Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature

Nalysnyk, Luba; Hernandez-Medina, Marisol; Krishnarajah, Girishanthy

doi:10.1111/j.1463-1326.2009.01160.x

Cited by 300 publications

(238 citation statements)

References 32 publications

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“…Several studies performed in patients with T2D have shown a direct association between glucose variability and the development or progression of retinopathy, cardiovascular disease and mortality. 55,56 In contrast, some studies in patients with T1D have shown that glucose variability has a small effect on the development of diabetic complications, with few studies reporting an association with microvascular complications, whereas it appears that there is no link with macrovascular disease. 55,56 Data from the DCCT showed no association between measures of glucose variability and microvascular…”

Section: Chronic Versus Acute Hyperglycemia In the Pathogenesis Of Vamentioning

confidence: 98%

“…57 Similarly, another study in patients with T1D could not confirm the association found in patients with T2D between oxidative stress and glucose variability. 55 Further studies are required to clarify the role of glucose variability as a potential additional component in the network of vascular complications of diabetes.…”

Section: Chronic Versus Acute Hyperglycemia In the Pathogenesis Of Vamentioning

confidence: 99%

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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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Section: Chronic Versus Acute Hyperglycemia In the Pathogenesis Of Vamentioning

confidence: 98%

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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“…Among those cases, type 2 diabetes mellitus (T2DM) typically occurred in overweight young adults as well as aged populations [3], with the underlying mechanism a relative deficiency of insulin due to abnormal insulin sensitivity and insulin resistance involving various transport pathways and key molecules. As a common chronic disease, T2DM easily induces age-matched disabilities and multiple organ dysfunctions or failure [4]. Meanwhile, the problem of T2DM-induced depression is also proposed and focused on in recent years.…”

Section: Introductionmentioning

confidence: 99%

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials

Wang

Zhang

HaiLi

et al. 2017

Food & Nutrition Research

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The present study was designed to systematically evaluate the clinical efficacy and safety of garlic supplement in the management of type 2 diabetes mellitus (T2DM). PubMed, EMBASE, the Cochrane Library, and China National Knowledge Internet (CNKI) were searched for relevant randomized controlled trials (RCTs) by using the terms garlic and T2DM up to April 2017. The quality of included RCTs was assessed by the Cochrane tool of risk of bias, and data of outcomes were pooled by REVMAN 5.3. Clinical factors were handled by meta-regression and subgroup analysis, and risk of publication bias was explored by inverted funnel plots. Nine RCTs involving 768 T2DM patients were included in the meta-analysis, and the dose of daily garlic (allicin) supplement ranged from 0.05g to 1.5g. A significant reduction in the level of fasting blood glucose in 1–2 weeks [SMD = −1.61, 95%CI (−2.89, −0.32)], 3–4 weeks [SMD = −2.87, 95%CI (−4.74, −1.00)], 12 weeks [SMD = −9.57, 95%CI (−12.39, −6.75)], and 24 weeks [SMD = −21.02, 95%CI (−32.47, −9.57)] was achieved in favour of the garlic group rather than the control group. Significantly decreased fructosamine and glycated hemoglobin (both in 12 and 24 weeks) were also found in garlic group. Meanwhile, significantly improved blood liquids of total cholesterol [SMD = −1.93, 95%CI (−2.98, −0.87), 3–4 weeks], high density lipoprotein [SMD = −0.41, 95%CI (−0.83, −0.00), 3–4 weeks] and low density lipoprotein [SMD = −3.47, 95%CI (−5.76, −1.18), 12 weeks] were confirmed after garlic administration. There was no significant difference in complications. Current data confirms that garlic supplement plays positive and sustained roles in blood glucose, total cholesterol, and high/low density lipoprotein regulation in the management of T2DM. Abbreviations: T2DM = type 2 diabetes mellitus; RCT = randomized controlled trial; SMD = standard mean difference; CI = confidence interval; FBG = fasting blood glucose; HbA1c = glycated hemoglobin; HDL = high density lipoprotein; LDL = low density lipoprotein.

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“…Landmark clinical trials have shown that lowering HbA1c reduces the risk of development and progression of diabetes complications,1, 2 which has led to a treatment focus on achieving the generally recommended target HbA1c of <7.0% 3. Although controversial,4, 5 in the past decade, a body of evidence has implicated glycaemic variability in the pathogenesis of diabetes complications, suggesting that glycaemic variability should also be considered a target for glucose‐lowering therapies 6, 7. Glycaemic variability refers to acute excursions in blood glucose levels, including hypoglycaemic events and postprandial hyperglycaemia, and may be known by some patients and physicians as daily glucose fluctuations 8.…”

Section: Introductionmentioning

confidence: 99%

Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

Frías

Nakhle²,

Ruggles

et al. 2016

Diabetes Obesity Metabolism

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AimTo assess the effects of once‐weekly exenatide on 24‐hour glucose control and variability.Materials and methodsThis double‐blind, placebo‐controlled trial randomized metformin‐treated adults with type 2 diabetes to once‐weekly exenatide 2.0 mg or placebo. Continuous glucose monitoring (CGM) was performed at baseline and weeks 4 and 10. The primary outcome was change in CGM‐measured 24‐hour mean glucose level.ResultsIn the once‐weekly exenatide (n = 60) and placebo (n = 56) groups (modified intention‐to‐treat population), the baseline glycated haemoglobin (HbA1c) concentrations were 8.2% and 8.0%, respectively, and the fasting plasma glucose (FPG) concentration was 9.86 and 9.32 mmol/L, respectively. Once‐weekly exenatide significantly (p < 0.001) reduced 24‐hour mean glucose level versus placebo (week 4, −1.44 vs −0.29 mmol/L; week 10, −1.71 vs −0.17 mmol/L), with consistent control throughout the week. Once‐weekly exenatide significantly reduced FPG and 2‐hour postprandial glucose (PPG) levels versus placebo at week 4 (FPG, −1.65 vs −0.11 mmol/L; PPG, −1.79 vs −0.11 mmol/L) and week 10 (FPG, −2.32 vs −0.28 mmol/L; PPG, −2.46 vs −0.33 mmol/L). At week 10, once‐weekly exenatide reduced the mean amplitude of glucose excursions (MAGE; −0.84 vs 0.16 mmol/L) and standard deviation (s.d.) of mean glucose (−0.35 vs 0.04 mmol/L). By week 10, once‐weekly exenatide‐treated participants spent more time in euglycaemia (once‐weekly exenatide, 77% vs placebo, 58%), less time in hyperglycaemia (22% vs 42%), and a similar time in hypoglycaemia (0.7% vs 0.3%). Common adverse events were injection‐site nodule (once‐weekly exenatide, 10.0% vs placebo, 0.0%), urinary tract infection (6.7% vs 8.9%) and nausea (6.7% vs 0.0%).ConclusionsIn metformin‐treated participants with type 2 diabetes, once‐weekly exenatide significantly improved daily glucose control and reduced glycaemic variability at weeks 4 and 10, as shown by reductions in 24‐hour glucose, FPG and PPG levels, MAGE and s.d., and increased time spent in euglycaemia.

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Glycaemic variability and complications in patients with diabetes mellitus: evidence from a systematic review of the literature

Cited by 300 publications

References 32 publications

Complications of Acute and Chronic Hyperglycemia

Complications of Acute and Chronic Hyperglycemia

Effect of garlic supplement in the management of type 2 diabetes mellitus (T2DM): a meta-analysis of randomized controlled trials

Exenatide once weekly improved 24‐hour glucose control and reduced glycaemic variability in metformin‐treated participants with type 2 diabetes: a randomized, placebo‐controlled trial

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