Cardiac Autonomic Neuropathy in Graves' Disease: Smoking and Age as Predictive Factors.

OBJECTIVES: Hypermetabolic state in Graves' disease (GD) has a great impact on heart homeostasis, acting directly on the heart muscle and modulating the autonomic nervous system. To characterize cardiac autonomic neuropathy (CAN) as a possible complication in patients with GD. METHODS: We evaluated euthyroid GD patients and a control group of healthy euthyroid people. CAN was assessed using autonomic tests of cardiovascular reflex and heart rate variability: respiratory, Valsalva, orthostatic and orthostatic hypotension tests, high frequency, low frequency, and very low-frequency bands. Transthoracic echocardiography was performed in GD patients. RESULTS: Sixty GD patients and 50 people in control group were assessed. CAN was diagnosed in 20% of GD and 14% in the control group. Among GD, 13.3% presented incipient, and 6.7% established CAN, while in the control group, it was verified incipient in 8% and established in 6% (P = .7479). All GD patients with CAN presented an alteration in the deep breathing test. Age and smoking were evidenced as factors associated with the presence of CAN, while higher TRAb values at diagnosis decreased the chance of CAN. CONCLUSIONS: The prevalence of CAN in euthyroid GD patients was 20%. Changes in the cardiac autonomic nervous system were identified, pointing to the importance of evaluating this complication in these patients. Smoking was a predictive factor for CAN, increasing its relationship with conditions that aggravate GD.

Childhood-Onset GH Deficiency versus Adult-Onset GH Deficiency: Relevant Differences Regarding Insulin Sensitivity.

The results of the studies on the pattern of insulin sensitivity (IS) are contradictory in patients with GH deficiency (GHD); however, the interference of the GHD onset stage, childhood or adulthood in the IS has not been assessed by euglycemic hyperinsulinemic clamp (EHC), a gold-standard method for the assessment of insulin sensitivity. In a prospective cross-sectional study, we assessed IS and body composition in 17 adults with hypopituitarism without GH replacement, ten with childhood-onset (COGHD) and seven with adulthood-onset (AOGHD) and compared them to paired control groups. COGHD presented higher IS (p = 0.0395) and a similar percentage of fat mass (PFM) to AOGHD. COGHD showed higher IS than the control group (0.0235), despite a higher PFM (0.0022). No differences were found between AODGH and the control group. In AOGHD and the control group, IS was negatively correlated with PFM (rs: −0.8214, p = 0.0234 and rs: −0.3639, p < 0.0344), while this correlation was not observed with COGHD (rs: −0.1152, p = 0.7514). Despite the higher PFM, patients with COGHD were more sensitive to insulin than paired healthy individuals, while patients with AOGHD showed similar IS compared to controls. The lack of GH early in life could modify the metabolic characteristics of tissues related to the glucose metabolism, inducing beneficial effects on IS that persist into adulthood. Thus, the glycometabolic findings in patients with COGHD seems to be not applicable to AOGHD.

Higher systemic inflammatory status and cardiovascular risk associated with Charcot arthropathy unrelated to infection or extremity amputation.

Purpose: People with diabetes and Charcot arthropathy have higher mortality than people with diabetes without this complication. Are the causes of this higher mortality exclusively infectious or of a cardiovascular origin? We aimed to study aspects related to cardiovascular risk and inflammation in a population of people with type 2 diabetes with and without Charcot arthropathy. Methods: A cross-sectional study was performed in people with diabetes and Charcot Eickenholtz III arthropathy, matched for sex and age, with two groups of people with diabetes without Charcot arthropathy with and without peripheral sensory-motor neuropathy, in the absence of active infection. All participants underwent clinical and laboratory evaluation at the time of the interview, and their cardiovascular risk was calculated according to the United Kingdom Prospective Diabetes Study (UKPDS) calculator. Results: We evaluated 69 people with type 2 diabetes (21 with Charcot arthropathy, 24 with diabetic peripheral neuropathy and 24 without this neuropathy), with a mean age between 57 and 61 years and with a diabetes duration of more than 10 years. Patients with Charcot arthropathy had a longer duration of diabetes; more frequency of dyslipidemia; and higher levels of uric acid, microalbuminuria and C-reactive protein than the other two groups. A total of 73.9% of the people evaluated had high or very high cardiovascular risk according to the UKPDS score. Conclusion: The people with type 2 diabetes presenting Charcot arthropathy had greater values of systemic inflammatory parameters, even in the chronic phase of the complication, with a higher risk of mortality unrelated to infections.

Cardiovascular Autonomic Reflex Tests and 7 Heart Rate Variability Indices for Early Diagnosis of Cardiovascular Autonomic Neuropathy in Type 2 Diabetes Individuals.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a common complication of type 2 Diabetes mellitus (T2D), and prevalence varies according to the methodology used. CAN should be diagnosed in the subclinical stage when an intensive treatment of T2D could avoid the progression to irreversible phases. OBJECTIVE: Determine the prevalence of early involvement (EI) of CAN in T2D individuals comparing two methodologies. METHODS: This was a cross-sectional study that included 183 T2D individuals who were monitored in a Tertiary centre. The diagnosis of CAN was based on the results of four cardiovascular autonomic reflex tests (CARTs: expiration-inspiration index, Valsalva maneuver, orthostatic test, and changes in blood pressure after standing) and of seven heart rate variability (7HRV) indices (CARTs plus the spectral analysis). The findings were validated in an independent cohort comprised of 562 T2D individuals followed in a Primary care setting. RESULTS: With the use of 7HRV, 30.6% and 77.8% of individuals in the Tertiary and in the Primary centers, respectively, were classified as without CAN; 25.1% and 15.3% as EI and 44.3% and 6.9% as definitive CAN, respectively. The use of CARTs decreased the proportion of individuals without CAN in both centers (7.1% and 47%) and increased the frequency of EI (30.6% and 36.6%) and definitive CAN (62.3% and 16.4%), respectively. The concordance between both evaluated methodologies was weak. CONCLUSION: Higher proportions of T2D individuals were diagnosed with EI and with definitive CAN with the use of CARTs.

Ocular Manifestations and Neuropathy in Type 2 Diabetes Patients With Charcot Arthropathy.

Objective: Diabetes can affect the eye in many ways beyond retinopathy. This study sought to evaluate ocular disease and determine any associations with peripheral neuropathy (PN) or cardiac autonomic neuropathy (CAN) in type 2 diabetes (T2D) and Charcot arthropathy (CA) patients. Design: A total of 60 participants were included, 16 of whom were individuals with T2D/CA, 21 of whom were individuals with T2D who did not have CA, and 23 of whom were healthy controls. Ocular surface evaluations were performed, and cases of dry eye disease (DED) were determined using the Ocular Surface Disease Index (OSDI) questionnaire, ocular surface staining, Schirmer test, and Oculus Keratograph 5M exams. All variables were used to classify DED and ocular surface disorders such as aqueous deficiency, lipid deficiency, inflammation, and ocular surface damage. Pupillary and retinal nerve fiber measurements were added to the protocol in order to broaden the scope of the neurosensory ocular evaluation. PN and CAN were ascertained by clinical examinations involving the Neuropathy Disability Score (for PN) and Ewing's battery (for CAN). Results: Most ocular variables evaluated herein differed significantly between T2D patients and controls. When the controls were respectively compared to patients with T2D and to patients with both T2D and CA, they differed substantially in terms of visual acuity (0.92 ± 0.11, 0.73 ± 0.27, and 0.47 ± 0.26, p=0.001), retinal nerve fiber layer thickness (96.83 ± 6.91, 89.25 ± 10.44, and 80.37 ± 11.67 µm, p=0.03), pupillometry results (4.10 ± 0.61, 3.48 ± 0.88, and 2.75 ± 0.81 mm, p=0.0001), and dry eye symptoms (9.19 ± 11.71, 19.83 ± 19.08, and 24.82 ± 24.40, p=0.03). DED and ocular surface damage also differed between individuals with and without CA, and were associated with PN and CAN. Conclusion: CA was found to be significantly associated with the severity of ocular findings. DED in cases of CA was also associated with PN and CAN. These findings suggest that intrinsic and complex neurosensory impairment in the eyes, peripheral sensory nerves, and the autonomic nervous system are somehow connected. Thus, a thorough ocular evaluation may be useful to highlight neurological complications and the impact of diabetes on ocular and systemic functions and structures.

Insulin Sensitivity Is Not Decreased in Adult Patients With Hypopituitarism Without Growth Hormone Replacement.

Decreased insulin sensitivity in patients with hypopituitarism without GH replacement (pHP-WGHR) remains conflicting in literature. It is known that these patients present a decrease in free fat mass and an increase in fat mass. Typically, these kinds of alterations in body composition are associated with a decrease in insulin sensitivity; however, there is no consensus if this association is found in pHP-WGHR. Thus, we investigated pHP-WGHR regarding insulin sensitivity by euglycemic hyperinsulinemic clamp, the gold standard method, and body composition. In a cross-sectional study, we evaluated 15 pHP-WGHR followed up in a Service of Neuroendocrinology and 15 individuals with normal pituitary function as a control group with similar age, gender and body mass index. Insulin sensitivity was evaluated by euglycemic hyperinsulinemic clamp and homeostatic model assessment insulin resistance (HOMA-IR). Kappa coefficient evaluated the agreement between these two methods. Percentage of fat mass, percentage of free fat mass, fat mass weight and free fat mass weight were assessed by electrical bioimpedance. The pHP-WGHR presented similar insulin sensitivity to control group by euglycemic hyperinsulinemic clamp, both by the M-value, (p = 0.0913) and by the area under the glucose infusion rate curve, (p = 0.0628). These patients showed lower levels of fasting glycemia (p = 0.0128), insulin (p = 0.0007), HOMA-IR (p = 0.009). HOMA-IR shows poor concordance with euglycemic hyperinsulinemic clamp (Kappa = 0.16) in pHP-WGHR, while in the control group the agreement was good (Kappa = 0.53). The pHP-WGHR presented higher values of percentage of fat mass (p = 0.0381) and lower values of percentage of free fat mass (p = 0.0464) and free fat mass weight (0.0421) than the control group. This study demonstrated that the insulin sensitivity evaluated by euglycemic hyperinsulinemic clamp in pHP-WGHR was similar to individuals with normal pituitary function, despite the pHP-WGHR presenting higher fat mass percentage. HOMA-IR was not a good method for assessing insulin sensitivity in pHP-WGHR.