Search

Aims: Studies of social inequality and risk of developing type 1 diabetes are inconsistent. The present review aimed to comprehensively review relevant literature and describe what has been reported on socio-economic status or parental occupation and risk of type 1 diabetes in children., Methods: We searched for publications between 1 January 1970 and 30 November 2021. We focused on the most recent and/or informative publication in cases of multiple publications from the same data source and referred to these as primary studies., Results: Our search identified 69 publications with relevant data. We identified eight primary cohort studies with individual-level data, which we considered the highest quality of evidence. Furthermore, we identified 13 primary case-control studies and 14 semi-ecological studies with area-level socio-economic status variables which provided a weaker quality of evidence. Four of eight primary cohort studies contained data on maternal education, showing non-linear associations with type 1 diabetes that were not consistent across studies. There was no consistent pattern on the association of parental occupation and childhood-onset type 1 diabetes., Conclusions: There is a need for more high-quality studies, but the existing literature does not suggest a major and consistent role of socio-economic status in the risk of type 1 diabetes., (© 2023 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: Our aim was to synthesize current evidence on the association between parental smoking and incidence of type 1 diabetes and islet autoantibody positivity (IA) in the offspring by conducting a systematic review and meta-analysis., Methods: We searched Medline, Embase, and Cochrane Library until January 21, 2021, for human studies with parental tobacco use as exposure, type 1 diabetes or IA as outcome, and hazard, risk, or odds ratios as effect estimates. Summary relative risks (RR) and 95% confidence intervals (CI) were estimated with random-effects models. Heterogeneity was quantified with the I 2  statistic, bias with the ROBINS-I tool, and the certainty of evidence with the GRADE tool., Results: We identified 535 records of which 23 were eligible including 25 927 cases of type 1 diabetes. Maternal smoking during pregnancy was associated with a reduced risk of type 1 diabetes (n = 22, RR 0.78, CI 0.71-0.86, I 2 =69%). Including only studies with low to moderate risk of bias indicated similar results with less heterogeneity (n = 14, RR 0.73, CI 0.68-0.79, I 2  = 44%). The certainty of evidence was graded as high. There was no clear association between type 1 diabetes and neither maternal (n = 6, RR 0.95, CI 0.78-1.14, I 2  = 0%) nor paternal (n = 6, RR 0.90, 0.70-1.17, I 2  = 68%) smoking during childhood. Furthermore, the association between maternal smoking during pregnancy and IA was weak (n = 4, RR 0.86, CI 0.44-1.65, I 2  = 71%)., Conclusions: Maternal smoking during pregnancy may reduce the risk of type 1 diabetes in the offspring. Further studies are needed to elucidate potential mechanisms underlying this association., Registration: Prospero CRD42021236717., (© 2022 The Authors. Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Aims: Aim of this study is to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, responsible for coronavirus disease 2019 (COVID-19), as a possible cause for type 1 diabetes by providing an illustrative clinical case of a man aged 45 years presenting with antibody-negative diabetic ketoacidosis post-recovery from COVID-19 pneumonia and to explore the potential for SARS-CoV-2 to adhere to human islet cells., Methods: Explanted human islet cells from three independent solid organ donors were incubated with the SARS-CoV-2 spike protein receptor biding domain (RBD) fused to a green fluorescent protein (GFP) or a control-GFP, with differential adherence established by flow cytometry., Results: Flow cytometry revealed dose-dependent specific binding of RBD-GFP to islet cells when compared to control-GFP., Conclusions: Although a causal basis remains to be established, our case and in vitro data highlight a potential mechanism by which SARS-CoV-2 infection may result in antibody-negative type 1 diabetes., (© 2021 Diabetes UK.)

Aims: To assess mortality and morbidity in the offspring of mothers with diabetes compared with a control cohort of offspring of mothers without diabetes., Methods: The mortality rate, percentage of days admitted to hospital, diagnostic categories and incidence of diabetes mellitus among 691 offspring of mothers with diabetes were compared with a control group of 168 831 offspring not exposed to maternal diabetes. Offspring of mothers with diabetes were identified from the North Jutland Pregnancy database (521 Type 1; 34 Type 2; 136 gestational diabetes) born between 1976 and 2003. Outcome data were retrieved from the National Registry of Patients with follow-up until 31 December 2011. In a subgroup with the longest hospital stay we reviewed hospital records for clinical details until 2016., Results: Mortality was 1.45% in the diabetes group compared with 1.36% in the control group. In the first 2 years, offspring exposed to diabetes spent significantly more time in hospital than the control offspring, but this difference faded to an insignificant difference of 0.04% of time spent in hospital between age 2 and 8 years. The offspring of mothers with diabetes had a sixfold increased risk of developing diabetes mellitus., Conclusions: The offspring of mothers with and without diabetes had almost identical mortality. The increased morbidity was restricted to the first 2 years of life, and was primarily attributable to a few individuals with very severe but probably non-diabetes-related disease burden. The large majority of offspring of mothers with diabetes experienced health conditions similar to those not exposed to diabetes., (© 2016 Diabetes UK.)

Aim: To detect features that might lead to the early diagnosis and treatment of aceruloplasminemia, as initiation of treatment before the onset of neurological symptoms is likely to prevent neurological deterioration., Methods: The PubMed and OMIM databases were searched for published cases of aceruloplasminemia. Diagnostic criteria for aceruloplasminemia were undetectable or very low serum ceruloplasmin, hyperferritinemia and low transferrin saturation. Clinical, biochemical and radiological data on the presentation and follow-up of the cases were extracted and completed through e-mail contact with all authors., Results: We present an overview of 55 aceruloplasminemia cases, including three previously unreported cases. Diabetes mellitus was the first symptom related to aceruloplasminemia in 68.5% of the patients, manifesting at a median age of 38.5 years, and often accompanied by microcytic or normocytic anaemia. The combination preceded neurological symptoms in almost 90% of the neurologically symptomatic patients and was found 12.5 years before the onset of neurological symptoms., Conclusions: There is a diagnostic window during which diabetes and anaemia are present although there is an absence of neurological symptoms. Screening for aceruloplasminemia in adult non-obese individuals presenting with antibody-negative, insulin-dependent diabetes mellitus and unexplained anaemia is recommended. The combination of ferritin and transferrin saturation provides a sensitive initial measure for aceruloplasminemia., (© 2015 The Authors. Diabetic Medicine © 2015 Diabetes UK.)

Aims: To investigate whether the presence of glutamic acid decarboxylase (GAD) autoantibodies post-partum in women with prior gestational diabetes mellitus was associated with changes in metabolic characteristics, including β-cell function and insulin sensitivity., Methods: During 1997-2010, 407 women with gestational diabetes mellitus were offered a 3-month post-partum follow-up including anthropometrics, serum lipid profile, HbA1c and GAD autoantibodies, as well as a 2-h oral glucose tolerance test (OGTT) with blood glucose, serum insulin and C-peptide at 0, 30 and 120 min. Indices of insulin sensitivity and insulin secretion were estimated to assess insulin secretion adjusted for insulin sensitivity, disposition index (DI)., Results: Twenty-two (5.4%) women were positive for GAD autoantibodies (GAD+ve) and the remainder (94.6%) were negative for GAD autoantibodies (GAD-ve). The two groups had similar age and prevalence of diabetes mellitus. Women who were GAD+ve had significantly higher 2-h OGTT glucose concentrations during their index-pregnancy (10.5 vs. 9.8 mmol/l, P = 0.001), higher fasting glucose (5.2 vs. 5.0 mmol/l, P = 0.02) and higher 2-h glucose (7.8 vs. 7.1 mmol/l, P = 0.05) post-partum. Fasting levels of C-peptide and insulin were lower in GAD+ve women compared with GAD-ve women (520 vs. 761 pmol/l, P = 0.02 and 33 vs. 53 pmol/l, P = 0.05) Indices of insulin sensitivity were similar in GAD+ve and GAD-ve women, whereas all estimates of DI were significantly reduced in GAD+ve women., Conclusion: GAD+ve women had higher glucose levels and impaired insulin secretion adjusted for insulin sensitivity (DI) compared with GAD-ve women. The combination of OGTT and GAD autoantibodies post-partum identify women with impaired β-cell function. These women should be followed with special focus on development of Type 1 diabetes., (© 2014 The Authors. Diabetic Medicine © 2014 Diabetes UK.)

Aims: To identify risk factors for diabetic ketoacidosis at diagnosis of Type 1 diabetes in children and adolescents., Methods: In three time periods (1986-1987, 1996-1997 and 2006-2007) 75, 86 and 245 patients, respectively, aged < 20 years were newly diagnosed with Type 1 diabetes in one tertiary care centre. In this retrospective comparative study, data of clinical characteristics, laboratory evaluation at diagnosis, as well as demographic data were retrieved from the patients' files. Comparative analyses were performed between patients presenting with or without diabetic ketoacidosis and between the three time periods., Results: Patients presenting with diabetic ketoacidosis were younger (9.2 ± 4.7 vs. 10.4 ± 4.7 years; P < 0.02), thinner (weight standard deviation score -0.59 ± 1.2 vs. -0.25 ± 1.1; P = 0.002) and less frequently had a first- and/or second-degree relative with Type 1 diabetes compared with those without diabetic ketoacidosis at presentation (16.0 vs. 31.2%, respectively; P = 0.001). Children with diabetic ketoacidosis were less likely to have had relevant testing before diagnosis than children without diabetic ketoacidosis. Children aged < 2 years presented more often with diabetic ketoacidosis than the older children (85 vs. 32%; P < 0.001). Children of Ethiopian origin had a higher rate of diabetic ketoacidosis at diagnosis than the rest of the cohort (57.8 vs. 33%; P = 0.04)., Conclusions: Factors affecting the risk of developing diabetic ketoacidosis at diagnosis of Type 1 diabetes may be related to the degree of awareness of symptoms of diabetes among parents and primary care physicians. Prevention programmes should aim at increasing awareness and consider the application of special measures to avoid diabetic ketoacidosis in children aged < 2 years and high-risk ethnic groups., (© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.)

Aims: To determine the prevalence of plasma vitamin D (25-dihydroxyvitamin D) insufficiency in individuals with Type 1 diabetes and to determine the cross-sectional and longitudinal associations of plasma vitamin D with insulin resistance., Methods: Participants from the SEARCH for Diabetes in Youth Study [n = 1426; mean age 11.2 years (sd 3.9)] had physician-diagnosed Type 1 diabetes [diabetes duration mean 10.2 months (sd 6.5)] with data available at baseline and follow-up (approximately 12 and 24 months after baseline). Insulin resistance was estimated using a validated equation. Cross-sectional and longitudinal multivariate logistic regression models were used to determine the association of plasma vitamin D with insulin resistance, adjusting for potential confounders., Results: Forty-nine per cent of individuals had plasma vitamin D < 50 nmol/l and 26% were insulin resistant. In cross-sectional multivariate analyses, participants who had higher plasma vitamin D (65 nmol/l) had lower odds of prevalent insulin resistance than participants with lower plasma vitamin D (25 nmol/l) (odds ratio 0.70, 95% CI 0.57-0.85). This association was attenuated after additional adjustment for BMI z-score, which could be a confounder or a mediator (odds ratio 0.81, 95% CI 0.64-1.03). In longitudinal multivariate analyses, individuals with higher plasma vitamin D at baseline had lower odds of incident insulin resistance, but this was not significant (odds ratio 0.85, 95% CI 0.63-1.14)., Conclusions: Vitamin D insufficiency is common in individuals with Type 1 diabetes and may increase risk for insulin resistance. Additional prospective studies are needed to determine the association between plasma vitamin D and insulin resistance, and to further examine the role of adiposity on this association., (© 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.)

Type 1 diabetes involves the specific destruction of the pancreatic islet β-cells, eventually resulting in a complete dependency of exogenous insulin. The clinical onset of diabetes is preceded by the appearance of autoantibodies against β-cell antigens. The human leukocyte antigen (HLA) region is the single most important genetic determinant of Type 1 diabetes susceptibility, yet variability in the HLA region has been estimated to explain only approximately 60% of the genetic influence of the disease. Over 50 identified non-HLA genetic polymorphisms support the notion that genetics alone cannot explain Type 1 diabetes. Several lines of evidence indicate that environmental triggers may be integral in inducing the onset of islet autoimmunity in genetically susceptible individuals. The association between environmental factors and the clinical onset is complicated by observation that the rate of progression to clinical onset may be affected by environmental determinants. Hence, the environment may be aetiological as well as pathogenic. Putative inductive mechanisms include viral, microbial, diet-related, anthropometric and psychosocial factors. Ongoing observational cohort studies such as The Environmental Determinants of Diabetes in the Young (TEDDY) study aim to ascertain environmental determinants that may trigger islet autoimmunity and either speed up or slow down the progression to clinical onset in subjects with persistent islet autoimmunity., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

It is widely accepted that Type 1 diabetes is a complex disease. Genetic predisposition and environmental factors favour the triggering of autoimmune responses against pancreatic β-cells, eventually leading to β-cell destruction. Over 40 susceptibility loci have been identified, many now mapped to known genes, largely supporting a dominant role for an immune-mediated pathogenesis. This role is also supported by the identification of several islet autoantigens and antigen-specific responses in patients with recent onset diabetes and subjects with pre-diabetes. Increasing evidence suggests certain viruses as a common environmental factor, together with diet and the gut microbiome. Inflammation and insulin resistance are emerging as additional cofactors, which might be interrelated with environmental factors. The heterogeneity of disease progression and clinical manifestations is likely a reflection of this multifactorial pathogenesis. So far, clinical trials have been mostly ineffective in delaying progression to overt diabetes in relatives at increased risk, or in reducing further loss of insulin secretion in patients with new-onset diabetes. This limited success may reflect, in part, our incomplete understanding of key pathogenic mechanisms, the lack of truly robust biomarkers of both disease activity and β-cell destruction, and the inability to assess the relative contributions of various pathogenic mechanisms at various time points during the course of the natural history of Type 1 diabetes. Emerging data and a re-evaluation of histopathological, immunological and metabolic findings suggest the hypothesis that unknown mechanisms of β-cell dysfunction may be present at diagnosis, and may contribute to the development of hyperglycaemia and clinical symptoms., (© 2012 The Author. Diabetic Medicine © 2012 Diabetes UK.)

Background: Fulminant Type 1 diabetes was originally reported as idiopathic Type 1 diabetes. Involvement of viral infections in the pathogenesis of fulminant T1D has been suggested, but the development of fulminant Type 1 diabetes after influenza vaccination has not been reported., Case Report: We report a case of fulminant Type 1 diabetes with thrombocytopenia following influenza vaccination. A 54-year-old man was admitted to hospital with hyperglycaemia and diabetic ketosis. Seven days before admission, he received a seasonal influenza vaccine for the prevention of influenza infection. On admission, blood glucose was 29 mmol/L and HbA1c 40 mmol/mol (5.9%). Fasting and 2-h C-peptide immunoreactivity were <0.0333 nmol/L and 0.0999 nmol/L, respectively. Anti-GAD and anti-IA-2 antibodies were negative, so no autoimmunity seemed to participate in the etiology. ELISPOT assay also showed no association with T cell-mediated autoimmunity. HLA genotypes were consistent with susceptibility to fulminant Type 1 diabetes. After the abrupt onset of diabetes, he showed mild thrombocytopenia, which has been observed for approximately 5 years after diabetes development., Conclusion: This is the first description of fulminant Type 1 diabetes after influenza vaccination. Our observation raises the possibility that influenza vaccination might trigger this condition via the TLR7 pathway., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Aims: To review and synthesize the published evidence on the possible association between childhood obesity and the subsequent risk of Type 1 diabetes., Methods: The PubMed database was systematically searched for studies using childhood obesity, BMI or %weight-for-height as the exposure variable and subsequent Type 1 diabetes as the outcome. Studies were only included if assessment of obesity preceded the diagnosis of Type 1 diabetes., Results: Eight case-control studies and one cohort study were included, comprising a total of 2658 cases. Of these nine studies, seven reported a significant association between childhood obesity, BMI or %weight-for-height and increased risk for Type 1 diabetes. Meta-analysis of the four studies that reported childhood obesity as a categorical exposure produced a pooled odds ratio of 2.03 (95% CI 1.46-2.80) for subsequent Type 1 diabetes; however, in those studies, age at obesity assessment varied from age 1 to 12 years. A dose-response relationship was supported by a continuous association between childhood BMI and subsequent Type 1 diabetes in a meta-analysis of five studies (pooled odds ratio 1.25 (95%CI 1.04-1.51) per 1 sd higher BMI)., Conclusion: There is overall evidence for an association between childhood obesity, or higher BMI, and increased risk of subsequent Type 1 diabetes. Several theories have been proposed for a causal relationship. Reduction in Type 1 diabetes should be considered as a potential additional benefit of preventing childhood obesity., (© 2010 The Authors. Diabetic Medicine © 2010 Diabetes UK.)

Aims: To examine perinatal risk factors for the onset of Type 1 diabetes before 6 years of age, in a 2000-2005 Australian birth cohort., Methods: Data from longitudinally linked delivery and hospital admission records (until June 2007) were analysed. Diabetes in mothers and children was identified from International Classification of Diseases 10 diagnosis codes in the hospital records., Results: There were 272 children admitted to hospital with a first diagnosis of diabetes out of 502 040 live births. Incidence for the infants born in 2000 was 16.0 per 100 000 person-years. Maternal Type 1 diabetes was a significant risk factor [crude relative risk (RR) 6.33], but maternal Type 2 diabetes and gestational diabetes were not significantly associated with diabetes in the child. Late preterm birth (34-36 weeks) (RR 1.64) and caesarean section (RR 1.30) increased the risk of a diabetes admission. Size-for-gestational-age was significantly associated with onset of diabetes (small-for-gestational age RR 0.48), but neither birth weight categories nor birth weight as a continuous variable were associated with risk of diabetes. Increasing maternal age was associated with an increased risk of diabetes in the child (RR 1.13 for each additional 5 years of age)., Conclusions: This study identified risk factors associated with onset of Type 1 diabetes before 6 years of age, in a recent birth cohort. Size-for-gestational-age had a consistent association with risk of early onset of Type 1 diabetes, small size being protective. Size-for-gestational-age measures should be preferred to birth weight thresholds when assessing risk of diabetes.

Background: Exenatide is an incretin mimetic licensed for treatment of Type 2 diabetes poorly controlled despite maximally tolerated doses of oral therapy. Similar in structure to the natural incretin hormone glucagon-like peptide 1 (GLP-1), it helps restore underlying pathophysiological abnormalities., Case Report: We report the successful use of exenatide, combined with insulin, in a 66-year-old woman initially diagnosed with Type 2 diabetes in 1989 but now exhibiting a Type 1 phenotype. Diet, lifestyle advice and oral glucose-lowering agents were commenced but persisting poor control necessitated insulin therapy in 2005. She later presented twice in diabetic ketoacidosis, suggesting conversion to a Type 1 phenotype (postprandial C-peptide < 94 pmol/l). Despite differing insulin regimens, control remained poor with frequent hyperglycaemic and hypoglycaemic excursions, severely impairing quality of life. Whilst an inpatient in 2007 [glycated haemoglobin (HbA(1c)) 10.2%, body mass index (BMI) 31.5 kg/m(2)] exenatide was commenced in an attempt to stabilize glycaemic control. Dramatic improvements were seen and continued. Eight months later, HbA(1c) had fallen by 2% with an 8-kg weight loss and 10-unit reduction in daily insulin dose. Quality of life dramatically improved. C-peptide remains undetectable., Conclusions: This patient with features of both Type 1 and Type 2 diabetes benefited greatly from exenatide with insulin therapy. The improvement seen in glycaemic control could not be attributable to enhanced insulin secretion but could be as a result of a combination of the other incretin effects (postprandial glucagon suppression, delayed gastric emptying and weight loss secondary to increased satiety) all improving insulin sensitivity, reducing insulin dose and smoothing control.

Aim: To determine the intravitreous concentration of monokine induced by interferon-gamma (Mig) in patients with diabetic retinopathy (DR) and the relation between Mig and vascular endothelial growth factor (VEGF)., Research Design and Methods: Vitreous samples were obtained at the time of vitrectomy from 41 eyes of 38 DR patients (30 with active DR and 11 with inactive DR) and from 15 eyes of 15 non-diabetic patients who had macular disease (control subjects). Human Mig and VEGF were quantified using a FACS Caliber flow cytometer., Results: The vitreous concentration of Mig was increased significantly in patients with both active and inactive DR [148.0 (31.6-997.2; median range) and 82.3 (25.7-347.7) pg/ml, respectively] compared with control subjects [21.0 (5.2-74.3) pg/ml; P < 0.0001 and P < 0.001, respectively]. In DR patients, a significant (P < 0.01) correlation was observed between vitreous concentrations of Mig and VEGF., Conclusion: Our results suggest that Mig may play an important role in the pathogenesis of DR and works in consort with VEGF in the progression of pathological angiogenesis in DR.

Aims: The aim of our study was to assess diurnal blood pressure (BP) and heart rate variability and their possible relationship to the duration of the QT interval in adolescents with Type 1 diabetes., Methods: In 48 normotensive, normoalbuminuric diabetic adolescents, with a mean (+/- sd) age of 17.3 (+/- 4.1) years and a mean (+/- sd) diabetes duration of 8.5 (+/- 3.3) years, 24-h ambulatory BP was recorded. In addition, 24-h heart rate (HR) monitoring was performed and QT and corrected QT (QTc) intervals were estimated as indices of autonomic function. The patients were divided into two groups according to the absence of a decrease (non-dippers) or the presence of a decrease (dippers) in nocturnal diastolic BP (DBP)., Results: In comparison with the dippers, the non-dippers showed reduced mean 24-h HR (79.6 vs. 84.0 beats/min, P = 0.05) and reduced mean daytime HR (81.3 vs. 86.0 beats/min, P = 0.05). The QT interval was prolonged in the non-dippers (366.3 vs. 347.5 ms, P = 0.015), and end systolic (28.7 vs. 25.9 mm, P = 0.004) and end diastolic left ventricular diameters (47.8 vs. 45.5 mm, P = 0.037) were greater. In stepwise multiple regression, HR variables were the most important factors affecting DBP ratio or the duration of the QT interval., Conclusions: In conclusion, normotensive diabetic adolescents with impaired nocturnal BP reduction also have impaired autonomic function tests, in association with prolonged QT interval and increased left ventricular diameters. These findings suggest that diabetic adolescents who have the 'non-dipper' phenomenon may need close follow-up for the possible development of vascular complications, such as cardiac arrhythmias and left-ventricular hypertrophy.

Aims: To investigate perinatal risk factors for childhood Type 1 diabetes in Western Australia, using a complete population-based cohort., Methods: Children born between 1980 and 2002 and diagnosed with Type 1 diabetes aged < 15 years (n = 940) up to 31 December 2003 were identified using a prospective population-based diabetes register with a case ascertainment rate of 99.8%. Perinatal data were obtained for all live births in Western Australia from 1980 to 2002 (n = 558 633) and record linkage performed to identify the records of cases., Results: The incidence of Type 1 diabetes increased by 13% for each 5-year increase in maternal age [adjusted incidence rate ratio (IRR) 1.13, 95% confidence interval (CI) 1.05, 1.21], by 13% for every 500-g increase in birth weight (adjusted IRR 1.13, 95% CI 1.04, 1.23). The incidence decreased with increasing birth order (adjusted IRR 0.89, 95% CI 0.82, 0.96) and increasing gestational age (adjusted IRR 0.84, 95% CI 0.77, 0.93). A higher incidence of Type 1 diabetes was associated with an urban vs. non-urban maternal address at the time of birth (adjusted IRR 1.38, 95% CI 1.18, 1.63), but no association was found with socio-economic status of the area., Conclusions: A higher incidence of Type 1 diabetes was associated with increasing maternal age, higher birth weight, lower gestational age, lower birth order and urban place of residence at the time of birth.

Aims: The main objective was to determine premature stroke risk in men and women in Sweden with previous hospital admission for Type 1 diabetes or without previous hospital admission., Methods: All individuals in Sweden aged 15-34 years at first hospital admission for Type 1 diabetes and aged 15-49 years at first hospital admission for stroke during the study period (1987-2001) were identified. Standardized incidence ratios (SIRs) were calculated to compare premature stroke risk between individuals admitted to hospital with Type 1 diabetes and individuals without hospital admission, after controlling for age, time period, occupation and geographical region. SIRs were also calculated for individuals with diabetic complications., Results: The overall SIRs for premature stroke in men and women with hospital admission for Type 1 diabetes were 17.94 [95% confidence interval (CI) 12.87, 24.36] and 26.11 (95% CI 18.81, 35.32), respectively. Men and women with diabetic nephropathy had the highest significant SIRs of premature stroke: 48.87 and 73.53, respectively., Conclusions: Our data indicate that young to middle-aged individuals with Type 1 diabetes had a considerably higher risk of premature stroke than those without Type 1 diabetes. This underscores the need to implement vigorous interventions in healthcare settings in order to decrease the risk of premature stroke in individuals with Type 1 diabetes.

Aims: To examine whether parents who lost a child have an increased risk of hospitalization because of Type 1 or Type 2 diabetes., Methods: We identified all parents who lost a child in Denmark from 1980 to 1996 (stress exposed), and compared them with parents randomly selected from all other parents in the country at that time without such a bereavement. Fifteen non-bereaved families were matched to each bereaved family for family size and the age of the children. First hospitalizations for Type 1 or Type 2 diabetes were monitored in these two groups up to 18 years after the bereavement. There were 21 062 parents in the bereaved cohort and 293 745 parents in the non-bereaved cohort. The study was based upon linkage of several national registers, and first-time hospitalization with diabetes (Type 1 or Type 2) was the end point., Results: Five hundred and fifty-one cases were hospitalized because of Type 1 diabetes and 1569 cases because of Type 2 diabetes. There was a 29% higher risk of hospitalization because of Type 1 diabetes [95% CI -5 to 75%; corresponding to a relative risk (RR) of 1.29; 95% CI 0.95-1.75] and a 44% higher risk of hospitalization because of Type 2 diabetes (95% CI 21-71%; corresponding to an RR of 1.44; 95% CI 1.21-1.71) in the bereaved cohort. The high risk of hospitalization because of Type 2 diabetes following bereavement was only statistically significant for mothers., Conclusions: Psychological stress may be a contributing cause of, or have prognostic importance for, both Type 1 and Type 2 diabetes, but a statistically significant association was only seen for Type 2 diabetes.

Animal models have been used extensively in diabetes research. Early studies used pancreatectomised dogs to confirm the central role of the pancreas in glucose homeostasis, culminating in the discovery and purification of insulin. Today, animal experimentation is contentious and subject to legal and ethical restrictions that vary throughout the world. Most experiments are carried out on rodents, although some studies are still performed on larger animals. Several toxins, including streptozotocin and alloxan, induce hyperglycaemia in rats and mice. Selective inbreeding has produced several strains of animal that are considered reasonable models of Type 1 diabetes, Type 2 diabetes and related phenotypes such as obesity and insulin resistance. Apart from their use in studying the pathogenesis of the disease and its complications, all new treatments for diabetes, including islet cell transplantation and preventative strategies, are initially investigated in animals. In recent years, molecular biological techniques have produced a large number of new animal models for the study of diabetes, including knock-in, generalized knock-out and tissue-specific knockout mice.

Aims and Methods: It has recently been hypothesized that weight gain in childhood accelerates the onset of Type 1 diabetes, as well as increasing its risk, and that Type 1 diabetes and Type 2 diabetes may be one and the same disorder of insulin resistance. An explanation is needed for the rising incidence of childhood diabetes and, to test the Accelerator Hypothesis, we examined the anthropometric measurements recorded from birth in 168 young people presenting with Type 1 diabetes between 1980 and 2002. Pre-onset as well as peri- and post-onset measurements of height and weight were available, and waist circumference was recorded at various intervals after onset., Results: The mean birth weight of the children and their height, weight and body mass index (BMI) at diagnosis lay close to the population mean. However, pre-onset and post-onset BMI were both well above the population mean, were closely correlated with each other (r = 0.79, P < 0.001) and (inversely) with age at onset (r = -0.30, P < 0.001). A significant correlation was also found between BMI standard deviation scores (sds) and year of diagnosis (r = 0.27, P < 0.001) and, importantly, waist circumference sds in the children with Type 1 diabetes was found to be substantially greater than average for the population [boys: +0.96 (sd 1.04), girls: +1.30 (sd 0.89)]., Conclusions: The data suggest that children with Type 1 diabetes have become progressively heavier at diagnosis over the past 20 years, and that the heavier child develops it earlier. Waist circumference, a proxy for visceral fat mass and insulin resistance, is substantially greater in children with Type 1 diabetes. Weight centile crossing appears to be an important environmental accelerator which may contribute to or account for the striking increase in both Type 1 diabetes and Type 2 diabetes in childhood. A reduction of body weight and improved lifestyle might reverse this trend in both types of diabetes.

Aims: To investigate perinatal risk factors for childhood Type 1 diabetes in a UK population cohort., Methods: Perinatal data have been routinely recorded in Northern Ireland for all births in the period 1971-86 (n = 447 663). Diabetes status at the age of 15 years was ascertained in this cohort by identifying 991 children from 1079 registered with Type 1 diabetes diagnosed from 1971 to 2001 and date of birth in the period 1971-86., Results: Increased Type 1 diabetes risk was associated with higher maternal age, paternal age, birth weight and birth weight for gestational and lower gestational age. After adjustment for maternal age, the association between Type 1 diabetes and paternal age remained significant [relative risk (RR) = 1.52 (1.10, 2.09) comparing father's age 35 years or more to less than 25 years] but not vice versa [RR = 1.11 (0.80, 1.54) comparing mother's age 35 years or more to less than 25 years]. Increased birth order was associated with a significant decrease in the risk of Type 1 diabetes [adjusted RR = 0.75 (0.62, 0.90) comparing birth order three or more with firstborn], but this only became apparent when adjustment was made for maternal age. Furthermore this association with birth order was significant only for diabetes diagnosed under the age of 5 years., Conclusions: Our analysis demonstrates, for the first time in a UK regional cohort setting, that maternal age and paternal age at delivery, birth order, birth weight and gestational age are significantly associated with Type 1 diabetes risk.

Aims: The aim of the study was to identify environmental risk factors for insulin-dependent diabetes mellitus (Type 1 DM) in childhood., Methods: A matched case-control study of Type 1 DM conducted in Lancashire and Cumbria, UK, using a structured interview. Cases (n=196, participation rate 83%) were children under 16 years of age diagnosed prior to October 1998 and attending diabetic clinics. Controls (n=381) were healthy children from the community matched by gender and by age (within a few days of birth). The data were analysed by logistic regression using the technique of Breslow and Day for matched case control studies., Results: The multivariate regression model showed that the following factors were significantly associated with the risk of developing Type 1 DM (odds ratio, 95% confidence intervals): sharing a room with a sibling (0.458, 0.290-0.721), social contact with other children when aged 6-11 months (0.439, 0.256-0.752), consumption of sugary food (0.080, 0.024-0.261), parental insulin dependent diabetes mellitus (10.651, 3.086-36.761), maternal thyroid disease (4.861, 1.681-14.058), consuming more than one pint of milk per day prior to school entry (0.498, 0.310-0.802), maternal smoking during pregnancy (0.373, 0.218-0.636), a father with no academic qualifications (0.504, 0.278-0.913), maternal age at time of birth (0.900, 0.854-0.948), maternal infections in pregnancy (2.453, 1.011-5.948), other maternal illnesses or conditions in pregnancy (2.007, 1.139-3.535), belonging to an Asian family (0.104, 0.028-0.394), and regular contact with pets and other animals (0.552, 0.309-0.987)., Conclusion: Many of the results are consistent with the hygiene hypothesis which links improved living standards with decreased exposure to microorganisms and increased risk of immune mediated disease in childhood. These findings challenge the idea that improved hygiene acts exclusively through a Th2 mechanism leading to atopic disease as Type 1 DM is mediated by a Th1 reaction. The association with maternal smoking could be due to recall bias but a causal link cannot be excluded with confidence.

Aims: Prospective studies of autonomic nerve function are rare. We have followed the progression of autonomic dysfunction in relation to nephropathy over 14 years in Type 1 diabetic patients., Methods: Autonomic nerve function was assessed by heart-rate responses to deep breathing (E/I ratio) and tilting (acceleration and brake indices) and by the postural blood pressure reaction in 58 patients, 43 of whom were reassessed after 14 years. Nephropathy was evaluated by the degree of albuminuria (albuminuria > 20 micro g/min or > 0.03 g/24 h) and glomerular filtration rate ((51)Cr-EDTA plasma clearance). The acceleration index had deteriorated after 7 years (P = 0.0155), whereas the E/I ratio (P = 0.0070) and the diastolic postural blood pressure reaction (P = 0.0054) had deteriorated 14 years after the baseline examination (age-corrected values). All those with albuminuria at the third examination showed signs of autonomic neuropathy at baseline (10 of 10) compared with only nine of 22 without (P = 0.0016). Multiple regression analysis showed that the association between autonomic dysfunction and future albuminuria was due to the E/I ratio. In addition, individuals with an abnormal postural diastolic blood pressure fall (n = 7) at baseline showed a greater fall in glomerular filtration rate more than others 7-14 years later [29 (16.5) ml/min/1.72 m(2) vs. 11 (9) ml/min/1.72 m(2); P = 0.0074]., Conclusion: Autonomic nerve function had deteriorated after 14 years. Autonomic neuropathy and abnormal postural diastolic blood pressure falls at baseline were associated with future renal complications., (Copyright 2004 Diabetes UK)

Aims: Pertussis has been implicated but not proven as a risk for Type 1 diabetes mellitus (DM). Previous studies have investigated paediatric, but not adult-onset Type 1 DM. We investigated association of pertussis exposures and Type 1 DM with follow-up into adulthood., Methods: Longitudinal analysis of 16 820 members (100 with Type 1 DM) of two nationally representative British birth cohorts (the 1970 British Cohort Study (BCS70) and the National Child Development Study (NCDS)) followed from birth to ages 30 years (BCS70) and 42 years (NCDS). Cox regression analysis with age of onset for Type 1 DM as the dependent variable investigated relationships with pertussis infection and immunization, modelled as time-dependent co-variates. Simultaneous adjustment was made for Wild measles, mumps and chickenpox infections; tetanus and smallpox immunizations; sex, parental social class and cohort. The potential confounding factors were modelled as fixed co-variates., Results: Cox regression analysis produced adjusted odds ratios (ORs) (with 95% confidence intervals (CIs)) of 2.21 (1.35-3.59) and 0.73 (0.49-1.05) for Type 1 DM (with onset at any age) associated with pertussis infections and immunization (trend over number of vaccinations), respectively. Adjusted ORs from Cox regression for Type 1 DM with onset after age 10 years are 2.59 (1.56-4.30) for pertussis infection and 0.63 (0.42-0.94) for pertussis immunization. None of the other infections or immunizations are notably associated with Type 1 DM., Conclusions: Some pertussis infections may be a risk for Type 1 DM and immunization may confer protection. Further research should consider delayed Type 1 DM following pertussis exposures.

Aims: Several reports have implicated nitric oxide (NO) in the angiogenic process. The assessment of NO stable end products, nitrite and nitrate (NOx), is commonly used as a measure of NO production in biological fluids. The aims of the study were to investigate NOx concentrations in the vitreous fluid of patients with proliferative diabetic retinopathy (PDR) and to evaluate the relationship between NOx and vascular endothelial growth factor (VEGF)., Patients and Methods: Serum and vitreous fluid samples were obtained simultaneously at the time of vitreoretinal surgery from 23 patients with PDR, and 17 control non-diabetic patients with non-proliferative ocular disease. NOx was determined by using the Griess reaction and VEGF levels were assessed by ELISA., Results: The intravitreous concentration of NOx was significantly elevated in patients with PDR in comparison with the control group (31.6 +/- 2.96 micromol/l vs. 18 +/- 2.46 micromol/l; P = 0.01). However, we did not detect any differences between NOx serum concentrations. We observed a correlation between serum and vitreous levels of NOx in diabetic patients (r = 0.79; P < 0.001), but not in the control group. Intravitreous levels of VEGF in patients with PDR were higher than those obtained in serum (1.42 ng/ml (0.12-7.62) vs. 0.12 ng/ml (0.03-0.42); P < 0.01). Vitreal levels of VEGF were strikingly higher in patients with PDR than in the control subjects (1.42 ng/ml (0.12-7.62) vs. 0.009 ng/ml (0.009-0.04); P < 0.001). No correlation between vitreal concentrations of NOx and VEGF was observed, either in diabetic patients or in the control group., Conclusions: NOx and VEGF are increased but not related in the vitreous fluid of diabetic patients with PDR. Our results suggest that serum diffusion could play a significant role in explaining the increase of NOx. By contrast, intraocular production seems to be the main factor responsible for the intravitreous enhancement of VEGF.

Introduction: Interferon-alpha (IFN-alpha) is now widely used in the treatment of chronic hepatitis C. Few patients have been reported as developing impaired glucose tolerance or diabetes mellitus (DM) using this therapy. The explanation for the development of DM in chronic hepatitis C treated with IFN-alpha is unclear. We report two patients who developed an abrupt onset of diabetes during IFN-alpha for chronic hepatitis C., Case Reports: Two male middle-aged patients were admitted to our hospital for an abrupt onset of diabetes, in diabetic ketoacidosis, with a very short duration of hyperglycaemic symptoms. Their clinical course was similar. Case 1 never demonstrated any markers of pancreatic immunogenicity. Case 2 had high levels of decarboxylase glutamic acid autoantibodies (GADAb), before the IFN-alpha treatment that persisted. We compared initial beta-cell function and metabolic control with a group of middle-aged patients from our hospital who had recently been diagnosed with Type 1 diabetes mellitus (DM1). In contrast to these, the onset of the disease was particularly severe with beta-cell function substantially impaired and displaying unstable short-term metabolic control., Conclusions: Type 1 diabetes should be considered as a potential complication if IFN is administered to patients with chronic hepatitis C. Its onset may be severe and result in short-term difficulties in metabolic control.

Aims: To determine the role of islet autoimmunity in the aetiology of different clinical subtypes of diabetes mellitus in young north Indian patients by measuring islet autoantibodies., Methods: In a cross-sectional study, 145 young patients with diabetes (onset < 30 years) were subdivided into the following categories: Type 1 diabetes (n = 83), malnutrition-modulated diabetes mellitus (MMDM, n = 31) and fibro-calculous pancreatic diabetes (FCPD, n = 31). MMDM subjects presented with emaciation and severe insulin-requiring but ketosis-resistant diabetes, while FCPD was associated with idiopathic chronic calcific pancreatitis. Antibodies to glutamic acid decarboxylase (GADA) and IA-2 (IA-2 A) were detected by immunoprecipitation of 35S-labelled recombinant antigens and cytoplasmic islet cell antibody (ICA) by indirect immunofluorescence., Results: GADA were present in a significant proportion (23%) of patients with MMDM. In contrast, IA-2 A was increased only among patients with Type 1 diabetes (22%), but not MMDM (3%, P < 0.05). Among patients with a duration of diabetes < 2 years, GADA and/or IA-2 A were found in 61% of Type 1 diabetic and 37% of MMDM patients (P < 0.01). MMDM patients who were positive for GADA had a shorter duration of diabetes, but did not differ in their age at onset of diabetes, body mass index, fasting plasma C-peptide, or frequency of thyroid microsomal and parietal cell antibodies. FCPD subjects had the lowest prevalence of autoantibodies: IA-2 and ICA were absent, while GADA were present in 7% (P < 0.05 vs. Type 1 diabetes)., Conclusions: GADA, though not IA-2 A, were present in a substantial proportion of patients with the MMDM variant of diabetes, suggesting that islet autoimmunity may play a role in its pathogenesis. In contrast, none of the islet antibodies was increased in subjects with FCPD, making it likely that it is a secondary type of diabetes.

Recent evidence is reviewed indicating increased oxidative damage in Type 1 and Type 2 diabetes mellitus as well as deficits in antioxidant defence enzymes and vitamins. Mechanisms are considered whereby hyperglycaemia can increase oxidative stress, and change the redox potential of glutathione and whereby reactive oxygen species can cause hyperglycaemia. It is argued that oxygen, antioxidant defences, and cellular redox status should now be regarded as central players in diabetes and the metabolic syndrome.

Aims: To investigate, by means of a twin-control study, whether there is a relationship between birth weight and Type 1 diabetes mellitus., Methods: In the youngest part (n = 20 888 pairs) of the Danish Twin Register, 95 twin pairs (26 monozygotic and 69 dizygotic) with Type 1 diabetes were identified. Information about birth weight and birth length, prematurity, maternal age and parity was obtained from midwives' records and from the Danish Medical Birth Registry and analysed using Student's two-sided t-test, Chi-square test and logistic regression., Results: Birth data were available for 83 diabetic and 51 healthy twin individuals, altogether 67 twin pairs (20 monozygotic and 47 dizygotic). Mean birth weight was 2537 g and 2565 g (NS) in monozygotic and dizygotic pairs and the corresponding length at birth 47.6 cm and 48.2 cm (NS). In pairs discordant for diabetes, the mean birth weight was 2538 g in twins with diabetes and 2549 g in twins without diabetes (NS). Logistic regression in discordant pairs showed no relationship between diabetes status and birth weight, birth length, birth order, sex or prematurity. Logistic regression in concordant vs. discordant pairs showed no effect of mean birth weight and birth length, maternal age, parity or weeks of prematurity., Conclusions: There is no association between Type 1 diabetes mellitus and birth weight in this study. Furthermore, variables related to birth weight and length cannot explain why some pairs are concordant while other remain discordant.

Evidence from case-control studies for the diabetogenicity of introduction of cow's milk-based formulas at early age in infancy is inconclusive. We followed siblings of children with Type 1 diabetes mellitus (Type 1 DM) to investigate a possible relationship between cow's milk consumption during infancy or later in childhood and the emergence of diabetes-associated autoantibodies and progression to clinical Type 1 DM. A cohort of 725 initially unaffected 0 to 25-year-old siblings of 801 index children with Type 1 DM diagnosed in 1986-1989 participated in the study (82% of those invited). The siblings were observed for Type 1 DM associated autoantibodies at intervals of 3-12 months for 4 years, starting from the diagnosis of Type 1 DM in the index child. The follow-up for Type 1 DM started at the same time and ended on 31 October 1995. The combined prevalence of Type 1 DM associated autoantibodies (islet cell antibodies (ICA), insulin autoantibodies (IAA), GAD autoantibodies (GADA), and/or antibodies to the insulinoma associated cDNA2 protein (IA-2A)) was 13.6% (95/697) at the beginning of the study. Of the initially seronegative siblings, 7.5% (45/602) converted to antibody positivity during 4 years, and of all siblings 4.6% (33/725) developed Type 1 DM during the total follow-up time. The age at introduction of supplementary milk feeding was not significantly related to seroconversion to positivity for Type 1 DM associated autoantibodies or to the development of Type 1 DM in the siblings. When adjusted for age, sex, infant feeding patterns, and maternal age and education, high milk consumption in childhood (> or =3 glasses daily) was associated with more frequent emergence of Type 1 DM-associated autoantibodies than low consumption (<3 glasses daily) (adjusted odds ratio 3.97, 95% confidence interval 1.3-11.7, p = 0.01). There was a non-significant association between high milk consumption and progression to clinical Type 1 DM (adjusted hazard ratio 2.75, 95% confidence interval 0.9-8.4, p = 0.07). To conclude, this study suggests that high consumption of cow's milk during childhood may be associated both with seroconversion to positivity for diabetes-associated autoantibodies and progression to clinical Type 1 DM among siblings of children with diabetes.

Enterovirus infections may initiate and accelerate the beta-cell damaging process leading to Type 1 (insulin-dependent) diabetes mellitus (Type 1 DM). Recent prospective studies have suggested that this can happen long before overt disease and even in utero. We describe an infant, followed regularly from birth, who progressed to clinical Type 1 DM at the age of 14 months. He had a strong enterovirus exposure exceptionally early in life; the first enterovirus infection occurred before the age of 3 months and the second between the age of 9 and 12 months. The first infection probably occurred at birth, when the child had symptoms of a respiratory infection. This infection was followed by the appearance of beta-cell autoimmunity, and clinical Type 1 DM was diagnosed shortly after the second infection. The child had a low level of maternal enterovirus antibodies and short duration of breast-feeding, both associated with increased risk for enterovirus infections during the fetal period and infancy. This case fits with the current hypothesis that enterovirus infections can induce the process resulting in Type 1 DM, especially when occurring early in life. Furthermore, this demonstrates the feasibility of the present study design, which is applicable also in large-scale birth-cohort studies.

In 1992 a national case-control study was conducted through the British Paediatric Association Surveillance Unit (BPASU) framework to evaluate both the incidence of IDDM in children under 5 in that year and the effects of various putative trigger factors in the disease pathogenesis. A total of 218 sets of matched case-control questionnaire data established that paternal IDDM (odds ratio (OR) = 16.11, 95% confidence interval (CI) 1.94-133.7, p < = 0.001) is independently associated with increased risk, and higher birth order (OR = 0.64, CI 0.44-0.94, p = 0.021) and paternal age greater than 25 years (age 25-39 OR = 0.52, CI 0.30-0.89; age 40 + OR = 0.23, CI 0.08-0.67, p = 0.009) with decreased risk of diabetes. Other factors previously implicated in the disease pathogenesis (birthweight, parental socio-economic status, infant feeding, and immunization record) showed no significant independent association with disease development.

Twin studies are a valuable way of determining the relative significance of genetic and environmental factors in the aetiology of disease. In diabetes mellitus, they are of importance, since the aetiologies of Type 1 (insulin-dependent) and Type 2 (non-insulin-dependent) diabetes mellitus are probably different. However the results of twin studies have not always been reliable. Strict adherence to methodological guidelines is necessary to ensure the validity of the results that are obtained. These guidelines relate to ascertainment of a twin sample, confirmation of zygosity, and effects of sampling. Critical review of twin studies in diabetes performed to date imply provisionally a very strong genetic input to the aetiology of Type 1 diabetes. In Type 2 diabetes genetic and environmental factors are probably of equal importance.

Environmental factors are important for the development of Type 1 diabetes mellitus. They likely account for changes in the incidence of this disease over time, as well as the well-documented differences in incidence in ethnically and genetically similar people living in different parts of the world. There is a relationship between early cow's milk exposure and the development of Type 1 diabetes in humans, and between early cow's milk exposure and the development of autoimmune diabetes in rodent models of Type 1 diabetes. Moreover, some immunological studies have suggested a possible mechanism whereby exposure to cow's milk protein could result in beta-cell directed autoimmunity and subsequent Type 1 diabetes. Although provocative, the existence of alternative explanations for these epidemiological and biological observations, suggest that the data are insufficient to conclude that the observed associations represent causal relationships or to mandate changes in recommendations for infant feeding. The question of whether or not avoidance of cow's milk protein in infancy will prevent Type 1 diabetes can, however, be tested in an international randomized clinical trial of infant diets, which is currently under review.

If environmental factors are important in the aetiology of insulin-dependent (Type 1) diabetes mellitus, primary schooling would be more likely to be shared by cases in an epidemic year compared with controls. We have examined a case control study, comparing primary schools attended. Cases were identified from an established register with known accurate ascertainment and compared with controls taken from a central register of all children and date of birth, sex, and race matched. Parents were asked to complete a structured questionnaire which included questions relating to the child's schooling. There were 187 cases with at least a first matched control. Thirty-two of the cases attended the same nursery or primary school as another case, 18 in the same academic year, compared with 12 controls attending the same school as another control (99% confidence interval (CI) for the difference between proportions 0.0572 - 0.107). Of these cases diagnosed in 1986, 9 attended the same school as another case. Spatial clustering occurs in Type 1 diabetes. This is further evidence of an environmental factor contributing to the genesis of the disease.

Many patients believe that their diabetes has been caused by stress or an adverse life event. Whereas there is strong evidence that psychological stress is related to a deterioration in glycaemic control in established diabetes, there is much less evidence that psychological stress can cause diabetes in humans de novo. It seems more likely that psychological stress produces a deterioration in glycaemia in the non-symptomatic patient which in turn makes diabetic symptoms and the diagnosis evident. The pathogenic mechanisms which have been suggested to relate psychological stress to diabetes are described and reviewed.

In a case-control design the feeding in infancy of newly diagnosed 7- to 14-year-old diabetic children (n = 426) was compared with that of age- and sex-matched non-diabetic children (n = 426) randomly selected from the Finnish population registry. All 7- to 14-year-old diabetic children diagnosed from September 1986 to the end of April 1989 from all hospitals which treat diabetic children in Finland were invited to participate in the study. Breast-feeding was initiated in almost all children, but during the birth years of this study population (1972-1982), an increase was observed in the duration of breast-feeding (whether alone or in combination with supplementary feeding) and in the age of introduction of supplementary milk feeding. The risk of Type 1 diabetes was decreased in the children who were totally breast-fed for at least 2 months (odds ratio (OR) 0.64, 95% confidence interval (CI) 0.42-0.98) or 3 months (OR 0.67, 95% CI 0.48-0.95) or exclusively breast-fed for at least 2 months (OR 0.60, 95% CI 0.41-0.89) or 3 months (OR 0.63, 95% CI 0.43-0.93). Those children who were younger than 2 months (OR 1.54, 95% CI 1.08-2.18) or 3 months (OR 1.52, 95% CI 1.11-2.08) at the time when supplementary milk feeding was begun had an increased risk of Type 1 diabetes. These associations remained significant after adjusting for the mother's education. The results suggest that early infant feeding patterns are associated with the risk of Type 1 diabetes developing at the age of 7 to 14 years.

Heritage studies involving populations that share a common genetic background but reside in different geographic areas have provided important insights into the aetiology of Type 1 diabetes. While Type 1 diabetes heritage research has focused on Iberian, Arab, Italian, Indian (Asian), and Oriental groups, little attention has been paid to the evaluation of the disease in populations with black African ancestry. Epidemiological data on the occurrence of Type 1 diabetes in New World black populations have thus far been limited to a few studies conducted mainly in African-Americans. Moreover, much of the available data is not population-based and are of limited value for making generalizations about the black populations studied. Despite the limitations, there is evidence that these populations may be important for studying the aetiology and natural history of Type 1 diabetes. Increased research in this area is warranted and should be based on population-based cohorts.

A case-control study was conducted to study the proposed inverse relationship between breast feeding and incidence of Type 1 diabetes mellitus. All Danish diabetic men born in Copenhagen during 1959-1964 and/or residing there for the first year of life (n = 119) were identified and a search made for their post-natal health visitor records. These include data on birth weight, birth length, immunizations, and feeding habits. A total of 77 cases were re-identified. No differences were found with respect to clinical characteristics between these cases and those not identified. For each diabetic subject, two control children with date of birth identical to the diabetic cases were drawn from health visitor records. Cases and controls did not differ with respect to maternal age, or birth weight or length. Overall, the statistical analysis failed to confirm the hypothesis of an association between duration of breast feeding and subsequent diabetes risk.