The Shape of the Glucose Response Curve During an Oral Glucose Tolerance Test: Forerunner of Heightened Glycemic Failure Rates and Accelerated Decline in β-Cell Function in TODAY

Abstract

Obese youth without diabetes with monophasic oral glucose tolerance test (OGTT) glucose response curves have lower insulin sensitivity and impaired b-cell function compared with those with biphasic curves. The OGTT glucose response curve has not been studied in youth-onset type 2 diabetes. Here we test the hypothesis that the OGTT glucose response curve at randomization in youth in the TODAY (Treatment Options for Type 2 Diabetes in Adolescents and Youth) study forecasts heightened glycemic failure rates and accelerated decline in b-cell function. RESEARCH DESIGN AND METHODS OGTTs (n = 662) performed at randomization were categorized as monophasic, biphasic, or incessant increase. Demographics, insulin sensitivity (1/fasting insulin), C-peptide index (4C 30 /4G 30), and b-cell function relative to insulin sensitivity (oral disposition index [oDI]) were compared among the three groups. RESULTS At randomization, 21.7% had incessant increase, 68.6% monophasic, and 9.7% biphasic glucose response curves. The incessant increase group had similar insulin sensitivity but significantly lower C-peptide index and lower oDI, despite similar diabetes duration, compared with the other two groups. Glycemic failure rates were higher in the incessant increase group (58.3%) versus the monophasic group (42.3%) versus the biphasic group (39.1%) (P < 0.0001). The 6-month decline in C-peptide index (32.8% vs. 18.1% vs. 13.2%) and oDI (32.2% vs. 11.6% vs. 9.1%) was greatest in incessant increase versus monophasic and biphasic with no difference in insulin sensitivity. CONCLUSIONS In the TODAY study cohort, an incessant increase in the OGTT glucose response curve at randomization reflects reduced b-cell function and foretells increased glycemic failure rates with accelerated deterioration in b-cell function independent of diabetes duration and treatment assignment compared with monophasic and biphasic curves. The shape of the OGTT glucose response curve could be a metabolic biomarker prognosticating the response to therapy in youth with type 2 diabetes.

The shape of the glucose response curve during an oral glucose tolerance test heralds β–cell function in a large Chinese population

“…In studies of nondiabetic individuals, the morphology of the monophasic glucose response curve is the dominant phenotype, up to 57–84% in adults [12, 13, 17, 22, 23] and 35–69% in obese youth at high risk for T2D [6, 7, 9, 10, 24]. Our study showed that about 88.3% of individuals had monophasic response curves and 11.7% had multiphasic response curves.…”

Challenges in the diagnosis of diabetes type in pediatrics

“…Following the immediate period around diagnosis, T1D is characterized by progression to complete insulin deficiency beyond the partial remission, or “honeymoon” period 62 . T2D is defined by insulin resistance, with typically elevated C‐peptide and insulin concentrations in the early stages of the disease 63 and gradual decline of beta cell function over time 62,64 . As mentioned above, patients with T2D may need insulin at diagnosis if they present with DKA or very high HbA1c level.…”

The shape of the glucose response curve during an OGTT heralds β−cell function in a large Chinese population

“…The present investigation revealed the following findings regarding the shape of OGTT curve in a large Chinese population: 1) multiphasic OGTT response curves were not rare in Chinese people, accounting for more than 10% of the population; 2) monophasic curves were more common in older In studies of nondiabetic individuals, the morphology of the monophasic glucose response curve is the dominant phenotype, up to 57-84% in adults [12,13,17,22,23] and 35-69% in obese youth at high risk for T2D [6,7,9,10,24]. Our study showed that about 88.3% of individuals had monophasic response curves and 11.7% had multiphasic response curves.…”