Incretin Effect in Women with Former Gestational Diabetes within a Short Period after Delivery

Background and Aims. Women with former gestational diabetes (fGDM) are characterized by impaired beta-cell function (BC). Incretin hormones contribute to insulin secretion after oral administration of glucose. We aimed to assess the possible role of incretins on altered insulin release in fGDM. Materials and Methods. We studied 104 fGDM women within 6 months after delivery and 35 healthy women after normal pregnancy (CNT) with a 75 g oral (OGTT) and a 0.33 g/kg intravenous (IVGTT) glucose test, both lasting 3 h. The ratio of suprabasal areas under the concentration curves for glucose (dAUCGL) and C-peptide (dAUCCP) evaluated BC during OGTT (BCOG) and IVGTT (BCIV). Incretin effect was computed in all fGDM and in fGDM with normal tolerance (fGDMNGT) and with impaired glucose regulation (fGDMIGR). Results. dAUCGL of fGDM was higher (P < 0.0001) than CNT for both tests; while dAUCCP were not different. BCOG and BCIV were lower in fGDM versus CNT (1.42 ± 0.17nmolCP/mmolGLUC versus 2.53 ± 0.61, P = 0.015 and 0.41 ± 0.03 versus 0.68 ± 0.10, P = 0.0006, respectively). IE in CNT (66 ± 4 %) was not different from that of all fGDM (59 ± 3) and fGDMNGT (60 ± 3), but higher than that of fGDMIGR (52 ± 6; P = 0.03). IE normalized to BMI was 2.77 ± 0.19 % m2/kg in CNT, higher than that of fGDMIGR (1.75 ± 0.21; P = 0.02) and also of fGDMNGT  (2.33 ± 0.11; P = 0.038). Conclusion. Compromised IE characterizes fGDMIGR. In both fGDM categories, regardless their glucose tolerance, IE normalized to BMI was reduced, signifying an intrinsic characteristic of fGDM. Therefore, the diminished IE of fGDM seems to reflect an early abnormality of the general beta-cell dysfunction in the progression toward type 2 diabetes

PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex

“Disclaimer: this is not the definitive version of record of this article. This manuscript has been accepted for publication inEuropean Journal of Endocrinology, but the version presented here has not yet been copy-edited, formatted or proofed. Consequently, Bioscientifica accepts no responsibility for any errors or omissions it may contain. The definitive version is now freely available at https://doi.org/10.1530/EJE-17-0227 2017.

Association of BMI, lipid-lowering medication, and age with prevalence of type 2 diabetes in adults with heterozygous familial hypercholesterolaemia: a worldwide cross-sectional study

Background: Statins are the cornerstone treatment for patients with heterozygous familial hypercholesterolaemia but research suggests it could increase the risk of type 2 diabetes in the general population. A low prevalence of type 2 diabetes was reported in some familial hypercholesterolaemia cohorts, raising the question of whether these patients are protected against type 2 diabetes. Obesity is a well known risk factor for the development of type 2 diabetes. We aimed to investigate the associations of known key determinants of type 2 diabetes with its prevalence in people with heterozygous familial hypercholesterolaemia. Methods: This worldwide cross-sectional study used individual-level data from the EAS FHSC registry and included adults older than 18 years with a clinical or genetic diagnosis of heterozygous familial hypercholesterolaemia who had data available on age, BMI, and diabetes status. Those with known or suspected homozygous familial hypercholesterolaemia and type 1 diabetes were excluded. The main outcome was prevalence of type 2 diabetes overall and by WHO region, and in relation to obesity (BMI ≥30·0 kg/m2) and lipid-lowering medication as predictors. The study population was divided into 12 risk categories based on age (tertiles), obesity, and receiving statins, and the risk of type 2 diabetes was investigated using logistic regression. Findings: Among 46 683 adults with individual-level data in the FHSC registry, 24 784 with heterozygous familial hypercholesterolaemia were included in the analysis from 44 countries. 19 818 (80%) had a genetically confirmed diagnosis of heterozygous familial hypercholesterolaemia. Type 2 diabetes prevalence in the total population was 5·7% (1415 of 24 784), with 4·1% (817 of 19 818) in the genetically diagnosed cohort. Higher prevalence of type 2 diabetes was observed in the Eastern Mediterranean (58 [29·9%] of 194), South-East Asia and Western Pacific (214 [12·0%] of 1785), and the Americas (166 [8·5%] of 1955) than in Europe (excluding the Netherlands; 527 [8·0%] of 6579). Advancing age, a higher BMI category (obesity and overweight), and use of lipid-lowering medication were associated with a higher risk of type 2 diabetes, independent of sex and LDL cholesterol. Among the 12 risk categories, the probability of developing type 2 diabetes was higher in people in the highest risk category (aged 55–98 years, with obesity, and receiving statins; OR 74·42 [95% CI 47·04–117·73]) than in those in the lowest risk category (aged 18–38 years, without obesity, and not receiving statins). Those who did not have obesity, even if they were in the upper age tertile and receiving statins, had lower risk of type 2 diabetes (OR 24·42 [15·57–38·31]). The corresponding results in the genetically diagnosed cohort were OR 65·04 (40·67–104·02) for those with obesity in the highest risk category and OR 20·07 (12·73–31·65) for those without obesity. Interpretation: Adults with heterozygous familial hypercholesterolaemia in most WHO regions have a higher type 2 diabetes prevalence than in Europe. Obesity markedly increases the risk of diabetes associated with age and use of statins in these patients. Our results suggest that heterozygous familial hypercholesterolaemia does not protect against type 2 diabetes, hence managing obesity is essential to reduce type 2 diabetes in this patient population. Funding: Pfizer, Amgen, MSD, Sanofi-Aventis, Daiichi-Sankyo, and Regeneron

Clinical Study Incretin Effect in Women with Former Gestational Diabetes within a Short Period after Delivery

Background and Aims. Women with former gestational diabetes (fGDM) are characterized by impaired beta-cell function (BC). Incretin hormones contribute to insulin secretion after oral administration of glucose. We aimed to assess the possible role of incretins on altered insulin release in fGDM. Materials and Methods. We studied 104 fGDM women within 6 months after delivery and 35 healthy women after normal pregnancy (CNT) with a 75 g oral (OGTT) and a 0.33 g/kg intravenous (IVGTT) glucose test, both lasting 3 h. The ratio of suprabasal areas under the concentration curves for glucose (dAUC GL ) and C-peptide (dAUC CP ) evaluated BC during OGTT (BC OG ) and IVGTT (BC IV ). Incretin effect was computed in all fGDM and in fGDM with normal tolerance (fGDM NGT ) and with impaired glucose regulation (fGDM IGR ). Results. dAUC GL of fGDM was higher (P &lt; 0.0001) than CNT for both tests; while dAUC CP were not different. BC OG and BC IV were lower in fGDM versus CNT (1.42 ± 0.17nmol CP /mmol GLUC versus 2.53 ± 0.61, P = 0.015 and 0.41 ± 0.03 versus 0.68 ± 0.10, P = 0.0006, respectively). IE in CNT (66 ± 4 %) was not different from that of all fGDM (59 ± 3) and fGDM NGT (60 ± 3), but higher than that of fGDM IGR (52 ± 6; P = 0.03). IE normalized to BMI was 2.77 ± 0.19 % m 2 /kg in CNT, higher than that of fGDM IGR (1.75 ± 0.21; P = 0.02) and also of fGDM NGT (2.33 ± 0.11; P = 0.038). Conclusion. Compromised IE characterizes fGDM IGR . In both fGDM categories, regardless their glucose tolerance, IE normalized to BMI was reduced, signifying an intrinsic characteristic of fGDM. Therefore, the diminished IE of fGDM seems to reflect an early abnormality of the general beta-cell dysfunction in the progression toward type 2 diabetes