Abstract
Objective: To explore the most suitable calculation method for insulin dosage in an insulin tolerance test (ITT) and to evaluate the clinical application value of the optimization coefficient (γ).Methods: In this study, 140 adult patients with congenital growth hormone deficiency (GHD) or acquired hypopituitarism were randomized into the following two groups: the conventional group (n = 70) and the optimized group (n = 70). Oral glucose tolerance tests (OGTTs), insulin release tests (IRTs), and ITTs were conducted. For ITTs, insulin doses were the product of body weight (kg) and related coefficient (0.15 IU/kg for the control group and γ IU/kg for the optimized group, respectively). Notably, γ was defined as −0.034 + 0.000176 × AUCINS + 0.009846 × BMI, which was based on our previous study.Results: In the ITTs, the rate of achieving adequate hypoglycemia with a single insulin dose was significantly higher for the optimized group compared with the conventional group (92.9 vs. 60.0%, P < 0.001). The optimized group required higher initial doses of insulin (0.23 IU/kg). Meanwhile, the two groups did not differ significantly in their nadir blood glucose (1.9 vs. 1.9 mmol/L, P = 0.828).Conclusion: This study confirmed that the proposed optimized calculation method for insulin dosage in ITTs led to more efficient hypoglycemia achievement, without increasing the incidence of serious adverse events.
Highlights
The insulin tolerance test (ITT), which was developed in the late 1960s [1, 2], is widely accepted as the gold standard for the assessment of patients with growth hormone deficiency (GHD) [3]
Patients were included in the study if they were ≥18 and ≤50 years old and displayed the following medical histories: [1] a history of congenital GHD diagnosed during childhood or having clinical signs and symptoms of congenital GHD, [2] a history of hypothalamic-pituitary diseases with the clinical signs and symptoms of GHD, or [3] a history of craniocerebral tumor therapy, wherein patients with sellar or pituitary tumors were beyond 6 months post-surgery
Venous blood samples were collected at rest in the morning after subjects had fasted overnight for measurement of the levels of blood glucose (BG), insulin (INS), glycated hemoglobin (HbA1c), serum insulin-like growth factor-1 (IGF-1), free thyroxine (FT4), testosterone (T), and estradiol (E2)
Summary
The insulin tolerance test (ITT), which was developed in the late 1960s [1, 2], is widely accepted as the gold standard for the assessment of patients with growth hormone deficiency (GHD) [3]. Homeostasis model of assessment for insulin resistance index (HOMA-IR), insulin sensitivity index (ISI), Area under curve of insulin (AUCINS), and area under curve of blood glucose (AUCBG) were calculated (Supplementary Table 1). All these patients had undergone the ITTs for evaluation of pituitary function. In ITTs, the initial dose of insulin did not adequately induce hypoglycemia (blood glucose value below 2.2 mmol/L or below 2.6 mmol/L with a 50% reduction from baseline) in 57.8% (32/56) patients [12]. Multiple stepwise linear regression analysis found that AUCINS and body mass index (BMI) were independent factors that affect the ultimate insulin dosage (Supplementary Table 3).
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