An investigation of causal relationships between prediabetes and vascular complications

Abstract

Prediabetes is a state of glycaemic dysregulation below the diagnostic threshold of type 2 diabetes (T2D). Globally, ~352 million people have prediabetes, of which 35–50% develop full-blown diabetes within five years. T2D and its complications are costly to treat, causing considerable morbidity and early mortality. Whether prediabetes is causally related to diabetes complications is unclear. Here we report a causal inference analysis investigating the effects of prediabetes in coronary artery disease, stroke and chronic kidney disease, complemented by a systematic review of relevant observational studies. Although the observational studies suggest that prediabetes is broadly associated with diabetes complications, the causal inference analysis revealed that prediabetes is only causally related with coronary artery disease, with no evidence of causal effects on other diabetes complications. In conclusion, prediabetes likely causes coronary artery disease and its prevention is likely to be most effective if initiated prior to the onset of diabetes.

Advanced glycation end-products, measured as skin autofluorescence, associate with vascular stiffness in diabetic, pre-diabetic and normoglycemic individuals: a cross-sectional study

“…Associations between skin AF and vascular stiffness tended to be stronger in prediabetes groups based on FPG or defined as any abnormal glycemic value compared to normoglycemic groups, whereas the relationships were not markedly different when prediabetes was based on HbA 1c or 2 h plasma glucose levels. This finding is supported by a recent Mendelian randomization (MR) study investigating causal effects of prediabetes on major diabetes-related complications, including coronary artery disease (CAD) [ 31 ]. Intriguingly, while FPG concentrations were causally related to CAD with a 26% higher odds of CAD per mmol/L increase in fasting glucose, no causal relationship between genetically elevated HbA 1c levels and diabetes complications could be detected in that study.…”

Prediabetes and risk of mortality, diabetes-related complications and comorbidities: umbrella review of meta-analyses of prospective studies

“…Out of the 4807 identified articles, 126 full-texts were assessed for eligibility, and finally, 16 articles were included in this umbrella review (Fig. 1) [7][8][9][10][23][24][25][26][27][28][29][30][31][32][33][34]. A detailed list of the excluded articles and the reasons for their exclusion is displayed in ESM Table 3.…”

“…CVD outcomes and CV mortality CV events [29] CV events [29] CV events [29] CV events [29] CV events [29] CV events [29] CV events [29] CV events [29] CV mortality [29] b CV mortality [29] b CV mortality [29] b CVD incidence [29] b CVD incidence [29] b CVD incidence [29] b CHD [29] CHD [29] CHD [29] CHD [29] CHD [29] CHD [29] Stroke [29] Stroke [29] Stroke [29] Stroke [29] Stroke [29] Stroke [29] Atrial fibrillation [24] Atrial fibrillation [24] Heart failure [34] Heart failure [34] Heart failure [34] Sudden cardiac death [25] . Microvascular outcomes Chronic kidney disease [8] Chronic kidney disease [8] Chronic kidney disease [30] c Chronic kidney disease [30] c . Cancer Total cancer [10] Total cancer [10] Total cancer [10] Total cancer [10] Stomach/colorectal cancer [10] Total liver cancer [10] Hepatocellular carcinoma [26] Hepatocellular carcinoma [26] Bronchus and lung cance...…”

Prevalence and Associated Factors of Kidney Dysfunction in Patients with Hypertension and/or Diabetes Mellitus from a Primary Care Population in Northwest China

“…Abbreviations: BMI, body mass index; FPG, fasting plasma glucose; TC, total cholesterol; TG, triglyceride. OR, odds ratio; CI, confidence interval.International Journal of General Medicine 2021:14 https://doi.org/10.2147/IJGM.S329604 DovePress 7575 stroke 36. It is noteworthy that FPG is independently associated with CKD in hypertensive patients who are without DM in the present study.…”