BMJ Open Diabetes Research & Care最新文献

Introduction: The prevalence of non-diabetic hyperglycemia (NDH) and type 2 diabetes mellitus (T2DM) is increasing. While T2DM is recognised to be associated with multimorbidity and early mortality, people with NDH are frequently thought to be devoid of such complications, potentially exposing individuals with NDH to suboptimal care. We therefore used the Discover London Secure Data Environment (SDE) dataset to appreciate the relationship of NDH/T2DM with multimorbidity, healthcare usage, and clinical outcomes.

Research design and methods: The dataset was retrospectively analysed between January 1, 2015 and December 31, 2020 to understand the relationship between NDH/T2DM and multimorbidity primary/secondary healthcare usage and clinical outcomes. This was compared with a cohort of individuals with thyroid disease but no NDH/T2DM.

Results: The dataset identified 152,384 and 124,190 adults with NDH and T2DM compared with 11,626 individuals with thyroid disease (control group). Individuals with NDH and individuals with T2DM had a high burden of disease, with only 13.1% of individuals with either NDH or T2DM not found to be suffering from at least one of the disease states of interest. The three most common comorbidities experienced by individuals with NDH were hypertension (41.4%), hypercholesterolemia (37.5%), and obesity (29.8%) compared with retinopathy (68.7%), hypertension (59.4%), and obesity (45.8%) in individuals with T2DM. Comparatively, the most common comorbidities in the control group were depression (30.8%), hypercholesterolemia (24.4%), and hypertension (17.1%). 28 (control group), 12 (NDH), and 16 (T2DM) primary care contacts per individual per year were identified, with 27,881, 282,371, and 314,880 inpatient admissions for the control, NDH, and T2DM cohorts, respectively. Prescription of drugs used to treat T2DM in individuals with NDH and T2DM was 27,772 (18.2%) and 109,361 (88.1%), respectively, accounting for approximately one in five individuals with NDH developing T2DM.

Conclusion: Both NDH and T2DM were associated with significant multimorbidity alongside primary and secondary care utilisation. Given the morbidity highlighted with NDH, we highlight the need for earlier detection of NDH, recognition of multimorbidity associated with both NDH and T2DM, as well as the need for the further implementation of interventions to prevent progression to T2DM/multimorbidity.

Introduction: Chronic hyperglycemia affects neutrophil functions, leading to reduced pathogen killing and increased morbidity. This impairment has been directly linked to increased glycemia, however, how this specifically affects neutrophils metabolism and their differentiation in the bone marrow is unclear and difficult to study.

Research design and methods: We used high-resolution respirometry to investigate the metabolism of resting and activated donor neutrophils, and flow cytometry to measure surface CD15 and CD11b expression. We then used HL-60 cells differentiated towards neutrophil-like cells in standard media and investigated the effect of doubling glucose concentration on differentiation metabolism. We measured the oxygen consumption rate (OCR), and the enzymatic activity of carnitine palmitoyl transferase 1 (CPT1) and citrate synthase during neutrophil-like differentiation. We compared the surface phenotype, functions, and OCR of neutrophil-like cells differentiated under both glucose concentrations.

Results: Donor neutrophils showed significant instability of CD11b and OCR after phorbol 12-myristate 13-acetate stimulation at 3 hours post-enrichment. During HL-60 neutrophil-like cell differentiation, there was a significant increase in surface CD15 and CD11b expression together with the loss of mitochondrial mass. Differentiated neutrophil-like cells also exhibited higher CD11b expression and were significantly more phagocytic. In higher glucose media, we measured a decrease in citrate synthase and CPT1 activities during neutrophil-like differentiation.

Conclusions: HL-60 neutrophil-like differentiation recapitulated known molecular and metabolic features of human neutrophil differentiation. Increased glucose concentrations correlated with features described in hyperglycemic donor neutrophils including increased CD11b and phagocytosis. We used this model to describe metabolic features of neutrophil-like cell differentiation in hyperglycemia and show for the first time the downregulation of CPT1 and citrate synthase activity, independently of mitochondrial mass.

Introduction: The objective of this study was to determine the burden of influenza disease in patients with or without diabetes in a population of American adults to understand the benefits of seasonal vaccination.

Research design and methods: We performed a retrospective cohort study using electronic medical records totaling 1,117,263 from two Louisiana healthcare providers spanning January 2012 through December 2017. Adults 18 years or older with two or more records within the study period were included. The primary outcome quantified was influenza-related diagnosis during inpatient (IP) or emergency room (ER) visits and risk reduction with the timing of immunization.

Results: Influenza-related IP or ER visits totaled 0.0122-0.0169 events per person within the 2013-2016 influenza seasons. Subjects with diabetes had a 5.6-fold more frequent influenza diagnosis for IP or ER visits than in subjects without diabetes or 3.7-fold more frequent when adjusted for demographics. Early immunization reduced the risk of influenza healthcare utilization by 66% for subjects with diabetes or 67% for subjects without diabetes when compared with later vaccination for the 2013-2016 influenza seasons. Older age and female sex were associated with a higher incidence of influenza, but not a significant change in risk reduction from vaccination.

Conclusions: The risk for influenza-related healthcare utilization was 3.7-fold higher if patients had diabetes during 2013-2016 influenza seasons. Early immunization provides a significant benefit to adults irrespective of a diabetes diagnosis. All adults, but particularly patients with diabetes, should be encouraged to get the influenza vaccine at the start of the influenza season.

Introduction: Evidence on the prevalence of foot problems among people with diabetes in India at a national level is lacking. Hence, this study was aimed to assess the burden of high-risk (HR) feet in people with diabetes across India.

Research design and methods: A cross-sectional national-level project 'Save the Feet and Keep Walking' campaign was conducted by the Research Society for the Study of Diabetes in India (RSSDI) from July 10, 2022 to August 10, 2022. A modified version of 3 min foot examination was used to assess the foot problems. Around 10 000 doctors with RSSDI membership were trained online to conduct foot screening and provided a standardised monofilament for detection of loss of protective sensation. People with diabetes aged >18 years who visited the clinics during the study period were examined for foot problems. Data were collected online using the semi-structured questionnaire. A total of 33 259 participants with complete information were included for the final analysis. The foot at risk was categorised based on International Working Group on the Diabetic Foot guidelines 2023.

Results: Nearly 75% of the participants were aged above 45 years. Around 49% had diabetes duration >5 years and uncontrolled diabetes (hemoglobin A1c >8%). Presence of history of foot ulcer (20%), lower limb amputation (15.3%), foot deformities (24.5%) and absence of diminished dorsal pedis and posterior tibial pulses (26.4%) was noted in the study participants. Around 25.2% of them had HR feet and highly prevalent among males. Diabetic kidney and retinal complications were present in 70% and 75.5% of people with HR feet. Presence of heel fissures (OR (95% CI) 4.6 (4.2 to 5.1)) and callus or corns (OR (95% CI) 3.6 (3.3 to 4.0)) were significantly associated with HR feet.

Conclusions: One-fourth of people with diabetes were found to have HR feet in India. The findings are suggestive of regular screening of people with diabetes for foot problems and strengthening of primary healthcare.

Introduction: The prevalence of obesity and glycemic dysfunction in adolescents has increased over the past several decades but less is known on how these conditions are associated with systemic inflammation in this population. This study determined the associations between cardiovascular disease (CVD) risk factors and inflammation among a nationally representative sample of US. adolescents.

Research design and methods: Cross-sectional analyses were conducted among 2693 adolescents aged 12-19 years who participated in the 2015 to March 2020 National Health and Nutrition Examination Surveys. Chronic inflammation was determined using laboratory measures for high-sensitivity C reactive protein (hs-CRP). Adjusted ORs (aOR, 95% CI) were calculated from logistic regression models to determine the association between CVD risk factors (obesity, overweight, dysglycemia, hypertension, hyperlipidemia) and elevated hs-CRP (>3.0 mg/L) while controlling for sociodemographic characteristics and other CVD risk factors.

Results: Overall, 15.3% of adolescents had elevated hs-CRP. Adolescents who were older (16-19 years vs 12-15 years), obese, had A1c ≥5.7% (≥39 mmol/mol), high total cholesterol, or low high-density lipoprotein had hs-CRP distributions that were more high risk (χ² p value <0.001). Adolescents with obesity or A1c ≥5.7% had a sixfold and a nearly twofold higher odds of elevated hs-CRP compared those without obesity and A1c <5.7% after full adjustment (aOR=6.39, 4.64 to 8.79 and aOR=1.70, 1.05 to 3.06, respectively). Adolescents with hypertension or hyperlipidemia were significantly more likely to have elevated hs-CRP compared with those without these conditions after adjustment for sociodemographic characteristics (aOR=2.46, 1.08 to 5.60 and aOR=2.19, 1.36 to 3.54, respectively), but the association was not significant after further adjustment for obesity.

Conclusions: Among US adolescents, obesity was strongly associated with elevated hs-CRP, a marker for future CVD risk. Given the obesity epidemic and the marked proportion with elevated CRP, concern should be given to future CVD risk in younger adults.

Introduction: The objectives of this study were to examine temporal trends in the incidence of bariatric surgery (Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG)) in patients with and without type 2 diabetes mellitus (T2DM). Outcomes of hospitalization and the impact of T2DM on these outcomes were also analyzed.

Research design and methods: We performed an observational study with the Spanish national hospital discharge database. Obese patients with and without T2DM who underwent RYGB and SG between 2016 and 2022 were identified. Propensity score matching (PSM) and logistic regression were used to compare patients with and without T2DM and to evaluate the effect of T2DM and other variables on outcomes of surgery. A variable "severity" was created to cover patients who died in hospital or were admitted to the intensive care unit (ICU).

Results: A total of 32,176 bariatric surgery interventions were performed (28.86% with T2DM). 31.57% of RYGBs and 25.53% of SG patients had T2DM. The incidence of RYGB and SG increased significantly between 2016 and 2022 (p<0.001), with a higher incidence in those with T2DM than in those without (incidence rate ratio 4.07 (95% CI 3.95 to 4.20) for RYGB and 3.02 (95% CI 2.92 to 3.14) for SG). In patients who underwent SG, admission to the ICU and severity were significantly more frequent in patients with T2DM than in those without (both p<0.001). In the multivariate analysis, having T2DM was associated with more frequent severity in those who received SG (OR 1.23; 95% CI 1.07 to 1.42).

Conclusions: Between 2016 and 2022, bariatric surgery procedures performed in Spain increased in patients with and without T2DM. More interventions were performed on patients with T2DM than on patients without T2DM. RYGB was the most common procedure in patients with T2DM. The presence of T2DM was associated with more severity after SG.

Introduction: To estimate the impact of reducing obesity, smoking, and physical inactivity (PIA) prevalence, and of introducing physical activity (PA) as an explicit intervention, on the prevalence, incidence, and mortality of type 2 diabetes mellitus (T2DM) in Oman.

Research design and methods: A deterministic population-level mathematical model was employed to investigate the impact of different scenarios for reducing T2DM risk factors on T2DM epidemiology. The model was stratified by sex, age group, risk factor status, T2DM status, and intervention status and parameterized with nationally representative data. Intervention scenarios were calculated and compared with a baseline (no-intervention) scenario for changes in T2DM prevalence, incidence, and mortality among adult Omanis between 2020 and 2050.

Results: In the no-intervention scenario, T2DM prevalence increased from 15.2% in 2020 to 23.8% in 2050. Achieving the goals of halting the rise of obesity, reducing smoking by 30%, and reducing PIA by 10% as outlined in the WHO's Global Action Plan for Non-communicable Diseases (implemented between 2020 and 2030 and then maintained between 2031 and 2050) would reduce T2DM prevalence by 32.2%, cumulative incidence by 31.3%, and related deaths by 19.3% by 2050. Halting the rise of or reducing obesity prevalence by 10%-50% would reduce T2DM prevalence by 33.0%-51.3%, cumulative incidence by 31.9%-53.0%, and related deaths by 19.5%-35.6%. Reducing smoking or PIA prevalence by 10%-50% would lead to smaller reductions of less than 5% in T2DM prevalence, cumulative incidence, and related deaths. Introducing PA with varying intensities at a 25% coverage would reduce T2DM prevalence by 4.9%-14.1%, cumulative incidence by 4.8%-13.8%, and related deaths by 3.4%-9.6% by 2050.

Conclusions: Intervention-for-prevention efforts targeting obesity reduction and introducing PA could result in major reductions in the T2DM burden. Prioritizing such interventions could alleviate the burden of T2DM in Oman and other countries with similarly high T2DM and obesity burdens.

Introduction: Diabetic polyneuropathy (DPN), a common complication of diabetes, can manifest as small, large, or mixed fiber neuropathy (SFN, LFN, and MFN, respectively), depending on the type of fibers involved. Despite evidence indicating small fiber involvement prior to large fiber involvement in type 1 diabetes mellitus (T1DM)-associated DPN, no evidence has been produced to determine the more prevalent subtype. We aim to determine the more prevalent type of nerve fiber damage-SFN, LFN, and MFN-in T1DM-associated DPN, both with and without pain.

Research design and methods: In this cross-sectional study, participants (n=216) were divided into controls; T1DM; T1DM with non-painful DPN (NP-DPN); and T1DM with painful DPN (P-DPN). DPN was further subgrouped based on neuropathy severity. The more prevalent type of fiber damage was determined applying small and large fiber-specific tests and three diagnostic models: model 1 (≥1 abnormal test); model 2 (≥2 abnormal tests); and model 3 (≥3 abnormal tests).

Results: MFN showed the highest prevalence in T1DM-associated DPN. No differences in neuropathy subtype were found between NP-DPN and P-DPN. DPN, with prevalent SFN plateaus between models 2 and 3. All models showed increased prevalence of MFN according to DPN severity. Model 3 showed increased DPN with prevalent LFN in early neuropathy. DPN with prevalent SFN demonstrated a similar, but non-significant pattern.

Conclusions: DPN primarily manifests as MFN in T1DM, with no differentiation between NP-DPN and P-DPN. Additionally, we propose model 2 as an initial criterion for diagnosing DPN with a more prevalent SFN subtype in T1DM. Lastly, the study suggests that in mild stages of DPN, one type of nerve fiber (either small or large) is more susceptible to damage.

Introduction: Prolonged hyperglycemia in diabetes mellitus can result in the development of diabetic nephropathy (DN) and increase the susceptibility to kidney failure. Low-intensity pulsed ultrasound (LIPUS) is a non-invasive modality that has demonstrated effective tissue repair capabilities. The objective of this study was to showcase the reparative potential of LIPUS on renal injury at both animal and cellular levels, while also determining the optimal pulse length (PL).

Research design and methods: We established a rat model of DN, and subsequently subjected the rats' kidneys to ultrasound irradiation (PL=0.2 ms, 10 ms, 20 ms). Subsequently, we assessed the structural and functional changes in the kidneys. Additionally, we induced podocyte apoptosis and evaluated its occurrence following ultrasound irradiation.

Results: Following irradiation, DN rats exhibited improved mesangial expansion and basement membrane thickening. Uric acid expression increased while urinary microalbumin, podocalyxin in urine, blood urea nitrogen, and serum creatinine levels decreased (p<0.05). These results suggest that the optimal PL was 0.2 ms. Using the optimal PL further demonstrated the reparative effect of LIPUS on DN, it was found that LIPUS could reduce podococyte apoptosis and alleviate kidney injury. Metabolomics revealed differences in metabolites including octanoic acid and seven others and western blot results showed a significant decrease in key enzymes related to lipolysis (p<0.05). Additionally, after irradiating podocytes with different PLs, we observed suppressed apoptosis (p<0.05), confirming the optimal PL as 0.2 ms.

Conclusions: LIPUS has been demonstrated to effectively restore renal structure and function in DN rats, with an optimal PL of 0.2 ms. The mechanism underlying the alleviation of DN by LIPUS is attributed to its ability to improve lipid metabolism disorder. These findings suggest that LIPUS may provide a novel perspective for future research in this field.