Diagnostic Criteria (Nonpregnant Adults)
| Diagnostic Test |
Prediabetes |
Diabetes |
Pearl |
| Fasting Glucose (FPG) |
100–125 mg/dL |
≥ 126 mg/dL |
Fast ≥8 hrs; affected by illness |
| Hemoglobin A1C |
5.7%–6.4% |
≥ 6.5% |
Weighted 2–3 mo average |
| 2-Hour 75g OGTT |
140–199 mg/dL |
≥ 200 mg/dL |
Most sensitive; preferred in CF |
| Random Glucose |
— |
≥ 200 mg/dL |
ONLY with classic symptoms / crisis |
CONFIRMATION RULE:
Asymptomatic --> 2 ABNORMAL TESTS REQUIRED (same draw or 2 visits)
Symptomatic --> 1 Random Glucose >= 200 mg/dL is DIAGNOSTIC!
⚠️ When A1C Lies (Use Blood Glucose Instead!)
Falsely LOW A1C:
- Hemolytic anemia
- Hemodialysis / ESRD
- Recent blood transfusion
- EPO therapy / Acute bleed
- Pregnancy (2nd/3rd trim)
Falsely HIGH A1C:
- Iron deficiency anemia (classic!)
- Vitamin B12 / Folate def.
- Severe hypertriglyceridemia
- Severe hyperbilirubinemia
- Splenectomy
Screening Quick Rule: ADA recommends screening all adults ≥35 y every 3 years. Screen at any age if BMI ≥25 (≥23 in Asian adults) + 1 risk factor. Screen prediabetes yearly!
Triage Matrix: Differentiating Diabetes Types
| Feature |
Type 2 DM (90-95%) |
Type 1 / LADA (5-10%) |
MODY (<5%) |
| Habitus |
Overweight (BMI ≥25) |
Lean (BMI <25 typical) |
Normal weight |
| Presentation |
Asymptomatic / Mild |
Catabolic, rapid wasting |
Mild (A1C <7.5%) |
| C-Peptide |
Normal or High |
Low / Absent (<200) |
Detectable |
| Antibodies |
Negative (<10%) |
Positive (GAD65, IA-2) |
Negative |
| Pedigree |
Polygenic / Common |
Usually sporadic (85%) |
Autosomal Dominant |
| Rx Target |
Lifestyle + Meds |
Absolute Insulin |
Sulfonylurea (MODY 1/3) |
🚨 4 Clinical Red Flags Prompting Autoantibody Testing
- The "Non-Responder": Patient strictly taking Metformin + 2nd agent but glycemia fails to improve or worsens.
- Rapid Catabolism: Unintentional marked weight loss, thirst, and fatigue in a non-obese adult.
- Checkpoint Inhibitor Diabetes: Acute DKA after immunotherapy (Nivolumab, Pembrolizumab).
- Secondary Pancreatic: Post-pancreatitis or CF (use 2h OGTT; avoid DPP-4i/GLP-1 RA).
Preceptor Pearl: If suspected LADA/T1D, order Anti-GAD65 first. If negative but suspicion remains, check IA-2, ZnT8, and a post-meal stimulated C-peptide.
Individualized A1C Targets
< 6.5% (Strict): Younger, newly diagnosed, long life expectancy, no CVD, achieved safely without hypoglycemia.
< 7.0% (Standard): Most nonpregnant adults; optimizes microvascular protection.
7.5% – 8.5% (Relaxed): Frail elderly (≥75y), severe CKD, dementia, high hypoglycemia risk, limited life expectancy.
ACCORD / ADVANCE / VADT TRIAL LESSON:
Tight control (<6.0%) in high-risk patients INCREASED MORTALITY by 22% (ACCORD)
Microvascular benefits take years; severe hypoglycemia kills in hours!
Ambulatory CGM International Consensus Targets
| Time In Range (TIR: 70–180 mg/dL) |
> 70% of the day (> 16.8 hrs/d) |
| Time Below Range (TBR: < 70 mg/dL) |
< 4% of the day (< 1 hr/d) |
| Very Low Hypoglycemia (< 54 mg/dL) |
< 1% (< 15 min/d; <1% in frail!) |
| Frail / High Hypo-Risk Adults |
TIR > 50%, TBR < 1% |
CGM Evidence: Lowers A1C by -0.31% and cuts hypoglycemia time by ~0.47 hours/day vs fingerstick BGM. Offer to all adults on insulin!
Evidence-Based Lifestyle Prescription
Dietary Patterns:
- Mediterranean: Extra virgin olive oil/nuts → 30% MACE drop (HR 0.70); A1C -0.39%.
- DASH: A1C -0.53%; lowers BP.
- MNT Referral: Registered Dietitian visit cuts A1C by 0.3% to 2.0%!
Physical Activity:
- Aerobic: ≥150 min/wk moderate-to-vigorous (brisk walk, swim).
- Resistance: 2–3 sessions/wk on non-consecutive days.
- Dose: 1100 MET-min/wk drops A1C by 0.4% to 1.0%.
Diabetes Remission (DiRECT Trial Protocol)
Definition: Sustained A1C < 6.5% for ≥ 3 months off all glucose-lowering drugs.
The Intervention: Total diet replacement with very-low-calorie formula (825–853 kcal/d) for 12–20 weeks, followed by stepped food reintroduction → 46% remission rate at 1 year in primary care practices!
Clinic Advice: Prescribe a 500–750 kcal/day deficit to target a 5%–15% weight reduction.
DSMES: Diabetes Self-Management Education and Support yields a pooled -0.60% A1C reduction. Refer all patients at diagnosis!
STEP 1: ASSESS CARDIO-RENAL-METABOLIC COMORBIDITIES FIRST!
(Independent of baseline A1C and independent of background Metformin)
1. Atherosclerotic CVD (Prior MI, Stroke, PAD, CAD)
Prescribe: GLP-1 RA (SC Semaglutide, Dulaglutide, Liraglutide) OR SGLT2i (Empagliflozin, Canagliflozin).
Evidence: 12–14% relative reduction in 3-point MACE (MI, stroke, CV mortality).
2. Heart Failure (HFrEF or HFpEF)
Prescribe: SGLT2 Inhibitor (Dapagliflozin 10 mg or Empagliflozin 10 mg daily).
Evidence: SGLT2i reduces CV death and HF hospitalization across the entire spectrum of EF.
Obesity HFpEF: Add SC Semaglutide or Tirzepatide (improves symptoms and 6-min walk distance).
⚠️ Avoid: Pioglitazone and Saxagliptin!
3. Chronic Kidney Disease (eGFR 20-60 or UACR > 30 mg/g)
Prescribe: SGLT2 Inhibitor (Canagliflozin, Dapagliflozin, Empagliflozin) + GLP-1 RA (Semaglutide).
Evidence: Slows eGFR loss, halts progression to dialysis, reduces kidney-related death.
4. No Comorbidities (Glycemia & Weight Primary)
First-Line: Metformin + Lifestyle. If A1C >1.5% above target, start dual therapy immediately!
When Is Insulin Mandatory First-Line?
- Ongoing catabolism (rapid unintended weight loss, ketosis).
- Severe hyperglycemic symptoms (marked polyuria, polydipsia).
- Marked hyperglycemia: A1C > 10% AND/OR Blood Glucose ≥ 300 mg/dL.
STEP-BY-STEP TITRATION ALGORITHM:
[1. START BASAL INSULIN]
Dose: 10 units daily OR 0.1 - 0.2 units/kg/day (Glargine / Degludec)
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v
[2. TITRATE TO MORNING FASTING TARGET (80 - 130 mg/dL)]
Fast > 130 mg/dL --> INCREASE +2 units every 3 days
Fast 80-130 mg/dL --> MAINTAIN current dose
Hypo (< 70 mg/dL) --> DECREASE dose by 2-4 units (or 10-20%)
|
v
[3. FASTING ON TARGET BUT A1C REMAINS HIGH? (Postprandial spikes)]
Add PRANDIAL (BOLUS) Insulin (Aspart / Lispro / Glulisine)
Start: 4 units (or 10% basal) before LARGEST meal of day.
Titrate: +1 to 2 units twice weekly based on 2h post-meal glucose (<180 mg/dL).
Clinical Insulin Pearls
- Injectable Preference: If injectable needed and not in catabolic crisis, try GLP-1 RA first before insulin (superior weight loss, near-zero hypoglycemia).
- Adding GLP-1 to Insulin: Drop basal insulin by 10–20% and stop or cut prandial boluses.
- Concentrated Insulins: If dose >200 U/day, use U-200, U-300 Glargine, or U-500 Regular to spare subcutaneous volume!
- NPO / Surgery: Cut basal by 50–80% (give 0.2–0.3 U/kg). NEVER omit basal completely!
Perioperative "When to Hold" Checklist
| Drug Class |
Holding Rule |
Clinical Rationale |
| SGLT2 Inhibitors |
HOLD 3 TO 4 DAYS PRIOR |
Prevents Euglycemic DKA (euDKA) triggered by surgery/fasting. |
| GLP-1 RA / Tirzepatide |
Weekly: HOLD 1 WEEK PRIOR
Daily: Hold morning of |
Delayed gastric emptying causes pulmonary aspiration under anesthesia. |
| Metformin |
HOLD DAY OF & 48h POST |
Prevents Lactic Acidosis if contrast-induced acute kidney injury occurs. |
| Sulfonylureas |
HOLD MORNING OF SURGERY |
Prevents severe intraoperative hypoglycemia while fasting. |
| Basal Insulin |
REDUCE BY 20% TO 50% |
Suppresses lipolysis/ketogenesis without causing severe hypoglycemia. |
⚠️ Euglycemic DKA: The Hidden Trap
In patients taking SGLT2i, severe ketoacidosis (vomiting, anion gap acidosis, high ketones) can occur with NORMAL blood glucose (<250 mg/dL)! Check blood/urine ketones in ANY sick patient on SGLT2i!
Deprescribing / De-intensification Rules
- Eliminate Glyburide in elderly (≥75y) or CKD → Prolonged fatal hypoglycemia!
- Adding Modern Drugs: When starting SGLT2i/GLP-1 RA, cut sulfonylureas by 50% (or stop) and reduce insulin by 10–20%.
- Acarbose Alert: Sucrose (table sugar) is blocked by acarbose! Must treat hypoglycemia with pure oral dextrose!
Primary Care Annual Maintenance Schedule
| Frequency |
Action Item |
Clinical Goal |
| Every 3 Months |
A1C (if uncontrolled / changed rx) |
Goal < 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 (Ophth/Optom) |
Screen diabetic retinopathy |
| Annually |
10g Monofilament & Pulse Exam |
Loss of protective sensation |
| Annually |
Lipid Panel & Liver AST/ALT |
Statin titration; MASLD screen |
| At Diagnosis |
DSMES & Dietitian (MNT) Referral |
Self-management training |
Bariatric / Metabolic Surgery Criteria
Refer if BMI ≥ 30.0 kg/m² (≥ 27.5 in Asian descent) with uncontrolled diabetes.
Benefits: High remission rate, reduced cardiovascular events, and reduced risk of 7 cancers (breast, colorectal, endometrial, pancreatic, ovarian, gallbladder, liver).
Endocrinology Referral Triggers:
- Atypical diabetes / Suspected LADA, MODY, or secondary diabetes.
- Refractory insulin resistance requiring > 200 units/day.
- Recurrent severe hypoglycemia or hypoglycemia unawareness.
- Patients seeking advanced tech (Automated Insulin Delivery / Insulin Pumps).