The Heritability of HbA1c and Fasting Blood Glucose in Different Measurement Settings

Abstract

I n an extended twin study we estimated the heritability of fasting HbA1c and blood glucose levels. Blood glucose was assessed in different settings (at home and in the clinic). We tested whether the genetic factors influencing fasting blood glucose levels overlapped with those influencing HbA1c and whether the same genetic factors were expressed across different settings. Fasting blood glucose was measured at home and during two visits to the clinic in 77 healthy families with same-sex twins and siblings, aged 20 to 45 years. HbA1c was measured during the first clinic visit. A 4-variate genetic structural equation model was used that estimated the heritability of each trait and the genetic correlations among traits. Heritability explained 75% of the variance in HbA1c. The heritability of fasting blood glucose was estimated at 66% at home and lower in the clinic (57% and 38%). Fasting blood glucose levels were significantly correlated across settings (0.34 < r < 0.54), mostly due to a common set of genes that explained between 53% and 95% of these correlations. Correlations between HbA1c and fasting blood glucoses were low (0.11 < r < 0.23) and genetic factors influencing HbA1c and fasting glucose were uncorrelated. These results suggest that in healthy adults the genes influencing HbA1c and fasting blood glucose reflect different aspects of the glucose metabolism. As a consequence these two glycemic parameters can not be used interchangeably in diagnostic procedures or in studies attempting to find genes for diabetes. Both contribute unique (genetic) information.

Genetic influences on the insulin response of the beta cell to different secretagogues

“…Design and participants This study used a twin/same-sex sibling design to address the genetic and environmental contribution to the variance of beta cell function in Dutch twin families recruited from the Netherlands Twin Register [24] as described previously [25]. The clamp tests were performed in 125 (58 men) healthy participants, aged 20 to 50 years and of European origin.…”

Is There a Relationship between Mean Blood Glucose and Glycated Hemoglobin?

“…86 Twin and family studies have shown that HbA1c levels are heritable in nondiabetic individuals. 80,91,92 In addition, significant correlation in HbA1c between monozygotic twins both concordant and discordant for type 1 diabetes, 80,93 as well as in siblings with type 1 diabetes, 94,95 suggests that some genetic factors influence HbA1c in individuals with and without diabetes. Studies involving twins showed the substantial contribution of genetic influences to the variance in fasting blood glucose levels as well as in HbA1c levels.…”

Genetic Dominance Influences Blood Biomarker Levels in a Sample of 12,000 Swedish Elderly Twins

“…There was a high level of intra-pair agreement on contact frequency for the 4317 pairs in which both twins responded (rho = 0.81). The average level of contact frequency within the pair was used for (Fenger et al, 2007) e (Goode et al,2007) f (Henneman et al, 2008) g (Isaacs et al, 2007) h (McQueen et al, 2003) i (Snieder et al, 1999) j (Souren et al, 2007) k (VelasquezMelendez et al, 2007) l (Chien et al, 2007) m (Iliadou et al,2005) n (Hokanson et al, 2003) o (Beekman et al, 2002) p (Iliadou et al, 2001) q (Middelberg et al, 2002) r (Santos et al, 2006) s (Snieder et al, 2001) t (Simonis-Bik et al, 2008) u (Berrahmoune et al, 2007) v (Fox et al, 2008) w (Lange et al, 2006) x (Su et al, 2008) y (Wessel et al, 2007) z (Worns et al, 2006) https://www. these pairs.…”