The Loss of Postprandial Glycemic Control Precedes Stepwise Deterioration of Fasting With Worsening Diabetes

Abstract

OBJECTIVE -The aim of the study was to determine whether the loss of fasting and postprandial glycemic control occurs in parallel or sequentially in the evolution of type 2 diabetes.RESEARCH DESIGN AND METHODS -In 130 type 2 diabetic patients, 24-h glucose profiles were obtained using a continuous glucose monitoring system. The individuals with type 2 diabetes were divided into five groups according to A1C levels: 1 (Ͻ6.5%, n ϭ 30), 2 (6.5-6.9%, n ϭ 17), 3 (7-7.9%, n ϭ 32), 4 (8 -8.9%, n ϭ 25), and 5 (Ն9%, n ϭ 26). The glucose profiles between the groups were compared. The overall glucose concentrations for the diurnal, nocturnal, and morning periods, which represent the postprandial, fasting, and the dawn phenomenon states, respectively, were also compared.RESULTS -Glucose concentrations increased steadily from group 1 to 5 in a stepwise manner. The initial differences in mean glucose concentrations reaching statistical significance occurred 1) between groups 1 and 2 (6.4 vs. 7.7 mmol/l, P ϭ 0.0004) for daytime postprandial periods, followed by differences; 2) between groups 2 and 3 (7.5 vs. 9.3 mmol/l, P ϭ 0.0003) for the morning periods (dawn phenomenon); and finally 3) between groups 3 and 4 (6.3 vs. 8.4 mmol/l, P Ͻ 0.0001) for nocturnal fasting periods.CONCLUSIONS -The deterioration of glucose homeostasis in individuals with type 2 diabetes progressed from postprandial to fasting hyperglycemia following a three-step process. The first step related to the three diurnal postmeal periods considered as a whole, the second step occurred during the morning period, and the third and final step corresponded to sustained hyperglycemia over the nocturnal fasting periods. Such a description of the key stages in the evolution of type 2 diabetes may be of interest for implementing antidiabetes treatment. Diabetes Care 30:263-269, 2007T he steady decline in the quality of glucose homeostasis (1) as observed in type 2 diabetes results from an increasing defect (2) in both insulin sensitivity and secretion (3). The data from the UK Prospective Diabetes Study indicate that the gradual increase in both A1C levels and fasting glucose concentrations is mainly due to a relentless linear deterioration in ␤-cell function from the time of diagnosis. In contrast, the years that precede the development of type 2 diabetes are characterized by a progressive decline in both insulin action and defects in the early phase of the insulin secretion (4,5). Such abnormalities lead to a progressive transition from normal glucose tolerance to impaired glucose tolerance and finally to frank type 2 diabetes. As impaired glucose tolerance is acknowledged as a prediabetic stage, it has been postulated that losses of postprandial glucose control occur before deterioration in fasting glucose concentration (4,6,7). In a previous study (8), we have demonstrated that postprandial glucose increments are predominant contributors to the overall hyperglycemia in patients with an A1C Ͻ7.3%, while fasting increments represent the major contributor to worsenin...

Ideal glycated hemoglobin cut‐off points for screening diabetes and prediabetes in a Chinese population

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Reduction of postprandial glucose by lixisenatide vs sitagliptin treatment in Japanese patients with type 2 diabetes on background insulin glargine: A randomized phase IV study (NEXTAGE Study)

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Longitudinal dynamics of body weight change in the development of type 2 diabetes

“…Monkeys that developed T2DM had shown considerable weight loss over several years before the development of T2DM and well in advance of the increase in FPG to overt T2DM levels (>126 mg/dL). Monnier et al's study on early signs of diabetes using 24-hour glucose monitoring in 130 T2DM patients with variable DM severity concluded that the first sign of diabetes in humans with T2DM was postprandial glycemia (20,21), while the fasting glucose was still below the diagnostic level of overt T2DM (6.3 mmol, 114 mg/dL) (20,21). They thus considered fasting hyperglycemia to be a late indicator (immediately preceding overt DM) of T2DM and prandial induced hyperglycemia leading by several years in the progression to T2DM.…”

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