Acute-onset autoimmune type 1 diabetes presenting with diabetic ketoacidosis in an obese adult

Abstract

Autoimmune type 1 diabetes mellitus (T1DM) has traditionally been associated with early onset disease and a lean phenotype; however, adult-onset disease increasingly presents with heterogeneous features that overlap with type 2 diabetes. We describe a 51-year-old obese man presenting with severe diabetic ketoacidosis (DKA). Laboratory evaluation demonstrated marked hyperglycemia (1297 mg/dL), metabolic acidosis (bicarbonate 7 mmol/L, anion gap 42), β-hydroxybutyrate >9 mmol/L, and hemoglobin A1c 13.3%. Autoimmune testing revealed strong glutamic acid decarboxylase antibody positivity with very low C-peptide, confirming profound insulin deficiency despite obesity. The patient improved with standard DKA management and was discharged on basal bolus insulin therapy. This case highlights the evolving phenotype of adult-onset autoimmune diabetes and emphasizes that obesity does not exclude T1DM. Early recognition using antibody testing and assessment of endogenous insulin secretion is essential to guide therapy and reduce recurrent metabolic decompensation.

KEY POINTS

• Autoimmune type 1 diabetes may present in obese adults with diabetic ketoacidosis; age and body habitus alone do not reliably distinguish diabetes subtype.

• In adults with new-onset diabetes and marked insulin deficiency, measurement of islet autoantibodies and C-peptide is essential to avoid misclassification and to guide timely initiation of insulin therapy.

CME

CME Information: https://ce.bswhealth.com/BUMC_Proceedings_CME_info

Credit Claim Process: To claim CME for this activity, read the entire article and go to http://ce.bswhealth.com/2026BUMC_Proceedings_Sep_T1DM. You will register for the course, pay any relevant fee, take the quiz, complete the evaluation, and claim your CME credit.

Dates for credit claim: September 1, 2026, to September 1, 2027.

For questions about CME credit, visit our website ce.bswhealth.com/contact-us.

CASE SUMMARY

A 51-year-old African American man with no significant past medical history presented with 3 days of generalized weakness, polyuria, polydipsia, and nocturia. He denied prior diabetes, hypertension, or hyperlipidemia and reported no recent weight loss. Family history was negative for autoimmune or endocrine disorders. The patient denied alcohol or illicit drug use and reported no recent infection or illness. He was not taking prescription medications or over-the-counter agents known to affect glucose metabolism.

On arrival, he was tachycardic (107 beats/min) and hypertensive (191/105 mm Hg). His body mass index was 45.8 kg/m². Initial laboratory evaluation (Table 1) demonstrated severe hyperglycemia (1297 mg/dL), high-anion-gap metabolic acidosis (bicarbonate 7 mmol/L, anion gap 42), and marked ketosis with β-hydroxybutyrate >9 mmol/L. Hemoglobin A1c was 13.3%. Electrolyte abnormalities included hyperkalemia (7.2 mmol/L) and hyponatremia (corrected sodium 128 mmol/L). Renal function was impaired with creatinine 3.32 mg/dL and blood urea nitrogen 44 mg/dL. Electrocardiogram, chest radiography, and renal ultrasonography were unremarkable. Additional laboratory values are summarized in Table 1.

Table 1.

Laboratory results

Laboratory test	Value	Reference range
Metabolic panel
Sodium	110	136–145 mmol/L
Potassium	7.2	3.5–5.1 mmol/L
Chloride	68	98–107 mmol/L
CO2 (bicarbonate)	7	22–29 mmol/L
Glucose	1297	70–99 mg/dL
Blood urea nitrogen	44	6–20 mg/dL
Creatinine	3.32	0.7–1.20 mg/dL
eGFR	22	>59 mL/min/1.73 m²
Anion gap	42	12–20
Calcium (total)	8.7	8.6–10.0 mg/dL
Total protein	7.9	6.4–8.3 g/dL
Albumin	4.6	3.5–5.2 g/dL
Globulin	3.3	2.4–4.0 g/dL
Alkaline phosphatase	118	44–147 U/L
AST	16	0–40 U/L
ALT	23	0–41 U/L
Total bilirubin	0.4	0.0–1.2 mg/dL
Arterial blood gas
Arterial pH	7.14	7.37–7.44
pCO2 (arterial)	23	34–45 mm Hg
pO2 (arterial)	74	78–92 mmHg
HCO3 (arterial)	8	23–30 mmol/L
Base excess	−21	−2.0–2 mmol/L
Oxygen saturation	90%	94%–99%
DKA/metabolic stress markers
CK	615	39–308 U/L
Beta-hydroxybutyrate	>9.00	<0.60 mmol/L
Magnesium	3.6	1.6–2.6 mg/dL
Complete blood count
White blood cells	8.32	4.0–11.0 × 10⁹/L
Red blood cells	4.93	4.2–5.9 × 10¹²/L
Hemoglobin	14.5	13.5–17.5 g/dL
Hematocrit	40.2	41%–53%
MCV	81.5	80–100 fL
MCH	29.4	27–33 pg
MCHC	36.1	32–36 g/dL
RDW	12.6	11%–15%
Platelets	154	150–450 × 10⁹/L
MPV	12.2	7.5–11.5 fL
Glycemic control
Hemoglobin A1c	13.3%	4.8%–5.6%
Autoimmune diabetes antibody panel
C-peptide	< 0.1 ng/mL	0.8–3.1 ng/mL
GAD-65 antibody	104 IU/mL (Positive)	<5 – Negative
IA-2 antibody	<5.4 U/mL (Negative)	Negative
ZnT8 antibody	<15 U/mL (Negative)	Negative
Insulin autoantibody	<0.4 U/mL (Negative)	Negative
Urinalysis
Urine specific gravity	1.026	1.005–1.030
Urine pH	5.0	4.5–8.0
Urine protein	Trace	Negative
Urine glucose	3+	Negative
Urine ketones	1+	Negative
Urine blood	2+	Negative
Urine red blood cells	2	0–2/HPF
Urine white blood cells	1	0–5/HPF
Urine casts	7	0–2/LPF

ALT indicates alanine aminotransferase; AST, aspartate aminotransferase; CK, creatine kinase; DKA, diabetic ketoacidosis; eGFR, estimated glomerular filtration rate; HCO_3, bicarbonate; GAD, glutamic acid decarboxylase; HPF, high-power field; IA-2, insulinoma-associated antigen-2; LPF, low-power field; MCH, mean corpuscular hemoglobin; MCHC, mean corpuscular hemoglobin concentration; MCV, mean corpuscular volume; MPV, mean platelet volume; pCO₂, partial pressure of carbon dioxide; pO₂, partial pressure of oxygen; RDW, red cell distribution width; ZnT8, zinc transporter-8.

The patient was admitted to the intensive care unit and treated with intravenous fluids, continuous insulin infusion, and electrolyte correction. Given the severity of presentation, the absence of prior diabetes, and marked insulin deficiency, autoimmune testing was obtained. In adults with new-onset diabetes, antibody testing should be considered when clinical features are atypical for type 2 diabetes mellitus (T2DM) or when insulin deficiency is suspected. Glutamic acid decarboxylase (GAD) antibodies were elevated at 104 IU/mL, whereas insulinoma-associated antigen-2, insulin autoantibodies, and zinc transporter-8 antibodies were negative. C-peptide was <0.1 ng/mL, indicating profound insulin deficiency. Metabolic abnormalities improved with therapy, and the patient was transitioned to subcutaneous basal bolus insulin with endocrinology follow-up arranged.

CLINICAL QUESTIONS

1. A 51-year-old obese adult presents with severe diabetic ketoacidosis and no prior history of diabetes. Which finding most strongly supports autoimmune T1DM rather than ketosis-prone diabetes or T2DM?

   1. Hemoglobin A1c of 13.3%

   2. Severe hyperglycemia with glucose >1000 mg/dL

   3. Positive GAD antibody with normal C-peptide

   4. Positive GAD antibody with markedly reduced C-peptide

2. Which statement best reflects the contemporary understanding of obesity in adult-onset type 1 diabetes?

   1. Obesity excludes autoimmune diabetes

   2. Obesity is uncommon in type 1 diabetes

   3. Obesity may coexist with autoimmune type 1 diabetes and cause diagnostic uncertainty

   4. Obesity eliminates the need for antibody testing

Answers are provided at the end of the article.

DISCUSSION

This case highlights the evolving phenotype of adult-onset autoimmune T1DM and the limitations of traditional clinical classification. Adults presenting with obesity and severe hyperglycemia are frequently presumed to have T2DM; however, autoimmune diabetes increasingly occurs outside classic phenotypic expectations.^1–3 The rising prevalence of obesity among individuals with T1DM further complicates clinical distinction and underscores the importance of biomarker-driven diagnosis.³

Adult-onset autoimmune T1DM exists along a spectrum ranging from slowly progressive disease to acute presentations with ketosis or diabetic ketoacidosis (DKA). Reports of elderly individuals with abrupt autoimmune diabetes demonstrate that age does not exclude T1DM and that insulin deficiency may be profound at diagnosis.^4–6 In adults presenting with DKA and no prior history of diabetes, the differential diagnosis includes acute-onset autoimmune T1DM, latent autoimmune diabetes in adults (LADA), and ketosis-prone diabetes (KPD). According to the Immunology of Diabetes Society definition, LADA is characterized by adult-onset diabetes, the presence of islet autoantibodies, and the absence of insulin requirement for at least the first several months after diagnosis.⁷ In contrast, this patient presented with severe DKA and immediate insulin dependence, findings more consistent with acute-onset autoimmune T1DM rather than LADA, which typically progresses more gradually.

KPD, also referred to as Flatbush diabetes, should also be considered in obese adults presenting with DKA, particularly in individuals of African ancestry. Patients with KPD may initially present with severe insulin deficiency but can recover β-cell function after metabolic stabilization.⁸ Under the Balasubramanyam classification system, KPD is further categorized by autoantibody status and β-cell functional reserve; a minority of patients fall into the A + β− subgroup, characterized by autoantibody positivity and absent β-cell reserve, which may clinically resemble autoimmune T1DM.⁸ Interpretation of C-peptide during acute DKA therefore requires caution, as glucotoxicity can transiently suppress β-cell function, and repeat testing after metabolic stabilization may help confirm persistent insulin deficiency. In the present case, strongly positive GAD antibodies supported autoimmune T1DM and made KPD less likely, although follow-up assessment of insulin secretion remains clinically important.

Diagnostic uncertainty in adults remains common. Patients with autoimmune diabetes are often misclassified as having T2DM, particularly when obesity or metabolic syndrome is present.^1,2,9 Clinical features alone are unreliable, and even DKA does not definitively distinguish autoimmune from nonautoimmune diabetes in adults, emphasizing the need for antibody testing and assessment of endogenous insulin secretion. Studies using high-specificity definitions demonstrate comparable disease severity across adult age groups, challenging the perception that later-onset disease is milder.¹⁰

Obesity introduces additional metabolic complexity. Insulin therapy and weight gain may reinforce each other, contributing to insulin resistance and a “double diabetes” phenotype.³ Population-based studies demonstrate that adult-onset T1DM is associated with increased mortality and cardiovascular risk, with overweight and obesity representing major modifiable contributors to adverse outcomes.¹¹ These findings highlight the importance of comprehensive cardiovascular risk management alongside glycemic control. Outpatient management should include close endocrinology follow-up, adjustment of insulin dosing, and monitoring of glycemic control and cardiovascular risk factors. In obese individuals with autoimmune diabetes, weight management is an important component of long-term care because excess adiposity may exacerbate insulin resistance and increase insulin requirements. Adjunct therapies such as GLP-1 receptor agonists and SGLT2 inhibitors have been explored in selected patients with T1DM and obesity to assist with weight reduction and glycemic control.³ However, their use requires careful monitoring because of potential risks, including euglycemic DKA.

Overall, this case illustrates the diagnostic challenge of distinguishing autoimmune T1DM from other forms of adult-onset diabetes, including KPD, in obese adults presenting with DKA. Early recognition using antibody testing and C-peptide assessment facilitates timely insulin initiation and may reduce recurrent metabolic decompensation.

ANSWERS TO CLINICAL QUESTIONS

Question 1, d. Autoimmune T1DM is characterized by β-cell autoimmunity and severe insulin deficiency. The presence of islet autoantibodies, such as GAD, supports autoimmune destruction of pancreatic β-cells, whereas markedly reduced C-peptide levels indicate impaired endogenous insulin production. In contrast, patients with KPD may present with severe hyperglycemia and DKA but can recover β-cell function after metabolic stabilization. Therefore, the combination of positive GAD antibodies and profoundly reduced C-peptide most strongly supports autoimmune T1DM.^2,8

Question 2, c. The traditional view that T1DM occurs primarily in lean individuals has been substantially revised. Contemporary studies demonstrate that overweight and obesity are increasingly common among individuals with autoimmune diabetes, contributing to diagnostic uncertainty when distinguishing T1DM from T2DM in adults. Obesity may also exacerbate insulin resistance, creating a “double diabetes” phenotype that complicates management. Recognition of this evolving phenotype underscores the importance of biomarker-based classification using autoantibodies and C-peptide rather than relying on body habitus alone.³

DISCLOSURE STATEMENT

The planners and faculty for this activity have no relevant financial relationships to disclose. The authors report no funding. The patient consented to publication of this case report.