Association between subclinical thyroid dysfunction and change in bone mineral density in prospective cohorts.

BACKGROUND: Subclinical hyperthyroidism (SHyper) has been associated with increased risk of hip and other fractures, but the linking mechanisms remain unclear. OBJECTIVE: To investigate the association between subclinical thyroid dysfunction and bone loss. METHODS: Individual participant data analysis was performed after a systematic literature search in MEDLINE/EMBASE (1946-2016). Two reviewers independently screened and selected prospective cohorts providing baseline thyroid status and serial bone mineral density (BMD) measurements. We classified thyroid status as euthyroidism (thyroid-stimulating hormone [TSH] 0.45-4.49 mIU/L), SHyper (TSH < 0.45 mIU/L) and subclinical hypothyroidism (SHypo, TSH ≥ 4.50-19.99 mIU/L) both with normal free thyroxine levels. Our primary outcome was annualized percentage BMD change (%ΔBMD) from serial dual X-ray absorptiometry scans of the femoral neck, total hip and lumbar spine, obtained from multivariable regression in a random-effects two-step approach. RESULTS: Amongst 5458 individuals (median age 72 years, 49.1% women) from six prospective cohorts, 451 (8.3%) had SHypo and 284 (5.2%) had SHyper. During 36 569 person-years of follow-up, those with SHyper had a greater annual bone loss at the femoral neck versus euthyroidism: %ΔBMD = -0.18 (95% CI: -0.34, -0.02; I2 = 0%), with a nonstatistically significant pattern at the total hip: %ΔBMD = -0.14 (95% CI: -0.38, 0.10; I2 = 53%), but not at the lumbar spine: %ΔBMD = 0.03 (95% CI: -0.30, 0.36; I2 = 25%); especially participants with TSH < 0.10 mIU/L showed an increased bone loss in the femoral neck (%Δ BMD = -0.59; [95% CI: -0.99, -0.19]) and total hip region (%ΔBMD = -0.46 [95% CI: -1.05, -0.13]). In contrast, SHypo was not associated with bone loss at any site. CONCLUSION: Amongst adults, SHyper was associated with increased femoral neck bone loss, potentially contributing to the increased fracture risk.

Association of peripheral neuropathy with circulating advanced glycation end products, soluble receptor for advanced glycation end products and other risk factors in patients with type 2 diabetes.

BACKGROUND: The pathogenesis of diabetic peripheral neuropathy remains uncertain and nonenzymatic glycoxidation is one of the contributing mechanisms. The aim of this study was to assess the respective relationship of diabetic peripheral neuropathy with glycoxidation, compared with other identified risk factors, in patients with type 2 diabetes. METHODS: We included 198 patients with type 2 diabetes and high risk for vascular complications. Circulating concentrations of three advanced glycation end products (carboxymethyllysine, methyl-glyoxal-hydroimidazolone-1, pentosidine) and of their soluble receptor (sRAGE) were measured. Peripheral neuropathy was assessed by the neuropathy disability score and by the monofilament test and defined as either an abnormal monofilament test and/or a neuropathy disability score ≥6. Multivariate regression analyses were performed adjusting for potential confounding factors for neuropathy: age, gender, diabetes duration, current smoking, systolic blood pressure, waist circumference, height, peripheral arterial occlusive disease, glycated haemoglobin, estimated glomerular filtration rate and lipid profile. RESULTS: Prevalence of peripheral neuropathy was 20.7%. sRAGE and carboxymethyllysine were independently and positively associated with the presence of peripheral neuropathy. No significant association was found between peripheral neuropathy and methyl-glyoxal-hydroimidazolone-1 or pentosidine. Waist circumference, height and peripheral arterial occlusive disease were independently associated with peripheral neuropathy. CONCLUSIONS: Carboxymethyllysine and sRAGE were independently associated with peripheral neuropathy in patients with type 2 diabetes. Although the conclusions are limited by the absence of a healthy control population, this study confirms the relationship between advanced glycoxidation and diabetic peripheral neuropathy, independently of other risk factors.

Influence of peripheral vascular calcification on efficiency of screening tests for peripheral arterial occlusive disease in diabetes--a cross-sectional study.

AIMS: Pulse palpation and ankle brachial index are recommended to screen for peripheral arterial occlusive disease in people with diabetes. However, vascular calcification can be associated with false negative tests (arteriopathy present despite normal screening tests). We therefore studied the impact of peripheral vascular calcification on the performance of these tests. METHODS: This cross-sectional study included 200 people with diabetes at high risk of cardiovascular disease. The main exclusion factor was an estimated glomerular filtration rate < 30 ml/min. Peripheral arterial occlusive disease was diagnosed by colour duplex ultrasonography and peripheral vascular calcification scored by computed tomography scan. We measured sensitivity, specificity, predictive values, accuracy and likelihood ratios of pulse palpation and ankle brachial index, and looked for the impact of calcification on false negative tests (arteriopathy present despite normal screening tests). RESULTS: Ankle brachial index alone had poor sensitivity and negative predictive value and high negative likelihood ratio. Pulse palpation had higher sensitivity and negative predictive value. An abnormal pulse palpation, defined by weak or missing pulses, combined with an abnormal ankle brachial index, had the highest sensitivity and negative predictive value (92.3 and 89.8%, respectively). Vascular calcification score was higher in patients with false negative tests, for both pulse palpation and ankle brachial index (P < 0.0001 for all). Ankle systolic blood pressure was higher in patients with false negative tests for pulse palpation (P = 0.004). CONCLUSIONS: Below-knee vascular calcification gave a high rate of false negative results for ankle brachial index. Refined pulse palpation combined with ankle brachial index remained the best strategy to screen for peripheral arteriopathy.

Influence of peripheral arterial occlusive disease on the Neuropad(®) test performance in patients with diabetes.

AIMS: The specificity of the Neuropad(®) test to screen for peripheral neuropathy is moderate, but this test has several advantages, such as self-use, educative value and good sensitivity. Use of the Neuropad is usually contra-indicated in the presence of peripheral arterial occlusive disease, a condition associated with skin dryness. The aim of this study was to assess the influence of peripheral arterial occlusive disease on the performance of the Neuropad for screening peripheral neuropathy, and to compare it with the monofilament test. METHODS: We included 200 patients with diabetes. Peripheral neuropathy was defined by a neuropathy disability score ≥ 6. The Neuropad was determined as normal or abnormal at 10 and 20 min, respectively, and its performance was compared in patients with and without peripheral arterial occlusive disease diagnosed by colour duplex ultrasonography. The performances of the Neuropad and of the monofilament test were compared. RESULTS: Prevalences of peripheral neuropathy and of peripheral arterial occlusive disease were 15.8 and 44%, respectively. At 10 min, sensitivity and negative predictive value were high (93.8 and 95.1%), while specificity and positive predictive value were poor (23.2 and 18.9%). The Neuropad performance was not significantly different between patients with and without arteriopathy. Between 10 and 20 min, there was significant loss of sensitivity and gain in specificity. The Neuropad at 10 min was more sensitive but less specific than the monofilament test. CONCLUSIONS: The reliability of the Neuropad is not significantly different in the presence or absence of peripheral arterial occlusive disease.