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1.
De Silva SN Weerasuriya N De Alwis NM De Silva MW Fernando DJ 《Diabetes research and clinical practice》2002,58(3):173-177
INTRODUCTION: An excess of maternal transmission of Type 2 diabetes mellitus has been reported in Europid populations, but not in South India. METHOD: A questionnaire-based survey was carried out in 1000 (502 male) people with Type 2 diabetes to establish whether there is an excess of maternal transmission and familial aggregation in a Sri Lankan population. RESULTS: Mean age of onset was 47+/-12 (+/-S.D.) years and duration of diabetes was 9+/-7 years. Thirty-seven percent reported parents with diabetes, 46.9% had no parents with diabetes, 16.1% did not know the diabetes status of at least one parent and there was no diabetes in the other. Of the probands, 59.4% had at least one affected relative. When both parents' diabetes status was known and only one was affected, diabetes was more common among mothers (n = 156) than fathers (n = 125) of probands (P < 0.001). A further 54 probands had both parents with diabetes. Mean age of onset and duration of the disease among probands with parental diabetes was 43.1+/-(11.1) and 9.6+/-(6.8). In the previous generation, 21.2% of maternal grandmothers and 17.3% of maternal grandfathers in the maternal diabetes group and 4.8% of maternal grandmothers and 17% of maternal grandfathers in the paternal diabetes group had diabetes. Diabetes in siblings and children was more common in those with mothers who had diabetes (53.8% and 4.5%) when compared with those in whom fathers had diabetes (42.4% and 1.6%) (P < 0.0001 and P < 0.01). CONCLUSION: Familial aggregation and excess maternal transmission were observed in people with Type 2 diabetes in Sri Lanka. 相似文献
2.
M. McCarthy P. Cassell T. Tran L. Mathias L.M. 't Hart J.A Maassen C. Snehalatha A. Ramachandran M. Viswanathan G.A. Hitman 《Diabetic medicine》1996,13(5):420-428
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 tRNALeu(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 tRNALeu(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. 相似文献
3.
B. D. Mitchell Ph.D. C. M. Kammerer L. J. Reinhart M. P. Stern J. W. MacCluer 《Diabetologia》1995,38(3):314-317
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 相似文献
4.
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. 相似文献
5.
M.D. Riley C.L. Blizzard D.J. McCarty G.B. Senator T. Dwyer P. Zimmet 《Diabetic medicine》1997,14(1):35-41
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. 相似文献
6.
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. 相似文献
7.
Familial Risk of Type I diabetes in European Children 总被引:1,自引:1,他引:1
The EURODIAB ACE Study Group The EURODIAB ACE Substudy Study Group 《Diabetologia》1998,41(10):1151-1156
Summary The characteristics of familial Type I (insulin-dependent) diabetes mellitus – that is Type I diabetes in a first degree
relative were investigated for children diagnosed before the age of 15 years using data from an international network of population-based
registries (the Eurodiab Ace network) and from a case-control study (Eurodiab Ace Substudy 2) conducted by eight of the network's centres. Ecological analysis across the 18 centres showed a positive association
between the population incidence rate of Type I diabetes and the prevalence of Type I diabetes in fathers of affected children
(Spearman's rank correlation coefficient r
s = 0.70, p < 0.001). A similar association was observed with the prevalence in sibling (r
s = 0.71, p < 0.001), but the association with prevalence in mothers was weaker and not significant. Pooling results from all centres
showed that a greater proportion of fathers (3.4 %) of affected children had Type I diabetes than mothers (1.8 %) giving a
risk ratio of 1.8 (95 % CI 1.4 to 2.5). Affected girls were more likely to have a father with Type I diabetes than affected
boys (odds ratio 1.56, 95 % CI 1.07 to 2.27), but there was no evidence of a similar finding for mothers or siblings. Children
with disease onset in the 0–4 year age-range were more likely to have an affected father than were children who were older
at onset, and similar although weaker associations were seen in mothers and siblings. This suggests that familial Type I diabetes
patients have a younger age at onset than non-familial patients. In conclusion, a positive association between the prevalence
of familial Type I diabetes and the population Type I diabetes incidence rate was shown and the characteristics of familial
Type I diabetes (younger age at onset and preferential transmission of disease from tather to child and particularly from
father to daughter) were described. [Diabetologia (1998) 41: 1151–1156]
Received: 16 February 1998 and in revised form: 4 May 1998 相似文献
8.
J. A. Fagerudd K. J. Pettersson-Fernholm C. Grönhagen-Riska P.-H. Groop 《Diabetologia》1999,42(5):519-526
Aims/hypothesis. There is substantial evidence for a role of genetic factors in the development of diabetic nephropathy. In Pima Indians,
a link between susceptibility to diabetic nephropathy and Type II (non-insulin-dependent) diabetes mellitus has been proposed.
In this study, our aim was to examine the association between a family history of Type II diabetes and diabetic nephropathy
in patients with Type I (insulin-dependent) diabetes mellitus. Methods. In a cross-sectional case-control study, we assessed the prevalence of Type II diabetes in the parents of 137 Type I diabetic
patients with diabetic nephropathy (albuminuria > 300 μg/min in two of three overnight urine collections) compared with the
parents of 54 Type I diabetic patients without nephropathy (albuminuria < 20 μg/min). Results. Thirty-four (25 %) of the patients with nephropathy compared with five (9 %) of the patients without nephropathy had a parental
history of Type II diabetes (p = 0.019). A parental history of Type II diabetes was associated with a three-fold risk [odds ratio 2.95 (95 % confidence
interval: 1.03 to 8.40), p = 0.043] of diabetic nephropathy after adjustment for sex, glycaemic control and family history of hypertension. Furthermore,
there was an excess of risk factors for development of Type II diabetes (higher fasting plasma glucose concentrations, higher
prevalence of hypertension, higher waist-hip ratio and a tendency towards more glucose intolerance) among previously non-diabetic
parents of patients with nephropathy. Conclusion/interpretation. Genetic or environmental factors or both related to familial Type II diabetes increase susceptibility to diabetic nephropathy
in patients with Type I diabetes. [Diabetologia (1999) 42: 519–526]
Received: 30 September 1998 and in final revised form: 28 December 1998 相似文献
9.
L. Yu H. P. Chase A. Falorni M. Rewers å Lernmark Dr. G. S. Eisenbarth 《Diabetologia》1995,38(11):1353-1357
Summary To help elucidate the mode of inheritance of insulin-dependent diabetes mellitus (IDDM), we measured GAD (glutamic acid decarboxylase) autoantibodies (GAD65Ab), insulin autoantibodies (IAA), and cytoplasmic islet cell autoantibodies (ICA) in 292 sequentially screened non-diabetic offspring of patients with IDDM. The prevalence of these islet autoantibodies was higher in offspring of diabetic fathers than in offspring of diabetic mothers. The prevalences of GAD65Ab, IAA, and ICA in the offspring of diabetic fathers were 11.5%, 10.8%, and 8.1% vs 2.1%, 1.4%, and 2.8%, respectively in the offspring of diabetic mothers (p<0.002, p<0.001, and p=0.06 NS). Amongst autoantibody-positive relatives the IAA and ICA levels were significantly higher in offspring of diabetic fathers than of diabetic mothers (p<0.002 and p<0.01, respectively). The frequencies of these autoantibodies were equal in male and female offspring. We conclude that IDDM mothers transmitted islet autoimmunity less frequently to their offspring than IDDM fathers. Given the markedly lower frequency of autoantibodies in offspring of mothers, larger sample sizes will be required to determine whether islet autoantibodies are influenced by age of IDDM onset of mothers, maternal age of pregnancy, and presence of diabetes in these mothers prior to conception.Abbreviations IDDM
Insulin-dependent diabetes mellitus
- GAD
glutamic acid decarboxylase
- GAD65Ab
glutamic acid decarboxylase autoantibodies
- IAA
insulin autoantibodies
- ICA
cytoplasmic islet cell autoantibodies
- JDF
Juvenile Diabetes Foundation 相似文献
10.
A. Dornhorst J.S.D. Nicholls A. Welch K. Ali S.P. Chan R.W. Beard 《Diabetic medicine》1996,13(3):226-231
The large-for-gestational-age (LGA) infant, defined as >90th birthweight percentile, is associated with mild disturbances of maternal glucose tolerance. In the UK the same birthweight percentile charts are used for all ethnic groups when assessing LGA infants. The influence of maternal hyperglycaemia on LGA infants of Asian (Indian Sub-continent) mothers in the UK is likely to be under-reported, as Asian birthweights tend to be lower than White/Europid birthweights. We assessed the number of LGA infants born consecutively to 21 Asian and 26 White/Europid mothers with gestational diabetes mellitus (GDM), delivered between 37 and 42 weeks gestation, and also in 34 Asian and 121 White/Europid mothers with a positive screening test for GDM but a normal 75 g oral glucose tolerance test (OGTT). Large-for-gestational-age infants were identified using both the standard UK percentile charts of the Medical Research Council and percentile charts constructed from 30418 Asian and 162477 White/Europid singleton births, delivered between 37 and 42 weeks gestation to non-diabetic mothers delivered in the North West Thames Region of England. The standard Medical Research Council percentile charts, compared with the ethnically derived charts, identified fewer LGA Asian (7/56 vs 15/56) but more White/Europid infants (33/147 vs 21/147). When correcting for ethnicity more Asian than White/Europid GDM mothers delivered LGA infants (9/21 vs 3/26, χ2 = 4.76, p < 0.05). The maternal 2 h OGTT plasma glucose was a significant independent contributor to birthweight in the Asian (r 2 = 0.319, p < 0.0005) but not the White/Europid infants, in whom gestational age and maternal height were significant independent contributors to birthweight (r2 = 0.158, p < 0.0001). We conclude that ethnic influences are important when defining LGA infants and that mild disturbances of maternal glycaemia have a greater influence on the birthweight of Asian than White/Europid infants. 相似文献
11.
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 相似文献
12.
Mother to child transmission of diabetes mellitus: does gestational diabetes program Type 2 diabetes in the next generation? 总被引:6,自引:0,他引:6
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. 相似文献
13.
C. Kelleher S. M. Kingston D. G. Barry M. M. Cole J. B. Ferriss G. Grealy C. Joyce D. J. O'Sullivan 《Diabetologia》1988,31(2):76-81
Summary The prevalence of hypertension was investigated in a systematically chosen sample of patients attending a diabetic clinic. One hundred ninety-one patients were classified as Type 1 (insulin-dependent), 183 were classified as Type 2 (non-insulin-dependent) and 12 were deemed unclassifiable. Two hundred fifty-five control subjects attending non-medical out-patient clinics were also examined under similar conditions. Hypertension was significantly (p<0.001) more common among Type 2 patients (38%) than among Type 1 patients (15%) or control subjects (16%). The difference between Type 2 patients and control subjects, but not between Type 2 and Type 1 patients, persisted when the influences of age and body mass index were controlled. We also investigated the prevalence of hypertension among the siblings of the hypertensive patients identified, together with a matched normotensive group. One hundred eighty-eight siblings were examined and historical details were obtained for a further 451 siblings. When age and body mass index were controlled for in examined siblings, the risk of hypertension was greater in those with a hypertensive proband than in those with a normotensive proband, in the control (p<0.06) and Type 1 (p<0.02) groups. Among the siblings of Type 2 probands, however, the risk of hypertension in those with a normotensive proband Was at least as great as in those with a hypertensive proband, and greater than in those with a normotensive proband in the control (p<0.10) or Type 1 (p<0.05) groups. The prevalence of cardiovascular deaths was also similar in the siblings of normotensive and hypertensive Type 2 probands. We conclude that in our diabetic clinic there is an excess of hypertension among Type 2 patients. There may also be an excess of hypertension among the siblings of Type 2 patients. 相似文献
14.
T. Lorenzen F. Pociot L. Stilgren O. P. Kristiansen J. Johannesen P. B. Olsen A. Walmar A. Larsen N. C. Albrechtsen P. C. Eskildsen O. O. Andersen J. Nerup 《Diabetologia》1998,41(6):666-673
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 相似文献
15.
C. M. Forsblom T. Kanninen M. Lehtovirta C. Saloranta L. C. Groop 《Diabetologia》1999,42(11):1359-1366
Abstract
Aims/hypothesis. To study whether albumin excretion rate is an inherited trait in families of patients with Type II (non-insulin-dependent)
diabetes mellitus. Methods. We used three different approaches. Heritability of albumin excretion rate was studied in 267 nuclear families from the
Botnia Study in Western Finland using parent-offspring regression. Albumin excretion rate was also measured in 206 non-diabetic
offspring of 119 Type II diabetic parents with or without albuminuria (albumin excretion rate > 20 μg/min). Finally, albumin
excretion rate was measured in altogether 652 siblings of 74 microalbuminuric and 320 normoalbuminuric probands. To study
the potential confounding effect of blood pressure, the heritability of blood pressure was estimated in 718 nuclear families.
Results. Using parent-offspring regression, the heritability of albumin excretion rate was about 30 %, being the strongest from mothers
to sons (35–39 % resemblance). The heritability for systolic blood pressure ranged from 10 to 20 % and for diastolic blood
pressure from 10 to 27 %. Offspring of albuminuric Type II diabetic parents had higher albumin excretion rates (median 5.4
[range 1.0–195] vs 4.0 [1.0–23] μg/min, p = 0.0001) and a higher frequency of microalbuminuria (11 vs 2 %, p = 0.012) than offspring of normoalbuminuric parents. Further, siblings of microalbuminuric probands had higher albumin excretion
rates than siblings of normoalbuminuric probands (4.1 [0.6–14.5] vs 3.6 [0.2–14.4] μg/min, p < 0.01). Conclusion/interpretation. The data suggest that albumin excretion rate is an inherited trait in families of patients with Type II diabetes. [Diabetologia
(1999) 42: 1359–1366]
Received: 10 February 1999 and in revised form: 18 June 1999 相似文献
16.
AIMS: Susceptibility to diabetic nephropathy has not yet been causally linked to any genetic factors. We investigated in nuclear families whether parental ambulatory blood pressure, lipids and urine albumin excretion were early markers of risk of microalbuminuria in young adults with Type 1 diabetes. SUBJECTS AND METHODS: A subset of 98 young adults from the Oxford Regional Prospective Study were followed from diagnosis until aged >or= 16 years and duration of diabetes >or= 5 years (probands). Of these subjects, 24 developed microalbuminuria (males >or= 3.5 mg/mmol; females >or= 4 mg/mmol) and were designated cases, whereas 74 were controls. Family medical history, 24-h ambulatory blood pressure, urine albumin to creatinine ratio (ACR), non-fasting lipid profile and apolipoproteins (A1 and B) were measured in mothers and fathers. RESULTS: The prevalence of a parental hypertension (taking anti-hypertensive medication or daytime blood pressure > 140/90 mmHg), was similar in cases and controls (29% vs. 35%; chi2 test, P = 0.3). The systolic blood pressure night to day ratio and also ACR were higher in the fathers of cases when compared with the fathers of controls [systolic 0.88 (0.08), n = 14 vs. 0.85 (0.12), n = 53, P = 0.041]; [ACR median (IQ range) 0.6 mg/mmol (0.2-16.9) vs. 0.47 mg/mmol (0.3-3.7), P = 0.049]. Paternal night-time systolic blood pressure, night to day systolic blood pressure ratio and ACR were correlated with an index of susceptibility to albuminuria (r = 0.25, P = 0.042, n = 69 and r = 0.28, P = 0.022, n = 0.67 and r = 0.24, P = 0.029, n = 0.85, respectively). CONCLUSIONS: Higher paternal ACR and night to day ratio of ambulatory blood pressure, but not parental hypertension or maternal factors, are associated with microalbuminuria in young adults with Type 1 diabetes. 相似文献
17.
Abstract
Aims/hypothesis. Our aim was to characterise the genetic and immunological features associated with Type I (insulin-dependent) diabetes mellitus
in a cohort of Indo-Aryan children resident in the United Kingdom.?Methods. Children with Type I diabetes (n = 53), unaffected first-degree relatives (n = 146) and unrelated healthy control children (n = 54) were typed for alleles of the HLA-DRB1, HLA-DQA1 and HLA-DQB1 genes. Islet cell antibodies and antibodies to glutamic acid decarboxylase, protein tyrosine phosphatase-2 (IA-2ic) and insulin
were measured in the diabetic and control children.?Results. The DRB1*03.DQA1*05.DQB1*02 haplotype was positively associated with the disease, occurring in 78 % of diabetic children compared with 22.6 % of healthy
children (p
c < 2.4 × 10–5). In simplex families, this haplotype was transmitted more frequently to the diabetic children than to their unaffected siblings
(p < 1 × 10–4). The DRB1*04.DQA1* 03.DQB1*0302 haplotype was also transmitted preferentially to the diabetic probands (p < 0.025) but was not associated with disease in the case control study. Islet-related autoantibodies were detected in 89.6
% of diabetic patients compared with 11.8 % of control children (p < 1 × 10–6). Although protein tyrosine phosphatase-2 autoantibodies were detected more frequently among DRB1*04-positive diabetic patients compared with patients lacking this allele, the overall frequency of these autoantibodies was
lower than observed in Europid diabetic subjects. This could reflect the absence of a disease association with DRB1*04 in
the Indo-Aryan cohort.?Conclusion/interpretation. Type I diabetes in our Indo-Aryan cohort is similar to the disease observed in Anglo-Europeans but has important immunogenetic
differences. The low frequency of protein tyrosine phosphatase-2 autoantibodies among the Indo-Aryan diabetic children could
have important implications for the design of future strategies for disease prediction in this population. [Diabetologia (2000)
43: 450–456]
Received: 2 September 1999 and in revised form: 8 November 1999 相似文献
18.
Summary Skin biopsies were performed to examine dermal capillary basement membranes for albumin by immunofluorescence microscopy in children and young adults with Type 1 (insulin-dependent) diabetes from simplex and multiplex families, their non-diabetic parents and control subjects. Circumferential vessel staining for albumin was 12.0 ±14.4% (mean ± SD) in diabetic patients from multiplex families, 18.8 ±20.0% in diabetic patients from simplex families, and 18.5 ±24.2% in unaffected parents from simplex families. These values were significantly higher (p < 0.005) than those obtained in unaffected parents from multiplex families (0.4 ± 0.9%) or control subjects (0.8 + 1.7%). There was no statistically significant difference between Type 1 diabetic probands from simplex or multiplex families and unaffected parents from simplex families. In the simplex families, positive capillary staining for albumin was present only in parents from families in which the diabetic proband had positive staining. In the parents, the presence of dermal capillary staining for albumin did not correlate with an abnormal glucose tolerance test or the presence of cytoplasmic islet cell antibodies. These observations suggest an abnormality in the dermal capillary basement membrane in some unaffected parents of Type 1 diabetic patients from simplex families. 相似文献
19.
Summary From July 1, 1977 to July 1, 1986, 3,503 incident cases of Type 1 (insulin-dependent) diabetes mellitus were registered in the Swedish childhood diabetes study. Using data from this register and from a case-referent study, including all incident Type 1 diabetic children in Sweden during one year and, for each patient, two referent children matched according to age, sex and county, we have studied the associations between Type 1 diabetes and familial Type 1 and Type 2 (non-insulin-dependent) diabetes, thyroid, adrenal, allergic, rheumatic, heart and bowel disease. The mean annual incidence per 100,000 during the nine year period was 25.1 for boys and 23.5 for girls. In 8.5% of the patients, one parent had Type 1 diabetes, 73% of whom were fathers. Fifty-six of the patients (1.7%) had a parent with Type 2 diabetes. The prevalence of parental Type 1 diabetes tended to be higher in patients with younger age at onset; whereas, the opposite was found for patients with parental Type 2 diabetes. In the case-referent study, the age-adjusted odds ratio for Type 1 diabetes when a first and/or second degree relative had Type 1 diabetes was 5.5 (95% confidence limits 4.0–7.7), and in accordance with the findings of the case register, the odds ratio tended to be highest in patients with the youngest age at onset. Season at onset of the patients was not associated with parental Type 1 diabetes. The odds ratio for Type 1 diabetes was significantly increased 3.3 (95% confidence limits: 2.3–4.6) when Type 2 diabetes was reported in relatives (three generations). Odds ratios were also significantly increased (p(0.05) when thyroid or rheumatic diseases were reported among relatives.It is concluded that although the majority of incident Type 1 diabetic children lack family history, parental Type 1 diabetes may influence the age at onset of the disease but has no effect on sex distribution of these children. An increased risk for Type 1 diabetes in children is also indicated when Type 2 diabetes, (non-insulin-treated) thyroid or rheumatic disease is reported in relatives. 相似文献
20.
P.R. Smith M.J. Dronsfield C.H. Mijovic A.T. Hattersley V.T.F. Yeung C. Cockram J.C.N. Chan A.H. Barnett S.C. Bain 《Diabetic medicine》1997,14(12):1026-1031
The mitochondrial DNA tRNALeu(UUR) A to G 3243 mutation is associated with maternally inherited diabetes in Caucasians and Japanese. In a Hong Kong Chinese population we have detected the 3243 mutation in 2 of 74 unrelated subjects with well characterized insulin-dependent (Type 1) diabetes mellitus (IDDM) and 2 of 75 unrelated subjects with young onset (<35 years) non-insulin-dependent diabetes (NIDDM). The 3243 mutation has only previously been associated with IDDM in Japanese. Racial differences in association of the mitochondrial 3243 mutation with IDDM suggest the influence of other genes that may increase its diabetogenic pathogenicity in Oriental races. We also found a significant excess of maternal inheritance of diabetes in the young onset NIDDM cohort, with a ratio of diabetic mothers to fathers of 2.4:1, p < 0.005. The 3243 mutation, however, only accounts for a small proportion of the observed excess maternal inheritance, and further study is needed to search for other diabetes associated mitochondrial DNA mutations. © 1997 John Wiley & Sons, Ltd. 相似文献