Diabetes research and clinical practice最新文献

Background

The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on calcium phosphate homeostasis in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) remain uncertain.

Methods

A retrospective observational cohort study of patients with T2DM at CKD stage G3b-5ND who received SGLT2i as compared to control from 1 January 2015 through 31 December 2021 was recruited. Propensity score assignment at 1:3 ratio by logistic regression was done. All patients were followed for 12 months. Outcomes were changes in phosphate level.

Results

We analyzed 1,450 SGLT2i users and 4,350 control subjects. At the 12^th month, SGLT2i users had a slower increase in phosphate levels (absolute change: −0.01 ± 0.28 vs + 0.14 ± 0.34 mmol/L; percentage change: −0.74 % ± 25.56 vs + 10.88 ± 28.15 %, P for both < 0.001). The proportion of patients with high phosphate was lower with SGLT2i (8.2 % vs 24.6 % increase). In the generalized estimating equation, SGLT2i was linked to a longitudinal reduction in phosphate (B −0.039, P<0.001).

Conclusions

SGLT2i can effectively slow down the progression of phosphate retention in advanced CKD with T2DM.

Type 2 diabetes (T2D) is associated with increased risk for chronic kidney disease (CKD). It is estimated that 40 % of people with diabetes have CKD, which consequently leads to increase in morbidity and mortality from cardiovascular diseases (CVDs). Diabetic kidney disease (DKD) is leading cause of CKD and end-stage renal disease (ESRD) globally. On the other hand, DKD is independent risk factor for CVDs, stroke and overall mortality. According to the guidelines, using spot urine sample and assessing urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are both mandatory methods for screening of CKD in T2D at diagnosis and at least annually thereafter. Diagnosis of CKD is confirmed by persistent albuminuria followed by a progressive decline in eGFR in two urine samples at an interval of 3 to 6 months. However, many patients with T2D remain underdiagnosed and undertreated, so there is an urgent need to improve the screening by detection of albuminuria at all levels of health care. This review discusses the importance of albuminuria as a marker of CKD and cardiorenal risk and provides insights into the practical aspects of methods for determination of albuminuria in routine clinical care of patients with T2D.

Aims

This systematic review was aimed to assess the association between magnitude of body weight loss (BWL) in type 2 diabetes (T2D) patients and cardiovascular (CV) risk in CV outcome trials (CVOTs).

Methods

We searched electronic databases (PubMed, Cochrane and Scopus) for available CVOTs, observational cohort studies or post hoc analyses of clinical trials of adult T2D patients investigated the association of BWL with CV outcomes and/or all-cause mortality.

Results

19 RCTs of novel glucose-lowering drugs (GLP-1RA, DPP-4i and SGLT2i) and 6 RCT or observational trial of different strategies (intensive treatment or standard care) were included (379.904 T2D patients). Higher BWL during GLP-1RA treatment, in comaprison to lower BWL, was associated with higher decrease in risk of MACE, while DPP-4i had not that effect. With SGLT2i the higher decrease in risk of MACE was associated with lower BWL. In contrast, in other different strategies, higher BWL lead to increase in risk for MACE and all-cause mortality.

Conclusions

In CVOTs, treatment of T2D patients resulted in BWL, which correlated with reduction in risk for CV outcomes, particularly with GLP-1 RAs. However, interventional non-CVOTs are warning that in the absence of structured behavioral intervention and relevant medication, the large BWL might be harmful for CV outcomes.

Objectives

Research design and methods

Results

Conclusions

Aims

We aim to determine the association of seven major candidate protein biomarkers and diabetic kidney disease (DKD) progression among Asians with young-onset type 2 diabetes mellitus (T2DM).

Methods

824 T2DM patients (onset ≤ 40 years old) were classified as DKD progressors based on yearly estimated glomerular filtration rate (eGFR) decline of >3 ml/min/1.73 m² or >40 % from baseline. Plasma leucine-rich α-2-glycoprotein 1 (pLRG1), tumor necrosis factor-receptor 1 (pTNF-R1), pigment epithelium-derived factor (pPEDF), urinary α-1-microglobulin (uA1M), kidney injury molecular 1 (uKIM-1), haptoglobin (uHP) and uromodulin (uUMOD) were measured using enzyme-linked immunoassays.

Results

Over 5.7 years of follow-up, 25.2 % of patients were DKD progressors. Elevated levels of pLRG1, pTNF-R1, pPEDF, uA1M, uKIM-1 and uHP were associated with DKD progression. The association between pTNF-R1 levels and DKD progression persisted after adjusting for clinical covariates (OR 1.84, 95 %CI 1.44–2.34, p < 0.001). The effects of pTNF-R1 were partially mediated through hyperglycemia (8 %) and albuminuria (10 %). Inclusion of pTNF-R1 in a clinical variable-based model improved the area under the receiver operating characteristics curve for predicting DKD progression by 0.02, from 0.72 (95 %CI 0.68–0.76) to 0.74 (95 %CI 0.70–0.78), p = 0.099.

Conclusions

Among seven major candidate proteins, pTNF-R1, partially mediated through hyperglycemia and albuminuria, robustly predicted DKD progression among Asians with young-onset T2DM.

Objective

This study aims to prospectively examine the association between temperatures and the occurrence of type 2 diabetes (T2D).

Methods

We used the CPH models to analyze 103,215 non-diabetic participants in the UK Biobank cohort who answered questions about workplace temperature, to evaluate the survival relationship, and the interaction effects of working environmental temperature and T2D-related genetic risk scores (GRS) on the occurrence of T2D. The occurrence of T2D was assessed by hospital inpatient records. The weighted T2D-related GRS were calculated.

Results

During 1,355,200.6 person-years follow-up, a total of 2436 participants were documented as having diagnosed T2D. After adjustment, compared to the comfortable group, the participants working in non-comfortable environmental temperature had greater risk of T2D (HR: 1.27, 95 %CI: 1.04 to 1.55, for cold; HR: 1.32, 95 %CI: 1.17 to 1.48 for hot; HR: 1.51, 95 %CI: 1.38 to 1.65 for alternate). Similarly, individuals exposed to different levels of genetic risk scores in alternating hot and cold work environments had a higher risk of developing type 2 diabetes.

Conclusions

This study found working in single non-comfortable environmental temperatures was associated with greater risk of T2D occurrence, and exposure to alternating environmental temperatures had the highest risk of range and severity.

Aims

To evaluate whether treatment with insulin is advantageous compared with oral anti-diabetic drugs (OAD) for patients newly diagnosed with type 2 diabetes with moderate hyperglycemia.

Methods

Patients newly diagnosed with type 2 diabetes with moderate hyperglycemia were recruited and randomized to receive insulin, metformin or sitagliptin treatment. The oral glucose tolerance test (OGTT) was performed before treatment and 6 months thereafter. The primary outcome was the glycohemoglobin (HbA1c) level change. For the secondary efficacy analysis, the β-cell function and insulin sensitivity were calculated from the OGTT, as was the proportion of subjects who reached the treatment target (HbA1c level < 7.0 % or < 6.5 %) at 6 months.

Results

We randomized 50 patients to the three groups and 32 patients who received the allocated treatment were analyzed. The change of HbA1c level in the insulin, metformin, and sitagliptin groups was − 2.06 ± 1.37 %, −0.43 ± 0.32 %, and − 1.62 ± 0.92 %, respectively. This change was smallest in the metformin group. There was no significant difference in the changes or final HbA1c levels between the insulin and sitagliptin groups. The treat-to-target (HbA1c level < 7.0 %) rates in the insulin, metformin and sitagliptin were 75 %, 50 % and 100 %, respectively. The treat-to-target rates were not significantly different among the three groups. The insulin secretion indices, including the Matsuda index and HOMA-IR, indicated that the groups did not differ after 6 months of therapy.

Conclusion

A 6-month course of basal insulin therapy did not benefit patients newly diagnosed with diabetes with moderate hyperglycemia in terms of insulin sensitivity or insulin secretion.

Aims

This study aimed to quantify preferences for the characteristics of a financial incentives program that would motivate adolescent engagement in type 1 diabetes (T1D) self-care.

Method

We performed a discrete choice experiment with 12–18 year-olds with T1D from two pediatric hospital endocrinology clinics (n = 317). We identified key attributes of incentives: (1) monthly value of the reward, (2) payment structure, and (3) difficulty of incentivized behaviors. In twelve choice questions, adolescents chose the incentive option from a pair of profiles that was more likely to motivate them to increase adherence to recommended self-care. Options presented were tailored to adolescents’ T1D technology use and perceived difficulty of completing each behavior. We analyzed data using a conditional logit model.

Results

The value of the reward accounted for 60.8% of preferences. Adolescents were willing to accept lower value rewards when incentive payments used positive vs. negative reinforcement (−$10.88 (95% CI: −$12.60, −9.24)) and preferred higher incentives for performing hard vs. easier behaviors (+$14.92 (95% CI: +$12.66, +$17.28)).

Conclusions

Stated preferences can inform intervention design. Future research will evaluate the external validity of the discrete choice experiment-informed intervention design by assessing adolescent health and behavioral outcomes in a randomized controlled trial.

Aims/hypothesis

To study the progression of HbA1c after diagnosis of type 1 diabetes in children and adolescents during 2010–2019 with emphasis on HbA1c nadir 3–6 months after onset.

Methods

Partial funding was secured for this study. The Swedish paediatric diabetes quality register SWEDIABKIDS has >95 % coverage of type 1 diabetes up to 18 years. A mixed model for repeated measurements was used to estimate differences in HbA1c between onset year periods.

Results

We followed 6,891 patients over two years from onset (48,292 HbA1c values). We found a gradual decrease in mean HbA1c 24 months after onset from 56.0 mmol/mol (7.28 %) in 2010/11 to 50.5 mmol/mol (6.77 %) in 2018/19, which is at the level of several recent intervention studies. The initial drop in HbA1c from onset until 3 and 6 months has become more pronounced in recent years. There was a significant positive correlation between HbA1c at 3 and 6 months with 12, 18 and 24 months. Percentage of severe hypoglycaemic coma was higher (5.1 % vs 3.4 %; p = 0.023) in 2010/2011 than 2018/2019, but the absolute risk of ketoacidosis was essentially unchanged, (1.5 % to 0.8 %, p = 0.110)

Conclusions/interpretation

There was a continuous decrease in HbA1c over the study period 2010–2019, which coincides in time with an increased use of diabetes technology and lowering the HbA1c target to 48 mmol/mol (6.5 %). The decrease in 2-year HbA1c was preceded by a lower HbA1c nadir, which may set the trajectories for coming HbA1c and be a modifiable factor for a long-term improvement in metabolic control.

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have been reported to increase the risk of acute pancreatitis (AP). This real-world study did not observe a higher frequency of AP with GLP-1RA exposure in adults with T2D and a prior history of AP regardless of etiology.