Letter to the Editor: One-Hour Postload Hyperglycemia is a Stronger Predictor of Type 2 Diabetes than Impaired Fasting Glucose

We read with interest the paper by Fiorentino et al (1), the outcomes of which highlight the hitherto relatively unappreciated relevance of the 60-minute plasma glucose value during an oral glucose tolerance test (OGTT) in predicting the subsequent progression to type 2 diabetes (2). This study indicates that plasma glucose greater than 8.6 mmol/L at 60 minutes (NGT-1h-high) is a stronger predictor than isolated impaired fasting glucose, possibly reflecting impairments in both insulin sensitivity and early insulin secretion. The authors do not comment specifically about the 30-minute plasma glucose levels during the OGTT (shown in Figure 1 and Table 1 of the report), which are of interest because they were substantially less in the NGT-1h-low than the other three groups (NGT-1h-high, isolated impaired fasting glucose, and impaired glucose tolerance), among which the levels were comparable.

Whereas there are numerous determinants of glycemia during an OGTT, including preprandial plasma glucose, secretion of insulin, glucagon, and incretins (glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1), small intestinal glucose absorption, and hepatic and peripheral glucose metabolism (3), studies conducted by us (4, 5) and others (6, 7) have established that the rate of gastric emptying plays a major role, particularly in determining the early glycemic response. Gastric emptying (GE) exhibits wide interindividual variability (∼1–4 kcal/min in health and greater in type 2 diabetes because some patients have delayed, and others have accelerated GE) but relatively low intraindividual variability (3). Moreover, relatively minor variations in gastric emptying can apparently impact glycemia substantially (8). Accordingly, it would have been of interest to know whether GE, which can be quantified noninvasively (8), differed between the normal glucose tolerance groups and contributed to differences in glycemia at 30 and 60 minutes. There is increasing evidence that relatively more rapid GE predisposes to the development of type 2 diabetes, as suggested many years ago (9), and we would speculate that in the NGT-1h-high group, the rate of GE was faster than in the NGT-1h-low group (5).

The oral disposition index (DI), calculated as the composite of the estimated insulin secretory response and insulin sensitivity, has emerged as a useful predictor of type 2 diabetes (10). In normal glucose tolerance, the relationship of insulin secretion with insulin sensitivity is hyperbolic, such that the product (ie, DI) is constant (10). In the study by Fiorentino et al (1), the DI was measured by calculating insulin secretion and sensitivity from two different experiments, ie, insulin secretory response derived from the OGTT and insulin sensitivity from an insulin clamp. Ideally, the DI should have been calculated from one experimental model, in this case the OGTT. Utzschneider et al (11) also advise that a hyperbolic relationship between the insulin secretory response (Δinsulin_30–0/Δglucose_30–0) and insulin resistance (1/fasting insulin) in the study population should be established prior to calculation of the DI. Fiorentino et al (1) suggest that the DI is less in the NGT-1h-high group, which is not surprising because both fasting and 30-minute insulin values during the OGTT are comparable, but the 30-minute glucose is predictably greater.

In conclusion, the study by Fiorentino et al (1) attests to the importance of the 1-hour glucose value during an OGTT as a predictor of type 2 diabetes and its superiority over more traditional measures of glucose tolerances. The determinants of a higher 60-minute glucose level, however, warrant additional exploration, and we believe that GE should be measured in prospective studies relating to diabetes progression.

Disclosure Summary: Authors have nothing to disclose.

Acknowledgments

Author contributions included the following: C.S.M., C.K.R., K.L.J., and M.H. contributed to the discussions relating to the content of the manuscript and were involved in writing it.

This work was supported by a National Health and Medical Research Council grant. K.L.J. is supported by a National Health and Medical Research Council Senior Career Development Award Grant 627011.

Abbreviations

 
• DI

  disposition index

 
• GE

  gastric emptying

 
• NGT-1h-high

  plasma glucose greater than 8.6 mmol/L at 60 minutes

 
• OGTT

  oral glucose tolerance test.

References