Increased incidence of genital warts among women and men with type 1 diabetes compared with the general population-results from a nationwide registry-based, cohort study.

AIMS: To estimate the incidence rates of genital warts (GWs) in women and men with type 1 diabetes compared to persons without diabetes. METHODS: In this nationwide registry-based cohort study, we included the entire population aged 15 to 49 years living in Denmark between 1996 and 2016. From national registries, we retrieved individual level information on diabetes status, diagnoses and treatment of GWs, and potential confounding variables. We used Poisson regression to model sex- and age-specific incidence rates of GWs in persons with type 1 diabetes and persons without diabetes. Based on the models, we computed sex-specific incidence rate ratios (IRRs) of GWs in persons with type 1 diabetes compared to persons without diabetes, overall and according to age. RESULTS: The analysis included 3,514,824 persons without type 2 diabetes and no GW diagnoses before baseline. The incidence rate of GWs in persons with type 1 diabetes was higher than in those without diabetes, both among women (IRR = 1.59; 95% CI, 1.42-1.78) and men (IRR = 1.36; 95% CI, 1.25-1.48). The pattern of increased incidence rates of GWs in persons with type 1 diabetes was seen at all ages. CONCLUSIONS: Persons with type 1 diabetes have higher incidence rates of GWs than persons without diabetes. This supports the importance of HPV vaccination of young girls and boys with type 1 diabetes.

Prospective association between late evening food consumption and risk of prediabetes and diabetes: the Whitehall II cohort study.

AIMS: We examined whether late evening food consumption was prospectively associated with the risk of developing prediabetes or diabetes in a large observational study of individuals with normoglycaemia. METHODS: Participants were 2642 men and women with normoglycaemia (HbA1c < 39 mmol/mol; < 5.7%) from the Whitehall II study. Time of last eating episode (TLEE) before the examination day was assessed at baseline. We studied the associations of TLEE with 5-year changes in HbA1c and risk of developing prediabetes or diabetes (HbA1c ≥ 39 mmol/mol; ≥ 5.7%). Potential heterogeneity in the association between TLEE and prediabetes or diabetes was examined using recursive partitioning modelling for time-to-event outcomes. RESULTS: There was a tendency of an overall association of TLEE with change in HbA1c but with little effect size [ß per 1-h increase in TLEE = 0.2 mmol/mol, 95% CI -0.0 to 0.3 (0.01%, -0.00 to 0.03); P = 0.055] and no association with the risk of developing prediabetes/diabetes (risk ratio per 1-h increase in TLEE = 1.03, 95% CI 0.94 to 1.13; P = 0.511). According to the recursive partitioning modelling, women with HbA1c ≤ 36 mmol/mol and TLEE after 21:00 had a 1.51 times (95% CI 1.16 to 1.93) higher 5-year risk of developing prediabetes or diabetes than those having their TLEE between 16:00 and 21:00 (35.4% vs. 23.5%; P = 0.003). CONCLUSIONS: There was no overall association of TLEE with the development of prediabetes or diabetes in the Whitehall II population. However, explorative analyses suggested that eating late in the evening was associated with increased risk of developing prediabetes/diabetes among women with good glycaemic control. Whether restricting late evening food consumption is effective and feasible for the prevention of Type 2 diabetes needs testing in randomized controlled trials.

Beta-blockers in noncardiac surgery: Did observational studies put us back on safe ground?

Based on landmark trials, international guidelines had for years promoted the use of beta-blockers in the setting of non-cardiac surgery. In 2011, concerns were raised regarding the integrity of some of the landmark trials, as the Dutch Erasmus Medical Center found some of them to be scientifically incorrect. Based on the remaining studies that were to be trusted, investigations showed that, in contrast to prior beliefs, the widespread use of perioperative beta-blockers might be harmful. A call for further investigations into the matter ushered in several observational studies evaluating the safety of perioperative beta-blocker therapy in specific patient subgroups. Within this review, we discuss important aspects for making these decisions, and compare the major observational studies and specific estimates of risk in subgroups of interest. We conclude that patients at high risk with heavy co-morbidities, such as heart failure, may benefit from beta-blocker therapy, whereas low-risk patients, such as patients with uncomplicated hypertension, may be at increased risk with beta-blocker therapy. We provide a critical review of current perioperative guidelines in view of the new observational data, suggesting that the recommended schematics, such as the Revised Cardiac Risk Index, for risk stratification of patients in this setting may be suboptimal. Further, we provide discussions of other aspects, including risk of sepsis, type of beta-blocker, and the potential of perioperative beta-blocker withdrawal, which may be important in guiding future studies. Summarising the current evidence, we argue that, after a precarious decade, we may just now, be back on safe ground.

Simulation-based point-of-care ultrasound training: a matter of competency rather than volume.

BACKGROUND: Point-of-care ultrasonography plays an increasingly important role in the initial resuscitation of critically ill patients but acquisition of the skill is associated with long learning curves. The skills required to perform ultrasound examinations can be practiced in a simulated setting before being performed on actual patients. The aim of this study was to investigate the learning curves for novices training the FAST protocol on a virtual-reality simulator. METHODS: Ultrasound novices (N = 25) were instructed to complete a FAST training program on a virtual-reality ultrasound simulator. Participants were instructed to continue training until they reached a previously established mastery learning level, which corresponds to the performance level of a group of ultrasound experts. Performance scores and time used during each FAST examination were used to determine participants' learning curves. RESULTS: The participants attained the mastery learning level within a median of three (range two to four) attempts corresponding to a median of 1 h 46 min (range 1 h 2 min to 3 h 37 min) of simulation training. The ultrasound novices' examination speed improved significantly with training, and continued to improve even after they attained the mastery learning level (P = 0.011). Twenty-three participants attained the mastery learning level. CONCLUSION: Novices can attain mastery learning levels using simulation-based ultrasound training with less than, on average, 2 h of practice. However, we found large variations in the amount of training needed, which raises questions about the adequacy of current volume-based models for determining ultrasound competency.

Decreasing incidence of foot ulcer among patients with type 1 and type 2 diabetes in the period 2001-2014.

AIM: Diabetic foot ulcer (DFU) is a serious complication to diabetes. The aim was to study the incidence of first DFU among patients with type 1 (T1DM) and type 2 diabetes (T2DM), stratified according to etiology: neuropathic, neuro-ischemic or ischemic, over a period of 14years (2001-2014). METHODS: DFU incidence rates were calculated from electronic patient record data from patients with T1DM and complicated T2DM from a large specialized diabetes hospital with a multidisciplinary foot clinic in Denmark. Poisson regression was used to model incidence of first DFU according to calendar year, diabetes type and etiology. RESULTS: Among 5640 patients with T1DM 255 developed a DFU, corresponding to an incidence of 5.8 (95% confidence interval (95%CI) 5.1-6.5) per 1000 patient years; this incidence dropped from 8.1 (95%CI 5.4-11.9) per 1000 patient years in 2002 to 2.6 (95%CI 1.3-5.3) in 2014 (p=0.0059). Among 6953 patients with T2DM 310 developed a DFU, corresponding to an incidence of 11.3 (95%CI 10.1-12.6) per 1000 patient years; this incidence dropped from 17.0 (95%CI 12.2-23.8) per 1000 patient years in 2002 to 8.7 (95%CI 5.3-14.1) per 1000 patient year (p=0.0260) in 2014. CONCLUSION: The incidence of DFU has decreased substantially in T1DM as well as in T2DM. This change was driven by a decrease in incidence of neuropathic ulcers.

Cohort study of preoperative blood pressure and risk of 30-day mortality after elective non-cardiac surgery.

BACKGROUND: Preoperative blood pressure (BP) thresholds associated with increased postoperative mortality remain unclear. We investigated the relationship between preoperative BP and 30-day mortality after elective non-cardiac surgery. METHODS: We performed a cohort study of primary care data from the UK Clinical Practice Research Datalink (2004-13). Parsimonious and fully adjusted multivariable logistic regression models, including restricted cubic splines for numerical systolic and diastolic BP, for 30-day mortality were constructed. The full model included 29 perioperative risk factors, including age, sex, comorbidities, medications, and surgical risk scale. Sensitivity analyses were conducted for age (>65 vs <65 years old) and the timing of BP measurement. RESULTS: A total of 251 567 adults were included, with 589 (0.23%) deaths within 30 days of surgery. After adjustment for all risk factors, preoperative low BP was consistently associated with statistically significant increases in the odds ratio (OR) of postoperative mortality. Statistically significant risk thresholds started at a preoperative systolic pressure of 119 mm Hg (adjusted OR 1.02 [95% confidence interval (CI) 1.01-1.02]) compared with the reference (120 mm Hg) and diastolic pressure of 63 mm Hg [OR 1.24 (95% CI 1.03-1.49)] compared with the reference (80 mm Hg). As BP decreased, the OR of mortality risk increased. Subgroup analysis demonstrated that the risk associated with low BP was confined to the elderly. Adjusted analyses identified that diastolic hypertension was associated with increased postoperative mortality in the whole cohort. CONCLUSIONS: In this large observational study we identified a significant dose-dependent association between low preoperative BP values and increased postoperative mortality in the elderly. In the whole population, elevated diastolic, not systolic, BP was associated with increased mortality.

High and low vitamin D level is associated with cardiovascular autonomic neuropathy in people with Type 1 and Type 2 diabetes.

AIM: To investigate the possible association between vitamin D deficiency and cardiovascular autonomic neuropathy in people with diabetes. METHODS: A total of 113 people with Type 1 or Type 2 diabetes [mean (interquartile range) diabetes duration 22.0 (12-31) years, mean (sd) age 56.2 (13.0) years, 58% men] underwent vitamin D (D2 and D3) assessment, and were screened for cardiovascular autonomic neuropathy using three cardiovascular reflex tests [heart rate response to deep breathing (E/I ratio), to standing (30/15 ratio) and to the Valsalva manoeuvre] and assessment of 5-min resting heart rate and heart rate variability indices. RESULTS: We found an inverse U-shaped association between serum vitamin D level and E/I ratio, 30/15 ratio and three heart rate variability indices (P < 0.05). Vitamin D level was non-linearly associated with cardiovascular autonomic neuropathy diagnosis (P < 0.05 adjusted for age and sex). Linear regression models showed that an increase in vitamin D level from 25 to 50 nmol/l was associated with an increase of 3.9% (95% CI 0.1;7.9) in E/I ratio and 4.8% (95% CI 4.7;9.3) in 30/15 ratio. Conversely, an increase from 125 to 150 nmol/l in vitamin D level was associated with a decrease of 2.6% (95% CI -5.8;0.1) and 4.1% (95% CI -5.8;-0.5) in the respective outcome measures. CONCLUSIONS: High and low vitamin D levels were associated with cardiovascular autonomic neuropathy in people with diabetes. Future studies should explore this association and the efficacy of treating dysvitaminosis D to prevent cardiovascular autonomic neuropathy.

Methylglyoxal is associated with changes in kidney function among individuals with screen-detected Type 2 diabetes mellitus.

AIMS: The glycolysis-derived metabolite methylglyoxal has been linked to clinical microvascular complications, including diabetic nephropathy. We aimed to further investigate the hypothesis that methylglyoxal is involved in decline in renal function by assessing the associations between measures of renal function during a 6-year follow-up in 1481 people with screen-detected Type 2 diabetes, as part of the Danish arm of the ADDITION-Europe trial (ADDITION-DK). METHODS: Biobank serum samples collected at ADDITION-DK baseline (2001-2006) and follow-up (2009-2010) were used in the current analysis of methylglyoxal. We assessed cross-sectional baseline and longitudinal associations between methylglyoxal and urinary albumin-to-creatinine ratio (ACR) or estimated GFR (eGFR), and between methylglyoxal and categories of albuminuria or reduced eGFR. RESULTS: Baseline methylglyoxal was positively associated with ACR at baseline (12% higher ACR per doubling in methylglyoxal levels), and change in methylglyoxal during 6 years of follow-up was inversely associated with change in eGFR (-1.6 ml/min/1.73 m2 per doubling in methylglyoxal change), in models adjusted for age, sex, HbA1c , systolic blood pressure, anti-hypertensive treatment, LDL-cholesterol, lipid-lowering treatment, C-reactive protein and smoking. CONCLUSIONS: In a population of people with screen-detected Type 2 diabetes, we observed associations between methylglyoxal and markers of renal function: 6-year change in methylglyoxal was inversely associated with 6-year change in eGFR. Also, methylglyoxal at baseline was positively associated with ACR at baseline. Our study lends further support to a role for methylglyoxal in the pathogenesis of diabetic nephropathy.

Increased healing in diabetic toe ulcers in a multidisciplinary foot clinic-An observational cohort study.

AIM: To study toe ulcer healing in patients with diabetic foot ulcers attending a multidisciplinary foot clinic over a 10 years period. METHODS: The study was retrospective, consecutive and observational during 2001 through 2011. The patients were treated according to the International Consensus on the Diabetic Foot. During the period the chiropodist staffing in the foot clinic was doubled; new offloading material and orthopedic foot corrections for recalcitrant ulcers were introduced. Healing was investigated in toe ulcers in Cox regression models. RESULTS: 2634 patients developed foot ulcers, of which 1461 developed toe ulcers; in 790 patients these were neuropathic, in 551 they were neuro-ischemic and in 120 they were critically ischemic. One-year healing rates increased in the period 2001-2011 from 75% to 91% for neuropathic toe ulcers and from 72% to 80% for neuro-ischemic toe ulcers, while no changes was observed for ischemic toe ulcers. Adjusted for changes in the patient population, the overall rate of healing for neuropathic and neuro-ischemic toe ulcers almost doubled (HR=1.95 [95% CI: 1.36-2.80]). CONCLUSION: The results show that the healing of toe ulcers improved. This outcome could not be explained by changes in the patient characteristics, but coincided with a number of improvements in organization and therapy.

Diabetes-related tuberculosis in Denmark: effect of ethnicity, diabetes duration and year of diagnosis.

BACKGROUND: The association between diabetes mellitus (DM) and tuberculosis (TB) has been established on the basis of cross-sectional studies; however, only a few longitudinal studies have been conducted, with inconsistent results. OBJECTIVE: To study the effect of ethnicity and the presence and duration of DM on the risk of incident TB based on 15 years of follow-up of the entire Danish population. DESIGN AND METHODS: Using Poisson regression analysis, we estimated TB incidence in individuals with DM vs. those without DM by linking nationwide DM and TB registers to the National Civil Register at case level. RESULTS: The TB rate ratio was 1.9 in individuals with DM compared to non-DM individuals, regardless of country of birth, with the exception of African-born individuals (rate ratio 0.5). The risk decreased drastically within the first 2 years after the diagnosis of DM; no association was found with longer durations of DM. The risk also decreased the later the year of DM diagnosis. CONCLUSIONS: The study confirmed DM as a risk factor for TB, except in the case of African-born individuals. Other non-DM risk factors for TB could act as effect-modifiers on the DM-TB association. Implementing earlier DM diagnosis and improving metabolic control may reduce the risk of DM-related TB.

Intensive multifactorial treatment modifies the effect of family history of diabetes on glycaemic control in people with Type 2 diabetes: a post hoc analysis of the ADDITION-Denmark randomized controlled trial.

AIM: To investigate whether intensive multifactorial treatment can reverse the predisposed adverse phenotype of people with Type 2 diabetes who have a family history of diabetes. METHODS: Data from the randomized controlled trial ADDITION-Denmark were used. A total of 1441 newly diagnosed patients with diabetes (598 with family history of diabetes) were randomized to intensive treatment or routine care. Family history of diabetes was defined as having one parent and/or sibling with diabetes. Linear mixed-effects models were used to assess the changes in risk factors (BMI, waist circumference, blood pressure, lipids and HbA1c ) after 5 years of follow-up in participants with and without a family history of diabetes. An interaction term between family history of diabetes and treatment group was included in the models to test for a modifying effect of the intervention. All analyses were adjusted for age, sex, baseline value of the risk factor and general practice (random effect). RESULTS: At baseline, participants with a family history of diabetes were younger and had a 1.1 mmol/mol (0.1%) higher HbA1c concentration at the time of diagnosis than those without a family history of diabetes. Family history of diabetes modified the effect of the intervention on changes in HbA1c levels. In the group receiving routine care, participants with a family history of diabetes experienced an improvement in HbA1c concentration that was 3.3 mmol/mol (0.3%) lower than the improvement found in those without a family history of diabetes after 5 years of follow-up. In the intensive treatment group, however, there was no difference in HbA1c concentrations between participants with and without a family history of diabetes after 5 years of treatment. CONCLUSIONS: Intensive treatment of diabetes may partly remove the adverse effects of family history of diabetes on glycaemic control. The effect of this improvement on long-term diabetic complications warrants further investigation.

The role of serum methylglyoxal on diabetic peripheral and cardiovascular autonomic neuropathy: the ADDITION Denmark study.

AIMS: Cardiovascular autonomic neuropathy and diabetic peripheral neuropathy are common diabetic complications and independent predictors of cardiovascular disease. The glucose metabolite methylglyoxal has been suggested to play a causal role in the pathogeneses of diabetic peripheral neuropathy and possibly diabetic cardiovascular autonomic neuropathy. The aim of this study was to investigate the cross-sectional association between serum methylglyoxal and diabetic peripheral neuropathy and cardiovascular autonomic neuropathy in a subset of patients in the ADDITION-Denmark study with short-term screen-detected Type 2 diabetes (duration ~ 5.8 years). METHODS: The patients were well controlled with regard to HbA(1c), lipids and blood pressure. Cardiovascular autonomic neuropathy was assessed by measures of resting heart rate variability and cardiovascular autonomic reflex tests. Diabetic peripheral neuropathy was assessed by vibration detection threshold (n = 319), 10 g monofilament (n = 543) and the Michigan Neuropathy Screening Instrument questionnaire (n = 966). Painful diabetic neuropathy was assessed using the Brief Pain Inventory short form (n = 882). RESULTS: No associations between methylglyoxal and cardiovascular autonomic reflex tests or any measures of diabetic peripheral neuropathy or painful diabetic neuropathy were observed. However, a positive association between methylglyoxal and several heart rate variability indices was observed, although these associations were not statistically significant when corrected for multiple testing. CONCLUSION: Serum methylglyoxal is not associated with cardiovascular autonomic neuropathy, diabetic peripheral neuropathy or painful diabetic neuropathy in this cohort of well-treated patients with short-term diabetes.

Geographic differences in the associations between impaired glucose regulation and cardiovascular risk factors among young adults.

AIMS: To assess geographic differences in the association between BMI, blood pressure and lipid levels with impaired glucose regulation among young adults from various geographical regions. METHODS: This was a cross-sectional study including data from 6987 participants aged ≤ 30 years from India, Singapore, Australia, Greenland, Kenya and Tanzania. Impaired glucose regulation was determined by the 75-g oral glucose tolerance test. For each geographical region, BMI, blood pressure and lipids were examined and compared between participants with normal glucose tolerance and those with impaired glucose regulation. Multiple logistic regression models were used to assess the association between risk factors and impaired glucose regulation. RESULTS: Indian and East African people had a higher prevalence of impaired glucose regulation compared with participants from other regions, despite their lower BMI. Compared with the other regions, blood pressure was lower among Indian and Singaporean people but higher in those from Greenland. Greenlanders had the highest, while Indian and East-African people, had the lowest level of HDL cholesterol. BMI was positively associated with impaired glucose regulation in all regions, and there were no statistically significant geographic differences. In the Indian, Singaporean and Australian participants, there was a positive association between blood pressure and impaired glucose regulation. Triglycerides were positively associated with and HDL cholesterol had no association with impaired glucose regulation in all geographical regions. CONCLUSIONS: Higher BMI and triglyceride levels were positively associated with prevalent impaired glucose regulation in all geographical regions. There were geographic differences in the association between impaired glucose regulation and blood pressure and lipids, probably reflecting environmental and genetic factors.

Association between serum bilirubin and cardiovascular disease in an overweight high risk population from the SCOUT trial.

BACKGROUND AND AIMS: An inverse relationship between (serum) total bilirubin and risk of cardiovascular disease has been reported previously, but longitudinal data on overweight and obese patients are lacking. We have investigated the relationship between total bilirubin and cardiovascular adverse events in a large group of patients with risk factors for cardiovascular disease who were enrolled in a large weight loss trial. METHODS AND RESULTS: Data from the Sibutramine Cardiovascular Outcomes (SCOUT) trial, including almost 10.000 overweight/obese high cardiovascular risk patients, were used. The relationship between total bilirubin level at screening and the primary outcome (i.e. non-fatal myocardial infarction, non-fatal stroke, resuscitated cardiac arrest or cardiovascular death) for the entire study period was investigated using Cox proportional hazards models. The population was divided into four groups based on total bilirubin levels (normal range 5-25 µmol/L). Time-dependent Cox analyses were also performed to adjust for weight loss over time. Initial analyses adjusted for sex, age and treatment allocation showed significantly reduced hazard ratios of 0.80 (95% confidence interval 0.68-0.94), 0.73 (0.62-0.86) and 0.77 (0.65-0.91), for the three higher total bilirubin groups: >8 and ≤10 µmol/L, >10 and ≤13 µmol/L and >13 µmol/L (5-95 interpercentile range for total bilirubin at screening; 6-19 µmol/L), compared to the lowest total bilirubin group ≤8 µmol/L. When adjusting for classical cardiovascular risk factors, estimates increased towards unity. Additional adjustment for indicators of liver function did not alter the results. A time-dependent Cox model, adjusted for weight loss, demonstrated a similar trend. CONCLUSION: Bilirubin was not a risk-factor independent from other traditional cardiovascular risk-factors in our population.

Reduced incidence of lower-extremity amputations in a Danish diabetes population from 2000 to 2011.

AIMS: Diabetic foot disease and amputations severely reduce quality of life and have major economic consequences. The aim of this study was to estimate time trends in the incidence of lower-extremity amputations in Danish people with diabetes. METHODS: We studied major and minor lower-extremity amputations from 2000 to 2011 among 11,332 people with diabetes from the Steno Diabetes Center. Amputations were identified by linkage of the electronic medical system with the National Patient Registry. Sex-specific incidence rates of amputations by age, diabetes duration, calendar time and diabetes type were modelled by Poisson regression. RESULTS: From 2000 to 2011, 384 incident lower-extremity amputations (205 major, 179 minor) occurred during 100,495 years of patient follow-up. From 2000 to 2011, the incidence of all lower-extremity amputations decreased by 87.5% among men and 47.4% among women with type 1 diabetes and by 83.3% among men and 79.1% among women with type 2 diabetes (P < 0.001). In particular, there was a decline in major lower-extremity amputations. In 2011, the incidence rates of major lower-extremity amputations were 0.25 (95% CI 0.07-0.82) among men and 0.21 (95% CI 0.06-0.71) among women per 1000 patient-years at age 50 years and 0.56 (95% CI 0.18-1.89) among men and 0.41 (95% CI 0.16-1.09) among women per 1000 patient-years at age 70 years. No significant change in incidence of minor amputations was observed. CONCLUSION: The incidence of major lower-extremity amputations reduced significantly from 2000 to 2011 in Danish people with diabetes followed at a diabetes specialist centre.

Reproducibility of ultrasonography for assessing abdominal fat distribution in a population at high risk of diabetes.

BACKGROUND: Visceral fat plays an important role in the development of metabolic disease independently of the effect of overall abdominal fat. Ultrasonography is an accessible method of accurately assessing abdominal fat distribution in epidemiological studies, but few details about the reproducibility of this method have been published. OBJECTIVE: The aim of this study was to investigate the reproducibility of ultrasonography in the assessment of abdominal fat distribution in a population at high risk of type 2 diabetes. DESIGN AND METHODS: Ultrasonography was used to estimate visceral and subcutaneous abdominal fat. Intra- and interobserver variation, short-term variation and variation between estimates in the fasting and non-fasting state were examined in three samples of 30, 33 and 23 participants from the ADDITION-PRO study. A variance components model was used to calculate intra- and interobserver variation, and Bland-Altman plots were drawn for all three substudies. RESULTS: Coefficients of variation for intra- and interobserver variation were in the range 3.4-6.1%, except for interobserver variation for subcutaneous fat (9.5%). Short-term variation over a median of 35 days had a coefficient of variation of 15%. The effect of a meal was primarily on the visceral estimates and did not extend beyond the first postprandial hour. Non-fasting visceral estimates were larger than fasting estimates. CONCLUSION: Both visceral and subcutaneous fat can be estimated with ultrasonography with adequate intra- and interobserver reproducibility by clinical researchers with limited training, making it a feasible method of assessing abdominal fat distribution in epidemiological studies.

Phylogenetic patterns of skeletal morphometrics and pelvic traits in relation to locomotor mode in frogs.

Frogs are one of the most speciose groups of vertebrate tetrapods (> 6200sp) with a diverse array of locomotor behaviours. Despite the impressive diversity in frog locomotor behaviours, there remains a paucity of information on the relationship between skeletal variation and locomotor mode in frogs and the evolutionary patterns in which these relationships are framed across the frog phylogeny. Our current understanding of the evolution of frog locomotion shows that hopping transitioned into jumping within the Neobatrachia where a variety of pelvic/hindlimb length patterns and locomotor niches have appeared, but this has yet to be studied over a broad taxonomic sample of frogs. Although limb length remains as the primary predictor of leaping performance, pelvic and sacral morphometrics have not been quantified in relation to limb proportions, body size and locomotor mode and previous studies have not sampled more than 24 families. We present a large-scale phylogenetic comparison of skeletal morphometrics in relation to locomotor mode in 188 genera from 37 families. Osteological variation in limb/pelvic girdle morphometrics and pelvic traits that are posited to be associated with locomotor mode were analysed to identify which aspects of the frog skeleton are the best descriptors of locomotor mode. Our results, contrary to previous work, reveal that the greatest axis of variation in frogs is represented by the shape of the sacrum with two pelvic morphologies evident in qualitative and quantitative ancestral trait reconstructions. Limb morphology was not significantly different across most locomotor modes, but we identified several outliers in hindlimb phylomorphospace. Patterns of sacral evolution together with hindlimb length outliers reveal how the general bauplan of this successful group of vertebrate tetrapods is constrained, has radiated and has converged on certain phenotypes to fill an array of locomotor modes.