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Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Endocrinology and Metabolism Research".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 18333

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Dr. Tomislav Bulum

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1. Vuk Vrhovac University Clinic for Diabetes, Endocrinology and Metabolic Diseases, Merkur University Hospital, Zagreb, Croatia
2. School of Medicine, University of Zagreb, Zagreb, Croatia
Interests: diabetes type 1; diabetes type 2; metabolic syndrome; diabetic nephropathy; diabetic retinopathy
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Dear Colleagues,

Diabetes is one of the most challenging health problems in the 21st century, and is projected to affect 700 million people by 2045. The most devastating components of diabetes are its chronic complications, leading to a high risk of morbidity and mortality and a high health system cost burden. In addition, the risk of developing cardiovascular diseases in patients with diabetes is more than double compared to subjects without diabetes. The majority of patients have type 2 diabetes associated with obesity and metabolic syndrome. In addition to type 2 diabetes, the central components of metabolic syndrome and obesity are hypertension and hypercholesterolemia. In patients with type 2 diabetes, there are also structural changes in low-density lipoprotein (LDL) cholesterol, resulting in the predominance of atherogenic small dense LDL cholesterol. The clustering of hypertension and hypercholesterolemia in patients with type 2 diabetes has a greater effect, leading to worse disease outcomes compared to individual risk factors. Studies have suggested that the optimal control of blood pressure and serum lipids, particularly LDL cholesterol, may reduce the risk of chronic complications of diabetes and cardiovascular diseases.

In view of this, we welcome submissions to this Special Issue on the relationship between hypertension, hypercholesterolemia and type 2 diabetes. Detailed knowledge of this complex interplay is needed to reduce the cardiovascular morbidity and mortality associated with type 2 diabetes.

Dr. Tomislav Bulum
Guest Editor

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Keywords

type 2 diabetes
hypertension
LDL-cholesterol
serum lipids
metabolic syndrome
cardiovascular disease
chronic complications
nephropathy

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Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes—2nd Edition in Biomedicines

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Research

12 pages, 1695 KiB

Open AccessArticle

Systolic and Diastolic Blood Pressure Are Independent Risk Factors for Diabetic Retinopathy in Patients with Type 2 Diabetes

by Tomislav Bulum, Martina Tomić, Romano Vrabec, Neva Brkljačić and Spomenka Ljubić

Biomedicines 2023, 11(8), 2242; https://doi.org/10.3390/biomedicines11082242 - 10 Aug 2023

Cited by 7 | Viewed by 1659

Abstract

Background and aims: Diabetic retinopathy (DR) is a microvascular complication of diabetes and represents the leading cause of blindness in working-age adults. The aim of this study was to investigate the risk factors for DR in patients with type 2 diabetes (T2DM) with and without diabetic nephropathy (DN). Methods: A total of 160 patients with T2DM were included in the study. Photodocumented retinopathy status was determined according to the EURODIAB protocol. Renal function was determined using creatinine-based estimated glomerular filtration rate (eGFR) and albumin-to-creatinine ratio (ACR). Binary univariate and multiple logistic regression analyses were performed to determine the main predictors of DR. Results: The prevalence of DR in this studied sample was 46.3%. No significant correlation was observed between DR and age, body mass index, serum lipids, and renal function. Binary logistic regression analysis (no DR/DR) showed that longer diabetes duration (p = 0.008), poor glycemic control (HbA1c) (p = 0.008), higher systolic blood pressure (p = 0.001), and diastolic blood pressure (p = 0.003) were the main predictors of DR in patients with T2DM. However, the influence of systolic blood pressure (AOR = 1.06, p = 0.004) and diastolic blood pressure (AOR = 1.12, p = 0.007) on DR development remained significant even after adjustment for diabetes duration and HbA1c. Conclusions: Our results suggest that systolic and diastolic blood pressure are independent risk factors for DR in patients with T2DM. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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11 pages, 1134 KiB

Open AccessArticle

Prediabetes, Non-Dipping Profile and Hypertension—A Recipe for Increased Arterial Stiffness

by Juraj Jug, Điđi Delalić, Valerija Bralić Lang, Tomislav Bulum and Ingrid Prkačin

Biomedicines 2023, 11(4), 1065; https://doi.org/10.3390/biomedicines11041065 - 1 Apr 2023

Cited by 1 | Viewed by 1793

Abstract

Background: Pulse wave velocity (PWV) is a known predictor of target organ damage, cardiovascular disease and overall mortality. The aim of this study was to compare the PWV values in subjects with prediabetes, a non-dipper profile and arterial hypertension with their values in healthy subjects. Methods: A total of 301 subjects, aged 40–70 years, without diabetes mellitus were included in this cross-sectional study (150 with prediabetes). They underwent a 24 h ambulatory blood pressure monitoring (ABPM). Subjects were divided into three hypertension groups (A = healthy, B = controlled hypertension, C = uncontrolled hypertension). Dipping status was determined according to ABPM results, and PWV was measured by an oscillometric device. Prediabetes was defined as having 2 separate fasting plasma glucose (FPG) measurements between 5.6 and 6.9 mmol/L. Results: The highest PWV values were found in group C (9.60 ± 1.34 vs. 8.46 ± 1.01 in group B vs. 7.79 ± 1.10 in group A; p < 0.001), in subjects with prediabetes (8.98 ± 1.31 m/s vs. 8.26 ± 1.22 m/s; p < 0.001) and in prediabetic non-dippers among age groups (p = 0.05). In the multivariate regression model age, blood pressure, nocturnal indices and FPG were shown as independent predictors of PWV values. Conclusion: Significantly higher PWV values were found in subjects with prediabetes and non-dipping profiles in all three examined hypertension groups. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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11 pages, 934 KiB

Open AccessArticle

The Impact of BMI Changes on the Incidence of Glomerular Hematuria in Korean Adults: A Retrospective Study Based on the NHIS-HEALS Cohort

by Yu-Jin Kwon, Mina Kim, Hasung Kim and Jung Eun Lee

Biomedicines 2023, 11(3), 989; https://doi.org/10.3390/biomedicines11030989 - 22 Mar 2023

Cited by 1 | Viewed by 1868

Abstract

Obesity and recurrent hematuria are known risk factors for chronic kidney disease. However, there has been controversy on the association between obesity and glomerular hematuria. This study aimed to investigate the association between body mass index (BMI) and weight change and recurrent and persistent hematuria in glomerular disease using a large-scale, population-based Korean cohort. Data were collected from the National Health Insurance Service-National Health Screening Cohort. Cox proportional hazards regression analysis was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for recurrent and persistent hematuria in glomerular disease according to the BMI group. Compared with the BMI 23–25 kg/m² group, the HR (95% CI) for incident recurrent and persistent hematuria in glomerular disease was 0.921 (0.831–1.021) in the BMI <23 kg/m² group, 0.915 (0.823–1.018) in the BMI 25–30 kg/m² group, and 1.151 (0.907–1.462) in the BMI ≥30 kg/m² group. Compared with the stable weight group, the HRs (95% CIs) for incident recurrent and persistent hematuria in glomerular disease were 1.364 (1.029–1.808) and 0.985 (0.733–1.325) in the significant weight loss and gain groups, respectively. Despite adjusting for confounders, this result remained significant. Baseline BMI was not associated with the risk of incident recurrent and persistent hematuria in glomerular disease. Weight loss greater than 10% was associated with the incidence of recurrent and persistent hematuria in glomerular disease. Therefore, maintaining an individual’s weight could help prevent recurrent and persistent hematuria in glomerular disease in middle-aged and older Korean adults. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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22 pages, 703 KiB

Open AccessArticle

Single Nucleotide Polymorphisms of the RAC1 Gene as Novel Susceptibility Markers for Neuropathy and Microvascular Complications in Type 2 Diabetes

by Iuliia Azarova, Elena Klyosova and Alexey Polonikov

Biomedicines 2023, 11(3), 981; https://doi.org/10.3390/biomedicines11030981 - 22 Mar 2023

Cited by 5 | Viewed by 2022

Abstract

Single nucleotide polymorphisms (SNP) in the RAC1 (Rac family small GTPase 1) gene have recently been linked to type 2 diabetes (T2D) and hyperglycemia due to their contribution to impaired redox homeostasis. The present study was designed to determine whether the common SNPs of the RAC1 gene are associated with diabetic complications such as neuropathy (DN), retinopathy (DR), nephropathy, angiopathy of the lower extremities (DA), and diabetic foot syndrome. A total of 1470 DNA samples from T2D patients were genotyped for six common SNPs by the MassArray Analyzer-4 system. The genotype rs7784465-T/C of RAC1 was associated with an increased risk of DR (p = 0.016) and DA (p = 0.03) in males, as well as with DR in females (p = 0.01). Furthermore, the SNP rs836478 showed an association with DR (p = 0.005) and DN (p = 0.025) in males, whereas the SNP rs10238136 was associated with DA in females (p = 0.002). In total, three RAC1 haplotypes showed significant associations (FDR < 0.05) with T2D complications in a sex-specific manner. The study’s findings demonstrate, for the first time, that the RAC1 gene’s polymorphisms represent novel and sex-specific markers of neuropathy and microvascular complications in type 2 diabetes, and that the gene could be a new target for the pharmacological inhibition of oxidative stress as a means of preventing diabetic complications. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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10 pages, 1406 KiB

Open AccessArticle

Predictors and Outcomes of SGLT2 Inhibitor Discontinuation in a Real-World Population after Hospitalization for Heart Failure

by Masaki Nakagaito, Teruhiko Imamura, Ryuichi Ushijima, Makiko Nakamura and Koichiro Kinugawa

Biomedicines 2023, 11(3), 876; https://doi.org/10.3390/biomedicines11030876 - 13 Mar 2023

Cited by 4 | Viewed by 2290

Abstract

Background: Sodium–glucose cotransporter 2 inhibitors (SGLT2i) reduce mortality and morbidity in patients with heart failure (HF), but are discontinued in some patients. Such patients may not enjoy favorable benefits of SGLT2i therapy. We evaluated the risk factors for SGLT2i discontinuation in a real-world population with HF. Methods: We retrospectively included consecutive patients who were hospitalized for HF and administered SGLT2i during the index hospitalization between February 2016 and September 2021. We assessed the baseline clinical factors associated with post-discharge discontinuation of SGLT2i. Results: This study included a total of 159 patients (median age = 73 years, 57 women). Among baseline characteristics, a lower serum albumin level (odds ratio = 0.23, 95% confidence interval = 0.07–0.76, p = 0.016) and a higher dose of furosemide (odds ratio = 1.02, 95% confidence interval = 1.00–1.05, p = 0.046) were independently associated with the future discontinuation of SGLT2i following index discharge. Patients who terminated SGLT2i (n = 19) had a higher incidence of HF recurrence or cardiovascular death during the 1-year therapeutic period (32% versus 11%, p = 0.020). Conclusions: Among patients who initiated SGLT2i during hospitalization for HF, lower serum albumin levels and higher doses of loop diuretic at index discharge were associated with the discontinuation of SGLT2i following index discharge. We should pay special attention to patients with such characteristics during the initiation of SGLT2i and during SGLT2i therapy. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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21 pages, 1219 KiB

Open AccessArticle

Mitochondrial DNA Polymorphism in HV1 and HV2 Regions and 12S rDNA in Perimenopausal Hypertensive Women

by Wojciech Kwaśniewski, Aleksandra Stupak, Alicja Warowicka, Anna Goździcka-Józefiak, Jerzy Mosiewicz and Jolanta Mieczkowska

Biomedicines 2023, 11(3), 823; https://doi.org/10.3390/biomedicines11030823 - 8 Mar 2023

Cited by 1 | Viewed by 2126

Abstract

Estrogens enhance cellular mitochondrial activity. The diminution of female hormones during menopause may have an effect on the mitochondrial genome and the expression of mitochondrial proteins. Hence, oxidative stress and the pro-inflammatory state contribute to the formation of systemic illnesses including arterial hypertension (AH). This study aimed to determine the types and frequency of mutations in the mitochondrial DNA (mtDNA) nucleotide sequence in the hypervariable regions 1 and 2 (HV1 and HV2) and the 12S RNA coding sequence of the D-loop in postmenopausal women with hypertension. In our study, 100 women were investigated, 53 of whom were postmenopausal and 47 of whom were premenopausal (53.9 ± 3.7 years vs. 47.7 ± 4.2 years, respectively). Of those studied, 35 premenopausal and 40 postmenopausal women were diagnosed with AH. A medical checkup with 24 h monitoring of blood pressure (RR) and heart rate was undertaken (HR). The polymorphism of the D-loop and 12S rDNA region of mtDNA was examined. Changes in the nucleotide sequence of mtDNA were observed in 23% of the group of 100 women. The changes were identified in 91.3% of HV1 and HV2 regions, 60.9% of HV1 segments, 47.5% of HV2 regions, and 43.5% of 12S rDNA regions. The frequency of nucleotide sequence alterations in mtDNA was substantially higher in postmenopausal women (34%) than in premenopausal women (10.6%), p = 0.016. A higher frequency of changes in HV1 + HV2 sections in postmenopausal women (30.2%) compared to the premenopausal group (10.6%) was detected, p = 0.011. Only postmenopausal women were found to have modifications to the HV2 segment and the 12S rDNA region. After menopause, polymorphism in the mtDNA region was substantially more frequent in women with arterial hypertension than before menopause (p = 0.030; 37.5% vs. 11.5%). Comparable findings were observed in the HV2 and HV1 regions of the AH group (35% vs. 11.5%), p = 0.015, in the HV1 segment (25% vs. 11.5%), p = 0.529, and in the HV2 segment, 12S rDNA (25% vs. 0%). More than 80% of all changes in nucleotide sequence were homoplasmic. The mtDNA polymorphisms of the nucleotide sequence in the HV1 and HV2 regions, the HV2 region alone, and the 12S RNA coding sequence were associated with estrogen deficiency and a more severe course of arterial hypertension, accompanied by symptoms of adrenergic stimulation. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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11 pages, 1249 KiB

Open AccessArticle

The Involvement of Endogenous Enkephalins in Glucose Homeostasis

by Vanessa Escolero, Laica Tolentino, Abdul Bari Muhammad, Abdul Hamid and Kabirullah Lutfy

Biomedicines 2023, 11(3), 671; https://doi.org/10.3390/biomedicines11030671 - 22 Feb 2023

Cited by 2 | Viewed by 1730

Abstract

Obesity has nearly tripled since 1975 and is predicted to continue to escalate. The surge in obesity is expected to increase the risk of diabetes type 2, hypertension, coronary artery disease, and stroke. Therefore, it is essential to better understand the mechanisms that regulate energy and glucose homeostasis. The opioid system is implicated in regulating both aspects (hedonic and homeostatic) of food intake. Specifically, in the present study, we investigated the role of endogenous enkephalins in changes in food intake and glucose homeostasis. We used preproenkephalin (ppENK) knockout mice and their wildtype littermates/controls to assess changes in body weight, food intake, and plasma glucose levels when mice were fed a high-fat diet for 16 weeks. Body weight and food intake were measured every week (n = 21–23 mice per genotype), and at the end of the 16-week exposure period, mice were tested using the oral glucose tolerance test (OGTT, n = 9 mice per genotype) and insulin tolerance test (n = 5 mice per genotype). Our results revealed no difference in body weight or food intake between mice of the two genotypes. However, HFD-exposed enkephalin-deficient mice demonstrated impaired OGTT associated with reduced insulin sensitivity compared to their wildtype controls. The impaired insulin sensitivity is possibly due to the development of peripheral insulin resistance. Our results reveal a potential role of enkephalins in the regulation of glucose homeostasis and in the pathophysiology of diabetes type 2. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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16 pages, 683 KiB

Open AccessArticle

Clinical and Pharmacotherapeutic Profile of Patients with Type 2 Diabetes Mellitus Admitted to a Hospital Emergency Department

by António Cabral Lopes, Olga Lourenço, Fátima Roque and Manuel Morgado

Biomedicines 2023, 11(2), 256; https://doi.org/10.3390/biomedicines11020256 - 18 Jan 2023

Viewed by 3245

Abstract

Type 2 diabetes mellitus (T2DM) is closely associated with other pathologies, which may require complex therapeutic approaches. We aim to characterize the clinical and pharmacological profile of T2DM patients admitted to an emergency department. Patients aged ≥65 years and who were already using at least one antidiabetic drug were included in this analysis. Blood glycemia, creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), and hemoglobin were analyzed for each patient, as well as personal pathological history, diagnosis(s) at admission, and antidiabetic drugs used before. Outcome variables were analyzed using Pearson’s Chi-Square, Fisher’s exact test, and linear regression test. In total, 420 patients were randomly selected (48.6% male and 51.4% female). Patients with family support showed a lower incidence of high glycemia at admission (p = 0.016). Higher blood creatinine levels were associated with higher blood glycemia (p = 0.005), and hyperuricemia (HU) (p = 0.001), as well as HU, was associated with a higher incidence of acute cardiovascular diseases (ACD) (p = 0.007). Hemoglobin levels are lower with age (p = 0.0001), creatinine (p = 0.009), and female gender (p = 0.03). The lower the AST/ALT ratio, the higher the glycemia at admission (p < 0.0001). Obese patients with (p = 0.021) or without (p = 0.027) concomitant dyslipidemia had a higher incidence of ACD. Insulin (p = 0.003) and glucagon-like peptide-1 agonists (GLP1 RA) (p = 0.023) were associated with a higher incidence of decompensated heart failure, while sulfonylureas (p = 0.009), metformin-associated with dipeptidyl peptidase-4 inhibitors (DPP4i) (p = 0.029) or to a sulfonylurea (p = 0.003) with a lower incidence. Metformin, in monotherapy or associated with DPP4i, was associated with a lower incidence of acute kidney injury (p = 0.017) or acute chronic kidney injury (p = 0.014). SGLT2i monotherapy (p = 0.0003), associated with metformin (p = 0.026) or with DPP4i (p = 0.007), as well as insulin and sulfonylurea association (p = 0.026), were associated with hydroelectrolytic disorders, unlike GLP1 RA (p = 0.017), DPP4i associated with insulin (p = 0.034) or with a GLP1 RA (p = 0.003). Insulin was mainly used by autonomous and institutionalized patients (p = 0.0008), while metformin (p = 0.003) and GLP1 RA (p < 0.0001) were used by autonomous patients. Sulfonylureas were mostly used by male patients (p = 0.027), while SGLT2 (p = 0.0004) and GLP1 RA (p < 0.0001) were mostly used by patients within the age group 65–85 years. Sulfonylureas (p = 0.008), insulin associated with metformin (p = 0.040) or with a sulfonylurea (p = 0.048), as well as DPP4i and sulfonylurea association (p = 0.031), were associated with higher blood glycemia. T2DM patients are characterized by great heterogeneity from a clinical point of view presenting with several associated comorbidities, so the pharmacotherapeutic approach must consider all aspects that may affect disease progression. Full article

(This article belongs to the Special Issue Recent Advances in Hypertension, Hypercholesterolemia and Type 2 Diabetes)

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