BMJ Open Diabetes Research & Care最新文献

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.

Introduction: The association between the gut microbiome and incident type 2 diabetes (T2D) is potentially partly mediated through sphingolipids, however these possible mediating mechanisms have not been investigated. We examined whether sphingolipids mediate the association between gut microbiome and T2D, using data from the Healthy Life in an Urban Setting study.

Research design and methods: Participants were of Dutch or South-Asian Surinamese ethnicity, aged 18-70 years, and without T2D at baseline. A case-cohort design (subcohort n=176, cases incident T2D n=36) was used. The exposure was measured by 16S rRNA sequencing (gut microbiome) and mediator by targeted metabolomics (sphingolipids). Dimensionality reduction was achieved by principle component analysis and Shannon diversity. Cox regression and procrustes analyses were used to assess the association between gut microbiome and T2D and sphingolipids and T2D, and between gut microbiome and sphingolipids, respectively. Mediation was tested familywise using mediation analysis with permutation testing and Bonferroni correction.

Results: Our study confirmed associations between gut microbiome and T2D and sphingolipids and T2D. Additionally, we showed that the gut microbiome was associated with sphingolipids. The association between gut microbiome and T2D was partly mediated by a sphingolipid principal component, which represents a dominance of ceramide species over more complex sphingolipids (HR 1.17; 95% CI 1.08 to 1.28; proportional explained 48%), and by Shannon diversity (HR 0.97; 95% CI 0.95 to 0.99; proportional explained 24.8%).

Conclusions: These data suggest that sphingolipids mediate the association between microbiome and T2D risk. Future research is needed to confirm observed findings and elucidate causality on a molecular level.

Introduction: Diabetic retinopathy (DR) is a common vascular complication of diabetes mellitus and a leading cause of vision loss worldwide. Endothelial cell (EC) heterogeneity has been observed in the pathogenesis of DR. Elucidating the underlying mechanisms governing EC heterogeneity may provide novel insights into EC-specific therapies for DR.

Research design and methods: We used the single-cell data from the Gene Expression Omnibus database to explore EC heterogeneity between diabetic retinas and non-diabetic retinas and identify the potential genes involved in DR. CCK-8 assays, EdU assays, transwell assays, and tube formation assays were conducted to determine the role of the identified gene in angiogenic effects.

Results: Our analysis identified three distinct EC subpopulations in retinas and revealed that Mitochondria-localized glutamic acid-rich protein (Mgarp) gene is potentially involved in the pathogenesis of DR. Silencing of Mgarp significantly suppressed the proliferation, migration, and tube formation capacities in retinal endothelial cells.

Conclusions: This study not only offers new insights into transcriptomic heterogeneity and pathological alteration of retinal ECs but also holds the promise to pave the way for antiangiogenic therapy by targeting EC-specific gene.

Introduction: The Environmental Determinants of Islet Autoimmunity (ENDIA) Study is an ongoing Australian prospective cohort study investigating how modifiable prenatal and early-life exposures drive the development of islet autoimmunity and type 1 diabetes (T1D) in children. In this profile, we describe the cohort's parental demographics, maternal and neonatal outcomes and human leukocyte antigen (HLA) genotypes.

Research design and methods: Inclusion criteria were an unborn child, or infant aged less than 6 months, with a first-degree relative (FDR) with T1D. The primary outcome was persistent islet autoimmunity, with children followed until a T1D diagnosis or 10 years of age. Demographic data were collected at enrollment. Lifestyle, clinical and anthropometric data were collected at each visit during pregnancy and clinical pregnancy and birth data were verified against medical case notes. Data were compared between mothers with and without T1D. HLA genotyping was performed on the ENDIA child and all available FDRs.

Results: The final cohort comprised 1473 infants born to 1214 gestational mothers across 1453 pregnancies, with 80% enrolled during pregnancy. The distribution of familial T1D probands was 62% maternal, 28% paternal and 11% sibling. The frequency of high-risk HLA genotypes was highest in T1D probands, followed by ENDIA infants, and lowest among unaffected family members. Mothers with T1D had higher rates of pregnancy complications and perinatal intervention, and larger babies of shorter gestation. Parent demographics were comparable to the Australian population for age, parity and obesity. A greater percentage of ENDIA parents were Australian born, lived in a major city and had higher socioeconomic advantage and education.

Conclusions: This comprehensive profile provides the context for understanding ENDIA's scope, methodology, unique strengths and limitations. Now fully recruited, ENDIA will provide unique insights into the roles of early-life factors in the development of islet autoimmunity and T1D in the Australian environment.

Trial registration number: ACTRN12613000794707.

Introduction: In this systematic review, we investigated the diagnostic accuracy of surrogate measures of insulin secretion based on fasting samples and the oral glucose tolerance test (OGTT). The first phase of insulin secretion was calculated using two gold standard methods; the hyperglycemic clamp (HGC) test and intravenous glucose tolerance test (IVGTT).

Research design and methods: We conducted searches in the PubMed, Cochrane Central, and Web of Science databases, the last of which was conducted at the end of June 2021. Studies were included that measured first-phase insulin secretion in adults using both a gold-standard reference method (either HGC or IVGTT) and one or more surrogate measures from either fasting samples, OGTT or a meal-tolerance test. QUADAS-2, a revised tool for the quality assessment of diagnostic accuracy studies, was used for quality assessment. Random-effects meta-analyses were performed to examine the correlation between first-phase measured with gold standard and surrogate methods.

Results: A total of 33 articles, encompassing 5362 individuals with normal glucose tolerance, pre-diabetes or type 2 diabetes, were included in our systematic review. Homeostatic model assessment (HOMA)-beta and Insulinogenic Index 30 (IGI(30)) were the surrogate measures validated in the largest number of studies (17 and 13, respectively). HOMA-beta's pooled correlation to the reference methods was 0.48 (95% CI 0.40 to 0.56) The pooled correlation of IGI to the reference methods was 0.61 (95% CI 0.54 to 0.68). The surrogate measures with the highest correlation to the reference methods were Kadowaki (0.67 (95% CI 0.61 to 0.73)) and Stumvoll's first-phase secretion (0.65 (95% CI 0.58 to 0.71)), both calculated from an OGTT.

Conclusions: Surrogate measures from the first 30 min of an OGTT capture the first phase of insulin secretion and are a good choice for epidemiological studies. HOMA-beta has a moderate correlation to the reference methods but is not a measure of the first phase specifically.

Prospero registration number: The meta-analysis was registered at PROSPERO (Id: CRD42020169064) before inclusion started.