Prevalence of the Metabolic Syndrome in Latin America and its association with sub-clinical carotid atherosclerosis: the CARMELA cross sectional study

Background

Poor control of type 2 diabetes results in substantial long-term consequences. Studies of new diabetes treatments are rarely designed to assess mortality, complication rates and costs. We sought to estimate the long-term consequences of liraglutide and rosiglitazone both added to glimepiride.

Methods

To estimate long-term clinical and economic consequences, we used the CORE diabetes model, a validated cohort model that uses epidemiologic data from long-term clinical trials to simulate morbidity, mortality and costs of diabetes. Clinical data were extracted from the LEAD-1 trial evaluating two doses (1.2 mg and 1.8 mg) of a once daily GLP-1 analog liraglutide, or rosiglitazone 4 mg, on a background of glimepiride in type 2 diabetes. CORE was calibrated to the LEAD-1 baseline patient characteristics. Survival, cumulative incidence of cardiovascular, ocular and renal events and healthcare costs were estimated over three periods: 10, 20 and 30 years.

Results

In a hypothetical cohort of 5000 patients per treatment followed for 30 years, liraglutide 1.2 mg and 1.8 mg had higher survival rates compared to the group treated with rosiglitazone (15.0% and 16.0% vs. 12.6% after 30 years), and fewer cardiovascular, renal, and ocular events. Cardiovascular death rates after 30 years were 69.7%, 68.4% and 72.5%, for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively. First and recurrent amputations were lower in the rosiglitazone group, probably due to a 'survival paradox' in the liraglutide arms (number of events: 565, 529, and 507, respectively). Overall cumulative costs per patient, were lower in both liraglutide groups compared to rosiglitazone (US$38,963, $39,239, and $40,401 for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively), mainly driven by the costs of cardiovascular events in all groups.

Conclusion

Using data from LEAD-1 and epidemiologic evidence from the CORE diabetes model, projected rates of mortality, diabetes complications and healthcare costs over the long term favor liraglutide plus glimepiride over rosiglitazone plus glimepiride.

Trial registration

LEAD-1 NCT00318422; LEAD-2 NCT00318461; LEAD-3 NCT 00294723; LEAD-4 NCT00333151; LEAD-5 NCT00331851; LEAD-6 NCT00518882.     

Effects of Long-Term Alendronate Treatment on a Large Sample of Pediatric Patients with Osteogenesis Imperfecta

Objective: Osteogenesis imperfecta (OI) is a group of inherited diseases characterized by reduced bone mass, recurrent bone fractures, and progressive bone deformities. Here, we evaluate the efficacy and safety of long-term treatment with alendronate in a large sample of Chinese children and adolescents with OI.Methods: In this prospective study, a total of 91 children and adolescents with OI were included. The patients received 3 years' treatment with 70 mg alendronate weekly and 500 mg calcium daily. During the treatment, fracture incidence, bone mineral density (BMD), and serum levels of the bone turnover biomarkers (alkaline phosphatase [ALP] and cross-linked C-telopeptide of type I collagen [β-CTX]) were evaluated. Linear growth speed and parameters of safety were also measured.Results: After 3 years of treatment, the mean annual fracture incidence decreased from 1.2 ± 0.8 to 0.2 ± 0.3 (P<.01). BMD at the lumbar spine and femoral neck significantly increased by 74.6% and 39.5%, with their BMD Z-score increasing from -3.0 to 0.1 and from -4.2 to -1.3, respectively (both P<.01 vs. baseline). In addition, serum ALP and β-CTX levels decreased by 35.6% and 44.3%, respectively (both P<.05 vs. baseline). Height significantly increased, but without an obvious increase in its Z-score. Patient tolerance of alendronate was good.Conclusion: Three years' treatment with alendronate was demonstrated for the first time to significantly reduce fracture incidence, increase lumbar spine and femoral neck BMD, and decrease bone turnover biomarkers in Chinese children and adolescents with OI.Abbreviations:ALP = alkaline phosphataseβ-CTX = cross-linked C-telopeptide of type I collagenBMD = bone mineral densityBP = bisphosphonateDXA = dual-energy X-ray absorptiometry25OHD = 25-hydroxyvitamin DOI = osteogenesis imperfectaPTH = parathyroid hormone     

The Associations Between Hypovitaminosis D,Higher Pth Levels With Bone Mineral Densities,And Risk Of The 10-Year Probability Of Major Osteoporotic Fractures In Chinese Patients With T2Dm

Objective: In the current study, we investigated the vitamin D status, and its relationships with parathyroid hormone (PTH) levels, bone mineral density (BMD), and the 10-year probability of fractures in Chinese patients with type 2 diabetes mellitus (T2DM).Methods: This was a cross-sectional study of 785 patients. BMDs at the lumbar spine (L2-4), femoral neck (FN), and total hip (TH) were measured by dual-energy X-ray absorptiometry (DXA). Serum levels of 25-hydroxyvitamin D (25(OH)D) and intact PTH were also quantified. The 10-year probability of fracture risk (major osteoporotic fracture &lsqb;MOF] and hip fracture &lsqb;HF]) was assessed using the fracture risk assessment tool (FRAX).Results: The prevalence of vitamin D deficiency was 82.3%, and the mean 25(OH)D level was 36.9 ± 15.2 nmol/L. The adequate group had higher BMDs at the FN and TH and lower MOF risk than the inadequate groups. Lower 25(OH)D was associated with higher PTH (r = -0.126, P<.001). PTH was negatively correlated with BMDs at 3 sites and positively correlated with MOF and HF, but this relationship disappeared in the adequate subgroup. Multivariate stepwise regression analysis revealed that PTH was the determinant of MOF (standard β = 0.073, P = .010) and HF (standard β = 0.094, P = .004).Conclusion: Our results identified a significantly high rate of vitamin D deficiency among Chinese patients with T2DM. PTH is an important risk factor responsible for the higher 10-year probability of osteoporotic fractures in diabetic patients, especially in those with lower vitamin D levels.Abbreviations: AKP = alkaline phosphatase; ALB = serum albumin; BMD = bone mineral density; BMI = body mass index; Ca = calcium; CKD = chronic kidney disease; Cr = creatinine; FN = femoral neck; FRAX = fracture risk assessment tool; HbA1c = glycated hemoglobin A1c; HF = hip fracture; L2-4 = lumbar spine; MOF = major osteoporotic fracture; 25(OH)D = 25-hydroxyvitamin D; P = phosphorus; PTH = parathyroid hormone; T2DM = type 2 diabetes mellitus; TH = total hip; UA = uric acid     

Liraglutide Achieves A1C Targets More often than Sitagliptin or Exenatide when Added to Metformin in Patients with Type 2 Diabetes and a Baseline A1C <8.0%

ObjectiveCompare the safety and efficacy of liraglutide to that of sitagliptin or exenatide as add-on to metformin in patients with type 2 diabetes (T2D) and glycated hemoglobin (A1C) <8.0%.MethodsPost hoc analysis of 26-week data from liraglutide 1.8 mg once daily (OD) versus exenatide 10 μg twice daily (LEAD-6) and liraglutide 1.8 mg OD versus sitagliptin 100 mg OD (LIRA-DPP-4); only patients treated as add-on to metformin with baseline A1C <8.0% were included. Efficacy analysis was performed on the intention-to-treat population with missing values imputed by last observation carried forward.ResultsMore patients achieved A1C targets (<7.0% and ≤6.5%) with liraglutide versus exenatide or sitagliptin; the difference was greatest for A1C ≤6.5% (LEAD-6: 65% versus 35%; odds ratio [OR]=3.37, 95% confidence interval [CI]: 1.31-8.63; P = .01 or LIRA-DPP-4: 53% versus 19%; OR = 4.78, 95% CI 2.10 to 10.87; P = .0002). Significantly more patients achieved a composite endpoint of A1C <7.0% with no weight gain or hypoglycemia with liraglutide compared with exenatide (78% versus 42%; OR = 4.99, 95% CI: 1.77 to 14.04; P = .0023) or sitagliptin (61% versus 21%; OR = 5.95, 95% CI: 2.66 to 13.29; P<.0001). All treatments were well tolerated, there was no major hypoglycemia and few patients (8 to 10%) experienced minor hypoglycemia.ConclusionWhen added to metformin in patients with an A1C <8.0%, more patients using liraglutide 1.8 mg reached A1C targets than with exenatide or sitagliptin. Sitagliptin had particularly low efficacy in this analysis. These data support the use of liraglutide 1.8 mg as a safe and effective alternative to sitagliptin or exenatide following metformin failure in patients with an A1C <8.0%. (Endocr Pract. 2013;19:64-72)     

Effects of Bisphosphonates on Osteoporosis Induced by Duchenne Muscular Dystrophy: A Prospective Study

Objective: Duchenne muscular dystrophy (DMD) is a severe X-linked progressive neuromuscular disease that brings a significantly increased risk of osteoporosis and bone fractures. We prospectively evaluated the effects of oral and intravenous bisphosphonates on the bones of children with DMD.Methods: This study included a total of 52 children with DMD. They were divided into zoledronic acid (ZOL), alendronate (ALN), and control groups according to bone mineral density (BMD) and history of fragility fractures. For 2 years, all patients took calcium, vitamin D, and calcitriol. Meanwhile, 17 patients received infusions of ZOL, and 18 patients received ALN. BMD, serum levels of alkaline phosphatase (ALP) and the cross-linked C-telopeptide of type I collagen (β-CTX) were evaluated.Results: After 24 months of treatment, the percentage changes in lumbar spine BMD were 23.2 ± 9.7% and 23.6 ± 8.8% in the ZOL and ALN groups (all P<.01 vs. baseline). The increases did not differ between the ZOL and ALN groups, but were significantly larger than those of the control group (P<.01). Serum β-CTX and ALP levels, respectively, were decreased by 44.4 ± 18.0% and 31.9 ± 26.7% in the ZOL group and by 36.0 ± 20.3% and 25.8 ± 14.4% in the ALN group (all P<.01 vs. baseline).Conclusion: Zoledronic acid and alendronate had similar protective effects to increase bone mineral density and reduce bone resorption in children with DMD, which were superior to treatment of calcium, vitamin D, and calcitriol.Abbreviations: 25OHD = 25 hydroxyvitamin D; ALN = alendro-nate; ALP = alkaline phosphatase; ALT = alanine aminotransferase; BMD = bone mineral density; BP = bisphosphonate; Ca = calcium; β-CTX = cross-linked C-telopeptide of type I collagen; DMD = Duchenne muscular dystrophy; FN = femoral neck; GC = glucocorticoid; LS = lumbar spine; ZOL = zoledronic acid     

Bone Mineral Density In Patients With Addison Disease On Replacement Therapy With Prednisolone

Objective: In primary adrenal insufficiency (PAI), replacement with prednisolone may result in lower bone mineral density (BMD) compared with hydrocortisone therapy. However, the number of patients studied on prednisolone is small and the results are conflicting. We conducted a cross-sectional study to determine BMD and its relation with therapy in patients on physiologic doses of prednisolone replacement.Methods: Forty-one consecutive patients (31 males, age &lsqb;mean ± SD] 50.9 ± 13.0 years), receiving prednisolone (hydrocortisone equivalent &lsqb;HCE] 13.0 ± 3.0 mg/m²) for 104 ± 95 months were studied. BMD was evaluated by dual-energy X-ray absorptiometry and compared with an age- and sex-matched reference group of healthy Indian subjects (n = 677).Results: Among males, BMD Z-scores (mean &lsqb;95% confidence interval {CI}]) at lumbar spine (-0.42 &lsqb;-0.80, -0.04]), femoral neck (-0.50 &lsqb;-0.95, -0.06]) and total hip (-0.58 &lsqb;-0.90, -0.26]) were significantly lower than the reference population. Z-scores in female patients did not differ from controls. Among postmenopausal females and males >50 years, 43% had osteoporosis (T-score ≤-2.5), as compared with 25% in the reference group (P = .04). There was no correlation between BMD Z-scores and HCE dose or duration of therapy. On multivariate regression analysis, body mass index was the only significant predictor of BMD. A high proportion of males (45%) had low serum testosterone (<300 ng/dL), but there was no correlation between testosterone and BMD.Conclusions: Male patients with PAI receiving physiologic prednisolone replacement had a small but significant diminution in BMD at all sites.Abbreviations:ACTH = adrenocorticotropic hormoneBAP = bone-specific alkaline phosphataseBMD = bone mineral densityBMI = body mass indexCI = confidence intervalHCE = hydrocortisone equivalent25 (OH) D3 = 25-hydroxyvitamin D3PAI = primary adrenal insufficiency     

Effects of Liraglutide 3.0 Mg on Weight and Risk Factors in Hispanic Versus Non-Hipanic Populations: Subgroup Analysis from Scale Randomized Trials

Objective: Scarce data exist on pharmacotherapy for obesity in Hispanic individuals. This post hoc analysis of pooled data from 4 phase 3a trials compared the efficacy and safety of liraglutide 3.0 mg versus placebo, as adjunct to a reduced-calorie diet and physical activity, in Hispanic versus non-Hispanic subgroups.Methods: We conducted the double-blind randomized, placebo-controlled trials in adults with a minimum body mass index (BMI) of 27 kg/m² with at least 1 comorbidity, or a minimum BMI of 30 kg/m², at clinical research sites worldwide. In this analysis, we investigated possible differences in treatment effects between 534 Hispanics (10.4% of the population) and 4,597 non-Hispanics (89.6%) through statistical tests of interaction between subgroups and treatment. Variables examined included mean and categorical weight change, cardiovascular risk markers, and safety data.Results: Both subgroups achieved clinically significant mean weight loss at end-of-treatment with liraglutide 3.0 mg versus placebo: Hispanics 7.0% versus 1.5%, treatment difference -5.1% (95% CI, -6.2 to -4.0); non-Hispanics 7.5% versus 2.3%, -5.2% (95% CI, -5.5 to -4.8). More individuals in both subgroups lost ≥5%, >10%, and >15% of their baseline weight with liraglutide 3.0 mg than with placebo. Efficacy endpoints generally did not vary with ethnicity (P>.05). Adverse events were comparable between ethnic subgroups, with more gastrointestinal disorders reported with liraglutide 3.0 mg than placebo.Conclusion: Efficacy and safety were largely similar between Hispanic and non-Hispanic subgroups. Results support that liraglutide 3.0 mg, used with a reduced-calorie diet and physical activity, can facilitate weight loss in Hispanic individuals.Abbreviations:A1c = glycated hemoglobinBMI = body mass indexCI = confidence intervalFPG = fasting plasma glucoseGLP-1 = glucagon-like peptide-1hsCRP = high-sensitivity C-reactive proteinSCALE = Satiety and Clinical Adiposity – Liraglutide Evidence in individuals with and without diabetesT2DM = type 2 diabetes mellitus     

The Clinical Characteristics and Efficacy of Bisphosphonates in Audlt Patients with Osteogenesis Impergecta

Objective: Osteogenesis imperfecta (OI) is characterized by low bone mass and recurrent fractures. Adults with OI are often treated with oral or intravenous bisphosphonates (BPs). We investigated the clinical phenotypes of adult OI patients and prospectively compared the efficacy of oral alendronate (ALN) with intravenous zoledronic acid (ZOL) in OI patients.Methods: This 24-month, observational, randomized clinical study included 60 adult patients with OI. We compared the differences in bone mineral density (BMD) and bone turnover biomarkers between OI adults and healthy subjects. Thereafter, OI patients were randomized at a 2:1 ratio to receive either weekly oral ALN 70 mg or once-yearly infusion of ZOL 5 mg. The efficacy outcomes were changes in BMD, bone turnover biomarkers, and fracture incidence.Results: Adult OI patients had significantly lower BMD and significantly higher cross-linked C-telopeptide of type I collagen (β-CTX) levels than age-/sex-/BMI-matched healthy subjects. A total of 52 patients completed the 24-month clinical study. BMD at lumbar spine, femoral neck, and total hip were equivalently elevated in the ALN (10.5, 13.2, and 14.7%, respectively) and ZOL (11.3, 13.7, and 11.7%, respectively; all P>.05) groups. Serum alkaline phosphatase decreased by 30.3% in the ALN group and 37.3% in the ZOL group (P =.12), and β-CTX decreased by 58.0% in the ALN group and 63.6% in the ZOL group (P =.48). Compared to the prior fracture rates, clinical fracture incidences were decreased in the ALN and ZOL groups (both P<.05).Conclusion: Adults with OI present significantly lower bone mass and higher bone resorption biomarkers than healthy populations. Oral ALN and intravenous ZOL are equally effective at increasing BMD and inhibiting bone turnover in adults with OI. The treatment may reduce fractures in this study, but further efforts are still needed to demonstrate the anti-fracture efficacy of BPs.Abbreviations:25OHD = 25-hydroxyvitamin DALN = alendronateALP = alkaline phosphataseBMD = bone mineral densityBMI = body mass indexBP = bisphosphonateβ-CTX = cross-linked C-telopeptide of type I collagenFN = femoral neckLS = lumbar spineOI = osteogenesis imperfectaRCT = randomized controlled trialTH = total hipZOL = zoledronic acid     

Does Baseline PTH Influence Recovery of Bone Mineral Density,Trabecular Bone Score and Bone Turnover Markers? A Prospective Study Following Curative PArathyroidectomy in Primary Hyperparathyroidism

Objective: This prospective study was carried out to assess trabecular bone score, bone mineral density (BMD), and bone biochemistry in Indian subjects with symptomatic primary hyperparathyroidism (PHPT), and to study the influence of baseline parathyroid hormone (PTH) on recovery of these parameters following curative surgery.Methods: This was a 2-year prospective study conducted at a tertiary care centre in southern India. Baseline assessment included demographic details, mode of presentation, bone mineral biochemistry, BMD, trabecular bone score (TBS), and bone turnover markers (BTMs). These parameters were reassessed at the end of the first and second years following curative parathyroid surgery.Results: Fifty-one subjects (32 men and 19 women) with PHPT who had undergone curative parathyroidectomy were included in this study. The mean (SD) age was 44.6 (13.7) years. The TBS, BTMs, and BMD at lumbar spine and forearm were significantly worse at baseline in subjects with higher baseline PTH (≥250 pg/mL) when compared to the group with lower baseline PTH (<250 pg/mL). At the end of 2 years, the difference between high versus low PTH groups (mean ± SD) persisted only for forearm BMD (0.638 ± 0.093 versus 0.698 ± 0.041 g/cm²; P =.01). However, on follow-up visits in the first and second year after curative parathyroidectomy, there was no significant difference in BTMs, BMD at the femoral neck, lumbar spine, and TBS between the 2 groups stratified by baseline PTH.Conclusion: The BMD at the forearm remained significantly worse in individuals with high baseline PTH even at 2 years after surgery, while other parameters including TBS improved significantly from baseline.Abbreviations: 25(OH)D = 25-hydroxyvitamin D; BMD = bone mineral density; BMI = body mass index; BTMs = Bone turnover markers; CTX = C-terminal telopeptide of type 1 collagen; DXA = dual energy X-ray absorptiometry; P1NP = N-terminal propeptide of type 1 procollagen; PHPT = primary hyperparathyroidism; PTH = parathyroid hormone; TBS = trabecular bone score     

Opportunistic Evaluation of Bone Mineral Density By Pet-Ct in Hodgkin Lymphoma Patients

Objective: Bone density loss and increased risk for osteoporosis are of concern in Hodgkin lymphoma (HL) patients. Routinely performed positron emission tomography–computed tomography (PET-CT) scans could be informative in assessing bone mineral density (BMD).Methods: This retrospective study included 80 adults with newly diagnosed HL treated with standard first-line chemotherapy regimens. PET-CT scans performed at diagnosis (PET-CT₁), at the end of chemotherapy (PET-CT₂), and at follow-up after remission (PET-CT₃) were used to assess BMD changes by measuring lumbar vertebrae CT attenuation. A CT attenuation threshold of 160 Hounsfield units was used to define abnormal BMD.Results: Following chemotherapy, comparison of PET-CT₂ with PET-CT₁ revealed a mean (standard deviation) 14.2% (10.4%) BMD reduction (P<.001). On PET-CT₃ performed at 14.6 (3.25) months after the last course of chemotherapy, a slight improvement (4.6% &lsqb;10.4%]) in comparison to PET-CT₂ was noted. Twelve patients (15%) converted from normal baseline BMD on PET-CT₁ to abnormal BMD after chemotherapy on PET-CT₂. Age, baseline BMD, and steroid cumulative dose were associated with BMD decline and risk for abnormal BMD after chemotherapy. No clinical fractures were reported, and only one rib fracture was incidentally captured (1.25%).Conclusion: HL patients treated with common first-line chemotherapies demonstrate a significant decline in bone density on routine PET-CT scans. Opportunistic use of PET-CT scan has the potential to detect HL patients at high risk for developing osteoporosis and to guide clinicians regarding monitoring and intervention.Abbreviations: BMD = bone mineral density; CT = computed tomography; DXA = dual-energy X-ray absorptiometry; HL = Hodgkin lymphoma; HU = Hounsfield units; L = lumbarvertebra; PET-CT = positron emission tomography-computed tomography; T = thoracic vertebra     

Zoledronic Acid Versus Alendronate In The Treatment of Children With Osteogenesis Imperfecta: A 2-Year Clinical Study

Objective: Bisphosphonates have been demonstrated to increase the bone mineral density (BMD) of osteogenesis imperfecta (OI) patients. We aimed to compare the efficacy and safety of intravenous zoledronic acid and oral alendronate in patients with OI.Methods: A total of 161 patients with OI ranging from 2 to 16 years old were included and randomized at a 2:1 ratio to receive either weekly oral alendronate (ALN) 70 mg or a once-yearly infusion of zoledronic acid (ZOL) for 2 years. The primary endpoints were percentage change from baseline in lumbar spine (LS) BMD and change in Z-scores of LS BMD.Results: A total of 136 patients with OI completed the 2-year clinical study, 90 of whom were assigned to receive ALN, while 46 received ZOL treatment. The percentage change in LS BMD was 60.01 ± 7.08% in the ALN group and 62.04 ± 5.9% in the ZOL group (P = .721). The corresponding BMD Z-score increased by 0.50 ± 0.05 in the ALN group and 0.71 ± 0.06 in the ZOL group (P = .013). ZOL was superior to ALN in reducing the clinical fracture rate (hazard ratio, 0.23; 95% confidence interval, 0.118 to 0.431). There was no difference in the incidence of severe side effects between the two groups.Conclusion: A once-yearly 5 mg infusion of ZOL and weekly oral ALN had similar effects in increasing BMD and reducing bone resorption in children and adolescents with OI. ZOL was superior to ALN in reducing the clinical fracture rate.Abbreviations: 25OHD = 25-hydroxyvitamin D; ALN = alendronate; ALP = alkaline phosphatase; β-CTX = cross-linked C-telopeptide of type I collagen; BMD = bone mineral density; BP = bisphosphonate; FN = femoral neck; LS = lumbar spine; OI = osteogenesis imperfecta; SAE = severe adverse event; ZOL = zoledronic acid     

Beyond Dxa: Advances in Clinical Applications of New Bone Imaging Technology

Dual-energy X-ray absorptiometry (DXA) is generally a very useful tool for assessing bone mineral density (BMD) and fracture risk. However, observational studies have shown that in certain instances, BMD as measured by DXA systematically over- or underestimates fracture risk. We herein describe the clinical conundrums encountered when assessing fracture risk by DXA in patients with primary hyperparathyroidism or type 2 diabetes and those of Chinese ethnicity. Furthermore, we discuss how advanced imaging technology that examines skeletal microarchitecture is furthering our understanding of fracture risk in these clinical situations.Abbreviations:BMD = bone mineral densityBMI = body mass indexBMS = bone material strengthBMT = bone microindentation testing3D = 3-dimensionalDM2 = type 2 diabetes mellitusDXA = dual-energy X-ray absorptiometryμFEA = microstructural finite element analysisFRAX = fracture risk assessment toolHRpQCT = high-resolution peripheral quantitative computed tomographyID = indentation distanceIDI = indentation distance increaseITS = individual trabecular segmentationPHPT = primary hyperparathyroidismPTH = parathyroid hormoneTBS = trabecular bone score     

Influence Of Diabetes And Hyperglycemia On Duration Of Stay In Patients Hospitalized With Congestive Heart Failure

ObjectiveTo analyze the influence of diabetes and hyperglycemia on duration of stay in patients hospitalized with congestive heart failure (CHF).MethodsWe conducted a retrospective review of data for patients admitted during a 6-month period with CHF to a community teaching hospital in Baltimore, Maryland. Patients were divided into diabetic and nondiabetic groups, and patients with diabetes were stratified by mean fasting plasma glucose levels into the following groups: < 110 mg/dL, 110 to 180 mg/dL, and > 180 mg/dL. The primary outcome was duration of hospitalization. Other variables included sex, age, ejection fraction, admission glucose, brain natriuretic peptide, creatinine, and other comorbidities.ResultsThe study cohort consisted of 142 patients, 49% of whom had diabetes. The duration of hospitalization was 3.23 days in the patients with diabetes versus 3.11 days in those without diabetes (P = .875). Patients with diabetes were significantly younger (71.8 versus 76.6 years; P = .027) and had a higher baseline mean creatinine level (1.4 versus 1.2 mg/dL; P = .010). Patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group (2.94 versus 3.41 days; P = .259). Only 9 patients had blood glucose levels > 180 mg/dL, and these patients had the longest hospitalizations (mean duration, 3.78 days).ConclusionThe prevalence of diabetes was higher in our study than in previously published studies of patients with CHF. Although patients with diabetes did not have significantly longer hospitalizations than those without diabetes, they were significantly younger and had higher baseline creatinine values. Hyperglycemia was an infrequent phenomenon among patients without diabetes. The patients with diabetes in the 110 to 180 mg/dL blood glucose group had shorter hospitalizations than did those in the < 110 mg/dL group, although this difference did not reach statistical significance. Many of the initial studies of tight glucose control were conducted in the surgical intensive care unit, but recently published evidence has raised doubt about applying these results to medical patients. We conclude that there may be no significant benefit in terms of duration of hospitalization in assigning patients with diabetes who have CHF exacerbations to tight glucose control regimens. A more liberal approach of maintaining glucose levels at 110 to 180 mg/dL may be acceptable. (Endocr Pract. 2008;14:691-696)     

Axial BMD in Diabetic and Nondiabetic Southeast Asians with HIP Fractures: Do Race and Body Mass Index Matter?

Objective: Obesity is less prevalent in Asian subjects with type 2 diabetes mellitus (T2DM) in contrast to Caucasians. Whether higher axial bone mineral density (BMD) often reported in T2DM is independent of body mass index (BMI) has not been clearly shown. BMD characterization in T2DM patients with hip fractures has also not been performed. We compared the BMD of Asian diabetic and nondiabetic patients with new hip fractures and explored how BMD was influenced by BMI.Methods: We included 255 diabetic and 148 nondiabetic patients. BMD adjusted for age; BMI; race; sex; renal function; and use of statins, proton pump inhibitors, steroids, anticonvulsants, and calcium and/or vitamin D supplements were compared between the groups. We were particularly interested in the BMD comparison between underweight diabetics and nondiabetics with hip fractures.Results: The presence of T2DM was associated with higher BMD (g/cm²) at the femoral neck (0.527 ± 0.103 vs. 0.491 ± 0.102, P<.01) and lumbar spine [LS] (0.798 ± 0.147 vs. 0.723 ± 0.156, P<.01). This association persisted after adjustment for multiple confounding variables including BMI. The age-, BMI-, and sex-adjusted LS BMD was higher in underweight (BMI <18.5 kg/m²) diabetics compared to similar weight nondiabetics (0.733 ± 0.126 vs. 0.649 ± 0.131 g/cm², P = .014).Conclusion: T2DM is independently associated with higher axial BMD in patients with new hip fractures. The finding of higher BMD even in underweight diabetics with hip fractures compared to their nondiabetic counterparts suggests that higher BMD in subjects with T2DM is not due to higher BMI.Abbreviations:BMD = bone mineral densityBMI = body mass indexCV = coefficient of variationDXA = dual-energy X-ray absorptiometryHbA1c = glycated hemoglobinIGF-1 = insulin growth factor-1LS = lumbar spine25(OH)D = 25-hydroxyvitamin DT2DM = type 2 diabetes mellitus     

Efficacy of antihyperglycemic therapies and the influence of baseline hemoglobin A(1C): a meta-analysis of the liraglutide development program

ObjectiveTo compare Iiraglutide versus common antihyperglycemic treatments in reducing hemoglobin A_1c (A1C) values across multiple levels of baseline glycemic control and in reaching glycemic targets.MethodsPooled patient data from 7 phase 3, multinational, randomized controlled trials in patients with type 2 diabetes were stratified by baseline A1C values into 5 categories: ≤ 7.5%, > 7.5% to 8.0%, > 8.0% to 8.5%, > 8.5% to 9.0%, and > 9.0%. The changes in A1C from baseline to week 26 of treatment and patient proportions reaching A1C targets of < 7.0% and ≤ 6.5% were compared between liraglutide (1.8 mg daily) and sitagliptin, glimepiride, rosiglitazone, exenatide, and insulin glargine across all baseline A1C categories.ResultsIrrespective of treatment, reductions in A1C levels were generally greater in groups with higher baseline A1C values. After 26 weeks of treatment, liraglutide produced the greatest reductions in A1C values across all baseline categories, ranging from 0.7% to 1.8% (baseline A1C categories ≤ 7.5% to > 9.0%, respectively), followed by insulin glargine (0.3% to 1.5%) and then by glimepiride (0.4% to 1.3%). Generally, larger percentages of patients achieved the A1C target of ≤ 6.5% with liraglutide therapy across all baseline categories (from 62% of patients with A1C values ≤ 7.5% to 10% of patients with A1C values > 9.0%) in comparison with other treatments (ranging from 49% to 0% of patients, respectively). Similarly, greater proportions of patients also reached the A1C target of < 7.0% with liraglutide therapy across all baseline categories (from 83% of patients with A1C values ≤ 7.5% to 25% of patients with A1C values > 9.0%) versus comparators (from 74% to 5% of patients, respectively).ConclusionAcross a wide spectrum of baseline A1C categories, liraglutide is an efficacious treatment option for patients with type 2 diabetes. (Endocr Pract. 2011;17: 906-913)     

Dual-Energy X-Ray Absorptiometry And Calculated Frax Risk Scores May Underestimate Osteoporotic Fracture Risk In Vitamin D-Deficient Veterans With Hiv Infection

Objective: We evaluated the utility of the Fracture Risk Assessment Tool (FRAX) in assessing fracture risk in patients with human immunodeficiency virus (HIV) and vitamin D deficiency.Methods: This was a retrospective study of HIV-infected patients with co-existing vitamin D deficiency at the Atlanta Veterans Affairs Medical Center. Bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DEXA), and the 10-year fracture risk was calculated by the FRAX algorithm. Two independent radiologists reviewed lateral chest radiographs for the presence of subclinical vertebral fractures.Results: We identified 232 patients with HIV and vitamin D deficiency. Overall, 15.5% of patients met diagnostic criteria for osteoporosis on DEXA, and 58% had low BMD (T-score between -1 and -2.5). The median risk of any major osteoporotic and hip fracture by FRAX score was 1.45 and 0.10%, respectively. Subclinical vertebral fractures were detected in 46.6% of patients. Compared to those without fractures, those with fractures had similar prevalence of osteoporosis (15.3% versus 15.7%; P>.999), low BMD (53.2% versus 59.3%; P = .419), and similar FRAX hip scores (0.10% versus 0.10%; P = .412). While the FRAX major score was lower in the nonfracture group versus fracture group (1.30% versus 1.60%; P = .025), this was not clinically significant.Conclusion: We found a high prevalence of subclinical vertebral fractures among vitamin D–deficient HIV patients; however, DEXA and FRAX failed to predict those with fractures. Our results suggest that traditional screening tools for fragility fractures may not be applicable to this high-risk patient population.Abbreviations:25(OH)D = 25-hydroxyvitamin DBMD = bone mineral densityBMI = body mass indexDEXA = dual-energy X-ray absorptiometryFRAX = Fracture Risk Assessment ToolHIV = human immunodeficiency virusIQR = interquartile rangePTH = parathyroid hormoneVA = Veterans AffairsWHO = World Health Organization     

Adding VFA to DXA Identifies Fracture Risk in a Way Not Duplicated by Other Measures

Objective: Published studies have demonstrated that adding vertebral fracture assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more patients with increased fracture risk than DXA alone. But who needs VFA? This study attempts to determine if some test other than VFA could duplicate the additional information obtained by performing VFA on all first-time patients. This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age, documented back pain, and nonvertebral fragility fractures.Methods: VFA was performed on 1,259 (all) DXA patients at their first visit from March 2010 through September 2013. All DXA and VFA results were read by the same International Society for Clinical Densitometry–certified clinician.Results: By DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by 36% of the original total patients. Eighty-three “normal bone mineral density” patients were changed to clinical osteoporosis. FRAX identified 53% of the patients with diagnosis changes. Historical height loss was not reliable. Increasing age correlated only weakly with clinical osteoporosis.Conclusion: These are modest numbers from a nonacademic referral practice and may not be typical of other populations. Thirty-six percent of our patients were misclassified by DXA alone, with fragility fractures already taken into account for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility fractures all failed to identify many of the patients identified by VFA. Seeing the lateral spine images obtained by VFA influenced patients and families. VFA on all first-time patients should be reconsidered.Abbreviations:BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; FRAX = Fracture Risk Assessment Tool; HL = height loss; ISCD = International Society for Clinical Densitometry; VF = vertebral fracture; VFA = vertebral fracture assessment     

Trabecular Bone Score Change Differs with Regard to 25(OH)D Levels in Patients Treated for Adult-Onset Growth Hormone Deficiency

Objective: Vitamin D is important in bone health. However, potential relationships of concomitant vitamin D deficiency with growth hormone deficiency (GHD) and the possibility that vitamin D inadequacy may alter the skeletal effects of growth hormone (GH) replacement therapy have not been adequately evaluated.Methods: A prospective study was conducted in adult-onset GHD patients treated with recombinant human GH (rhGH) for 2 years. Trabecular bone score (TBS), lumbar spine (LS) bone mineral density (BMD), total hip (TH) BMD, and 25-hydroxyvitamin D (25(OH)D) levels were assessed at baseline and 24 months. The study cohort was divided based on 25(OH)D levels into 2 groups with the cutoff defined as the 50^th percentile at each follow-up time point.Results: Fifty-seven patients (29 males/28 females, mean age 34.4 years) were studied. After 24 months of GH replacement, LS BMD increased by 7.6% and TH BMD increased by 4.5% (both P<.05), with no difference according to 25(OH)D levels. TBS increased (+1.39 ± 3.6%) in those whose 25(OH)D was above the 50^th percentile but decreased (-1.36 ± 5.6%, P<.05) in the cohort below the 50^th percentile of 25(OH)D. Positive correlations were observed between baseline levels of IGF-1 and 25(OH)D (R = 0.37, P<.001) and between 24-month 25(OH)D and TBS (R = 0.25, P<.05).Conclusion: A differential effect of GH on TBS change was observed; TBS increased only in the cohort with 25(OH)D above the 50^th percentile. Vitamin D sufficiency may be required to obtain optimal effects of GH treatment on bone quality, as assessed by TBS, in GHD adults.Abbreviations:AO-GHD = adult-onset GHDBMD = bone mineral densityBMI = body mass indexCa = calciumCTx = carboxyterminal collagen crosslinksCV = coefficient of variationDXA = dual energy X-ray absorptiometryECLIA = enzyme-labeled chemiluminescent immunometric assayGH = growth hormoneGHD = growth hormone deficiencyIGF-1 = insulin-like growth factor 1LS BMD = lumbar spine BMDOC = osteocalcin25(OH)D = 25-hydroxyvitamin DP = phosphorusPTH = parathyroid hormonerhGH = recombinant human GHTBS = trabecular bone scoreTH BMD = total hip BMD     

Adult Hypophosphatasia Treated with Teriparatide: Report of 2 Patients and Review of the Literature

Objective: Hypophosphatasia (HPP) is a rare inherited metabolic bone disease from deficient activity of the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). Reportedly, teriparatide (parathyroid hormone 1–34) can benefit the adult form of HPP, including fracture healing. We studied 2 women with adult HPP given teripa-ratide and reviewed the reports of 6 additional patients.Methods: A 68-year-old black woman (patient 1) described low-trauma fractures and had subnormal serum alkaline phosphatase (ALP) activity. Biochemical findings were consistent with HPP. Mutation analysis revealed a heterozygous defect in exon 10 of TNSALP (ALPL). Teriparatide was injected daily for 2 years. Four years later, she fractured her right hip. Treatment was resumed for 8 months without further fractures. A 53-year-old white woman (patient 2) reported low-trauma fractures and had subnormal serum ALP. Mutation analysis revealed a heterozygous defect in exon 8 of TNSALP. She injected teriparatide daily for 2 years. One year later, bone mineral density (BMD) declined and treatment was resumed for 3 months. When she sustained a sacral fracture, teriparatide was administered for a further 18 months.Results: Patient 1's serum ALP increased while receiving teriparatide and returned to baseline after its discontinuation. BMD remained unchanged, but no fractures were sustained. Patient 2's serum ALP increased, but the improvement was not sustained. Femoral neck BMD increased significantly during the first cycle, declined significantly afterwards, and was regained during course of teriparatide.Conclusion: Teriparatide shows some benefit for adult HPP.Abbreviations:ALP = alkaline phosphataseBMD = bone mineral densityBSAP = bone-specific alkaline phosphataseCTX = C-telopeptideDXA = dual-energy X-ray absorptiometryFN = femoral neckHPP = hypophosphatasiaLS = lumbar spinePEA = phosphoethanolaminePLP = pyridoxal 5′-phosphatePTH = parathyroid hormoneSQ = subcutaneousTNSALP = tissue-nonspecific isoenzyme of alkaline phosphataseTPTD = teriparatide     

The Emerging Role Of Adjunctive Noninsulin Antihyperglycemic Therapy In The Management Of Type 1 Diabetes

Objective: Review available data on adjunctive therapies for type 1 diabetes (T1D), with a special focus on newer antihyperglycemic agents.Methods: Published data on hypoglycemia, obesity, mortality, and goal attainment in T1D were reviewed to determine unmet therapeutic needs. PubMed databases and abstracts from recent diabetes meetings were searched using the term “type 1 diabetes” and the available and investigational sodium-glucose cotransporter (SGLT) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, dipeptidyl peptidase 4 inhibitors, and metformin.Results: The majority of patients with T1D do not meet glycated hemoglobin (A1C) goals established by major diabetes organizations. Hypoglycemia risks and a rising incidence of obesity and metabolic syndrome featured in the T1D population limit optimal use of intensive insulin therapy. Noninsulin antihyperglycemic agents may enable T1D patients to achieve target A1C levels using lower insulin doses, which may reduce the risk of hypoglycemia. In pilot studies, the SGLT2 inhibitor dapagliflozin and the GLP-1 receptor agonist liraglutide reduced blood glucose, weight, and insulin dose in patients with T1D. Phase 2 studies with the SGLT2 inhibitor empagliflozin and the dual SGLT1 and SGLT2 inhibitor sotagliflozin, which acts in the gut and the kidney, have demonstrated reductions in A1C, weight, and glucose variability without an increased incidence of hypoglycemia.Conclusion: Newer antihyperglycemic agents, particularly GLP-1 agonists, SGLT2 inhibitors, and dual SGLT1 and SGLT2 inhibitors, show promise as adjunctive treatment for T1D that may help patients achieve better glucose control without weight gain or increased hypoglycemia.Abbreviations:A1C = glycated hemoglobinBMI = body mass indexCI = confidence intervalDKA = diabetic ketoacidosisDPP-4 = dipeptidyl peptidase 4GLP-1 = glucagonlike peptide 1PYY = polypeptide tyrosine tyrosineSGLT = sodium-glucose cotransporterSGLT1 = sodium-glucose cotransporter 1SGLT2 = sodium-glucose cotransporter 2T1D = type 1 diabetesT2D = type 2 diabetesTDD = total daily dosage