P. Buffier

Specifically PNPLA3-Mediated Accumulation of Liver Fat in Obese Patients with Type 2 Diabetes

CONTEXT Recently, it has been shown in the general population that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC), independently of visceral adiposity and insulin resistance. OBJECTIVE In this study, we set out to determine whether LFC, evaluated using (1)H-MR spectroscopy, was associated with PNPLA3 rs738409 polymorphism in people with type 2 diabetes. We also evaluated the influence of this polymorphism on the relationship between LFC and either visceral adiposity or carotid intima media thickness (CIMT). DESIGN, SETTINGS, AND PARTICIPANTS A total of 218 type 2 diabetic patients were included in this study. MAIN OUTCOME MEASURES LFC, area of visceral fat, and CIMT were measured. RESULTS A total of 139 (63.7%) patients had steatosis. The rs738409 minor G allele was associated with LFC. The number of patients with steatosis was significantly higher among minor G allele carriers in comparison to C allele homozygote carriers (70.3 vs. 57.2%; P=0.04) In the subgroup of C allele homozygote carriers, LFC correlated with body mass index (r=0.27; P=0.003) and visceral fat area (r=0.30; P=0.002), but not with CIMT. In the subgroup of minor G allele carriers, LFC correlated inversely with CIMT (r=-0.23; P=0.03), but not with body mass index or with visceral fat area. In multivariate logistic regression, the relationship between the highest quartile of CIMT and steatosis was different according to adiponutrin polymorphism. CONCLUSIONS This study confirms that in people with type 2 diabetes, LFC is related to rs738409 polymorphism. The lack of a relationship with visceral obesity and the inverse correlation with CIMT suggest that fatty liver associated with the minor G allele of the PNPLA3 rs738409 polymorphism may not be linked to metabolic disorders.

Circulating Apelin is increased in patients with type 1 or type 2 diabetes and is associated with better glycaemic control

Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism.

Retinol-Binding Protein 4 Is an Independent Factor Associated With Triglycerides and a Determinant of Very Low-Density Lipoprotein–Apolipoprotein B100 Catabolism in Type 2 Diabetes Mellitus

Objective—Retinol-binding protein 4 (rbp4) is an adipokine secreted by adipocytes and liver, whose levels are elevated in type 2 diabetes mellitus (T2DM). Plasma levels of rbp4 and triglycerides are strongly correlated in T2DM. However, we do not know whether this association is direct or indirect via liver fat content, and the link between rbp4 and triglyceride metabolism remains unknown. Methods and Results—Liver fat measurement by proton spectroscopy was performed in 221 patients with T2DM, and an in vivo kinetic study with stable isotopes was carried out in 14 patients with T2DM. In multivariate analysis, triglycerides were associated positively with rbp4 (&bgr;=0.273, P<0.0001), apolipoprotein (apo) B (&bgr;=0.258, P<0.0001), and liver fat (&bgr;=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (&bgr;=−0.442, P<0.0001). rbp4 was correlated positively with apoB100 very-low-density lipoprotein (VLDL) pool (r=0.62, P=0.017) and negatively with VLDL-apoB100 total fractional catabolic rate (r=−0.66, P=0.001). In multivariate analysis, rbp4 (P=0.015), plasma triglycerides (P=0.024), and sex (P=0.026) were independently associated with VLDL-apoB100 total fractional catabolic rate. Conclusion—In T2DM, plasma rbp4 level is associated with plasma triglycerides, independently of liver fat content. There is a strong independent negative correlation between plasma rbp4 and VLDL-apoB100 total fractional catabolic rate. These data suggest that rbp4 may be involved in the pathophysiology of hypertriglyceridemia in T2DM by reducing VLDL catabolism.

PNPLA3 polymorphism influences liver fibrosis in unselected patients with type 2 diabetes

Context: Recently, it has been shown that an allele in the adiponutrin (PNPLA3) gene was strongly associated with increased liver fat content (LFC) and liver fibrosis independent of visceral adiposity and insulin resistance.

Characteristics of diabetic patients and diabetes care in cardiac rehabilitation

BACKGROUND Although diabetes is associated with a high cardiovascular risk, very little information is available about diabetic patients enrolled in cardiac rehabilitation (CR). AIMS To analyse the characteristics of diabetic patients and diabetes care in CR. METHODS From the database of 700 patients enrolled in CR during a 29-month period, we analysed data from all patients with glucose metabolism disorders (n=105) and 210 matched normoglycaemic patients. RESULTS A total of 105 patients with glucose metabolism disorders (type 1 diabetes, n=5; type 2 diabetes, n=84; impaired fasting glucose, n=16) were enrolled in a CR programme (15% of whole population). Fifteen per cent of patients with type 2 diabetes and all patients with impaired fasting glucose were diagnosed during CR. These 105 patients were older and had a higher body mass index, a larger waist circumference, higher fasting blood glucose and triglyceride concentrations and lower low-density lipoprotein cholesterol concentrations than non-diabetic patients; they also had higher rates of hypertension (P=0.001) and dyslipidaemia (P=0.02). They were more frequently referred to CR for peripheral artery disease (P=0.001), coronary heart disease+peripheral artery disease (P=0.007) and primary prevention (P=0.009). The intervention of a diabetologist was needed for 42.6% of patients because of uncontrolled or newly diagnosed diabetes. CONCLUSION In the present study, we showed that (1) the proportion of patients with diabetes in CR is lower than expected, (2) many glucose metabolism disorders are diagnosed during CR, (3) patients with glucose metabolism disorders show a more severe cardiovascular risk profile than normoglycemic patients, and (4) the intervention of a diabetologist is needed during CR for many patients with diabetes.

Expert opinion on the metabolic complications of new anticancer therapies: Tyrosine kinase inhibitors

Tyrosine kinase inhibitors (TKI) interfere with glucose metabolism. Contrasting effects have been reported, even for a given molecule. Hyperglycemia rates range between 15 and 40%; nilotinib seems to be the molecule most liable to induce diabetes. Metabolic effects range from metabolic syndrome to onset of diabetes, requiring treatment based on insulin resistance, although pathophysiology is unclear. It is noteworthy that fulminant diabetes has never been reported under TKIs. TKIs may lead to hypoglycemia in type 1 or 2 diabetes. Several cases have been reported of improvement in glycemia and in HbA1c, with reduction or even termination of insulin therapy, mainly under imatinib and sunitinib. Fasting glucose levels should be checked before, during and after treatment, plus HbA1C in diabetic patients, with reinforced self-monitoring. These side-effects are transient and never contraindicate continuation of TKIs. Dyslipidemia under TKI has been reported, concerning both LDL-cholesterol and triglycerides. Although variations seem to be slight, lipid assessment is recommended before, during and after treatment.

Endocrine side-effects of new anticancer therapies: Overall monitoring and conclusions

The present final consensus statement of the French Society of Endocrinology lays out the assessments that are to be systematically performed before and during anticancer treatment by immunotherapy, tyrosine kinase inhibitors or mTOR inhibitors, even without onset of any endocrinopathy. It also discusses the CTCAE adverse event grading system in oncology and the difficulty of implementing it for endocrine side-effects of these anticancer treatments. Notably, this is why certain treatment steps applied in other side-effects (e.g., high-dose corticosteroids, contraindications to immunotherapy, etc.) need to be discussed before implementation for endocrine side-effects.

Expert opinion on immunotherapy induced diabetes

Immunotherapy often incurs side-effects, mainly involving the skin, digestive tract and endocrine system. The most frequent endocrine side-effects involve the pituitary and thyroid glands. Cases of insulin-dependent diabetes, whether autoimmune or not (type 1 or 1B) have been reported with PD-1/PD-L1 inhibitors, alone or in association with anti-CTLA-4 antibodies, and were systematically associated with sudden-onset insulinopenia, frequently leading to ketoacidosis or fulminant diabetes, requiring first-line insulin therapy. This adverse effect has not so far been reported with anti-CTLA-4 monotherapy.