Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

Gorst, Catherine; Kwok, Chun Shing; Aslam, Saadia; Buchan, Iain; Kontopantelis, Evangelos; Myint, Phyo Kyaw; Heatlie, Grant; Loke, Yoon K.; Rutter, Martin K.; Mamas, Mamas A.

doi:10.2337/dc15-1188

Cited by 421 publications

(431 citation statements)

References 47 publications

(154 reference statements)

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“…In addition, respondents were not always able to respond accurately. Corroborating the literature (4,(24)(25) , the present study presented a positive statistical relationship between inadequate glycemic control and the occurrence of DM-related complications, although this variable was not maintained in the final model, perhaps because it was closely linked to the duration of diabetes.…”

Section: Discussionsupporting

confidence: 77%

Factors associated with glycemic control in people with diabetes at the Family Health Strategy in Pernambuco

Lima

Fontbonne

Carvalho

et al. 2016

Rev. esc. enferm. USP

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Objective: Identifying factors associated with glycemic control in people with type 2 Diabetes Mellitus (DM) registered in the Family Health Strategy (FHS) in Pernambuco, Brazil. Method: Associations between glycemic control (glycosylated hemoglobin A lower or equal to 7%) presented by people with DM and variables related to sociodemographic conditions, lifestyle, characteristics of diabetes, treatment and follow-up of patients by health services were investigated by multiple regression. Results: More than 65% of the participants presented inadequate glycemic control, especially those with lower age, longer illness duration, more annual contacts with FHS and complex therapeutic regimen. People with DM without referrals to specialists presented greater glycemic control. Associations with education level and obesity did not remain significant in the multivariate model. Conclusion: The evolution of diabetes hinders adequate control, however, attention to younger people with DM and referrals to specialists are factors that can improve glycemic control. DESCRIPTORS

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Section: Discussionsupporting

confidence: 77%

Factors associated with glycemic control in people with diabetes at the Family Health Strategy in Pernambuco

Lima

Fontbonne

Carvalho

et al. 2016

Rev. esc. enferm. USP

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“…This is the first analysis to consider the relationship between clinically significant variations in glycaemic control and mortality in older people. While previous studies have shown that variability in HbA1c increases hazard for diabetes complications and mortality, 11,18,19 these studies were not specific to older people and used variability estimations based on standard deviation(SD) of the mean HbA1c. Whereas our variability metric was weighted for clinically significant change in HbA1c (≥ 0·5%,5·5 mmol/mol) and we also considered the frequency and direction of variation to provide more granularity in our interpretation.…”

Section: Discussionmentioning

confidence: 99%

Mean HbA1c, HbA1c variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study

Forbes

Murrells

Mulnier

et al. 2018

The Lancet Diabetes & Endocrinology

156

151

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Evidence before this studyWe have searched PubMed and Scopus from 1990-2017, to identify relevant studies that contain terms for older people; all-cause mortality; glycaemic control; glycaemic variability (with synonyms). We also identified current international guidelines for older people. Overall, the data on optimal glycaemic targets for older people are scant, particularly from prospective studies. In terms of the association between glycaemic control and mortality in older populations the finding have suggested a 'J' shaped distribution in that relationship, although the point at which a significant mortality hazard is observed at the lower end of the glycaemic range has varied between studies. In terms of glycaemic variability, it has been identified that longer term variations in glycaemic control are associated with mortality risk. However, these analyses have not been graduated for magnitude or direction of variability. In addition, previous analyses have not considered the impact of low HbA1c levels, which are associated with mortality risk independent of diabetes intervention. Added value of this studyIn this large population study we are the first group to consider both glycaemic control and glycaemic variability together. We have also employed a new metric for variability which considers exposure to clinically significant changes in glycaemic control. This metric enabled us to assess the direction of change as well as the overall variability. Integrating glycaemic control and variability in our modelling enabled us to consider the importance of stability as a potential factor in understanding the mortality hazard in this population. Additional nuances to our analysis include: consideration of low HbA1c values; higher levels of granularity compared to previous studies in terms of glycaemic thresholds, with 0.5%(5.5mmol/l) HbA1c increments; consideration of gender differences; and the distinction between those who develop diabetes in midlife and those who develop it in older age. Implications of all the available evidenceOur data suggest that we may need to rethink how we consider glycaemic targets in the older diabetes population, in a number of ways: firstly, that variability expresses significant hazard in older people; secondly, that variability may be independent of diabetes therapies and may be related to other factors related to aging; thirdly, stability seems to attenuate hazard in medium to higher ranges of glycaemic control; and finally, there may be some important gender differences in relation to glycaemic control and hazard which are not considered in current guidelines. Therefore, while we recognise that observational data can often raise more questions than answers; we would advocate that we reconsider glycaemic control not simply as a target to direct therapeutic management, but as an important piece of information in relation to assessing individual risk. Perhaps in the past we have been too polarised in our view of glycaemia as purely indicative of optimal control, rather than as a p...

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“…41,48,51 During recent years, the effect of long-term glucose variability, as assessed by the intraindividual variability of HbA1c values across visits, on retinopathy, nephropathy, and cardiovascular complications has also been documented. 52 However, HbA1c measurement does not give any information about individual daily glucose fluctuations (short-term fluctuations or acute hyperglycemia). In patients with marked fluctuations in glucose concentrations who are exposed to the risk of both hyperglycemia and hypoglycemia, HbA1c levels may still indicate adequate metabolic control.…”

Section: Chronic Versus Acute Hyperglycemia In the Pathogenesis Of Vamentioning

confidence: 99%

Complications of Acute and Chronic Hyperglycemia

Marcovecchio¹

2017

US Endocrinology

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Hyperglycemia is due to a dysregulation in the complex mechanisms implicated in glucose homeostasis. Chronic hyperglycemia, as measured by hemoglobin A1c (HbA1c), is a key risk factor for the development of microvascular and macrovascular complications, which in turn negatively influence the prognosis of patients with diabetes. Several studies have shown that acute hyperglycemia can add to the effect of chronic hyperglycemia in inducing tissue damage. Acute hyperglycemia can manifest as high fasting plasma glucose (FPG) or high postprandial plasma glucose (PPG) and can activate the same metabolic and hemodynamic pathways as chronic hyperglycemia. Glucose variability, as expressed by the intraday glucose fluctuations from peaks to nadirs, is another important parameter, which has emerged as an HbA1c-independent risk factor for the development of vascular complications, mainly in the context of type 2 diabetes. Treatments able to decrease HbA1c have been associated with positive effects in terms of reducing risk for the development and progression of complications. Further studies are required to clarify the impact of strategies more specifically targeting components of acute hyperglycemia, to improve outcomes in patients with diabetes. KeywordsHyperglycemia, complications, vascular, acute, chronic Disclosure: M Loredana Marcovecchio has nothing to disclose in relation to this article. No funding was received in the publication of this article. This study involves a review of the literature and did not involve any studies with human or animal subjects performed by any of the authors.Authorship: Thel named author meets the International Committee of Medical Journal Editors (ICMJE) criteria for authorship of this manuscript, takes responsibility for the integrity of the work as a whole, and has given final approval to the version to be published.Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any non-commercial use, distribution, adaptation and reproduction provided the original author(s) and source are given appropriate credit. From glucose homeostasis to hyperglycemiaGlucose homeostasis is maintained by a complex neurohormonal system, which modulates peripheral glucose uptake, hepatic glucose production, and exogenous glucose utilization following food ingestion.1,2 This allows the maintenance of plasma glucose concentrations within normal range, with average values of around 90 mg/dl throughout a 24-hour period, postmeal concentration below 140 mg/dl, and minimal values, such as those after moderate fasting or exercise, above 55 mg/dl. 1,2Hormones implicated in glucose regulation include insulin, glucagon, amylin, glucagon-like petide-1 (GLP-1), glucose-dependent insulinotropic peptide, epinephrine, cortisol, and growth hormone. These hormones act on several target tissues, including muscle, liver, adipocyte, and brain to regulate glucose levels. 3Insulin is a key glucoregulatory hormone, produced by pancreatic β-cells, whose levels are low durin...

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Long-term Glycemic Variability and Risk of Adverse Outcomes: A Systematic Review and Meta-analysis

Cited by 421 publications

References 47 publications

Factors associated with glycemic control in people with diabetes at the Family Health Strategy in Pernambuco

Factors associated with glycemic control in people with diabetes at the Family Health Strategy in Pernambuco

Mean HbA1c, HbA1c variability, and mortality in people with diabetes aged 70 years and older: a retrospective cohort study

Complications of Acute and Chronic Hyperglycemia

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