Association of Serum 25-Hydroxyvitamin D With Cardiovascular Outcomes and All-Cause Mortality in Individuals With Prediabetes and Diabetes: Results From the UK Biobank Prospective Cohort Study
Peizhen ZhangDan GuoBingyan XuChensihan HuangShunyu YangWeiwei WangWenhui LiuYajuan DengKangli LiDeying LiuJiayang LinXueyun WeiYan HuangHuijie Zhang
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OBJECTIVE To examine the associations of circulating 25-hydroxyvitamin D (25[OH]D) concentrations with cardiovascular disease (CVD) and all-cause mortality in individuals with prediabetes and diabetes from the large population-based UK Biobank cohort study. RESEARCH DESIGN AND METHODS A total of 67,789 individuals diagnosed with prediabetes and 24,311 with diabetes who had no CVD or cancer at baseline were included in the current study. Serum 25(OH)D concentrations were measured at baseline. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% CIs for cardiovascular outcomes and mortality after 10–14 years. RESULTS After multivariable adjustment, higher serum 25(OH)D levels were significantly and nonlinearly associated with lower risk of cardiovascular outcomes and all-cause mortality among participants with prediabetes and diabetes (all P nonlinearity < 0.05). Compared with those in the lowest category of 25(OH)D levels (<25 nmol/L), participants with prediabetes in the highest category of 25(OH)D levels (≥75 nmol/L) had a significant association with lower risk of cardiovascular events (HR 0.78; 95% CI 0.71–0.86), coronary heart disease (CHD) (HR 0.79; 95% CI 0.71–0.89), heart failure (HR 0.66; 95% CI 0.54–0.81), stroke (HR 0.75; 95% CI 0.61–0.93), CVD mortality (HR 0.43; 95% CI 0.32–0.59), and all-cause mortality (HR 0.66; 95% CI 0.58–0.75). Likewise, these associations with cardiovascular events, CHD, heart failure, CVD mortality, and all-cause mortality were observed among participants with diabetes, except for stroke. CONCLUSIONS These findings highlight the importance of monitoring and correcting vitamin D deficiency in the prevention of CVD and mortality among adults with prediabetes and diabetes.Keywords:
Prediabetes
Aim: To investigate the effect of oral consumption of engineered mesoporous silica particles, SiPore15®, on long-term blood glucose levels and other metabolic parameters in individuals with prediabetes and newly diagnosed Type 2 diabetes. Method: An open-label, single-arm, multicenter trial was conducted in which SiPore15 was consumed three times daily for 12 weeks. Hemoglobin A1c (HbA1c, primary end point) and an array of metabolic parameters were measured at baseline and throughout the trial. Result: SiPore15 treatment significantly reduced HbA1c by a clinically meaningful degree and improved several disease-associated parameters with minimal side effects. Conclusion: The results from this study demonstrate the potential use of SiPore15 as a treatment for prediabetes that may also delay or prevent the onset of Type 2 diabetes.
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Mortality in type 2 diabetes, is determined not only by classical complications, but also by comorbidities, and is linked to hyperglycaemia and apparent even in prediabetes. We aimed to comprehensively investigate, in a population-based cohort, health burden defined as the presence of comorbidities in addition to classical complications and cardiometabolic risk factors, in not only type 2 diabetes but also prediabetes. Such population-based study has not been performed previously. Extensive phenotyping was performed in 3,410 participants of the population-based Maastricht Study (15.0% prediabetes and 28.6% type 2 diabetes) to assess presence of 17 comorbidities, six classical complications, and ten cardiometabolic risk factors. These were added up into individual and combined sum scores and categorized. Group differences were studied with multinomial regression analyses adjusted for age and sex. Individuals with type 2 diabetes and prediabetes, as compared to normal glucose metabolism (NGM), had greater comorbidities, classical complications, cardiometabolic risk factors and combined sum scores (comorbidities sum score ≥ 3: frequencies (95% CI) 61.5% (57.6;65.4) and 41.2% (36.5;45.9) vs. 25.4% (23.5;27.4), p-trend < 0.001; classical complications ≥ 2 (26.6% (23.1;30.1; P < 0.001 vs. NGM) and 10.1% (7.8;12.7; P = 0.065 vs NGM) vs. 8.0% (6.9;9.3)); cardiometabolic risk factors ≥ 6 (39.7% (35.9;43.4) and 28.5% (24.5;32.6) vs. 14.0% (12.5;15.6); p-trend < 0.001); combined ≥ 8 (66.6% (62.7;70.5) and 48.4% (43.7;53.1) vs. 26.0%(24.1;28.0), p-trend < 0.001). Type 2 diabetes and prediabetes health burden was comparable to respectively 32 and 14 years of ageing. Our population-based study shows, independently of age and sex, a considerable health burden in both type 2 diabetes and prediabetes, which to a substantial extent can be attributed to comorbidities in addition to classical complications and cardiometabolic risk factors. Our findings emphasize the necessity of comorbidities' awareness in (pre)diabetes and for determining the exact role of hyperglycaemia in the occurrence of comorbidities.
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Abstract: The onset of type 2 diabetes increases the risk of vascular complications and death. We know now that that this risk begins long before the diabetes diagnosis. Prediabetes and type 2 diabetes are not separate entities in practice and exist within a continuum of dysglycaemia and vascular risk that increases in severity over time. This excess risk requires early intervention with lifestyle therapy supported with pharmacologic antidiabetic therapy, intensified promptly where necessary throughout the duration of the diabetes continuum. Metformin is an evidence-based treatment for preventing prediabetes and improves cardiovascular outcomes in people with type 2 diabetes from diagnosis onwards. Newer agents (SGLT2 inhibitors and GLP-1 agonists) are appropriate for people presenting with type 2 diabetes and significant cardiovascular comorbidity. Additional therapies should be used without delay to achieve patients' individualised HbA1c goals and to minimise cardiovascular risk. Keywords: prediabetes, type 2 diabetes, diabetes complications, antidiabetic therapy
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The article discusses the pathogenesis, methods of diagnosis, prevention, and treatment of insulin resistance, prediabetes, and type 2 diabetes. According to international recommendations, the first-line therapy for type 2 diabetes is metformin and lifestyle modification (correction of excess weight, regular physical activity), which have shown high effectiveness in large-scale clinical studies.
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Different prediabetic states precede overt type 2 diabetes. Prediabetes also carries an increased cardiovascular risk per seand may be divided into fasting hyperglycemia, impaired glucose tolerance and intermediate hyperglycemia. Mixed forms of these are very common. Prediabetes develops insidiously for many years and usually produces no symptoms until very late. It is possible to prevent prediabetes from progressing to manifest type 2 diabetes and it can also be made to revert to normoglycemia. The importance of lifestyle interventions, pharmacological treatment, surgical treatment and community efforts is discussed.
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The hazard ratio and median survival time are the routine indicators in survival analysis. We briefly introduced the relationship between hazard ratio and median survival time and the role of proportional hazard assumption. We compared 110 pairs of hazard ratio and median survival time ratio in 58 articles and demonstrated the reasons for the difference by examples. The results showed that the hazard ratio estimated by the Cox regression model is unreasonable and not equivalent to median survival time ratio when the proportional hazard assumption is not met. Therefore, before performing the Cox regression model, the proportional hazard assumption should be tested first. If proportional hazard assumption is met, Cox regression model can be used; if proportional hazard assumption is not met, restricted mean survival times is suggested.风险比（hazard ratio，HR）和中位生存时间是生存分析时的常规分析和报告指标。本文简要介绍了HR和中位生存时间的关系以及比例风险假定在这两者之间的作用，分析了检索出的58篇文献中的110对风险比和中位生存时间比的差异，并通过实例阐明了产生这种差异的原因。结果表明，在不满足比例风险假定时，Cox回归模型计算得到的风险比是不合理的，且与中位生存时间之比不等价。因此，在使用Cox回归模型前，应先进行比例风险假定的检验，只有符合比例风险假定时才能使用该模型；当不符合比例风险假定时，建议使用限制性平均生存时间。.
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