Agnès Räkel

Osteoporosis among patients with type 1 and type 2 diabetes.

Both diabetes and fractures are prevalent in adults. The relationship between diabetes and osteoporosis is complex and, although it has been investigated extensively, the subject remains controversial. While low bone mineral density (BMD) is consistently observed in type 1 diabetes, the relationship is less clear in type 2 diabetes, with some studies reporting modestly increased or unchanged BMD. Both type 1 and type 2 diabetes have been associated with a higher risk of fractures. Despite discrepancies between BMD and fracture rates, clinical trials uniformly support the fact that new bone formation and bone microarchitecture and, thus, bone quality, are altered in both types of diabetes. Although a causal association between diabetes and osteoporosis cannot be established on the basis of existing data, it is possible to conclude from many studies and from a better understanding of the physiopathology of diabetes that it can increase the risk of fractures through skeletal (decreased BMD and bone quality) and extraskeletal (increased risk of falls) factors. Even though osteoporosis screening or prophylactic treatment in all patients with type 1 and type 2 diabetes is not being recommended at present, such patient populations should be given general guidelines regarding calcium and vitamin D intakes, exercise and the avoidance of potential risk factors for osteoporosis. The extent of diagnostic and therapeutic interventions should be based on the individuals risk profile for fractures.

Overproduction of an amino‐terminal form of PTH distinct from human PTH(1–84) in a case of severe primary hyperparathyroidism: influence of medical treatment and surgery

Objective  Rare patients with severe primary hyperparathyroidism present with large parathyroid tumours, severe hypercalcaemia, very high PTH levels and osteitis fibrosa cystica. Some of these patients display a large amount of C‐PTH fragments in circulation and present with a higher C‐PTH/I‐PTH ratio than seen in less severe cases of primary hyperparathyroidism. We wanted to determine how PTH levels and circulating PTH high‐performance liquid chromatography (HPLC) profiles analysed with PTH assays having different epitopes could be affected by medical and surgical treatment in such patients.

New-onset diabetes after transplantation: Risk factors and clinical impact

With improvements in patient and graft survival, increasing attention has been placed on complications that contribute to long-term patient morbidity and mortality. New-onset diabetes after transplantation (NODAT) is a common complication of solid-organ transplantation, and is a strong predictor of graft failure and cardiovascular mortality in the transplant population. Risk factors for NODAT in transplant recipients are similar to those in non-transplant patients, but transplant-specific risk factors such as hepatitis C (HCV) infection, corticosteroids and calcineurin inhibitors play a dominant role in NODAT pathogenesis. Management of NODAT is similar to type 2 diabetes management in the general population. However, adjusting the immunosuppressant regimen to improve glucose tolerance must be weighed against the risk of allograft rejection. Lifestyle modification is currently the strategy with the least risk and the most benefit.

Role of zoledronic acid in the prevention and treatment of osteoporosis

Taken once a year, intravenous zoledronic acid (Zol) (Reclast® or Aclasta®) is a third-generation nitrogen-containing bisphosphonate that is effective compared with placebo in reducing the risk of fractures in patients with postmenopausal osteoporosis and recent low-trauma hip fracture. In glucocorticoid-induced osteoporosis, there is no significant difference between Zol and risedronate for new fractures. Improvements in bone mineral density and early reduction of bone remodeling markers are observed in postmenopausal osteoporosis, recent low-trauma hip fracture, and glucocorticoid-induced osteoporosis. Given that Zol is generally well tolerated and very convenient, it is an interesting therapeutic option for aging patients who take multiple oral drugs, who have adherence or gastrointestinal tolerance issues, and who have an indication for oral bisphosphonates. Zol is not recommended for patients with severe renal impairment. Vitamin D deficiency should be corrected before the administration of Zol.

Does Diabetes Increase the Risk for Fractures After Solid Organ Transplantation? A Nested Case-Control Study

To assess the risk of fractures after a solid organ transplantation among diabetic versus nondiabetic patients, we conducted a nested case‐control study. Pretransplant diabetes was associated with a 2‐fold increase in post‐transplant fractures.

Canadian Diabetes Association Technical Review:The Diabetic Foot and Hyperbaric Oxygen Therapy

RESUME Foot ulcers are a significant source of morbidity, mortality and diminished quality of life for patients with diabetes. Hyperbaric oxygen therapy (HBOT) has been proposed as a possible treatment. In this technical review, the results of clinical trials on the use of HBOT for diabetic foot ulcers are reviewed. Many of the studies examining the role of HBOT in the treatment of diabetic ulcers have been retrospective, nonrandomized and noncontrolled. In addition, most studies have included small patient populations with heterogeneous classes of ulcers. However, results of these studies suggest that HBOT may accelerate wound healing and reduce amputation in a subset of patients with diabetic ulcers. Most patients with Wagner grade 1 and 2 ulcers will heal with carefully administered conventional care (local wound care and efficacious offloading). Appropriate candidates for HBOT are patients with long-standing nonhealing Wagner grade 3 or higher ulcers with an adequately perfused capillary bed in the wound area (best assessed by the transcutaneous oxygen tension [TcPO 2] response to 100% oxygen challenge).

Weight gain after orthotopic liver transplantation: Is nonalcoholic fatty liver disease cirrhosis a risk factor for greater weight gain?

Posttransplant weight gain is common after orthotopic liver transplantation. We sought to determine the extent of weight gain at 5 years after transplantation in patients with nonalcoholic fatty liver disease (NAFLD) cirrhosis versus patients with other types of cirrhosis (non‐NAFLD). We studied 126 liver transplants performed between 2005 and 2007 at Saint Luc Hospital, University of Montreal. Seventeen of the 126 patients (13.5%) had NAFLD cirrhosis. Ascites volume was difficult to assess, so we used the body mass index (BMI) at 3 months as the reference BMI. All patients gained weight after transplantation, but BMI increased significantly more and earlier among the NAFLD patients [4.8 versus 1.5 kg/m2 at 1 year (P = 0.001), 5.0 versus 2.3 kg/m2 at 2 years (P = 0.01), and 5.6 versus 2.6 kg/m2 at 5 years (P = 0.009)] in comparison with non‐NAFLD patients in unadjusted analyses. The greatest BMI increase over time was investigated with univariate and multivariate logistic regression analyses. The BMI increase was divided into tertiles for each period of time observed. The greatest BMI increase over time was defined as the top tertile of BMI increase. After adjustments for potential confounders (ie, total cholesterol, diabetes, and length of hospital stay), NAFLD was no longer associated with a risk of a greater BMI increase [odds ratio (OR) = 3.73 at 1 year (P = 0.11), OR = 2.15 at 2 years (P = 0.34), and OR = 2.87 at 5 years (P = 0.30)]. These findings suggest the need for multidisciplinary, early, and close weight monitoring for all patients. All patients could benefit from pretransplant counseling regarding weight gain and its consequences. Liver Transpl 20:1266‐1274, 2014.

Impact of Resistance Training on Factors Involved in the Development of New-Onset Diabetes After Transplantation in Renal Transplant Recipients: An Open Randomized Pilot Study.

OBJECTIVES New-onsetdiabetes after transplant (NODAT) is a major contributor to cardiovascular disease after transplantation. Kidney transplantation (KT) recipients have low levels of exercise capacity. Resistance training (RT) might be of special benefit in this population because underlying disease and immunosuppressive drugs favour muscle loss and insulin resistance. The aim of this study was to assess the feasibility of implementing an RT program within a population of KT recipients and its impact on the incidence of NODAT and cardiometabolic risk factors. METHODS This pilot study was an open-randomized study. We randomized 24 patients with a 1:1 allocation to 2 parallel groups, the exercise group (E) or the control group (C). The E group was submitted to RT 3 times a week for 16 weeks. Anthropometric, body composition, cardiometabolic risk factors, muscle strength, cardiorespiratory fitness and well-being were measured before and after 16 weeks. RESULTS Of the 24 recruited participants, 20 completed the study (10 in the E group and 10 in the C group). No injuries were reported. The intervention was associated with a significant increase in muscle strength (p=0.003). A significant group effect, in favour of the E group, was detected for the well-being score (p=0.03). However, no changes in body composition, cardiometabolic risk factors or cardiorespiratory fitness were noted for either group after the intervention. CONCLUSIONS This pilot study suggests that RT appears to be secure and feasible and improves strength and well-being in patients after KT. However, it does not improve cardiometabolic risk factors.

Association Between Metformin Adherence and All-Cause Mortality Among New Users of Metformin: A Nested Case-Control Study:

Background: Metformin presents better survival rates than other oral antidiabetics in the treatment of type 2 diabetes. However, these benefits may be dampened by inadequate treatment adherence. Objective: We aimed to investigate the relationship between adherence level to metformin therapy and all-cause mortality over 10 years in incident metformin users. Methods: A nested case-control study was conducted using a large cohort of beneficiaries of the Quebec public drug insurance plan, aged 45 to 85 years, who initiated metformin between 2000 and 2009. Each case of all-cause death during follow-up was matched with up to 10 controls. Adherence to metformin was measured using the medication possession ratio (MPR). Conditional logistic regression models were used to estimate rate ratios (RRs) for mortality between adherent (MPR ≥ 80%) and nonadherent patients (MPR < 80%). Subgroup analyses were conducted according to age (45-64 and 65-85 years) and comedication use (antihypertensive/cardiovascular drugs and statins). Results: The cohort included 82 720 incident metformin users, followed up for 2.4 [0.8-4.4] years (median [interquartile range]) and 4747 cases of all-cause deaths. Analyses revealed decreased mortality risks after long-term adherence to metformin. Specifically, RRs were 0.84 (95% CI = [0.71-0.98]) and 0.69 [0.57-0.85] after 4 to 6 and ≥6 years of adherence to metformin, respectively. Survival benefits of long-term adherence (≥4 years) were also observed across most subgroups and particularly in patients using neither antihypertensive/cardiovascular drugs nor statins (0.57 [0.41-0.77]). Conclusions: Long-term adherence to metformin is associated with decreased risks of all-cause mortality in incident metformin users. Further research should investigate whether survival benefits vary according to the comorbidity burden of patients.

Hypomagnesemia During Teriparatide Treatment in Osteoporosis: Incidence and Determinants: HYPOMAGNESEMIA DURING TERIPARATIDE TREATMENT

In our clinical experience, we have encountered patients who developed hypomagnesemia after the introduction of teriparatide. Some trials have reported hypomagnesemia as an adverse event during teriparatide treatment, but this issue had never been studied specifically. Our objective was twofold: 1) determine the incidence of hypomagnesemia (serum magnesium <0.7 mmol/L) associated with teriparatide in a retrospective cohort and 2) identify the predisposing factors to hypomagnesemia in this cohort. We reviewed the files of 53 patients treated for severe osteoporosis with teriparatide for 6 to 24 months between May 2008 and January 2016. Serum magnesium levels were measured at 0, 3, 6, 12, 18, and 24 months. In the full cohort, we observed an average decrease of serum magnesium of 0.075 mmol/L, 0.069 mmol/L, 0.085 mmol/L, 0.086 mmol/L (p < 0.001) at 3, 6, 12 months, and at the end of the treatment, respectively. The cumulative incidence of hypomagnesemia during treatment with teriparatide was 35.9% (19 patients). Patients’ older age (71.1 versus 65.1 years; p = 0.05) and lower baseline level of magnesium before teriparatide treatment (0.81 mmol/L versus 0.85 mmol/L; p = 0.03) were significant risk factors for teriparatide‐induced hypomagnesemia. The average decrease of serum magnesium was greater in the patients who developed hypomagnesemia compared with normomagnesemic patients at 3 months (0.110 mmol/L versus 0.054 mmol/L; p = 0.02), 6 months (0.139 mmol/L versus 0.036 mmol/L; p < 0.001), and 12 months (0.156 mmol/L versus 0.048 mmol/L; p < 0.001). Serum calcium, creatinine, and parathyroid hormone remained normal throughout the treatment period. We observed a statistically significant decrease in the serum magnesium levels in patients treated with teriparatide for severe osteoporosis. Older age and lower baseline magnesium were significant determinants of hypomagnesemia. Closer monitoring of serum magnesium level should be considered in these patients.