Characteristic phenotype of Chinese patients with adult-onset diabetes who are autoantibody positive by 3-Screen ICA™ ELISA

Aims To assess the prevalence of diabetes-associated autoantibodies in Chinese patients recently diagnosed with adult-onset diabetes and to evaluate the potential role of the autoantibody markers for characterization of disease phenotype in the patient population. Methods The study included 1273 recent-onset adult patients with phenotypic type 2 diabetes mellitus (T2DM). Serum samples were tested using the 3-Screen ICA™ ELISA (3-Screen) designed for combined measurement of GADAb and/or IA-2Ab and/or ZnT8Ab. 3-Screen positive samples were then tested for individual diabetes-associated and other organ-specific autoantibodies. Clinical characteristics of patients positive and negative in 3-Screen were analysed. Results Forty-four (3.5%) of the T2DM patients were positive in 3-Screen, and 38 (86%) of these were also positive for at least one of GADAb, IA-2Ab and ZnT8Ab in assays for the individual autoantibodies. 3-Screen positive patients had lower BMI, higher HbA1c, lower fasting insulin levels and lower fasting C-peptide levels compared to 3-Screen negative patients. Analysis using a homeostatic model assessment (HOMA2) indicated that HOMA2-β-cell function was significantly lower for the forty-four 3-Screen positive patients compared to 3-Screen negative patients. Twenty (45%) 3-Screen positive patients were also positive for at least one thyroid autoantibody. Conclusions The 3-Screen ELISA has been used successfully for the first time in China to detect diabetes autoantibodies in patients with phenotypic T2DM. 3-Screen positive patients presented with poorer β cell function.

What Was Known About Childhood Diabetes Mellitus Before the Discovery of Insulin?

It has been widely reported by historians that physicians were aware of two distinct types of diabetes mellitus by the 1880s, and that these were both similar to and the direct forerunners of type 1, juvenile-onset and type 2, adult-onset diabetes. The writings of prominent specialist physicians practicing just prior to the discovery of insulin in 1921–1922 were reviewed and there is little evidence that experts believed that adult and childhood diabetes were different. In fact, more than a decade passed after the discovery of insulin before diabetes in children and adults even began to be distinguished. Childhood diabetes was exceedingly rare in the early 20th century and diabetes was believed to be primarily a chronic disease of adults. It is interesting to speculate about what might have happened if the first pancreatic extract tests had been performed on adult-onset diabetics with insulin-resistant diabetes mellitus. Clearly, the results would have been disappointing and the discovery of insulin delayed. This essay explores how the test subject decision was made. It is fortuitous that a 14 year old boy with what was unequivocally type 1 diabetes was selected to be the first insulin recipient, and the rest is history.

289Birthweight and risks of adult-onset diabetes in women who are and are not overweight

Background Higher adult body mass index (BMI) increases diabetes risk, whereas, paradoxically, lower birthweight is associated with higher risks of adult-onset diabetes. Increased diabetes risks associated with low birthweight might be due to increased risks among those who become overweight or obese as adults but evidence on risks among those of normal BMI is limited. Methods In the Million Women Study, 413,516 women without prior diabetes, at mean age 60(SD5) years, reported their birthweight, and current height and weight. Birthweight and BMI at age 60 years were validated against recorded values at similar ages. Participants were followed for diabetes by electronic linkage to national hospital admissions records. Cox regression yielded multivariable-adjusted relative risks (RRs) for diabetes, overall and subdivided simultaneously by categories of birthweight and adult BMI. Results During 15(SD3) years follow-up, 24,528 women had hospital admissions with diabetes, first recorded at average age 70(SD6) years. Adult-onset diabetes risks increased strongly with increasing adult BMI (RR per 5 kg/m2 increase: 2.03, 95% CI 2.01-2.06). Compared to those with birthweight 3.0-3.4 kg, RRs of diabetes for birthweight <2.5 kg and ≥4.0 kg were 1.35(1.30-1.38) and 0.73(0.70-0.75), respectively. The association between low birthweight and increased diabetes risk was strongly evident among women who were of normal BMI, overweight and obese (p < 0.0001 for each). Conclusions At every level of adult adiposity, there were strong inverse associations between birthweight and adult-onset diabetes risk. Key messages While adult adiposity increases diabetes risk, there is a strong and independent increase in diabetes risk with decreasing birthweight.

Novel subgroups of adult-onset diabetes and their outcomes: relationship between previous cardiovascular events and microvascular complications

Background Type 2 Diabetes Mellitus (T2DM) is a global scale problem, closely related to genetic and environmental factors, such as aging, family history, diet, lack of physical exercise, physical inactivity and obesity, which contribute to the increase in its prevalence. Methods 191 participants (EG) with T2DM with the average of 70.3 years (SD = 8.3) and 36 with pre-diabetes (CG) with an average of 62 years (SD = 10.3) who participated in clinical trials at Clinical Research Unit in Cardiology of Coimbra Hospital and Universitary Centre without cognitive difficulties, were divided in 5 different clusters. These were established based on six different variables: body mass index (BMI), age of each individual, age at diagnosis of DMT2, glycated haemoglobin value (HbA1c), homeostatic model that estimates the function of β cells (HOMA2-B) and insulin resistance (HOMA2-IR). Results Cluster 1 presented pre-diabetic individuals (15.9%), while diabetic individuals were divided into clusters 2 (1.8%), 3 (17.6%), 4 (21.1%) and 5 (43.6%). Regarding the study of the prevalence of previous cardiovascular events, the majority of individuals present in the different clusters had history of acute myocardial infarction (AMI). For the prevalence of microvascular complications, only chronic kidney disease (CKD) was found in the vast majority of different groups. It was observed a dependency relationship between previous AMI and CKD in clusters 3 (P = 5.16E-5; P < 0.05), 4 (P = 0.0004; P < 0.05) and 5 (P = 0.0023; P < 0.05). Conclusions It was possible to create different clusters in a sample of the Portuguese population and to observe the existence of dependency relationships between different previous cardiovascular events and microvascular complications.

Improving clinical utility of GAD65 autoantibodies by electrochemiluminescence assay and clinical phenotype when identifying autoimmune adult-onset diabetes

Aims/hypothesis It is important to differentiate the two major phenotypes of adult-onset diabetes, autoimmune type 1 diabetes and non-autoimmune type 2 diabetes, especially as type 1 diabetes presents in adulthood. Serum GAD65 autoantibodies (GADA) are the most sensitive biomarker for adult-onset autoimmune type 1 diabetes, but the clinical value of GADA by current standard radiobinding assays (RBA) remains questionable. The present study focused on the clinical utility of GADA differentiated by a new electrochemiluminescence (ECL) assay in patients with adult-onset diabetes. Methods Two cohorts were analysed including 771 diabetic participants, 30–70 years old, from the Action LADA study (n = 6156), and 2063 diabetic participants, 20–45 years old, from the Diabetes in Young Adults (DiYA) study. Clinical characteristics of participants, including requirement of early insulin treatment, BMI and development of multiple islet autoantibodies, were analysed according to the status of RBA-GADA and ECL-GADA, respectively, and compared between these two assays. Results GADA was the most prevalent and predominant autoantibody, >90% in both cohorts. GADA positivity by either RBA or ECL assay significantly discriminated clinical type 1 from type 2 diabetes. However, in both cohorts, participants with ECL-GADA positivity were more likely to require early insulin treatment, have multiple islet autoantibodies, and be less overweight (for all p < 0.0001). However, clinical phenotype, age at diagnosis and BMI independently improved positive predictive value (PPV) for the requirement of insulin treatment, even augmenting ECL-GADA. Participants with GADA detectable by RBA, but not confirmed by ECL, had a phenotype more similar to type 2 diabetes. These RBA-GADA positive individuals had lower affinity GADA compared with participants in which GADA was confirmed by ECL assay. Conclusions/interpretation Detection of GADA by ECL assay, given technical advantages over RBA-GADA, identified adult-onset diabetes patients at higher risk of requiring early insulin treatment, as did clinical phenotype, together allowing for more accurate clinical diagnosis and management. Graphical abstract

Insulin micro-secretion in Type 1 diabetes and related microRNA profiles

The aim of this cross-sectional study was to compare plasma C-peptide presence and levels in people without diabetes (CON) and with Type 1 diabetes and relate C-peptide status to clinical factors. In a subset we evaluated 50 microRNAs (miRs) previously implicated in beta-cell death and associations with clinical status and C-peptide levels. Diabetes age of onset was stratified as adult (≥ 18 y.o) or childhood (< 18 y.o.), and diabetes duration was stratified as ≤ 10 years, 10–20 years and > 20 years. Plasma C-peptide was measured by ultrasensitive ELISA. Plasma miRs were quantified using TaqMan probe-primer mix on an OpenArray platform. C-peptide was detectable in 55.3% of (n = 349) people with diabetes, including 64.1% of adults and 34.0% of youth with diabetes, p < 0.0001 and in all (n = 253) participants without diabetes (CON). C-peptide levels, when detectable, were lower in the individuals with diabetes than in the CON group [median lower quartile (LQ)–upper quartile (UQ)] 5.0 (2.6–28.7) versus 650.9 (401.2–732.4) pmol/L respectively, p < 0.0001 and lower in childhood versus adult-onset diabetes [median (LQ–UQ) 4.2 (2.6–12.2) pmol/L vs. 8.0 (2.3–80.5) pmol/L, p = 0.02, respectively]. In the childhood-onset group more people with longer diabetes duration (> 20 years) had detectable C-peptide (60%) than in those with shorter diabetes duration (39%, p for trend < 0.05). Nine miRs significantly correlated with detectable C-peptide levels in people with diabetes and 16 miRs correlated with C-peptide levels in CON. Our cross-sectional study results are supportive of (a) greater beta-cell function loss in younger onset Type 1 diabetes; (b) persistent insulin secretion in adult-onset diabetes and possibly regenerative secretion in childhood-onset long diabetes duration; and (c) relationships of C-peptide levels with circulating miRs. Confirmatory clinical studies and related basic science studies are merited.

Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review

Type 2 diabetes (adult onset diabetes) is the most common type of diabetes, accounting for around 90% of all diabetes cases with insulin resistance and insulin secretion defect. The key goal of anti-diabetic therapy is to increase the development of insulin, immunity and/or decrease the amount of blood glucose. While many synthetic compounds have been produced as anti-diabetic agents, due to their side effects and limited effectiveness, their usefulness has been hindered. This systematic review investigated the bioactive compounds reported to possess activities against type 2 diabetes. Three (3) databases, PubMed, ScienceDirect, and Google Scholar, were searched for research articles published between January 2010 and October 2020. A total of 6464 articles were identified, out of which 84 articles were identified to be eligible for the study. From the data extracted, it was found that quercetin, Kaempferol, Rosmarinic acid, Cyanidin, Rutin, Catechin, Luteolin, and Ellagic acid were the most cited bioactive compounds, which all falls within the class of polyphenolic compounds. The major sources of these bioactive compounds include citrus fruits, grapes, onions, berries, cherries, broccoli, honey, apples, green tea, Ginkgo biloba, St. John's wort, green beans, cucumber, spinach, tea, Rosmarinus officinalis, Aloe vera, Moringa oleifera, tomatoes, potatoes, oregano, lemon balm, thyme, peppermint, Ocimum basilicum, red cabbage, peas, olive oil, and walnut. In conclusion, the data collected in our study indicates that consumption of polyphenolic/flavonoids rich food and vegetables as a routine diet could considerably reduce the risk of T2DM and also benefits insulin sensitivity and other chronic inflammations.