Unmasking Fracture Risk in Type 2 Diabetes: The Association of Longitudinal Glycemic Hemoglobin Level and Medications

Abstract Context Fracture risk is underestimated in people with type 2 diabetes (T2D). Objective To investigate the longitudinal relationship of glycated hemoglobin (HbA1c) and common medications on fracture risk in people with T2D. Design Retrospective cohort study was conducted using de-identified claims and EHR data obtained from the OptumLabs ® Data Warehouse during 01/01/2007 to 09/30/2015. For each individual, the study was conducted within a two-year HbA1c observation period and a two-year fracture follow-up period. Setting Population-based study. Participants 157,439 individuals with T2D [age ≥ 55 years with mean HbA1c value ≥ 6%] were selected from 4,018,250 US Medicare Advantage/Commercial enrollee with T2D diagnosis. Main Outcome Measures. All fractures and fragility fractures were measured. Results With covariates adjusted, poor glycemic control in T2D individuals was associated with an 29% increase of all fracture risk, compared to T2D individuals with adequate glycemic control (HR: 1.29, 95% CI 1.22-1.36). Treatment with metformin (HR: 0.88, 95% CI 0.85-0.92) and DPP4 inhibitors (HR: 0.93, 95% CI 0.88-0.98) were associated with a reduced all fracture risk, while insulin (HR: 1.26, 95% CI 1.21-1.32), thiazolidinediones (HR: 1.23, 95% CI 1.18-1.29), meglitinides (HR: 1.12, 95% CI 1.00-1.26) were associated with an increased all fracture risk (All p-value < 0.05). Bisphosphonates were associated similarly with increased fracture risk in T2D group and in non-diabetic group. Conclusions Longitudinal two-year HbA1c is independently associated with an elevated all fracture risk in T2D individuals during a two-year follow-up period. Metformin and DPP4 inhibitors can be used for management of T2D fracture risk.

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Does Sitagliptin Affect the Rate of Osteoporotic Fractures in Type 2 Diabetes? Population-Based Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2015-4180 ◽

2016 ◽

Vol 101 (5) ◽

pp. 1963-1969 ◽

Cited By ~ 21

Author(s):

Sumit R. Majumdar ◽

Robert G. Josse ◽

Mu Lin ◽

Dean T. Eurich

Keyword(s):

Type 2 Diabetes ◽

Cohort Study ◽

Fracture Risk ◽

Large Population ◽

Osteoporotic Fractures ◽

Population Based ◽

Increased Risk ◽

Multivariable Analyses

Abstract Context: Type 2 diabetes and osteoporosis are both common, chronic, and increase with age, whereas type 2 diabetes is also a risk factor for major osteoporotic fractures (MOFs). However, different treatments for type 2 diabetes can affect fracture risk differently, with metaanalyses showing some agents increase risk (eg, thiazolidinediones) and some reduce risk (eg, sitagliptin). Objective: To determine the independent association between new use of sitagliptin and MOF in a large population-based cohort study. Design, Setting, and Subjects: A sitagliptin new user study design employing a nationally representative Unites States claims database of 72 738 insured patients with type 2 diabetes. We used 90-day time-varying sitagliptin exposure windows and controlled confounding by using multivariable analyses that adjusted for clinical data, comorbidities, and time-updated propensity scores. Main Outcomes: We compared the incidence of MOF (hip, clinical spine, proximal humerus, distal radius) in new users of sitagliptin vs nonusers over a median 2.2 years follow-up. Results: At baseline, the median age was 52 years, 54% were men, and median A1c was 7.5%. There were 8894 new users of sitagliptin and 63 834 nonusers with a total 181 139 person-years of follow-up. There were 741 MOF (79 hip fractures), with 53 fractures (4.8 per 1000 person-years) among new users of sitagliptin vs 688 fractures (4.0 per 1000 person-years) among nonusers (P = .3 for difference). In multivariable analyses, sitagliptin was not associated with fracture (adjusted hazard ratio 1.1, 95% confidence interval 0.8–1.4; P = .7), although insulin (P < .001), sulfonylureas (P < .008), and thiazolidinedione (P = .019) were each independently associated with increased fracture risk. Conclusions: Even in a young population with type 2 diabetes, osteoporotic fractures were not uncommon. New use of sitagliptin was not associated with fracture, but other commonly used second-line agents for type 2 diabetes were associated with increased risk. These data should be considered when making treatment decisions for those with type 2 diabetes at particularly high risk of fractures.

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Androgen receptor reduced sensitivity is associated with increased mortality, poor glycemic control and BMI in men with type 2 diabetes - a 14-year follow up study

Endocrine Abstracts ◽

10.1530/endoabs.65.p190 ◽

2019 ◽

Author(s):

Adrian Heald ◽

Ghasem Yadegarfar ◽

Mark Livingston ◽

Helene Fachim ◽

Mark Lunt ◽

...

Keyword(s):

Type 2 Diabetes ◽

Androgen Receptor ◽

Glycemic Control ◽

Poor Glycemic Control ◽

Follow Up Study

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The program of personalized support in type 2 diabetes on insulin therapy: 9 months follow-up of glycemic control

10.26226/morressier.59d51842d462b80296ca3596 ◽

2017 ◽

Author(s):

Mayorov Alexander

Keyword(s):

Type 2 Diabetes ◽

Glycemic Control ◽

Insulin Therapy

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Impact of type 2 diabetes and microvascular complications on mortality and cardiovascular outcomes in a multiethnic Asian population

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001413 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001413

Author(s):

Jonathan Yap ◽

Kamalesh Anbalakan ◽

Wan Ting Tay ◽

Daniel Ting ◽

Carol Yim Cheung ◽

...

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Glycemic Control ◽

Microvascular Complications ◽

Population Based ◽

Cardiovascular Outcomes ◽

Microvascular Complication ◽

The Impact ◽

Hba1c Levels

IntroductionDiabetes mellitus is a growing public health epidemic in Asia. We examined the impact of type 2 diabetes, glycemic control and microvascular complications on mortality and cardiovascular outcomes in a multiethnic population-based cohort of Asians without prior cardiovascular disease.Research design and methodsThis was a prospective population-based cohort study in Singapore comprising participants from the three major Asian ethnic groups: Chinese, Malays and Indians, with baseline examination in 2004–2011. Participants with type 1 diabetes and those with cardiovascular disease at baseline were excluded. Type 2 diabetes, Hemoglobin A1c (HbA1c) levels and presence of microvascular complications (diabetic retinopathy and nephropathy) were defined at baseline. The primary outcome was all-cause mortality and major adverse cardiovascular events (MACEs), defined as a composite of cardiovascular mortality, myocardial infarction, stroke and revascularization, collected using a national registry.ResultsA total of 8541 subjects were included, of which 1890 had type 2 diabetes at baseline. Subjects were followed for a median of 6.4 (IQR 4.8–8.8) years. Diabetes was a significant predictor of mortality (adjusted HR 1.74, 95% CI 1.45 to 2.08, p<0.001) and MACE (adjusted HR 1.64, 95% CI 1.39 to 1.93, p<0.001). In those with diabetes, higher HbA1c levels were associated with increased MACE rates (adjusted HR (per 1% increase) 1.18, 95% CI 1.11 to 1.26, p<0.001) but not mortality (p=0.115). Subjects with two microvascular complications had significantly higher mortality and MACE compared with those with only either microvascular complication (adjusted p<0.05) and no microvascular complication (adjusted p<0.05).ConclusionDiabetes is a significant predictor of mortality and cardiovascular morbidity in Asian patients without prior cardiovascular disease. Among patients with type 2 diabetes, poorer glycemic control was associated with increased MACE but not mortality rates. Greater burden of microvascular complications identified a subset of patients with poorer outcomes.

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POS0163 INCIDENT FRACTURE RISK PREDICTION USING THE FRAGILITY SCORE CALCULATED BY LUMBAR SPINE RADIOFREQUENCY ECHOGRAPHIC MULTI SPECTROMETRY (REMS) SCANS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2021-eular.2311 ◽

2021 ◽

Vol 80 (Suppl 1) ◽

pp. 294.2-294

Author(s):

D. Ciardo ◽

P. Pisani ◽

F. A. Lombardi ◽

R. Franchini ◽

F. Conversano ◽

...

Keyword(s):

Lumbar Spine ◽

Fracture Risk ◽

Fragility Fracture ◽

Osteoporotic Fractures ◽

Fragility Fractures ◽

Bone Fragility ◽

P Value ◽

T Score ◽

Caucasian Women

Background:The main consequence of osteoporosis is the occurrence of fractures due to bone fragility, with important sequelae in terms of disability and mortality. It has been already demonstrated that the information about bone mass density (BMD) alone is not sufficient to predict the risk of fragility fractures, since several fractures occur in patients with normal BMD [1].The Fragility Score is a parameter that allows to estimate skeletal fragility thanks to a trans-abdominal ultrasound scan performed with Radiofrequency Echographic Multi Spectrometry (REMS) technology. It is calculated by comparing the results of the spectral analysis of the patient’s raw ultrasound signals with reference models representative of fragile and non-fragile bones [2]. It is a dimensionless parameter, which can vary from 0 to 100, in proportion to the degree of fragility, independently from BMD.Objectives:This study aims to evaluate the effectiveness of Fragility Score, measured during a bone densitometry exam performed with REMS technology at lumbar spine, in identifying patients at risk of incident osteoporotic fractures at a follow-up period of 5 years.Methods:Caucasian women with age between 30 and 90 were scanned with spinal REMS and DXA. The incidence of osteoporotic fractures was assessed during a follow-up period of 5 years. The ability of the Fragility Score to discriminate between patients with and without incident fragility fractures was subsequently evaluated and compared with the discriminatory ability of the T-score calculated with DXA and with REMS.Results:Overall, 533 women (median age: 60 years; interquartile range [IQR]: 54-66 years) completed the follow-up (median 42 months; IQR: 35-56 months), during which 73 patients had sustained an incident fracture.Both median REMS and DXA measured T-score values were significantly lower in fractured patients than for non-fractured ones, conversely, REMS Fragility Score was significantly higher (Table 1).Table 1.Analysis of T-score values calculated with REMS and DXA and Fragility Score calculated with REMS. Median values and interquartile ranges (IQR) are reported. The p-value is derived from the Mann-Whitney test.Patients without incident fragility fracturePatients with incident fragility fracturep-valueT-score DXA[median (IQR)]-1.9 (-2.7 to -1.0)-2.6 (-3.3 to -1.7)0.0001T-score REMS[median (IQR)]-2.0 (-2.8 to -1.1)-2.7 (-3.5 to -1.9)<0.0001Fragility Score[median (IQR)]29.9 (25.7 to 36.2)53.0 (34.2 to 62.5)<0.0001By evaluating the capability to discriminate patients with/without fragility fractures, the Fragility Score obtained a value of the ROC area under the curve (AUC) of 0.80, higher than the AUC of the REMS T-score (0.66) and of the T-score DXA (0.64), and the difference was statistically significant (Figure 1).Figure 1.ROC curve comparison of Fragility Score, REMS and DXA T-score values in the classification of patients with incident fragility fractures.Furthermore, the correlation between the Fragility Score and the T-score values was low, with Pearson correlation coefficient r=-0.19 between Fragility Score and DXA T-score and -0.18 between the Fragility Score and the REMS T-score.Conclusion:The Fragility Score was found to be an effective tool for the prediction of fracture risk in a population of Caucasian women, with performances superior to those of the T-score values. Therefore, this tool presents a high potential as an effective diagnostic tool for the early identification and subsequent early treatment of bone fragility.References:[1]Diez Perez A et al. Aging Clin Exp Res 2019; 31(10):1375-1389.[2]Pisani P et al. Measurement 2017; 101:243–249.Disclosure of Interests:None declared

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Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2020-001948 ◽

2021 ◽

Vol 9 (1) ◽

pp. e001948

Author(s):

Marion Denos ◽

Xiao-Mei Mai ◽

Bjørn Olav Åsvold ◽

Elin Pettersen Sørgjerd ◽

Yue Chen ◽

...

Keyword(s):

Type 2 Diabetes ◽

Family History ◽

Genetic Predisposition ◽

Effect Modification ◽

P Value ◽

Family History Of Diabetes ◽

Increased Risk ◽

History Of

IntroductionWe sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.Research design and methodsThis prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995–1997) and HUNT3 (2006–2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).ResultsOver 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).ConclusionSerum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.

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