Diabetic ketoacidosis in an adult with beta-ketothiolase deficiency (BKD) involving a novel ACAT1 variant : first report of established diabetes in BKD and a review of the literature.

BACKGROUND: Diabetes presenting in young adults is often challenging to classify. Diabetic ketoacidosis is typically seen in autoimmune type 1 diabetes mellitus and more rarely in young onset type 2 diabetes mellitus. Beta-ketothiolase deficiency (BKD) is a rare autosomal recessive condition affecting isoleucine catabolism and ketone body metabolism. BKD typically manifests in childhood as recurrent episodes of ketoacidosis, the frequency of which tends to reduce with age. There is a paucity of data with respect to the co-existence of persistent dysglycemia with BKD. CASE PRESENTATION AND LITERATURE REVIEW: We present a novel case of diabetes presenting as diabetic ketoacidosis in a 34-year-old man with BKD, with genetically confirmed compound heterozygosity for variants in ACAT1, including a novel ACAT1 c.481T>C, p.(Tyr161His) variant. Diabetes in people with BKD presents unique diagnostic and management challenges. To further contextualize our findings, we conducted a comprehensive narrative review of the existing literature with respect to dysglycemia in those with BKD, especially in adulthood. There are no existing reports describing diabetes in adults with BKD. Stress hyperglycemia is not uncommon when children with BKD are acutely unwell, with several pediatric case reports describing short-lived hyperglycemia but normal HbA1c measurements during metabolic crises (indicating the absence of persistent hyperglycemia). CONCLUSIONS: This is the first report of diabetic ketoacidosis in an adult with BKD, with an elevated HbA1c consistent with persistent hyperglycemia. This case highlights the importance of checking HbA1c in people with BKD and hyperglycemia in order to uncover potential coexisting diabetes, facilitating timely management and preventing complications. Increased reporting on the longitudinal outcomes of those with rare metabolic disorders is essential for identifying potential associations with conditions like diabetes.

Timing of minor and major amputation in patients with diabetes-related foot ulceration admitted to two public tertiary referral hospitals in Australia.

BACKGROUND: There is limited information regarding the number of patients with diabetes-related foot ulceration (DFU) who receive minor or major amputation, and how quickly these amputations occur. This study aimed to identify the incidence of index minor and major amputation among inpatients with DFU over 4 years, and where amputation occurred during the patient's index DFU-related admission, investigate prognostic factors. METHODS: The incidence of index minor and major amputation, and the admission sequence during which amputation occurred were identified from DFU-related admissions to two public hospitals during 2014-2018. Where minor or major amputation occurred during the patient's index DFU-related admission, prognostic factors were investigated using logistic regression. RESULTS: DFU-related hospital admissions were required by 564 patients. The incidence of minor amputation over 4 years was 34% (n = 193). The incidence of minor amputation during the patient's index DFU-related admission was 28% (n = 155), which was associated with requiring revascularisation (odds ratio [OR] 2.33, 95% CI 1.53-3.55, P < 0.001). The incidence of major amputation over 4 years was 8% (n = 45). The incidence of major amputation during the patient's index DFU-related admission was 6% (n = 31), which was associated with having more comorbidities (OR 1.58, 95% CI 1.10-2.26, P = 0.01) and receiving care for a mental health condition (OR 3.85, 95% CI 1.48-10.01, P = 0.006). CONCLUSION: Most amputations occurred during the patient's index DFU-related hospital admission. Major amputation during a patient's index admission was associated with more comorbidities and mental health conditions.

Myocardial fibrosis in Type 2 Diabetes is associated with functional and metabolomic parameters.

AIMS: To identify biomarkers of cardiomyopathy in patients with type 2 diabetes mellitus (T2DM) using cardiovascular magnetic resonance (CMR) and to identify associations between functional status, metabolomic profile and myocardial fibrosis. METHODS: In this prospective case control study, patients (n = 49) with T2DM without significant coronary artery disease, and matched controls (n = 18) underwent CMR, cardiopulmonary exercise testing, and plasma metabolomic analyses. RESULTS: Patients with T2DM (n = 49, median [interquartile range] age 61 [56-63] years, 61% male, diabetes duration 11 [7-20] years), historical HbA1c 7.6% (60 mmol/mol) (6.9-8.6) and matched controls (n = 18) were examined. Study patients had increased myocardial extracellular volume (ECV) (26.9 [23.8-30.0] vs 23.4 [22.4-25.5) %, p < 0.001). Increased ECV was associated with male sex (p = 0.04), time with T2DM (p = 0.02), reduced peak VO2 (R2 = 0.48, p = 0.01), increased circulating choline (p = 0.002) and cysteamine (p = 0.002) both of which were also associated with reduced peak VO2 (p < 0.025 and 0.014 respectively). CONCLUSIONS: Patients with well-controlled T2DM without significant coronary disease exhibit focal and diffuse myocardial fibrosis and diffuse myocardial fibrosis is associated with reduced exercise tolerance and metabolites. Plasma metabolites may provide mechanistic insights into diffuse myocardial fibrosis, and cardiopulmonary fitness.

Ramadan and gestational diabetes: maternal and neonatal outcomes.

AIMS: The impact of Ramadan exposure to Gestational Diabetes Mellitus (GDM) pregnancies is not known. We therefore aimed to assess the association of Ramadan with maternal and neonatal outcomes among pregnant women with GDM. METHODS: Retrospective cohort study of 345 Muslim women with singleton pregnancies who attended a major Sydney teaching hospital during the period 1989-2010, was undertaken. Exposure to Ramadan was stratified by the: (1) total pregnancy days exposed to Ramadan, (2) duration (hours) of daily fasting and (3) trimester of exposure. Maternal and neonatal outcomes were examined by exposure status, and never exposed pregnancies were comparator in all three analyses. Fasting status was not recorded. RESULTS: We found no significant effect of Ramadan exposure on mean birthweight, macrosomia and maternal outcomes. However, we found a significant trend for increased neonatal hyperbilirubinemia with increasing Ramadan days exposure and later trimester exposure (ptrend ≤ 0.02 for both), with adjusted OR 3.9 (p=0.03) for those with ≥ 21 days exposure to Ramadan and adjusted OR 4.3 (p=0.04) for third trimester exposure. Conversely longer Ramadan exposure and late trimester exposure were independently associated with a lower prevalence of neonatal hypoglycaemia (adjusted OR 0.4 and 0.3 for ≥ 21 days and third trimester exposure, respectively). Furthermore, neonatal hypoglycaemia decreased for the fasting period of > 15 h group (adjusted OR 0.2, p = 0.01). CONCLUSIONS: Ramadan exposure is associated with reduced neonatal hypoglycaemia, with no effect on birthweight, implying more favourable glycaemic control. However, the fourfold excess of neonatal hyperbilirubinemia indicates a need for further study of Ramadan and GDM.

Testing the Feasibility and Dietary Impact of a "Produce Prescription" Program for Adults with Undermanaged Type 2 Diabetes and Food Insecurity in Australia.

BACKGROUND: There is growing interest in Food is Medicine programs that incorporate food-based interventions into health care for patients with diet-related conditions. OBJECTIVES: We aimed to test the feasibility of a "produce prescription" program and its impact on diet quality for people with type 2 diabetes (T2D) experiencing food insecurity in Australia. METHODS: We conducted a pre-post intervention study in n = 50 adults experiencing food insecurity with T2D and glycated hemoglobin (HbA1c) ≥8%. Once enrolled, participants received healthy food boxes weekly free of charge, with the contents sufficient to create 2 meals/d, 5 d/wk for the entire household, over 12 wk. Participants were also provided with tailored recipes and behavioral change support. The primary outcome was change in diet quality assessed by 24-h diet recalls. Secondary outcomes included differences in cardiovascular disease risk factors; blood micronutrients; and feasibility indicators. Differences in the baseline and 12-wk mean primary and secondary outcomes were assessed by paired t tests. RESULTS: Participants were older adults with mean ± SD age 63 ± 9 y (range: 40-87 y), HbA1c 9.8% ± 1.5%, and 46% were female. Overall, 92% completed the final study follow-up for the primary outcome. Compared with baseline, diet quality improved at week 12, with an increase in the mean overall diet quality (Alternate Healthy Eating Index score) of 12.9 (95% CI: 8.7, 17.1; P < 0.001), driven by significant improvements in vegetables, fruits, whole grains, red/processed meat, trans fat, sodium, and alcohol consumption. Blood lipids also improved (total:HDL cholesterol: -0.48; 95% CI: -0.72, -0.24; P < 0.001), and there was significant weight loss (-1.74 kg; 95% CI: -2.80, -0.68 kg, P = 0.002), but no changes in other clinical outcomes. Participants reported high levels of satisfaction with the program. CONCLUSIONS: These findings provide strong support for an adequately powered randomized trial to assess effects of produce prescription as an innovative approach to improve clinical management among individuals with T2D experiencing food insecurity. This trial was registered at https://anzctr.org.au/ as ACTRN12621000404820.

Young adult onset type 2 diabetes versus type 1 diabetes: Progression to and survival on renal replacement therapy.

BACKGROUND: Young-onset type 2 diabetes is an aggressive disease characterized by development of diabetic complications, including nephropathy, early in the disease course. However, within the cohort of young-onset type 1 and type 2 diabetes there are limited comparative data regarding progression to ESKD requiring renal replacement therapy or renal-related death (RRT/RRD). METHODS: Probabilistic linkage of data from the RPAH Diabetes Centre, National Death Index and Australian and New Zealand Dialysis and Transplant Registry was undertaken. Cumulative Incidence Competing Risk and Cox Proportional Hazards Modelling approaches were utilized to examine progression to ESKD in young-onset type 1 and type 2 diabetes (age of diagnosis 15-35 years). FINDINGS: Unadjusted incidence rates (95% CI) of RRT/RRD in young-onset type 1 and type 2 diabetes were 3.1 (2.3-4.0) and 4.6 (3.7-5.7) per 1000 person years respectively. After adjustment for gender, ethnicity and duration of diabetes, the HR (95% CI) of RRT/RRD in young-onset type 2 diabetes was 2.0 (1.4-2.9). The HR remained higher after further adjustment for first available cholesterol, HbA1c and systolic blood pressure but not BMI. For those who progressed to RRT, prognosis was similar irrespective of diabetes type; cumulative incidence of mortality was 40% in both young-onset type 1 and type 2 diabetes after 6 years of dialysis. INTERPRETATION: Progression to RRT/RRD is greater in young-onset type 2 diabetes than in young-onset type 1 diabetes. The increased progression is associated with increased BMI. However, once ESKD is reached, individuals with young-onset type 1 and type 2 diabetes do equally poorly.

An Enhanced SMS Text Message-Based Support and Reminder Program for Young Adults With Type 2 Diabetes (TEXT2U): Randomized Controlled Trial.

BACKGROUND: Clinic attendance, metabolic control, engagement in self-management, and psychological health are suboptimal in young-onset (age of onset <40 years) type 2 diabetes. OBJECTIVE: We examined the effectiveness of an enhanced SMS text message-based support and reminder program in improving clinic attendance, metabolic control, engagement in self-management, and psychological health in young-onset type 2 diabetes. METHODS: A 12-month, parallel-arm, randomized controlled trial comparing an enhanced, semipersonalized SMS text message-based intervention (incorporating 1-8 supportive and/or informative text messages per month) against standard care was conducted in a specialized clinic for young adult type 2 diabetes. The primary outcome was maintenance of 100% attendance at scheduled quarterly clinical appointments. Secondary outcomes included (1) metabolic indices, (2) pathology and self-monitored blood glucose (SMBG) data availability, and (3) psychosocial well-being. RESULTS: A total of 40 participants were randomized, and 32 completed their 12-month study visit. The average participant age was 32.7 (SD 5.1) years, 50% (20/40) were male, and baseline glycated hemoglobin A1c (HbA1c) was 7.3% (SD 1.9%) (56 mmol/mol, SD 20). A higher proportion of the intervention group achieved 100% attendance (12/21, 57%, vs 5/19, 26%, for the control group); Kaplan-Meier analysis demonstrated significantly greater cumulative attendance in the intervention group (P=.04). There were no between-group differences in HbA1c, BMI, lipids, or availability of pathology and SMBG data. Odds of recording an improvement in the Diabetes Empowerment Scale-Short Form score were higher in the intervention group at 6 months (odds ratio [OR] 4.3, 95% CI 1.1-17), with attenuation of this effect at study end (OR 3.1, 95% CI 0.9-11). Program acceptability was high; >90% of participants would recommend the program to new patients. CONCLUSIONS: An enhanced SMS text message-based support and reminder program doubled scheduled clinic attendance rates for patients with young-onset type 2 diabetes. The program was highly acceptable and provided early support for patient empowerment but had no significant effect on measures of metabolic control or self-management. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12618000479202); https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373579.

Secular Trends in Information Communications Technology: Access, Use, and Attitudes of Young and Older Patients With Diabetes.

BACKGROUND: Advances in information communications technology (ICT) provide opportunities for enhanced diabetes care. Knowledge of the more acceptable communication modalities in patients of different ages will help to inform the direction of future innovations. METHODS: An anonymous ICT survey (examining access and use of mobile phones, computers, tablets, and the Internet and attitudes toward e-mail, Web-based consultations, and online peer-support) was conducted at the Royal Prince Alfred Hospital Diabetes Centre in Sydney, Australia. Survey deployment occurred during 4-month periods in 2012 and 2017. Respondents were stratified by current age (<40 or ≥40 years). RESULTS: A total of 614 unselected patients (20% with type 1 diabetes, 55% with type 2 diabetes, 13% with gestational diabetes mellitus, and 12% with an undisclosed type of diabetes) completed the survey. Access to ICT increased from 89% in 2012 to 97% in 2017. The most commonly owned device was a mobile phone (87% ownership in 2017). Increase in mobile Internet usage in the <40 years of age subgroup was significant (P = 0.04). Significant increases in Internet access and smartphone feature use were observed in patients aged ≥40 years (P ≤0.001 for all). Overall use of short message service (SMS, or text messaging) was high (90 and 80% for ages <40 and ≥40 years, respectively). Use of digital applications was low, even among the young (45% in 2017). Comfort with online consultations (40%) and support groups (32%) was also low. CONCLUSION: Access to and acceptance and use of ICT is high, especially in those <40 years of age; however, the greatest increases were seen in those aged ≥40 years. High penetrance of mobile phones and text messaging in all age-groups would suggest that innovations involving an SMS platform have the greatest potential to enhance diabetes care.

Maternal vs paternal diabetes: The parental history is different in younger onset versus older onset type 2 diabetes.

BACKGROUND: A number of previous studies exploring family history of type 2 diabetes have reported a predominance of maternal diabetes. These studies have not explicitly compared parental history of diabetes across the spectrum of disease onset from youth to later adulthood. METHODS: Family history data from 11,467 patients with type 2 diabetes were extracted from the RPA Diabetes Centre database. Parental histories of diabetes were compared across a range of age of diagnosis strata (15-<30, 30-<40, 40-<50, 50-<60 and 60-<70 years). For the young-onset group (diagnosed between 15 and 30 years of age), associations between parental history of diabetes and the presence of cardio-metabolic risk factors and diabetic complications were also explored. RESULTS: For the total cohort and within each age of diagnosis strata, more individuals reported maternal history than paternal history of diabetes. The young-onset group demonstrated the highest prevalence of any parental history of diabetes (60.7%), the highest combined maternal and paternal history (15.8%) and the smallest differential between maternal (25.1%) and paternal (19.7%) history of diabetes. Within the young-onset group, no significant association between parental history and cardio-metabolic risk factors or diabetic complications were identified after a median of 15.0 years of diabetes exposure. CONCLUSION: Overall, our results demonstrate a consistent maternal excess of diabetes which could be consistent with an underlying epigenetic effect. However, the differential between maternal and paternal history is significantly lower in the young-onset group. Earlier emergence of type 2 diabetes may therefore reflect a different interaction and impact of genetic and environmental factors.

José Antonio Alzate, animal instruments and reliable knowledge in New Spain in the eighteenth century. / José Antonio Alzate, instrumentos animales y conocimiento fiable en Nueva España, siglo XVIII.

In the eighteenth century, naturalists in Europe and the Americas, being engaged in various practices for investigating nature, collected and observed live and dead animals in order to obtain and test various types of useful knowledge to science and natural history. The possibility that these specimens could be used as objects of study as well as instruments of observation gave these natural history collections a dimension that can be problematized nowadays from an epistemological and ontological perspective. This article demonstrates this phenomenon, based on the analysis of some of the practices of the naturalist José Antonio Alzate in New Spain.

En el siglo dieciocho los naturalistas europeos y americanos llevaron a cabo distintas prácticas de reconocimiento de la naturaleza, en las cuales, la recolección y el estudio de animales vivos y muertos permitieron obtener y comprobar distintos conocimientos útiles para la ciencia y la historia natural. La posibilidad de que los especímenes fueran utilizados como objetos de estudio, igual que como instrumentos de observación, generó en las colecciones de historia natural una dimensión que hoy puede problematizarse desde la epistemología y la ontología. Este artículo muestra dicho fenómeno, desde el análisis de algunas prácticas realizadas por el naturalista José Antonio Alzate en Nueva España.

José Antonio Alzate, instrumentos animales y conocimiento fiable en Nueva España, siglo XVIII / José Antonio Alzate, animal instruments and reliable knowledge in New Spain in the eighteenth century

Resumen En el siglo dieciocho los naturalistas europeos y americanos llevaron a cabo distintas prácticas de reconocimiento de la naturaleza, en las cuales, la recolección y el estudio de animales vivos y muertos permitieron obtener y comprobar distintos conocimientos útiles para la ciencia y la historia natural. La posibilidad de que los especímenes fueran utilizados como objetos de estudio, igual que como instrumentos de observación, generó en las colecciones de historia natural una dimensión que hoy puede problematizarse desde la epistemología y la ontología. Este artículo muestra dicho fenómeno, desde el análisis de algunas prácticas realizadas por el naturalista José Antonio Alzate en Nueva España.

Abstract In the eighteenth century, naturalists in Europe and the Americas, being engaged in various practices for investigating nature, collected and observed live and dead animals in order to obtain and test various types of useful knowledge to science and natural history. The possibility that these specimens could be used as objects of study as well as instruments of observation gave these natural history collections a dimension that can be problematized nowadays from an epistemological and ontological perspective. This article demonstrates this phenomenon, based on the analysis of some of the practices of the naturalist José Antonio Alzate in New Spain.

The Parkinson's disease and restless legs syndrome/Willis-Ekbom disorder link: evidences, biases and clinical relevance.

Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disorder (RLS/WED) are relatively common diseases in the realm of movement disorders. The fact that both may, as expected, co-occur and typically share a similar remarkable response to dopaminergic treatment raised the interest in exploration of additional shared features that throughout the years cruised fields as diverse as phenomenology, epidemiology, genetics, pathology, and clinical studies. In this review, we describe and critically examine the evidence and biases of a conceivable overlap of these two disorders, trying to shed light onto two main sources of confusion: (1) are PD and RLS/WED reciprocal risk factors? and (2) what are the main mimics of RLS/WED in PD?

The Parkinson's disease and restless legs syndrome/Willis-Ekbom disorder link: evidences, biases and clinical relevance / A conexão doença de Parkinson: síndrome das pernas inquietas / doença de Willis-Ekbom: evidências, vieses e relevância clínica

ABSTRACT Parkinson's disease (PD) and restless legs syndrome/Willis-Ekbom disorder (RLS/WED) are relatively common diseases in the realm of movement disorders. The fact that both may, as expected, co-occur and typically share a similar remarkable response to dopaminergic treatment raised the interest in exploration of additional shared features that throughout the years cruised fields as diverse as phenomenology, epidemiology, genetics, pathology, and clinical studies. In this review, we describe and critically examine the evidence and biases of a conceivable overlap of these two disorders, trying to shed light onto two main sources of confusion: (1) are PD and RLS/WED reciprocal risk factors? and (2) what are the main mimics of RLS/WED in PD?

RESUMO A doença de Parkinson (DP) e a síndrome das pernas inquietas/doença de Willis-Ekbom (SPI/DWE) são doenças relativamente comuns no campo dos distúrbios do movimento. O fato de que ambas podem, como esperado, ocorrer de forma simultânea e usualmente apresentarem resposta favorável ao tratamento dopaminérgico levaram ao interesse em explorar características compartilhadas adicionais. Ao longo dos últimos anos, essa busca percorreu campos diversos como a fenomenologia, epidemiologia, genética, patologia e estudos clínicos. Nesta revisão, analisamos e discutimos criticamente as evidências e os vieses de sobreposição concebíveis dessas duas doenças, tentando esclarecer duas perguntas sem resposta precisa até o momento: (1) DP e SPI/DWE representam fatores de risco recíprocos? e (2) quais são os principais mimetizadores da SPI/DWE na DP?

Data collection on retinopathy as a public health tool: The Hubble telescope equivalent of looking back in time.

OBJECTIVE: To test whether the rate of diabetic retinopathy development in a population calculated from the prevalence of retinopathy and duration of diabetes can be used to assess their prior glycemic control. RESEARCH DESIGN AND METHODS: 9281 patients with type 2 diabetes (T2DM) were grouped by duration of diabetes and plotted against the % of retinopathy in each band. The slope was used to calculate retinopathy development/year (RD/y). We correlated the RD/y with updated HbA1c within groups of different ethnicity, age of diabetes onset, year of the eye examination, socio-economic status and fluency in English. RESULTS: Differences in ethnicity, age of diabetes onset and year of the eye examination affect RD/y to a degree predictable from their respective updated HbA1c. No such relationship with updated HbA1c was evident when a factor has no apparent effect on RD/y. CONCLUSIONS: This relationship between prevalence of retinopathy and duration of diabetes can be used to assess future retinopathy burden. Perhaps more intriguing, the camera can be reversed to allow an estimate of prior glycemic control of a population from its retinopathy prevalence. Health care organizations can use this method to project future needs and to assess adequacy of prior glycemic control.

Baseline HbA1c to Identify High-Risk Gestational Diabetes: Utility in Early vs Standard Gestational Diabetes.

Context: The increasing prevalence of gestational diabetes mellitus (GDM) necessitates risk stratification directing limited antenatal resources to those at greatest risk. Recent evidence demonstrates that an early pregnancy glycated hemoglobin (HbA1c ≥5.9% (41 mmol/mol) predicts adverse pregnancy outcomes. Objective: To determine the optimal HbA1c threshold for adverse pregnancy outcomes in GDM in a treated multiethnic cohort and whether this differs in women diagnosed <24 vs ≥24 weeks' gestation (early vs standard GDM). Design and Setting: This was a retrospective cohort study undertaken at the Royal Prince Alfred Hospital Diabetes Antenatal Clinic, Australia, between 1991 and 2011. Patients and Interventions: Pregnant women (N = 3098) underwent an HbA1c (single-laboratory) measurement at the time of GDM diagnosis. Maternal clinical and pregnancy outcome data were collected prospectively. Main Outcome Measure: The association between baseline HbA1c and adverse pregnancy outcomes in early vs standard GDM. Results: HbA1c was measured at a median of 17.6 ± 3.3 weeks' gestation in early GDM (n = 844) and 29.4 ± 2.6 weeks' gestation in standard GDM (n = 2254). In standard GDM, HbA1c >5.9% (41 mmol/mol) was associated with the greatest risk of large-for-gestational-age (odds ratio [95% confidence interval] = 2.7 [1.5-4.9]), macrosomia (3.5 [1.4-8.6]), cesarean section (3.6 [2.1-6.2]), and hypertensive disorders (2.6 [1.1-5.8]). In early GDM, similar HbA1c associations were seen; however, lower HbA1c correlated with the greatest risk of small-for-gestational-age (P trend = 0.004) and prevalence of neonatal hypoglycemia. Conclusions: Baseline HbA1c >5.9% (41 mmol/mol) identifies an increased risk of large-for-gestational-age, macrosomia, cesarean section, and hypertensive disorders in standard GDM. Although similar associations are seen in early GDM, higher HbA1c levels do not adequately capture risk-limiting utility as a triage tool in this cohort.

An Inverse Relationship Between Age of Type 2 Diabetes Onset and Complication Risk and Mortality: The Impact of Youth-Onset Type 2 Diabetes.

OBJECTIVE: This study compared the prevalence of complications in 354 patients with T2DM diagnosed between 15 and 30 years of age (T2DM15-30) with that in a duration-matched cohort of 1,062 patients diagnosed between 40 and 50 years (T2DM40-50). It also examined standardized mortality ratios (SMRs) according to diabetes age of onset in 15,238 patients covering a wider age-of-onset range. RESEARCH DESIGN AND METHODS: Complication status was assessed according to a standard protocol and extracted from our electronic database. Survival status was ascertained by data linkage with the Australian National Death Index. SMRs were calculated in comparison with the background Australian population and analyzed according to age of onset. RESULTS: After matching for duration, despite their younger age, T2DM15-30 had more severe albuminuria (P = 0.004) and neuropathy scores (P = 0.003). T2DM15-30 were as commonly affected by metabolic syndrome factors as T2DM40-50 but less frequently treated for hypertension and dyslipidemia (P < 0.0001). An inverse relationship between age of diabetes onset and SMR was seen, which was the highest for T2DM15-30 (3.4 [95% CI 2.7-4.2]). SMR plots adjusting for duration show that for those with T2DM15-30, SMR is the highest at any chronological age, with a peak SMR of more than 6 in early midlife. In contrast, mortality for older-onset groups approximates that of the background population. CONCLUSIONS: The negative effect of diabetes on morbidity and mortality is greatest for those diagnosed at a young age compared with T2DM of usual onset. These results highlight the growing imperative to direct attention toward young-onset T2DM and for effective interventions to be applied before middle age.

Gestational Diabetes Mellitus in Early Pregnancy: Evidence for Poor Pregnancy Outcomes Despite Treatment.

OBJECTIVE: Recent guidelines recommend testing at <24 weeks of gestation for maternal dysglycemia in "high-risk" women. Evidence to support the early identification and treatment of gestational diabetes mellitus (GDM) is, however, limited. We examined the prevalence, clinical characteristics, and pregnancy outcomes of high-risk women with GDM diagnosed at <24 weeks of gestation (early GDM) and those with pre-existing diabetes compared with GDM diagnosed at ≥24 weeks of gestation, in a large treated multiethnic cohort. RESEARCH DESIGN AND METHODS: Outcomes from 4,873 women attending a university hospital antenatal diabetes clinic between 1991 and 2011 were examined. All were treated to standardized glycemic targets. Women were stratified as pre-existing diabetes (n = 65) or GDM diagnosed at <12 weeks of gestation (n = 68), at 12-23 weeks of gestation (n = 1,247), or at ≥24 weeks of gestation (n = 3,493). RESULTS: Hypertensive disorders in pregnancy including pre-eclampsia, preterm delivery, cesarean section, and neonatal jaundice (all P < 0.001) were more prevalent in women with pre-existing diabetes and early GDM. Macrosomia (21.8% vs. 20.3%, P = 0.8), large for gestational age (39.6% vs. 32.8%, P = 0.4), and neonatal intensive care admission (38.5% vs. 39.7%, P = 0.9) in women in whom GDM was diagnosed at <12 weeks of gestation were comparable to rates seen in women with pre-existing diabetes. CONCLUSIONS: Despite early testing and current best practice treatment, early GDM in high-risk women remains associated with poorer pregnancy outcomes. Outcomes for those in whom GDM was diagnosed at <12 weeks of gestation approximated those seen in pre-existing diabetes. These findings indicate the need for further studies to establish the efficacy of alternative management approaches to improve outcomes in these high-risk pregnancies.

Identifying Glucokinase Monogenic Diabetes in a Multiethnic Gestational Diabetes Mellitus Cohort: New Pregnancy Screening Criteria and Utility of HbA1c.

OBJECTIVE: Glucokinase monogenic diabetes (GCK-maturity-onset diabetes of the young [MODY]) should be differentiated from gestational diabetes mellitus (GDM) because management differs. New pregnancy-specific screening criteria (NSC) have been proposed to identify women who warrant GCK genetic testing. We tested NSC and HbA1c in a multiethnic GDM cohort and examined projected referrals for GCK testing. RESEARCH DESIGN AND METHODS: Using a GDM database, 63 of 776 women had a postpartum oral glucose tolerance test suggestive of GCK-MODY. Of these 63 women, 31 agreed to undergo GCK testing. NSC accuracy and HbA1c were examined. Projected referrals were calculated by applying the NSC to a larger GDM database (n = 4,415). RESULTS: Four of 31 women were confirmed as having GCK-MODY (prevalence ∼0.5-1/100 with GDM). The NSC identified all Anglo-Celtic women but did not identify one Indian woman. The NSC will refer 6.1% of GDM cases for GCK testing, with more Asian/Indian women referred despite lower disease prevalence. Antepartum HbA1c was not higher in those with GCK-MODY. CONCLUSIONS: The NSC performed well in Anglo-Celtic women. Ethnic-specific criteria should be explored.