Glycemic Variability in Type 2 Diabetes Mellitus

Johnson, Eric L.

doi:10.1007/978-1-4614-5441-0_13

Cited by 31 publications

(9 citation statements)

References 115 publications

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“…In addition to inducing insulin resistance, persistent hyperglycemia impairs insulin secretion by pancreatic β-cells [19]. Chronic hyperglycemia will also cause detrimental effects on macrovascular and microvascular systems, inducing overproduction of NADH and mitochondrial reactive oxygen species (ROS) that inhibit GAPDH activity [20,21,22]. This inhibition further activates the alternative glucose metabolic pathways, which leads to increased ROS production involved in glucotoxicity that is responsible for the exacerbation of diabetes and the development of diabetic complications [22,23,24,25].…”

Section: Introductionmentioning

confidence: 99%

Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models

et al. 2019

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Diseases involving inflammation and oxidative stress can be exacerbated by high blood glucose levels. Due to tight metabolic regulation, safely reducing blood glucose can prove difficult. The ketogenic diet (KD) reduces absolute glucose and insulin, while increasing fatty acid oxidation, ketogenesis, and circulating levels of β-hydroxybutyrate (βHB), acetoacetate (AcAc), and acetone. Compliance to KD can be difficult, so alternative therapies that help reduce glucose levels are needed. Exogenous ketones provide an alternative method to elevate blood ketone levels without strict dietary requirements. In this study, we tested the changes in blood glucose and ketone (βHB) levels in response to acute, sub-chronic, and chronic administration of various ketogenic compounds in either a post-exercise or rested state. WAG/Rij (WR) rats, a rodent model of human absence epilepsy, GLUT1 deficiency syndrome mice (GLUT1D), and wild type Sprague Dawley rats (SPD) were assessed. Non-pathological animals were also assessed across different age ranges. Experimental groups included KD, standard diet (SD) supplemented with water (Control, C) or with exogenous ketones: 1, 3-butanediol (BD), βHB mineral salt (KS), KS with medium chain triglyceride/MCT (KSMCT), BD acetoacetate diester (KE), KE with MCT (KEMCT), and KE with KS (KEKS). In rested WR rats, the KE, KS, KSMCT groups had lower blood glucose level after 1 h of treatment, and in KE and KSMCT groups after 24 h. After exercise, the KE, KSMCT, KEKS, and KEMCT groups had lowered glucose levels after 1 h, and in the KEKS and KEMCT groups after 7 days, compared to control. In GLUT1D mice without exercise, only KE resulted in significantly lower glucose levels at week 2 and week 6 during a 10 weeks long chronic feeding study. In 4-month and 1-year-old SPD rats in the post-exercise trials, blood glucose was significantly lower in KD and KE, and in KEMCT groups, respectively. After seven days, the KSMCT group had the most significantly reduced blood glucose levels, compared to control. These results indicate that exogenous ketones were efficacious in reducing blood glucose levels within and outside the context of exercise in various rodent models of different ages, with and without pathology.

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Section: Introductionmentioning

confidence: 99%

Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models

et al. 2019

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“…A recent review concluded that ambulatory 24-h glucose should be considered in addition to HbA 1c and fasting glucose when evaluating the comparative effectiveness of therapeutic regimens (10). In addition, there is evidence that glycemic variability might be an independent risk factor for longer-term vascular complications (11)(12)(13).…”

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confidence: 99%

Comparative Effectiveness of Basal-BolusVersusPremix Analog Insulin on Glycemic Variability and Patient-Centered Outcomes during Insulin Intensification in Type 1 and Type 2 Diabetes: A Randomized, Controlled, Crossover Trial

Testa¹,

Gill

Su³

et al. 2012

The Journal of Clinical Endocrinology & Metabolism

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Context:In patients with diabetes, intraday glucose variability might predict health outcomes independently from glycosylated hemoglobin (HbA 1c ).Objective: Our objective was to evaluate patient satisfaction (PS), quality of life (QoL), glycemic control, and variability during insulin intensification to HbA 1c below 7.0%.Patients, Design, and Setting: Eighty-two type 1 and 306 insulin-treated type 2 diabetes patients (47% male; age 54 Ϯ 11 yr; HbA 1c ϭ 7.8 Ϯ 0.7%) participated in this multicenter, randomized, crossover trial at 52 U.S. centers. Interventions:Interventions included insulin glargine plus premeal glulisine (n ϭ 192) vs. twice-daily premix 75/25 or 70/30 analog insulin (n ϭ 196) for 12 wk and crossed to the alternate arm for 12 wk. Main Outcome Measures:Main outcome measures included PS and QoL questionnaires, 3-d continuous glucose monitoring (CGM), and HbA 1c every 4 -8 wk.Results: Mean Ϯ SE HbA 1c change was Ϫ0.39 Ϯ 0.09% for glargine-glulisine and Ϫ0.05 Ϯ 0.09% for premix (P Ͻ 0.0001). The PS net benefit scale (0 -100) improved from 51.1 to 60.5 Ϯ 1.2 for glargineglulisine and worsened to 45.4 Ϯ 1.2 for premix (P Ͻ 0.0001). The PS regimen acceptance scale was comparable (P ϭ 0.33). Overall QoL favored glargine-glulisine (P Ͻ 0.001), as did perceived health (P Ͻ 0.0001), symptom distress (P Ͻ 0.0001), general health perceptions (P Ͻ 0.01), and psychosocial (P Ͻ 0.02). CGM daily glucose mean, daily glucose SD (glycemic variability), and percent time over 140 mg/dl were lower for glargine-glulisine by 13.1 Ϯ 2.7 mg/dl, 5.9 Ϯ 1.4 mg/dl, and 7.3 Ϯ 1.6%, respectively (all P Ͻ 0.0001), with no difference in CGM percent time below 70 mg/dl (P ϭ 0.09). Symptomatic hypoglycemia rates were comparable. HbA 1c , mean CGM daily glucose, and glycemic variability were independent predictors of PS net benefit. Conclusions:Patient satisfaction was impacted more positively by improved QoL, reduced glucose variability, and better glycemic control with a basal-bolus regimen than negatively by the burden of additional injections, thereby facilitating insulin intensification and the ability to achieve HbA 1c below 7.0%.

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“…Previously, oxidative stress was shown to be a leading factor of the pathogenesis of fetal malformations caused by hyperglycemia [53,54]; further, it increases the rates of spontaneous abortions, recurrent miscarriage, preeclampsia and intrauterine growth restriction [55]. Oxidative stress induced by glycemic variability may be associated with the microvascular and macrovascular complications of DM [56,57].…”

Section: Glycemic Variability Hypoglycemic Risk and Pregnancy Outcomesmentioning

confidence: 99%

Detemir potential applications in the treatment of diabetes during pregnancy: proven benefits and perspectives

et al. 2016

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Glycemic Variability in Type 2 Diabetes Mellitus

Cited by 31 publications

References 115 publications

Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models

Exogenous Ketones Lower Blood Glucose Level in Rested and Exercised Rodent Models

Comparative Effectiveness of Basal-BolusVersusPremix Analog Insulin on Glycemic Variability and Patient-Centered Outcomes during Insulin Intensification in Type 1 and Type 2 Diabetes: A Randomized, Controlled, Crossover Trial

Detemir potential applications in the treatment of diabetes during pregnancy: proven benefits and perspectives

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