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Pharmaceutics Jun 2023Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic... (Review)
Review
Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.
PubMed: 37513978
DOI: 10.3390/pharmaceutics15071791 -
Diabetology & Metabolic Syndrome May 2023Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which...
BACKGROUND
Diabetes is one of the chronic conditions with a high burden all around the world. Macrovascular and microvascular involvement are among the common mechanisms by which diabetes can impact patients' lives. Endocan as an inflammatory endothelial biomarker has been shown to increase in several communicable and non-communicable diseases. Herein, we aim to investigate the role of endocan as a biomarker in diabetes as a systematic review and meta-analysis.
METHODS
International databases, including PubMed, Web of Science, Scopus, and Embase were searched for relevant studies assessing blood endocan in diabetic patients. Estimation of the standardized mean difference (SMD) and 95% confidence interval (CI) for comparison of circulating endocan levels between diabetic patients and non-diabetic controls were conducted through random-effect meta-analysis.
RESULTS
Totally, 24 studies were included, assessing 3354 cases with a mean age of 57.4 ± 8.4 years. Meta-analysis indicated that serum endocan levels were significantly higher in diabetic patients in comparison with healthy controls (SMD 1.00, 95% CI 0.81 to 1.19, p-value < 0.01). Moreover, in the analysis of studies with only type-2 diabetes, the same result showing higher endocan was obtained (SMD 1.01, 95% CI 0.78 to 1.24, p-value < 0.01). Higher endocan levels were also reported in chronic diabetes complications such as diabetic retinopathy, diabetic kidney disease, and peripheral neuropathy.
CONCLUSION
Based on our study's findings, endocan levels are increased in diabetes, however, further studies are needed for assessing this association. In addition, higher endocan levels were detected in chronic complications of diabetes. This can help researchers and clinicians in recognizing disease endothelial dysfunction and potential complications.
PubMed: 37189201
DOI: 10.1186/s13098-023-01076-z -
Frontiers in Endocrinology 2023Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This...
INTRODUCTION
Diabetic neuropathy (DN) is a prevalent and debilitating complication of diabetes, imposing a significant burden on individuals and healthcare systems worldwide. This study presents a comprehensive analysis of the global research landscape in DN, aiming to provide scientists, funders, and decision-makers with valuable insights into the current state of research and future directions.
METHODS
Through a systematic review of published articles, key trends in DN research, including epidemiology, diagnosis, treatment strategies, and gaps in knowledge, are identified and discussed.
RESULTS
The analysis reveals an increasing prevalence of DN alongside the rising incidence of diabetes, emphasizing the urgent need for effective prevention and management strategies. Furthermore, the study highlights the geographical imbalance in research activity, with a majority of studies originating from high-income countries.
DISCUSSION
This study underscores the importance of fostering international collaboration to address the global impact of DN. Key challenges and limitations in DN research are also discussed, including the need for standardized diagnostic criteria, reliable biomarkers, and innovative treatment approaches. By addressing these gaps, promoting collaboration, and increasing research funding, we can pave the way for advancements in DN research and ultimately improve the lives of individuals affected by this debilitating condition.
Topics: Humans; Diabetic Neuropathies; Forecasting; Prevalence; Diabetes Mellitus
PubMed: 38034004
DOI: 10.3389/fendo.2023.1220896 -
The Cochrane Database of Systematic... Mar 2023Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood... (Review)
Review
BACKGROUND
Diabetic retinopathy is a common complication of diabetes and a leading cause of visual impairment and blindness. Research has established the importance of blood glucose control to prevent development and progression of the ocular complications of diabetes. Concurrent blood pressure control has been advocated for this purpose, but individual studies have reported varying conclusions regarding the effects of this intervention.
OBJECTIVES
To summarize the existing evidence regarding the effect of interventions to control blood pressure levels among diabetics on incidence and progression of diabetic retinopathy, preservation of visual acuity, adverse events, quality of life, and costs.
SEARCH METHODS
We searched several electronic databases, including CENTRAL, and trial registries. We last searched the electronic databases on 3 September 2021. We also reviewed the reference lists of review articles and trial reports selected for inclusion.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) in which either type 1 or type 2 diabetic participants, with or without hypertension, were assigned randomly to more intense versus less intense blood pressure control; to blood pressure control versus usual care or no intervention on blood pressure (placebo); or to one class of antihypertensive medication versus another or placebo.
DATA COLLECTION AND ANALYSIS
Pairs of review authors independently reviewed the titles and abstracts of records identified by the electronic and manual searches and the full-text reports of any records identified as potentially relevant. The included trials were independently assessed for risk of bias with respect to outcomes reported in this review.
MAIN RESULTS
We included 29 RCTs conducted in North America, Europe, Australia, Asia, Africa, and the Middle East that had enrolled a total of 4620 type 1 and 22,565 type 2 diabetic participants (sample sizes from 16 to 4477 participants). In all 7 RCTs for normotensive type 1 diabetic participants, 8 of 12 RCTs with normotensive type 2 diabetic participants, and 5 of 10 RCTs with hypertensive type 2 diabetic participants, one group was assigned to one or more antihypertensive agents and the control group to placebo. In the remaining 4 RCTs for normotensive participants with type 2 diabetes and 5 RCTs for hypertensive type 2 diabetic participants, methods of intense blood pressure control were compared to usual care. Eight trials were sponsored entirely and 10 trials partially by pharmaceutical companies; nine studies received support from other sources; and two studies did not report funding source. Study designs, populations, interventions, lengths of follow-up (range less than one year to nine years), and blood pressure targets varied among the included trials. For primary review outcomes after five years of treatment and follow-up, one of the seven trials for type 1 diabetics reported incidence of retinopathy and one trial reported progression of retinopathy; one trial reported a combined outcome of incidence and progression (as defined by study authors). Among normotensive type 2 diabetics, four of 12 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; two trials reported combined incidence and progression. Among hypertensive type 2 diabetics, six of the 10 trials reported incidence of diabetic retinopathy and two trials reported progression of retinopathy; five of the 10 trials reported combined incidence and progression. The evidence supports an overall benefit of more intensive blood pressure intervention for five-year incidence of diabetic retinopathy (11 studies; 4940 participants; risk ratio (RR) 0.82, 95% confidence interval (CI) 0.73 to 0.92; I = 15%; moderate certainty evidence) and the combined outcome of incidence and progression (8 studies; 6212 participants; RR 0.78, 95% CI 0.68 to 0.89; I = 42%; low certainty evidence). The available evidence did not support a benefit regarding five-year progression of diabetic retinopathy (5 studies; 5144 participants; RR 0.94, 95% CI 0.78 to 1.12; I = 57%; moderate certainty evidence), incidence of proliferative diabetic retinopathy, clinically significant macular edema, or vitreous hemorrhage (9 studies; 8237 participants; RR 0.92, 95% CI 0.82 to 1.04; I = 31%; low certainty evidence), or loss of 3 or more lines on a visual acuity chart with a logMAR scale (2 studies; 2326 participants; RR 1.15, 95% CI 0.63 to 2.08; I = 90%; very low certainty evidence). Hypertensive type 2 diabetic participants realized more benefit from intense blood pressure control for three of the four outcomes concerning incidence and progression of diabetic retinopathy. The adverse event reported most often (13 of 29 trials) was death, yielding an estimated RR 0.87 (95% CI 0.76 to 1.00; 13 studies; 13,979 participants; I = 0%; moderate certainty evidence). Hypotension was reported in two trials, with an RR of 2.04 (95% CI 1.63 to 2.55; 2 studies; 3323 participants; I = 37%; low certainty evidence), indicating an excess of hypotensive events among participants assigned to more intervention on blood pressure.
AUTHORS' CONCLUSIONS
Hypertension is a well-known risk factor for several chronic conditions for which lowering blood pressure has proven to be beneficial. The available evidence supports a modest beneficial effect of intervention to reduce blood pressure with respect to preventing diabetic retinopathy for up to five years, particularly for hypertensive type 2 diabetics. However, there was a paucity of evidence to support such intervention to slow progression of diabetic retinopathy or to affect other outcomes considered in this review among normotensive diabetics. This weakens any conclusion regarding an overall benefit of intervening on blood pressure in diabetic patients without hypertension for the sole purpose of preventing diabetic retinopathy or avoiding the need for treatment for advanced stages of diabetic retinopathy.
Topics: Humans; Diabetic Retinopathy; Blood Pressure; Macular Edema; Diabetes Mellitus, Type 2; Hypertension; Antihypertensive Agents; Randomized Controlled Trials as Topic
PubMed: 36975019
DOI: 10.1002/14651858.CD006127.pub3 -
Nutrients Nov 2022Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. The evidence connecting dietary intake and DR is emerging, but uncertain. We... (Review)
Review
Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. The evidence connecting dietary intake and DR is emerging, but uncertain. We conducted a systematic review to comprehensively summarize the current understanding of the associations between dietary consumption, DR and diabetic macular edema (DME). We systematically searched PubMed, Embase, Medline, and the Cochrane Central Register of Controlled Trials between January 1967 to May 2022 for all studies investigating the effect of diet on DR and DME. Of the 4962 articles initially identified, 54 relevant articles were retained. Our review found that higher intakes of fruits, vegetables, dietary fibers, fish, a Mediterranean diet, oleic acid, and tea were found to have a protective effect against DR. Conversely, high intakes of diet soda, caloric intake, rice, and choline were associated with a higher risk of DR. No association was seen between vitamin C, riboflavin, vitamin D, and milk and DR. Only one study in our review assessed dietary intake and DME and found a risk of high sodium intake for DME progression. Therefore, the general recommendation for nutritional counseling to manage diabetes may be beneficial to prevent DR risk, but prospective studies in diverse diabetic populations are needed to confirm our findings and expand clinical guidelines for DR management.
Topics: Humans; Diabetic Retinopathy; Macular Edema; Prospective Studies; Risk Factors; Diet, Mediterranean; Eating; Diabetes Mellitus
PubMed: 36501054
DOI: 10.3390/nu14235021 -
BMJ Open Diabetes Research & Care May 2020Mouse models are frequently used to study diabetes-associated ulcers, however, whether these models accurately simulate impaired wound healing has not been thoroughly... (Meta-Analysis)
Meta-Analysis Review
Mouse models are frequently used to study diabetes-associated ulcers, however, whether these models accurately simulate impaired wound healing has not been thoroughly investigated. This systematic review aimed to determine whether wound healing is impaired in mouse models of diabetes and assess the quality of the past research. A systematic literature search was performed of publicly available databases to identify original articles examining wound healing in mouse models of diabetes. A meta-analysis was performed to examine the effect of diabetes on wound healing rate using random effect models. A meta-regression was performed to examine the effect of diabetes duration on wound healing impairment. The quality of the included studies was also assessed using two newly developed tools. 77 studies using eight different models of diabetes within 678 non-diabetic and 720 diabetic mice were included. Meta-analysis showed that wound healing was impaired in all eight models. Meta-regression suggested that longer duration of diabetes prior to wound induction was correlated with greater degree of wound healing impairment. Pairwise comparisons suggested that non-obese diabetic mice exhibited more severe wound healing impairment compared with mice, streptozotocin-induced diabetic mice or high-fat fed mice at an intermediate stage of wound healing (p<0.01). Quality assessment suggested that the prior research frequently lacked incorporation of key clinically relevant characteristics. This systematic review suggested that impaired wound healing can be simulated in many different mouse models of diabetes but these require further refinement to become more clinically relevant.
Topics: Animals; Diabetes Complications; Diabetes Mellitus, Experimental; Disease Models, Animal; Mice; Ulcer; Wound Healing
PubMed: 32467222
DOI: 10.1136/bmjdrc-2019-000982 -
Nutrients Apr 2023The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract,... (Review)
Review
The Mediterranean diet (MD) is a healthy diet pattern that can prevent chronic age-related diseases, especially age-related eye diseases (AREDs) including cataract, glaucoma, age-related macular degeneration (AMD), diabetic retinopathy (DR) and dry eye syndrome (DES). In this study, we systematically reviewed studies in the literature that had reported associations between adherence to the MD and the five above-mentioned AREDs. Randomized controlled trials as well as prospective and retrospective observational studies were included; 1164 studies were identified, of which 1, 2, 9, 2 and 4 studies met our eligibility criteria for cataract, glaucoma, AMD, DR, and DES, respectively. According to these studies, higher MD adherence was associated with reduced risks of incident DR, incident AMD and progression to late AMD, but whether early and neovascular AMD could be alleviated remained to be debated. The results regarding the effects of the MD on DES were mixed, with three studies reporting an associations between MD and decreased severity or incidence of DES, whereas one study reported the opposite. No significant associations were observed between the MD and cataract or glaucoma. Generally, convincing evidence suggested a protective effect of the MD against AMD and DR. However, the evidence for cataract, glaucoma, and DES was less conclusive, and high-quality studies are needed for comprehensive evaluations of the potential benefits of MD on these eye diseases.
Topics: Humans; Angiogenesis Inhibitors; Diet, Mediterranean; Prospective Studies; Retrospective Studies; Vascular Endothelial Growth Factor A; Visual Acuity; Wet Macular Degeneration; Glaucoma; Cataract; Diabetic Retinopathy
PubMed: 37432187
DOI: 10.3390/nu15092043 -
BMJ Open Diabetes Research & Care Jun 2021In this study, we determined the reamputation-free survival to both limbs and to the contralateral limb only following an index amputation of any-level and assessed... (Meta-Analysis)
Meta-Analysis Review
In this study, we determined the reamputation-free survival to both limbs and to the contralateral limb only following an index amputation of any-level and assessed whether reamputation rates have changed over time. We completed a systematic search using PubMed and screened a total of 205 articles for data on reamputation rates. We reported qualitative characteristics of 56 studies that included data on reamputation rates and completed a meta-analysis on 22 of the studies which enrolled exclusively participants with diabetes. The random-effects meta-analysis fit a parametric survival distribution to the data for reamputations to both limbs and to the contralateral limb only. We assessed whether there was a temporal trend in the reamputation rate using the Mann-Kendall test. Incidence rates were high for reamputation to both limbs and to the contralateral limb only. At 1 year, the reamputation rate for all contralateral and ipsilateral reamputations was found to be 19% (IQR=5.1%-31.6%), and at 5 years, it was found to be 37.1% (IQR=27.0%-47.2%). The contralateral reamputation rate at 5 years was found to be 20.5% (IQR=13.3%-27.2%). We found no evidence of a trend in the reamputation rates over more than two decades of literature analyzed. The incidence of lower extremity reamputation is high among patients with diabetes who have undergone initial amputations secondary to diabetes, and rates of reamputation have not changed over at least two decades.
Topics: Amputation, Surgical; Diabetes Mellitus; Diabetic Foot; Humans; Incidence; Lower Extremity; Reoperation
PubMed: 34112651
DOI: 10.1136/bmjdrc-2021-002325 -
Diabetes Care Dec 2022Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related... (Review)
Review
BACKGROUND
Physical activity is a cornerstone in diabetes management; however, evidence synthesis on the association between physical activity and long-term diabetes-related complications is scarce.
PURPOSE
To summarize and evaluate findings on physical activity and diabetes-related complications, we conducted a systematic review and meta-analysis.
DATA SOURCES
We searched PubMed, Web of Science, and the Cochrane Library for articles published up to 6 July 2021.
STUDY SELECTION
We included prospective studies investigating the association between physical activity and incidence of and mortality from diabetes-related complications, i.e., cardiovascular disease (CVD), coronary heart disease, cerebrovascular events, heart failure, major adverse cardiovascular events, and microvascular complications such as retinopathy and nephropathy, in individuals with diabetes.
DATA EXTRACTION
Study characteristics and risk ratios with 95% CIs were extracted. Random-effects meta-analyses were performed, and the certainty of evidence and risk of bias were evaluated with use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools.
DATA SYNTHESIS
Overall, 31 studies were included. There was moderate certainty of evidence that high versus low levels of physical activity were inversely associated with CVD incidence, CVD mortality (summary risk ratio 0.84 [95% CI 0.77, 0.92], n = 7, and 0.62 [0.55, 0.69], n = 11), and microvascular complications (0.76 [0.67, 0.86], n = 8). Dose-response meta-analyses showed that physical activity was associated with lower risk of diabetes-related complications even at lower levels. For other outcomes, similar associations were observed but certainty of evidence was low or very low.
LIMITATIONS
Limitations include residual confounding and misclassification of exposure.
CONCLUSIONS
Physical activity, even below recommended amounts, was associated with reduced incidence of diabetes-related complications.
Topics: Humans; Prospective Studies; Diabetes Complications; Diabetes Mellitus; Exercise; Cardiovascular Diseases
PubMed: 36455117
DOI: 10.2337/dc22-0886 -
JAMA Network Open Dec 2022Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Peripheral neuropathies are common conditions and can result in numbness, paresthesia, motor deficits, and pain. There is increasing evidence for the use of biomarkers as clinical indicators of the presence, severity, and prognosis of nerve lesions; however, biomarker identification has largely been focused on disorders of the central nervous system, and less is known about their role in the peripheral nervous system.
OBJECTIVE
To assess blood-based biomarker concentrations associated with nerve involvement in patients with peripheral neuropathy compared with control participants.
DATA SOURCES
Ovid, MEDLINE, Embase, and CINAHL were searched from inception to September 23, 2021.
STUDY SELECTION
Observational studies reporting on blood biomarkers in patients diagnosed with peripheral neuropathy were included. This review was preregistered on PROSPERO and followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. Data were abstracted by 1 investigator and independently reviewed by a second.
DATA EXTRACTION AND SYNTHESIS
Data were meta-analyzed when at least 2 studies reported the same biomarker with comparable methodology. Fixed-effects models were used when only 2 studies were included; random-effects models were used when more than 2 studies were included.
MAIN OUTCOMES AND MEASURES
The outcome of interest was concentration of biomarkers.
RESULTS
This review included 36 studies reporting on 4414 participants, including 2113 control participants and 2301 patients with peripheral neuropathy with 13 distinct peripheral neuropathy diagnoses. Diabetic neuropathy was the most common neuropathy diagnosis (13 studies), followed by Charcot-Marie-Tooth disease (6 studies) and Guillain-Barre syndrome (6 studies). Overall, 16 different blood-based biomarkers associated with nerve involvement were evaluated. The most used were neurofilament light chain, S100B, brain-derived neurotrophic factor, and neuron-specific enolase. Patients with peripheral neuropathy demonstrated significantly higher levels of neurofilament light chain compared with controls (standardized mean difference [SMD], 0.93 [95% CI, 0.82 to 1.05]; P < .001). There were no significant differences in levels of S100B (SMD, 1.10 [95% CI, -3.08 to 5.28]; P = .38), brain-derived neurotrophic factor (SMD, -0.52 [95% CI, -2.23 to 1.19]; P = .40), or neuron-specific enolase (SMD, -0.00 [95% CI, -1.99 to 1.98]; P = .10) in patients with peripheral neuropathy compared with control participants.
CONCLUSIONS AND RELEVANCE
The findings of this systematic review and meta-analysis support the use of neurofilament light chain as a blood-based measure associated with the presence of neuronal injury in patients with peripheral neuropathy.
Topics: Humans; Adult; Brain-Derived Neurotrophic Factor; Biomarkers; Diabetic Neuropathies; Prognosis; Pain
PubMed: 36574244
DOI: 10.1001/jamanetworkopen.2022.48593