

Polyuria = excessive urination;

polydipsia = excessive thirst;

polyphagia = excessive hunger/appetite

What other symptoms can occur with hyperglycemia? (besides the 3 P’s)

Fatigue, blurry vision, and weight loss;

T1D may initially present as DKA

When should diabetes screening begin regardless of risk factors?

Age 35 years

Who should be screened for diabetes before routine age-based screening?

Asymptomatic adults who are overweight or obese with ≥1 additional risk factor

How often should diabetes screening be repeated if results are normal?

At least every 3 years

Patients on which type of medications or which conditions warrant screening for diabetes before 35 years old?

Patients taking drugs that increase BG and patients with HIV or pancreatitis

What are the 3 types of tests used to diagnose prediabetes or diabetes?

A1C,

plasma glucose (fasting or random),

oral glucose tolerance test (OGTT)

What does A1C measure?

average BG over the past 3 months

What does fasting plasma glucose measure?

BG after ≥8-hour fast indicates the BG at that moment in time

Which test is preferred to diagnose diabetes? How many positive tests are required for a diagnosis of diabetes?

There is no preferred test;

at least 2 tests unless there is a clear clinical diagnosis with classic symptoms and a random BG of >/= 200

What are the diagnostic criteria for diabetes?

A1C ≥6.5%;

FPG ≥126 mg/dL;

2-hour OGTT ≥200 mg/dL;

or random BG ≥200 mg/dL with classic hyperglycemia symptoms

What are the diagnostic criteria for prediabetes?

A1C 5.7–6.4%;

FPG 100–125 mg/dL;

or 2-hour OGTT 140–199 mg/dL

When does an abnormal diabetes test require confirmation?

A single positive test should be confirmed with a second abnormal test unless there is a clear clinical diagnosis, such as classic hyperglycemia symptoms + random BG ≥200 mg/dL