Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011854 (type 1 diabetes)
 20,749 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Increased visceral adipose tissue is thought to contribute to impaired glucose tolerance. We studied 10 men with non-insulin dependent diabetes (NIDDM) before and after a 12-week intervention study using dexfenfluramine. Subjects had a mean body mass index (BMI) of 26.4 +/- 1.7 kg/m2 and had an abdominal distribution of body fatness (waist-to hip ratio > 0.9). Anthropometric indices, biochemistry, macronutrient intake from 7-day food records as well as a euglycaemic glucose clamp and magnetic resonance imaging (MRI) were performed at week 0 and week 12. Abdominal adipose tissue area measured by MRI was reduced from 854 +/- 270 cm2 to 666 +/- 231 cm2 (p = 0.003) due mainly to a selective 32% reduction in visceral fat area from 484 +/- 230 cm2 to 333 +/- 72 cm2 (p = 0.002). Insulin sensitivity improved from 0.29 +/- 0.13 [min-1 (mU/L)] to 0.54 +/- 0.21 [min-1 (mU/L)] (p = 0.01) and C-peptide levels reduced from 0.77 +/- 0.24 mumol/L to 0.58 +/- 0.15 mumol/L (p = 0.002). The reductions in fasting glucose and glycated haemoglobin failed to achieve significance. Fasting total cholesterol and triglyceride levels significantly reduced (p = < 0.001 and p = 0.021 respectively). There was a reduction in total energy intake (p = 0.005) due to a significant reduction in calories obtained from fat (p < 0.001). Thus dexfenfluramine was shown to be a useful adjunct therapy for the reduction of visceral fat in abdominally-obese men with NIDDM with an associated improvement in insulin sensitivity.
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PMID:Reduction of visceral adipose tissue and improvement of metabolic indices: effect of dexfenfluramine in NIDDM. 878 40

The importance of islet cell antibodies (ICA) as a predictor of insulin dependent diabetes mellitus (IDDM) has been emphasized by several investigators since 1974. The ICA was also detected in patients with various immune-mediated diseases such as auto-immune thyroiditis. Schistosomiasis is a wide-spread helminthic disease which affects more than 200 million patients all over the world. Immunological abnormalities and pancreatic affection are features of the disease. We studied the prevalence of ICA in 40 children with schistosomiasis (20 males and 20 females), 14 children with IDDM, and 30 of the non-diabetic siblings of patients with IDDM, and evaluated the oral glucose tolerance and early release of insulin after an i.v. load of glucose in children with schistosomiasis, diabetics' siblings, and 10 normal age-matched controls. The age of onset of IDDM and duration of the disease were 6.5 +/- 2.3 and 4.1 +/- 1.2, respectively, and the age of onset and duration of schistosomiasis were 8.3 +/- 2.7 and 2.5 +/- 1.5 years, respectively. Sex, consanguinity, history of previous virus diseases (mumps, measles and rubella), and sex maturity rating did not differ among the three study groups; however, children with schistosomiasis were significantly older. The prevalence of ICA was 50 per cent in children with IDDM, 13 per cent in the diabetics' siblings, and 25 per cent of children with schistosomiasis. Glucose tolerance was normal in children with schistosomiasis and diabetics' siblings. Early release of insulin after i.v. glucose load was significantly lower in children with schistosomiasis compared to the other two groups. In conclusion, the high prevalence of ICA and the decreased early release of insulin in response to an i.v. glucose load in children with schistosomiasis suggest that auto-immune aggression against the islet cells contributes in the pathogenesis of pancreatic disease in these patients, and might increase the risk for developing glucose intolerance and diabetes.
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PMID:High prevalence of islet cell antibody and defective insulin release in children with schistosomiasis. 882 Jun 21

An A-to-G mutation at np3243 in tRNA(Leu) (UUR) gene of the mitochondrial DNA has been described to associate with diabetes mellitus. This exists within the sequence that is important for binding termination factor, which ends the transcription of one of the two major transcripts. We investigated the prevalence of this mutation in randomly selected 276 NIDDM+ 24 IGT, 94 IDDM, and 115 non-diabetic control subjects. The mutation was also reported to exist frequently in slowly progressive IDDM. We recruited 116 juvenile onset autoimmune Type 1 diabetes and 154 autoimmune thyroid diseases to see if this mutation is involved in autoimmunity. We identified this mutation in 3 of 300 NIDDM+IGT (1%). None from IDDM or control group, nor from autoimmune disease group had this mutation. The patients with this mutation did not have cerebro-muscular symptoms as were observed in MELAS. One patient had only slight glucose intolerance indicating diabetes with this mutation may have various phenotypes. Genetic area around tRNA(Leu) (UUR) is a hot spot for pathological mutations. We directly sequenced this area of mtDNA from diabetes and identified a new polymorphism in ND-1 gene, which is situated downstream of tRNALeu (UUR) gene. We screened 154 IDDM and 254 NIDDM+ IGT patients, and identified it in 3 NIDDM and 2 IGT subjects. Both of the NIDDM patients had bilateral hearing impairment. None from 207 non-diabetic control subjects and IDDM were positive for this mutation. Its prevalence was a little more than that of an A-G mutation at np3243.
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PMID:Mitochondrial gene mutations that affect the binding of the termination factor and their prevalence among Japanese diabetes mellitus. 884 39

By directly sequencing amplified DNA from 30 patients with non-insulin-dependent diabetes mellitus (NIDDM) who had diabetic family members, we identified a G-to-A mutation at np 3316 in the ND-1 gene of the mitochondrial DNA (mtDNA). DNA from 254 patients with NIDDM or impaired glucose tolerance (IGT), from 154 patients with insulin dependent diabetes mellitus (IDDM) and from 207 non-diabetic control subjects was screened for this substitution. The mutation existed in 5 of 254 Japanese NIDDM or IGT patients (2.0%), but not in other subjects. Its prevalence was significantly higher in NIDDM than in other patients or non-diabetic control subjects. The association of the G-A mutation at np 3316 with glucose intolerance suggests the importance of this area for the development of diabetes.
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PMID:A G-to-A substitution at nucleotide position 3316 in mitochondrial DNA is associated with Japanese non-insulin-dependent diabetes mellitus. 885 17

Wistar rats with non-insulin dependent diabetes induced by neonatal streptozotocin (STZ) administration were raised either in large or in small litters. The STZ-treated rats from small litters showed a higher body weight as well as increased blood glucose levels compared with vehicle- and STZ-treated rats reared in large nests at an age of 8 weeks. The higher body weight of these rats was maintained until an age of 15 weeks, whereas the basal blood glucose was normalized. However, both STZ-treated groups exhibited an impaired glucose tolerance. During pregnancy only the glucose tolerance of the STZ-treated animals from large nests was improved although not normalized. The STZ-treated rats from small nests failed to adapt to pregnancy because the blood glucose levels after glucose load were similar to values found in the virgin state. The body weight of pregnant STZ treated rats raised in small litters was significantly lower than in vehicle- or STZ-terated rats from large nests. The number of fetuses per litter was similar in all groups tested. Compared with the vehicle-treated rats from large litters the fetal body weight of STZ-treated rats from small nests was decreased and that of STZ rats raised in large litters was increased. These results suggest that the rats with the more impaired glucose tolerance produce growth-retarded pups and, conversely, rats with rather mild impairment have bigger fetuses than the vehicle-treated ones. In the present study we have examined for the first time the combined effects of postnatal overnutrition and pregnancy on glucose homeostasis of rats treated neonatally with STZ. Our data demonstrate that postnatal overnutrition is an aggravating factor in the development of a diabetic state in these rats, especially at times when the insulin requirement is higher such as puberty and pregnancy.
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PMID:Influence of postnatal overnutrition and pregnancy on non-insulin dependent diabetes induced in Wistar rats by neonatal streptozotocin. 886 3

The prevalence of diabetes mellitus in Korea has increased tremendously during the past several decades. In addition to the explosive increase of diabetes mellitus, the clinical characteristics of diabetes mellitus in Korea seems to be quite different from those of Western countries. Most patients with non-insulin-dependent diabetes mellitus (NIDDM) are non-obese and many of them lose weight significantly during the course of developing diabetes. The pathogenic mechanism(s) underlying this phenotype is still unclear. A subgroup of patients known as slow onset IDDM exists, but this could not explain the majority of non-obese NIDDM in Korea. In order to examine whether insulin resistance/hyperinsulinaemia is important in the development of NIDDM we conducted the following studies. Fasting plasma glucose and insulin concentration were measured in subjects with normal glucose tolerance, impaired glucose tolerance and diabetes mellitus. The peak plasma insulin level was much lower than that of Pima Indians or Caucasians. We also found that the insulin sensitivity index measured by euglycemic hyperinsulinaemic clamp in the first degree relatives of Korean NIDDM patients was not lower than that in a control group. This data suggests that insulin resistance, or hyperinsulinaemia, does not play a major role in the development of NIDDM in Korea. Taken together with the rarity of obese NIDDM in Korea, it maybe suggested that the insulin secretory capacity of Korean people being smaller than Western people they cannot compensate for the insulin resistance imposed by recent changes in life style.
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PMID:Non-insulin-dependent diabetes mellitus (NIDDM) in Korea. 889 74

So far, a wealth of data originating from in vitro or animal experiments has been collected supporting the concept that the gut hormone, glucagon-like peptide-1 (GLP-1) may serve as a model molecule for the design of a new drug for the treatment of diabetes mellitus. This is supported by observations that GLP-1 has potent insulinotropic action in patients with non-insulin-dependent diabetes mellitus (NIDDM). It enhances beta-cell sensitivity to glucose stimulated insulin secretion. GLP-1 may also have a role in the treatment of impaired glucose tolerance, where the beta-cell is already insensitive to changes in plasma glucose concentrations. It may, as has previously been shown in animal models of 'prediabetes', delay the progressive decline in glucose tolerance to NIDDM. The glucose-dependent action of this peptide is an important feature in the treatment of NIDDM as it will protect against hypoglycaemic reactions, the most serious acute side-effect of antidiabetic therapy. Glucose utilization may be enhanced which would improve metabolic control in both NIDDM and IDDM. A glucagon lowering effect will further enhance metabolic control. This article reviews current experiences of the effects of GLP-1 in human studies. It points out the outcomes and limitations of previous trials and discusses future directions for the investigation of its potential use as a new agent in diabetes treatment.
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PMID:Human studies with glucagon-like-peptide-1: potential of the gut hormone for clinical use. 891 78

In vitro, cytokines like interleukin-1-beta (IL-1-B) and tumour necrosis factor-alpha (TNF-A) inhibit insulin release and can destroy islet B-cells. We measured blood levels of IL-1-B, TNF-A, and islet cell antibody (ICA) in 20 children with IDDM, 20 of their non-diabetic siblings, 20 children with thalassemia major on long-term hypertransfusion therapy and iron chelation, and 10 normal age-matched children. In the non-diabetic and thalassemic children we investigated the early phase of insulin release after i.v. glucose (0.5 g/kg, 30 per cent solution) and evaluated tolerance to oral glucose (1.75 g/ kg). Circulating IL-1-B and TNF-A concentrations were significantly higher in IDDM-siblings (33.7 +/- 12.7 pg/ml and 655 +/- 165 pg/ml, respectively) v. normal children (21.1 +/- 6.4 pg/ml and 383 +/- 122 pg/ml, respectively). Thalassemic children had no detectable circulating ICA. The prevalence of ICA was 30 per cent in children with IDDM and 60 per cent of their siblings. Impaired oral glucose tolerance was detected in five children with thalassemia (25 per cent), but in none of the IDDM-siblings. The early phase of insulin release was significantly depressed in thalassemic children (peak insulin = 29.2 +/- 5.1 mIU/ml) v. normal children (52.3 +/- 9.5 mIU/ml) and IDDM-siblings (45.3 +/- 12.4 mIU/ml). It appears that thalassemic children had significantly decreased insulin secretion and impaired glucose tolerance, however, the mechanism of B-cell dysfunction is not mediated by ICA nor by cytokines.
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PMID:Interleukin-1-beta, tumour necrosis factor-alpha, islet-cell antibody, and insulin secretion in children with thalassemia major on long-term blood transfusion. 900 65

We conducted a pilot study of immunosuppression with low dose cyclosporine in first degree relatives of diabetic patients with immunologic and metabolic criteria for preclinical diabetes: islet cell antibodies (ICA) > or = 20 Juvenile Diabetes Foundation (JDF) units, first phase insulin response < 10th percentile and impaired glucose tolerance. Cyclosporine was given at an initial dose of 7.5 mg/kg*d and tapered after the end of the first year. Six cyclosporine-treated relatives were compared to nine historical controls followed at the same or at different centres. All untreated patients developed diabetes within 12 months (5.9 +/- 1.1 months). Four of the cyclosporine-treated subjects developed diabetes at 5, 24, 24 and 47 months while the other two are non diabetic 47 and 57 months after entry into the trial (time to diabetes > 34 +/- 8 months, P < 0.001 vs the control group; Mann-Whitney test). First phase insulin response increased to normal values in two patients. These results suggest that reversible functional impairment, in association with beta-cell destruction, contributes to the failure of insulin secretion in preclinical type 1 diabetes.
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PMID:Cyclosporine delays but does not prevent clinical onset in glucose intolerant pre-type 1 diabetic children. 911 76

Diabetes, known since antiquity, has been defined by glycosuria. In 1886, when Minkowski demonstrated that pancreatectomized dogs developed diabetes, the islets of Langerhans became a focus of the search for an active principle culminating in the discovery and the isolation of insulin in 1921 by Banting, Best and Collip. In 1959, the radioimmunoassay of Yalow and Berson solidified the concept of insulin resistance in non-insulin dependent diabetes (NIDDM). In 1971, the insulin receptor was defined as a cell surface protein that initiated the insulin signal transduction cascade. Today, we know that NIDDM accounts for at least 90% of all diabetes worldwide and involves approximately 100 million people. The microvascular complications of NIDDM are the same as for insulin dependent diabetes (IDDM) and are related to the intensity and duration of hyperglycaemia. Further, it is clear from the Diabetes Control and Complications Trial (DCCT) that all microvascular complications can be reduced with intensive control of the blood glucose. Macrovascular disease is also accelerated in NIDDM, including both hypertension and dyslipidemia. The major risk factor for NIDDM are age, obesity, physical inactivity, and genetic background. The earliest features seen in individuals destined to develop NIDDM is insulin resistance, but for hyperglycaemia to ensure there must be a defect in insulin secretion. Thus, insulin resistance defines the prehyperglycaemic phase of NIDDM, but varying degrees of insulin secretory deficiency define the hyperglycaemic phase. Macrovascular risk occurs throughout the lifetime of the individual, whereas microvascular risk ensues with the inception of hyperglycaemia. Tomorrow, we will understand more clearly whether lifestyle changes, such as diet and exercise, or new classes of drugs, can delay or prevent NIDDM. Clinical trials are now beginning to test whether impaired glucose tolerance (IGT) can be delayed or prevented from moving to overt NIDDM. The genetics of NIDDM are under intense study. Mutations in the insulin receptor lead to NIDDM in a small number of patients, and mutations in the glucokinase gene lead to maturity onset diabetes of the young (MODY). Work is now underway to study other candidate genes as well as work on positional cloning techniques to identify diabetes genetic loci. The hormone Leptin has just been discovered and is a major regulator of body weight. In summary, the most important new emphasis on the treatment of NIDDM is the recognition of the importance of hyperglycaemia and our ability to both treat and possibly prevent this metabolic perturbation. This joins the longer-term emphasis on cardiovascular risk reduction from both treatment and prevention of hypertension and dyslipidemia.
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PMID:Non-insulin dependent diabetes--the past, present and future. 928 27


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