Endocrine

Type 1 diabetes: outpatient insulin management and monitoring

Clinical Overview and When to Suspect Type 1 Diabetes

— Peak incidence at ages 4–6 and 10–14, but adult-onset T1D (LADA) is increasingly recognized and often misclassified as T2D

— HLA-DR3/DR4 confer the strongest genetic risk; concordance in identical twins ~50%

— Lean body habitus, age <35 at onset, rapid symptom progression (weeks, not years)

— Polyuria, polydipsia, unintentional weight loss, nocturnal enuresis in children

— DKA at presentation or with intercurrent illness

— Personal/family history of autoimmunity: Hashimoto thyroiditis, celiac disease, Addison, vitiligo, pernicious anemia

— Failure of oral agents within months in a presumed "T2D" patient → suspect LADA

— Loss of endogenous insulin AND glucagon counter-regulation → wider glycemic excursions

— "Honeymoon phase" of partial β-cell recovery may transiently reduce insulin needs in first 3–12 months — do not stop insulin

— Lifelong exogenous insulin is required; sulfonylureas and most non-insulin agents are ineffective

Type 1 diabetes (T1D) is autoimmune β-cell destruction causing absolute insulin deficiency, accounting for ~5–10% of all diabetes in the US

When to suspect T1D over T2D in the outpatient setting:

Pathophysiology pearls relevant to outpatient management:

Step 3 management: A young, thin patient previously labeled "T2D" who develops unprovoked DKA or fails metformin should be screened with GAD-65, IA-2, ZnT8 antibodies, and C-peptide before assuming oral therapy will work.

Board pearl: Always check TSH and tissue transglutaminase IgA at T1D diagnosis and periodically — the polyglandular autoimmune association is heavily tested in Step 3 ambulatory vignettes.

Presentation Patterns and Key History

— Current regimen: basal insulin (type, dose, time), prandial insulin (carb ratio, correction factor), pump vs MDI

— Frequency of fingersticks or CGM use, time-in-range (TIR), glucose management indicator (GMI)

— Hypoglycemia history: number of events/week, severe hypoglycemia (requiring assistance), nocturnal episodes, hypoglycemia unawareness

— DKA episodes in past year and triggers (missed insulin, infection, pump failure)

— Sick-day plan literacy, glucagon prescription on hand and not expired

— Carb counting accuracy, meal timing, alcohol use, exercise patterns

— Foot self-exam, dental care, contraception/pregnancy plans

— Hypoglycemia unawareness → loss of autonomic warning symptoms, raises severe hypoglycemia risk 6-fold; relaxing targets for 2–3 weeks can restore awareness

— Recurrent DKA in a young adult → consider insulin omission for weight loss ("diabulimia"), pump malfunction, or undiagnosed infection

— Dawn phenomenon (early-AM hyperglycemia from cortisol/GH surge) vs Somogyi effect (rebound from nocturnal hypoglycemia)

— Insurance/insulin affordability — rationing is a tested cause of recurrent DKA

— Depression screening (PHQ-2/9) — comorbid in ~25% of T1D and worsens adherence

— Eating disorder screening, especially adolescent/young adult females

Classic new-onset T1D triad: polyuria, polydipsia, weight loss — but Step 3 stems usually focus on the established T1D patient in clinic

Outpatient visit history checklist (the Step 3 "what to ask" list):

Red-flag historical features:

Psychosocial history is exam-relevant:

Step 3 management: When a teen with T1D presents with weight loss and elevated A1c despite "good adherence," screen for insulin omission as disordered eating before escalating doses.

Key distinction: Dawn phenomenon → check 3 AM glucose normal or high; Somogyi → 3 AM glucose low. The fix differs: increase vs decrease basal.

Physical Exam Findings and Functional Assessment

— BMI trend (sudden drop → uncontrolled hyperglycemia or eating disorder; rise → overinsulinization)

— Orthostatic BP — autonomic neuropathy or volume depletion

— Blood pressure goal <130/80 in T1D with risk factors per ADA

— Lipohypertrophy at repeated injection sites → erratic insulin absorption, a tested cause of unexplained glycemic variability; rotate sites

— Necrobiosis lipoidica diabeticorum — yellow-brown atrophic plaques on shins

— Acanthosis nigricans is uncommon in T1D (suggests insulin resistance — think "double diabetes" or T2D)

— Vitiligo (autoimmune association)

— Carotid bruits, diminished pedal pulses, capillary refill

— Resting tachycardia may signal cardiac autonomic neuropathy

— 10-g monofilament at plantar surfaces (1st, 3rd, 5th metatarsal heads and great toe)

— 128-Hz tuning fork vibration at great toe, ankle reflexes, pinprick

— Loss of protective sensation defines high-risk foot

— Calluses, fissures, ulcers, Charcot deformity (midfoot collapse, warm swollen foot without pain — easily mistaken for cellulitis)

— Nail care, interdigital maceration

T1D outpatient exam is largely about screening for complications and injection-site issues, not establishing diagnosis

Vital signs and general:

Skin and injection sites:

Thyroid exam: goiter or nodularity → screen TSH (Hashimoto comorbidity)

Cardiovascular and vascular:

Neurologic — required annual exam:

Foot inspection:

Funduscopic screening: dilated exam by optometry/ophthalmology — annual once T1D duration ≥5 years

CCS pearl: On a CCS case of T1D follow-up, order foot exam, dilated eye exam, BP, weight at every visit — these are scored as appropriate ambulatory actions even when the chief complaint is glycemic control.

Board pearl: A warm, swollen, painless foot with intact pulses in a long-standing T1D patient is Charcot neuroarthropathy until proven otherwise — non–weight-bearing and urgent imaging.

Diagnostic Workup — Initial Labs and Monitoring

— Islet autoantibodies: GAD-65 (most sensitive in adults), IA-2, ZnT8, insulin autoantibody (IAA, mostly in children)

— C-peptide (fasting or random with concurrent glucose): low/undetectable supports T1D; preserved C-peptide in a thin adult on insulin suggests LADA early or MODY

— Plasma glucose and HbA1c ≥6.5% (or fasting ≥126, random ≥200 with symptoms, OGTT 2-hr ≥200)

— HbA1c every 3 months if not at goal or regimen changing; every 6 months if stable at target

— General target A1c <7%, individualized: <6.5% if achievable without hypoglycemia; <8% in limited life expectancy, hypoglycemia unawareness, or extensive comorbidity

— Pediatric target also <7% (recently tightened from <7.5%)

— Urine albumin-to-creatinine ratio (UACR) and eGFR — start at 5 years post-diagnosis in T1D, then yearly

— Fasting lipid panel — statin indicated for age ≥40 with diabetes, or younger with ASCVD risk factors

— TSH (especially at diagnosis, then every 1–2 years or with symptoms)

— Tissue transglutaminase IgA + total IgA at diagnosis; rescreen if symptoms develop

— LFTs before statin initiation and periodically

— Goal time-in-range (70–180 mg/dL) >70%, time-below-range (<70) <4%, time <54 <1%

— GMI (CGM-derived estimated A1c) may differ from lab A1c — use both

Confirming T1D at diagnosis (when uncertainty exists, especially in adults):

Routine outpatient monitoring labs:

Annual screening labs:

CGM/SMBG data review:

Step 3 management: When A1c and GMI disagree, suspect conditions altering hemoglobin turnover (hemoglobinopathies, recent transfusion, iron deficiency, CKD with EPO) — trust CGM data.

Key distinction: Microalbuminuria screening in T1D starts at 5 years post-diagnosis; in T2D it starts at diagnosis because onset is unknown.

Diagnostic Workup — Advanced and Confirmatory Studies

— Negative autoantibodies + young age + family history across generations → consider MODY (especially HNF1A, GCK, HNF4A) → genetic testing

— GCK-MODY: stable mild fasting hyperglycemia, A1c usually 5.6–7.6%, does not require treatment outside pregnancy

— HNF1A-MODY: responds to low-dose sulfonylureas, not insulin initially — major Step 3 pivot

— Measure with simultaneous glucose; uninterpretable if glucose <70

— Stimulated (mixed-meal tolerance test) C-peptide <0.6 ng/mL supports T1D

— Hashimoto: TPO antibodies if TSH abnormal

— Addison: morning cortisol, ACTH stim if fatigue, hyperpigmentation, hyponatremia, unexplained hypoglycemia, or falling insulin requirements

— Celiac: anti-tTG IgA; confirmatory EGD with duodenal biopsy if positive

— Pernicious anemia: B12, anti-intrinsic factor antibodies if macrocytosis or neuropathy out of proportion

— No routine stress testing in asymptomatic T1D

— ECG at baseline and as clinically indicated; CAC scoring may refine risk in selected adults

— Baseline A1c (target <6.5% preconception), TSH, UACR, dilated eye exam — retinopathy can rapidly worsen during pregnancy

— Continuous glucose monitor (CGM) — standard of care for nearly all T1D

— Hybrid closed-loop pump candidacy: motivation, carb-counting literacy, financial coverage

When initial labs are ambiguous, expand the workup:

C-peptide interpretation nuances:

Autoimmune comorbidity workup if symptomatic or screen-positive:

Cardiovascular risk assessment:

Pre-pregnancy or pregnancy planning:

Diabetes technology evaluation:

Board pearl: A patient with T1D whose insulin requirements suddenly fall, with new fatigue, salt craving, or hyperpigmentation → think Addison disease, not "better control." Order morning cortisol immediately.

Step 3 management: Genetic testing for MODY is appropriate when a young patient has autoantibody-negative diabetes with strong autosomal dominant family history — can change therapy from insulin to sulfonylurea.

Risk Stratification and Management Logic

— Highest function, motivated, numerate: hybrid closed-loop insulin pump + CGM (gold standard)

— Motivated but not pump-ready: multiple daily injections (MDI) with basal-bolus + CGM

— Limited resources or new diagnosis: MDI with basal-bolus + SMBG, transition to CGM ASAP

— Cognitive impairment, elderly, hypoglycemia-prone: simplified regimen with relaxed targets

— 0.4–0.5 units/kg/day at diagnosis (lower if honeymoon phase, higher in puberty/illness)

— Split: ~50% basal, ~50% bolus divided across meals

— Rule of 500: 500 ÷ TDD = grams of carb covered by 1 unit of rapid insulin (carb ratio)

— Rule of 1800 (or 1500 for regular insulin): 1800 ÷ TDD = mg/dL drop per 1 unit (correction factor)

— Preprandial 80–130 mg/dL, postprandial peak <180 mg/dL, A1c <7%

— Pediatric same A1c target; bedtime/overnight 80–140

— Pregnancy: fasting <95, 1-hr postprandial <140, 2-hr <120, A1c <6% if no hypoglycemia

— Duration ≥5 years, suboptimal A1c, HTN, dyslipidemia, smoking → more frequent retinal and renal screening

All T1D patients require exogenous insulin — there is no diet/exercise-only path. The management question is which insulin regimen and which delivery method.

Stratification framework for choosing regimen:

Total daily dose (TDD) initial estimate:

Carb ratio and correction factor estimation:

Glycemic targets (ADA):

Risk stratification for complications drives screening intensity:

CCS pearl: On a CCS case of a newly diagnosed T1D adult in clinic, initial orders should include basal-bolus insulin prescription, glucagon kit, CGM referral, diabetes education referral, nutrition consult, ophthalmology in year 5, and labs (A1c, lipids, TSH, UACR, tTG).

Board pearl: Sliding-scale insulin alone is never appropriate long-term management for T1D — always pair with scheduled basal-bolus.

Pharmacotherapy — Insulin Regimens in Detail

— Glargine U-100 (Lantus, Basaglar): once daily, ~24 hr, mild peak

— Glargine U-300 (Toujeo): flatter, longer (~30 hr), less nocturnal hypoglycemia

— Detemir (Levemir): 12–20 hr, often BID

— Degludec (Tresiba): >42 hr, very flat, most forgiving of timing variability

— NPH: peaks at 4–10 hr → higher nocturnal hypoglycemia risk, mostly historical/cost-driven

— Rapid-acting analogs: lispro, aspart, glulisine — onset 10–20 min, peak 1–2 hr, duration 3–5 hr; inject 0–15 min before meals

— Ultra-rapid: faster aspart (Fiasp), lispro-aabc (Lyumjev) — onset ~5 min, useful for postprandial spikes and pumps

— Regular insulin: onset 30 min, peak 2–4 hr — inject 30 min premeal; largely outdated for T1D bolus

— Glargine 0.2 u/kg at bedtime + rapid-acting at each meal using carb ratio and correction factor, plus correction for premeal glucose

— Uses rapid-acting insulin only; basal delivered as continuous microboluses

— Hybrid closed-loop systems (e.g., Tandem Control-IQ, Medtronic 780G, Omnipod 5) automate basal and correction boluses using CGM input — patient still announces meals

— Pramlintide (amylin analog): preprandial injection, reduces postprandial spikes; reduce bolus insulin 50% when starting to avoid hypoglycemia

— Metformin, GLP-1 agonists, SGLT2 inhibitors are not FDA-approved for T1D; SGLT2i carry euglycemic DKA risk in T1D and should generally be avoided on boards

Basal insulin options (long-acting analogs preferred over NPH):

Prandial (bolus) insulin options:

Typical MDI regimen example:

Pump therapy:

Adjunctive agents in T1D:

Step 3 management: When titrating basal insulin, target fasting glucose 80–130 by adjusting basal 2 units every 3 days; if fasting normal but lunch/dinner pre-meal glucose drifts up, the issue is bolus, not basal.

Board pearl: A T1D patient on an SGLT2 inhibitor presenting with nausea, abdominal pain, and "normal" glucose 180 with anion-gap acidosis has euglycemic DKA — stop the SGLT2i.

Insulin Pump and CGM Technology — Practical Management

— Dexcom G7, Freestyle Libre 3, Medtronic Guardian — interstitial glucose every 1–5 min

— Standard of care for all T1D regardless of age; covered by Medicare for insulin-treated diabetes

— Alerts for hypoglycemia and rapid changes critical for hypoglycemia unawareness

— Time-in-range (70–180) >70%, time <70 <4%, time <54 <1%, time >250 <5%

— Each 10% increase in TIR ≈ A1c reduction of ~0.5%

— Tethered (Tandem, Medtronic) or patch (Omnipod)

— Basal rates programmable hourly; supports variable basal for dawn phenomenon, exercise, illness

— Pump failure → DKA within 4–6 hours because no long-acting depot exists; patient must have backup pen

— Algorithm adjusts basal and gives auto-corrections based on CGM trend

— Demonstrated A1c reduction ~0.3–0.5% and TIR improvement of 10–15%

— Still requires meal announcement and carb counting

— Aerobic exercise → lower basal 50–80% starting 60–90 min before; consume 15–30 g carbs per 30 min

— Anaerobic/resistance → may transiently raise glucose

— Illness: check ketones (blood β-hydroxybutyrate preferred) if glucose >250 or symptomatic; never stop basal, give correction every 2–3 hours

— Rotate infusion sites every 2–3 days, CGM sensors per device specs

— Lipohypertrophy and scarring at overused sites → erratic absorption

Continuous glucose monitors (CGM):

CGM-driven targets (international consensus):

Insulin pumps:

Hybrid closed-loop systems:

Sick day and exercise rules with technology:

Site care:

CCS pearl: On a CCS case of pump failure with rising glucose and positive ketones, immediate orders: rapid-acting insulin by pen (not pump), increase fluids, recheck glucose/ketones in 2 hr, replace infusion set, instruct on ED return criteria.

Board pearl: A pump-treated T1D patient with new hyperglycemia and ketones should always inject insulin by pen while troubleshooting — assume pump delivery failure.

Special Populations — Elderly and Renal/Hepatic Impairment

— Healthy older adult: A1c <7.0–7.5%

— Complex/intermediate health (multiple comorbidities, mild cognitive impairment): A1c <8.0%

— Very complex/poor health (dementia, end-stage chronic illness): A1c <8.5%, focus on avoiding hypoglycemia and symptomatic hyperglycemia

— Simplify to once-daily basal analog + simplified mealtime dosing if MDI becomes unsafe

— Avoid NPH and premixed insulins → unpredictable peaks → falls and fractures

— Deintensify if frequent hypoglycemia, weight loss, or time below range >4%

— Involve family/caregivers; ensure CGM with hypo alerts

— Insulin is partially cleared by kidneys; as eGFR falls, insulin requirements often decrease by 25–50% at eGFR <30

— Watch for unexplained hypoglycemia as a sign of progressive CKD

— UACR ≥30 mg/g → start ACE inhibitor or ARB for renoprotection; finerenone and SGLT2 inhibitors are approved in T2D but not standard in T1D due to DKA risk

— Avoid metformin if eGFR <30 (rarely used in T1D anyway)

— Reduced gluconeogenesis → increased hypoglycemia risk, especially nocturnal

— Use lower basal doses and longer-acting analogs with flat profile (degludec, glargine U-300)

— Glucose lower on dialysis days; reduce basal 25%

— A1c less reliable due to anemia/EPO/transfusions — use CGM-derived GMI

Older adults with T1D now commonly live into their 70s–80s; management priorities shift toward hypoglycemia avoidance

Geriatric targets (ADA):

Practical adjustments:

Renal impairment:

Hepatic impairment:

Dialysis patients:

Step 3 management: An 82-year-old with T1D, A1c 6.4%, and three documented hypoglycemic episodes per week needs deintensification, not congratulations — lower basal, raise A1c target to <8%.

Key distinction: "Good A1c" in an elderly T1D patient may mask dangerous hypoglycemia — always review CGM time-below-range, not just A1c.

Special Populations — Pregnancy, Pediatrics, and Other Subgroups

— Target A1c <6.5% (ideally <6%) preconception to reduce congenital malformations

— Folic acid 400–800 mcg daily; higher if on anticonvulsants

— Baseline dilated eye exam, UACR, TSH, BP

— Discontinue ACE/ARB, statin, and most non-insulin agents before conception

— Insulin requirements fall in first trimester (hypoglycemia risk), then rise 50–100% in 2nd–3rd trimesters

— Targets: fasting <95, 1-hr postprandial <140, 2-hr <120; A1c <6% if achievable without hypoglycemia

— Preferred insulins: detemir, NPH, glargine, aspart, lispro (all category B/considered safe)

— Retinopathy can worsen rapidly — eye exam each trimester

— Aspirin 81–162 mg daily from 12 weeks for preeclampsia prevention in pregestational diabetes

— Increased risk of preeclampsia, macrosomia, polyhydramnios, neonatal hypoglycemia

— Insulin requirements drop dramatically after placental delivery — reduce basal by 50% immediately postpartum

— Breastfeeding lowers glucose → reduce doses, snack before nursing

— Same A1c <7% goal

— Honeymoon phase common in first year; do not discontinue insulin

— Puberty raises insulin needs (GH-mediated insulin resistance)

— Annual TSH, celiac screen; annual lipid panel starting age 2; dilated eye exam at age 11 or puberty after 3–5 years duration

— School plans (504 plan in US), glucagon training for school staff

— High risk for adherence lapses, diabulimia, alcohol-related hypoglycemia

Preconception care (essential exam-relevant content):

Pregnancy management:

Labor and postpartum:

Pediatrics:

Adolescents/young adults:

Board pearl: A pregnant T1D patient at 8 weeks with sudden severe hypoglycemia is exhibiting the first-trimester drop in insulin requirements — anticipate by reducing basal ~10–20%.

Step 3 management: Stop ACE inhibitor and statin at the preconception visit, not after a positive pregnancy test — Step 3 grades anticipatory care.

Complications and Adverse Outcomes

— DKA: hyperglycemia + anion gap acidosis + ketonemia; triggers include infection, insulin omission, pump failure, MI, pancreatitis, SGLT2 inhibitor use (euglycemic DKA), cocaine, pregnancy

— Severe hypoglycemia: glucose <54, often <40 with neuroglycopenia; risks: alcohol, missed meals, exercise, autonomic neuropathy, beta-blockers masking symptoms, renal insufficiency

— Hypoglycemia unawareness affects ~25% of long-standing T1D; reversible with 2–3 weeks of strict avoidance

— Retinopathy: nonproliferative → proliferative; macular edema; screen annually after 5 years duration; treat with anti-VEGF, focal laser, or panretinal photocoagulation

— Nephropathy: UACR ≥30 = albuminuria; start ACEi/ARB, BP <130/80; SGLT2i and finerenone are T2D-evidence-based and used cautiously off-label in T1D specialty settings

— Neuropathy: distal symmetric polyneuropathy (treat with duloxetine, pregabalin, gabapentin, TCAs), autonomic (gastroparesis, orthostasis, ED, neurogenic bladder)

— ASCVD risk 2–10× general population; statin for all T1D ≥40 (moderate intensity if no ASCVD, high intensity if ASCVD or multiple risk factors)

— BP target <130/80; first line ACEi/ARB if albuminuria, otherwise ACEi/ARB, thiazide, or CCB

— Diabetic foot ulcers, Charcot arthropathy, osteoporosis (T1D associated with lower BMD)

— Periodontal disease, frozen shoulder, Dupuytren contracture, cheiroarthropathy

— Necrobiosis lipoidica, granuloma annulare

— Depression, anxiety, eating disorders, diabetes distress — screen annually

Acute complications:

Microvascular complications (DCCT/EDIC long-term data):

Macrovascular:

Other:

Mental health:

Board pearl: Gastroparesis presenting as erratic postprandial glucose with early hypoglycemia followed by late hyperglycemia in long-standing T1D — confirm with gastric emptying scintigraphy, treat with small frequent meals, metoclopramide (short-term), erythromycin.

Step 3 management: Annual UACR + eGFR is non-negotiable; positive screen on a single sample requires 2 of 3 abnormal in 3–6 months before diagnosing CKD.

When to Escalate Care — ED, Inpatient, or Consult

— DKA: glucose typically >250 (or euglycemic if SGLT2i), anion gap ≥12, ketonemia, bicarbonate <18; especially with vomiting, altered mentation, dehydration

— Severe hypoglycemia with seizure, loss of consciousness, or requiring third-party rescue and recurrent at home

— Hyperglycemia >300 with ketones unresponsive to home correction within a few hours

— Suspected acute coronary syndrome, stroke, sepsis in a hyperglycemic patient

— Pump failure with rising ketones unable to be managed at home

— Charcot foot suspicion → urgent off-loading and imaging; admit if uncertain or infected

— Deep or infected foot ulcer with systemic signs, exposed bone, osteomyelitis suspicion

— All T1D should ideally co-manage with endocrinology

— Pump initiation, hybrid closed-loop, recurrent DKA or severe hypoglycemia, pregnancy planning, unstable A1c despite optimized regimen

— Ophthalmology annually after year 5 (or sooner with symptoms)

— Podiatry for high-risk feet (neuropathy, deformity, prior ulcer)

— Nephrology when eGFR <30, rapidly declining function, or UACR >300 despite ACEi/ARB

— Cardiology for known ASCVD or abnormal stress testing

— Mental health for depression, eating disorder, diabetes distress

— Maternal-fetal medicine for any T1D pregnancy

— Certified diabetes care and education specialist (CDCES) at diagnosis, with regimen change, with complication onset, and annually thereafter — covered by Medicare

Send to the ED / consider inpatient admission:

Outpatient endocrinology referral:

Specialty consults to coordinate from primary care:

CCS pearl: Recurrent DKA in a young adult warrants inpatient stabilization, social work consult, mental health evaluation, and CDCES re-education — repeating "increase insulin and discharge" is a wrong-answer pattern.

Board pearl: Severe hypoglycemia at home managed by intramuscular or intranasal glucagon is now standard — every T1D patient and family member should have a glucagon kit and know how to use it.

Key Differentials — Other Forms of Diabetes

— Older, overweight/obese, gradual onset, family history, acanthosis nigricans, no autoantibodies, preserved C-peptide

— Responds to metformin, GLP-1 RA, SGLT2i

— Adult onset (>30), often initially diagnosed as T2D, autoantibody-positive (usually GAD), progresses to insulin dependence within months to a few years

— Avoid sulfonylureas (accelerate β-cell loss); insulin earlier

— Strong autosomal dominant family history across ≥3 generations, young onset (<25), lean, antibody-negative, preserved C-peptide

— GCK-MODY: mild stable fasting hyperglycemia, no treatment except in pregnancy

— HNF1A/HNF4A-MODY: sulfonylurea-responsive

— Genetic testing changes management

— Almost always monogenic (KCNJ11, ABCC8); sulfonylurea-responsive, not T1D

— Pancreatogenic (type 3c): post-pancreatitis, pancreatic cancer, cystic fibrosis, hemochromatosis — loss of both insulin and glucagon → brittle control

— Endocrinopathies: Cushing, acromegaly, pheochromocytoma, glucagonoma, hyperthyroidism

— Drug-induced: glucocorticoids, atypical antipsychotics (olanzapine, clozapine), thiazides at high dose, calcineurin inhibitors, protease inhibitors, immune checkpoint inhibitors (can cause autoimmune T1D)

— Onset in pregnancy, screen at 24–28 weeks with 50-g GLT or 75-g OGTT; resolves postpartum but raises future T2D risk

When a patient looks "atypical," walk through diabetes subtypes:

Type 2 diabetes:

Latent autoimmune diabetes in adults (LADA):

MODY (monogenic diabetes):

Neonatal diabetes (<6 months of age):

Secondary diabetes:

Gestational diabetes:

Key distinction: A thin, antibody-negative young adult with diabetes and family history across generations is MODY until disproven — sending them home on insulin without genetic testing is a tested error.

Board pearl: A patient on pembrolizumab or nivolumab who develops sudden hyperglycemia with DKA has checkpoint inhibitor–induced autoimmune diabetes — treat as T1D, do not rechallenge with the drug for diabetes recovery.

Key Differentials — Mimics of Hyperglycemia/Hypoglycemia Symptoms

— Diabetes insipidus (central or nephrogenic): dilute urine, normal/elevated sodium, normal glucose

— Primary polydipsia: psychogenic, lithium-associated, dilute urine, low normal sodium

— Hypercalcemia, hypokalemia → nephrogenic DI picture

— Hyperthyroidism (often co-occurs with T1D — check TSH)

— Malignancy, malabsorption (celiac association), Addison disease, eating disorder, HIV

— Anxiety/panic disorder: adrenergic symptoms without true hypoglycemia (Whipple triad not met)

— Cardiac arrhythmia (palpitations, presyncope)

— Pheochromocytoma: episodic catecholamine surges

— Postprandial reactive hypoglycemia (especially post-bariatric surgery)

— Adrenal insufficiency: persistent hypoglycemia with falling insulin requirements — order morning cortisol

— Alcoholic ketoacidosis (often hypoglycemic, history of binge + vomiting)

— Starvation ketosis (mild, glucose normal)

— Lactic acidosis (sepsis, ischemia, metformin), uremia, salicylate, methanol, ethylene glycol — use MUDPILES

— Pancreatitis can both cause and mimic DKA — check lipase

— Stress hyperglycemia (sepsis, MI, steroids) — recheck after recovery; A1c distinguishes acute from chronic

Polyuria/polydipsia differential beyond diabetes:

Weight loss differential in suspected new T1D:

Hypoglycemia mimics in a known T1D patient — when symptoms persist despite "normal" glucose:

DKA mimics (anion gap metabolic acidosis):

Hyperglycemia without true diabetes:

Key distinction: True hypoglycemia requires Whipple triad — symptoms, documented low glucose, resolution with glucose. Adrenergic symptoms with glucose 90 are not hypoglycemia.

Step 3 management: When a T1D patient reports frequent "lows" but CGM shows glucose 80–110 at those moments, the issue is rapid rate of fall or anxiety, not hypoglycemia — counsel and treat anxiety, do not raise basal target.

Long-Term Plan and Comprehensive Risk Reduction

— A1c <7% with individualization; CGM TIR >70%

— Quarterly A1c, ongoing CGM review, annual regimen reassessment

— Statin therapy: all T1D age ≥40 (moderate intensity); high intensity if ASCVD or multiple risk factors; consider statin age 20–39 with risk factors

— BP target <130/80; first-line ACEi or ARB with albuminuria

— Aspirin 81 mg for secondary prevention; primary prevention only if age 50–70 with high ASCVD risk and low bleeding risk (selective)

— Tobacco cessation counseling at every visit

— Annual UACR, eGFR

— ACEi/ARB titrated to maximum tolerated when albuminuria present

— BP control, glycemic control, sodium restriction

— Dilated exam annually starting 5 years post-diagnosis; more often with retinopathy

— Daily self-inspection, well-fitted shoes, podiatry for high-risk feet, annual comprehensive foot exam in clinic

— Influenza annually, COVID-19 per schedule, pneumococcal (PCV20 once or PCV15 then PPSV23), hepatitis B series for unvaccinated adults <60 (recommended for all adults with diabetes), Tdap/Td, RSV if ≥60, zoster if ≥50

— Mediterranean or DASH-style diet, regular aerobic + resistance exercise (with carb adjustment)

— Limited alcohol with food (alcohol → delayed hypoglycemia)

— Annual depression and diabetes distress screening

T1D management is multi-axis — glycemic, vascular, renal, ophthalmic, mental health, lifestyle

Glycemic axis:

Cardiovascular risk reduction:

Renal protection:

Eye care:

Foot care:

Vaccinations:

Lifestyle:

Mental health:

Step 3 management: At every T1D follow-up, the "longitudinal checklist" includes BP, weight, foot exam, smoking, vaccines, statin status, ACEi/ARB if indicated, and depression screen — these are reliably tested CCS actions.

Board pearl: Hepatitis B vaccination is recommended for all adults with diabetes under 60, frequently missed and frequently tested.

Follow-Up, Monitoring, and Counseling

— Routine T1D follow-up every 3 months (aligns with A1c testing)

— Newly diagnosed, regimen change, pregnancy, recurrent hypo/DKA: every 2–4 weeks until stable

— CDCES/RD visits at diagnosis and at least annually

— CGM/SMBG data: TIR, hypoglycemia events, glycemic variability (CV <36%)

— Current insulin doses and adjustments since last visit

— Hypoglycemia episodes, glucagon availability and expiration

— Sick-day plan, ketone strip availability

— Injection sites or pump site condition

— Medication adherence and affordability

— UACR, eGFR, lipids, TSH, foot exam, dilated eye exam

— Vaccines current

— Mental health screening (PHQ-9, GAD-7, diabetes distress scale)

— Dental visit

— Hypoglycemia recognition and treatment: "Rule of 15" — 15 g fast carbs, recheck in 15 min, repeat if still <70

— Glucagon administration training for family/cohabitants

— Alcohol education — never drink on empty stomach, snack before bed

— Exercise planning — reduce insulin or eat carbs preemptively

— Sick-day rules — never stop basal, check ketones, hydrate, dose corrections every 2–3 hr

— Travel: extra supplies (×2), prescriptions, carry insulin in carry-on

— Driving: check glucose before driving, treat if <90, carry fast carbs

— Pediatric-to-adult transition is high-risk — formal transition program reduces DKA admissions

— Hospital discharge: reconcile basal/bolus doses, verify supplies, schedule follow-up within 1–2 weeks

Follow-up cadence:

Each visit, review:

Annual or scheduled monitoring:

Counseling priorities:

Transitions of care:

CCS pearl: Schedule follow-up in 2 weeks after any insulin regimen change or hospital discharge, and 3 months for stable T1D — both timelines are scoreable.

Board pearl: Adolescent-to-adult care transition is a named tested vulnerability period — DKA rates spike in young adults aged 18–25 due to fragmented care.

Ethical, Legal, and Patient Safety Considerations

— Pump and CGM initiation require discussion of benefits, alarm fatigue, cost, and skin reactions

— Minors: assent from adolescent + parental consent; pediatric T1D care must respect emerging autonomy

— Sexual health, contraception, mental health, and substance use discussions should occur without parents present during part of every adolescent visit

— A teen with T1D requesting contraception or pregnancy planning has confidentiality protections varying by state — know your local law

— Patients must be counseled that severe hypoglycemia can impair driving; CGM data may be subpoenaed after motor vehicle crashes

— Commercial driver licensing has insulin-treated diabetes provisions (FMCSA) requiring medical certification and CGM review

— Some occupations restricted (military pilots, certain transit roles)

— Concerns for child neglect (e.g., parents withholding insulin) trigger child protective services reporting

— Diabulimia (insulin omission for weight loss) is a recognized eating disorder — mental health referral, not punitive response

— Insulin rationing is a major cause of recurrent DKA; assess affordability at every visit

— Federal $35/month Medicare insulin cap, state laws, and patient assistance programs

— Documenting and addressing cost barriers is a patient-safety obligation

— Hospital discharge without insulin Rx, glucagon, or follow-up = high readmission risk

— Pediatric-to-adult transition without warm handoff increases DKA

— Pump-treated patients admitted to hospital: pumps may continue under written self-management policy if patient is capable; otherwise convert to subcutaneous basal-bolus

— In dying patients, deintensify aggressively — comfort-focused, allow higher A1c, prevent symptomatic hypo/hyperglycemia

Informed consent and shared decision-making:

Confidentiality and adolescents:

Driving and occupational safety:

Mandatory reporting and patient safety:

Insulin affordability and rationing:

Transition-of-care hazards:

End-of-life care:

Step 3 management: A patient with recurrent DKA who admits to rationing insulin due to cost requires a social work consult, patient assistance program enrollment, and switch to lower-cost regimens (e.g., human NPH/regular if needed) — refusing to address cost is a wrong answer.

Board pearl: Documenting insulin omission as eating disorder behavior triggers mental health referral, not discharge with stricter instructions.

High-Yield Associations and Rapid-Fire Facts

— APS type 2 (most common): T1D + Hashimoto/Graves + Addison ± vitiligo, celiac, pernicious anemia

— APS type 1 (APECED): mucocutaneous candidiasis + hypoparathyroidism + Addison; AIRE gene mutation

Autoimmune polyglandular syndromes:

HLA associations: DR3, DR4 (especially DR3/DR4 heterozygotes); DR2 protective

Honeymoon phase: weeks to ~1 year, partial β-cell recovery, lower insulin needs — never stop insulin completely

DCCT/EDIC takeaway: intensive control reduces microvascular complications and, with long-term follow-up, macrovascular events — "metabolic memory"

C-peptide: absent/low in T1D, preserved in T2D/MODY; key disambiguating test

Diabetic ketoacidosis triad: hyperglycemia, anion gap, ketonemia; bicarbonate <18

Rule of 500 (carb ratio), Rule of 1800 (correction factor), Rule of 15 (hypoglycemia treatment)

A1c interpretation pitfalls: falsely low in hemolysis, recent transfusion, EPO; falsely high in iron deficiency, splenectomy, uremia

Vaccines for diabetes: influenza, pneumococcal, hepatitis B (if <60), COVID-19, Tdap, RSV ≥60, zoster ≥50

Screening start times in T1D: retinopathy and nephropathy at 5 years post-diagnosis; lipids and BP from diagnosis

Drugs that worsen glycemic control: glucocorticoids, atypical antipsychotics (olanzapine, clozapine), thiazides high-dose, beta-blockers (mask hypo symptoms but don't significantly worsen glucose), tacrolimus, protease inhibitors, checkpoint inhibitors (autoimmune T1D)

Glucagon kits: every T1D patient; nasal (Baqsimi) and prefilled pens (Gvoke) easier than reconstitution

Insulin storage: unopened in fridge; in-use pen/vial good at room temp ~28 days (varies by product); discard if frozen or visibly altered

Charcot foot: warm, swollen, painless, deformed midfoot in neuropathic patient — non–weight-bearing immediately

Diabulimia: insulin omission as eating disorder behavior — recurrent DKA + young female + high A1c + weight loss

Board pearl: Falling insulin requirements + fatigue + hyperpigmentation in T1D = Addison disease; check morning cortisol.

Key distinction: Hypoglycemia unawareness reverses with 2–3 weeks of strict hypoglycemia avoidance — temporarily raise glucose targets.

Board Question Stem Patterns

Pattern 1 — "Misclassified T2D": Thin 28-year-old labeled T2D fails metformin within 6 months; presents with mild DKA. Best next step → GAD-65 antibodies, C-peptide, start insulin. Diagnosis: LADA.

Pattern 2 — "Dawn vs Somogyi": Morning hyperglycemia in T1D — 3 AM glucose is the discriminator. Low at 3 AM → decrease evening basal (Somogyi). Normal/high at 3 AM → increase evening basal or shift timing (dawn).

Pattern 3 — "Falling insulin needs": Long-standing T1D, A1c improving without changes, fatigue, salt craving, orthostasis → Addison disease → morning cortisol, ACTH stim.

Pattern 4 — "Pump failure": Pump-treated T1D, glucose 380, ketones positive, nausea → inject rapid-acting by pen now, hydrate, replace infusion set, recheck.

Pattern 5 — "Euglycemic DKA": T1D on off-label SGLT2 inhibitor with abdominal pain, anion gap, glucose 190 → DKA, treat as such and stop SGLT2i.

Pattern 6 — "Recurrent DKA young adult": Look for insulin rationing (cost), diabulimia, pump failure, undiagnosed infection — not "increase insulin and discharge."

Pattern 7 — "Charcot vs cellulitis": Warm, swollen, painless foot in neuropathic T1D with intact pulses → Charcot, non–weight-bearing, MRI/X-ray; cellulitis would be painful with systemic signs.

Pattern 8 — "Preconception": T1D patient planning pregnancy → stop ACEi and statin, optimize A1c <6.5%, folic acid, baseline eye/renal exam.

Pattern 9 — "First-trimester hypoglycemia": Pregnant T1D at 8 weeks with new lows → reduce basal, anticipate further reductions until ~16 weeks.

Pattern 10 — "Hypoglycemia unawareness": Frequent severe lows without warning → relax targets 2–3 weeks to restore counter-regulation.

Pattern 11 — "Elderly with low A1c and falls": A1c 6.3% in 80-year-old with hypoglycemia → deintensify, raise target to <8%.

Pattern 12 — "T1D + celiac": New diarrhea, weight loss, iron deficiency anemia in T1D → check tTG IgA + total IgA, EGD to confirm.

CCS pearl: Recognize the pattern in the first 30 seconds — most T1D stems hinge on a single pivot (cost, autoimmunity, technology failure, pregnancy, age) — once identified, the management chain is formulaic.

Board pearl: When the stem mentions "insulin requirements have decreased," reflexively consider renal decline, Addison, celiac, eating disorder, or hypothyroidism — these are the tested differentials.

One-Line Recap

Type 1 diabetes is a lifelong absolute insulin-deficient autoimmune disease requiring basal-bolus insulin (MDI or pump), CGM-guided titration to an A1c <7% and time-in-range >70%, vigilant hypoglycemia avoidance, and a structured longitudinal program of statin/ACEi/BP control, annual renal-retinal-foot-mental health screening, and timely escalation for DKA, severe hypoglycemia, or atypical features pointing to LADA, MODY, Addison, celiac, or thyroid disease.

Core regimen: basal (glargine/degludec/detemir) + rapid-acting bolus (lispro/aspart) using carb ratio (Rule of 500) and correction factor (Rule of 1800); CGM standard of care

Targets: A1c <7% (individualized <6.5% to <8.5%), TIR >70%, time <70 <4%; preconception/pregnancy <6.5% and <6%; older complex patients <8–8.5%

Never-miss screening: annual UACR/eGFR + dilated eye exam (both starting at 5 years post-diagnosis), lipids, TSH, tTG IgA at diagnosis, foot exam every visit, depression annually, vaccines including hepatitis B if <60

High-yield pivots: falling insulin needs → Addison/renal/celiac/hypothyroid; recurrent DKA → cost/diabulimia/pump failure/SGLT2i; misclassified T2D in lean adult → LADA (GAD-65, C-peptide); painless swollen foot → Charcot until disproven

Step 3 management mantra: treat the patient longitudinally — at every visit ask about hypoglycemia, glucagon availability, sick-day plan, affordability, and mental health, and act on the data before the A1c result returns