Diabetes: ALL Material

What causes hyperglycemia in diabetes, 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

What are the usual glycemic targets for nonpregnant adults with diabetes?

A1C <7%;

preprandial BG 80–130 mg/dL;

2-hour postprandial BG <180 mg/dL

What are the glycemic targets during pregnancy?

Preprandial BG <95 mg/dL;

1-hour postprandial BG <140 mg/dL;

2-hour postprandial BG <120 mg/dL

When may the usual A1C goal be individualized?

Lower if achievable without significant hypoglycemia;

higher (<8%) may be appropriate with severe hypoglycemia risk or limited life expectancy

What is point-of-care A1C testing?

Provides immediate results and can assess glucose control but is not typically recommended for diagnosis

A patient with sickle cell has presented for a P-O-C diabetic screening test, which test should not be done and what is the alternative ?

A1C should not be used;

fructosamine is the alternative

When is fructosamine useful and what period does it reflect?

Alternative when A1C cannot be used; reflects glycemic control over the past 2–4 weeks

How can patients monitor their own blood glucose?

Fingerstick glucose meter or continuous glucose monitoring (CGM)

What is time in range (TIR) and which patients are utilizing it?

Percentage of time BG values are within the target range; utilized by patients who have CGMs

What are the recommended TIR goals?

70% for most adults; >50% may be appropriate for older adults or those with complex health conditions

How often should A1C be assessed?

Every 3 months if not meeting goals; every 6 months if at goal

How does A1C correlate with estimated average glucose (eAG)?

A1C 6% ≈ eAG 126 mg/dL;

each additional 1% A1C increases eAG by ≈28 mg/dL

What weight parameters should be monitored in patients with diabetes?

Actual body weight, BMI, and waist circumference at least annually

What is the recommended weight-loss goal for patients with overweight or obesity?

At least 5–7% of body weight; medications and/or surgery may be needed

What dietary pattern is recommended for patients with diabetes?

Natural carbohydrate sources (vegetables, fruits, whole grains, legumes, dairy) + lean protein;

limit refined carbohydrates and added sugars

What are the recommended alcohol limits for patients with diabetes?

≤1 drink/day for women; ≤2 drinks/day for men

How should patients with T1D manage carbohydrates with mealtime insulin?

Count carbohydrates and adjust prandial (meal time) insulin doses based on carbohydrate intake

A carbohydrate serving is ____ grams. What are some examples of 1 carbohydrate servings?

15 g;

1 small piece of fruit, 1 slice of bread, or 1/3 cup cooked rice/pasta

What physical activity is recommended for patients with diabetes?

≥150 minutes/week of moderate-intensity aerobic activity spread over ≥3 days

How should prolonged sedentary time be reduced in patients with diabetes?

Stand at least every 30 minutes during long periods of sitting

Which natural products are commonly used to lower BG in T2D?

Cinnamon, alpha-lipoic acid, chromium, magnesium, and ginseng;

evidence is limited and most patients still require prescription medications

What are the two categories of long-term diabetes complications?

Microvascular (small-vessel) and macrovascular (large-vessel/ASCVD) complications

What are the major microvascular complications of diabetes?

Retinopathy, nephropathy, peripheral neuropathy, and autonomic neuropathy

(all the -pathys)

What are important consequences of diabetic peripheral neuropathy?

Loss of sensation, especially in the feet → ↑ risk of foot infections and amputations

What are manifestations of diabetic autonomic neuropathy?

Gastroparesis, loss of bladder control, and erectile dysfunction

What are the major macrovascular complications of diabetes?

macrovascular = ASCVD

CAD including MI, cerebrovascular disease including stroke (CVA), and peripheral artery disease (PAD)

(all deal with ❤ )

What major conditions is diabetes a leading cause of?

Lower-extremity amputations, kidney disease, and blindness

What is the primary cause of death in patients with diabetes?

Cardiovascular disease; occurs about twice as often as in the general population

What daily foot care should patients with diabetes perform?

Wash, dry, and examine feet daily; moisturize tops and bottoms but not between the toes; Wear socks and shoes, elevate feet when sitting, and trim toenails with a nail file

How often should diabetic foot examinations be performed?

Feet examined at each office visit + comprehensive foot exam annually

Which antiplatelet therapy is recommended for ASCVD secondary prevention in diabetic patients?

ASA

What aspirin regimen is recommended for ASCVD secondary prevention in diabetes?

Aspirin 75–162 mg/day, usually 81 mg/day (baby asa)

Is aspirin routinely recommended for primary ASCVD prevention in diabetes and why?

No; bleeding risk is about equal to benefit for most patients; consider only if high risk

What is the antiplatelet alternative for diabetic patients with a salicylate allergy?

Clopidogrel 75 mg/day

What antithrombotic combination may be used in diabetic patients with CAD/PAD?

Aspirin + low-dose rivaroxaban

Is ASA safe in pregnancy? if so what is it used for?

yes; to ↓ risk of preeclampsia

What are the diabetic retinopathy screening recommendations for T2D?

Dilated eye exam at diagnosis;

if retinopathy present: annual testing;

if no retinopathy: test every 1–2 years

Which vaccines are specifically recommended for patients with diabetes in addition to age-appropriate vaccines?

Hepatitis B series;

influenza annually;

pneumococcal,

COVID-19,

and RSV vaccines

How should diabetic neuropathy be screened?

Annual monitoring with 10-g monofilament OR Ipswich touch test + 1 other sensation test (pinprick, temperature, or vibration)

How often should patients with diabetes receive a comprehensive foot exam?

At least annually; refer high-risk patients to a podiatrist

What medications can be used to treat diabetic neuropathy?

Gabapentin, pregabalin, SNRIs (e.g., duloxetine), TCAs, or sodium channel blockers

When should bone mineral density be monitored in patients with diabetes?

DXA every 2–3 years at age ≥65 or earlier if risk factors are present

When should osteoporosis treatment be considered in a diabetic patient?

T-score ≤−2.5 or history of fragility fracture

When are high intensity statins utilized for cholesterol control in diabetic patients?

comorbid ASCVD

Age 40-75 years with >/1 ASCVD risk factor

What are the LDL goals for cholesterol control in diabetic patients who have:

1. comorbid ASCVD

2. Age 40-75 years with >/1 ASCVD risk factor

1. LDL < 55

2. LDL < 70

When are moderate intensity statins utilized for cholesterol control in diabetic patients?

age 40-75 with no ASCVD

age 20-39 with ASCVD risk factors

What statin intensity is recommended for the following diabetic patients?

1. 45 year old with CAD (coronary artery disease)

2. 69 year old with 14 pack years

3. 52 year old with no ASCVD

4. 78 year old with aortic atherosclerotic disease

5. 27 year old with LDL 124

1. high

2. high

3. moderate

4. high

5. moderate

What are the high-intensity statin doses?

Atorvastatin 40–80 mg/day or rosuvastatin 20–40 mg/day

What can be added if LDL remains above goal on a maximally tolerated statin in a diabetic patient?

Ezetimibe or a PCSK9 inhibitor

When is icosapent ethyl (Vascepa) considered in diabetes?

LDL controlled + TG 150–499 mg/dL + ASCVD or ASCVD risk factors