Personality types in individuals with type 1 and type 2 diabetes.

OBJECTIVE: The Type A personality, characterized by impatience, strong career ambition and competitiveness, is associated with greater sensitivity to external stress. Type 1 diabetes (T1D) is an auto-immune disease, which is potentially influenced by stress, unlike type 2 diabetes (T2D). The aim of this study was to assess whether individuals with T1D and T2D exhibited significant differences on the Type A personality scale. We also assessed the personality in patients with thyroid auto-immune diseases to validate potential links between auto-immune disease and Type A. DESIGN AND METHODS: The Bortner questionnaire was used to assess Type A personality in 188 patients with T1D, 430 patients with T2D and 85 patients with auto-immune thyroid disease (Graves' disease or Hashimoto thyroiditis). RESULTS: Type A Bortner scores were significantly higher in T1D patients than in T2D patients (188±34 vs 177±36, p<0.0001). Patients with auto-immune thyroid diseases and T1D patients had similar Type A Bortner scores (189±33 vs 188±34, p=0.860). CONCLUSION: Patients with auto-immune T1D have higher Type A scores than T2D patients. Furthermore, patients with auto-immune thyroid disease also have elevated Type A scores similar to those observed in type 1 diabetes, suggesting that an elevated Type A score in T1D is potentially related to its autoimmune origin. This suggests a possible link between Type A personality and auto-immune diseases via stress-triggering psychobiological pathways. The different personality score between T1D and T2D is an important factor to consider that could influence the diabetes self-care coping strategies and long-term prognosis.

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.

Expert opinion on the metabolic complications of mTOR inhibitors.

Using mTOR inhibitors (mTORi) as anticancer drugs led to hyperglycemia (12-50%) and hyperlipidemia (7-73%) in phase-III trials. These high rates require adapted treatment in cancer patients. Before initiating mTORi treatment, lipid profile screening should be systematic, with fasting glucose assay in non-diabetic patients and HbA1C in diabetic patients. After initiation, lipid profile monitoring should be systematic, with fasting glucose assay in non-diabetic patients, every 2 weeks for the first month and then monthly. The HbA1C target is≤8%, before and after treatment initiation in known diabetic patients and in case of onset of diabetes under mTORi. LDL-cholesterol targets should be adapted to general health status and cardiovascular and oncologic prognosis. If treatment is indicated, pravastatin should be prescribed in first line; atorvastatin and simvastatin are contraindicated. Fenofibrate should be prescribed for hypertriglyceridemia>5g/l resisting dietary measures adapted to oncologic status. In non-controllable hypertriglyceridemia exceeding 10g/l, mTORi treatment should be interrupted and specialist opinion should be sought.

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.

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.

GCKR polymorphism influences liver fat content in patients with type 2 diabetes.

AIMS: It has recently been shown that an allele in the glucokinase regulatory protein (GCKR) gene was associated with increased liver fat content in obese children. In this study, we set out to determine whether GCKR rs1260326 polymorphism was associated with liver fat content in patients with type 2 diabetes. METHODS: Three hundred and eight patients with type 2 diabetes were included in this study. Liver fat content was evaluated using 1H-MR spectroscopy. RESULTS: In our population, carriers of the rs1260326 minor T allele had a higher liver fat content than did carriers of the C allele homozygote (12.4 ± 9.6 vs. 10.3 ± 9.1 %, p = 0.03). The number of patients with steatosis was significantly higher in minor T allele carriers than in C allele homozygote carriers (70.7 vs. 55.4 %; p = 0.008). In multivariate analysis, the predictive variables for steatosis were BMI [odds ratio (OR) 1.08; 95 % confidence interval (CI) 1.03-1.13; p = 0.002], statin therapy (yes) [OR 0.54; 95 % CI 0.31-0.94; p = 0.03], metformin therapy (yes) [OR 2.67; 95 % CI 1.50-4.75; p < 0.001], and rs1260326 GCKR polymorphism (TT+CT) [OR 1.99; 95 % CI 1.14-3.47; p = 0.01]. CONCLUSIONS: This study shows that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fat content was related to GCKR rs1260326 polymorphism independent of BMI, triglyceride levels, and age.

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.

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

CONTEXT: Apelin is an adipokine expressed in several tissues and it appears to be involved in energy metabolism. OBJECTIVE: The aim of this study was to determine serum apelin levels in a large cohort of patients with type 1 and type 2 diabetes and control subjects and to correlate the results with glycaemic control. DESIGN AND PARTICIPANTS: One hundred and thirty patients with type 1 diabetes, 98 patients with type 2 diabetes and 162 controls were enrolled in the study. Apelin levels were measured by enzyme-linked immunosorbent assay. RESULTS: Serum apelin levels were significantly higher in type 1 and type 2 diabetic patients than in controls (P < 0·0001). Serum apelin levels were higher in type 1 than in type 2 diabetic patients (P = 0·02). In multivariate analysis, serum apelin levels were higher in patients with type 1 diabetes and in patients with type 2 diabetes versus controls. We found a negative correlation between glycosylated haemoglobin and serum apelin levels in all diabetic patients (r = -0·17, P = 0·008) and in patients with type 2 diabetes (r = -0·24 P = 0·01). No correlation was found in type 1 diabetic patients. CONCLUSION: Our study showed that apelin concentrations were increased in diabetic patients. This rise, which was greater in type 1 than in type 2 diabetic patients, suggests that obesity is not the main determinant of plasma apelin levels. The negative correlation with glycosylated haemoglobin in patients with type 2 diabetes could indicate that apelin plays a role in glycaemic balance and even insulin sensitivity.

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 (ß=0.273, P<0.0001), apolipoprotein (apo) B (ß=0.258, P<0.0001), and liver fat (ß=0.191, P=0.002) and negatively with high-density lipoprotein cholesterol (ß=-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. CONCLUSIONS: 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. OBJECTIVE: In this study, we set out to determine whether the PNPLA3 rs738409 polymorphism was associated with liver fibrosis in unselected patients with type 2 diabetes. DESIGN, SETTING AND PARTICIPANTS: Two hundred and thirty-four patients with type 2 diabetes were included in this study. MAIN OUTCOME MEASURES: LFC was evaluated using (1) H-MR spectroscopy; fibrosis was measured using the non-invasive FibroTest(®). RESULTS: Advanced liver fibrosis (stage F2 or above) was observed in 10.2% of the patients while 149 (63.6%) patients had steatosis. The prevalence of steatosis and fibrosis was higher in minor G allele carriers than that in C allele homozygote carriers (70.3 vs 57.1%; P=0.04 and 14.7 vs 7.5%; P=0.07 respectively). In multivariate analysis, the predictive variables for advanced liver fibrosis were age (≥60) (P=0.005), sex (female) (P=0.004) and rs 738409 PNPLA3 polymorphism (P=0.01); body mass index (BMI) and LFC were not associated with liver fibrosis. CONCLUSIONS: This study confirms that in patients with type 2 diabetes who were not selected for liver abnormalities, liver fibrosis was related to the rs738409 polymorphism independent of BMI or LFC.

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.