Diabetes for Doctors

n-3 Fatty Acid Biomarkers and Incident Type 2 Diabetes: An Individual Participant-Level Pooling Project of 20 Prospective Cohort Studies

OBJECTIVE

Prospective associations between n-3 fatty acid biomarkers and type 2 diabetes (T2D) risk are not consistent in individual studies. We aimed to summarize the prospective associations of biomarkers of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), docosapentaenoic acid (DPA), and docosahexaenoic acid (DHA) with T2D risk through an individual participant-level pooled analysis.

RESEARCH DESIGN AND METHODS

For our analysis we incorporated data from a global consortium of 20 prospective studies from 14 countries. We included 65,147 participants who had blood measurements of ALA, EPA, DPA, or DHA and were free of diabetes at baseline. De novo harmonized analyses were performed in each cohort following a prespecified protocol, and cohort-specific associations were pooled using inverse variance–weighted meta-analysis.

RESULTS

A total of 16,693 incident T2D cases were identified during follow-up (median follow-up ranging from 2.5 to 21.2 years). In pooled multivariable analysis, per interquintile range (difference between the 90th and 10th percentiles for each fatty acid), EPA, DPA, DHA, and their sum were associated with lower T2D incidence, with hazard ratios (HRs) and 95% CIs of 0.92 (0.87, 0.96), 0.79 (0.73, 0.85), 0.82 (0.76, 0.89), and 0.81 (0.75, 0.88), respectively (all P < 0.001). ALA was not associated with T2D (HR 0.97 [95% CI 0.92, 1.02]) per interquintile range. Associations were robust across prespecified subgroups as well as in sensitivity analyses.

CONCLUSIONS

Higher circulating biomarkers of seafood-derived n-3 fatty acids, including EPA, DPA, DHA, and their sum, were associated with lower risk of T2D in a global consortium of prospective studies. The biomarker of plant-derived ALA was not significantly associated with T2D risk.

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Cardiovascular and Renal Disease Burden in Type 1 Compared With Type 2 Diabetes: A Two-Country Nationwide Observational Study

OBJECTIVE

Type 1 diabetes (T1D) and type 2 diabetes (T2D) increase risks of cardiovascular (CV) and renal disease (CVRD) compared with diabetes-free populations. Direct comparisons between T1D and T2D are scarce. We examined this by pooling full-population cohorts in Sweden and Norway.

RESEARCH DESIGN AND METHODS

A total of 59,331 patients with T1D and 484,241 patients with T2D, aged 18–84 years, were followed over a mean period of 2.6 years from 31 December 2013. Patients were identified in nationwide prescribed drug and hospital registries in Norway and Sweden. Prevalence and event rates of myocardial infarction (MI), heart failure (HF), stroke, chronic kidney disease (CKD), all-cause death, and CV death were assessed following age stratification in 5-year intervals. Cox regression analyses were used to estimate risk.

RESULTS

The prevalence of CV disease was similar in T1D and T2D across age strata, whereas CKD was more common in T1D. Age-adjusted event rates comparing T1D versus T2D showed that HF risk was increased between ages 65 and 79 years, MI between 55 and 79 years, and stroke between 40 and 54 years (1.3–1.4-fold, 1.3–1.8-fold, and 1.4–1.7-fold, respectively). CKD risk was 1.4–3.0-fold higher in T1D at all ages. The all-cause death risk was 1.2–1.5-fold higher in T1D at age >50 years, with a similar trend for CV death.

CONCLUSIONS

Adult patients with T1D compared with those with T2D had an overall greater risk of cardiorenal disease (HF and CKD) across ages, MI and all-cause death at middle-older ages, and stroke at younger ages. The total age-adjusted CVRD burden and risks were greater among patients with T1D compared with those with T2D, highlighting their need for improved prevention strategies.

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Glycemic Outcome Associated With Insulin Pump and Glucose Sensor Use in Children and Adolescents With Type 1 Diabetes. Data From the International Pediatric Registry SWEET

OBJECTIVE

Insulin delivery methods, glucose-monitoring modalities, and related outcomes were examined in a large, international, diverse cohort of children and adolescents with type 1 diabetes from the Better Control in Pediatric and Adolescent Diabetes: Working to Create Centers of Reference (SWEET) -Registry.

RESEARCH DESIGN AND METHODS

Participants with type 1 diabetes of ≥1 year, aged ≤18 years, and who had documented pump or sensor usage during the period August 2017–July 2019 were stratified into four categories: injections–no sensor (referent); injections + sensor; pump–no sensor; and pump + sensor. HbA1c and proportion of patients with diabetic ketoacidosis (DKA) or severe hypoglycemia (SH) were analyzed; linear and logistic regression models adjusted for demographics, region, and gross domestic product per capita were applied.

RESULTS

Data of 25,654 participants were analyzed. The proportions of participants (adjusted HbA1c data) by study group were as follows: injections–no sensor group, 37.44% (8.72; 95% CI 8.68–8.75); injections + sensor group, 14.98% (8.30; 95% CI 8.25–8.35); pump–no sensor group, 17.22% (8.07; 95% CI 8.03–8.12); and pump + sensor group, 30.35% (7.81; 95% CI 7.77–7.84). HbA1c was lower in all categories of participants who used a pump and/or sensor compared with the injections–no sensor treatment method (P < 0.001). The proportion of DKA episodes was lower in participants in the pump + sensor (1.98%; 95% CI 1.64–2.48; P < 0.001) and the pump–no sensor (2.02%; 95% CI 1.64–2.48; P < 0.05) groups when compared with those in the injections–no sensor group (2.91%; 95% CI 2.59–3.31). The proportion of participants experiencing SH was lower in pump–no sensor group (1.10%; 95% CI 0.85–1.43; P < 0.001) but higher in the injections + sensor group (4.25%; 95% CI 3.65–4.95; P < 0.001) compared with the injections–no sensor group (2.35%; 95% CI 2.04–2.71).

CONCLUSIONS

Lower HbA1c and fewer DKA episodes were observed in participants using either a pump or continuous glucose monitoring (CGM) or both. Pump use was associated with a lower rate of SH. Across SWEET centers, use of pumps and CGM is increasing. The concomitant use of pump and CGM was associated with an additive benefit.

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Cardiovascular, Renal, and Metabolic Outcomes of Dapagliflozin Versus Placebo in a Primary Cardiovascular Prevention Cohort: Analyses From DECLARE-TIMI 58

OBJECTIVE

International guidelines propose prescribing sodium–glucose cotransporter 2 (SGLT2) inhibitors to patients with type 2 diabetes (T2D) as secondary prevention in patients with established atherosclerotic cardiovascular disease (ASCVD) or for primary prevention of cardiovascular events in high-risk patients with multiple risk factors (MRF) for ASCVD. The current analyses expand on the cardiovascular renal and metabolic effects of SGLT2 inhibitors in MRF patients.

RESEARCH DESIGN AND METHODS

In DECLARE-TIMI 58, 17,160 patients with T2D and MRF (59.4%) or established ASCVD (40.6%) were randomized to dapagliflozin versus placebo; patients were followed for a median of 4.2 years. The cardiovascular and renal outcomes in the MRF cohort were studied across clinically relevant subgroups for treatment effect and subgroup-based treatment interaction.

RESULTS

Among patients with MRF, the reduction with dapagliflozin in risk of cardiovascular death or hospitalization for heart failure (CVD/HHF) (hazard ratio [HR] 0.84, 95% CI 0.67–1.04) and the renal-specific outcome (HR 0.51, 95% CI 0.37–0.69) did not differ from that for patients with ASCVD (Pinteraction 0.99 and 0.72, respectively). The effect on CVD/HHF was entirely driven by a reduction in HHF (HR 0.64, 95% CI 0.46–0.88). The benefits of dapagliflozin on HHF and on the renal-specific outcome, among the subset with MRF, were directionally consistent across clinically relevant subgroups. At 48 months, HbA1c, weight, systolic blood pressure, and urinary albumin–to–creatinine ratio were lower with dapagliflozin versus placebo and estimated glomerular filtration rate was higher (P < 0.001).

CONCLUSIONS

In patients with T2D and MRF, dapagliflozin reduced the risk of HHF and adverse renal outcomes regardless of baseline characteristics. These analyses support the benefit of dapagliflozin for important outcomes in a broad primary prevention population.

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Interferent Effect of Hydroxyurea on Continuous Glucose Monitoring

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