Alain Gautier

Markers of Recurrence and Long-Term Morbidity in Craniopharyngioma: A Systematic Analysis of 171 Patients

CONTEXT Craniopharyngiomas are often associated with an unfavorable prognosis, but data on their long-term consequences are sparse. OBJECTIVE The aim of the study was to identify markers of recurrence and factors associated with compromised social rehabilitation and altered quality of life in a large cohort of patients with either childhood-onset (CO) or adult-onset craniopharyngioma. METHODS Retrospective analysis was performed for 171 patients treated for craniopharyngioma in two academic centers in France between 1972 and 2009. For each subject, data were collected concerning clinical presentation, imaging features, visual sequelae, endocrine and metabolic impact, treatment modalities (surgery, radiotherapy), recurrence-free survival rate, and social insertion, as well as answers to the WHO-QOL BREF questionnaire. RESULTS A total of 65 CO and 106 adult-onset patients were reviewed. If CO was diagnosed before the age of 10 yr, this was associated with a higher incidence of obesity, blindness, and panhypopituitarism, and only 40.7% of subjects had adequate work or school attendance compared to 72.4% of patients with later disease onset. Initial symptoms of intracranial hypertension (SIHT), pterional surgery, and multiple surgery were associated with obesity and poorer social insertion. No determinant of quality of life was identified. In the subgroup of patients treated in the 1990s and later, the progression rate was 59.4% in patients with residual tumor on magnetic resonance imaging compared with a 19.8% recurrence rate in the group with apparently complete resection. Recurrence/progression correlates significantly with male gender, early onset (before 10 yr), and SIHT, but only SIHT at presentation remained a significant predictor with multivariate analysis. CONCLUSIONS Craniopharyngioma continues to be associated with severe outcomes. Higher morbidity rates are found in patients with early-onset disease (before 10 yr), initial SIHT, or in whom pterional surgery was required. Markers of recurrence are difficult to identify, with SIHT being the most powerful predictor.

Associations between visceral adipose tissue, inflammation and sex steroid concentrations in men

In men, obesity and the metabolic syndrome are accompanied by decreased testosterone levels, but little is known about the associations between visceral adipose tissue (VAT), VAT‐related inflammation and sex steroids.

Increases in Waist Circumference and Weight As Predictors of Type 2 Diabetes in Individuals With Impaired Fasting Glucose: Influence of Baseline BMI: Data from the DESIR study

OBJECTIVE To evaluate in impaired fasting glucose (IFG) the relative importance of increases in waist circumference and weight on progression to type 2 diabetes. RESEARCH DESIGN AND METHODS The 9-year incidence of diabetes was studied in 979 men and women with baseline IFG, from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort. RESULTS Increases in both waist circumference and weight were significantly associated with diabetes incidence. Standardized odds ratios (95% CI) were 1.79 (1.45–2.21) and 1.86 (1.51–2.30), respectively, after controlling for baseline risk factors. The impact of waist circumference increase was greater for BMI <25 kg/m2 (2.40 [1.63–3.52]) than for BMI ≥25 kg/m2 (1.66 [1.28–2.16]) and persisted after adjusting for concurrent changes in either insulinemia or the homeostasis model assessment of insulin resistance index. Weight change had a similar impact in both BMI groups. CONCLUSIONS In individuals with IFG, it is important to monitor and prevent increases in waist circumference, in particular for those with BMI <25 kg/m2.

Role of sex steroids, intrahepatic fat and liver enzymes in the association between SHBG and metabolic features

SHBG and liver enzymes levels are both associated with the risk of type 2 diabetes. However, the relationship between SHBG with liver enzymes and intrahepatic fat content remain poorly understood.

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

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.

Are the Same Clinical Risk Factors Relevant for Incident Diabetes Defined by Treatment, Fasting Plasma Glucose, and HbA1c?

OBJECTIVE To compare incidences and risk factors for diabetes using seven definitions, with combinations of pharmacological treatment, fasting plasma glucose (FPG) ≥7.0 mmol/L, and HbA1c ≥6.5%. RESEARCH DESIGN AND METHODS Participants aged 30–65 years from the Data from an Epidemiological Study on the Insulin Resistance Syndrome (DESIR) cohort were followed for 9 years. RESULTS More men had incident diabetes as defined by FPG ≥7.0 mmol/L and/or treatment than by HbA1c ≥6.5% and/or treatment: 7.5% (140/1,867) and 5.3% (99/1,874), respectively (P < 0.009); for women incidences were similar: 3.2% (63/1,958) and 3.4% (66/1,954). Known risk factors predicted diabetes for almost all definitions. Among those with incident diabetes by FPG alone versus HbA1c alone, there were more men (78 vs. 35%), case patients were 8 years younger, and fewer were alcohol abstainers (12 vs. 35%) (all P < 0.005). A diabetes risk score discriminated well between those with and without incident diabetes for all definitions. CONCLUSIONS In men, FPG definitions yielded more incident cases of diabetes than HbA1c definitions, in contrast with women. An FPG-derived risk score remained relevant for HbA1c-defined diabetes.

Effects of Genetic Susceptibility for Type 2 Diabetes on the Evolution of Glucose Homeostasis Traits Before and After Diabetes Diagnosis: Data From the D.E.S.I.R. Study

OBJECTIVE To assess the impact of genetic susceptibility on evolution toward type 2 diabetes (T2D) by analyzing time trajectories of fasting glucose, glycated hemoglobin (HbA1c), insulin sensitivity (homeostasis model assessment [HOMA2%S]), and β-cell secretion (HOMA2%B) in a large nondiabetic cohort. We also examined whether baseline HbA1c modified the effect of genetic predisposition on the time trajectories. RESEARCH DESIGN AND METHODS Time trajectories were drawn in 4,744 participants from the French Data from an Epidemiological Study on the Insulin Resistance Syndrome (D.E.S.I.R.) cohort based on samples collected every 3 years over a 9-year follow-up. Trajectories were analyzed according to the TCF7L2 common variant, a family history of T2D, and a combination of at-risk alleles from nine T2D-associated genes. RESULTS There was a marked decrease in HOMA2%B in parallel to a steep increase in HbA1c over the 3 years before incident diabetes, which was not influenced by genetic predisposition when considered alone. However, after the onset of T2D, the TCF7L2 at-risk variant was associated with a greater decrease in HOMA2%B. There was a joint effect of a family history of T2D with the presence of the TCF7L2 risk allele with a greater rise in HbA1c conferred by the coexistence of a family history and the T risk allele. An HbA1c ≥5.7% at baseline was associated with a greater increase in both glycemia and HbA1c levels in the presence of a combination of diabetes at-risk alleles. CONCLUSIONS After incident T2D, TCF7L2 at-risk variants were associated with a faster decrease in β-cell function compared with those with the CC genotype. There was a joint effect of family history of T2D and TCF7L2 risk variant on the rise in glycemia and the decrease in insulin secretion at the end of follow-up, suggesting the joint influence of the combination of diabetes genetic predisposition with familial factors on the evolution of glycemia over time.