Introduction
Diabetes mellitus (DM) is a non-communicable chronic disease with high prevalence as well as among the main health and social issues worldwide [1–3]. The data discussed in the article by the International Diabetes Federation (IDF) indicates that in 2021, there were 537 million patients with this disease, and by 2045, this figure will reach 783 million [4, 5]. Based on International epidemiological research, the number of patients having DM continues to increase steadily and cardiovascular disease has been one of the major causes of deaths among diabetics. More specifically, risks of death in these types of patients are especially high due to such complications as ischaemic heart disease, heart failure and stroke [6, 7]. It is also demonstrated that the risk of coronary heart disease, stroke, and heart failure among patients with DM is 2–4 times more than it is in the general population [8]. Conventional methods of evaluating glycaemic control in DM rely upon the determination of blood glucose level of the average level of glycated haemoglobin (HbA1c) as a measurement of the average level in 8–12 weeks, and is commonly used as a standardised measure of average level of glycaemic control [9]. HbA1c does not however capture the day/night changes in glycaemia, fails to capture the frequency, duration and degree of episodes of hypoglycaemia and hyperglycaemia, nor does it take care of glycaemic variability which is a parameter that defines the changes in glucose levels over time in relation to the day [10, 11]. It has been demonstrated that glycaemic variability bears an independent pathophysiological meaning not dependant on the level of HbA1c, and might be linked with the risk of vascular complications in diabetic patients [12, 13]. Specifically, great glycaemia variations are linked to augmented oxidative stress, pro-inflammatory signalling pathway mobilization, and endothelial incapacitation -processes that are involved in the development of atherosclerosis, coupled with the incidence of cardiovascular events [14, 15]. Clinical and experimental evidence evidences that augmented glycaemic variability is related to indicators of oxidative harm, augmented endothelial cell adhesion molecule expression, and disturbed vascular responsiveness heightens the vulnerability of patients with diabetes to macro- and microvascular issues [16].
Nocturnal hyperglycaemia is given particular consideration because it is usually asymptomatic, and it is not taken seriously when glucose is self-managed through the conventional method. The causes of nocturnal glycemic profile disorientation can be the dawn effect, inadequate basal insulin treatment, insulin resistance, or false choice of hypoglycemic treatment. In its turn, nocturnal hyperglycaemia is granted with stimulation of sympathetic nervous system, circadian rhythms, and adverse shifts in the daily blood pressure pattern [17, 18].
Continuous glucose monitoring (CGM) intentions offer much greater opportunities in the evaluation of glycaemic control than conventional approaches as the measures provide the possibility of constant monitoring of glucose dynamics and delivery of dynamic data on such measures as: time in range (TIR), time above/below target range, and glycaemic variability (GV). The significance of this is that the measures provided by CGM show the changes in glycaemia, which are not necessarily evident in spot measures or of HbA1c and are linked to the occurrence of vascular complications in DM [19, 20]. Moreover, we can use CGM data to examine how glycaemic variability is related to a progression of atherosclerosis and macro and microvascular complications, such as the endothelial impairment such as carotid intima-media thickness and endothelial functional changes. These parameters give a more in-depth insight into the effects of the daily glucose variability and night-time glucose variability on the health of the cardiovascular system and make it possible to stratify the cardiovascular risks in DM patients and improve the efficiency of the treatment process and the threat of severe complications [21, 22, 23].
The aim of the study: to assess the role of nocturnal hyperglycaemia and glycaemic variability in the development of cardiovascular risk in patients with type 2 DM.
Materials and methods
The research was carried out in the Ternopil Regional Hospital, which was selected as the representative sample to gather the patients and further analyze and interpret the data. There were 50 patients with type 2 DM aged between 40 to 75 years who had over one year of duration of the disease in the study. Every participant was put on stable hypoglycaemic treatment of not less than 3 months before being included in the study. Inclusion criteria included a confirmed diagnosis of type 2 DM and the capability of patients to do continuous glucose monitoring of a minimum of 10 days. The patients were not allowed in the study who had acute cardiovascular events recently, under 6 months, decompensated comorbidities, or acute infectious processes.
The analysis was based on the average night-time glycaemia (22:00 to 06:00) and established measures of parameters of Night-time TIR (time in the target glucose range (3.9–10.0 mmol/L)) and Night-time TAR (time above target range) and the glycaemic variability, measured as standard deviation (SD), coefficient of variation (CV) and mean amplitude of glycaemic excursions (MAGE).
Blood pressure, body mass index, lipid profile, glycated haemoglobin (HbA1c) level, duration of DM, and the existence of the concomitant cardiovascular diseases, specifically arterial hypertension and dyslipidaemia, were measured in all patients. This enabled us to determine the association between glycaemia levels, variability as well as their association with key cardiovascular risk factors among patients.
The data were processed using descriptive statistics, correlation analysis and multiple regression. A p-value below 0.05 was used to determine statistical significance which enabled us to identify significant associations between glycaemic indicators and cardiovascular risks.
Results and discussion
In this study, 50 patients with type 2 DM were analyzed according to the set inclusion criteria and completed the course of CGM. The average age of the study participants was 59.8±8.6 years with a range of 41–74 years. Men comprised 48 per cent. of the total patients (n=24), women 52 per cent. (n=26). The average length of DM was 9.1±4.3 years.
Hypertension of the arteries was identified in 76 percent (n=38) and dyslipidaemia in 68 percent (n=34). The mean body mass index (BMI) was 31.2±4.1 kg/m 2 which was grade I-II obese to most of the patients. The average level of glycated haemoglobin (HbA1c) was 7.9±1.1% at the inclusion of the study, which poses poor glycaemic control in a good percentage of the sample.
The continuous glucose monitoring data were analysed and revealed night-time glycaemic profile was not favourable in a majority of patients. Mean night (22:00–06:00) glucose level was 9.6±1.8 mmol/L. The mean Night-time TIR (time within the target range of 3.9–10.0 mmol/L) was 58.4±16.9%. Simultaneously, Night-time TIR in 62% of the patients (n=31) was lower than the recommended value of 70 percent, which demonstrates that nocturnal hyperglycaemia was very common in this group. The time proportion out of range above the target (Night-time TAR) was 36.7±18.2%. Nocturnal hypoglycaemia was uncommon and did not have a clinically significant effect on the total glycaemic profile.
There was increased glycaemic variability in the sample of patients. The SD of glucose (mean) was 2.3±0.6 mmol/L, the CV (34.7±6.8) was 34.7±6.8 and the MAGE was 4.9±1.4 mmol/L. The CV value was found to be above 36% (percentile of 58) in 29 patients (n=29), this is a clinically significant value of glycemic variability. Even in the patients with rather acceptable levels of HbA1c, high MAGE values (>5.0 mmol/L) were shown in 46% of the subjects, which means that there were pronounced glycaemic variability despite apparently acceptable levels of HbA1c.
The patients were separated into two groups according to the level of Night-time TIR: group 1: Night-time TIR ≥70% (n=19); group 2: Night-time TIR <70% (n=31).
Patients whose Night-time TIR was less than 70 percent, boasted of a much higher systolic blood pressure (142±12 mmHg vs. 132±10 mmHg, p<0.01) and a poorer lipid profile, especially with regard to low-density lipoproteins (LDL) and triglycerides. Moreover, glycaemic variability in the group with low Night-time TIR was also much greater: CV and MAGE were considerably greater than in patients with a sufficient control of the night-time glycaemic level (p<0.05 with both these measures).
The results of the correlation analysis have shown that there is significant negative correlation between Night-time TIR and systolic blood pressure (r=–0.42; p=0.003) which means that there is a correlation between nocturnal hyperglycaemia and an unfavourable haemodynamic profile. The glucose CVand the integral cardiovascular risk were also positively correlated with each other (r=0.39; p=0.006), and so was the case with MAGE and triglyceride levels (r=0.34; p=0.01).
Multiple regression analysis, performed after adjusting for age, sex, HbA1c level, DM duration, and the presence of arterial hypertension, showed that Night-time TIR <70% (β=–0.31; p=0.01), CV >36% (β=0.28; p=0.02), and MAGE >5.0 mmol/L (β=0.25; p=0.03) are independent predictors of increased cardiovascular risk.
Findings validate that night-time hyperglycaemia and glycaemic variability are essential in developing cardiovascular risk among type 2 DM patients, irrespective of conventional measures of glycaemic management, especially temperatures of HbA1c. This paper proves that night-time glycaemic perturbation is a widespread occurrence and relates with unfavourable haemodynamic and metabolic phenotypes.
The pathophysiological processes of the adverse effect of nocturnal hyperglycaemia on the cardiovascular system are complex. High glucose levels in the night are linked to symptoms such as the activation of sympathetic nervous system, abnormalities in the rhythms of secretion of circadian hormones, and alterations in the daily curve of blood pressure. This, on the other hand, leads to the emergence of the so-called non-dipper phenomenon (or reverse-dipper) that is a predictor of cardiovascular events on its own.
It is also essential that the independent association between glycaemic variability (CV, MAGE) and cardiovascular risk found in our study. Abnormal glycaemic variability is a marker of poor metabolic regulation and is always linked with more intense oxidative stress relative to stable hyperglycaemia. Variations in glucose levels lead to the release of inflammatory cascades, endothelial injury and speed-up of atherosclerosis.
It is interesting to note that in the case of multiple regression analysis, night-time TIR, CV and MAGE were found to have independent prognostic value even after the factor HbA1c, duration of DM and presence of hypertension was controlled. This points out the weakness of the reliance of HbA1c as the only glycaemic control marker and explains why CGM should be expanded in clinical use.
Our study findings are in line with other international research findings that indicate time in range (TIR) is a stronger predictor of the risk of micro- and macrovascular complication as compared to HbA1c. Simultaneously, the earlier literature has concentrated on total daily TIR, whereas our information also highlights the night-time as the most vulnerable time slot.
The obtained results are highly practical in a clinical perspective. They point out that, one of the potential directions that can be taken by the prevention of cardiovascular complications in patients with type 2 DM is the optimisation of night-time glycaemic control. This can entail the correction of the basal insulin treatment, the application of the long-acting medication, and the customisation of the therapeutic plans with the CGM indicators.
Nocturnal hyperglycaemia and glycaemic variability should not be in terms of quality indicators of glycaemic control, but should be discussed as indicators of cardiovascular risk, which needs to be actively identified and managed in everyday clinical practice.
Conclusion
Nocturnal hyperglycaemia is a frequent and clinically important event in patients with type 2 DM. Independent prognostic variables of cardiovascular risk are night-time TIR and glycaemic variability indicators. Night CGM indicators should be analyzed as part of the regular clinical practice to enhance glycaemic control and avoid cardiovascular problems.
References
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Оцінка впливу нічної гіперглікемії та варіабельності глікемії на серцево-судинний ризик у пацієнтів із цукровим діабетом 2-го типу. Роль безперервного моніторингу глюкози
Тернопільський національний медичний університет імені І.Я. Горбачевського, Тернопіль, Україна
Резюме. Поширеність цукрового діабету (ЦД) є однією з важливих медико-соціальних проблем світу, а серцево-судинні захворювання є основною причиною смертності пацієнтів із ЦД. Збільшення кількості пацієнтів із ЦД 2-го типу та необхідність розуміння кореляції глікемічного контролю та серцево-судинних ускладнень впливають на розробку нових практик оцінки ризику таких пацієнтів. Звичайна методика визначення глікемічного контролю за допомогою рівня глікованого гемоглобіну (HbA1c) не враховує ключових моментів, як-от зміни рівня глюкози протягом дня, які потенційно можуть підвищити ризик серцево-судинних проблем. Дані свідчать про те, що глікемічна варіабельність, тобто наявність нічної варіабельності рівня глюкози в крові, чинить значний патофізіологічний вплив на прогресування атеросклерозу та інших станів судинних структур. Мета: оцінити, як нічна гіперглікемія та глікемічна варіабельність зумовлюють серцево-судинний ризик у пацієнтів із ЦД 2-го типу. Об’єкт і методи дослідження. Дослідження проведено в Тернопільській обласній лікарні за участю 50 пацієнтів із ЦД 2-го типу віком 40–75 років. Кожен пацієнт перебував під безперервним моніторингом рівня глюкози (continuous glucose monitoring — CGM) протягом щонайменше 10 днів. Нічні глікемічні параметри, проаналізовані за допомогою CGM, включали час перебування в діапазоні (time in range — TIR), час перебування вище / нижче діапазону та глікемічна варіабельність. Також вимірювали такі фактори серцево-судинного ризику, як артеріальний тиск, ліпідний профіль та HbA1c. Результати. Результати показали, що пацієнти з ЦД 2-го типу схильні до нічної гіперглікемії, і у 62% пацієнтів відмічено нічний TIR менше рекомендованих 70%. Це пов’язано з високим систолічним артеріальним тиском та погіршенням ліпідного профілю. Більша глікемічна варіабельність пов’язана з вищим серцево-судинним ризиком та розвитком оксидативного стресу та атеросклерозу. Результати множинного регресійного аналізу показали, що нічний TIR <70%, CV (coefficient of variation) >36%, MAGE (mean amplitude of glycaemic excursions) >5,0 ммоль/л є незалежними предикторами високого серцево-судинного ризику, незалежно від інших змінних. Висновок. Результати отриманих даних підтверджують важливість вимірювання нічних глікемічних параметрів та змін глікемії для покращення оцінки серцево-судинного ризику у пацієнтів із ЦД 2-го типу. Враховуючи високу важливість впливу нічної гіперглікемії на метаболічні та гемодинамічні параметри, у клінічну практику слід запровадити CGM для кращого контролю глікемії та серцево-судинних ускладнень.
Ключові слова: цукровий діабет, нічна гіперглікемія, глікемічна варіабельність, безперервний моніторинг рівня глюкози, серцево-судинний ризик.
Information about the author:
Krytskyy Taras I. — PhD, MD, Associate Professor, Department of Internal Medicine № 1, I. Horbachevsky Ternopil National Medical University, Ternopil, Ukraine. orcid.org/0000-0002-7476- 2775 |
Інформація про автора:
Крицький Тарас Ігорович — кандидат медичних наук, доцент, доцент кафедри внутрішньої медицини № 1 Тернопільського національного медичного університету імені І.Я. Горбачевського, Тернопіль, Україна. orcid.org/0000-0002-7476-2775 |
Надійшла до редакції/Received: 27.02.2026
Прийнято до друку/Accepted: 02.03.2026
