Diabetes CVD Research Articles

Overview of anti-inflammatory diets and their promising effects on non-communicable diseases.

An anti-inflammatory diet is characterised by incorporating foods with potential anti-inflammatory properties, including fruits, vegetables, whole grains, nuts, legumes, spices, herbs and plant-based protein. Concurrently, pro-inflammatory red and processed meat, refined carbohydrates and saturated fats are limited. This article explores the effects of an anti-inflammatory diet on non-communicable diseases (NCD), concentrating on the underlying mechanisms that connect systemic chronic inflammation, dietary choices and disease outcomes. Chronic inflammation is a pivotal contributor to the initiation and progression of NCD. This review provides an overview of the intricate pathways through which chronic inflammation influences the pathogenesis of conditions including obesity, type II diabetes mellitus, CVD, autoinflammatory diseases, cancer and cognitive disorders. Through a comprehensive synthesis of existing research, we aim to identify some bioactive compounds present in foods deemed anti-inflammatory, explore their capacity to modulate inflammatory pathways and, consequently, to prevent or manage NCD. The findings demonstrated herein contribute to an understanding of the interplay between nutrition, inflammation and chronic diseases, paving a way for future dietary recommendations and research regarding preventive or therapeutic strategies.

Exploring the link between leptin levels and metabolic syndrome in elderly Indian patients: Implications for family medicine and primary care practices.

The metabolic syndrome (MetS), according to the Adult Treatment Panel III of the National Cholesterol Education Programme, is a collection of metabolic abnormalities that includes one, two, or all three of the following traits: obesity in the abdomen, dyslipidemia, hypertension, fasting blood sugar, or insulin resistance. This study's aim was to assess the relationship between fasting serum leptin and MetS in elderly adults with T2DM in the Northern Indian population. The following information was collected from all the participants: (1) anthropometric data, (2) biochemical data, and (3) a lifestyle questionnaire on sociodemographic data, dietary practices, smoking, and alcohol intake to identify their risk factors for diabetes mellitus, CVD, and hypertension. A total of 36 older participants (56.30%) had a history of hypertension, while 29 elderly participants (44.61%) had diabetes mellitus. A total of 32 elderly participants (49.2%) had MetS, and this group had higher serum leptin (P 0.003), body weight (P = 0.019), BMI (P 0.001), waist circumference (P 0.001), CRP (P = 0.021), insulin (P = 0.001), and HOMA-IR (P = 0.003) values as well as higher percentages of females (P = 0.001), and those with type 2 diabetes mellitus (P = 0.002) and hypertension (P = 0.039) than those in the non-MetS group. In older persons with T2DM, our study discovered a favorable correlation between serum leptin and MetS. It can act as a standalone indicator of MetS, offering a way to spot populations at risk for associated consequences and enabling early intervention.

Association of Carnosinase-1 Gene Polymorphism with Serum Carnosine and Carnosinease-1 Isoform Levels in Type 2 Diabetics with Cardiovascular Diseases in Iraq

Background: Genetic variations in the carnosinase-1 gene, which may also be associated with cardiovascular issues and result in a higher serum carnosinease-1 level, may affect the levels of carnosine and carnosine synthase in diabetes patients. Objective: To examine the impact of the Carnosineas-1 gene polymorphism SNP (rs 2887) on blood levels of carnosine and carnosine synthase-1 and their relationship to CVD in diabetes. Method: The serum concentrations of carnosine and carnosineas-1 were determined using ELISA-specific kits. The carnosineas-1 gene (CN1) was subjected to the high-resolution melt technique (HRM) with the purpose of identifying gene polymorphisms. Results: Carnosinase-1 levels were considerably raised in the T2DM with CVD group, but serum carnosine levels were significantly higher in both groups. SNPs had little impact on serum carnosine levels, whereas polymorphisms had a big impact on carnosinase-1 levels. Conclusion: By raising serum levels of carnosenease-1, which in turn increases carnosine breakdown, the SNP (rs2887) of the carnosinase-1 gene contributes indirectly to the development of CVD in T2DM.

Tackling the adverse health effects of excess body fat in breast cancer: where does physical activity fit in?

Weight gain is commonly observed during and after breast cancer treatment due to chemotherapy and endocrine therapies, induced menopause, changes in metabolism and food intake and decreased physical activity. Systematic reviews show that women who are overweight or obese at diagnosis, and those who gain weight, have poorer breast cancer survival outcomes than women of a healthy weight, irrespective of menopausal status. Excess body weight after breast cancer also increases the risk of type 2 diabetes mellitus and CVD. The adverse impact of excess body weight on survival outcomes is clearly shown for women with oestrogen receptor-positive (ER+) breast cancer, which accounts for 70 % of all breast cancer cases. Higher body fat is thought to increase the risk of ER+ recurrence because of increased aromatase activity. However, this could be compounded by other risk factors, including abnormal insulin and adipokine metabolism, impaired anti-tumour immunity and chronic low-grade systemic inflammation. Observational evidence linking poorer survival outcomes with excess body fat and low physical activity in women recovering from early-stage curative-intent breast cancer treatment is reviewed, before reflecting on the proposed biological mechanisms. The issues and sensitivities surrounding exercise participation amongst overweight breast cancer patients is also discussed, before providing an overview of the co-design process involved in development of an intervention (support programme) with appropriate content, structure and delivery model to address the weight management challenges faced by overweight ER+ breast cancer patients.

Projecting the incidence and costs of major cardiovascular and kidney complications of type 2 diabetes with widespread SGLT2i and GLP-1 RA use: a cost-effectiveness analysis

Aims/hypothesisWhether sodium–glucose co-transporter 2 inhibitors (SGLT2is) or glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are cost-effective based solely on their cardiovascular and kidney benefits is unknown. We projected the health and economic outcomes due to myocardial infarction (MI), stroke, heart failure (HF) and end-stage kidney disease (ESKD) among people with type 2 diabetes, with and without CVD, under scenarios of widespread use of these drugs.MethodsWe designed a microsimulation model using real-world data that captured CVD and ESKD morbidity and mortality from 2020 to 2040. The populations and transition probabilities were derived by linking the Australian Diabetes Registry (1.1 million people with type 2 diabetes) to hospital admissions databases, the National Death Index and the ESKD Registry using data from 2010 to 2019. We modelled four interventions: increase in use of SGLT2is or GLP-1 RAs to 75% of the total population with type 2 diabetes, and increase in use of SGLT2is or GLP-1 RAs to 75% of the secondary prevention population (i.e. people with type 2 diabetes and prior CVD). All interventions were compared with current use of SGLT2is (20% of the total population) and GLP-1 RAs (5% of the total population). Outcomes of interest included quality-adjusted life years (QALYs), total costs (from the Australian public healthcare perspective) and the incremental cost-effectiveness ratio (ICER). We applied 5% annual discounting for health economic outcomes. The willingness-to-pay threshold was set at AU$28,000 per QALY gained.ResultsThe numbers of QALYs gained from 2020 to 2040 with increased SGLT2i and GLP-1 RA use in the total population (n=1.1 million in 2020; n=1.5 million in 2040) were 176,446 and 200,932, respectively, compared with current use. Net cost differences were AU$4.2 billion for SGLT2is and AU$20.2 billion for GLP-1 RAs, and the ICERs were AU$23,717 and AU$100,705 per QALY gained, respectively. In the secondary prevention population, the ICERs were AU$8878 for SGLT2is and AU$79,742 for GLP-1 RAs.Conclusions/interpretationAt current prices, use of SGLT2is, but not GLP-1 RAs, would be cost-effective when considering only their cardiovascular and kidney disease benefits for people with type 2 diabetes.Graphical abstract

Kidney function measures and cardiovascular outcomes in people with diabetes: the Hoorn Diabetes Care System cohort

Aims/hypothesisBoth manifestations of kidney disease in diabetes, reduced eGFR (ml/min per 1.73 m2) and increased urinary albumin/creatinine ratio (UACR, mg/mmol), may increase the risk of specific CVD subtypes in adults with diabetes.MethodsWe assessed the prospective association between annually recorded measures of eGFR and UACR and the occurrence of myocardial infarction (MI), CHD, stroke, heart failure (HF) and cardiovascular mortality in 13,657 individuals with diabetes (53.6% male, age 62.3±12.1 years) from the Hoorn Diabetes Care System cohort, using data obtained between 1998 and 2018. Multivariate time-dependent Cox regression models adjusted for cardiovascular risk factors were used to estimate HRs and 95% CI. Associations of eGFR were adjusted for UACR values and vice versa. Effect modification by sex was investigated for all associations.ResultsAfter a mean follow-up period of 7 years, event rates per 1000 person-years were 3.08 for MI, 3.72 for CHD, 1.12 for HF, 0.84 for stroke and 6.25 for cardiovascular mortality. Mildly reduced eGFR (60–90 ml/min per 1.73 m2) and moderately to severely reduced eGFR (<59 ml/min per 1.73 m2) were associated with higher risks of MI (HR 1.52; 95% CI 1.10, 2.12 and HR 1.69; 95% CI 1.09, 2.64) and CHD (HR 1.67; 95% CI 1.23, 2.26 and HR 2.01; 95% CI 1.34, 3.02) compared with normal eGFR (>90 ml/min per 1.73 m2). Mildly reduced eGFR was associated with a higher risk of stroke (HR 2.53; 95% CI 1.27, 5.03). Moderately increased UACR (3–30 mg/mmol) and severely increased UACR (>30 mg/mmol) were prospectively associated with a higher cardiovascular mortality risk in men and women (HR 1.87; 95% CI 1.41, 2.47 and HR 2.78; 95% CI 1.78, 4.34) compared with normal UACR (<3 mg/mmol). Significant effect modification by sex was observed for the association between UACR and HF. Because there were a limited number of HF events within the category of UACR >30 mg/mmol, categories were combined into UACR <3.0 and >3.0 mg/mmol in the stratified analysis. Women but not men with UACR >3.0 mg/mmol had a significantly higher risk of HF compared with normal UACR (HR 2.79; 95% CI 1.47, 5.28).Conclusions/interpretationThis study showed differential and independent prospective associations between manifestations of early kidney damage in diabetes and several CVD subtypes, suggesting that regular monitoring of both kidney function measures may help to identify individuals at higher risk of specific cardiovascular events.Graphical abstract

Additive predictive value of low testosterone level in hypertensive men with hypercholesterolemia

Abstract Purpose Hypercholesterolemia is common in hypertensive patients and its presence increases the risk of cardiovascular (CV) complications. Decreased concentration of testosterone appears commonly in men with hypertension, and is an independent predictor of CV events. We investigated the utility of testosterone concentration measurement as an aid in the risk prediction of CV events in men with arterial hypertension and high LDL levels. Methods A cohort of 321 men with arterial hypertension and without known diabetes or atherosclerotic CVD (mean age: 54±9 years) were followed for the occurrence of major adverse cardiovascular events (MACE), (CV death, coronary artery disease, stroke). Total testosterone (TT) and LDL levels were measured in all patients. We used Cox proportional hazards regression to analyze the associations between LDL, serum testosterone and CV outcomes. Results During a mean follow-up of 6 years (range: 1–11 years), 31 (9.5%) patients demonstrated a MACE. Patients in the CV-event group were older and they had higher LDL and lower baseline TT levels compared to subjects in the event-free survival group (all P&amp;lt;0.01) while BMI, systolic blood pressure and smoking exposure (pack-years) were similar. Based on the observed distribution of baseline LDL levels the study cohort was divided in two groups: low LDL (&amp;lt;130 mg/dl) and high LDL (≥130 mg/dl). According to baseline TT level distribution the study cohort was divided in two groups: normal TT (&amp;gt;4.0 ng/mL) and low TT (≤4.0 ng/mL). Subjects in the high LDL group, had no increased risk of MACE compared to subjects in the low LDL group (HR 1.35; 95% CI 0.75–2.04) in the multivariable model. Moreover, there was no statistically significant association between low TT and risk of MACE. HR for low TT vs high TT was 1.48 (95% CI 0.85–2.16). We then subdivided the two LDL (high vs low) groups into subgroups according to presence of low or normal TT. Cox regression analysis revealed that the subgroup of men with both low TT and high LDL had an almost 2-fold higher risk of MACEs compared to the other three LDL/TT subgroups (adjusted hazard ratio: 2.07; 95% CI 0.94–3.56, P=0.035). Figure 1 shows the cardiac event-free survival curve of males with both baseline low TT and high LDL level with that of males in the other three LDL/TT subgroups (log rank: 11.3, P=0.008). Conclusion Low testosterone concentration is associated with a shorter event-free period in hypertensive patients with higher LDL levels. The measurement of testosterone concentration may be useful to further stratify the risk of middle-aged men with arterial hypertension and hypercholesterolemia. Funding Acknowledgement Type of funding sources: None.

Prevalence of Comorbidities Among COPD Patients: A Comparative Case-Control Study in Kashmir

Background: COPD is a chronic inflammatory lung disease characterized by airflow limitation, which is a result of continuous and consistent use of tobacco smoke or exposure of respiratory tract to noxious stimuli or recurrent childhood respiratory tract infection. Methods: A cross section of population from one of the assembly constituencies of Srinagar city has been taken as an area of sampling. A sample size of about 400 subjects was taken from three different electoral wards based on random table method as per defined inclusion criteria. Results: Majority of the COPD patients accounting for (33.8%) were aging from 40 to 50 years, followed by (31.1%) falling in the age interval (61-70) years. The present study revealed that commonest comorbidities among COPD patients were hypertension (56.7%), Osteoporosis (41%), anxiety (32.4%), diabetes (24.3%) and HTN CVD (22.9%). Conclusion: The present study demonstrated that the prevalence of chronic diseases like hypertension, diabetes, HTN CVD, RA osteoporosis, anxiety, proximal myopathy, and insomnia are significantly higher among COPD cases compared to healthy controls. Keywords: Chronic obstructive pulmonary disease, respiratory tract infection, comorbidities

Aortic intima media thickness in children and adolescents with type 1 diabetes: A systematic review.

AimsGreater aortic intima media thickness (aIMT), a marker of subclinical atherosclerosis, can identify individuals at risk of CVD. This systematic review with meta‐analysis compared aIMT in youth with type 1 diabetes and healthy controls.MethodsA systematic search of published literature (to July 2021) was undertaken using electronic databases MEDLINE, EMBASE, Scopus, CINAHL and AMED. Eligible studies reported aIMT in participants aged <20 years with type 1 diabetes and healthy controls. Meta‐analysis was used to combine outcome data, presented as forest plots. Moderator analysis and metaregression were conducted to identify study and participant characteristics associated with aIMT. Publication bias was assessed by funnel plot inspection.ResultsMeta‐analysis of nine studies (n = 1030 with type 1 diabetes and n = 498 healthy control participants) indicated, with high heterogeneity (I2 98%), that youth with type 1 diabetes have higher aIMT compared with healthy controls (mean difference [95% CIs]: 0.11 [0.04, 0.18] mm, P = 0.003). Factors associated with greater aIMT in type 1 diabetes compared to controls included: use of a phased array probe versus linear array probe; longer diabetes duration; higher insulin dose; higher BMI z score and waist circumference; higher LDL cholesterol; higher triglycerides; and higher diastolic blood pressure.ConclusionsType 1 diabetes in youth is associated with higher aIMT compared with healthy control individuals. Longer duration of diabetes and major CVD risk factors were also associated with higher aIMT. Together, these findings provide a strong rationale for targeting modifiable risk factors in CVD prevention. Registered in PROSPERO on 8 August 2019 (CRD42019137559).

Lifestyle interventions in pregnancy targeting GDM prevention: looking ahead to precision medicine.

Gestational diabetes mellitus (GDM) is the most prevalent pregnancy-related endocrinopathy, affecting up to 25% of pregnancies worldwide. Pregnant individuals who develop GDM have an increased risk of complications during pregnancy and birth, as well as future development of type 2 diabetes mellitus and CVD. This increased risk is subsequently passed along to the offspring, perpetuating a cycle of metabolic dysfunction across generations. GDM prevention strategies have had mixed results for many years, but more recent systematic reviews and meta-analyses have suggested potential new avenues of prevention. The objective of this review is to summarise the literature examining the efficacy of lifestyle interventions for the prevention of GDM and to uncover if specific individual-level characteristics influence this outcome. Based on the present literature, we determined that future trials should be designed to understand if initiation of lifestyle intervention in the preconception period is more effective to reduce GDM. Furthermore, trials initiated during pregnancy should be developed through the lens of precision prevention. That is, trials should tailor intervention approaches based on individual-level risk defined by the presence of modifiable and non-modifiable risk factors. Finally, future interventions might also benefit from just-in-time adaptive intervention designs, which allow for interventions to be modified in real-time based on objective assessments of an individual's response.

Separating the direct effects of traits on atherosclerotic cardiovascular disease from those mediated by type 2 diabetes

Aims/hypothesisType 2 diabetes and atherosclerotic CVD share many risk factors. This study aimed to systematically assess a broad range of continuous traits to separate their direct effects on coronary and peripheral artery disease from those mediated by type 2 diabetes.MethodsOur main analysis was a two-step Mendelian randomisation for mediation to quantify the extent to which the associations observed between continuous traits and liability to atherosclerotic CVD were mediated by liability to type 2 diabetes. To support this analysis, we performed several univariate Mendelian randomisation analyses to examine the associations between our continuous traits, liability to type 2 diabetes and liability to atherosclerotic CVD.ResultsEight traits were eligible for the two-step Mendelian randomisation with liability to coronary artery disease as the outcome and we found similar direct and total effects in most cases. Exceptions included fasting insulin and hip circumference where the proportion mediated by liability to type 2 diabetes was estimated as 56% and 52%, respectively. Six traits were eligible for the analysis with liability to peripheral artery disease as the outcome. Again, we found limited evidence to support mediation by liability to type 2 diabetes for all traits apart from fasting insulin (proportion mediated: 70%).Conclusions/interpretationMost traits were found to affect liability to atherosclerotic CVD independently of their relationship with liability to type 2 diabetes. These traits are therefore important for understanding atherosclerotic CVD risk regardless of an individual’s liability to type 2 diabetes.Graphical abstract

Frailty and Comorbidities in Adult People Living with HIV a Case Study in Uzumba Maramba Pfungwe District, Mashonaland East Province, Zimbabwe

Some evidence suggests that HIV itself is associated with frailty; a syndrome typically viewed as being related to ageing. The researcher determines the prevalence and predictors of frailty in a population of HIV infected individuals at Mutawatawa Hospital in UMP district, Mashonaland East, Zimbabwe. He also determined the association between frailty and comorbidities. A retrospective cohort study of 153 adults (&gt;30 years) people living with HIV was used. The mean age of the study participants was 44.49 and a median of 41. The majority were female (62.7%). Frailty as defined by standardized assessment comprised of ≥3 of weight loss, low physical activity, exhaustion, weak grip strength and slow waling time. 64.7% of the study participants were found to be frail. Independent predictors of frailty were evaluated using Binary logistic regression. Association between frailty and comorbidities was determined using Binary logistic regression. CD4 count was a strong predictor of frailty (OR=1.33; 95% CI: 1.03-5.74, p=0.026). Age was also a strong predictor of frailty (OR=2.993; 95% CI: 1.049-3.039, p=0.023). Type-2 Diabetes Mellitus (OR=3.59; 95% CI: 1.028-4.53; p=0.029), CVD (OR= 1.632; 95% CI: 1.117-22.735; p=0.015) and dyslipidemia (OR=0.713; 95% CI: 1.020-25.275; p=0.042) were strongly associated with frailty. Lower CD4 counts and older age were strong predictors of frailty in HIV infected populations. Earlier initiation of ART may be protective. Type-2 Diabetes Mellitus, CVD and Dyslipidemia were strongly associated with frailty. A cardiovascular exercise regimen can help overcome frailty.

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) refers to chronic hyperglycemia during pregnancy in women with no diabetic history before pregnancy. As per the surveys it is estimated that gestational diabetes affects 16% of pregnancies worldwide. This percentage is increasing day by day. Most of the cases of GDM suffer from glucose intolerance because of impaired pancreatic β-cell during pregnancy. Although GDM vanishes after delivery but may cause fetal macrosomia, type-2 diabetes, and maternal CVD are some of the main outcomes of gestational diabetes. In the long-term effect of GDM, a child may suffer from obesity, type-2 diabetes as well as heart diseases at later ages [1]. Several factors work as a root cause of GDM like pregnancy after 35 years of age, genetic history of diabetes, obesity, nutrients deficiency (especially micronutrients), and high consumption of western diet. Gestational diabetes opens ways for diabetes and obesity from generation to generation. At present time, under advanced medical technologies, we still have no instant procedure for treating gestational diabetes completely except modifying diet and physical activity to maintain GDM till delivery. Oral medications of gestational diabetes work well but can cause long-term health issues in both mother and child. To manage these consequences of GDM and to develop the latest strategies it is important to understand gestational diabetes from its roots [2-3]. Public health researchers and clinicians are highly concerned about the alarming situation of the increased number of gestational diabetes all over the world. This condition is directly causing economic crisis as well as declining health conditions of the vast number of populations. Due to the lack of treatments for GDM, researchers often debate upon several interventions to treat gestational diabetes mellitus. The main concern for researching GDM is higher complications during pregnancies due to gestational diabetes. These complications include higher chances of C-sections, shoulder dystocia in case of vaginal delivery, and more chances that the infant is born with a hypoglycemic condition. Medical petitioners often recommended oral glycemic control medications, healthy weight management, and exercise to females diagnosed with GDM but, these strategies are not enough. It is mandatory to rule out more possible causes and indicators of gestational diabetes mellitus before it appears. It is a need of hours to upgrade strategies and interventions to protect future generations from the outcomes of GDM. It can only be possible with advanced research, experiments and surveys so we can play a potent role in developing emerging techniques for the best possible treatment of gestational diabetes mellitus for future generations [4].

Gestational Diabetes Mellitus

Gestational diabetes mellitus (GDM) refers to chronic hyperglycemia during pregnancy in women with no diabetic history before pregnancy. As per the surveys it is estimated that gestational diabetes affects 16% of pregnancies worldwide. This percentage is increasing day by day. Most of the cases of GDM suffer from glucose intolerance because of impaired pancreatic β-cell during pregnancy. Although GDM vanishes after delivery but may cause fetal macrosomia, type-2 diabetes, and maternal CVD are some of the main outcomes of gestational diabetes. In the long-term effect of GDM, a child may suffer from obesity, type-2 diabetes as well as heart diseases at later ages [1]. Several factors work as a root cause of GDM like pregnancy after 35 years of age, genetic history of diabetes, obesity, nutrients deficiency (especially micronutrients), and high consumption of western diet. Gestational diabetes opens ways for diabetes and obesity from generation to generation. At present time, under advanced medical technologies, we still have no instant procedure for treating gestational diabetes completely except modifying diet and physical activity to maintain GDM till delivery. Oral medications of gestational diabetes work well but can cause long-term health issues in both mother and child. To manage these consequences of GDM and to develop the latest strategies it is important to understand gestational diabetes from its roots [2-3]. Public health researchers and clinicians are highly concerned about the alarming situation of the increased number of gestational diabetes all over the world. This condition is directly causing economic crisis as well as declining health conditions of the vast number of populations. Due to the lack of treatments for GDM, researchers often debate upon several interventions to treat gestational diabetes mellitus. The main concern for researching GDM is higher complications during pregnancies due to gestational diabetes. These complications include higher chances of C-sections, shoulder dystocia in case of vaginal delivery, and more chances that the infant is born with a hypoglycemic condition. Medical petitioners often recommended oral glycemic control medications, healthy weight management, and exercise to females diagnosed with GDM but, these strategies are not enough. It is mandatory to rule out more possible causes and indicators of gestational diabetes mellitus before it appears. It is a need of hours to upgrade strategies and interventions to protect future generations from the outcomes of GDM. It can only be possible with advanced research, experiments and surveys so we can play a potent role in developing emerging techniques for the best possible treatment of gestational diabetes mellitus for future generations [4].

Metformin improves glycemic variability in adults with type 1 diabetes mellitus: an open-label randomized control trial.

IntroductionMetformin has been demonstrated to enhance cardioprotective benefits in type 1 diabetes (T1DM). Although glycemic variability (GV) is associated with increased risk of CVD in diabetes, there is a scarcity of research evaluating the effect of metformin on GV in T1DM.Objectives In the present study, the effects of adjuvant metformin therapy on GV and metabolic control in T1DM were explored.Patients and methodsA total of 65 adults with T1DM were enrolled and subjected to physical examination, fasting laboratory tests, and continuous glucose monitoring, and subsequently randomized 1:1 to 3 months of 1000–2000 mg metformin daily add-on insulin (MET group, n = 34) or insulin (non-MET group, n = 31). After, baseline measurements were repeated.ResultsThe mean amplitude of glycemic excursions was substantially reduced in MET group, compared with non-MET group (–1.58 (–3.35, 0.31) mmol/L vs 1.36 (–1.12, 2.24) mmol/L, P = 0.004). In parallel, the largest amplitude of glycemic excursions (–2.83 (–5.47, –0.06) mmol/L vs 0.45 (–1.29, 4.48) mmol/L, P = 0.004), the s.d. of blood glucose (–0.85 (–1.51, 0.01) mmol/L vs –0.14 (–0.68, 1.21) mmol/L, P = 0.015), and the coefficient of variation (–6.66 (–15.00, 1.50)% vs –1.60 (–6.28, 11.71)%, P = 0.012) all demonstrated improvement in the MET group, compared with the non-MET group. Significant reduction in insulin dose, BMI, and body weight was observed in patients in MET, not those in non-MET group.ConclusionAdditional metformin therapy improved GV in adults with T1DM, as well as improving body composition and reducing insulin requirement. Hence, metformin as an adjunctive therapy has potential prospects in reducing the CVD risk in patients with T1DM in the long term.

Effects of ertugliflozin on kidney composite outcomes, renal function and albuminuria in patients with type 2 diabetes mellitus: an analysis from the randomised VERTIS CV trial

Aims/hypothesisIn previous work, we reported the HR for the risk (95% CI) of the secondary kidney composite endpoint (time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death) with ertugliflozin compared with placebo as 0.81 (0.63, 1.04). The effect of ertugliflozin on exploratory kidney-related outcomes was evaluated using data from the eValuation of ERTugliflozin effIcacy and Safety CardioVascular outcomes (VERTIS CV) trial (NCT01986881).MethodsIndividuals with type 2 diabetes mellitus and established atherosclerotic CVD were randomised to receive ertugliflozin 5 mg or 15 mg (observations from both doses were pooled), or matching placebo, added on to existing treatment. The kidney composite outcome in VERTIS CV (reported previously) was time to first event of doubling of serum creatinine from baseline, renal dialysis/transplant or renal death. The pre-specified exploratory composite outcome replaced doubling of serum creatinine with sustained 40% decrease from baseline in eGFR. In addition, the impact of ertugliflozin on urinary albumin/creatinine ratio (UACR) and eGFR over time was assessed.ResultsA total of 8246 individuals were randomised and followed for a mean of 3.5 years. The exploratory kidney composite outcome of sustained 40% reduction from baseline in eGFR, chronic kidney dialysis/transplant or renal death occurred at a lower event rate (events per 1000 person-years) in the ertugliflozin group than with the placebo group (6.0 vs 9.0); the HR (95% CI) was 0.66 (0.50, 0.88). At 60 months, in the ertugliflozin group, placebo-corrected changes from baseline (95% CIs) in UACR and eGFR were −16.2% (−23.9, −7.6) and 2.6 ml min−1 [1.73 m]−2 (1.5, 3.6), respectively. Ertugliflozin was associated with a consistent decrease in UACR and attenuation of eGFR decline across subgroups, with a suggested larger effect observed in the macroalbuminuria and Kidney Disease: Improving Global Outcomes in Chronic Kidney Disease (KDIGO CKD) high/very high-risk subgroups.Conclusions/interpretationAmong individuals with type 2 diabetes and atherosclerotic CVD, ertugliflozin reduced the risk for the pre-specified exploratory composite renal endpoint and was associated with preservation of eGFR and reduced UACR.Trial registrationClinicalTrials.gov NCT01986881Graphical abstract

Postprandial Glucose Spikes, an Important Contributor to Cardiovascular Disease in Diabetes?

Clinical trials investigating whether glucose lowering treatment reduces the risk of CVD in diabetes have thus far yielded mixed results. However, this doesn't rule out the possibility of hyperglycemia playing a major causal role in promoting CVD or elevating CVD risk. In fact, lowering glucose appears to promote some beneficial long-term effects, and continuous glucose monitoring devices have revealed that postprandial spikes of hyperglycemia occur frequently, and may be an important determinant of CVD risk. It is proposed that these short, intermittent bursts of hyperglycemia may have detrimental effects on several organ systems including the vasculature and the hematopoietic system collectively contributing to the state of elevated CVD risk in diabetes. In this review, we summarize the potential mechanisms through which hyperglycemic spikes may increase atherosclerosis and how new and emerging interventions may combat this.

Association of early-onset diabetes, prediabetes and early glycaemic recovery with the risk of all-cause and cardiovascular mortality.

The increasing incidence of diabetes among young adults is a disease burden; however, the effects of early-onset diabetes, prediabetes and glycaemic recovery on CVD or mortality remain unclear. We aimed to investigate the association of these factors with 10year all-cause mortality, CVD mortality and CVD incidence in Korean young adults. This large and longitudinal cohort study included data from the Korean National Health Insurance Service-National Health Information Database; 2,502,375 young adults aged 20-39years without diabetes mellitus and CVD at baseline were included. Glycaemic status was measured twice, first in 2002-2003 and second in 2004-2005. Changes in fasting glucose levels were evaluated according to fasting glucose status: normal fasting glucose (NFG; <5.5mmol/l), impaired fasting glucose (IFG; 5.5-6.9mmol/l), and diabetic fasting glucose (DFG; ≥7.0mmol/l). Primary outcomes were all-cause and CVD mortality risk. The secondary outcome was incidence of CVD, including acute myocardial infarction and stroke. All outcomes arose from the 10year follow-up period 1 Jan 2006 to 31 December 2015. Individuals with NFG at baseline, who were subsequently newly diagnosed with diabetes and prediabetes (IFG), had increased all-cause mortality (HR [95% CI] 1.60 [1.44, 1.78] and 1.13 [1.09, 1.18], respectively) and CVD incidence (1.13 [1.05, 1.23] and 1.04 [1.01, 1.07], respectively). In those with DFG at baseline, early recovery to NFG and IFG was associated with decreased all-cause mortality (0.57 [0.46, 0.70] and 0.65 [0.53, 0.81], respectively) and CVD incidence (0.70 [0.60, 0.81] and 0.78 [0.66, 0.91], respectively). Among patients with IFG at baseline, early recovery to NFG was associated with decreased CVD mortality (0.74 [0.59, 0.93]). Early-onset diabetes or prediabetes increased CVD risks and all-cause mortality after the 10year follow-up. Furthermore, recovery of hyperglycaemia could reduce the subsequent 10year risk for CVD incidence and all-cause mortality. Graphical abstract.

Primary Cardiovascular Disease Prevention: Risk Factors Control vs. Imaging Subclinical Atherosclerosis

The burden of cardiovascular disease in developed countries has shown dramatic improvements over the last 50 years, largely due the identification and control of major risk factors including, smoking hypertension and high cholesterol. However, due to the significant increase in obesity and diabetes CVD incidence rates will not reduce as far over over the next years. Risk prediction in asymptomatic individuals remains a major challenge. Primary preventive treatment is currently based on the assessment of individual’s global risk mainly through screening of conventional risk factors and their treatment with lifestyle intervention and pharmacotherapy, often based on multivariate risk equations, and yet a large proportion of CVD still occurs in individuals who are classified as carrying low- or intermediate-risk according to the risk scores. Atherosclerosis is the most common pathophysiologic process underlying CVD, often after a prolonged asymptomatic phase during which it may be possible to modify the course of the disease. Unlike conventional probabilistic risk scores, non-invasive imaging techniques such as carotid intima-media thickness (CIMT) along with plaque assessment (Figure 2), measured by B-mode ultrasound, and coronary calcium scoring (CAC) detected by CT scan have the advantage of direct visualization of the consequences of atherosclerosis on the arterial system. We consider the proposal that imaging of subclinical atherosclerosis is superior to risk equations as it directly identifies the disease and can effectively predict the risk of future CV events in low- and intermediate-risk individuals. In addition, imaging can improve the adherence to guidelines based treatment in patients and their physicians.

P5325A possible paradoxical association between LDL-cholesterol in myocardial infarction patients and relation to major adverse outcomes - a 10-year nationwide cohort study

Abstract Background Cardiovascular disease (CVD) risk increases with the level of LDL-cholesterol (LDL-C), and LDL-C lowering treatment improves prognosis. Less is known about LDL-C levels at myocardial infarction (MI) admission and long-term prognosis. Purpose To investigate admission LDL-C levels in relation to mortality, recurrent MI and baseline characteristics. Methods Patients admitted with an MI in Sweden and recorded in the MI-registry (SWEDEHEART) 2006–2016 were included and followed until 2018. Associations between baseline LDL-C, mortality and MI were assessed with Cox regression analysis, adjusting for risk factors (eg. age, diabetes, prior CV events) and lipid lowering therapy. Results Of 126,669 patients (median age: 70) admitted with MI, 26.2% (n=32,883) had ongoing statin therapy, and the median LDL-C was 2.96 (interquartile range 2.23, 3.74) mmol/L. During median follow-up of 4.2 years, 31,024 died and 17,896 had an MI (table). Patients with higher LDL-C were younger, had substantially fewer comorbidities such as diabetes and prior CVD (p&lt;0.001). In this analysis there was an interaction with ongoing statin-use (p=0.0025). When dividing patients by LDL-C into quartiles, statin naive in the highest LDL-C quartile (3.95 mmol/L) had a lower risk of death compared to patients in the lowest quartile (2.62 mmol/L) HR 0.86 (95% CI 0.83–0.90). For patients with ongoing statin, the risk was also lower with higher LDL-C (2.84 mmol/L) compared to lower LDL-C (1.72 mmol/L) HR 0.88 (95% CI 0.81–0.96). No association was observed between LDL-C and recurrent MI. Table 1. Event rate for mortality and myocardial infarction (MI) by LDL quartile groups Q1 Q2 Q3 Q4 LDL-C (mmol/L) Statin naive &lt;2.62 2.62–3.26 3.26–3.95 &gt;3.95 Ongoing &lt;1.72 1.72–2.21 2.21–2.84 &gt;2.84 Mortality Statin naive 0.074 (6553) 0.049 (4596) 0.037 (3706) 0.030 (2949) Ongoing 0.10 (3297) 0.075 (2769) 0.062 (2462) 0.055 (2157) MI Statin naive 0.034 (2808) 0.026 (2292) 0.024 (2269) 0.023 (2094) Ongoing 0.064 (1796) 0.055 (1792) 0.048 (1694) 0.044 (1557) Event/year (n of events) stratified by statin treatment at index event. Conclusions In this real-world population with over 126,000 patients and 10 years of follow-up, higher LDL-C at the time of the MI was associated with a markedly better prognosis in patients with and without prior statin therapy. This paradox may, despite adjustment, be caused by a substantially lower CVD baseline risk in patients with higher LDL-C pertaining to a lower burden of risk factors, younger age, and fewer prior CVD events as well as a highly treatable risk factor.