What is the most likely diagnosis in a 49‑year‑old male with a BMI of 17.7 kg/m², hypothyroidism diagnosed at age 44, sensorineural hearing loss, absent fasting and stimulated C‑peptide, negative glutamic acid decarboxylase (GAD), insulinoma‑associated antigen‑2 (IA‑2) and zinc transporter‑8 (ZnT8) antibodies, and requiring only 16 U total daily basal‑bolus insulin with mild hypoglycemia?

Diagnosis: Antibody-Negative Type 1 Diabetes (Idiopathic Type 1B)

This patient has antibody-negative type 1 diabetes (idiopathic type 1B), characterized by absent C-peptide, severe initial hyperglycemia, absolute insulin requirement, and negative autoantibodies despite a classic type 1 phenotype. 1

Key Diagnostic Features Supporting This Classification

Clinical Presentation:

• Lean BMI of 17.71 kg/m² strongly favors type 1 over type 2 diabetes 2
• Severe initial hyperglycemia (A1c 14.8%) with rapid metabolic decompensation despite absence of ketoacidosis 1
• Absent fasting and stimulated C-peptide confirms complete β-cell failure and absolute insulin deficiency 3
• Age 44 at diagnosis falls within the range for adult-onset type 1 diabetes, which can occur even in the 8th and 9th decades 1

Autoantibody Profile:

• Negative GAD, IA-2, and ZnT8 antibodies do not exclude type 1 diabetes, as 5–10% of true type 1 diabetes patients are antibody-negative 2
• The absence of all three major autoantibodies indicates idiopathic type 1 diabetes (type 1B) rather than immune-mediated type 1A 1
• In antibody-negative patients with classic type 1 features (lean, acute onset, absolute insulin requirement), the diagnosis remains type 1 diabetes 2

Insulin Requirements:

• Current total daily dose of only 16 units reflects preserved insulin sensitivity in a lean individual, not residual β-cell function 4
• The low insulin requirement is explained by the patient's very low BMI (17.71 kg/m²) and absence of insulin resistance 2
• Rapid improvement in A1c from 14.8% to 10.7% within one month, then to 8.4%, demonstrates appropriate response to exogenous insulin replacement 3

Why This Is NOT Type 2 Diabetes

Critical distinguishing features:

• BMI < 25 kg/m² (specifically 17.71) strongly argues against type 2 diabetes 2
• Absent C-peptide (both fasting and stimulated) confirms absolute insulin deficiency, incompatible with type 2 diabetes 2, 3
• Immediate and absolute insulin requirement from diagnosis excludes type 2 diabetes 4
• No features of metabolic syndrome or insulin resistance 2

Why This Is NOT LADA (Latent Autoimmune Diabetes in Adults)

LADA requires positive autoantibodies:

• LADA is defined by the presence of GAD antibodies in 60% of cases, with 92% positive predictive value for insulin requirement within 3 years 2
• This patient has negative GAD, IA-2, and ZnT8 antibodies, excluding autoimmune diabetes 4, 2
• LADA typically shows gradual progression to insulin dependence over 3–5 years, not immediate absolute insulin requirement 2

Why This Is NOT Monogenic Diabetes (MODY)

MODY is excluded by:

• Absent C-peptide rules out MODY, which maintains β-cell function 2
• Initial A1c of 14.8% is too severe for MODY, which typically presents with modest hyperglycemia (A1c < 7.5%) 2
• Absolute insulin requirement from diagnosis is incompatible with MODY 2
• Age 44 at diagnosis is outside the typical MODY presentation window 2

Idiopathic Type 1B Diabetes: A Distinct Entity

Characteristics of type 1B:

• Some forms of type 1 diabetes have no known etiology and lack evidence of β-cell autoimmunity 1
• These individuals have permanent insulinopenia and absolute insulin requirement but no autoantibodies 1
• Only a minority of type 1 diabetes patients fall into this category 1
• The pathogenesis involves β-cell destruction through non-autoimmune mechanisms 1, 5

Fulminant type 1 diabetes variant:

• A subset of antibody-negative type 1B diabetes presents with remarkably abrupt onset, absent autoantibodies, and severe metabolic decompensation 5
• These patients show T-lymphocyte infiltrates in the exocrine pancreas without insulitis 5
• High serum pancreatic enzyme concentrations may be present 5

Associated Autoimmune Conditions

Hypothyroidism and hearing loss:

• Hypothyroidism diagnosed at age 44 is consistent with Hashimoto thyroiditis, which commonly coexists with type 1 diabetes 1
• Sensorineural hearing loss is associated with hypothyroidism and may improve with thyroid hormone replacement 6, 7
• The presence of hypothyroidism supports an autoimmune predisposition, even though diabetes-specific autoantibodies are absent 1

Current Management Assessment

Insulin therapy:

• Basal-bolus regimen with 16 units total daily dose is appropriate for this lean patient 4, 3
• The low dose reflects insulin sensitivity, not residual β-cell function 4
• 1–2 hypoglycemia episodes in 4 months is acceptable but requires dose adjustment 4

Glycemic control:

• A1c improvement from 14.8% to 8.4% demonstrates effective insulin replacement 3
• Target A1c < 7.0% should be pursued with careful titration to avoid hypoglycemia 4, 3

Ongoing Management Recommendations

Monitoring:

• Self-monitoring of blood glucose ≥ 4 times daily or continuous glucose monitoring is strongly recommended 4, 3
• Target glucose range 90–180 mg/dL (5–10 mmol/L) 4
• Screen for other autoimmune conditions including celiac disease and Addison disease 1, 3
• Monitor thyroid function regularly given established hypothyroidism 1

Insulin optimization:

• Adjust basal and prandial insulin doses to achieve A1c < 7.0% while minimizing hypoglycemia 4, 3
• Consider insulin analogs over human insulin to reduce hypoglycemia risk 4
• Evaluate for insulin pump or hybrid closed-loop system 4

Patient education:

• Teach carbohydrate counting and insulin-to-carbohydrate ratios 4
• Train on hypoglycemia recognition and glucagon administration 4, 3
• Emphasize that this is permanent insulin-requiring diabetes despite negative antibodies 1, 2

Critical Pitfall to Avoid

Do not misclassify as type 2 diabetes based on:

• Negative autoantibodies (5–10% of type 1 diabetes is antibody-negative) 2
• Low insulin requirements (explained by lean body habitus and insulin sensitivity) 4, 2
• Adult age at diagnosis (type 1 diabetes can present at any age) 1

This patient requires lifelong insulin therapy and should be managed as type 1 diabetes regardless of antibody status. 1, 2, 3