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Diabetology, Volume 3, Issue 4 (December 2022) – 12 articles

Cover Story (view full-size image): Nearly 40% of adults with type 2 diabetes (T2D) experience early morning rises in glucose due to increased hepatic glucose production, decreased glucose clearance, impaired insulin production and secretion, or a combination of these. Increasing prevalence of T2D and the frequency of poor glycemic control, coupled with low adherence to diabetes pharmacotherapy, highlights the need for lifestyle interventions to improve fasting glucose. This pilot study aimed to determine the acute effect of consuming almond butter as an evening snack on fasting and overnight interstitial glucose, compared to a no-snack control, in people with T2D not on insulin therapy. We utilized continuous glucose monitoring to analyze overnight glucose trends and to evaluate individual differences in glycemic excursions. View this paper
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5 pages, 239 KiB  
Review
Sources of Free and Added Sugars and Their Nutritional Impact in Diabetic Patients
by Tatiana Fernandes, Ana Faria and Helena Loureiro
Diabetology 2022, 3(4), 634-638; https://doi.org/10.3390/diabetology3040049 - 12 Dec 2022
Cited by 1 | Viewed by 1671
Abstract
A high consumption of sugar leads to an increase in caloric intake, which in turn will lead to a higher risk of developing health issues. Foods contain both naturally occurring sugars and added sugars. The World Health Organization recommends that the daily intake [...] Read more.
A high consumption of sugar leads to an increase in caloric intake, which in turn will lead to a higher risk of developing health issues. Foods contain both naturally occurring sugars and added sugars. The World Health Organization recommends that the daily intake of free sugars be below 10% of the total daily energy intake. Food performs a key role in maintaining an adequate glycaemic control in people with diabetes. However, there is a low compliance to dietary recommendations, namely in the amount of sugar intake. This review article aims to assess and compare the intake of various types of sugars in the general population and among individuals with and without a diabetes diagnosis, identify the food sources that contribute to the intake of free and added sugars, and understand their impact on health. Studies performed on the general population found that the consumption of sugar was high, and that children and teens are more likely to exceed the recommended amounts. It was found that diabetics consume less total and added sugar than non-diabetics, as well as a less sugary drinks. Guidelines and public health policy measures aimed at limiting the intake of free and added sugars are needed in order to minimize the consumption of foods high in empty calories. Full article
14 pages, 600 KiB  
Study Protocol
Multicenter, Open Label, Randomized Controlled Superiority Trial for Availability to Reduce Nocturnal Urination Frequency: Study Protocol for a TOP-STAR Study
by Hanako Nakajima, Hiroshi Okada, Akinori Kogure, Takafumi Osaka, Takeshi Tsutsumi, Toru Tanaka, Goji Hasegawa, Shinichi Mogami, Kazuteru Mitsuhashi, Noriyuki Kitagawa, Yoshitaka Hashimoto, Miho Yano, Muhei Tanaka, Akane Kitamura, Michiyo Ishii, Naoto Nakamura, Akio Kishi, Emi Ushigome, Masahide Hamaguchi and Michiaki Fukui
Diabetology 2022, 3(4), 620-633; https://doi.org/10.3390/diabetology3040048 - 07 Dec 2022
Cited by 1 | Viewed by 1927
Abstract
Nocturia is a common disease in patients with type 2 diabetes mellitus that can reduce the quality of life. Sodium glucose co-transporter 2 (SGLT2) inhibitors increase the urine volume and are often discontinued when polyuria occurs, although tofogliflozin, which has a short half-life [...] Read more.
Nocturia is a common disease in patients with type 2 diabetes mellitus that can reduce the quality of life. Sodium glucose co-transporter 2 (SGLT2) inhibitors increase the urine volume and are often discontinued when polyuria occurs, although tofogliflozin, which has a short half-life in the blood, may improve nocturia by managing hyperglycemia and hypertension, without aggravating nocturia. As excessive sodium intake worsens nocturia and increases urine volume, sodium restriction is also effective in managing nocturia. This multicenter, open-label, randomized parallel-group trial will examine 80 patients with type 2 diabetes who experienced nocturia. After the baseline examination, the patients are randomly stratified into two groups and receive tofogliflozin treatment with or without sodium restriction for 12 weeks. The primary outcome is nocturia frequency at 12 weeks. The secondary outcomes are the frequency of daytime urine, changes in urine volume, and changes in home blood pressure. Full article
(This article belongs to the Special Issue Diabetology: Feature Papers 2022)
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5 pages, 532 KiB  
Commentary
Insulin Injection-Related Skin Lipodystrophies: Blemish or Pathology?
by Felice Strollo, Ersilia Satta and Sandro Gentile
Diabetology 2022, 3(4), 615-619; https://doi.org/10.3390/diabetology3040047 - 01 Dec 2022
Cited by 1 | Viewed by 1780
Abstract
The number of adult individuals with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. The main local complications of insulin injection are lipohypertrophies (LHs), i.e., subcutaneous nodules consisting of aggregates of macro-adipocytes and fibrin. These nodules result from errors repeatedly made by patients [...] Read more.
The number of adult individuals with insulin-treated diabetes mellitus (DM) is steadily increasing worldwide. The main local complications of insulin injection are lipohypertrophies (LHs), i.e., subcutaneous nodules consisting of aggregates of macro-adipocytes and fibrin. These nodules result from errors repeatedly made by patients while injecting insulin. Despite being very common, LH lesions/nodules due to incorrect insulin injection techniques are often flat and hardly visible and thus require thorough deep palpation examination and ultrasonography (US) for detection. Identifying LHs is crucial, especially in elderly and frail subjects, because they may eventually result in poor diabetes control due to associated unpredictable insulin release patterns. Raising awareness of the adequate detection of LHs and their clinical consequences is crucial and urgent. A call to action is required on this topic at all levels of undergraduate and postgraduate education. Full article
(This article belongs to the Special Issue Diabetology: Feature Papers 2022)
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9 pages, 726 KiB  
Review
Diet Modifications towards Restoration of Insulin Sensitivity and Daily Insulin Fluctuations in Diabetes
by Ana Magalhães, Cátia Barra, Ana Borges and Lèlita Santos
Diabetology 2022, 3(4), 606-614; https://doi.org/10.3390/diabetology3040046 - 22 Nov 2022
Viewed by 2797
Abstract
The circadian rhythm is essential in order to maintain metabolic homeostasis and insulin sensitivity. Disruption of circadian mechanisms is associated with the development of metabolic diseases, such as diabetes. Lifestyle changes such as an equilibrated diet and physical activity are known to improve [...] Read more.
The circadian rhythm is essential in order to maintain metabolic homeostasis and insulin sensitivity. Disruption of circadian mechanisms is associated with the development of metabolic diseases, such as diabetes. Lifestyle changes such as an equilibrated diet and physical activity are known to improve glycaemic control in diabetic patients. One of the mechanisms possibly involved in such an improvement is the restoration of insulin circadian rhythms. There are several available dietary schemes based on circadian rhythms. Some of them are associated with better regulation of daily insulin fluctuations and the improvement of Type 2 Diabetes and metabolic syndrome. In the current review, we aim to explore how the different types of diet can impact glucose metabolism and insulin sensitivity in patients with diabetes, highlighting the interactions with the mechanisms of circadian insulin rhythm and the prevention of hyperinsulinemia. Full article
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10 pages, 644 KiB  
Review
Gut Metabolism of Sugars: Formation of Glycotoxins and Their Intestinal Absorption
by Tamaeh Monteiro-Alfredo and Paulo Matafome
Diabetology 2022, 3(4), 596-605; https://doi.org/10.3390/diabetology3040045 - 10 Nov 2022
Cited by 3 | Viewed by 2712
Abstract
Glycotoxins include the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds of sugar metabolism. Glycotoxins and products of the Maillard reaction are present in high concentrations in foods rich in sugars and processed at high [...] Read more.
Glycotoxins include the group of advanced glycation end-products (AGEs) and their precursors, most of them highly reactive intermediary compounds of sugar metabolism. Glycotoxins and products of the Maillard reaction are present in high concentrations in foods rich in sugars and processed at high temperatures and are often associated with the flavour of the food. Proteins undergoing this type of molecular modification are targets for gut peptidases and may be absorbed into circulation. AGEs are associated with the toxic effects of glucose in diabetic patients, and some studies have shown that they also contribute to metabolically unhealthy obesity and prediabetes development. Restriction of dietary glycotoxins was shown to improve insulin resistance in humans. However, the real contribution of dietary AGEs to such mechanisms is still not understood. This review summarizes the current knowledge about glycotoxin formation from dietary sugars, their digestion throughout the gastrointestinal system, and the mechanisms of their intestinal absorption. Full article
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13 pages, 1073 KiB  
Review
The Bitter Side of Sugar Consumption: A Mitochondrial Perspective on Diabetes Development
by Mariana S. Diniz, Carolina Tocantins, Luís F. Grilo and Susana P. Pereira
Diabetology 2022, 3(4), 583-595; https://doi.org/10.3390/diabetology3040044 - 07 Nov 2022
Cited by 4 | Viewed by 10000
Abstract
Type 2 diabetes (T2D) has increased worldwide at an alarming rate. Metabolic syndrome (MetS) is a major risk factor for T2D development. One of the main reasons for the abrupt rise in MetS incidence, besides a sedentary lifestyle, is the westernized diet consumption, [...] Read more.
Type 2 diabetes (T2D) has increased worldwide at an alarming rate. Metabolic syndrome (MetS) is a major risk factor for T2D development. One of the main reasons for the abrupt rise in MetS incidence, besides a sedentary lifestyle, is the westernized diet consumption, with high content of industrialized foods, rich in added dietary sugars (DS), mainly sucrose and fructose. It has been suggested that a higher intake of DS could impair metabolic function, inducing MetS, and predisposing to T2D. However, it remains poorly explored how excessive DS intake modulates mitochondrial function, a key player in metabolism. This review explores the relationship between increased consumption of DS and mitochondrial dysfunction associated with T2D development, pointing to a contribution of the diet-induced accumulation of advanced glycation end-products (AGEs), with brief insights on the impact of maternal high-sugar diet and AGEs consumption during gestation on offspring increased risk of developing T2D later in life, contributing to perpetuate T2D propagation. Full article
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22 pages, 4377 KiB  
Article
Augmentation and Evaluation of an Olive Oil Based Polyherbal Combination against Diabetic Cardiomyopathy in Experimental Model of Rodents
by Arshiya Shamim, Hefazat H. Siddiqui, Tarique Mahmood, Tanveer A. Wani, Seema Zargar, Mohammad Haris Siddiqui, Alvina Farooqui, Farogh Ahsan, Mohammad Shariq, Saba Parveen, Muhammad Wahajuddin, Pranay Wal and Akash Ved
Diabetology 2022, 3(4), 561-582; https://doi.org/10.3390/diabetology3040043 - 02 Nov 2022
Viewed by 1673
Abstract
Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, [...] Read more.
Diabetes mellitus is a metabolic disorder that is prima facie a cause for numerous macro and micro vascular complications. A common macroscopic complication associated with diabetes is cardiomyopathy. Cardiomyopathy refers to diseases of the heart muscle, where the heart muscle becomes enlarged, thick, or rigid. As cardiomyopathy worsens, the heart becomes weaker and is unable to conduct the right amount of blood through the body and maintain a normal electrical rhythm. This can lead to heart failure or arrhythmias. Chronic diabetes is one of the instigating factors behind the etiology of this cardiac complication. Type-II diabetes is associated with impaired glucose metabolism that increases the dependence of a diabetic heart on fatty acid oxidation to meet its functional demands, resulting in mitochondrial uncoupling, glucotoxicity, lipotoxicity and initially subclinical cardiac dysfunction that finally gives way to heart failure. The increasing diabetic population with cardiac disorders and the ironically decreasing trend in newer medications to counter this complication leave us at a crossroads for pharmacological management of diabetic cardiomyopathy. Keeping this in view, the present study proclaims a newly developed polyherbal combination (PHC) with three herbs, namely Tinospora cordifolia, Withania somnifera and Boerhavia diffusa based in olive oil and administered in fixed dose (PHC-6 and PHC-10) to screen its cardioprotective potential against a well-established experimental model for diabetic cardiomyopathy. The three herbs mentioned have been known through the traditional literature for their antidiabetic and cardioprotective roles, hence they became the obvious choice. The study follows an experimental model proposed by Reed et al., where the capacity of the β-cell is unobtrusively impeded without totally compromising insulin release, bringing about a moderate disability in glucose resilience. Various sophisticated parameters, namely intraventricular septum thickness of hearts, Western blot of α/β- MHC monoclonal antibody (Ab), cardiac pyruvate dehydrogenase (PDH) activity, medium chain acyl coenzyme A dehydrogenase (MCAD) enzyme, etc. showed promising results where treatment with PHC (PHC-6 and PHC-10) significantly (*** p < 0.001 and **** p < 0.0001) prevented the symptoms of cardiomyopathy in subsequent groups when compared to disease control group. Full article
(This article belongs to the Special Issue Nutrition, Lifestyles, and Metabolomics in Diabetes)
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12 pages, 583 KiB  
Review
Impact of Dietary Sugars on Gut Microbiota and Metabolic Health
by Karina Garcia, Gonçalo Ferreira, Flávio Reis and Sofia Viana
Diabetology 2022, 3(4), 549-560; https://doi.org/10.3390/diabetology3040042 - 28 Oct 2022
Cited by 6 | Viewed by 6983
Abstract
Excessive sugar consumption is a risk factor for the development of several disorders, including metabolic, cardiovascular, neurological conditions and even some cancers, and has been linked to increased morbidity and mortality. The popularization of the typical Western diet, featured by an excessive intake [...] Read more.
Excessive sugar consumption is a risk factor for the development of several disorders, including metabolic, cardiovascular, neurological conditions and even some cancers, and has been linked to increased morbidity and mortality. The popularization of the typical Western diet, featured by an excessive intake of saturated fats and added sugars and a low consumption of unprocessed fruits, vegetables and fiber, may directly affect the composition and functionality of the gut microbiota, staggering the balance of the intestinal microbiome that ultimately culminates into gut dysbiosis. Although added sugars in the form of nutritive and non-nutritive sweeteners are generally considered as safe, a growing body of evidence correlate their consumption with adverse effects on gut microbial ecosystem; namely an abnormal synthesis of short-chain fatty acids, altered intestinal barrier integrity and chronic inflammation that often fuel a panoply of metabolic conditions. Accordingly, this work revisited the available preclinical evidence concerning the impact of different types of dietary sugars—nutritive and non-nutritive sweeteners—on gut microbiota and metabolic health. Future research should consider gender and species vulnerability when the impact of such substances on GM community and metabolic health is scrutinized in order to guide their adequate use at doses relevant to human use. Full article
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10 pages, 1111 KiB  
Article
Glucocorticoid Receptor Blockers Pretreatment Did Not Improve Infarct Volume in Type-2 Diabetic Mouse Model of Stroke
by Rashmi Kumari and Lisa Willing
Diabetology 2022, 3(4), 539-548; https://doi.org/10.3390/diabetology3040041 - 21 Oct 2022
Cited by 1 | Viewed by 1357
Abstract
Impaired glucocorticoid signaling in diabetes mellitus and its relation to suppressed immune function and hyperglycemia during acute stroke has been shown to be detrimental. Therefore, the aim of this study was to examine the effect of glucocorticoid receptor (GCR) blockers in a type-2 [...] Read more.
Impaired glucocorticoid signaling in diabetes mellitus and its relation to suppressed immune function and hyperglycemia during acute stroke has been shown to be detrimental. Therefore, the aim of this study was to examine the effect of glucocorticoid receptor (GCR) blockers in a type-2 diabetic mouse model following hypoxia–ischemia (HI). We induced stroke in diabetic db/db and non-diabetic db/+ mice by unilateral common carotid artery ligation followed by 20 min of HI. Mice were pretreated with RU-486, GCRII blocker (40 mg/kg), intraperitoneally, the day before, during stroke and post-HI. Blood and brain samples were collected at 24 h post-HI to measure blood glucose, corticosterone and infarct size. Similarly, another set of mice was pretreated with RU-486 + spironolactone, GCR1 blocker (25 mg/kg) subcutaneously for a week before inducing stroke and during recovery. Samples were collected at 48 h post-HI for various analyses. RU-486 treatment did not lower the blood glucose significantly, but RU-486 + spironolactone decreased the blood glucose in db/db mice post-HI. However, none of the treatment groups decreased the ischemia-induced serum corticosterone level or infarct size. This study suggests that even though GCR blockers improve hyperglycemia, they did not improve the infarct volume. Full article
(This article belongs to the Special Issue Brain and Diabetes)
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15 pages, 2724 KiB  
Article
Investigating the Protective Effects of a Rhenium (V) Compound with Uracil-Derived Ligands on Liver Damage Associated with Prediabetes in Diet-Induced Prediabetic Rats
by Angezwa Siboto, Akinjide Moses Akinnuga, Muhammed Bilaal Ismail, Irvin Noel Booysen, Ntethelelo Hopewell Sibiya, Phikelelani Ngubane and Andile Khathi
Diabetology 2022, 3(4), 524-538; https://doi.org/10.3390/diabetology3040040 - 17 Oct 2022
Cited by 2 | Viewed by 1502
Abstract
Non-alcoholic fatty liver disease (NAFLD) is associated with prediabetes and can be treated by using a combination of metformin and dietary modification. However, people often fail to adhere to dietary modifications and become more dependent on pharmaceutical intervention, and this affects the effectiveness [...] Read more.
Non-alcoholic fatty liver disease (NAFLD) is associated with prediabetes and can be treated by using a combination of metformin and dietary modification. However, people often fail to adhere to dietary modifications and become more dependent on pharmaceutical intervention, and this affects the effectiveness of the drug. In this study, we investigated the effects of rhenium (V) compound with uracil-derived ligands on liver health in diet-induced prediabetic rats in both the presence and absence of dietary modification. Prediabetic male Sprague Dawley rats were treated with the rhenium (V) compound for 12 weeks in both the presence and absence of dietary modification while monitoring fasting blood glucose levels. Antioxidant enzyme activity, inflammation markers and liver enzymes were measured together with liver glycogen and plasma triglycerides after sacrificing. The administration of rhenium (V) compound to prediabetic rats in both the presence and absence of dietary modification resulted in reduced concentrations of fasting blood glucose and triglycerides. There was also reduced liver glycogen, oxidative stress and liver enzymes while increasing antioxidant enzymes. Altogether, the rhenium (V) compound ameliorated liver injury and prevented hepatotoxicity. Full article
(This article belongs to the Special Issue Diabetology: Feature Papers 2022)
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10 pages, 501 KiB  
Article
Neurocognitive Disorders in Post and Long Covid Patients: Preliminary Data, Gender Differences and New Diabetes Diagnosis
by Concetta Mezzatesta, Sara Bazzano, Rosa Gesualdo, Simone Marchese, Maria Luisa Savona, Mario Tambone Reyes and Vincenzo Provenzano
Diabetology 2022, 3(4), 514-523; https://doi.org/10.3390/diabetology3040039 - 06 Oct 2022
Cited by 1 | Viewed by 1656
Abstract
The research is based on a clinical observation of the neurological and neuro-cognitive status of 300 patients, belonging to the Partinico Hospital and the Post-Long Covid clinic, which had contracted the SARS-CoV-2 virus in the period between April 2021 and May 2022. In [...] Read more.
The research is based on a clinical observation of the neurological and neuro-cognitive status of 300 patients, belonging to the Partinico Hospital and the Post-Long Covid clinic, which had contracted the SARS-CoV-2 virus in the period between April 2021 and May 2022. In this paper, we present the analysis of the first 100 patients subjected to a neurocognitive screening protocol. The procedure consists of tests that examine the mechanism of different brain domains to check for the presence of cognitive deficits that arose after the negativization of the viral infection. Through a neurocognitive protocol, the research aims to investigate different brain areas and mental functioning. This allowed us to raise the possibility that the presence of cognitive alterations may be related to the evidence of point-like brain alterations (from the cortex to the trunk) visible through neuroimaging techniques. In the article, we highlight the hypothesis that SARS-covid 2, as stated in recently published studies, can produce an alteration of executive functions such as to configure a real dysexecutive syndrome. This research evaluates the symptomatic gender variability within the sample, the presence of important differences in the affective state, and provides a first observation of the impact of SARS-CoV-2 in diabetic pathology as well. Full article
(This article belongs to the Special Issue Gender Difference in Diabetes)
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12 pages, 1836 KiB  
Article
A Pilot Study of the Effect of Evening Almond Butter Consumption on Overnight and Fasting Interstitial Glucose
by Emily A. Johnston, Nelson A. Roque, Barbara H. Cole, Michael P. Flanagan, Penny M. Kris-Etherton and Kristina S. Petersen
Diabetology 2022, 3(4), 502-513; https://doi.org/10.3390/diabetology3040038 - 26 Sep 2022
Viewed by 2727
Abstract
Approximately 40% of patients with type 2 diabetes (T2D) experience an early-morning rise in fasting glucose that is not effectively treated by available oral hypoglycemic agents. This study aimed to determine the acute effect of consuming almond butter as an evening snack on [...] Read more.
Approximately 40% of patients with type 2 diabetes (T2D) experience an early-morning rise in fasting glucose that is not effectively treated by available oral hypoglycemic agents. This study aimed to determine the acute effect of consuming almond butter as an evening snack on fasting and overnight interstitial glucose, compared to a no-snack control, in people with T2D. Adults with T2D, not taking insulin, were recruited to participate in this two-week randomized, controlled, crossover pilot study. Participants received 2 tbsp of natural almond butter as an evening snack, or a no-snack control, for one week each. Glucose was measured by continuous glucose monitor (CGM). Analyses were performed using linear mixed effect modeling in R. Ten adults (60% female; age: 57 ± 5.6 years) completed the study. The intervention did not significantly influence fasting glucose [4–6 a.m.; β = 5.5, 95% CI = [−0.9, 12.0], p = 0.091; Marginal R2 = 0.001, Conditional R2 = 0.954] or overnight glucose (12–3 a.m.; β = 5.5, 95% CI = [−0.8, 11.8], p = 0.089; Marginal R2 = 0.001, Conditional R2 = 0.958). Significant variability in continuously measured glucose was observed. These findings will inform the design of a larger investigation. Full article
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