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  • Author: Beverley Balkau x
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Free access

Liver iron overload is associated with elevated SHBG concentration and moderate hypogonadotrophic hypogonadism in dysmetabolic men without genetic haemochromatosis

Alain Gautier, Fabrice Lainé, Catherine Massart, Laure Sandret, Xavier Piguel, Pierre Brissot, Beverley Balkau, Yves Deugnier, and Fabrice Bonnet

Aims

To assess the relation between moderate iron overload on sex hormone binding globulin (SHBG) levels and gonadotroph function in men with dysmetabolic iron overload syndrome and the effects of phlebotomy.

Methods

The relationship between magnetic resonance imaging assessed liver iron concentration (LIC) and plasma ferritin levels with total testosterone, bioavailable testosterone (BT), SHBG and LH levels, were studied in 50 men with moderate dysmetabolic iron excess, in the absence of genetic haemochromatosis, who were randomised to phlebotomy therapy or to normal care.

Results

Four patients (8%) had low total testosterone (<10.4 nmol/l) and 13 patients (26%) had low BT (<2.5 nmol/l). In the entire population, those with LIC above the median (90 μmol/l) had a higher mean SHBG (P=0.028), lower LH (P=0.039) than those with LIC below the median. In multivariable analysis (adjusted for age, and fasting insulin) LIC was significantly associated with SHBG (positively) and LH (negatively). Patients in the highest quartile of SHBG had higher LIC (P=0.010) and higher ferritinaemia (P=0.012) than those in the three other quartiles. Iron depletion by venesection did not significantly improve any hormonal levels.

Conclusions

Hypogonadism is not infrequent in men with dysmetabolic iron overload syndrome. Liver iron excess is associated with increased plasma SHBG and moderate hypogonadotrophic hypogonadism. Phlebotomy therapy needs further investigation in symptomatic hypogonadal men with dysmetabolic iron excess.

Free access

Smallness for gestational age interacts with high mobility group A2 gene genetic variation to modulate height

Nabila Bouatia-Naji, Marion Marchand, Christine Cavalcanti-Proença, Samia Daghmoun, Emmanuelle Durand, Jean Tichet, Michel Marre, Beverley Balkau, Philippe Froguel, and Claire Lévy-Marchal

Objective

Height variability is largely under genetic control, although identifying the genetic variants involved has been until recently challenging. Smallness for gestational age (SGA) is a risk factor for adult short stature. Genome-wide association studies have identified a single nucleotide polymorphism (SNP) (rs1042725) in the high mobility group A2 gene (HMGA2) that consistently associates with height variability but its interaction with SGA is unknown.

Design

We assess the contribution of rs1042725 SNP and height variability in a French population and the impact of rs1042725 on SGA status at birth and height at adulthood in SGA individuals.

Methods

We genotyped rs1042725 in 4710 healthy participants from the Data from an Epidemiological Study on the Insulin Resistance syndrome (DESIR) cohort, 743 normal birth weight and 660 SGA individuals from the Haguenau study.

Results

rs1042725 is associated with increased height in the cohort participants (0.36 cm 95% CI (0.12–0.61) per C allele, P=0.004) but not with the SGA status or birth length. Interestingly, rs1042725 had a stronger effect on height in SGA participants (0.94 cm 95% CI (0.24–1.64) per C allele, P=0.009), especially in men (1.45 cm 95% CI (0.44–2.46) per C allele, P=0.005) in whom rs1042725 may explain 3% of height variability. SGA men carrying at least one C allele copy experienced more frequent catch-up in height (P add=0.07; P dom=0.03).

Conclusions

Our study supports further the contribution of HMGA2 rs1042725 to height variability in European populations and shows an increased effect on height in SGA individuals where this variant favors height catch-up.

Free access

Elevated heart rate predicts β cell function in non-diabetic individuals: the RISC cohort

Fabrice Bonnet, Jean-Philippe Empana, Andrea Natali, Lucilla Monti, Alain Golay, Katarina Lalic, Jacqueline Dekker, Andrea Mari, Beverley Balkau, and on behalf of the RISC Study Group

Context

Elevated heart rate has been associated with insulin resistance and incident type 2 diabetes but its relationship with β-cell function is not known. Our aim was to investigate whether baseline heart rate is associated with β-cell function and hyperglycaemia.

Methods

We used the prospective RISC cohort with 1005 non-diabetic individuals who had an oral glucose tolerance test (OGTT) at baseline and after 3 years. Impaired glucose regulation was defined as a fasting plasma glucose ≥6.1 mmol/l or a 2-h plasma glucose ≥7.8 mmol/l. Insulin sensitivity was assessed by the OGIS index and insulin secretion and β-cell glucose sensitivity at both baseline and 3 years.

Results

Baseline heart rate was positively related to both fasting (P<0.0001) and 2 h glucose levels (P=0.02) at year 3 and predicted the presence of impaired glucose regulation at year 3 in a logistic regression model adjusting for insulin sensitivity at inclusion (OR/10 beats per min: 1.31; 95% CI (1.07–1.61); P=0.01). Baseline heart rate was associated with lower insulin sensitivity (β=−0.11; P<.0001), a decrease in both β-cell glucose sensitivity (β=−0.11; P=0.003) and basal insulin secretion rate (β=−0.11; P=0.002) at 3 years in an adjusted multivariable regression model. Baseline heart rate predicted the 3-year decrease in β-cell glucose sensitivity (β=−0.10; P=0.007) and basal insulin secretion (β=−0.12; P=0.007).

Conclusions

Heart rate predicts β-cell function and impaired glucose regulation at 3 years in non-diabetic individuals, independently of the level of insulin sensitivity. These findings suggest a possible effect of the sympathetic nervous system on β-cell dysfunction, which deserves further investigation.

Free access

Mentally tiring work and type 2 diabetes in women: a 22-year follow-up study

Guy Fagherazzi, Gaelle Gusto, Douae El Fatouhi, Francesca Romana Mancini, Beverley Balkau, Marie-Christine Boutron-Ruault, and Fabrice Bonnet

Hypothesis

Previous work suggested no or inconsistent associations between components of work-related stress and type 2 diabetes risk, but suggested sex-specific differences should be further investigated, as women potentially had higher risks.

Methods

We analyzed data from 73 517 women, mostly teachers, from the E3N cohort study followed for 22 years (1992–2014), to study the association between mentally tiring work, used as a proxy of job demands, and type 2 diabetes risk. Univariate and multivariable Cox regression models were used to estimate hazard ratios and 95% confidence intervals.

Results

A total of 4187 incident cases of type 2 diabetes cases were observed. There was a higher type 2 diabetes risk for women with a ‘Very mentally tiring work’ when compared to women with ‘Little or not mentally tiring work’ (HR = 1.21 (1.09–1.35)). This association was independent of unhealthy lifestyle and traditional metabolic factors. An interaction between mentally tiring work and BMI was detected (P < 0.0001), with a stronger association being observed in non-overweight women, HR = 1.26 (1.08–1.47) vs HR = 1.14 (0.98, 1.32), in overweight women.

Conclusions

We observed an increased risk of type 2 diabetes associated with mentally tiring work, used as a proxy of job demands. These observational results suggest the importance of taking into consideration the potential long-term metabolic impact of work-related stress for women working in a demanding environment. Increased support for such women should be investigated in intervention studies.