Diabetic ketoacidosis in T2DM with COVID-19 linked to severe insulin resistance, inflammation, not insulinopenia
Background
Diabetic ketoacidosis (DKA) is a serious complication of diabetes, traditionally associated with absolute insulin deficiency in Type 1 Diabetes Mellitus (T1DM). However, its presentation and underlying mechanisms in Type 2 Diabetes Mellitus (T2DM) patients, particularly during acute systemic stress like SARS-CoV-2 infection (COVID-19), are less understood. While diabetes is a known risk factor for severe COVID-19 outcomes, the specific drivers of DKA in this context, especially regarding β-cell function and insulin resistance, remain unclear. This gap in understanding hinders targeted management strategies for this high-risk population.
Study Design
A retrospective, single-center, case-control study was conducted at Ain Shams University Isolation Hospital from August 2021 to August 2022. The study enrolled 70 adult patients with confirmed T2DM and COVID-19, divided into two equal groups: 35 DKA cases and 35 non-DKA controls. Clinical, laboratory, and outcome data were extracted from medical records. Key parameters assessed included fasting C-peptide levels to evaluate β-cell function, and markers like D-dimer and HOMA-IR to quantify systemic inflammation and insulin resistance, respectively.
Results
Fasting C-peptide levels, a marker of β-cell function, showed no significant difference between the DKA and non-DKA groups (median difference: -0.06 ng/mL, 95% CI -0.28 to 0.16; p=0.363). This finding suggests that absolute insulin deficiency was not the primary cause of DKA in this cohort. The DKA group was significantly older (mean difference: 9.8 years, 95% CI 4.2 to 16.0; p=0.003) and had a longer median diabetes duration (median difference: 3.7 years, 95% CI 1.3 to 6.1; p=0.009). These patients also exhibited increased levels of inflammatory and stress markers, including D-dimer (mean difference: 0.21 ng/mL, 95% CI 0.05 to 0.37; p=0.020) and HOMA-IR (median difference: 1.93, 95% CI 0.45 to 3.60; p=0.012), indicating severe insulin resistance. Importantly, mortality was significantly higher in the DKA group.
Mortality was 22.9% in the DKA group compared to 0% in the non-DKA group, representing a risk difference of 22.9% (95% CI 8.4% to 37.4%; p=0.003).
Key Findings
- Fasting
C-peptidelevels did not differ significantly between DKA and non-DKA groups (p=0.363). - DKA patients were significantly older (mean difference: 9.8 years, p=0.003) and had longer diabetes duration (median difference: 3.7 years, p=0.009).
- DKA patients showed increased
D-dimer(mean difference: 0.21 ng/mL, p=0.020) andHOMA-IR(median difference: 1.93, p=0.012). - Mortality was significantly greater in the DKA group (22.9% vs. 0%, p=0.003).
Why It Matters
This study reframes the understanding of DKA in T2DM patients experiencing acute stress from COVID-19, shifting focus from absolute insulinopenia to severe insulin resistance and systemic inflammation. Clinicians should be highly vigilant for DKA in older T2DM patients with longer diabetes duration and COVID-19, even if their C-peptide levels appear adequate. This suggests that managing inflammation and insulin resistance, rather than solely focusing on insulin replacement, might be crucial in preventing or mitigating DKA in this specific population. The significantly increased mortality highlights the urgent need for aggressive monitoring and early intervention, potentially involving anti-inflammatory strategies or intensified insulin sensitization, to improve outcomes in these vulnerable patients. This insight could inform future protocols for managing T2DM patients during acute infections.
diabetic ketoacidosis
type 2 diabetes
covid-19
insulin resistance
inflammation
mortality