Pericardial- Rather than Intramyocardial Fat Is Independently Associated with Left Ventricular Systolic Heart Function in Metabolically Healthy Humans.

BACKGROUND: Obesity is a major risk factor to develop heart failure, in part due to possible lipotoxic effects of increased intramyocardial (MYCL) and/or local or paracrine effects of pericardial (PERI) lipid accumulation. Recent evidence suggests that MYCL is highly dynamic and might rather be a surrogate marker for disturbed energy metabolism than the underlying cause of cardiac dysfunction. On the other hand, PERI might contribute directly by mechanic and paracrine effects. Therefore, we hypothesized that PERI rather than MYCL is associated with myocardial function. METHODS: To avoid potential confounding of metabolic disease 31 metabolically healthy subjects (age: 29±10yrs; BMI: 23±3kg/m2) were investigated using 1H-magnetic resonance spectroscopy and imaging. MYCL and PERI, as well as systolic and diastolic left ventricular heart function were assessed. Additionally, anthropometric data and parameters of glucose and lipid metabolism were analyzed. Correlation analysis was performed using Pearson's correlation coefficient. Linear regression model was used to show individual effects of PERI and MYCL on myocardial functional parameters. RESULTS: Correlation analysis with parameters of systolic heart function revealed significant associations for PERI (Stroke Volume (SV): R = -0.513 p = 0.001; CardiacIndex (CI): R = -0.442 p = 0.014), but not for MYCL (SV: R = -0.233; p = 0.207; CI: R = -0.130; p = 0.484). No significant correlations were found for E/A ratio as a parameter of diastolic heart function. In multiple regression analysis CI was negatively predicted by PERI, whereas no impact of MYCL was observed in direct comparison. CONCLUSIONS: Cardiac fat depots impact left ventricular heart function in a metabolically healthy population. Direct comparison of different lipid stores revealed that PERI is a more important predictor than MYCL for altered myocardial function.

Short-term hyperinsulinemia and hyperglycemia increase myocardial lipid content in normal subjects.

Increased myocardial lipid content (MYCL) recently has been linked to the development of cardiomyopathy in diabetes. In contrast to steatosis in skeletal muscle and liver, previous investigations could not confirm a link between MYCL and insulin resistance. Thus, we hypothesized that cardiac steatosis might develop against the background of the metabolic environment typical for prediabetes and early type 2 diabetes: combined hyperglycemia and hyperinsulinemia. Therefore, we aimed to prove the principle that acute hyperglycemia (during a 6-h clamp) affects MYCL and function (assessed by (1)H magnetic resonance spectroscopy and imaging) in healthy subjects (female subjects: n = 8, male subjects: n = 10; aged 28 ± 5 years; BMI 22.4 ± 2.6 kg/m(2)). Combined hyperglycemia (202.0 ± 10.6 mg/dL) and hyperinsulinemia (110.6 ± 59.0 µU/mL) were, despite insulin-mediated suppression of free fatty acids, associated with a 34.4% increase in MYCL (baseline: 0.20 ± 0.17%, clamp: 0.26 ± 0.22% of water signal; P = 0.0009), which was positively correlated with the area under the curve of insulin (R = 0.59, P = 0.009) and C-peptide (R = 0.81, P < 0.0001) during the clamp. Furthermore, an increase in ejection fraction (P < 0.0001) and a decrease in end-systolic volume (P = 0.0002) were observed, which also were correlated with hyperinsulinemia. Based on our findings, we conclude that combined hyperglycemia and hyperinsulinemia induce short-term myocardial lipid accumulation and alterations in myocardial function in normal subjects, indicating that these alterations might be directly responsible for cardiac steatosis in metabolic diseases.

Effects of insulin therapy on myocardial lipid content and cardiac geometry in patients with type-2 diabetes mellitus.

AIMS/HYPOTHESIS: Recent evidence suggests a link between myocardial steatosis and diabetic cardiomyopathy. Insulin, as a lipogenic and growth-promoting hormone, might stimulate intramyocardial lipid (MYCL) deposition and hypertrophy. Therefore, the aim of the present study was to investigate the short-term effects of insulin therapy (IT) on myocardial lipid content and morphology in patients with T2DM. METHODS: Eighteen patients with T2DM were recruited (age 56 ± 2 years; HbA1c: 10.5 ± 0.4%). In 10 patients with insufficient glucose control under oral medication IT was initiated due to secondary failure of oral glucose lowering therapy (IT-group), while 8 individuals did not require additional insulin substitution (OT-group). In order to assess MYCL and intrahepatic lipid (IHLC) content as well as cardiac geometry and function magnetic resonance spectroscopy (MRS) and imaging (MRI) examinations were performed at baseline (IT and OT) and 10 days after initiation of IT. Follow up measurements took place 181 ± 49 days after IT. RESULTS: Interestingly, basal MYCLs were 50% lower in IT- compared to OT-group (0.41 ± 0.12 vs. 0.80 ± 0.11% of water signal; p = 0.034). After 10 days of IT, an acute 80%-rise in MYCL (p = 0.008) was observed, while IHLC did not change. Likewise, myocardial mass (+13%; p = 0.004), wall thickness in end-diastole (+13%; p = 0.030) and concentricity, an index of cardiac remodeling, increased (+28%; p = 0.026). In the long-term MYCL returned to baseline, while IHCL significantly decreased (-31%; p = 0.000). No acute changes in systolic left ventricular function were observed. CONCLUSIONS/INTERPRETATION: The initiation of IT in patients with T2DM was followed by an acute rise in MYCL concentration and myocardial mass.

Prevalence of endocrine disorders in morbidly obese patients and the effects of bariatric surgery on endocrine and metabolic parameters.

BACKGROUND: Several endocrine abnormalities, including hypothyroidism and Cushing's syndrome (CS), are considered as causative factors of obesity. The aim of this study was to evaluate the prevalence of endocrine disorders and obesity-associated co-morbidities, as well as the impact of substantial weight loss. METHODS: Screening was performed in 433 consecutive morbidly obese patients (age 41 ± 12 years; BMI 47 ± 6.9 kg/m(2); women 76%). A 1-mg dexamethasone suppression test (1-mg DST) was conducted to exclude CS, and thyrotropin (TSH) was measured to exclude hypothyroidism. Insulin sensitivity was estimated from oral glucose tolerance tests employing the Clamp-like index. Examinations were carried out at baseline, as well as at 6 and 12 months postoperatively. RESULTS: The prevalence of CS was below 0.6%. Before surgery, TSH was elevated compared to an age- and sex-matched normal weight control group (2.4 ± 1.2 vs. 1.5 ± 0.7 µU/ml; p < 0.001). The NCEP criteria of metabolic syndrome (MetS) were fulfilled by 39.5% of the patients. Impaired glucose tolerance and diabetes mellitus were observed in 23.5% and 22.6%, respectively. Seventy-two percent were insulin resistant. During follow-up, weight (BMI 47 ± 6.9 vs. 36 ± 6.4 vs. 32 ± 6.6 kg/m(2); p < 0.001) and TSH decreased significantly (2.4 ± 1.2 vs. 1.8 ± 1.0 vs. 1.8 ± 1.0 µU/ml; p < 0.001). Serum cortisol was higher in the MetS(+)-group compared to the MetS(-)-group (15.0 ± 6.3 vs. 13.5 ± 6.3 µg/dl; p = 0.003). CONCLUSIONS: CS appears to be a rare cause of morbid obesity. Normalization of slightly elevated thyrotropin after weight loss suggests that obesity causes TSH elevation rather than the reverse.