Fracture Risk in Type 2 Diabetes: Current Perspectives and Gender Differences

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporotic fractures, resulting in disabilities and increased mortality. The pathophysiological mechanisms linking diabetes to osteoporosis have not been fully explained, but alterations in bone structure and quality are well described in diabetic subjects, likely due to a combination of different factors. Insulin deficiency and dysfunction, obesity and hyperinsulinemia, altered level of oestrogen, leptin, and adiponectin as well as diabetes-related complications, especially peripheral neuropathy, orthostatic hypotension, or reduced vision due to retinopathy may all be associated with an impairment in bone metabolism and with the increased risk of fractures. Finally, medications commonly used in the treatment of T2DM may have an impact on bone metabolism and on fracture risk, particularly in postmenopausal women. When considering the impact of hypoglycaemic drugs on bone, it is important to balance their potential direct effects on bone quality with the risk of falling-related fractures due to the associated hypoglycaemic risk. In this review, experimental and clinical evidence connecting bone metabolism and fracture risk to T2DM is discussed, with particular emphasis on hypoglycaemic treatments and gender-specific implications.

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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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CANCER OF THE ORGANS OF THE REPRODUCTIVE SYSTEM IN WOMEN WITH TYPE 2 DIABETES. EFFECTS OF ANTIDIABETIC THERAPY

Wiadomości Lekarskie ◽

10.36740/wlek202005124 ◽

2020 ◽

Vol 73 (5) ◽

pp. 967-971

Author(s):

Tamara S. Vatseba

Keyword(s):

Type 2 Diabetes ◽

Combination Therapy ◽

Postmenopausal Women ◽

Reproductive System ◽

Uterine Cancer ◽

Antidiabetic Therapy ◽

Increased Risk ◽

Risk Of Cancer ◽

The Impact

The aim: to investigate the prevalence of cancer of the reproductive system in women with type 2 diabetes, and to examine the impact of antidiabetic therapy on cancer risk of this localization. Materials and methods: The study included a retrospective analysis of medical records of women with T2D with first diagnosed cancer during 2012-2016. The bases for the study were specialized medical institutions in Ivano-Frankivsk region. The obtained results were processed using statistical programs “Microsoft Excel” and “Statistika-12”. Results: Breast, uterine, and ovarian cancer were detected in 202 postmenopausal women, 63.92% from the total number of cancer cases in women. An increased risk of breast [OR = 1.24; 95% CI (1.04 – 1.50) P = 0.019] and uterine cancer [OR = 1.32; 95% CI (1.02 – 1.69) P = 0.040] has been identified. Most often, before the detection of cancer, women received combination therapy with sulfonylurea and metformin (83 patients (57.64%)) with BMI 32.64 ± 3.69 kg/m2. The difference between risk of cancer on metformin monotherapy and on sulfonylurea monotherapy [OR = 2.17; 95% CI (0.88 – 5.36) P = 0.141] or on combination therapy [OR = 1.68; 95% CI (0.76 – 3.74) P = 0.276] was not found. Conclusions: Postmenopausal women have an increased risk of breast and uterine cancer and are recommended to be screened for these diseases

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Obstructive Sleep Apnoea and Type 2 Diabetes

US Endocrinology ◽

10.17925/use.2014.10.01.35 ◽

2014 ◽

Vol 10 (01) ◽

pp. 35 ◽

Cited By ~ 1

Author(s):

Abd A Tahrani ◽

Asad Ali ◽

◽

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Medical Condition ◽

Diabetes Type 2 ◽

Sleep Apnoea ◽

Obstructive Sleep ◽

Increased Risk ◽

Osa Treatment ◽

The Impact

With the growing prevalence of obesity, the burden of type 2 diabetes is increasing. Obstructive sleep apnea (OSA) is a very common medical condition that is associated with increased risk for cardiovascular disease and mortality. Obesity is a common risk factor for OSA and type 2 diabetes and hence it is not surprising that OSA and type 2 diabetes are interlinked. OSA has been shown to be an independent risk factor for the development of incident pre-diabetes/type 2 diabetes. OSA is also associated with worse glycemic control and vascular disease in patients with type 2 diabetes. However, evidence for the benefits of OSA treatment in patients with type 2 diabetes is still lacking. The aim of this article is to provide an overview of OSA, the relationships between OSA and dysglycemia and the impact of OSA in patients with type 2 diabetes, highlighting recent advances in the field.

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Increased risk of osteoporotic fractures in patients with Cushing's syndrome

Acta Endocrinologica ◽

10.1530/eje.0.1460051 ◽

2002 ◽

pp. 51-56 ◽

Cited By ~ 72

Author(s):

P Vestergaard ◽

J Lindholm ◽

JO Jorgensen ◽

C Hagen ◽

HC Hoeck ◽

...

Keyword(s):

Fracture Risk ◽

Cushing’S Syndrome ◽

Osteoporotic Fractures ◽

Cushing's Syndrome ◽

Time Interval ◽

Pituitary Disease ◽

Background Population ◽

Increased Risk ◽

And Gender ◽

Self Administered Questionnaire

OBJECTIVE: To evaluate if fracture risk was increased in patients with Cushing's syndrome due to the increased endogenous cortisol production. DESIGN: Cohort. METHODS: A self-administered questionnaire was mailed to 125 patients with Cushing's syndrome diagnosed between 1985 and 1999 in Denmark. The response of each patient was compared with that of three age- and gender-matched control subjects randomly drawn among respondents to the same questionnaire from the background population. RESULTS: One hundred and four patients (83%) responded. The median age of the patients was 48 years (range 19-85 years). Sixty-eight had pituitary disease, 28 had adrenal disease, four had had both pituitary and adrenal surgery while four had not undergone surgery at the time of the study. The median time from diagnosis to surgery was 0.2 (range 0-3) years. Eighty-six percent were cured following surgery. There was an increased fracture risk within the last 2 years prior to diagnosis (incidence rate ratio 6.0, 95% confidence intervals (CI): 2.1-17.2). More than 2 years prior to diagnosis and following diagnosis there was no difference in fracture risk between patients and controls. The patients had more low-energy fractures than the controls (relative risk 5.4, 95% CI: 1.4-20.1). There was no difference in fracture risk between patients with adrenal or pituitary disease. CONCLUSIONS: Patients with Cushing's syndrome had an increased fracture risk in a narrow time interval before diagnosis, while no increase in fracture risk could be demonstrated after diagnosis and treatment.

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Diabetes increases the risk of breast cancer: a meta-analysis

Endocrine Related Cancer ◽

10.1530/erc-12-0242 ◽

2012 ◽

Vol 19 (6) ◽

pp. 793-803 ◽

Cited By ~ 58

Author(s):

Prue J Hardefeldt ◽

Senarath Edirimanne ◽

Guy D Eslick

Keyword(s):

Breast Cancer ◽

Type 2 Diabetes ◽

Reference Lists ◽

Meta Analysis ◽

Statistical Significance ◽

Increased Risk ◽

And Gender ◽

Study Participants

The aim of this meta-analysis was to collate and analyse all primary observational studies investigating the risk of breast cancer (BC) associated with diabetes. In addition, we aimed to complete subgroup analyses by both type of diabetes and gender of study participants to further clarify the origin of any such association between the two. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect and Google Scholar with additional cross-checking of reference lists. Collated data were assessed for heterogeneity and a pooled odds ratio (OR) calculated. Forty-three studies were included in the meta-analysis with 40 studies investigating BC in women and six studies investigating BC in men. Overall, we found a significantly increased risk of BC associated with diabetes in women (OR 1.20, 95% confidence interval (CI) 1.13–1.29). After subgroup analysis by type of diabetes, the association was unchanged with type 2 diabetes (OR 1.22, 95% CI 1.07–1.40) and nullified with gestational diabetes (OR 1.06, 95% CI 0.79–1.40). There were insufficient studies to calculate a pooled OR of the risk of BC associated with type 1 diabetes. There was an increased risk of BC in males with diabetes mellitus; however, the results did not reach statistical significance (OR 1.29, 95% CI 0.99–1.67). In conclusion, diabetes increases the risk of BC in women. This association is confirmed in women with type 2 diabetes and supports the hypothesis that diabetes is an independent risk factor for BC.

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Obstructive Sleep Apnoea and Type 2 Diabetes

European Endocrinology ◽

10.17925/ee.2014.10.01.43 ◽

2010 ◽

Vol 10 (1) ◽

pp. 43 ◽

Cited By ~ 5

Author(s):

Abd A Tahrani ◽

Asad Ali ◽

◽

Keyword(s):

Type 2 Diabetes ◽

Risk Factor ◽

Obstructive Sleep Apnoea ◽

Medical Condition ◽

Diabetes Type 2 ◽

Sleep Apnoea ◽

Obstructive Sleep ◽

Increased Risk ◽

The Impact

With the growing prevalence of obesity, the burden of type 2 diabetes is increasing. Obstructive sleep apnoea (OSA) is a very common medical condition that is associated with increased risk of cardiovascular disease and mortality. Obesity is a common risk factor for OSA and type 2 diabetes and hence it is not surprising that OSA and type 2 diabetes are interlinked. OSA has been shown to be an independent risk factor for the development of incident pre-diabetes/type 2 diabetes. OSA is also associated with worse glycaemic control and vascular disease in patients with type 2 diabetes. However, evidence for the benefits of OSA treatment in patients with type 2 diabetes is still lacking. The aim of this article is to provide an overview of OSA, the relationships between OSA and dysglycaemia and the impact of OSA in patients with type 2 diabetes, highlighting recent advances in the field.

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Associations between Aquaglyceroporin Gene Polymorphisms and Risk of Type 2 Diabetes Mellitus

BioMed Research International ◽

10.1155/2018/8167538 ◽

2018 ◽

Vol 2018 ◽

pp. 1-7 ◽

Cited By ~ 2

Author(s):

Yijun Wang ◽

Gang Chen ◽

Qingyun Tu ◽

Junxia Wu ◽

Yu Qin ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Diseases ◽

Proteinase K ◽

Nucleotide Polymorphisms ◽

Chinese Han ◽

Single Nucleotide ◽

Increased Risk ◽

Polymerase Chain ◽

And Gender

Objectives. AQP7 and AQP9 represent glycerol channel in adipose tissue and liver and have been associated with metabolic diseases. We aimed to investigate the associations between genetic variants in AQP7 and AQP9 genes and the risk of type 2 diabetes (T2DM) in Chinese population. Methods. Blood samples were drawn from 400 T2DM patients and 400 age- and gender-matched controls. Genomic DNA was extracted by proteinase K digestion and phenol–chloroform extraction. Genotyping of 5 single nucleotide polymorphisms (SNPs) in AQP7 (rs2989924, rs3758269, and rs62542743) and AQP9 (rs57139208, rs16939881) was performed by the polymerase chain reaction assay with TaqMan probes. Results. The subjects with rs2989924 GA+AA genotypes had 1.47-fold increased risk of T2DM (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.06-2.04), compared to those with GG genotype, and this association remained significant after adjustment for covariates (OR 1.66, 95% CI 1.07-2.57). When compared with rs3758269 CC genotype, the subjects with CT+TT genotypes had 45% decreased T2DM risk after multivariate adjustment (OR 0.55, 95% CI 0.35-0.85). The associations were evident in elder and overweight subjects and those with central obesity. No association was observed between AQP9 SNPs and T2DM risk. Conclusions. AQP7 SNP rs2989924 and rs3758269 were associated with T2DM risk in Chinese Han population.

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Dipeptidyl Peptidase-4 Inhibitors as a Third-Line Oral Antihyperglycaemic Agent in Patients with Type 2 Diabetes Mellitus: The Impact of Ethnicity

International Journal of Endocrinology ◽

10.1155/2014/354040 ◽

2014 ◽

Vol 2014 ◽

pp. 1-5

Author(s):

X. Zhang ◽

B. Brooks ◽

L. Molyneaux ◽

E. Landy ◽

R. Banatwalla ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dipeptidyl Peptidase ◽

Dipeptidyl Peptidase 4 ◽

Asian Patients ◽

Dipeptidyl Peptidase 4 Inhibitors ◽

Before And After ◽

Third Line ◽

And Gender ◽

The Impact

Aims. The aim of this study is to examine the efficacy of adding a dipeptidyl peptidase-4 (DPP-4) inhibitor to patients with type 2 diabetes inadequately controlled by metformin and sulphonylurea combination treatment. The response of Asian and non-Asian patients to this regimen was also examined.Methods. The medical and computerized records of 80 patients were examined. These patients had baseline HbA1c levels ranging from 7.0 to 12.5% and had a DPP-4 inhibitor add-on therapy for a minimum period of 12 weeks. The primary endpoint was the change in HbA1c level before and after DPP-4 inhibitor treatment.Results. During oral triple therapy, there was a reduction of HbA1c from 8.3% (7.7–8.9) to 7.2% (6.8–7.6) and 26 patients (32.5%) achieved an HbA1c <7%. Poor baseline glycaemic control, lower BMI, and younger age were associated with a better response, but duration of diabetes and gender did not affect outcome. The HbA1c reduction was not different between Asians and non-Asians group [−1.00% (0.6–1.3) vs −0.90% (0.4–1.6)].Conclusions. DPP-4 inhibitor as a third-line add-on therapy can achieve significant glycaemic improvement in patients with type 2 diabetes inadequately controlled on the combination of metformin and sulphonylurea. The improvement in HbA1c was similar between Asian and non-Asian patients.

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Interactions between genetic polymorphisms of glucose metabolizing genes and smoking and alcohol consumption in the risk of type 2 diabetes mellitus

Applied Physiology Nutrition and Metabolism ◽

10.1139/apnm-2017-0232 ◽

2017 ◽

Vol 42 (12) ◽

pp. 1316-1321 ◽

Cited By ~ 4

Author(s):

Kaiping Gao ◽

Yongcheng Ren ◽

Jinjin Wang ◽

Zichen Liu ◽

Jianna Li ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Lifestyle Factors ◽

Environment Interaction ◽

Nucleotide Polymorphisms ◽

Gene Environment ◽

Increased Risk ◽

The Impact

The impact of gene-environment interaction on diabetes remains largely unknown. We aimed to investigate if interaction between glucose metabolizing genes and lifestyle factors is associated with type 2 diabetes mellitus (T2DM). Interactions between genotypes of 4 glucose metabolizing genes (MTNR1B, KCNQ1, KLF14, and GCKR) and lifestyle factors were estimated in 722 T2DM patients and 759 controls, using multiple logistic regression. No significant associations with T2DM were detected for the single nucleotide polymorphisms of MTNR1B, KLF14 and GCKR. However, rs151290 (KCNQ1) polymorphisms were found to be associated with risk of T2DM. Compared with AA, the odds ratios (ORs) of AC or CC genotypes for developing T2DM were 1.545 (P = 0.0489) and 1.603 (P = 0.0383), respectively. In stratified analyses, the associations were stronger in smokers with CC than smokers with AA (OR = 3.668, P = 0.013); drinkers with AC (OR = 5.518, P = 0.036), CC (OR = 8.691, P = 0.0095), and AC+CC (OR = 6.764, P = 0.016) than drinkers with AA. Compared with nondrinkers with AA, drinkers who carry AC and CC had 12.072-fold (P = 0.0007) and 8.147-fold (P = 0.0052) higher risk of developing T2DM. In conclusions, rs151290 (KCNQ1) polymorphisms are associated with increased risk of T2DM, alone and especially in interaction with smoking and alcohol.

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