What Is the Best Predictor of Future Type 2 Diabetes?

Abdul‐Ghani, Muhammad; Williams, Ken; DeFronzo, Ralph A.; Stern, Michael P.

doi:10.2337/dc06-1331

Cited by 318 publications

(319 citation statements)

References 27 publications

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“…The OGTT-derived index of beta cell function, the insulinogenic index, computed as the suprabasal serum insulin increment divided by the corresponding plasma glucose increment in the first 30 min (ΔI30/ΔG30) [15,17,18] was calculated. From the OGTT data, the Matsuda index [19] was calculated.…”

Section: Methodsmentioning

confidence: 99%

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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Aims/hypothesis The cholesterol absorption inhibitor ezetimibe has been shown to ameliorate non-alcoholic fatty liver disease (NAFLD) pathology in a single-armed clinical study and in experimental animal models. In this study, we investigated the efficacy of ezetimibe on NAFLD pathology in an open-label randomised controlled clinical trial. Methods We had planned to enrol 80 patients in the trial, as we had estimated that, with this sample size, the study would have 90% power. The study intervention and enrolment were discontinued because of the higher proportion of adverse events (significant elevation in HbA 1c ) in the ezetimibe group than in the control group. Thirty-two patients with NAFLD were enrolled and randomised (allocation by computer program). Ezetimibe (10 mg/day) was given to 17 patients with NAFLD for 6 months. The primary endpoint was change in serum aminotransferase level. Secondary outcomes were change in liver histology (12 control and 16 ezetimibe patients), insulin sensitivity including a hyperinsulinaemic-euglycaemic clamp study (ten control and 13 ezetimibe patients) and hepatic fatty acid composition (six control and nine ezetimibe patients). Hepatic gene expression profiling was completed in 15 patients using an Affymetrix gene chip. Patients and the physician in charge knew to which group the patient had been allocated, but people carrying out measurements or examinations were blinded to group. Results Serum total cholesterol was significantly decreased in the ezetimibe group. The fibrosis stage and ballooning score were also significantly improved with ezetimibe treatment. However, ezetimibe treatment significantly increased HbA 1c and was associated with a significant increase in hepatic longchain fatty acids. Hepatic gene expression analysis showed coordinate downregulation of genes involved in skeletal muscle development and cell adhesion molecules in the ezetimibe treatment group, suggesting a suppression of stellate cell development into myofibroblasts. Genes involved in the L-carnitine pathway were coordinately downregulated by ezetimibe treatment and those in the steroid metabolism pathway upregulated, suggestive of impaired oxidation of long-chain fatty acids. Conclusions/interpretation Ezetimibe improved hepatic fibrosis but increased hepatic long-chain fatty acids and HbA 1c in patients with NAFLD. These findings shed light on previously unrecognised actions of ezetimibe that should be examined further in future studies.

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Section: Methodsmentioning

confidence: 99%

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

et al. 2014

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“…In NAFLD, insulin resistance is universal, but impaired pancreatic beta cell function was also found in non-diabetic patients with NASH [133]. The different tissue insulin sensitivity also needs attention.…”

Section: Implications For Future Researchmentioning

confidence: 99%

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

et al. 2012

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Aims/hypothesis Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum ranging from simple steatosis to non-alcoholic steatohepatitis (NASH): NAFLD causes an increased risk of cardiovascular disease, diabetes and liverrelated complications (the latter confined to NASH). The effect of proposed treatments on liver disease, glucose metabolism and cardiovascular risk in NAFLD is unknown. We reviewed the evidence for the management of liver disease and cardiometabolic risk in NAFLD. Methods Publications through November 2011 were systematically reviewed by two authors. Outcomes evaluated though standard methods were: histological/radiological/biochemical features of NAFLD, variables of glucose metabolism and cardiovascular risk factors. Seventy-eight randomised trials were included (38 in NASH, 40 in NAFLD): 41% assessed post-treatment histology, 71% assessed glucose metabolism and 88% assessed cardiovascular risk factors. Lifestyle intervention, thiazolidinediones, metformin and antioxidants were most extensively evaluated. Results Lifestyle-induced weight loss was safe and improved cardio-metabolic risk profile; a weight loss ≥7% improved histological disease activity, but was achieved by <50%

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“…13,14 Based on epidemiologic data, about 60% of adults with T2D when assessed 5 years prior to diagnosis present either IGT or IGF. 15 During more recent years there has been a lot of interest in identifying even earlier signs of dysglycemia, predictive of future risk of diabetes.…”

Section: Prediabetes and Other Earlier Forms Of Dysglycemiamentioning

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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What Is the Best Predictor of Future Type 2 Diabetes?

Cited by 318 publications

References 27 publications

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

The effects of ezetimibe on non-alcoholic fatty liver disease and glucose metabolism: a randomised controlled trial

Impact of current treatments on liver disease, glucose metabolism and cardiovascular risk in non-alcoholic fatty liver disease (NAFLD): a systematic review and meta-analysis of randomised trials

Complications of Acute and Chronic Hyperglycemia

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