Diabetes Care最新文献

Objective: This study aimed to investigate the association between continuous glucose monitoring (CGM)-derived glycemic metrics and different insulin treatment modalities using real-world data.

Research design and methods: A cross-sectional study at Steno Diabetes Center Copenhagen, Denmark, included individuals with type 1 diabetes using CGM. Data from September 2021 to August 2022 were analyzed if CGM was used for at least 20% of a 4-week period. Individuals were divided into four groups: multiple daily injection (MDI) therapy, insulin pumps with unintegrated CGM (SUP), sensor-augmented pumps with low glucose management (SAP), and automated insulin delivery (AID). The MDI and SUP groups were further subdivided based on CGM alarm features. The primary outcome was percentage of time in range (TIR: 3.9-10.0 mmol/L) for each treatment group. Secondary outcomes included other glucose metrics and HbA1c.

Results: Out of 6,314 attendees, 3,184 CGM users were included in the analysis. Among them, 1,622 used MDI, 504 used SUP, 354 used SAP, and 561 used AID. Median TIR was 54.0% for MDI, 54.9% for SUP, 62,9% for SAP, and 72,1% for AID users. The proportion of individuals achieving all recommended glycemic targets (TIR >70%, time above range <25%, and time below range <4%) was significantly higher in SAP (odds ratio [OR] 2.4 [95% CI 1.6-3.5]) and AID (OR 9.4 [95% CI 6.7-13.0]) compared with MDI without alarm features.

Conclusions: AID appears superior to other insulin treatment modalities with CGM. Although bias may be present because of indications, AID should be considered the preferred choice for insulin pump therapy.

Objective: Tirzepatide is a novel single-molecule glucose-dependent insulinotropic polypeptide/glucagon-like peptide 1 receptor agonist, which demonstrated unprecedented improvements in glycemic control and body weight reduction, in the SURPASS phase 3 program. In this exploratory analysis, we aimed to characterize tirzepatide-treated participants who achieved HbA1c <5.7% and evaluate changes in clinical markers associated with long-term cardiometabolic health.

Research design and methods: Baseline characteristics and change from baseline to week 40 for several efficacy and safety parameters were analyzed according to HbA1c attainment category (<5.7%, 5.7-6.5%, and >6.5%) using descriptive statistics in participants taking ≥75% of treatment doses, without rescue medication, in the SURPASS 1-4 trials (N = 3,229). Logistic regression models with tirzepatide doses adjusted as a covariate were used to obtain odds ratios and assess the impact of patient characteristics achieving an HbA1c <5.7%.

Results: Tirzepatide-treated participants who achieved HbA1c <5.7% were slightly younger, with a shorter duration of diabetes and lower HbA1c value at baseline compared with those who did not achieve HbA1c <5.7%. In addition, they showed greater improvements in HbA1c, body weight, waist circumference, blood pressure, liver enzymes, and lipid parameters without increasing hypoglycemia risk.

Conclusions: Normoglycemia was unprecedently achieved in a significant proportion of participants in the SURPASS clinical program, without increasing hypoglycemia risk, and was associated with an overall improvement in metabolic health.

Objective: To examine sex differences in children with newly diagnosed type 1 diabetes (T1D) with respect to age at diagnosis, presence of autoantibodies (GAD antibody [GADA], insulinoma-associated protein 2 [IA-2A], insulin autoantibody [IAA], and zinc transporter 8 autoantibody), and HLA risk.

Research design and methods: A population-based nationwide sample of 3,645 Swedish children at T1D diagnosis was used.

Results: Girls were younger at T1D diagnosis (9.53 vs. 10.23 years; P < 0.001), more likely to be autoantibody-positive (94.7% vs. 92.0%; P = 0.002), more often positive for multiple autoantibodies (P < 0.001), more likely to be positive for GADA (64.9% vs. 49.0%; P < 0.001), and less likely to be positive for IAA (32.3% vs. 33.8%; P = 0.016). Small sex differences in HLA risk were found in children <9 years of age.

Conclusions: The disease mechanisms leading to T1D may influence the immune system differently in girls and boys.

Objective: To investigate the association between duration of type 2 diabetes and cancer incidence.

Research design and methods: In the Clinical Practice Research Datalink database, we identified 130,764 individuals with type 2 diabetes aged ≥35 years at diagnosis who were linked to hospital and mortality records. We used sex-stratified Royston-Parmar models with two timescales to estimate incidence rates of all cancers, the four commonest cancers in the U.K. (colorectal, lung, prostate, breast), and the obesity-related cancers (e.g., liver, ovary) between 1 January 1998 and 14 January 2019, by age and diabetes duration.

Results: During 1,089,923 person-years, 18,977 incident cancers occurred. At the same age, rates of all cancers in men and women did not vary across durations ranging from diagnosis to 20 years; conversely, for any duration, there was a strong, positive association between age and cancer rates. In men, the rate ratio (95% CI) comparing 20 with 5 years of duration was 1.18 (0.82-1.69) at 60 years of age and 0.90 (0.75-1.08) at 80 years; corresponding ratios in women were 1.07 (0.71-1.63) and 0.84 (0.66-1.05). This pattern was observed also for the four commonest cancers. For obesity-related cancers, although rates were generally higher in individuals with a higher BMI, there was no association with duration at any level of BMI.

Conclusions: In this study, we did not find evidence of an association between duration of type 2 diabetes and risk of cancer, with the higher risk observed for longer durations related to ageing.

Objective: To examine the associations between age at type 2 diabetes diagnosis and the relative and absolute risk of all-cause and cause-specific mortality in England.

Research design and methods: In this cohort study using primary care data from the Clinical Practice Research Datalink, we identified 108,061 individuals with newly diagnosed type 2 diabetes (16-50 years of age), matched to 829,946 individuals without type 2 diabetes. We estimated all-cause and cause-specific mortality (cancer, cardiorenal, other [noncancer or cardiorenal]) by age at diagnosis, using competing-risk survival analyses adjusted for key confounders.

Results: Comparing individuals with versus without type 2 diabetes, the relative risk of death decreased with an older age at diagnosis: the hazard ratio for all-cause mortality was 4.32 (95% CI 3.35-5.58) in individuals diagnosed at ages 16-27 years compared with 1.53 (95% CI 1.46-1.60) at ages 48-50 years. Smaller relative risks by increasing age at diagnosis were also observed for cancer, cardiorenal, and noncancer or cardiorenal death. Irrespective of age at diagnosis, the 10-year absolute risk of all-cause and cause-specific mortality were higher in individuals with type 2 diabetes; yet, the absolute differences were small.

Conclusions: Although the relative risk of death in individuals with versus without type 2 was higher at younger ages, the 10-year absolute risk of all investigated causes of death was small and similar in the two groups. Further multidecade studies could help estimate the long-term risk of complications and death in individuals with early-onset type 2 diabetes.

Objective: To investigate gastrointestinal infection episodes (GIEs) in relation to the appearance of islet autoantibodies in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort.

Research design and methods: GIEs on risk of autoantibodies against either insulin (IAA) or GAD (GADA) as the first-appearing autoantibody were assessed in a 10-year follow-up of 7,867 children. Stool virome was characterized in a nested case-control study.

Results: GIE reports (odds ratio [OR] 2.17 [95% CI 1.39-3.39]) as well as Norwalk viruses found in stool (OR 5.69 [1.36-23.7]) at <1 year of age were associated with an increased IAA risk at 2-4 years of age. GIEs reported at age 1 to <2 years correlated with a lower risk of IAA up to 10 years of age (OR 0.48 [0.35-0.68]). GIE reports at any other age were associated with an increase in IAA risk (OR 2.04 for IAA when GIE was observed 12-23 months prior [1.41-2.96]). Impacts on GADA risk were limited to GIEs <6 months prior to autoantibody development in children <4 years of age (OR 2.16 [1.54-3.02]).

Conclusions: Bidirectional associations were observed. GIEs were associated with increased IAA risk when reported before 1 year of age or 12-23 months prior to IAA. Norwalk virus was identified as one possible candidate factor. GIEs reported during the 2nd year of life were associated with a decreased IAA risk.

Objective: We validated longitudinally a typology of diabetes-specific family functioning (named Collaborative and Helpful, Satisfied with Low Involvement, Want More Involvement, and Critically Involved) in adults with type 2 diabetes.

Research design and methods: We conducted k-means cluster analyses with nine dimensions to determine if the typology replicated in a diverse sample and if type assignment was robust to variations in sampling and included dimensions. In a subsample with repeated assessments over 9 months, we examined the stability and validity of the typology. We also applied a multinomial logistic regression approach to make the typology usable at the individual level, like a diagnostic tool.

Results: Participants (N = 717) were 51% male, more than one-third reported minority race or ethnicity, mean age was 57 years, and mean hemoglobin A1c (HbA1c) was 7.9% (63 mmol/mol; 8.7% [72 mmol/mol] for the longitudinal subsample). The typology was replicated with respect to the number of types and dimension patterns. Type assignment was robust to sampling variations (97% consistent across simulations). Type had an average 52% stability over time within participants; instability was not explained by measurement error. Over 9 months, type was independently associated with HbA1c, diabetes self-efficacy, diabetes medication adherence, diabetes distress, and depressive symptoms (all P < 0.05).

Conclusions: The typology of diabetes-specific family functioning was replicated, and longitudinal analyses suggest type is more of a dynamic state than a stable trait. However, type varies with diabetes self-management and well-being over time as a consistent independent indicator of outcomes. The typology is ready to be applied to further precision medicine approaches to behavioral and psychosocial diabetes research and care.

Objective: It is not known if incidence rates for diabetic distal symmetric polyneuropathy (DSPN) are decreasing, as they are for other diabetic complications. Here, we investigated incidence rates of DSPN in type 1 and type 2 diabetes in a large population-based study.

Research design and methods: In the period 1996 to 2018, 19,342 individuals were identified at a Danish tertiary diabetes center. Vibration perception threshold was assessed by biothesiometry and repeated throughout the study. Exclusion of prevalent DSPN cases or missing data left data on 9,473 individuals for analysis of DSPN using a cutoff of >25 V and on 2,783 individuals for analysis using an age-, sex-, and height-specific cutoff. Poisson regression analysis was used to model incidence rates of DSPN for both cutoff types and separately for diabetes types. Covariates were sex, age, diabetes duration, and calendar time.

Results: Incidence rates (95% CI) of DSPN decreased from 1996 to 2018 (e.g., from 4.78 [3.60-6.33]/100 person-years [PY] to 1.15 [0.91-1.47]/100 PY for 40-year-old men with type 1 diabetes and from 16.54 [11.80-23.18]/100 PY to 8.02 [6.63-9.69]/100 PY for 60-year-old men with type 2 diabetes, when using >25 V as the cutoff value). Analyses using age-, sex-, and height-specific cutoff values demonstrated similar incidence patterns by calendar time without sex differences. For type 1 diabetes, decreasing incidence rates were seen with older age.

Conclusions: Incidence rates for DSPN are declining in type 1 and type 2 diabetes, possibly due to improved diabetes treatment. This causality remains to be explored. Distinct age-related patterns indicate that the pathophysiology of DSPN may differ between diabetes types.