HLA-A,B, C and DR antigens in young South African blacks with Type 1 (insulin-dependent) diabetes mellitus

Summary The HLA status of South African black Type 1 (insulin-dependent) diabetic patients with age of onset under 35 years was compared with that of healthy black control subjects. HLA-A, B and C antigens were determined in 94 patients and 995 control subjects, while DR typing was carried out on 56 patients and 195 control subjects. There was a significant increase in the frequency of DR4 in patients as compared with control subjects (P < 0.01; relative risk 3.4). DR3/DR4 heterozygosity was associated with a greater relative risk for developing Type 1 diabetes mellitus (3.7) than the presence of DR3 alone (relative risk 1.6). A significant negative association was observed between the presence of BW42 and Type 1 diabetes in this population sample (P < 0.04; relative risk 0.3). A similar trend was observed with regard to DR2, the corrected p value just attaining statistical significance (p < 0.05; relative risk 0.1).     

Hospitalization because of diabetes and bereavement: a national cohort study of parents who lost a child.

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.     

The complement component C4 in black Americans with Type 1 (insulin-dependent) diabetes mellitus

Summary The complement component C4 variants C4A4, C4B 4 and C4B QO were found to be significantly increased in 64 black patients with Type 1 (insulin-dependent) diabetes compared with 169 black control subjects, yielding relative risks of 3.3, 2.9 and 3.4, respectively. The increased frequencies of C4B 4 and C4B QO in black Type 1 diabetic patients are similar to those found in Caucasoid Type 1 diabetic patients. The data suggest that Type 1 diabetes in black Americans may be partially due to admixture of genes from whites.     

Class II HLA DNA polymorphisms in Type 1 (insulin-dependent) diabetic patients of North Indian origin

Summary Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQβ and DXα DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQβ/DXα pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%,p<0.001, relative risk=5.12 (95% confidence limits: 1.96–13.4)). A DQβ polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%,p<0.02, relative risk = 0.10 (95% confidence limits: 0.02–0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DRβ polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%,p<10⁻⁶, relative risk = 12.1 (95% confidence limits: 4.32–33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.     

Oral contraceptive use and the risk of Type 2 (non-insulin-dependent) diabetes mellitus in a large prospective study of women

Summary We examined the association between oral contraceptive use and incidence of Type 2 (non-insulin-dependent) diabetes mellitus among 115117 female nurses free of diabetes, cardiovascular disease and cancer in 1976 and followed-up for 12 years. During 1237440 person years of follow-up, 2276 women who provided information on oral contraceptive use were clinically diagnosed with Type 2 diabetes. Women who used oral contraceptives in the past had only a slight and marginally increased relative risk of 1.10 (95% confidence interval 1.01, 1.21) compared to those women who had never used oral contraceptives after controlling for known risk factors of disease. We found no evidence of increased risk with longer duration of use or with shorter interval since last use. Current users did not have an increased risk of Type 2 diabetes (relative risk = 0.86, 95% confidence interval 0.46, 1.61) when compared to women who had never used the drug. There was no effect modification by obesity, family history of diabetes, or physical activity. These data suggest that past or current oral contraceptive use does not substantially influence subsequent risk of Type 2 diabetes.     

Diabetes mellitus and the incidence of hip fracture: results from the Nord-Trøndelag Health Survey

Abstract Aims/hypothesis. To study if people with Type I (insulin-dependent) or Type II (non-insulin-dependent) diabetes mellitus have increased risk of hip fracture. Methods. The study population consisted of 35 444 people 50 years of age and older, attending a health screening in a Norwegian county. They were followed up with respect to hip fracture for 9 years, and 1643 new hip fractures were recorded. Results. The relative risk of hip fracture for women with Type I diabetes compared with women without diabetes was 6.9 (95 % confidence interval 2.2–21.6) adjusted for age, body mass index and daily smoking. The relative risk for men was nearly the same, but not statistically significant. Among women 50–74 years of age with Type II diabetes for more than 5 years, the relative risk was 1.8 (95 % confidence interval 1.1–2.9). This increased risk persisted when insulin-treated women were excluded from the analysis. After additional adjustment for possible medical consequences of diabetes (impaired vision, impaired motor abilities and history of stroke) the relative risk among women 50–75 years of age with Type II diabetes was reduced to 1.5 (95 % confidence interval 0.9–2.5). Conclusion/interpretation. We found an increased risk of hip fracture in women younger than 75 years with Type I diabetes or with Type II diabetes of long duration. In older men, there was an increased risk associated with Type II diabetes of shorter duration. Whether the increased risk is attributed to reduced bone mass or to factors associated with falling has not been determined. [Diabetologia (1999) 42: 920–925] Received: 4 January 1999 and in revised form: 29 March 1999     

The Swedish childhood diabetes study — results from a nine year case register and a one year case-referent study indicating that Type 1 (insulin-dependent) diabetes mellitus is associated with both Type 2 (non-insulin-dependent) diabetes mellitus and autoimmune disorders

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.     

The HLA-D associations of Type 1 (insulin-dependent) diabetes in Punjabi Asians in the United Kingdom

Summary Type 1 (insulin-dependent) diabetes is less common in Asian Indians than in white Caucasoids. Forty-five Punjabi Asians with Type 1 diabetes and 96 racially matched control subjects were HLA-DR typed. DR3 was increased in diabetic patients vs control subjects (82% vs 38%, p<10^–5) with relative risk 7.7 and etiological fraction 0.72. DR4 was increased in diabetic patients vs control subjects (31% vs 7%, p<0.003) with relative risk 5.7 and etiological fraction 0.26. DR2 showed a negative association (relative risk 0.19, etiological fraction –0.28), as did DR7 (relative risk 0.21, etiological fraction –0.33). HLA-DQ-chain gene probing using restriction enzyme BamHI in 43 diabetic patients and 90 control subjects showed that the DR1-associated 6.2 and 3.2kb fragments were less common in diabetic patients than in the control subjects (12% vs 36%, p<0.02). A 12kb fragment was associated with DR4 in both diabetic patients and control subjects. DR3 is the major susceptibility factor for Type 1 diabetes in Punjabi Asians and DR4 is a second marker. Gene probing indicates that the same DR4 subset is associated with the condition as in white Caucasoids. DR1 and its associated DQ restriction fragments are reduced in Asian Type 1 diabetic patients making it unlikely that DR1 haplotypes carry a predisposing factor in this racial group. We conclude that the genetic component of Type 1 diabetes in Punjabis shows differences from that of the white Caucasoid population and that the lower frequency of DR4 in this population may contribute to the lower prevalence of Type 1 diabetes.     

Perinatal risk factors for early onset of Type 1 diabetes in a 2000–2005 birth cohort

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.     

Glycaemic control during early pregnancy and fetal malformations in women with Type I diabetes mellitus

Aims/hypothesis. To assess the relation between glycaemic control in early pregnancy and the risk of congenital malformations in offspring of mothers with Type I (insulin-dependent) diabetes mellitus.¶Methods. From 1988–1997, we prospectively collected data from 691 pregnancies and 709 offspring of 488 women with Type I diabetes in a specific geographic area in Southern Finland. Glycated haemoglobin A_{1 c} at less than 14 weeks of gestation was used as the indicator of glycaemic control. The malformations were diagnosed either by ultrasonography in pregnancy or during the neonatal period. We also studied 729 non-selected control pregnancies in women without diabetes.¶Results. The numbers of major fetal malformations were 30 (4.2 %) in patients with Type I diabetes and 10 (1.2 %) in the control subjects (relative risk 3.1; 95 % confidence interval: 1.6 to 6.2). Even women whose HbA_{1 c} was only slightly raised (5.6 to 6.8 %, ie 2.0 to 5.9 standard deviation units) showed a relative risk of 3.0 (95 % confidence interval: 1.2 to 7.5). Haemoglobin A_{1 c} retained its statistically significant association with the occurrence of malformations after adjusting for White's class, age at onset of diabetes, duration of diabetes, parity, smoking and participation in pre-pregnancy counselling.¶Conclusions/interpretation. Even a slightly raised HbA_{1 c} during early pregnancy in women with Type I diabetes carries an increased risk for fetal malformations. Therefore normoglycaemia should be strived for during early pregnancy. [Diabetologia (2000) 43: 79–82]     

Haematocrit and risk of development of Type 2 diabetes mellitus in middle-aged Japanese men.

AIMS: To investigate the association between haematocrit and risk of development of diabetes. Methods The study enrolled 2953 normoglycaemic [fasting plasma glucose (FPG) < 6.1 mmol/l and taking no hypoglycaemic medication] Japanese men aged 35-59 years and free of medication for hypertension and history of cardiovascular disease. FPG was measured at periodic annual health examinations from May 1994 through May 2001. Men in whom Type 2 diabetes mellitus (FPG > or = 7.0 mmol/l or receiving hypoglycaemic medication) was found during repeated surveys were classified as having Type 2 diabetes. RESULTS: The estimated incidence rates for Type 2 diabetes during 7 years of follow-up were 3.1% [[95% confidence interval (CI) 1.6, 4.6]], 4.6% (2.8, 6.4), 5.0% (3.2, 6.9), 6.4% (4.4, 8.5), and 11.5% (8.9, 14.2) for respective haematocrit levels of < 42.6, 42.6-44.0, 44.1-45.3, 45.4-46.8, and >/= 46.9% (the log-rank test: P < 0.001). After controlling for potential predictors of diabetes, the respective relative risks for Type 2 diabetes were 1.0 (reference), 1.52 (95% CI 0.81, 2.86), 1.24 (0.66, 2.31), 1.57 (0.86, 2.88), and 2.30 (1.30, 4.08) (P for trend = 0.002). From stratified analyses by presence or absence of a risk factor, a linear association of haematocrit level with risk of development of Type 2 diabetes was also observed. CONCLUSION: These results indicate that haematocrit contributes to the risk of developing Type 2 diabetes.     

Incidence of cardiovascular disease in Type 1 (insulin-dependent) diabetic subjects with and without diabetic nephropathy in Finland

Summary This study evaluates the impact of diabetic nephropathy on the incidence of coronary heart disease, stroke and any cardiovascular disease in the Finnish population, which has a high risk of Type 1 (insulin-dependent) diabetes mellitus and cardiovascular disease. We performed a prospective analysis of the incidence of coronary heart disease, stroke and cardiovascular disease in all Type 1 subjects in the Finnish Type I diabetes mellitus register diagnosed before the age of 18 years between 1 January 1965 and 31 December 1979 nationwide. The effect of age at onset of diabetes, attained age at the end of follow-up, sex, diabetes duration and of the presence of diabetic nephropathy on the risk for cardiovascular disease was evaluated. Cases of nephropathy, coronary heart disease, stroke and all cardiovascular diseases were ascertained from the nationwide Finnish Hospital Discharge Register and National Death Register using computer linkage with the Type I diabetes mellitus register. Of the 5148 Type 1 diabetic patients followed up, 159 had a cardiovascular event of which 58 were coronary heart diseases, 57 stroke events and 44 other heart diseases. There were virtually no cases of cardiovascular disease before 12 years diabetes duration. The cumulative incidence of cardiovascular disease by the age of 40 years was 43 % in Type 1 diabetic patients with diabetic nephropathy, compared with 7 % in patients without diabetic nephropathy, similarly in men and women. The relative risk for Type 1 diabetic patients with diabetic nephropathy compared with patients without diabetic nephropathy was 10.3 for coronary heart disease, 10.9 for stroke and 10.0 for any cardiovascular disease, similarly in men and women. The presence of nephropathy in Type I diabetic subjects increases not only the risk of coronary heart disease, but also of stroke by tenfold. [Diabetologia (1998) 41: 784–790] Received: 14 August 1997 and in final revised form: 2 March 1998     

Impact of cigarette smoking on the incidence of Type 2 diabetes mellitus in middle-aged Japanese men: the Osaka Health Survey.

AIMS: To assess the impact of cigarette smoking on the incidence of Type 2 diabetes mellitus (DM) in middle-aged Japanese men. METHODS: The study enrolled 6250 men aged 35-60 years and free of diabetes, impaired fasting glucose and hypertension at entry. Type 2 DM was defined by a fasting plasma glucose level > or =7.0 mmol/l or physician-diagnosed Type 2DM. RESULTS: Four hundred and fifty cases of Type 2 DM were confirmed during the 60904 person-years follow-up. After adjustment for multiple covariates, including age, body mass index, alcohol consumption, physical activity, parental history of diabetes and the level of fasting plasma glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol and haematocrit, the relative risk of Type 2 DM among current smokers compared with non-smokers was 1.47 (95% confidence interval (CI) 1.14-1.92). Men who smoked >30 cigarettes/day had a multivariate-relative risk of 1.73 (95% CI 1.20-2.48) compared with non-smokers. The number of cigarettes smoked daily and the pack-year values were positively related to the development of Type 2 DM in a dose-dependent manner (P for trends = 0.0026 and 0.001, respectively). CONCLUSIONS: A cigarette smoking habit is an independent risk factor for Type 2 DM.     

Processed meat intake and incidence of Type 2 diabetes in younger and middle-aged women

Aim/hypothesis The aim of this study was to investigate the association between processed and other meat intake and incidence of Type 2 diabetes in a large cohort of women.Methods Incident cases of Type 2 diabetes were identified during 8 years of follow-up in a prospective cohort study of 91246 U.S. women aged 26 to 46 years and being free of diabetes and other major chronic diseases at baseline in 1991.Results We identified 741 incident cases of confirmed Type 2 diabetes during 716276 person-years of follow-up. The relative risk adjusted for potential non-dietary confounders was 1.91 (95% CI: 1.42–2.57) in women consuming processed meat five times or more a week compared with those consuming processed meat less than once a week (p<0.001 for trend). Further adjustment for intakes of magnesium, cereal fibre, glycaemic index, and caffeine or for a Western dietary pattern did not appreciably change the results and associations remained strong after further adjustment for fatty acid and cholesterol intake. Frequent consumption of bacon, hot dogs, and sausage was each associated with an increased risk of diabetes. While total red meat (beef or lamb as main dish, pork as main dish, hamburger, beef, pork or lamb as sandwich or mixed dish) intake was associated with an increased risk of diabetes, this association was attenuated after adjustment for magnesium, cereal fiber, glycaemic index, and caffeine (relative risk: 1.44; 95% CI: 0.92–2.24).Conclusion/interpretation Our data suggest that diets high in processed meats could increase the risk for developing Type 2 diabetes.Abbreviations RR relative risk     

Amylin gene promoter mutations predispose to Type 2 diabetes in New Zealand Maori

AIMS/HYPOTHESIS: Amylin gene mutations are known to predispose Chinese and Japanese subjects, but not Caucasian subjects, to Type 2 diabetes. New Zealand Maori, who have a high prevalence of Type 2 diabetes, have genetic origins in South East Asia. Amylin gene mutations could therefore predispose New Zealand Maori to Type 2 diabetes. METHODS: The amylin gene was screened for mutations in the proximal promoter region, exons 1 and 2, intron 1, and coding region of exon 3 by polymerase chain reaction amplification and direct sequencing of 131 Type 2 diabetic Maori patients and 258 non-diabetic Maori control subjects. RESULTS: We identified three new amylin gene mutations: two mutations in the promoter region (-215T>G and -132G>A) and a missense mutation in exon 3 (Q10R). The -215T>G mutation was observed in 5.4% of Type 2 Maori diabetic patients and predisposed the carrier to diabetes with a relative risk of 7.23. The -215T>G mutation was inherited with a previously described amylin promoter polymorphism (-230A>C) in 3% of the Maori with Type 2 diabetes, which suggests linkage disequilibrium exists between these two mutations. The -230A>C polymorphism on its own, however, was not associated with Type 2 diabetes in Maori subjects. The -132G>A and Q10R mutations were both observed in 0.76% of Type 2 diabetic patients and were absent in non-diabetic subjects. CONCLUSION/INTERPRETATION: The amylin gene mutations identified in this study are associated with Type 2 diabetes in 7% of Maori. Amylin is likely to be an important susceptibility gene for Type 2 diabetes in Maori people.     

Parental age at delivery, birth order, birth weight and gestational age are associated with the risk of childhood Type 1 diabetes: a UK regional retrospective cohort study.

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.     

Screening for Type 2 diabetes in the accident and emergency department.

AIM: To assess the proportion of patients, aged 40 years and over, attending an inner city accident and emergency department that have Type 2 diabetes, and the proportion previously undiagnosed, and to assess whether the identification of undiagnosed Type 2 diabetes is feasible in this setting. METHODS: Five hundred unselected people participated. All completed a demographic questionnaire regarding risk factors for diabetes. In those without known diabetes, random capillary blood glucose (CBG) was measured. If this was greater than 7.0 mmol/l, patients were asked to return for two fasting blood glucose tests. Diagnosis of diabetes was based on World Health Organization criteria. RESULTS: Of the 500 participating subjects, 73 were already known to have Type 2 diabetes. Of the remaining 427 subjects, 36 had CBG>7.0 mmol/l. All 36 returned for fasting blood tests: 13 fulfilled the diagnostic criteria for Type 2 diabetes, eight for impaired fasting glucose (IFG), and 15 had normal fasting glucose values. The prevalence of Type 2 diabetes was therefore 17.2%, including 2.6% with a new diagnosis, and 14.6% with pre-existing disease; 1.6% were found to have IFG. Body mass index was greater in those with Type 2 diabetes (previously and newly diagnosed) [27.1 (5.15) (mean+/-standard deviation)] vs. 25.8 (4.70) kg/m2; unpaired t-test P=0.0213), and those with Type 2 diabetes were more likely to be of black and minority ethnic origin (57 vs. 28%; chi2 P<0.001) and to have a first-degree family history of diabetes (45 vs. 23%; chi2 P<0.001). CONCLUSIONS: It can be estimated from this survey that, annually, this case-finding methodology could identify 539 (95% CI 249-828) people aged 40 years and over attending our accident and emergency department with previously undiagnosed Type 2 diabetes.     

A prospective study of mortality among middle-aged diabetic patients (the London cohort of the WHO Multinational Study of Vascular Disease in Diabetics) II: associated risk factorin

Summary Potential risk factors have been examined for association with mortality over a 10–12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 year in at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both sexes with Type 2 (non-insulin-dependent) diabetes mellitus and in women with Type 1 (insulin-dependent) diabetes mellitus; both systolic blood pressure (men) and hypertension (both sexes) (as a categorical variable) are significant in Type 1 diabetes. Hypertension is also significantly associated with all-cause mortality in multivariate analysis in both sexes with Type 1 diabetes as proteinuria is in women with Type 2 diabetes. There is an unexpected negative association between plasma creatinine and all-cause mortality in men with Type 2 diabetes. Systolic blood pressure and hypertension are also significantly linked with cardiovascular mortality in Type 1 diabetes, hypertension having an estimated relative risk of 18.6 in multivariate analysis. Serum cholesterol and proteinuria showed the strongest associations with cardiovascular mortality in Type 2 diabetes. Proteinuria is associated with non-cardiovascular mortality in both types of diabetes in univariate but not multivariate analysis. In multivariate analysis hypertension (Type 1 diabetes) and diabetes duration (Type 2 diabetes) are associated with non-cardiovascular mortality. Hypertension and proteinuria have the most consistent associations with mortality in the different analyses with the effect of hypertension appearing stronger in Type 1 diabetes and proteinuria in Type 2 diabetes. Some other proven risk factors in non-diabetic populations had inconstant or absent associations in this group: other, as yet undefined, factors may be important in diabetes.     

Familial aggregation in type 1 (insulin-dependent) diabetes mellitus: a study from south India

An analysis of 617 Type 1 (insulin-dependent) diabetic patients from 587 families was made. In 33 families (5.6%) there was more than one Type 1 diabetic patient. In 98 families (16.7%) positive family history of Type 2 (non-insulin-dependent) diabetes was present. There was a linear correlation between the age at diagnosis of the proband and that of the sibling (r = 0.73, p less than 0.001) in the Type 1 multiplex families. The risk of Type 1 diabetes in relatives was found to be 2.7% by Li Mantel estimate, which is lower than that reported among Europeans. The cumulative risk was higher (p less than 0.001) in the relatives of Type 1 diabetic patients with age at diagnosis less than or equal to 10 years.     

Activation of the innate immune system as a predictor of cardiovascular mortality in Type 2 diabetes mellitus.

AIMS: Activation of innate immunity may play a major role in the development and pathophysiology of Type 2 diabetes; we therefore investigated whether a marker of innate immunity (serum sialic acid) predicts cardiovascular disease (CVD) and all-cause mortality in Type 2 diabetes. METHODS: Type 2 diabetic subjects (n=128, age 31-64 years at outset) participating in the Lewisham Diabetes Survey were followed up for a mean of 12.8 years. Baseline measurements were made of serum sialic acid and known or putative risk factors for CVD. Cause of death was coded from death certificates, post mortem examination and hospital records. RESULTS: Fifty-six (43%) subjects had died after 12.8 years. The major cause of death was CVD (71.4%), predominantly coronary heart disease (62.5%). Baseline variables significantly associated with CVD mortality were sialic acid and CVD (borderline significance smoking and cholesterol). In multivariate analysis, significant independent predictors of CVD mortality were sialic acid [standardized relative risk (95% confidence interval) 1.53 (1.12, 2.10)], age, male sex and existing CVD. CONCLUSIONS: Activated innate immunity (low-grade inflammation) is a risk factor for CVD mortality in Type 2 diabetes, independently of other known risk factors, including existing CVD. Since activation of the innate immune system predicts Type 2 diabetes, it may be a common antecedent of both Type 2 diabetes and CVD.