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Query: UMLS:C0011854 (type 1 diabetes)
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The traditional role of twin studies has been to assess the relative role of genetic factors as a first step in defining the genetic architecture of complex traits. This has been based on the realization that monozygotic pairs (MZ) share all their genes, while dizygotic pairs (DZ) share 50% of their genes on average. Thus, greater similarity of MZ pairs compared to DZ pairs has been taken as prima facie evidence of the role of genetic factors. This is true provided the environmental similarity of MZ pairs is not greater than for DZ pairs for effects relevant to the trait in question. This first step in genetic studies was carried out long ago in many research areas, but not in others. More detailed knowledge of the genetic architecture of traits is then obtained by other means. In this paper, we give a brief overview of some results for metabolic diseases (ischaemic heart disease, hypertension, subarachnoid haemorrhage, NIDDM and IDDM) using the classical twin approach in a large, unselected population-based twin cohort. We also outline approaches to using twins that we believe will continue to be useful, particularly for the study of environmental effects.
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PMID:Twin studies in metabolic diseases. 141 22

Lipoprotein(a) [Lp(a)] is an LDL particle in which apoliporotein B-100 is attached to a large plasminogen-like protein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated, and plasma Lp(a) concentrations above 20-30 mg dl-1 are an independant risk factor for ischaemic heart disease (IHD). To investigate whether Lp(a) could be important for the high cardiovascular mortality rate in patients with insulin dependent diabetes mellitus (IDDM), we determined Lp(a) concentrations and phenotypes in a group of 108 men (median age 32 years) with IDDM without nephropathy. A group of 40-year-old men (n = 466) served as controls. The median Lp(a) concentration was 7.4 mg dl-1 [95% CI 4.9 to 11.7] in the diabetic patients and 6.3 mg dl-1 [95% CI 5.2 to 7.0] in controls. The Lp(a) concentration exceeded 30 mg dl-1 in 22% of IDDM patients and in 20% of controls (P = 0.13). Moreover, the distribution of apo(a) phenotypes did not differ between patients and control. Lp(a) levels and apo(a) phenotypes are thus apparently the same in IDDM patients without nephropathy and controls. These findings do not exclude the possibility that Lp(a) may be increased in patients with nephropathy in whom coronary artery disease frequently co-exist or that Lp(a) in a given concentration is more atherogenic in IDDM patients than in persons without IDDM.
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PMID:Normal lipoprotein(a) concentrations and apolipoprotein(a) isoforms in patients with insulin-dependent diabetes mellitus. 142 59

The effect of residual C-peptide secretion in longer standing IDDM on glycaemic control and the prevalence and evolution of complications over 2 years was evaluated. Thirty-one subjects with IDDM of 15.4 (1.5) years duration (mean SEM)) and residual C-peptide secretion, were matched for age, duration of diabetes and body mass index with 31 subjects without detectable C-peptide secretion. At trial entry and over 2 years, levels of HbA1, fructosamine and mean blood glucose were essentially similar in both groups. Levels of glycated albumin (GSA) were significantly higher in the C-peptide negative group after 3 and 9 months (P less than 0.05). An increased prevalence of proliferative retinopathy in the C-peptide negative group and of peripheral vascular disease in the C-peptide secretor group was apparent at entry to the study (both P less than 0.05), although no significant differences were observed after 1 or 2 years. There was no difference in the prevalence of peripheral or autonomic neuropathy, hypertension, nephropathy or ischaemic heart disease. Subjects with C-peptide concentrations greater than 0.100 pmol/ml at entry to this study had lower daily insulin requirements after 1 and 2 years, but behaved like the larger group with any detectable C-peptide secretion in all other respects. Residual C-peptide secretion was lost after 1 year in 7 patients, in whom glycaemic control during the year had been particularly poor. Insulin antibody titres were no different in the 2 groups at any time point. This study suggests that residual C-peptide secretion in longer standing IDDM confers the potential for limited improvements in glycaemic control. This effect appears to be insufficient to prevent the evolution of microvascular complications over a 2-year period. Residual C-peptide secretion and relative hyperinsulinaemia may be associated with an excess of peripheral vascular disease.
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PMID:The relevance of persistent C-peptide secretion in type 1 (insulin-dependent) diabetes mellitus to glycaemic control and diabetic complications. 235 Oct 37

Left ventricular heart function was investigated by means of two dimensional (2D) echocardiography and pulsed Doppler (PD) echocardiography in 17 young consecutive patients aged 17-38 years (mean 26.6 y.) with type I diabetes mellitus of short duration (mean 5.5 y.) whose stress ECG showed no signs of ischemic heart disease and who had no other organic complications of diabetes. The series was compared with 13 healthy volunteers (mean age 25.5 y.). No differences were found between diabetics and controls in systolic function parameters (left ventricular fractional shortening, interventricular septum shortening, left ventricular posterior wall shortening, left ventricular endsystolic dimension) as established by 2D. The parameters of left ventricular diastolic filling (maximal velocity of the rapid filling period E, its maximal time and duration of the whole phase) were established by PD and computer assisted approach. These parameters were studied also during atrial systole A and the E/A ratio was determined. All findings were comparable in the group of diabetics and controls, with the only statistically significant difference (p less than 0.05) in the duration of A which was shortened in the diabetics.
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PMID:[Left ventricular function in patients with recent onset of type I diabetes mellitus]. 275 32

Due to the recent knowledge that the distribution of fat deposits would be a better predictor of cardiovascular disease than the degree of obesity, some risk factors for atherosclerosis were evaluated in middle age type II male diabetics and in obese subjects with and without glucose intolerance. In non-insulin dependent diabetes, abdominal adiposity reflected by the waist/hip-circumference (WHR) was related to parameters of metabolic control, lipid parameters, blood rheology, insulin status, hypertension and known vascular complications in three different groups. In the groups with abdominal obesity, the mean annual HbA1 is significantly (p less than 0.01) higher than the group without an abdominal fat mass distribution. Atherogenic index is significantly increased in the group with the highest WHR. HDL-cholesterol levels are significantly decreased in both groups with upper body fat distribution. A highly significant (p less than 0.001) correlation was present between WHR and HDL-cholesterol and WHR and total/HDL-cholesterol ratio; this significant correlation remains after correction for body mass index. Whole blood and plasma viscosity and fibrinogen levels are significantly (p less than 0.05) increased in diabetics with upper body fat accumulation and could be compared to patients with proven coronary ischemic heart disease. The frequency of peripheral vascular disease, coronary ischemic heart disease and hypertension is most prominent in diabetics with an abdominal fat mass distribution. Systolic blood pressure even seems to be increased in non-obese diabetics with the highest WHR. A correlation could be found between WHR and both systolic and diastolic blood pressure. When corrected for body mass index the same significant correlation between WHR and blood pressure remained. Both fasting and postprandial insulin and C-peptide values may be the link between abdominal fat deposits and all metabolic disturbances. These results confirm the negative effect of an excess of abdominally located fat cells, even without manifest obesity, on diabetes metabolic control, lipid fractions, hypertension, insulin behaviour, blood rheology and cardiovascular complications. In obese patients with upper body fat accumulation a higher prevalence of glucose intolerance and diabetes is present, in contrast to their counterparts with lower body fat deposit. Both fasting glycemia, insulin and insulin area are significantly (p less than 0.005) increased in the group with the greatest WHR.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Body fat mass distribution. Influence on metabolic and atherosclerotic parameters in non-insulin dependent diabetics and obese subjects with and without impaired glucose tolerance. Influence of weight reduction. 280 Jun 85

Patients with insulin dependent diabetes mellitus who develop proteinuria may die prematurely, whereas those who do not develop this complication have a comparatively normal life span. The excess mortality in diabetics with proteinuria is from cardiovascular as well as renal disease, but the reason is unclear. Risk factors for vascular disease were therefore assessed in 22 insulin dependent diabetics with proteinuria, but not renal failure, who were matched for sex, age, duration of diabetes, and glycated haemoglobin (HbA1) values with a similar number who had normal urinary albumin excretion rates. Macrovascular disease (ischaemic heart disease and peripheral vascular disease) was present in 10 patients with proteinuria but in only three with normal albumin excretion rates, and proliferative retinopathy was detected in 11 and four patients in the two groups. There was no significant excess of smokers in the group with proteinuria. Blood pressure was, however, higher in the patients with proteinuria--mean systolic pressure 161 (SD 18) mm Hg compared with 135 (19) mm Hg (95% confidence interval of difference between means 15 to 38 mm Hg); mean diastolic pressure 90 (SD 12) mm Hg compared with 79 (15) mm Hg (confidence interval 3 to 19 mm Hg). The concentration of serum high density lipoprotein (HDL) cholesterol isolated by precipitation was lower in the patients with proteinuria (confidence interval 0.02 to 0.41 mmol/l). Their concentration of HDL2 cholesterol isolated by ultracentrifugation was also decreased (confidence interval 0.02 to 0.40 mmol/l), whereas HDL3 cholesterol tended to be increased (confidence interval -0.01 to 0.23 mmol/l). There was also a trend for serum cholesterol concentrations to be higher in the presence of proteinuria (confidence interval -0.39 to 1.20 mmol/l). The aggregation of risk factors for atherosclerosis in insulin dependent diabetes mellitus complicated by proteinuria helps to explain the increased prevalence of ischaemic heart disease and peripheral vascular disease reported in these patients. Early renal disease in insulin dependent diabetes may have an important role in hypertension and altered lipoprotein metabolism.
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PMID:Influence of proteinuria on vascular disease, blood pressure, and lipoproteins in insulin dependent diabetes mellitus. 311 68

Diabetic nephropathy, a rarely listed cause of end-stage renal failure (ESRF) among patients starting renal replacement therapy (RRT) in the early seventies, has progressively gained in importance and become one of the major reasons for the continuous growth of the patient population on RRT in most European countries. Amongst new patients commencing RRT in 1985, the acceptance rate varied between 3 and 12 per million population for type I diabetes mellitus and between one and four per million population for type II diabetes mellitus. Nordic countries, particularly Sweden and Finland, had the highest acceptance rate of young patients with type I diabetes mellitus whose median ages were 38-42 years. In most central and southern European countries the median age of patients with type I diabetes mellitus varied between 50 and 58 years. The high number of young patients with type I diabetes mellitus and ESRF in Nordic countries point to a different natural history of this disease. It cannot be excluded, however, that the higher median age in other countries might result from doctors mistakenly diagnosing type I disease in patients with type II disease who need insulin treatment. Patients with type II diabetes mellitus had a similar age distribution at start of RRT throughout Europe and their median ages clustered around 60 years in most countries. The contribution of haemodialysis, peritoneal dialysis and renal transplantation was analysed for diabetic compared to non-diabetic ESRF. Despite large geographical differences in the proportional use of methods of treatment, a general trend to apply CAPD more frequently in diabetic as compared to non-diabetic patients was observed, and this was true for countries with both predominant haemodialysis and predominant transplant programmes. Transplantation without prior dialysis was performed in 17% of Swedish and 30% of Norwegian patients with type I diabetes mellitus. In order to better explain the mortality of patients with diabetic ESRF, the proportional distribution of causes of death was analysed. Myocardial ischaemia and infarction was confirmed to be the leading cause of death in patients with diabetes mellitus on RRT. The coronary death rate was estimated to be 10 times greater in young patients with type I diabetes mellitus as compared to their non-diabetic counterparts. Other cardiovascular as well as infectious causes were recorded in a similar proportion of deaths in diabetics as in non-diabetics. Cancer deaths, however, appeared to be definitely less frequent in patients on RRT due to diabetic nephropathy.
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PMID:Renal replacement therapy in patients with diabetic nephropathy, 1980-1985. Report from the European Dialysis and Transplant Association Registry. 314 13

To clarify the prognosis of Japanese diabetics, 143 patients with IDDM, 3394 with NIDDM and 384 with IGT who had visited the Diabetes Center of the Tokyo Women's Medical College from 1976 through 1980 were followed up during 3-7 years. The follow-up rates of the patients with IDDM, NIDDM and IGT were 100.0%, 99.6% and 99.7%, respectively. The mortality rates per 1000 person-years among the patients with IDDM, NIDDM and IGT were 8.73%, 25.24 and 13.72, respectively. On the other hand, the ratios of observed number of deaths among diabetics to expected number of deaths among a sex- and age-matched general population were 3.39 in IDDM, 1.55 in NIDDM and 1.03 in IGT. The leading cause of death in IDDM was acute cardiac failure and in both NIDDM and IGT, malignant neoplasms. In NIDDM, a statistically significant excess of deaths from diabetes mellitus itself, ischemic heart disease and malignant neoplasms was observed compared with the general population. This is the first report concerning mortality and causes of death among Japanese diabetics separately for IDDM, NIDDM and IGT.
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PMID:Mortality of Japanese diabetics in a seven-year follow-up study. 374 61

Diabetes mellitus is associated with severe and premature cardiovascular disease. The reasons for this have not been identified. It is now apparent that diabetics often have elevated circulating insulin levels compared to non-diabetics. In non-insulin dependent diabetes this is due to the associated obesity while in insulin treated diabetics exogenous insulin is responsible for hyperinsulinaemia between meals and at night. Two reports of high insulin levels in non-insulin dependent diabetics with cardiovascular disease are consistent with clinical and epidemiological studies linking hyperinsulinaemia with coronary, cerebral and peripheral arterial disease in non-diabetics. The arterial wall is an insulin sensitive tissue. Insulin promotes proliferation of arterial smooth muscle cells and enhances lipid synthesis and low density lipoprotein receptor activity. Insulin also promotes experimental atherosclerosis in a number of species. The evidence linking hyperinsulinaemia to the cardiovascular complications and diabetes is suggestive but incomplete and much more information on predictive factors for arterial disease in diabetes is urgently required. Diabetes mellitus is associated with severe and premature cardiovascular disease (reviewed by Stout 1982). Ischaemic heart disease, stroke and peripheral vascular disease are all more common in diabetics, particularly diabetic women. Although there is evidence for the existance of a specific diabetic cardiomyopathy, much of the cardiovascular disease in diabetics is due to atherosclerosis and its complications. Arterial disease in diabetics in distinct from microvascular disease affecting capillaries, and does not differ morphologically or biochemically from atherosclerosis in non-diabetics. The reason for the increased incidence of atherosclerosis in diabetes has not been established. Both non-insulin dependent and insulin dependent diabetes appear to be associated with cardiovascular disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hyperinsulinaemia--a possible risk factor for cardiovascular disease in diabetes mellitus. 390 79

The prevalence of glaucoma and ocular hypertension was investigated in an epidemiological study of diabetics traced by registration of prescriptions on insulin and oral hypoglycaemic agents (OHA) on the island of Falster (inhabitants 44 498), Denmark. Among 533 diabetics (227 insulin- and 306 OHA-treated) the prevalence rate of primary open angle glaucoma and ocular hypertension was 6.0% and 3.0%, respectively. Neovascular glaucoma occurred in 2.1% of all diabetics and in 21.3% of diabetics with proliferative retinopathy. Open angle glaucoma was more prevalent (P less than 0.01) in type 2 diabetes mellitus compared with type 1 diabetes mellitus. No difference in the prevalence of neovascular glaucoma was found between type 1 and type 2 diabetics. The occurrence of open angle glaucoma correlated positively (P less than 0.01) to the current age (greater than 65 years) in both groups and the diabetes onset age (greater than 40 years) in insulin-treated diabetics. Neovascular glaucoma correlated positively (P less than 0.05) with diabetic macrovascular complications in total (myocardial infarction, ischemic heart disease, arterial hypertension, cerebrovascular stroke, gangrene/amputation), neuropathy and severe microvascular complications (proliferative retinopathy, retinovascular occlusion). Diabetics with open angle glaucoma and ocular hypertension showed a higher frequency (P less than 0.05) of ischemic heart disease, arterial hypertension and retinovascular occlusion compared with diabetics without glaucoma or ocular hypertension.
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PMID:The prevalence of glaucoma and ocular hypertension in type 1 and 2 diabetes mellitus. An epidemiological study of diabetes mellitus on the island of Falster, Denmark. 663 28


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