View of Hyperglycemia Effects on Blood Pressure in Adults: A Systematic Review and Meta-Analysis

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https://doi.org/10.37231/ajmb.2023.1.S.665 https://journal.unisza.edu.my/ajmb

Hyperglycemia Effects on Blood Pressure in Adults: A Systematic Review and Meta- Analysis

Nur Latifa Ja’afar¹, Wan-Arfah Nadiah¹, Holifa Saheera Asmara^1*, Asheila Meramat²

1Faculty of Health Science, Universiti Sultan Zainal Abidin, Gong Badak Campus, 21300 Kuala Terengganu, Terengganu, Malaysia.

2Department of Basic Medical Science, Faculty of Medicine & Health Science, Universiti Malaysia Sarawak, 94300 Kota Samarahan, Sarawak,Malaysia.

Corresponding author: [email protected]

Received: 31^st July 2023 Accepted: 9^th November 2023 Published: 24^th December 2023

Abstract

A higher-than-normal blood glucose level characterizes hyperglycemia, the primary metabolic feature of type 2 diabetes mellitus (T2DM) caused by insulin resistance and β-cell dysfunction. As a consequence of tissue or organ damage, hyperglycemia can cause an increase in blood pressure, according to previous research. The paucity of data makes comprehending the relationship between hyperglycemia and elevated blood pressure challenging. A detailed evaluation and meta-analysis were performed to investigate how hyperglycemia influences blood pressure. In addition, this study provides information on hyperglycemia biomarkers associated with the progression of high blood pressure. This investigation utilized a systematic review and a meta-analysis following the PRISMA recommendations. A comprehensive literature search was conducted on relevant literature published between 2012 and 2022, utilizing electronic database systems such as PubMed, ScienceDirect, and Google Scholar. The random effects model was employed to combine odds ratios (OR). The meta-analysis included eleven out of the 23 studies by employing the Review Manager software. This analysis revealed the effects of hyperglycemia and normal blood glucose on blood pressure in adults (OR=2.18; 95% CI, 1.14 to 4.18). The microvascular complication (OR=1.27; 95% CI, 1.20 to 1.35) and arterial stiffness (MD=-5.93; 95% CI, -11.23 to -0.65) are factors that may contribute to the progression of hyperglycemia to high blood pressure. HbA1c was possibly the most effective biomarker for hyperglycemia (MD=1.81; 95% CI, 0.44 to 3.02). In conclusion, hyperglycemia significantly affects BP in adults, and both mechanisms identified, including microvascular complication and arterial rigidity, are associated with elevated BP in a hyperglycemic state.

Keywords

Hyperglycemia, Type 2 Diabetes Mellitus, Blood Pressure, Hypertension, HbA1c, Vascular Stiffness Introduction

Hyperglycemia is when the glucose concentration in the bloodstream exceeds the normal threshold, specifically surpassing 149 mg/dl (7.8 mmol/L)^[1]. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and dysfunction of β-cells, key metabolic factors^[2]. Furthermore, a study revealed a notable coexistence of elevated blood glucose levels and hypertension in the young adult population^[3].

Asian Journal of Medicine and Biomedicine

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Observational and clinical trial data indicate that inpatient hyperglycemia is associated with an increased risk of complications and mortality, a more extended hospital stay, and a higher admission rate to the intensive care unit in patients with or without a prior diagnosis of diabetes. In 2004, approximately 3.4 million people perished due to hyperglycemia^[4]. Hypertension is associated with hyperglycemia over time^[5]. It has been observed that youthful adults frequently exhibit high blood glucose and hypertension^[3]. Blood pressure is the force exerted by the arteries, the body's primary blood vessels, as blood circulates against the artery walls. Hypertension accounts for approximately 7.5 million fatalities or 12.8% of global mortality^[4].

The hemoglobin A1c (HbA1c) biomarker is commonly used to identify the presence and severity of hyperglycemia. A biomarker is a biological molecule found in blood^[6,7], other body fluids^[8,9], or tissues^[8]

that indicates whether a condition is normal or abnormal. Glycemic control monitoring requires serum HbA1c measurement, observing the patient's genuine current glycated HbA1c^[10]. In addition, other biomarkers include fructosamine^[11], glycated albumin^[12], triglycerides^[13], CRP, IL6, IL18^[14], and others with limitations such as moderate sensitivity and specificity and inaccuracy in certain clinical conditions.

Hyperglycemia is a metabolic disorder caused by defects in the metabolism of carbohydrates, fats, and proteins owing to impaired insulin secretion or action. According to a previous study, hyperglycemia increased in adults due to obesity and declining activity^[15]. However, a paucity of available data impedes a complex relationship between hyperglycemia and high blood pressure and the underlying mechanism by which prolonged hyperglycemia affects blood pressure. Subsequently, data regarding the precise factors that affected blood pressure in long-term hyperglycemia are insufficient to determine the factor responsible for the blood pressure increases^[3,4].

Literature Review

Hyperglycemia Affects Blood Pressure

Hyperglycemia occurs when glucose levels exceed 7.0 mmol/L (126 mg/dl) when fasting and 11.0 mmol/L (200 mg/dl) 2 hours after meals. When the fasting plasma glucose level decreases between 100 and 125 mg/dL, a patient has prediabetes or impaired glucose tolerance^[16]. The loss of pancreatic β-cells or the development of insulin resistance causes an increase in blood glucose levels. Many people may not recognize hyperglycemia symptoms until their blood sugar levels significantly increase.

Hyperglycemia typically occurs in individuals with diabetes or prediabetes due to overeating and insufficient physical activity^[17]. In addition, hyperglycemia occurs in critically ailing or injured individuals, indicating non-diabetic hyperglycemia. Pancreatic disorders and hormonal imbalances also cause hyperglycemia in individuals with certain health conditions^[18].

By interacting with glucoregulatory hormones, insulin, and counterregulatory hormones such as glucagon, cortisol, catecholamines, and growth hormone, glucose metabolism is maintained. Insulin controls glucose synthesis in the liver by inhibiting gluconeogenesis and glycogenolysis^[19]. Insulin promotes protein synthesis^[20], glucose uptake, and glycogen synthesis in insulin-sensitive tissues such as muscle^[21] while inhibiting glycogenolysis and protein degradation, depending on blood levels. Insulin inhibits lipolysis, oxidation of free fatty acids, and ketogenesis^[22].

Abnormally elevated hepatic glucose production is the primary pathophysiological issue. Rapid proteolysis and decreased protein synthesis increase the availability of gluconeogenic precursors such as alanine and glutamine, increasing hepatic glucose production. Increasing muscle glycogenolysis is necessary for lactate production, and glycerol production precedes lipolysis^[22].

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Hyperglycemia and high blood pressure share common causes and risk factors, and a person with either condition is more likely to develop the other. Hyperglycemia and hypertension are closely associated due to shared risk factors, such as endothelial dysfunction, vascular inflammation, arterial remodeling, atherosclerosis, dyslipidemia, and obesity^[23]. Then, elevated blood pressure is associated with an increase in the volume of circulatory fluid and peripheral vascular resistance^[24].

Patients with hyperglycemia exhibit increased peripheral arterial resistance due to vascular remodeling and elevated body fluid content due to insulin resistance-induced hyperinsulinemia and hyperglycemia^[25]. According to these findings, hypertension is caused by increased fluid content within the body^[26]. Similarly, vascular remodeling has progressed in diabetic patients with T2DM after the mid-stage. Peripheral vascular resistance also contributed to hypertension and demonstrated that the risk of hypertension was 1.5 to 2.0 times higher in diabetic patients than non-diabetic patients, whereas approximately one-third of hypertensives develop T2DM^[24].

Microvascular Complication of Hyperglycemia Affects Blood Pressure

Untreated hyperglycemia has the potential to give rise to a range of life-threatening consequences, one of which is damage to the peripheral vascular system. Hyperglycemia necessitates prompt medical intervention and should be efficiently managed to enhance the prognosis^[16].

Stimulating the sympathetic nervous system can influence the regulation of arteriolar constriction and dilatation. The autonomic nervous system^[27] regulates blood pressure, a critical factor in modulating short- term fluctuations during stress and physical exertion^[27,28].

In addition, the etiology of hypertension is predominantly ascribed to the interaction between the autonomic nervous system and the renin-angiotensin system, in conjunction with other factors such as circulating volume and recently identified hormonal influences^[29]. The involvement of epinephrine and norepinephrine can be observed in the pathophysiology of hypertension. Both chemicals are crucial in the body's physiological response, known as the fight-or-flight response. Upon entering the bloodstream, they elicit increased blood pressure and blood sugar levels^[1].

Potential Biomarker of Hyperglycemia Associated with Blood Pressure

HbA1c is a blood biomarker to indicate the presence and extent of hyperglycemia^[30]. HbA1c is generated by binding glucose to the amino-terminal group of a hemoglobin subunit. A diagnosis of diabetes is determined by an HbA1c level equal to or greater than 6.5% (48 mmol/mol), while prediabetes is indicated by HbA1c levels ranging from 5.7% to 6.4% (39-46 mmol/mol)^[31].

Experts have found a correlation between HbA1c levels and mortality and mortality^[7]. The HbA1c marker is a more accurate way to identify microvascular complications^[32] as they are more effective in assessing chronic glycemic control. Additionally, HbA1c levels offer advantages such as increased convenience, improved stability during pre-analytic processes^[33], and reduced fluctuations during periods of stress^[34]. Materials and Methods

Study design

This study is a meta-analysis to evaluate hyperglycemia's impact on blood pressure levels in adult individuals. Systematic literature reviews adhere to the guidelines set forth by the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) to ensure methodological rigor and comprehensive reporting. The acquisition of research is accomplished through a systematic exploration of electronic databases such as PubMed, ScienceDirect, and Google Scholar. Pertinent and interconnected research is employed to mitigate the potential for an elevated bias percentage within this study. The research was conducted between October 2022 until June 2023.

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Research Question Using the PICO Model

The research question for this systematic review and meta-analysis was formulated according to the PICO framework. The PICO framework highlights four elements, i.e., population (P), intervention (I), control (C), and outcome (O), to be included while formulating the research question in a systematic review:

1. What is the mechanism of the hyperglycemia state (intervention) that can progress to blood pressure (outcomes) in adults (population)?

2. What are the potential hyperglycemia biomarkers (intervention) that affect blood pressure (outcome) in adults (population)?

Systematic Literature Review Investigation

A comprehensive literature search was conducted by searching the relevant and related literature from 2012 until 2022 in electronic database platforms such as PubMed, ScienceDirect, and Google Scholar to identify and determine hyperglycemia's effect on blood pressure in adults. Besides that, the published article was selected only in the English language, full-text and abstract articles were used and analyzed for the next step. The keyword used in this study includes 'effects of hyperglycemia on blood pressure in adults, 'hyperglycemia effects on hypertension', 'mechanism of blood pressure in hyperglycemic state', 'hyperglycemia linked to increasing blood pressure', 'pathophysiology of blood pressure in high blood glucose in adults', and 'hyperglycemia biomarker associated with blood pressure', were used to aid in the finding of outcome in this study.

Study selection

The selection of the study started with a comprehensive search in a systematic review including many studies that fulfil the inclusion and exclusion criteria by using various electronic data platforms such as ScienceDirect, Google Scholar and PubMed. The duplicate studies were eliminated from the literature search to ensure no duplication or overlap of information in this study. However, from the duplicate study, only one was selected for analysis. Next, the title and abstracts were screened manually, whether they were related and relevant to this study before assessing the studies.

Inclusion criteria

The team of investigators employed specific criteria to choose patients with T2DM and hypertension, along with relevant scientific material. Furthermore, the above-mentioned publication was disseminated between 2012 and 2022 to utilise the extracted data that has been verified and authenticated. The inquiry used full-text and abstract sources to obtain the most recent and comprehensive information.

Exclusion criteria

The investigation deliberately excluded another organism, demanding the involvement of a human participant. In addition, this study excluded individuals diagnosed with hyperglycemia who also had cystic fibrosis and pancreatic cancer.

Data Extraction

All the relevant data were extracted, such as year of publication, first author name, study design, primary or secondary causes of hyperglycemia, the hyperglycemia biomarker used associated with high blood pressure, the effect on blood pressure in adults with hyperglycemia and its mechanism, and level of blood pressure either high or normal blood pressure.

Literature Quality Evaluation

Cochrane's Q and I² statistics were used to measure the heterogeneity. Cochrane's Q statistic is based on a chi-square test, while I² statistics focus on score heterogeneity between 0% and 100%. Then, the forest plot

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was applied for bias assessment using funnel plot analysis followed by measuring forest plot asymmetry.

The forest plot provides a quick summary of the finding.

Statistical Analysis

Meta-analysis was carried out using Review Manager Software, capable of performing a meta-analysis on the data entered and displaying the graft result. The 95% confidence interval (CI) was applied to determine the effect estimates. Therefore, a confidence interval merely assesses how well the sample represents the population under consideration. The confidence level of the CI is the probability that the confidence interval includes the true mean value within a population.

The model employed in this study is the random effect model. Utilizing the random effects model in meta- analysis enables the accommodation of heterogeneity by positing that the effects follow a distribution.

Heterogeneity pertains to the variability observed in the outcomes of different studies. The forest was used due to effective graphical displays for summarizing meta-analysis results. The studies included were represented by a box and a horizontal line through the box. Each forest plot has a vertical line, the 'no effect' line, corresponding to the value one (1 %) for binary outcomes such as OR and 0 for continuous outcomes.

Results

Article Screening

Before applying any exclusion criteria, 44 articles were identified through online databases such as PubMed, Google Scholar, and Science Direct. After eliminating duplicate articles, 44 unique articles remained in the dataset. Subsequently, 21 articles were excluded based on examining their titles and abstracts, as they were found to have been published outside the designated timeframe of 2012 to 202.2.

The reviewed article focuses on the secondary complications associated with hyperglycemia. The exclusion of the remaining 12 articles was primarily attributed to their focus on animal subjects and other factors, including incomplete data and irrelevant information concerning the present study. The present meta- analysis comprised a total of 11 articles. The articles selection process is summarized in the PRISMA flow chart (Figure 1).

Study Characteristic

Five studies included such as Edeoga et al. (2017), Midha et al. (2015), Sasaki et al. (2020), Wheeler et al.

(2020) and Kotruchin et al. (2018) were used to explore the effect of hyperglycemia state that can progress to blood pressure, four articles selected which were from Hurst et al. (2015), Ma et al. (2022), Kobayashi et al. (2021), and Wakasugi et al. (2021) for the mechanism of hyperglycemia effects on blood pressure.

Articles from Ma et al. (2022) and Zhao et al. (2021) were used in potential biomarkers that affect the level of blood pressure.

Risk of Bias within the Study

An assessment of bias within the included studies was conducted using RevMan Software. Then, the Funnel plot was tested for asymmetry and found to have a minimal risk of publication bias.

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Figure 1: PRISMA flow chart Blood Glucose Levels Affect Blood Pressure

The current study seeks to identify four scholarly articles that examine the correlation between blood glucose levels and blood pressure. Among a sample of 6,808 adults, it was observed that 5,240 individuals diagnosed with hyperglycemia experienced an elevation in their blood pressure levels. Among a sample size of 8954 individuals, it was observed that 3988 adults with normoglycemia exhibited normal blood pressure, as depicted in Figure 2. The effects of increased blood pressure in hyperglycemia were statistically significant (OR=2.18; 95% CI, 1.14 to 4.15; p=0.02), with high heterogeneity I²=95%.

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Figure 2: Blood glucose levels affect blood pressure

Based on the forest plot above, the Edeoga et al. 2017 and Midha et al. (2015) are not significant due to the value of 95% CI includes the one at the horizontal axis, and the articles passed through the vertical line marked at one, with OR values of 1.31 (95% CI, 0.96 to 1.78) and 0.5 (95% CI, 0.17 to 1.45), respectively.

While the study by Sasaki et al. (2020) and Wheeler et al. (2020) are significant due to the value of 95% CI does not include one, the p-value < 0.05, and does not pass through the vertical line in the forest plot with the OR values of 3.09 (95% CI, 2.84 to 3.37) and 6.01 (95% CI, 4.31 to 8.27), respectively.

Microvascular Complication in Hyperglycemia State Affects Blood Pressure

Two articles demonstrate that the microvascular complication of hyperglycemia leads to an increase in blood pressure (Figure 3). Among 38707 adults, 4748 adults with microvascular complications lead to increases in blood pressure, compared to 2239 adults with non-microvascular complications in hyperglycemia.

Figure 3: Microvascular complication in hyperglycemia state progress to increase blood pressure.

The position of the diamond from the forest plot shows its favor on the microvascular complication contributing to high blood pressure in adults in a hyperglycemia state. The results obtained are shown in Figure 3. The mechanism of microvascular complication in hyperglycemia state progress to increase blood pressure was statistically significant (OR=1.27; 95% CI, 1.20 to 1.35; p<0.00001), with considerably low heterogeneity I²=0%.

Arterial stiffness causes Blood Pressure

Two studies in Figure 4, which were from Kobayashi et al. (2021) and Wakasugi et al. (2021), provide data on the association of arterial stiffness in changing the blood pressure level in adults. There was a statistically significant mean difference (MD) of -5.93 (95% CI, -11.23 to -0.63; p=0.03), with considerably low heterogeneity (I²=45%) found in this analysis.

Figure 4: Arterial stiffness affects blood pressure.

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Potential HbA1c Biomarker in High Blood Pressure Prediction

Two studies in Figure 5 provide data on measuring HbA1c biomarkers on different blood pressure levels.

The results show the forest plot of the mean difference of HbA1c biomarker measurement on high and normal blood pressure. This analysis is statistically significant with an MD of 1.81 (95% CI, 0.44 to 3.18;

p=0.01). However, it has high heterogeneity (I²=97%).

Figure 5: Association of HbA1c biomarker and High Blood Pressure Discussion

Based on the present study's findings, it is evident that Wheeler et al. (2020) have demonstrated a significant association between T2DM and hypertension. Specifically, their analysis reveals that a substantial majority of participants diagnosed with T2DM (98.3%) exhibit a higher likelihood of also having hypertension than participants without T2DM (90.5%). According to the study conducted by Sasaki et al.

(2020), a majority of diabetic patients (63.8%) were found to have coexisting hypertension, while a smaller proportion (36.3%) of participants exhibited normal fasting glucose levels. The results presented in this study are substantiated by a meta-analysis of randomized controlled trials, which demonstrated a significant correlation between elevated sugar consumption and increased systolic and diastolic blood pressures^[35].

Moreover, this study analyzed a notable disparity in the occurrence of diabetes among participants who developed hypertension (92%) compared to those who did not (38%), and this impact is statistically significant. Hyperglycemia exhibits a 2.18-fold increased likelihood of impacting blood pressure levels in adult individuals. Furthermore, this study demonstrated a potentially significant correlation between hyperglycemia and blood pressure levels. However, due to the presence of high heterogeneity, the meta- analysis conducted was deemed inappropriate.

However, the analysis presented in this study has been verified by a separate study that involved the inclusion of Japanese patients diagnosed with T2DM and no prior record of clinically evident cardiovascular disease. These individuals were selected as participants to examine the relationship between metrics derived from continuous glucose monitoring and arterial stiffness. The data revealed a notable disparity in the prevalence of hypertension among patients with T2DM when comparing those with high arterial stiffness (65.1%) to those with low arterial stiffness (53.7%)^[36].

In the current study analysis, the study conducted by Hurst et al. (2015), the data presented indicated that the number of participants was more significant among individuals with T2DM who experienced the progression of microvascular complications leading to hypertension, in comparison to those with T2DM and non-microvascular complications. The analysis revealed that microvascular damage significantly contributes to developing high blood pressure in patients with T2DM. The forest plot indicates a higher likelihood of increased blood pressure in individuals with microvascular complications than those without it. The statistical significance of the analysis suggests a notable low in heterogeneity, thereby validating the appropriateness of conducting a meta-analysis.

The above analysis is supported by a study wherein they include individuals with hyperglycemia who experience microvascular complications, which exhibit an increased likelihood of developing hypertension

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compared to those with non-microvascular complications^[23,37]. In addition, a study wherein they performed an analysis on measurements of arterial stiffness. The findings indicated that diabetic patients aged 30 to 65 exhibited significantly higher systolic and pulse pressure values than non-diabetic individuals^[38].

Furthermore, this study also discovered a substantial difference in HbA1c values between people with diabetes (65.4%) and those without diabetes (40.4%). Interestingly, this analysis is supported by a study that demonstrated that the participants with diabetic peripheral neuropathy with high HbA1C level was significant and increased three times from 6.9% to 28.5%^[39].

Conclusion

In conclusion, the results obtained from this study demonstrate a significant positive correlation between hyperglycemia and elevated blood pressure levels among the adult demographic. The progression of elevated blood pressure in individuals with hyperglycemia is attributed to microvascular complications and arterial stiffness. Furthermore, there exists a strong correlation between both factors. The association between micro- and macrovascular complications in individuals diagnosed with T2DM has been observed to be linked to a subsequent increase in arterial stiffness. This increase in arterial stiffness, in turn, plays a role in the progression of hypertension. Moreover, the HbA1c biomarker is commonly used to detect changes in blood pressure in hyperglycemic individuals, owing to its relationship with problems or factors that can raise blood pressure.

Funding

The authors received no specific funding for this work.

Acknowledgements

We want to thank the statistician for analyzing and interpreting the database analysis.

Conflict of Interest Disclosure None to declare

References

1. Güemes M, Rahman SA, Hussain K. What is a normal blood glucose? Arch Dis Child.

2016;101(6):569-574. doi:10.1136/archdischild-2015-308336

2. Lima JEBF, Moreira NCS, Sakamoto-Hojo ET. Mechanisms underlying the pathophysiology of type 2 diabetes: From risk factors to oxidative stress, metabolic dysfunction, and hyperglycemia. Mutat Res - Genet Toxicol Environ Mutagen. 2022;874-875(March):2022-2024.

doi:10.1016/j.mrgentox.2021.503437

3. Ruiz LD, Zuelch ML, Dimitratos SM, Scherr RE. Adolescent Obesity: Diet Quality, Psychosocial Health, and Cardiometabolic Risk Factors. Nutrients. 2019;12(1):43. doi:10.3390/nu12010043 4. Midha T. Correlation between hypertension and hyperglycemia among young adults in India. World

J Clin Cases. 2015;3(2):171. doi:10.12998/wjcc.v3.i2.171

5. Przezak A, Bielka W, Pawlik A. Hypertension and Type 2 Diabetes—The Novel Treatment Possibilities. Int J Mol Sci. 2022;23(12). doi:10.3390/ijms23126500

6. Guo W, Zhou Q, Jia Y, Xu J. Increased levels of glycated hemoglobin A1c and iron deficiency anemia:

A review. Med Sci Monit. 2019;25:8371-8378. doi:10.12659/MSM.916719

7. Dorcely B, Katz K, Jagannathan R, et al. Novel biomarkers for prediabetes, diabetes, and associated complications. Diabetes, Metab Syndr Obes. 2017;10:345-361. doi:10.2147/DMSO.S100074

8. Rescalli A, Varoni EM, Cellesi F, Cerveri P. Analytical Challenges in Diabetes Management: Towards Glycated Albumin Point-of-Care Detection. Biosensors. 2022;12(9):1-22.

doi:10.3390/bios12090687

9. Shah V, Pareikh D, Manjunatha B. Salivary alpha-amylase–biomarker for monitoring type II

(10)

diabetes. J Oral Maxillofac Pathol. 2021;25(3):441. doi:10.4103/jomfp.jomfp_84_21

10. Little RR, Roberts WL. A review of variant hemoglobins interfering with hemoglobin A1c measurement. J Diabetes Sci Technol. 2009;3(3):446-451. doi:10.1177/193229680900300307 11. Gounden V, Ngu M, Anastasopoulou C, Jialal I. Fructosamine. Published online 2023:29262081.

12. Zendjabil et al. M. Clinica Chimica Acta Glycated albumin. Clin Chim Acta. 2020;502(November 2019):240-244. https://doi.org/10.1016/j.cca.2019.11.007

13. Wang L, Cong HL, Zhang JX, et al. Triglyceride-glucose index predicts adverse cardiovascular events in patients with diabetes and acute coronary syndrome. Cardiovasc Diabetol. 2020;19(1):1-11.

doi:10.1186/s12933-020-01054-z

14. Loporchio DF, Tam EK, Cho J, et al. Cytokine levels in human vitreous in proliferative diabetic retinopathy. Cells. 2021;10(5):1-10. doi:10.3390/cells10051069

15. Basiak-Rasała A, Różańska D, Zatońska K. Food Groups in Dietary Prevention of Type 2 Diabetes.

Rocz Panstw Zakl Hig / Ann Natl Inst Hyg. 2019;70(4):347-357. doi:10.32394/rpzh.2019.0086

16. Mouri Mi, Badireddy M. Hyperglycemia. Vol 180.; 2023.

http://www.ncbi.nlm.nih.gov/pubmed/31242164

17. Kalsbeek MJT, Yi CX. The infundibular peptidergic neurons and glia cells in overeating, obesity, and diabetes. Handb Clin Neurol. 2021;180:315-325. doi:10.1016/B978-0-12-820107-7.00019-7 18. Andersen DK, Korc M, Petersen GM, et al. Diabetes, pancreatogenic diabetes, and pancreatic cancer.

Diabetes. 2017;66(5):1103-1110. doi:10.2337/db16-1477

19. Norton L, Shannon C, Gastaldelli A, DeFronzo RA. Insulin: The master regulator of glucose metabolism. Metabolism. 2022;129(2022):155142. doi:10.1016/j.metabol.2022.155142

20. Kolb H, Kempf K, Röhling M, Martin S. Insulin: Too much of a good thing is bad. BMC Med.

2020;18(1):1-12. doi:10.1186/s12916-020-01688-6

21. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2021;10(3):785-809. doi:10.1002/cphy.c190029.

22. Dhatariya K, Corsino L, Umpierrez GE, et al. Management of Diabetes and Hyperglycemia in Hospitalized Patients. Essentials Hosp Med. Published online 2013:537-551.

doi:10.1142/9789814354912_0046

23. Petrie JR, Guzik TJ, Touyz RM. Diabetes, Hypertension, and Cardiovascular Disease: Clinical Insights and Vascular Mechanisms. Can J Cardiol. 2018;34(5):575-584. doi:10.1016/j.cjca.2017.12.005 24. Gyselaers W. Hemodynamic pathways of gestational hypertension and preeclampsia. Am J Obstet

Gynecol. 2022;226(2):S988-S1005. doi:10.1016/j.ajog.2021.11.022

25. Tzamaloukas AH, Ing TS, Siamopoulos KC, et al. Body fluid abnormalities in severe hyperglycemia in patients on chronic dialysis: theoretical analysis. J Diabetes Complications. 2007;21(6):374-380.

doi:10.1016/j.jdiacomp.2007.05.007

26. McMahon EJ, Bauer JD, Hawley CM, et al. A randomized trial of dietary sodium restriction in CKD. J Am Soc Nephrol. 2013;24(12):2096-2103. doi:10.1681/ASN.2013030285

27. Foëx P, Sear JW. Hypertension: Pathophysiology and treatment. Contin Educ Anaesthesia, Crit Care Pain. 2004;4(3):71-75. doi:10.1093/bjaceaccp/mkh020

28. Stehouwer C DA, Geijselaers SL, Sep SJ, et al. The Role of Hyperglycemia, Insulin Resistance, and Blood Pressure in Diabetes-Associated Differences in Cognitive PerformancedThe Maastricht Study.

Diabetes Care. 2017;40. doi:10.2337/dc17-0330

29. Beevers G. ABC of hypertension: The pathophysiology of hypertension. BMJ. 2001;322(7291):912- 916. doi:10.1136/bmj.322.7291.912

30. Lyons TJ, Basu A. Biomarkers in diabetes: Hemoglobin A1c, vascular and tissue markers. Transl Res.

2012;159(4):303-312. doi:10.1016/j.trsl.2012.01.009

31. Florkowski C. HbA1c as a diagnostic test for diabetes mellitus - Reviewing the evidence. Clin Biochem Rev. 2013;34(2):75-83.

32. Škrha J, Šoupal J, Škrha J, Prázný M. Glucose variability, HbA1c and microvascular complications.

Rev Endocr Metab Disord. 2016;17(1):103-110. doi:10.1007/s11154-016-9347-2

(11)

33. Duan D, Kengne AP, Echouffo-Tcheugui JB. Screening for Diabetes and Prediabetes. Endocrinol Metab Clin North Am. 2021;50(3):369-385. doi:10.1016/j.ecl.2021.05.002

34. Kuroda M, Shinke T, Otake H, et al. Effects of daily glucose fluctuations on the healing response to everolimus-eluting stent implantation as assessed using continuous glucose monitoring and optical coherence tomography. Cardiovasc Diabetol. 2016;15(1):1-14. doi:10.1186/s12933-016-0395-4 35. DiNicolantonio JJ, Lucan SC. The wrong white crystals: Not salt but sugar as aetiological in

hypertension and cardiometabolic disease. Open Hear. 2014;1(1):1-8. doi:10.1136/openhrt-2014- 000167

36. Wakasugi S, Mita T, Katakami N, et al. Associations between continuous glucose monitoring-derived metrics and arterial Stiffness in Japanese patients with type 2 diabetes. Cardiovasc Diabetol.

2021;20(1):1-12. doi:10.1186/s12933-020-01194-2

37. Boutouyrie P, Chowienczyk P, Humphrey JD, Mitchell GF. Arterial Stiffness and Cardiovascular Risk in Hypertension. Circ Res. 2021;128(7):864-886. doi:10.1161/CIRCRESAHA.121.318061

38. Smulyan H, Lieber A, Safar ME. Hypertension, Diabetes Type II, and their association: Role of arterial stiffness. Am J Hypertens. 2016;29(1):5-13. doi:10.1093/ajh/hpv107

39. Su J bin, Zhao L hua, Zhang X lin, et al. HbA1c variability and diabetic peripheral neuropathy in type 2 diabetic patients. Cardiovasc Diabetol. 2018;17(1):1-9. doi:10.1186/s12933-018-0693-0