Family history and risk of type 1 diabetes mellitus

The aim of the study was to evaluate association of type 1 diabetes in children and adolescents with positive family history of type 1 diabetes, type 2 diabetes, and thyroid, adrenal, rheumatic, allergic, celiac and some other diseases. A case-control study was conducted in Belgrade. The case group comprised 105 subjects ≤ 16 years old who were for the first time hospitalized because of type 1 diabetes during the period 1994–1997. For each case, two controls were chosen among children and adolescents treated for skin diseases. Cases and controls were individually matched by age (± one year), sex and place of residence (all were from Belgrade). In the statistical analyses we used χ²-test, Fisher's exact test and univariate and multivariate logistic regressions. According to multivariate logistic regression analysis, risk of type 1 diabetes was significantly associated with a positive family history for type 1 diabetes (OR=4.04; 95% CI, 2.31–7.07), allergic diseases (OR=3.32; 95% CI, 1.63–6.76), celiac and Crohn's diseases (OR=11.02; 95% CI, 1.14–106.89) and other diseases (thrombocytopenia, alopecia areata, psoriasis, chronic uveitis and pernicious anemia; OR=3.63; 95% CI, 1.05–12.48). Received: 10 August 2000 / Accepted in revised form: 15 April 2002     

Serum 25-hydroxyvitamin D level during early pregnancy and type 1 diabetes risk in the offspring

Aims/hypothesis  

Vitamin D deficiency during the fetal period or infancy is one of the suggested environmental factors for type 1 diabetes and for its increasing incidence. To test this hypothesis we compared serum 25-hydroxyvitamin D (25(OH)D) levels during early pregnancy in mothers of children who subsequently developed type 1 diabetes (case mothers) with mothers of non-diabetic healthy children (control mothers) of the same age.     

Family history of type 1 and type 2 diabetes and risk of latent autoimmune diabetes in adults (LADA)

BackgroundA family history of diabetes (FHD) is a strong predictor of diabetes risk, yet has rarely been investigated in latent autoimmune diabetes in adults (LADA). This study therefore investigated the risk of LADA and type 2 diabetes (T2D) in relation to FHD, taking into account the type of diabetes in relatives.MethodsData from a population-based study were used, including incident cases of LADA [glutamic acid decarboxylase antibody (GADA)-positive, n = 378] and T2D (GADA-negative, n = 1199), and their matched controls (n = 1484). First-degree relatives with disease onset at age < 40 years and taking insulin treatment were classified as type 1 diabetes (T1D) or, if otherwise, as T2D. Odds ratios (ORs) were adjusted for age, gender, BMI, education and smoking. Cases were genotyped for high- and low-risk HLA genotypes.ResultsBoth FHD–T1D (OR: 5.8; 95% CI: 3.2–10.3) and FHD–T2D (OR: 1.9; 95% CI: 1.5–2.5) were associated with an increased risk of LADA, whereas the risk of T2D was associated with FHD–T2D (OR: 2.7; 95% CI: 2.2–3.3), but not FHD–T1D. In LADA patients, FHD–T1D vs FHD–T2D was associated with higher GADA but lower C-peptide levels, lower prevalence of low-risk HLA genotypes (5.0% vs 28.6%, respectively; P = 0.038) and a tendency for higher prevalence of high-risk genotypes (90.0% vs 69.1%, respectively; P = 0.0576).ConclusionThe risk of LADA is substantially increased with FHD–T1D but also, albeit significantly less so, with FHD–T2D. This supports the idea of LADA as a mix of both T1D and T2D, but suggests that the genes related to T1D have greater impact. LADA patients with FHD–T1D had more T1D-like features, emphasizing the heterogeneity of LADA.     

Parental history of type 2 diabetes mellitus, metabolic syndrome, and cardiometabolic risk factors in Asian Indian adolescents

The objective was to study the influence of parental history of type 2 diabetes mellitus on prevalence of the metabolic syndrome (MS) and other cardiometabolic risk factors in Asian Indian adolescents. Adolescents aged 12 to 19 years (N = 321) were recruited from the Chennai Urban Rural Epidemiology Study. Based on parental diabetic status, 3 groups were studied: group 1, offspring of parents with normal glucose tolerance (n = 105); group 2, offspring of 1 diabetic parent (n = 114); and group 3, offspring of 2 diabetic parents (n = 102). Subjects underwent blood pressure and anthropometric measurements as well as an oral glucose tolerance test and a fasting lipid profile. Metabolic syndrome was diagnosed using the International Diabetes Federation definition. Body mass index (P < .001) and waist and hip circumference (P < .05 for group 2 and P < .001 for group 3) were significantly higher in groups 2 and 3 compared with group 1. High-density lipoprotein cholesterol was significantly lower in groups 2 and 3 compared with group 1 (P < .05). Serum triglycerides were significantly higher in group 3 (P < .05) compared with the other 2 groups. Adolescents in group 3 (P < .001) and group 2 (P < .05) were significantly more overweight and had more abdominal obesity compared with those in group 1. Impaired fasting glucose and impaired glucose tolerance were also significantly higher in group 3 compared with the other 2 groups. High blood pressure showed an increasing trend from group 1 to group 3 (P for trend < .05). Two metabolic abnormalities were present in 7.6%, 14.9%, and 22.5% of adolescents in groups 1, 2, and 3, respectively (trend χ²: 9.04, P = .003). Prevalence of MS was higher in groups 2 and 3 compared with group 1 but did not reach statistical significance because of small numbers. The cardiometabolic profile of the parents was similar to that of the adolescents. Parental history of type 2 diabetes mellitus increases risk of not only glucose intolerance but also other cardiometabolic risk factors like overweight, low high-density lipoprotein cholesterol, and high blood pressure in Asian Indian adolescents.     

Lipid disorders in type 1 diabetes

Patients with type 1 diabetes (T1D) also present with lipid disorders. Quantitative abnormalities of lipoproteins are observed in T1D patients with poor glycaemic control (increased plasma triglycerides and low-density lipoprotein [LDL] cholesterol) or nephropathy (increased triglycerides and LDL cholesterol, low level of high density lipoprotein [HDL] cholesterol). In cases of T1D with optimal glycaemic control, plasma triglycerides and LDL cholesterol are normal or slightly decreased, while HDL cholesterol is normal or slightly increased. Several qualitative abnormalities of lipoproteins, which are potentially atherogenic, are observed in patients with T1D, even in those with good metabolic control. These abnormalities include increased cholesterol-to-triglyceride ratios within very low-density lipoprotein (VLDLs), increased triglycerides in LDLs and HDLs, compositional changes in the peripheral layer of lipoproteins, glycation of apolipoproteins, increased oxidation of LDLs and an increase in small, dense LDL particles. These qualitative changes in lipoproteins are likely to impair their function. In vitro, VLDLs and LDLs from patients with T1D induced abnormal responses in the cellular cholesterol metabolism of human macrophages. HDLs from patients with T1D are thought to be less effective in promoting cholesterol efflux from cells, and have been shown to have reduced antioxidative and vasorelaxant properties. These qualitative abnormalities are not fully explained by hyperglycaemia and may be partly due to peripheral hyperinsulinaemia associated with subcutaneous insulin administration. However, the precise consequences of these qualitative lipid changes on the development of cardiovascular disease in T1D are, as yet, unknown.     

Parental smoking and risk of coeliac disease in offspring

OBJECTIVE: In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. MATERIAL AND METHODS: The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. RESULTS: Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy (p = 0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR = 1.64; 95% CI OR =0.80-3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR) =0.89; 95% CI AOR = 0.27-2.93; p =0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR = 1.94; 95% CI AOR =0.69-5.47; p =0. 203). CONCLUSIONS: No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed.     

Parental smoking and risk of coeliac disease in offspring

Objective. In adults, smoking seems to give protection against coeliac disease (CD). But, only one study has thus far investigated the association between maternal smoking during pregnancy and risk of CD in offspring. However, that study did not adjust for duration of exclusive breastfeeding, or look at passive smoking after birth. Material and methods. The current study was part of a prospective cohort study of infants born between 1 October 1997 and 1 October 1999 (the ABIS study; All Babies in Southeast Sweden). Data on smoking and exclusive breastfeeding were obtained through questionnaires distributed at infant birth and at 1 year of age. Coeliac disease was confirmed through small-bowel biopsy. Subgroup analyses were carried out according to maternal body mass index. Results. Nine out of 53 (17%) children with CD as opposed to 1699 out of 15,344 (11.1%) non-coeliac children had mothers who had smoked during pregnancy (p=0.172). Mothers who had smoked during pregnancy were hence not at increased risk of having a child with CD (OR=1.64; 95% CI OR=0.80–3.37). Adjusting for duration of exclusive breastfeeding and the sex of infants in some 9585 children with data on exclusive breastfeeding lowered the OR for CD in mothers who smoked (adjusted OR (AOR)=0.89; 95% CI AOR=0.27–2.93; p=0.843). Parents who smoked during the child's first year of life were not at increased risk of having an offspring with CD (OR=1.94; 95% CI AOR=0.69–5.47; p=0. 203). Conclusions. No association was found between CD and parental smoking habits during pregnancy or during the child's first year of life. However, further studies with larger numbers of coeliac children are needed.     

Association of parental cardiovascular risk factors with offspring type 1 diabetes mellitus insulin sensitivity

AimThis study aimed to determine whether the insulin resistance (IR) and lipid profiles in Type 1 Diabetes (T1D) offspring are associated with IR and other cardiovascular risk factors in their parents.MethodsThis study included 99 T1D patients (19.6 ± 4.0 yrs.), 85 mothers and 60 fathers. Parents' IR was assessed by HOMA-IR, and the insulin sensitivity in T1D patients was assessed by the estimated Glucose Disposal Rate (eGDR).ResultsThe eGDR in the T1D offspring was negatively related to age (p = 0.023), weight (p = 0.004), LDL (p = 0.026), and microalbuminuria (p = 0.019). Maternal Type 2 Diabetes (p < 0.001) and HOMA-IR (p = 0.029) were negatively related to eGDR in their T1D offspring. The maternal HOMA-IR and the proband's eGDR were positively (p = 0.012) and negatively (p = 0.042) associated with the birth weight of the T1D offspring, respectively. We didn't find an association with the fathers' profiles.ConclusionsIn a cohort of offspring with T1D the insulin sensitivity was related to the IR, lipid profile, and the presence of T2D only in their mothers. Precocious screening and treatment of these risk factors beyond glycemic control will benefit T1D with this background.     

The contribution of parental alcohol use disorders and other psychiatric illness to the risk of alcohol use disorders in the offspring

Background: Few population‐based studies have investigated associations between parental history of alcoholism and the risk of alcoholism in offspring. The aim was to investigate in a large cohort the risk of alcohol use disorders (AUD) in the offspring of parents with or without AUD and with or without hospitalization for other psychiatric disorder (OPD). Methods: Longitudinal birth cohort study included 7,177 men and women born in Copenhagen between October 1959 and December 1961. Cases of AUD were identified in 3 Danish health registers and cases of OPD in the Danish Psychiatric Central Register. Offspring registration with AUD was analyzed in relation to parental registration with AUD and OPD. Covariates were offspring gender and parental social status. Results: Both maternal and paternal registration with AUD significantly predicted offspring risk of AUD (odds ratios 1.96; 95% CI 1.42 to 2.71 and 1.99; 95% CI 1.54 to 2.68, respectively). The association between maternal, but not paternal, OPD and offspring AUD was also significant (odds ratios 1.46; 95% CI 1.15 to 1.86 and 1.26; 95% CI 0.95 to 1.66, respectively). Other predictors were male gender and parental social status. A significant interaction was observed between paternal AUD and offspring gender on offspring AUD, and stratified analyses showed particularly strong associations of both paternal and maternal AUD with offspring AUD in female cohort members. Conclusions: Parental AUD was associated with an increased risk of offspring AUD independent of other significant predictors, such as gender, parental social status, and parental psychiatric hospitalization with other diagnoses. Furthermore, this association appeared to be stronger among female than male offspring. The results suggest that inherited factors related to alcoholism are at least as important in determining the risk of alcoholism among daughters as among sons.     

Hemostatic disorders in type 1 diabetes mellitus

This review summarizes current knowledge of the adverse effects of type 1 diabetes mellitus on coagulation and fibrinolysis. Although further larger studies are needed to provide more definitive information, patients with type 1 diabetes exhibit a proinflammatory/procoagulant condition deriving from increased platelet adhesiveness, activation of the coagulation system, and decreased plasma fibrinolytic potential. This review also focuses on recent data from large prospective studies suggesting a strong association between procoagulant imbalance and development of chronic vascular complications in people with type 1 diabetes. It is likely that a greater appreciation of the intimate interactions between endothelial integrity, coagulation and fibrinolytic factors, and platelets in type 1 diabetes will provide a greater understanding of the risk of developing cardiovascular disease and microvascular complications such as nephropathy and retinopathy in this patient population.     

The natural history of type 1A diabetes

We can now predict the development of Type 1A (Immune Mediated) diabetes primarily through the determination of four biochemically characterized islet autoantibodies [insulin, GAD65, IA-2 (ICA512) and (Znt8)]. Prediction is possible because beta-cell destruction is chronically progressive and very slow in most, but not all individuals. We can also prevent type 1A diabetes in animal models and a major goal is the prevention of type 1A diabetes in man with multiple clinical trials underway.     

Congenital anomalies in the offspring of women with type 1, type 2 and gestational diabetes.

AIM: To determine the frequency of major congenital anomalies in the offspring of women with gestational diabetes (GDM), classified according to their postpartum glucose tolerance status. METHODS: A prospective study of pregnancies in women with Type 1 diabetes (n = 221), Type 2 diabetes (n = 317) and GDM (n = 1822) between 1985 and 2000 (15 years). Congenital anomalies were detected by antenatal ultrasound or postnatal examination. RESULTS: The frequency of major congenital anomalies in the offspring was 5.9% (95% confidence interval (CI) 3.2-9.8) for women with Type 1 diabetes; 4.4% (95% CI 2.4-7.3) for women with Type 2 diabetes; and 1.4% (95% CI 0.9-2.0) for women with GDM. Two hundred and thirty-seven women with GDM (13%) had diabetes diagnosed on early (6-week) postpartum glucose tolerance testing. The frequency of major congenital anomalies in their offspring was 4.6% (95% CI 2.3-8.2), compared with 0.9% (95% CI 0.5-1.5) for the remainder of the GDM group (P < 0.0001). CONCLUSIONS: GDM is not a homogeneous group with regard to the risk of major congenital anomalies. In those with diabetes on early postpartum testing, who are likely to have had unrecognized Type 2 diabetes antedating their pregnancy, the rate of major congenital anomalies is the same as for women with established Type 1 or Type 2 diabetes. In the remainder of the GDM group, the rate does not differ from the non-diabetic background rate.     

Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

Aims/hypothesis

We evaluated the intake of vitamin D by pregnant Finnish women and examined associations between maternal intake of vitamin D and the development of advanced beta cell autoimmunity and type 1 diabetes in their offspring.

Methods

The research was carried out within the Diabetes Prediction and Prevention study (DIPP), which is a population-based birth cohort of infants at genetic risk of type 1 diabetes. Mothers of 3,723 infants born between 1997 and 2002 completed a validated 181-item food frequency questionnaire, which included questions on dietary supplements. The offspring were observed at 3 to 12 month intervals for the appearance of autoantibodies associated with type 1 diabetes and for the development of clinical type 1 diabetes.

Results

Maternal mean daily intake of vitamin D was 5.1 µg from food and 1.3 µg from supplements. The maternal intake of vitamin D, either from food or from supplements, was not associated with the risk of advanced beta cell autoimmunity/type 1 diabetes in offspring (HR [95% CI] for intake of vitamin D from food 1.25 [0.80–1.95], for vitamin D intake from supplements 1.05 [0.95–1.16]), or with the risk of type 1 diabetes alone (HR [95% CI] for intake of vitamin D from food 0.84 [0.41–1.72], for vitamin D intake from supplements 1.09 [0.99–1.20]).

Conclusions/interpretation

Maternal intake of vitamin D either from food or supplements during pregnancy is not associated with advanced beta cell autoimmunity/type 1 diabetes or with type 1 diabetes alone in Finnish offspring carrying increased genetic susceptibility to type 1 diabetes.