T2D Clinical Pocket Cards (4x6" Laminated Format)

CARD 01 Screening & Diagnosis JAMA 2025;334:985

Diagnostic Thresholds (Nonpregnant)

Test	Prediabetes	Diabetes Mellitus
Fasting Glucose (FPG)	100–125 mg/dL	≥ 126 mg/dL (7.0 mmol/L)
Hemoglobin A1C	5.7%–6.4%	≥ 6.5% (48 mmol/mol)
2-hr 75g OGTT	140–199 mg/dL	≥ 200 mg/dL (11.1 mmol/L)
Random Glucose	—	≥ 200 mg/dL + symptoms

CONFIRMATION RULE: Asymptomatic: Needs 2 abnormal tests (same sample or 2 visits) Symptomatic: Classic symptoms + Random >=200 = 1 test diagnostic!

⚠️ When A1C Lies (Use Blood Glucose!)

Falsely LOW A1C (↓ RBC lifespan)	Falsely HIGH A1C (↑ RBC lifespan)
• Hemolytic anemia • Hemodialysis / ESRD • Blood transfusion / Acute bleed • EPO therapy • Pregnancy (2nd/3rd trimester)	• Iron deficiency anemia (classic!) • Vit B12 / Folate deficiency • Splenectomy • Severe hypertriglyceridemia • Severe hyperbilirubinemia

Screening Rule: ADA: ALL adults ≥35 y every 3 yrs. ANY age if BMI ≥25 (≥23 Asian) + 1 risk factor. Screen prediabetes yearly!

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CARD 02 "Is it Really T2D?" DiffDx JAMA 2025;334:985

Differential Matrix (Table 1 Summary)

Feature	T2D (90-95%)	T1D / LADA (5-10%)	MODY (<5%)
Onset	Usually ≥35 y	Any age (indolent in adult)	Usually <25 y
Habitus	Overweight (BMI≥25)	Lean (BMI<25 typical)	Normal weight
Symptoms	Mild / Asymptom.	Rapid catabolism / thirst	Mild (A1C<7.5%)
DKA Risk	Rare (or on SGLT2i)	High / Frequent	Very unlikely
Antibodies	Negative (<10%)	Positive (GAD65/IA2)	Negative
C-Peptide	Normal / High	Low (<200 pmol/L)	Detectable
Genetics	Polygenic	Sporadic (85%)	Autosomal Dom.
Rx Target	Oral / Incretins	Absolute Insulin	SU (MODY 1/3)

🚨 4 Red Flags for Immediate Workup

1. "Non-Responder": Glucose rises despite strict oral meds.
2. Rapid Catabolism: Rapid weight loss, muscle wasting, ketosis.
3. Checkpoint Inhibitor: Acute DKA post Nivolumab/Pembrolizumab.
4. Pancreatic: Post-pancreatitis (use OGTT; avoid DPP4i/GLP-1).

Testing Triage: Order Anti-GAD65 first. If negative but suspicion remains, check IA-2, ZnT8, and post-meal stimulated C-peptide.

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CARD 03 Targets & Ambulatory CGM JAMA 2025;334:985

Individualized A1C Targets

Target	Clinical Profile	Trial Rationale
< 6.5%	Younger, newly diagnosed, long life expectancy, no CVD, motivated.	Achieve safely WITHOUT hypoglycemia.
< 7.0%	Most nonpregnant adults. Standard target.	Optimizes microvascular event reduction (UKPDS).
7.5–8.5%	Older (≥75y), frail, severe CKD, dementia, high hypo risk, limited LE.	ACCORD Warning: Tight control in high-risk ↑ mortality by 22%!

CGM Consensus Metrics (Ambulatory)

Metric	Standard Goal	Older / High-Risk Goal
Time in Range (70–180 mg/dL)	> 70% (>16.8 h/d)	> 50% (>12 h/d)
Time Below Range (< 70 mg/dL)	< 4% (<1 h/d)	< 1% (<15 min/d)
Severe Hypo (< 54 mg/dL)	< 1% (<15 min/d)	Strict Avoidance

CGM Evidence: Lowers A1C by -0.31% and cuts hypoglycemia time by ~0.47 h/day. Offer to all patients on insulin!

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CARD 04 Lifestyle Rx & Remission JAMA 2025;334:985

Evidence-Based Lifestyle Rx

• Medical Nutrition Therapy (MNT): Referral to Registered Dietitian cuts A1C by 0.3% to 2.0% at 6 months!
• Mediterranean Diet: PREDIMED trial showed 30% drop in MACE (HR 0.70) with extra virgin olive oil/nuts; A1C -0.39%.
• DASH Diet: Lowers A1C by -0.53%; reduces blood pressure.
• DSMES: Diabetes education lowers A1C by -0.60%.

Physical Activity Prescription

• Aerobic: ≥150 min/wk moderate-to-vigorous (brisk walk, swim), spread over ≥3 days (no >2 consecutive days off).
• Resistance: 2–3 sessions/wk on non-consecutive days (preserves muscle mass during weight loss).
• Optimal Dose: 1100 MET-min/wk (~244 min/wk) → 0.4–1.0% A1C drop.

Diabetes Remission (DiRECT Protocol)

REMISSION: Sustained A1C < 6.5% for >= 3 months OFF ALL MEDS! - Total diet replacement: 825-853 kcal/d formula for 12-20 wks - Stepped food reintroduction: 46% REMISSION at 1 yr in primary care! - Primary Care Rx: 500-750 kcal/d deficit -> 5% to 15% weight loss.

Clinic Pearl: Weight loss of 10–15% can induce diabetes remission, reverse MASLD steatosis, and reduce cardiovascular risk.

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CARD 05 Non-Insulin Drug Matrix JAMA 2025;334:985

Pharmacotherapy Matrix (Table 2 Summary)

Class	A1C ↓	Wt	Hypo	Renal Limits & Key Pearls
Metformin (500–2000mg)	1–2%	↔/↓	No	eGFR<30: Contraind; 30-45: max 1000mg. Switch XR for GI upset. Check B12.
SGLT2i (Empa, Dapa)	0.5%	↓ 2-4kg	No	Cardiorenal benefit down to dialysis! Hold 3-4 d pre-op (euDKA risk).
GLP-1 RA (Sema, Dula)	1.5–2.5%	↓ 4-8kg	No	Proven MACE & CKD benefit. Titrate monthly for nausea. MTC/MEN2 contra.
Dual GIP/GLP1 (Tirzepatide)	2–2.5%	↓ >10kg	No	Highest weight loss; HFpEF benefit. Titrate q4w by 2.5mg increments.
DPP-4i (Sita, Lina)	<0.5%	↔	No	Linagliptin: NO renal adjust! Saxa: HF risk! DO NOT combine with GLP-1.
TZD (Pioglitazone)	1–2%	↑	No	Contraindicated in NYHA III/IV HF! Edema, bone fractures. 15-30mg best.
SU (Glip, Glimep)	1–2%	↑	YES	AVOID Glyburide! Take only with meals. Glipizide safest in CKD.

GLP-1 Dose Equivalence Guide

Oral Sema 14mg ~= SC Sema 0.5mg ~= Dula 1.5mg ~= Lira 1.8mg ~= Tirz 2.5mg

Cost Warning: SGLT2i/GLP-1 are $$$$. Use manufacturer assistance / co-pay cards. Metformin, SU, and TZD remain low-cost ($) pillars.

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CARD 06 Comorbidity-First Rx JAMA 2025;334:985

Paradigm Shift: Organ Protection First!

Assess ASCVD, Heart Failure & CKD FIRST! Prescribe SGLT2i or GLP-1 RA INDEPENDENT of baseline A1C and INDEPENDENT of background Metformin!

1. Atherosclerotic CVD (Prior MI, Stroke, PAD, CAD)

• First Choice: GLP-1 RA (SC Semaglutide, Dulaglutide, Liraglutide) OR SGLT2i (Empagliflozin, Canagliflozin).
• Benefit: 12–14% reduction in 3-point MACE.

2. Heart Failure (HFrEF or HFpEF)

• First Choice: SGLT2 Inhibitor (Dapagliflozin 10mg or Empagliflozin 10mg).
• Benefit: ↓ CV death & HF hospitalizations across all ejection fractions!
• Obesity HFpEF: Add SC Semaglutide or Tirzepatide.
• AVOID: Pioglitazone (fluid overload) & Saxagliptin!

3. Chronic Kidney Disease (eGFR 20-60 or UACR > 30 mg/g)

• First Choice: SGLT2i (Cana, Dapa, Empa) + GLP-1 RA (Semaglutide).
• Benefit: Halts progression to dialysis, slows eGFR decline, ↓ renal death.
• Continue SGLT2i down to dialysis initiation!

No Comorbidities? Metformin + Lifestyle. If A1C >1.5% above target, start dual therapy immediately!

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CARD 07 Insulin Initiation & Titration JAMA 2025;334:985

When is Insulin Mandatory First-Line?

1. Ongoing catabolism (rapid unintended weight loss, ketosis).
2. Severe hyperglycemic symptoms (polyuria, polydipsia).
3. Marked hyperglycemia: A1C > 10% AND/OR Blood Glucose ≥ 300 mg/dL.

Basal Insulin Titration Protocol

1. START BASAL: Glargine or Degludec Dose: 10 units/day OR 0.1 to 0.2 units/kg/day (bedtime/morning) | v 2. TITRATE TO MORNING FASTING TARGET (80 - 130 mg/dL): • Fasting > 130 mg/dL: INCREASE +2 units every 3 days. • Fasting 80-130 mg/dL: MAINTAIN current dose. • Hypo (< 70 mg/dL): DECREASE dose by 2-4 units (or 10-20%). | v 3. ADD PRANDIAL (BOLUS) IF A1C STAYS HIGH DESPITE NORMAL FASTING: • Start 4 units (or 10% basal) before LARGEST meal of the day. • Titrate by +1-2 units twice weekly based on 2-hr post-meal (<180).

Clinical Insulin Pearls

• Incretin First: If injectable needed without catabolism, try GLP-1 RA first.
• Adding GLP-1 to Insulin: Cut basal by 10–20%; stop or reduce boluses.
• Concentrated Insulins: If >200 U/d, use U-200, U-300 Glargine, or U-500 Regular.
• NPO / Surgery: Cut basal by 50–80% (give 0.2–0.3 U/kg). NEVER omit basal!

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CARD 08 Holds, euDKA & Safety JAMA 2025;334:985

Perioperative "When to Hold" Checklist

Drug Class	Holding Rule	Clinical Rationale
SGLT2i	HOLD 3–4 DAYS PRIOR	Prevents Euglycemic DKA during operative fasting.
GLP-1 RA / Tirzepatide	Weekly: HOLD 1 WK PRIOR Daily: Hold day of	Delayed gastric emptying causes pulmonary aspiration.
Metformin	Hold day of & 48h post	Prevents Lactic Acidosis if contrast AKI occurs.
Sulfonylurea	Hold morning of surgery	Prevents severe intraoperative hypoglycemia.
Basal Insulin	Reduce by 20% to 50%	Suppresses ketogenesis while preventing hypo.

⚠️ Euglycemic DKA (euDKA): The Hidden Trap

Severe ketoacidosis with NORMAL blood glucose (<250 mg/dL) on SGLT2i! Triggers: surgery, infection, low carbs, dehydration. Check blood/urine ketones in ANY unwell patient on SGLT2i!

De-intensification & Hypo Pearls

• Eliminate Glyburide in elderly (≥75y) / CKD → Fatal prolonged hypo!
• Adding SGLT2i/GLP-1: Cut SU dose by 50% (or stop) and insulin by 10–20%.
• Acarbose Alert: Sucrose is blocked! Must treat hypoglycemia with pure oral dextrose (glucose tabs), not table sugar or juice!

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CARD 09 Clinic Checklist & Referrals JAMA 2025;334:985

Primary Care Maintenance Schedule

Frequency	Action Item	Clinical Target
Every 3 Months	A1C (if uncontrolled / med changed)	Target <7.0% (individualized)
Every 6 Months	A1C (if stable at goal)	Assess sustained control
Every Visit	BP, Weight, Visual Foot Check	BP <130/80; detect pre-ulcers
Annually	Spot UACR & eGFR	Detect albuminuria (>30 mg/g)
Annually	Dilated Eye Exam (Ophthalmology)	Screen diabetic retinopathy
Annually	10g Monofilament & Pulse Exam	Loss of protective sensation
Annually	Lipid Panel & Liver AST/ALT	Statin therapy; MASLD screen
At Diagnosis	DSMES & Dietitian (MNT) Referral	Empower self-management

Bariatric / Metabolic Surgery

Refer if BMI ≥ 30.0 kg/m² (≥27.5 in Asian descent) with uncontrolled diabetes. Induces remission; ↓ CV events; reduces risk of 7 obesity-related cancers!

Endocrinology Referral Triggers:
1. Suspected LADA, MODY, or secondary diabetes.
2. Refractory insulin resistance requiring > 200 units/day.
3. Recurrent severe hypoglycemia or hypoglycemia unawareness.
4. Automated Insulin Delivery (AID) / Insulin pump candidates.

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