Glycemic Variability Correlates Strongly With Postprandialβ-Cell Dysfunction in a Segment of Type 2 Diabetic Patients Using Oral Hypoglycemic Agents

Abstract

OBJECTIVEGlucose fluctuations trigger activation of oxidative stress, a main mechanism leading to secondary diabetes complications. We evaluated the relationship between glycemic variability and β-cell dysfunction.RESEARCH DESIGN AND METHODSWe conducted a cross-sectional study in 59 patients with type 2 diabetes (aged 64.2 ± 8.6 years, A1C 6.5 ± 1.0%, and BMI 29.8 ± 3.8 kg/m2[mean ± SD]) using either oral hypoglycemic agents (OHAs) (n = 34) or diet alone (nonusers). As a measure of glycemic variability, the mean amplitude of glycemic excursions (MAGE) was computed from continuous glucose monitoring data recorded over 3 consecutive days. The relationships between MAGE, β-cell function, and clinical parameters were assessed by including postprandial β-cell function (PBCF) and basal β-cell function (BBCF) obtained by a model-based method from plasma C-peptide and plasma glucose during a mixed-meal test as well as homeostasis model assessment of insulin sensitivity, clinical factors, carbohydrate intake, and type of OHA.RESULTSMAGE was nonlinearly correlated with PBCF (r = 0.54, P < 0.001) and with BBCF (r = 0.31, P = 0.025) in OHA users but failed to correlate with these parameters in nonusers (PBCF P = 0.21 and BBCF P = 0.07). The stepwise multiple regression analysis demonstrated that PBCF and OHA combination treatment were independent contributors to MAGE (R2 = 0.50, P < 0.010), whereas insulin sensitivity, carbohydrate intake, and nonglycemic parameters failed to contribute.CONCLUSIONSPBCF appears to be an important target to reduce glucose fluctuations in OHA-treated type 2 diabetes.

Glycemic Variability in Patients With Early Type 2 Diabetes: The Impact of Improvement in β-Cell Function

“…In 42 patients with C-peptide-negative T1DM who received intraportal implantation of cultured islet cell grafts, Gillard et al (18) reported that greater functional b-cell mass of the implant (assessed by glucose clamp) was associated with a reduction in glycemic oscillation, as assessed by the CV of fasting glucose. Moreover, in a study of 59 patients with T2DM who underwent continuous glucose monitoring, postprandial b-cell function (measured by a model-based method during a mixed-meal test) was found to be an independent determinant of glycemic variability on multiple linear regression analyses (17). Similarly, poorer b-cell function on OGTT was associated with increased glycemic variability in participants spanning the spectrum of glucose tolerance from normal to prediabetes to T2DM (19).…”

“…Specifically, cross-sectional studies in both T2DM and T1DM have reported an association between poorer b-cell function and increased glucose variability (17)(18)(19). However, it is not known whether improvement of b-cell function can reduce glycemic variability.…”

Glucose concentrations in blood and tissue - a pilot study on variable time lag

“…Not only hyperglycaemia but also glucose oscilations were considered [25][26][27][28] . Rawlings 29 created a user-friendly Continuous Glucose Monitoring User Interface for Diabetes Evaluation (CGM-GUIDE © ).…”

Lower beta cell function relates to sustained higher glycated albumin to glycated hemoglobin ratio in Japanese patients with type 2 diabetes

“…Recent studies suggest that the effect of treatment strategy on glycemic variability is relatively small [9,10,33,34]. Whether this was due to insufficient control of glycemic variability with current therapy or to other factors affecting GA/HbA1c should be addressed in future prospective studies.…”