Young-onset Diabetes Research Articles

Early-onset type 2 diabetes

AimTo compare long-term outcomes among three groups with different ages of diabetes onset. Method66,520 paired age-, and sex-matched persons with and without type 2 diabetes were selected from the Taiwan National Health Insurance Research Database from 2000 to 2012. Cox proportional hazards models were used to compare the outcomes. Using late-onset diabetes as a reference, adjusted difference in differences analyses were performed to assess excessive odds comparing diabetes versus non-diabetes for young-onset diabetes (YOD) and early-onset diabetes in the risks of mortality and vascular complications. ResultsPersons with type 2 diabetes, irrespective of the onset age, had higher associated risks of all-cause mortality and vascular complications than their matched counterparts without diabetes. Compared to the odds of complications between those with diabetes and non-diabetes in the late-onset diabetes group, the excess odds in YOD are generally greater than in the early-onset diabetes (for stroke: 1.90 vs. 1.32; heart failure: 2.03 vs. 1.58; myocardial infarction: 3.02 vs. 1.56; and microvascular complications: 3.52 vs. 3.01). ConclusionsDiabetes with different ages of onset may imply distinct long-term health outcomes. The persons with young-onset and early-onset diabetes seem to bear excess risk for mortality and vascular complications.

Migration and diabetes incidence among Chinese adults in Canada, China, Hong Kong, and Taiwan: An international population-based comparative study from 2000 to 2017

AimsWe conducted an international population-based study comparing the incidence of young- (age 20–39 years) and usual- (age ≥ 40 years) onset diabetes among Chinese-Canadian immigrants; their source populations (mainland China, Hong Kong, Taiwan); and other Canadians. MethodsUsing population-based data (2000–17; n = 3.4 million cases), we calculated incidence rates and incidence rate ratios comparing the average incidence for each cohort. ResultsThe average incidence of young-onset diabetes (YOD) among immigrants from China, Hong Kong, and Taiwan was 165.5, 121.0, and 78.4 per 100,000 person-years respectively. Immigrants from China and Hong Kong had higher YOD incidence than their source populations (RR China: 2.59, 2.44–2.74; Hong Kong: 1.64, 1.49–1.81), while immigrants from Taiwan had lower rates versus Taiwan (RR 0.63, 0.45–0.86). YOD incidence among immigrants from China increased sharply by 8.3% (3.3–13.6%) per year from 2011 onward—over twice the annual increase among non-Chinese Canadians. The average incidence rates of usual-onset diabetes among immigrants from China, Hong Kong, and Taiwan were higher than (RR 1.77, 1.73–1.81), similar to (0.98, 0.96–1.01), and lower than (0.36, 0.32–0.40) those in each source population respectively. ConclusionsDiabetes incidence among Chinese migrants is unexpectedly heterogeneous, varying according age at migration, territory of origin, and the occurrence of diabetes in the source population.

Zinc transporter 8 autoantibody testing requires age-related cut-offs

IntroductionZinc transporter 8 autoantibodies (ZnT8A) are biomarkers of beta cell autoimmunity in type 1 diabetes that have become more widely available to clinicians in recent years. Robust control population-defined thresholds...

Outcomes of second-line oral antidiabetic drugs in persons with young-onset type 2 diabetes

AimPeople with young-onset diabetes (YOD) exhibit a higher risk of morbidity and mortality than those with late-onset diabetes. Few studies have explored the preferred management of diabetes in such patients. We compared the risks of hospitalization and mortality among people with YOD to whom second-line oral antidiabetic drugs (OADs) were administered. Methods7257 people taking second-line OADs after initial metformin therapy were enrolled during 2009–2014. Using add-on sulfonylureas (SUs) as a reference, the multivariable Cox regression model was used to compare the hospitalization and mortality risks among 5 categories of second-line OADs: alpha-glucosidase inhibitors, meglitinide, dipeptidyl peptidase-4 (DPP-4) inhibitors, SUs, and thiazolidinediones. ResultsAfter baseline characteristics, comorbidities, duration of diabetes, and drug use were controlled, the adjusted hazard ratios and 95% confidence interval for all-cause, cardiovascular, and non-infection hospitalization and all-cause mortality for metformin plus DPP-4 inhibitors were 0.62 (0.52–0.73), 0.49 (0.29–0.85), 0.64 (0.54–0.76), and 0.50 (0.27–0.92), respectively, when compared with the data for metformin plus SUs. ConclusionsAmong people with YOD, taking add-on DPP-4 inhibitors was associated with lower risks of all-cause hospitalization and mortality than taking add-on SUs. DPP-4 inhibitors thus seem to be a suitable second-line OAD for such patients.

Young age at diabetes diagnosis amplifies the effect of diabetes duration on risk of chronic kidney disease: a prospective cohort study.

We postulated that the increased lifetime risk of chronic kidney disease (CKD) in young-onset diabetes is attributable to both long disease duration and more aggressive disease. We examined whether age at diabetes diagnosis modifies the effect of diabetes duration on risk of CKD. We included 436,744 people with incident type 2 diabetes in the Hong Kong Diabetes Surveillance Database (HKDSD) and 16,979 people with prevalent type 2 diabetes in the Hong Kong Diabetes Register (HKDR). We used Poisson models to describe joint effects of age at diabetes diagnosis, diabetes duration and attained age on incidence of CKD in HKDSD. We used Cox proportional hazards models to examine interaction effect of age at diabetes diagnosis and diabetes duration on risk of CKD with adjustment for confounders in HKDR. During a median follow-up of 5.3years, 134,043 cases of CKD were recorded in the HKDSD. The incidence rate ratio for CKD comparing people of the same attained age but diagnosed with diabetes at ages 5years apart was higher for people with a younger age at diabetes diagnosis, but decreased with increasing age at diabetes diagnosis. During a median follow-up of 6.3years, 6500 people developed CKD in the HKDR. The increased risk of CKD with longer diabetes duration decreased with older age at diabetes diagnosis. The adjusted HR for CKD associated with 5year increase in diabetes duration was 1.37 (95% CI 1.13, 1.65) in people with diabetes diagnosed at 20-29years and 1.01 (95% CI 0.87, 1.18) in those diagnosed at ≥70years. Young age at diabetes diagnosis amplified the effect of increasing diabetes duration on increased risk of CKD.

1133-P: Monogenic Diabetes in Chinese with Young-Onset Diabetes

Background: The clinical course of monogenic diabetes in Chinese is not well established. We determined the prevalence of mutation and variants of uncertain significance (VUS) in a panel of monogenic diabetes genes in a prospective cohort of Chinese with young-onset diabetes, and examined clinical characteristics and outcome of the affected individuals. Methods: From patients enrolled in Hong Kong Diabetes Register between 1995-2012, DNA samples of 316 Chinese with non-type 1 diabetes diagnosed age <40 years were sequenced. A targeted panel of 34 genes related to monogenic diabetes was designed with AmpliSeq (Illumina). Variants were interpreted based on American College of Medical Genetics and Genomics Standards and Guidelines. Incident complications including cardiovascular disease (CVD) and death were captured until 2019. Baseline characteristics and complications were compared between patients with and without pathogenic/ likely pathogenic variants or VUS. Results: 24 (7.6%) patients had pathogenic/likely pathogenic variants and 39 (12.3%) had VUS in one or more monogenic diabetes genes. At baseline, patients with pathogenic/likely pathogenic variants had lower HbA1c (6.9 ± 1.0 vs. 7.9 ± 2.1%, p=0.02) and urine ACR (0.74 [0.44 - 2.03] vs. 1.71 [0.68 - 9.90] mg/mmol, p=0.01), and lower frequency of hypertension (20.8 vs. 46.9%, p=0.02) than those without mutation. Patients with and without VUS were similar for all characteristics. Over a median follow-up of 15.3 years, 4.3% of patients with pathogenic/likely pathogenic variants vs. 14.7% without mutation developed CVD (p=0.22), and 2.3% vs. 9.2% died (p=0.49). For patients with and without VUS, the frequencies were 14.7% vs. 14.7% (p=1.00) for incident CVD and 5.1% vs. 9.9% (p=0.55) for death. Conclusion: One in five Chinese with young-onset diabetes had either mutation or VUS in monogenic diabetes genes. Patients with monogenic diabetes gene mutation had more favorable metabolic profile but did not differ in incident complication compared with those with no mutation. Disclosure S. Tsoi: None. C. K. P. Lim: Stock/Shareholder; Self; GemVCare Ltd. R. C. Ma: Other Relationship; Self; AstraZeneca, Medtronic, Research Support; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Novo Nordisk, Pfizer Inc., Sanofi-Aventis, Tricida, Inc. E. S. H. Lau: None. B. Fan: None. E. Chow: Research Support; Self; Medtronic, Speaker’s Bureau; Self; Novartis Pharmaceuticals Corporation, Sanofi-Aventis. A. P. Kong: Advisory Panel; Self; Lilly Diabetes, Speaker’s Bureau; Self; Abbott, AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Sanofi, Stock/Shareholder; Self; Aptorum. J. C. Chan: Consultant; Self; Bayer AG, Boehringer Ingelheim International GmbH, MSD Corporation, Sanofi, Other Relationship; Self; Asia Diabetes Foundation, GemVCare, Research Support; Self; Applied Therapeutics, AstraZeneca, Hua Medicine, Lilly Diabetes, Merck KGaA. A. Luk: None. Funding Research Grants Council of Hong Kong (14114918); Research Impact Fund (R4012-18)

Werner Syndrome

A 36-year-old male presented with young-onset diabetes and advanced peripheral vascular disease. He had a history of bilateral juvenile cataracts and premature aged appearance. Closer scrutiny unraveled multiple endocrine and nonendocrine abnormalities. Genetic studies revealed a novel pathogenic variant (homozygous c.3233+2T>c) confirming and expanding the mutation spectrum of Werner syndrome. This report highlights the need for precise diagnosis, which has important implications for prognosis and genetic counseling.

Young Onset Diabetes in South Asia-what should we contemplate on?

No abstract available.

Clinical experience from a regional monogenic diabetes referral centre in Singapore

AimsMonogenic diabetes (also known as maturity-onset diabetes of the young or MODY) affects a subset of individuals with young-onset diabetes. We report our diagnostic work-up experience for such individuals. MethodsServing as a regional secondary-care diabetes centre in a multi-ethnic population, we receive referrals to evaluate MODY from endocrinologists in both public and private practice. Key criteria for consideration of genetic-testing are onset age ≤ 35, negative GAD antibody, no history of diabetic ketoacidosis, strong family history of diabetes and BMI < 32.5 kg/m2. A monogenic diabetes registry was set up since 2017 to study their disease trajectories. ResultsWe identified 30 out of 175 (17.1%) individuals with likely pathogenic/pathogenic variants. Importantly, 29 out of 30 (96.7%) occurred in clinically actionable genes. A continuous scale combining BMI, hs-CRP and HDL provided 80% (P < 0.001) diagnostic accuracy for MODY in our cohort, achieving a negative predictive value of 0.93 and sensitivity at 0.76. Subtyping MODY prior to genetic testing (if desired) will require specialist domain knowledge and additional biomarkers due to its genetic heterogeneity. ConclusionsThrough systematic and structured evaluation, the prevalence of MODY is non-trivial (17.1%) in a referral centre. Diagnostic algorithm combining clinical criteria and readily available biomarkers can support clinical decision for MODY genetic testing.

Young-onset diabetes, nutritional therapy and novel insulin delivery systems: a report from the 21st Hong Kong Diabetes and Cardiovascular Risk Factors - East Meets West Symposium.

The prevalence and incidence of young-onset diabetes are increasing in many parts of the world, with the most rapid increase occurring in Asia, where one in five people with diabetes are diagnosed below the age of 40 years. Accumulation of glycaemic burden from an early age significantly increases the lifetime risks of developing complications from diabetes. Despite impending health threats, young people fare worse in the control of blood glucose and other metabolic risk factors. Challenges in the management of young-onset diabetes are compounded by heterogeneity of the underlying causes, pathophysiology and clinical phenotypes in this group. Effective characterization of people with diabetes has implications in steering the choice of glucose-lowering drugs, which, in turn, determines the clinical outcome. Medical nutritional therapy is key to effective management of people with diabetes but dietary adherence is often suboptimal among younger individuals. A recently published consensus report on nutritional therapy addresses dietary management in people with prediabetes as well as diabetes, and summarizes clinical evidence regarding macronutrient and micronutrient composition as well as eating patterns in people with diabetes. For people with type 1 diabetes, automated insulin delivery systems have rapidly evolved since the concept was first introduced at the National Institute of Health and the Juvenile Diabetes Research Foundation in 2005. The subsequent development of a type 1 diabetes simulator, developed using detailed human physiology data on carbohydrate metabolism replaced the need for pre-clinical animal studies and facilitated the seamless progression to artificial pancreas human clinical trials.

176-LB: Ethnic Differences in Cardiovascular Complications of Young-Onset Diabetes (YOD)

Introduction: YOD (age at diagnosis [AAD]&amp;lt;40 years) is associated with greater cardiovascular disease (CVD) risk than usual-onset diabetes (UOD, AAD≥40 years). It is unknown whether this pattern varies by ethnicity. Methods: We included adults in Ontario, Canada with incident diabetes (2002-12, followed to 2018). We matched each case with ≤5 diabetes-free controls by age, sex, and ethnicity. The outcome was CVD (coronary artery disease, congestive heart failure, stroke, peripheral revascularization, lower extremity amputation). We constructed Cox proportional hazards models to estimate the association between AAD and CVD relative to controls. Results: We included 411,030 cases (3.5% South Asian; 4.3% Chinese) and 2,000,035 controls. The hazard ratios (HR) for CVD in UOD versus controls were higher in Chinese (2.38, 2.2-2.5) and South Asian (2.5, 2.4-2.7) people than White people (1.9, 1.9-1.9; pinteraction&amp;lt;0.0001). The HR for CVD in YOD versus controls were similar across ethnicities (Chinese: 5.2, 3.6-7.3; South Asian: 4.4, 3.7-5.3; White: 4.6, 4.4-4.8). In YOD and controls, Chinese and South Asian people had lower hazard of CVD than White people. In UOD, CVD hazard was lowest in Chinese people, and similar in South Asian and White people. Discussion: Although Chinese and South Asian people have a lower hazard of CVD compared to White people, YOD is associated with a 4- to 5-fold greater hazard of CVD across ethnicities. Disclosure C. Ke: None. T. Stukel: None. A. Luk: Research Support; Self; Bayer Healthcare Pharmaceuticals Inc., Roche Pharma. Other Relationship; Self; Merck Sharp &amp; Dohme Corp. J.C. Chan: None. B.R. Shah: None. Funding Canadian Institutes of Health Research; South Asian Network Supporting Awareness and Research

1457-P: Clinical, Biochemical, and Genetic Profile of Patients with Young-Onset Diabetes in North India

Background: Increasing prevalence of diabetes (type 1 and type 2) and obesity along with declining age of onset of type 2 diabetes, often create a diagnostic error in subtyping patients with young onset diabetes. Correct diagnosis of type of diabetes in this age group has clinical implications for management and longterm prognosis. In this study, we aimed to profile all consecutive young onset diabetes patients with respect to their clinical, biochemical, and genetic characteristics. Material and Methods: In this prospective study, conducted at a tertiary facility, all patients with diabetes onset between 18-30 years and diabetes duration less than 5 years were included. Assessment included detailed clinical and biochemical evaluation, autoantibody testing, c-peptide and genetic screening. Results: Total 100 patients were studied, out of which 80% were males and 55% were obese. Mean age of onset and median duration of diabetes were 24.98 ± 3.27 years and 18.0 months respectively. Initial clinical presentation was weight loss and osmotic symptoms in 58%, diabetic ketoacidosis in 5% and 25% patients were incidentally diagnosed. 20.8% of clinically autoimmune diabetes patients had negative antibody testing, 35.5% of clinically nonautoimmune diabetes had positive antibody testing. Overall, evidence of autoimmunity and decreased insulin secretion were found in 45% and 45% patients respectively. Ultrasound abdomen revealed small/atrophic pancreas in 9% of patients out of which nearly half did not had history of pancreatitis. Three patients were detected as MODY (1 = HNF1A and 2 = PAX4 mutations). One patient had Wolfram like syndrome (WFS1 mutation), 30 patients had variants of unknown significance. Conclusion: Evidence of autoimmunity was seen in 45%, monogenic diabetes in 4%, obesity in 55% of the study population. Higher incidence and aggressive nature of diabetes in young individuals are probably due to contributing effect of autoimmunity accompanied by increasing prevalence of obesity. Disclosure P.K. Reddy: None. G. Jevalikar: None. A.A. Singhal: None. P. Kaur: None. A. Gupta: None. S.K. Mishra: None. J.S. Wasir: None. M.S. Kuchay: Speaker’s Bureau; Self; Abbott, Boehringer Ingelheim International GmbH, Novo Nordisk A/S. B. Bansal: None. K. Farooqui: None. H. Kaur: None. A. Mithal: Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Johnson &amp; Johnson, Lilly Diabetes, Novo Nordisk A/S.

1661-P: NHG-KTPH Monogenic Diabetes Registry: Understanding Monogenic Diabetes in a Multiethnic Asian Population in Singapore

Introduction: Monogenic diabetes (also known as maturity-onset diabetes of the young or MODY) is a rare genetic disorder with an undetermined prevalence in Singapore. The NHG-KTPH Monogenic Diabetes Registry was set up in mid-2017 to capture longitudinal data of individuals genetically diagnosed with monogenic diabetes to study their prevalence and disease trajectories. Methods: Patients with clinical phenotype suggestive of monogenic diabetes i.e., diabetes onset =&amp;lt;45 years old, BMI &amp;lt;32.5 kg/m2 and GAD autoantibody-negative were recruited and subjected to genetic testing comprising of next-generation 16-MODY gene panel sequencing, mt.3242A&amp;gt;G TaqMan genotyping and multiplex ligation-dependent probe amplification (MLPA) for 4 common MODY genes. Genetic variants annotated as likely pathogenic/pathogenic according to ACMG guidelines were validated using Sanger sequencing. Individuals with such variant(s) were included in the Registry. EQ-5D-5L instrument was also administered for quality of life assessment. Results: Among 171 patients who were subjected to MODY genetic testing, 26 (15%) were found to harbor likely pathogenic/pathogenic variants. 93% of these variants were found in common MODY genes (HNF1A, HNF4A, GCK, HNF1B, MT-TL1) that had important clinical implications. Biomarkers such as C-peptide, hs-CRP and HDL were significantly different in those with likely pathogenic/pathogenic variants than those without. Discussion: Monogenic diabetes is present in 15% of our study participants with young-onset diabetes, which is greater than the reported 5% in UK. Clinical demographics and biomarkers can be further evaluated to improve the pick-up rate of monogenic diabetes among young-onset diabetes, with specific calibration applied to different subtypes of monogenic diabetes. This will improve cost-effectiveness of genetic testing and facilitate implementation of precision medicine for individuals with monogenic diabetes. Disclosure S. Ang: None. C. Tan: None. Y. Kon: None. L. Xia: None. S. Lim: None.

2174-PUB: Profiling of Young Diabetes in India: A Cross-Sectional Analysis Report

Aim: The purpose of this study was to profile young-onset (defined as up to age 40 years) diabetes patients in India. Methods: The current analysis is a retrospective data analysis of young-onset diabetes patients. Young age diabetes is defined as patients diagnosed with diabetes between 18 to 40 years of age. T1DM and other secondary diabetes were excluded while profiling these patients. Patient’s data was extracted from EMRs of Apollo Sugar Outpatient clinics (n=35) from January 2018 to October 2019. Descriptive statistics were applied to analyze the data and report the results. Results: Of the total 85568 diabetes patient’s records, 4152 (5%) young diabetes patients were identified as fulfilling the criteria of T2DM of early-onset. Males were 2495 (60%) and females were 1657(40%). Mean blood pressure was 122/78 mmHg, average BMI was 28.4 kg/m2, 15% had hypertension, 39% had dyslipidemia and 1% had CAD. Positive family history was recorded in 5% of patients, and 1% were recorded to have current or past smoking. Mean HbA1c was 8.4%, FBG and PPBG were 190 mg/dL and 273mg/dL. Mean cholesterol 179mg/dL, HDL 40mg/dL, LDL 111 mg/dL, and TG 232 mg/dL and creatinine 0.9mg/dL. The average no of antidiabetes drugs prescribed was 2. Nearly 36% of the patients were on oral agents and insulins, 30% were on statins. Conclusions: In our cross-sectional analysis 5% of patients over 18 month’s period had a diagnosis fulfilled the criteria for early-onset diabetes. There was a male preponderance. The average BMI was considerably higher. The majority had poor control and greater than a third of patients were on insulin. Other comorbidities such as hypertension and dyslipidemia were also prevalent. The higher BMI poor control and presence of comorbidities are ominous predicting a higher progression to complications given the longer disease burden in these patients. Our data indicate the need for further efforts in preventing detecting and treating diabetes in this young group of patients. Disclosure N. Nk: None. C. Dwarakanath: None. V. S: None. M. Rm: None. N. Bs: None. S. Das: None. K. Dash: None. S. Paladugu: None. K. Seshadri: None.

108-OR: Application of a European Genetic Risk Score for Type 1 Diabetes in a Han-Chinese Population

Increasing childhood obesity and young-onset diabetes have made clinically distinguishing between type 1 diabetes (T1D) and type 2 diabetes (T2D) more difficult. A Genetic risk score (GRS) for T1D was developed in European populations, with good discrimination of diabetes type. Here, we aim to evaluate T1D-GRS in a Han-Chinese cohort. We utilized whole genome genotyping data for 533 nondiabetic controls, 182 patients with T1D, and 6,209 patients with T2D. We computed the T1D-GRS for each subject using 30 T1D associated SNPs. The mean ages of the controls, T1D, and T2D subjects were 47±11, 32±15, and 57±13 years, respectively. Violin plots of the GRS for the 3 groups are shown in the Figure, along with p-values. The mean GRS across the controls, T1D, and T2D were 0.242, 0.256, and 0.242, respectively. The area under the curve (AUC) for GRS in T1D vs. T2D was 0.677 (95% CI: 0.635-0.718), and 0.678 (95% CI: 0.631-0.725) for T1D patients vs. controls. We conclude that T1D-GRS detects significant differences in T1D genetic risk between T1D and non-T1D in a Han-Chinese population, with subjects with T1D having a higher score. Further refinement incorporating single nucleotide polymorphisms (SNPs) specific for a Han-Chinese population is currently underway, and is expected to further improve classification of T1D in Han-Chinese. Disclosure R. Wan: None. S.A. Sharp: None. C.H.T. Tam: None. M.N. Weedon: None. J.C. Chan: None. W. Hagopian: Consultant; Self; Novo Nordisk Inc. R.A. Oram: None. R.C. Ma: Advisory Panel; Self; AstraZeneca. Stock/Shareholder; Self; GemVCare. Other Relationship; Self; AstraZeneca, Bayer Healthcare Pharmaceuticals Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Tricida Inc. Funding Research Grants Council (T12-402/13N); Research Impact Fund (CUR4012-18)

1628-P: Extreme Survival in a Low SES Population with Early-Onset Diabetes

Low-income African Americans (AA) and Whites with extreme duration of young-onset diabetes (YODM) are a unique population. Traits of this population surviving w/DM for 50 yrs can provide clues to longevity in YODM, particularly in the poor and underserved. Persons ≥50 yrs old (59% female, 60% AA) from the Southern Community Cohort Study diagnosed w/DM &amp;lt; age 30 (n=649), classified by DM duration ≥ 50 yrs (extreme duration, n=96) or &amp;lt;50 yrs (shorter duration, n=553), or w/o DM (n=33,939) at cohort entry were included. We used multinomial logistic regression (OR, 95% CI) to compare traits across groups and Cox models (HR, 95% CI) to assess mortality risk and factors linked w/survival after cohort entry. Mean age was 63, 54, and 57 in those w/extreme, shorter and no DM, respectively. Mean age at DM diagnosis was 5 and 23 in those w/extreme and shorter duration. Compared to shorter duration, those w/extreme duration had a lower BMI at age 21 (OR=0.93, 0.89-0.98) but higher BMI (OR=1.04, 1.01-1.08) at study entry. They were 40 to 50% less likely to have glaucoma and cataracts, but no difference in hx of stroke or CAD. By contrast, they had 1.5 to 3-fold greater risk vs. those w/o DM. In Cox models, those w/shorter duration YODM were at 3.2 times greater mortality risk vs. those w/o DM (HR=3.23, 2.76-3.77), but risk increased only marginally in extreme duration vs. those w/o DM (HR=1.39, 0.98-1.98). No racial difference in survival was seen in extreme (HR=1.04, 0.39-2.77) or shorter duration DM (HR=1.04, 0.72-1.49), though AA w/o DM were at slightly increased mortality risk vs. Whites (HR=1.09, 1.03-1.16). In YODM, diagnosis before age 6 was linked w/lower mortality (HR=0.57, 0.33-0.96) vs. those ≥ age 6. This low-income population w/extreme duration of YODM diagnosed mainly in very early childhood is characterized by a relatively lean BMI in young-but not later adulthood, and appear relatively protected from certain DM and age-related complications. Our data also suggests that in the low SES, AA are not any less likely to survive ≥50 yrs w/DM than Whites. Disclosure E. Campos: None. H.A. Keenan: None. M.F. Lopes-Virella: None. W.J. Blot: None. B. Conway: None. Funding 5U01CA202979-04

SAT-650 Novel Insights into the Entero-Insular Axis in Fibrocalcific Pancreatic Diabetes: An Isoglycemic Intravenous Glucose Infusion (IIGI) Study from India

In tropical countries including India, one of the common causes for young onset diabetes mellitus (DM) is “Fibro Calcific Pancreatic Diabetes” (FCPD) characterized by progressive pancreatic destruction. Despite this, glucagon has been found to be elevated in FCPD (1,2). The L-Cells in gut produce glucagon like peptide- 1 (GLP-1) and oxyntomodulin which are products of glucagon gene, thus raising probability of extra-pancreatic glucagon in FCPD. To test this hypothesis we performed 75grams oral glucose tolerance test (OGTT) followed by IIGI on separate days on nine FCPD and six healthy subjects. The latter procedure ensured matched glucose levels achieved during OGTT. Glucagon and incretins were measured at nine pre-specified time points. We found an increase in L-Cell products: GLP-1 (44.5±9.2pM vs. 12.4±4.5pM, p=0.02) and Oxyntomodulin (1252±350pg/ml vs. 859.8±165pg/ml, p=0.43) along with significant rise in glucagon during OGTT (98.8±13pg/ml vs. 63.4±7pg/ml, p=0.03) despite flat basal & stimulated C-peptide (0.43±0.14ng/ml and 1.09±0.3ng/ml, respectively) and Pancreatic polypeptide (12.3±0.0pg/ml and 14.7±1.7pg/ml, respectively) levels.Paradoxically, gastric inhibitory polypeptide (GIP) levels were low in FCPD (106.8±40.3pg/ml vs. 557.8±96.4pg/ml, p=0.003). We speculate that the hyperglucagonemia is extra-pancreatic (L-Cell) in origin and may also contribute to the dichotomous incretin response in FCPD.

The medications and health care utilization of patients newly diagnosed with type 2 diabetes mellitus: A nationwide population-based cohort study

The prevalence of young-onset diabetes (YOD) is increasing in Asia, but little is known about the metabolic control, associated complications, or medical behavior in this population. Our aim was to assess the prevalence of young-onset and late-onset type 2 diabetes mellitus (T2DM) and their associated risk factors and medical behaviors in Taiwan. Data were collected from the National Health Insurance Research Database of Taiwan on 11,244 patients from 2008 to 2013. We classified patients with young-onset diabetes if they were diagnosed before 40 years of age and late-onset diabetes (LOD) if diagnosed at 40 years of age or older. We analyzed the prevalence, medication, and medical behaviors between these groups. We enrolled 2556 newly diagnosed T2DM patients in 2012. Demographics and comorbidities were recorded from YOD (n = 311) and LOD (n = 2245) patients. Most newly diagnosed patients started with monotherapy and almost half of them with sulfonylurea. The prevalence of YOD in Taiwan is up to 12%. In terms of treatment, 42% of T2DM patients are treated in clinics, 58% in hospital, and 25.2% by an endocrinologist. Our study highlights the rising trend of YOD in Taiwan. National endeavors are urgently needed for early diagnosis, effective management, and primary prevention of diabetes.

Real-world data reveal unmet clinical needs in insulin treatment in Asian people with type 2 diabetes: the Joint Asia Diabetes Evaluation (JADE) Register.

AimsTo explore the pattern of insulin use and glycaemic control in Asian people with type 2 diabetes, stratified by gender, young‐onset diabetes (YOD; diagnosed before age 40 years), and diabetic kidney disease (DKD; estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73m2).Materials and methodsWe conducted a cross‐sectional analysis of 97 852 patients from 11 Asian countries/regions (2007–2017) included in the prospective Joint Asia Diabetes Evaluation (JADE) Register.ResultsAmong 18 998 insulin users (47% women, mean ± SD age 59.2 ± 11.7 years, diabetes duration 13.2 ± 8.3 years, glycated haemoglobin [HbA1c] 72 ± 21.4 mmol/mol [8.74 ± 1.95%], median total daily insulin dose [TDD] 0.27–0.82 units/kg), 25% and 29.5% had YOD and DKD, respectively. Premixed (44%) and basal‐only (42%) insulin were the most common regimens. Despite being more commonly treated with these two regimens with higher insulin dosages, patients with YOD had worse HbA1c levels than their late‐onset peers (73 ± 20.5 vs. 71 ± 21.2 mmol/mol [8.82 ± 1.87% vs. 8.66 ± 1.94%]; P < 0.001). Fewer women than men attained an HbA1c level < 53 mmol/mol (7%; 15.7% vs 17.1%; P = 0.018). Adjusting for age, diabetes duration, TDD, HbA1c, eGFR, and use of oral glucose‐lowering drugs at baseline, the odds of self‐reported hypoglycaemia were higher in women (vs. men: adjusted odds ratio [aOR] 1.16, 95% confidence interval [CI] 1.05–1.28) and in patients with DKD treated with a premixed regimen (1.81 [95% CI 1.54–2.13] vs. 1.34 [95% CI 1.16–1.54] in non‐DKD; P interaction < 0.001). Compared to basal‐only regimens, premixed and basal‐bolus regimens had similar HbA1c reductions but were independently associated with increased odds of hypoglycaemia (1.65 [95% CI 1.45–1.88] and 1.88 [95% CI 1.58–2.23], respectively).ConclusionsIn this Asian population, there were varying patterns of insulin regimens with suboptimal glycaemic control, despite relatively high TDDs, which were influenced by gender, DKD, and YOD status.

Wolfram syndrome with childhood glaucoma: A rare case report with review of literature

Wolfram syndrome (WFS) is a rare neurodegenerative disorder characterized by young-onset diabetes mellitus, central diabetes insipidus, optic nerve atrophy, and hearing loss. The ophthalmic association of this order has been limited to optic nerve atrophy. We report here a case of WFS and its disease course with childhood glaucoma as a rare ophthalmic manifestation which has been reported just once earlier. The patient had young-onset diabetes mellitus (insulin dependent), diabetes insipidus, and optic-disc pallor suggestive of partial optic atrophy. However, hearing assessment was normal at the time of presentation and in due course of disease. Glaucoma is one of the rare possible ocular manifestations of WFS which should be highly considered while evaluating patient with this disorder.