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Purpose of ReviewWe provide a review of monogenic diabetes in young children and adolescents with a focus on recognition, management, and pharmacological treatment.Recent FindingsMonogenic forms of diabetes account for approximately 1–2% of diabetes in children and adolescents, and its incidence has increased in recent years due to greater awareness and wider availability of genetic testing. Monogenic diabetes is due to single gene defects that primarily affect beta cell function with more than 30 different genes reported. Children with antibody-negative, C-peptide-positive diabetes should be evaluated and genetically tested for monogenic diabetes. Accurate genetic diagnosis impacts treatment in the most common types of monogenic diabetes, including the use of sulfonylureas in place of insulin or other glucose-lowering agents or discontinuing pharmacologic treatment altogether.SummaryDiagnosis of monogenic diabetes can significantly improve patient care by enabling prediction of the disease course and guiding appropriate management and treatment.

Purpose of ReviewCardiovascular (CV) disease is a major cause of mortality in type 2 diabetes mellitus (T2D). Dyslipidemia is prevalent in children with T2D and is a known risk factor for CVD. In this review, we critically examine the epidemiology, pathophysiology, and recommendations for dyslipidemia management in pediatric T2D.Recent FindingsDyslipidemia is multifactorial and related to poor glycemic control, insulin resistance, inflammation, and genetic susceptibility. Current guidelines recommend lipid screening after achieving glycemic control and annually thereafter. The desired lipid goals are low-density lipoprotein cholesterol (LDL-C) < 100 mg/dL, high-density lipoprotein cholesterol (HDL-C) > 35 mg/dL, and triglycerides (TG) < 150 mg/dL.SummaryIf LDL-C remains > 130 mg/dL after 6 months, statins are recommended with a treatment goal of < 100 mg/dL. If fasting TG are > 400 mg/dL or non-fasting TG are > 1000 mg/dL, fibrates are recommended. Although abnormal levels of atherogenic TG-rich lipoproteins, apolipoprotein B, and non-HDL-C are commonly present in pediatric T2D, their measurement is not currently considered in risk assessment or management.

Aims/hypothesisCurrent clinical guidelines for childhood-onset monogenic diabetes outside infancy are mainly focused on identifying and testing for dominantly inherited, predominantly MODY genes. There are no systematic studies of the recessively inherited causes of monogenic diabetes that are likely to be more common in populations with high rates of consanguinity. We aimed to determine the contribution of recessive causes of monogenic diabetes in paediatric diabetes clinics and to identify clinical criteria by which to select individuals for recessive monogenic diabetes testing.MethodsWe conducted a cross-sectional study of 1093 children from seven paediatric diabetes clinics across Turkey (a population with high rates of consanguinity). We undertook genetic testing of 50 known dominant and recessive causes of monogenic diabetes for 236 children at low risk of type 1 diabetes. As a comparison, we used monogenic diabetes cases from UK paediatric diabetes clinics (a population with low rates of consanguinity).ResultsThirty-four children in the Turkish cohort had monogenic diabetes, equating to a minimal prevalence of 3.1%, similar to that in the UK cohort (p = 0.40). Forty-one per cent (14/34) had autosomal recessive causes in contrast to 1.6% (2/122) in the UK monogenic diabetes cohort (p < 0.0001). All conventional criteria for identifying monogenic diabetes (parental diabetes, not requiring insulin treatment, HbA1c ≤ 58 mmol/mol [≤7.5%] and a composite clinical probability of MODY >10%) assisted the identification of the dominant (all p ≤ 0.0003) but not recessive cases (all p ≥ 0.2) in Turkey. The presence of certain non-autoimmune extra-pancreatic features greatly assisted the identification of recessive (p < 0.0001, OR 66.9) but not dominant cases.Conclusions/interpretationRecessively inherited mutations are a common cause of monogenic diabetes in populations with high rates of consanguinity. Present MODY-focused genetic testing strategies do not identify affected individuals. To detect all cases of monogenic paediatric diabetes, it is crucial that recessive genes are included in genetic panels and that children are selected for testing if they have certain non-autoimmune extra-pancreatic features in addition to current criteria.

Purpose of ReviewBreastfeeding has short- and long-term benefits for child health. In this systematic review, we updated a review on the association between breastfeeding and type 2 diabetes.Recent FindingsA meta-analysis published in 2015 reported that breastfeeding protects against type 2 diabetes (pooled odds ratio, 0.65 (95% confidence interval, 0.48; 0.86)). In the present update, we identified three recently published studies. An internet-based study reported that at a mean age of 25.6 years, exclusive breastfeeding in the first 6 months protected against type 2 diabetes (odds ratio, 0.63 (95% confidence interval, 0.41; 0.95)). In a retrospective cohort, those subjects who had been breastfed before hospital discharge were less likely of presenting diabetes (odds ratio, 0.83 (95% confidence interval, 0.69; 0.99)). In a case-control study, the odds of type 2 diabetes in adolescents was lower for those exclusively breastfed at hospital discharge (odds ratio, 0.52 (95% confidence interval, 0.36; 0.74)). In the meta-analysis, the pooled odds ratio was 0.67 (95% confidence interval, 0.56; 0.80).SummaryThe updated systematic review and meta-analysis suggests that breastfeeding protects from type 2 diabetes.

Purpose of ReviewThe metabolic syndrome is a pathological state in which one of the key components is insulin resistance. A wide spectrum of body compartments is involved in its pathophysiology. Genetic and environmental factors such as diet and physical activity are both related to its etiology. Reversible modulation of gene expression without altering the DNA sequence, known as epigenetic modifications, has been shown to drive this complex metabolic cluster of conditions. Here, we aim to examine some of the recent research of specific epigenetically mediated mechanisms and microbiota-induced epigenetic modifications on the development of adipose tissue and obesity, β-cell dysfunction and diabetes, and hepatocytes and non-alcoholic fatty disease.Recent FindingsDNA methylation patterns and histone modifications have been identified in this context; the integrated analysis of genome, epigenome, and transcriptome is likely to expand our knowledge of epigenetics in health and disease. Epigenetic modifications induced by diet-related microbiota or metabolites possibly contribute to the insulin-resistant state.SummaryThe identification of epigenetic signatures on diabetes and obesity may give us the possibility of developing new interventions, prevention measures, and follow-up strategies.

Purpose of ReviewThe purpose of this review is to provide an update on the recent body of evidence emerging for type 2 diabetes as identified through the SEARCH for Diabetes in Youth study.Recent FindingsThis body of evidence illustrates that type 2 diabetes continues to increase in incidence, although this increase may be partially attributable to increased surveillance. Disease management is influenced by the transition from adolescent to adult care and psychosocial factors may also contribute. This evidence also describes a high prevalence of disease-associated complications and comorbidities. Risk factors for cardiovascular disease are also highly prevalent.SummaryThe SEARCH for Diabetes in Youth study continues to inform our understanding of the descriptive epidemiology and natural history of type 2 diabetes in youth. As the cohort matures, new opportunities emerge for building on our understanding of how youth-onset type 2 diabetes impacts future health.

Purpose of ReviewThis review focuses on the complex interactions between hyperglycemia and bone fragility and the effects of antidiabetic medications on bone metabolism.Recent FindingsType 2 diabetes (T2D) is associated with increased risk of bone fracture even in those with increased or normal bone mineral density (BMD). The pathophysiology of diabetic bone disease is not completely understood, but it is thought to be multifactorial and associated with complex cross talk among factors such as AGEs, IGF-1, enteric hormones, and pro-inflammatory cytokines. Treatment for T2D may have an impact on bone metabolism.SummaryDiabetic bone disease should be considered a serious complication of long-standing T2D.

Purpose of ReviewTo provide an update on knowledge the role of genetics in youth-onset type 2 diabetes (T2D).Recent FindingsThe prevalence in youth of T2D, once thought to be exclusively a disease of adults, has increased by over 35% since 2001. Youth with T2D tend to have higher rates of complications, more aggressive disease, with more rapid loss of beta-cell function and a less favorable response to treatment than adults. Obesity is the most important risk factor for T2D, and the rise in childhood overweight and obesity appears responsible for the dramatic increase in T2D in youth. However, some obese children do not develop T2D, consistent with genetic differences in susceptibility to the disease in the setting of obesity and insulin resistance, currently far less well characterized in youth than in adults. Recent studies have begun to show associations of several established adult T2D genetic risk variants with youth-onset T2D and related glycemic quantitative traits, including the strongest known cross-population T2D genetic contributor TCF7L2. Maturity-onset diabetes of the young (MODY), a diabetes subtype distinct from type 1 diabetes (T1D) and T2D, is now known to result from a highly penetrant gene mutation in one of several genes. MODY has been shown to account for or contribute to at least 4.5% of clinically diagnosed T2D, even among those who are overweight or obese, impacting treatment decisions. The recently formed ProDiGY (Progress in Diabetes Genetics in Youth) Consortium is using genome-wide association studies and whole exome sequencing to understand the genetic architecture of T2D in youth, including how it differs from that of adults.SummaryThe limited amount of research conducted to date on the genetics of youth-onset T2D, which tends to be a more aggressive disease than adult T2D, suggests some overlap with genes involved in adult T2D and a sizeable influence of highly penetrant monogenic diabetes variants. The ProDiGY Consortium is expected to provide a more comprehensive understanding of youth T2D genetics.

Purpose of ReviewTo present current data on the coexistence of attention deficit hyperactivity disorder (ADHD) and the metabolic syndrome and type 2 diabetes mellitus in adults and children and to discuss possible mechanisms.Recent FindingsEmerging data suggest that risk factors for obesity and insulin resistance such as diabetes during pregnancy and intrauterine growth failure may also have a role in the development of ADHD. Furthermore, ADHD and obesity share lifestyle factors, such as abnormal eating patterns, binge eating, and a sedentary lifestyle. ADHD is a risk factor for components of the metabolic syndrome, particularly obesity and type 2 diabetes mellitus, and also hypertension, both in adults and youth.SummaryAssociations of ADHD with obesity, diabetes, and hypertension have been ascertained, and various mechanisms have been proposed. Research is needed to decipher the shared genetic, pharmacological, and lifestyle risk factors. Individuals with ADHD should be treated as a high-risk group for cardiometabolic complications.

Purpose of Review Pervasive disparities in T2DM among minority adults are well-documented, and scholars have recently focused on the role of social determinants of health (SDOH) in disparities. Yet, no research has summarized what is known about racial/ethnic disparities in youth-onset T2DM. This review summarizes the current literature on racial/ethnic disparities in youth-onset T2DM, discusses SDOH that are common among youth with T2DM, and introduces a conceptual model on the possible role of SDOH in youth-onset T2DM disparities. Recent Findings Minority youth have disparities in the onset of T2DM, quality of life, and family burden. Low family income and parental education and high youth stress are common negative SDOH among families of youth with T2DM. No studies have examined the role of SDOH in racial/ethnic disparities in youth-onset T2DM. Summary Future research should examine whether SDOH contribute to disparities in T2DM prevalence and psychosocial outcomes among minority youth.