Paternal Diabetes Research Articles

The association between paternal diabetes mellitus and successful pregnancy-Examined in a nationwide population undergoing reproductive treatment.

About 15% of all pregnancies end in pregnancy loss. As most studies have focused on maternal factors little is known regarding the influence of paternal factors on the chance of successful pregnancy. This cohort study aims to assess the chance of biochemical pregnancy, clinical pregnancy, and live-born children in couples where the male partner has diabetes mellitus (DM). We performed a nationwide cohort study. Couples undergoing assisted reproductive technology treatment from 2006 to 2019 were included. The exposed cohorts comprised embryo transfers in couples with paternal type 1 DM (T1DM), type 2 DM (T2DM), or mixed type DM (TMDM). The unexposed cohort included embryo transfers in couples without paternal DM. A total of 101,875 embryo transfers were included. Of these, 503 males had T1DM, 225 males had T2DM, 263 males had TMDM, and 100,884 did not have DM. For paternal T1DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.97 (95% CI 0.77-1.23), 1.08 (95% CI 0.65-1.79), and 0.75 (95% CI 0.49-1.14), respectively. For paternal T2DM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy, and live-born child were 0.80 (95% CI 0.56;1.16), 0.67 (95% CI 0.32-1.41), and 1.03 (95% CI 0.48-2.20), respectively. For the paternal TMDM, the adjusted OR for achieving a biochemical pregnancy, clinical pregnancy and livebirth were 0.95 (95% CI 0.67-1.33), 1.31 (95% CI 0.56-2.92), and 1.19 (95% CI 0.59-2.38), respectively. Paternal DM was not associated with a statistically significant decreased chance of biochemical pregnancy, clinical pregnancy, or live birth.

In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort.

10560 Background: Thyroid cancer ranks as the fifth most common cancer in women globally, with 90% of cases classified as differentiated thyroid cancer (DTC). Currently, thyroid cancer etiology remains largely unknown, with childhood exposure to ionizing radiation and obesity among the few established modifiable risk factors. Considering that DTC is diagnosed at relatively younger ages compared to many other cancers, with higher incidence in females versus males, the current study aimed to investigate in-utero and newborn exposures in relation to adult female DTC incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer living in the U.S. (including Puerto Rico), we included 47810 women who were cancer-free at baseline (2003–2009). At baseline, participants provided information on their birth and newborn characteristics, and characteristics of their parents before and during pregnancy. Using Cox proportional hazards regression models, we assessed the association between in-utero and newborn factors and self-reported DTC incidence during follow-up. The models were adjusted for attained age (timescale), race/ethnicity, BMI, smoking status, personal history of benign thyroid disease, educational level, household annual income, and Area Deprivation Index. Results: The median age at baseline of the study population was 55.4 (interquartile range [IQR]: 48.9-62.1). During follow-up (median: 13.1 years, IQR: 11.5-15), 233 women were diagnosed with DTC, with medical records available for 72% of cases. Factors associated with a higher incidence of DTC included gestational hypertension or hypertension-related disorders (15 exposed cases, HR= 1.87, 95%CI 1.10-3.16), and higher birth weight (for every additional kilogram HR=1.13, 95%CI 1.00-1.27). The HR for maternal pre-pregnancy or gestational diabetes was 2.33 (5 exposed cases, 95%CI 0.96-5.67). Conversely, being born at least two weeks before the due date was associated with a lower incidence (6 exposed cases, HR=0.35, 95%CI 0.15-0.79). These associations remained consistent when restricting to advanced-stage and large-sized DTCs. We observed no associations for participants’ birth order, time since last pregnancy of the participants' mother, multiple versus singleton birth, ever having been breastfed, parental smoking during pregnancy or age at delivery, maternal morning sickness, or paternal diabetes. Conclusions: In this study, maternal diabetes, maternal hypertension, and birth weight were associated with higher female DTC incidence while being born at least two weeks before the due date was associated with lower DTC incidence. These findings provide evidence that in-utero and newborn exposures may have a long-term influence on thyroid cancer development.

Risk factors for cerebral palsy in children in Taiwan.

To determine the significant risk factors of cerebral palsy (CP) in Taiwanese children and the associations between infant-related and parent-related factors. Data from 1 459 093 infants and their parents in Taiwan's national databases collected between 2009 and 2016 were used. The cohort with CP included children diagnosed with CP between birth and age 3 years; a total of 3254 children with CP were included in the final analysis. Hierarchical logistic regression models were used to estimate the odds ratio for the risk factors of CP. The hierarchical logistic regression models indicated that significant risk factors associated with CP are suburban location, low income, maternal and paternal diabetes mellitus, paternal substance abuse, paternal seizure disorder, male sex, birth by Cesarean section, singleton birth, low birthweight, being born extremely and very preterm, intraventricular hemorrhage, and periventricular leukomalacia, as well as tube feeding, ventilator use, and dopamine administration within 6 months of age. In addition to common maternal and infant risk factors, we identified significant paternal risk factors associated with CP, including diabetes mellitus, seizure disorder, and substance abuse. The combination of maternal, paternal, and infant risk factors in CP holds great promise for early identification and intervention.

Inadequate care and excessive overprotection during childhood are associated with the presence of diabetes mellitus in adulthood in a general Japanese population: a cross-sectional analysis from the Hisayama Study

ObjectiveTo investigate associations between parenting styles during childhood and diabetes in adulthood in a Japanese community.MethodsIn 2011, 710 community-dwelling Japanese residents aged ≥ 40 years were assessed for the presence of diabetes and for their perceptions of the parenting style of their parents, as measured using the “care” and “overprotection” scales of the Parental Bonding Instrument. Care and overprotection scores for each parent were dichotomized by age-specific median values. Diabetes mellitus was defined as a fasting plasma glucose level of ≥ 7.0 mmol/L, a 2-h post-loaded glucose level of ≥ 11.1 mmol/L, HbA1c ≥ 6.5%, and/or the current use of insulin or oral glucose-lowering agents. The odds ratios (ORs) for prevalent diabetes were calculated using a logistic regression model.ResultsThe prevalence of diabetes was 14.9%. Subjects with a high paternal overprotection score had a significantly greater likelihood of prevalent diabetes than those with a low paternal overprotection score after adjusting for confounders (OR 1.71, 95% confidence interval [CI] 1.06–2.77), while there was no significant association between paternal care and diabetes. Additionally, the multivariable-adjusted ORs for the presence of diabetes were significantly higher in subjects with a low maternal care score (OR 1.61, 95%CI 1.00–2.60) or in subjects with a high maternal overprotection score (OR 1.73, 95%CI 1.08–2.80). Moreover, the subjects with a low care score and high overprotection score for both their father and mother had a significantly higher multivariable-adjusted OR of diabetes than those with a high care score and low overprotection score for both parents (OR 2,12, 95%CI 1.14–3.95).ConclusionsThis study suggests that inadequate care and excessive overprotection during childhood may contribute to the development of diabetes in adulthood.

Low birthweight is associated with a higher incidence of type 2 diabetes over two decades independent of adult BMI and genetic predisposition

Aims/hypothesisLow birthweight is a risk factor for type 2 diabetes. Most previous studies are based on cross-sectional prevalence data, not designed to study the timing of onset of type 2 diabetes in relation to birthweight. We aimed to examine associations of birthweight with age-specific incidence rate of type 2 diabetes in middle-aged to older adults over two decades.MethodsAdults aged 30–60 years enrolled in the Danish Inter99 cohort in 1999–2001 (baseline examination), with information on birthweight from original birth records from 1939–1971 and without diabetes at baseline, were eligible. Birth records were linked with individual-level data on age at diabetes diagnosis and key covariates. Incidence rates of type 2 diabetes as a function of age, sex and birthweight were modelled using Poisson regression, adjusting for prematurity status at birth, parity, polygenic scores for birthweight and type 2 diabetes, maternal and paternal diabetes history, socioeconomic status and adult BMI.ResultsIn 4590 participants there were 492 incident type 2 diabetes cases during a mean follow-up of 19 years. Type 2 diabetes incidence rate increased with age, was higher in male participants, and decreased with increasing birthweight (incidence rate ratio [95% CI per 1 kg increase in birthweight] 0.60 [0.48, 0.75]). The inverse association of birthweight with type 2 diabetes incidence was statistically significant across all models and in sensitivity analysis.Conclusions/interpretationA lower birthweight was associated with increased risk of developing type 2 diabetes independent of adult BMI and genetic risk of type 2 diabetes and birthweight.Graphical

Individual or familial diabetes in relation to eight cardiovascular diseases: A two-sample Mendelian randomization study

Background and aimsDiabetes is associated with increased risk of certain cardiovascular diseases, yet the causality remains to be determined. Meanwhile, given that first-degree relatives share 50% of genes, the effect of familial diabetes is also worthy of attention. Therefore, we sought to investigate the causal relations of individual or familial diabetes with eight cardiovascular diseases, including myocardial infarction, hypertension, atrial fibrillation, heart failure, cardiac death, pulmonary embolism, transient ischemic attack, and ischemic stroke. Methods and resultsApplying two-sample Mendelian randomization, we selected instruments for genetic predisposition to individual or familial diabetes based on published genome-wide association studies. The primary analyses were conducted using the random-effects inverse-variance weighted method. We found that genetically predicted individual diabetes was causally associated with higher risks of myocardial infarction (odd ratio [OR] = 1.09; 95% confidence interval [CI]: 1.05–1.13; P < 0.0001), hypertension (OR = 1.08; 95% CI: 1.03–1.13; P = 0.0006), and ischemic stroke (OR = 1.10; 95% CI: 1.05–1.15; P < 0.0001). Genetically predicted paternal diabetes could increase the risk of ischemic stroke (OR = 1.16; 95% CI: 1.04–1.30; P = 0.0061). Genetically predicted maternal diabetes could increase the risk of myocardial infarction (OR = 1.18; 95% CI: 1.09–1.29; P = 0.0001). Genetically predicted siblings’ diabetes was causally associated with higher risks of myocardial infarction (OR = 1.17; 95% CI: 1.08–1.27; P = 0.0001) and hypertension (OR = 1.19; 95% CI: 1.06–1.34; P = 0.0036). No significant differences were observed in other outcomes. ConclusionThis study supports causal effects of not only individual but also familial diabetes on the development of cardiovascular diseases, which will help realize the potential effect of family history in the prevention of cardiovascular diseases.

Maternal Diabetes in Youth-Onset Type 2 Diabetes Is Associated With Progressive Dysglycemia and Risk of Complications.

Prenatal exposures, including undernutrition, overnutrition, and parental diabetes, are recognized risk factors for future cardiometabolic disease. There are currently no data on effects of parental diabetes on disease progression or complications in youth-onset type 2 diabetes (T2D). We analyzed effects of parental diabetes history on glycemic outcomes, β-cell function, and complications in a US cohort of youth-onset T2D. Participants (N = 699) aged 10 to 17 years with T2D were enrolled at 15 US centers and followed for up to 12 years as part of the TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) and TODAY2 follow-up studies. Information about diabetes diagnosis in biological mothers was available for 621 participants (never = 301; before or during pregnancy = 218; after pregnancy = 102) and in biological fathers for 519 (no diabetes = 352; paternal diabetes = 167). Maternal, but not paternal, diabetes was associated with loss of glycemic control over time, defined as glycated hemoglobin A1c greater than or equal to 8% for more than 6 months (P = .001). Similarly, maternal, but not paternal, diabetes was associated with increased risk of glomerular hyperfiltration (P = .01) and low heart rate variability (P = .006) after 12 years of follow-up. Effects were largely independent of age, sex, race/ethnicity, and household income. Maternal diabetes during vs after pregnancy had similar effects on outcomes. Maternal diabetes, regardless of whether diagnosed during vs after pregnancy, is associated with worse glycemic control, glomerular hyperfiltration, and reduced heart rate variability in youth with T2D in TODAY. The strong associations of diabetes outcomes with maternal diabetes suggest a possible role for in utero programming.

Paternal diabetes programs sex-dependent placental alterations and fetal overgrowth.

The aim of this study was to evaluate the paternal programming of sex-dependent alterations in fetoplacental growth and placental lipid metabolism regulated by peroxisome proliferator-activated receptor (PPAR) target genes in F1 diabetic males born from F0 pregestational diabetic rats. F1 control and diabetic male rats were mated with control female rats. On day 21 of gestation, F2 male and female fetoplacental growth, placental lipid levels, and protein and mRNA levels of genes involved in lipid metabolism and transport were evaluated. Fetal but not placental weight was increased in the diabetic group. Triglyceride, cholesterol and free fatty acid levels were increased in placentas of male fetuses from the diabetic group. The mRNA levels of Pparα and Pparγ coactivator 1α (Pgc-1α) were increased only in placentas of male fetuses from the diabetic group. Protein levels of PPARα and PGC-1α were decreased only in placentas of male fetuses from the diabetic group. No differences were found in Pparγ mRNA and protein levels in placentas from the diabetic group. The mRNA levels of genes involved in lipid synthesis showed no differences between groups, whereas the mRNA levels of genes involved in lipid oxidation and transport were increased only in placentas of male fetuses from the diabetic group. In conclusion, paternal diabetes programs fetal overgrowth and sex-dependent effects on the regulation of lipid metabolism in the placenta, where only placentas of male fetuses show an increase in lipid accumulation and mRNA expression of enzymes involved in lipid oxidation and transport pathways.

Paternal diabetes screening: Obstetrician's novel and noble obligation to an unborn child

Paternal diabetes screening: Obstetrician's novel and noble obligation to an unborn child

Gestational Diabetes Mellitus (GDM) Risk for Declared Family History of Diabetes, in Combination with BMI Categories

Whether categories of family history of diabetes can act as independent risk factors for gestational diabetes mellitus (GDM-1, -2) has not yet been established, and neither has it been established how categories of body mass index (BMI) affect these relationships. A group of 912 women without chronic diseases, recruited in the first trimester, was investigated: 125 (13.7%) women developed GDM-1 (treated with diet); 21 (2.3%) women developed GDM-2 (treated with insulin); and a control group consisted of 766 non-diabetic women. A multiple logistic regression was used to evaluate adjusted odds ratios (AOR (95% confidence intervals)) of GDM-1 and GDM-2 for declared diabetes in the parents or grandparents (separately). These relationships were investigated in the whole cohort and subgroups of pre-pregnancy BMI. (1) Some categories of the family history were independent risk factors of GDM-1 or GDM-2. Compared to ‘absence of diabetes in the family’, women with diabetes in the father had a 3.68-fold increase in GDM-1 risk (AOR-b = 3.68 (2.23–6.07)), and women with diabetes in the mother had a 2.13-fold increase in GDM-1 risk (AOR-b = 2.13 (1.1–4.14)) and a 4.73-fold increase in GDM-2 risk (AOR-b = 4.73 (1.26–17.77)). Women with diabetes in the grandmother had a 2.34-fold increase in GDM-1 risk (AOR-b = 2.34 (1.29–4.24)). (2) The cumulative assessment of diabetes in the parents and/or grandparents was not related to the intensification of the risk of GDM, except for the increased risk of GDM-1 for diabetes in both mother and grandmothers simultaneously (AOR-b = 8.80 (1.16–66.57)), however, this group was very small. (3) The analyses in the subgroups of BMI categories showed that diabetes in the father was also an independent risk factor of GDM in the subgroup of pregnant women with normal BMI. In the subgroups of overweight and/or obesity, the risk of GDM for paternal and maternal diabetes was approximately twice as high as compared to the results of pregnant women with normal BMIs. Additionally, apart from the maternal influence of diabetes, the results suggest a significant influence of diabetes in the father on the risk of GDM, even (interestingly) in lean pregnant women.

1135-P: Type 2 Diabetes Modulates DNA Methylation in Human Sperm

Paternal obesity and diabetes are associated with cardiometabolic risk in offspring. To test the hypothesis that paternal metabolism could exert these effects via modulation of the sperm epigenome, we collected motile sperm at two study visits 3 months apart in men with and without T2D (NCT03860558). Sperm DNA methylation was quantified in 32 samples using the Infinium MethylationEPIC array. HbA1c was higher in men with T2D vs. controls (7.6±1.1% vs. 5.2±0.2%, n=9 vs. 7, p&amp;lt;0.0001). Age (49.6±7.5 vs. 40.9±12.3 years, p=0.1), BMI (34.4±6.7 vs. 30.3±4.0 kg/m2, p=0.17), waist circumference and fat % were similar. There were no differences in sperm concentration or motility, testosterone, LH, estradiol, or prolactin levels. Methylation data were pre-processed using Partek Genomics Suite 7.19. After filtering cross-reactive probes and probes overlapping with SNP, 790508 probes were analyzed. Two-way ANOVA (disease group/time as factors) revealed 7 CpG sites differentially methylated between control and T2D (FDR q&amp;lt;0.05, differences in beta&amp;gt;0.2), including sites annotated to SLFN5, MMAA, and LOC101927829. All 7 sites were hypermethylated in T2D, with mean difference in beta of 26.4%. Paired analysis between study visits for individual participants revealed no significant CpG, indicating stability of sperm methylation over time. Genes annotated to differentially methylated CpG at both study visits (n=89, nominal p&amp;lt;0.01) were enriched for genes involved in morphogenesis and neuron development; the majority of these CpG also had higher methylation in T2D. In a linear regression model, 10 CpG sites showed positive and 2 sites showed negative association with HbA1c (FDR q&amp;lt;0.05). In summary, DNA methylation is altered in motile sperm from men with T2D, with hypermethylation at significant CpG sites. These alterations may reflect differential transcriptional regulation at developmentally important loci, and should be investigated as potential contributors to the impact of paternal metabolism on offspring. Disclosure L. Su: None. D. Wolfs: None. M. Hivert: None. J. Patel: None. L. Richardson: None. C. O. Charmant: None. E. M. Isganaitis: None. M. Patti: Consultant; Self; Cello Health, Fractyl Laboratories, Inc., MBX, Poxel SA, WGBH, Other Relationship; Self; Xeris Pharmaceuticals, Inc., Research Support; Self; Dexcom, Inc. Funding National Institutes of Health (R21HD091974)

Parental health status in relation to the nutrition literacy level of their children: Results from an epidemiological study in 1728 Greek students

BACKGROUND: Children’s dietary behaviors seem tract into adulthood and as a result preventing strategies to establish healthy behaviors from early stages of life are needed. Nutrition knowledge is essential for behavioral change. OBJECTIVE: To examine whether the status of parental health related to their children’s nutrition literacy level through their perceptions mainly of healthy eating attitudes METHODS: A cross-sectional survey was conducted in Greece among 1,728 schoolchildren aged 10–12 years old. The sample was collected in the school setting during the school years of 2014–2016. Children completed anonymously a self-administered questionnaire about their knowledge and perceptions of a healthy diet while their parents completed another suitable questionnaire about family health status. RESULTS: Paternal BMI status and hypertension were inversely associated with the level of nutrition literacy of their children by b = –0.043 (95%CI: (–0.082, –0.003; p = 0.036) and by b = –0.600 (95%CI: –1.181, –0.019; p = 0.043), respectively. Parental health status, specifically, paternal diabetes and maternal dyslipidemia were associated with children’s higher level of nutrition literacy by b = 0.729 (95%CI: 0.002, 1.456; p = 0.049) and by b = 0.730 (95%CI: 0.086, 1.374; p = 0.026), respectively. CONCLUSIONS: Parental health status partially affects, either negatively or positively, the level of nutrition literacy of their children. This impact depends on whether parents follow nutritional recommendations to improve their health.

Paternal metabolic and cardiovascular programming of their offspring: A systematic scoping review.

BackgroundThere is lots of evidence that maternal peri-gestational metabolic, genomic and environmental conditions are closely linked to metabolic and cardiovascular outcomes in their offspring later in life. Moreover, there is also lotsof evidence that underlining mechanisms, such as molecular as well as epigenetic changes may alter the intrauterine environment leading to cardio-metabolic diseases in their offspring postnatal. But, there is also increasing evidence that cardio-metabolic diseases may be closely linked to their paternal metabolic risk factors, such as obesity, Type 2 Diabetes and other risk factors.ObjectiveTo analyse the evidence as well as specific risk factors of paternal trans-generational programming of cardio-metabolic diseases in their offspring.MethodsWithin a systematic scoping review, we performed a literature search in MEDLINE (PubMed) and EMBASE databases in August 2020 considering original research articles (2000–2020) that examined the impact of paternal programming on metabolic and cardiovascular offspring health. Epidemiological, clinical and experimental studies as well as human and animal model studies were included.ResultsFrom n = 3.199 citations, n = 66 eligible studies were included. We selected n = 45 epidemiological as well as clinical studies and n = 21 experimental studies. In brief, pre-conceptional paternal risk factors, such as obesity, own birth weight, high-fat and low-protein diet, undernutrition, diabetes mellitus, hyperglycaemia, advanced age, smoking as well as environmental chemical exposure affect clearly metabolic and cardiovascular health of their offspring later in life.ConclusionsThere is emerging evidence that paternal risk factors, such as paternal obesity, diabetes mellitus, nutritional habits, advanced age and exposure to environmental chemicals or cigarette smoke, are clearly associated with adverse effects in metabolic and cardiovascular health in their offspring. Compared to maternal programming, pre-conceptional paternal factors might also have also a substantial effect in the sense of trans-generational programming of their offspring and need further research.

A Novel HNF4A Mutation Causing Three Phenotypic Forms of Glucose Dysregulation in a Family

Maturity-onset diabetes of the young (MODY) classically describes dominantly inherited forms of monogenic diabetes diagnosed before 25 years of age due to pancreatic β-cell dysfunction. In contrast, mutations in certain MODY genes can also present with transient or persistent hyperinsulinemic hypoglycemia in newborn infants, reflecting instead β-cell dysregulation. Of the MODY genes described to date, only hepatocyte nuclear factor-4-alpha (HNF4A; MODY1) and hepatocyte nuclear factor-1-alpha (HNF1A; MODY3) mutations may result in a biphasic phenotype of hypoglycemia in early life and hyperglycemia in later life. We report a family with a novel HNF4A mutation with diverse phenotypic presentations of glucose dysregulation. The proband was a term, appropriate-for-gestational age male infant with symptomatic hypoglycemia on day 3 of life needing high glucose infusion rate to maintain normoglycemia. He was born to a non-obese and non-diabetic mother. Glucose regulation was optimized using diazoxide upon confirmation of hyperinsulinism. Cascade genetic screening identified the same mutation in his father and elder sister, but mother was negative. Father was diagnosed with Type 1 diabetes at 15 years of age that required insulin therapy. Proband's elder sister, born at term appropriate for gestational age, presented with transient neonatal hypoglycemia needing parenteral glucose infusion for a week followed by spontaneous resolution. The paternal grandparents were negative for this mutation, confirming a paternal de novo mutation and autosomal dominant inheritance in this family. This pedigree suggests that the presence of early-onset paternal diabetes should prompt molecular testing in infants presenting in the newborn period with diazoxide-responsive hyperinsulinemic hypoglycemia, even in the absence of maternal diabetes and macrosomia.

Metabolic diseases affect male reproduction and induce signatures in gametes that may compromise the offspring health.

The most prevalent diseases worldwide are non-communicable such as obesity and type 2 diabetes. Noteworthy, the prevalence of obesity and type 2 diabetes is expected to steadily increase in the next decades, mostly fueled by bad feeding habits, stress, and sedentarism. The reproductive function of individuals is severely affected by abnormal metabolic environments, both at mechanical and biochemical levels. Along with mechanical dysfunctions, and decreased sperm quality (promoted both directly and indirectly by metabolic abnormalities), several studies have already reported the potentially harmful effects of metabolic disorders in the genetic and epigenetic cargo of spermatozoa, and the epigenetic inheritance of molecular signatures induced by metabolic profile (paternal diet, obesity, and diabetes). The inheritance of epigenetic factors towards the development of metabolic abnormalities means that more people in reproductive age can potentially suffer from these disorders and for longer periods. In its turn, these individuals can also transmit this (epi)genetic information to future generations, creating a vicious cycle. In this review, we collect the reported harmful effects related to acquired metabolic disorders and diet in sperm parameters and male reproductive potential. Besides, we will discuss the novel findings regarding paternal epigenetic inheritance, particularly the ones induced by paternal diet rich in fats, obesity, and type 2 diabetes. We analyze the data attained with in vitro and animal models as well as in long-term transgenerational population studies. Although the findings on this topic are very recent, epigenetic inheritance of metabolic disease has a huge societal impact, which may be crucial to tackle the ‘fat epidemic’ efficiently.

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

BackgroundA 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. MethodsFamily 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. ResultsFor 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. ConclusionOverall, 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.

Paternal diabetes programs metabolic disorders in the placenta and the fetus

Paternal diabetes programs metabolic disorders in the placenta and the fetus

Maternal diabetes and risk of childhood acute lymphoblastic leukaemia in the offspring

Background:Maternal diabetes may be linked to childhood acute lymphoblastic leukaemia (ALL) in the offspring.Methods:We assessed the association between maternal pregestational or gestational diabetes and offspring risk of childhood ALL in a register-based study, including all singletons born in Denmark during 1996–2015 (n=1 187 482).Results:Adjusted hazard ratios of childhood ALL were 2.91 (95% confidence interval (CI): 1.30–6.51) for maternal pregestational diabetes and 1.75 (95% CI: 1.02–2.98) for maternal gestational diabetes. Paternal diabetes did not alter offspring ALL risk, and we found no association between offspring ALL and later maternal risk of diabetes.Conclusions:Regardless that absolute ALL risk among offspring of women with diabetes remains low, our findings suggest that characteristics of the diabetic intrauterine environment promote ALL development. This offers a setting for future research into the biological mechanisms underlying childhood ALL.

Transgenerational inheritance of susceptibility to diabetes-induced male subfertility

Male infertility is a worldwide problem associated with genetic background, environmental factors, and diseases. One of the suspected contributing factors to male infertility is diabetes mellitus. We investigated the molecular and morphological changes in sperms and testicular tissue of diabetic males. The study was performed in streptozotocin-induced type 1 diabetes mouse model. Diabetes decreased sperm concentration and viability and increased sperm apoptosis. Changes in protamine 1/protamine 2 ratio indicated reduced sperm quality. The testicular tissue of diabetic males showed significant tissue damage, disruption of meiotic progression, and changes in the expression of genes encoding proteins important for spermiogenesis. Paternal diabetes altered sperm quality and expression pattern in the testes in offspring of two subsequent generations. Our study revealed that paternal diabetes increased susceptibility to infertility in offspring through gametic alternations. Our data also provide a mechanistic basis for transgenerational inheritance of diabetes-associated pathologies since protamines may be involved in epigenetic regulations.

Relationship Between Parental Diabetes and Presentation of Metabolic and Glycemic Function in Youth With Type 2 Diabetes: Baseline Findings From the TODAY Trial.

Children whose parents have diabetes are at increased risk for developing type 2 diabetes. This report assessed relationships between parental diabetes status and baseline demographics, anthropometrics, metabolic measurements, insulin sensitivity, and β-cell function in children recently diagnosed with type 2 diabetes. The sample included 632 youth (aged 10-17 years) diagnosed with type 2 diabetes for <2 years who participated in the TODAY clinical trial. Medical history data were collected at baseline by self-report from parents and family members. Youth baseline measurements included an oral glucose tolerance test and other measures collected by trained study staff. Youth exposed to maternal diabetes during pregnancy (whether the mother was diagnosed with diabetes prior to pregnancy or had gestational diabetes mellitus) were diagnosed at younger ages (by 0.6 years on average), had greater dysglycemia at baseline (HbA1c increased by 0.3% [3.4 mmol/mol]), and had reduced β-cell function compared with those not exposed (C-peptide index 0.063 vs. 0.092). The effect of maternal diabetes on β-cell function was observed in non-Hispanic blacks and Hispanics but not whites. Relationships with paternal diabetes status were minimal. Maternal diabetes prior to or during pregnancy was associated with poorer glycemic control and β-cell function overall but particularly in non-Hispanic black and Hispanic youth, supporting the hypothesis that fetal exposure to aberrant metabolism may have long-term effects. More targeted research is needed to understand whether the impact of maternal diabetes is modified by racial/ethnic factors or whether the pathway to youth-onset type 2 diabetes differs by race/ethnicity.