Analysis of Comorbidities, Clinical Outcomes, and Parathyroidectomy in Adults With Primary Hyperparathyroidism.

Importance: Patients with primary hyperparathyroidism (pHPT) appear to have an increased risk of fractures and other comorbidities, such as cardiovascular disease, although results from previous studies have been inconsistent. Evidence of the association of parathyroidectomy (PTX) with these outcomes is also limited because of the lack of large well-controlled trials. Objective: To investigate whether untreated pHPT was associated with an increased risk of incident fractures and cardiovascular events (CVEs) and whether PTX was associated with a reduced risk of these outcomes. Design, Setting, and Participants: This cohort study included all patients who were diagnosed with pHPT at hospitals in Sweden between July 1, 2006, and December 31, 2017. Each patient was matched with 10 control individuals from the general population by sex, birth year, and county of residence. The patients were followed up until December 31, 2017. Data analyses were performed from October 2021 to April 2022. Main Outcomes and Measures: The primary outcomes were fractures, CVEs, and death. Cumulative incidence of events was estimated using the 1-minus Kaplan-Meier estimator of corresponding survival function. Cox proportional hazards regression models were used to calculate hazard ratios (HRs). Results: A total of 16 374 patients with pHPT were identified (mean [SD] age, 67.5 [12.9] years; 12 806 women [78.2%]), with 163 740 control individuals. The follow-up time was 42 310 person-years for the pHPT group and 803 522 person-years for the control group. Compared with the control group, the pHPT group had a higher risk of any fracture (unadjusted HR, 1.39; 95% CI, 1.31-1.48), hip fracture (unadjusted HR, 1.51; 95% CI, 1.35-1.70), CVEs (unadjusted HR, 1.45; 95% CI, 1.34-1.57), and death (unadjusted HR, 1.72; 95% CI, 1.65-1.80). In a time-dependent Poisson regression model, PTX was associated with a reduced risk of any fracture (HR, 0.83; 95% CI, 0.75-0.93), hip fracture (HR, 0.78; 95% CI, 0.61-0.98), CVEs (HR, 0.84; 95% CI, 0.73-0.97), and death (HR, 0.59; 95% CI, 0.53-0.65). Conclusions and Relevance: Results of this study suggest that pHPT is associated with increased risk of fractures, CVEs, and death, highlighting the importance of identifying patients with this condition to prevent serious unfavorable outcomes. The reduced risk of these outcomes associated with PTX suggests a clinical benefit of surgery.

Type 2 Diabetes and Risk of Hip Fractures and Non-Skeletal Fall Injuries in the Elderly: A Study From the Fractures and Fall Injuries in the Elderly Cohort (FRAILCO).

Questions remain about whether the increased risk of fractures in patients with type 2 diabetes (T2DM) is related mainly to increased risk of falling or to bone-specific properties. The primary aim of this study was to investigate the risk of hip fractures and non-skeletal fall injuries in older men and women with and without T2DM. We included 429,313 individuals (aged 80.8 ± 8.2 years [mean ± SD], 58% women) from the Swedish registry "Senior Alert" and linked the data to several nationwide registers. We identified 79,159 individuals with T2DM (45% with insulin [T2DM-I], 41% with oral antidiabetics [T2DM-O], and 14% with no antidiabetic treatment [T2DM-none]) and 343,603 individuals without diabetes. During a follow-up of approximately 670,000 person-years, we identified in total 36,132 fractures (15,572 hip fractures) and 20,019 non-skeletal fall injuries. In multivariable Cox regression models where the reference group was patients without diabetes and the outcome was hip fracture, T2DM-I was associated with increased risk (adjusted hazard ratio (HR) [95% CI] 1.24 [1.16-1.32]), T2DM-O with unaffected risk (1.03 [0.97-1.11]), and T2DM-none with reduced risk (0.88 [0.79-0.98]). Both the diagnosis of T2DM-I (1.22 [1.16-1.29]) and T2DM-O (1.12 [1.06-1.18]) but not T2DM-none (1.07 [0.98-1.16]) predicted non-skeletal fall injury. The same pattern was found regarding other fractures (any, upper arm, ankle, and major osteoporotic fracture) but not for wrist fracture. Subset analyses revealed that in men, the risk of hip fracture was only increased in those with T2DM-I, but in women, both the diagnosis of T2DM-O and T2DM-I were related to increased hip fracture risk. In conclusion, the risk of fractures differs substantially among patients with T2DM and an increased risk of hip fracture was primarily found in insulin-treated patients, whereas the risk of non-skeletal fall injury was consistently increased in T2DM with any diabetes medication. © 2016 American Society for Bone and Mineral Research.

Type 2 Diabetes Mellitus Is Associated With Better Bone Microarchitecture But Lower Bone Material Strength and Poorer Physical Function in Elderly Women: A Population-Based Study.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of fractures according to several studies. The underlying mechanisms remain unclear, although small case-control studies indicate poor quality of the cortical bone. We have studied a population-based sample of women aged 75 to 80 years in Gothenburg, randomly invited from the population register. Areal bone mineral density (aBMD) was measured by dual-energy X-ray absorptiometry (Hologic Discovery A), bone microarchitecture by high-resolution peripheral quantitative computed tomography (HR-pQCT; ExtremeCT from Scanco Medical AG), and reference point indentation was performed with Osteoprobe (Active Life Scientific). Women with T2DM (n = 99) had higher aBMD compared to controls (n = 954). Ultradistal tibial and radial trabecular bone volume fraction (+11% and +15%, respectively), distal cortical volumetric BMD (+1.6% and +1.7%), cortical area (+11.5% and +9.3%), and failure load (+7.7% and +12.9%) were higher in diabetics than in controls. Cortical porosity was lower (mean ± SD: 1.5% ± 1.1% versus 2.0% ± 1.7%, p = 0.001) in T2DM in the distal radius but not in the ultradistal radius or the tibia. Adjustment for covariates (age, body mass index, glucocorticoid treatment, smoking, physical activity, calcium intake, bone-active drugs) eliminated the differences in aBMD but not in HR-pQCT bone variables. However, bone material strength index (BMSi) by reference point indentation was lower in T2DM (74.6 ± 7.6 versus 78.2 ± 7.5, p < 0.01), also after adjustment, and women with T2DM performed clearly worse in measures of physical function (one leg standing: -26%, 30-s chair-stand test: -7%, timed up and go: +12%, walking speed: +8%; p < 0.05-0.001) compared to controls. In conclusion, we observed a more favorable bone microarchitecture but no difference in adjusted aBMD in elderly women with T2DM in the population compared to nondiabetics. Reduced BMSi and impaired physical function may explain the increased fracture risk in T2DM. © 2016 American Society for Bone and Mineral Research.

Copeptin, insulin-like growth factor binding protein-1 and sitagliptin: A report from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction study.

PURPOSE: To investigate whether sitagliptin affects copeptin and osmolality, suggesting arginine vasopressin activation and a potential for fluid retention, compared with placebo, in patients with a recent acute coronary syndrome and newly discovered type 2 diabetes or impaired glucose tolerance. A second aim was to confirm whether copeptin correlated with insulin-like growth factor binding protein-1. METHODS: Fasting blood samples were used from the BEta-cell function in Glucose abnormalities and Acute Myocardial Infarction trial, in which patients recently hospitalized due to acute coronary syndrome and with newly detected abnormal glucose tolerance were randomized to sitagliptin 100 mg once daily (n = 34) or placebo (n = 37). Copeptin, osmolality and insulin-like growth factor binding protein-1 were analysed at baseline and after 12 weeks. RESULTS: Copeptin and osmolality were unaffected by sitagliptin. There was no correlation between copeptin and insulin-like growth factor binding protein-1. CONCLUSION: Sitagliptin therapy does not appear to be related to activation of the arginine vasopressin system.

[Skin lightening products are a part of everyday life in many parts of the world. Corticosteroids, hydroquinone and mercury are common ingredients]. / Hudblekningsprodukter en del av vardagen i stora delar av världen - Kortikosteroider, hydrokinon och kvicksilver vanliga ingredienser.

During the past decade, attention has been drawn towards the globally increased usage of skin-lightening (bleaching) products which are manufactured and sold, particularly in Africa and Asia, but also via the internet and in local shops all over North America and Europe. The active ingredients include hydroquinone, mercury and potent corticosteroids which can have severe health effects.  After investigating a patient at our clinic where the symptoms and findings could be linked to the use of bleaching products, we started to search the literature for similar cases. We found a global epidemic of health disorders related to skin lightening products. With this article we want to increase the awareness among Swedish physicians of this growing and harmful cosmetic trend.

The predictive value of inflammatory activity and markers of the adipo-insular axis on restenosis in patients with type 2 diabetes.

AIMS: Patients with type 2 diabetes (T2DM) have a high restenosis rate after percutaneous coronary intervention (PCI). This study investigated whether markers of inflammation and the adipo-insular axis associated with T2DM and poor metabolic control were able to predict restenosis after PCI in T2DM patients. METHODS AND RESULTS: The predictive value of traditional and non-traditional risk markers, including IL-1ß, IL-6, TNF-α, hsCRP, interferon gamma, leptin, IGF-I, insulin, proinsulin and NT-proBNP, was investigated in 82 patients with T2DM. A re-angiography 6 months after the index percutaneous coronary intervention (PCI) revealed that 43% of the patients had a restenosis. In a multiple regression analysis, the only independent predictors of restenosis were fasting glucose before the PCI and previous myocardial infarction (odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.92; p = 0.015 and OR 8.00, 95% CI 2.49-25.67; p ≤ 0.001, respectively). None of the other markers remained as significant predictors. CONCLUSION: Fasting glucose prior to the PCI was an independent predictor of restenosis in patients with T2DM while analyses of a variety of markers related to inflammation and the adipo-insular axis did not add any further information.

The impact of infarct type on the reliability of early oral glucose tolerance testing in patients with myocardial infarction.

BACKGROUND: Previously unknown glucose perturbations are common in patients with myocardial infarction (MI). We evaluated the accuracy of an early oral glucose tolerance test OGTT in relation to the extent of the MI. MATERIAL AND METHODS: An OGTT was performed in 134 patients with MI without known diabetes (DM) after 4-5 days (predischarge) and 3 months. The MI was classified as transmural (TMI; n=70) or subendocardial (SEMI; n=102). RESULTS: Predischarge TMI-patients had normal GT, impaired GT or DM in 31%, 33% and 36%. These proportions were 35%, 39% and 26% after 3 months. The corresponding proportions in SEMI-patients were 35%, 35% and 30% and 35%, 40% and 25%. At admission and the first 2 days fasting glucose was higher in TMI than SEMI-patients. CONCLUSION: The outcome of an early OGTT is valid but the test should not be performed earlier than 4-5 days after the event especially in patients with extensive infarctions.

Implications of abnormal glucose metabolism in patients with coronary artery disease.

Abnormal glucose metabolism and type 2 diabetes mellitus (T2DM) are becoming increasingly common. It has been recently confirmed that the period of time prior to the development of diabetes, when patients have impaired glucose tolerance, may also predispose them to increased cardiovascular risk. Therefore prevention and management of T2DM and its antecedents must have high priority when allocating healthcare resources. The present review summarises some information on detection, management and treatment of abnormal glucose metabolism in patients with established coronary artery disease, highlighting the importance of early detection of abnormal glucose metabolism in order to prevent the progression of prediabetes to T2DM and to delay the occurrence of those macrovascular and microvascular complications that impair quality of life and diminish survival.

Early detection and integrated management of dysglycemia in cardiovascular disease: a key factor for decreasing the likelihood of future events.

Dysglycemia is widespread among patients with coronary artery disease. It is indeed more common than normoglycemia in these patients. Coexistence of cardiovascular disease and dysglycemia presents significant health risks, and evidence suggests that both conditions should be treated early to reduce the development of complications. Guidelines recommend testing for prediabetes and type 2 diabetes in the cardiology setting and highlight the use of therapies that treat metabolic and cardiovascular risk factors. Blood glucose levels have previously been the interest of diabetologists, but modern integrated management approaches should include assessment by a cardiologist. We propose that postprandial blood glucose testing be carried out routinely in all patients with coronary artery disease, and that newly diagnosed dysglycemia be actively managed.

Oral glucose tolerance test: a reliable tool for early detection of glucose abnormalities in patients with acute myocardial infarction in clinical practice: a report on repeated oral glucose tolerance tests from the GAMI study.

OBJECTIVE: Previously undetected glucose abnormalities are common in patients with acute myocardial infarction (AMI). We evaluated long-term reliability of early glucometabolic classification of patients with AMI by repeated oral glucose tolerance tests (OGTTs). RESEARCH DESIGN AND METHODS: A glucometabolic OGTT-based classification was obtained in 122 patients by measuring capillary whole-blood glucose. The classification was performed on three occasions, before hospital discharge and 3 and 12 months thereafter. RESULTS: At discharge, 34, 31, and 34% were classified as having normal glucose tolerance, impaired glucose tolerance (IGT), or type 2 diabetes, respectively, and 93% of all patients with type 2 diabetes were still classified with type 2 diabetes (n = 27) or IGT (n = 12) after 12 months. The agreements between the OGTTs at discharge and 3 and 12 months were kappa = 0.35, P < 0.001, and kappa = 0.43, P < 0.001, respectively. CONCLUSIONS: The outcome of an OGTT performed in AMI patients at hospital discharge reliably informs on long-term glucometabolic state.

IGF binding protein 1 predicts cardiovascular morbidity and mortality in patients with acute myocardial infarction and type 2 diabetes.

OBJECTIVE: There are indications that the IGF system is related to both type 2 diabetes and cardiovascular disease (CVD). We tested the hypothesis that low IGF-I and high IGF-binding protein (IGFBP)-1 predict future cardiovascular mortality and morbidity in patients with acute myocardial infarction (AMI) and type 2 diabetes. RESEARCH DESIGN AND METHODS: The Diabetes Mellitus Insulin-Glucose Infusion in Acute Myocardial Infarction (DIGAMI) 2 Trial recruited 1,253 patients with type 2 diabetes and AMI, of whom 575 were enrolled in a biochemical program with repeated blood sampling. Primary and secondary end points included adjudicated cardiovascular mortality and a composite of cardiovascular events (cardiovascular death, reinfarction, or stroke). Multiple Cox proportional hazard regression was used to study the relationship between the end points and the variables. Admission variables were used for the survival analysis and for blood glucose, and A1C updated mean values during follow-up were also available. RESULTS: During a median follow-up period of 2.2 years, 131 (23%) patients died from all-cause mortality and 102 (18%) from CVD, whereas 175 patients (30%) suffered from at least one cardiovascular event. The independent predictors for cardiovascular death in the Cox regression model were (as hazard ratio [HR] [95% CI]): ln updated mean blood glucose (12.2 [5.8-25.7]), age (+5 years) (1.5 [1.4-1.7]), ln IGFBP-1 (1.4 [1.1-1.8]), and ln serum creatinine at admission (2.4 [1.3-4.2]). The model predicting cardiovascular events contained the same variables (ln IGFBP-1 at admission, 1.2 [1.0-1.4]). CONCLUSIONS: High levels of IGFBP-1 at admission are associated with increased risk for cardiovascular mortality and morbidity in type 2 diabetes patients with AMI.