Key result
The diabetes-associated TT genotype at rs7903146 in TCF7L2 was associated with increased disorderliness of fasting insulin pulses compared to the CC genotype (ApEn 1.19 vs 1.10, P=0.03).
Why the study?
Type 2 diabetes has been associated with decreased insulin pulse frequency and amplitude, and it was hypothesized that the TCF7L2 rs7903146 T allele alters these insulin pulse characteristics.
Does the T allele at rs7903146 in TCF7L2 alter pulsatile insulin secretion in nondiabetic subjects?
Observational (n=29)
No
Does the T allele at rs7903146 in TCF7L2 alter pulsatile insulin secretion in nondiabetic subjects?
Diabetes-associated variation in TCF7L2 is associated with decreased orderliness and pulse dispersion of insulin secretion, suggesting ApEn and FDI as potential novel markers of β cell health.
Answers are grounded in this paper and cite their sources.
TCF7L2 rs7903146 variation was associated with altered fasting insulin pulse orderliness in nondiabetics; hypothesis-generating for ApEn/FDI as β-cell markers.
BACKGROUNDMetabolic disorders such as type 2 diabetes have been associated with a decrease in insulin pulse frequency and amplitude. We hypothesized that the T allele at rs7903146 in TCF7L2, previously associated with β cell dysfunction, would be associated with changes in these insulin pulse characteristics.METHODSTwenty-nine nondiabetic subjects (age 46 ± 2, BMI 28 ± 1 kg/m2) participated in this study. Of these, 16 were homozygous for the C allele at rs7903146 and 13 were homozygous for the T allele. Deconvolution of peripheral C-peptide concentrations allowed the reconstruction of portal insulin secretion over time. These data were used for subsequent analyses. Pulse orderliness was assessed by approximate entropy (ApEn), and the dispersion of insulin pulses was measured by a frequency dispersion index (FDI) after a Fast Fourier Transform (FFT) of individual insulin secretion rates.RESULTSDuring fasting conditions, the CC genotype group exhibited decreased pulse disorderliness compared with the TT genotype group (1.10 ± 0.03 vs. 1.19 ± 0.04, P = 0.03). FDI decreased in response to hyperglycemia in the CC genotype group, perhaps reflecting less entrainment of insulin secretion during fasting.CONCLUSIONDiabetes-associated variation in TCF7L2 is associated with decreased orderliness and pulse dispersion, unchanged by hyperglycemia. Quantification of ApEn and FDI could represent novel markers of β cell health.FUNDINGThis work was funded by US NIH (DK78646, DK116231), University of Padova research grant CPDA145405, and Mayo Clinic General Clinical Research Center (UL1 TR000135).
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LAURENTI et al. (2020) conducted an observational in Healthy volunteers (nondiabetic) (n=29). TT genotype at rs7903146 in TCF7L2 vs. CC genotype at rs7903146 in TCF7L2 was evaluated on Fasting insulin pulse disorderliness (Approximate Entropy) (p=0.03). The diabetes-associated TT genotype at rs7903146 in TCF7L2 was associated with increased disorderliness of fasting insulin pulses compared to the CC genotype (ApEn 1.19 vs 1.10, P=0.03).
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