Lipid peroxidation in type 2 diabetes: relationship with macrovascular disease?

Background: Macrovascular disease is the leading cause of death in diabetes. The increased risk of atherosclerosis in diabetes may be partly explained by increased lipid peroxidation.Methods: We assessed lipid peroxidation in subjects with type 2 diabetes with (n=23) and without (n=23) macrovascular complications versus healthy age-matched controls (n=13). The diabetic groups were matched for glycemic control (mean HbA_1c=9%), and for age and had similar known duration of diabetes.Results: Plasma TBARS were comparable between diabetic subjects with and without macrovascular complications (1.89±0.32 and 1.81±0.28 μmol/l) and elevated compared to healthy controls (1.64±0.26 μmol/l, p=0.025). Ratios of IgG and IgM antibodies to oxidized vs. native LDL were comparable between diabetic subjects and controls, and also between diabetic subjects with or without macrovascular complications. The lag phase, an index of the resistance of LDL to oxidation, was significantly longer in diabetic patients with macrovascular complications (66±8 min) vs. those without macrovascular complications and controls (resp. 59±7 and 56±7 min, p<0.05). An explanation may be the frequent use of drugs with possible antioxidant potential, e.g. beta-blocking agents, ACE-inhibitors and calcium entry blockers by these patients. Surprisingly, plasma vitamin E levels were higher in diabetic subjects.Conclusions: We found no evidence of increased lipid peroxidation in diabetic subjects with macrovascular complications, but an increased resistance to oxidation in this group, probably due to an altered antioxidant status. The increased TBARS level in diabetic subjects contrasts with the other indices of lipid peroxidation and may be related to prevalent hyperglycemia and should therefore be interpreted cautiously.     

β-Cell function in type 2 diabetes

Different in vivo tests explore different aspects of β-cell function. Because intercorrelation of insulin secretion indices is modest, no single in vivo test allows β-cell function to be assessed with accuracy and specificity comparable to insulin sensitivity. Physiologically-based mathematical modeling is necessary to interpret insulin secretory responses in terms of relevant parameters of β-cell function. Models can be used to analyze intravenous glucose tests, but secretory responses to intravenous glucose may be paradoxical in subjects with diabetes. Use of oral glucose (or mixed meal) data may be preferable not only for simplicity but also for physiological interpretation.     

Severity of coronary artery disease in type 2 diabetes mellitus: Does the timing matter?

AimThe aim of our study was to compare the angiographic changes in 53 nondiabetic patients, 54 type 2 diabetic patients of less than 5 years of duration, 41 patients with 5–10 years of diabetes, and 27 with more than 10 years of diabetic duration.MethodsIn this cross-sectional study, 175 patients, who underwent coronary angiogram for the evaluation of the coronary artery disease (CAD), were recruited. Based on the angiographic findings, syntax score, vessel score, and coronary collaterals grading were analyzed. The biochemical analysis was done by using the auto analyzer.ResultsA significant increase in the mean syntax score (p = 0.019), vessel score (p = 0.007), and coronary collateral grade (p = 0.008) was observed in the patients with 5–10 years of diabetes when compared to those with less than 5 years of diabetic duration. There was no significant difference in the mean syntax score (p = 0.979), vessel score (p = 0.299), and collateral grade (p = 0.842) between the patients with 5–10 years and more than 10 years of diabetes. The difference in the mean syntax score (p = 0.791), vessel score (p = 0.098), and collateral grade (p = 0.661) between the nondiabetic and the patients with less than 5 years of diabetes was not significant.ConclusionA significant structural change in the coronary arteries was found among the patients with 5–10 years of diabetes.     

Use of pioglitazone in people with type 2 diabetes mellitus with coronavirus disease 2019 (COVID-19): Boon or bane?

Background and aimsPeople with type 2 diabetes mellitus (T2DM) have increased morbidity and mortality due to coronavirus disease-19(COVID-19). It has been speculated that use of pioglitazone might increase such risk. The aim of our brief commentary is to review the safety of pioglitazone in people with T2DM and mild/moderate COVID-19.MethodsWe searched PubMed database using specific keywords related to our aims till May 15, 2020. Full text of relevant articles published in English language were retrieved and reviewed.ResultsMedications, including pioglitazone, that upregulate tissue expression of angiotensin converting enzyme 2 (ACE2), might have a dual role in COVID-19; on the one hand they might increase risk of infection as SARS-CoV2 uses ACE2 as a coreceptor to enter alveolar cells, but on the other hand, by reducing angiotensin II levels, they can protect against acute lung injury. There is no evidence to date that pioglitazone upregulates ACE2 in the alveolar cells; rather, there is evidence from animal studies of upregulation of ACE2 in insulin sensitive tissues, which might have a protective effect on lung injury. Moreover by moderating the exaggerated host proinflammatory response, pioglitazone can potentially reduce SARS-CoV-2 driven hyperinflammation.ConclusionsPioglitazone has more potential for benefit than harm, and can be continued in people with T2DM and mild/moderate COVID-19, unless there are specific contraindications for its use. There is an urgent need to assess clinically relevant outcomes in people with diabetes and COVID-19 based upon baseline antidiabetes therapy, in particular pioglitazone.     

Is there a role for physical activity in preventing cognitive decline in people with mild cognitive impairment?

Mild cognitive impairment (MCI) is a common clinical syndrome that identifies people at high risk of developing dementia. Although treatments for MCI are currently unavailable, preliminary evidence has identified potential neuro-protective effects of physical activity, which may lead to improved outcomes. However, there is uncertainty regarding the effectiveness, feasibility and acceptability of this treatment strategy. These uncertainties require further investigation before physical activity interventions can be recommended for routine care.     

What type of diabetes do young people have?

Although type 1 diabetes remains the most common type of diabetes in the pediatric population, there has been a dramatic rise in type 2 diabetes in youth. Clinical distinctions between these two major types have become blurred. As genetic and biochemical measures become more affordable and available, practical applications of these measures to better understand diabetes type in youth and the implications of diabetes type on the evolution of the disease are needed.     

Does health literacy predict cardiometabolic marker trajectories among people with diabetes? A longitudinal mixed-effect analysis

AimsTo assess trajectories in cardiometabolic markers among people with type 1 and type 2 diabetes with varying health literacy levels.MethodsSurvey data assessing self-reported health literacy among 1401 people with type 1 diabetes and 910 people with type 2 diabetes were linked to prospective clinical data. Mixed effects modelling was used to identify the impact of three health literacy domains on trajectories of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and glycated hemoglobin (HbA1c).ResultsHigh health literacy scores in some domains were associated with attenuated HbA1c trajectories, while associations with LDL-C and SBP were weak or absent, particularly among participants with type 2 diabetes. The domain “Ability to Actively Manage Health” had the strongest association with HbA1c (P < 0.001). Exponential changes over time were not observed. Differences in the estimated progression of cardiometabolic markers by health literacy levels did not reach statistical significance.ConclusionLow health literacy was associated with suboptimal glycaemic levels in type 1 and type 2 diabetes. There was inconclusive evidence of associations between health literacy, BP, and LDL-C. Development in cardiometabolic markers did not indicate faster diabetes progression among people with low health literacy.     

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.     

Is diabetes associated with cognitive impairment and cognitive decline among older women? Study of Osteoporotic Fractures Research Group

BACKGROUND: The long-term effect of type 2 diabetes on cognitive function is uncertain. OBJECTIVE: To determine whether older women with diabetes have an increased risk of cognitive impairment and cognitive decline. DESIGN: Prospective cohort study. SETTING: Four research centers in the United States (Baltimore, Md; Portland, Ore; Minneapolis, Minn; and the Monongahela Valley, Pennsylvania). PARTICIPANTS: Community-dwelling white women 65 years and older (n = 9679). MEASUREMENTS: Physician-diagnosed diabetes and other aspects of health history were assessed by interview. Three tests of cognitive function, the Digit Symbol test, the Trails B test, and a modified version of the Mini-Mental State Examination (m-MMSE), were administered at baseline and 3 to 6 years later. Change in cognitive function was defined by the change in the score for each test. Major cognitive decline was defined as the worst 10th percentile change in the score for each test. RESULTS: Women with diabetes (n = 682 [7.0%]) had lower baseline scores than those without diabetes on all 3 tests of cognitive function (Digit Symbol and Trials B tests, P<.01; m-MMSE, P = .03) and experienced an accelerated cognitive decline as measured by the Digit Symbol test (P<.01) and m-MMSE (P = .03). Diabetes was also associated with increased odds of major cognitive decline as determined by scores on the Digit Symbol (odds ratio = 1.63; 95% confidence interval, 1.20-2.23) and Trails B (odds ratio, 1.74; 95% confidence interval, 1.27-2.39) tests when controlled for age, education, depression, stroke, visual impairment, heart disease, hypertension, physical activity, estrogen use, and smoking. Women who had diabetes for more than 15 years had a 57% to 114% greater risk of major cognitive decline than women without diabetes. CONCLUSION: Diabetes is associated with lower levels of cognitive function and greater cognitive decline among older women.