New-onset Type Research Articles

Biliopancreatic diversion for severe obesity: long-term weight maintenance and occurrence of nutritional complications are two facets of the same coin.

Despite the widespread clinical use of hypoabsorptive metabolic bariatric surgery, very long-term outcomes are still lacking. The aim of the study was to assess the long-term safety and efficacy of biliopancreatic diversion at 30 years in patients with class 3 obesity (BMI over 40 kg/m2). This retrospective single-centre study used data from a prospectively collected database on a sample of consecutive patients submitted to biliopancreatic diversion with a minimum follow-up of 30 years. Outcomes assessed included overall survival, long-term weight loss and weight maintenance, remission of obesity-related co-morbidities, and short- and long-term surgical and/or nutritional or metabolic complications. Among 199 consecutive patients (136 female, 63 male) who had surgery between November 1992 and April 1994, the mean age at operation was 38 (range 14-69) years and mean preoperative BMI was 48.7 (32.0-74.3) kg/m2. At baseline, 91 of 199 patients (45.7%) had type 2 diabetes. At 20 and 30 years, 122 (61%) and 38 (19%) of the 199 patients respectively were available for follow-up. At 30 years, the overall mortality rate was 12% (23 of 199). Surgical complications were concentrated in the short-term follow-up, whereas nutritional or metabolic complications increased progressively over time. A nutritional complication was diagnosed in 73 of 122 patients (60%) at 20 years and 28 of 38 (74%) at 30 years. Weight loss and glycaemic control were maintained throughout the follow-up; mean % total weight loss was 32.8 (range 14.1-50.0) at 1 year and 37.7 (range 16.7-64.8) at 30 years. One patient presented with recurrence of type 2 diabetes at 20 and 30 years; there were no patients with new-onset type 2 diabetes. Biliopancreatic diversion leads to good and sustained weight maintenance up to 30 years with low perioperative risk, but at the cost of a high long-term prevalence of nutritional complications.

Predictive biomarkers of rapidly developing insulin deficiency in children with type 1 diabetes

IntroductionThe rate of progression to complete insulin deficiency varies greatly in type 1 diabetes. This constitutes a challenge, especially when randomizing patients in intervention trials aiming to preserve beta cell...

Diagnosis of hepatic steatosis and steatohepatitis in people with new-onset type 2 diabetes: a multidisciplinary approach.

Non-Alcoholic-Fatty-Liver-Disease (NAFLD) is the most common cause of chronic liver disease in Western countries; closely linked to obesity and type 2 diabetes (T2DM), it is an additional cardiovascular risk factor. The aim of this study is to investigate the prevalence of NAFLD at T2DM onset. 122 newly diagnosed T2DM patients were enroled; NAFLD was diagnosed using ultrasound and fibrosis risk calculated with an FIB4-score. Intermediate and high-risk patients were referred to a hepatologist and underwent transient elastography (TE). At T2DM diagnosis, 25% of patients were overweight, 47% were obese; ultrasound steatosis was present in 79% of patients; the average FIB-4 score was 1.4 (0.7). The NAFLD population was characterised by higher presence of obesity (60%, p 0.06); hypertension (56%, p 0.00); AST (26.3 (23.6) UI/L; p 0.00); ALT (49.3(41.0) UI/L p 0.00); FIB-4 score (1.6 (0.8); p 0.00). Among patients referred to a hepatologist, at TE, 65% had severe steatosis, 22% significant fibrosis and 25% advanced fibrosis. This is the first proposal of a NAFLD screening model at T2DM diagnosis. The high prevalence of fibrosis found at the early stage T2DM confirms the compelling need for early management of NAFLD through cost-effective screening and long-term monitoring algorithms.

The COVID-19 Pandemic Increased the Incidence of New-Onset Type One Diabetes in Children.

Background: The impact of the COVID-19 pandemic on the incidence rate of childhood type 1 diabetes (T1D) is controversial. Our aim was to analyze the incidence of new-onset T1D among children aged 0-17 before and during the COVID-19 pandemic in Israel. Methods: Data obtained from the national T1D registry for children aged 0-17 were analyzed for the pre-pandemic (1997-2019) and pandemic (2020-2022) periods. In the pre-pandemic period, 7246 children with newly diagnosed T1D were compared with 1490 children diagnosed during the pandemic period. Results: T1D incidence significantly increased in the 0-17 age group from a mean of 12.9/105 (pre-pandemic) to 17.7/105 and 16.7/105 during the first two years of the pandemic (2020 and 2021, respectively) (p = 0.0001). Stratifying by age group (0-4, 5-9, 10-14, and 15-17) revealed a significant increase in the 5-9, 10-14, and 15-17 groups, both in 2020 (p = 0.0001) and in 2021 (p = 0.0001). The incidence rate in the 0-4 age group showed no change in the first year of the pandemic (2020) (p = 0.4). However, in the second year of the pandemic (2021), there was a significant increase from 6.3/105 in the pre-pandemic period to 9.1/105 (p = 0.001). Anti-COVID-19 vaccination in 2022 led to a significant decrease in the incidence rates in the 10-14 and 15-17 age groups (p = 0.03 and p = 0.02, respectively). Conclusion: The COVID-19 pandemic was associated with a significant increase in the incidence of new-onset T1D in prepubertal and pubertal children. Anti-COVID-19 vaccination decreased the incidence rate significantly only in pubertal children.

Analysis of association between new-onset type 2 diabetes mellitus and pancreatic cancer: retrospective research

Introduction. Pancreatic cancer is characterized by an extremely unsatisfactory prognosis, despite the development of technologies for the treatment of this pathology. In more than 80 % of patients at the time of the initial request for medical care, the disease is represented by a locally advanced or metastatic stage. Currently used methods of treatment of this nosology are most effective at the early stages of the disease. The absence of characteristic clinical, instrumental and laboratory symptoms, as well as organizational measures for the early detection of this neoplasia creates certain difficulties for effective treatment. Type 2 diabetes is probably one of the risk factors for the development of pancreatic cancer. Epidemiological studies have shown that newly diagnosed type 2 diabetes is associated with a 1.5–2.0-fold increased risk of developing pancreatic cancer in patients over 50 years of age. Insulin resistance and its associated hyperglycemia, hyperinsulinemia, and inflammation are thought to be the main mechanisms contributing to the development of diabetes-related pancreatic cancer. New-onset type 2 diabetes mellitus may be a preclinical sign of pancreatic cancer, and patients with newly diagnosed diabetes may constitute a population in which pancreatic cancer can be detected at an early stage, that will significantly improve the results of treatment.
 Objective. To analyze the relationship between new-onset type 2 diabetes mellitus and the development of pancreatic cancer.
 Material and methods. A retrospective analysis of the medical records of patients with a confirmed diagnosis of pancreatic cancer, who were treated at the Academician A.M. Granov Russian Scientific Center of Radiology and Surgical Technologies from 2019 to 2022, was carried out. As a source of information, data from medical records of inpatient and outpatient treatment cards were used. In total, the data of 203 persons were studied: morphologically confirmed pancreatic ductal adenocarcinoma was diagnosed in 172 patients (group I), in 31 patients pancreatic tumors had a different histological structure: acinar carcinoma, neuroendocrine tumors (group II). Group I excluded 8 patients without diabetes mellitus who were taking medications, which affect the blood glucose levels. The frequency of occurrence of type 2 diabetes mellitus in the groups was analyzed and then the statistical significance was assessed using the calculation of Fisher's exact test. Group I was analyzed by sex and age, then patients from group I aged 50–75 years were divided into 3 subgroups depending on the glycemic profile: 1) patients with long-term type 2 diabetes mellitus (anamnesis more than 3 years); 2) patients with new-onset type 2 diabetes mellitus (anamnesis less than 3 years); 3) patients without disorders of glucose metabolism. In the subgroup of patients with a long history of type 2 diabetes mellitus, the fact of disease decompensation was additionally assessed.
 Results. Type 2 diabetes mellitus was more common in patients with pancreatic ductal adenocarcinoma (p 0.01, Fisher's exact test p = 0.0012) than in other pancreatic neoplasms. The age of patients in group I ranged from 36 to 81 years. The average age of men was 61 ± 8.5 years. The average age of women was 58.9 ± 8.2 years. Among patients of group I aged 50–75 years, new-onset type 2 diabetes mellitus occurred in 78 (68.4 %) persons, type 2 diabetes mellitus with an anamnesis of more than 3 years was detected in 19 (16.6 %) patients, normal metabolism of glucose was observed in 17 (14 %) patients. Of 19 patients with a long anamnesis of type 2 diabetes mellitus (more than 3 years), decompensation in the form of impaired glycemic control was observed in 12 (63.2 %) patients before the diagnosis of pancreatic cancer, in 7 (36.8 %) patients no signs of decompensation of the course of type 2 diabetes mellitus were registered.
 Conclusions. New-onset type 2 diabetes mellitus occurred in 78 (64.4 %) patients over 50 years of age with pancreatic ductal adenocarcinoma. The data obtained indicate the feasibility of conducting studies to identify patients aged 50–70 years with newly diagnosed type 2 diabetes in the risk group for the development of pancreatic cancer and examine this contingent at the stage of primary health care. Further retrospective as well as prospective multicenter studies on the association between newly diagnosed type 2 diabetes mellitus and the risk of developing pancreatic cancer are required.

Oxidative Balance Score and New-Onset Type 2 Diabetes Mellitus in Korean Adults without Non-Alcoholic Fatty Liver Disease: Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) Cohort.

The oxidative balance score (OBS) is a novel composite of pro- and anti-oxidative markers for assessing the risk of cardiometabolic diseases and non-alcoholic fatty liver disease (NAFLD). However, it has not yet been established whether the OBS is related to type 2 diabetes mellitus (T2DM), especially in a population without NALFD. Therefore, we aimed to investigate the longitudinal effect of the OBS on T2DM in a large cohort of Korean adults without NALFD. Data were assessed from 9798 participants without NALFD from the Korean Genome and Epidemiology Study-Health Examinees (KoGES-HEXA) cohort. The participants were divided into three groups according to OBS tertiles, identified as T1-T3. We prospectively assessed the hazard ratios (HRs) with 95% confidence intervals (CIs) for new-onset T2DM using multivariable Cox proportional hazard regression models over 6 years following the baseline survey. During the mean 3.5 years of follow-up, 145 individuals (1.48%; 56 men and 89 women) developed T2DM. The HRs of T2DM for the OBS tertiles were 0.79 (95% CI, 0.53-1.18) and 0.60 (95% CI, 0.39-0.93) in the T2 and T3 groups after adjusting for metabolic parameters in subjects without NALFD, respectively; however, the T2 group did not show statistical significance toward a decrease in incident T2DM. A low OBS may be a useful predictive marker in new-onset T2DM for middle-aged and older subjects without NALFD. This implies that the OBS could be an additional valuable tool for assessing the incidence of T2DM among individuals without NAFLD.

Relative poverty is associated with increased risk of diabetic ketoacidosis at onset of type 1 diabetes in children. A Swedish national population-based study in 2014-2019.

The aim of the study was to estimate the effect of household relative poverty on the risk of diabetic ketoacidosis at diagnosis of children with type 1 diabetes using an international standard measurement of relative poverty. A national population-based retrospective study was conducted. The Swedish National Diabetes Register (NDR) was linked with data from Sweden's public statistical agency (Statistics Sweden). Children who were diagnosed with new-onset type 1 diabetes in the period of 2014-2019 were common identifiers. The definition of diabetic ketoacidosis was venous pH <7.30 or a serum bicarbonate level <18 mmol/L. The exposure variable was defined according to the standard definition of the persistent at-risk-of-poverty rate used by the statistical office of the European Union (Eurostat) and several other European public statistical agencies. Univariate and multi-variable analyses were used to calculate the effect of relative poverty on the risk of diabetic ketoacidosis. Children from households with relative poverty had a 41% higher risk of diabetic ketoacidosis (1.41, CI 1.12-1.77, p = 0.004) and more than double the risk of severe diabetic ketoacidosis (pH <7.10) (RR 2.10, CI 1.35-3.25, p = 0.001), as compared to children from households without relative poverty. Relative poverty significantly increases the risk of diabetic ketoacidosis at onset of type 1 diabetes in children, even in a high-income country with publicly reimbursed health care.

Analiza učestalosti i dužine trajanja kliničke remisije u pacijenata sa novootkrivenim tipom 1 dijabetesa

Introduction: Clinical remission (CR) phase, in other words, euglycaemia, in the absence of insulin therapy (complete CR) or with a reduced daily dose of insulin (partial CR) can be achieved in some patients with new-onset type 1 diabetes (T1D) after the introduction of insulin therapy. Unfortunately, there is still not enough information about the factors influencing the induction and duration of remission. Material and methods: This research included 62 patients with the diagnosis of new-onset T1D, who were treated at the Clinic of Endocrinology, Diabetes and Metabolic Diseases, University Clinical Centre of Serbia in 2019 and 2020. Demographic, clinical and laboratory data were acquired from medical records. Descriptive statistical methods, Fisher's exact probability test, Pearson's chi-square test, Student's t test, Mann Whitney U test and Spearman's correlation coefficient were used for statistical analysis. Results: Clinical remission was inducted in 46.8% of patients and its average duration was 11.2 months. Patients with CR had remarkably lower HbA1c values (9.9 ± 2.8 vs 11.8 ± 2.4%; p=0.007) and lost less weight (4 vs 12 kg, p&lt;0.001) compared to patients without CR. Additionally, C peptide levels at the beginning and 6 minutes after the glucagon test were remarkably higher in patients with CR compared to patients without CR (p&lt;0.001). At the same time, remarkably more patients with CR had autoantibodies detected compared to those without CR (GAD 100% vs 72.4% i IA2-2A 81.8% vs 34.5%; p=0.001). The duration of CR was remarkably correlated with the level of C peptide at the beginning and 6 minutes after the glucagon test (p&lt;0.001). Conclusion: Patients with CR (46.8%) had better metabolic control, less weight loss, better endogenous insulin reserve capacity and less frequent presence of autoantibodies to beta cell antigens at disease onset. At the same time, the duration of CR was associated with an initially better, preserved, endogenous insulin reserve.

Phenotypic characterization of nonautoimmune diabetes in adult Ugandans with low body mass index.

Type 2 diabetes is common in relatively lean individuals in sub-Saharan Africa. It is unclear whether phenotypic differences exist between underweight and normal-weight African patients with type 2 diabetes. This study compared specific characteristics between underweight (body mass index <18.5 kg/m2) and normal-weight (body mass index of 18.5-24.9 kg/m2) adult Ugandans with new-onset nonautoimmune diabetes. We collected the demographic, clinical, anthropometric, and metabolic characteristics of 160 participants with nonobese new-onset type 2 diabetes (defined as diabetes diagnosed <3 months, body mass index <25 kg/m2, and absence of islet-cell autoimmunity). These participants were categorized as underweight and normal weight, and their phenotypic characteristics were compared. Of the 160 participants with nonobese new-onset type 2 diabetes, 18 participants (11.3%) were underweight. Compared with those with normal weight, underweight participants presented with less co-existing hypertension (5.6% versus 28.2%, p = 0.04) and lower median visceral fat levels [2 (1-3) versus 6 (4-7), p < 0.001], as assessed by bioimpedance analysis. Pathophysiologically, they presented with a lower median 120-min post-glucose load C-peptide level [0.29 (0.13-0.58) versus 0.82 (0.39-1.50) nmol/l, p = 0.04] and a higher prevalence of insulin deficiency (66.7% versus 31.4%, p = 0.003). This study demonstrates that nonautoimmune diabetes occurs in underweight individuals in sub-Saharan Africa and is characterized by the absence of visceral adiposity, reduced late-phase insulin secretion, and greater insulin deficiency. These findings necessitate further studies to inform how the prevention, identification, and management of diabetes in such individuals can be individualized.

Impact of lifestyle modification on nonalcoholic fatty liver with prediabetes and type 2 diabetes

Prediabetes is characterized by impaired glucose uptake and insulin sensitivity in the muscle, as well as a significant risk of developing diabetes, chronic renal disease, cardiovascular disease, and death. A definite bidirectional connection exists between pre-diabetes, diabetes, and NAFLD. The presence of NAFLD is associated with the subsequent development of new-onset type 2 diabetes (T2DM). There was a 6-fold rise in new-onset diabetes in people whose fatty liver severity progressed from mild to moderate or severe over 5 years, and a decrease in T2DM incidence comparable to that in those without steatosis. Insulin resistance is a common pathophysiological mechanism across metabolic illnesses, including prediabetes, diabetes, and NAFLD. As a result, better names for metabolically linked metabolic fatty liver disease have been considered. Lifestyle is the cornerstone of treatment for patients with prediabetes, T2DM, and NAFLD. Several significant randomized controlled trials show that a customized low-calorie meal plan and behavioral change are highly effective in preventing or delaying prediabetes, type 2 diabetes, and improving other cardiometabolic markers (such as blood pressure, lipids, and inflammation). Several drugs already approved for the treatment of prediabetes and diabetes are beneficial for NAFLD/NASH.

Metformin treatment is associated with reduced risk of hypoglycaemia, major adverse cardiovascular events, and all-cause mortality in patients with post-pancreatitis diabetes mellitus: a nationwide cohort study.

Post-pancreatitis diabetes mellitus (PPDM) is a frequent complication of pancreatitis and is associated with an increased risk of adverse outcomes. Metformin is recommended for the treatment of PPDM, but evidence of its risk-benefit profile is limited. In a pharmaco-epidemiologic study, we investigated the association between metformin treatment and adverse outcomes in patients with PPDM. In a Danish nationwide population-based cohort study, we included adults (≥18 years) with incident PPDM or type 2 diabetes between 2009 and 2018. Post-pancreatitis diabetes mellitus was categorised into acute and chronic subtypes (PPDM-A and PPDM-C). Associations between metformin treatment and severe hypoglycaemia, major adverse cardiovascular events (MACE), and all-cause mortality were examined across the diabetes subgroups using Cox regression analysis. Treatments with metformin, insulin, and other glucose-lowering therapies were handled as time-varying exposures. We included 222 337 individuals with new-onset type 2 diabetes and 3781 with PPDM, of whom 2305 (61%) were classified as PPDM-A and 1476 (39%) as PPDM-C. Treatment with metformin was associated with a lower risk of severe hypoglycaemia (adjusted hazard ratio [HR] 0.41, 95% CI 0.27-0.62, P < .0001), MACE (HR 0.74, 95% CI 0.60-0.92, P = .0071), and all-cause mortality (HR 0.56, 95% CI 0.49-0.64, P < .0001) in patients with PPDM. In sensitivity analyses and among individuals with type 2 diabetes, metformin treatment exhibited comparable trends of risk reduction. Metformin is associated with a lower risk of adverse outcomes, including all-cause mortality in patients with PPDM, supporting the use of metformin as a glucose-lowering therapy for these patients.

Increased risk of incident mental disorders in adults with new-onset type 1 diabetes diagnosed after the age of 19: A nationwide cohort study

AimThis 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. MethodsWe 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. ResultsThe 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. ConclusionsIn 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.

Addressing common sources of bias in studies of new-onset type 2 diabetes following COVID that use electronic health record data

Observational studies based on cohorts built from electronic health records (EHR) form the backbone of our current understanding of the risk of new-onset diabetes following COVID. EHR-based research is a powerful tool for medical research but is subject to multiple sources of bias. In this viewpoint, we define key sources of bias that threaten the validity of EHR-based research on this topic (namely misclassification, selection, surveillance, immortal time, and confounding biases), describe their implications, and suggest best practices to avoid them in the context of COVID-diabetes research.

The Association between Serum 25-Hydroxyvitamin D3 Levels and Pro-Inflammatory Markers in New-Onset Type 2 Diabetes Mellitus and Prediabetes.

In this study, we aimed to reveal the pro-inflammatory effects of serum 25-hydroxyvitamin D3 (Vit D) deficiency and insufficiency in new-onset type 2 diabetes mellitus (T2DM) and prediabetes. We recruited 84 prediabetes patients, 94 new-onset T2DM patients and 113 healthy participants. We measured the levels of C-reactive protein (CRP), fibrinogen, ferritin, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in the serum of the participants. ANOVA Bonferroni and Kruskal-Wallis Dunn tests were used to compare the inflammation markers and vitamin D levels between the groups. Based on covariance analysis with age, gender and BMI, the Vit D levels of the T2DM group were significantly lower (p < 0.003). Pro-inflammatory markers and CRP were significantly higher in prediabetic and diabetic subjects. In the prediabetes group, IL-1β, IL-6, IL-8, TNF-α and MAPK were significantly higher in those with Vit D insufficiency and deficiency groups. In the T2DM group, IL-1β, IL-6, IL-8, TNF-α, NF-κB, MAPK and CRP were significantly higher in those with Vit D insufficiency and deficiency. Our study emphasizes the pro-inflammatory effects of Vit D deficiency and insufficiency in new-onset type 2 diabetes mellitus and prediabetes.

Association Between New-Onset Type 2 Diabetes and Cardiac Conduction Diseases: A Prospective Cohort Study.

Cardiac conduction diseases can lead to life-threatening outcomes. However, the evidence on risk factors for conduction disease that is needed to underpin prevention strategies is limited. The present study aimed to determine the association between type 2 diabetes and cardiac conduction diseases. This study included 101 080 participants free of prevalent diabetes and cardiac conduction diseases at baseline from the Kailuan Study. All participants were monitored biennially until December 31, 2020. During follow-up, 14 397 participants were diagnosed as having type 2 diabetes. For each case subject, 1 control subject was randomly selected, matched for age (±1 year) and sex. The final analysis comprised 10 744 case-control pairs. Cox regression models with age as the underlying time scale were used. During a median follow-up of 5.46 years, 571 incident events occurred, including 164 atrioventricular blocks, 414 bundle-branch blocks (BBBs), 274 right BBBs, and 210 left BBBs. After adjustment for potential confounders, participants with type 2 diabetes diagnosed had greater relative risks for most outcomes relative to controls, with hazard ratios of 1.42 (95% CI, 1.18-1.67) for conduction diseases, 1.40 (95% CI, 1.00-1.96) for atrioventricular blocks, 1.43 (95% CI, 1.16-1.75) for BBBs, and 1.69 (95% CI, 1.15-2.49) for left BBBs. In contrast, no association between diabetes and right BBB was observed. In this study, participants with type 2 diabetes are at an increased risk of cardiac conduction disease but not associated with the development of right BBB.

Baricitinib and β-Cell Function in Patients with New-Onset Type 1 Diabetes

BackgroundJanus kinase (JAK) inhibitors, including baricitinib, block cytokine signaling and are effective disease-modifying treatments for several autoimmune diseases. Whether baricitinib preserves β-cell function in type 1 diabetes is unclear.MethodsIn this phase 2, double-blind, randomized, placebo-controlled trial, we assigned patients with type 1 diabetes diagnosed during the previous 100 days to receive baricitinib (4 mg once per day) or matched placebo orally for 48 weeks. The primary outcome was the mean C-peptide level, determined from the area under the concentration–time curve, during a 2-hour mixed-meal tolerance test at week 48. Secondary outcomes included the change from baseline in the glycated hemoglobin level, the daily insulin dose, and measures of glycemic control assessed with the use of continuous glucose monitoring.ResultsA total of 91 patients received baricitinib (60 patients) or placebo (31 patients). The median of the mixed-meal–stimulated mean C-peptide level at week 48 was 0.65 nmol per liter per minute (interquartile range, 0.31 to 0.82) in the baricitinib group and 0.43 nmol per liter per minute (interquartile range, 0.13 to 0.63) in the placebo group (P=0.001). The mean daily insulin dose at 48 weeks was 0.41 U per kilogram of body weight per day (95% confidence interval [CI], 0.35 to 0.48) in the baricitinib group and 0.52 U per kilogram per day (95% CI, 0.44 to 0.60) in the placebo group. The levels of glycated hemoglobin were similar in the two trial groups. However, the mean coefficient of variation of the glucose level at 48 weeks, as measured by continuous glucose monitoring, was 29.6% (95% CI, 27.8 to 31.3) in the baricitinib group and 33.8% (95% CI, 31.5 to 36.2) in the placebo group. The frequency and severity of adverse events were similar in the two trial groups, and no serious adverse events were attributed to baricitinib or placebo.ConclusionsIn patients with type 1 diabetes of recent onset, daily treatment with baricitinib over 48 weeks appeared to preserve β-cell function as estimated by the mixed-meal–stimulated mean C-peptide level. (Funded by JDRF International and others; BANDIT Australian New Zealand Clinical Trials Registry number, ACTRN12620000239965.)

Plasma Metabolites Related to the Consumption of Different Types of Dairy Products and Their Association with New-Onset Type 2 Diabetes: Analyses in the Fenland and EPIC-Norfolk Studies, United Kingdom.

To identify metabolites associated with habitual dairy consumption and investigate their associations with type 2 diabetes (T2D) risk. Metabolomics assays were conducted in the Fenland (n = 10,281) and EPIC-Norfolk (n = 1,440) studies. Using 82 metabolites assessed in both studies, we developed metabolite scores to classify self-reported consumption of milk, yogurt, cheese, butter, and total dairy (Fenland Study-discovery set; n = 6035). Internal and external validity of the scores was evaluated (Fenland-validation set, n = 4246; EPIC-Norfolk, n = 1440). The study assessed associations between each metabolite score and T2D incidence in EPIC-Norfolk (n = 641 cases; 16,350 person-years). The scores classified low and high consumers for all dairy types with internal validity, and milk, butter, and total dairy with external validity. The scores were further associated with lower incident T2D: hazard ratios (95% confidence interval) per standard deviation: milk 0.71 (0.65, 0.77); butter 0.62 (0.57, 0.68); total dairy 0.66 (0.60, 0.72). These associations persisted after adjustment for known dairy-fat biomarkers. Metabolite scores identified habitual consumers of milk, butter, and total dairy products, and were associated with lower T2D risk. These findings hold promise for identifying objective indicators of the physiological response to dairy consumption.

Post-Hypoglycemic hyperglycemia are highly relevant markers for stratification of glycemic variability and partial remission status of pediatric patients with new-onset type 1 diabetes.

To evaluate whether parameters of post-hypoglycemic hyperglycemia (PHH) correlated with glucose homeostasis during the first year after type 1 diabetes onset and helped to distinguish pediatric patients undergoing partial remission or not. In the GLUREDIA (GLUcagon Response to hypoglycemia in children and adolescents with new-onset type 1 DIAbetes) study, longitudinal values of clinical parameters, continuous glucose monitoring metrics and residual β-cell secretion from children with new-onset type 1 diabetes were analyzed during the first year after disease onset. PHH parameters were calculated using an in-house algorithm. Correlations between PHH parameters (i.e., PHH frequency, PHH duration, PHH area under the curve [PHHAUC]) and glycemic homeostasis markers were studied using adjusted mixed-effects models. PHH parameters were strong markers to differentiate remitters from non-remitters with PHH/Hyperglycemia duration ratio being the most sensitive (ratio<0.02; sensitivity = 86% and specificity = 68%). PHHAUC moderately correlated with parameters of glucose homeostasis including TIR (R2 = 0.35, p-value < 0.05), coefficient of variation (R2 = 0.22, p-value < 0.05) and Insulin-Dose Adjusted A1c (IDAA1C) (R2 = 0.32, p-value < 0.05) and with residual β-cell secretion (R2 = 0.17, p-value < 0.05). Classification of patients into four previously described glucotypes independently validated PHH parameters as reliable markers of glucose homeostasis and improved the segregation of patients with intermediate values of IDAA1C and estimated C-peptide (CPEPEST). Finally, a combination of PHH parameters identified groups of patients with specific patterns of hypoglycemia. PHH parameters are new minimal-invasive markers to discriminate remitters from non-remitters and evaluate glycemic homeostasis during the first year of type 1 diabetes. PHH parameters may also allow patient-targeted therapeutic management of hypoglycemic episodes.

“It changed everything we do”: A mixed methods study of youth and parent experiences with a pilot exercise education intervention following new diagnosis of type 1 diabetes

AimsThis pilot study delivered a comprehensive exercise education intervention to youth with new-onset type 1 diabetes (T1D) and their parents to increase knowledge and confidence with physical activity (PA) shortly after diagnosis. MethodsYouth initiated continuous glucose monitoring (CGM) and PA trackers within 1 month of diagnosis. Youth and their parents received the 4-session intervention over 12 months. Participants completed self-report questionnaires at baseline, 6- and 12-months. Surveys were analyzed using linear mixed effects models. Semi-structured interviews and focus groups explored experiences with the exercise education intervention. Groups and interviews were audio-recorded, transcribed, and analyzed using content analysis. ResultsA total of 16 parents (aged 46 ± 7 years; 88 % female; 67 % non-Hispanic White) and 17 youth (aged 14 ± 2 years; 41 % female; 65 % non-Hispanic White) participated. Worry about hypoglycemia did not worsen throughout the study duration. Parents and youth reported increased knowledge and confidence in managing T1D safely and preventing hypoglycemia during PA following receiving the tailored exercise education intervention. ConclusionThis study assessed a novel structured exercise education program for youth and their parents shortly following T1D diagnosis. These results support the broad translation and acceptability of a structured exercise education program in new-onset T1D.

C-peptide and metabolic outcomes in trials of disease modifying therapy in new-onset type 1 diabetes: an individual participant meta-analysis

Metabolic outcomes in type 1 diabetes remain suboptimal. Disease modifying therapy to prevent β-cell loss presents an alternative treatment framework but the effect on metabolic outcomes is unclear. We, therefore, aimed to define the relationship between insulin C-peptide as a marker of β-cell function and metabolic outcomes in new-onset type 1 diabetes. 21 trials of disease-modifying interventions within 100 days of type 1 diabetes diagnosis comprising 1315 adults (ie, those 18 years and older) and 1396 children (ie, those younger than 18 years) were combined. Endpoints assessed were stimulated area under the curve C-peptide, HbA1c, insulin use, hypoglycaemic events, and composite scores (such as insulin dose adjusted A1c, total daily insulin, U/kg per day, and BETA-2 score). Positive studies were defined as those meeting their primary endpoint. Differences in outcomes between active and control groups were assessed using the Wilcoxon rank test. 6 months after treatment, a 24·8% greater C-peptide preservation in positive studies was associated with a 0·55% lower HbA1c (p<0·0001), with differences being detectable as early as 3 months. Cross-sectional analysis, combining positive and negative studies, was consistent with this proportionality: a 55% improvement in C-peptide preservation was associated with 0·64% lower HbA1c (p<0·0001). Higher initial C-peptide levels and greater preservation were associated with greater improvement in HbA1c. For HbA1c, IDAAC, and BETA-2 score, sample size predictions indicated that 2-3 times as many participants per group would be required to show a difference at 6 months as compared with C-peptide. Detecting a reduction in hypoglycaemia was affected by reporting methods. Interventions that preserve β-cell function are effective at improving metabolic outcomes in new-onset type 1 diabetes, confirming their potential as adjuncts to insulin. We have shown that improvements in HbA1c are directly proportional to the degree of C-peptide preservation, quantifying this relationship, and supporting the use of C-peptides as a surrogate endpoint in clinical trials. JDRF and Diabetes UK.