Diabetes & metabolism最新文献

It is notable that monogenic forms of diabetes are exceedingly uncommon, with only 28 genes thus far identified. Such conditions frequently result in the dysfunction of pancreatic cells responsible for insulin production. Mutation in the TRMT10A gene leads to a rare genetic disease that is associated with endocrine and metabolic disorders, including diabetes and short stature. This article presents a review of the existing literature on the subject, describing the association between TRMT10A gene mutation and diabetes. It also presents the clinical case of a young girl with type 1 diabetes and facial dysmorphia. TRMT10A gene mutation has been linked to syndromic juvenile diabetes in a manner analogous to Wolfram's syndrome. This form of diabetes, which manifests in early childhood and is associated with microcephaly, epilepsy and intellectual disability, is caused by mutations in the gene for homolog A of tRNA methyltransferase 10 (TRMT10A).

This emphasizes the importance of using a targeted panel to recognize previously unidentified monogenic diabetes among early-onset non-insulin-dependent diabetes in the absence of obesity and autoimmunity.

In view of the aforementioned data, it is recommended that TRMT10A sequencing be considered in children or adults with early-onset diabetes and a history of intellectual disability, microcephaly and epilepsy.

Aim

Postprandial glycemic fluctuations after gastrectomy are seen in patients with gastric cancer but, no studies have investigated the association between gastrectomy and type 2 diabetes mellitus (T2DM) in gastric cancer survivors. This study aimed to elucidate the relationship between gastrectomy (total or subtotal) and incident T2DM. In addition, we explored whether vitamin B12 supplementation modulates this risk among patients who have undergone total gastrectomy.

Methods

In this large nationwide population-based retrospective cohort study using the National Health Insurance Service database of South Korea, we identified patients aged >20 years who underwent gastrectomy from 2008 to 2015 (n = 150,074) and age- and sex-matched controls without gastrectomy (n = 301,508). A Cox proportional hazards model was used.

Results

During the median follow-up duration of 4.4 years after the 2-year time lag after gastrectomy, of the 78,006 subjects, 4,597 (5.9 %) developed T2DM. Compared with matched controls, the adjusted hazard ratio (AHR[95 % confidence interval]) for T2DM of patients with total gastrectomy was 1.34[1.23;1.47]. The corresponding AHR after subtotal gastrectomy was 0.81[0.76;0.86]. Among the patients with total gastrectomy, the risk of T2DM was significantly increased in those who did not receive any vitamin B12 supplementation (AHR=1.60[1.33;1.92]), whereas the risk of T2DM was lower (close to being statistically significant) in those who received continuous vitamin B12 supplementation after gastrectomy (AHR=0.70[0.49;1.01]).

Conclusion

These results show a significantly reduced risk of T2DM in gastric cancer patients undergoing subtotal gastrectomy and a significantly increased risk of T2DM in gastric cancer patients undergoing total gastrectomy, which is mitigated by continuous vitamin B12 supplementation.

Objective

Optimal weight loss involves decreasing adipose tissue while preserving lean muscle mass. Identifying molecular mediators that preserve lean muscle mass is therefore a clinically important goal. We have shown that circulating, postprandial FGF19 levels are lower in patients with obesity and decrease further with comorbidities such as type 2 diabetes and MASLD. Preclinical studies have shown that FGF15 (mouse ortholog of human FGF19) is necessary to protect against lean muscle mass loss following metabolic surgery-induced weight loss in a mouse model of diet-induced obesity. We evaluated if non-surgical weight loss interventions also lead to increased systemic levels of FGF19 and whether FGF19 levels are predictive of lean muscle mass following rapid weight loss in human subjects with obesity.

Research design and methods

Weight loss was induced in 176 subjects with obesity via a very low-energy diet, VLED (800 kcal/d) in the form of total liquid meal replacement for 3-4 months. We measured plasma FGF19 levels at baseline and following VLED-induced weight loss. Multiple linear regression was performed to assess if FGF19 levels were predictive of lean mass at baseline (obesity) and following VLED.

Results

Postprandial levels of FGF19 increased significantly following VLED-weight loss. Multiple linear regression analysis showed that baseline (obesity) FGF19 levels, but not post VLED FGF19 levels, significantly predicted the percent of lean muscle mass after VLED-induced weight loss, while controlling for age, sex, and the baseline percent lean mass.

Conclusion

These data identify gut-muscle communication and FGF19 as a potentially important mediator of the preservation of lean muscle mass during rapid weight loss.

Objective

Although insulin resistance (IR) has been recognized to be a causal component in various diseases, current information on the relationship between IR and long-term mortality in the general population is limited and conclusions varied among different IR indicators and different populations. We aimed to assess associations between different measurements of IR with long-term all-cause mortality and cardiovascular mortality risk for the general population.

Research design and methods

We included 13,909 individuals from the Third National Health and Nutrition Examination Survey. Mortality was identified via National Death Index information until December 31, 2019. IR was measured using fasting insulin, homeostasis model assessment of IR (HOMA-IR), homeostasis model assessment of β-cell function, quantitative insulin sensitivity check index (QUICKI), insulin-to-glucose ratio (IGR), triglyceride glucose (TyG) index, TyG-body mass index (TyG-BMI), and hypertriglyceridemic-waist phenotype.

Results

During median 25-year follow-up, 5,306 all-cause mortality events occurred. After multivariate adjustment, variables significantly associated with elevated all-cause mortality risk were (hazard ratio [95 % confidence interval]): higher insulin (1.07 [1.02;1.13]); HOMA-IR (1.08 [1.03;1.13]); IGR (1.05 [1.00;1.11]); TyG (1.07 [1.00;1.14]); TyG-BMI (1.24 [1.02;1.51]); lower QUICKI (0.91 [0.86–0.96]). After stratification by diabetes status, higher insulin, HOMA-IR, TyG-BMI and lower QUICKI were significantly associated with increased risk of all-cause mortality in both diabetes and non-diabetes populations (all P for interaction > 0.05). Higher TyG (adjusted HR 1.17 [1.09;1.26], P for interaction = 0.018) and hypertriglyceridemic-waist phenotype (adjusted HR 1.26 [1.08;1.46], P for interaction = 0.047) were significantly associated with increased risk of all-cause mortality in patients with diabetes, however, these associations could not be seen in people without diabetes. Similar results were observed between the above-mentioned IR indicators and cardiovascular death.

Conclusions

Fasting insulin, HOMA-IR, TyG-BMI, and QUICKI may indicate mortality risk in diabetes and non-diabetes populations, with TyG and the hypertriglyceridemic-waist phenotype showing particular relevance for individuals with diabetes. Further studies are needed to validate these findings and determine their broader applicability.

Aims

The objective of this study was to assess overall and segmented trends in the incidence of type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) in children and adolescents younger than 20 years, from 2002 to 2022.

Methods

This study used registry data on physician-diagnosed T1DM or T2DM from primary and secondary sources, covering the German federal state of North Rhine-Westphalia with 18 million inhabitants. The ages at T1DM and T2DM onset ranged from 0 to 19 and 10–19 years, respectively. The main outcomes were direct age- and/or sex-standardized incidence rates per 100,000 person-years (PYs) and trends estimated as annual percentage changes (APCs), both with 95 % confidence intervals. The segmented trends for subperiods were based on joinpoint regression models.

Results

From 2002–2022, 17,470 and 819 persons had incident T1DM and T2DM, respectively. The total number of PYs was 73,743,982 for T1DM and 39,210,453 for T2DM, with a mean coverage rate of 98 % for T1DM and 90 % for T2DM. The standardized T1DM incidence increased from 17.6 [16.3;18.9} in 2002 to 33.2 [31.3;35.1] in 2022, with an APC of 2.7 % [2.3 %;3.1 %]. The standardized T2DM incidence increased from 1.3 [0.8;1.7] in 2002 to 2.8 [2.0;3.6] in 2022, with an APC of 6.4 % [4.9 %;8.0 %]. There were four different segmented trends for T1DM and T2DM, with the incidence peaking in 2021 and subsequently declining.

Conclusions

The incidence rates of T1DM and T2DM have increased over the past 20 years, with a wave-like pattern during the Covid-19 pandemic.

Aims

To evaluate the impact of onset time, duration, and severity of various types of hypertensive disorders of pregnancy (HDP) on the risk of incident DM.

Methods

We used data from the ongoing French nationwide prospective cohort study CONCEPTION. We included all primiparous women in CONCEPTION who delivered between 2010 and 2018 (n = 2,816,793 women). Follow-up spanned from childbirth to 31 December 2021. HDP and incident DM onset during follow-up were identified using algorithms combining ICD-10 coded diagnoses during hospitalization and/or medication dispensing. We used Cox models to assess the associations between incident DM and preexisting chronic hypertension, gestational hypertension (GH), and various phenotypes of pre-eclampsia.

Results

Pre-eclampsia and GH alone occurred in 2.6 % and 4.6 % of the population, respectively. During follow-up (mean = 4.5 years), 16,670 women had incident DM. The cumulative incidences of DM were 15.8 % and 1.8 % in women who had pre-eclampsia during pregnancy with and without concomitant gestational diabetes, respectively. The risk of DM was higher after HDP (all types) irrespective of gestational diabetes status during pregnancy. In women without gestational diabetes, compared with those who had no HDP, the risk of incident DM was higher in women who had GH (adjusted hazard ratio, aHR = 1.97 [1.81–2.16]), pre-eclampsia (aHR = 2.42 [2.21–2.65]), and preexisting chronic hypertension prior to pregnancy (aHR = 3.35 [3.03–3.70]). Pre-eclampsia duration was significantly associated with a higher risk of DM.

Conclusion

Women who experienced an HDP had twice the risk of developing DM. Early blood glucose assessment and blood pressure monitoring should be more widely recommended after HDP diagnosis.

Objectives

We aimed to assess the clinical effects of dietary education intervention utilizing the nudge strategy in individuals with type 2 diabetes mellitus (T2DM).

Background

The global prevalence of T2DM and its associated complications presents a significant health challenge. While the benefits of dietary education intervention for blood glucose management are widely acknowledged, patients often struggle to adhere to dietary recommendations. The implementation of the nudge strategy may offer a promising solution to change unhealthy dietary behavior and enhance diabetes control among individuals with T2DM.

Methods

This is a sub-study within a broader cluster-randomized trial that evaluated the effects of nudge-based dietary education and traditional dietary education intervention. Measurements of HbA1c, fasting blood glucose (FBG), body mass index (BMI), blood lipid levels, blood pressure, dietary behavior, and diabetes distress were assessed at baseline and 3 months after the intervention in 147 individuals with T2DM from six primary care practices in Beijing, China.

Results

All outcome measurements were complete at two time points for 134 participants. Results showed that compared to the control group, the intervention group achieved a significantly greater reduction in HbA1c, FBG, BMI, total cholesterol, low-density lipoprotein cholesterol, blood pressure, total energy intake, carbohydrate intake, fat intake, and protein intake and had lower diabetes distress. The intervention group also maintained HDL-C levels and had a significantly greater increase in vegetable intake, while changes in triglycerides were similar in the two groups.

Conclusion

The present study provides evidence that nudge strategy-based dietary education intervention is effective in improving blood glucose, BMI, blood lipid levels, and blood pressure and facilitating changes in patients' dietary behavior and diabetes distress. These findings suggest that implementing nudge strategies can contribute to the optimization of T2DM dietary management and overall patient well-being.

Aim

Bariatric surgery is highly effective for the treatment of obesity in individuals without (OB¹) and in those with type 2 diabetes (T2D²). However, whether bariatric surgery triggers similar or distinct molecular changes in OB and T2D remains unknown. Given that individuals with type 2 diabetes often exhibit more severe metabolic deterioration, we hypothesized that bariatric surgery induces distinct molecular adaptations in skeletal muscle, the major site of glucose uptake, of OB and T2D after surgery-induced weight loss.

Methods

All participants (OB, n = 13; T2D, n = 13) underwent detailed anthropometry before and one year after the surgery. Skeletal muscle biopsies were isolated at both time points and subjected to transcriptome and methylome analyses using a comprehensive bioinformatic pipeline.

Results

Before surgery, T2D had higher fasting glucose and insulin levels but lower whole-body insulin sensitivity, only glycemia remained higher in T2D than in OB after surgery. Surgery-mediated weight loss affected different subsets of genes with 2,013 differentially expressed in OB and 959 in T2D. In OB differentially expressed genes were involved in insulin, PPAR signaling and oxidative phosphorylation pathways, whereas ribosome and splicesome in T2D. LASSO regression analysis revealed distinct candidate genes correlated with improvement of phenotypic traits in OB and T2D. Compared to OB, DNA methylation was less affected in T2D in response to bariatric surgery. This may be due to increased global hydroxymethylation accompanied by decreased expression of one of the type 2 diabetes risk gene, TET2, encoding a demethylation enzyme in T2D.

Conclusion

OB and T2D exhibit differential skeletal muscle transcriptome responses to bariatric surgery, presumably resulting from perturbed epigenetic flexibility.