The association of chronic complications with time in tight range and time in range in people with type 1 diabetes: a retrospective cross-sectional real-world study.

AIMS/HYPOTHESIS: The aim of this study was to evaluate the association of chronic complications with time in tight range (TITR: 3.9-7.8 mmol/l) and time in range (TIR: 3.9-10.0 mmol/l) in people with type 1 diabetes. METHODS: The prevalence of microvascular complications (diabetic retinopathy, diabetic nephropathy and diabetic peripheral neuropathy [DPN]) and macrovascular complications according to sensor-measured TITR/TIR was analysed cross-sectionally in 808 adults with type 1 diabetes. Binary logistic regression was used to evaluate the association between TITR/TIR and the presence of complications without adjustment, with adjustment for HbA1c, and with adjustment for HbA1c and other confounding factors (sex, age, diabetes duration, BMI, BP, lipid profile, smoking, and use of statins and renin-angiotensin-aldosterone system inhibitors). RESULTS: The mean TITR and TIR were 33.9 ± 12.8% and 52.5 ± 15.0%, respectively. Overall, 46.0% had any microvascular complication (34.5% diabetic retinopathy, 23.8% diabetic nephropathy, 16.0% DPN) and 16.3% suffered from any macrovascular complication. The prevalence of any microvascular complication, diabetic retinopathy, diabetic nephropathy and a cerebrovascular accident (CVA) decreased with increasing TITR/TIR quartiles (all ptrend<0.05). Each 10% increase in TITR was associated with a lower incidence of any microvascular complication (OR 0.762; 95% CI 0.679, 0.855; p<0.001), diabetic retinopathy (OR 0.757; 95% CI 0.670, 0.856; p<0.001), background diabetic retinopathy (OR 0.760; 95% CI 0.655, 0.882; p<0.001), severe diabetic retinopathy (OR 0.854; 95% CI 0.731, 0.998; p=0.048), diabetic nephropathy (OR 0.799; 95% CI 0.699, 0.915; p<0.001), DPN (OR 0.837; 95% CI 0.717, 0.977; p=0.026) and CVA (OR 0.651; 95% CI 0.470, 0.902; p=0.010). The independent association of TITR with any microvascular complication (OR 0.867; 95% CI 0.762, 0.988; p=0.032), diabetic retinopathy (OR 0.837; 95% CI 0.731, 0.959; p=0.010), background diabetic retinopathy (OR 0.831; 95% CI 0.705, 0.979; p=0.027) and CVA (OR 0.619; 95% CI 0.426, 0.899; p=0.012) persisted after adjustment for HbA1c. Similar results were obtained when controlling for HbA1c and other confounding factors. CONCLUSIONS/INTERPRETATION: TITR and TIR are inversely associated with the presence of microvascular complications and CVA in people with type 1 diabetes. Although this study was not designed to establish a causal relationship, this analysis adds validity to the use of TITR and TIR as key measures in glycaemic management. TRIAL REGISTRATION: ClinicalTrials.gov NCT02601729 and NCT02898714.

Relapse and side effects of steroid therapy beyond 3 years in autoimmune pancreatitis: A multicenter retrospective study.

BACKGROUND: The impact of extended steroid administration on patients with autoimmune pancreatitis after a 3-year maintenance period remains poorly understood. This study analyzed the advantage and disadvantage of continuing steroid therapy beyond 3 years. METHODS: In this retrospective multicenter study across 17 institutions, patients who successfully completed 3 years of maintenance therapy without experiencing relapse were categorized into two groups: the maintenance therapy discontinuation group, who discontinued steroid therapy after the initial 3-year period, and maintenance therapy continuation group, who continued steroid therapy beyond 3 years. The cumulative relapse rate after 3 years of maintenance therapy was the primary outcome. Relapse predictors were compared using the Gray test for cumulative relapse incidence by specific factor. RESULTS: Of 211 patients, 105 experienced no relapse during the 3-year maintenance therapy and were divided into two groups: 69 in the maintenance therapy discontinuation group and 36 in the maintenance therapy continuation group. The relapse rate was lower in the maintenance therapy continuation group than in the maintenance therapy discontinuation group (P = 0.035). Predictors of relapse after 3 years included cessation of maintenance therapy (hazard ratio [HR] = 3.76; 95 % confidence interval [CI] = 1.07-13.3, P = 0.040) and renal involvement (HR = 2.88; 95 % CI = 1.04-7.99, P = 0.042). The maintenance therapy continuation group showed a significantly higher prevalence of macrovascular complications, compared with the maintenance therapy discontinuation group (P = 0.005). CONCLUSIONS: Cessation of steroid maintenance therapy and renal involvement were predictors of relapse after 3 years of maintenance therapy. However, the long-term use of steroids may increase the risk of macrovascular complications.

The coexistence of low muscle mass and obesity evaluated by dual energy X-ray absorptiometry, rather than low muscle mass or obesity alone, is associated with macrovascular but not microvascular complications in patients with type 2 diabetes mellitus.

AIM: The prevalence of the coexistence of low muscle mass and obesity is increasing, particularly with a rising trend observed in patients diagnosed with type 2 diabetes mellitus (T2DM). However, the association between the coexistence of low muscle mass and obesity and diabetic complications remains unclear. This study aimed to investigate these associations in patients with T2D. MATERIALS AND METHODS: A retrospective study was conducted, including 2387 hospitalized patients with T2DM. Data on demographic characteristics, biochemical parameters, diabetic complications and body composition was from electronic health records. The participants were categorized as control, low muscle mass, obesity and the coexistence of the low muscle mass and obesity groups according to the body compositions evaluated by dual-energy X-ray absorptiometry. Multiple logistic regression models were applied to assess the associations between the pattern of body composition and complications of diabetes. RESULTS: After adjustment for potential confounders, compared with patients in the control group, the odds ratios [95% confidence intervals (CIs)] of macrovascular complications of diabetes were 0.62 (95% CI, 0.27-1.39) for those in the low muscle mass group, 1.12 (95% CI, 0.59-2.11) in the obesity group, and 2.43 (95% CI, 1.16-5.07) in the coexistence of the low muscle mass and obesity group, respectively; the odds ratios (95% CIs) of microvascular complications of diabetes were 0.86 (95% CI, 0.52-1.43) for those in the low muscle mass group, 0.82 (95% CI, 0.53-1.26) in the obesity group, and 1.21 (95% CI, 0.69-2.15) in the coexistence of the low muscle mass and obesity group, respectively. CONCLUSION: According to our findings, the coexistence of low muscle mass and obesity, rather than low muscle mass or obesity alone, was significantly associated with a higher prevalence of macrovascular complications in hospitalized patients with T2DM. This association was not observed for diabetic microvascular complications.

Effect of delay in treatment intensification in people with type 2 diabetes and suboptimal glycaemia after basal insulin initiation: A real-world observational study.

AIM: Despite global recommendations for type 2 diabetes mellitus treatment to maintain optimal glycaemic targets, a significant proportion of people remain in suboptimal glycaemic control. Our objective was to investigate the impact of intensification delay after basal insulin (BI) initiation on long-term complications in people with suboptimal glycaemia. MATERIALS AND METHODS: We conducted a retrospective cohort study in individuals with type 2 diabetes mellitus initiated on BI. Those with suboptimal glycaemia (glycated haemoglobin ≥7% or ≥53 mmol/mol) within 12 months of BI initiation were divided into early (treatment intensified within 5 years), or late (≥5 years) intensification groups. We estimated the age-stratified risks of micro- and macrovascular complications among these groups compared with those with optimal glycaemia (glycated haemoglobin <7%). RESULTS: Of the 13 916 people with suboptimal glycaemia, 52.5% (n = 7304) did not receive any treatment intensification. In those aged <65 years, compared with the optimal glycaemia group late intensification was associated with a 56% higher risk of macrovascular complications (adjusted hazard ratio 1.56; 95% confidence intervals 1.08, 2.26). In elderly people (≥65 years), late intensification was associated with a higher risk of cardiovascular-related death (1.62; 1.03, 2.54) and a lower risk of microvascular complications (0.26; 0.08, 0.83). CONCLUSIONS: Those who had late intensification were at an increased risk of cardiovascular death if they were ≥65 years and an increased risk of macrovascular complications if they were <65 years. These findings highlight the critical need for earlier intensification of treatment and adopting personalized treatment strategies to improve patient outcomes.

Prevalence, patterns, and determinants of vascular complications of type 2 diabetes in a teaching hospital in Addis Ababa, Ethiopia: a retrospective study.

BACKGROUND: Patients with type 2 diabetes mellitus (T2D) have an increased risk of vascular complications. Despite the rise in the prevalence of T2D and its complications throughout the globe, there is a paucity of data regarding the prevalence and determinants of vascular complications of T2D in Ethiopia. Hence, this study aimed to assess the prevalence, patterns, and determinants of the microvascular and macrovascular complications of T2D among adult patients attending a teaching hospital in Addis Ababa, Ethiopia. METHODS: A retrospective study was done by reviewing the electronic health records of adult patients with T2D attending the general medical and endocrine referral clinics of Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia, from June 1, 2023, to November 30, 2023. Statistical Package for Social Sciences (SPSS), version 25, was used to analyze the data. Descriptive analysis was used to summarize the sociodemographic, clinical, and laboratory profiles as well as the patterns of vascular complications of T2D. Bivariate and multivariate logistic regression models were fitted, and the crude odds ratio (COR) and adjusted odds ratio (AOR), together with the 95% confidence interval (CI), were computed to identify the determinants of microvascular and macrovascular complications of T2D. RESULTS: A total of 272 patients with T2D were included in this study; 50.5% were females, and the mean (± standard deviation) age was 56.3 ± 12.8 years. The majority of patients (62.5%) had diabetes for ≥ 5 years. More than half (51.5%) had poor glycemic control with glycated haemoglobin (HbA1c) value of ≥ 7%. The overall prevalence of vascular complications was 39%. The prevalence of microvascular complications was 23.5%, the most common being neuropathy (11.8%), and the prevalence of macrovascular complications was 21%, the most common being coronary artery disease (12.1%). The determinants of microvascular complications were age ≥ 60 years (AOR = 2.25, 95% CI: 1.17, 4.33), diabetes duration of ≥ 5 years (5-10 years [AOR = 3.13, 95% CI: 1.37, 7.18], and > 10 years [AOR = 3.88, 95% CI: 1.66, 9.06], and HbA1c value of ≥ 7% (AOR = 2.21, 95% CI: 1.14, 4.28). The odds of developing macrovascular complications were higher with diabetes duration of ≥ 5 to 10 years (AOR = 2.89, 95% CI: 1.37, 6.12) as compared with diabetes duration of < 5 years. CONCLUSIONS: This study demonstrated a high prevalence of microvascular and macrovascular complications in adult patients with T2D. Older age, prolonged duration of diabetes, and poor glycemic control were identified as the determinants for the development of microvascular complications  of T2D, while prolonged duration of diabetes was the determining factor for the development of macrovascular complications. Hence, targeted initiatives are required to enhance the prevention and early detection of vascular complications of T2D in resource-limited countries like Ethiopia.

Preventing diabetes complications.

The key aim of diabetes management is to prevent complications, which are a major cause of morbidity and mortality. At an individual level, people with diabetes are less likely than they were several decades ago to experience classical macrovascular and microvascular complications as a result of improvements in modifiable cardiovascular risk factors and preventive healthcare. However, a significant burden of diabetes complications persists at a population level because of the increasing incidence of diabetes, as well as longer lifetime exposure to diabetes because of younger diagnosis and increased life expectancy. Trials have shown that the most effective strategy for preventing complications of diabetes is a multifactorial approach focussing simultaneously on the management of diet, exercise, glucose levels, blood pressure and lipids. In addition to the cornerstone strategies of addressing diet, exercise and lifestyle measures, the introduction of newer glucose-lowering agents, including sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 agonists, have brought about a paradigm shift in preventing the onset and progression of complications of type 2 diabetes, particularly cardiovascular and renal disease. The improvement in rates of classical complications of diabetes over time has been accompanied by a growing awareness of non-traditional complications, including non-alcoholic fatty liver disease. These emerging complications may not respond to a glycaemic-centred approach alone and highlight the importance of foundational strategies centred on lifestyle measures and supported by pharmaceutical therapy to achieve weight loss and reduce metabolic risk in patients living with diabetes.

Investigation of the Systemic Immune Inflammation (SII) Index as an Indicator of Morbidity and Mortality in Type 2 Diabetic Retinopathy Patients in a 4-Year Follow-Up Period.

Background and Objectives: This study aimed to investigate the relationship between the systemic immune inflammation (SII) index and the development of micro and macro complications and mortality within the first year and the following three years in type 2 diabetic retinopathy patients. Materials and Methods: The retrospective study included 523 type 2 diabetic retinopathy patients seen in the endocrinology outpatient clinic of our hospital between January and December 2019. Their demographic and clinical characteristics were analyzed using descriptive statistics. The normal distribution of quantitative data was assessed by the Shapiro-Wilk test. Mann-Whitney U, McNemar-Chi-square, and Cochran's Q tests were used to analyze the SII values and complication rates over time. An ROC analysis determined the sensitivity and specificity of SII. A multiple linear regression analysis examined the relationship between variables and SII, while Spearman's test assessed the correlation between CRP and SII. p < 0.05 was accepted as significant. Results: The mean age of patients was 63.5 ± 9.3 years, with mean SII values of 821.4 ± 1010.8. Higher SII values were significantly associated with acute-chronic renal failure, peripheral arterial disease, and hospitalization rates in both the first year and the following three years (p < 0.05 for all). Significant cut-off values for SII were found for micro- and macrovascular complications and death within the first year (p < 0.05 for all). The ROC curve analysis identified an optimal SII cut-off value of >594.0 for predicting near-term (1-year) complications and mortality, with a sensitivity of 73.8% and specificity of 49.4% (area under the ROC curve: 0.629, p = 0.001). Multiple linear regression indicated that smoking of at least 20 pack-years had a significant positive effect on SII. The Spearman test showed a weak positive correlation between SII and CRP. Conclusions: High SII values predict both early and late acute-chronic renal failure, peripheral arterial disease, and hospitalizations in patients with type 2 diabetic retinopathy. The study also shows that high SII values may predict microvascular and macrovascular complications of type 2 DM and mortality risk in the early period in patients with type 2 diabetic retinopathy. In addition, comorbidities and inflammatory habits, such as long-term smoking, should be considered in the clinical use of SII.

Sex differences in type 2 diabetes.

The prevalence of type 2 diabetes mellitus is increasing in both sexes, but men are usually diagnosed at a younger age and lower body fat mass than women. Worldwide, an estimated 17.7 million more men than women have diabetes mellitus. Women appear to bear a greater risk factor burden at the time of their type 2 diabetes diagnosis, especially obesity. Moreover, psychosocial stress might play a more prominent role in diabetes risk in women. Across their lifespan, women experience greater hormone fluctuations and body changes due to reproductive factors than men. Pregnancies can unmask pre-existing metabolic abnormalities, resulting in the diagnosis of gestational diabetes, which appears to be the most prominent risk factor for progression to type 2 diabetes in women. Additionally, menopause increases women's cardiometabolic risk profile. Due to the progressive rise in obesity, there is a global increase in women with pregestational type 2 diabetes, often with inadequate preconceptual care. There are differences between men and women regarding type 2 diabetes and other cardiovascular risk factors with respect to comorbidities, the manifestation of complications and the initiation of and adherence to therapy. Women with type 2 diabetes show greater relative risk of CVD and mortality than men. Moreover, young women with type 2 diabetes are currently less likely than men to receive the treatment and CVD risk reduction recommended by guidelines. Current medical recommendations do not provide information on sex-specific or gender-sensitive prevention strategies and management. Thus, more research on sex differences, including the underlying mechanisms, is necessary to increase the evidence in the future. Nonetheless, intensified efforts to screen for glucose metabolism disorders and other cardiovascular risk factors, as well as the early establishment of prophylactic measures and aggressive risk management strategies, are still required for both men and women at increased risk of type 2 diabetes. In this narrative review we aim to summarise sex-specific clinical features and differences between women and men with type 2 diabetes into risk factors, screening, diagnosis, complications and treatment.

Diabetes in a hospital cohort of persons living with HIV: a descriptive and comparative study in French Guiana.

BACKGROUND: In French Guiana (population 294,000) the prevalence of type 2 diabetes (10%) and of HIV(1.1%) are very high. Our objective was to determine the prevalence of diabetes and its complications in a HIV cohort. MATERIALS AND METHODS: We enrolled HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals between January 1, 1992 and December 31, 2021 in the French Hospital Database for HIV (FHDH) a national database compiling data from all French regions. RESULTS: There was no difference of diabetes prevalence between men (8.2%) and women (8.8%), P = 0.4. Patients with diabetes were older (56 years ± 13.4) than those without diabetes (44.7 years ± 13.6) and prevalence increased with age. The proportion of persons with diabetes was greater among virologically suppressed persons (10%) than those with a detectable viral load under antiretroviral treatment (5.8%). Persons with diabetes had substantially greater CD4 counts at diagnosis than persons without diabetes. The majority of macro and microvascular complications were observed in people with diabetes. Persons with diabetes and HIV were significantly less likely to have had AIDS (1.6 versus 2.2 per 100 person-years, respectively). Overall, 374 persons living with HIV of 4167 had died (9%) the proportion of persons with diabetes among the dead was greater than those who did not die 11.7% versus 8.1%, respectively, p = 0.017. However, persons with diabetes were older and hence died older, 62.3 years (SD = 1.9) for deceased persons with diabetes versus 50.4 years (SD = 0.8), P < 0.0001. However, using Cox regression to adjust for age, initial CD4 count, country of birth there was no significant difference in the Hazard for death between persons with diabetes and persons without diabetes (aHR = 0.99, 95%CI = 0.65-1.5), P = 0.9. CONCLUSIONS: The prevalence of diabetes in our HIV cohort was high. Persons with diabetes had greater CD4 counts, earlier care, and greater virological suppression than persons without diabetes. There were no significant differences between persons with diabetes and without diabetes in terms of survival.

Machine Learning for Predicting Micro- and Macrovascular Complications in Individuals With Prediabetes or Diabetes: Retrospective Cohort Study.

BACKGROUND: Micro- and macrovascular complications are a major burden for individuals with diabetes and can already arise in a prediabetic state. To allocate effective treatments and to possibly prevent these complications, identification of those at risk is essential. OBJECTIVE: This study aimed to build machine learning (ML) models that predict the risk of developing a micro- or macrovascular complication in individuals with prediabetes or diabetes. METHODS: In this study, we used electronic health records from Israel that contain information about demographics, biomarkers, medications, and disease codes; span from 2003 to 2013; and were queried to identify individuals with prediabetes or diabetes in 2008. Subsequently, we aimed to predict which of these individuals developed a micro- or macrovascular complication within the next 5 years. We included 3 microvascular complications: retinopathy, nephropathy, and neuropathy. In addition, we considered 3 macrovascular complications: peripheral vascular disease (PVD), cerebrovascular disease (CeVD), and cardiovascular disease (CVD). Complications were identified via disease codes, and, for nephropathy, the estimated glomerular filtration rate and albuminuria were considered additionally. Inclusion criteria were complete information on age and sex and on disease codes (or measurements of estimated glomerular filtration rate and albuminuria for nephropathy) until 2013 to account for patient dropout. Exclusion criteria for predicting a complication were diagnosis of this specific complication before or in 2008. In total, 105 predictors from demographics, biomarkers, medications, and disease codes were used to build the ML models. We compared 2 ML models: logistic regression and gradient-boosted decision trees (GBDTs). To explain the predictions of the GBDTs, we calculated Shapley additive explanations values. RESULTS: Overall, 13,904 and 4259 individuals with prediabetes and diabetes, respectively, were identified in our underlying data set. For individuals with prediabetes, the areas under the receiver operating characteristic curve for logistic regression and GBDTs were, respectively, 0.657 and 0.681 (retinopathy), 0.807 and 0.815 (nephropathy), 0.727 and 0.706 (neuropathy), 0.730 and 0.727 (PVD), 0.687 and 0.693 (CeVD), and 0.707 and 0.705 (CVD); for individuals with diabetes, the areas under the receiver operating characteristic curve were, respectively, 0.673 and 0.726 (retinopathy), 0.763 and 0.775 (nephropathy), 0.745 and 0.771 (neuropathy), 0.698 and 0.715 (PVD), 0.651 and 0.646 (CeVD), and 0.686 and 0.680 (CVD). Overall, the prediction performance is comparable for logistic regression and GBDTs. The Shapley additive explanations values showed that increased levels of blood glucose, glycated hemoglobin, and serum creatinine are risk factors for microvascular complications. Age and hypertension were associated with an elevated risk for macrovascular complications. CONCLUSIONS: Our ML models allow for an identification of individuals with prediabetes or diabetes who are at increased risk of developing micro- or macrovascular complications. The prediction performance varied across complications and target populations but was in an acceptable range for most prediction tasks.

Precision prognostics for the development of complications in diabetes.

Individuals with diabetes face higher risks for macro- and microvascular complications than their non-diabetic counterparts. The concept of precision medicine in diabetes aims to optimise treatment decisions for individual patients to reduce the risk of major diabetic complications, including cardiovascular outcomes, retinopathy, nephropathy, neuropathy and overall mortality. In this context, prognostic models can be used to estimate an individual's risk for relevant complications based on individual risk profiles. This review aims to place the concept of prediction modelling into the context of precision prognostics. As opposed to identification of diabetes subsets, the development of prediction models, including the selection of predictors based on their longitudinal association with the outcome of interest and their discriminatory ability, allows estimation of an individual's absolute risk of complications. As a consequence, such models provide information about potential patient subgroups and their treatment needs. This review provides insight into the methodological issues specifically related to the development and validation of prediction models for diabetes complications. We summarise existing prediction models for macro- and microvascular complications, commonly included predictors, and examples of available validation studies. The review also discusses the potential of non-classical risk markers and omics-based predictors. Finally, it gives insight into the requirements and challenges related to the clinical applications and implementation of developed predictions models to optimise medical decision making.

Registry-based randomised clinical trials: a remedy for evidence-based diabetes care?

This narrative review describes a new approach to navigation in a challenging landscape of clinical drug development in diabetes. Successful outcome studies in recent years have led to new indications and guidelines in type 2 diabetes, yet the number of clinical trials in diabetes is now declining. This is due to many environmental factors acting in concert, including the prioritisation of funding for other diseases, high costs of large randomised clinical trials, increase in regulatory requirements and limited entry of novel candidate drugs. There is a need for novel and cost-effective paradigms of clinical development to meet these and other challenges. The concept of registry-based randomised clinical trials (RRCTs) is an attractive option. In this review we focus on type 2 diabetes and the prevention of cardiovascular and microvascular comorbidities and mortality, using the Swedish SMARTEST trial as an example of an RRCT. We also give some examples from other disease areas. The RRCT concept is a novel, cost-effective and scientifically sound approach for conducting large-scale diabetes trials in a real-world setting.

Combined evaluation of arterial stiffness, glycemic control and hypertension for macrovascular complications in type 2 diabetes.

BACKGROUND: Arterial stiffness, glycemic control and blood pressure are risk factors of macrovascular complications in type 2 diabetes. This study aimed to investigate the combined association of arterial stiffness, glycemic control and hypertension status with the occurrence of diabetic macrovascular complication. METHODS: A total of 1870 patients of diabetes were enrolled from Beijing Health Management Cohort between 2008 and 2018 as baseline, and then followed for macrovascular complication onset. We proposed a composite risk score (0-4) by arterial stiffness severity, pool glycemic control and hypertension status. Cox model was used to estimate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: The mean age (SD) of this population was 59.90 (12.29) years. During a median follow-up of 4.0 years, 359 (19.2%) patients developed macrovascular complication. Compared to the normal arterial stiffness and good glycemic control group, patients with severe arterial stiffness and pool glycemic control had the highest risk of macrovascular complications (HR: 2.73; 95% CI: 1.42-5.25). Similarly, those of severe arterial stiffness and hypertension had the highest risk (HR: 2.69; 95% CI: 1.61-4.50). Patients of the composite score > 2 had a significantly increased risk of macrovascular complication. CONCLUSION: This study suggested the clinical importance of combined evaluation of arterial stiffness, glycemic control and hypertension status for the risk stratification and management of macrovascular complication of type 2 diabetes.

Spatial Reorganization of Liquid Crystalline Domains of Red Blood Cells in Type 2 Diabetic Patients with Peripheral Artery Disease.

In this work, we will investigate if red blood cell (RBC) membrane fluidity, influenced by several hyperglycemia-induced pathways, could provide a complementary index of HbA1c to monitor the development of type 2 diabetes mellitus (T2DM)-related macroangiopathic complications such as Peripheral Artery Disease (PAD). The contextual liquid crystalline (LC) domain spatial organization in the membrane was analysed to investigate the phase dynamics of the transition. Twenty-seven patients with long-duration T2DM were recruited and classified in DM, including 12 non-PAD patients, and DM + PAD, including 15 patients in any stage of PAD. Mean values of RBC generalized polarization (GP), representative of membrane fluidity, together with spatial organization of LC domains were compared between the two groups; p-values < 0.05 were considered statistically significant. Although comparable for anthropometric characteristics, duration of diabetes, and HbA1c, RBC membranes of PAD patients were found to be significantly more fluid (GP: 0.501 ± 0.026) than non-PAD patients (GP: 0.519 ± 0.007). These alterations were shown to be triggered by changes in both LC microdomain composition and distribution. We found a decrease in Feret diameter from 0.245 ± 0.281 µm in DM to 0.183 ± 0.124 µm in DM + PAD, and an increase in circularity. Altered RBC membrane fluidity is correlated to a spatial reconfiguration of LC domains, which, by possibly altering metabolic function, are associated with the development of T2DM-related macroangiopathic complications.

Hyper-reactive platelets and type 2 diabetes. / 高敏性血小板与2åž‹ç³–å°¿ç— .

Type 2 diabetes mellitus is a progressive process. With the course of the disease progress, microvascular and macrovascular complications always happen. Thrombotic events caused by macrovascular complications, including coronary heart diseases and cerebrovascular diseases, are the main fatal factor for the patients with type 2 diabetes. Endothelial dysfunction, coagulative activation, impaired fibrinolysis, together with hyper-reactive platelets contribute to the diabetic prothrombotic state, which is strongly related to the macrovascular complications. In particular, the hyper-reactive platelets play a fundamental role among them. Type 2 diabetes is characterized by several metabolic dysfunctions such as hyperglycemia, insulin resistance and shortage, oxidative stress, systemic inflammation, obesity, and dyslipidemia. These metabolic dysfunctions work together to promote the formation of hyper-reactive platelets, which are distinctive in type 2 diabetes. The regular antiplatelet drugs, like aspirin, show limited inhibitory effect on them. Hence, studying the mechanism behind the hyper-reactive platelets could provide a brand-new view on the prevention of macrovascular complications and cardiovascular events in type 2 diabetes.

SUBCLINICAL HYPOTHYROIDISM AS A CONTRIBUTOR TO MACROVASCULAR COMPLICATIONS IN PATIENTS WITH TYPE 2 DIABETES MELLITUS.

This study aimed to evaluate changes of the lipid panel data in patients with comorbid type 2 diabetes mellitus (T2DM) and subclinical hypothyroidism (SCH) and to identify the probable prognostic values of the lipid profile for macrovascular complication (MVC) development. The study included 370 patients presented with only T2DM and 30 patients suffering from both T2DM and SCH. Receiver operating characteristic (ROC) analysis was used to identify prognostically significant values of the lipid profile with the optimal ratio of sensitivity and specificity for MVC development. All lipid profile values in the patients with T2DM combined with SCH were significantly higher compared to those with only T2DM. At the same time, SCH + T2DM increased the risk of exceeding target levels of triglycerides by 2.9 times and HDL-C by 4.1 times. Analysis of lipid profile values according to macrovascular involvement showed that total cholesterol, LDL-C and non-HDL-C in patients with T2DM and SCH were significantly higher compared to those with only T2DM. The levels of triglycerides >1.65 mmol/L, non-HDL-C >3.74 mmol/L and remnant cholesterol >0.74 mmol/L determined by the ROC analysis can be used for stratification of patients with T2DM combined with SCH into the category of increased risk of MVC development.

Diabetes in People with HIV.

PURPOSE OF REVIEW: To discuss the diagnosis, treatment, and complications of diabetes in people with HIV (PWH) and to review HIV-related factors that may contribute to the development of diabetes or alter decisions in the care and treatment of PWH with diabetes. RECENT FINDINGS: For those patients with atherosclerotic cardiovascular disease, heart failure, and/or chronic kidney disease, GLP-1 receptor agonists and SGLT-2 inhibitors should be considered for use. Evidence for this recommendation is, however, based on studies that were not conducted in populations consisting solely of PWH. Diabetes is a significant comorbidity in PWH and adds to their already heightened risk of cardiovascular disease. HIV-specific factors, including interactions of antiretroviral therapy with medications that either treat diabetes and/or prevent cardiovascular disease, should be evaluated.

Clinical features of and risk factors for normoalbuminuric diabetic kidney disease in hospitalized patients with type 2 diabetes mellitus: a retrospective cross-sectional study.

BACKGROUND: Normoalbuminuric diabetic kidney disease (NADKD) is a newly defined DKD, the clinical features and pathogenesis for which are still being understood. This study aimed to investigate the features and risk factors for NADKD in patients with type 2 diabetes mellitus (T2DM). METHODS: A retrospective cross-sectional study was conducted. The related clinical and laboratory data of patients with T2DM hospitalized between August 2012 and January 2020 were collected for statistical analysis. We classified the patients with T2DM into four groups on the basis of the presence or absence of albuminuria and reduced estimated glomerular filtration rate (eGFR). Analysis of variance, the Kruskal-Wallis test, and the chi-square test were used to compare the groups. Binary logistic regression analyses with a forward stepwise method were performed to explore the risk factors for renal dysfunction in hospitalized patients with normoalbuminuric T2DM. RESULTS: Among the 1620 patients evaluated, 500 (30.9%) had DKD, of which 9% had NADKD. The prevalence of stroke, cardiovascular events, carotid plaque, and peripheral arterial disease in NADKD was significantly higher than in a non-DKD control group (normoalbuminuric T2DM patients with eGFR of ≥60 ml/min/1.73 m2). Regression analyses revealed that three significant independent factors were associated with NADKD: age (OR = 1.089, confidence interval [CI] 95% [1.055-1.123], p < 0.001), previous use of renin-angiotensin system inhibitors (RASIs; OR = 2.330, CI 95% [1.212-4.481], p = 0.011), and glycated hemoglobin (HbA1c; OR = 0.839, CI 95% [0.716-0.983], p = 0.03). CONCLUSIONS: NADKD is mainly associated with macrovascular rather than microvascular complications. NADKD is more common in patients with normoalbuminuric T2DM with older age, previous use of RASIs, and good glycemic control.

Impact of bariatric surgery on the development of diabetic microvascular and macrovascular complications.

BACKGROUND: While bariatric surgery has been shown to improve type 2 diabetes (DM) control in the obese population, the effect on long-term DM complications has been less thoroughly investigated. The purpose of this study was to assess the development of microvascular and macrovascular complications in obese DM patients undergoing bariatric surgery. METHODS: New York patients' records from the SPARCS database in years 2006-2012 were used to identify obese patients with DM. Patients undergoing bariatric surgery were compared with patients managed medically, matched for age and gender. Patients were grouped based on baseline presence of controlled or uncontrolled DM and followed over time for the development of micro- and macrovascular complications. Cumulative incidence of complications was estimated with death treated as a competing risk event. Multivariable proportional sub-distribution hazards models were used to compare the risk of complications among different patient groups after adjusting for possible confounding factors. RESULTS: A total of 88,981 patients were reviewed, including 15,585 (18%) that were treated with bariatric surgery. Surgery patients had significantly lower risk of microvascular complications compared to non-surgery patients (controlled diabetes: HR = 0.40, 95% CI 0.37-0.42; uncontrolled diabetes: HR = 0.51, 95% CI 0.37-0.71). Similarly, the surgical patients were noted to have a significantly lower risk for macrovascular complications compared to non-surgery patients (controlled diabetes: HR = 0.43, 95% CI 0.40-0.46; uncontrolled diabetes: HR = 0.44, 95% CI 0.28-0.69). Cumulative incidence of microvascular complications was lower at 1, 5 and 9 years for the surgical groups for controlled and uncontrolled DM. Similar trends were observed for the macrovascular complications. CONCLUSIONS: Bariatric surgery appears to prevent complications of DM. Bariatric surgery patients with DM experienced significantly lower rates of microvascular and macrovascular complications, compared to non-surgically treated comparison group. Bariatric surgery was noted to offer protective benefits for both complicated and non-complicated DM patients. This reduced rate of complications was sustained in the long term.

Fracture Patterns in Type 1 and Type 2 Diabetes Mellitus: A Narrative Review of Recent Literature.

PURPOSE OF REVIEW: In this narrative review, we have summarized the literature on fracture risk in T1DM and T2DM with a special focus on fracture site, time patterns, glucose-lowering drugs, and micro- and macrovascular complications. RECENT FINDINGS: T1DM and T2DM were associated with an overall increased fracture risk, with preferent locations at the hip, vertebrae, humerus, and ankle in T1DM and at the hip, vertebrae, and likely humerus, distal forearm, and foot in T2DM. Fracture risk was higher with longer diabetes duration and the presence of micro- and macrovascular complications. In T2DM, fracture risk was higher with use of insulin, sulfonylurea, and thiazolidinediones and lower with metformin use. The increased fracture risk in T1DM and T2DM concerns specific fracture sites, and is higher in subjects with longer diabetes duration, vascular complications, and in T2DM with the use of specific glucose-lowering medication.