Klinefelter syndrome, insulin resistance, metabolic syndrome, and diabetes: review of literature and clinical perspectives

Klinefelter syndrome (KS), the most frequent chromosomic abnormality in males, is associated with hypergonadotropic hypogonadism and an increased risk of cardiovascular diseases (CVD). The mechanisms involved in increasing risk of cardiovascular morbidity and mortality are not completely understood. Insulin resistance, metabolic syndrome, and type 2 diabetes are more frequently diagnosed in KS than in the general population; however, the contribution of hypogonadism to metabolic derangement is highly controversial. Whether this dangerous combination of risk factors fully explains the CVD burden of KS patients remains unclear. In addition, testosterone replacement therapy only exerts a marginal action on the CVD system. This review summaries the current understandings of the complex relationship between KS, metabolic syndrome and cardiovascular risk in order to plan future studies and improve current strategies to reduce mortality in this high-risk population. Since fat accumulation and distribution seem to play a relevant role in triggering metabolic abnormalities, an early diagnosis and a tailored intervention strategy with drugs aimed at targeting excessive visceral fat deposition appear necessary in patients with KS

Baseline Characteristics.

<p>NT-proBNP: N-terminal-pro-B-type natriuretic peptide; BNP: Brain natriuretic peptide; HTN: Hypertension; DM: Diabetes mellitus; NYHA: New York Heart Association; LVEF: Left ventricular ejection fraction; ACE-I: Angiotensin converting enzyme inhibitor; ARB: Angiotensin receptor blocker; BB: Beta-blocker; MRA: Mineralocorticoid receptor antagonist; NA: Not available. Data on NYHA class, age, follow-up and LVEF are reported as mean.</p

One study removed analysis for all-cause hospitalization.

<p>Rows represent the results of meta-analysis of all studies except the omitted study named in that row.</p

Odds ratios of all-cause hospitalization.

<p>Solid squares represent odds ratios in trials and have a size proportional to the number of events. The 95% confidence intervals for individual trials are denoted by lines and those for the pooled odd ratios by empty diamonds.</p

One study removed analysis for all-cause mortality.

<p>Rows represent the results of meta-analysis of all studies except the omitted study named in that row.</p

Odds ratios of all-cause mortality.

<p>Solid squares represent odds ratios in trials and have a size proportional to the number of events. The 95% confidence intervals for individual trials are denoted by lines and those for the pooled odd ratios by empty diamonds.</p

Flow chart showing the progress through the stages of the meta-analysis.

<p>Flow chart showing the progress through the stages of the meta-analysis.</p

Odds ratios of heart failure-related hospitalization.

<p>Solid squares represent odds ratios in trials and have a size proportional to the number of events. The 95% confidence intervals for individual trials are denoted by lines and those for the pooled odd ratios by empty diamonds.</p

One study removed analysis for heart failure-related hospitalization.

<p>Rows represent the results of meta-analysis of all studies except the omitted study named in that row.</p

DataSheet_1_Impact of serum leptin and adiponectin levels on brain infarcts in patients with mild cognitive impairment and Alzheimer’s disease: a longitudinal analysis.docx

IntroductionThe adipokines leptin and adiponectin have been associated with atherosclerosis and the risk of cerebral infarcts. Pre-clinical studies, however, suggest a protective role against ischemic brain damage. In this study we analyzed the relationship between serum leptin and adiponectin levels and the onset or progression of brain infarcts in subjects with mild cognitive impairment (MCI) and Alzheimer’s disease (AD).MethodsAll data were extracted from the ADNI database. The final population included 566 subjects, with 58 healthy controls, 396 MCI and 112 AD. All patients with available serum leptin and adiponectin levels at baseline were selected. Demographics, neuropsychological test results, CSF biomarkers, regional brain metabolism with FDG-PET data and the number of brain infarcts on longitudinal MRI scans were extracted.ResultsLeptin levels were significantly lower in patients with MCI than controls at baseline, while adiponectin levels were not different between the groups. Multivariate logistic regression analysis at baseline for the presence of brain infarcts showed a predictive value for leptin but not for adiponectin. Multivariate longitudinal analysis showed that age was the only significant predictor of brain infarcts development at 15-year follow-up, while serum leptin and adiponectin levels did not play a role in this population.DiscussionThe evidence on the pathogenetic or protective role of adipokines on ischemic brain damage is mixed. In this MCI and AD population, serum leptin and adiponectin were not associated with the development of brain infarcts; therefore, these results do not support the use of adipokines as biomarkers of cerebrovascular pathology in this population.</p