Association between Smoking Status and the Risk of Hip Fracture in Patients with Type 2 Diabetes: A Nationwide Population-Based Study

Background Limited longitudinal evidence exists regarding the potential association between smoking status and hip fracture among individuals with type 2 diabetes. We investigated this association using large-scale, nationwide cohort data for the Korean population. Methods This nationwide cohort study included 1,414,635 adults aged 40 and older who received Korean National Health Insurance Service health examinations between 2009 and 2012. Subjects with type 2 diabetes were categorized according to their smoking status, amount smoked (pack-years), number of cigarettes smoked per day, and duration of smoking. The results are presented as hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between smoking status parameters and risk of hip fracture in multivariable Cox proportional hazard regression analysis. Results Compared with never-smokers, an increased adjusted HR (aHR) for hip fracture was observed in current smokers (1.681; 95% CI, 1.578 to 1.791), and a comparable aHR for hip fracture was found in former smokers (1.065; 95% CI, 0.999 to 1.136). For former smokers who had smoked 20 pack-years or more, the risk was slightly higher than that for never-smokers (aHR, 1.107; 95% CI, 1.024 to 1.196). The hip fracture risk of female former smokers was similar to that of female current smokers, but the hip fracture risk in male former smokers was similar to that of male never-smokers. Conclusion Smoking is associated with an increased risk of hip fracture in patients with type 2 diabetes. Current smokers with diabetes should be encouraged to quit smoking because the risk of hip fracture is greatly reduced in former smokers

TEM morphology of representative SPN phages.

<p>Each phage name is indicated in the upper left corner of the picture. The representative tails of each group of phage were marked with boxes and the enlarged pictures were shown on the right. (A) Phages using flagella as a receptor. (B) Phages using BtuB as a receptor. (C) Phages using LPS as a receptor.</p

Characteristics of the isolated <i>S</i>. Typhimurium-specific bacteriophages and their identified receptors.

a<p>F-I and F-II, flagella-specific phage group; B, BtuB-specific phage group; L, LPS-specific phage group.</p>b<p><i>flgK</i>, <i>fliR</i> mutations were complemented using pACYC184 vector expressing the <i>flgK</i>⁺ or <i>fliR</i>⁺ gene.</p>c<p><i>btuB</i> mutation was complemented using pACYC184 vector expressing the <i>btuB</i>⁺ gene.</p>d<p><i>rfaL</i> mutation was complemented using pUHE21-<i>lacI</i>^q vector expressing the <i>rfaL</i>⁺ gene.</p

Cross-resistance of phage-resistant <i>Salmonella</i> to the different receptor group phages.

<p>F, B, and L marked in the phage heads indicate group F, group B, and group L phages, respectively. Each receptor in the phage-resistant strains is white-colored. (A) Group F phage-resistant strain is sensitive to group B and group L phages. (B) Group L phage-resistant strain is sensitive to group F and group B phages, but resistant to group L phages, due to modification of O-antigen of LPS. Modified O-antigen is indicated by white triangles. (C) Group B phage-resistant strain is sensitive to group F, but resistant to group B as well as group L phages, probably due to putative interaction between BtuB and O-antigen of LPS. (D) Group L (SPN9TCW phage)-resistant strain is sensitive to group F, but resistant to group B as well as group L phages, probably due to putative interaction between BtuB and O-antigen of LPS.</p

Host receptors of SPN phages.

<p>F, F-I, F-II, B, and L marked in the phage heads indicate group F, group F-I, group F-II, group B, and group L phages, respectively. (A) Group F, group B, and group L phages use flagella (FliC/FljB), BtuB, and O-antigen of LPS as host receptors, respectively. (B) Group F-I and group F-II phages use FliC (grey-colored) and FliC/FljB (black-colored) in the host flagella.</p

Host range of bacteriophages isolated.

a<p>Lytic spectrum: I contains SPN2T, SPN3C, and SPN13B; II contains SPN8T and SPN9T; III contains SPN11T, SPN16C; IV, SPN4S, and SPN19; V contains SPN5T and SPN6T; VI contains SPN7C and SPN9C, VII, SPN10H; VIII contains SPN12C and SPN17T; IX, SPN14; X, SPN18; XI contains SPN1S, SPN2TCW, SPN4B, SPN6TCW, SPN8TCW, and SPN13U; XII, SPN9TCW.</p>b<p>C, clear plaque; T, turbid plaque; I, inhibition zone; –, no infection.</p>c<p>Prophage-cured strain of S. Typhimurium LT2.</p>d<p>NCTC, National Collection of Type Cultures; ATCC, American Type Culture Collection; IVI, International Vaccine Institute.</p

Genetic map of the receptor gene clusters and the mutated genes of resistant strains.

<p>Genes involved in the synthesis of flagella (<i>flgK, fliQ, fliC</i> and <i>fljB</i>), BtuB (<i>btuB</i>), and LPS (<i>rfaL</i> and <i>rfbG</i>) inactivated by transposon insertion were indicated by open arrows. Black arrow marked with hin is a promoter that transcribes the <i>fljB</i> gene. The numbers are locus-tag numbers indicating the locations of the genes in the genome sequence.</p

Flagellin-targeting phages: receptor and sensitivity patterns based on specific gene mutation.

a<p>F-I, flagella-targeting phage group I; F-II, flagella-targeting phage group II.</p>b<p>S, sensitive to infection; R, resistant to infection.</p