Diabetes & metabolism最新文献

Aim

This population-based study aimed to investigate the risk of mental disorders in adults with new-onset type 1 diabetes mellitus compared to the general population without diabetes.

Methods

We selected 10,391 adults with new-onset type 1 diabetes and 51,995 adults in the general population without diabetes with a median follow-up of 7.94 years using the National Health Insurance Database in South Korea between January 2009 and December 2020. The adjusted hazard ratios (aHRs) were estimated for the occurrence of mental disorders.

Results

The incidence of mental disorders was more than twice as high in patients with new-onset type 1 diabetes (66 per 1000 person-years) than in those without diabetes (29 per 1000 person-years). The aHR [95 % confidence interval] comparing adults with new-onset type 1 diabetes with those without diabetes were 2.20 [2.12.2.29] for mental disorders, 3.16 [2.99.3.35], for depression, 2.55 [2.32.2.80] for mood disorders, 1.89 [1.80.1.97] for anxiety and stress related disorders, 2.50 [1.48.4.22] for eating disorders, 2.62 [1.45.4.73] for personality and behavior disorders and 4.39 [3.55.5.43] for alcohol and drug misuse disorders. When new-onset type 1 diabetes occurred at the age of 41 to 50, the aHR of developing mental illness was 2.43 [2.19.2.70], compared to those without diabetes.

Conclusions

In this nationwide prospective study, new-onset type 1 diabetes in adulthood was significantly associated with a higher risk of mental disorders than in the general population without diabetes.

Objective

Randomized controlled trials (RCTs) have demonstrated the superiority of metabolic surgery (MS) over medical therapy (MT) in patients with obesity and type 2 diabetes, leading, to a joint statement in 2016 proposing MS to patients with class I obesity and uncontrolled glycemia. Yet, these RCTs included few patients with class I obesity (body mass index 30–35 kg/m²) and even fewer patients with overweight. Our aim was to provide an updated systematic review (SR) with meta-analysis (MA) of RCTs reporting diabetes remission (DR) after MS in these patients.

Research design and methods

We included in the SR with MA only RCTs with at least 24-month follow-up found in Medline, Cochrane Library, Embase, and LiSSA between January 2008 and September 2022 comparing DR post-MT versus post-MS. We calculated relative risk (RR) and 95 % confidence intervals (CIs) using the Mantel-Haenszel random-effects approach to examine differences in DR between patients allocated to MS versus MT.

Results

DR was significantly higher in MS versus MT after 36 months’ follow-up in patients with obesity (RR = 6.65 [95 %CI 2.24;19.79]; I² = 27 %; 5 trials, 404 patients), but also specifically in patients with class I obesity (RR = 5.27 [1.31;21.23]; I² = 0 %; 4 trials, 80 patients). Furthermore, and in line with previous results, all additional MAs performed in patients with obesity in this work favor MS (specifically Roux-en-Y gastric bypass) over MT at 24, 36 (only) and 60 months of follow-up.

Conclusions

Although the data available in patients with class I obesity and type 2 diabetes remains limited, MA shows higher rates of DR after MS compared with MT after 36 months’ follow-up in these patients. Consequently, the French National Authority for Health French (HAS) recommends MS for these patients.

Objective

Heterozygous pathogenic or likely pathogenic (P/LP) PDX1 variants cause monogenic diabetes. We comprehensively examined the phenotypes of carriers of P/LP PDX1 variants, and delineated potential treatments that could be efficient in an objective of precision medicine.

Methods

The study primarily involved a family harboring a novel P/LP PDX1 variant. We then conducted an analysis of documented carriers of P/LP PDX1 variants, from the Human Gene Mutation Database (HGMD), RaDiO study, and Type 2 Diabetes Knowledge Portal (T2DKP) including 87 K participants.

Results

Within the family, we identified a P/LP PDX1 variant encoding p.G232S in four relatives. All of them exhibited diabetes, albeit with very different ages of onset (10–40 years), along with caudal pancreatic agenesis and childhood-onset obesity. In the HGMD, 79 % of carriers of a P/LP PDX1 variant displayed diabetes (with differing ages of onset from eight days of life to 67 years), 63 % exhibited pancreatic insufficiency and surprisingly 40 % had obesity. The impact of P/LP PDX1 variants on increased risk of type 2 diabetes mellitus was confirmed in the T2DKP. Dipeptidyl peptidase 4 inhibitor (DPP4i) and glucagon-like peptide-1 receptor agonist (GLP1-RA), enabled good glucose control without hypoglycemia and weight management.

Conclusions

This study reveals diverse clinical presentations among the carriers of a P/LP PDX1 variant, highlighting strong variations in diabetes onset, and unexpectedly high prevalence of obesity and pancreatic development abnormalities. Clinical data suggest that DPP4i and GLP1-RA may be the best effective treatments to manage both glucose and weight controls, opening new avenue in precision diabetic medicine.

With the rising tide of fatty liver disease related to metabolic dysfunction worldwide, the association of this common liver disease with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the old term non-alcoholic fatty liver disease (NAFLD). In 2023, a modified Delphi process was led by three large pan-national liver associations. There was consensus to change the fatty liver disease nomenclature and definition to include the presence of at least one of five common cardiometabolic risk factors as diagnostic criteria. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). The change of nomenclature from NAFLD to MAFLD and then MASLD has resulted in a reappraisal of the epidemiological trends and associations with the risk of developing CKD. The observed association between MAFLD/MASLD and CKD and our understanding that CKD can be an epiphenomenon linked to underlying metabolic dysfunction support the notion that individuals with MASLD are at substantially higher risk of incident CKD than those without MASLD. This narrative review provides an overview of the literature on (a) the evolution of criteria for diagnosing this highly prevalent metabolic liver disease, (b) the epidemiological evidence linking MASLD to the risk of CKD, (c) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of developing CKD, and (d) the potential drug treatments that may benefit both MASLD and CKD.

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium-glucose cotransporter 2 inhibitors (SGLT2is), while developed as antihyperglycaemic medications for the treatment of type 2 diabetes, have proven to reduce major cardiovascular adverse events (MACEs) and hospitalization for heart failure (especially for SGLT2is) in dedicated cardiovascular outcome trials. The contribution of the glucose-lowering effect in the cardiovascular protection is uncertain and may differ between the two drug classes.

Methods

This narrative review compares the relative effects of glycated hemoglobin (HbA1c) reduction on the cardiovascular protection provided by GLP-1RAs and SGLT2is in placebo-controlled cardiovascular outcome trials by using the results of either post-hoc mediation analyses or meta-regression studies.

Results

Both mediation and meta-regression analyses suggest that the lower cardiovascular risk with GLP-1RAs partially but substantially tracks with their glucose-lowering effect, especially when considering the reduction in nonfatal strokes. In contrast, similar analyses fail to demonstrate any significant contribution of the glucose-lowering effect with SGLT2is, not only on MACEs but also on heart failure issues.

Conclusion

The contribution of improved glucose control in cardiovascular protection is limited, but is much greater for GLP-1RAs than for SGLT2is. Of note, such mediation or meta-regression analyses are exploratory and can only be viewed as hypothesis generating.

Aims

Although the hypothesis that metformin is beneficial for patients with diabetes and heart failure (HF) has been steadily raised, there is limited data on metformin use in patients with acute HF. We analyzed the association of metformin on all-cause mortality in hospitalized patients with type 2 diabetes and acute HF.

Methods

The Korean Acute Heart Failure registry prospectively enrolled patients hospitalized for acute HF from 2011 to 2014. Among this cohort, we analyzed patients with diabetes with baseline estimated glomerular filtration rate (eGFR) of 30 ml/min/1.73 m² or more. We analyzed the all-cause mortality and re-hospitalization for HF within 1 year after discharge. Inverse probability treatment weighting method was used to adjust baseline differences on metformin treatment.

Results

The study analyzed data from 1,309 patients with HF and diabetes (mean age 69 years, 56 % male). Among them, 613 (47 %) patients were on metformin at admission. During the median follow-up period of 11 months, 132 (19 %) and 74 (12 %) patients not receiving and receiving metformin treatment died, respectively. The mortality rate was lower in metformin users than in non-users (hazard ratio 0.616 [0.464–0.819] P<0.001). After adjustment, metformin was significantly associated with a lower risk for the mortality (hazard ratio 0.677 [0.495–0.928] P=0.015). In subgroup analyses, this association remains significant irrespective of baseline kidney function (eGFR <60 or ≥60 ml/min/1.73 m², P-for-interaction=0.176) or left ventricular ejection fraction (<40 %, 40–49 %, or ≥50 %, P-for-interaction=0.224).

Conclusions

Metformin treatment at the time of admission was associated with a lower risk for 1-year mortality in patients with diabetes, hospitalized for acute HF.

Aim

Advanced glycation end products (AGEs) play a role in kidney disease in type 2 diabetes mellitus (T2DM). However, there have been no prior controlled clinical trials examining the effects of specific diets on AGE metabolism and their impact on kidney function. Our aim was to assess whether modulating AGE metabolism resulting in reduced AGEs levels, after consumption of two healthy diets, could delay kidney function decline in patients with T2DM and coronary heart disease (CHD).

Methods

T2DM patients (540 out of 1002 patients from the CORDIOPREV study), with estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73 m², were classified based on their baseline kidney function: normal eGFR (≥ 90 ml/min/1.73 m²), mildly decreased eGFR (60- < 90 ml/min/1.73 m²) and moderately decreased eGFR (<60 ml/min/1.73 m²). Serum AGE levels, methylglyoxal (MG) and N-carboximethyllysine (CML), and gene expression related to AGE metabolism (AGER1, RAGE, and GloxI mRNA) were measured before and after 5-years of dietary intervention (a Mediterranean diet or a low-fat diet).

Results

Mediterranean diet produced a lower declined of eGFR compared to the low-fat diet only in patients with mildly decreased eGFR (P = 0.035). Moreover, Mediterranean diet was able to decrease MG levels and increase GloxI expression in normal and mildly decreased eGFR patients (all P < 0.05). One standard deviation increment of MG levels after dietary intervention resulted in a 6.8-fold (95 % CI 0.039;0.554) higher probability of eGFR decline.

Conclusion

Our study showed that lowering circulating AGE levels, specifically MG, after following a Mediterranean diet, might be linked to the preservation of kidney function, evidenced by a decreased decline of eGFR in T2DM patients with CHD. Patients with mildly decreased eGFR could potentially benefit more from AGE reduction in maintaining kidney function.

Objective

The aim of the TELESUR-GDM study was to demonstrate the non-inferiority of the onset of maternal, fœtal, and neonatal complications for patients with gestational diabetes mellitus (GDM) monitored by myDiabby HealthcareⓇ (app group) compared to patients with a classical glycaemic blood monitoring by diary (control group).

Materials and methods

TELESUR-GDM was a retrospective, monocentric, and non-inferiority study including 349 patients in the app group and 295 patients in the control group. The primary outcome was a composite score based on maternal, foetal, and neonatal complications. The statistical analysis used chi square or Student t tests for categorical or continuous variables, and Dunnett–Gent test for non-inferiority.

Results

In the app and control groups, 46.3 % and 53.7 % of the patients respectively, observed complications. Non-inferiority of telemonitoring by application vs diary was confirmed (odds ratio=0.79 [95 % CI 0.58;1.07], P < 0.001). Caesarean section, labour induction, and insulin treatment rates were: 20 vs 23 % (P = 0.4), 36 vs 28 % (P = 0.047), and 22 vs 23 % (P = 0.8) in the app vs control group, respectively. Macrosomia, intrauterine growth restriction, neonatal hypoglycaemia, and neonatal jaundice rates were: 4.3 vs 6.1 % (P = 0.4), 6.9 vs 3.1 % (P = 0.04), 1.7 vs 14 % (P < 0.001), and 8.6 vs 1.0 % (P < 0.001), in the app versus control group, respectively.

Conclusion

GDM glycaemic telemonitoring compared to patients with classic glycaemic monitoring by diary was not inferior in terms of maternal, fœtal, and neonatal complications. Neonatal hypoglycaemia, a life-threatening event, was significantly reduced despite the observation of more neonatal jaundice cases.

Objective

To assess real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes mellitus (T1DM).

Methods

We conducted a multicenter retrospective study in Spain including data from 250 people living with T1DM receiving dapagliflozin as add-on therapy to insulin (80.8 % on-label use). The number of diabetic ketoacidosis (DKA) events was calculated over a 12-month follow-up (primary outcome). Changes in body weight, HbA1c, total daily insulin dose, and continuous glucose monitoring (CGM) metrics from baseline (at dapagliflozin prescription) to 12 months were also evaluated.

Results

A total of five DKA events (2.4 % [95 % CI 0.3;4.5] were reported in patients with a 12-month follow-up, n = 207): two events related to insulin pump malfunction, two events related to concomitant illnesses, and one event related to insulin dose omission. DKA events were more frequent among insulin pump users than among participants on multiple daily injections (7.7 % versus 1.2 %). Four of the reported DKA events occurred within the first six months after initiation of dapagliflozin. No deaths or persistent sequelae due to DKA were reported. No severe hypoglycemia episodes were reported. Significant reductions in mean body weight (−3.3 kg), HbA1c (−0.6 %), and total daily insulin dose (−8.6 %), P < 0.001, were observed 12 months after dapagliflozin prescription. Significant improvements in TIR (+9.3 %), TAR (−7.2 %), TBR (−2.5 %), and coefficient of variation (−5.1 %), P < 0.001, were also observed in the subgroup of patients with available CGM data. Finally, an improvement in urinary albumin-to-creatinine ratio (UACR) was found among participants with UACR ≥ 30 mg/g at baseline (median decrease of 99 mg/g in UACR, P = 0.001).

Conclusion

The use of dapagliflozin in people living with T1DM has an appropriate safety profile after careful selection of participants and implementation of strategies to reduce the risk of DKA (i.e., prescribed according to the recommendations of the European Medicines Agency), and also leads to clinical improvements in this population.

Purpose

According to the preclinical data, sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2is) may exert anticancer effects. Here, we clarified the cancer-specific mortality (primary outcome) and all-cause mortality (secondary outcome) of SGLT2is and their dose-dependency in patients with cancer undergoing standard curative treatments.

Methods

We analyzed data from patients with type 2 diabetes mellitus (T2DM) diagnosed with cancer between January 1, 2016, and December 31, 2018, enrolled from the Taiwan Cancer Registry database. Kaplan-Meier method was used to estimate all-cause mortality and cancer-specific mortality, comparing survival curves between SGLT2i users and nonusers using the stratified log-rank test. Cox proportional hazards regression was conducted to identify independent predictors for all-cause and cancer-specific mortality among the covariates.

Results

We performed 1:2 propensity score matching of our data, which yielded a final cohort of 50,133 patients with cancer; of them, 16,711 and 33,422 were in the SGLT2i user and nonuser groups, respectively. The adjusted hazard ratio (aHR) for cancer-specific and all-cause mortality in SGLT2i users compared with nonusers was 0.21 (95 % confidence interval [CI]: 0.20–0.22) and 0.22 (95 % CI: 0.21–0.23). We divided the patients into four subgroups stratified by quartiles (Q) of cumulative defined daily doses per year (cDDDs), and all-cause and cancer-specific mortality was noted to significantly decrease with increases in dosage (from Q1 to Q4 cDDDs) in SGLT2i users compared with in nonusers (P < 0.001).

Conclusion

SGLT2is increase overall survival and cancer-specific survival in patients with cancer in a dose-dependent manner.