Diabetes & metabolism最新文献

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.

Objective

The effects of nonalcoholic fatty liver disease on the risk of end-stage renal disease (ESRD) remain unclear. We investigated the association between the fatty liver index (FLI) and risk of ESRD in patients with type 2 diabetes.

Methods

This population‐based observational cohort study enrolled patients with diabetes who underwent health screening between 2009 and 2012 and utilized data from the Korean National Health Insurance Services. The FLI functioned as a surrogate marker for the presence of hepatic steatosis. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m² calculated using the Modification of Diet in Renal Disease equation. We performed Cox proportional hazards regression.

Results

Incident ESRD developed in 19,476 of 1,900,598 patients with type 2 diabetes during a median follow-up of 7.2 years. After adjusting for conventional risk factors, patients with high FLI scores had a higher risk for ESRD: FLI, 30–59 [hazard ratio (HR) = 1.124; 95% confidence interval (CI), 1.083–1.166]; FLI ≥ 60 [HR = 1.278; 95% CI, 1.217–1.343] compared with those with FLI < 30. The association between a high FLI score (≥ 60) and incident ESRD was more prominent in women than in men (male, FLI ≥60: HR, 1.106; 95% CI = 1.041–1.176 and female, FLI ≥ 60: HR, 1.835; 95% CI = 1.689–1.995). The association between a high FLI score (≥ 60) and the risk of ESRD differed according to baseline kidney function. High FLI scores increased the risk of ESRD (HR = 1.268; 95% CI, 1.198–1.342) in patients with CKD at baseline.

Conclusion

High FLI scores are associated with a greater risk of ESRD in patients with type 2 diabetes with CKD at baseline. Close monitoring and appropriate management of hepatic steatosis may aid in preventing the progression of kidney dysfunction in patients with type 2 diabetes and CKD.

Aims

Glycemic thresholds used to diagnose gestational diabetes mellitus (GDM) are a continued subject of debate. Lower glycemic thresholds identify women with milder GDM for whom treatment benefit is unclear. We compared adverse maternal and neonatal outcomes in treated and untreated women with mild hyperglycemia.

Methods

We reviewed 11 553 patient charts from two tertiary care centers and included singleton pregnancies >32-week gestation. GDM was diagnosed using the one- or two-step 75 g oral glucose tolerance test (OGTT) depending on the center. All OGTT results were reviewed. Women with glycemic values falling between the thresholds of the two tests, referred to as intermediate hyperglycemic (IH), defined as FPG 5.1–5.2 mmol/L, 1 h PG 10.0–10.5 mmol/L, or 2 h PG 8.5–8.9 mmol/L at 75 g OGTT, were untreated at center A and treated at center B.

Results

There were 630 women with IH, 334 were untreated (center A) and 296 who were treated (center B). After adjusting for covariates, untreated IH women had significantly higher rates of gestational hypertension (aOR 6.02, P = 0.002), large for gestational age (LGA) (aOR 3.73, P < 0.001) and birthweights > 4000 g (aOR 3.35, P = 0.001). Our results indicate that treating 11 women with IH would prevent one LGA birth and treating 13 would prevent 1 birthweight > 4000 g.

Conclusion

The diagnosis of GDM using the two-step OGTT fails to identify subgroups of women with mild hyperglycemia that would benefit from treatment to lower the risk for adverse maternal and neonatal outcomes. Treatment of women with mild hyperglycemia decreased the risk of LGA and birthweight >4000 g by 3-fold.