BMJ Open Diabetes Research & Care最新文献

Introduction: To compare the clinical outcomes and healthcare utilization of patients enrolled in the multidisciplinary Diabetic Foot in Primary and Tertiary (DEFINITE) Care program with a matched historical cohort and estimate the program's long-term cost-effectiveness using simulation.

Research design and methods: This study consisted of two components: a 1-year observational outcome evaluation and a long-term simulation-based cost-effectiveness analysis (CEA). We conducted an observational study to analyze 2798 patients with diabetic foot ulcers (DFUs) enrolled in the program between June 2020 and June 2021 (DEFINITE Care group) and 5462 patients with DFUs from June 2016 to December 2017 as historical controls. One-to-one propensity score matching (PSM) with replacement was conducted to estimate the treatment effect of the program on clinical outcomes and healthcare utilization over 1 year. For the simulation component, a long-term CEA was performed using a Markov state transition model on a simulated cohort of 10 000 patients with DFUs over a 20-year period, assessing transitions between health states, including minor and major amputations and death. The incremental cost-effectiveness ratio (ICER) was calculated for the DEFINITE Care program relative to routine care.

Results: The estimation of average treatment effects based on propensity scores showed that the DEFINITE Care group exhibited a 9% lower mortality, 5% higher lower extremity amputation (LEA)-free survival, yet a 5% higher minor LEA rate compared with the matched historical controls. Additionally, they experienced fewer inpatient admissions (0.98 fewer episodes) and shorter hospital stays (5.5 fewer days) within 1 year (p-value <0.001). The ICER was US$22 707 (SE: 430) per quality-adjusted life year gained, indicating long-term cost-effectiveness. Probabilistic sensitivity analysis supported these findings.

Conclusions: The integrated multidisciplinary DEFINITE Care program improved LEA-free survival, reduced inpatient admissions and length of stay within 1 year and demonstrated long-term cost-effectiveness managing DFUs.

Introduction: Altered serum levels of growth hormones, adipokines, and exocrine pancreas enzymes have been individually linked with type 1 diabetes (T1D). We collectively evaluated seven such biomarkers, combined with islet autoantibodies (AAb) and genetic risk score (GRS2), for their utility in predicting AAb/T1D status.

Research design and methods: Cross-sectional serum samples (n=154 T1D, n=56 1AAb+, n=77 ≥2AAb+, n=256 AAb-) were assessed for IGF1, IGF2, adiponectin, leptin, amylase, lipase, and trypsinogen (n=543, age range 2.7-30.0 years) using random forest modeling.

Results: GRS2, age, lipase, trypsinogen, and AAb against ZnT8, GAD65, and insulin were the most informative markers. Notably, these variables were differentially informative according to AAb/T1D status. Higher GRS2 (p<0.001) and lower lipase levels (p=0.002) favored ≥2AAb+ versus AAb- classification. AAb against ZnT8 (p<0.01), GAD65 (p=0.021), or insulin (p=0.01) each independently favored ≥2AAb+ versus 1AAb+ classification. Reduced trypsinogen (p<0.001) and increased lipase levels (p<0.001) favored recent-onset T1D versus ≥2AAb+ classification.

Conclusions: Among the serological markers tested, lipase and trypsinogen levels were the most informative for differentiating among clinical groups, with the utility of each enzyme varying according to GRS2 and AAb/T1D status. These data support exocrine pancreas enzymes as candidates for longitudinal follow-up.

Introduction: Lifestyle determinants of 2-hour glucose concentration in people with type 2 diabetes and interindividual differences need to be identified.

Research design and methods: 38 participants with type 2 diabetes, treated with lifestyle advice and/or metformin, tracked their physical activity, sleep and dietary intake, while continuously monitoring interstitial glucose concentrations for 11 periods of four consecutive days each. A linear mixed-effects model was used to quantify the effect of sleep, stress, current glucose, carbohydrate intake and exercise on glucose levels 2 hours later.

Results: The final model identified carbohydrate intake (grams) in the past 5 min as well as in the past 30 min, sleep duration during the previous night (hours) and physical activity (metabolic equivalents) over the past 12 hours as significant fixed effects that influenced glucose concentrations 2 hours later. In addition, carbohydrate intake in the past 5 and past 30 min, and physical activity in the past and future 30 min were included as random or individualized effects. Although carbohydrate intake led to increased glucose concentrations in 2 hours in all individuals, the magnitude of this effect varied between individuals. The physical activity on glucose concentrations in 2 hours varied among individuals as well, in terms of magnitude and in terms of direction (showing either increase or decline).

Conclusions: Carbohydrate intake, sleep and physical activity at specific points in time have both fixed as well as individualized effects on glucose concentrations 2 hours later in individuals with type 2 diabetes. Interindividual differences in glycemic response to lifestyle components call for personalized advice in the management of type 2 diabetes.

Introduction: There are limited data regarding the associations between public transportation reliance, availability, and diabetic foot ulcer (DFU)-related amputations.

Research design and methods: We used visit-level data from the Georgia 2016-2019 Healthcare Cost and Utilization Project database and obtained transportation variables from open sources. Using Bayesian spatial-temporal models, we assessed the associations between transportation and DFU-related amputations within each quartile of poverty status indicators at the ZIP code tabulation area (ZCTA) level. We used the proportion of adults who use public transportation to commute, distance to nearest transit stop, and per capita expense on public transportation as proxies for public transportation reliance, availability, and both, respectively.

Results: Of 114 606 DFUs, 21 388 (19%) were associated with a major or minor amputation. Among ZCTAs at the highest income quartile, reduced amputation risk was associated with the proportion of adults who use public transportation to commute to work (relative risk (RR)=0.29, 95% CI 0.09 to 0.97 per IQR increase of 1.13%) and per capita expense on public transportation (RR=0.78, 95% CI 0.63 to 0.78 per IQR increase of 6 cents). In metropolitan Georgia, a 1 IQR (261 m) increase in distance to the nearest transit stop was associated with lower amputation risk among ZCTAs at the lowest income quartile (RR=0.47, 95% CI 0.26 to 0.85).

Conclusion: In Georgia, public transportation reliance and availability are protective against DFU-related amputations in high-income but not among low-income ZCTAs. Reducing disparities in DFU-related amputations requires interventions to mitigate transportation barriers to care.

Introduction: Ethnic disparities in the prevalence and pathophysiology of type 2 diabetes are well documented, but prospective data on insulin dynamics vis-à-vis pre-diabetes/early dysglycemia risk in diverse populations are scant.

Research design and methods: We analyzed insulin secretion, sensitivity, and clearance among participants in the Pathobiology of Prediabetes in a Biracial Cohort (POP-ABC) study. The POP-ABC study followed initially normoglycemic offspring of parents with type 2 diabetes for 5.5 years, the primary outcome being incident dysglycemia. Assessments included anthropometry, oral glucose tolerance test, insulin sensitivity (hyperinsulinemic euglycemic clamp, HEC), insulin secretion (intravenous glucose tolerance test, IVGT), and disposition index (DI). Insulin clearance was derived as the molar ratio of plasma C peptide to insulin and by calculating the metabolic clearance rate during HEC.

Results: POP-ABC participants who completed IVGT and HEC at baseline (145 African American, 123 European American; 72% women; mean age 44.6±10.1 years) were included in the present analysis. The baseline fasting plasma glucose was 91.9±6.91 mg/dL (5.11±0.38 mmol/L) and 2-hour plasma glucose was 123±25.1 mg/dL (6.83±1.83 mmol/L). African American offspring of parents with type 2 diabetes had higher insulin secretion and DI, and lower insulin sensitivity and clearance, than their European American counterparts. During 5.5 years of follow-up, 91 of 268 participants developed incident dysglycemia and 177 maintained normoglycemia. In Cox proportional hazards models, insulin secretion (HR 0.997 (95% CI 0.996 to 0.999), p=0.005), insulin sensitivity (HR 0.948 (95% CI 0.913 to 0.984), p=0.005), DI (HR 0.945 (95% CI 0.909 to 0.983), p=0.005) and basal insulin clearance (HR 1.030 (95% CI 1.005 to 1.056), p=0.018) significantly predicted incident dysglycemia.

Conclusions: Insulin sensitivity, secretion, and clearance differ significantly in normoglycemic African American versus European American offspring of parents with type 2 diabetes and are associated with the risk of incident dysglycemia.

Introduction: This analysis aimed to investigate diabetes-specific psychological outcomes among adults with type 1 diabetes (T1D) using hybrid closed-loop (HCL) versus standard therapy.

Research design and methods: In this multicenter, open-label, randomized, controlled, parallel-group clinical trial, adults with T1D were allocated to 26 weeks of HCL (MiniMed™ 670G) or standard therapy (insulin pump or multiple daily injections without real-time continuous glucose monitoring). Psychological outcomes (awareness and fear of hypoglycemia; and diabetes-specific positive well-being, diabetes distress, diabetes treatment satisfaction, and diabetes-specific quality of life (QoL)) were measured at enrollment, mid-trial and end-trial. Linear mixed models were conducted, using restricted maximum likelihood estimation, unadjusted and adjusted (for covariates: age, sex, diabetes duration, glycated hemoglobin, recent severe hypoglycemia, pre-trial insulin delivery modality, enrollment and mid-study scores).

Results: 120 participants (mean age 44±12 years) were randomized to intervention (n=61) or standard therapy (n=59). At 13 weeks, the HCL group had better diabetes-specific positive well-being than the standard therapy group (unadjusted: Δ=1.0, p=0.025; adjusted: Δ=1.1, p=0.01), which was maintained at 26 weeks (unadjusted: Δ=0.9, p=0.042; adjusted: Δ=1.0, p=0.023). At 26 weeks, the HCL group also had less diabetes distress (adjusted: Δ=-6.4, p=0.039), fear of hypoglycemia ("maintain high": adjusted: Δ=-0.8, p=0.034; and "worry": adjusted: Δ=-1.8, p=0.048), and perceived "unacceptably high glucose levels" (unadjusted: Δ=-1.1, p<0.001; adjusted: Δ=-1.1, p<0.001). HCL did not improve diabetes treatment satisfaction, diabetes-specific QoL, hypoglycemia awareness, or perceived frequency of unacceptably low glucose levels.

Conclusions: These findings imply that HCL offers important psychological benefits. In particular, improvement in diabetes-specific positive well-being was observed 13 weeks after HCL initiation and maintained at 26 weeks. Reduction in the perceived frequency of hyperglycemia was also apparent by 26 weeks. Adjusted analyses showed significant reductions in diabetes distress and fear of hypoglycemia at 26 weeks, suggesting these benefits were apparent for people with particular characteristics.

Trial registration number: Australian New Zealand Clinical Trials Registry: ACTRN12617000520336.

Introduction: The balance of trace elements plays an important role in diabetic kidney disease (DKD) patients. However, studies on the differences in urinary trace elements across different DKD stages are scarce. This study aimed to explore the associations between nine essential trace elements and DKD.

Research design and methods: This cross-sectional analysis included 830 diabetic patients. Participants were classified into non-DKD (NDKD) and DKD, the latter was further grouped into mid and end DKD based on estimated glomerular filtration rate (eGFR), and the case and control were matched based on age and sex. The concentration of urinary trace elements was measured with inductively coupled plasma mass spectrometry.

Results: Urinary concentrations of copper (Cu) and manganese (Mn) in DKD patients were significantly higher than that of NDKD patients, whereas that of iron (Fe), cobalt, selenium, and nickel (Ni) of DKD were lower. Positive correlations between urinary Mn/Cu and the risk of mid-stage and end-stage DKD were revealed by conditional logistic regression, while Fe and Ni were negatively associated with the risk of DKD. In mixed effect analyses, no significant trend was found for joint trace element exposure and risk of mid DKD, while negative associations between combined effects of trace elements and the risk of end DKD were observed.

Conclusions: This study revealed different associations between trace elements and the risk of mid and end DKD using both single and mixture effect modeling. The results suggested that the urinary trace element profile might be associated with the progression of DKD, which provides important insights for understanding the pathogenesis of DKD and developing individualized nutritive management strategies.

Introduction: Previous studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.

Research design and methods: Twenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m²) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m²) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP >233 dB/m.

Results: A CAP >233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A "cut-off" value of 15,620 uIU/mL^-1*180 min^-1 provided a 75% sensitivity and 75% specificity for CAP >233 dB/m.

Conclusions: Our results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.

Background: Type 2 ketone-prone diabetes mellitus (T2KPDM) is thought to occur in men of African descent, with obesity who experienced prolonged hyperglycemia; the role of medication non-adherence as a contributing cause remains unstudied.

Research design and methods: This was a retrospective study of unique adults (>18 years) who sought emergency care one of four hospitals in the greater Detroit area. Patients were identified on the basis of a laboratory order for a ß-hydroxybutyrate concentration. Two research coordinators abstracted 119 data fields. Patients were divided into four phenotypes: (1) no prior DM, (2) type 2 DM without prior ketosis, (3) type 2 with prior ketosis and (4) type 1 DM. A ß-hydroxybutyrate >20 mg/dL defined diabetic ketoacidosis (DKA). A directed acyclic graph was constructed to diagram a causal pathway.

Results: Of 450 patients, 326 were non-type I and 37% of these had DKA. Concentrations of ß-hydroxybutyrate, glucose, bicarbonate were not different between non-type1 versus type 1 DM patients. Admission rates to the ICU and hospital lengths of stay were similar between the four phenotypes with DKA. We found no association with sex, race or body mass index. Unadjusted odds for DKA were significant for non-adherence (odds=1.74, 95% CI 1.08 to 2.21) arrival by Emergency Medical Services (odds=0.54, 95% CI 0.33 to 0.86) and private or Medicare insurance (odds=6.80, 95% CI 4.00 to 11.60). The median HbA1C was statistically higher in patients with DKA (median 11.3%) versus those without DKA (median 9.5%, Mann-Whitney U p<0.001) and was also higher in patients with a history of non-adherence. In multivariable analysis, non-adherence was found to be a mediator of DKA with T2KPDM.

Conclusions: in Detroit, MI, prior ketosis and private or Medicare health insurance were significantly associated with new or recurrent DKA in T2KPDM. Medication non-adherence had a mediating role.

Introduction: Maturity-onset diabetes of the young (MODY) and neonatal diabetes mellitus (NDM) are the most prevalent causes of monogenic diabetes. MODY is an autosomal dominant condition with onset in childhood and young adulthood, while NDM is defined with diabetes onset within 6 months of age and can be caused by dominant, recessive, X-linked genes or by chromosomal abnormalities. Here, we describe a rare case of monogenic diabetes in a patient who is homozygous for an INS gene variant.

Research design and methods: The index patient, a male diagnosed with type 2 diabetes, was treated with low-dose insulin and metformin. Blood plasma was collected under fasting conditions for analysis. MODY screening was performed using a next-generation sequencing panel. In silico analysis of the insulin variant's three-dimensional structure and its interaction with the insulin receptor was conducted. Insulin receptor affinity and downstream signaling potency were evaluated in vitro.

Results: Auto-immune diabetes was excluded. A homozygous missense variant of the INS gene (c.130G>A, p.Gly44Arg) was identified in the patient. The combination of three different insulin assays showed that the biosynthesis of proinsulin into insulin was intact. In silico analysis of the mutant insulin 3D structure revealed that the INS variant is likely to affect insulin receptor binding and subsequent in vitro analysis suggested reduced potency in downstream signaling.

Conclusions: The homozygous c.130G>A variant in the INS gene results in reduced insulin receptor binding and signaling potency. This, combined with pancreatic β-cell apoptosis or dedifferentiation supposedly, has contributed in the late-onset of monogenic diabetes in the index patient.