Early-onset Type 2 Diabetes Mellitus Research Articles

Are treatment options used for adult-onset type 2 diabetes mellitus (equally) available and effective for children and adolescents?

Youth-onset type 2 diabetes mellitus (T2DM), influenced by an increase in obesity, is a rising problem worldwide. Pathophysiological mechanisms of this early-onset T2DM include both peripheral and hepatic insulin resistance, along with increased hepatic fasting glucose production accompanied by inadequate first and second-phase insulin secretion. Moreover, the incretin effect is reduced. The initial presentation of type 2 diabetes can be dramatic and symptoms may overlap with those of type 1 diabetes mellitus. Therefore, immediate therapy should address hyperglycemia and associated metabolic derangements irrespective of ultimate diabetes type, while further therapy adjustments are prone to patients’ phenotype. New agents with proven glycemic and beyond glycemia benefits, such as Glucagon-like polypeptide 1 receptor agonists and Sodium-glucose cotransporter-2 inhibitors, used in the adult population of T2DM patients, might become increasingly important in the treatment armamentarium. Moreover, metabolic surgery is an option for markedly obese (body mass index > 35 kg/m2) children and adolescents suffering from T2DM who have uncontrolled glycemia and/or serious comorbidities when lifestyle and pharmacologic interventions fail. In this mini-review, we will discuss the potential of treatment options considering new data available from randomized control trials, including individuals with adult-onset type diabetes mellitus.

Race/Ethnicity and Other Predictors of Early-Onset Type 2 Diabetes Mellitus in the US Population.

Among US adults aged 20 + years in the USA with previously diagnosed type 2 diabetes mellitus (T2DM), we aimed to estimate the prevalence of early-onset T2DM (onset at age < 50.5years) and to test associations between early-onset T2DM and race/ethnicity, and other hypothesized predictors. We pooled data from the annual National Health and Nutrition Examination Surveys (NHANES) over the years 2001 through 2018. We tested hypotheses of association and identified predictors using stepwise logistic regression analysis, and 11 supervised machine learning classification algorithms. After appropriate weighting, we estimated that among adults in the USA aged 20 + years with previously diagnosed T2DM, the prevalence of early-onset was 52.9% (95% confidence intervals, 49.6 to 56.2%). Among Non-Hispanic Whites (NHW) the prevalence was 48.6% (95% CI, 44.6 to 52.6%), among Non-Hispanic Blacks: 56.9% (95% CI, 51.8 to 62.0%), among Hispanics: 62.7% (95% CI, 53.2 to 72.3%). In the final multivariable logistic regression model, the top-3 markers predicting early-onset T2DM in males were NHB ethnicity (OR = 2.97; 95% CI: 2.24-3.95) > tobacco smoking (OR = 2.79; 95% CI: 2.18-3.58) > high education level (OR = 1.65; 95% CI: 1.27-2.14) in males. In females, the ranking was tobacco smoking (OR = 2.59; 95% CI: 1.90-3.53) > Hispanic ethnicity (OR = 1.49; 95% CI: 1.08-2.05) > obesity (OR = 1.30; 95% CI: 0.91-1.86) in females. The acculturation score emerged from the machine learning approach as the dominant marker explaining the race disparity in early-onset T2DM. The prevalence of early-onset T2DM was higher among NHB and Hispanic people, than among NHW people. Independently of race/ethnicity, acculturation, tobacco smoking, education level, marital status, obesity, and hypertension were also predictive.

Comparisons of clinical outcomes between newly diagnosed early- and late-onset T2DM: a real-world study from the Shanghai Hospital Link Database.

The aim of this study was to compare the differences in incident population, comorbidities, and glucose-lowering drug prescriptions between newly diagnosed patients with early-onset type 2 diabetes mellitus (T2DM) and those with late-onset T2DM to provide real-world evidence for clinical practice. This study was based on the Shanghai Hospital Link Database (SHLD). Anonymized electronic medical record (EHR) data from 2013 to 2021 were included in this study. Newly diagnosed patients with T2DM were defined as those without related diagnostic records or glucose-lowering medicine prescriptions in the past 3 years. Early-onset T2DM was defined as patients who were aged 18-40 years old at the first visit for T2DM to represent those who were born after the 1980s. And late-onset T2DM was defined as those aged 65-80 years old to represent those who were born in a relatively undeveloped period. Descriptive statistical analyses were performed to describe their incidence number, glucose-lowering drug prescriptions, and comorbidities at the first visit to the hospital between two T2DM groups. There were a total of 35,457 newly diagnosed patients with early-onset T2DM and 149,108 newly diagnosed patients with late-onset T2DM included in this study. Patients with late-onset T2DM constituted the majority and their number increased by 2.5% on average by years, while the number of patients with early-onset T2DM remained stable each year. Compared with late-onset T2DM patients, more early-onset T2DM patients had dyslipidemia at the first visit to hospitals (9.5% vs 7.7%, P < 0.01) despite their significant age differences. Patients with early-onset T2DM were more likely to use metformin (74.8% vs 46.5, P < 0.01), dipeptidyl peptidase-4 inhibitors (DDP-4i) (16.7% vs 11.2%, P < 0.01), thiazolidinediones (TZD) (14.9% vs 8.4%, P < 0.01), sodium glucose cotransporter 2 inhibitors (SGLT2-i) (0.8% vs 0.3%, P < 0.01), and glucagon-like peptide 1 receptor agonists (GLP-1 RA) (3.7% vs 0.5%, P < 0.01) at their first visit to the hospital. Different characteristics were observed between patients with early-onset T2DM and those with late-onset T2DM. Compared with patients with late-onset T2DM, those with early-onset T2DM were more prone to dyslipidemia and had novel organ-protective drugs prescribed.

Impact of albuminuria on early-onset type 2 diabetes mellitus: a nationwide population-based study.

Early-onset diabetes mellitus has a significant lifetime burden and is associated with higher morbidity and mortality. Since insulin resistance is one of the mechanisms of podocyte injury, we aimed to evaluate the effect of albuminuria on newly developed early-onset type 2 diabetes mellitus (T2DM). We screened 6,891,399 subjects aged ≥20 and <40 years without a history of prediabetes or diabetes from the Korean National Health Insurance Service database between 2009 and 2012. A multivariate Cox proportional hazard model was used to identify the impact of albuminuria on early-onset T2DM. Among a total of 5,383,779 subjects, 62,148 subjects (1.2%) developed early-onset diabetes over 7.3 ± 1.2 years. Albuminuria was significantly associated with early-onset T2DM (adjusted hazard ratio [aHR], 1.62; 95% confidence interval [CI], 1.55-1.70) after adjustment for age, sex, anthropometric data, physical exercise status, serum glucose, and total cholesterol. The risk of early-onset T2DM increased more in subjects with more components of metabolic syndrome (MetS). Among each component of MetS, hypertriglyceridemia was prominently associated with early-onset T2DM (aHR, 2.02; 95% CI, 1.81-2.25) in subjects with albuminuria. Dipstick albuminuria was significantly associated with early-onset T2DM in young adult populations. Close monitoring of albuminuria is warranted for disease risk modification, especially in subjects with MetS.

Analysis of protein expression changes in patients with prediabetes using proteomics approaches.

Proteomics and metabolomics are widely used in the study of diabetes, but rarely in prediabetes research. This study aimed to explore the mechanisms of early-onset type 2 diabetes mellitus (T2DM) by analyzing proteomic changes at different stages of glucose metabolism. A total of 40 individuals undergoing routine physical health examinations between December 2016 and April 2017 were enrolled. Subjects were divided into four groups based on fasting blood glucose (FPG) levels: FPG < 5.6mmol/L (group A); FPG ≥ 5.6mmol/L and <6.1mmol/L (group B); FPG ≥ 6.1mmol/L and <7.0mmol/L (group C); and FPG ≥ 7.0mmol/L (group D). Each group had 10 cases. Sera from these 40 subjects were analyzed by label-free quantitative liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS). LC/MS/MS with selected reaction monitoring mode was also performed for qualitative and quantitative metabolomics analysis. Differentially expressed proteins were identified. Partial least squares discriminant analysis (PLS-DA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to analyze the differentially expressed metabolites. A total of 202 differentially expressed proteins were screened and were identified as mainly secreted proteins. Comparing group A with group B, 32 proteins were up-regulated and 18 proteins were down-regulated. Comparing group A with group C, 24 proteins were up-regulated and 24 proteins were down-regulated. Comparing group A with group D, 19 proteins were up-regulated and 17 proteins were down-regulated. The fold change for up-regulated proteins was >1.2, p < 0.05, while the fold change for down-regulated proteins was <-1.2, p < 0.05. PLS-DA and OPLS-DA revealed 113 differentially expressed metabolites. Correlation analysis of differentially expressed metabolites of group A versus group B revealed that among the down-regulated differential proteins, transforming growth factor β-induced protein ig-h3 correlated negatively with metabolite L-saccharin, while among the up-regulated differential proteins, apolipoprotein C-IV correlated negatively with metabolite 3-methyloxindole. Among all differentially expressed proteins, 19 proteins were associated with early initiation of chronic inflammation, including CD14 and CSF-1R, which were newly identified in the early onset of T2DM. Many proteins are differentially expressed between prediabetes and after T2DM diagnosis, although the specific mechanism remains unclear. The expression level of CD14 was significantly up-regulated and that of CSF-1R was significantly down-regulated when FPG was ≥5.6mmol/L, suggesting that CD14 and CSF-1R may be important markers for early-onset T2DM and may serve as new targets for T2DM treatment.

Early-onset Type 2 Diabetes Mellitus and Cardiometabolic Risk in India

Introduction: The Indian patient phenotype with early-onset type 2 diabetes mellitus (T2DM) merits a more holistic understanding of the cardiometabolic risk profile. As per the principles of precision medicine, such understanding can help appraise the clinical place of interventions like sodium-glucose cotransporter-2 inhibition (SGLT2-i), for this population. Methodology: This observational study represents cases with T2DM, aged ≤40 years, who were newly initiated on empagliflozin on top of standard therapy. Analysis was performed for demographics and clinical characteristics at baseline and 3 months following empagliflozin use. Parameters for analysis included clinical and laboratory indicators of glycemic control, adiposity, insulin sensitivity, inflammation, and derived indicators for cardiometabolic risk. Descriptive statistics have been used for the analysis. Further, subgroups by body mass index (BMI) status (&lt; or ≥25 kg/m2) have been compared for certain continuous variables, using an unpaired t-test. Results: The study included 70 patients, with a mean age of nearly 36 years. The mean BMI was 25.57 kg/m2; approximately 43% of patients had a BMI ≥25 kg/m2. The nonobese patients had a higher triglyceride-glucose index and lower fasting insulin levels, compared to obese patients. The risk of advanced nonalcoholic steatohepatitis was low in this population. The addition of empagliflozin to background therapy improved the HbA1c level by 1.21% with 44% goal-achievement and other metabolic parameters. Weight loss and anthropometric changes were modest. Empagliflozin use was associated with meaningful improvements in cardiometabolic parameters, including triglyceride-glucose index, atherogenic index of plasma, homeostatic model assessment for insulin resistance, quantitative insulin-sensitivity check index, visceral adiposity index, Fibrosis-4 index, and aspartate transaminase-to-platelet ratio index scores, in this population. Insulin resistance remained higher than normal in most patients, despite improvement with empagliflozin use over 3 months. Conclusion: The study findings for people with early-onset T2DM in India indicate: (1) the need for opportunistic screening for T2DM at an earlier age; (2) a high prevalence of insulin resistance regardless of obesity status; (3) meaningful improvements in overall cardiometabolic risk profile with SGLT2-i use; and (4) the importance of long-term optimization of diabetes care in this population.

The interplay between diabetes mellitus and menopause: clinical implications.

The menopausal transition is an impactful period in women's lives, when the risk of cardiovascular disease is accelerated. Similarly, diabetes mellitus profoundly impacts cardiovascular risk. However, the interplay between menopause and diabetes mellitus has not been adequately studied. The menopausal transition is accompanied by metabolic changes that predispose to diabetes mellitus, particularly type 2 diabetes mellitus (T2DM), as menopause results in increased risk of upper body adipose tissue accumulation and increased incidence of insulin resistance. Equally, diabetes mellitus can affect ovarian ageing, potentially causing women with type 1 diabetes mellitus and early-onset T2DM to experience menopause earlier than women without diabetes mellitus. Earlier age at menopause has been associated with a higher risk of T2DM later in life. Menopausal hormone therapy can reduce the risk of T2DM and improve glycaemic control in women with pre-existing diabetes mellitus; however, there is not enough evidence to support the administration of menopausal hormone therapy for diabetes mellitus prevention or control. This Review critically appraises studies published within the past few years on the interaction between diabetes mellitus and menopause and addresses all clinically relevant issues, such as the effect of menopause on the development of T2DM, and the management of both menopause and diabetes mellitus.

Ethnic-Specific Type 2 Diabetes Risk Factor PAX4 R192H Is Associated with Attention-Specific Cognitive Impairment in Chinese with Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) has been shown to increase the risks of cognitive decline and dementia. Paired box gene 4 (PAX4), a transcription factor for beta cell development and function, has recently been implicated in pathways intersecting Alzheimer's disease and T2DM. In this report, we evaluated the association of the ethnic-specific PAX4 R192H variant, a T2DM risk factor for East Asians which contributes to earlier diabetes onset, and cognitive function of Chinese T2DM patients. 590 Chinese patients aged 45-86 from the SMART2D study were genotyped for PAX4 R192H variation using Illumina OmniExpress-24 Array. The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) which had been validated in the Singapore population was administered to assess five cognitive domains: immediate memory, visuospatial/constructional, language, attention, and delayed memory. Multiple linear regression was used to assess the association of the R192H risk allele and cognitive domains. Patients with two PAX4 R192H risk alleles showed significantly lower attention index score (β= -8.46, 95% CI [-13.71, -3.21], p = 0.002) than patients with wild-type alleles after adjusting for age, gender, diabetes onset age, HbA1c, body-mass index, renal function, lipid profiles, systolic blood pressure, metformin usage, smoking history, education level, Geriatric Depression Scale score, and presence of APOEɛ4 allele. Ethnic-specific R192H variation in PAX4 is associated with attention-specific cognitive impairment in Chinese with T2DM. Pending further validation studies, determining PAX4 R192H genotype may be helpful for early risk assessment of early-onset T2DM and cognitive impairment to improve diabetes care.

Health consequences of early-onset compared with late-onset type 2 diabetes mellitus.

ABSTRACTBackgroundAlthough cumulating evidence has suggested that early-onset type 2 diabetes mellitus (T2DM) conferred on patients a broader tendency for complications beyond vascular ones, a comprehensive analysis of patterns of complications across all relevant systems is currently lacking.MethodWe prospectively studied 1 777 early-onset (age at diagnosis ≤ 45 years) and 35 889 late-onset (>45 years) T2DM patients with matched unexposed individuals from the UK Biobank. Diabetes-specific and -related complications were examined using phenome-wide association analysis, with patterns identified by comorbidity network analysis. We also evaluated the effect of lifestyle modifications and glycemic control on complication development.ResultsThe median follow-up times for early-onset and late-onset T2DM patients were 17.83 and 9.39 years, respectively. Compared to late-onset T2DM patients, patients with early-onset T2DM faced a significantly higher relative risk of developing subsequent complications that primarily affected sense organs [hazard ratio (HR) 3.46 vs. 1.72], the endocrine/metabolic system (HR 3.08 vs. 2.01), and the neurological system (HR 2.70 vs. 1.81). Despite large similarities in comorbidity patterns, a more complex and well-connected network was observed for early-onset T2DM. Furthermore, while patients with early-onset T2DM got fewer benefits (12.67% reduction in pooled HR for all studied complications) through fair glycemic control (median HbA1c ≤ 53 mmol/mol) compared to late-onset T2DM patients (18.01% reduction), they seemed to benefit more from favorable lifestyles, including weight control, healthy diet, and adequate physical activity.ConclusionsOur analyses reveal that early-onset T2DM is an aggressive disease resulting in more complex complication networks than late-onset T2DM. Aggressive glucose-lowering intervention, complemented by lifestyle modifications, are feasible strategies for controlling early-onset T2DM-related complications.

Sex Differences in Insulin Sensitivity and Glomerular Function in African Green Monkeys

In the United States, it is estimated that approximately 10.5% of the population has diabetes of which 90% are classified as insulin resistant expressing Type 2 Diabetes Mellitus (T2DM). T2DM is one of the leading causes of end stage renal disease (ESRD) accounting for approximately 40% of new ESRD cases. Previous studies have reported a more prevalent decrease in renal function in glucose intolerant males when compared to pre‐menopausal females. Males also have been reported to have earlier onset and higher prevalence of T2DM compared to pre‐menopausal females. Renal injury can be present before the onset of T2DM however, sex differences in renal injury have yet to be assessed in humans. A subpopulation of African Green Monkeys (AGM; Chlorocebus aethiops sabaeus) in the Caribbean exhibit spontaneous glucose intolerance and co‐morbidities such as insulin insensitivity, and hypertension. The AGM also shares similar genomic expression and metabolic phenotypes to humans making them optimal for translatable diabetes research. We hypothesize that female AGM are protected against renal injury and early onset T2DM. Systolic blood pressure (SBP) was measured by forearm plethysmography. Glucose tolerance was assessed via conscious and anesthetized oral glucose tolerance tests (OGTT). All AGM were fasted 12‐18 hours prior to study with water provided ad libitum. Blood glucose was measured at 0, 15, 30, 60, 90, and 120 min after an oral glucose load. Conscious AGM OGTT were delivered as 0.75g glucose/kg body weight. Sedated AGM (ketamine, 15mg/kg, i.m.), received 5g/dl glucose and 15 ml/kg in water by oral gavage. Venous blood samples were collected at timepoints 0, 30, 60, and 120 minutes post glucose administration. Urine samples were collected for 3 days post OGTT. Kidney histology was performed by staining 10µm sections with Periodic‐Acid Schiff stain (PAS). A minimum of 10 glomeruli were identified at 400x magnification per animal then analyzed with ImageJ. There were no differences between lightly sedated or conscious OGTT. All AGM in this study were normotensive and there were no sex differences in blood pressure between male and female AGM (F=11; 113.9±3.73 mmHg, M=6; 117.6 ± 6.3mmHg). Female AGM OGTT area under the curve (AUC) over 120 minutes post glucose load were lower compared to male AGM (F; 11,961.5± 710.6 min x mg/dl, M; 14,076.3±710.6 min x mg/dl, p&lt;0.05). There were no significant differences in plasma insulin at all time points between male and female AGM (F; 2,013± 1,007 min x mIU/L, M; 5,940± 1,424.6 min x mIU/L) despite the lower glucose AUC in females. Renal glomerular function was assessed by measuring plasma creatinine, urinary albumin, and urinary albumin to creatinine ratio (UACR). Plasma creatinine was not different between male and females (F; 1.35±0.2 mg/dl, M; 1.77±0.25 mg/dl). Microalbuminuria was present in both male and female AGMs, in the absence of sex differences (F; 98.43±23.1 ng/ml, M; 81.15±29.2 ng/ml). UACRs were not different between male and female AGM. Glomerular injury was assessed by determining the intensity of glomerular PAS stain. PAS stain intensity was not different in male and female AGM (F=3; 178.3 ± 8.6, M=3; 181.6± 8.6) regardless of OGTT sensitivity. Together these data suggest that female AGM are more insulin sensitive than male AGM and may be protected against early onset T2DM. Despite differences in OGTT in male and female AGM, microalbuminuria suggested onset of renal dysfunction. We conclude that the AGM provides a strong nonhuman primate model of T2DM for the long‐term study of sex differences in the mechanisms of ESRD.

Clinical Features and Vitreous Biomarkers of Early-Onset Type 2 Diabetes Mellitus Complicated with Proliferative Diabetic Retinopathy.

PurposeTo compare the clinical features and vitreous biomarkers of proliferative diabetic retinopathy (PDR) between patients with early-onset and late-onset type 2 diabetes mellitus (T2DM).Materials and MethodsThis case-control study analyzed the clinical data of 74 patients with PDR who underwent vitrectomy. The patients were divided into the early-onset (T2DM diagnosis age ≤ 40 years, n = 39) and late-onset (T2DM diagnosis age > 40 years, n = 35) groups. Thirty-six specimens were collected, and the liquid chip technology was used to detect the content of 27 types of cytokines in the vitreous. Differences in clinical features and cytokine levels between the two groups were evaluated. Bonferroni correction was applied for multiple comparisons.ResultsCompared with the late-onset group, the levels of hemoglobin A1c (HbA1c) and total cholesterol were significantly higher in the early-onset group (P < 0.001 and P = 0.009, respectively). Patients with early-onset T2DM PDR had worse visual prognoses and a higher rate of postoperative recurrent vitreous hemorrhage. The results of cytokine detection showed that the levels of interleukin-4 (IL-4), IL-6, IL-8, IL-9, granulocyte colony-stimulating factor, interferon-γ, interferon-inducible 10 kDa, monocyte chemotactic protein 1, macrophage inflammatory protein (MIP)-1α, and MIP-1β in the early-onset group were significantly higher than those in the late-onset group (p < 0.0026). Age at diabetes diagnosis and HbA1c, IL-4, and regulated upon activation, normal T cell expressed and secreted levels were independent risk factors for visual acuity after undergoing vitrectomy.ConclusionEarly-onset T2DM PDR patients had poor blood glucose and lipid metabolism, higher levels of inflammatory factors, and worse visual prognosis. Stricter metabolic management and earlier anti-inflammatory interventions may be required for patients with early-onset T2DM.

Association Analysis Between Different Diabetic Family History and Gender with Diagnosed Age of Type 2 Diabetes Mellitus: A Cross-Sectional Study in Tianjin, China.

BackgroundType 2 diabetes mellitus (T2DM) was previously considered a common disease in middle-aged and older people, but the age of diagnosis of T2DM is advancing every year, and the trend toward a younger age is obvious. Early-onset T2DM is a clinical syndrome caused by genetic and environmental factors. This study aimed to investigate the association between diabetic family history and gender with the diagnosed age of T2DM.MethodsThe newly diagnosed T2DM patients admitted to the diabetes identification center of Tianjin 4th Central Hospital (TJ4thch) from October 2017 to June 2020 were registered. According to whether the diagnosis age is over 40 years old, patients were divided into 2 groups (early-onset T2DM group and late-onset T2DM group). In the study, the T2DM family history was divided into 5 types: (a) Father T2DM: father with T2DM, but not the mother; (b) Mother T2DM: mother with T2DM, but not the father; (c) Both parents with T2DM; (d) Another relative(s) (other than the parents) with a history of T2DM; and (e) Without a family history of T2DM. The diagnosed age with different genders and diabetic family history was compared. Multivariate logistic regression analysis was used to investigate the association factors of early-onset T2DM.ResultsA total of 3725 patients completed the survey. There were 589 patients (15.8%) with early-onset T2DM, and 2469 patients (66.3%) had a diabetic family history. The T2DM-diagnosed age in males was lower than in females (51.7 ± 11.2 vs 54.0 ± 10.2, P = .000). The result was also reflected in the different T2DM family histories (with Both parents T2DM, 46.7 ± 11.1 vs 48.5 ± 10.3, P = .271; with Father T2DM, 46.8 ± 10.8 vs 49.8 ± 11.3, P = .005; with Mother T2DM, 50.4 ± 10.6 vs 52.3 ± 10.2, P = .019; with Other T2DM family history, 54.0 ± 10.8 vs 55.7 ± 9.5, P = .008; with no T2DM family history, 53.0 ± 11.0 vs 55.9 ± 9.3, P = .000). The order of the T2DM-diagnosed age in the different groups was Both parents T2DM (47.5 ± 11.0) and Father T2DM (47.9 ± 11.1) family history < that with Mother T2DM family history (51.1 ± 10.5) < that with Other T2DM family history (54.7 ± 10.3) and no T2DM family history (54.1 ± 10.5). Logistic regression analysis indicated that gender (OR, 1.733; P = .000), Father T2DM history (OR, 2.738; P = .000), Mother T2DM history (OR, 1.536; P = .001), Both parents T2DM (OR, 2.866; P = .000) and body mass index (OR, 1.108, P = .000) were correlated with early-onset T2DM.ConclusionPatients with early-onset T2DM tend to have a more obvious T2DM family history in China. This survey shows that when a parent has a T2DM family history, especially the father with T2DM, male patients are diagnosed with T2DM earlier. We need more intensive screening for diabetes in children with a family history of diabetes, especially in male children.

The risk factors potentially influencing risk of serious illness/death in people with diabetes, following SARS-CoV-2 infection: What needs to be done from here

Since early 2020 the whole world has been challenged by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus coronavirus disease 2019 (COVID-19) and the associated global pandemic [1]. People with diabetes are particularly at high risk of becoming seriously unwell after contracting this virus [2,3]. As yet we do not fully understand the underlying factors which contribute to such risk and their respective contributions to outcomes. In this regard, Barron et al. [4] reported an odds ratio (OR) for in-hospital COVID-19-related death of 2.03 (1.97–2.09) in people with type 2 diabetes mellitus (T2DM). A body of work is emerging in relation to the reasons why people with diabetes are more likely to become seriously unwell and in some cases die following a COVID-19 infection. Two recent landmark articles [5,6] have brought into sharp focus the factors that mediate increased risk of serious consequences of a COVID-19 infection in relation to hospital admission and mortality for vaccinated individuals and for nonvaccinated individuals in England. For the postvaccination study [6] the risk algorithm explained 74.1% of the variation in time to COVID-19 related death. An early COVID-19 pandemic study from Mexico [7] concluded that early-onset T2DM conferred an increased risk of hospitalization and obesity conferred an increased risk for ICU admission and intubation. The predictive score for COVID-19 lethality included age ≥65 years, diabetes, early-onset diabetes, obesity, age <40 years, chronic kidney disease, hypertension, immunosuppression and significantly discriminated lethal from nonlethal COVID-19 cases. We previously showed that in one area of the UK, the month-by-month mortality rate for people with T2DM was up to 2.2 times higher than that in the same month averaged over the previous 5 years in the early stages of the COVID-19 pandemic, with age the strongest independent predictor of death [8]. Work is continuing to understand how much a previous diagnosis of diabetes type 1 diabetes mellitus (T1DM) or T2DM increases the risk of becoming seriously unwell following a COVID-19 infection vs. absence of diabetes as a diagnosis. Since these early studies, the advent of treatment of hospitalized patients with Dexamethasone has significantly reduced mortality rates across the world. In patients hospitalized with COVID-19, the use of dexamethasone resulted in lower 28-day mortality among those who were receiving either invasive mechanical ventilation or oxygen alone at randomization [9]. Potential pathogenetic links between the SARS-CoV-2 virus and diabetes include the influence of glucose homeostasis and potentially altered immune status on the progression of the viral infection once established [10]. COVID-19 infection aggravates inflammation and alters immune system responses, leading to difficulties in blood glucose control. COVID-19 infection also increases the risk of thromboembolism and is more likely to induce cardiopulmonary failure in patients with diabetes than in patients without diabetes [11]. All of these mechanisms are now believed to contribute to the poor prognosis of some patients with preexisting diabetes and a COVID-19 infection. In conclusion, as the COVID-19 pandemic moves into a new phase in Europe and some other parts of the world, much remains to be determined about why having diabetes increases the risk of serious consequences of a COVID-19 infection. The COVID-19 global pandemic poses considerable health hazards, for patients with diabetes. The estimation of risk will require the combination of population based studies using primary and secondary care data and studies that evaluate the immunologic, metabolic and haematologic response following a COVID-19 infection at both a specific tissue and a whole body level, while keeping in mind that basic strategies such as optimizing pharmacologic management for patients at elevated cardiometabolic risk, with targeted choice of glucose lowering, antihypertensive and lipid lowering medications are as relevant to current and future research as to everyday clinical practice. Acknowledgements There was no external funding for this study. The data that support the findings of this study are available from the corresponding author upon reasonable request. Conflicts of interest There are no conflicts of interest.

Altered Gray Matter Volume, Functional Connectivity, and Degree Centrality in Early-Onset Type 2 Diabetes Mellitus.

Background: Structural and functional brain alterations that underlie cognitive decline have been observed in elderly adults with type 2 diabetes mellitus (T2DM); however, whether these alterations can be observed in patients with early-onset T2DM remains unclear. Therefore, we aimed to describe the abnormalities in brain volume and functional patterns in patients with early-onset T2DM in the present study.Methods: We enrolled 20 patients with early-onset T2DM and 20 healthy controls (HCs). Changes in brain volume were assessed using voxel-based morphology (VBM), while changes in brain function were assessed using degree centrality (DC) and functional connectivity (FC).Results: Compared to HCs, patients with early-onset T2DM exhibited gray matter reductions in the left orbital superior, middle, and inferior frontal gyri as well as the right superior frontal gyrus. The gray matter reductions in the right superior frontal gyrus were negatively associated with the urine albumin to creatinine ratio. Furthermore, increased DC values were observed in the left superior temporal gyrus, left Heschl gyrus, and left hippocampus in patients with early-onset T2DM. An FC analysis of these regions revealed elevated connectivity in the right precuneus, left inferior parietal gyrus, left Heschl gyrus, bilateral post-central gyrus, bilateral insula, bilateral superior temporal gyrus, and bilateral medial and paracingulate gyrus. Furthermore, the FC of the hubs to the superior temporal gyrus, insula, and Heschl gyrus was increased and positively correlated with trail making test-B.Conclusion: Decreased local gray matter volume and increased DC and FC may represent the neurobiological mechanism underlying cognitive dysfunction in patients with early-onset T2DM.

Early-onset of type 2 diabetes mellitus is a risk factor for diabetic nephropathy progression: a biopsy-based study.

Several studies show that patients with early-onset diabetes have higher risk of diabetic complications than those diagnosed in middle age. However, whether early-onset of type 2 diabetes mellitus (T2DM) is a risk factor for diabetic nephropathy (DN) progression remains unclear, especially a lack of data in biopsy-confirmed cohort. In This study, we enrolled 257 patients with T2DM and biopsy-confirmed DN to investigate the role of early-onset T2DM in DN progression. Participants were divided into two groups according to the age of T2DM diagnosis: early-onset group (less than 40 years) and later-onset group (40 years or older). We found that patients with early-onset T2DM had higher glomerular grades and arteriolar hyalinosis scores than those in later-onset group. After adjusted for confounding factors, early-onset of T2DM remained an independent predictor of end-stage renal disease (ESRD) for patients with DN. In conclusion, although with the comparable renal function and proteinuria, patients with early-onset T2DM and DN had worse renal pathological changes than those with later-onset. Early-onset of T2DM might be an important predictor of ESRD for patients with DN, which called more attention to early supervision and prevention for patients with early-onset T2DM and DN.

Risk of Depression among Early Onset Type 2 Diabetes Mellitus Patients

Methodology: Biochemically confirmed type 2 diabetes mellitus (T2DM) patients (n = 1,114) were recruited from the outpatient department of 2 tertiary care hospitals in Dhaka, Bangladesh. Face-to-face interview was conducted using a semi-structured questionnaire containing sociodemographic parameters and relevant information about depression and diabetes. Biochemical test results and treatment-related information were taken from patients’ records. The Hospital Anxiety and Depression Scale (HADS) was used to screen all patients for psychiatric manifestation. Those diagnosed by HADS were subsequently reassessed using structured clinical interview for DSM-5 Disorders – Clinician Version. T2DM diagnosed at age <40 years were considered as early onset T2DM. Association between age of onset category and depression was assessed using multivariable mixed-effect logistic regression adjusting for random variation of the area of residence and plausible confounders. Results: Around a third of the participants (32.5%) were diagnosed with T2DM before the age of 40 years. Early onset T2DM patients were found to have 57% increase in the risk of developing depression (OR 1.57; 95% CI 1.13–2.28; p = 0.011) in comparison to those with usual onset T2DM (≥40 years). Among other factors a positive family history for diabetes (OR 1.33; 95% CI 1.03–1.78; p = 0.038), poor glycemic control (OR 1.31; 95% CI 1.03–1.68; p = 0.028), presence of 1, or more diabetic complications (OR 1.37; 95% CI 1.03–1.78; p = 0.011) also showed increased risk of depression. Conclusion: Early onset T2DM patients are at greater risk of developing depression. The finding is likely to help in setting preventive strategies aiming to reduce the presence of concomitant depression symptoms among diabetes.

To Tell or Not to Tell: Disclosure and Self-Management among Adults with Early-Onset Type 2 Diabetes: A Qualitative Study

Background: Adults with early-onset Type 2 Diabetes Mellitus (T2DM) are an emerging high-risk population who may experience social challenges related to diabetes management. Objective: To explore the disclosure of T2DM and how disclosure affects diabetes self-management and the psychosocial adjustment to life with diabetes among adults with early-onset T2DM. Methods: A qualitative study was conducted using Systematic Text Condensation (STC). Data was derived from semi-structured interviews with 15 individuals with T2DM ≤ 46 years (10 women and 5 men) recruited from diverse settings using purposeful sampling. Results: Most informants disclosed their diabetes to a close relative shortly after receiving the diagnosis. This led to immediate emotional support and overall positive disclosure experiences. However, informants often hesitated to disclose their condition to others due to shame, fear of negative judgement or social exclusion. Over time, the majority of informants became more open about their condition, which often resulted in emotional and practical self-management support. Those most reluctant to disclosing their diabetes struggled with shame and negative diabetes-related emotions, which had negative effects on their diabetes self-management. Conclusion: Disclosure of T2DM seemed important for the social, emotional and practical management of diabetes among adults with early-onset T2DM. The disclosure was most often accompanied by feelings of shame and fear of condemnation. Professional guidance to support disclosure and interventions to address stigma may improve well-being and diabetes self-management in this population.

Early-Onset Type 2 Diabetes Misdiagnosed as Type 1 Diabetes in a 15-Year-Old Nigerian Girl: A Case Report

Type 2 diabetes mellitus (T2DM) is emerging as a new clinical disorder among children and adolescents. Although there is increasing prevalence of this clinical entity among adolescents worldwide, its diagnosis among Nigerian children and adolescents is still uncommon, hence, the reason many physicians still misdiagnose T2DM in adolescents as type 1 diabetes mellitus for reason of age of onset. Here, we present a 15-year old, overweight, girl who presented with history of polyuria, polydipsia and weight loss; her blood glucose level was 14.3 mmol/l, glycated haemoglobin 12.4% and glycosuria (3+), with no ketonuria or proteinuria. She was initially diagnosed as type 1 diabetes and managed with multiple doses of insulin by the pediatric team until she was later reviewed by the endocrinology unit. The diagnosis was later changed to early-onset T2DM (Youth-onset T2DM) based on a BMI of 29.75 kg/m2, presence of acanthosis nigricans, absence of ketosis, preserved beta-cell function as shown by normal serum C-peptide levels, absence of anti-glutamic acid decarboxylase (GAD) antibodies and islet cell antibody, and also response to oral anti-diabetic agents while her insulin therapy was discontinued. Therefore, a possibility of T2DM should be suspected in childhood and adolescent with diabetes associated with overweight or obesity, relatives with T2DM and features of insulin resistance (IR) like acanthosis nigricans, hypertension, dyslipidaemia, non-alcoholic fatty liver disease (NAFLD), hyperandrogenism, or polycystic ovarian syndrome (PCOS).

Clinical Features and Microvascular Complications Risk Factors of Early-onset Type 2 Diabetes Mellitus.

The aim of this research was to study the clinical features and microvascular complications risk factors of early-onset type 2 diabetes mellitus (T2DM). We analyzed the clinical data from 1421 T2DM inpatients at Wuhan Union Hospital. Subjects were divided into early-onset T2DM group (diagnostic age <40 years) and late-onset T2DM group (diagnostic age >40 years). All subjects underwent a standardized assessment of microvascular complications. Data were compared with independent-samples t test or Chi-square test. Multiple logistic regression was used to determine the risk factors of microvascular complications. Patients with early-onset T2DM were more inclined to have a lower systolic blood pressure (SBP), a longer duration of diabetes and higher levels of body mass index (BMI), uric acid (UA), fasting plasma glucose (FPG), total cholesterol (TC)- triglyceride (TG) and glycosylated hemoglobin (HbA1c) than those with late-onset T2DM (P<0.05). The prevalence of diabetic retinopathy (DR) was significantly higher and that of diabetic peripheral neuropathy (DPN) was significantly lower in early-onset group than in late-onset group (P<0.05). For DN, UA was an independent risk factor in early-onset T2DM. SBP and TG were independent risk factors in late-onset T2DM. For DR, duration of diabetes and SBP were independent risk factors in early-onset T2DM. Duration of diabetes, SBP and HbA1c were independent risk factors in late-onset T2DM. This study demonstrated that the clinical characteristics of early-onset T2DM were metabolic disorders, including glucose metabolism, lipid metabolism and amino acid metabolism. Early-onset T2DM was more likely to be associated with DR. The potential pathogenesis of early and late-onset T2DM might be different. The management of metabolic risk factors especially HbA1c, SBP, TG and UA is advised to be performed in the early stage of diabetes.

P4470Identification of four genes as novel susceptibility loci for early-onset type 2 diabetes mellitus, metabolic syndrome, or hyperuricemia in Japanese

Abstract Background Given that early-onset type 2 diabetes mellitus (T2DM), metabolic syndrome, and hyperuricemia have been shown to have strong genetic components, statistical power of a genetic association study may be increased by focusing on early-onset subjects with these conditions. Although genome-wide association studies have identified various genes and loci significantly associated with T2DM, metabolic syndrome, and hyperuricemia, genetic variants that contribute to predisposition to these conditions in Japanese individuals remain to be identified definitively. Purpose The purpose of the study was to identify genetic variants that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia in Japanese. We have now performed exome-wide association studies (EWASs) for early-onset subjects with T2DM, metabolic syndrome, or hyperuricemia and corresponding controls. Methods A total of 8102 individuals aged ≤65 years was enrolled in the study. The EWAS for T2DM was performed with 7407 subjects (1696 cases, 5711 controls), that for metabolic syndrome with 4215 subjects (2296 cases, 1919 controls), and that for hyperuricemia with 7919 subjects (1365 cases, 6554 controls). Single nucleotide polymorphisms (SNPs) were genotyped with Illumina Human Exome-12 DNA Analysis BeadChip or Infinium Exome-24 BeadChip arrays. The relation of allele frequencies for 31,210, 31,521, or 31,142 SNPs that passed quality control to T2DM, metabolic syndrome, or hyperuricemia, respectively, was examined with Fisher's exact test. To compensate for multiple comparisons of genotypes with T2DM, metabolic syndrome, or hyperuricemia, we applied Bonferroni's correction for statistical significance of association. Results The EWAS of allele frequencies revealed that four, six, or nine SNPs were significantly associated with T2DM (P&lt;1.60 × 10–6), metabolic syndrome (P&lt;1.59 × 10–6), or hyperuricemia (P&lt;1.61 × 10–6), respectively. Multivariable logistic regression analysis with adjustment for age and sex revealed that three, six, or nine SNPs were significantly related to T2DM (P&lt;0.0031), metabolic syndrome (P&lt;0.0021), or hyperuricemia (P&lt;0.0014). After examination of the association of identified SNPs to T2DM-, metabolic syndrome-, or hyperuricemia-related traits, linkage disequilibrium of the SNPs, and results of previous genome-wide association studies, we have newly identified ZNF860 and OR4F6 as susceptibility loci for T2DM, OR52E4 and OR4F6 for metabolic syndrome, and HERPUD2 for hyperuricemia. Conclusion Given that OR4F6 was significantly associated with both T2DM and metabolic syndrome, we thus newly identified four genes (ZNF860, OR4F6, OR52E4, HERPUD2) that confer susceptibility to early-onset T2DM, metabolic syndrome, or hyperuricemia. Determination of genotypes for the SNPs in these genes may prove informative for assessment of the genetic risk for T2DM, metabolic syndrome, or hyperuricemia in Japanese.