Hypoglycaemia, thrombosis and vascular events in diabetes

King, Rhodri; Ajjan, Ramzi

doi:10.1080/14779072.2016.1215916

Cited by 15 publications

(15 citation statements)

References 33 publications

(34 reference statements)

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“…It should be noted that HbA1c measures average glucose levels and does not address glucose variability or hypoglycaemia, both of which appear to be associated with adverse vascular outcome . In particular, higher insulin doses, commonly used in DD, may lead to increased risk of hypoglycaemia, which, in turn, enhances the inflammatory/thrombotic milieu, thus contributing to vascular pathology . Moreover, the potential for larger fluctuations in glucose levels in this population may implicate glucose variability in the increased risk of complications; however, these are merely hypotheses at present and studies are required to establish whether individuals with DD experience more hypoglycaemic events and/or higher glucose variability, particularly in those with well controlled HbA1c.…”

Section: Potential Mechanisms For Increased Complications In Ddmentioning

confidence: 99%

“…55,56 In particular, higher insulin doses, commonly used in DD, may lead to increased risk of hypoglycaemia, 57 which, in turn, enhances the inflammatory/thrombotic milieu, thus contributing to vascular pathology. 58 Moreover, the potential for larger fluctuations in glucose levels in this population may implicate glucose variability in the increased risk of complications; however, these are merely hypotheses at present and studies are required to establish whether individuals with DD experience more hypoglycaemic events and/or higher glucose variability, particularly in those with well controlled HbA1c. If a difference is detected, longitudinal studies are warranted to understand the relationship between these glycaemic markers and vascular complications in DD.…”

Section: Role Of Glycaemiamentioning

confidence: 99%

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Double diabetes: A distinct high‐risk group?

Kietsiriroje

Pearson

Campbell

et al. 2019

Diabetes Obesity Metabolism

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The term double diabetes (DD) has been used to refer to individuals with type 1 diabetes (T1D) who are overweight, have a family history of type 2 diabetes and/or clinical features of insulin resistance. Several pieces of evidence indicate that individuals who display features of DD are at higher risk of developing future diabetes complications, independently of average glucose control, measured as glycated haemoglobin (HbA1c) concentration. Given the increased prevalence of individuals with features of DD, pragmatic criteria are urgently required to identify and stratify this group, which will help with subsequent implementation of more effective personalized interventions. In this review, we discuss the potential criteria for the clinical identification of individuals with DD, highlighting the strengths and weaknesses of each definition. We also cover potential mechanisms of DD and how these contribute to increased risk of diabetes complications. Special emphasis is placed on the role of estimated glucose disposal rate (eGDR) in the diagnosis of DD, which can be easily incorporated into clinical practice and is predictive of adverse clinical outcome. In addition to the identification of individuals with DD, eGDR has potential utility in monitoring response to different interventions. T1D is a more heterogeneous condition than initially envisaged, and those with features of DD represent a subgroup at higher risk of complications. Pragmatic criteria for the diagnosis of individuals with DD will help with risk stratification, allowing a more personalized and targeted management strategy to improve outcome and quality of life in this population.

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Section: Potential Mechanisms For Increased Complications In Ddmentioning

confidence: 99%

Section: Role Of Glycaemiamentioning

confidence: 99%

Double diabetes: A distinct high‐risk group?

Kietsiriroje

Pearson

Campbell

et al. 2019

Diabetes Obesity Metabolism

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“…However, intensively treating glycaemia predisposes to hypoglycaemia, which in itself increases the risk of vascular events [ 7 ]. Mechanisms for hypoglycaemia-induced vascular damage include the induction of an inflammatory and prothrombotic milieu due to low glucose levels [ 8 ]. To further complicate matters, large fluctuations in glucose control, typically seen in individuals with inadequate insulin dosing, are also thought to be associated with vascular damage through increased oxidative stress and an enhanced inflammatory response [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Control in Type 1 Diabetes: Is Adjunctive Therapy the Way Forward?

et al. 2018

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Despite advances in insulin therapies, patients with type 1 diabetes (T1DM) have a shorter life span due to hyperglycaemia-induced vascular disease and hypoglycaemic complications secondary to insulin therapy. Restricting therapy for T1DM to insulin replacement is perhaps an over-simplistic approach, and we focus in this work on reviewing the role of adjuvant therapy in this population. Current data suggest that adding metformin to insulin therapy in T1DM temporarily lowers HbA1c and reduces weight and insulin requirements, but this treatment fails to show a longer-term glycaemic benefit. Agents in the sodium glucose co-transporter-2 inhibitor (SGLT-2) class demonstrate the greatest promise in correcting hyperglycaemia, but there are safety concerns in relation to the risk of diabetic ketoacidosis. Glucagon-like peptide-1 agonists (GLP-1) show a modest effect on glycaemia, if any, but significantly reduce weight, which may make them suitable for use in overweight T1DM patients. Treatment with pramlintide is not widely available worldwide, although there is evidence to indicate that this agent reduces both HbA1c and weight in T1DM. A criticism of adjuvant studies is the heavy reliance on HbA1c as the primary endpoint while generally ignoring other glycaemic parameters. Moreover, vascular risk markers and measures of insulin resistance—important considerations in individuals with a longer T1DM duration—are yet to be fully investigated following adjuvant therapies. Finally, studies to date have made the assumption that T1DM patients are a homogeneous group of individuals who respond similarly to adjuvant therapies, which is unlikely to be the case. Future longer-term adjuvant studies investigating different glycaemic parameters, surrogate vascular markers and harder clinical outcomes will refine our understanding of the roles of such therapies in various subgroups of T1DM patients.

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“…The drive for tighter glycaemic control has led to an increased prevalence of hypoglycaemia, which has shown an association with increased mortality . A number of mechanisms have been implicated including: cardiac dysrhythmias; increased production of vascular inflammatory molecules; and enhanced thrombotic environment (summarised in Figure ).…”

Section: The Role Of Glycaemia In Diabetes Complicationsmentioning

confidence: 99%

Glucose monitoring in diabetes: from clinical studies to real‐world practice

2019

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Lowering glucose levels in diabetes prevents microvascular complications and long‐term macrovascular disease. HbA1c has long been used to guide management decisions, but it fails to address hypoglycaemia and glycaemic variability, both of which are associated with adverse clinical outcome. While self‐monitoring of blood glucose (SMBG) has had a pivotal role in improving glycaemia in diabetes, it provides incomplete glucose data and can be inconvenient to patients. Continuous glucose monitoring (CGM) has the advantage of greater convenience, comprehensive glucose measurements and hypoglycaemia alarms; the latter are particularly useful in individuals with hypoglycaemia unawareness. However, these devices are relatively expensive, limiting widespread use, and most require continued capillary glucose testing for calibration. The newer flash continuous glucose monitoring (FCGM) device has the advantage of lower costs, long sensor life and factory calibration, negating the need for routine SMBG. However, the lack of hypoglycaemia alarms can be an issue, although a newer generation of sensors will have alarm capability but yet to be released in the UK. Studies have conclusively shown that CGM and FCGM improve glycaemic parameters in individuals with type 1 diabetes, and studies in type 2 diabetes are also promising but limited to draw definitive conclusions on the best subgroup(s) to benefit from this technology. Despite some reluctance to use CGM and FCGM due to costs and lack of familiarity, there has been a gradual shift from SMBG to these newer glucose monitoring strategies in those with type 1 diabetes, thus improving glycaemic control and the quality of life of these individuals. Copyright © 2019 John Wiley & Sons.

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Hypoglycaemia, thrombosis and vascular events in diabetes

Cited by 15 publications

References 33 publications

Double diabetes: A distinct high‐risk group?

Double diabetes: A distinct high‐risk group?

Metabolic Control in Type 1 Diabetes: Is Adjunctive Therapy the Way Forward?

Glucose monitoring in diabetes: from clinical studies to real‐world practice

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