European Journal of Cardiovascular Medicine

Stroke is a major public health concern that leads to significant mortality and long-term disability worldwide. By the year 2020, it was projected to become the second leading cause of death globally. Most stroke survivors show some degree of recovery in their functional abilities; however, the extent, rate, and pattern of recovery vary widely among individuals.¹ Stroke severity and patient age are considered the most important predictors of outcome in the acute phase.² Other influencing factors include pre-stroke functional status, comorbidities, underlying etiology, and the vascular territory involved.³

Diabetes mellitus is an established risk factor for stroke. Studies have shown that individuals with diabetes tend to experience more severe neurological deficits and poorer functional recovery following stroke compared to non-diabetic individuals.⁴ Hyperglycemia, seen in nearly one-third of patients with acute ischemic stroke, has been linked to increased mortality regardless of age or initial stroke severity.⁵ However, limited research has examined the impact of pre-stroke glycemic control on clinical outcomes. A 2011 study involving 3,627 first-ever ischemic stroke patients reported that hemoglobin A1c (HbA1c) levels at admission were a significant independent predictor of neurological and functional outcomes.⁶

HbA1c reflects the average blood glucose concentration over the preceding 8–12 weeks, as glucose irreversibly binds to hemoglobin during the 120-day lifespan of red blood cells.⁷ In the Diabetes Control and Complications Trial, an HbA1c level of 6% corresponded to an average serum glucose of approximately 135 mg/dL, making it a reliable indicator of long-term glycemic status.⁷ Unlike fasting or postprandial glucose levels, HbA1c is not affected by short-term variations due to meals, physical activity, or medication use.⁸ It also serves as an independent predictor of diabetic complications, with the risk of macrovascular events—such as cardiovascular death, myocardial infarction, or stroke—being significantly lower when HbA1c levels are maintained below 7%.⁸

Approximately 30–40% of patients presenting with acute ischemic stroke have hyperglycemia, which may result from either pre-existing diabetes mellitus or an acute stress response. Type 2 diabetes, which affects over 220 million people globally, is rising rapidly across Asian populations and confers a two- to six-fold higher risk of ischemic stroke. Persistent hyperglycemia during acute stroke is associated with unfavorable outcomes, prompting growing interest in optimizing glycemic management in these patients.⁹ ¹⁰

HbA1c levels are widely used as a therapeutic target for preventing cardiovascular complications in diabetic patients.¹¹ The American Diabetes Association recommends an HbA1c threshold of ≥6.5% for the diagnosis of diabetes, based on its strong correlation with microvascular complications. Compared with fasting glucose, HbA1c offers several advantages—it can be measured in a non-fasting state, has greater reproducibility, and remains stable under varied physiological conditions. However, its limitation lies in the lack of global standardization, which can lead to variations in results between laboratories and countries.¹²

Despite the rising burden of diabetes and ischemic stroke among Asian populations—and the emerging recognition of HbA1c as a predictor of cardiovascular risk—data exploring the association between HbA1c levels and ischemic stroke risk in Indian patients remain limited. Hence, the present study aimed to evaluate the relationship between HbA1c levels and the risk of ischemic stroke among Indian patients without known diabetes.

In recent years, rapid socioeconomic and lifestyle transitions in Asian countries, including India, have contributed to an increased incidence of cardiovascular diseases, particularly stroke.¹³ ¹⁴ The prevalence of diabetes and prediabetes in the region has nearly doubled over the past decade.¹⁵–¹⁷ Both conditions are associated with a higher risk of ischemic stroke and poorer recovery outcomes.¹⁸ ¹⁹ Given these trends, the predictive role of glycated hemoglobin (HbA1c) in identifying individuals at risk of ischemic stroke has become an important focus of current research.²⁰ ²¹

Aims and Objectives

1. To analyze the role of HbA1c in predicting the risk of ischemic stroke among the Indian population without diagnosed diabetes.
2. To compare HbA1c levels between ischemic stroke patients with and without diabetes.

This single-center, descriptive, case–control study was conducted among inpatients admitted to the Department of General Medicine, PGIMER & Capital Hospital, Bhubaneswar, Odisha, over a period of six months, from October 2024 to March 2025. All patients aged 18 years and above, of either gender, were eligible for inclusion in the study.

Inclusion Criteria

·         Patients diagnosed with acute ischemic stroke

·         Patients with Type 2 Diabetes Mellitus

Exclusion Criteria

·         Intracerebral hemorrhage

·         Space-occupying lesions

·         Subarachnoid hemorrhage

·         Cerebral venous thrombosis

·         Transient ischemic attacks

·         Recurrent cerebrovascular events

A semi-structured proforma was designed to collect information on sociodemographic characteristics, detailed medical history, clinical examination findings, and results of relevant investigations conducted at PGIMER & Capital Hospital. The medical history emphasized ischemic stroke symptoms and risk factors, including glycemic status at the time of admission.

Laboratory parameters such as HbA1c, fasting and random blood glucose, lipid profile, and blood pressure (BP) were recorded for all participants. HbA1c was measured at admission, corresponding to the time of stroke onset. Height and weight were measured using standard techniques, and Body Mass Index (BMI) was calculated as weight (kg) divided by height squared (m²). Smoking history was also documented.

A total of 240 participants were enrolled—comprising 120 diabetic and 120 non-diabetic ischemic stroke patients—who met the inclusion criteria and provided written informed consent. All patients presented with focal neurological symptoms suggestive of stroke and were evaluated within one week of symptom onset. The diagnosis of ischemic stroke was made by the attending Medicine consultant based on clinical history, neurological examination, and confirmation by neuroimaging (CT scan and/or MRI of the brain).

Patients with uncertain or atypical diagnostic features were excluded from the analysis.

Routine laboratory investigations included: Complete blood count (CBC), Liver function tests (LFT), Renal function tests (RFT), Serum electrolytes, ECG and chest X-ray, Fasting and random blood glucose, Urine routine examination, Echocardiography, Coagulation profile, HbA1c, Lipid profile

The lipid profile consisted of measurements of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TGL-C). Diagnosis of diabetes mellitus was made according to the American Diabetes Association (ADA, 2011) criteria.

Plasma venous glucose levels were measured within 24 hours of admission for all participants. HbA1c estimation was performed to differentiate between stress hyperglycemia and chronic hyperglycemia. Patients with elevated blood glucose but normal HbA1c were classified as having stress hyperglycemia, while those with elevated HbA1c were identified as newly diagnosed diabetics.

Accordingly, participants were categorized into four groups:

1.       Euglycemic individuals: No history of diabetes, normal glucose and HbA1c levels

2.       Stress hyperglycemia: No history of diabetes, elevated glucose at admission, normal HbA1c

3.       Newly diagnosed diabetics: No history of diabetes, elevated HbA1c levels

4.       Known diabetics: Previously diagnosed and on treatment for diabetes

Data were analyzed using R software (version 4.3.2). Descriptive statistics were presented as mean ± standard deviation (SD) for continuous variables and frequencies with percentages for categorical variables. Comparisons between the diabetic and non-diabetic ischemic stroke groups were made for variables including age, gender, BMI, smoking status, fasting blood sugar (FBS), HbA1c, HDL-C, LDL-C, TGL-C, TC, systolic blood pressure (SBP), and diastolic blood pressure (DBP). A p-value of <0.05 was considered statistically significant.

A total of 240 patients admitted with acute ischemic stroke were included in the study. Among them, 120 (50%) were known diabetics and 120 (50%) were non-diabetic individuals. The mean age of the study population was 56.5 ± 2.4 years, with a slightly higher proportion of males (57.5%) compared to females (42.5%).

The age distribution of the study participants is presented in Table I. The majority of patients were between 51 and 70 years of age, accounting for approximately 58% of the total study population. The largest subgroup was observed in the 61–70 years age bracket (30%), followed by 51–60 years (27.9%). Only 4.2% of patients were below 40 years of age. Overall, diabetic stroke patients tended to be slightly older than non-diabetic individuals, indicating an age-related increase in the prevalence of both diabetes and ischemic stroke.

Table I: Age-wise Distribution of Patients (n = 240)

The classification of patients based on their glycaemic status is shown in Table II. Among the total participants, 50% were known diabetics, while 5.4% were newly diagnosed with diabetes at the time of admission. Stress hyperglycemia was observed in 12.9% of patients, and 31.7% were euglycemic.

These findings suggest that nearly two-thirds of ischemic stroke patients presented with either pre-existing diabetes or some form of hyperglycemia, highlighting the close association between altered glycemic status and ischemic stroke occurrence.

Table II: Classification of Patients According to Glycaemic Status (n = 240)

A comparative analysis between diabetic and non-diabetic ischemic stroke patients is presented in Table III. The mean age of diabetic patients (58.9 ± 2.1 years) was slightly higher than that of non-diabetic individuals (54.1 ± 1.8 years). Although the difference was not statistically significant (p = 0.56), it suggests that stroke occurs at a relatively older age among diabetics. The mean HbA1c level was significantly higher in diabetic patients (7.85 ± 2.30) compared to non-diabetic individuals (6.25 ± 2.10), with a p-value < 0.01, indicating poor long-term glycemic control among diabetics.

Other biochemical and physiological parameters—such as fasting blood sugar, lipid profile (HDL-C, LDL-C, TGL-C, TC), and blood pressure (SBP and DBP)—showed higher mean values in diabetics than non-diabetics, though the differences were not statistically significant (p > 0.05).

Table III: Comparison between Individuals With and Without Diabetes Among Stroke Patients (n = 240)

These findings highlight the necessity of stringent glycaemic control and routine HbA1c monitoring to reduce the risk and severity of ischemic stroke, especially among diabetic patients.

Diabetes mellitus is a chronic metabolic disorder that has reached epidemic proportions globally, with a particularly rapid rise in prevalence across developing countries, including India. The disease exhibits considerable variability in its distribution, diagnostic thresholds, and associations with cardiovascular and cerebrovascular complications.

Prediabetes has also emerged as a significant independent risk factor for stroke, although many patients who experience an acute stroke are unaware of their prediabetic state. Measurement of glycated hemoglobin (HbA1c) has therefore become an accepted and practical method for identifying individuals with undiagnosed diabetes or prediabetes. HbA1c reflects the mean blood glucose levels over the preceding 8–12 weeks and serves as a reliable indicator not only for diagnosing diabetes but also for assessing long-term glycemic control and predicting vascular outcomes. Well-maintained and stable glucose levels substantially reduce the risk of cardiovascular and cerebrovascular complications.²²

In the present study conducted at PGIMER & Capital Hospital, Bhubaneswar, patients with ischemic stroke and diabetes exhibited significantly higher mean HbA1c levels (7.85 ± 2.30%) compared to non-diabetic stroke patients (6.25 ± 2.10%, p < 0.01). This finding underscores the strong association between poor glycemic control and ischemic stroke occurrence and aligns with prior research suggesting that elevated HbA1c is a key determinant of vascular injury.

Our findings are in agreement with those of Myint et al., who studied over 10,000 individuals and reported that the relative risk for stroke increased progressively with higher HbA1c levels—0.7, 0.8, and 2.8 for HbA1c categories of 5–5.4%, 5.5–6.9%, and ≥7%, respectively, compared with those having HbA1c < 5%.²⁰ ²¹ Similarly, a Mexican study demonstrated that both diabetes and prediabetes were highly prevalent among hospitalized patients with ischemic stroke, recommending routine HbA1c screening for all stroke admissions to identify undiagnosed cases. ²¹

The current study further observed that diabetic patients tended to be older and had higher mean values of fasting blood sugar, lipid parameters, and blood pressure compared to non-diabetics, although these differences did not reach statistical significance. This trend suggests that chronic hyperglycemia contributes cumulatively to vascular damage, thereby predisposing individuals to ischemic events. The significant rise in HbA1c levels among diabetic stroke patients emphasizes the need for intensive glycemic control as part of stroke prevention strategies.

Limitations

The study had certain limitations. The diagnosis of diabetes was based on medical history, previous health records, fasting glucose, and HbA1c levels; however, an oral glucose tolerance test (OGTT) was not performed. Although recent guidelines consider fasting glucose and HbA1c sufficient for diagnosing diabetes, some cases of impaired glucose tolerance might have been missed. Additionally, this was a single-center, short-duration study, which may limit the generalizability of the findings. Larger, multicentric studies with longitudinal follow-up would provide stronger evidence of the relationship between HbA1c and ischemic stroke outcomes.

The present study demonstrates a clear association between glycemic status and ischemic stroke in both diabetic and non-diabetic individuals. Elevated HbA1c levels were significantly correlated with stroke occurrence, highlighting poor glycemic control as a major contributing factor. Hyperglycemia observed in non-diabetic patients likely reflects an acute stress response, which may worsen neurological injury and influence prognosis.

Effective monitoring and management of blood glucose—both in diabetic and non-diabetic patients—should therefore be an integral part of acute stroke care. Routine HbA1c testing for all stroke admissions can help identify undiagnosed diabetes or prediabetes, allowing for early intervention and improved long-term outcomes.

1.       Wolfe CD. The impact of stroke. Br Med Bull. 2000;56:275–286.

2.       Adams HP Jr, Davis PH, Leira EC, Chang KC, Bendixen BH, Clarke WR, et al. Baseline NIH Stroke Scale score strongly predicts outcome after stroke: a report of the Trial of Org 10172 in Acute Stroke Treatment (TOAST). Neurology. 1999;53:126–131.

3.       Frankel MR, Morgenstern LB, Kwiatkowski T, Lu M, Tilley BC, Broderick JP, et al. Predicting prognosis after stroke: a placebo group analysis from the NINDS rt-PA Stroke Trial. Neurology. 2000;55:952–959.

4.       Muir KW, Weir CJ, Murray GD, Povey C, Lees KR. Comparison of neurological scales and scoring systems for acute stroke prognosis. Stroke. 1996;27:1817–1820.

5.       Andersen KK, Andersen ZJ, Olsen TS. Predictors of early and late case fatality in a nationwide Danish study of 26,818 patients with first-ever ischemic stroke. Stroke. 2011;42:2806–2812.

6.       Knoflach M, Matosevic B, Rucker M, Furtner M, Mair A, Wille G, et al. Functional recovery after ischemic stroke: a matter of age—data from the Austrian Stroke Unit Registry. Neurology. 2012;78:279–285.

7.       Petty GW, Brown RD Jr, Whisnant JP, Sicks JD, O'Fallon WM, Wiebers DO. Ischemic stroke subtypes: a population-based study of functional outcome, survival, and recurrence. Stroke. 2000;31:1062–1068.

8.       Nedeltchev K, der Maur TA, Georgiadis D, Arnold M, Caso V, Mattle HP, et al. Ischemic stroke in young adults: predictors of outcome and recurrence. J Neurol Neurosurg Psychiatry. 2005;76:191–195.

9.       Ergul A, Li W, Elgebaly MM, Bruno A, Fagan SC. Hyperglycemia, diabetes and stroke: focus on the cerebrovasculature. Vascul Pharmacol. 2009;51:44–49.

10.    Ramachandran A, Ma RC, Snehalatha C. Diabetes in Asia. Lancet. 2010;375:408–418.

11.    Tahara Y, Shima K. Kinetics of HbA1c, glycated albumin, and fructosamine and analysis of their weight functions against preceding plasma glucose levels. Diabetes Care. 1995;18:440–447.

12.    American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2011;34(Suppl 1):S62–S69.

13.    Burke TA, Venketasubramanian RN. The epidemiology of stroke in the East Asian region: a literature-based review. Int J Stroke. 2006;1:208–215.

14.    Nomani AZ, Nabi S, Ahmed S, et al. High HbA1c is associated with higher risk of ischemic stroke in Pakistani population without diabetes. Stroke Vasc Neurol. 2016;1:e000018.

15.    Qureshi MS, Iqbal M, Nomani AZ. Rapidly increasing prevalence and associations of diabetes mellitus in a rural community of Pakistan. J Diabetol. 2014;3:3. Available from: http://www.journalofdiabetology.org

16.    de Vegt F, Dekker JM, Ruhé HG, et al. Hyperglycaemia is associated with all-cause and cardiovascular mortality in the Hoorn population: the Hoorn Study. Diabetologia. 1999;42:926–933.

17.    Selvin E, Coresh J, Shahar E, et al. Glycaemia (haemoglobin A1c) and incident ischemic stroke: the Atherosclerosis Risk in Communities (ARIC) Study. Lancet Neurol. 2005;4:821–826.

18.    Hu GC, Hsieh SF, Chen YM, et al. Relationship of initial glucose level and all-cause death in patients with ischemic stroke: the roles of diabetes mellitus and glycated hemoglobin level. Eur J Neurol. 2012;19:884–891.

19.    Pradhan AD, Rifai N, Buring JE, et al. Hemoglobin A1c predicts diabetes but not cardiovascular disease in nondiabetic women. Am J Med. 2007;120:720–727.

20.    Park S, Barrett-Connor E, Wingard DL, et al. GHb is a better predictor of cardiovascular disease than fasting or post-challenge plasma glucose in women without diabetes: The Rancho Bernardo Study. Diabetes Care. 1996;19:450–456.

21.    Myint PK, Sinha S, Wareham NJ, et al. Glycated hemoglobin and risk of stroke in people without known diabetes in the EPIC-Norfolk prospective population study: a threshold relationship? Stroke. 2007;38:271–275.

22.    Huisa BN, Roy G, Kawano J, et al. Glycosylated hemoglobin for diagnosis of prediabetes in acute ischemic stroke patients. J Stroke Cerebrovasc Dis. 2013;22:e564–e567.