Diabetes & metabolism最新文献

Glucagon-like peptide 1 (GLP-1) is a hormone of the incretin family, secreted in response to nutrient ingestion, and plays a role in metabolic homeostasis. GLP-1 receptor agonist has a peripheral and a central action, including stimulation of glucose-dependent insulin secretion and insulin biosynthesis, inhibition of glucagon secretion and gastric emptying, and inhibition of food intake. Through their mechanism, their use in the treatment of type 2 diabetes has been extended to the management of obesity, and numerous trials are being conducted to assess their cardiovascular effect. Type 2 diabetes appears to share common pathophysiological mechanisms with the development of cognitive disorders, such as Alzheimer's and Parkinson's disease, related to insulin resistance. In this review, we aim to examine the pathological features between type 2 diabetes and dementia, GLP-1 central effects, and analyze the relevant literature about the effect of GLP-1 analogs on cognitive function of patients with type 2 diabetes but also without. Results tends to show an improvement in some brain markers (e.g. hippocampal connections, cerebral glucose metabolism, hippocampal activation on functional magnetic resonance imaging), but without being able to demonstrate a strong correlation to cognitive scores. Some epidemiological studies suggest that GLP-1 receptor agonists may offer a protective effect, by delaying progression to dementia when diabetic patients are treated with GLP-1 receptor agonists. Ongoing trials are in progress and may provide disease-modifying care for Alzheimer's disease and Parkinson's disease patients in the future.

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a condition characterized by liver fat accumulation and metabolic abnormalities. Given the potential impact of MAFLD on patient health, it is important to understand its association with major adverse cardiovascular events (MACE) such as myocardial infarction (MI) and stroke. In the prospective UK Biobank cohort, we sought to elucidate the association of MAFLD and its subtypes with incident MI and stroke. In this study, we analyzed the data of 325,129 participants in the UK Biobank and calculated relative risks for MI and stroke using Cox regression analysis. Among 325,129 participants over a median duration of 12.8 years follow-up, participants with MAFLD were significantly more likely to experience a MI (hazard ratio [HR] = 1.35, 95% confidence interval [CI: 1.29;1.41] P < 0.001) or a stroke (HR = 1.26 [1.18–1.33] P < 0.001) compared to those without MAFLD. In addition, diabetic, overweight with metabolic dysfunction (MD), and lean MAFLD subtypes were significantly associated with an increased risk for MI and stroke, whereas overweight without MD subtype did not appear to be associated with this risk. Our findings also revealed graded associations between liver fibrosis scores and risk of MI and stroke in MAFLD patients. However, only diabetic, and overweight patients with MD subtypes exhibited graded associations between liver fibrosis score and the risk of MI and stroke among the MAFLD subtypes. Furthermore, the risk alleles traits of fatty liver did not enhance the effect of MAFLD on the risk of MI and stroke. In conclusion, a diagnosis of MAFLD is associated with an increased risk of MI or stroke, and the assessment of MAFLD and its subtypes should be a component of the cardiovascular risk assessment.

Aims

This study evaluated the efficacy and safety of enavogliflozin, a novel sodium-glucose cotransporter 2 inhibitor, versus dapagliflozin in Korean patients with type 2 diabetes mellitus (T2DM) inadequately controlled with metformin and gemigliptin.

Methods

In this multicenter, double-blind, randomized study, patients with inadequate response to metformin (≥ 1000 mg/day) plus gemigliptin (50 mg/day) were randomized to receive enavogliflozin 0.3 mg/day (n = 134) or dapagliflozin 10 mg/day (n = 136) in addition to the metformin plus gemigliptin therapy. The primary endpoint was change in HbA1c from baseline to week 24.

Results

Both treatments significantly reduced HbA1c at week 24 (–0.92% in enavogliflozin group, –0.86% in dapagliflozin group). The enavogliflozin and dapagliflozin groups did not differ in terms of changes in HbA1c (between-group difference: –0.06%, 95% confidence interval [CI]: –0.19, 0.06) and fasting plasma glucose (between-group difference: –3.49 mg/dl [–8.08;1.10]). An increase in urine glucose-creatinine ratio was significantly greater in the enavogliflozin group than in the dapagliflozin group (60.2 g/g versus 43.5 g/g, P < 0.0001). The incidence of treatment-emergent adverse events was similar between the groups (21.64% versus 23.53%).

Conclusions

Enavogliflozin, added to metformin plus gemigliptin, was well tolerated and as effective as dapagliflozin in the treatment of patients with T2DM.

Background

Whether diabetes and genetic susceptibility of kidney diseases modifies the relationship between ultra-processed foods (UPF) consumption and incident chronic kidney disease (CKD) remains uncertain. We aimed to investigate the association between UPF consumption and new-onset CKD in participants with and without diabetes, and explore whether genetic risks of kidney diseases may modify the association.

Methods

153,985 participants who were free of CKD at baseline and provided 24-h dietary recalls in the UK Biobank were included. UPF was defined according to the NOVA classification. The energy contribution of UPF was calculated by dividing the energy intake of UPF by the total energy intake. The study outcome was new-onset CKD, ascertained by self-report data and data linkage with primary care, hospital admissions, and death registry records.

Results

During a median follow-up of 12.1 years, 4,058 participants developed new-onset CKD. There was a significant positive association between UPF consumption and new-onset CKD in total participants (per 10% increment, adjusted hazard ratio (HR) 1.04; 95% confidence interval (CI) [1.01;1.06]. The positive association between UPF consumption and risk of new-onset CKD was significantly stronger in participants with diabetes (per 10% increment, adjusted HR 1.11 [1.05;1.17]) than in those without diabetes (per 10% increment, adjusted HR 1.03 [1.00;1.05]; P-interaction = 0.005). Genetic risks of kidney diseases did not significantly modify the positive association in those with or without diabetes (all P-interactions > 0.05).

Conclusion

There was a significantly stronger positive association between UPF consumption and new-onset CKD in participants with diabetes compared with those without diabetes.

Aims

Increasing attention has been paid to the potential metabolic benefits of ketone bodies, but the clinical relevance of ketone bodies in newly diagnosed type 2 diabetes mellitus (T2D) remains unclear. We investigated the clinical implications of ketone bodies at the time of diagnosis in patients with drug-naïve T2D.

Methods

Clinical data including serum β-hydroxybutyrate (βHB) levels, were collected from 369 patients with newly diagnosed drug-naïve T2D from 2017 to 2021. Subjects were categorized into four βHB groups based on the level of initial serum βHB. The associations of initial serum βHB and urinary ketone levels with glucometabolic indices were analyzed.

Results

Higher serum βHB group was associated with higher levels of glycemic parameters including glycated hemoglobin (HbA1c) with lower levels of indices for insulin secretory function at the point of initial diagnosis of T2D. Nevertheless, higher serum βHB group was an independent determinant of a greater relative improvement in HbA1c after 6 months of anti-diabetic treatment, regardless of the type of anti-diabetic drug. In addition, patients in higher serum βHB group were more likely to have well-controlled HbA1c levels (≤6.5%) after 6 months of anti-diabetic treatment.

Conclusion

In patients with newly diagnosed T2D, a higher initial βHB level was a significant predictive marker of greater glycemic improvement after antidiabetic treatment, despite its associations with hyperglycemia and decreased insulin secretion at baseline.

Bariatric/metabolic surgery and sodium-glucose cotransporter 2 inhibitors (SGLT2is) are becoming increasingly popular for the management of overweight/obese patients with type 2 diabetes mellitus (T2DM). Consequently, the chance that a patient undergoing bariatric/metabolic surgery is also treated with an SGLT2i would be rather common in clinical practice. Both risks and benefits have been reported. On the one hand, several cases of euglycemic diabetic ketoacidosis have been reported within the few days/weeks after bariatric/metabolic surgery. The causes are diverse but a drastic reduction in caloric (carbohydrate) intake most probably plays a crucial role. Thus, SGLT2is should be stopped a few days (and even more if a pre-operative restricted diet is prescribed to reduce liver volume) before the intervention and reintroduced only when the caloric (carbohydrate) intake is sufficient. On the other hand, SGLT2is may exert a favorable effect to reduce the risk of postprandial hypoglycemia, a complication reported among patients who have been treated with bariatric/metabolic surgery. An increased hepatic glucose production and a reduced production of interleukin-1β have been proposed as possible underlying mechanisms for this protective effect. Finally, whether SGLT2is could prolong diabetes remission following surgery and improve the prognosis of patients with T2DM who benefit from bariatric/metabolic surgery remains to be investigated.

Objectives

The classical glycosylated hemoglobin A1c threshold of 6.5% is an insensitive screening test for cystic fibrosis-related diabetes (CFRD). We sought to identify CF-specific A1C thresholds associated with 1) risk of progression to CFRD and 2) changes in body mass index (BMI) and forced expiratory volume (FEV1).

Methods

We studied the cross sectional and longitudinal associations between A1c, BMI, and FEV1 in 2 cohorts of 223 children (followed for up to 8 years) and 289 adults (followed for a mean of 7.5 ± 4.3 years) with CF but without diabetes at baseline and undergoing regular assessments including Oral Glucose Tolerance Test (OGTT).

Results

For the onset of OGTT-defined CFRD optimal A1c threshold was 5.9% in adults (sensitivity: 67% and specificity: 71%) and 5.7% for children (sensitivity: 60% and specificity: 47%). Kaplan-Meier analysis of progression to CFRD according to baseline A1C showed increased the risk of developing CFRD for A1c ≥ 6.0% in adults (P = 0.002) and ≥ 5.5% in children (p = 0.012). Temporal changes in BMI and FEV1 according to baseline A1C in adults were assessed with a linear mixed-effect model, BMI significantly increased over time in subjects with a baseline A1c < 6%, but those with a A1C ≥ 6.0% gained significantly less weight over time (P = 0.05). There was no difference in FEV1 according to baseline A1c category.

Conclusion

An A1C above 6% may be associated with a high risk of developing CFRD and a lower probability of weight gain in both adults and children with CF.

Aim

To compare the frequencies and types of congenital heart defects for infants of women without and with pre-gestational diabetes, type 1 and type 2 diabetes (T1DM, T2DM) and to identify risk factors.

Methods

All live births between 2012 and 2020 were screened for maternal diabetes and infant congenital heart defects using the French Medical Information System Program in Medicine, Surgery and Obstetrics database (PMSI-MCO). Incidences of these defects were estimated, and a logistic model evaluated maternal and fetal prognostic risk factors.

Results

Overall, 6,038,703 mothers did not have pre-gestational diabetes (no-diabetes), 23,147 had T1DM, and 14,401 had T2DM. The incidence of infant congenital disease was 6.2% for the no-diabetes group, 8.0%, for women with T1DM, and 8.4% for women with T2DM (P < 0.001); for congenital heart defects, incidences were respectively 0.8%, 3.0% and 2.7% (P < 0.001). In comparison with the no-diabetes group, the odds ratios (95%CI) of coronary heart defects were 2.07 (1.91;2.24) (P < 0.001) for women with T1DM and 2.20 (1.99;2.44) (P < 0.001) for women with T2DM, with no difference between T1DM and T2DM (P = 0.336). cesarian section, small and large for gestational age, and prematurity were also associated with an increased risk of congenital heart defects.

Conclusion

In this study we observed higher incidences of congenital heart defects in infants of women with pre-gestational diabetes compared to women without pre-gestational diabetes, with no difference between women with T1DM or T2DM. These data call for intensifying preconception care and justify systematic cardiac echography in selected fetuses.