Type 1 diabetes intervention trials.
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Journal Article↗
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Diabetes nutrition and complications trial (DNCT): food intake and targets of diabetes treatment in a sample of Spanish people with diabetes. Diabetes and Nutrition Study Group of the Spanish Diabetes Association (GSEDNu).
OBJECTIVE: To know the nutritional pattern of people with diabetes in Spain and that pattern's relationship with targets of metabolic control. RESEARCH DESIGN AND METHODS: The Diabetes Nutrition and Complications Trial (DNCT) is a prospective multicenter study designed to determine the nutritional behavior of diabetic patients in Spain using 7-day food diaries. A total of 337 diabetic patients, 144 (70 men and 74 women) with type I and 193 (81 men and 112 women) with type II diabetes, satisfactorily completed the 7-day food diaries from May 1993 to December 1994. RESULTS: The median energy intake of the Spanish diabetic subjects was between 1,453 and 2,217 kcal/day (6.1-9.3 MJ/day), distributed as follows: 38-40% from carbohydrate, 19-23% from protein, and 36-41.5% from fat (11.1-13.9% saturated fatty acids, 4.6-5.8% polyunsaturated fatty acids, and 19.7-21.9% monounsaturated fatty acids). Of the subjects, 69% had a cholesterol level <5.6 mmol, 97% had an HDL cholesterol level >0.9 mmol, and 85% had a triglyceride level <1.7 mmol, while <36% had an HbA(1c) value >8%. CONCLUSIONS: People with diabetes in Spain have near-optimal serum lipid levels and maintain reasonably good blood glucose control and BMI, suggesting that diabetes management that includes the usual Spanish diet, which is low in carbohydrates and high in fat, especially monounsaturated fat, might be adequate.
Adolescent↗
[Diabetes mellitus and pregnancy--the current status. II. Diabetes types 1 and 2, diabetic nephropathy and diabetic retinopathy. The effect of diabetes on pregnancy and of pregnancy on diabetes. Diagnostic monitoring].
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Adolescent↗
Familial diabetes aggregation in type I diabetics: gestational diabetes an apparent risk factor for increased diabetes susceptibility in the offspring.
A significantly decreased familial diabetes aggregation on the maternal side of insulin-dependent diabetic children born between 1974 and 1984 as compared to those born between 1960 and 1973 was observed. This phenomenon was explained by an increased prevention of hyperglycaemia during pregnancy since 1974, particularly of gestational diabetes in women with familial diabetes aggregation. A highly significant predominance of Type II diabetes was found in great-grandmothers of infantile-onset diabetics on the maternal side as compared to the paternal side. This finding may suggest that gestational diabetes, which can represent a risk factor for diabetes transmission on the maternal side, is often followed by "extragestational" type II diabetes in higher age. This conclusion is supported by the data of familial diabetes aggregation obtained in insulin-dependent infantile- or juvenile-onset diabetics, when familial diabetes aggregation was ascertained as late as at least 20 years after birth of the diabetics. In this case, a significant predominance of familial diabetes aggregation in first- and second-degree relatives, particularly in grandmothers, was found on the maternal side as compared to the paternal side. All these findings are consistent with a teratogenetic effect of gestational diabetes on diabetes susceptibility in the offspring, which can be prevented by avoiding hyperglycaemia in pregnant women and hyperinsulinism in foetuses.
Adolescent↗
Complexities in ETS-domain transcription factor function and regulation: lessons from the TCF (ternary complex factor) subfamily. The Colworth Medal Lecture.
The ETS-domain transcription factor family can be divided into a series of subfamilies. Elk-1 represents the founding member of the ternary complex factor (TCF) subfamily. By focusing on the TCF subfamily, we can demonstrate the complexities that exist in the function and regulation of ETS-domain transcription factors. This article focuses on Elk-1 in detail and summarizes the functions of other TCFs. The key themes covered include the domain structure of the TCFs, the mechanisms of complex formation with serum response factor, regulation of TCFs by mitogen-activated protein kinase cascades, and transcriptional regulatory properties of the TCFs. Finally, the emerging role of the TCFs in vivo is discussed. A picture is developing indicating that, while these proteins exhibit significant sequence and functional conservation, key differences in their structure and regulation are being identified which may relate to unique functions of these proteins in vivo.
Amino Acid Sequence↗
Diabetic retinopathy in pediatric patients with type-1 diabetes: effect of diabetes duration, prepubertal and pubertal onset of diabetes, and metabolic control.
OBJECTIVE: The objective of this study was to determine the contribution of prepubertal and pubertal onset and duration of diabetes to the development of diabetic retinopathy. STUDY DESIGN: A total of 1391 standardized fundus examinations (stereo fundus-photography) were performed in 441 children or adolescents with type-1 diabetes (median age 15.5 years, median duration of diabetes 6.3 years). RESULTS: Mild nonproliferative retinopathy was present in 72 patients (median age 19.9 years). Life table analysis revealed a median duration of diabetes until retinopathy was first diagnosed at 16.6 years (95% confidence interval: 15.3 to 18.3). Patients were stratified according to diabetes onset before or in puberty (> or = 10.4 years in girls, > or = 12.2 years in boys). In children with a prepubertal onset of diabetes, retinopathy occurred after a pubertal duration of 10.9 years compared with 15.1 years in children with onset of diabetes in puberty (p < 0.01), demonstrating the additional risk conveyed by the prepubertal years of diabetes. Long-term metabolic control had a significant influence on the prevalence of retinopathy: patients with a median HbA1c > or = 7.5% had development of retinopathy on average after 15.5 years compared with 18.3 years in patients with lower HbA1c values (p < 0.05). CONCLUSION: Both prepubertal and pubertal duration of diabetes are relevant for the development of background retinopathy. Good metabolic control should be attempted irrespective of age.
Adolescent↗
Effect of intensive diabetes treatment on the development and progression of long-term complications in adolescents with insulin-dependent diabetes mellitus: Diabetes Control and Complications Trial. Diabetes Control and Complications Trial Research Group.
The Diabetes Control and Complications Trial has demonstrated that intensive diabetes treatment delays the onset and slows the progression of diabetic complications in subjects with insulin-dependent diabetes mellitus from 13 to 39 years of age. We examined whether the effects of such treatment also occurred in the subset of young diabetic subjects (13 to 17 years of age at entry) in the Diabetes Control and Complications Trial. One hundred twenty-five adolescent subjects with insulin-dependent diabetes mellitus but with no retinopathy at baseline (primary prevention cohort) and 70 adolescent subjects with mild retinopathy (secondary intervention cohort) were randomly assigned to receive either (1) intensive therapy with an external insulin pump or at least three daily insulin injections, together with frequent daily blood-glucose monitoring, or (2) conventional therapy with one or two daily insulin injections and once-daily monitoring. Subjects were followed for a mean of 7.4 years (4 to 9 years). In the primary prevention cohort, intensive therapy decreased the risk of having retinopathy by 53% (95% confidence interval: 1% to 78%; p = 0.048) in comparison with conventional therapy. In the secondary intervention cohort, intensive therapy decreased the risk of retinopathy progression by 70% (95% confidence interval: 25% to 88%; p = 0.010) and the occurrence of microalbuminuria by 55% (95% confidence interval: 3% to 79%; p = 0.042). Motor and sensory nerve conduction velocities were faster in intensively treated subjects. The major adverse event with intensive therapy was a nearly threefold increase of severe hypoglycemia. We conclude that intensive therapy effectively delays the onset and slows the progression of diabetic retinopathy and nephropathy when initiated in adolescent subjects; the benefits outweigh the increased risk of hypoglycemia that accompanies such treatment.
Adolescent↗
NeuroD/BETA2 gene variability and diabetes: no associations to late-onset type 2 diabetes but an A45 allele may represent a susceptibility marker for type 1 diabetes among Danes. Danish Study Group of Diabetes in Childhood, and the Danish IDDM Epidemiology and Genetics Group.
Mutations in the NeuroD/BETA2 gene have been shown to associate with type 2 diabetes. In the present study, we examined mutations in the NeuroD/BETA2 gene for association with either type 1 or 2 diabetes. Three variants were identified in patients with type 2 diabetes: Ala45Thr (allelic frequency 0.36, 95% CI 0.31-0.41), Pro197His (0.01), and Ser259Ser (0.01). Ala45Thr and Pro197His were not associated with type 2 diabetes, but the transmission disequilibrium test showed unequal transmission of the A45 allele to offspring with type 1 diabetes (chi2 = 5.90, P < 0.02, odds ratio 1.55, 95% CI 0.91-2.63). This association could not be explained by linkage disequilibrium between the Ala45 allele and IDDM7 (D2S152), which is also located on chromosome 2q32. When tested in vitro, the biological activity of Thr45 (117+/-36% vs. Ala45) and His197 (90+/-28% vs. Pro197) on the regulation of the human insulin gene promoter appeared normal. In conclusion, mutations in the NeuroD/BETA2 gene are not a common cause of late-onset type 2 diabetes among Danes. However, in the type 1 diabetic Danish population, the Ala45Thr variant of NeuroD/BETA2 may represent a susceptibility marker independent of IDDM7 on chromosome 2q32.
Age of Onset↗
The effect of intensive diabetes treatment on the progression of diabetic retinopathy in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial.
OBJECTIVE: To determine the magnitude of the decrease in the risk of retinopathy progression observed with intensive treatment and its relationship to baseline retinopathy severity and duration of follow-up. DESIGN: Randomized clinical trial, with 3 to 9 years of follow-up. SETTING AND PATIENTS: Between 1983 and 1989, 29 centers enrolled 1441 patients with insulin-dependent diabetes mellitus aged 13 to 39 years, including 726 patients with no retinopathy and a duration of diabetes of 1 to 5 years (primary prevention cohort) and 715 patients with very mild to moderate nonproliferative diabetic retinopathy and a duration of diabetes of 1 to 15 years (secondary intervention cohort). Ninety-five percent of all scheduled examinations were completed. INTERVENTIONS: Intensive treatment consisted of the administration of insulin at least three times a day by injection or pump, with doses adjusted based on self-blood glucose monitoring and with the goal of normoglycemia. Conventional treatment consisted of one or two daily insulin injections. OUTCOME MEASURES: Change between baseline and follow-up visits on the Early Treatment Diabetic Retinopathy Study retinopathy severity scale, assessed with masked gradings of stereoscopic color fundus photographs obtained every 6 months. RESULTS: Cumulative 8.5-year rates of retinopathy progression by three or more steps at two consecutive visits were 54.1% with conventional treatment and 11.5% with intensive treatment in the primary prevention cohort and 49.2% and 17.1% in the secondary intervention cohort. At the 6- and 12-month visits, a small adverse effect of intensive treatment was noted ("early worsening"), followed by a beneficial effect that increased in magnitude with time. Beyond 3.5 years of follow-up, the risk of progression was five or more times lower with intensive treatment than with conventional treatment. Once progression occurred, subsequent recovery was at least two times more likely with intensive treatment than with conventional treatment. Treatment effects were similar in all baseline retinopathy severity subgroups. CONCLUSIONS: The results of the Diabetes Control and Complications Trial strongly support the recommendation that most patients with insulin-dependent diabetes mellitus use intensive treatment, aiming for levels of glycemia as close to the nondiabetic range as is safely possible.
Adolescent↗
Preventing cancer, cardiovascular disease, and diabetes: a common agenda for the American Cancer Society, the American Diabetes Association, and the American Heart Association.
Collectively, cardiovascular disease (including stroke), cancer, and diabetes account for approximately two thirds of all deaths in the United States and about 700 billion dollars in direct and indirect economic costs each year. Current approaches to health promotion and prevention of cardiovascular disease, cancer, and diabetes do not approach the potential of the existing state of knowledge. A concerted effort to increase application of public health and clinical interventions of known efficacy to reduce prevalence of tobacco use, poor diet, and insufficient physical activity-the major risk factors for these diseases-and to increase utilization of screening tests for their early detection could substantially reduce the human and economic cost of these diseases. In this article, the ACS, ADA, and AHA review strategies for the prevention and early detection of cancer, cardiovascular disease, and diabetes, as the beginning of a new collaboration among the three organizations. The goal of this joint venture is to stimulate substantial improvements in primary prevention and early detection through collaboration between key organizations, greater public awareness about healthy lifestyles, legislative action that results in more funding for and access to primary prevention programs and research, and reconsideration of the concept of the periodic medical checkup as an effective platform for prevention, early detection, and treatment.
Cardiovascular Diseases↗
[Mortality of diabetic patients in Warsaw--22 year prospective observation (1973/74-1995). I. Mortality of diabetic patients with type 2 diabetes (non-insulin-dependent-diabetes)].
In the period 1973/74-1995 a prospective observation was carried out on 4420 diabetic patients (1990 males and 2430 females) aged 30-68 years, with type 2 (non-insulin dependent diabetes) of 1-10 years duration. During the 22-years period nearly 80% of initial cohort died. The risk of death were 2-times higher in diabetes than in the samples of general population observed at the same time. The death risk from cardiovascular disease were over 3-times higher than in general population. The relevant risk ratio has been found over 5-times higher for coronary heart disease, which were unlike to results from the differences in death ascertainment between diabetics and the city dwellers. The all-causes ratio of death and cardiovascular diseases were the same for women and men but it was selectively higher for females then males group for coronary heart disease and cerebrovascular diseases. Among diabetic cohort the risk of death was also higher for neoplasms, especially in women.
Adult↗
[Glycemic regulation and management of essential hypertension in diabetics with type 2 diabetes mellitus; the 'United Kingdom prospective diabetes study' of diabetic complications].
Patients with type 2 diabetes mellitus often develop micro- and macrovascular complications. In 25% of them, complications are already present at the time of diagnosis. The principal objective of the United Kingdom prospective diabetes study was to determine if good blood glucose control and adequate treatment of hypertension in patients with type 2 diabetes mellitus can prevent development of diabetes-related complications. The question was also studied if they way in which this blood glucose control was achieved and the way of treating the blood pressure affected the prognosis. Blood glucose control was found to reduce the incidence of--especially--microvascular complications. Oral hypoglycaemic agents and insulin both play an important part in achieving good control. Treatment with metformin reduced mortality due to cardiovascular disease in obese patients. Strict control of the blood pressure reduced development of micro- and macrovascular complications; the mortality from diabetes-related disorders and the numbers of patients suffering a stroke or heart failure. Non of the antihypertensive drugs used (an ACE inhibitor and a beta-blocking agent) offered any advantages over the other.
Adrenergic beta-Antagonists↗
UK Prospective Diabetes Study. XII: Differences between Asian, Afro-Caribbean and white Caucasian type 2 diabetic patients at diagnosis of diabetes. UK Prospective Diabetes Study Group.
Clinical and biochemical variables and prevalence of complications at diagnosis of diabetes were assessed in 5098 Type 2 diabetic patients in the UK Prospective Diabetes Study of whom 82% were white Caucasian, 10% Asian of Indian origin, and 8% Afro-Caribbean. The Asian patients were (p < 0.001) younger (mean age 52.3, 47.0, 51.0 years), less obese (BMI 29.3, 26.7, 27.9 kg m-2), had a greater waist-hip ratio, lower blood pressure (systolic 145, 139, 144, diastolic 87, 86, 89 mmHg) and prevalence of hypertension. They were more often sedentary (19, 39, 15%), more often abstained from alcohol (21, 55, 25%) and had a greater prevalence of first degree relatives with known diabetes (36, 44, 34%). The Afro-Caribbean patients had (p < 0.001) higher fasting plasma glucose (11.9, 11.3, 12.5 mmol l-1), more severely impaired beta-cell function (45, 35, 28% normal) and less impaired insulin sensitivity (23, 19, 27% normal) by homeostasis model assessment, lower triglyceride (1.8, 1.8, 1.3 mmol l-1), and higher HDL-cholesterol (1.05, 1.03, 1.17 mmol l-1). Prevalence of a history of myocardial infarction, stroke or intermittent claudication at diagnosis was similar. The prevalence of ischaemic ECG (Minnesota code), microalbuminuria (urine albumin > 50 mg l-1), retinopathy ('191' grading of retinal photographs), and neuropathy (abnormal vibration perception threshold or absent leg reflexes) was also similar. At diagnosis of Type 2 diabetes there were no differences in prevalence of complications between white Caucasian, Asian, and Afro-Caribbean patients although differences were found in other clinical and biochemical variables.
Adult↗
Nerve conduction measures in mild diabetic neuropathy in the Early Diabetes Intervention Trial: the effects of age, sex, type of diabetes, disease duration, and anthropometric factors. Tolrestat Study Group for the Early Diabetes Intervention Trial.
We evaluated nerve conduction measures at baseline from 429 patients enrolled in a multicenter diabetic neuropathy study. We defined neuropathy by using recently proposed recommendations but included only patients who had measurable sural and peroneal responses and quantitative vibration thresholds. Patients with type II diabetes were older than type I patients (54.5 versus 39.1 years), were heavier (body mass index [BMI] of 30.9 versus 25.5 kg/m2, and in general had lower evoked amplitudes. The effects of diabetes type upon nerve conduction measures disappeared when age and BMI were included in regression models. The men had lower amplitudes and conduction velocities and longer latencies than the women. The effect of gender was greatly reduced when height was included in the regression models, but gender continued to be a significant predictor of median sensory amplitude, most conduction velocities, and most latencies in these models. The relationships between nerve conduction measures and age, sex, and anthropometric factors were similar for patients with type II, but not those with type I, diabetes to the relationships reported for normal subjects. This may be a result of greater homogeneity with respect to degree of neuropathy for type II patients than for type I patients. These findings are important in designing and interpreting clinical studies of diabetic neuropathy.
Adult↗
Glycation and carboxymethyllysine levels in skin collagen predict the risk of future 10-year progression of diabetic retinopathy and nephropathy in the diabetes control and complications trial and epidemiology of diabetes interventions and complications participants with type 1 diabetes.
Several mechanistic pathways linking hyperglycemia to diabetes complications, including glycation of proteins and formation of advanced glycation end products (AGEs), have been proposed. We investigated the hypothesis that skin collagen glycation and AGEs predict the risk of progression of microvascular disease. We measured glycation products in the skin collagen of 211 Diabetes Control and Complications Trial (DCCT) volunteers in 1992 who continued to be followed in the Epidemiology of Diabetes Interventions and Complications study for 10 years. We determined whether the earlier measurements of glycated collagen and AGE levels correlated with the risk of progression of retinopathy and nephropathy from the end of the DCCT to 10 years later. In multivariate analyses, the combination of furosine (glycated collagen) and carboxymethyllysine (CML) predicted the progression of retinopathy (chi2 = 59.4, P < 0.0001) and nephropathy (chi2 = 18.2, P = 0.0001), even after adjustment for mean HbA(1c) (A1C) (chi2 = 32.7, P < 0.0001 for retinopathy) and (chi2 = 12.8, P = 0.0016 for nephropathy). The predictive effect of A1C vanished after adjustment for furosine and CML (chi2 = 0.0002, P = 0.987 for retinopathy and chi2 = 0.0002, P = 0.964 for nephropathy). Furosine explained more of the variation in the 10-year progression of retinopathy and nephropathy than did CML. These results strengthen the role of glycation of proteins and AGE formation in the pathogenesis of retinopathy and nephropathy. Glycation and subsequent AGE formation may explain the risk of these complications associated with prior A1C and provide a rational basis for the phenomenon of "metabolic memory" in the pathogenesis of these diabetes complications.
Adult↗
[Casuistical contributions to the effect of sulfonylurea in various special forms of diabetes mellitus: steroid diabetes, diabetes with hemochromatosis, renal diabetes & diabetes with a high insulin resistance].
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Diabetes Mellitus↗
Prevalence of multivessel coronary artery disease in patients with diabetes mellitus plus hypothyroidism, in patients with diabetes mellitus without hypothyroidism, and in patients with no diabetes mellitus or hypothyroidism.
BACKGROUND: We report the prevalence of significant multivessel coronary artery disease (CAD) (>50% stenosis) in patients with diabetes plus hypothyroidism, in patients with diabetes without hypothyroidism, and in patients without diabetes or hypothyroidism who had significant CAD documented by coronary angiography. METHODS: We performed a retrospective analysis in 100 patients selected randomly with significant CAD documented by coronary angiography to investigate the prevalence of significant multivessel CAD in patients with diabetes, in patients with hypothyroidism, and in patients without diabetes or hypothyroidism. RESULTS: Significant 3-4-vessel CAD was present in 9 of 10 patients (90%), mean age 73 +/- 11 years, with diabetes plus hypothyroidism, in 10 of 25 patients (40%), mean age 63 +/- 9 years, with diabetes without hypothyroidism, and in 10 of 65 patients (15%), mean age 68 +/- 12 years, without diabetes or hypothyroidism (p <.001 comparing diabetes plus hypothyroidism with no diabetes or hypothyroidism; p <.01 comparing diabetes plus hypothyroidism with diabetes without hypothyroidism; and p <.02 comparing diabetes without hypothyroidism with no diabetes or hypothyroidism). Significant 2-4-vessel CAD was present in 10 of 10 patients (100%) with diabetes plus hypothyroidism, in 20 of 25 patients (80%) with diabetes without hypothyroidism, and in 37 of 65 patients (57%) with no diabetes or hypothyroidism (p <.01 comparing diabetes plus hypothyroidism with no diabetes or hypothyroidism; and p <.05 comparing diabetes without hypothyroidism with no diabetes or hypothyroidism). CONCLUSIONS: In patients with diabetes mellitus plus hypothyroidism, the prevalence of 3-vessel or 4-vessel CAD was significantly higher than in patients with diabetes mellitus without hypothyroidism or in patients with no diabetes mellitus or hypothyroidism. In patients with diabetes mellitus without hypothyroidism, the prevalence of 3-vessel or 4-vessel CAD was significantly higher than in patients without diabetes mellitus or hypothyroidism.
Age Distribution↗
Higher incidence of diabetic nephropathy in type 2 than in type 1 diabetes in early-onset diabetes in Japan.
BACKGROUND: Whether the type of diabetes, race, and year and age of diagnosis affect the incidence of diabetic vascular complications is unknown. That both type 1 and type 2 diabetes occur in the young Japanese population prompted us to investigate whether the type of diabetes and the year of diagnosis are related to the incidence of nephropathy. METHODS: Of the 17,256 diabetic patients who visited the outpatient clinic at our diabetes center between 1965 and 1990, 1578 (9.1%) had early-onset diabetes (diagnosed before the age of 30); of these, 620 (39%) had type 1, and 958 (61%) had type 2 diabetes. The incidence of nephropathy was analyzed in the patients according to postpubertal duration and year of diagnosis. RESULTS: The cumulative incidence of nephropathy after 30 years of postpubertal diabetes was significantly higher (P < 0.0001) in type 2 diabetic patients (44.4%, 95% CI, 37.0 to 51.8%) than in type 1 diabetic patients (20.2%, 95% CI, 14.9 to 25.8%). The incidence of nephropathy among type 1 diabetic patients has declined during the past two decades, whereas it has not among type 2 diabetic patients. The rate ratio for type 2 diabetic patients diagnosed between 1980 and 1984 relative to type 1 diabetic patients diagnosed in the same period was 2.74 (95% CI, 1. 17 to 6.41). CONCLUSIONS: The incidence of nephropathy has declined in Japanese patients with type 1 but not in those with type 2 diabetes. In young Japanese patients, because of the higher incidence of nephropathy in type 2 diabetes and the higher prevalence of type 2 than type 1 diabetes, type 2 diabetes is likely the major cause of diabetic nephropathy.
Adolescent↗