Familial Aggregation of Type 2 (Non-insulin-dependent) Diabetes Mellitus in South India; Absence of Excess Maternal Transmission

The family histories of 976 South Indian Type 2 diabetic patients were recorded in a questionnaire-based survey to establish whether the excess maternal transmission of Type 2 diabetes reported in low prevalence Europid populations was also evident in this medium prevalence population. In 450 families (46.1 %), no parental history of diabetes was reported. In 423 families with one parent diabetic, 222 fathers (52.5 %) and 201 (47.5 %) mothers were diabetic. In the remaining 103 (10.6 %) families, both parents were diabetic. In contrast to previous studies, we found no evidence for substantial maternal excess in the transmission of diabetes (325 diabetic fathers vs 304 mothers; p = 0.4; p = 0.07 when compared using life table methods). The age of diagnosis of diabetes in probands was lower than that of their diabetic parents (p < 0.001): furthermore increasing parental history of diabetes was associated with an earlier diagnosis of diabetes in probands (p < 0.001). These results emphasize the extensive familial aggregation of Type 2 diabetes in this population but fail to replicate the evidence for excess maternal transmission evident in lower prevalence Europid populations, suggesting ethnic differences in the extent of this phenomenon.     

Grandparents as interactive and social support agents for families with young infants

The role of grandparents in infancy was examined in a comparative analysis of grandparent-infant grandchild and parent-infant interaction patterns. A second focus of the study was an exploration of the extent to which grandparents function as social support agents for their adult children and infant grandchildren. Grandparents (30 grandmothers and 21 grandfathers) and parents (30 mothers and 30 fathers) of seven-month-old infants were observed in individual five-minute dyadic play sessions with the infant in the parents' homes, yielding twenty minutes of agent-infant interaction. The observations were scored using both time-sampling and global coding schemes. Information on grandparental support to the young parents and infants, relative to other social support sources, were also obtained from grandparents and parents. Results indicated that both grandmothers and grandfathers are active interactive and support agents, with a pattern of similarities and differences in interactive style across generation and gender. Although there was a high degree of overlap in parent and grandparent interaction styles, parents were rated as more competent. Gender consistencies were found between female agents (mothers and grandmothers) and male agents (fathers and grandfathers). High levels of intergenerational contact were reported, with both parents and grandparents highly satisfied with the contact. The results of this study support an expanded view of the effects of various agents in young children's social environment.     

Mother to child transmission of diabetes mellitus: does gestational diabetes program Type 2 diabetes in the next generation?

AIM: Type 2 diabetes is frequently familial. Hyperglycaemia in pregnancy might act in addition to genetic factors to cause diabetes in the children of mothers with gestational diabetes mellitus (GDM). The first manifestation of this in female offspring is likely to be GDM in their own pregnancies. We compared the incidence of GDM in daughters of diabetic mothers and diabetic fathers to determine if in utero exposure to hyperglycaemia increased the risk of a diabetes-prone phenotype in offspring. METHODS: We analysed the outcome of a GDM screening programme in women with a family history of diabetes in their mother (n = 535), father (n = 566), both parents (n = 77) or neither (n = 4672). RESULTS: GDM was twice as common in the daughters of diabetic mothers (11%) than diabetic fathers (5%, P = 0.002). Women with two diabetic parents were no more likely to have GDM than women with only a diabetic mother. CONCLUSIONS: Genetic predisposition to GDM should be equally shared by daughters of diabetic mothers and fathers. An excess of maternal transmission of diabetes is consistent with an epigenetic effect of hyperglycaemia in pregnancy acting in addition to genetic factors to produce diabetes in the next generation.     

Parental History of Diabetes in an Insulin-treated Diabetes Registry

To confirm observations of an excess maternal transmission of Type 2 (non-insulin dependent) diabetes mellitus in a setting which minimizes potential biases and confounders, we explored the patterns of maternal and paternal diabetes in a cohort (n = 1775) of subjects with insulin-treated diabetes mellitus (ITDM) in Tasmania, Australia. In order to identify individuals with Type 1 diabetes or insulin-treated Type 2 diabetes, cases were classified into groups based on their age at diagnosis and subsequent time to commencement of insulin. Individuals initially diagnosed younger than age 30 (predominantly Type 1 diabetes cases) reported a similar percentage of mothers and fathers with diabetes, but individuals diagnosed at age 30 or older (predominantly insulin-treated Type 2 diabetes) reported a maternal excess of diabetes. Having an elevated body mass index was associated with a higher frequency of maternal diabetes, but not of paternal diabetes. Because both childhood-onset Type 1 diabetes and adult-onset insulin-treated Type 2 diabetes cases were subject to the same potential study biases, these results offer support for an excess maternal role in Type 2 diabetes transmission. © 1997 by John Wiley & Sons, Ltd.     

Is there an excess in maternal transmission of NIDDM?

Summary Family studies have demonstrated that there is a strong genetic component to the aetiology of non-insulin-dependent diabetes mellitus (NIDDM), although the mode of inheritance is unknown. A number of recent family history studies, including one in Mexican Americans, have suggested that there is an excess of maternal transmission of NIDDM. Family history studies are subject to various types of bias, however, and the potential for bias in many of these studies has not been thoroughly evaluated. We therefore tested the hypothesis that diabetes is more likely to be transmitted from mothers than from fathers using data collected from a large family study of low-income Mexican Americans in San Antonio, Texas. The parents and offspring from 318 different nuclear families attended our medical clinic, where they received a 2-h oral glucose test. Diabetes was diagnosed on the basis of World Health Organization criteria. The sibships were classified into diabetic sibships (at least one sibling in the sibship was diabetic; n=54) and non-diabetic siblings (no diabetic siblings; n=264). The prevalence of diabetes among mothers of diabetic siblings was 61.4% (27 of 44) compared to 64.3% (18 of 28) among fathers of diabetic siblings (rate ratio=0.95; 95% confidence interval: 0.51–1.84). For the non-diabetic sibships, the prevalence of diabetes was 31.7% (78 of 246) and 28.9% (37 of 128) among mothers and fathers, respectively (rate ratio=1.09; 95% confidence interval: 0.73–1.67). These data provide no evidence for an excess maternal transmission of diabetes in Mexican Americans.Abbreviations NIDDM Non-insulin-dependent diabetes mellitus - OGTT glucose tolerance test - IDDM insulin-dependent diabetes     

Familial clustering of juvenile thyroid autoimmunity: higher risk is conferred by human leukocyte antigen DR3-DQ2 and thyroid peroxidase antibody status in fathers

Thyroid autoimmunity is one of the most common immune disorders in females, and its polygenic background remains to be elucidated. The human leukocyte antigen (HLA) DQ region of chromosome 6 has been shown to confer susceptibility to thyroid autoimmune disease. The aim of our present investigation was to determine whether the transmission of high risk HLA DQ to patients with thyroid autoimmunity differs when transmission is from fathers as opposed to when transmission is from mothers. We studied 91 juvenile patients with chronic lymphocytic thyroiditis (68 females and 23 males; mean age, 10.5 +/- 3.9 yr), 12 patients with Graves' disease (all females; mean age, 8.8 +/- 4.0 yr), 53 healthy siblings, and their parents for thyroid function, antibodies, ultrasound, and DNA typing for HLA DQ susceptibility alleles. We observed an increased rate of transmission for the DQA1*0501-DQB1*0201 (DQ2) haplotype [35 of 53 transmitted (66%); P = 0.02]. This allele was preferentially transmitted by fathers [21 of 27 (78%); P < 0.004], whereas the maternal DQ2 haplotypes were not transmitted more often than expected. Subsequently, families were stratified as follows according to the parental thyroid peroxidase antibody (TPOAb) status: no parent, only mothers, only fathers, and both parents positive. There was no significant maternal transmission disequilibrium in any subset, but the paternal HLA DQ2 was preferentially transmitted [11 of 14 cases (79%); P = 0.03] in the group of TPOAb-positive mothers, and we observed a similar trend in the group of TPOAb- positive fathers (P = 0.08). Also, the portion of offspring affected by Graves' disease was significantly higher in TPOAb-positive than in TPOAb-negative fathers (P < 0.02). In conclusion, our findings demonstrate a significant effect of paternal HLA DQ alleles as well as antibody status on susceptibility to thyroid autoimmune disease in juvenile patients.     

Childhood Type 1 diabetes mellitus and parental occupations involving social mixing and infectious contacts: two population-based case-control studies.

AIMS: To test the hypothesis that increased exposure to infections, through parental jobs involving high levels of social mixing, reduces the risk of childhood Type 1 diabetes mellitus. METHODS: Two population-based case-control studies of children diagnosed with Type 1 diabetes mellitus from Yorkshire (0-15 years) and Northern Ireland (0-14 years) included 220 and 189 cases and 433 and 465 controls, respectively. Parental occupations were coded using a standard occupational classification. Each job was allocated to high, medium or low levels of social mixing according to a predefined categorization. Odds ratios (OR) for the risk of childhood Type 1 diabetes were estimated for parental social mixing by age at diagnosis. RESULTS: Childhood Type 1 diabetes mellitus was not associated with high levels of parental occupational social mixing (Yorkshire - mothers: OR 1.07, 95% confidence interval (CI) 0.76-1.50; fathers: 1.15, 0.75-1.76; Northern Ireland - heads of household, usually the father: 0.78, 0.49-1.25). A larger proportion of mothers (39%) compared to fathers (18% Yorkshire, 17% Northern Ireland) had jobs involving high levels of social mixing. Mothers with high social mixing jobs conferred a nonsignificant reduced risk of Type 1 diabetes among children diagnosed under 5 years of age (0.58, 0.24-1.38) compared to those diagnosed at age 5 years and above (1.14, 0.77-1.69). CONCLUSIONS: No association between parental occupational social mixing and the risk of childhood Type 1 diabetes mellitus was detected for all ages combined. Mothers were more likely to have jobs involving high levels of social mixing than fathers. The possible protective effect of maternal high occupational social mixing on children diagnosed below 5 years of age merits further investigation.     

Relationship of adolescent polycystic ovary syndrome to parental metabolic syndrome

CONTEXT: We determined the relationship of metabolic syndrome (MBS) to polycystic ovary syndrome (PCOS). OBJECTIVE: We tested the hypothesis that parental MBS is related to the PCOS phenotype in their offspring. DESIGN/SETTING: We phenotyped for MBS and PCOS in our General Clinical Research Center. PATIENTS: Girls with PCOS, 12-19 yr old (n = 36, including one pair of siblings), and their parents (35 mothers, 19 fathers) were recruited from the Pediatric Endocrinology Clinic. Healthy girls, 12-19 yr old (n = 21), were recruited as a reference population. INTERVENTIONS: We measured anthropometrics, blood pressure, fasting lipids and androgens, oral glucose tolerance, and ultrasonographically determined polycystic ovary status. MAIN OUTCOME MEASURES: MBS in parents, and PCOS features in mothers, were related to the presence of PCOS features in probands. RESULTS: Fathers had strikingly high prevalence of excess adiposity (94% were obese or overweight) and MBS (79%). Premenopausal mothers more commonly had MBS (36%) than features of PCOS (< or =22%). Polycystic ovaries in proband offspring of premenopausal mothers were associated with maternal polycystic ovaries only in a minority of cases. Proband polycystic ovary status was completely concordant to fathers' MBS status (P = 0.008), but not their own or their mothers' MBS status, in families whose premenopausal mothers lacked polycystic ovaries. Proband prevalence of MBS was 27.8%, 3-fold greater than expected for obesity status. CONCLUSION: Familial factors related to paternal MBS seem to be fundamental to the pathogenesis of PCOS.     

Birthweight of Babies Born to Mothers with Type 1 Diabetes: is it Related to Blood Glucose Control in the First Trimester?

A retrospective study of 133 pregnancies in women with Type 1 diabetes was performed, and the 116 which progressed beyond 28 weeks were further analysed. Despite good maternal blood glucose control (mean (+/- SE) HbA1 levels 8.6 +/- 0.2% at the end of the first trimester; 6.9 +/- 0.2% at delivery; normal range 4.0-8.5%), 38% of babies had birthweights above the 90th centile and operative intervention occurred in 77 deliveries (66%). There was no significant correlation between birthweight and HbA1 level at any stage of pregnancy, but mothers with babies above the 90th centile for weight had a higher HbA1 at the end of the first trimester than mothers with babies below the 90th centile (9.3 +/- 0.5 vs 7.9 +/- 0.2%, p less than 0.05). In contrast there was no difference in the HbA1 levels at delivery (7.0 +/- 0.3 vs 6.8 +/- 0.2%). The perinatal mortality rate was 17.7 per 1000 births. The results confirm that in Type 1 diabetes large babies are common despite good blood glucose control, and suggest that maternal blood glucose control in the first trimester may be an important determinant of birthweight.     

Influence of a familial history of diabetes on the clinical characteristics of patients with Type 2 diabetes mellitus.

AIMS: To evaluate the roles of maternal and paternal diabetes and diabetes in relatives other than parents on the clinical characteristics in Type 2 diabetes mellitus. METHODS: A total of 2,113 Type 2 diabetic patients were recruited, and those with diabetic mothers, diabetic fathers, diabetic relatives other than parents and no known diabetic relatives, were considered separately. RESULTS: The prevalence of diabetes in the mother, father and other relatives was 25.5, 6.5 and 21.2%, respectively. No difference in the clinical characteristics was found in patients with diabetes in the mother or father. Patients with parental diabetes were significantly younger, with higher LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis than those without familial diabetes; on multiple logistic regression, only age (P = 0.0003), age at diabetes diagnosis (P = 0.0014) (inverse association), and LDL-cholesterol (P = 0.030) remained significantly associated with parental diabetes. Patients with diabetic relatives other than parents displayed significantly higher total and LDL-cholesterol, prevalence of retinopathy and lower age at diabetes diagnosis that those with no known diabetic relatives; on multiple logistic regression, only age at diabetes diagnosis was inversely associated with diabetes in relatives other than parents (P = 0.013). CONCLUSIONS: The data do not indicate a different influence of maternal and paternal diabetes on the clinical characteristics of Type 2 diabetic patients, while there is evidence that parental diabetes brings to an earlier onset of the disease and higher LDL-cholesterol values; the presence of diabetes in relatives other than parents constituted a small risk for earlier manifestation of the disease.     

Predictors of IDDM recurrence risk in offspring of Danish IDDM patients

Summary It has previously been observed that offspring of mothers with insulin-dependent diabetes mellitus (IDDM) have a lower risk of IDDM than offspring of IDDM affected fathers. To assess the offspring IDDM recurrence risk in a Danish population-based study and to investigate parental and offspring-related biological variables that might influence this risk, we identified 2726 IDDM probands and their 2826 offspring from a background population of 1.725 million people (33 % of the Danish population). Current age of probands was 20–65 years and their age at IDDM onset was 30 years or less. Sixty-nine offspring (2.4 %) were affected with IDDM. The sex difference in the parental-offspring IDDM transmission rate was confirmed. The cumulative IDDM risk up to age 30 years was found to be significantly decreased in maternal offspring compared to paternal offspring (2.3 ± 0.6 and 5.7 ± 0.9 %, RR = 2.40, 95 % CI 1.30–4.47; p = 0.004) only if parents were diagnosed with IDDM before birth of the offspring. However, due to the low number of diabetic offspring of probands diagnosed with IDDM after offspring birth, this observation needs to be confirmed in a larger population. In a subpopulation of the 2380 offspring, whose parents were all diagnosed with IDDM before offspring birth, the recurrence risk was significantly increased in offspring of male probands diagnosed up to age 17 years compared to offspring of fathers diagnosed at older ages (8.5 ± 1.8 and 3.6 ± 1.0 %; RR = 2.27, 95 % CI 1.21–4.25; p = 0.006). No such relation was found in maternal offspring. Using the Cox proportional hazards model on this offspring subpopulation we found that paternal age at IDDM onset was the only statistically significant predictor of IDDM recurrence risk. Our findings may be important for counselling families in which one parent has IDDM. [Diabetologia (1998) 41: 666–673] Received: 14 July 1997 and in revised form: 29 December 1997     

Evaluation of the Importance of Maternal History of Diabetes and of Mitochondrial Variation in the Development of NIDDM

In 79 South Indian nuclear pedigrees ascertained via probands with NIDDM and both parents living, parental diabetic status was established through previously diagnosed NIDDM (n = 97) or oral glucose tolerance testing (n = 61). There was no significant difference between diabetes prevalence in mothers and fathers (60 vs 53 (76 % vs 67 %), respectively, p = 0.22). ‘Age at diabetes diagnosis’ survival curves did differ according to parental gender (p = 0.02) but this may reflect gender differences in health provision rather than pathophysiology. No maternal excess effects of the magnitude evident in previous studies were detected, suggesting either ethnic differences or overestimation of the maternal effect when reported histories of parental diabetes have been used. The tRNA^Leu(UUR) gene region was studied for diabetes-associated variation given the role of mutations in this gene in some pedigrees displaying maternal transmission of NIDDM. None of 142 unrelated South Indian NIDDM subjects displayed the MELAS mutation at nt3243. However, sequencing identified two variants of potential importance: (a) at nt3290 in the tRNA^Leu(UUR) gene, seen in 7/142 diabetic and 1/85 control subjects (p = 0.11), (b) at nt3316 in the ND1 gene (4/142 vs 1/85 subjects, respectively (p = 0.51)). Further studies are needed to determine the relevance of these variants to the development of NIDDM.     

Prevalence and levels of filaria-specific urinary IgG4 among children less than five years of age and the association of antibody positivity between children and their mothers

An enzyme-linked immunosorbent assay (ELISA) to detect filaria-specific urinary IgG4 was tested in samples from 203 children less than five years old and their parents (165 mothers and 127 fathers) in Sri Lanka. There were four IgG4-positive children within 58 days after birth, suggesting the transfer of the antibody from mothers. No positive children were found between days 65 and 417. After day 1,000, the number of the positive individuals and the level of IgG4 increased quickly. The children of urinary IgG4-positive parents showed a higher IgG4 positive rate than those of negative parents. The children of positive mothers had a higher prevalence than those of negative mothers, whereas, the positivity of the fathers was not associated with that of their children. Collecting urine samples was easy to perform and well accepted because of its non-invasiveness. The ELISA will be useful for monitoring filarial infections in very young children, who are a sentinel population for evaluating the intensity of filariasis transmission and effectiveness of control measures.     

Fuenlabrada study: lipid and lipoprotein levels in children and adolescents associated with ischemic cardiopathy prevalence among their relatives

The prevalence of coronary heart disease (CHD) was studied in parents and grandparents of 2,419 children surveyed for lipid levels. Children and their families were divided into 3 groups depending on the level of each lipid and lipoprotein studied in children: high greater than or equal to 95 percentile (p), medium 5-95 p, and low less than 5 p. Total cholesterol (Chol) and triglycerides (TG) were determined by enzymatic techniques in autoanalyzer. C-HDL was determined by precipitation method. C-LDL and C-VLDL were obtained by Friedewald-Fredrickson's equation. The prevalence of CHD in parents and grandparents was ascertained from clinical history. Fathers of children in the high groups of Chol, TG, C-LDL/C-HDL, and low group of C-HDL had increased prevalence of CHD compared with those of the low groups of Chol, TG, C-LDL, C-LDL/C-HDL and high group of C-HDL. The strongest association was with C-HDL. Maternal and paternal grandfathers of children in the high groups of Chol had also increased prevalence of CHD compared with those of low group of Chol. There was no association with any other variable. The association was not significant neither in mothers nor in maternal and paternal grandmothers. Childhood lipid and lipoprotein levels could identify families at elevated risk for CHD.     

A nationwide population-based study of the familial aggregation of Type 1 (insulin-dependent) diabetes mellitus in Denmark

Summary The objective of the present study was to assess the prevalence of familial aggregation of Type 1 (insulin-dependent) diabetes mellitus among Danish families with a diabetic child aged 20 years or less and to compare epidemiological data for familial and sporadic cases. We attempted to identify all patients with Type 1 diabetes aged 0–19 years in Denmark treated at paediatric departments or at departments of internal medicine. This comprises more than 98% of all patients with Type 1 diabetes in this age group. Patients were identified through the local diabetic out-patient registry and asked to complete a questionnaire regarding data on diabetes onset and family history. Of 1574 probands 1419 agreed to participate (90.2%). Additional cases of Type 1 diabetes were found in 171 families (12.8%). Of these 115 were parent-offspring affected families, and in 56 families at least two siblings had Type 1 diabetes and healthy parents. Significant correlation in age at onset of Type 1 diabetes in concordant siblings was observed (r=0.5, p=0.0004). Significantly more probands had an affected father with Type 1 diabetes than a mother affected (p<0.0001). Heterogeneity in epidemiological characteristics was observed between familial and sporadic cases, i.e. familial index cases were younger at onset of the disease, their parents were younger at birth of the index case, and there was no difference in gender of familial cases in contrast to sporadic cases where significantly more males were found. Over a 4-year period (1986–1989) an increasing trend in incidence was observed. However, an increase in incidence compared to previous Danish data from the 1970s and 1980 s could not be demonstrated.The Danish Study Group of Diabetes in Childhood is an association of paediatricians with a special interest in diabetes research. For participating departments in the present study see Acknowledgements     

Helicobacter pylori infection occurs via close contact with infected individuals in early childhood

BACKGROUND: The manner in which Helicobacter pylori is transmitted is of fundamental importance when considering strategies for its control, yet, to date, the exact mode of transmission remains uncertain. METHODS: The seroprevalence of H. pylori in a relatively isolated rural town in Japan (A-town) was examined to analyse the H. pylori infection route. The immunoglobulin G antibodies against H. pylori in 1684 subjects who had received public health examinations in A-town were determined with an enzyme-linked immunosorbent assay. The seroprevalence was compared in five areas according to the water source. The possibility and frequency of intrafamilial infection was analysed by comparing the seroprevalence among family members residing in the same home. RESULTS: The seroprevalence of H. pylori did not differ significantly between the five areas examined. Seropositivity was significantly more common in the children whose mothers were seropositive (45.0%, 27/60) than in the children whose mothers were seronegative (10.0%, 2/20; odds ratio (OR) = 7.36, P = 0.0036, 95% confidence interval (CI) = 1.57-34.59). Seropositivity was significantly more common in the children whose older siblings were seropositive (55.0%, 22/40) than in the children whose older siblings were seronegative (23.5%, 20/85; OR = 3.97, P = 0.00051, 95% CI = 1.79-8.84). There was no significant relationship in seroprevalence between children and fathers, grandchildren and grandfathers, grandchildren and grandmothers, or within couples. Seropositivity was significantly more common in the adolescents who had attended a nursery school (44.4%, 20/45) than in the adolescents who had not attended a nursery school (25.6%, 109/426) (OR = 2.33, P = 0.0070, 95% CI = 1.24-4.36). CONCLUSIONS: The acquisition of H. pylori infection occurs by close contact with infected individuals in early childhood, especially via contact with infected mothers and other infected children.     

The Swedish childhood diabetes study — social and perinatal determinants for diabetes in childhood

Summary Using the Swedish childhood diabetes register, a nationwide, case-referent study was performed from September 1, 1985 to August 31, 1986. Based on the information from a mailed questionnaire sent to all incident diabetic children and for each diabetic child — two referent children matched according to age, sex, and county, we have analysed perinatal events and aspects of the social environment as possible risk factors for Type 1 (insulin-dependent) diabetes in childhood. A significantly larger proportion of the mothers of the diabetic children were older than 40 years compared to those of the referent children (33% and 24%, p=0.01 respectively). A smaller percentage of mothers of the diabetic children had a high educational level compared to mothers of referent children (10% and 15%, p=0.03 respectively) and 39% of the fathers of the diabetic children were manual workers compared to 31% of the fathers of referent children (p=0.03). Perinatal events did not differ between diabetic and referent children. In children 0–6 years, the duration of breast-feeding was significantly shorter in diabetic children than among referent children (median duration for diabetic children 5 months compared to 6 months for referent children p=0.03). When considering the presence of Type 1 diabetes among relatives, maternal age over 40 years, low educational level of the mother, and the father being a manual worker as risk factors, the presence of 1 to 4 of any of these risk factors increased the relative risk for Type 1 diabetes cumulatively from 1.2–7.5. In conclusion, breast-feeding habits and probably other factors dependent on maternal age and the social status of the family may further increase the risk for Type 1 diabetes in genetically susceptible individuals.     

Maternal type 1 diabetes reduces the risk of islet autoantibodies: relationships with birthweight and maternal HbA1c

AIMS/HYPOTHESIS: The risk of type 1 diabetes is reduced in the children of mothers with type 1 diabetes compared with children of fathers with type 1 diabetes. We asked whether children of mothers with type 1 diabetes also have a decreased risk of developing islet autoantibodies, and which factors associated with maternal diabetes contribute to a reduced islet autoantibody risk in offspring. METHODS: Singleton offspring of a mother (n = 1,008) or father with type 1 diabetes (n = 578) from the BABYDIAB study were included. Children were followed from birth for the development of islet autoantibodies defined as two or more autoantibodies to insulin, glutamic acid decarboxylase or insulinoma antigen 2 in two or more blood samples. RESULTS: Islet autoantibody risk was lower in children of mothers with type 1 diabetes (5 year risk, 3.2% vs 5.7% in children of fathers with type 1 diabetes; p = 0.04). Among factors that differed between pregnancies from mothers with and without type 1 diabetes, birthweight was associated with islet autoantibody risk. Risk was reduced in children with birthweights in the lower (adjusted HR 0.33; 95% CI 0.14-0.75; p = 0.009) and upper (HR 0.45; 95% CI 0.21-0.97; p = 0.04) tertiles compared with the middle tertile. A sub-analysis of maternal HbA(1c) suggested that moderately elevated third trimester maternal HbA(1c) was also associated with a reduced islet autoantibody risk in children of mothers with type 1 diabetes (5.7-7%; HR 0.38; 95% CI 0.15-0.96; p = 0.04 vs children of mothers with HbA(1c) < 5.7%). CONCLUSIONS/INTERPRETATION: The risk of islet autoimmunity is modified by maternally influenced events such as birthweight.     

Is human Type 2 diabetes maternally inherited? Insights from an animal model

AIMS: Patients with Type 2 diabetes mellitus more often report a history of an affected mother than father. However, in the few studies where both parents and offspring have been directly tested, this apparent maternal excess has not been confirmed. Rodent models of diabetes have the advantage that all parents and offspring can undergo glucose tolerance testing at a specific age in adult life. The aim of this study was to gain insights into the inheritance of human Type 2 diabetes by using a rat model. METHODS: Goto Kakizaki (GK) rats (a model of Type 2 diabetes) were mated with non-diabetic Wistar rats. Offspring were produced from 20 GK female vs. Wistar male and 20 Wistar female vs. GK male crosses. Fasting blood glucose was measured at 6 weeks and 3 months of age and an intravenous glucose tolerance test (0.8 g/kg) performed at 6 months of age. RESULTS: Wistar mothers produced litters with almost twice as many viable offspring as GK mothers (14.1 vs. 7.4, P < 0.001). Despite the larger litter size, offspring in the two groups were of comparable weight at 6 weeks and 6 months of age. At 3 months of age, male offspring of Wistar mothers were heavier than offspring of GK mothers (415.7 g vs. 379.5 g, P = 0.016) but this difference was not sustained at 6 months of age. Fasting blood glucose at all ages and average blood glucose during the glucose tolerance test were similar in both groups. CONCLUSIONS: We therefore conclude that there is no evidence for maternal transmission of diabetes in the GK rat. Mothers were able to adjust their supply of milk so that offspring attained similar weights independent of litter size. The weight of the offspring remained independent of litter size into adult life.     

Childhood diabetes in Saudi Arabia.

In Suleimania Children's Hospital, Riyadh, Saudi Arabia, 110 diabetic children were diagnosed and followed over a 5-year period (1985-1989). Seventy-five percent (82/110) were of Saudi origin and 54% (59/110) female. Their parents were often related, 31% (34/110) being first degree cousins, and 12% (13/110) second degree cousins. First degree family history was positive for Type 1 diabetes in 28% (31/110). Among these cases, siblings accounted for 26%, fathers 2%, and mothers none. Family history was also positive for Type 2 diabetes in 35% (38/110) and for both Type 1 diabetes and Type 2 diabetes in 14% (15/110). Mean age at onset was 5.9 years (7 months to 12 years). Thirty percent (33/110) of the patients were under 3 years of age on admission. The most common clinical presentation was diabetic ketoacidosis, seen in 67% of the patients (74/110).