Self-reported walking pace, polygenic risk scores and risk of coronary artery disease in UK biobank.

BACKGROUND AND AIMS: Both polygenic risk scores (PGS) and self-reported walking pace have been shown to predict cardiovascular disease; whether combining both factors produces greater risk differentiation is, however, unknown. METHODS AND RESULTS: We estimated the 10-year absolute risk of coronary artery disease (CAD), adjusted for traditional risk factors, and the C-index across nine PGS and self-reported walking pace in UK Biobank study participants between Mar/2006-Feb/2021. In 380,693 individuals (54.8% women), over a median (5th, 95th percentile) of 11.9 (8.3, 13.4) years, 2,603 (1.2%) CAD events occurred in women and 8,259 (4.8%) in men. Both walking pace and genetic risk were strongly associated with CAD. The absolute 10-year risk of CAD was highest in slow walkers at high genetic risk (top 20% of PGS): 2.72% (95% CI: 2.30-3.13) in women; 9.60% (8.62-10.57) in men. The risk difference between slow and brisk walkers was greater at higher [1.26% (0.81-1.71) in women; 3.63% (2.58-4.67) in men] than lower [0.76% (0.59-0.93) and 2.37% (1.96-2.78), respectively] genetic risk. Brisk walkers at high genetic risk had equivalent (women) or higher (men) risk than slow walkers at moderate-to-low genetic risk (bottom 80% of PGS). When added to a model containing traditional risk factors, both factors separately improved risk discrimination; combining them resulted in the greatest discrimination: C-index of 0.801 (0.793-0.808) in women; 0.732 (0.728-0.737) in men. CONCLUSION: Self-reported slow walkers at high genetic risk had the greatest risk of CAD, identifying a potentially important population for intervention. Both PGS and walking pace contributed to risk discrimination.

Trends in 30-day readmissions following hospitalisation for heart failure by sex, socioeconomic status and ethnicity.

Background: Reducing the high patient and economic burden of early readmissions after hospitalisation for heart failure (HF) has become a health policy priority of recent years. Methods: An observational study linking Hospital Episode Statistics to socioeconomic and death data in England (2002-2018). All first hospitalisations with a primary discharge code for HF were identified. Quasi-poisson models were used to investigate trends in 30-day readmissions by age, sex, socioeconomic status and ethnicity. Findings: There were 698,983 HF admissions, median age 81 years [IQR 14].In-hospital deaths reduced by 0.7% per annum (pa), whilst additional deaths at 30-days remained stable at 5%. Age adjusted 30-day readmissions (21% overall), increased by 1.4% pa (95% CI 1.3-1.5). Readmissions for HF (6%) and 'other cardiovascular disease (CVD)' (3%) remained stable, but readmissions for non-CVD causes (12%) increased at a rate of 2.6% (2.4-2.7) pa. Proportions were similar by sex but trends diverged by ethnicity. Black groups experienced an increase in readmissions for HF (1.8% pa, interaction-p 0.03) and South Asian groups had more rapidly increasing readmission rates for non-CVD causes (interaction-p 0.04). Non-CVD readmissions were also more prominent in the least (15%; 15-15) compared to the most affluent group (12%; 12-12). Strongest predictors for HF readmission were Black ethnicity and chronic kidney disease, whilst cardiac procedures were protective. For non-CVD readmissions, strongest predictors were non-CVD comorbidities, whilst cardiologist care was protective. Interpretation: In HF, despite readmission reduction policies, 30-day readmissions have increased, impacting the least affluent and ethnic minority groups the most. Funding: NIHR.

Association of working shifts, inside and outside of healthcare, with severe COVID-19: an observational study.

BACKGROUND: Health and key workers have elevated odds of developing severe COVID-19; it is not known, however, if this is exacerbated in those with irregular work patterns. We aimed to investigate the odds of developing severe COVID-19 in health and shift workers. METHODS: We included UK Biobank participants in employment or self-employed at baseline (2006-2010) and with linked COVID-19 data to 31st August 2020. Participants were grouped as neither a health worker nor shift worker (reference category) at baseline, health worker only, shift worker only, or both, and associations with severe COVID-19 investigated in logistic regressions. RESULTS: Of 235,685 participants (81·5% neither health nor shift worker, 1·4% health worker only, 16·9% shift worker only, and 0·3% both), there were 580 (0·25%) cases of severe COVID-19. The odds of severe COVID-19 was higher in health workers (adjusted odds ratio: 2·32 [95% CI: 1·33, 4·05]; shift workers (2·06 [1·72, 2·47]); and in health workers who worked shifts (7·56 [3·86, 14·79]). Being both a health worker and a shift worker had a possible greater impact on the odds of severe COVID-19 in South Asian and Black and African Caribbean ethnicities compared to White individuals. CONCLUSIONS: Both health and shift work (measured at baseline, 2006-2010) were independently associated with over twice the odds of severe COVID-19 in 2020; the odds were over seven times higher in health workers who work shifts. Vaccinations, therapeutic and preventative options should take into consideration not only health and key worker status but also shift worker status.

Leisure-time physical activity and life expectancy in people with cardiometabolic multimorbidity and depression.

BACKGROUND: Whether and to what extent leisure-time physical activity at the recommended levels of 150-min moderate activity is associated with survival in people with cardiometabolic multimorbidity and depression is unknown. METHODS: UK Biobank participants were classified into groups: (i) no disease; (ii) diabetes; (iii) cardiovascular disease (CVD); (iv) depression; (v) diabetes and CVD; (vi) diabetes and depression; (vii) CVD and depression; (viii) diabetes, CVD and depression. Leisure-time physical activity was categorized as active (meeting recommendations) or inactive. Survival models were applied to estimate life expectancy. RESULTS: A total of 480 940 participants were included (median age, 58 years; 46% men; 95% white), of whom 74% with cardiometabolic multimorbidity and depression were inactive. During a mean follow-up of 7 years, 11 006 deaths occurred. At age of 45 years, being physically active was associated with 2.34 (95% confidence interval: 0.93, 3.54) additional years of life compared with being inactive in participants with diabetes; corresponding estimates were 2.28 (1.40, 3.16) for CVD; 2.15 (0.05, 4.26) for diabetes and CVD; and 1.58 (1.27, 1.89) for no disease. Participants with a combination of diabetes, CVD and depression, being active was associated with 6.81 (-1.50, 15.31) additional years compared with being inactive; corresponding estimates were 3.07 (-2.46, 8.59) for diabetes and depression; 2.34 (-1.24, 5.91) for CVD and depression; and 0.80 (-0.46, 2.05) for depression. A similar pattern was found at 65 years. CONCLUSIONS: Meeting the recommended level of physical activity was associated with a longer life expectancy in people with cardiometabolic multimorbidity but not in those with depression.

Diabetic foot infections: a comprehensive overview.

Diabetic foot ulcers (DFUs), a micro-vascular complication, are associated with a substantial increase in morbidity and mortality. DFUs are a complicated mixture of neuropathy, peripheral arterial diseases, foot deformities, and infections. Foot infections are frequent and potentially devastating complications. Infection prospers in more than half of all foot ulcers and is the factor that most often leads to lower extremity amputation. The complications of microbial flora span the spectrum from superficial cellulitis to chronic osteomyelitis and gangrenous extremity lower limb amputations. Wounds without confirmed soft tissue or bone infections do not require antibiotic therapy. Mild and moderate infections need empiric therapy covering Gram-positive cocci, while severe infections caused by drug-resistant organisms require broad-spectrum anti-microbials targeting aggressive Gram-negative aerobes and obligate anaerobes.

Selectivity of beta-blockers, cardiovascular and all-cause mortality in people with hypoglycaemia: An observational study.

BACKGROUND AND AIMS: The association of beta-blockers and their selectivity with mortality and cardiovascular events in patients with and without hypoglycaemia is unknown. METHODS AND RESULTS: Insulin-treated patients with diabetes were identified within the UK CPRD database. All-cause deaths, cardiovascular events, and hypoglycaemic episodes were captured to assess the interaction between beta-blocker therapy and selectivity with hypoglycaemia. 13,682 patients, of which 2036 (14.9%) with at least one hypoglycaemic episode, were included; 3148 deaths and 1235 cardiovascular events were recorded during a median of 2.3 and 4.7 years in patients with and without incident hypoglycaemia, respectively. Treatment with any beta-blocker was not associated with risk of death in both patients with and without hypoglycaemia, without significant interaction. Compared to no therapy, non-selective beta-blockers were associated with higher risk of death in patients without hypoglycaemia (hazard ratio (HR) 2.93 [1.26-6.83] in the fully adjusted model) but not in those with hypoglycaemia; interactions was not significant. For beta1-selective beta-blockers, there was no association with mortality in both patients with and without hypoglycaemia, without significant interaction. After missing data imputation, results were consistent for non-selective beta-blockers (HR in patients without hypoglycaemia 1.59 [1.22-2.08]) while indicated a reduced risk of death for beta1-selective beta-blockers in patients with hypoglycaemia (HR 0.76 [0.61-0.94]). Due to few cardiovascular events, complete-case analysis compared only any vs no beta-blocker therapy and indicated no associations with therapy or interaction by hypoglycaemia. CONCLUSION: In patients with hypoglycaemic episodes, treatment with beta1-selective beta-blockers may potentially reduce the risk of death. These explorative findings and the potential role of confounding by indication need to be evaluated in other studies.

Cardiovascular efficacy and safety of sodium-glucose co-transporter-2 inhibitors and glucagon-like peptide-1 receptor agonists: a systematic review and network meta-analysis.

AIMS: To compare the cardiovascular efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in adults with Type 2 diabetes. METHODS: Electronic databases were searched from inception to 22 October 2018 for randomized controlled trials designed to assess the cardiovascular efficacy of SGLT2 inhibitors or GLP-1RAs with regard to a three-point composite measure of major adverse cardiovascular events (non-fatal stroke, non-fatal myocardial infarction and cardiovascular mortality). Cardiovascular and safety data were synthesized using Bayesian network meta-analyses. RESULTS: Eight trials, including 60 082 participants, were deemed eligible for the network meta-analysis. Both SGLT2 inhibitors [hazard ratio 0.86 (95% credible interval 0.74, 1.01]) and GLP-1RAs [hazard ratio 0.88 (95% credible interval 0.78, 0.98)] reduced the three-point composite measure compared to placebo, with no evidence of differences between them [GLP-1RAs vs SGLT2 inhibitors: hazard ratio 1.02 (95% credible interval 0.83, 1.23)]. SGLT2 inhibitors reduced risk of hospital admission for heart failure compared to placebo [hazard ratio 0.67 (95% credible interval 0.53, 0.85)] and GLP-1RAs [hazard ratio 0.71 (95% credible interval 0.53, 0.93)]. No differences were found between the two drug classes in non-fatal stroke, non-fatal myocardial infarction, cardiovascular mortality, all-cause mortality or safety outcomes. CONCLUSIONS: SGLT2 inhibitors and GLP-1RAs reduced the three-point major adverse cardiovascular event risk compared to placebo, with no differences between them. Compared with GLP-1RAs and placebo, SGLT2 inhibitors led to a larger reduction in hospital admission for heart failure risk.

Meta-analysis of the influence of lifestyle changes for preoperative weight loss on surgical outcomes.

BACKGROUND: The aim was to investigate whether preoperative weight loss results in improved clinical outcomes in surgical patients with clinically significant obesity. METHODS: This was a systematic review and aggregate data meta-analysis of RCTs and cohort studies. PubMed, MEDLINE, Embase and CINAHL Plus databases were searched from inception to February 2018. Eligibility criteria were: studies assessing the effect of weight loss interventions (low-energy diets with or without an exercise component) on clinical outcomes in patients undergoing any surgical procedure. Data on 30-day or all-cause in-hospital mortality were extracted and synthesized in meta-analyses. Postoperative thromboembolic complications, duration of surgery, infection and duration of hospital stay were also assessed. RESULTS: A total of 6060 patients in four RCTs and 12 cohort studies, all from European and North American centres, were identified. Most were in the field of bariatric surgery and all had some methodological limitations. The pooled effect estimate suggested that preoperative weight loss programmes were effective, leading to significant weight reduction compared with controls: mean difference -7·42 (95 per cent c.i. -10·09 to -4·74) kg (P < 0·001). Preoperative weight loss interventions were not associated with a reduction in perioperative mortality (odds ratio 1·41, 95 per cent c.i. 0·24 to 8·40; I2 = 0 per cent, P = 0·66) but the event rate was low. The weight loss groups had shorter hospital stay (by 27 per cent). No differences were found for morbidity. CONCLUSION: This limited preoperative weight loss has advantages but may not alter the postoperative morbidity or mortality risk.

Body mass index and mortality in people with and without diabetes: A UK Biobank study.

BACKGROUND AND AIMS: To investigate the association of body mass index with all-cause, cardiovascular and cancer mortality in individuals with and without diabetes. METHODS AND RESULTS: We used data on 490,852 participants from the UK Biobank, with linkage to national mortality data between 2006 and 2016. Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (95%CI) for all-cause, cardiovascular and cancer mortality within body mass index categories in people with and without diabetes adjusting for potential confounders. 24,789 (5.0%) participants reported having diabetes at baseline. Over a median follow-up of 6.9 years, 13,896 participants died, of which 1800 had diabetes. Compared with normal body mass index (18.5-24.9 kg/m2), mortality risk in the overweight group (25.0-29.9 kg/m2) was 33% lower in people with diabetes (HR 0.67, 95%CI 0.62-0.73) and 12% lower in participants without (HR 0.88, 95%CI 0.85-0.90). For class I obesity (30.0-34.9 kg/m2), mortality risk was 35% lower in participants with diabetes (HR 0.65, 95%CI 0.59-0.71) and 5% lower in participants without (HR 0.95, 95%CI 0.91-0.99). For class III obesity (≥40 kg/m2), there was a 10% non-significant lower mortality risk compared to normal body mass index in people with diabetes (HR 0.90, 95%CI 0.77-1.05); in contrast, the risk was 29% higher in people without diabetes (HR 1.29, 95%CI 1.13-1.45). Similar patterns were observed for cardiovascular mortality but not for cancer mortality. CONCLUSION: The impact of obesity on the risk of mortality was dependent on the presence of diabetes: for the same level of obesity, mortality risk was higher in people without diabetes compared to those with diabetes.

Platelet indices and glucose control in type 1 and type 2 diabetes mellitus: A case-control study.

BACKGROUND AND AIMS: The relationship between platelet indices and glucose control may differ in type 1 (T1DM) and type 2 (T2DM) diabetes. We aimed to investigate differences in mean platelet volume (MPV), platelet count, and platelet mass between patients with T1DM, T2DM, and healthy controls and to explore associations between these platelet indices and glucose control. METHODS AND RESULTS: A total of 691 T1DM and 459 T2DM patients and 943 control subjects (blood donors) were included. HbA1c was measured in all subjects with diabetes and 36 T1DM patients further underwent 24 h-continuous glucose monitoring to estimate short-term glucose control (glucose mean and standard deviation). Adjusting for age and sex, platelet count was higher and MPV lower in both T1DM and T2DM patients vs control subjects, while platelet mass (MPV × platelet count) resulted higher only in T2DM. Upon further adjustment for HbA1c, differences in platelet count and mass were respectively 19.5 × 109/L (95%CI: 9.8-29.3; p < 0.001) and 101 fL/nL (12-191; p = 0.027) comparing T2DM vs T1DM patients. MPV and platelet count were significantly and differently related in T2DM patients vs both T1DM and control subjects; this difference was maintained also accounting for HbA1c, age, and sex. Platelet mass and the volume-count relationship were significantly related to HbA1c only in T1DM patients. No associations were found between platelet indices and short-term glucose control. CONCLUSION: By accounting for confounders and glucose control, our data evidenced higher platelet mass and different volume-count kinetics in subjects with T2DM vs T1DM. Long-term glucose control seemed to influence platelet mass and the volume-count relationship only in T1DM subjects. These findings suggest different mechanisms behind platelet formation in T1DM and T2DM patients with long-term glycaemic control being more relevant in T1DM than T2DM.

Cardiovascular risk factors and incident albuminuria in screen-detected type 2 diabetes.

BACKGROUND: It is unclear whether cardiovascular risk factor modification influences the development of renal disease in people with type 2 diabetes identified through screening. We determined predictors of albuminuria 5 years after a diagnosis of screen-detected diabetes within the ADDITION-Europe study, a pragmatic cardiovascular outcome trial of multifactorial cardiovascular risk management. METHODS: In 1826 participants with newly diagnosed, screen-detected diabetes without albuminuria, we explored associations between risk of new albuminuria (≥2.5 mg mmol-1 for males and ≥3.5 mg mmol-1 for females) and (1) baseline cardio-metabolic risk factors and (2) changes from baseline to 1 year in systolic blood pressure (ΔSBP) and glycated haemoglobin (ΔHbA1c ) using logistic regression. RESULTS: Albuminuria developed in 268 (15%) participants; baseline body mass index and active smoking were independently associated with new onset albuminuria in 5 years after detection of diabetes. In a model adjusted for age, gender, baseline HbA1c and blood pressure, a 1% decrease in HbA1c and 5-mm Hg decrease in SBP during the first year were independently associated with lower risks of albuminuria (odds ratio), 95% confidence interval: 0.76, 0.62 to 0.91 and 0.94, 0.88 to 1.01, respectively. Further adjustment did not materially change these estimates. There was no interaction between ΔSBP and ΔHbA1c in relation to albuminuria risk, suggesting likely additive effects on renal microvascular disease. CONCLUSIONS: Baseline measurements and changes in HbA1c and SBP a year after diagnosis of diabetes through screening independently associate with new onset albuminuria 4 years later. Established multifactorial treatment for diabetes applies to cases identified through screening.

Efficacy and safety of sodium-glucose co-transporter-2 inhibitors in type 2 diabetes mellitus: systematic review and network meta-analysis.

AIM: To assess the comparative efficacy and safety of sodium-glucose co-transporter-2 (SGLT2) inhibitors in adults with type 2 diabetes. METHODS: We electronically searched randomized controlled trials (≥24 weeks) including canagliflozin, dapagliflozin or empagliflozin that were published up to 3 November 2015. Data were collected on cardiometabolic and safety outcomes and synthesized using network meta-analyses. RESULTS: A total of 38 trials (23 997 participants) were included. Compared with placebo, all SGLT2 inhibitors reduced glycated haemoglobin (HbA1c), fasting plasma glucose (FPG), body weight and blood pressure, and slightly increased HDL cholesterol. Canagliflozin 300 mg reduced HbA1c, FPG and systolic blood pressure and increased LDL cholesterol to a greater extent compared with other inhibitors at any dose. At their highest doses, canagliflozin 300 mg reduced: HbA1c by 0.2% [95% confidence interval (CI) 0.1-0.3] versus both dapagliflozin 10 mg and empagliflozin 25 mg; FPG by 0.6 mmol/l (95% CI 0.3-0.9) and 0.5 mmol/l (95% CI 0.1-0.8) versus dapagliflozin and empagliflozin, respectively; and systolic blood pressure by 2 mmHg (95% CI 1.0-3.0) versus dapagliflozin; and increased LDL cholesterol by 0.13 mmol/l (95% CI 0.03-0.23) and 0.15 mmol/l (95% CI 0.06-0.23) versus dapagliflozin and empagliflozin, respectively. The highest doses of inhibitors had similar effects on body weight reduction. Canagliflozin 300 and 100 mg increased the risk of hypoglycaemia versus placebo, dapagliflozin 10 mg and empagliflozin 10 mg [odds ratios (ORs) 1.4-1.6]. Dapagliflozin 10 mg increased the risk of urinary tract infection versus placebo and empagliflozin 25 mg (ORs 1.4). All inhibitors similarly increased the risk of genital infection (ORs 4-6 versus placebo). CONCLUSIONS: Although they increase the risk of genital infection, SGLT2 inhibitors are effective in improving cardiometabolic markers in type 2 diabetes, with canagliflozin 300 mg performing better in this respect than other inhibitors. Further studies will clarify whether these differences are likely to translate into differing long-term outcomes.

Association between direct measurement of active serum calcium and risk of type 2 diabetes mellitus: A prospective study.

BACKGROUND AND AIMS: Previous prospective studies showing a positive association between serum calcium and incidence of type 2 diabetes mellitus (T2DM) have relied on total calcium or an indirect estimate of active, ionized calcium (iCa). We aimed to assess this relationship using a direct measurement of iCa. METHODS AND RESULTS: iCa and cardiometabolic risk factors were measured in a population-based sample of 2350 men without a known history of T2DM at baseline. Associations between iCa levels and incident cases of T2DM (self-reported, ascertained with a glucose tolerance test, or determined by record linkage to national registers) were estimated using Cox regression analyses adjusted for potential confounders. At baseline, mean (standard deviation) age was 53 (5) years and mean iCa 1.18 (0.05) mmol/L. During a median follow-up of 23.1 years, 140 new cases of T2DM were recorded. In a multivariable analysis adjusted for age, body mass index, systolic blood pressure, serum HDL-cholesterol, and family history of T2DM, there was no association comparing second (hazard ratio 0.84; 95% confidence interval 0.59-1.18), third (0.77; 0.52-1.14), or fourth (0.98; 0.69-1.39) vs first quartile of iCa (p for trend 0.538); further adjustment for C-reactive protein, physical activity level, and triglycerides did not change the estimates (p for trend 0.389). CONCLUSION: In this study, we did not find evidence of an association between direct measurement of active calcium and risk of T2DM. Further studies are needed to confirm our findings and define the relationship between factors influencing indirect calcium estimation and incident T2DM.

Serum fructosamine and risk of cardiovascular and all-cause mortality: a 24-year prospective population-based study.

BACKGROUND AND AIMS: The association between fructosamine and cardiovascular complications is not well established. We sought to evaluate whether serum fructosamine may be a risk factor for cardiovascular and all-cause mortality in nondiabetic subjects. METHODS AND RESULTS: Fructosamine and other cardiovascular risk factors were measured in a sample of 1909 nondiabetic middle-aged men without a known history of coronary heart disease (CHD) at baseline. Associations between baseline fructosamine levels and fatal CHD and cardiovascular disease (CVD) events, and all-cause mortality were estimated using a Cox regression analysis, progressively adjusted for potential confounders. Mean baseline age was 52 years and 30% were smokers. During a median follow-up of 24 years (interquartile range: 18-26 years), 177 (9%) fatal CHD, 289 (15%) fatal CVD, and 728 (38%) all-cause mortality events occurred. In analyses adjusted for several conventional risk factors (i.e., age, systolic blood pressure, smoking, LDL- and HDL-cholesterol), the hazard ratios (HRs) comparing top vs bottom quartile of serum fructosamine levels resulted: 1.33 (95% CI: 0.97, 1.82; p = 0.078) for CHD death and 0.93 (0.72, 1.19; p = 0.567) for CVD death, and 1.04 (0.89, 1.22; p = 0.617) for all-cause mortality. In similar comparisons, further adjustments for body mass index, alcohol consumption, C-reactive protein, and fasting plasma glucose did not materially change these estimates. The exclusion of participants with prevalent CVD at baseline yielded similar results. CONCLUSION: In our cohort of nondiabetic men without known CHD, baseline fructosamine levels were not independently associated with cardiovascular and all-cause mortality. Further studies are warranted to confirm these results in other populations.

Atherosclerotic coronary plaque in subjects with diabetic neuropathy: the prognostic cardiovascular role of Charcot neuroarthropathy--a case-control study.

The aim of this study was to investigate the severity of coronary artery disease (CAD) and the plaque composition in neuropathic type 2 diabetic subjects with and without Charcot neuroarthropathy (CN) undergoing multidetector computed tomography coronary angiography (MDCT-CA). The study was a single-center, observational, with unmatched case-control design. We selected 17 CN patients and 18 patients with diabetic neuropathy (DN) without CN. In all the patients, multidetector computed tomography was performed to assess the coronary artery calcium score (CACS) and degree of coronary artery stenosis. Patients were classified as positive in the presence of significant CAD if there was at least one stenosis >50 % on MDCT-CA. The invasive coronary angiography was performed in case of significant stenosis detected with MDCT-CA, both as reference to standard and eventually as treatment. Groups were matched for age, sex, and traditional CAD risk factors. As compared to DN individuals, CN exhibited higher rates of significant coronary stenoses (p = 0.027; OR 7.7 [1.3-43.5]). However, no significant differences were observed in the CACS, which reflects plaque burden, in the two groups (p = 0.759). No significant differences were observed comparing CACS distribution in all subjects for stenosis higher/equal or lower than 50 % (p = 0.320). Finally, no significant differences were observed comparing CACS distribution in CN and DN subjects for coronary stenoses higher/equal or lower than 50 %. Our results suggest that CN patients have a higher prevalence of severe coronary plaques compared to DN patients. Nevertheless, coronary plaques in CN patients did not exhibit an increased degree of calcification.

Fields of application of continuous subcutaneous insulin infusion in the treatment of diabetes and implications in the use of rapid-acting insulin analogues.

In western countries, diabetes mellitus, because of macrovascular and microvascular complications related to it, is still an important cause of death. Patients with type 1 diabetes mellitus (T1DM) have a six-time higher risk of mortality than healthy patients. Since the Diabetes Control and Complications Trial (DCCT) established how an intensive therapy is necessary to prevent diabetes mellitus complications, many studies have been conducted to understand which method is able to reach an optimal metabolic control. In the past 30 years continuous subcutaneous insulin infusion established/introduced as a validate alternative to multiple daily injections. Several trials demonstrated that, when compared to MDI, CSII brings to a better metabolic control, in terms of a reduction of glycated hemoglobin and blood glucose variability, hypoglycemic episodes and improvement in quality of life. Because of their pharmacokinetic and pharmacodynamic characteristics, rapid-action insulin analogues are imposed as best insulin to be used in CSII. The rapid onset and the fast reached peak make them better mimic the way how pancreas secretes insulin. CSII by pump is not free from issues. Catheter occlusions, blockages, clogs can arrest insulin administration. The consequent higher levels of glycemic values, can easily bring to the onset of ketoacidosis, with an high risk for patients' life. Aspart is a rapid analogue obtained by aminoacidic substitution. It is as effective as lispro and glulisine in gaining a good metabolic control and even better in reducing glucose variability. Some studies tried to compare rapid analogues in terms of stability. Obtained data are controversial. An in vivo study evidenced higher stability or glulisine, while studies in vitro highlighted a higher safety of aspart. Nowadays it is not possible to assess which analogues is safer. When the infusion set is changed every 48 hours equivalent rates of occlusions have been observed.

Metformin improves endothelial function in type 1 diabetic subjects: a pilot, placebo-controlled randomized study.

AIMS: Several studies have investigated the effects of metformin treatment in patients with type 1 diabetes mellitus (T1DM). No study has hitherto examined its effects on endothelial function in these patients. In this study we sought to evaluate the effect of metformin on endothelial function in type 1 diabetic patients. METHODS: Forty-two uncomplicated T1DM patients were randomized in a placebo-controlled, double-blind, 6-month trial to treatment with either metformin or placebo. Glycometabolic and clinical parameters as well as flow-mediated dilation (FMD) and nitrate-mediated dilation (NMD) of the right brachial artery were measured at baseline and at the end of the study. Glycaemic variability (GV, calculated from continuous glucose monitoring data) and a biomarker of oxidative stress [urinary 8-iso-prostaglandin F2α (PGF2α)] were also assessed. RESULTS: Baseline data were similar in the two groups. Compared with placebo, metformin significantly reduced body weight [-2.27 kg (95% confidence interval: -3.99; -0.54); p = 0.012] whilst improved FMD [1.32% (0.30; 2.43); p = 0.013] and increased PGF2α [149 pg/mg creatinine (50; 248); p = 0.004]. Notably, the improvement of FMD did not correlate with the decrease of body weight (r(2) < 1%). NMD, haemoglobin A1c, GV, daily insulin dose and other parameters did not significantly change after the treatment comparing the two groups. CONCLUSIONS: Our pilot trial showed that, in uncomplicated type 1 diabetic subjects, metformin improved FMD and increased PGF2α, a marker of oxidative stress, irrespective of its effects on glycaemic control and body weight. Randomized, blinded clinical trials are needed to evaluate the benefits and risks of metformin added to insulin in type 1 diabetes.

The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes.

BACKGROUND: Interindividual variability in response to aspirin has been popularized as 'resistance'. We hypothesized that faster recovery of platelet cyclooxygenase-1 activity may explain incomplete thromboxane (TX) inhibition during the 24-h dosing interval. OBJECTIVE: To characterize the kinetics and determinants of platelet cyclooxygenase-1 recovery in aspirin-treated diabetic and non-diabetic patients. PATIENTS/METHODS: One hundred type 2 diabetic and 73 non-diabetic patients on chronic aspirin 100 mg daily were studied. Serum TXB(2) was measured every 3 h, between 12 and 24 h after a witnessed aspirin intake, to characterize the kinetics of platelet cyclooxygenase-1 recovery. Patients with the fastest TXB(2) recovery were randomized to aspirin 100 mg once daily, 200 mg once daily or 100 mg twice daily, for 28 days and TXB(2) recovery was reassessed. RESULTS AND CONCLUSIONS: Platelet TXB(2) production was profoundly suppressed at 12 h in both groups. Serum TXB(2) recovered linearly, with a large interindividual variability in slope. Diabetic patients in the third tertile of recovery slopes (≥ 0.10 ng mL(-1) h(-1) ) showed significantly higher mean platelet volume and body mass index, and younger age. Higher body weight was the only independent predictor of a faster recovery in non-diabetics. Aspirin 100 mg twice daily completely reversed the abnormal TXB(2) recovery in both groups. Interindividual variability in the recovery of platelet cyclooxygenase activity during the dosing interval may limit the duration of the antiplatelet effect of low-dose aspirin in patients with and without diabetes. Inadequate thromboxane inhibition can be easily measured and corrected by a twice daily regimen.

Combined atherogenic effects of celiac disease and type 1 diabetes mellitus.

OBJECTIVE: Previous studies have shown a high cardiovascular risk in patients with autoimmune diseases, such as type 1 diabetes mellitus (T1DM). Conversely, few data are available about patients with celiac disease (CD). The aim of our study was to assess carotid intima-media thickness (c-IMT), in patients with T1DM, CD or both (T1DM+CD) as compared with age- and sex-matched healthy individuals (H). METHODS: We enrolled 120 patients, 30 with T1DM, 30 with CD, 30 with T1DM+CD and 30 H. Clinical, metabolic and anthropometric data were collected. All T1DM patients were on insulin while all CD patients were on a gluten-free diet. c-IMT was evaluated by high frequency linear digital ultrasound. RESULTS: c-IMT was significantly greater in patients with T1DM+CD than in patients with T1DM or CD (P<0.001 for both), while no difference was found between T1DM and CD. Moreover, c-IMT was greater in CD than in H (P<0.001). Glycemic control and disease duration were similar between T1DM+CD and T1DM. Lipid and anthropometric parameters were similar among groups. Furthermore, in a pooled multivariate analysis, only age and disease type were significantly correlated with c-IMT (P<0.001 for both). CONCLUSION: Our study demonstrates that celiac patients have greater c-IMT as compared with healthy individuals. Thus, non-invasive monitoring of c-IMT in CD might be useful in preventing cardiovascular disease. Moreover, patients with T1DM+CD show more severe subclinical atherosclerosis as compared with those presenting T1DM or CD only, suggesting that the association of these autoimmune diseases might accelerate the atherosclerotic process.