Long-term Complications Of Type Research Articles

Long-term complications of type 1 diabetes

Long-term complications of type 1 diabetes

The urgency to treat optimally and to target: Avoiding long-term complications in type 2 diabetes with a focus on GLP-1 receptor agonists

The wave of diabetes continues to increase in Canada and around the world. According to national data, 3.4 million Canadians were living with diabetes (type 1 and type 2 combined) in 2017–2018, compared to 1.3 million in 2000–2001. It is well-accepted that diabetes is a major cause of death and is the leading cause of renal failure, lower limb amputations and blindness in adults.

Relationships Between the Cumulative Incidences of Long-term Complications in Type 1 Diabetes: The DCCT/EDIC Study.

To describe the relationships between the cumulative incidences of long-term complications in individuals with type 1 diabetes (T1D) and assess whether observed associations are independent of age, duration of diabetes, and glycemic levels. Proliferative diabetic retinopathy (PDR), clinically significant macular edema (CSME), reduced estimated glomerular filtration rate (eGFR), amputations, cardiovascular disease (CVD), and mortality were assessed in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study over ∼30 years. The cumulative incidence of complications ranged from 3% (amputations) to 37% (CSME). There were large differences in the cumulative incidence of PDR between participants with versus without prior CSME (66% vs. 15%), reduced eGFR (59% vs. 29%), and amputation (68% vs. 32%); reduced eGFR with or without prior PDR (25% vs. 9%), amputation (48% vs. 13%), and CVD (30% vs. 11%); CVD with or without prior reduced eGFR (37% vs. 14%) and amputation (50% vs. 16%); and mortality with or without prior reduced eGFR (22% vs. 9%), amputation (35% vs. 8%), and CVD (25% vs. 8%). Adjusted for age, duration of T1D, and mean updated HbA1c, the complications and associations with higher risk included PDR with CSME (hazard ratio [HR] 1.88; 95% CI 1.42, 2.50), reduced eGFR (HR 1.41; 95% CI 1.01, 1.97), and CVD (HR 1.43; 95% CI 1.06, 1.92); CSME with higher risk of PDR (HR 3.94; 95% CI 3.18 4.89), reduced eGFR (HR 1.49; 95% CI 1.10, 2.01), and CVD (HR 1.35; 95% CI 1.03, 1.78); reduced eGFR with higher risk of CVD (HR 2.09; 95% CI 1.44, 3.03), and death (HR 3.40; 95% CI 2.35, 4.92); amputation(s) with death (HR 2.97; 95% CI 1.70, 2.90); and CVD with reduced eGFR (HR 1.59; 95% CI 1.08, 2.34) and death (HR 1.95; 95% CI 1.32, 2.90). Long-term micro- and macrovascular complications and mortality are highly correlated. Age, diabetes duration, and glycemic levels do not completely explain these associations.

PSUN200 Effect of carbohydrate counting education in children and adolescents with type I diabetes

Abstract Background The achievement and maintenance of normoglycemia is one of the most important goals to prevent both short and long-term complications in type 1 diabetes mellitus (T1DM). As carbohydrate acts as the primary macronutrient affecting postprandial glycemic response, carbohydrate counting is crucial in adjusting prandial insulin doses to preserve postprandial blood glucose within normal limits. The purpose of this study is to evaluate the effect of carbohydrate counting education in children and adolescents with T1DM. Method: A retrospective chart review of 128 diagnosed T1DM patients who underwent carbohydrate counting education was conducted. All subjects were diagnosed with T1DM before December 2019, and were educated carbohydrate counting before December 2020 in pediatric endocrinology, Severance Children's Hospital, Seoul, Korea. We analyzed the data including clinical characteristics, education on carbohydrate counting, and glycated hemoglobin A1c (HbA1c) levels. Results In 128 T1DM subjects educated, 48 (38%) were male. Their mean age at diagnosis was 8.6 ± 4.0 (years) and mean age at the time of education was 22.6 ± 7.8 (years). Overall, HbA1c levels at 3, 6, and 12 months after education showed a significant decrease compared to the baseline. The mean ±SD(standard deviation) HbA1c level, which was 8.8 ±1.9 (%) at the baseline, decreased to 8.3 ±1.7 at 3 months, 8.3 ±1.7 at 6 months, and 8.3 ±1.7 at 12 months after education. In multivariate linear regression analyses, only the value of baseline HbA1c (P<0.001) as an indicator of DM management was significantly correlated with decrease in HbA1c. Conclusions In our study, carbohydrate counting education seems effective in glycemic control in patients with type 1 diabetes mellitus, but the decrease in HbA1c seems not enough. The effect of education differs according to the degree of glycemic management. For patients with poor management, providing proper education of carbohydrate counting can make improvement in glycemic control. For well-managed patients, more advanced approach beyond traditional education appears to be required. With proper education, better blood glucose control can be expected to reduce complications and improve quality of life in T1DM patients. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Omic characterization of the endothelial model mimicking glucose variability

Background and Aims : Glycemic variability (GV), a complex phenomenon affecting subjects with diabetes, is one of the main contributors to the risk to develop both acute and long-term complications in type 1 (T1D) and type 2 (T2D) subjects. The characteristic cellular phenotype induced by GV is scarcely defined. Aims of this study are: 1) to describe a global pattern about the regulation of the major proteins differentially expressed in a cellular (human endothelial cells) model of GV and 2) the role of microRNAs on the pathways activated during the in-vitrolong-term exposures to GV.

Physiologic Insulin Resensitization as a Treatment Modality for Insulin Resistance Pathophysiology.

Prevalence of type 2 diabetes increased from 2.5% of the US population in 1990 to 10.5% in 2018. This creates a major public health problem, due to increases in long-term complications of diabetes, including neuropathy, retinopathy, nephropathy, skin ulcers, amputations, and atherosclerotic cardiovascular disease. In this review, we evaluated the scientific basis that supports the use of physiologic insulin resensitization. Insulin resistance is the primary cause of type 2 diabetes. Insulin resistance leads to increasing insulin secretion, leading to beta-cell exhaustion or burnout. This triggers a cascade leading to islet cell destruction and the long-term complications of type 2 diabetes. Concurrent with insulin resistance, the regular bursts of insulin from the pancreas become irregular. This has been treated by the precise administration of insulin more physiologically. There is consistent evidence that this treatment modality can reverse the diabetes-associated complications of neuropathy, diabetic ulcers, nephropathy, and retinopathy, and that it lowers HbA1c. In conclusion, physiologic insulin resensitization has a persuasive scientific basis, significant treatment potential, and likely cost benefits.

Impact of a history of gestational diabetes on long-term complications of type 2 diabetes

Patients with gestational diabetes mellitus (GDM) have a higher risk of developing type 2 diabetes mellitus (T2DM) as well as cardiovascular disease regardless of progression to T2DM. Prior studies have also demonstrated that patients with GDM who develop T2DM may be at an increased risk of microvascular complications, although actual event rates are low and long-term follow up is lacking. This study aims to examine whether a history of GDM predicts more severe long-term complications of T2DM.

ROLE OF TLR2, TLR4 GENE POLYMORPHISM IN DEVELOPING MICROVASCULAR COMPLICATIONS IN ADOLESCENTS WITH TYPE 1 DIABETES MELLITUS

Long-term complications of type 1 diabetes mellitus (T1DM) in children and adolescents are an important problem in modern medicine. Recently, the role of immune mechanisms, in particular, chronic inflammation, in the development of both T1DM and its microvascular complications has been actively discussed. Activation of Toll-like receptor 2 (TLR2) and Toll-like receptor 4 (TLR4) leads to hyperproduction of proinflammatory cytokines, chemokines, adhesion molecules involved in the formation of diabetic microvascular complications. At the same time, TLR2 and TLR4 gene polymorphism alters the immune susceptibility to the endogenous ligands, which may increase the risk of diabetic microangiopathies. The aim of this study is to evaluate the frequency of genotypes and alleles of TLR2 and TLR4 genes distribution and to determine the content of TNFα, IL-1, VCAM-1, fractalkine, endothelin-1 in adolescents with T1DM with microvascular complications. We examined 139 adolescents with T1DM from 14 to 18 years old and 56 healthy teenagers. Patients with T1DM were divided into two groups: Group I – patients with poor glycemic control (HbA1C > 9.0%), (n = 64); Group II – patients with satisfactory glycemic control of T1DM (HbA1C ≤ 9.0%), (n = 75), including adolescents with optimal (HbA1C < 7.5%) and suboptimal glycemic control (7.5% ≤ HbA1C ≤ 9.0%) (ISPAD clinical practice consensus guidelines 2014). According to the presence of microvascular complications, the groups were subdivided into subgroups: Iа (n = 49), IIа (n = 38) – adolescents with verified microvascular disorders: diabetic retinopathy, nephropathy and neuropathy; Ib (n = 15), IIb (n = 37) – without microvascular complications. Allelic variants of TLR genes were determined using test systems GosNII genetics (Moscow). The content of cytokines in blood serum was carried out by the method of enzyme-linked immunosorbent assay “BIOSCIENCE”. Data were analyzed using software packages Statistica version 6.0. The assessment of TLR2 (Arg753Gln) and TLR4 (Thr399Ile) polymorphism distribution did not reveal significant differences between the observed subgroups and the control. In Ia and IIa subgroups (with complications) Asp299Gly variant was noted to be significantly less common when compared to subgroups Ib, IIb and controls. The presence of Gly allele in TLR4 gene was found to disrupt the expression of TNFα and VCAM-1 and can be considered protective for the development of microvascular complications.

Do Long-Term Complications of Type 2 Diabetes Increase Susceptibility to Geriatric Syndromes in Older Adults?

Background and Objectives: Type 2 diabetes is one of the common chronic diseases in the elderly. It is thought that long-term complications of type 2 diabetes will negatively affect the quality of life in elderly individuals. It is possible that geriatric syndromes, especially frailty syndrome, are associated with diabetic complications, too. In this study, we aimed to evaluate the effect of macrovascular and microvascular complications of type 2 diabetes on frailty and other geriatric syndromes. In addition, the effect of these complications on quality of life was also reviewed. Materials and Methods: We conducted a cross-sectional study for four months. Comprehensive geriatric assessment tests were done on all patients. The Fried frailty index (FFI) was used for the evaluation of frailty syndrome. We assessed malnutrition by mini nutritional assessment short-form (MNA-SF), and Global Leadership Initiative on Malnutrition criteria (GLIM). The EWGSOP 2 criteria were used for the diagnosis of sarcopenia. Quality of life (QoL) was evaluated using the short form-36 (SF-36) questionnaire. Data analysis was done by SPSS version 22. Results: 237 females and 142 males with a mean age of 71.7 ± 6.1 years were included in the study. The frequency of macrovascular and microvascular complications was 41.4% and 68.1%, respectively. Frailty was found to be associated with macrovascular complications (p = 0.003). Handgrip strength, skeletal muscle mass index, and gait speed were decreased in the presence of macrovascular complications (p = 0.043, p < 0.001, p < 0.001). QoL was also decreased in patients with macrovascular complications (p = 0.003). Nutritional status and handgrip strength were negatively affected in patients with diabetic neuropathy (p = 0.019, p = 0.014). Polypharmacy was also found to be associated with macrovascular complications (p < 0.001, p < 0.001). Macrovascular complications were 2.5 times more common in malnourished patients according to GLIM and 3.2 times more common in patients with decreased gait speed. Conclusion: In this study, we observed that both macrovascular and microvascular complications of diabetes increase susceptibility to geriatric syndromes in elderly individuals. It could be useful to conduct prospective studies in which we can compare the effectiveness of treatment methods on this subject.

Long-term complications of type 1 diabetes: what do we know and what do we need to understand?

Long-term complications of type 1 diabetes (T1D) include microvascular complications and macrovascular disease. Despite the important advances in the treatment of T1D of the last decades, these complications still represent the leading cause of morbidity and mortality in patients with T1D. Extensive evidence indicates that structural and functional alterations of the kidney, retina, nerves and large arteries occur already in the first years after the onset of diabetes. We performed a comprehensive review of the available evidence on screening, diagnosis, prevention and treatment of vascular complications of T1D. In particular, we focused on three major challenges related to long-term complications of T1D: 1) finding of new biomarkers and diagnostic methods able to identify early signs of complications; 2) identifying specific risk factors for the development of these complications; 3) identifying and implementing new therapeutic strategies able to prevent the development and progression of vascular complications.

Poor Glycemic Control and the Contributing Factors Among Type 2 Diabetes Mellitus Patients Attending Outpatient Diabetes Clinic at Mbarara Regional Referral Hospital, Uganda

BackgroundGlycemic control is associated with long-term complications in type 2 diabetes management. However, updated reports on glycemic control that are crucial to reducing diabetes mellitus complications remain scarce.ObjectiveThe objective of this study is to evaluate glycemic control and contributing factors among type 2 diabetes mellhitus patients attending the outpatient diabetic clinic at Mbarara Regional Referral Hospital.MethodsA cross-sectional study was conducted at Mbarara Regional Referral Hospital outpatient diabetes clinic between July and October 2020. Participants were subjected to a questionnaire-based interview and glycosylated hemoglobin (HbA1C) was determined as a marker of glycemic control among participants. The collected data was entered into and analyzed by Stata version 13. The odds ratio was used to determine the strength of association between variables. The cut-off value for all statistical significance tests was set at p<0.05 with CI of 95%.ResultsA total of 223 participants were interviewed, and the majority (188, 84.3%) had poor glycemic control (HbA1C ≥7%). Importantly, 81.7% (49/60) and 90.0% (99/110) of those who did not adhere to diet and physical exercise recommendations respectively, had poor glycemic control. Multivariate logistic regression revealed that poor glycemic control was more prevalent among participants aged 25–60 years (AOR=4.48, 95%CI: 1.56–14.50, p-value=0.009) and those aged above 60 years (AOR=4.28, 95%CI: 1.18–15.58, p-value= 0.03) compared to the youth, 18–24 years of age.ConclusionThe prevalence of poor glycemic control among type 2 diabetes patients in this study is high and patient’s age was identified to be an independent risk factor. We recommend any intervention by the hospital that promotes diabetes education and optimizes lifestyle and medication adherence; ultimately to achieve good glycemic control especially for adult patients.

Serum Anti-Collagen IV IgM and IgG Antibodies as Indicators of Low Vascular Turnover of Collagen IV in Patients with Long-Term Complications of Type 2 Diabetes.

Thickening of the vascular basement membrane (BM) is a fundamental structural change in the small blood vessels in diabetes. Collagen type IV (CIV) is a major component of the BMs, and monitoring the turnover of this protein in type 2 diabetes (T2D) can provide important information about the mechanisms of vascular damage. The aim of the study was through the use of non-invasive biomarkers of CIV (autoantibodies, derivative peptides, and immune complexes) to investigate vascular turnover of CIV in patients with long-term complications of T2D. We measured serum levels of these biomarkers in 59 T2D patients with micro- and/or macrovascular complications and 20 healthy controls using an ELISA. Matrix metalloproteinases-2 and -9 (MMP-2 and MMP-9) were also tested. In the T2D group, significantly lower levels of CIV markers and significantly higher levels of MMP-2 and MMP-9 were found compared to controls. A significant positive correlation was found between IgM antibody levels against CIV and MMP-2. These findings suggest that vascular metabolism of CIV is decreased in T2D with long-term complications and show that a positive linear relationship exists between MMP-2 levels and CIV turnover in the vascular wall.

Insulin pump therapy

Intensive insulin therapy is the mainstay of diabetes care as it prevents or delays the long term complications of Type 1 diabetes mellitus. Insulin pump therapy can deliver improved diabetes control and at the same time reduce the number and serious nature of any hypoglycaemic episodes. The therapy is not associated with an increased risk of diabetic ketoacidosis. Pump therapy should follow National Institute for Health and Care Excellence Guidelines and be instigated and supported by teams experienced in insulin pump therapy, with skills and competences to ensure sustained positive outcomes. Continuous glucose monitoring further improves blood glucose control providing continuous feedback with warnings of rapid changes in glucose and/or attainment of high or low glucose concentrations. Continuous glucose monitoring is cost effective by reducing fear of hypoglycaemia, blood glucose finger prick testing and a marked reduction in hypoglycaemic episodes. The hybrid closed loop systems offering algorithm driven insulin adjustment based on sensor readings are now commercially available bringing into play more effective and safer insulin delivery with a further step change in diabetes control and well being.

Association between fasting insulin and C-reactive protein among adults without diabetes using a two-part model: NHANES 2005\u20132010

IntroductionChronic inflammation is associated with the development, progression and long-term complications of type 2 diabetes. Hyperglycemia is associated with chronic low-grade inflammation, and thus has become the focus of many screening and treatment recommendations. We hypothesize that insulin may also be associated with inflammation and may be an additional factor to consider in screening and treatment.MethodsThis study used National Health and Nutrition Examination Survey data from 2005 to 2010 to analyze the association between fasting insulin and C-reactive protein (CRP). A two-part model was used due to the high number of values reported as 0.1 mg/L. Two models were analyzed, both with and without the addition of waist circumference to other covariates in the model.ResultsThe final sample included 4527 adults with a mean age of 43.31 years. In the first model, higher fasting insulin was associated with increased odds of CRP > 0.1 mg/L (OR = 1.02, p < .001) and with higher CRP (β = 0.03, p < .001). In the adjusted model, including waist circumference as a covariate, higher fasting insulin was not associated with CRP > 0.1 mg/L (OR = 1.00, p = .307) but the association between higher fasting insulin and higher continuous CRP remained significant (β = 0.01, p = .012).ConclusionThis study found that higher fasting insulin is associated with higher CRP. These results suggest that treatment approaches that simultaneously decrease insulin levels as well as glucose levels may provide additive anti-inflammatory effects, and therefore may improve long-term outcomes for adults with type 2 diabetes.

Risk of morbidity and mortality in patients with type 2 diabetes treated with sodium-glucose cotransporter-2 inhibitor and/or dipeptidyl peptidase-4 inhibitor: a nationwide study

IntroductionMortality and disability in diabetes mellitus are determined mostly by cardiovascular complications and cancer. The impact of dipeptidyl peptidase-4 inhibitor (DPP-4i) and sodium-glucose cotransporter-2 inhibitor (SGLT2i) monotherapy or combination on...

304-OR: 5-Hydroxymethylcytosines in Circulating Cell-Free DNA Reveal Diabetic Nephropathy

Background: Long-term complications of type 2 diabetes (T2D) are the major causes for T2D-related disability and mortality. Notably, diabetic nephropathy (DN) has become the most frequent cause of end-stage renal disease in most countries. A clinically convenient, noninvasive approach for monitoring the development of DN would improve the overall life quality of patients with T2D and help reduce healthcare burden through preventive interventions. Methods: A selective chemical labeling strategy, the 5hmC-Seal, was used to profile genome-wide 5-hydroxymethylcytosines (5hmC), an emerging class of epigenetic markers implicated in complex diseases including diabetes, in patient-derived circulating cell-free DNA (cfDNA) in plasma. Differentially modified 5hmC marker genes were identified through the pair-wise comparisons among T2D patients with DN (DN) (n=12), T2D patients with non-DN complications(non-DN) (n=29), and T2D controls with no complications (T2D) (n=14),respectively. Results: A panel of 271 differentially modified genes (fold-change &amp;gt; 10% and nominal p-value &amp;lt; 0.05) were detected between T2D and DN, involving genes and pathways relevant to synthesis of bile acids and bile salts, fatty acid metabolism(ACAA2), mitochondrial gene expression (POLRMT), and ion transport (OTX1, SRI). In addition, a 4-gene 5hmC marker panel (DNAH1, RAB11FIP4, POLRMT, RAB36) was found to be differentially modified among T2D, DN and non-DN patients. Further analysis indicated that this 4-gene signature showed capacity for differentiating DN from T2D (AUC= 83%; 95% confidence interval [66-100%]), healthy individuals (AUC= 83% [64-100%]), and non-DN (AUC = 88% [76-100%]). Conclusion: The 5hmC profiles in cfDNA reflect epigenetic changes in T2D and DN that have the potential to be a clinically convenient, noninvasive approach for monitoring the presence and severity of diabetic retinopathy in high risk T2D patients. Disclosure C. Zeng: None. Y. Yang: None. Z. Zhang: None. C. He: Advisory Panel; Self; Shanghai Epican Genetech Co., Ltd. W. Zhang: Advisory Panel; Self; Shanghai Epican Genetech Co., Ltd. S. Liu: None.

Visit-to-Visit Variability of Clinical Risk Markers Is Predictive of Long-Term Complications in Type 1 Diabetes

Background: Clinical characteristics such as HbA1c, systolic blood pressure (SBP), albuminuria and estimated glomerular filtration rate (eGFR) are important when treating type 1 diabetes (T1D). We investigated the variability in these measures as risk markers for micro- and macrovascular complications. Methods: This prospective study included 1062 individuals with T1D. Visit-to-visit variability (VVV) of HbA1c, SBP, albuminuria, and eGFR was calculated as the SD of the residuals in individual linear regression models using all available measures in a specified period of 3 years (SVVV) as well as the entire follow-up (CVVV). Endpoints included: composite cardiovascular events (CVE) defined as myocardial infarction, non-fatal stroke, coronary arterial intervention, or peripheral arterial intervention; end-stage kidney disease (ESKD) defined as chronic kidney disease stage 5, chronic dialysis, or kidney transplantation; eGFR-decline ≥30%; and mortality. Adjustment included age, sex, cholesterol, HbA1c, SBP, body mass index, smoking, albuminuria, eGFR, and intercept and slope of respective regression models. Findings: SVVV and CVVV for every exposure associated significantly with each other (p<0·05) (R=0·42-0·88 depending on exposure). SBP SVVV was significantly associated with CVE (adjusted hazard ratio per doubling, CI 95%: 1·38, 1·09-1·76), ESKD (2·00, 1·27-3·13) and mortality (1·47, 1·16-1·89). HbA1c SVVV was significantly associated with development of ESKD (1·76, 1·02-1·51) and mortality (2·01, 1·56-2·59); albuminuria SVVV with eGFR-decline (1·26, 1·15-1·38) and ESKD (1·24, 1·02-1·51), but neither CVE nor mortality. Adjusted eGFR SVVV was only associated with eGFR-decline (1·12, 1·03-1·21). CVVV of all exposures were significantly associated with risk of all endpoints, except for eGFR CVVV with the endpoints CVE and mortality. Interpretation: In T1D, higher short- and long-term VVV of basic clinical risk markers add important risk stratification information for the development of micro- and macrovascular complications. Funding Statement: No external funding to declare. Declaration of Interests: P.R. reports giving lectures for AstraZeneca, Bayer, Eli Lilly, and Novo Nordisk; serving as a consultant for AstraZeneca, Bayer, Gilead, Sanofi Aventis, and Novo Nordisk, with all fees given to Steno Diabetes Center Copenhagen; and having equity interest in Novo Nordisk. All other authors declare no competing interests. Ethics Approval Statement: All participants gave informed written consent and the study complied with the Declaration of Helsinki. The research protocol, as well as all further activities, were reviewed and approved by the local ethics committee.

Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Type 2 Diabetes

Effects of Short-term Intensive Insulin Therapy on Long-term Complications in Type 2 Diabetes

4-O-methylhonokiol ameliorates type 2 diabetes-induced nephropathy in mice likely by activation of AMPK-mediated fatty acid oxidation and Nrf2-mediated anti-oxidative stress

Diabetic nephropathy (DN) is one of the most serious long-term complications of type 2 diabetes (T2D). 4-O-methylhonokiol (MH) is one of the biologically active ingredients extracted from the Magnolia stem bark. In this study, we aim to elucidate whether treatment with MH can ameliorate or slow-down progression of DN in a T2D murine model and, if so, whether the protective response of MH correlates with AMPK-associated anti-oxidant and anti-inflammatory effects. To induce T2D, mice were fed normal diet (ND) or high fat diet (HFD) for 3 months to induce insulin resistance, followed by an intraperitoneal injection of STZ to induce hyperglycemia. Both T2D and control mice received gavage containing vehicle or MH once diabetes onset for 3 months. Once completing 3-month MH treatment, five mice from each group were sacrificed as 3 month time-point. The rest mice in each group were sacrificed 3 months later as 6 month time-point. In T2D mice, the typical DN symptoms were induced as expected, reflected by increased proteinuria, renal lipid accumulation and lipotoxic effects inducing oxidative stress, and inflammatory reactions, and final fibrosis. However, these typical DN changes were significantly prevented by MH treatment for 3 months and even at 3 months post-MH withdrawal. Mechanistically, MH renal-protection from DN may be related to lipid metabolic improvement and oxidative stress attenuation along with increases in AMPK/PGC-1α/CPT1B-mediated fatty acid oxidation and Nrf2/SOD2-mediated anti-oxidative stress. Results showed the preventive effect of MH on the renal oxidative stress and inflammation in DN.

Sustained virological response to hepatitis C treatment decreases the incidence of complications associated with type 2 diabetes.

The role of hepatitis C (HCV) eradication on the long-term complications of type 2 diabetes mellitus remains incompletely studied. To investigate whether antiviral treatment impacted risk of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy among diabetic patients from the four US health systems comprising the Chronic Hepatitis Cohort Study (CHeCS). We included CHeCS HCV patients with diagnosis codes for type 2 diabetes who were on antidiabetic medications. Patients were followed until an outcome of interest, death, or last health system encounter. The effect of treatment on outcomes was estimated using the competing risk analysis (Fine-Gray subdistribution hazard ratio [sHR]), with death as a competing event. Among 1395 HCV-infected patients with type 2 diabetes, 723 (52%) were treated with either interferon-based or direct-acting antivirals (DAAs); 539 (75% of treated) achieved sustained virological response (SVR). After propensity score adjustment to address treatment selection bias, patients with SVR demonstrated significantly decreased risk of acute coronary syndrome (sHR=0.36; P<0.001), end-stage renal disease (sHR=0.46; P<0.001), stroke (sHR=0.34; P<0.001), and retinopathy (sHR=0.24; P<0.001) compared to untreated patients. Results were consistent in subgroup analyses of DAA-treated patients and interferon-treated patients, an analysis of cirrhotic patients, as well as in sensitivity analyses considering cause-specific hazards, exclusion of patients with on-treatment retinopathy, and treatment status as a time-varying covariate. Successful HCV treatment among patients with type 2 diabetes significantly reduces incidence of acute coronary syndrome, end-stage renal disease, ischaemic stroke, and retinopathy, regardless of cirrhosis. Our findings support the importance of HCV antiviral therapy among patients with type 2 diabetes to reduce the risk of these extrahepatic outcomes.