Diabetic Micro Research Articles

Assessment of cardiac and skeletal muscle metabolites using 1H-MRS and chemical-shift encoded magnetic resonance imaging: Impact of diabetes, RAGE, and DIAPH1.

Diabetes affects metabolism and metabolite concentrations in multiple organs. Previous preclinical studies have shown that receptor for advanced glycation end products (RAGE, gene symbol Ager) and its cytoplasmic domain binding partner, Diaphanous-1 (DIAPH1), are key mediators of diabetic micro- and macro-vascular complications. In this study, we used 1H-Magnetic Resonance Spectroscopy (MRS) and chemical shift encoded (CSE) Magnetic Resonance Imaging (MRI) to investigate the metabolite and water-fat fraction in the heart and hind limb muscle in a murine model of type 1 diabetes (T1D) and to determine if the metabolite changes in the heart and hind limb are influenced by (a) deletion of Ager or Diaph1 and (b) pharmacological blockade of RAGE-DIAPH1 interaction in mice. Nine cohorts of male mice, with six mice per cohort, were used: wild type non-diabetic control mice (WT-NDM), WT-diabetic (WT-DM) mice, Ager knockout non-diabetic (RKO-NDM) and diabetic mice (RKO-DM), Diaph1 knockout non-diabetic (DKO-NDM), and diabetic mice (DKO-DM), WT-NDM mice treated with vehicle, WT-DM mice treated with vehicle, and WT-DM mice treated with RAGE229 (antagonist of RAGE-DIAPH1 interaction). A Point Resolved Spectroscopy (PRESS) sequence for 1H-MRS, and multi-echo gradient recalled echo (GRE) for CSE were employed. Triglycerides, and free fatty acids in the heart and hind limb obtained from MRS and MRI were compared to those measured using biochemical assays. Two-sided t-test, non-parametric Kruskal-Wallis Test, and one-way ANOVA were employed for statistical analysis. We report that the results were well-correlated with significant differences using MRI and biochemical assays between WT-NDM and WT-DM, as well as within the non-diabetic groups, and within the diabetic groups. Deletion of Ager or Diaph1, or treatment with RAGE229 attenuated diabetes-associated increases in triglycerides in the heart and hind limb in mice. These results suggest that the employment of 1H-MRS/MRI is a feasible non-invasive modality to monitor metabolic dysfunction in T1D and the metabolic consequences of interventions that block RAGE and DIAPH1.

Hepatitis C virus antibody seropositivity is associated with albuminuria but not peripheral artery disease in patients with type 2 diabetes

Hepatitis C virus (HCV) infection is prevalent in patients with type 2 diabetes mellitus (DM). We aimed to investigate whether HCV antibody (Ab) seropositivity is associated with diabetic micro- and macro-vascular diseases. In this hospital-based cross-sectional study, we retrospectively collected data from patients who participated in the diabetes pay-for-performance program and underwent HCV Ab screening in the annual comprehensive assessment between January 2021 and March 2022. We examined the relationships of HCV Ab seropositivity with the spot urinary albumin-to-creatinine ratio (UACR) and ankle-brachial index (ABI) in patients aged ≥ 50 years with type 2 DM. A total of 1758 patients were enrolled, and 85 (4.83%) of the enrolled patients had HCV Ab seropositivity. Multivariable regression analyses revealed that albuminuria showed a dose-dependent association with HCV Ab seropositivity (UACR [30–299 mg/g]: odds ratio [OR] = 1.463, 95% confidence interval [CI] 0.872‒2.456); UACR [≥ 300 mg/g]: OR = 2.300, 95% CI 1.160‒4.562; P for trend = 0.015) when compared with normal albuminuria (UACR < 30 mg/g). However, the proportion of patients with peripheral arterial disease, defined as an ABI ≤ 0.9, was not significantly different between the groups with and without HCV Ab seropositivity (3.5% vs. 3.9%, P = 0.999). In conclusion, severely increased albuminuria, but not the ABI, showed a significant association with HCV Ab seropositivity in patients aged ≥ 50 years with type 2 DM.

Association between macro- and microvascular damage and sarcopenia index in individuals with type 2 diabetes mellitus.

Sarcopenia was recently reported to be relevant to an increased macro-and microvascular disease risk. Sarcopenia index (SI) has been identified as a surrogate marker for sarcopenia. The aim of the present study was to investigate the association between macro- and microvascular disease and SI in patients with type 2 diabetes mellitus (T2DM). A total of 783 patients with T2DM were enrolled in this cross-sectional study. The SI was calculated by (serum creatinine [mg/dL]/cystatin C [mg/L])×100. The subjects were divided into three groups according to SI tertiles: T1 (41.27-81.37), T2 (81.38- 99.55), and T3 (99.56-192.31). Parameters of macro- and microvascular complications, including diabetic retinopathy (DR), micro- and macroalbuminuria (MAU), diabetic peripheral neuropathy (DPN), and lower extremity peripheral artery disease (LEAD) were evaluated. Multivariate logistic regression analysis revealed that when taking the top tertile of SI as a reference, an increasing trend of the prevalence of DR, MAU, DPN, and LEAD were presented (all P for trend <0.05), where the OR (95% CI) for DR prevalence was 1.967 (1.252-3.090) in T2, 2.195 (1.278-3.769) in T1, for MAU was 1.805 (1.149-2.837) in T2, 2.537 (1.490-4.320) in T1, for DPN was 2.244 (1.485-3.391) in T2, 3.172 (1.884-5.341) in T1, and for LEAD was 2.017 (1.002-4.057) in T2, 2.405 (1.107-5.225) in T1 (all P<0.05). Patients with lower SI were more inclined to have an increased risk of macro- and microvascular damage in T2DM population, which may be related to sarcopenia.

RATIONALE FOR PRESCRIBING ANTICOAGULANT THERAPY IN THE COMPLEX TREATMENT OF PURULENT-NECROTIC COMPLICATIONS OF DIABETIC FOOT SYNDROME

Abstract. This article is based on the study of hemostasis indicators in 25 patients with diabetic foot syndrome. Diabetic foot syndrome (DFS) develops against the background of diabetic neuropathy, micro- and macroaniopathy, osteoarthropathy, which lead to frequent traumatization of the soft tissues of the foot, infection with the subsequent development of purulent-necrotic processes on the foot, and in the course of progression leads to high limb amputations. According to the international federation, which deals with the problem of diabetes mellitus (DM), the 21st century is considered a pandemic of DM. It should be noted that the number of patients with diabetes is increasing every year. Patients with diabetes are characterized by an atherothrombotic state caused by multiple disorders in the hemostasis system. Hemostatic disorders in patients with diabetes are complex and include activation of natural mechanisms of the coagulation system, inhibition of fibrinolytic activity, and various platelet dysfunctions.&#x0D; The purpose of the study is to substantiate the appointment of anticoagulation therapy in patients with SDS.&#x0D; Materials and methods. On the basis of KNP KMKL No. 6 in Kyiv in 2023, for a period of 6 months, 69 patients with SDS were treated. The state of indicators of the coagulation link of the hemostasis system in 49 people was studied. At the same time, 26 patients had purulent-necrotic complications of the neuroischemic form of SDS, 23 people were healthy (comparison group). The patients were divided according to the article and age, according to the duration of diabetes mellitus, and according to the stages according to Wagner. The following indicators were determined for patients: prothrombin index (PTI), plasma recalcification time, fibrinogen, B-naphthol test, ethanol test, Willebrand factor, endothelin-1, coagulation factor (VIII), fibronectin.&#x0D; The results of the study and their discussion: Based on the study, 61.5 % of patients with SDS are of working age. Of them, 57.7 % are men, 42.3 % are women. The largest number of patients with SDS is observed in the group of patients who have had diabetes for more than 10 years - 57.7 %, and the largest number of patients with stage III-IV according to Wagner - 88.5 %. In patients with diabetes with neuroischemic form of SDS, the PTI level is increased by 28.8 % and the prothrombin time is shortened by 21 %, which indicates an increase in the activity of external blood clotting mechanisms. An increase in fibrinogen by 29.7 % indicates an increase in the activity of coagulation hemostasis. Willebrand factor increased by 34.5 %, coagulation factor (VIII) increased by 20.3 %, fibronectin increased by 83.01 %, which indicates an increase in aggregation and procoagulant processes, which in turn increases thrombus formation.&#x0D; Conclusion. Thus, with diabetic foot syndrome, hypercoagulation is observed, which leads to an increase in the level of thrombus formation, which justifies the appointment of anticoagulant therapy in the complex treatment of diabetic foot syndrome.

Management of hyperglycaemia in people with obesity

Diabetes and obesity are closely interlinked. Obesity is a major risk factor for the development of type 2 diabetes mellitus and appears to be an important risk factor for diabetic micro- and macrovascular complications. Management of hyperglycaemia in people with diabetes is important to reduce diabetes-related complications. Previously, there was a significant tension between management of hyperglycaemia and mitigating weight gain. Older drugs, such as sulfonylureas, glitazones, and insulin, although effective antihyperglycaemic agents, tend to induce weight gain. There is now an increasing recognition in people with obesity and diabetes that the focus should be on aiding weight loss, initially with improvements in diet and physical activity, possibly with the use of low-calorie diet programmes. Subsequent addition of metformin and newer agents, such as sodium-glucose transporter-2 inhibitors and glucagon-like peptide-1 analogues, will aid glucose control and weight reduction, and offer cardiovascular and renal protection. These drugs are now much higher in the therapeutic pathway in many national and international guidelines. Bariatric surgery may also be an effective way to manage hyperglycaemia or induce remission in individuals with both obesity and diabetes.

Improvement of time in range and glucose management indicator in Type 1 and Type 2 Diabetes Mellitus patients after introduction of continuous Glucose monitoring in internal medicine residency clinic

Continuous glucose monitoring (CGM)-derived time in range (TIR) correlates with Glucose management indicator(GMI) which correlates with hemoglobin A1c (HbA1c) among patients with type 1 and type 2 diabetes mellitus. Compare to HbA1c it has better correlation with glucose control, because HbA1c can be influenced by conditions like anemia, Chronic kidney disease, Cirrhosis of the liver etc. With our current project we wanted to introduce CGM not in specialized endocrine clinic, but in Internal medicine Residency clinic. The CGM team had 12 Internal Medicine and Transitional year Residents who were functioning under the supervision of Board Certified Endocrinologist who was a member of the clinic also. Twenty Five patients -85% with type 2 DM and 15% with type 1 DM on multiple injections of Insulin per day-3-4, self-monitored their blood Glucose(SMBG). They were given CGM- Dexcom G6 in the clinic. In the first 2- weeks after the switch the TIR of the blood glucose of the patients-70-180 mg/dl was 18%. Their average blood glucose was 286 mg/dl, GMI was 11.21%. During then first 2- weeks after initiation of CGM the patients were educated in length by our CGM team about their diet, physical activity, how to adjust their Insulin based on their blood glucose levels as well as how to treat the hypoglycemia. Members of the CGM team were contacting the patients twice a week to adjust patients treatment with Insulin and other per oral antidiabetic medications and or injectable – GLP1-RAG if needed after consultation with the Endocrinologist in the clinic based on the shared information between the clinic and the patients. Once a month the patients were seen in the clinic by member of the CGM team as well. The patients were followed for 2- years. After 3- months on CGM and followed for the 2 years thereafter the patients TIR improved from 18 % to 74%, GMI decreased from 11.21% to 7.04% and the average blood glucose decreased from 286 mg/dl to 158 mg/dl. There was also significant reduction of the hypoglycemia. Twenty percent of the patients were able to discontinue their Insulin and be treated only with oral antidiabetic medications plus/minus GLP1-RAG and have GMI less than 7%. We have showed that targeted TIR – above 70% which has been associated recently with diabetic micro and macrovascular complications in diabetic patients can be achieved not only in specialized endocrine clinics , but in Internal Medicine residency clinic and can be adopted by other Internal Medicine Residency programs in USA.

A correlation study of arterial stiffness, cardiac autonomic neuropathy and lipid profile in type 2 diabetes mellitus patients

Objectives: Micro and macrovasculopathy are common complications of undertreated or undiagnosed type 2 diabetes mellitus (T2DM) patients. One of the underlying factors of macrovasculopathy is arterial stiffness, which may lead to cardiovascular and cerebrovascular diseases. Understandably, diabetic micro and macrovasculopathy affect vital functions, which may affect the well-being of the individual. However, few studies have attempted to determine arterial stiffness, cardiac autonomic neuropathy (CAN) and lipid profile separately in South Asian population and examined its associations with T2DM. Moreover, there is a need to understand the mechanistic links among cardiovascular risk factors. This forms the basis of the present study. Materials and Methods: T2DM patients of 53–62 years and age- and gender-matched healthy control subjects were recruited in the cross-sectional and observational study (n = 30 each, eight women). Anthropometric measurements, physiological parameters such as resting heart rate, peripheral blood pressure (PBP), central blood pressure (CBP), augmentation index% (AIx%), brachial-ankle pulse wave velocity and lead II ECG for analysis of heart rate variability parameters were recorded after obtaining the consent of the study participants. The lipid profile and fasting blood glucose were also analysed. Results: Peripheral systolic blood pressure was significantly higher (P = 0.05) in T2DM patients. Dyslipidaemia was evident in T2DM patients. Atherogenic index of plasma (AIP) was also significantly higher in T2DM patients. Correlation analysis revealed a positive association between AIx% with PBP and CBP as well as between AIP index and central systolic blood pressure, serum triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels. AIP index was found to be negatively associated with HF (nu). Serum TG, high-density lipoprotein cholesterol (HDL-C) levels and AIP index have emerged as significant independent predictors of T2DM vasculopathy by multiple regression analysis. Conclusion: In the present study, atherogenic dyslipidaemia was observed in T2DM patients in combination with increased serum levels of TG, VLDL-C and decreased serum levels of HDL-C. Moreover, AIP index, a predictor cardiovascular risk, was found to be significantly higher in T2DM patients. Dyslipidaemia was found to be associated with dysregulation of autonomic nervous system in those patients. A positive association between noninvasive, surrogate markers of arterial stiffness with PBP and CBP indicates that enhanced arterial stiffness may elevate systemic arterial pressure. Therefore, early screening of T2DM patients for the estimation of serum lipid profile, arterial stiffness and cardiac autonomic neuropathy may be performed to unravel diabetic vasculopathy.

Therapeutic Potential of Clove Essential Oil in Diabetes: Modulation of Pro-Inflammatory Mediators, Oxidative Stress and Metabolic Enzyme Activities.

Type 1 diabetes is characterized by insulin deficiency due to the destruction of pancreatic β cells, leading to hyperglycemia, which in turn induces vascular complications. In the current study, we investigated the effect of intraperitoneal administration of clove essential oil (CEO: 20 mg/kg body weight) on certain oxidative stress and glucose metabolism enzymes, as well as the expression of proinflammatory mediators. Administration of CEO to diabetic rats showed a significant decline in blood glucose levels, total cholesterol, and xanthine oxidase, compared to the streptozotocin group. Furthermore, these treated rats elicited a notable attenuation in the levels of lipid peroxides, and thiols groups in both liver and brain tissues. The activities of antioxidant and metabolic enzymes were reverted to normality in diabetic upon CEO administration. In addition to its protective effects on red blood cell hemolysis, CEO is a potent α-amylase inhibitor with an IC50 =298.0±2.75 μg/mL. Also, treatment of diabetic rats with CEO significantly reduced the iNOS expression in the spleen. Our data showed that CEO has potential beneficial effects on diabetes, which can possibly prevent the pathogenesis of diabetic micro- and macrovascular complications.

High MBL-expressing genotypes are associated with deterioration in renal function in type 2 diabetes.

Accumulating evidence support that mannan-binding lectin (MBL) is a promising prognostic biomarker for risk-stratification of diabetic micro- and macrovascular complications. Serum MBL levels are predominately genetically determined and depend on MBL genotype. However, Type 1 diabetes (T1D) is associated with higher MBL serum levels for a given MBL genotype, but it remains unknown if this is also the case for patients with T2D. In this study, we evaluated the impact of MBL genotypes on renal function trajectories serum MBL levels and compared MBL genotypes in newly diagnosed patients with T2D with age- and sex-matched healthy individuals. Furthermore, we evaluated differences in parameters of insulin resistance within MBL genotypes. In a cross-sectional study, we included 100 patients who were recently diagnosed with T2D and 100 age- and sex-matched individuals. We measured serum MBL levels, MBL genotype, standard biochemistry, and DEXA, in all participants. A 5-year clinical follow-up study was conducted, followed by 12-year data on follow-up biochemistry and clinical status for the progression to micro- or macroalbuminuria for the patients with T2D. We found similar serum MBL levels and distribution of MBL genotypes between T2D patients and healthy individuals. The serum MBL level for a given MBL genotype did not differ between the groups neither at study entry nor at 5-year follow-up. We found that plasma creatinine increased more rapidly in patients with T2D with the high MBL expression genotype than with the medium/low MBL expression genotype over the 12-year follow-up period (p = 0.029). Serum MBL levels did not correlate with diabetes duration nor with HbA1c. Interestingly, serum MBL was inversely correlated with body fat percentage in individuals with high MBL expression genotypes both at study entry (p=0.0005) and 5-years follow-up (p=0.002). Contrary to T1D, T2D is not per se associated with increased MBL serum level for a given MBL genotype or with diabetes duration. Serum MBL was inversely correlated with body fat percentage, and T2D patients with the high MBL expression genotype presented with deterioration of renal function.

Cognitive Dysfunction and Diabetes

Diabetes mellitus and cognitive dysfunction are highly prevalent in the aging population. In the aging society, clinicians will be increasingly tasked with managing elderly patients who have both cognitive dysfunction and diabetes. A growing number of epidemiological and clinical studies confirmed that diabetes is associated with an increase in the risk of cognitive dysfunction and dementia. Cognitive dysfunction is of particular importance because it is associated with poor self-management ability, poor diabetes management with more frequent severe hypoglycemic episodes, and increased risk of cardiovascular morbidity and mortality. Current diabetes guidelines recommend screening for cognitive dysfunction in older and high-risk patients and providing individualized guidance for patients with cognitive dysfunction. Nonetheless, there is limited awareness among clinicians regarding this subject compared to other diabetic micro- and macrovascular complications. Recently, there has been increasing understanding in this field through multimodal neuroimaging and biomarkers for early detection of cognitive dysfunction in diabetes. In addition, new agents such as glucagon-like peptide 1 receptor agonists showed promising protective effects against cognitive dysfunction and dementia in patients with type 2 diabetes. In this review, we summarize the relationship between diabetes and cognitive dysfunction, especially dementia, and some contributing factors and pathogenesis of dementia in diabetes. We also review how anti-diabetic medications may influence cognitive dysfunction and clinical management guidance.

Fatty liver and atherogenic dyslipidemia have opposite effects on diabetic micro- and macrovascular disease

Background and aimsNon-alcoholic fatty liver (FL) is comorbid with obesity, metabolic syndrome and type 2 diabetes. Atherogenic dyslipidaemia (AD), frequent in FL, is associated with risk of micro- and macrovascular complications. Given the paradoxical ocular protection of FL in T2DM, we studied how FL modulates micro- and macrovascular complications as a function of AD. MethodsCross-sectional factorial analysis of 744 diabetic patients in whom FL, identified by ultrasonography, was present in 68%. AD, defined by low HDL-C plus elevated TG, was present in 45%. Four groups were analysed as regards cardiometabolic features, micro-/macroangiopathies, cataract and ocular hypertonia: FL[-]AD[-] (n = 171); FL[-]AD[+] (n = 66); FL[+]AD[-] (n = 235); and FL[+]AD[+] (n = 272). ResultsAge, gender and glycemic control were similar across groups. Prevalence of overall macroangiopathy and coronary artery disease were higher in patients with AD, irrespective of FL. Overall macroangiopathy was higher, by 64% in FL[-]AD[+] and by 38% in FL[+]AD[+]. Coronary artery disease was higher, by 128%, in FL[-]AD[+], and by 67%, in FL[+]AD[+]. (Micro)albuminuria was more frequent (+55%) in FL[-] AD[+] compared to FL[-] AD[-]. Retinopathy prevalence was 35% in FL[-], unaffected by AD. Retinopathy frequency was much lower in FL[+], irrespective of AD, decreased by −47% in FL[+]AD[-] and −32% in FL[+]AD[+] (vs. FL[-]AD[-]). Ocular hypertonia was present in 13%, and its prevalence was also markedly lower (−31%) in FL[+]. Cataract frequency was 29%, also lesser in FL[+] (24% vs. 39%), irrespective of AD. ConclusionsMulti-level eye protection in diabetes is linked to non-alcoholic fatty liver independently of atherogenic dyslipidemia.

Diabetic macrovascular complications of the lower extremities: Ultrasound dopplerography and morphological diagnostics

Background and Aims : The main cause of disability and mortality in patients with diabetes mellitus is late vascular complications, including diabetic micro- and macroangiopathy of the lower extremities. Timely diagnosis of and adequate treatment can prevent the development of diabetic foot syndrome. The aim of the work was to investigate the Doppler ultrasonographic manifestations and morphological changes of lower extremity vessels in patients with diabetes.

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy.

Diabetes mellitus (DM) is a frequent medical problem, affecting more than 4% of the population in most countries. In the context of diabetes, the vascular endothelium can play a crucial pathophysiological role. If a healthy endothelium—which is a dynamic endocrine organ with autocrine and paracrine activity—regulates vascular tone and permeability and assures a proper balance between coagulation and fibrinolysis, and vasodilation and vasoconstriction, then, in contrast, a dysfunctional endothelium has received increasing attention as a potential contributor to the pathogenesis of vascular disease in diabetes. Hyperglycemia is indicated to be the major causative factor in the development of endothelial dysfunction. Furthermore, many shreds of evidence suggest that the progression of insulin resistance in type 2 diabetes is parallel to the advancement of endothelial dysfunction in atherosclerosis. To present the state-of-the-art data regarding endothelial dysfunction in diabetic micro- and macroangiopathy, we constructed this literature review based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We interrogated five medical databases: Elsevier, PubMed, PMC, PEDro, and ISI Web of Science.

Update of Indoles: Promising molecules for ameliorating metabolic diseases.

Obesity and metabolic disorders have gradually become public health-threatening problems. The metabolic disorder is a cluster of complex metabolic abnormalities which are featured by dysfunction in glucose and lipid metabolism, and results from the increasing prevalence of visceral obesity. With the core driving factor of insulin resistance, metabolic disorder mainly includes type 2 diabetes mellitus (T2DM), micro and macro-vascular diseases, non-alcoholic fatty liver disease (NAFLD), dyslipidemia, and the dysfunction of gut microbiota. Strategies and therapeutic attention are demanded to decrease the high risk of metabolic diseases, from lifestyle changes to drug treatment, especially herbal medicines. Indole is a parent substance of numerous bioactive compounds, and itself can be produced by tryptophan catabolism to stimulate glucagon-like peptide-1 (GLP-1) secretion and inhibit the development of obesity. In addition, in heterocycles drug discovery, the indole scaffold is primarily found in natural compounds with versatile biological activity and plays a prominent role in drug molecules synthesis. In recent decades, plenty of natural or synthesized indole deriviatives have been investigated and elucidated to exert effects on regulating glucose hemeostasis and lipd metabolism. The aim of this review is to trace and emphasize the compounds containing indole scaffold that possess immense potency on preventing metabolic disorders, particularly T2DM, obesity and NAFLD, along with the underlying molecular mechanisms, therefore facilitate a better comprehension of their druggability and application in metabolic diseases.

Associations Between the Macular Microvasculatures and Subclinical Atherosclerosis in Patients With Type 2 Diabetes: An Optical Coherence Tomography Angiography Study.

ObjectiveTo investigate the associations between the macular microvasculature assessed by optical coherence tomography angiography (OCTA) and subclinical atherosclerosis in patients with type 2 diabetes.MethodsWe included patients with type 2 diabetes who received comprehensive medical and ophthalmic evaluations, such as carotid ultrasonography and OCTA at a hospital-based diabetic clinic in a consecutive manner. Among them, 254 eyes with neither diabetic macular edema (DME) nor history of ophthalmic treatment from 254 patients were included. The presence of increased carotid intima-media thickness (IMT) (>1.0 mm) or carotid plaque was defined as subclinical atherosclerosis. OCTA characteristics focused on foveal avascular zone (FAZ) related parameters and parafoveal vessel density (VD) were compared in terms of subclinical atherosclerosis, and risk factors for subclinical atherosclerosis were identified using a multivariate logistic regression analysis.ResultsSubclinical atherosclerosis was observed in 148 patients (58.3%). The subclinical atherosclerosis group were older (p < 0.001), had a greater portion of patients who were men (p = 0.001) and who had hypertension (p = 0.042), had longer diabetes duration (p = 0.014), and lower VD around FAZ (p = 0.010), and parafoveal VD (all p < 0.05). In the multivariate logistic regression analysis, older age (p ≤ 0.001), male sex (p ≤ 0.001), lower VD around FAZ (p = 0.043), lower parafoveal VD of both superficial capillary plexus (SCP) (p = 0.011), and deep capillary plexus (DCP) (p = 0.046) were significant factors for subclinical atherosclerosis.ConclusionThe decrease in VD around FAZ, and the VD loss in parafoveal area of both SCP and DCP were significantly associated with subclinical atherosclerosis in patients with type 2 diabetes, suggesting that common pathogenic mechanisms might predispose to diabetic micro- and macrovascular complications.

Effect of Structured Diabetes Education on Diabetic Angiopathies Among Kidney Transplant Recipients With Posttransplant Diabetes: Kuwait Experience

Diabetes knowledge among kidney transplant recipients with posttransplant diabetes has not been exhaustively assessed. Here, we evaluated the effects of structured diabetes education on development of diabetic micro- and macroangiopathies in kidney transplant patients with posttransplant diabetes. This prospective randomized controlled study categorized 210 renal transplant patients with posttransplant diabetes mellitus into 2:1 groups according to type of diabetes education. Group 1 (n = 140) received structured education, and group 2 (n = 70) received conventional education. Patient data were collected through patient identification and metabolic control parameter forms. Most patients in groups 1 and 2, respectively, were Kuwaiti (60.7% vs 58.6%), men (57.9% vs 68.6%), and had high school-level education (43.6% vs 48.6%). Chronic glomerulonephritis was the original disease in 36.4% versus 35.4% of patients. Most patients (72.8% vs 78.6% in group 1 vs 2) received pretransplant hemodialysis. At study start, the rate of patients with diabetic neuropathy was comparable between groups (32.4% vs 27.9%). Moreover, after completion of 24 months of education, neurological evaluation by electromyograph and nerve conduction studies did not show any significant differences between the groups (P > .05). Similarly, the number of patients with fundus imaging showing retinopathy was comparable between groups at start and end of study (P > .05). Although macroangiopathic events were higher in group 1, this finding was not significant (P > .05). However, although the percentage of patients with nephropathy was comparable in both groups at start of study, the percentage decreased significantly in group 1 at 24 months after completion of education compared with group 2 and baseline value (P = .016). Structured diabetes education was associated with reduced diabetic nephropathy but had no significant effects on other micro- or macroangiopathies. However, we recommend education for all kidney transplant recipients with diabetes.

The state of functional activity of neutrophils in patients with various variants of carbohydrate metabolism disorders who have had SARS-COV-2S infection

According to the Federal State Statistics Service of the Russian Federation, there has been a significant increase in the prevalence of prediabetes and type 2 diabetes mellitus (DM). Type 2 diabetes is characterized by frequent disability due to the progression of complications of diabetes and high mortality. Domestic and foreign authors have shown that neutrophils play an important role in the development of diabetic micro- and macroangiopathies. It has been shown that in DM, changes in the functional activity of neutrophils are observed, manifested in a decrease in chemotactic activity, changes in phagocytic activity, leukotriene production, and secretion of lysosomal enzymes. According to the results of previous studies, ambiguous data were obtained on the effect of high hyperglycemia in DM on the phagocytic activity of neutrophils. Thus, foreign authors have shown that in DM, when the target levels of glycemic control are not reached, the phagocytic activity of neutrophils is inhibited. Other researchers have found that with DM, activation of the phagocytic function of neutrophils is detected, but at the same time, the reaction of neutrophils to additional stimulation with latex (according to the results of the HCT test), a decrease in the expression of adhesion molecules on their surface and the ability to form extracellular traps occurs. Neutrophils, being the main cells of innate immunity, play an important role in the antiviral response. Patients with impaired carbohydrate metabolism are at high risk of severe course and unfavorable outcome of SARS-CoV-2 infection. The course and outcome of an infectious disease depends on how the effector functions of neutrophils are realized. The aim of the study was to study the features of the functional activity of neutrophils in patients with various variants of carbohydrate metabolism disorders who had SARS-CoV-2 infection. The study included 20 patients with impaired carbohydrate metabolism who had suffered SARS-CoV-2 infection, the control group included 15 clinically healthy volunteers. In all groups, the phagocytic activity of latex particles with a diameter of 1.7 microns was evaluated by neutrophils (phagocytosis activity, phagocytosis intensity, phagocytic number); spontaneous and induced NBT activity of neutrophils by morphological method. A significant increase in the absorption capacity of peripheral blood neutrophils, an increase in the phagocytic activity of leukocytes in the group of patients with impaired carbohydrate metabolism was revealed. A simultaneous increase in the indicators of spontaneous and induced HCT tests was found in the group of patients with impaired glucose tolerance and in the group of patients with type 2 diabetes mellitus. The observed disorders in the phagocytic link are an important factor in reducing the overall immunoreactivity of patients, which determines the long rehabilitation period. Identifying the features of innate immunity in patients with various variants of carbohydrate metabolism disorders who have suffered from SARS-CoV-2 infection will further help develop an individual strategy for the prevention and treatment of these diseases.

A systematic review of preclinical animal studies on fenofibrate’s potential role in type 1 diabetic micro-vascular complications

Fenofibrate is a peroxisome-proliferator-activator α agonist and it is a widely used drug for hyperlipidemia since its approval in 2004. So, in this review we are focusing on the effect of fenofibric acid’s mechanism to alleviate type 1 diabetic micro vascular complications like diabetic retinopathy, diabetic cardiomyopathy in animal models, since the drug is safe, efficacious and more economical when compared with the currently available treatment strategies for juvenile diabetic complications and also a profound observation is needed due to the rarity of research in these therapeutic areas. Important preclinical animal studies published from January 2001 to June 2020 were recognised from databases like PubMed and Cochrane central register of controlled trials. Reviewers screened the articles based on the selection criteria and risk of bias was determined using Systematic Review Centre for Laboratory animal Experimentation risk of bias tool for animal studies. Our literature search yielded a total of 5 studies and after pooling up the data from the 5 preclinical studies, we found that Fenofibrate have the efficacy to prevent type 1 diabetic complications, chiefly diabetic retinopathy and those mechanisms are dependent on peroxisome-proliferator-activator and fibroblast growth factor-21 pathways. Fenofibrate is a well safe and moreover, cost effective medication in preventing type 1 diabetic micro vascular complications especially diabetic retinopathy and also in maintaining the glucose homeostasis in apart from its anti-dyslipidemic effect.

Epidemiological Aspects of Diabetic Retinopathy at the Center of the Application of the Diploma of Specialised Studies in Ophthalmology (Cadeso)/Donka-Conakry

Purpose: The authors analyzed the epidemiological and clinical aspects of diabetic retinopathy at the Center for the Application of the Specialized Studies Diploma in Ophthalmology, Gamal Abdel Nasser University (CHU/ Donka) Conakry. Diabetic retinopathy (eye damage: eye and retina) is a serious complication of diabetes that affects 50% of type 2 diabetic patients. The eyes are particularly sensitive to damage to a small vessel. Diabetic retinopathy (DR) is the retinal localization of diabetic micro angiopathy resulting in impaired blood flow in the affected territories, the consequences of which will determine the clinical manifestations of the disease. DR is the leading cause of vision loss in adults of working age. Patients and Methods: This is a longitudinal prospective study carried out at CADES/O concerning 198 diabetic patients. The selection criteria were that the media be transparent and the fundus accessible over a period of six months from February to July 2018. Results: A total of 73 patients (37%) presented with diabetic retinopathy with an average age of 49.5 +/− 9 years. The sex ratio (M/F) was 0.6 with a female predominance of 59%. Liberal profession patients were the most numerous 47.5%. Type 2 diabetes was the most common (85.86%). Diabetes fundus assessment was the most common reason for consultation (52%). Arterial hypertension was the most incriminated risk factor (45.45%) followed by the poor balance of diabetes (40.90%), and the age of diabetes (28.28%). 9.5% had diabetic retinopathy complicated by rubella iris, neovascular glaucoma and retinal detachment. Conclusion: Diabetic retinopathy is a common condition for which early detection and regular monitoring must be the rule to prevent, slow down or avoids irreversible blindness if possible, induced by this pathology by a good balance of diabetes and good control of associated risk factors.

Do diabetic complications influence cancer-related events in people with type 2 diabetes? A cohort approach

AimTo investigate whether diabetic micro- and macrovascular complications (mMVC) influence cancer-related events in people with type 2 diabetes. MethodsPeople with type 2 diabetes from the SURDIAGENE cohort were characterized (duration of diabetes, HbA1c, mMVC, history of cancer) and prospectively followed-up for death and cancer-related events (occurrence, dissemination and cancer-related death). ResultsBetween 2002 and 2012, 1468 participants (58% men, mean age 64.8 ± 10.7 years, mean duration of diabetes 14.5 ± 9.9 years at baseline) were enrolled. At baseline, 119 (8%) had a personal history of cancer. Incident cancer occurred in 207 (14%) patients during a mean follow-up of 7.3 ± 3.7 years and was associated with older age, smoking status and personal history of cancer. mMVC were not associated with cancer-related events, considering cancer occurrence, node/metastasis dissemination and cancer-specific death. Risk of all-cause mortality was increased in diabetic patients cumulating cancer history and mMVC (HR 1.73, 95%CI 1.25-2.38) compared to those with neither cancer nor mMVC. In our cohort, cancer-related death was not associated with mMVC (HR 1.05, 95%CI 0.67-1.64), but conversely history of cancer was significantly associated with cardiovascular-related death (HR 2.41, 95%CI 1.36-4.26). ConclusionIn our cohort, mMVC were not associated with cancer-related events, while history of cancer was significantly associated with cardiovascular death.