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Background: Glycemic variability is a novel predictor for diabetic complications. Different studies have demonstrated contradictory results for the association between HbA1c variability and diabetic retinopathy. We aimed to assess the relationship between visit-to-visit variability in glycemic profile (HbA1c, 2hPP, and FBS) and diabetic retinopathy. Methods: Patients with type 2 diabetes were monitored for the development of retinopathy for 10 years. The association between the incidence of retinopathy and glycemic variability was assessed via Cox regression analysis, and coefficient of variation for glycemic indices was compared using independent sample t -test. Results: Patients with diabetic retinopathy had significantly higher glycemic profile variability. The incidence of retinopathy was positively correlated with cv-FBS10% (10% of coefficient of variance), cv-FBS20%, cv-2hpp10%, and cv-HbA1c5%. Our analysis revealed that the higher variability of FBS increased the incidence and progression of retinopathy (HR: 12.29, p -value = 0.003). Conclusion: Our findings demonstrated glycemic profile variability as an independent risk factor for diabetic retinopathy in patients with type 2 diabetes and support glycemic profile variability measurement in addition to common glycemic parameters to improve risk stratification in patients with type 2 diabetes. Further investigation is required to demonstrate the long-term effects of alleviating glycemic variability on the prognosis of patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background and Objectives. Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder in western countries. Although the etiology of NAFLD is unknown, insulin resistance is a key mechanism of lipid deposition in hepatocytes leading to steatosis and potentially steatohepatitis in patients with diabetes. These factors accelerate the progression of atherosclerosis and development of cardiovascular diseases (CVD). Methods and Results. In this prospective cohort study, 1197 patients with type 2 diabetes (T2D) were divided into two groups (360 patients with NAFLD and 847 without NAFLD) and were followed for a median of 5 years for the incidence of CVD. Cox regression analysis was used to assess the association between NAFLD, liver enzyme level, aspartate aminotransferase to platelet ratio index (APRI), and the incidence risk of CVD and its subgroups (i.e., myocardial infarction, chronic heart disease, coronary artery bypass grafting, and percutaneous coronary intervention). There was a significant positive association between CVD incidence and NAFLD (HR = 1.488, 95% CI = 1.041–2.124, p value = 0.029). Although patients with NAFLD had higher levels of ALT and AST levels (p value = <0.001), there was no significant association between liver enzymes and the incidence risk of CVD when adjusted for different variables. Furthermore, NAFLD was associated with NAFLD APRI Q (2), APRI Q (3), and APRIQ (4) (1.365 (1.046–1.781), 1.623 (1.234–2.135), and 3.373 (2.509–4.536)), respectively. Conclusion. NAFLD increased the incidence risk of CVD in T2D. However, there was no association between liver enzymes (ALT, AST, ALK‐P, and GGT) and a higher incidence risk of CVD in T2D when adjusted for confounding variables. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of pentoxifylline (PTX) in combination with losartan compared to the high dose of losartan alone on serum markers of diabetic nephropathy such as HSP70, copeptin, CRP, and TNFα in patients with type 2 diabetes and nephropathy. Methods: A single-center, randomized, double-blind, open-label clinical trial was conducted. Sixty-two patients were eligible and allocated to "PTX + losartan" and "high-dose losartan" arms of the trial using software for random number generation. The first arm received 400 mg PTX two times a day (BD) plus 50 mg losartan daily, while the second arm received 50 mg losartan two times a day (BD) for 12 weeks. Comparison of the biomarkers' levels before and after treatment was done using paired sample t test variance. ANCOVA was applied to evaluate the comparative efficacy of the two interventions. The effect size was calculated and reported for each biomarker. Results: Urine albumin excretion (UAE), hs-CRP, and HbA1c significantly decreased in both trial arms compared to the baseline measures. Copeptin and TNFα showed significant differences (after vs before) only in the losartan group (p = 0.017 and p = 0.043, respectively). The losartan arm was more successful in reducing TNFα, copeptin, HSP70, systolic blood pressure (SBP), and diastolic blood pressure (DBP) values (p = 0.045, effect size = 7.3%; p = 0.018, effect size 10.1%; p = 0.046, effect size 4.7%, p = 0.001, effect size 23%; p = 0.012, effect size 10.2%, respectively) and the PTX arm was associated with a superior reduction of UAE and hs-CRP levels (p = 0.018, effect size 9.1%; p = 0.028, effect size 9.2%, respectively). Conclusion: Add-on PTX to losartan may have more effective anti-inflammatory and anti-albuminuric roles and therefore may be more applicable in the management of diabetic nephropathy compared with high-dose losartan alone. Trail Registration: Trial number IRCT 20121104011356N10. [ABSTRACT FROM AUTHOR]

Coronary heart disease (CHD) is one of the major causes of mortality and morbidity in patients with type 2 diabetes mellitus. In this study, we aimed to assess the association between visit-to-visit variability of fasting blood sugar (FBS), HbA1c, blood sugar 2 h post-prandial (BS2hpp), lipid indices, creatinine, systolic and diastolic blood pressure (SBP, DBP) and incident CHD in patients with type 2 diabetes during a median follow-up of ten years. The current case-cohort study consisted of 1500 individuals with type 2 diabetes, followed up for the occurrence of CHD from 2002 to 2019. The patients had at least four annual follow-ups during which glycemic and lipid profile were measured. Co-efficient of variance (CV) for each parameter was calculated by 10-21 measurements. Cox regression analysis was performed to assess the association between CV of glycemic indices, lipid profile, blood pressure, creatinine, weight and incident CHD during the follow-up period. Hazard ratios (HR) were adjusted for the confounding variables. Glycemic indices variability (i.e., CV-HbA1c, CV-FBS, and CV-BS2hpp), were significantly higher in the group with incident CHD (P=0.034, P=0.042, and P=0.044, respectively). Hazard ratios were 1.42 (95 % CI=1.13-2.09) for CV-HbA1c, 1.37 (95 % CI=1.02-2.10) for CV-FBS, and 1.16 (95 % CI=1.01-1.63) for CV-BS2hpp (P=0.012, P=0.046, P=0.038, respectively). Creatinine was significantly higher in the group with incident CHD (P=0.036) and it was significantly associated with higher incidence of CHD (HR=1.14, 95 % CI=1.02-2.17, P=0.048). Visit to visit variability of glycemic indices of the patients with type 2 diabetes is associated with incident CHD independent of their baseline and mean values. [ABSTRACT FROM AUTHOR]