Walking pace and microvascular complications among individuals with type 2 diabetes: A cohort study from the UK Biobank.

INTRODUCTION: Walking pace is associated with various health-related outcomes. The aim of this study was to investigate the association between self-reported walking pace and the incidences of diabetic microvascular complications among participants with type 2 diabetes (T2D). METHODS: Self-reported walking pace was classified as brisk, average, or slow. The outcomes were the incidences of diabetic retinopathy, diabetic neuropathy, and diabetic nephropathy. COX proportional hazards models adjusted for sociodemographic, lifestyle, and health-related factors were used to estimate hazard ratios (HRs) and 95% CIs. RESULTS: A total of 14 518 participants with T2D in the UK Biobank (mean age 59.7 ± 7.0 years, 5028 [34.6%] women) were included. During a median follow-up of 12.5 (interquartile range: 11.6-13.4) years, 2980 participants developed diabetic microvascular complications. After adjusting for confounding factors, and compared with brisk walkers, slow walkers had a multivariable-adjusted HR of 1.98 (95% CI 1.58, 2.47) for composite diabetic microvascular complications, 1.54 (95% CI 1.11, 2.14) for diabetic retinopathy, 3.26 (95% CI 2.08, 5.11) for diabetic neuropathy, and 2.32 (95% CI 1.91, 2.82) for diabetic nephropathy. Average walking pace was associated with a higher risk for diabetic nephropathy (HR 1.51, 95 CI% 1.27-1.79) compared with brisk walking. Additionally, ≥1 diabetic microvascular complication occurred in 447 (14.7%) of participants with brisk walking pace, 1702 (19.5%) with average walking pace, and 831 (30.4%) with slow walking pace. Time from study recruitment to first diagnosis was shorter in participants who reported a slow walking pace, compared with brisk or average walkers. Among participants who had diabetic nephropathy as their first diagnosis, slow walking pace was associated with subsequent risk of a second diabetic microvascular complication (HR 3.88, 95 CI% 2.27-6.60). CONCLUSIONS: Self-reported slow walking pace is associated with a higher risk of diabetic microvascular complications among participants with T2D in this population-based cohort study.

Incidence rates and predictors of microvascular and macrovascular complications in patients with type 2 diabetes: Results from the longitudinal global discover study.

BACKGROUND: Micro- and macrovascular complications are a major cause of morbidity and mortality in people with type 2 diabetes (T2D). We sought to understand the global incidence rates and predictors of these complications. METHODS: We examined the incidence of vascular complications over 3 years of follow-up in the DISCOVER study-a global, observational study of people with T2D initiating second-line glucose-lowering therapy. Hierarchical Cox proportional hazards regression models examined factors associated with development of micro- and macrovascular complications during follow-up. RESULTS: Among 11,357 people with T2D from 33 countries (mean age 56.9 ± 11.7 years, T2D duration 5.7 ± 5.1 years, HbA1c 8.4 ± 1.7%), 19.0% had a microvascular complication at enrolment (most commonly neuropathy), and 13.2% had a macrovascular complication (most commonly coronary disease). Over 3 years of follow-up, 16.0% developed an incident microvascular complication, and 6.6% had an incident macrovascular complication. At the end of 3 years of follow-up, 31.5% of patients had at least one microvascular complication, and 16.6% had at least one macrovascular complication. Higher HbA1c and smoking were associated with greater risk of both incident micro- and macrovascular complications. Known macrovascular complications at baseline was the strongest predictor for development of new microvascular complications (HR 1.40, 95% CI 1.21 -1.61) and new macrovascular complications (HR 3.39, 95% CI 2.84 -4.06). CONCLUSIONS: In this global study, both the prevalence and 3-year incidence of vascular complications were high in patients with relatively short T2D duration, highlighting the need for early risk-factor modification.

Predictors of outcome in diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia.

OBJECTIVE: The incidence of chronic limb-threatening ischemia in diabetic patients is increasing. The factors influencing outcome after infrapopliteal revascularization in these patients are largely unknown. Therefore, this study aims to identify the impact of perioperative glucose control on the long-term outcomes in this patient cohort, and furthermore to identify other factors independently associated with outcome. METHODS: Consecutive diabetic patients undergoing infrapopliteal endovascular revascularization for chronic limb-threatening ischemia were identified. Patients' demographics, procedural details, daily capillary blood glucose, and hemoglobin A1C levels were collected and analyzed against the study end points using Kaplan-Meier and Cox regression analysis. RESULTS: A total of 437 infrapopliteal target vessels were successfully crossed in 203 patients. Amputation-free survival by Kaplan-Meier (estimate (standard error)%) was 74 (3.3)% and 63 (3.7)%, primary patency was 61 (4.2)% and 50 (4.9)%, assisted primary patency was 69 (5.2)% and 55 (6.1)%, and secondary patency was 71 (3.8)% and 59 (4.1)% at 1 year and 2 years, respectively. Cox regression analysis showed high perioperative capillary blood glucose levels to be an independent predictor of binary restenosis (hazard ratio [HR], 1.49; 95% confidence interval [CI], 1.31-1.1.78; P = .015). Postprocedural dual-antiplatelet therapy was found to be an independent predictor of amputation-free survival (HR, 1.69; 95% CI, 1.04-2.75; P = .033), and freedom from major adverse limb events (HR: 1.96; 95% CI, 1.16-3.27; P = .023) and baseline estimated glomerular filtration rate was significantly associated with better amputation-free survival (HR, 0.52; 95% CI, 0.31-0.87; P = .014). CONCLUSIONS: Poor perioperative glycemic control is associated with a higher incidence of restenosis after infrapopliteal revascularization in diabetic patients. Dual antiplatelet therapy is associated with better outcomes in this group.

What is the impact of microvascular complications of diabetes on severe COVID-19?

Evidence suggests severe coronavirus disease-19 (COVID-19) infection is characterised by pulmonary and systemic microvasculature dysfunction, specifically, acute endothelial injury, hypercoagulation and increased capillary permeability. Diabetes, which is also characterised by vascular injury in itself, confers an increased risk of adverse COVID-19 outcomes. It has been suggested that pre-existing endothelial dysfunction and microvascular disease in diabetes will exacerbate the vascular insults associated with COVID-19 and thus lead to increased severity of COVID-19 infection. In this article, we evaluate the current evidence exploring the impact of microvascular complications, in the form of diabetic retinopathy and nephropathy, in individuals with COVID-19 and diabetes. Future insights gained from exploring the microvascular injury patterns and clinical outcomes may come to influence care delivery algorithms for either of these conditions.

The association between carotid disease, arterial stiffness and diabetic retinopathy in type 2 diabetes: the Fremantle Diabetes Study Phase II.

AIM: To determine whether macrovascular disease assessed by carotid ultrasonography and arterial stiffness by pulse wave velocity are independently associated with diabetic retinopathy in type 2 diabetes. METHODS: A random subgroup of surviving participants with type 2 diabetes from the Fremantle Diabetes Study Phase II were invited to take part in this sub-study in 2018-2019. In addition to standardized questionnaires, a physical examination and fasting biochemical tests, each underwent dilated colour fundus photography, carotid arterial ultrasonography with measurement of the intima-media thickness (IMT) and quantification of the degree of stenosis, and pulse wave analysis calculation of the carotid-femoral pulse wave velocity (cfPWV). The cross-sectional association between arterial disease parameters and diabetic retinopathy was assessed using generalized estimating equation models which enabled both eyes to be included in the analysis. RESULTS: Some 270 participants [mean ± sd age 72 ± 9 years, 153 (57%) men and median (IQR) diabetes duration 15 (11-22) years] were included in analysis. Of 524 assessable eyes, 82 (16%) had diabetic retinopathy. In multivariable analysis, significant independent associates of diabetic retinopathy were age at diabetes diagnosis (inversely), HbA1c , insulin treatment and urinary albumin to creatinine ratio (all P ≤ 0.022), as well as cfPWV [odds ratio (OR) 1.13, 95% confidence interval (CI) 1.03, 1.23 per 1 m/s increase; P = 0.008] and common carotid artery (CCA) IMT ≥1 mm (OR 2.95, 95% CI 1.21, 7.23; P = 0.018). CONCLUSIONS: The association between diabetic retinopathy and CCA IMT suggests that carotid disease may share cardiovascular risk factors with diabetic retinopathy. The association between diabetic retinopathy and cfPWV may reflect the consequences of altered intravascular haemodynamics.

TCF7L2 gene polymorphism as a risk for type 2 diabetes mellitus and diabetic microvascular complications.

BACKGROUND: Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic condition with various genetics and environmental influences that affects the capacity of the body to produce or use insulin resulting in hyperglycemia, which may lead to variable complications. It is one of the world's rising health problems. There is emerging evidence that some genetic polymorphisms can impact the risk of evolving T2DM. We try to determine the relationship of (rs7903146) variant of the Transcription factor 7-like 2 (TCF7L2) gene with T2DM and its microvascular complications. METHODS AND RESULTS: This case-control study included 180 subjects: 60 diabetic patients without complications, 60 diabetic patients with microvascular complications and 60 matched healthy controls. Genotypes of rs7903146 (C/T) SNP in the TCF7L2 gene were evaluated by real-time polymerase chain reaction via TaqMan allelic discrimination. Logistic regression was used to detect the most independent factor for development of diabetes and diabetic microvascular complications. Variant homozygous TT and heterozygous CT genotypes were significantly increased in diabetic without complications and diabetic with complications groups than controls (p = 0.003, 0.001) respectively. The T allele was more represented in both patient groups than controls with no significant difference between patient groups. TT genotype as well as T allele was significantly associated with increased T2DM risk. CONCLUSION: The T allele of rs7903146 polymorphism of TCF7L2 confers susceptibility to development of T2DM. However, no significant association was found for diabetic complications.

Diabetic kidney disease in patients with type 2 diabetes mellitus: a cross-sectional study.

AIM: Diabetic kidney disease (DKD) is a major long-term complication of diabetes mellitus (DM). Given the paucity of data on DKD in Jordan, we aimed to evaluate the prevalence, characteristics and correlates of DKD in Jordanian patients with type 2 DM. METHODS: This cross-sectional study included 1398 adult patients with type 2 DM who sought medical advice in the endocrinology clinic between March and September 2019. Demographic, clinical and laboratory data were reviewed. DKD was defined as reduced eGFR, and/or albuminuria. Three regression models were constructed to identify factors associated with CKD stages, albuminuria and DKD. RESULTS: Overall, 701 (50.14%) patients had DKD, with a median age of 59.71 ± 11.36  years. Older age, high triglycerides, and low high-density lipoprotein were associated with DKD (multivariable odds ratio [OR]: 1.02, 95% confidence interval [CI]: 1.01-1.03, p < 0.01; OR: 1.1, 95% CI: 1.01-1.2; and OR: 0.98, 95% CI: 0.97-0.99, p < 0.01 respectively). Metformin and renin-angiotensin system blockers were negatively associated with albuminuria and chronic kidney disease stages (p < 0.01). CONCLUSION: Our study demonstrated that approximately one half of patients with type 2 DM had DKD. Further studies are necessary to understand this high prevalence and the underlying factors. Future research are needed to assess implementing targeted community-based intervention.

The Importance of Prognostic Nutritional Index in Predicting Acute Renal Failure After On-Pump Coronary Artery Bypass Operations in Patients with Insulin-Dependent Diabetes Mellitus.

BACKGROUND: After coronary artery bypass graft (CABG) operations, acute kidney injury (AKI) appears at 5-30% rates, and this rate increases even more in patients with diabetes mellitus (DM). Prognostic nutritional index (PNI) is known as a valuable parameter that affects cardiovascular surgery outcomes. In this current study, we aimed to investigate the importance of PNI value in predicting AKI after on-pump CABG operations in insulin-dependent diabetic patients. METHODS: A total of 254 consecutive patients with insulin- dependent diabetes who underwent on-pump CABG in our clinic between January 2016 and January 2020 retrospectively were included in this study. In the postoperative period, patients were registered as the renal failure group (Group 1), and those who did not develop renal failure were registered as Group 2. RESULTS: A total of 255 patients with DM were included in the study. There were 82 patients in Group 1 and 173 patients in Group 2. There was no difference between the groups, in terms of age, gender, smoking, and hyperlipidemia rates. Hypertension rate significantly was higher in Group 2 (P = .001). In multivariate logistic regression analysis, hypertension (OR: 1.226, 95% CI: 1.114-2.459, P = .026), need for inotropic support (OR: 1.128, 95% CI: 1.070-1.784, P = .033), increased blood product use (OR: 1.291, 95% CI: 1.112-2.156, P = .021) preoperative high creatinine (OR: 3.563, 95% CI: 2.497-5.559, P < .001), and PNI (OR: 1.327, 95% CI: 1.118-2.785, P = .012) were independent predictors of AKI. CONCLUSION: In our study, we determined PNI value as an independent predictor in predicting acute renal injury occurring after on-pump CABG operations in patients with insulin-dependent DM.

Peripheral Artery Disease on The Prognosis Value of Patients with Stable Coronary Artery Disease Undergoing Percutaneous Coronary Intervention: A Retrospective, Single-Center Cohort Study.

OBJECTIVE: The purpose of this investigation aimed to clarify the impact of peripheral artery disease (PAD) on the prognosis value of patients with stable coronary artery disease (CAD) who underwent percutaneous coronary intervention (PCI). METHODS: The SPSS 16 software was used for secondary analysis of DRYAD database data. A total of 204 patients were enrolled from Shinonoi General Hospital for newly diagnosed stable CAD and received PCI performance between October 2014 and October 2017. Patients with old myocardial infarction (MI) were excluded. We divided patients into two groups with PAD and without PAD. The primary endpoints were major adverse cardiac events (MACE, defined as all-cause death, non-fatal MI, and non-fatal stroke) and cardiovascular events (defined as cardiovascular death, non-fatal MI, and non-fatal stroke). The secondary outcomes were the individual components of the composite primary outcomes. The median follow-up time was 783 days. RESULTS: No statistical difference was found between PAD and non-PAD patients of lesional characteristics. Spearman's rank correlations indicate diabetes mellitus (DM) (P = 0.019) and HbA1c (P = 0.009) are positively correlated with PAD. In Kaplan-Meier analysis, patients with PAD predicted poor prognosis in MACE (P < 0.05) and cardiovascular events (P < 0.05). In Multivariable Cox proportional hazards analysis, patients with PAD independently predicted MACE and cardiovascular events. CONCLUSIONS: PAD is a significant mediator for the prognosis of patients with stable CAD who underwent PCI treatment.

Reduced Sirtuin1 signalling exacerbates diabetic mice hindlimb ischaemia injury and inhibits the protective effect of a liver X receptor agonist.

Diabetes mellitus causes endothelial dysfunction, which further exacerbates peripheral arterial disease (PAD). Improving endothelial function via reducing endothelial oxidative stress (OS) may be a promising therapy for diabetic PAD. Activation of liver X receptor (LXR) inhibits excessive OS and provides protective effects on endothelial cells in diabetic individuals. Therefore, we investigated the effects of LXR agonist treatment on diabetic PAD with a focus on modulating endothelial OS. We used a streptozotocin-induced diabetes mouse model combined with a hindlimb ischaemia (HLI) injury to mimic diabetic PAD, which was followed by LXR agonist treatment. In our study, the LXR agonist T0901317 protected against HLI injury in diabetic mice by attenuating endothelial OS and stimulating angiogenesis. However, a deficiency in endothelial Sirtuin1 (SIRT1) largely inhibited the therapeutic effects of T0901317. Furthermore, we found that the underlying therapeutic mechanisms of T0901317 were related to SIRT1 and non-SIRT1 signalling, and the isoform LXRß was involved in LXR agonist-elicited SIRT1 regulation. In conclusion, LXR agonist treatment protected against HLI injury in diabetic mice via mitigating endothelial OS and stimulating cellular viability and angiogenesis by LXRß, which elicited both SIRT1-mediated and non-SIRT1-mediated signalling pathways. Therefore, LXR agonist treatment may be a promising therapeutic strategy for diabetic PAD.

Male and female sexual dysfunction in diabetic subjects: Focus on new antihyperglycemic drugs.

The association between diabetes mellitus (and its micro- and macro-vascular complications) and erectile dysfunction is widely known and the presence of hypogonadism may further complicate sexual dysfunction and quality of life, given the association between hypogonadism and reduced libido, ejaculatory disorders, and depressive symptoms. However, the recent introduction of novel antidiabetic agents with a wide range of mechanism of action may have a significant impact both on male and female sexuality directly (by inducing side effects as urinary tract infections) and indirectly (improving metabolic status and reducing diabetes complications behind sexual dysfunctions). To date only few papers are reporting the sexual effects of these treatments and, often, these are not comparable in their results. Conversely, female sexual dysfunctions are somehow under-investigated. Data on prevalence is heterogeneous and specific pathogenic mechanisms, as well as the burden of psychological factors, are still heatedly debated. The aim of this narrative review is to summarize current knowledge and stressing out the need to diagnose male and female sexual dysfunctions also in light of the impact of treatments with novel antidiabetic agents. This would highlight the still unmet needs for sexual care in a diabetes care setting and could represent an incentive for future discussions, as well as a required theoretical starting point for studies on this subject.

Impact of Cardio-Renal-Metabolic Comorbidities on Cardiovascular Outcomes and Mortality in Type 2 Diabetes Mellitus.

BACKGROUND: We evaluated the incremental contribution of chronic kidney disease (CKD) to the risk of major adverse cardiovascular (CV) events (MACE), heart failure (HF), and all-cause mortality (ACM) in type 2 diabetes mellitus (T2DM) patients and its importance relative to the presence of other cardio-renal-metabolic (CaReMe) comorbidities. METHODS: Patients (≥40 years) were identified at the time of T2DM diagnosis from US (Humedica/Optum) and UK (Clinical Practice Research Datalink) databases. Patients were monitored post-diagnosis for modified MACE (myocardial infarction, stroke, ACM), HF, and ACM. Adjusted hazard ratios were obtained using Cox proportional-hazards regression to evaluate the relative risk of modified MACE, HF, and ACM due to CKD. Patients were stratified by the presence or absence of atherosclerotic CV disease (ASCVD) and age. RESULTS: Between 2011 and 2015, of 227,224 patients identified with incident T2DM, 40,063 (17.64%) had CKD. Regardless of prior ASCVD, CKD was associated with higher risk of modified MACE, HF, and ACM; this excess hazard was more pronounced in older patients with prior ASCVD. In time-to-event analyses in the overall cohort, patients with T2DM + CKD or T2DM + CKD + hypertension + hyperlipidemia had increased risks for modified MACE, HF, and ACM versus patients with T2DM and no CaReMe comorbidities. Patients with CKD had higher risks for and shorter times to modified MACE, HF, and ACM than those without CKD. CONCLUSION: In T2DM patients, CKD presence was associated with higher risk of modified MACE, HF, and ACM. This may have risk-stratification implications for T2DM patients based on background CKD and highlights the potential importance of novel renoprotective strategies.

Predictors of intra-hospital mortality in patients with diabetic foot ulcers in Nigeria: data from the MEDFUN study.

BACKGROUND: Diabetic foot ulcers (DFU) are associated with high morbidity and mortality globally. Mortality in patients hospitalized for DFU in Nigeria is unacceptably high. This study was undertaken to determine factors that predict mortality in patients hospitalized for DFU in Nigeria. METHODS: The current study was part of Multi-centre Evaluation of Diabetic Foot Ulcer in Nigeria (MEDFUN), an observational study conducted in six tertiary healthcare institutions across the 6 geopolitical zones of Nigeria. Consecutive type 1 or 2 diabetic patients hospitalized for DFU who consented to participate were recruited and subjected to relevant clinical, biochemical, and radiological assessments and multidisciplinary care until discharge or death. Data for type 1 diabetes mellitus (DM) patients were expunged from current mortality analysis due to their small number. RESULTS: Three hundred and twenty-three type 2 DM subjects with mean age and mean duration of DM of 57.2 ± 11.4 years and 8.7 ± 5.8 years respectively participated in this study. The median duration of ulcers was 39 days with a range of 28 to 54 days and the majority (79.9%) presented with advanced ulcers of at least Wagner grade 3. Mortality of 21.4% was recorded in the study, with the highest mortality observed among subjects with Wagner grade 5. Variables significantly associated with mortality with their respective p values were DM duration more than 120 months (p 0.005), ulcer duration > 1 month (p 0.020), ulcer severity of Wagner grade 3 and above (p 0.001), peripheral arterial disease (p 0.005), proteinuria (p < 0.001), positive blood cultures (p < 0.001), low HDL (p < 0.001), shock at presentation (p < 0.001), cardiac failure (p 0.027), and renal impairment (p < 0.001). On Multivariate regression analysis, presence of bacteraemia (OR 5.053; 95% CI 2.572-9.428) and renal impairment (OR 2.838; 95% CI 1.349-5.971) were significantly predictive of mortality independent of other variables. CONCLUSIONS: This study showed high intra-hospital mortality among patients with DFU, with the majority of deaths occurring among those with advanced ulcers, bacteraemia, cardiac failure, and renal impairment. Prompt attention to these factors might help improve survival from DFU in Nigeria.

Cerebral Arteriovenous Malformations as Acquired Lesions: Case Reports and Review of the Literature.

Cerebral arteriovenous malformations (AVMs) are generally attributed to congenital lesions that arise from aberrant vasculogenesis between the fourth and eighth weeks of embryonic life. However, this dogma has been challenged by several recent observations, one of which is de novo formation of AVMs. Forty cases of de novo AVMs were published between 2000 and 2019, all of which involved a history of intracranial insult, such as vascular abnormalities or nonvascular conditions, prior to AVM diagnosis. We hereby present two unique operative cases of ruptured de novo AVMs in older adult patients. Case 1 is novel in the sense that the patient did not experience any kind of environmental trigger ("second hit") such as a previous intracranial insult, while Case 2 serves as the second report of a de novo AVM patient with a medical history of Bell's palsy. Although the exact mechanisms of AVM formation remain to be elucidated, it is likely to be a multifactorial process related to environmental and hemodynamic factors.

The association between vascular complications during pregnancy in women with Type 1 diabetes and congenital malformations.

AIMS: To assess the association between vascular complications of diabetes and the risk of congenital malformations in pregnant women with Type 1 diabetes. METHODS: We conducted an observational retrospective cohort study in women with Type 1 diabetes who received care consecutively from three tertiary care diabetes-in-pregnancy clinics in Calgary, Alberta, Canada. Multivariable logistic regression was used to assess the association between vascular complications (retinopathy, nephropathy and pre-existing hypertension) and congenital malformations in offspring of women with Type 1 diabetes. RESULTS: Of 232 women with Type 1 diabetes, 49 (21%) had at least one vascular complication and there were 52 babies with congenital malformations. Maternal age (31.8 ± 5.0 vs. 29.4 ± 4.7 years, P < 0.01), diabetes duration (20.9 ± 6.7 vs. 11.2 ± 7.4 years, P < 0.01) and pre-eclampsia rate (12.5% vs. 1.3%, P < 0.01) were higher in mothers with vascular complications than in those without. Multivariable analyses showed that vascular complications were not associated with an increased risk of congenital malformations (odds ratio 1.16, 95% confidence interval 0.46 to 2.88). CONCLUSIONS: Vascular complications are common, occurring in one-fifth of pregnant women with Type 1 diabetes, and in this study do not appear to be associated with an increased risk of congenital malformations in children.

Depressive symptoms and cerebral microvascular disease in adults with Type 1 diabetes mellitus.

AIM: To assess the prevalence of, and risk factors for, depressive symptoms, comparing a sample of middle-aged adults with and without juvenile-onset Type 1 diabetes mellitus, and to determine if depressive symptoms were associated with white matter hyperintensity volume among those with Type 1 diabetes. METHODS: Depressive symptoms and white matter hyperintensities were compared between adults (age range 30-65 years) with juvenile-onset Type 1 diabetes (n=130) and adults without Type 1 diabetes (n=133). The association of Type 1 diabetes with depression was computed before and after adjustment for white matter hyperintensities. Among the Type 1 diabetes group, the primary associations of interest were between depressive symptoms (Beck Depression Inventory score ≥10) and white matter hyperintensities (n=71), hyperglycaemia and physical activity. Associations between depressive symptoms and diabetes-related complications, cognitive impairment, smoking and self-reported disability were examined. Analyses were controlled for education, sex, age and antidepressant use. RESULTS: Depressive symptoms were more prevalent among those with vs those without Type 1 diabetes (28% vs 3%; P<0.001). White matter hyperintensities explained 40% of the association of Type 1 diabetes with depressive symptoms, while Type 1 diabetes had a direct effect of 68% on depressive symptoms. Among those with Type 1 diabetes, depressive symptoms were related to white matter hyperintensity volume, a 16-year average HbA1c ≥58 mmol/mol (7.5%), and lower physical activity levels. Associations with other characteristics were not significant. CONCLUSION: These findings suggest a cerebrovascular origin for depressive symptoms in adults with Type 1 diabetes, perhaps triggered by hyperglycaemia. Future longitudinal studies should investigate whether targeting hyperglycaemia and physical inactivity alleviates depressive symptoms, possibly by slowing the development of cerebral microvascular disease, in people with Type 1 diabetes.

Sample size considerations for stratified cluster randomization design with binary outcomes and varying cluster size.

Stratified cluster randomization trials (CRTs) have been frequently employed in clinical and healthcare research. Comparing with simple randomized CRTs, stratified CRTs reduce the imbalance of baseline prognostic factors among different intervention groups. Due to the popularity, there has been a growing interest in methodological development on sample size estimation and power analysis for stratified CRTs; however, existing work mostly assumes equal cluster size within each stratum and uses multilevel models. Clusters are often naturally formed with random sizes in CRTs. With varying cluster size, commonly used ad hoc approaches ignore the variability in cluster size, which may underestimate (overestimate) the required number of clusters for each group per stratum and lead to underpowered (overpowered) clinical trials. We propose closed-form sample size formulas for estimating the required total number of subjects and for estimating the number of clusters for each group per stratum, based on Cochran-Mantel-Haenszel statistic for stratified cluster randomization design with binary outcomes, accounting for both clustering and varying cluster size. We investigate the impact of various design parameters on the relative change in the required number of clusters for each group per stratum due to varying cluster size. Simulation studies are conducted to evaluate the finite-sample performance of the proposed sample size method. A real application example of a pragmatic stratified CRT of a triad of chronic kidney disease, diabetes, and hypertension is presented for illustration.

Malnutrition assessed by controlling nutritional status is correlated to carotid atherosclerosis in patients with type 2 diabetes.

Diabetes and malnutrition sometimes overlap. Little is known about the relationship between malnutrition and subclinical atherosclerosis in patients with type 2 diabetes. This cross-sectional study investigated this relationship in patients with type 2 diabetes. We evaluated the relationships between malnutrition assessed by controlling nutritional status (CONUT) score and subclinical atherosclerosis assessed by carotid intima-media thickness (IMT) and carotid plaque scores in 461 consecutive patients with type 2 diabetes. Nutritional assessment indicated that 38% of patients were malnourished (CONUT ≥3). Carotid IMT and carotid plaque scores were significantly higher in patients with malnutrition. Multivariate linear regression analyses revealed that a high CONUT score (CONUT ≥3) was correlated with mean IMT (ß = 0.196, p = 0.043) and max IMT (ß = 0.243, p = 0.011) in patients taking statins and was also correlated with mean IMT (ß = 0.287, p = 0.004), max IMT (ß = 0.308, p = 0.002), and plaque score (ß = 0.190, p = 0.044) in patients not taking statins after adjusting for age, sex, duration of diabetes, body mass index, hemoglobin A1c, creatine, smoking, and hypertension. Our results demonstrate a relationship between malnutrition and subclinical atherosclerosis in patients with type 2 diabetes.

Levels of adhesion molecules in peripheral blood correlat with stages of diabetic retinopathy and may serve as bio markers for microvascular complications.

BACKGROUND: Proliferative diabetic retinopathy is a devastating complication of diabetes mellitus, developing within 15 years in 50% of patients with type 1 diabetes mellitus (DM) and in 10% of patients with type 2 DM. The correlation between levels of inflammatory markers in the peripheral blood and retinopathy staging has not been studied yet, and the purpose of this prospective study was to find a possible association between inflammation and staging of diabetic retinopathy. METHODS: A prospective (pilot) study that measured level of adhesion molecules in the peripheral blood of 10 healthy subjects and 30 patients with type 2 diabetes mellitus. Patients were grouped by the degree of retinopathy: 10 without retinopathy, 10 with non-proliferative retinopathy [NPDR] and 10 with proliferative retinopathy [PDR]. After signing the consent form, an ophthalmologic examination was performed, and 10 mL of blood was drawn. In order to assess adhesion molecules' level serum samples were collected, frozen, and stored at a temperature of -80 °C until analysis was performed as one batch. RESULTS: 10 healthy volunteers and 30 patients were enrolled. Healthy volunteers were younger (36.6 ±â€¯7.9 years) compared to patients (no retinopathy 64.5 ±â€¯10.8 years, NPDR 71.4 ±â€¯8.9 years, and PDR 63.3 ±â€¯11.6 years) (p = .0003 for all groups of patients in comparison with the healthy subjects). VCAM-1 levels were increased by retinopathy staging - starting from 81.86 ±â€¯3.80 ng/ml (healthy), 105.55 ±â€¯1.37 ng/ml (no retinopathy), 111.78 ±â€¯4.14 ng/ml (NPDR), and 123.45 ±â€¯3.99 ng/ml (PDR), with a significant difference between healthy and patients without retinopathy (p = .03), between no retinopathy and NPDR (p = .001), and between NPDR and PDR (p < .0001). E selectin was increased in correlation with severity of the retinopathy, with a significant difference between groups of patients (p = .03 between healthy subjects and T2DM patients without retinopathy, p = .001 between patients with T2DM no retinopathy and NPDR, p < .0001 between NPDR and PDR). CONCLUSIONS: We found a significant increase in levels of adhesion molecules (VCAM-1) and selectins (E-selectin) in parallel with increased severity of diabetic retinopathy, with a significant difference of inflammatory markers between stages of retinopathy.

Cardiovascular autonomic neuropathy and bone metabolism in Type 1 diabetes.

AIM: To investigate the association between cardiovascular autonomic neuropathy and bone metabolism in people with Type 1 diabetes. METHODS: We assessed cardiovascular autonomic neuropathy in 329 people with Type 1 diabetes according to heart rate response to deep breathing, to standing and to the Valsalva manoeuvre, and 2-min resting heart rate. More than one pathological non-resting test was defined as cardiovascular autonomic neuropathy. Bone mineral density of the femoral neck (BMDfn) was assessed by dual energy X-ray absorptiometry. Serum parathyroid hormone levels and other bone markers were measured. RESULTS: The mean (sd) age of the participants was 55.6 (9.4) years, 52% were men, and the mean (sd) diabetes duration was 40 (8.9) years, HbA1c 62 (9) mmol/mol and estimated GFR 78 (26) ml/min/1.73m2 . In all, 36% had cardiovascular autonomic neuropathy. Participants with cardiovascular autonomic neuropathy had 4.2% (95% CI -8.0 to -0.2; P=0.038) lower BMDfn and 33.6% (95% CI 14.3 to 53.8; P=0.0002) higher parathyroid hormone levels compared with participants without cardiovascular autonomic neuropathy in adjusted models. Higher resting heart rate remained associated with higher parathyroid hormone level and lower BMDfn after additional adjustment for eGFR (P<0.0001 and P = 0.042, respectively). CONCLUSIONS: The presence of cardiovascular autonomic neuropathy was associated with reduced BMDfn and increased levels of parathyroid hormone. Kidney function may either confound or mediate these findings. Cardiovascular autonomic neuropathy could be associated with increased risk of osteoporosis in Type 1 diabetes. Whether cardiovascular autonomic neuropathy directly affects bone metabolism detrimentally or if this association is mediated via decreased kidney function should be investigated further.