Although osteoarthritis (OA) has been suggested as another component of metabolic syndrome (MetS), weight-independent associations between MetS and knee OA or intensity of arthritic knee pain remain unclear. The objective of the study was to evaluate the above associations and suggest possible mechanisms. This was a cross-sectional study using the fifth Korean National Health and Nutrition Examination Survey (2010). A total of 2363 adults (≥50 y of age) who had completed both laboratory examinations and an evaluation for radiographic knee OA participated in the study. Radiographic knee OA was defined as a Kellgren/Lawrence grade of 2 or greater, and the intensity of arthritic knee pain was assessed using a self-reported numeric rating scale. MetS was diagnosed based on National Cholesterol Education Program-Adult Treatment Panel III criteria, and insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance index. In a multivariable logistic regression analysis, MetS was associated with radiographic knee OA (adjusted odds ratio 1.49; 95% confidence interval 1.23-1.79; P < .001). This association was not changed significantly after further adjusting for homeostasis model assessment-estimated insulin resistance but became nonsignificant after adjusting for weight or body mass index. Age-, sex-, and weight (or body mass index)-adjusted mean score of knee pain was significantly higher in subjects with more components of MetS (P for trend = .010 or .035, respectively). The association between MetS and radiographic knee OA can be largely explained by an excessive weight but not by insulin resistance, a key pathophysiology of MetS. Because accumulation of MetS components appears to be associated with a higher intensity of knee pain, independently of weight, appropriate treatment for MetS may be helpful for subjects with knee pain.

The association between insulin resistance and bone mass is still not clear. The purpose of this study was to evaluate the association between insulin resistance and bone mass. This was a cross-sectional survey of the nationally representative population. A total of 3113 men (aged ≥20 years) from the fourth Korean National Health and Nutrition Examination Survey of 2008-2009 were included. Bone mineral density (BMD) was measured using dual-energy x-ray absorptiometry. Osteopenia and osteoporosis were defined using the World Health Organization T score criteria. Fasting plasma insulin and glucose levels were measured, and insulin resistance was evaluated using the homeostasis model assessment-estimated insulin resistance (HOMA-IR) index. Age-, height-, and weight-adjusted mean BMD values significantly decreased as quartiles of HOMA-IR and the fasting plasma insulin level increased (P for trends <.001). In multivariable logistic regression analyses, participants who had a higher HOMA-IR or fasting plasma insulin level had a higher odds ratio for osteoporosis/osteopenia. Interestingly, the association between fasting plasma insulin level and whole-body BMD differed by the degree of insulin resistance. In the lowest quartile of HOMA-IR, the fasting insulin level was positively associated with BMD. As insulin resistance increased, however, the fasting insulin level was inversely associated with BMD, and this relationship became more significant as the degree of insulin resistance increased. In a nationally representative sample of Korean men, insulin resistance and the fasting plasma insulin level were inversely associated with bone mass. Further studies are required to confirm this association and reveal the underlying mechanisms.

Background: In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results: From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all‐cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD ( P <0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HR _adjusted ], 2.88; 95% CI, 1.52–7.19; P =0.024; group 4: HR _adjusted , 4.00; 95% CI, 1.41–11.35; P =0.009). Conclusions: In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long‐term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4‐fold difference in long‐term cardiovascular events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04485234.