Late-onset Diabetes Research Articles

Metabolic Stress Levels Influence the Ability of Myelin Transcription Factors to Regulate β-Cell Identity and Survival.

A hallmark of type 2 diabetes (T2D) is endocrine islet β-cell failure, which can occur via cell dysfunction, loss-of-identity, and/or death. How each is induced remains largely unknown. Here, we use mouse β-cells that are deficient for Myelin transcription factors (Myt TFs, including Myt1, 2, and 3) to address this question. We have reported that inactivating all three Myt genes in pancreatic progenitor cells (MytPancΔ) causes β-cell failure and late onset diabetes in mice. Their lower expression in human β-cells is correlated with β-cell dysfunction and SNPs in MYT2 and MYT3 are associated in higher risk of T2D. We now show that these Myt TF-deficient postnatal β-cells also de-differentiate by reactivating several progenitor markers. Intriguingly, mosaic Myt TF inactivation in only a portion of islet β-cells does not results in overt diabetes, but this creates a condition where Myt TF-deficient β-cells stay alive while activating several markers of Ppy-expressing islet cells. By transplanting MytPancΔ islets into the anterior eye chambers of immune-compromised mice, we directly show that glycemic and obesity-related conditions influence cell fate, with euglycemia inducing several Ppy+ cell markers while hyperglycemia and insulin resistance inducing additional cell death. These findings suggest that the observed β-cell defects in T2D depend on not only their inherent genetic/epigenetic defects, but also the metabolic load.

The Relationship Between Age at Diabetes Onset and Clinical Outcomes in Newly Diagnosed Type 2 Diabetes: A Real-World Two-Center Study.

This study was developed with the goal of clarifying whether there is any relationship between type 2 diabetes mellitus (T2DM) age of onset and clinical outcomes for patients in National Metabolic Management Centers (MMC). From September 2017 - June 2022, 864 total T2DM patients were recruited in MMC and assigned to those with early-onset and late-onset diabetes (EOD and LOD) based on whether their age at disease onset was ≤ 40 or > 40 years. All patients received standardized management. Baseline and 1-year follow-up data from these two groups of patients were assessed. Associations between onset age and other factors were evaluated with a multivariate linear regression approach, adjusting for appropriate covariates. Outcomes in particular subgroups were also assessed in stratified analyses. Markers of dysregulated glucose metabolism and BMI values were significantly higher among EOD patients as compared to LOD patients. Subjects in both groups exhibited significant improvements in several disease-related parameters on 1-year follow-up after undergoing metabolic management. EOD patients exhibited significantly greater percentage reductions in HbA1c levels (-28.49 (-44.26, -6.45)% vs -13.70 (-30.15,-1.60)%, P =0.017) relative to LOD patients following adjustment for confounders. Significant differences were also detected between these groups when focused on subgroups of patients who were male, exhibited a BMI ≥ 25, an HbA1c ≥ 9, or had a follow-up frequency < 2. Data from a 1-year follow-up time point suggest that a standardized metabolic disease management model can promote effective metabolic control in newly diagnosed T2DM patients, particularly among individuals with EOD.

Young-onset type 2 diabetes mellitus enhances proteinuria, but not glomerular filtration rate decline: A Japanese cohort study.

The time course of chronic kidney disease in young-onset type 2 diabetes mellitus remains unclear. We compared the trajectories of proteinuria and estimated glomerular filtration rate (eGFR) decline between young-onset (aged ≤40 years) and late-onset (aged >40 years) type 2 diabetes mellitus in a Japanese multicenter cohort. Participants without diabetic kidney disease were divided into two groups according to age at diagnosis: young- and late-onset. The primary endpoint was eGFR <60 mL/min/1.73 m2, proteinuria or both. Multivariable Cox proportional hazards were calculated to estimate incidence. Among 626 participants with type 2 diabetes mellitus, 78 (12.4%) had young-onset and 548 (87.6%) had late-onset diabetes. The incidence of eGFR <60 mL/min/1.73 m2 was lower (16.7% vs 33.5%, P = 0.003), but that of proteinuria was higher (46.2% vs 28.9%, P = 0.002) in the young-onset type 2 diabetes mellitus group. The Kaplan-Meyer curve showed that young-onset type 2 diabetes mellitus was associated with a decreased hazard ratio (HR) for eGFR <60 mL/min/1.73 m2 and an increased HR for proteinuria compared with late-onset type 2 diabetes mellitus. In the multivariate Cox analysis, young-onset type 2 diabetes mellitus increased the HR (95% confidence interval) of proteinuria (1.53, 95% confidence interval 1.03-2.26), but did not change the eGFR <60 mL/min/1.73 m2 HR. Young-onset type 2 diabetes mellitus has a lower HR of eGFR <60 mL/min/1.73 m2 and an increased HR of proteinuria compared with late-onset type 2 diabetes mellitus, indicating that young-onset type 2 diabetes mellitus has a different time course for the development of proteinuria and subsequent eGFR decline.

Cardiovascular risk factors and vascular complications in adults with earlyand late-onset diabetes in Mexico. Ensanut 2018

Objective. To inform the prevalence of cardiovascular risk factors and vascular complications in Mexican adults with early- and late-onset diabetes. Materials and methods. Information from adults aged 20 years and over participating in the Encuesta Nacional de Salud y Nutrición 2018 was used. To compare variables, chi-square tests and Student’s t-test were performed. Multiple logistic regression models of having micro and macrovascular complications were obtained. Results. Prevalence of diagnosed hypertension on early and late diabetes onset were 37.8 and 51.5%, dyslipidemia 42.6 and 43.8%, tobacco consumption 13.5 and 10.2% and obesity 46.5 and 43.0%, respectively. The average time since diagnosis was 16.9 years for those with early-onset diabetes and 8.9 years for those with late-onset. Peripheral vascular disease in the group with early-onset diabetes was 13.5% (20.2% in those with 10 years and more of diabetes duration), and 5.3% in late-onset diabetes group (7.2% in those with 10 years and more of diabetes duration). Conclusion. Adults with earlyonset diabetes presented higher proportion of macrovascular complications, probably due to the longer exposure time to hyperglycemia. Patients with early-onset diabetes require intensive treatment to prevent cardiovascular events. Patients with late-onset diabetes require management of age-related comorbidities as hypertension and dyslipidemia.

Longitudinal changes in diet quality and food intake before and after diabetes awareness in American adults: the Coronary Artery Risk Development in Young Adults (CARDIA) study

IntroductionLimited longitudinal research is available examining how American adults make dietary changes after learning they have diabetes. We examined the associations between diabetes awareness and changes in dietary quality and...

Changing landscape of diabetes in Asia - What are the unmet needs?

The incidence rates of type 2 diabetes among adults in Asia have been stable, but the rates in youth and young adults have increased. In territory-wide surveillance in Hong Kong, Special Administrative Region of People's Republic of China, all-cause mortality rates among people with diabetes have exhibited a declining trend in the past 15 years, with a narrowing in the mortality gap between people with and without diabetes. At the same time, the improvement in survival resulted in a changing age structure and disease profile of people with diabetes, towards an increasing proportion of older people with long diabetes duration and multi-morbidities. Reductions in event rates were not observed in the youngest age group who also had the least gains in risk factor control and uptake in organ protective drugs over time. A young age at diabetes diagnosis, associated with exposure to high glycemic burden from an early age, predicted higher risks of complications and premature mortality compared with later-onset of diabetes. People presenting with type 2 diabetes below 40 years of age were 5-fold more likely to die and their life expectancy was shortened by 8 years than age-matched counterparts without diabetes. Analysis of population-based data in Hong Kong Chinese identified hypertension followed by chronic kidney disease as the leading contributor to mortality in young people, indicating that efforts to optimize non-glycemic risk factors and organ protection are as important in young individuals as it is in the older population.

Characterising diabetes in Kazakhstan: a cluster analysis

Abstract Background Diabetes is a global pandemic, affecting 537 million adults worldwide in 2021. Diabetes is much more complex than the classification into type 1 diabetes and type 2 diabetes suggests. We aimed to identify homogeneous groups of patients with diabetes based on routinely collected measurements using unsupervised, data-driven cluster analysis. Methods We analyzed the data from Electronic Medical Records of 558 patients with newly diagnosed diabetes from 4 outpatient clinics in Astana. We performed a k-means cluster analysis of 9 routinely measured variables using the KMeans function (iterations=3 million) from the Scikit-Learn Python library. Results Cluster 1, consisting of 176 (31,5%) patients, was defined by late-onset diabetes, relatively low blood pressure (BP) and body mass index (BMI), moderate metabolic derangements, and comparably low glomerular filtration rate (GFR). The 83 (14,9%) patients in cluster 2 were characterized by a late manifestation of diabetes, high BP and BMI, relatively poor glycemic control, moderate dyslipidemia, and comparably low GFR. Cluster 3, including 98 (17,6%) patients, was represented by a low age at onset, comparably low BP and BMI, moderately poor glycemic and lipid controls, and high GFR. The 110 (19,7%) patients in cluster 4 had late-onset diabetes, high BP and BMI, subcompensated diabetes, poor lipid control, and relatively low GFR. Cluster 5, which involved 91 (16,3%) patients, was characterized by comparably low BP and BMI, poor glycemic control, modest dyslipidemia, and high GFR. Conclusions We intend to continue the project for further conducting a prospective study with dynamic monitoring of study participants, tracking specific patterns in the development of diabetic complications in each cluster. The results of this work will contribute to the development of a model for identifying patients with an initially predictable course of diabetes and a high risk of its complications at the time of diagnosis. Key messages • We identified five clusters of patients with diabetes with clinically significant characteristics in each cluster. • Identification of subgroups of patients with an initially predictable course can be useful for recognizing those at highest risk of complications and applying personalized treatment strategies.

Comparison of beta-cell function between Hong Kong Chinese with young-onset type 2 diabetes and late-onset type 2 diabetes

AimsWe compared beta-cell function in Chinese with type 2 diabetes diagnosed at age < 40 years (young-onset diabetes, YOD) and ≥ 40 years (late-onset diabetes, LOD). MethodsIn this cross-sectional study, we selected participants from two cohorts of people with type 2 diabetes recruited in 1996–2012 (n = 4,376) and 2020–2021 (n = 794). Multivariable linear regression models were applied to compare homeostasis model assessment of beta-cell function (HOMA2-%B) and fasting plasma C-peptide across diabetes duration at enrolment between YOD and LOD. ResultsThe YOD group (n = 1,876, mean [SD] age: 39.9 [7.5] years, median [IQR] diabetes duration: 6 [2–12] years) was more likely to have family history of diabetes (61.6 % vs 43.6 %), obesity (41.9 % vs 26.8 %), dyslipidaemia (61.7 % vs 54.4 %), and worse glycaemic control (mean HbA1c 7.7 % vs 7.4 %) than those with LOD (n = 3,294, age: 60.8 [10.6] years, diabetes duration: 5 [1–10] years). When compared to people with LOD, HOMA2-%B and fasting plasma C-peptide were lower in the YOD group, consistently among those with BMI < 27.5 kg/m2 and HOMA2-IR ≤ 1.6 (median value), adjusted for year at enrolment, sex, diabetes duration, family history of diabetes, HbA1c, weight and lipid indices (p < 0.01). Cross-sectionally, the slopes of decline in HOMA2-%B by diabetes duration were greater in YOD than LOD among individuals with BMI < 27.5 kg/m2 (p-interaction = 0.015). ConclusionsChinese with YOD had accelerated loss of beta-cell function than those with LOD especially in non-obese individuals.

Prevalence of early and late onset of chronic diseases and multimorbidity and its association with physical, mental and functional health among older Indian adults

BackgroundIdentifying people with early and late onset of chronic conditions might help target the subpopulations that are more vulnerable to negative mental, physical and functional health outcomes. The current study aimed to examine the association of early and late onset of chronic single and multiple morbidities with self-perceived physical and mental health, functional limitations and physical inactivity among older Indian adults.MethodsCross-sectional study was conducted using data from the Longitudinal Ageing Study in India (LASI) Wave 1 (2017–2018). The total sample size for the present study was 31,386 older adults age 60 years or older. Multivariable binary logistic regression analysis was used to establish the association between the outcomes (poor perceived physical/mental health, functional difficulty and physical inactivity) and explanatory variables (early [ = < 50 years of age] and late [> 50 years]) onset of chronic illnesses such as hypertension, diabetes, heart attack, heart disease, stroke, cancer, lung disease, arthritis, osteoporosis and psychiatric disease).ResultsOverall, 24.21% of the sample population had poor self-perceived physical health, whereas 8.67% of participants had poor self-perceived mental health. The prevalence of difficulty in ADL, difficulty in IADL, and physical inactivity was 23.77%, 48.36%, and 68.9%, respectively. Odds of poor perceived mental health were higher for the respondents with early as well as late onset of hypertension, stroke, and arthritis; while individuals with late onset of diabetes, and heart disease had higher odds of poor perceived mental health than those without chronic disease. Individuals with early onset of single morbidity were more likely to report ADL difficulty (adjusted odds ratio [AOR]: 1.33, confidence interval [CI]: 1.06–1.67); while those with late onset of single (AOR: 1.34, CI: 1.17–1.53) and multimorbidity (AOR: 1.91, CI: 1.63–2.24) were more likely to report ADL difficulty compared with individuals without morbidity. Individuals with early as well as late-onset of multimorbidity had more than two times higher odds of reporting poor physical health, poor mental health and IADL difficulty compared with individuals without chronic disease.ConclusionsThe present study revealed that early and/or late onset of chronic single and/or multiple morbidities significantly predicted poor self-perceived physical and mental health, functional limitations and physical inactivity among older Indian adults. The findings further suggest that late onset of chronic diseases such as cancer and stroke and multi-morbidity had stronger associations with physical inactivity that may help identify high risk groups for screening and support.

Diagnostic Challenge of Adult-onset Type 1 Diabetes Mellitus in a Remote Hospital

Type 1 Diabetes Mellitus (T1DM) is a chronic endocrinological disease due to an autoimmune process. The prevalence of T1DM is 9.5% worldwide, with the incidence of 15 out of 100,000 people, ranging from childhood to 40 years of age. Autoimmunity-related late-onset Diabetes Mellitus (DM) patients could be diagnosed as classic T1DM or latent autoimmune diabetes in adults (LADA). A 30-year-old male patient with unremarkable previous medical history was admitted to the emergency room with dyspnea for the last three days that was worsened six-hour before admission. Physical examinations showed a body Mass Index (BMI) of 18.75 kg/m2, irregular pulse, and Kussmaul breathing. The patient was diagnosed with diabetic ketoacidosis (DKA) on May 23, 2019. He was discharged with subcutaneous insulin pen injections. Two years later, he was readmitted with DKA due to discontinuing his treatment. He stated that the reason for stopping the insulin was because he was tired of injecting it. The patient was hospitalized and was discharged with oral antidiabetic agents to cope with his injection tiredness issue. One week later, the patient complained of dyspnea and was diagnosed with recurrent DKA. He was hospitalized and prescribed subcutaneous insulin. In this kind of situation, a diagnosis of LADA for patients presenting with DKA without prior history of DM in early adulthood needs to be considered. In contrast to the classic T1DM, the need for insulin occurs late in LADA. Affordable and widely available ancillary examinations are needed, including in remote hospitals. Finally, motivational support for patients is as important as the pharmacological treatment since lifelong insulin injections are needed.

Risk of developing chronic kidney disease in young-onset Type 2 diabetes in Korea

We investigated the risk of developing chronic kidney disease (CKD) in patients with young-onset Type 2 diabetes (YOD, diagnosed age < 40 years). We enrolled 84,384 patients aged 20–64 who started anti-diabetic medication between 2010 and 2011 from the Korea National Health Insurance Sharing Service; patients with Type 1 diabetes or a history of CKD were excluded. Multivariate logistic regression analyses were performed to adjust for YOD-distinct variables and compare the incidence of CKD between YOD and late-onset diabetes (LOD, diagnosed age ≥ 40 years). During the median observation period of 5.16 years (interquartile range: 4.58–5.77 years), 1480 out of 77,039 LOD patients and 34 out of 7345 YOD patients developed CKD. Patients with YOD had distinct baseline characteristics compared with the patients with LOD. The odds ratio of developing CKD in patients with YOD over LOD was 1.70 (95% CI 1.15–2.51) after adjusting clinically distinct variables. The increased CKD odds in YOD compared with LOD was greater in the non-smoking group (OR 2.03, 95% CI 1.26–3.26) than in the smoking group (OR 1.49, 95% CI 0.74–2.98, p = 0.0393 for interaction). Among YOD patients, hypertension (34.76% vs. 64.71%, p = 0.0003), dyslipidemia (46.87% vs. 73.53%, p = 0.0019), and sulfonylurea use (35.54% vs. 52.94%, p = 0.0345) were associated with CKD development. YOD patients have a greater risk of developing CKD than LOD patients after adjusting clinically distinct variables.

1355-P: Risk of Chronic Kidney Disease in Early-Onset Type 2 Diabetes in Mexico

Patients with early onset type 2 diabetes (EOD) seem to be at increased risk of developing complications. Screening and diagnosis for CKD is poorly executed in primary care (PC) of low-and-middle income countries. Thus, we aimed to analyze the presence of CKD in EOD in comparison with later-onset diabetes (LOD). Data were obtained from the largest cohort of patients with T2D evaluated for CKD within the PC in Mexico (DIABEMPIC). EOD and LOD were defined as the age of diagnosis &amp;lt;40 and ≥40 years, respectively. CKD assessment included albuminuria through urinary albumin-creatinine ratio (≥30mg/g for CKD) and estimated glomerular filtration rate (eGFR≤60 ml/min/1.73m2 for CKD). A total of 1,592 patients were included. The burden of CKD at different diabetes durations are shown in Table 1. The prevalence of overall CKD was significantly higher in the EOD group (p&amp;lt;0.008), associated to a greater presence of albuminuria; a higher prevalence of albuminuria was observed after 10 years of diagnosis in the EOD (p&amp;lt;0.0001). In the univariate analysis, EOD was associated with an increased risk of CKD (OR 1.33, 95%CI 1.08-1.65). In conclusion, EOD patients presented a higher risk of CKD, particularly on account for albuminuric-CKD phenotype, even though they are comparatively younger. Our results enhance the need for the management of risk factors and proper screening of CKD in T2D, especially in EOD, in PC settings, and through albuminuria measurement. Disclosure R.Silva-tinoco: Speaker's Bureau; AstraZeneca, Boehringer Ingelheim Inc., Novo Nordisk. J.Mejia-vilet: None. J.Ochoa-moreno: None. J.Serna: None. O.Lopez-arellano: None. T.Cuatecontzi-xochitiotzi: None. E.B.Guzman-olvera: None. V.Delatorre-saldaña: None. A.Galindez-fuentes: None. L.Castillo-martinez: None. F.Bernal-ceballos: None. V.Rios-carbajal: None. N.Torres-sandoval: None.

1263-P: Gender Differences in the Impact of Low Muscle Mass on Type 2 Diabetes Incidence—Eighteen-Year Follow-up Data from the Prospective Korean Genome and Epidemiology Study

Background: Current evidence suggests that diminished muscle mass is associated with an increased risk of diabetes. This study aimed to investigate whether the effect of low muscle mass (LMM) on incident diabetes varied depending on the tracking period using a prospective, longitudinal design. Methods: We recruited 6968 subjects without diabetes, aged 40 to 69 years, from the Korean Genomes and Epidemiology study and followed them to monitor the development of type 2 diabetes mellitus (T2DM). A standard 75-g oral glucose tolerance test was conducted at every 2-year follow-up visit. Skeletal muscle mass was assessed using bioelectrical impedance analysis, and a weight-adjusted skeletal muscle mass was defined as muscle mass index (MMI). We assessed the relationship between LMM, the sex-specific lowest tertile of MMI, and the risk of developing T2DM using Cox regression models. Results: Of 6968 (47.4% men), 1846 progressed diabetes during the 18-year follow-up. LMM was associated with an increased risk of T2DM at 10 years and 10-18 years of follow-up in both genders after adjustment for confoundings. After additional adjustment for waist circumference, men with LMM were at significant risk of incident diabetes during the 10-year follow-up (hazard ratio [HR] 1.54, 95% confidence interval [CI] 1.28-1.86) but lost significance in 10-18 years., whereas women with LMM were at significantly increased risk (HR 1.32, 95% CI 1.03-1.69) only in 10-18 years. Over 18 years, LMM in men was consistently associated with an increased risk of diabetes from the initial period (at 2-year follow-up), whereas LMM in women has been shown to increase risk in the late period (from 12-year follow-up). Conclusion: This study showed that LMM is an independent risk factor for T2DM with gender differences over time. LMM was a constant risk factor for diabetes in men, whereas it affected the later onset of diabetes in women. Disclosure E.Kim: None. Y.Cho: None. O.Hong: None. S.Moon: None. J.Han: None. S.Yoo: None. N.H.Cho: None.

Effect of Anti-Diabetic Medications on Dental Implants: A Scoping Review of Animal Studies and Their Relevance to Humans.

Animal studies have ascertained that hyperglycemia adversely affects bone metabolism and dental implant osseointegration. However, diabetic patients show low occurrence of unfavorable hard or soft peri-implant tissue changes, differences that are possibly due to treatment with anti-diabetic medications. This scoping review aimed to systematically examine the effects of these drugs on implant outcomes and explore the predictive modality of animal studies for clinical practice according to type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Three electronic databases (MEDLINE, EBSCOHost, and Cochrane) were searched according to the PRISMA-ScR standards for studies on diabetic animals that received titanium implants and anti-diabetic treatments. Risk assessment was performed using the SYRCLE Risk-of-Bias (RoB) tool. Twenty-one papers were included, encompassing six types of medications. Fifteen studies were on T1DM animals, and only six involved T2DM models. T1DM animals were treated with non-insulin drugs in four investigations, while insulin was utilized in 11 other studies. In T2DM experiments, five administered non-insulin drugs, and only one applied locally delivered insulin. Only insulin in T1DM studies produced a positive influence on bone-implant contact (BIC), bone mineral content, and removal torque values. Inappropriate drug selection, inadequate glycemic control, and high RoB depict a mismatch between the research focus and the translational rationale to clinical practice. There remains a knowledge gap regarding T2DM investigations due to the lack of studies. More data are needed concerning intraoral implants and the performance of osseointegrated implants in patients with a later onset of diabetes. Future research should reflect the pathophysiology and treatment of each type of diabetes to ensure clinical applicability.

S94 Pre-Existing, Early Onset and Late Onset Diabetes in Chronic Pancreatitis: Do Outcomes Differ?

Introduction: Diabetes secondary to endocrine insufficiency in chronic pancreatitis (CP) may develop at any time during the course of the disease. Not much is known about the clinical characteristics and outcomes in these patients. Hence we sought to evaluate differences in pre-existing diabetes, early-onset diabetes, and late-onset diabetes in CP patients. Methods: We retrospectively reviewed CP patients seen at our Pancreas Center between 2016 and 2021. We divided the patients into four groups based on a co-diagnosis of diabetes: those without diabetes, those with pre-existing diabetes (more than 2 years before CP diagnosis), those with early-onset diabetes (diagnosed within 2 years before or 2 years after CP diagnosis), and those with late-onset diabetes (diagnosed 2 years after CP diagnosis). Patients with diabetes after surgery were excluded. We then compared the clinical characteristics, parameters of glucose control, and outcomes. Results: We identified 450 patients with CP: 271 without diabetes, 99 with pre-existing diabetes, 51 with early-onset diabetes and 29 with late-onset diabetes. Early-onset diabetes patients were younger (54.1 vs 57.3 vs 62.5 vs 61.9 years) and more likely to have alcohol-related CP (45.1% vs 31.7% vs 32.3% vs 31%) compared to the other three groups (p< 0.05). Early-onset diabetics had a higher mean HbA1C level (8.02% vs 5.11% vs 7.71% vs 7.66%) and were more likely to be on insulin (78.4% vs 0% vs 48.4% vs 65.5%, p< 0.05). Early-onset diabetics used more opioids (64.7% vs 43.9% vs 55.1% vs 44.8%) and gabapentinoids (66.7% vs 43.5% vs 48% vs 60.7%) compared to other groups (p< 0.05). Patients who developed diabetes after the diagnosis of CP had significantly higher rates of exocrine insufficiency, anatomical complications and interventions for pain control. Other demographics and common complications are outlined in Table: There was no significant difference in pancreatic cancer in the four groups (p=0.7). Conclusion: Our study suggests that CP patients who are younger and use alcohol, are at higher risk of having early-onset diabetes after CP diagnosis. This population should be screened earlier as they have poorer glucose control and higher insulin requirement compared those with pre-existing and late-onset diabetes. Also, patients who develop diabetes after CP diagnosis have worse outcomes and use more resources. Long-term prospective studies are needed to generate more robust data. Table 1. - Demographics, clinical characteristics, and resource utilization of CP patients with and without diabetes No diabetes N=271 Pre-existing diabetes N=99 Early-onset diabetes (< 2 years) N=51 Late-onset diabetes ( >2years) N=29 P-value Mean age in years (SD) 57.3 (16.0) 62.5 (12.8) 54.1 (13.5) 61.9 (11.5) 0.002 Mean age at diagnosis of CP (SD) 45.0 (16.2) 53.0 (14.5) 41.2 (15.5) 47.8 (13.4) <0.001 Female sex (%) 133 (49.6%) 43 (43.4%) 22 (43.1%) 13 (44.8%) 0.659 White race (%) 201 (75.6%) 71 (71.7%) 34 (66.7%) 24 (82.8%) 0.34 Mean number of follow up years in pancreas center 7.84 (5.36) 7.86 (6.68) 8.74 (5.49) 12.1 (5.05) 0.004 Etiology of CP <0.001 Alcohol 86 (31.7%) 32 (32.3%) 23 (45.1%) 9 (31.0%) Genetic 8 (2.95%) 2 (2.02%) 3 (5.88%) 1 (3.45%) Idiopathic 88 (32.5%) 21 (21.2%) 8 (15.7%) 6 (20.7%) Smoking 69 (25.5%) 36 (36.4%) 15 (29.4%) 11 (37.9%) Other 20 (7.38%) 8 (8.08%) 2 (3.92%) 2 (6.90%) History of recurrent acute pancreatitis (%) 214 (78%) 69 (69.6%) 35 (68.6%) 21 (72.4%) 0.943 Chronic abdominal pain (%) 205 (79.2%) 80 (80.8%) 48 (94.1%) 23 (79.3%) 0.094 Splanchnic vein thrombosis(%) 22 (8.43%) 15 (15.3%) 7 (13.7%) 8 (27.6%) 0.013 Pseudocyst (%) 81 (30.9%) 39 (39.8%) 25 (49.0%) 14 (48.3%) 0.027 Biliary obstruction (%) 30 (11.7%) 22 (22.7%) 9 (17.6%) 7 (24.1%) 0.031 Vitamin D deficiency (%) 78 (32.1%) 45 (51.7%) 23 (48.9%) 20 (83.3%) <0.001 Mean Hba1c Level (SD) 5.11 (1.15) 7.71 (1.38) 8.02 (1.61) 7.66 (0.98) <0.001 On insulin (%) 0 48 (48.4%) 40 (78.4%) 19 (65.5%) <0.001 Pancreatic malignancy (%) 10 (3.88%) 4 (4.08%) 3 (5.88%) 0 (0.00%) 0.709 Exocrine pancreatic insufficiency (%) 144 (53.1%) 65 (65.7%) 36 (70.6%) 21 (72.4%) 0.014 Opioid use (%) 116 (43.9%) 54 (55.1%) 33 (64.7%) 13 (44.8%) 0.024 Non-opioid controlled medications (%) 63 (24.0%) 32 (32.7%) 17 (33.3%) 10 (34.5%) 0.220 Gabapentinoid use (%) 114 (43.5%) 47 (48.0%) 34 (66.7%) 17 (60.7%) 0.012 Medical marijuana use (%) 19 (7.66%) 8 (8.60%) 9 (18.8%) 3 (10.7%) 0.120 Mean number of flares requiring hospitalization (SD) 2.02 (3.42) 2.55 (3.18) 3.06 (3.44) 2.41 (3.39) 0.202 Recurrent ED visits (%) 15 (5.75%) 9 (9.18%) 4 (8.00%) 2 (6.90%) 0.617 Mean total abdominal imaging since diagnosis (SD) 4.28 (3.60) 5.64 (4.53) 7.49 (6.43) 7.28 (4.52) < 0.001 Celiac block for pain (%) 27 (10.3%) 12 (12.2%) 17 (33.3%) 6 (21.4%) < 0.001 Pancreatic surgery for pain (%) 22 (8.43%) 9 (9.18%) 15 (29.4%) 13 (46.4%) < 0.001

Radiographic Bone Healing in Minimally Invasive Floating Metatarsal Osteotomy for Neuropathic Plantar Metatarsal Head Ulcers - A Retrospective Cohort Study.

Minimally invasive floating metatarsal osteotomy is an option for treating neuropathic ulcers under the metatarsal heads. This study presents the radiographic results of the floating metatarsal osteotomy. We reviewed files and radiographs at least 4 months after a floating metatarsal osteotomy in patients with diabetic neuropathy. In 71 osteotomies in 54 patients with late onset diabetes (mean age 61 ± 9, mean HbA1c 7.9 ± 1.9%), the primary ulcer healed within 3.5 ± 1.4 weeks. Of 66 osteotomies where radiographs were available 10 had non-union (15%, all asymptomatic), 15 (23%) had hypertrophic callus formation and 41 (62%) had normal union. One patient developed an ulcer under the hypertrophic callus. This necessitated callus resection. Asymptomatic non-union may happen in 15% of floating osteotomies, but the osteotomies appear to be relatively safe and effective for neuropathic plantar metatarsal head ulcers. Hypertropic callus causing local re-ulceration is rare and can be managed surgically.

Characteristics of Glycemic Control and Long-Term Complications in Patients with Young-Onset Type 2 Diabetes.

BackgroundThe prevalence of young-onset diabetes (YOD) has been increasing worldwide. As the incidence of YOD increases, it is necessary to determine the characteristics of YOD and the factors that influence its development and associated complications.MethodsIn this retrospective study, we recruited patients who were diagnosed with type 2 diabetes mellitus between June 2001 and December 2021 at a tertiary hospital. The study population was categorized according to age: YOD (age <40 years), middle-age-onset diabetes (MOD, 40≤ age <65 years), and late-onset diabetes (LOD, age ≥65 years). We examined trends in glycemic control by analyzing fasting glucose levels during the first year in each age group. A Cox proportional-hazards model was used to determine the relative risk of developing complications according to glycemic control trends.ResultsThe fasting glucose level at the time of diagnosis was highest in the YOD group (YOD 149±65 mg/dL; MOD 143±54 mg/dL; and LOD 140±55 mg/dL; P=0.009). In the YOD group, glucose levels decreased at 3 months, but increased by 12 months. YOD patients and those with poor glycemic control in the first year were at a higher risk of developing complications, whereas the risk in patients with LOD was not statistically significant.ConclusionYOD patients had higher glucose levels at diagnosis, and their glycemic control was poorly maintained. As poor glycemic control can influence the development of complications, especially in young patients, intensive treatment is necessary for patients with YOD.

Risk factors for new-onset diabetes mellitus following acute pancreatitis: a prospective study.

Acute pancreatitis (AP) is increasingly recognized as a major cause of diabetes, however, the frequency and risk factors associated with new-onset diabetes are not well established. We aimed to assess the frequency and risk factors associated with new-onset diabetes, the time of diabetes occurrence, and the difference between early and late-onset diabetes following an AP episode. This prospective study included adult patients with AP admitted to a tertiary referral center, followed-up for one year to assess the occurrence of postpancreatitis diabetes. Diabetes was defined in accordance with World Health Organization criteria and the severity of AP was assessed based on the 2012 revised Atlanta classification. Of 329 patients with AP, 29 (8.8%) were diagnosed with diabetes secondary to AP. Of these, 21 (6.37%) had early-onset diabetes (within one month after the acute episode) whereas 8 (2.42%) had late-onset diabetes (more than one month after the AP episode). Obesity and acute necrosis were more frequent in patients with new-onset diabetes compared to those without (55.2% vs. 33.4%, p=0.040 and 31% vs. 7.7%, p<0.01), and remained statistically significant in multivariate analysis. No statistically significant differences were found between these groups regarding sex, age, etiology and severity of AP. The patients with early-onset diabetes were older than those with late-onset (61 vs. 45 years old), in univariate and multivariate analysis (p=0.018 and p=0.038, OR=0.87). Less than 10% of patients with AP developed diabetes within 1 year, particularly obese patients and those with acute pancreatic necrosis of more than 50%. Patients aged over 61 years old developed diabetes in the first month after the acute episode of AP.

Surveillance for Pancreatic Cancer in Chronic Pancreatitis

Pancreatic cancer can arise in the background of chronic pancreatitis (CP). The relative risks for pancreatic cancer in CP vary considerably according to other contributing factors such as disease duration, excess alcohol consumption, tobacco consumption, eating habits, physical activity, and late-onset diabetes. The incidence of pancreatic cancer is estimated to be about 10 per 105 per year, and the incidence and prevalence of CP are estimated to be 5-12 per 105 and 50 per 105 per year, respectively. The pooled relative risk estimates for pancreatic cancer in CP patients range from 2.7 to 13.3. Subsets of CP subjects with a family history of pancreatic cancer or those with newly developed diabetes over the age of 50 have a higher risk for pancreatic cancer. However, the prevalence of pancreatic cancer is not high enough to justify general screening of the adult CP population. Thus, it is necessary to select subsets of CP cohorts with a significantly high risk of pancreatic cancer. We need a better overall disease model that can define the interaction of multiple risk factors and their cumulative or potential effects on pancreatic cancer.

Features of the course of type 2 diabetes mellitus in young people

The increase in the prevalence of type 2 diabetes mellitus (T2DM) worldwide in young people determines the high relevance in studying the course of this disease. There are difficulties in awareness of this pathology in young people, both in specialists and in patients due to the fact that the long-term outcomes of T2DM in young people are poorly understood. This leads to late diagnosis of diabetes and longer exposure to hyperglycemia leads to high risks of microand macrovascular complications. Clinical symptoms of T2DM with a debut at a young age are different in patients, so this disease is not always diagnosed on time. T2DM in young people (18–45 years) has a more aggressive course, the decrease in the level of β-cells occurs faster than in patients with late-onset T2DM. The risk of developing complications in T2DM with onset at a young age is higher than in late-onset diabetes, mainly due to the longer duration of the disease. With a duration of T2DM in young people of 13.3 ± 1.8 years it was shown that the incidence of nephropathy, neuropathy and retinopathy was 54.8%, 32.4% and 13.7%, respectively. According to the literature, in patients with T2DM at a young age, life expectancy is reduced by 14 and 16 years in males and females, respectively. The course of T2DM is more aggressive in relation to young patients than to middle-aged and elderly patients. T2DM with a debut at a young age is a socially significant disease, due to a decrease in the quality of life, the development of diabetic complications and early disability of the working population.