Mechanisms of Diabetic Complications

2013 ◽  
Vol 93 (1) ◽  
pp. 137-188 ◽  
Author(s):  
Josephine M. Forbes ◽  
Mark E. Cooper
Keyword(s):  
Diabetic Complications ◽  
Filtration Rate ◽  
Microvascular Complications ◽  
Disease Process ◽  
Underlying Disease ◽  
Heart Attacks ◽  
Current Therapies ◽  
Per Se

It is increasingly apparent that not only is a cure for the current worldwide diabetes epidemic required, but also for its major complications, affecting both small and large blood vessels. These complications occur in the majority of individuals with both type 1 and type 2 diabetes. Among the most prevalent microvascular complications are kidney disease, blindness, and amputations, with current therapies only slowing disease progression. Impaired kidney function, exhibited as a reduced glomerular filtration rate, is also a major risk factor for macrovascular complications, such as heart attacks and strokes. There have been a large number of new therapies tested in clinical trials for diabetic complications, with, in general, rather disappointing results. Indeed, it remains to be fully defined as to which pathways in diabetic complications are essentially protective rather than pathological, in terms of their effects on the underlying disease process. Furthermore, seemingly independent pathways are also showing significant interactions with each other to exacerbate pathology. Interestingly, some of these pathways may not only play key roles in complications but also in the development of diabetes per se. This review aims to comprehensively discuss the well validated, as well as putative mechanisms involved in the development of diabetic complications. In addition, new fields of research, which warrant further investigation as potential therapeutic targets of the future, will be highlighted.

scholarly journals The role of epigenetics in the pathology of diabetic complications

2010 ◽  
Vol 299 (1) ◽  
pp. F14-F25 ◽  
Author(s):  
Louisa M. Villeneuve ◽  
Rama Natarajan
Keyword(s):  
Diabetic Complications ◽  
Animal Studies ◽  
Microvascular Complications ◽  
Treatment Options ◽  
Metabolic Memory ◽  
Epigenetic Changes ◽  
Methylation Patterns

Diabetes is associated with significantly accelerated rates of several debilitating microvascular complications such as nephropathy, retinopathy, and neuropathy, and macrovascular complications such as atherosclerosis and stroke. While several studies have been devoted to the evaluation of genetic factors related to type 1 and type 2 diabetes and associated complications, much less is known about epigenetic changes that occur without alterations in the DNA sequence. Environmental factors and nutrition have been implicated in diabetes and can also affect epigenetic states. Exciting research has shown that epigenetic changes in chromatin can affect gene transcription in response to environmental stimuli, and changes in key chromatin histone methylation patterns have been noted under diabetic conditions. Reports also suggest that epigenetics may be involved in the phenomenon of metabolic memory observed in clinic trials and animal studies. Further exploration into epigenetic mechanisms can yield new insights into the pathogenesis of diabetes and its complications and uncover potential therapeutic targets and treatment options to prevent the continued development of diabetic complications even after glucose control has been achieved.

Structure of concomitant somatic pathology in patients different age groups before ophthalmic surgery

2021 ◽  
pp. 182-185
Author(s):  
M.A. Esina ◽  
◽  
E.E. Filimonova ◽  
L.V. Pavlyushchenko ◽  
◽  
...  
Keyword(s):  
Age Groups ◽  
State Institution ◽  
Federal State ◽  
Ophthalmic Surgery ◽  
Cerebrovascular Accidents ◽  
Heart Attacks ◽  
Preoperative Stage ◽  
Stage 1

Purpose. Analysis of structure somatic pathology in patients different age groups before planned ophthalmic surgery. Material and methods. Analyzed 1200 medical records patients previously operated in the Khabarovsk branch of the S. Fyodorov Eye Microsurgery Federal State Institution, 3 age groups were formed. The 1st group included 11 patients under age of 40 years (0.9%), the 2nd group – 234 patients from 41 to 60 years (19.5%), the 3rd group – 955 patients over 60 years (79.6%). In each of the groups, the frequency and structure of concomitant somatic pathology, the degree of its compensation were studied. Results. In the 1st group, 54.5% of patients were somatically healthy, 45.5% had a pathology, represented mainly by stage 1 hypertension and type 1 diabetes. All of them were compensated, there were no difficulties in preparing for the operation in this group. In the 2nd group, 90.2% of patients had somatic pathology. The leading positions were occupied by hypertension and type 2 diabetes, the respiratory system pathologies, rheumatic diseases and the carriage of chronic hepatitis B and C viruses were added. Treatment correction at the preoperative stage was required for 2 patients (0.9%), after which the patients were operated. In 3rd group, 100% of patients had somatic pathology. Its structure did not differ much from the 2nd group, but there were also complications such as heart attacks, acute cerebrovascular accidents, complicated diabetes. Correction of therapy was carried out in 61 people (6.4%), 60 of them were successfully operated, one did not appear for hospitalization. Conclusion. Somatic burden increased and degree of compensation for diseases decreased with increasing age of patients. Successful operations are facilitated by individual approach to patient, taking into account the existing pathology and preoperative preparation. Key words: patient's age, somatic burden, hypertension, diabetes mellitus, compensation.

scholarly journals Differential effects of minocycline on microvascular complications in murine models of type 1 and type 2 diabetes

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Stephanie A. Eid ◽  
Phillipe D. O’Brien ◽  
Lucy M. Hinder ◽  
John M. Hayes ◽  
Faye E. Mendelson ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Microvascular Complications ◽  
Murine Models ◽  
Differential Effects

Clinical profile and incidence of microvascular complications of childhood and adolescent onset type 1 and type 2 diabetes seen at a tertiary diabetes center in India

2020 ◽  
Author(s):  
Anandakumar Amutha ◽  
Unnikrishnan Ranjit ◽  
Ranjit Mohan Anjana ◽  
Coimbatore Subramaniam Shanthi R. ◽  
Ramachandran Rajalakshmi ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Microvascular Complications ◽  
Clinical Profile ◽  
Onset Type ◽  
Diabetes Center

scholarly journals Declining trends of diabetic nephropathy, retinopathy and neuropathy with improving diabetes care indicators in Japanese patients with type 2 and type 1 diabetes (JDDM 46)

2018 ◽  
Vol 6 (1) ◽  
pp. e000521 ◽  
Author(s):  
Hiroki Yokoyama ◽  
Shin-ichi Araki ◽  
Koichi Kawai ◽  
Katsuya Yamazaki ◽  
Osamu Tomonaga ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Chronic Kidney Disease ◽  
Type 1 Diabetes ◽  
Kidney Disease ◽  
Diabetes Care ◽  
Microvascular Complications ◽  
Treatment Target ◽  
Younger Patients

ObjectiveWe examined changes in prevalence of diabetic microvascular/macrovascular complications and diabetes care indicators for adults in Japan with type 2 and type 1 diabetes over one decade.Research design and methodsTwo independent cohorts were recruited with the same inclusion criteria in 2004 (cohort 1: 3319 with type 2 and 286 with type 1 diabetes) and in 2014 (cohort 2: 3932 with type 2 and 308 with type 1 diabetes). Prevalence of complications and care indicators including achieving treatment targets for glycemia, blood pressure, lipid control, body mass index (BMI), and smoking were compared. In addition, patients in cohort 1 were re-examined in 2014 and their data were compared with the baseline data of each cohort.ResultsIn type 2 diabetes, the prevalence of nephropathy, retinopathy, neuropathy, chronic kidney disease, current smoking and stroke significantly decreased, with improvements in achieving treatment target rates in cohort 2 two as compared with cohort 1. In type 1 diabetes, the prevalence of nephropathy, retinopathy, chronic kidney disease, and hemoglobin A1Cvalues significantly decreased. Decreases in prevalence of microvascular complications in type 2 diabetes were similarly found in each age-matched and sex-matched group, whereas younger patients exhibited marked increase in BMI and lower treatment target achieving rates compared with elderly patients. Regarding normoalbuminuric renal impairment, only a slight increase in the prevalence was observed both in type 2 and type 1 diabetes. In cohort 1, re-examined in 2014, care indicators were significantly improved from 2004, while complications increased with getting 10 years older.ConclusionsWe observed declining trends of diabetic microvascular complications with improvement in diabetes care indicators in type 2 and type 1 diabetes. Younger patients with type 2 diabetes exhibited marked increase in BMI and lower rates of achieving treatment targets compared with elderly patients, which remains a concern.

A Review of Pramlintide in the Management of Diabetes

2009 ◽  
Vol 1 ◽  
pp. CMT.S2369
Author(s):  
Caroline Messer ◽  
Dina Green
Keyword(s):  
Microvascular Complications ◽  
Effective Means ◽  
Postprandial Glucose ◽  
Tight Glycemic Control ◽  
Minimal Risk ◽  
Patients With Diabetes ◽  
Insulin Dependent

Tight glycemic control in type 1 and type 2 diabetes reduces the risk for microvascular complications, including retinopathy, nephropathy, and neuropathy. Yet, despite intensive insulin regimens, many insulin-dependent patients are unable to achieve euglycemic states. This review will focus on pramlintide, an equipotent amylin analog, and its role in the management of diabetes. Pramlintide lowers glucose through the same mechanisms as amylin: it slows gastric emptying, suppresses the postprandial rise of glucagon in patients with diabetes, and promotes satiety. Long-term clinical trials have shown that the use of pramlintide as an adjunct to insulin minimizes postprandial glucose excursions and reduces both HbA1C and body weight when compared to placebo. Although its effects on HbA1C are modest, pramlintide has gained popularity as a result of its relatively few contraindications, limited side effects, minimal risk for hypoglycemia, and potential for weight loss. The combination of insulin and pramlintide may provide an effective means for patients with diabetes to meet their HbA1C goals.

Genetic Polymorphisms of Antioxidant and Antiglycation Enzymes and Diabetic Complications. How Much Can we Learn from the Genes?

2017 ◽  
Vol 126 (01) ◽  
pp. 7-13
Author(s):  
Dimitrios Oikonomou ◽  
Jan Benedikt Groener ◽  
Ruan Cheko ◽  
Zoltan Kender ◽  
Lars Kihm ◽  
...  
Keyword(s):  
Diabetic Complications ◽  
Diabetes Mellitus Type 1 ◽  
Diabetic Complication ◽  
Clinical Use ◽  
Oxygen Species ◽  
Patients With Diabetes ◽  
Genetically Determined ◽  
Novel Therapeutic

AbstractThere is growing evidence that reactive metabolites, such as reactive oxygen species and dicarbonyls contribute to diabetic complications. Formation, accumulation, and detoxification of these metabolites are controlled by several enzymes, some of which have genetically determined levels of expression or function. This review not only gives an overview of the different SNPs studied in patients with diabetes mellitus type 1 and type 2, but in addition attempts to bridge the gap between a genetic study and clinical use. Therefore, not only the results of the studies are reviewed, but also their use in identification of subgroups where an increased or decreased risk for a diabetic complication is described, as well as their use in developing novel therapeutic options based on understanding the contribution of an enzyme to a given complication.

scholarly journals Comparison of Glomerular Filtration Rate Estimation from Serum Creatinine and Cystatin C in HNF1A-MODY and Other Types of Diabetes

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Magdalena Szopa ◽  
Maria Kapusta ◽  
Bartlomiej Matejko ◽  
Tomasz Klupa ◽  
Teresa Koblik ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Glomerular Filtration Rate ◽  
Serum Creatinine ◽  
Glomerular Filtration ◽  
Cystatin C ◽  
Filtration Rate ◽  
Glomerular Filtration Rate Estimation ◽  
Measured Gfr

Introduction. We previously showed that in HNF1A-MODY the cystatin C-based glomerular filtration rate (GFR) estimate is higher than the creatinine-based estimate. Currently, we aimed to replicate this finding and verify its clinical significance. Methods. The study included 72 patients with HNF1A-MODY, 72 with GCK-MODY, 53 with type 1 diabetes (T1DM), 70 with type 2 diabetes (T2DM), and 65 controls. Serum creatinine and cystatin C levels were measured. GFR was calculated from creatinine and cystatin C using the CKD-EPI creatinine equation (eGRF-cr) and CKD-EPI cystatin C equation (eGFR-cys), respectively. Results. Cystatin C levels were lower (p<0.001) in the control (0.70±0.13 mg/L), HNF1A (0.75±0.21), and GCK (0.72±0.16 mg/L) groups in comparison to those with either T1DM (0.87±0.15 mg/L) or T2DM (0.9±0.23 mg/L). Moreover, eGFR-cys was higher than eGRF-cr in HNF1A-MODY, GCK-MODY, and the controls (p=0.004; p=0.003; p<0.0001). This corresponded to 8.9 mL/min/1.73 m2, 9.7 mL/min/1.73 m2, and 16.9 mL/min/1.73 m2 of difference. Additionally, T1DM patients had higher eGFR-cr than eGFR-cys (11.6 mL/min/1.73 m2; p=0.0004); no difference occurred in T2DM (p=0.91). Conclusions. We confirmed that eGFR-cys values in HNF1A-MODY patients are higher compared to eGFR-cr. Some other differences were also described in diabetic groups. However, none of them appears to be clinically relevant.

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