Young-Onset Type 2 Diabetes and Its Association with Variant Angina in an Adolescent

Introduction

Amidst the global demographic shift toward an aging population, the management of chronic conditions like diabetes, hypertension, coronary heart disease, angina pectoris, and heart failure has grown in significance. However, a concerning trend has emerged: chronic diseases are now disproportionately impacting younger populations. Among these, cardiac autonomic dysfunction is a well-documented consequence of diabetes. Specifically, diabetes-associated cardiovascular autonomic neuropathy (CAN) damages the autonomic nerve fibers that regulate the heart and blood vessels [1]. Moreover, the autonomic nervous system has been implicated in the etiology of vasospastic angina (VSA) [2]. Although cases of young individuals with both diabetes and angina are infrequent, this report describes a case of early-onset type 2 diabetes mellitus (T2DM) accompanied by variant angina. Within this context, we explore the relationship between these 2 conditions, their diagnostic considerations, and therapeutic approaches, drawing upon pertinent scholarly literature for insights.

Case Report

Our patient was a 25-year-old Han Chinese man who had no history of hypertension or heart disease and denied smoking. He had been aware of elevated blood glucose levels for more than 5 years, with a family history of hereditary diabetes. He had not monitored his blood glucose regularly or received standardized treatment. Nine hours before going to the hospital, he had intermittent chest tightness in the anterior cardiac area, without any obvious cause. Each episode lasted from several seconds to a few minutes and was accompanied by radiating pain in the left back. The pain was unrelated to emotional stress or physical activity and was not associated with dizziness, headache, vision problems, syncope, diaphoresis, diarrhea, or abdominal pain. He presented to the emergency department for evaluation. The first electrocardiogram (ECG) after admission showed sinus tachycardia with inverted T waves in leads II, III, and aVF (Figure 1). Cardiac markers, including CK-MB, myoglobin (MYO), troponin T (TnT), D-dimer (DD), and NT-proBNP, were normal. The initial diagnosis was: (1) chest pain (possible coronary heart disease or myocarditis); and (2) type 2 diabetes to be confirmed. In the emergency department he received aspirin 300 mg, clopidogrel 300 mg, antiplatelet, atorvastatin 10 mg, metoprolol succinate 47.5 mg to control ventricular rate, and isosorbide mononitrate 10 mg to relieve chest pain. Two hours after admission, he had increased chest pain with radiation from the left shoulder and back. Secondary review of a 12-lead electrocardiogram (ECG) revealed ST-segment elevation in leads I, II, aVL and V2–V6 (Figure 2), showing significant dynamic changes compared to previous recordings. The follow-up 12-lead electrocardiogram (ECG) showed sinus tachycardia with inverted T waves in leads II, III, and aVF (Figure 3). Further testing for cardiac biomarkers, including creatine kinase-MB (CK-MB), myoglobin (MYO), and troponin T (TnT), were negative. The persistent chest pain, unrelieved by initial interventions, raised concern for acute myocardial infarction. Emergency coronary angiography was performed, revealing no stenosis in the left main coronary artery; no significant stenosis in the left anterior descending (LAD) artery, but a myocardial bridge in the mid-portion of the LAD with a 40% compression during systole; no significant stenosis in the left circumflex (LCX) artery; no significant stenosis in the right coronary artery (RCA); with TIMI flow grade 3 in both the left and right coronary arteries (Figure 4). After the procedure, the chest pain gradually resolved. Further tests confirmed a diagnosis of type 2 diabetes, with an HbA1c level of 9.6%. Oral glucose tolerance tests (OGTT) showed fasting glucose of 9.94 mmol/L, 1-hour postprandial glucose of 19.78 mmol/L, and 2-hour postprandial glucose of 22.79 mmol/L. Insulin and C-peptide release testing showed a delayed insulin peak, confirming insulin resistance. The patient was diagnosed with T2DM and treated with acarbose, metformin, and empagliflozin. A 24-hour Holter ECG revealed sinus rhythm, with an average heart rate of 88 beats/min (slightly elevated), intermittent ST-segment elevation, ST-T-wave changes, and reduced heart rate variability (HRV), indicative of autonomic nervous dysfunction. Cardiac MRI showed no significant abnormalities in left ventricular morphology and function, but some segments showed decreased extracellular volume (ECV) and delayed peak time in myocardial perfusion imaging (Figure 5), possibly indicating heart damage. Transthoracic echocardiography showed that ejection fraction 55%, ventricular size, septal thickness, and wall motion were normal, without significant abnormalities. The final clinical diagnoses were variant angina (VA) and type 2 diabetes mellitus. The patient was treated with acarbose 50 mg once a day, metformin 500 mg once a day, aspirin 100 mg once a day, atorvastatin 10 mg once a day to stabilize plaque, metoprolol succinate 47.5 mg once a day, and Nicodil 5 mg once a day, which relieved the chest pain. After 6 days of hospitalization, he was discharged from the hospital after re-examination of myocardial enzyme spectra and electrocardiograms.

Discussion

Type 2 diabetes mellitus (T2DM) diagnosed before the age of 25 is categorized as young-onset type 2 diabetes (YO-T2D) [3]. This form of diabetes is gaining prevalence, especially in China, India, and the United States [4]. YO-T2D is distinguished by insulin resistance in key tissues – skeletal muscle, liver, and adipose tissue – along with impaired β-cell function and a relative lack of insulin [5]. T2DM is linked to a spectrum of complications, including diabetic nephropathy, retinopathy, neuropathy, coronary heart disease (CHD), and disorders of the autonomic nervous system. The autonomic nervous system is pivotal for regulating heart rate and vascular function in both health and disease states. Its dysfunction in diabetes is common and is correlated with a heightened risk of cardiovascular events [6]. Heart rate variability (HRV), a standard metric for assessing autonomic function, often reveals a decrease in T2DM patients [7]. Autonomic dysfunction increases the risk of variant angina. The risk of neuropathy decreases by 5% for each additional year of age at diabetes diagnosis [8]. Identifying young-onset type 2 diabetes (YO-T2D) at an early stage is of paramount importance. This risk is especially pronounced among young people with a family history of diabetes, underscoring the importance of early and proactive screening within healthcare settings. Early intervention is crucial to slow the progression of diabetic autonomic neuropathy and coronary artery atherosclerosis, thereby potentially reducing the occurrence of variant angina and preventing its complications, such as myocardial infarction. The U.S. Food and Drug Administration (FDA) has approved the use of metformin and insulin for treating YO-T2D, with the recent inclusion of glucagon-like peptide-1 (GLP-1) receptor agonists in the therapeutic arsenal [9]. Beyond pharmacological interventions, dietary management and weight reduction are also key components in YO-T2D control [10]. These strategies, when combined, form a multifaceted approach to managing YO-T2D and mitigating its long-term cardiovascular complications.

Variant angina, alternatively termed vasospastic angina (VSA), is characterized by chest discomfort stemming from myocardial ischemia caused by spasming of the epicardial coronary arteries, which precipitates a sudden constriction of the arterial lumen, leading to a reduced supply of blood and oxygen to the heart muscle. It is difficult to distinguish between variable angina pectoris and early myocardial infarction in clinical practice, because markers of myocardial damage in early myocardial infarction can also be normal. Earlier coronary angiography and timely and effective intervention can benefit these patients. The etiology of coronary artery spasm is not fully elucidated, yet research suggests that autonomic dysregulation, specifically a disruption in the equilibrium between the sympathetic and parasympathetic nervous systems, contributes to the occurrence of nocturnal variant angina (VSA) episodes [11]. Concurrent with these episodes, patients often exhibit ischemic ST-segment alterations on electrocardiograms (ECGs), which typically return to normal after the symptoms have resolved. When VSA episodes are not evident on the ECG, diagnostic confirmation of coronary artery spasm can be facilitated through pharmacological provocation tests. These tests, which may involve the use of ergonovine, acetylcholine, or hyperventilation, are conducted in a catheterization laboratory [12], but the safety of this method has been controversial. Some scholars have proposed use of noninvasive testing, which involves intravenous administration of ergonovine maleate at 5-minute intervals, each followed by a 12-lead ECG and continuous monitoring of left ventricular wall motion. A positive test result is transient ST-segment elevation or depression exceeding 0.1 mV (as per ECG standards), occurring 0.08 seconds after the J point, or by the identification of reversible regional wall motion abnormalities (RWMAs) through 2D echocardiography. When the result is positive, immediate administration of 0.25 mg of intravenous nitroglycerin and sublingual nitroglycerin can mitigate procedure-related risks [13]. In clinical practice, calcium channel blockers (CCBs) are recognized as the most effective pharmacological therapy for variant angina (VSA). This includes both dihydropyridine drugs, such as nifedipine, amlodipine, and felodipine, and non-dihydropyridine drugs, such as verapamil and diltiazem. Nicorandil also demonstrates efficacy in treating and preventing coronary artery spasm. Our patient developed chest pain after receiving Nicodil, and will continue to be followed up. Beyond pharmacological interventions, lifestyle adjustments, such as quitting smoking and managing lipid levels, blood pressure, and blood glucose, can significantly reduce the frequency of VSA episodes [14].

Timeline: Symptoms appeared 9 hours before admission. Coronary angiography was performed 2 hours after admission to confirm the diagnosis and provide treatment. After 6 days of hospitalization, relevant auxiliary examinations were completed and the patient was then discharged.

Compliance and discomfort of the intervention: symptom relief was not obvious in the initial intervention patients, but gradually improved after a clear diagnosis in patients with oral administration of Nicorandil.

Conclusions

There are 2 lessons to be learned from this report. First, it is critical for families with a history of diabetes to have children of sick parents or relatives get to the hospital in a timely manner to receive appropriate diagnostic tests. This proactive approach is essential for early detection of diabetes, which can be hereditary. Upon confirmation of the disease, immediate medical intervention is advised to mitigate the risk of serious cardiovascular issues such as autonomic dysfunction related to vascular spastic angina pectoris. Early treatment can also slow the progression of other chronic complications associated with diabetes, including nephropathy, retinopathy, and peripheral neuropathy. Second, it is difficult to distinguish between variable angina pectoris and early acute myocardial infarction, so coronary angiography should be performed as early as possible to avoid delayed treatment.