Association between varying cut-points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta-analysis

Gujral, Unjali P.; Jagannathan, Ram; He, Siran; Huang, Minxuan; Staimez, Lisa R.; Wei, Jingkai; Singh, Nanki; Narayan, K M Venkat

doi:10.1136/bmjdrc-2020-001776

Cited by 40 publications

(37 citation statements)

References 19 publications

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“…1 Prediabetes and diabetes represent a glycemic continuum and both are associated with vascular complications as well as a high all-cause mortality rate. 2 The term abnormal glucose tolerance (Abnl-GT) is used when people with prediabetes and diabetes are analyzed together. 3 To address the challenge of Abnl-GT in Africa, more information is needed on both etiology and presentation.…”

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confidence: 99%

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Ishimwe

Wentzel

Shoup

et al. 2021

BMJ Open Diab Res Care

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IntroductionUncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America.Research design and methodsOral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan.ResultsThe prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m2), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm2), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group.ConclusionsBeta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ.Trial registration numberNCT00001853.

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confidence: 99%

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Ishimwe

Wentzel

Shoup

et al. 2021

BMJ Open Diab Res Care

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“…It is well documented that chronic hyperglycemia accelerated the accumulation of advanced glycation end products (AGEs) in many tissues, influencing the occurrence of chronic microvascular and macrovascular complications found in patients with diabetes (2)(3)(4)(5). Even though prediabetes is a condition with hyperglycemia which is lower than the threshold for the diagnosis of diabetes, prediabetes can also lead to similar chronic microvascular and macrovascular complications to those found in individuals with diabetes (6,7). However, there is no evidence to show the association between the accumulation of AGEs and those complications found in prediabetes.…”

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confidence: 99%

Receptors of Advanced Glycation End Product (RAGE) Suppression Associated With a Preserved Osteogenic Differentiation in Patients With Prediabetes

et al. 2022

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Type 2 diabetes is widely documented for osteogenic differentiation defect and impaired bone quality, which is related to the skeletal accumulation of advanced glycation end products (AGEs). Prediabetes is a condition in which hyperglycemia is lower than the threshold for the diagnosis of diabetes. Prediabetic animal models consistently demonstrate impaired osteogenic differentiation and deteriorated bone microarchitecture. However, no evidence shows defects in osteoblast development and skeletal effects of AGEs in prediabetic individuals. Therefore, it remains to be elucidated whether impaired osteogenic differentiation ability and altered cellular response to AGEs occur in patients with prediabetes. This cross-sectional study included 28 patients with prediabetes as defined by impaired fasting glucose criteria, fasting plasma glucose (FPG) between 100–125 mg/dl and 17 age-matched normoglycemic controls to elucidate osteogenic differentiation and AGER expression in the PBMC derived from those individuals. The PBMC-isolated from both groups showed similar rates of expression of osteoblast-specific genes, namely, ALPL, BGLAP, COL1A1, and RUNX2/PPAR (89.3% and 88.2%, p = 1.000), and showed comparable levels of expression of those genes. By using age- and pentosidine-matched normoglycemic individuals as references, the PBMC-isolated from prediabetic patients demonstrated lower expression of both AGER and BAX/BCL2. The expression of AGER and BAX/BCL2 significantly correlated to each other (r = 0.986, p <0.0001). The multivariate analysis demonstrated that serum pentosidine is an independent risk factor for AGER expression. With logistic regression analysis, the area under the ROC curve (AUC) for serum pentosidine at the cut-off level of 2.1 ng/ml and FPG at 100 mg/dl, which is a cut-off point for prediabetes, was significantly higher for predicting AGER expression than that of serum pentosidine alone (0.803 vs 0.688, p = 0.048), indicating that serum pentosidine was a good predictor of AGER expression in prediabetic individuals. In conclusion, this study demonstrated a preserved osteogenic differentiation in the PBMC derived from prediabetic individuals. In addition, those PBMC with preserved osteogenic differentiation potential showed the suppression of both cellular RAGE and apoptotic-related signals. Serum pentosidine was an independent risk factor for cellular RAGE expression and is conceivably a good predictor for AGER suppression in prediabetic individuals.

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“…Included patients were adults (mean ages ranged from 37 to 79 years old), and studies compared outcomes for those with prediabetes versus normoglycemic patients, using the same ADA definitions as the above systematic review. 1 The With atherosclerotic heart disease primary outcomes were all-cause mortality and composite cardiovascular events. The median follow-up time was 8.8 years, and 79 of the trials (N51,737,739) were included in the above systematic review.…”

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confidence: 99%

“…Data from systematic reviews and meta-analyses of prospective cohort studies and post-hoc analysis of clinical trials. 1,2 HbA1c=glycosylated hemoglobin of 5.7–6.4%; HR=hazard ratio (reference number 1); IFG=impaired fasting plasma glucose (100–125 mg/dL); IGT=impaired glucose tolerance (plasma glucose 140–199 mg/dL, measured 2 hours after an oral glucose tolerance test); RR=relative risk (reference number 2).…”

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Does prediabetes increase the risk of all-cause mortality and cardiovascular disease?

Kühn¹,

Egwuatu²,

Shupe³

2022

EBPR

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Prediabetes in the general population and in patients with history of atherosclerotic heart disease is associated with an increase in all-cause mortality when using impaired fasting glucose (100-125 mg/dL) to define prediabetes and is associated with an increase in composite cardiovascular disease when using any of the three American Diabetes Association definitions for prediabetes (SOR: A, systematic reviews with meta-analyses).

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Association between varying cut-points of intermediate hyperglycemia and risk of mortality, cardiovascular events and chronic kidney disease: a systematic review and meta-analysis

Cited by 40 publications

References 19 publications

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

Receptors of Advanced Glycation End Product (RAGE) Suppression Associated With a Preserved Osteogenic Differentiation in Patients With Prediabetes

Does prediabetes increase the risk of all-cause mortality and cardiovascular disease?

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